SA Ophthalmology Journal Autumn | Vol16•No2

SA Ophthalmology Journal The official journal of the Ophthalmological Society of South Africa Earn 3 CPD points

AUTUMN 2021 | Vol 16 • No 2

SERUM EYE DROPS: A SOUTH AFRICAN PERSPECTIVE TN Glatt, B Rhode, R Cockeran, C Poole

ALCOHOL COTTON BUD TECHNIQUE FOR REMOVAL OF CORNEAL EPITHELIUM AT THE SLIT LAMP IN CORNEAL CROSSLINKING S Ballim, S Mahomed

RAPID ASSESSMENT OF AVOIDABLE BLINDNESS IN MASVINGO PROVINCE, ZIMBABWE: CONSIDERATIONS FOR RESOURCE-LIMITED SETTINGS D Minnies, B Macheka, J Joseph, C Cook

EFFICACY AND SAFETY OF ZIV-AFLIBERCEPT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN A GHANAIAN POPULATION IZ Braimah, YS Adam, WM Amoaku

NEUROMYELITIS OPTICA AND OTHER CAUSES OF DEMYELINATING OPTIC NEURITIS IN CHILDREN DD Shastry, J Olivier, C Cullen

Introducing the Next Big Advancement in the Maintenance of Normal Vision1

NEW

CEBROLUX™ NEURO FACTOR A multivitamin and mineral supplement containing nutrients and a neuroprotective agent Citicoline1 ( )

Reference: 1. CEBROLUX™ NF powder for oral solution (package insert). South Africa: Soflens (Pty) Ltd; 2019.

Scheduling status: S0 Proprietary name and dosage form: CEBROLUX™ NF powder for oral solution. Composition: Each 3g sachet contains: Citicoline (Cognizin®) 250 mg, Vitamin C 60 mg, Vitamin B3 12 mg, Vitamin E 8,2 mg, Zinc 6,25 mg, Vitamin B5 4,5 mg, Vitamin B6 1,05 mg, Vitamin B2 1,05 mg, Vitamin B1 0,83 mg, Vitamin A 600 μg, Folic acid 150 μg, Biotin 37,5 μg and Vitamin B12 1,875 μg. Bausch & Lomb Incorporated. CEBROLUXTM is a trademark of Bausch & Lomb Incorporated or its affiliates. COGNIZIN® is a registered trademark of KYOWA HAKKO BIO CO., LTD. This unregistered medicine has not been evaluated by the SAHPRA for its quality, safety or intended use. For full prescribing information, refer to the Professional Information. Applicant: Soflens (Pty) Ltd. Reg. No.: 1968/011787/07. 254 Hall Street, Centurion, 0157. Tel: +27 10 025 2100. www. bausch.co.za BL503/21

SA Ophthalmology Journal The official journal of the Ophthalmological Society of South Africa ISSN: 2218-8304

Contents

Autumn 2021 Vol 16 • No 2

Editor-in-Chief

Prof Nagib du Toit journaleditor@ossa.co.za

Managing Editor

Patricia Botes | 083 266 8200 pat.botes@ponynet.co.za

Layout & Design: Allison McCallum Advertising Sales

Charissa Piek | 082 306 1205 charissa.piek@newmedia.co.za

Expert Board

Professors: Trevor Carmichael, Colin Cook, Nagib du Toit, Prisilla Makunyane, Ismail Mayet, Anthony Murray, Derrick Smit, Sue Williams Doctors: Eric Albrecht, Hassan Alli, Naseer Ally, Stephen Cook, Linett du Toit, Leonard Heydenrych, Mpopi Lenake, Aubrey Makgotloe, Hamza Mustak, James Rice, Chris Tinley, Linda Visser

Subscriptions

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Publishing Team

General Manager: Dev Naidoo Publishing Manager: Johann Gerber Johann.Gerber@newmedia.co.za Production Manager: Angela Silver Art Director: David Kyslinger

Contact New Media Johannesburg Ground floor, Media Park, 69 Kingsway Avenue, Auckland Park, 2092 Tel: 011 877 6111 Fax: 011 713 9024 Postal Address: PO Box 784698, Sandton 2146 www.medicalacademic.co.za Printing: Printed and bound by Paarlmedia Published by New Media, a division of Media24 (Pty) Ltd

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COVER PIC: Fundus photograph showing extensive subretinal/retinal haemorrhage extending from the disc margin to the fovea

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FROM THE EDITOR

SA Ophthalmology Journal attracting submissions from other parts of Africa N du Toit

6 9 15

GUIDELINES FOR AUTHORS ORIGINAL STUDY

Serum eye drops: a South African perspective TN Glatt, B Rhode, R Cockeran, C Poole

ORIGINAL STUDY

Alcohol cotton bud technique for removal of corneal epithelium at the slit lamp in corneal crosslinking S Ballim, S Mahomed

20

ORIGINAL STUDY

Rapid assessment of avoidable blindness in Masvingo Province, Zimbabwe: considerations for resource-limited settings D Minnies, B Macheka, J Joseph, C Cook

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The reproduction, without permission of any articles or photographs in this publication is forbidden and copyright is expressly reserved to NewMedia under the Copyright Act of 1978 as amended.

The views expressed by contributors to and advertisers in the journal and the inclusion or exclusion of any medicine or procedure, do not necessarily reflect the views of the publisher or editorial board.

While every effort is made to ensure accurate reproduction, the authors, advisers, publishers and their employees or agents shall not be responsible or in any way liable for errors, omissions or inaccuracies in the publication, whether arising from negligence or otherwise or for any consequences arising therefrom.

ORIGINAL STUDY

Efficacy and safety of ziv-aflibercept in patients with neovascular age-related macular degeneration in a Ghanaian population IZ Braimah, YS Adam, WM Amoaku

33

CASE REPORT

Neuromyelitis optica and other causes of demyelinating optic neuritis in children DD Shastry, J Olivier, C Cullen

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Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

From t he Editor

SA Ophthalmology Journal attracting submissions from other parts of Africa

W

elcome to our second edition of the SA Ophthalmology Journal for 2021. Thankfully, the Covid-19 pandemic seems to have subsided for now, but we do not really know what to expect next.

We have also recently had the tragedy of the mountain fire which devastated several historical buildings at UCT and its surrounds. This year, it seems, will continue to be an eventful one.

In our second edition of 2021 we have included a few interesting original studies and a case report. We have a study from the South African National Blood Service on serum eye drops; a study which reports a novel technique for corneal epithelial debridement during corneal crosslinking; a RAAB assessment conducted in Zimbabwe in conjunction with the UCT Community Eye Health Institute; a paper on CNV treatment (age-related macular degeneration) in a Ghanaian population; and a report on neuromyelitis optica in children.

We have had a few queries from authors regarding the so-called ‘75% rule’. This rule pertains to the guideline that at least three-quarters of published articles in a South African DHET-accredited journal should come from different institutions.

SA Ophthalmology Journal has been peer-reviewed since mid-2018 and accredited since the beginning of 2020.

During our first year of accreditation, four editions were published and these included articles from several different universities/sites/sources,

viz. UCT (5), Witwatersrand (5), KZN (3), Stellenbosch (2), WSU (1), Kimberley (1), Limpopo (1), Zimbabwe (1) and Nigeria (1).

Over these four editions of 2020, the SA Ophthalmology Journal averaged 80% per issue on the above rule. These facts should alleviate the above concerns. As mentioned, we have also included an article from Ghana in this issue. It is clear that the SA Ophthalmology Journal is now attracting submissions from the Southern African region, as well as West Africa.

On another interesting note, it is known that there are academic rankings used for universities internationally on an annual basis. The most well-known of these are the Quacquarelli Symonds (QS) and the Times Higher Education (THE) world university rankings. Between 2004 and 2009, QS produced the rankings in partnership with THE, but from 2010 onwards, THE produced their own rankings in partnership with Thomson Reuters.

THE used a slightly different methodology to the original rankings when they split from QS. In partnership with Elsevier, the QS system comprises global overall, as well as subject, rankings. Factors that are considered in creating the rankings are: Academic peer review (weighting 40%); Faculty/Student ratio (20%); Citations per faculty (20%); Employer reputation (10%); International student ratio (5%); and International staff ratio (5%). Based on the above, UCT has consistently (over the past few years – including recent and current rankings – been rated as first in

Africa (QS world ranking 220 – out of 1 000 universities from 80 different locations), with Wits second (QS 403) and Cairo third (QS 411). In the South African context, we find the University of Johannesburg third (QS 439) and Stellenbosch University fourth (QS 456). This is followed by Pretoria, Rhodes, KZN, North-West and the University of the Western Cape. In contrast, THE uses rankings for more than 1 500 universities across 93 countries – in South Africa, these are quoted as (in descending order): UCT (THE world ranking 155), Wits (201–250), Stellenbosch (251–300) and KZN (351–400). This information should make for some healthy competition.

Please continue to support us with your valuable submissions. The SA Ophthalmology Journal team encourages all our readers to continue to take care. 

Prof Nagib du Toit

MBChB(UCT), DipOphth(SA), FRCS(Ed), FCOphth(SA), MMed(UCT), PhD(UCT)

Editor-in-Chief: South African Ophthalmology Journal

When

GLAUCOMA

works on the nerves

causing tunnel vision, it’s time to reduce IOP

TEST • TREAT • PRESERVE

1,2

sight

Novartis South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View 2090. Tel. +27 11 347 6600. Co. Reg. No. 1946/020671/07. ZA2104080511. Exp. 30/03/2023

41339/04/21

References: 1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet 2004; 363:1711-20. 2. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311(18):1901-1911.

S4 TRAVATAN® Eye Drops, solution (0,004 %). Reg. No. 36/15.4/0333. Composition: 40 μ g of travoprost per ml in a sterile ophthalmic solution, preserved with polyquaternium-1 (POLYQUAD) 0,001 % (m/v). S4 DUOTRAV® eye drops, solution.

Reg. No. A40/15.4/0511. Composition: 1 ml of solution contains 40 μg travoprost and 6,83 mg timolol maleate equivalent to 5 mg timolol, preserved with 0,001 % (m/v) polyquaternium-1 (POLYQUAD®). S3 AZOPTIC® Eye Drops, suspension.

Reg. No. 34/15.4/0382. Composition: A sterile, aqueous suspension containing 10 mg brinzolamide per ml with benzalkonium chloride 0,01 % (m/v) as preservative. S4 AZARGA® eye drops, suspension. Reg. No. 44/15.4/0046. Composition: 1 ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate). Preservative: benzalkonium chloride 0,01 % (w/v). Note: Before prescribing, consult full prescribing information.

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Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

Guideline s for aut hor s

South African Ophthalmology Journal guidelines for authors

T

he SA Ophthalmology Journal is a peer-reviewed scientific journal and the official mouthpiece of the Ophthalmological Society of South Africa.

It appears on a quarterly basis.

1. A cover sheet is to be submitted with each manuscript. It should contain the title of the manuscript, the names of all authors in the correct sequence, their academic status and affiliations.

The main author should include his/her name, address, phone and email address.

2. The South African Ophthalmology Journal invites review articles, original studies and case reports for submission. Articles should be the original, unpublished work of the stated author. All materials submitted for publication must be submitted exclusively for publication in this journal. Written permission from the author or copyright holder must be submitted with previously published figures, tables or articles.

3. The Editor reserves the right to shorten and stylise any material accepted for publication.

4. Authors are solely responsible for the factual accuracy of their work.

5. Articles should be between 2 000

and 3 000 words in length. A 200word abstract should state the main conclusions and clinical relevance of the article.

6. All articles are to be in English and are to follow the Vancouver style.

7. Abbreviations and acronyms should be defined on first use and kept to a minimum.

8. Tables should carry Roman numerals, I, II etc., and illustrations Arabic numbers 1, 2 etc.

9. References should be numbered consecutively in the order that they are first mentioned in the text and listed at the end in numerical order of appearance. Identify references in the text by Arabic numerals in superscript after punctuation, e.g. …trial.13 10. The following format should be used for references: Articles: Kaplan FS, August CS, Dalinka MK. Bone densitometry observation of osteoporosis in response to bone marrow transplantation. Clin Orthop 1993;294:173-78.

Chapter in a book: Young W. Neurophysiology of spinal cord injury. In: Errico TJ, Bauer

The CPD questions now have to be completed online.

To complete the questionnaire, go to https://www.medicalacademic. co.za/courses/sa-ophthalmologyjournal-cpds-autumn-2021

RD, Waugh T (eds). Spinal Trauma.

Philadelphia: JB Lippincott; 1991: 377-94.

11. Articles are to be submitted by email to the Editor-in-Chief, Prof Nagib du Toit at the following email address: journaleditor@ossa.co.za The text should be in MS Word. Pages should be numbered consecutively in the following order wherever possible: Title page, abstract, introduction, materials and methods, results, discussion, acknowledgements, tables and illustrations, references.

12. All figures, tables and photographs should also be submitted electronically. Each figure must have a separate self-explanatory legend. The illustrations, tables and graphs should not be embedded in the text file, but should be provided as separate individual graphic files, and clearly identified. The figures should be saved as a 300 dpi jpeg file.

Tables should be saved in a PowerPoint document or also as a 300 dpi jpeg.

13. Authors should declare any interests, financial or otherwise, regarding the publication of their article and should also indicate whether the submission forms part of an 'MMed dissertation by publication' by stating so clearly on the title page. 

Erratum In the previous issue of SA Ophthalmology Journal, March 2021 vol 16 no 1, there was an error in the designations of two of the authors of the article, ‘Adenovirus and human papillomavirus in the pathogenesis of pterygium’ by EB van der Merwe, J Maritz, KE Delaney and D Smit.

L Maritz and KE Delaney are both from the Division of Medical Virology at Stellenbosch University, not Medical Microbiology as previously given.

Prevention and treatment of pain and inflammation associated with cataract surgery and reduction in the risk of macular oedema associated with cataract surgery1

NEVANAC® INDICATED FOR: • Prodrug structure delivers relief to key tissues2,3 • 63 % of patients had complete inflammation clearing at Day 14 4 • 83 % of patients were pain-free at Day 14 • Established safety and tolerability with minimal discomfort in clinical trials4,5

SCHEDULING STATUS: S3 NEVANAC Eye drops, suspension Reg. No. 42/15.4/1006. COMPOSITION: 1 ml of suspension contains 1 mg nepafenac. Preservatives: benzalkonium chloride 0.005 % (m/v) and disodium edetate 0.01 % (m/v). PHARMACOLOGICAL CLASSIFICATION: A.15.4 Ophthalmic preparations, Anti-inflammatory agents, non-steroids. INDICATIONS: Prevention and treatment of pain and inflammation associated with cataract surgery and reduction in the risk of macular oedema associated with cataract surgery. DOSAGE AND DIRECTIONS FOR USE: Use in adults: Use the lowest effective dose for the shortest possible duration of treatment. Instill 1 drop of NEVANAC in the conjunctival sac of the affected eye(s) 3 times daily, beginning 1 day prior to cataract surgery, continued on the day of surgery and for the first 2 weeks of the postoperative period. Treatment can be extended to the first 3 weeks of the postoperative period, as directed by the clinician. An additional drop should be administered 30-120 minutes prior to surgery. Treatment can be extended for up to 60 days to reduce the risk of macular oedema associated with cataract surgery. Paediatric patients: The efficacy and safety of NEVANAC in patients below the age of 18 years has not been established. Geriatric patients: No dose adjustment is warranted in these patients as no overall difference in safety and efficacy have been observed in this population. Use in hepatic and renal impairment: NEVANAC has not been studied in patients with hepatic disease or renal impairment. No dose adjustment is warranted in these patients. Shake well before use. If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Keep the bottle tightly closed when not in use. CONTRAINDICATIONS: Hypersensitivity to the active substance, to any of the excipients, or to other non-steroidal anti-inflammatory drugs (NSAIDs) - Heart failure - History of gastrointestinal bleeding or perforation (PUB’s) related to previous NSAIDs. Active or history of recurrent ulcer / haemorrhage / perforations - In patients in whom attacks of asthma, urticaria or acute rhinitis are precipitated by aspirin or other NSAIDs. WARNINGS AND SPECIAL PRECAUTIONS: Use of topical NEVANAC may result in keratitis. Continued use of topical NEVANAC may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of NEVANAC and should be monitored closely for corneal health. Topical NEVANAC may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of NEVANAC and topical steroids may increase the potential for healing problems. Post-marketing experience with topical NSAIDs such as NEVANAC suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases, rheumatoid arthritis or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse reactions which may become sight threatening. NEVANAC should be used with caution in these patients. Prolonged use of NEVANAC may increase patient risk for occurrence and severity of corneal adverse reactions. NEVANAC may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery. NEVANAC should be used with caution in patients with known bleeding tendencies or who are receiving other medicines which may prolong bleeding time. NEVANAC contains benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses. Contact lens wear is not recommended during the postoperative period following cataract surgery. Patients should be advised not to wear contact lenses during treatment with NEVANAC. Benzalkonium chloride, used as a preservative in NEVANAC, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since NEVANAC contains benzalkonium chloride, close monitoring is required with frequent or prolonged use. An acute ocular infection may be masked by the topical use of NEVANAC. NEVANAC does not have antimicrobial properties. In case of ocular infection, NEVANAC should be used with care with anti- infectives. Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NEVANAC therapy. In view of NEVANAC’s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients. The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal (GI) bleeding and perforation (PUBs) which may be fatal. The risk of GI bleeding or perforation is higher with increasing doses of NEVANAC, in patients with a history of ulcers and the elderly. When GI bleeding or ulceration occurs in patients receiving NEVANAC, treatment with NEVANAC should be stopped. NEVANAC should be given with caution to patients with a history of GI disease as the condition may be exacerbated.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. NEVANAC should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. There is a potential for cross-sensitivity of NEVANAC® to aspirin, phenylacetic acid derivatives, and other NSAIDs. Effects on ability to drive and use machines: If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery. Pregnancy: NEVANAC should not be used during pregnancy. NEVANAC is contraindicated in the third trimester of pregnancy. Lactation: It is unknown whether NEVANAC is excreted in human milk. NEVANAC should not be used in women breastfeeding their infants. INTERACTIONS: Neither nepafenac nor amfenac inhibit any of the major human cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4) metabolic activities in vitro at concentrations up to 300 ng/ml. Therefore, interactions involving CYP-mediated metabolism of concomitantly administered medicines are unlikely. In vitro studies have demonstrated a low potential for interactions. Interactions mediated by protein binding are also unlikely. Use of NEVANAC with another NSAID concomitantly could result in an increase in side effects.

SIDE-EFFECTS: NEVANAC: Uncommon: keratitis, allergic conjunctivitis, punctate keratitis, eye pain, foreign body sensation in eyes, eyelid margin crusting. Rare: hypersensitivity, headache, dizziness, blurred vision, eye pruritus, dry eye, eye discharge, photophobia, eye irritation, increased lacrimation, blepharitis, nausea, allergic dermatitis. Frequency unknown: corneal perforation, ulcerative keratitis, corneal thinning, corneal opacity, corneal abrasion, corneal scar, impaired healing (cornea), visual acuity reduced, eye swelling, ocular hyperaemia, vomiting, blood pressure increased. Other NSAIDs: oedema, hypertension and cardiac failure, peptic ulcers, perforation or gastrointestinal bleeding, nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, malaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease, gastritis. Bullous reactions, including Stevens- Johnson syndrome and toxic epidermal necrolysis. Presentation/Pack size: 8 ml round, colourless low density polyethylene bottle and dispensing plug with white polypropylene screw cap containing 5 ml suspension. Note: Before prescribing consult full prescribing information. This BSS is for use on promotional material linked to MCC approved package insert dated 20.03.2018 References: 1. NEVANAC® Eye Drops, Suspension, Approved Package Insert; Novartis South Africa (Pty) Ltd, 20 March 2018 2. Gamache DA, Graff G, Brady MT, Spellman JM, Yanni JM. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. assessment of anti-inflammatory efficacy. Inflammation. 2000; 24(4):357-370. 3. Ke T-L, Graff G, Spellman JM, Yanni JM. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. in vitro bioactivation and permeation of external ocular barriers. Inflammation. 2000; 24(4):371-384. 4. Lane SS, Modi SS, Lehmann RP, Holland EJ. Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery. J Cataract Refract Surg. 2007; 33:53-58. 5. Nardi M, Lobo C, Bereczki A, Cano J, Zagato E, Potts S, et al; International C-04-65 Study Group. Analgesic and anti-inflammatory effectiveness of nepafenac 0.1% for cataract surgery. Clin Ophthalmol. 2007; 1(4):527-533.

Novartis South Africa (Pty) Ltd. Magwa Crescent West, Waterfall City, Jukskei View 2090. Tel. +27 11 347 6600. Co. Reg. No. 1946/020671/07. ZA2102041025. Exp.: 01/2023

40996 02/21

(nepafenac ophthalmic suspension) 1 mg/ml

Or iginal s tud y Serum eye drops SA

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

9

Serum eye drops: a South African perspective TN Glatt MBBCh, FCPath Haematology, MMed Haematology; Cell processing and manipulation specialist, Cellular Therapy ORCID: https://orcid.org/0000-0002-5458-5791 B Rhode BTech; Head: Cellular Therapy Laboratory R Cockeran PhD; Head: Cell Processing and Growth Laboratories ORCID: https://orcid.org/0000-0001-9227-6124 C Poole MBChB; Lead consultant: Cellular Therapy and Novel Products ORCID: https://orcid.org/0000-0002-7077-4859 Department of Cellular Therapy and Novel Products, South African National Blood Service, Johannesburg, South Africa Corresponding author: Dr Tanya Glatt, SANBS, 1 Constantia Boulevard, Constantia Kloof, 1709; tel: 011 761 9000; email: tanya.glatt@sanbs.org.za

Abstract Background: Serum eye drops are used in the management of severe ocular surface diseases including dry eye syndrome.

These eye drops are produced from the serum component of autologous or allogeneic blood donations.

Methods: This manuscript describes the manufacturing process, quality control and biochemical content of serum eye drops produced by the South African National Blood Service (SANBS), as well as questionnaire-based feedback from patients using this product.

Results: SANBS eye serum production and quality control is in line with international practices. The patient feedback shows that the use of these eye drops significantly improves dry and painful eyes, overall quality of life and the execution of daily tasks.

Introduction

Internationally the use of blood-derived products as a therapeutic modality for severe ocular surface disease (OSD) has increased significantly in recent years.1,2 This treatment option includes serum eye drops (SEDs) produced from the patient’s own blood (autologous blood donation) or from an alternate (allogeneic) blood donation. Dry eye syndrome is the most common condition treated with SEDs. 3 Other documented conditions include persistent corneal epithelial defects, limbal stem cell deficiency, corneal ulcers, chemical burns, recurrent corneal erosions, ocular surface involvement of Stevens-Johnson syndrome and graft versus host disease. 2,4 SEDs are also useful in the management of postoperative recovery after surface-based corneal laser refractive procedures. In general,

Conclusion: We can therefore conclude that SANBS produces high quality serum eye drops, which are in line with international published content investigations and which meet patient expectations.

Keywords: serum, eye drops, dry eye syndrome, therapy, ocular surface disease Funding: No financial support was received by any of the authors for performing this research.

Conflict of interest: The authors have no conflicts of interest to declare.

SEDs are reserved for patients who are non-responsive or partially responsive to standard therapy or where prompt recovery of a corneal epithelial defect is required. 2 The safety of SEDs and their effect on corneal epithelial cell migration and proliferation are well established. 5-7 The benefit of SEDs is two-fold: first, they act as a physical replacement to natural tears by offering lubrication of the ocular surface, and secondly, as a biochemical replacement to natural tears due to growth factor and cytokine content which aid ocular surface repair. 8-11 SEDs are typically produced by blood services as part of their extended programme of operation as blood services have the infrastructure to collect, test and process blood products to ensure adequate quality standards are

maintained throughout the production process.12 The South African National Blood Service (SANBS) has been producing SEDs in South Africa since 2002. This manuscript serves to report on the production, biochemical properties and patient-reported efficacy of the SEDs produced by SANBS.

Methods

The study was approved by the SANBS Human Research Ethics Committee (registration number: REC-270606-013, clearance certificate number: 2020/0539).

Study setting and SED production Patients suffering from severe OSD who have failed standard therapy or who are recovering from surface-based corneal laser refractive procedures are potential candidates for SED therapy.

10

Or iginal s tud y Serum eye drops SA

Ophthalmologists in public and private practice across South Africa prescribe SEDs for their patients by completing a SANBS SED request form. SEDs are produced at the Cellular Therapy Laboratory (CTL) at SANBS’s head office in Constantia Kloof, Johannesburg, South Africa. Patient details are captured on the laboratory information system, and they include whether the patient is fit for an autologous blood donation or if an allogeneic blood donor is required. As SEDs do not need to be ABO matched, a family member such as a spouse may donate if a blood donor is required. Alternatively, a routine blood donor is sought. The donor is contacted and referred to their closest SANBS blood donor centre for blood collection.

All donors for SEDs are required to fulfil routine blood donation criteria.13 Following routine donor screening, a unit of whole blood is collected into a ‘dry’ pack (without anticoagulant) and sent to CTL for SED preparation.

SEDs are produced under sterile conditions in a biological safety cabinet and are in line with international SED production guidelines. 2 Routine testing for transfusion-transmissible infections, which include HIV, hepatitis B (HBV), hepatitis C (HCV) and syphilis (TPHA) is performed. Infectious disease-marker testing is performed at the SANBS Donation Testing Laboratory using the Procleix Ultrio Plus (Grifols, Barcelona, Spain) and Abbott Prism ChLia (Abbott, Delkenheim, Germany) assays. The whole blood unit is centrifuged to separate it into different components and the serum is removed. The serum is filtered, diluted with saline and aliquoted into dropper bottles under sterile conditions. Each SED batch yields 34 dropper bottles which do not contain preservatives, thus a sample from each batch is tested for bacterial and fungal sterility. Fungal and bacterial sterility testing is performed at the Quality Control Laboratory using Bact/ALERT 3D (Biomerieux, Marcy-l’Etoile, France). The bottles are stored at −20 °C and are only released to the patient when both the sterility and infectious disease results are negative. If any infectious disease markers, bacterial or fungal growth are positive, the product is destroyed and the treating doctor notified to arrange an alternative donation.

When the SEDs are ready for collection, the patient is notified telephonically. The frozen SEDs are transported on dry ice to the blood donor centre most convenient for the patient. Once collected, the SEDs

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

need to be stored in a home freezer.

The patient removes a single bottle at a time and keeps this in the fridge. Each SED bottle may be used for three days and discarded thereafter. The remaining SEDs are stable in the home freezer for at least three months. Directions for use are dependent on indication and patient symptoms, with frequency of use ranging from every 15 minutes to twice per day.12

Biochemical quantification

During the December 2019 to June 2020 period, SEDs produced in the CTL were tested for pH and growth factors. The pH was measured using the Eutech pH 510 bench meter (Thermo Scientific, Waltham, Massachusetts, USA) and the growth factors using a Multiplex Magnetic Luminex Assay (R&D Systems, Minneapolis, MN, USA) according to manufacturers’ instructions. Growth factors reported on in published research studies were selected for analysis; these included epidermal growth factor (EGF), plateletderived growth factor (PDGF), brainderived growth factor (BDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF).

Patient feedback questionnaire

SANBS composed a patient feedback questionnaire to ascertain what the patients’ experiences of the SANBSproduced SEDs were. Patients receiving SEDs are routinely contacted telephonically to arrange the collection of their eye drops. During the period of December 2019 to June 2020, these patients were also asked if they would voluntarily participate in a de-identified patient feedback questionnaire. If they agreed, responses were captured on a paper-based system by the caller. Data analysis was performed by a staff member who was not involved in speaking to the patients and was blinded to all patient identifiers.

Statistical analysis

Demographic data on all patients who received SEDs from January 2015 to December 2019 was extracted from the CTL laboratory information system and included sex, age, ethnic group, type of SED used (from autologous or allogeneic blood donations) and indication for SED use. Demographic data was expressed as a percentage of the total or as average values and ranges. Biochemical analysis results were expressed as the mean ± standard deviation (SD).

Patient feedback questionnaire responses were captured on an Excel spreadsheet, and imported into STATA for additional statistical analysis. All questions where participants rated services or improvements from 1 to 10 were converted into a percentage and expressed as an average percentage.

The percentage of patients who reported improvement as well as the average percentage of improvement were calculated. The ‘yes’, ‘no’ or ‘not applicable’ answers were expressed as a percentage of ‘yes’ or ‘no’ answers while the ‘not applicable’ answers were excluded.

Results

In the five-year period from January 2015 to December 2019, SANBS produced a total of 671 SED batches for 114 patients from both the private and public sectors across the country (Table I). The majority of our patients were female (75.4%), while

Table I: Comparison of demographic data of all patients using serum eye drops from 2015–2019 and of patients who participated in the patient feedback questionnaire All SED Questionnaire patients respondents Age (years) 60 (21–92)

60 (31–89)

Male

28 (24.5)

5 (14.7)

Female

86 (75.4)

29 (85.3)

Average (range) Sex (n, %)

Ethnic group (n, %) Black African

13 (11.4)

5 (14.7)

White

95 (83.3)

26 (76.5)

Coloured

1 (0.9)

1 (2.9)

Asian/Indian

5 (4.3)

2 (5.9)

Type of SED (n, %) Allogeneic

79 (69.3)

21 (61.8)

Autologous

35 (30.7)

13 (38.2)

Indication for SED use Dry eye syndrome

78 (68.4)

31 (91.2)

Keratoconjunctivitis

11 (9.6)

2 (5.9)

Neurotrophic keratitis

3 (2.6)

1 (2.9)

Keratopathy

1 (0.9)

0

Corneal ulcers

2 (1.8)

0

Not stated

19 (16.7)

0

Total (n=patients; SEDs)

114; 671

34; 34

Or iginal s tud y Serum eye drops SA

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

11

Table II: Biochemical parameters and SEDs produced at SANBS as compared with published values pH

VEGF (pg/ml)

EGF (pg/ml)

SANBS

7.6

119.1±52.6

360.7±84.4

3 249.1±751.9

14 550.2±2 250.1

12.9±7.4

115.3±59.6

Bradley, 200814

NP

65.6±34.5

199.7±64.7

2 437.4±614.3

10 153.9± 2 667.2

8.30±1.8

129.3±46.1

Lopez-Garcia, 201415

7.5

NP

440.0±70.0

NP

NP

NP

NP

NP

58.4 (64.5–95.5)

316.3 (314.0–361.4)

15 75.4 (1490.2–1 808.0)

NP

NP

NP

De Pascale, 201517

NP

NP

199.74±64.74

1 700

NP

8.3±1.75

57.39±14.28

Levy, 2019

NP

316.6±846.8

189.7±101.2

NP

NP

NP

NP

Rauz, 201010

7.4

NP

500

NP

NP

NP

NP

Tsubota, 1999

NP

NP

510 (±80)

NP

NP

NP

NP

Zhang, 2020

NP

304.3±202.1

884.3±303.6

2 880.0±1 188.0

NP

4.9±4.0

922.5±215.4

Buzzi, 2018

16

11

18

19

PDGF (pg/ml)

BDGF (pg/ml)

FGF-b (pg/ml) HGF (pg/ml)

BDGF: brain-derived growth factor, EGF: epidermal growth factor, FGF-b: fibroblast growth factor beta, HGF: hepatocyte growth factor, PDGF: platelet-derived growth factor, VEGF: vascular endothelial growth factor, NP: not performed the average patient age was 60 years with a range of 21 to 92 years. The ethnic origin comprised 11.4% black African; 83.3% white; 4.3% Asian/Indian and less than 1% Coloured patients. Allogeneic blood donations comprised 69.3% of SEDs produced while 30.7% were produced from autologous blood donation. The main reason for using allogeneic blood donations was failure of patient to fulfil criteria to donate an autologous blood unit including age, haemoglobin level and medical comorbidities. Other reasons included patient preference and distance from a blood donation site (data not shown). The most common indication for SEDs use in our patient population was dry eye syndrome (68.4%), which includes dry eye syndrome secondary to Sjogren’s disease.

The pH and growth factor concentrations of SEDs produced at SANBS between December 2019 to June 2020 are shown in Table II and compared to published values. Although there are no defined reference ranges, SANBS parameters were well within international publication ranges.

All fungal and bacterial sterility results for SEDs produced at SANBS between December 2019 and June 2020 were negative. All HIV, HBV and HCV results were negative; however, one autologous SED tested positive for TPHA resulting in the requirement for an allogeneic donor for this patient.

A total of 51 patients were contacted to participate in the patient feedback questionnaire. Thirty-four patients agreed to partake in the questionnaire, thus a response rate of 67% was achieved (Table I).

Respondents were asked to rate if, and by how much, SEDs improved visual symptoms and their ability to perform

daily tasks. All of the respondents indicated that the use of SED relieved their dry eyes and improved their reading ability (Table III). The respondents were extremely satisfied with the SED bottles, labels, instructions and delivery. The majority of the respondents (88%) indicated that the use of SED had a major positive impact in their lives.

Table III: Patient feedback on effect of SEDs on symptoms and task performance % of patients Average % of Improvement reporting improvement of symptoms improvement reported Dry eyes

100%

82%

Painful eyes

95%

74%

Itchy eyes

92%

73%

Red eyes

88%

71%

Poor vision

95%

81%

Light sensitivity

87%

70%

Blurred vision

91%

76%

Improvement of tasks Reading

100%

80%

Driving at night

89%

66%

Computer work

75%

79%

Watching TV

92%

85%

Discussion

This is the first publication to our knowledge investigating the use of SEDs in the South African context. In this study, the average SED user was 60 years of age, predominantly white, female, and used the product for dry eye syndrome. Our patient profile is comparable to international literature20 demonstrating that dry eye

syndrome is most common in older white females. However, from a South African perspective, our results may also suggest a lack of awareness of SEDs as a treatment option for dry eye syndrome in the other population groups, which may result in the majority of South Africans who could benefit from SEDs not having access to this treatment option.

The majority (69.3%) of our SEDs are from allogeneic donors. This compares with international literature2,21 and, based on the average age of our SED users, is an expected finding, as SED blood donors are required to fulfil all usual blood donor criteria. Distance to blood donor site is a common indication for allogeneic donations. While autologous SEDs are recommended if medically and logistically feasible, 2 allogeneic SEDs enable patients from across South Africa access to this treatment despite living far from a SANBS blood donation site.

A commonly used tool to measure the effect of SEDs on the patient’s disease status is via a patient feedback questionnaire, 2,8,22 as regardless of objective ophthalmologic assessment, a fundamental treatment objective is an improvement in patient-reported symptoms. 8 Although this study is limited by a patient feedback questionnaire response rate of 67%, the respondents’ demographic details are comparable to those of all SEDs users between 2015 and 2019 and therefore this population group was deemed an adequate representation of the patient population. The positive effect of SEDs on patient-reported symptoms was noteworthy, and included both the number of respondents who reported improvement in symptoms as well as the proportion by which the SEDs improved symptoms. Improvement in dry eyes, painful eyes and itchy eyes

12

Or iginal s tud y Serum eye drops SA

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

was reported in 100%, 95% and 92% of respondents respectively. Daily tasks of living such as reading, night-driving, working on the computer and watching TV were improved in 100%, 89%, 75% and 92% respectively. These findings are significant as SEDs are reserved for patients who have not responded to standard therapy and have therefore tried multiple treatment options without success.

In this study, biochemical parameters including pH and growth factors concentrations of SANBS SEDs were tested and compared with international research.

Currently there are no defined standard reference ranges for these tests and there are large variations in published results.

Different testing platforms and processing techniques, including the dilution factor with normal saline, are likely contributors to these variations.

To our knowledge SANBS is currently the only producer of autologous and allogeneic SEDs from whole blood donations in South Africa. Due to the already established rigorous quality infrastructure at SANBS, including molecular testing of all blood products for infectious disease markers and clean room facilities, we are able to produce SEDs of a quality standard comparable with international SEDs manufacturers.

by SANBS offer a safe and effective treatment option.

Conclusion

5. Freire V, Andollo N, Etxebarria J, Duran JA,

SEDs produced by SANBS have been shown to be effective at reducing patient-reported symptoms in patients suffering from severe OSD including dry and painful eyes, as well as significantly improving daily living activities such as driving, watching TV and working on a computer. This has a positive impact on quality of life for patients with this chronic and debilitating disease. There appears to be a significant underuse of SEDs in South Africa currently, the reasons of which should be investigated as the requirement for this product is likely to increase for multiple reasons including the increase in laser surgery, chemotherapy and transplants occurring nationally.

SANBS has the infrastructure, expertise and experience to collect, formulate and distribute high-quality SEDs to patients across the country. While SEDs should not be considered as first-line therapy in OSD, for patients where standard treatments are ineffective, SEDs produced

b

Acknowledgements

The authors would like to thank Dr Karin van den Berg for guidance provided in the development of the manuscript, the patients who volunteered to answer the questionnaire, and the staff of the Cellular Therapy Laboratory at SANBS.

References

1. Giannaccare G, Versura P, Buzzi M, Primavera L, Pellegrini M, Campos EC. Blood derived eye drops for the treatment of cornea and ocular surface diseases. Transfus Apher Sci. 2017;56(4):595-604.

2. Clinical Guidelines: Serum eye drops for the treatment of severe ocular surface disease.

The Royal College of Ophthalmologists https://www.rcophth.ac.uk/wp-content/ uploads/2017/11/Serum-Eye-DropsGuideline.pdf. 2017.

3. Drew VJ, Tseng CL, Seghatchian J, Burnouf T. Reflections on dry eye syndrome treatment: therapeutic role of blood products. Front Med. (Lausanne). 2018;5:33.

4. Shtein RM, Shen JF, Kuo AN, Hammersmith KM, Li JY, Weikert MP. Autologous serumbased eye drops for treatment of ocular surface disease: a report by the American Academy of Ophthalmology. Ophthalmology.

2020;127(1):128-33.

Morales MC. In vitro effects of three blood derivatives on human corneal epithelial cells.

Invest Ophthalmol Vis Sci. 2012;53(9):5571-78.

6. Poon AC, Geerling G, Dart JK, Fraenkel GE, Daniels JT. Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol.

2001;85(10):1188-97.

7. Akyol-Salman I. Effects of autologous serum eye drops on corneal wound healing after superficial keratectomy in rabbits. Cornea.

2006;25(10):1178-81.

8. Noble BA, Loh RS, MacLennan S, Pesudovs K, Reynolds A, Bridges LR, et al. Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease. Br J Ophthalmol. 2004;88(5):647-52.

9. Matsumoto Y, Dogru M, Goto E, Ohashi Y, Kojima T, Ishida R, et al. Autologous serum application in the treatment of neurotrophic keratopathy. Ophthalmology.

2004;111(6):1115-20.

10. Rauz S, Saw VP. Serum eye drops, amniotic

membrane and limbal epithelial stem cells-tools in the treatment of ocular surface disease. Cell Tissue Bank. 2010;11(1):13-27.

11. Levy N, Wang Yin GH, Noharet R, Ghazouane R, Grimaud F, Aboudou H, et al. A retrospective analysis of characteristic features of responder patients to autologous serum eye drops in routine care. Ocul Surf.

2019;17(4):787-92.

12. Yamada C, King KE, Ness PM. Autologous serum eyedrops: literature review and implications for transfusion medicine specialists. Transfusion. 2008;48(6):1245-55.

13. SANBS. South African National Blood Serviced donation process https://sanbs. org.za/donation-process/ Accessed 13 September 2020.

14. Bradley JC, Bradley RH, McCartney DL, Mannis MJ. Serum growth factor analysis in dry eye syndrome. Clin Exp Ophthalmol.

2008;36(8):717-20.

15. Lopez-Garcia JS, Garcia-Lozano I, Rivas L, et al. Autologous serum eye drops diluted with sodium hyaluronate: clinical and experimental comparative study. Acta Ophthalmol. 2014;92(1):e22-29.

16. Buzzi M, Versura P, Grigolo B, et al. Comparison of growth factor and interleukin content of adult peripheral blood and cord blood serum eye drops for cornea and ocular surface diseases. Transfus Apher Sci. 2018;57(4):549-55.

17. De Pascale MR, Lanza M, Sommese L, Napoli C. Human serum eye drops in eye alterations: an insight and a critical analysis.

J Ophthalmol. 2015;2015:396410.

18. Tsubota K, Goto E, Fujita H, Ono M, Inoue H, Saito I, et al. Treatment of dry eye by autologous serum application in Sjogren’s syndrome. Br J Ophthalmol. 1999;83(4):390-95.

19. Zhang J, Crimmins D, Faed JM, Flanagan P, McGhee CNJ, Patel DV. Characteristics of platelet lysate compared to autologous and allogeneic serum eye drops. Transl Vis Sci Technol. 2020;9(4):24.

20. Schein OD, Hochberg MC, Munoz B, Tielsch JM, Bandeen-Roche K, Provost T, et al.

Dry eye and dry mouth in the elderly: a population-based assessment. Arch Intern Med. 1999;159(12):1359-63.

21. Marchand M, Harissi-Dagher M, Germain M, Thompson P, Robert MC. Serum drops for ocular surface disease: national survey of Canadian cornea specialists. Can J Ophthalmol. 2018;53(3):266-71.

22. Siedlecki AN, Smith SD, Siedlecki AR, Hayek SM, Sayegh RR. Ocular pain response to treatment in dry eye patients. Ocul Surf.

2020;18(2):305-11. 

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Or iginal s tud y Novel removal of corneal epithelium

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

15

Alcohol cotton bud technique for removal of corneal epithelium at the slit lamp in corneal crosslinking S Ballim MBChB, FC Ophth(SA), MMed Ophth(UKZN); Honorary lecturer, School of Clinical Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa ORCID: https://orcid.org/ 0000-0001-5088-0606 S Mahomed MBChB, MMed(PHM), PhD(PHM); Senior lecturer, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa ORCID: https://orcid.org/0000-0001-7095-9186 Corresponding author: Dr Shaheer Ballim, Postnet Suite 247, Private Bag X10, Musgrave Road, Durban, 4062, South Africa; tel: +27 31 2075450; email: shaheerballim@gmail.com

Abstract Aim: To describe the procedure and patient outcomes of a novel technique for the removal of corneal epithelium during corneal crosslinking.

Methods: This is a retrospective case series of patients who underwent epithelium-off corneal crosslinking for keratoconus using a new technique to remove the corneal epithelium at a private ophthalmology clinic. Demographic and clinical data, keratometry, rate of epithelial healing, degree of corneal haze and incidence of any complications were recorded over a median follow-up period of 36 weeks. The corneal epithelium was removed at the slit lamp under topical anaesthesia. A cotton bud dampened in 70% alcohol facilitated easy and non-traumatic removal of the epithelium in an 8–9 mm diameter for subsequent corneal crosslinking.

Results: Thirty-six eyes of 23 patients had crosslinking using this technique. The median number of days to epithelial closure was three (range two to six). Of the 27 eyes not lost to follow-up, 23 eyes (85.19%) showed decrease or stability (within 1 dioptre) of Kmax. The procedure did not inhibit the effect of corneal crosslinking for keratoconus. Fifteen eyes (55.55%) showed

Introduction

Corneal crosslinking is an important aspect in the management of patients with keratoconus. The procedure has been shown to prevent progression of the disease, and in some cases improve vision, by strengthening and stiffening the cornea.1 The most effective technique includes removal of the corneal epithelium as part of the procedure. 2 The standard Dresden protocol involves epithelial removal of the central 7 mm. 3 The corneal epithelium has shown to be a significant barrier to the corneal absorption of hydrophilic molecules such as riboflavin.4 Removal of the epithelium therefore markedly improves uptake of riboflavin into the corneal stroma in preparation for ultraviolet radiation in corneal crosslinking.

Various techniques and instruments have been reported for removal of the

improvement in visual acuity, 11 eyes (40.70%) showed stability of visual acuity, and one eye (3.70%) showed deterioration in visual acuity by one line or more. There was one case of sterile corneal infiltrates (2.78%); no other complications were noted.

All patients found the procedure acceptable in terms of patient experience and comfort. The technique used minimal resources and time.

Conclusion: The findings of this study suggest that this novel technique may be provide a safe and effective method for removing corneal epithelium before corneal crosslinking.

Keywords: corneal epithelium removal, keratoconus, crosslinking, resource-constrained Funding: No financial support was received by any of the authors for performing this research.

Conflict of interest: The authors have no conflicts of interest to declare.

corneal epithelium. These instruments include a blunt spatula,1,5 a blunt knife,6 and an ophthalmic scalpel.7,8 The use of specialised instruments has also been reported such as an Amoils epithelial scrubber/brush, and an Epi Clear device (Orca Surgical).9-11 The choice of instrument is often based on the surgeon’s preference.

Corneal epithelium can also be removed with ablative laser as in transepithelial photorefractive keratectomy.12-14 Some of these instruments, and the chemical solutions used, are not easily available in resource-constrained settings.

In South Africa, there are no standard guidelines to indicate how the corneal epithelium should be removed. Anecdotal reports include manual removal with a blunt instrument, spatula or blade; and use of 20% ethyl alcohol solution in a ring or well to soak the epithelium before removal

with a cotton bud or microsponge. The technique described in this research was originally necessitated in the context of a public health sector eye clinic in South Africa due to a lack of easily available equipment and consumables, together with the challenge of a high disease burden of keratoconus. The technique was found to be safe, cost-effective and timeefficient (author’s anecdotal experience).

The technique was then successfully implemented in private practice.

The aims of the study are to describe a novel technique for the removal of corneal epithelium at the slit lamp during corneal crosslinking, to audit the safety and efficacy of the technique and to describe patient outcomes.

Materials and methods

This retrospective observational

16

Or iginal s tud y Novel removal of corneal epithelium

descriptive case series comprised 36 eyes of 23 patients with keratoconus who underwent epithelial removal for corneal crosslinking treatment at a private corneal practice in Durban, South Africa.

Ethics approval was obtained from the University of KwaZulu-Natal Bioethical Research Committee (BE567/18). Informed consent was obtained from all patients prior to treatment. The study adhered to the tenets of the Declaration of Helsinki.

The inclusion criteria were all patients who underwent the specified technique of epithelial removal before corneal crosslinking and who were assessed clinically and with Scheimpflug tomography preoperatively at the study site from January 2017 to August 2018. Clinical diagnosis of keratoconus was confirmed

by Scheimpflug tomography. Progression of keratoconus was established by deteriorating visual acuity and refractive error or deteriorating serial topography or corneal thickness. All eyes were assessed to have a residual stromal thickness of at least 400 microns obtainable at the commencement of ultraviolet radiation and maintainable throughout ultraviolet radiation with isotonic or hypotonic riboflavin as guided by intraoperative pachymetry. The thinnest preoperative pachymetry was 396 microns. Comorbidities other than atopic conjunctivitis were noted.

Patients with active ocular inflammation or

infections, corneal scar, corneas deemed too thin to achieve a stromal bed of 400 microns at the time of ultraviolet radiation, or patients requiring general anaesthetic were excluded.

All patients underwent ophthalmic examination including distance visual acuity testing with best available correction, slit-lamp biomicroscopy and Scheimpflug-based corneal topography/ tomography (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany) preoperatively.

All procedures were performed by a single surgeon. Topical anaesthesia with two drops of tetracaine hydrochloride 1% spaced two minutes apart was followed by two drops of povidone iodine 5% into the conjunctival sac, two minutes apart.

Eyelids were cleaned with povidone iodine and a sterile wire speculum was inserted to keep the eye open for the removal of the epithelium. The patient’s head was positioned at the slit lamp and a beam of height 8–9 mm was used for illumination, to aid with measurement of the intended epithelial defect. A sterile cotton bud (from a sterile pack or a dry pus swab) was dampened by contact with a 70% isopropyl alcohol-saturated pad (commonly used for skin disinfection) (Figure 1). This ensured that the cotton bud was not soaked as would have been the case if it was dipped into a 70% alcohol solution. The alcoholdampened cotton bud was then used

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

to contact the corneal epithelium in an 8–9 mm circular area in a repeated ‘dabbing’ fashion for 10–15 seconds. This resulted in a loosening of the epithelial sheet of the cornea in the central 8–9 mm zone. The epithelium was then wiped off in a circular shearing manoeuvre to the desired size of epithelial removal. The speculum was then removed and the crosslinking procedure was commenced (Table I).

Table I: Corneal crosslinking methods Parameter

Variable

Treatment target

Ectasia

Fluence (total) (J/cm ) 5.31 to 5.4 2

Soak time and interval (minutes)

30(q2)

Intensity (mW)

5.9 to 9

Treatment time (minutes)

10 to 15

Epithelium status

Off

Chromophore

Riboflavin (various)

Chromophore carrier Hydroxypropyl methylcellulose USP 10 mg Chromophore osmolarity

Iso-osmolar/ hypo-osmolar

Chromophore concentration

0.1%

Light source

Lightmed

Irradiation mode (interval)

Continuous

Protocol modifications

Not applicable

Protocol abbreviation Not applicable in manuscript

Figure 1. Alcohol cotton bud removal of corneal epithelium

Riboflavin-phosphate 0.1% was instilled every 1–2 minutes for 30 minutes.

Hypotonic 0.5% riboflavin solution was used in cases where the stromal bed was less than 400 microns in thickness.

Topical tetracaine hydrochloride 1% was instilled every 10 minutes. Pachymetry was performed before ultraviolet light radiation. Continuous ultraviolet A light was then radiated on the central 8–9 mm of the cornea for 10 to 15 minutes to achieve a fluence of 5.31 J/cm2 to 5.4 J/cm2 (Lightlink CXL, Lightmed Corporation, CA). A bandage contact lens or 72-hour collagen corneal shield and topical preservative-free chloramphenicol 0.5% was applied at the end of the procedure.

Dexamethasone 0.1% with tobramycin 0.3% was prescribed for two weeks after surgery.

The bandage contact lens was removed 2–3 days postoperatively.

Or iginal s tud y Novel removal of corneal epithelium

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

Subjective reports of any pain during the epithelial removal were recorded.

Slit-lamp biomicroscopy was performed 2–7 days postoperatively to assess for corneal haze and number of days to epithelial closure. Patients were required to have repeated visits for examination and Scheimpflug scans (Pentacam, Oculus Optikgeräte GmbH, Wetzlar, Germany).

Not all patients had follow-up of a year or more at the time of data collection.

Those patients that were not lost to followup were recorded with postoperative topographic and tomographic parameters: maximum simulated keratometry values representing anterior corneal steepness (Kmax), and pachymetry at the thinnest point of the cornea as measured by the Scheimpflug scan. Evidence of corneal haze, distance visual acuity testing with best available correction and evidence of any complications were noted.

The data was analysed using SPSS version 25. Quantitative data was summarised using the mean and standard deviation. The Shapiro-Wilk test was used to test for normal distribution. The paired samples t-test was used to compare preoperative and postoperative Kmax and corneal thickness. A p-value of less than 0.05 was considered significant.

Results

Thirty-six eyes of 23 patients underwent epithelial removal with the described technique for corneal crosslinking during the study period. The median age of the patients was 23 years (range 12–34).

Twenty-eight of the eyes were from male patients and eight eyes were from female patients. There was one eye with

Figure 2. Visual acuity at follow-up

17

Table II: Changes in Scheimpflug tomography (n=27) Preoperative

Postoperative

p

Mean Kmax (range)

60.19±7.75 (45.8–83.3)

59.49±8.18 (45.3–81.7)

0.055

Mean pachymetry (range)

453.74±32.67 (397–537) 431.37±39.58 (369–520) 0.000

co-existent quiescent herpes zoster ophthalmicus uveitis and two eyes of one patient with bilateral preoperative dry eye.

No other comorbidities were noted.

The mean preoperative Kmax was 59.34 D±7.48 (range: 45.8–83.3). The mean preoperative pachymetry at the thinnest point was 450.67 µm±33.30 (range: 396–537) before epithelial removal and application of hypotonic riboflavin if necessary. No eyes had preoperative haze. All patients found the epithelial removal to be acceptably comfortable without reports of pain at the time of epithelial removal. All eyes had greater than 400 µm of residual stromal thickness measured by ultrasound pachymetry (Ocuscan RxP, Alcon, Texas, USA) immediately before commencement of ultraviolet light radiation.

At the first postoperative review (2–7 days post-surgery), 22 (61.11%) eyes had haze associated with the crosslinking.

The median number of days to epithelial closure was three (range two to six). There was one case of sterile corneal infiltrates (2.78%). No other complications were noted.

Nine of 36 eyes were lost to follow-up. Of the remaining 27 eyes, the median followup postoperatively with repeat Scheimpflug scan was 36 weeks (range: 3–83). There was no significant change in the mean Kmax from 60.19 preoperatively to 59.49 postoperatively (Table II). Objective haze was observed in 13 eyes (48.15%). Twentythree eyes (85.19%) showed decrease or

stability (within 1 dioptre) of Kmax. One eye (3.70%) showed deterioration in visual acuity by one line or more, 11 eyes (40.7%) showed stability of visual acuity and 15 eyes (55.55%) showed improvement in visual acuity by one line or more (Figure 2).

Discussion

This is the first published report of the use of a 70% alcohol-dampened cotton bud for removal of the corneal epithelium in a South African setting. The use of alcohol assists in the removal of corneal epithelium by breaking the hemidesmosome anchors to the basement membrane, thus mobilising the stratified squamous epithelium as a sheet from the basement membrane at the level of the lamina lucida, without damaging the basement membrane.15,16 This process facilitates quick and non-traumatic removal of the corneal epithelium. There are numerous reports of alcohol-assisted manual techniques, all of which use a 20% alcohol solution. These reports include using an alcohol well for 20 seconds, alcohol-soaked filter paper (20% alcohol) for 60 seconds and 20% ethyl alcohol in a 9 mm ring for 40 seconds, followed by manual epithelial debridement with cellulose sponge, rotating brush or blunt spatula.17-20 Corneal haze is the most common reported complication of corneal crosslinking. The incidence of corneal haze differs greatly among study populations ranging from 10–90%. 21 Our corneal haze

18

Or iginal s tud y Novel removal of corneal epithelium

incidence of 61% on first postoperative visit and 41% at the time of postoperative scans is in keeping with other studies. It is likely that this incidence will decrease further with longer postoperative follow-up of our cohort of patients. Our only other reported complication was sterile infiltrates in one eye. We had no cases of microbial keratitis, permanent scars or golden striae. In our study, all epithelial defects were healed at one week. This is a favourable outcome compared to other reports where up to 25% of patients had a persistent epithelial defect even after one week and 20% of patients had punctate epitheliopathy in the first three months. 22 Most eyes (96%) showed stabilisation or improvement of visual acuity. Deterioration in visual acuity was only found in one eye (3.70%), which is much lower than that reported in a review of 45 studies of corneal crosslinking with epithelial removal. 22 The mean steepness of the cornea as reflected by Kmax was stable postoperatively suggestive of halted progression of the keratoconus. There was a significant decrease in the mean corneal thickness postoperatively. Twenty-three of 27 (85.19%) showed flattening or stability of maximum curvature (within 1 dioptre).

The positive postoperative findings demonstrate the effectiveness of this novel technique of epithelial removal.

The limitations of this study include the short follow-up period and loss to follow-up.

The factors that may have contributed to loss to follow-up include financial resources, and some patients did not think that followup was necessary despite being contacted by the practice. The lack of a standardised scale to assess pain is not ideal for the assessment of surgical outcomes and complications. The biochemical effect of isopropyl alcohol (as opposed to ethanol) on the cornea requires histological investigation to determine its mechanism of action and potential toxicity. The use of isopropyl alcohol as opposed to ethanol, and the 70% concentration used, was based on the type of alcohol swabs available in our setting, where ethanol-soaked swabs are not commercially available.

Conclusion

The technique described uses minimal time and resources, and may provide a safe and effective option for removal of the corneal epithelium. The technique has a low complication rate without hindering the effect of the subsequent crosslinking and is found to be acceptable to patients with regard to comfort. Further research is

required to assess the long-term effects of 70% isopropyl alcohol on the cornea.

Case-controlled and histological studies are indicated to confirm these outcomes before planned training and implementation of this technique in resource-constrained settings where safe and cheap methods for the removal of corneal epithelium are needed.

References

1. Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK. United States multicenter clinical trial of corneal collagen crosslinking for keratoconus treatment. Ophthalmology.

2017;124(9):1259-70.

2. Bikbova G, Bikbov M. Standard corneal collagen crosslinking versus transepithelial iontophoresis-assisted corneal crosslinking, 24 months follow-up: randomized control trial. Acta Ophthalmol. 2016;94(7):e600-e606.

3. Wollensak G, Spoerl E, Seiler T. Riboflavin/ ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus. Am J of Ophthalmol. 2003;135(5):620-27.

4. Baiocchi S, Mazzotta C, Cerretani D, Caporossi T, Caporossi A. Corneal crosslinking: Riboflavin concentration in corneal stroma exposed with and without epithelium. J Cataract Refract Surg. 2009;35(5):893-99.

5. Bouheraoua N, Jouve L, Borderie V, Laroche L. Three different protocols of corneal collagen crosslinking in keratoconus: conventional, accelerated and iontophoresis. J Vis Exp. 2015(105):53119.

6. Soeters N, van Bussel E, van der Valk R, Van der Lelij A, Tahzib NG. Effect of the eyelid speculum on pachymetry during corneal collagen crosslinking in keratoconus patients.

J Cataract Refract Surg. 2014;40(4):575-81.

7. Abbondanza M, Felice V, Abbondanza G. Corneal crosslinking in a 10-year-old child with stage III keratoconus. Nepal J Ophthalmol. 2016;8(16):174-77.

8. Rechichi M, Mazzotta C, Daya S, Mencucci R, Lanza M, Meduri A. Intraoperative OCT pachymetry in patients undergoing dextran-free riboflavin UVA accelerated corneal collagen crosslinking. Curr Eye Res. 2016;41(10):1310-15.

9. Shafik Shaheen M, Lolah MM, Pinero DP. The 7-Year Outcomes of epithelium-off corneal crosslinking in progressive keratoconus. J Refract Surg. 2018;34(3):181-86.

10. Shetty R, Nagaraja H, Pahuja NK, Jayaram T, Vohra V, Jayadev C. Safety and efficacy of epi-Bowman keratectomy in photorefractive keratectomy and corneal collagen crosslinking: a pilot study. Curr Eye Res. 2016;41(5):623-29.

11. Stojanovic A, Zhou W, Utheim TP. Corneal collagen crosslinking with and without epithelial removal: a contralateral study with

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

0.5% hypotonic riboflavin solution. Biomed Res Int. 2014;2014:619398.

12. Chen X, Stojanovic A, Xu Y, et al. Medium- to long-term results of corneal crosslinking for keratoconus using phototherapeutic keratectomy for epithelial removal and partial stromal ablation. J Refract Surg.

2017;33(7):488-95.

13. Kapasi M, Dhaliwal A, Mintsioulis G, Jackson WB, Baig K. Long-term results of phototherapeutic keratectomy versus mechanical epithelial removal followed by corneal collagen crosslinking for keratoconus. Cornea. 2016;35(2):157-61.

14. Pahuja N, Kumar NR, Francis M, et al.

Correlation of clinical and biomechanical outcomes of accelerated crosslinking (9 mW/ cm(2) in 10 minutes) in keratoconus with molecular expression of ectasia-related genes. Cur Eye Res. 2016;41(11):1419-23.

15. Dua HS, Lagnado R, Raj D, et al. Alcohol delamination of the corneal epithelium: an alternative in the management of recurrent corneal erosions. Ophthalmology.

2006;113(3):404-11.

16. Mencucci R, Paladini I, Brahimi B, Menchini U, Dua HS, Romagnoli P. Alcohol delamination in the treatment of recurrent corneal erosion: an electron microscopic study. Br J Ophthalmol. 2010;94(7):933-39.

17. Cagil N, Sarac O, Cakmak HB, Can G, Can E. Mechanical epithelial removal followed by corneal collagen crosslinking in progressive keratoconus: short-term complications. J Cataract Refract Surg. 2015;41(8):1730-37.

18. Gaster RN, Ben Margines J, Gaster DN, Li X, Rabinowitz YS. Comparison of the effect of epithelial removal by transepithelial phototherapeutic keratectomy or manual debridement on crosslinking procedures for progressive keratoconus. J Refract Surg.

2016;32(10):699-704.

19. Gu S, Fan Z, Wang L, Tao X, Zhang Y, Mu G. Corneal collagen crosslinking with hypoosmolar riboflavin solution in keratoconic corneas. Biomed Res Intl.

2014;2014:754182.

20. Gu SF, Fan ZS, Wang LH, et al. A short-term study of corneal collagen crosslinking with hypo-osmolar riboflavin solution in keratoconic corneas. Int J Ophthalmol.

2015;8(1):94-97.

21. Razmjoo H, Rahimi B, Kharraji M, Koosha N, Peyman A. Corneal haze and visual outcome after collagen crosslinking for keratoconus: A comparison between total epithelium off and partial epithelial removal methods. Adv Biomed Res. 2014;3:221.

22. Shalchi Z, Wang X, Nanavaty MA. Safety and efficacy of epithelium removal and transepithelial corneal collagen crosslinking for keratoconus. Eye. 2015;29(1):15-29. 

20

Or iginal s tud y RAAB in Zimbabwe

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

Rapid assessment of avoidable blindness in Masvingo Province, Zimbabwe: considerations for resource-limited settings D Minnies, NDMT Clin Path, NHDMT, MPH, PhD (Public Health); Director: Community Eye Health Institute, Division of Ophthalmology, University of Cape Town, South Africa ORCID: https://orcid.org/0000-0002-9173-782X B Macheka, MBChB, MMed(Ophth); Lead Government Ophthalmologist, Ministry of Health and Child Care, Zimbabwe J Joseph, MBChB, MMed(Ophth), Provincial Ophthalmologist, Masvingo Province, Ministry of Health, Zimbabwe C Cook, MBChB, DO, MPH, FRCOphth SA; Emeritus Professor, Division of Ophthalmology, University of Cape Town, South Africa ORCID: https://orcid.org/0000-0001-5661-7390 Corresponding author: Dr Deon Minnies, H53 Old Main Building, Groote Schuur Hospital, Observatory 7925, South Africa; tel: +27 21406 6039; email: d.minnies@uct.ac.za

Abstract Background: A rapid assessment of avoidable blindness was conducted to assess the situation of blindness and visual impairment in Masvingo Province, Zimbabwe, using the standard rapid assessment of avoidable blindness (RAAB) methodology.

Methods: A sample size of 3 756 was calculated by RAAB software, using an estimated prevalence of blindness of 3.0%±0.7% with 95% confidence interval based on previous RAAB findings in the region. The sampling was done using multistage systematic cluster random sampling, with 76 clusters of 50 people aged 50 years or above selected with probability proportional to size (PPS). A total of 3 795 people were examined, representing a response rate of 99.9%. Examination procedures included measurement of visual acuity (VA) with available correction and pinhole correction, assessment of lens status and examination of the fundus with a direct ophthalmoscope.

Data was collected using the RAAB smartphone application.

Results: The sample prevalence of bilateral blindness with available correction (presenting VA <3/60) in the better eye was 3.6% (95% confidence interval: 2.9–4.2). Untreated cataract (65.2%) was the most common cause of blindness followed by

Introduction

The Vision Loss Expert Group reported that, in 2015, the prevalence of blindness was 36 million globally,1 and that a further 216.6 million people were moderately to severely visual impaired, making a total of 253 million people with vision loss.2 The World Health Organization (WHO) defines blindness as ‘presenting visual acuity worse

glaucoma (16.3%) and non-trachomatous corneal opacity (10.4%).

Just over half (52.2%) of people blind due to cataract (presenting VA <3/60) had undergone surgery. Of the eyes operated for cataract, 59.7% could see 6/18 or better (‘Good outcome’) while 25.7% could not see 6/60 (‘Poor outcome’) with available correction.

Conclusion: There is a need to further strengthen the capacity of the Masvingo provincial eye care programme through effective planning, monitoring and management of eye care services to meet high performance targets, nationally and globally.

Keywords: rapid assessment of avoidable blindness, blindness, visual impairment, Zimbabwe Funding: The source of the funding is from a grant from Christian Blind Mission (CBM), as part of a project being implemented by Zimbabwe Council for the Blind.

Conflict of interest: The authors declare they have no conflicts of interest with regard to this study.

than 3/60’; severe visual impairment as ‘presenting visual acuity worse than 6/60 but better than 3/60’; moderate visual impairment as ‘presenting visual acuity worse than 6/18 but better than 6/60’ and functional low vision as incurable presenting visual acuity worse than 6/18 but with light perception, all in the better eye. 3 Almost 90% of people affected by

blindness or visual impairment live in low- and middle-income countries, and more than 75% of visual impairment is avoidable.4 About half of the 47 countries in sub-Saharan Africa whose data contributed to the Vision Atlas had population surveys done, and 36% of countries had a national blindness prevention committee/national eye care strategy in place.4

Or iginal s tud y RAAB in Zimbabwe

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

Rapid assessment of avoidable blindness (RAAB) surveys are widely used to determine the burden of blindness and visual impairment for the purpose of planning and advocacy for eye care services. 5 The RAAB is a complete system, ready to be used by local eye care teams, and includes provision for training, data collection and analysis.6 The 11 RAAB surveys conducted in the southern region of sub-Saharan Africa between 2009 and 2017 show that the blindness prevalence in people aged 50 years or above ranged from 1.3–7.1%, with a median of 3.3%.4 Cataract surgical coverage ranged from 10–96% (median 49%) in operated eyes in sample with best correction. Posterior segment disease caused a median of 24.6% (range 15.9–67.6%) of blindness.

According to the National Census of 2012, Masvingo Province, Zimbabwe, had a population of 1.5 million people,7 with 11.9% of the population aged 50 years or above. Eye care services are provided through tertiary, secondary and primary levels of care amid severe shortages of equipment, consumables and eye health specialists nationally. 8 Even so, in 2016, a total of 14 898 eye care outpatient consultations, 2 499 refractions and 1 612 cataract operations were performed.9 The cataract surgical rate of over 1 000 per million is double the national average of approximately 500 per million.10 A RAAB was conducted in Masvingo Province to obtain baseline information as part of a national strategy to improve eye care services in rural provinces. The aim was to determine the magnitude and causes of avoidable blindness and visual impairment in people aged 50 years and above. Additionally, the cataract surgical coverage, the outcomes of cataract surgery and the barriers to uptake of cataract surgery were determined.

Methods

This was a population-based crosssectional study.

A sample size adequate to demonstrate a prevalence of blindness of 3.0% ± 0.7% with 95% confidence was calculated by the RAAB software, using the standard formula for finite populations: Sample size = Z*Z(P(1-P))/D*D, where Z = percentile of the standard normal distribution, P = expected prevalence of the condition and D = half the width of the desired sample confidence interval This was adjusted for non-participation (10%) and design effect (1.5) due to clustering, resulting in a sample size of

21

Table I. Eligible persons, coverage, absentees and refusals Examined

Not available

Refused

Not capable

n

%

n

%

n

%

n

1 533

99.7%

3

0.2%

1

0.1%

0

0.0% 1 537 100.0%

Females 2 262 100.0%

1

0.0%

0

0.0%

0

0.0% 2 263 100.0%

Total

4

0.1%

1

0.0%

0

0.0% 3 800 100.0%

Males

3 795

99.9%

3 756. A sampling frame was created and consisted of 261 enumeration areas, called wards in Masvingo Province. Sampling was done using multi-stage systematic cluster random sampling. Using the cluster selection module in the RAAB software, 76 clusters of 50 people aged 50 years or above (i.e. a total of 3 800 people) were selected with probability proportional to size, followed by random selection of participants within the sampled clusters.

Five examination teams, four of which comprised ophthalmic nurses and the other comprising two ophthalmologists, completed a five-day training programme led by a certified RAAB trainer. The ophthalmologist team was assigned the ‘gold standard’ role for the interobserver variation (IOV) test. The IOV test is a means of achieving validity of the field data. The aim is to achieve high interobserver agreement (kappa coefficient values of 0.7–0.8 or higher for each of the teams) when performing the examination procedures.

The training covered the key knowledge and skills aspects required for collecting data for analysis to produce the RAAB results. This included standardised selection, enrolment and procedures to examine participants, as well as coding of major causes of vision loss in each eye and the person examined.

Additionally, the examination teams were trained in the use of the RAAB software as well as the posting of the records to the database for analysis. Standardised meanings for ‘place’ and ‘cost of surgery’ were also defined during the training. Four cluster informers and a survey coordinator received training in aspects of sampling, monitoring and data administration.

Data was collected using the RAAB software on smartphones. Minimal

%

Total n

%

demographic information was captured for the purpose of identification, analysis and referral to an eye clinic, if indicated.

Interviews were conducted in the respondents’ homes in the local language.

Examination procedures included measurement of visual acuity (VA) with available correction (i.e. their own spectacles) and pinhole correction, assessment of lens status in each eye with distant direct ophthalmoscopy and fundoscopy with a direct ophthalmoscope through a dilated pupil if VA<6/18 and not due to cataract, corneal scar or refractive error.

Using the RAAB software for analysis, the following indicators were determined from the data collected: the prevalence of blindness, severe visual impairment (SVI) and moderate visual impairment (MVI); the prevalence of avoidable blindness, SVI and MVI; the prevalence of blindness, SVI and MVI from cataract, the main causes of blindness, SVI and MVI; the prevalence of aphakia and/or pseudophakia; the cataract surgical coverage, i.e. the proportion of people needing surgery who actually had surgery; the visual outcome of cataract surgery; barriers to cataract surgery; prevalence of uncorrected refractive errors and uncorrected presbyopia; and various cataract surgery service indicators (age at time of surgery, place, costs and type of surgery, cause of visual impairment after cataract surgery).

All indicators were subdivided by sex and age group. The WHO definitions of blindness and visual impairment were used. Avoidable causes of blindness and visual impairment were grouped under treatable (e.g. cataract, refractive error and uncorrected aphakia), or preventable (e.g. surgical complications, corneal opacity, diabetic retinopathy and glaucoma).

Table II. Sample prevalence of blindness, severe (SVI) and moderate (MVI) visual impairment - bilateral PVA Males n

% (95% CI)

Blindness

53

Severe VI

32

Moderate VI Functional low vision

Females

Total

n

% (95% CI)

n

% (95% CI)

3.5 (2.4–4.5)

82

3.6 (2.8–4.5)

135

3.6 (2.9–4.2)

2.1 (1.2–2.9)

53

2.3 (1.7–3.0)

85

2.2 (1.7–2.8)

104

6.8 (5.2–8.3)

157

6.9 (5.8–8.1)

261

6.9 (5.8–7.9)

28

1.8 (1.1–2.5)

42

1.9 (1.2–2.5)

70

1.8 (1.4–2.3)

22

Or iginal s tud y RAAB in Zimbabwe

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

Posterior segment diseases accounted for 22.2% of bilateral blindness.

In Masvingo Province, 52.2% of people who were blind due to cataract (VA<3/60) had been operated on: 50.0% of males and 52.8% of females. The coverage for people with VA<6/60 was 40.8% (males 37.0% and females 42.2%) and for people with VA<6/18 was 26.5% (22.8% males and 28.5% females).

Of the 191 eyes operated for cataract, 114 (59.7%) could see 6/18 or better (‘Good outcome’) and 25.7% could not see 6/60 (‘Poor outcome’) with available correction (Table IV). Overall, 67.3% of poor outcomes were caused by sequelae to cataract surgery with poor selection (18.4%) and surgical technique (14.2%) the second and third most common causes of poor visual outcomes respectively.

‘Cost’ (48.2%), ‘Need not felt’ (18.3%) and ‘Cannot access treatment’ (18.3%) were the main reasons participants who were blind due to untreated cataract did not go for surgery. Females were more likely to

Table III. Principal cause of blindness, severe (SVI) and moderate (MVI) visual impairment in persons (PVA) Blindness

Severe VI

Moderate VI

1. Refractive error

0

0.0%

5

5.9%

56

21.5%

2. Aphakia uncorrected

0

0.0%

0

0.0%

0

0.0%

88

65.2%

63

74.1%

182

69.7%

3. Cataract untreated 4. Cataract surgical complications

2

1.5%

4

4.7%

4

1.5%

5. Trachomatous corneal opacity

1

0.7%

2

2.4%

1

0.4%

6. Non-trachomatous corneal opacity

14

10.4%

2

2.4%

5

1.9%

7. Phthisis

0

0.0%

0

0.0%

0

0.0%

8. Onchocerciasis

0

0.0%

0

0.0%

0

0.0%

9. Glaucoma

22

16.3%

7

8.2%

6

2.3%

10. Diabetic retinopathy

1

0.7%

0

0.0%

0

0.0%

11. ARMD

0

0.0%

0

0.0%

0

0.0%

12. Other posterior segment disease

7

5.2%

2

2.4%

7

2.7%

13. All other globe/CNS abnormalities

0

0.0%

0

0.0%

0

0.0%

135 100.0%

85

100.0%

Total

Results

Of the 3 800 people aged 50 years or above who were eligible, 3 795 people were examined, representing a response rate of 99.9% (Table I). The sample comprised 1 533 males and 2 262 females, 40.4% and 59.6% of the sample, respectively.

The sample prevalence of bilateral blindness with available correction (presenting visual acuity or PVA <3/60) in people aged 50 years or above in the better eye was 3.6% (95% confidence interval: 2.9–4.2); 3.5% in males and 3.6% in females. The prevalence ratios of severe and moderate visual impairment are shown in Table II. Extrapolating to the Masvingo Province, an estimated 6 684 people aged 50 years or above were bilaterally blind, an age and sex-adjusted prevalence of 3.9% (3.2–4.5).

A further 4 362 people aged 50 years or above were severely visually impaired (SVI) and another 12 964 people had moderate visual impairment (MVI). Among them, 3 508 people aged 50 years or above had functional low vision (FLV), requiring low vision services.

Untreated cataract was the most common cause of bilateral blindness at 65.2%, followed by glaucoma (16.3%) and non-trachomatous corneal opacity (10.4%) (Table III). Untreated cataract (74.1%) was also the main cause of bilateral SVI, followed by glaucoma (8.2%) and uncorrected refractive error (5.9%).

Uncorrected refractive error (21.5%) was the second most common cause (after untreated cataract, 69.7%) of bilateral MVI. A total of 94.8% of bilateral blindness in persons was considered avoidable, 65.2% treatable, 11.1% preventable by primary eye

261 100.0%

care and 18.5% preventable by specialised ophthalmic services (Figure 1). A total of 5.2% was considered not avoidable and required rehabilitation/low vision services.

Figure 1: Blindness, SVI and MVI in persons by intervention category

Table IV. Post-op presenting VA and causes of borderline and poor outcome (eyes) Selection Surgery Spectacles

Sequelae

Can see 6/12

Total

n

n

n

n

n

Total

Good: can see 6/18

0

0

0

0

114

114

Borderline: can see 6/60

1

12

7

8

0

28

Poor: cannot see 6/60

9

7

0

33

0

49

Total

10

19

7

41

114

191

Or iginal s tud y RAAB in Zimbabwe

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

23

Figure 2. Barriers to cataract surgery in sample (bilateral BCVA<6/60 due to cataract) report ‘cost’ (56.8%) compared to males (30.2%) (Figure 2).

The prevalence of total refractive errors was 4.6% (males 4.8% and females 4.4%) with 1.6% prevalence for uncorrected refractive error, equally occurring in males and females. The prevalence of uncorrected presbyopia was high (93.0%) (Table V).

Glaucoma was the most common posterior segment cause of blindness in persons (16.3%) and eyes (10.4%). Diabetic retinopathy caused blindness in 0.7% and 0.5% eyes and people respectively.

The age- and sex-adjusted prevalence of functional low vision, not caused by cataract, refractive error, uncorrected aphakia or pseudophakia with posterior capsular opacity) and requiring low vision services was 1.8% (1.4–2.3).

50 years and above of 3.7% and 3.1% respectively was reported.11 This was also higher than the median prevalence of blindness of the most recent 11 RAAB surveys (3.3%) conducted in the southern sub-Saharan African region.4 Although the cataract surgical coverage in Masvingo is higher than both the Manicaland and the sub-regional median, it still means that cataract blindness is inadequately controlled. The age- and sex-adjusted results show that there were 3 628 cataract-blind people, more than double the number of cataract surgeries performed in a year. Careful selection of bilaterally blind people should be a priority to reduce the number of cataractblind people in the province.

Visual outcomes after cataract surgery are below the recommended standards of the WHO, 8 mainly because of sequelae of surgery, suggesting that review of procedures, closer monitoring and improved case-finding and follow-up are necessary for improvement.

Glaucoma is the main posterior segment cause of blindness and low vision; therefore, further investments should be

Discussion

There was a higher sample and age- and sex-adjusted prevalence of blindness in Masvingo Province when compared to the Manicaland RAAB findings in 2016, when a sample and age- and sex-adjusted prevalence of blindness in people aged

Table V. Uncorrected refractive error and uncorrected presbyopia Males n

Females

Total

%

n

%

73

4.8%

100

4.4%

173

4.6%

Uncorrected refractive errors 24

1.6%

37

1.6%

61

1.6%

Uncorrected presbyopia

92.1%

2 116

93.6%

3 528

93.0%

Total refractive errors

1 412

n

%

made to improve this aspect of ophthalmic services in the province.

Further considerations

Low-resource settings like Zimbabwe face particular challenges which can present limitations to the conduct of research or the interpretation of the findings.

One of these is the low availability of ophthalmic medical staff for the conduct of RAABs, which creates a dependency on non-physician ophthalmic staff to do examinations and diagnosis independently of ophthalmologists in the field. This may affect diagnostic accuracy, especially for conditions in the posterior segment disease group, which may be more difficult to diagnose. The clinical monitoring and support provided by the ophthalmologists during the data collection period has been crucial to help overcome these challenges and needs to be further explored.

Another challenge is the differences in service uptake, quality and accessibility between sexes and across age groups, mostly because of socioeconomic reasons.

In the Masvingo RAAB, the age and sex distribution of the sample mirrors that of the population in the survey area (female ratio in sample 0.596, female ratio in population 0.603). However, ‘Cost’ is a greater barrier to access of cataract surgery for women, compared to men.

The possible extension to general health service uptake and participation in research needs to be carefully considered.

24

Or iginal s tud y RAAB in Zimbabwe

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

A further concern is the high response rate (of almost 100%), because it may suggest low autonomy on the part of the participant, due to fear or ignorance.

It may also be because of incorrect enumeration practices, which could be the source of selection bias and therefore adversely affect the findings. This practice should be thoroughly addressed during training and in-field monitoring.

As cataract surgery is still the main strategy to reduce avoidable blindness, there is a need to further strengthen the capacity of the Masvingo provincial eye care programme. This may involve human resource development to improve the quality and the quantity of cataract operations. Making cataract surgery more affordable, perhaps by reducing the patient fees, providing subsidies and transport to increase access, could return favourable outcomes.

According to the WHO, the challenges of low cataract surgical coverage, low cataract surgical quality, and high user cost of services need to be addressed through effective planning, monitoring and management of eye care services to meet high performance targets, nationally

and globally.12 These findings of the RAAB survey in Masvingo Province should help to build a strategy for investments in overall eye care programme development in the province and in the country.

Acknowledgements

Glob Health. 2017;5(12):e1234.

3. World Health Organization. https://www.who. int/news-room/fact-sheets/detail/blindnessand-visual-impairment accessed 22 July 2019.

4. IAPB Vision Atlas http://atlas.iapb.org/ accessed 22 July 2019.

5. Ackland P. The accomplishments of

This population-based survey was organised by the Ministry of Health and Child Care, in collaboration with CBM, Zimbabwe Council for the Blind and the Community Eye Health Institute, University of Cape Town. The research was funded through Standard Chartered Bank, Seeing is Believing project.

Dr Susan Lewallen reviewed the draft and gave valuable input for improvement.

References

the global initiative VISION 2020: The Right to Sight and the focus for the next 8 years of the campaign. Indian J Ophthalmol. Sep-Oct 2012;60(5):380-86. doi: 10.4103/0301-4738.100531.

6. RAAB Repository http://raabdata.info/ repository/ accessed 22 July 2019.

7. Zimbabwe National Statistics Agency. Census 2012. Provincial report Masvingo. Population Census Office. Harare.

8. Ministry of Health and Childcare. National Eye

1. Bourne RRA, Flaxman SR, Braithwaite T, Cicinelli MV, et al. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health.

2017:5(9):e888-e897.

2. Flaxman SR, Bourne RR, Resnikoff S, Ackland P, et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet

Health Strategy (2014–2018) for Zimbabwe.

9. Cook C. CBM P1596 Masvingo Province Eye Care Programme Project visit report 10/05/2017.

10. Zulu F. A situation analysis of eye care services in Zimbabwe. Lusaka: Sightsavers International. 2005.

11. Ministry of Health and Child Care, Zimbabwe.

Report on rapid assessment of avoidable blindness, Manicaland Province, Zimbabwe.

12. World Health Organization. 2013. Universal eye health: a global action plan 2014–2019. 

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Or iginal s tud y IVZ in neovascular AMD

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

25

Efficacy and safety of ziv-aflibercept in patients with neovascular age-related macular degeneration in a Ghanaian population IZ Braimah MBChB, FGCS, FWACS; Senior lecturer and consultant ophthalmologist, Department of Surgery (Eye), University of Ghana Medical School, Korle-Bu, Accra; Lions International Eye Centre, Korle-Bu Teaching Hospital, Korle-Bu, Accra, Ghana ORCID ID: https://orcid.org/0000-0002-2573-9026 YS Adam MBBS; Consultant ophthalmologist, Lions International Eye Centre, Korle-Bu Teaching Hospital, Korle-Bu, Accra, Ghana WM Amoaku MBChB, FRCS(Ed), FRCOphth, PhD; Associate Professor/Reader, Academic Ophthalmology, DCN, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK ORCID ID: https://orcid.org/0000-0001-5028-7984 Corresponding author: Winfried M Amoaku, tel: +441158231014; email: winfried.amoaku@nottingham.ac.uk

Abstract Background: To report on the efficacy and safety of intravitreal ziv-aflibercept (IVZ) in a Ghanaian population with neovascular age-related macular degeneration (nAMD).

Methods: In this retrospective, observational study, the medical records of patients with nAMD who had been treated with IVZ, 1.25 mg/0.05 ml, as part of routine clinical practice on pro re nata basis with a minimum follow-up of 6 months, were retrieved and analysed.

Results: Twenty-four eyes of 23 patients were included in this study. Their mean age was 67.7±8.8 yrs, and mean duration of follow-up was 11.4±4.0 months. Nine (37.5%) eyes were presumed to have polypoidal choroidal vasculopathy (PCV).

The mean baseline best-corrected visual acuity (BCVA) was 1.1±0.7 logMAR; there was significant improvement in BCVA at 3 and 6 months compared to baseline (p<0.01). Seventy-nine per cent of eyes had visual gain of at least one logMAR BCVA line at 6 months post-initiation of IVZ. The mean CMT at baseline was 332.4±138.8 μm; there was significant reduction in CMT at

Introduction

Suppor ts

3, 6 and 12 months compared to baseline (p<0.01). One case of culture-proven endophthalmitis was successfully treated with pars plana vitrectomy and intravitreal antimicrobials.

Conclusion: IVZ at 1.25 mg was associated with significant improvement in visual and anatomic outcomes in Ghanaian eyes with nAMD. There was one serious adverse event with unfavourable visual outcome.

Keywords: ziv-aflibercept, endophthalmitis, Ghana, neovascular macular degeneration, optical coherence tomography Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest: The authors have no conflicts of interest to declare.

Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of nAMD.4 While ranibizumab (Lucentis, Genentech/Novartis) and aflibercept (Eylea, Regeneron /Bayer) have been approved by the United State of America (USA) Food and Drugs Agency (FDA) and European Medicines Agency (EMA) for intravitreal use in patients with nAMD, bevacizumab (Avastin, Genentech/Roche) and ziv-aflibercept (Regeneron/Sanofi) have been approved by both agencies for the treatment of colorectal cancers. 5,6 The Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) and Inhibition of VEGF in Age-related

Choroidal Neovascularisation (IVAN)

have reported that ranibizumab all 3 layers of the tear film | Preservative free trials and bevacizumab have similar efficacy in

Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness worldwide.1 There are significant differences in the prevalence of different types of AMD including neovascular AMD (nAMD) between different ethnic groups. 2 The prevalence of early AMD is higher among people of European ancestry compared to African and Asian ancestry. 2 Late AMD is more prevalent among people of European ancestry compared to African ancestry. 2 Polypoidal choroidal vasculopathy (PCV), a variant of nAMD, has been found to be more prevalent among Asians and African Americans compared to Caucasians. 3

patients with nAMD.7,8 The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2 studies have shown that aflibercept has similar efficacy as ranibizumab in nAMD.9,10 Bevacizumab is widely used off-label for the treatment of nAMD due to its cost-effectiveness compared to ranibizumab.11 Aflibercept is expensive and beyond the reach of many patients in developing and low- to middle-income countries in the world. Zivaflibercept (an intravenous formulation of aflibercept) has been used off-label for the treatment of nAMD and there are

Or iginal s tud y IVZ in neovascular AMD

26

few published reports of the safety and efficacy of this drug.12-15 In a randomised double blind intervention study of Ghanaian eyes

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

with choroidoretinal vascular diseases, our group found that the short-term use of intravitreal ziv-aflibercept (IVZ) was safe.16 There is no data on the efficacy of

off-label use of ziv-aflibercept in a West African population with nAMD to date. We evaluated the outcome of treatment with IVZ in a Ghanaian population with nAMD.

Table I: Clinical characteristics of individual study eyes No Age

Sex Prior Rx BCVA Fundus features

SD-OCT features

FFA features Diagnosis

1

58

M

4 BZ

0.18

Multiple recurrent haemorrhagic PEDs, peripapillary polyp

SRF, multiple PEDs, TLP, DLS

Occult CNV

PCV

2

66

M

18 BZ 6 RZ

0.48

Recurrent multiple haemorrhagic PEDs

Multiple PED, PED notch, DLS, TLP

Not done

PCV

3

65

F

3 BZ

1

Haemorrhagic PED, drusens, exudates

IRF, SRF, PED

Not done

nAMD

4

76

F

5 BZ

1.3

Haemorrhagic PED drusens, RPE atrophy

SRF, multiple PED, DLS Occult CNV

nAMD

5

69

F

1 BZ

1

Haemorrhagic PED, subretinal haemorrhage, exudates

SRF, multiple PED, TLP, Not done DLS

PCV

6

50

F

No

2.3

Massive peripapillary and submacular haemorrhage, polyps, breakthrough vitreous haemorrhage, PED,

SRF, multiple PED, TLP, Occult CNV PED notch

PCV

7

75

M

No

0.64

Drusens, RPE atrophy/depigmentation

SRF, irregular RPE, disruption of ISO band

Occult CNV

nAMD

8

79

F

No

0.78

Drusens, RPE abnormalities

SRF, PED

Classic CNV nAMD

9

68

M

No

0.78

Haemorrhagic PED, polyp, exudates

SRF, IRF, TLP multiple PED, PED notch

Occult CNV

10

87

M

0.64

SRNV, drusens and haemorrhage

IRF, subretinal hyperreflective tissue

Classic CNV nAMD

11

77

M

No

1.3

Drusens, exudates, PED, geographic atrophy, exudates

IRF, SRF, multiple PEDs Occult CNV

nAMD

12

77

M

No

1.5

Drusens, RPE atrophy, exudates haemorrhage,

IRF, SRF, multiple PED

nAMD

13

55

F

No

1.3

SRNV, drusens, haemorrhage, exudates IRF, subretinal hyperreflective tissue, SRF

Classic CNV nAMD

14

56

F

No

0.4

Reticular pseudo-drusen, SRNV

IRF, subretinal hyperreflective tissue, SRF

Classic CNV nAMD

15

62

F

No

2.3

Massive subretinal haemorrhage, exudates

Multiple PEDs, PED notch, TLP

Occult CNV

16

59

F

No

1

Drusen, SRNV, haemorrhage

IRF, PED, subretinal hyper-reflective tissue

Classic CNV nAMD

17

64

F

No

1.8

Drusen, SRNV, haemorrhage

SRF, subretinal hyperreflective tissue

Classic subfoveal CNV

nAMD

18

72

F

No

1.8

Haemorrhagic PED intraretinal and subretinal haemorrhage, exudates

Multiple PEDs, PED notch, TLP

Occult CNV

PCV

19

77

M

No

0.3

Peripapillary subretinal haemorrhage, exudates

PED, IRF, SRF

Occult CNV

PPCNV

20 66

M

No

1.3

PED, macular atrophy

Multiple PED, PED notch, DLS, SRF

Occult CNV

PCV

21

68

F

No

2.3

PED, subretinal fibrosis, exudates, haemorrhages

IRF, SRF, multiple PED

Not done

nAMD

22 65

M

No

1.8

Drusen, subretinal haemorrhage, subretinal fibrosis

IRF, SRF, subretinal hyper-reflective tissue

Occult CNV

nAMD

23 62

F

No

0.32

PED, subretinal haemorrhage, exudates Multiple PED, DLS, PED notch

Not done

PCV

24

F

2BZ

0.48

Drusens, RPE abnormalities

Occult CNV

nAMD

72

No

SRF, PED

Occult CNV

PCV

PCV

BCVA=best-corrected visual acuity, BZ=bevacizumab, CNV=choroidal neovascularisation, DLS=double layer sign, ISO=inner segment outer segment, IRF=intraretinal fluid, PPCNV=peripapillary CNV, SRF=subretinal fluid, SRNV=subretinal neovascular membrane, RB=ranibizumab, RPE=retinal pigment epithelium, RX=treatment, TLP=thumb-like polyp

Or iginal s tud y IVZ in neovascular AMD

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

Materials and methods

This retrospective interventional study involved patients with nAMD who were treated with IVZ from October 2016 to February 2018 at the Eye Centre, KorleBu Teaching Hospital, Accra. The study adhered to the tenets of the Declaration of Helsinki and the study protocol was approved by the Ethical and Protocol Review Committee of the College of Health Sciences, University of Ghana.

Inclusion and exclusion criteria and case definition

The inclusion criteria were patients aged 50 years and older with active nAMD, who were treatment naïve or had not received any previous anti-VEGF treatment for at least 3 months prior to initiation of IVZ, and had a minimum follow-up of 6 months. The diagnosis of nAMD was based on clinical features and supportive investigations including colour fundus photograph (CFP), fundus fluorescein angiography (FFA) (Zeiss 450 fundus camera) and SD-OCT (3D OCT-2000, Topcon, Tokyo, Japan). Eyes with active nAMD satisfied the following criteria for inclusion: presence (or recurrence) of intraretinal or subretinal haemorrhage, abnormal retinal thickness particularly with evidence of intraretinal, subretinal, or subpigment epithelial fluid accumulation optimally confirmed by SD-OCT, and new or persistent leakage shown on FFA. Other criteria included choroidal neovascular membrane (CNV) hyperfluorescence on FFA with increase in size in the late phase unless solely due to dry fibrotic membrane with late staining which does not classically increase in size and visual acuity deterioration considered likely to represent CNV activity.

A presumptive diagnosis of polypoidal choroidal vasculopathy (PCV) was made if slit lamp biomicroscopy or CFP showed a paucity of drusen, massive subretinal or subretinal pigment epithelium (subRPE) haemorrhage with or without retinal exudates, orange subretinal nodule(s) and recurrent serous or haemorrhagic pigment epithelial detachment (PED) supported by any three of the following SD-OCT B-scan features of: multiple PEDs, highly protruded PED, double-layer hyper-reflective lines, notched PED and rounded subRPE hyporeflective area.17,18 The exclusion criteria included intraocular surgery within 3 months of initial IVZ injection in the study eye, laser photocoagulation or intravitreal corticosteroid or anti-VEGF within 3 months of IVZ, patients with CNV from causes other than nAMD, and myopia ≥−6.0 dioptres.

Demographic and clinical characteristics of patients

The demographic and clinical characteristics of the patients recorded include age, sex, systemic comorbidities, affected eye, presenting complaint, duration of symptoms, type of previous anti-VEGF injection, number of previous anti-VEGF injection and time interval since last injection, diagnosis and status of fellow eye at baseline. Best-corrected visual acuity (BCVA) recorded using a Snellen chart and converted to logMAR values, intraocular pressure (IOP), lens status, and central macular thickness (CMT) at baseline and at 3, 6, and 12 months and the last follow-up visit were recorded. The number of IVZ injections received at 3, 6, and 12 months and at the last follow-up visit were also recorded.

27

The interval between the last injection of IVZ and the last follow-up visit were calculated. The status of the macular and number of recurrences at the last followup visit were recorded. The type of ocular and systemic adverse events occurring during the period were also recorded.

Intravitreal injections

IVZ (1.25 mg/0.05 ml) was given on a monthly basis until the macula was dry (absence of intraretinal and subretinal fluid). Subsequent injections were given on pro re nata (PRN) basis. The criteria for retreatment (recurrence of disease activity) included VA loss of at least one line on the Snellen visual acuity chart with evidence of fluid in the macula, increase in CMT of at least 100 μm or the presence of new macula haemorrhage.

Figure 1. Fundus photographs and SD-OCT B-scans of a 66-year-old male presenting with multiple recurrent haemorrhagic pigment epithelial detachments (PEDs).

PED notch (green arrow), sharppeaked PEDs (red arrowheads), double layer sign (black arrowheads). Retinal pigment hyperplasia and atrophy (red star) a result of previous laser photocoagulation of haemorrhagic PED. A, E: Presentation with third recurrence of disease activity (large haemorrhagic dome-shaped PED) after 12 bevacizumab and six ranibizumab injections. B, F: Reduction of PED height after additional three bevacizumab injections. C, G: Six months after initiation of ziv-aflibercept 1.25 mg/0.05 ml injection.

D, H: Fourth recurrence of disease activity 15 months after initiation of ziv-aflibercept

28

Or iginal s tud y IVZ in neovascular AMD

Outcome measures

The primary outcome measure is BCVA at 6 months follow-up. Secondary outcome measures are BCVA at 3 and 12 months and at the last follow-up visit, CMT at 3, 6, and 12 months and at the last follow-up visit, the proportion of eyes that gained at least one, two and three BCVA lines from baseline, number of recurrences and maximum treatment-free interval at the last follow-up visit, and ocular and systemic adverse events.

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

vitreous haemorrhage at presentation (Figure 3). The vitreous haemorrhage

was observed to clear at 10 months after initiation of IVZ therapy.

Statistical analysis

SPSS V.24 (IBM, Chicago, Illinois, USA) was used for statistical analyses. Continuous variables were presented as mean and standard deviation. Categorical variables were compared using chi-square or Fisher’s exact test. Pre- and post-injection changes in BCVA, IOP and CMT were compared using the paired t-test. The frequencies of ocular and systemic adverse events were computed. A p-value <0.05 was considered statistically significant.

Figure 2. Fundus photographs (A, C), SD-OCT (B, D) and FFA (E, F) of a 68-year-old male with presumptive diagnosis of PCV PEDS: red arrows, polyp: blue arrows

Results Demographic and clinical characteristics

Twenty-four eyes of 23 patients (14 females) were included in this study, and 14 eyes had follow-up duration of at least 12 months at the last visit. The mean age ± standard deviation (range) was 67.7±8.8 yrs (50–87 yrs) and the mean duration of follow-up was 11.4±4.0 months (6–16 months). The presenting complaint was blurred vision at presentation in all eyes except two who had metamorphopsia, and the mean duration of visual complaint was 7.6±7.9 months (2 weeks to 24 months). Systemic comorbidities (number) among the patients included in this study were systemic hypertension (11), diabetes mellitus (five), asthma (two) and sickle cell disease (one). Six patients had glaucoma in the affected eye. Five eyes were pseudophakic and 19 phakic. Six eyes had previous anti-VEGF injections prior to IVZ, the mean number of previous antiVEGF injections was 6.5±8.7 (1–24) and these eyes were free of injections for a mean of 9.8±7.7 months (range, 3–20 months) prior to switching to IVZ. The baseline demographic and clinical characteristics of study eyes are summarised in Table I. Nine (37.5%) of the eyes (five females and four males) with diagnosis of nAMD were presumed to have PCV based on clinical features. Representative cases of PCV are shown in Figures 1 and 2. One patient with presumptive diagnosis of PCV with extensive subretinal haemorrhage had breakthrough

Figure 3. Fundus photograph, fluorescein angiography and SD-OCT of 50-year-old female with presumed PCV A: Fundus photograph showing extensive subretinal/retinal haemorrhage extending from the disc margin to the fovea; B: SD-OCT showing subretinal haemorrhage (red arrow), PED notch (red arrowhead), thumb-like polyp (blue arrowhead); C, D: fluorescein angiography showing masking of fluorescence (C) and leakage in the late venous phase (D)

Or iginal s tud y IVZ in neovascular AMD

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

Table II: Visual and anatomic changes following intravitreal ziv-aflibercept injection at 3, 6 and 12 months and at the last follow-up visit compared to baseline p-value β

Parameter

Results

Age, mean±SD, (range), years

67.7±8.8 (50–87)

Number of IVZ injections, mean±SD, (range) 3 months 6 months 12 months Last visit

2.6±0.6 (1–3) 3.8±1.2 (1–6) 5.9±2.0 (1–8) 5.2±2.6 (2–10)

IOP, mean±SD, (range), mmHg Baseline 3 months 6 months 12 months (n=14) Last visit

16.1±3.7 (10–25) 15.9±3.1 (10–21) 16.2±3.0 (12–22) 15.4±3.3 (8–21) 15.5±2.7 (10–22)

0.7311 0.9360 0.4468 0.5021

BCVA, logMAR, mean±SD, (range) Baseline 3 months 6 months 12 months Last visit

1.12±0.7 (0.18–2.3) 0.78±0.6 (0.18–2.3) 0.79±0.6 (0.08–2.3) 0.71±0.4 (0.18–1.5) 0.76±0.6 (0.02–2.3)

0.0002 0.0017 0.0921 0.0006

BCVA gain at 6 months, frequency, (%) At least 1 line At least 2 lines At least 3 lines

19/24 (79.2) 9/24 (37.5) 6/24 (25.0)

BCVA gain at 12 months, frequency, (%) At least 1 line At least 2 lines At least 3 lines

11/14 (78.6) 4/14 (28.6) 1/14 (7.1)

CMT, mean±SD, range, μm Baseline 3 months 6 months 12 months Last visit

332.4±138.8 (163–645) 188.6±60.2 (90–363) 193.6±75.5 (91–414) 185.6±81.2 (86–414) 210.8±106.8 (81–590)

Presence of intraretinal fluid, yes/total no, (%) Baseline 3 months 6 months 12 months Last visit

14/24 (58.3) 4/23 (17.4) 4/23 (17.4) 4/14 (28.6) 4/23 (17.4)

0.0065 0.0065 0.1008 0.0065

Presence of subretinal fluid, yes/total no, (%) Baseline 3 months 6 months 12 months Last visit

20/24 (83.3) 2/23 (8.7) 1/23 (4.3) 3/14 (21.4) 1/23 (4.3)

<0.0001 <0.0001 0.0003 <0.0001

Presence of PED, yes/total no, (%) Baseline 3 months 6 months 12 months Last visit

20/24 (83.3) 10/23 (43.5) 6/23 (26.1) 3/14 (21.4) 6/23 (26.4)

0.0248 0.0001 0.0003 0.0001

-

<0.0001 0.0001 0.0073 0.0024

Β=paired samples t-test calculated by comparison of means at baseline to 3, 6 and 12 months and at the last follow-up visit, =Fischer’s exact test, BCVA=best-corrected visual acuity, CMT=central macular thickness, IOP=intraocular pressure, IVZ=intravitreal ziv-aflibercept, logMAR=logarithm of minimum angle of resolution, no=number of eyes, PED=retinal pigment epithelial detachment, SD=standard deviation

29

A total of 127 injections of IVZ were given over the study period. The mean number of anti-VEGF injections at 3, 6 and 12 months and at the last follow-up visit were 2.6±0.6 (1–3), 3.8±1.2 (1–6), 5.9±2.0 (1–8) and 5.2±2.6 (2–10), respectively. The maximum treatment-free interval was 3.7±2.9 (1–12) months, median 3 months at the last followup visit, and mean number of visits was 8.6±2.9 (4–14) at the last follow-up visit.

The mean IOP was 16.1±3.7 (10–25) mmHg at baseline and there was no significant difference in the mean IOP at 3, 6 and 12 months and at the last follow-up visit compared to baseline (Table II).

Visual outcome

Seventy-nine per cent of eyes had visual gain of at least one BCVA line at 6 months post-initiation of IVZ and the visual gain was maintained at 12 months (Table II). Only one (4.1%) eye had a visual decline of more than three Snellen acuity lines at 6 months and at the last follow-up visit due to occurrence of endophthalmitis. The mean baseline BCVA was 1.12±0.7 logMAR and there was significant improvement in BCVA to 0.78±0.6 and 0.79±0.6 respectively, at 3 and 6 months, and at the last visit (0.76±0.6) compared to baseline BCVA (Table II). Although there was improvement in the mean BCVA at 12 months (0.71±0.4) compared to baseline, the difference was not statistically significant.

Anatomic outcome

CMT at baseline was 332.4±138.8 μm and there was significant reduction in CMT at 3, 6 and 12 months and at the last visit compared to baseline (Table II). Intraretinal fluid was present in 14/24 (58.3%) eyes at baseline compared to 4/23 (17.4%) eyes at the last follow-up visit. Subretinal fluid was present in 20/24 (83.3%) eyes at baseline compared to 1/23 (4.3%) at the last visit.

Retinal pigment epithelial detachment was present in 20/24 (83.3%) eyes at baseline compared to 6/23 (26.4%) eyes at the last visit (Table II).

At the last follow-up visit, 14 (60.9%), one (4.3%) and one (4.3%) eyes, had one, two and three recurrences of disease activity, respectively. Among the 14 eyes which had a follow-up visit of at least 12 months, nine (64.3%) and two (14.3%) had one and two recurrences of disease activity respectively, at 12 months. One eye with classic CNV and follow-up duration of 15 months had persistent intraretinal fluid attributed to vitreomacular traction syndrome.

Adverse events

One eye in a 77-year-old male with

30

Or iginal s tud y IVZ in neovascular AMD

uncontrolled diabetes mellitus developed endophthalmitis in the right eye two days after the fourth injection of IVZ for a peripapillary choroidal neovascularisation (Figure 4). His BCVA prior to initiation of IVZ was 0.32 logMAR and improved to 0.18 logMAR after three injections of IVZ. Visual acuity at presentation with painful loss of vision was hand motion. He had vitreous tap and intravitreal injection of vancomycin 1 mg/0.1 ml, ceftazidime 2 mg /0.1 ml and dexamethasone 0.4 mg/0.1 ml. Culture of vitreous specimen isolated Staphylococcus epidermidis. Visual acuity declined further to perception of light seven days after intravitreal injection of antibiotics, and the eye developed hypotony (IOP = 2 mmHg) associated with choroidal detachment which was observed on B-scan ultrasonography.

He subsequently had pars plana lensectomy and pars plana vitrectomy. Fundus examination postoperative showed clear ocular media and round pre-retinal exudates (Figure 4). A presumptive diagnosis of fungal endophthalmitis was made and he was started on oral fluconazole 200 mg daily for seven days and had intravitreal voriconazole 100 mcg/0.1 ml and vancomycin 1 mg/0.1 ml on the seventh day postoperative. He subsequently had an additional six IVZ injections and secondary implantation of posterior chamber intraocular lens. His BCVA at the last follow-up visit was 0.78 logMAR (6/36 Snellen equivalent). No other serious ocular or systemic adverse event was observed in this study.

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

of 30 patients with nAMD.15 They observed improvements in both the CMT and BCVA after receiving monthly IVZ (1.25 mg/0.05 ml) for three consecutive months.15 It was further observed that the treatment-naïve cases had better anatomic response (p=0.008) and improvement in BCVA compared to those who were resistant to bevacizumab or ranibizumab injections (p=0.008).15 Braimah et al. reported on the one-year outcome of IVZ in 16 eyes with nAMD who were non-responsive to bevacizumab or ranibizumab.12 One-third of the eyes had a visual gain of one logMAR line and there was an average reduction of 2.5 injections.12 They concluded that a reduction in the frequency of injections of intravitreal anti-VEGF could result in reduced cost to both patients and the healthcare system.12 The use of IVZ is off-label. Guo et al. assessed the one-year VA response to aflibercept in patients with nAMD using pooled data from clinical trials and observational studies.19 They reported a VA

improvement of 7.37 letters at 12 months following use of aflibercept.19 The standard dose of aflibercept is 2 mg/0.05 ml. However, Schmidt-Erfurth et al. have reported that both the 0.5 mg and 2 mg doses of aflibercept achieved comparable visual outcome in the VIEW studies.10 We used 1.25 mg/0.05 ml of IVZ in our study and observed a median difference in VA of −0.16 logMAR (eight letters improvement) in 14 eyes that achieved follow-up of 12 months. Several studies have reported that the 1.25 mg/0.05 ml of IVZ was safe and effective in eyes with retinal vascular diseases.12-15 The safety of IVZ appears similar to other anti-VEGFs.20 Singh et al. reported the occurrence of one case of culture-proven endophthalmitis following 5 914 injections of ziv-aflibercept using pooled data across nine centres.20 Our case of endophthalmitis in this study is the same case reported by Singh et al.20 The rate of endophthalmitis of 0.78% in this study, although it appears

Discussion

In this study, there was a significant improvement in the visual and anatomic outcome at 3, 6, and 12 months and at the last follow-up visit following IVZ injection for nAMD. In a prospective non-randomised study of the safety and efficacy of IVZ in 14 eyes with nAMD, de Oliveira Dias et al. reported improvement in BCVA from 0.95±0.41 from baseline to 0.75±0.51 at 52 weeks (p=0.0066).14 Despite the difference of no ‘loading’ of three-monthly injections of IVZ, the VA improvement at 6 and 12 months in this study were similar to that observed

by De Oliveira Dias et al.14 Although the VA outcomes were significant at the primary endpoint, and at other times, the lack of significant difference in VA at 12 months may be due to the small number of patients included in this study. There was significant improvement in the mean CMT in our study at 12 months as observed by De Oliveira Dias et al.14 Mansour et al. reported on the 3-month outcome of IVZ in a cohort

Figure 4. Fundus images of 77-year-old male with peripapillary choroidal neovascularisation who developed endophthalmitis following fourth injection of IVZ Colour photo, late phase fluorescein angiogram and OCT at presentation (A, B, C, D). E: Anterior segment photograph showing cornea haze, hypopyon (red arrow), and fibrin over pupil; F: SD-OCT image at 1 week after pars plana lensectomy (PPL) and vitrectomy (PPV); G: Fundus photograph 1 week after PPL and PPV showing lens fragments (black arrow) and round pre-retinal lesions. Fundus photograph (H) and SD-OCT B-scan (I) 12 months after onset of endophthalmitis

Or iginal s tud y IVZ in neovascular AMD

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

quite high, can be attributed to the small sample size and lower number of injections in this series.

Although indocyanine green angiography (ICGA) is the gold standard for diagnosis, SD-OCT is increasingly becoming a useful imaging modality for the diagnosis of PCV.17,18,21 De Salvo et al. retrospectively compared the SD-OCT and ICGA of 51 eyes of 44 patients who had one or more serous/ haemorrhagic PED due to PCV or occult CNV.17 They reported that the presence of four SD-OCT features (multiple PED, PED notch, sharp PED peak and sub-RPE hyporeflective lumen within hyper-reflective lesions) had high sensitivity and specificity for differentiating PCV from occult CNV with high positive and negative predictive values.17 In a prospective study of 188 eyes by Liu et al., the presence of two out of three SD-OCT features (PED, doublelayer sign, and thumb-like polyps) had 89.4% sensitivity and 85.3% specificity in distinguishing PCV from nAMD.18 In a retrospective study of the CFP, SD-OCT and FFA of 119 eyes with serosanguinous maculopathy (thus PCV, nAMD and central serous chorioretinopathy) Chaikitmongkol et al. reported that combined CFP and SD-OCT provided the highest sensitivity, high specificity and positive predictive value in the diagnosis of PCV.21 We do not have access to ICGA to confirm the diagnosis of PCV in our series. The use of slit lamp biomicroscopy findings, CFP and SD-OCT showed the presence of PCV in 37.5% of our study eyes. The high prevalence of PCV in this series is supported by previous reports of a higher prevalence of PCV in people of African and Asian descent.2,22 The limitations of this study include small sample size, retrospective design, lack of access to ICGA to confirm the diagnosis of PCV and non-uniform followup. We have demonstrated the potential efficacy of 1.25 mg IVZ in an African population despite these limitations.

Clinical, CFP and SD-OCT features were very supportive of the diagnosis of PCV despite lack of access to ICGA.

Conclusion

We conclude from this retrospective series that 1.25 mg IVZ administered on a PRN basis in nAMD eyes was associated with significant reduction in CMT at 3, 6 and 12 months and at the last follow-up visit. There was improvement in visual outcomes at 3, 6 and 12 months, and at the last follow-up visit compared to baseline VA. There was one serious adverse event (endophthalmitis) in this study with

31

unfavourable visual outcome. There is the need for a large prospective study on the efficacy of IVZ in nAMD in African populations. There is further need for a study that would categorise the various types of AMD in African populations.

11. Shah GK ST. 2017 Global Trends in Retina

Acknowledgements

12. Braimah IZ, Agarwal K, Mansour A,

The authors wish to thank the staff of the medical records department, treatment room and outpatient clinic of the Eye Centre, Korle-Bu Teaching Hospital, for their support while this study was being conducted. We express our gratitude to participants who voluntarily consented for their images to be included in this study.

References

1. Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol.

2012;96(5):614-18.

2. Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y, et al. Global prevalence of agerelated macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e16.

3. Imamura Y, Engelbert M, Iida T, Freund KB, Yannuzzi LA. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol.

2010;55(6):501-15.

4. Hera R, Keramidas M, Peoc’h M, et al.

Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration. Am J Ophthalmol. 2005;139(4):589-96.

5. Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. Oncologist.

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6. Chung C, Pherwani N. Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer. American journal of health-system pharmacy : Am J Health syst Pharm. 2013;70(21):1887-96.

7. Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology.

2012;119(7):1399-411.

8. Martin DF, Maguire MG, Fine SL, et al.

Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results.

Ophthalmology. 2012;119(7):1388-98.

9. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology.

2012;119(12):2537-48.

10. Schmidt-Erfurth U, Kaiser PK, Korobelnik

JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology.

2014;121(1):193-201.

Survey. Chicago, IL. 2017.

Chhablani J. One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular agerelated macular degeneration. Br J Ophthalmol.2018;102(1):919-16.

13. Chhablani J, Narayanan R, Mathai A, Yogi R, Stewart M. Short-term safety profile of intravitreal ziv-aflibercept. Retina.

2016;36(6):1126-31.

14. de Oliveira Dias JR, Costa de Andrade G, Kniggendorf VF, et al. Intravitreal zivaflibercept for neovascular age-related macular degeneration: 52-week results. Retina.

2019;39(4):648-55.

15. Mansour AM, Chhablani J, Antonios RS, et al.

Three-month outcome of ziv-aflibercept for exudative age-related macular degeneration.

Br J Ophthalmol. 2016;100(12):1629-33.

16. Braimah IZ, Kenu E, Amissah-Arthur KN, Akafo S, Kwarteng KO, Amoaku WM. Safety of intravitreal ziv-aflibercept in choroidoretinal vascular diseases: A randomised double-blind intervention study. PLoS One. 2019;14(10):e0223944.

17. De Salvo G, Vaz-Pereira S, Keane PA, Tufail A, Liew G. Sensitivity and specificity of spectral-domain optical coherence tomography in detecting idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol.

2014;158(6):1228-38.e1.

18. Liu R, Li J, Li Z, Yu S, Yang Y, Yan H, et al. Distinguishing polypoidal choroidal vasculopathy from typical neovascular age-related macular degeneration based on spectral domain optical coherence tomography. Retina. 2016;36(4):778-86.

19. Guo MY, Cheng J, Etminan M, Zafari Z, Maberley D. One year effectiveness study of intravitreal aflibercept in neovascular age-related macular degeneration: a meta-analysis. Acta Ophthalmol. 2019;97(1):e1-e7.

20. Singh SR, Stewart MW, Chattannavar G, et al. Safety of 5914 intravitreal ziv-aflibercept injections. Br J Ophthalmol. 2019;103:805-10.

21. Chaikitmongkol V, Khunsongkiet P, Patikulsila D, et al. Color fundus photography, optical coherence tomography, and fluorescein angiography in diagnosing polypoidal choroidal vasculopathy. Am J Ophthalmol.

2018;192:77-83.

22. Ciardella AP, Donsoff IM, Huang SJ, Costa DL, Yannuzzi LA. Polypoidal choroidal vasculopathy. Surv Ophthalmol.

2004;49(1):25-37. 

EFFECTIVE, T ARGETED action against the M OST PPREVALENT REVALENT MOST EFFECTIVE, TARGETED bacterial conjunctivitis causing pathogens 1-7 One effec ve drop in the morning . . .

. . . and one at night 8

Effective T TWICE W I CE D DAILY AILY treatment for bacterial conjunctivitis 8,9 across A LL A GE G ROUPS ALL AGE GROUPS

1. Arrata M. Fusidic acid viscous eye drops, Fucithalmic®, in bacterial con�unc�vi�s. A review of three controlled clinical studies with chloramphenicol and framyce�n eye drops. Acta XXV Concilium Ophthalmologicum.

Proceedings of the XXVth Interna�onal Congress of Ophthalmology, Rome, May 4-10, 1986; 1038-1042. 2. Medicines.org.uk. (2019). Fusidic Acid 1% Viscous Eye Drops - Summary of Product Characteris�cs (SmPC) - (eMC). h ps://www.medicines.org.uk/emc/product/5188/smpc. Accessed 28.06.2019. 3. Optometric clinical prac�ce guideline. Care of the pa�ent with con�unc�vi�s. Reference guide for clinicians. © American Optometric Associa�on 1995, 2002. 4. Epling J. Bacterial Con�unc�vi�s. BMJ Clin Evid 2012; pii: 0704. 5. Orden Mar�nez B, Mar�nez Ruiz R, Millán Pérez R. Bacterial con�unc�vi�s: most prevalent pathogens and their an�bio�c sensi�vity. An Pediatr (Barc). 2004;61(1):32-36. 6. Centre for Disease Control (CDC). Pink Eye. h ps://www.cdc.gov/con�unc�vi�s/clinical.html. Accessed 28.06.2019. 7. Dirdal, M. (1987). Fucithalmic® in acute con�unc�vi�s. Acta Ophthalmologica, 65(2), pp.129-133. 8. Fucithalmic package insert. Approved by MCC 02 April 2013. 9. Jackson WB, Low DE, Da ani D, Whitsi PF, Leeder RG, Macdougall R. Treatment of acute bacterial con�unc�vi�s: 1% fusidic acid viscous drops vs 0.3% tobramycin drops. Can J Ophthalmol 2002; 37:228-237. FUC_A4 20_01

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Neuromyelitis optica and other causes of demyelinating optic neuritis in children DD Shastry MBChB, FC Ophth(SA); Registrar ORCID: https://orcid.org/0000-0002-2727-172X J Olivier MRCOphth, MMed(Ophth); Head of Department of Ophthalmology C Cullen MBBCh, FC Ophth(SA), Fellowship (Paediatric Ophthalmology and Adult Strabismus); Sessional Consultant Dr George Mukhari Academic Hospital, Department of Ophthalmology, Sefako Makgatho Health Sciences University, South Africa Corresponding author: Dr DD Shastry, Department of Ophthalmology, PO Box 66, Medunsa, GaRankuwa 0204; email: dimple_deepa@hotmail.com; cell: 0724322398

Abstract Optic neuritis in childhood is one of the most frequent presentations of an acquired demyelinating syndrome.

Paediatric optic neuritis is, however, an infrequent clinical presentation.

We present an interesting case of an 8-year-old female with optic atrophy in the left eye accompanied by a right optic neuritis who subsequently developed a lower limb paralysis and right-sided blindness within a few weeks of discharge. Radiological imaging revealed demyelinating lesions of the transverse spinal cord. A diagnosis of neuromyelitis optica (NMO) was made and the patient was treated with immunosuppressive therapy.

This article describes the presentation of paediatric optic neuritis as well as the differences between three common aetiologies thereof, namely neuromyelitis optica (NMO), acute

Introduction

Paediatric optic neuritis (PON) is an uncommon clinical presentation and may be challenging to manage. There are few published case series in the literature, mainly from Europe and North America, with limited data from Asia and subSaharan Africa. The incidence in Canada is approximately 0.2 per 100 000.1 From the majority of these case series, <10% of children with ON are documented to develop a demyelinating condition.2 ON in children presents differently from adults; children are more likely to have more severe visual deficit, a preceding viral illness or vaccination and bilateral optic nerve swelling. The Optic Neuritis Treatment Trial (ONTT) conducted on an adult population provided invaluable long-term data on visual outcomes in patients with ON as well as their risk of developing multiple sclerosis (MS). The treatment guidelines provided

disseminated encephalomyelitis (ADEM) and paediatric multiple sclerosis (MS).

Management of paediatric optic neuritis is largely based on adult trials. It is necessary for the clinician to bear the diagnosis in mind if young patients present with similar clinical features.

Ruling out such conditions is important to prevent permanent vision loss or other neurologic impairment.

Keywords: neuromyelitis optica, acute disseminated encephalomyelitis, multiple sclerosis, paediatric, optic neuritis Funding: No funding was received for this study.

Conflict of interest: The authors declare they have no conflicts of interest with regard to this study.

by the study are currently the standard of care for adult ON. It was demonstrated that at 15 years, the visual outcomes were good with 72% of patients enrolled to the study having a visual acuity better than or equal to 20/20 in the eye which had ON, and 66% of patients having better than or equal to 20/20 visual acuity in both eyes.3 MS developed in only a small subgroup of patients.3 In contrast, far less is known about the spectrum and outcomes of ON in children.

Parainfectious causes are the most common aetiology of ON in children, while the most common aetiology in adults is MS. When PON occurs as a self-limiting isolated event it carries no prognostic implication with regard to the rest of the nervous system. Most children recover visual acuity spontaneously; however, in the cases that fail to recover, the impact on vision is lasting and may take the form of prominent lowcontrast vision, colour perception and visual

field deficits. Current management of PON is mainly based on adult trials and the results of the ONTT where IV methylprednisolone, if given within the first 15 days after onset, may accelerate visual recovery compared to placebo or oral steroids. 3 For most children with ON the recommended firstline treatment is IV methylprednisolone (20–30 mg/kg/d; maximum dose of 1 g/d) for 3–5 days; thereafter tapering prednisone over two weeks (1 mg/kg/d orally).

Additional therapies (IV immunoglobulin G and plasma exchange) may be considered in children with diffuse central nervous system involvement who do not show response to IV methylprednisolone.

Acquired demyelinating syndromes in childhood commonly present with unilateral ON, followed by rapid bilateral involvement. Frequent relapses have a cumulative effect on visual loss.

Herein lies the importance of PON to

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the ophthalmologist. While the initial disturbances may be limited to visual deficits, further investigations will reveal a specific aetiology. The aim of this article is to describe the differences between three common aetiologies of PON, namely neuromyelitis optica (NMO), acute

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disseminated encephalomyelitis (ADEM) and paediatric multiple sclerosis (MS) in presentation, diagnosis, treatment and prognosis (see summary in Table I). ADEM and MS are immune-mediated conditions while NMO is antibody-mediated. Ruling out these conditions is paramount to

preventing permanent vision loss and other neurologic impairment.

Case presentation

A previously healthy 8-year-old girl was brought to the Ophthalmology Department with the concern of a sudden deterioration

Table I: Summary of features in NMO, ADEM and paediatric MS Neuromyelitis optica Definition

Acute disseminated encephalomyelitis Paediatric multiple sclerosis

Chronic inflammatory disease Immune-mediated demyelinating associated with a disease-specific auto- disorder of the CNS antibody which affects the CNS

Presenting Recurrent episodes of optic neuritis features and myelitis: These two features may occur either alone or in combination Limited or no recovery resulting in permanent blindness and/or limb paralysis Within five years of onset half of patients lose functional vision4,5

Dysregulation of the immune system followed by recurrent episodes of demyelination in the CNS

Acute or subacute onset of Polyfocal presentation at clinical CNS demyelinating disease onset: disease with encephalopathy and Impaired vision, walking, balance, polysymptomatic neurologic features bladder and bowel control, Various neurologic features may numbness, tingling sensation occur concurrently (optic neuritis, and fatigue weakness, gait abnormalities and Other features more common paraesthesias) due to multiple in children: inflammatory lesions in the brain Symptomatic encephalopathy-like and spinal cord white matter headache, vomiting and altered Deficits progress rapidly and are level of consciousness most pronounced within two to five days13 A preceding prodromal period is common

Prevalence Less than 1– 4.4/100 0004

Demo­ graphics

Estimated incidence 0.3–0.6 per 12 Paediatric cases account for only 3.4% 100 000 per year of all NMO cases4

Incidence: <1% under 10 years of age

Female dominance

Male predominance

Children before the age of 16 years

Average age of onset 12 years

Median age of 5–8 years

3–10% under 16 years of age15

Patho­ Autoantibodies (AqP4-IgG) that target physiology aquaporin-4 (AqP4) channels causing cell-meditated cytotoxicity

Antigenic determinants of infecting pathogen may be shared with myelin autoantigens

Dysregulation of the immune system followed by recurrent episodes of demyelination in the CNS

Diagnosis

Ranges from 17–80%

Preceding non-specific viral or bacterial infection

Associated with a relapsing course

Identified in 72–77% of patients13,14

CSF analysis demonstrates oligoclonal bands in 40–50% of paediatric MS cases16

Demographic and disease-related characteristics differ between seropositive and seronegative patients

Onset of symptoms classically two to four weeks following an infection13,14

T2-weighted MRI:4,6

T2-weighted and fluid-attenuated inversion recovery (FLAIR):14

AqP4-IgG seropositivity 6,7

Neuro­ imaging findings

High signal, central longitudinal spinal cord lesions Spanning over three or more vertebral segments Brain lesions show gadolinium enhancement Optic nerve high signal longitudinal lesions extending over more than half of the length of the optic nerve in T2-weighted

CSF analysis in two-thirds of patients reveals lymphocyte predominance, mild pleocytosis and/or increased protein concentration

Ill-defined lesions in deep and subcortical white matter varying in number and size Bilateral cerebral involvement Large confluent intramedullary lesions in the spinal cord may span multiple segments with variable contrast enhancement

T2-weighted and T2-FLAIR:16 Multiple well-demarcated hypointense lesions in periventricular, spinal cord, juxtacortical and infratentorial white matter

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Table I: Summary of features in NMO, ADEM and paediatric MS continued Treatment

Neuromyelitis optica

Acute disseminated encephalomyelitis Paediatric multiple sclerosis

No curative treatment for NMO:

First line therapy for ADEM:

Multidisciplinary approach:

Acute attacks should be treated as Systemic corticosteroids of IV Physical therapy, occupational soon as possible to prevent irreversible methylprednisolone (20–30 mg/kg therapy and counselling optic nerve injury per day for three to five days) Treatment aimed at relieving some High dose of IV methylprednisone (1 g Thereafter oral prednisone of the disease symptoms, such as daily) is given for three to five days10 (1–2 mg/kg per day) for one to fatigue, and improving quality of life two weeks tapered over two to six Plasma exchange or IV immunoglobulin Corticosteroids used in the acute weeks14 therapy used in cases unresponsive to setting to reduce inflammation steroid treatment

IV immunoglobulin and IV immunoglobulin and plasma plasmapheresis are alternate Immunosuppressive therapy is advised exchange may be used for children therapies for steroid unresponsive to be initiated following stabilisation who cannot tolerate corticosteroids cases after the acute attack Disease-modifying therapies Interferon beta or glatiramer acetate is currently the first-line treatment in children with MS15 Prognosis

Monophasic or relapsing:

Monophasic disease with a >90% of patients suffer further relapses, favourable outcome making the prognosis challenging5 Neurologic improvement seen within days of treatment, and full Relapse rates: recovery occurs within weeks 60% within the first year

Slower disease course in children Frequent relapses Significant disability accumulation at a younger age with significant impact on quality of life

90% within three years Prognosis: not favourable in patients with relapses as neurological injuries are cumulative and remissions are not constant of vision in both her eyes. She reported difficulty in seeing for the past five days.

The mother was concerned as the child had no prodromal symptoms, previous illness or trauma in the preceding weeks. Her systemic physical, including neurological, examination was normal.

Her visual acuity in both eyes revealed light perception with a relative afferent pupillary defect in the left eye. The left optic disc was pale and suggestive of optic atrophy. The right fundus examination showed a swollen optic disc with a blurred disc margin. The optic disc was pink and well perfused with no peripheral lesions or haemorrhages of the retina. The mother was not aware of any loss of vision in the left eye prior to consultation. A working diagnosis of optic neuritis (ON) was made.

The patient was admitted for treatment with high dose intravenous (IV) steroids (1 g/day IV for three days) followed by oral steroids for 11 days (1 mg/kg per day). The initial diagnostic work-up, which included tests for viral serology TORCH-S (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, syphilis), as well as a brain magnetic resonance imaging (MRI) scan, was normal (Figure 1). After completing the steroid treatment, the patient’s vision in the right eye had returned to 20/20 (6/6) and

Figure 1. MRI brain and C-spine (T1-weighted) demonstrating normal initial study

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Figure 2 and 3. MRI spine demonstrating diffuse longitudinal high signal changes in the cervical and thoracic area on T2-weighted imaging extending more than four vertebrae levels (indicated with yellow arrow) all the disc changes had resolved at followup two weeks later. The left eye vision remained at light perception.

Two months later, she was brought to the emergency department and re-admitted to the hospital with an acute inability to walk.

She had started limping three days prior and was unable to see with her right eye.

At this time, she also had urinary retention, associated headaches and loss of weight.

The cranial nerves and sensation were otherwise intact, with normal strength and deep tendon reflexes of the upper limbs.

There was significantly reduced power of both lower limbs with absent reflexes and decreased tone and accompanying neck stiffness. Treatment was initiated for a meningitis while awaiting brain contrast tomography (CT) and lumbar puncture results. The CT and lumbar puncture results were unremarkable. A subsequent MRI orbit and spine was performed which showed longitudinal extensive spinal lesions over more than three segments (Figures 2–4). In the absence of encephalopathy, a presumptive diagnosis of neuromyelitis optica (NMO) was made. High dose IV methylprednisolone therapy was prescribed.

Despite treatment and physiotherapy rehabilitation, the patient’s symptoms and lower limb paralysis remained unchanged throughout the time of admission of four weeks. A follow-up examination of her right fundus revealed a pale optic disc, in keeping with light perception vision from optic atrophy. The high dose IV steroid treatment was changed to oral course and then gradually tapered. The patient was

subsequently discharged home to continue physiotherapy rehabilitation. Over the next three months, she had some improvement in her lower limb power.

The patient presented again six months later, with an acute onset of difficulty in breathing with bilateral coarse crepitations on auscultation as well as decreased upper limb strength. Blood tests for aquaporin-4 (AqP4) antibodies were negative. She was treated with IV antibiotics and IV immunoglobulin (Polygam) and recovered from the respiratory tract infection.

Gradually, she also regained some upper and lower limb power. There have been no further events in the past 18 months.

However, the vision in both eyes remains unchanged at <20/200 (light perception).

Discussion Neuromyelitis optica

Neuromyelitis optica (NMO) is a chronic inflammatory disease associated with a disease-specific autoantibody which affects the central nervous system (CNS).

Recurrent episodes of ON and myelitis are presenting features, often with limited or no recovery, resulting in permanent blindness and/or limb paralysis. Other features associated with spinal cord lesions include urinary dysfunction. Global incidence and prevalence rates of NMO are lacking. In the developed world, the estimated prevalence ranges from less than 1 to 4.4/100 000.4 Paediatric cases are rare and account for only 3.4% of all NMO cases.4 In non-Caucasian patients, there is a female dominance and average age of

onset of 12 years. A first event of ON occurs in 50–70% of childhood NMO cases and transverse myelitis may occur in 30–50%.

These two features may occur either alone or in combination.4,5 Within five years of onset half of the patients lose functional vision, suggesting that paediatric onset may be associated with more frequent and disabling ON.5 NMO was previously regarded as a variant of MS but has recently been grouped under the class of neuromyelitis optica spectrum of disorders (NMOSD).4 The differential diagnoses of NMOSD includes various autoimmune, vascular, infectious or neoplastic aetiologies. In the early stages of disease, patients with NMOSD may have limited presenting features. Conditions such as MS, ADEM, idiopathic acute transverse myelitis, idiopathic ON, sarcoidosis, CNS lymphoma and systemic lupus erythematosus may have overlapping clinical signs and must be excluded before a diagnosis of NMOSD can be made, as the treatment differs vastly.

The following tests are recommended to exclude these conditions: full blood count with differential, serum chemistry, blood sedimentation, coagulation studies, Treponema pallidum hemagglutination assay, antibodies associated with connective disorders (ANA/ENA, anti-ds-DNA antibodies, lupus anticoagulant, antiphospholipid antibodies, ANCA, etc.), vitamin B12, folic acid and analysis for copper deficiency.4 Based on clinical presentation, urine chemistry and sedimentation as well as cerebrospinal fluid (CSF) analysis should also be performed.

Research efforts into the cellular

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mechanisms of NMO are being directed at autoantibodies (AqP4-IgG) that target aquaporin-4 (AqP4) channels. Cell-meditated cytotoxicity may occur when AqP4-IgG binds to AqP4 on the cell membrane of astrocytes, initiating complement- and antibodydependent inflammation cascades. AqP4‑IgG seropositivity ranges from 17–80% and is associated with a relapsing course.6,7 The Aqp4-IgG laboratory assay may not be readily available; however, it is a highly specific diagnostic test used to predict long-term prognosis and therapeutic response. Demographic and disease-related characteristics differ between seropositive and seronegative NMO patients. The diagnosis of NMOSD with AqP4-IgG requires the presence of at least one core clinical feature of NMOSD in either cerebrum, brainstem, dorsal medullar, optic nerve or spinal cord and positive AqP4-IgG, where alternative diagnosis have been excluded.8 The diagnosis of NMOSD without AqP4-IgG requires one clinical event involving at least one of the typical anatomic regions together with additional MRI criteria beyond longitudinally extensive transverse myelitis.6 The typical features of NMO on T2-weighted MRI are high signal, central longitudinal spinal cord lesions spanning

over three or more vertebral segments.

Contrast agents and follow-up examinations are recommended as one-third of patients with brain lesions show gadolinium enhancement in a cloud-like pattern.4 Optic nerve involvement is demonstrated as high signal longitudinal lesions which extend over more than half of the length of the optic nerve in T2-weighted or short T1-inversion recovery images.6 Most children present with acute transverse myelitis more often at relapses than at presentation. The role of optical coherence tomography in ophthalmology as an adjunct to diagnosis and disease progression monitoring has not yet been established.9 At present there is no curative treatment for NMO. Acute attacks in all patients with suspected NMOSD should be treated as soon as possible while diagnostic tests are underway to prevent irreversible optic nerve injury. A high dose of IV methylprednisone (1 g daily) is given for three to five days.10 Plasma exchange or IV immunoglobulin therapy is used in cases unresponsive to steroid treatment. Following stabilisation after the acute attack, it is advised that every patient with NMOSD be started on immunosuppressive therapy. Azathioprine, methotrexate, mycophenolate or rituximab

Figure 4. MRI spine demonstrating diffuse longitudinal high signal changes in the cervical and thoracic area on T1-weighted imaging (indicated with yellow arrow)

37

may be considered and continued for up to five years after the attack.10 Seronegative NMO follows a monophasic course and immunosuppressive therapy may be tapered after some years of disease stability. The future of therapies may lie in anti-IL6 receptor, anti-complement and anti-AqP4-ab biologicals which are currently being investigated.11 The nature of NMO is either monophasic or relapsing. More than 90% of patients suffer further relapses, making the prognosis challenging.5 Within the first year 60% of patients suffer a relapse and 90% relapse within three years. The prognosis of patients with relapses is not favourable as neurological injuries are cumulative and remissions are not constant.

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating disorder of the CNS that also presents with ON and an acute onset encephalopathy. The pathogenesis of ADEM is thought to occur when antigenic determinants of an infecting pathogen may be shared with those of myelin autoantigens (myelin oligodendrocyte protein and myelin basic protein).12 In 72–77% of patients a preceding non-specific viral or bacterial infection can be identified, with onset of symptoms classically occurring two to four weeks following an infection.13,14 Acute disseminated encephalomyelitis has an estimated incidence of around 0.3–0.6 per 100 000 per year.12 It is usually a monophasic disease with a median age of 5–8 years at presentation and a male predominance.

Acute disseminated encephalomyelitis produces multiple inflammatory lesions in the brain and spinal cord white matter causing various neurologic symptoms, which may occur concurrently at presentation.

ON, weakness, gait abnormalities and paraesthesias are dependent on the location of these lesions. A preceding prodromal period may accompany symptoms such as malaise, headache, irritability, fever, nausea and vomiting.

Acute disseminated encephalomyelitis progresses rapidly and deficits are most pronounced within two to five days.13 The major diagnostic criteria of ADEM are an acute or subacute onset of clinical CNS demyelinating disease with encephalopathy and polysymptomatic neurologic features.12 Encephalopathy is a differentiating feature of ADEM from other syndromes and is an essential symptom for a diagnosis of ADEM. Encephalopathy may present

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with subtle behavioural changes, such as lethargy or irritability, or with alterations in level of consciousness and coma in more severe cases. In two-thirds of patients the CSF analysis will reveal a lymphocyte predominance, mild pleocytosis and/or increased protein concentration.13 The characteristic patterns of CNS lesions on MRI imaging are most notable on T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging in the deep and subcortical white matter. Lesions vary in number and size, with diameters from <5 mm to 5 cm, and are ill-defined. Bilateral cerebral involvement and lesions in the thalamus and basal ganglia are common and highly suggestive of ADEM. Large confluent intramedullary lesions in the spinal cord may span multiple segments and demonstrate variable contrast enhancement on imaging.14 At least two additional MRI scans are recommended at follow-up over a period of five years after the first negative scan.12 First-line therapy for ADEM is systemic corticosteroids consisting of IV methylprednisolone 20–30 mg/kg per day for three to five days. Thereafter oral prednisone is continued at 1–2 mg/kg per day for one to two weeks with tapering over two to six weeks.14 IV immunoglobulin and plasmapheresis are alternate therapies for steroid unresponsive cases.

The majority of children with ADEM are reported to have a favourable outcome.

Neurologic improvement is seen within days of treatment and full recovery occurs within weeks.14

Multiple sclerosis

Multiple sclerosis (MS) is most commonly diagnosed in young adults. Paediatric MS (early-onset MS or juvenile MS) is diagnosed in children before the age of 16 years. Although it occurs infrequently in children, there is a global increase in incidence and prevalence in this subgroup of patients. The incidence of MS is between 3% and 10% under 16 years of age and less than 1% under 10 years of age.15 Paediatric MS differs from adult MS in its disease course and clinical features. Children experience a slower disease course with more frequent relapses, which causes significant disability to accumulate by early adulthood. It is suggested that the condition is caused by dysregulation of the immune system followed by recurrent episodes of demyelination in the CNS. Research efforts are being directed towards identifying a genetic susceptibility and specific environmental triggers of MS.16

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Children can have a polyfocal presentation at disease onset corresponding to areas within the brain, optic nerves or spinal cord of acute inflammation and demyelination. A wide range of manifestations may result from ON, sensory, brainstem-cerebellar and motor involvement, resulting in impaired vision, walking, balance, bladder and bowel control, numbness, tingling sensation and fatigue.15 Other features more common in children include symptomatic encephalopathy like headache, vomiting and altered level of consciousness. In 15–20% of MS children, the symptoms may be similar to ADEM.16 The CSF analysis of paediatric MS patients demonstrates the presence of oligoclonal bands in 40–50% of cases, which is distinctly less than in adults.16 Features of MS on MRI are best recognised using T2-weighted sequences and T2 FLAIR image sequences, which demonstrate multiple well-demarcated hypointense lesions in the periventricular and spinal cord as well as juxtacortical and infratentorial white matter. Absence of typical ‘black holes’, diffuse bilateral lesions and fewer than two periventricular lesions differentiates ADEM from MS patients. The revised McDonald criteria (2010) are used for diagnosis of paediatric MS which evaluates the presence of disseminated lesions on clinical and MRI findings.16 The risk of PON evolving into MS increases with age, the presence of lesions on brain MRI at initial presentation and new lesions in different sites on follow-up MRI.15 However, the true risk of development of MS is still uncertain in this subset of patients.17 Data on the optimal therapy of MS in the paediatric population is not well established. A multidisciplinary approach towards management is recommended, which includes physical therapy, occupational therapy and counselling.

Symptom severity depends on the duration of the disease and severity of MS.16 Treatment is aimed at relieving some of the symptoms of the disease, such as fatigue, and improving quality of life. Corticosteroids are used in the acute setting to reduce inflammation. IV immunoglobulin and plasma exchange may be used for children who cannot tolerate corticosteroids. Paediatric MS is treated with the same disease-modifying therapies as for adult patients with MS. Interferon beta or glatiramer acetate is currently the first-line treatment in children with MS, demonstrating a favourable safety profile.15 Paediatric MS is an underdiagnosed and undertreated condition with slow progression. Overall development of

disability is variable and may be moderate to severe but this is often reached at a younger age with significant impact on quality of life.

Conclusion

PON, though rare, is of significance to the ophthalmologist due to its association with neuroinflammatory diseases as the first presentation (NMO, ADEM, MS).

The clinical signs differ from adult ON making a thorough systemic examination, neuroimaging and cerebrospinal fluid findings imperative for determining an aetiology. While the risk of developing MS in children with monosymptomatic ON and an abnormal brain MRI is unclear, it is likely less than in adults. However, it is recommended that these children be followed up closely.

Steroids may alter the visual outcome in cases of NMO but typically only accelerate visual recovery. Timely initiation of diseasemodifying therapies in these patients can limit axonal damage earlier in the disease process thereby delaying disability accumulation, improve long-term prognosis and possibly visual recovery. Research efforts to further our knowledge into the mechanisms of these conditions and to identify the genetic and environmental risk factors are ongoing and may lead to more reliable preventative, diagnostic and treatment strategies in the future.

Acknowledgements

1. Professor J Olivier and Dr C Cullen for editing the final manuscript.

2. The Department of Radiology for providing the electronic images.

References

1. Yeh EA, Graves JS, Benson LA, Benson LA, Wassmer E, Waldman A. Pediatric optic neuritis. Neurology. 2016 Aug 30;87(9 supp. 2).

Available at: https://n.neurology.org/ content/87/9_Supplement_2/S53.long

2. Borchert M, Liu GT, Pineles and Waldman AT. Pediatric optic neuritis: what is new. J Neuroophthalmol. 2017 Sep;37(1): 14-S22.

Available at: https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6149212/

3. Optic Neuritis Study Group. Visual function 15 years after optic neuritis – a final follow-up report after the Optic Neuritis Treatment Trial.

Ophthalmology. 2008 Jun;115(6):1079-82.e5.

Epub 2007 Nov 5.

Available at: https://www.aaojournal.org/ article/S0161-6420(07)00857-3/fulltext

4. Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, et al. and Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis

C as e rep or t Paediatric optic neuritis

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

optica: Recommendations of the

8. Kim SM, Kim SJ, Lee H, Kuroda H, Palace J, Fujihara K. Differential diagnosis of

Neurol. 2014;261:1-16.

neuromyelitis optica spectrum disorders. Ther

disseminated encephalomyelitis: Updates on

Published online 2013 Nov 23. doi: 10.1007/

Adv Neurol Disord. 2017;10(7):265-89. Available

an inflammatory CNS syndrome. Neurology.

s00415-013-7169-7

at: https://www.ncbi.nlm.nih.gov/pmc/

2016;87(9 suppl 2):S38-45. Available at:

Available at: https://www.ncbi.nlm.nih.gov/

articles/PMC5476332/

https://n.neurology.org/content/87/9_

9. Bichuetti DB, de Camargo AS, Falcão AB, et al.

5. Zarei S, Eggert J, Franqui-Dominguez L, Carl

The retinal nerve fiber layer of patients with neuromyelitis optica and chronic relapsing

in children: differential diagnosis from

optic neuritis is more severely damaged

multiple sclerosis on the basis of clinical

characteristics of neuromyelitis optica

than patients with multiple sclerosis. J

course. Korean J Pediatr. 2011;54(6):234-40.

patients in Puerto Rico. Surg Neurol Int.

Neuroophthalmol. 2013 Sep;33(3):220-24.

Available at: https://www.ncbi.nlm.nih.gov/

Published online 2018 Dec 3. doi: 10.4103/sni.

Available at: https://www.ncbi.nlm.nih.gov/ pubmed/23917443

10. Kowarik MC, Soltys J, Bennett JL. The Treatment of neuromyelitis optica. J

pmc/articles/PMC6293609/

Neuroophthalmol. 2014 Mar;34(1):70-82.

Neuromyelitis optica spectrum disorders in children and adolescents. Neurology.

Available at: https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC4208473/

11. Crout TM, Parks LP, Majithia V. Neuromyelitis optica (Devic’s syndrome): an appraisal. Curr

Available at: https://pdfs.

Rheumatol Rep. 2016 Aug;18(8):54.

b8cda08c6200a73c5ebe5c06a403e370024c.pdf 7. Levin MH, Bennett JL, Verkman AS. Optic

sclerosis: a review. BMC Neurol. 2018;18(27).

Published online 2018 Mar 9. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5845207/ 16. Inaloo S, Haghbin S. Multiple sclerosis in

2016;87(2):S59-S6. semanticscholar.org/d7a4/

pmc/articles/PMC3174358/ 15. Alroughani R, Boyko A. Pediatric multiple

Available at: https://www.ncbi.nlm.nih.gov/

6. Tenembaum S, Chitnis T, Nakashima I, et al.

Supplement_2/S38.long 14. Lee YJ. Acute disseminated encephalomyelitis

review of neuromyelitis optica and clinical

sni_224_18

13. Pohl D, Alper G, Van Haren K, et al. Acute

Y, Boria F, Stukova M et al. Comprehensive

2018;9:242.

Acute_Disseminated_Encephalomyelitis.12.aspx

Neuromyelitis Optica Study Group (NEMOS). J

pmc/articles/PMC3895189/

39

Available at: https://link.springer.com/article/1 0.1007%2Fs11926-016-0599-3

children. Iran J Child Neurol. 2013;7(2):1-10.

Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC3943036/ 17. Waldman A, Stull LB, Galetta SL, Balcer L,

12. Gray MP, Gorelick MH. Acute disseminated

Liu GT. Paediatric optic neuritis and risk

neuritis in neuromyelitis optica. Prog Retin

encephalomyelitis. Pediatric Emergency Care.

of multiple sclerosis: meta-analysis of

Eye Res. 2013 Sep;36:159-71.

2016;32(6):395-400. Available at:

observational studies. J AAPOS. 2011;15(5):441-

Available at: https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC3770284/

https://journals.lww.com/peconline/fulltext/2016/06000/

46. Available at: https://www.ncbi.nlm.nih.gov/ pubmed/22108356. 

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42 MESSAGE FROM THE PRESIDENT

New beginnings

46 OPHTHALMOLOGY AND PHILATELY

B Mbambisa

44 CLIVE’S CORNER Potpourri C Novis

Ophthalmology-related scientists J Surka

50 BOOK REVIEW

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42

Me s s age f rom t he Pre sident

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

NEW BEGINNINGS N

ew beginnings can be periods of anticipation, excitement and hope. We are able to look back at what we have been through and look forward to a different future. When the clock strikes midnight at the end of each calendar year, parties and fireworks often welcome in the New Year.

Over the years, this has been a familiar sight.

The recent transition from 2020 to 2021, however, was more subdued than in previous years. In some countries, this was due to lockdown restrictions and perhaps in other regions, a sense of uncertainty. Uncertainty as to whether 2021 really would be a better year, or whether we would experience much of the same. Was there really much to look forward to?

The vaccination race started at the end of 2020, as nations raced to vaccinate their populations and hopefully prevent the rising numbers of new infections and deaths. South Africa is still on the starting blocks with many questions as to when and how the full rollout of vaccines will happen. Healthcare workers have had an opportunity to be vaccinated as part of the Sisonke Phase 3b study, but we have yet to begin general population vaccination. As we close the first quarter of 2021, we are still not entirely sure what 2021 will look like. What we do know, is that we have had to learn to adjust and live with uncertainty.

Despite lockdowns, fear and loss, life has had to continue. It looks different to

the way we did many things pre-Covid.

Many of us are sick of hearing about the ‘new normal’. We want to go back to a life before masks and social distancing. Despite all the disappointments of the last few months, some of us have learnt new skills and realised that we could live without some of the things we thought we couldn’t live without.

The new term of office of the incoming OSSA EXCO also looked quite different.

The new OSSA President usually receives the Presidential chain from the previous President at a banquet held at our annual OSSA Congress. Due to Covid-19, our congresses for 2020 and 2021 unfortunately had to be cancelled. The functions of the Executive Committee have quietly continued in the background. True to the times we are living in, I took over from Prof Linda Visser at a Zoom meeting held in March 2021 and our new EXCO took office.

I would like to thank Prof Visser for the way she has ably led EXCO during some uncharted waters, particularly in the last year. OSSA and OMG are more united than they have been in a long time and my hope is that this will continue.

Dr Johann Serfontein has brought stability and direction in his many roles within OSSA and OMG and I was looking forward to working with him as National Operations Manager of OSSA. As he wraps up his time working within the ophthalmic community,

I wish him and his family all the best in their new life abroad.

The EXCO I am about to lead looks quite different from the one I joined as a young ophthalmologist. I am excited by the diversity and energy this new EXCO brings. My hope is that this diversity will allow us to explore different perspectives and meet the needs of all ophthalmologists in South Africa.

This new beginning is an opportunity to build on the gains our Society and profession have made so far and work towards an environment in which Ophthalmology and ophthalmologists may thrive. It is a time to continue to work for the vision that OSSA has to provide attainable, best quality visual health for all. 

Dr Bayanda Mbambisa MBBCh(Wits), DA(SA), FCOphth(SA), MMed(Ophth)

President: Ophthalmological Society of South Africa bmbambisa@gmail.com

44

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

Clive’s Cor ner

Potpourri 1. Face mask-associated ocular issues Some face masks interfere with the airflow around the eyes. If the top of the mask is not sealed properly, expired air is diverted upwards towards the eyes. If the mask is sealed but the seal is too high up on the cheeks, interference with lower-lid function can occur. This can all lead to ocular irritation, dryness and even keratopathy.

Patients should be instructed to take breaks from mask wear, use lubricants, and do blink exercises. Blink exercises are performed by pressing the index fingers just outside of the lateral canthi and then consciously blinking ten times without feeling muscle contraction with the finger.

It has also been suggested that face masks can predispose patients to ocular infection and postoperative or post-intravitreal injection endophthalmitis by redirecting

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airflow, together with microorganisms, towards the eyes.

Face masks can also cause artifacts on visual field testing either by directly blocking a part of the visual field or by fogging up the lens.

I also instruct patients having YAG to remove the mask or to tape it down at the top as it often causes fogging of the YAG contact lens.

her thanking me profusely for this advice.

She had been to a physiotherapist who, over a one-month period, had treated her back and neck. This is what she said on the email: ‘All the ocular symptoms were relieved gradually as the spasm was worked out of my back and neck.’

3. Reverse pupil block

tr.

2. Neck problems Several months ago, I saw a patient (who is an optometrist with a PhD) with ocular discomfort and a foreign body feeling in the one eye. It had been going on for a few months.

She had seen two other optometrists who could find no FB and nothing wrong. She was given Alrex drops plus lubricants, which helped little.

I also could find no FB and no cause for the irritation. I then asked her about her neck, and she did indeed have neck spasms.

Now it is well known that neck spasms and other neck abnormalities can cause ocular pain (especially retrobulbar pain). But I never thought that ocular discomfort and FB feeling could be caused by neck issues. However, as I had no other treatment to offer her, I advised her to see her GP about her neck problem.

A few days ago, I received an email from

Broke the reverse pupil block ? IOL in the sulcus? Watch out for reverse pupil block (RPB). The mechanism for RPB is thought to be the passing of aqueous from the ciliary body via the choroid and angle into the AC. The IOL blocks the aqueous from going back through the pupil and pressure builds up in the AC. Another mechanism is thought to be the forming of a flap valve between the IOL and the posterior iris. This one-way valve lets fluid through anteriorly but blocks its flow posteriorly.

You can suspect RPB at the slit lamp if you see a deep AC, concavity of the iris, and iris transillumination defects.

Regardless of the mechanism, a peripheral iridotomy is usually curative.

RPB can also lead to pigment dispersion glaucoma and the UGH syndrome. Making a PI with the YAG laser or surgically during phaco should help to avoid these nasty consequences. RPB is more common in myopic eyes and post-vitrectomised eyes.

Therefore, a surgical PI should definitely be cut if a sulcus IOL is to be placed in these eyes.

4. Azomid Be careful when prescribing Azomid tablets! Azomid is the generic for Diamox – but it’s also the generic for the antibiotic azithromycin.

Autumn 2021 • Vol 16 | No 2 SA Ophthalmology Journal

5. F lu can cause neuroophthalmological anomalies Covid-19 can cause conjunctivitis, retinitis and neuro-ophthalmological anomalies. But so can the common flu. The Canadian Journal of Ophthalmology March 2021 reported a case of a 38-year-old woman who presented with new onset left ptosis plus diplopia. Two days prior she had nasal congestion, cough, fever and myalgias. Examination revealed a pupil-sparing third nerve palsy. MRI showed a mild enlargement of the left oculomotor nerve. Nasopharyngeal swab was positive for influenza A. She was treated conservatively, and symptoms resolved within two weeks.

They did not mention if a Covid PCR test was done on the nasopharyngeal swab.

I had never heard of this and that he was teaching me something new.

Photo credit: Syamsul Alam / Shutterstock.com

This should never have been allowed to happen and I don’t think that azithromycin is available as Azomid in South Africa. But if you google Azomid, you will find that it could refer to either one. To add to the ambiguity, the dosages are the same: 250 mg tablets.

Diamox has not been available in SA for several years now. Therefore, if I want to bring a very high pressure down rapidly I prescribe Azomid. But I always write ‘generic of Diamox’ in brackets just in case the pharmacist googles Azomid and thinks it’s the antibiotic.

Talking about rapid lowering of IOP, Combigan is probably the most efficient drop for this. Combigan is an alpha agonist (brimonidine) plus a beta blocker (Timolol). A prostaglandin analogue is great for long-term IOP control but takes several weeks to work.

Clive’s Cor ner

45

central cornea, the fluid may give a falsely low reading. Therefore, in these patients you should measure the IOP with an Icare or Tonopen on the corneal periphery.

Another issue to be aware of is that corneal epithelial healing may be delayed or problematic in these patients. This is because surface healing may be slower due to flap denervation and possible neurotrophic keratopathy. If cataract, glaucoma or retinal surgery is performed, extra care needs to be taken not to disturb the epithelium. Some vitreoretinal surgeons have a low threshold for debriding the corneal epithelium to improve intraoperative visualisation, so beware if the patient has had previous Lasik or PRK. For further discussion and references on any of these topics, please email me at clivenovis@mweb.co.za. 

7. Lasik interface problems I retired from Lasik/PRK surgery about two years ago. My stress levels took a big turn for the better after that. But even if you do not perform keratorefractive surgery, you obviously have to be familiar with ocular problems that can occur in these patients related to that surgery.

One of the issues that all ophthalmologists need to be aware of, is Lasik interface fluid collection. Years after Lasik, fluid can collect in the interface due to trauma, inflammation, increased IOP or endothelial insufficiency.

Increased IOP may be missed in these patients because if you measure over the

Dr Clive Novis Dip Optom, MBBCh(Wits), MMed(Wits), FCS(Ophth)

clivenovis@mweb.co.za

OPTICAL Your partner in vision since 1989

6. R emoving a corneal FB using a hair The other day I saw a young man with a metallic corneal foreign body after grinding without safety goggles. He told me that he had tried to remove it himself but failed. I asked him how he tried to remove it. He said ‘with a hair’ ! He plucked a hair from his head and, holding it like dental floss, he rubbed the FB on the cornea in an effort to dislodge it.

When he saw the surprised look on my face he explained that this was a common method for removing ocular FBs among welders, grinders and boilermakers. I confessed that

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46

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

Opht halmolog y and philately

Ophthalmologyrelated scientists J

uzer Surka is an ophthalmologist and enthusiastic philatelist, who first started collecting stamps and commemorative envelopes at a young age. In subsequent years he has focused his collection and research on medically themed stamps, and more specifically, on those relating to the field of Ophthalmology, where he has collected to date in the region of around 60 original stamps.

In 2005, as a member of the National Committee for the Prevention of Blindness, he was instrumental in getting the South African Postal Service to release a stamp to raise awareness around the prevention of blindness – an elegant, plain white stamp with the word ‘Hello’ written in Braille. It was a first of its kind in the history of South African philately.

Philately is the study and collection of postage stamps. As stamp collecting gained in popularity over the years and around the world, collectors became more specialised in their areas of interests and collections; medical philately being no exception. Many countries have produced stamps on a wide range of medical topics, from health promotion and disease prevention to medical advances and notable clinicians. Ophthalmology has its fair share of stamps, and discovering them can be a fun and interesting way to learn about some of the history and heritage of the specialty.

In this series, we intend to look at various ophthalmology-related stamps, starting with famous clinicians and scientists. We hope the reader finds this to be informative and fun.

Hermann von Helmholtz (1821–1894) Helmholtz was not an ophthalmologist but he specialised in Anatomy and Physiology. His first important scientific achievement, an 1847 treatise on the conservation of energy, was written in the context of his medical studies and philosophical background.

Helmholtz was a pioneer in the scientific study of human vision and audition. Inspired by psychophysics, he was interested in the relationships between measurable physical stimuli and their correspondent human perceptions.

Hermann von Helmholtz stamps issued by (above left) East Germany (1950); (above right) West Germany (1971) and (below) West Germany (1994)

In 1851, Helmholtz inaugurated the modern era in Ophthalmology with the invention of the ophthalmoscope; the ophthalmoscope became the model for all forms of endoscopy that followed. It is often compared in importance with two earlier inventions, the telescope (17th century) and the stethoscope (early 19th century).

Helmholtz’s interests at that time were increasingly focused on the physiology of the senses. His main publication, titled Handbuch der Physiologischen Optik (Handbook of Physiological Optics or Treatise on Physiological Optics), provided empirical theories on depth perception, colour and motion perception, and became the fundamental reference work in his field during the second half of the nineteenth century. In the third and final volume, published in 1867, Helmholtz described the importance of unconscious inferences for perception. The Handbuch was first translated into English under the editorship of James PC Southall on behalf of the Optical Society of America in 1924/25.

His theory of accommodation went unchallenged until the final decade of the 20th century.

Hasan Ibn al-Haytham (965–1039) Abu Ali al-Hasan ibn al-Haytham was an Arab mathematician, astronomer and physicist of the Islamic Golden age, and is known in the West as Alhazen. Also sometimes referred to as ‘the father of modern optics’, he made significant contributions to the principles of optics and visual perception in particular.

His most influential work is titled Kitab al-Manaẓir (Book of Optics), written during the period 1011–1021, which survived in a Latin edition.

Hasan Ibn al-Haytham stamps issued by (top) Pakistan (1969); (middle) Qatar (1971); (bottom) Jordan (1971)

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References: 1. Novartis SA (Pty) Ltd. Vsiqq® approved Professional Information. 06 October 2020. 2. Dugel PU, Koh A, Ogura Y, et al; on behalf of the HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72–123. 3. Data on file. RTH258-C002 Clinical Study Report. Novartis.

2018. 4. Data on file. RTH258-C001 Clinical Study Report. Novartis. 2018.

SCHEDULING STATUS: S4 Vsiqq® 120 mg/ml solution for injection, Registration Number: 54/15.4/0489 COMPOSITION: One ml solution for injection contains 120 mg of brolucizumab. Each vial contains 27,6 mg brolucizumab in 0,23 ml solution.

Contains sugar: sucrose – A vial contains 13,3 mg sucrose.

PHARMACOLOGICAL CLASSIFICATION / ATC: ATC code: S01LA06 INDICATIONS: Vsiqq® is indicated for the treatment of neovascular (wet) age-related macular degeneration.

POSOLOGY AND METHOD OF ADMINISTRATION: Single-use vial for intravitreal use only. Each vial should only be used for the treatment of a single eye. Vsiqq® must be administered by a qualified medical practitioner. The recommended dose for Vsiqq® is 6 mg (0,05 ml) administered by intravitreal injection every 4 weeks (monthly) for the first three doses. Thereafter, Vsiqq® is administered every 12 weeks (3 months). The medical practitioner may individualise treatment intervals based on disease activity as assessed by visual acuity and/or anatomical parameters. The treatment interval could be as frequent as every 8 weeks (2 months). Special patient populations: Renal impairment: No dose adjustment is required. Hepatic impairment: No dose adjustment is required. Elderly: No dose adjustment is required. Paediatric patients: Safety and efficacy have not been established.

CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients. Active or suspected ocular or periocular infection. Active intraocular inflammation. Pregnancy and lactation.

WARNINGS AND SPECIAL PRECAUTIONS FOR USE: Endophthalmitis, retinal detachment, retinal vasculitis and/or retinal vascular occlusion: Intravitreal injections, including those with Vsiqq®, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection techniques must always be used when administering Vsiqq®. Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of Vsiqq®. Patients should be instructed to report any symptoms suggestive of the above-mentioned events without delay. Intraocular pressure increases: Transient increases in intraocular pressure have been seen within 30 minutes of injection, similar to those observed with intravitreal administration of other VEGF inhibitors. Sustained intraocular pressure increases have also been reported. Both intraocular pressure and perfusion of the optic nerve head must be monitored and managed appropriately. Vsiqq® contains sucrose which may have an effect on the glycaemic control of patients with diabetes mellitus. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take Vsiqq®.

FERTILITY, PREGNANCY AND LACTATION: Women of childbearing potential/contraception in males and females: Women of childbearing potential should use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with Vsiqq® and for at least one month after the last dose when stopping treatment with Vsiqq®.

Pregnancy: Based on the anti-VEGF mechanism of action, brolucizumab must be regarded as potentially teratogenic and embryo/foetotoxic. Therefore, brolucizumab should not be used during pregnancy.

Breastfeeding: Because of the potential for adverse drug reactions in the breastfed newborn/infant, breastfeeding is not recommended during treatment and for at least one month after the last dose when stopping treatment with Vsiqq®.

Fertility: VEGF inhibition has been shown to affect follicular development, corpus luteum function and fertility. Based on the mechanism of action of Vsiqq®, there is a potential risk for female reproduction, and to embryofoetal development.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Patients may experience temporary visual disturbances after an intravitreal injection with Vsiqq® and the associated eye examination and should therefore be advised not to drive or use machinery until visual function has recovered sufficiently.

INTERACTIONS: No formal interaction studies have been performed.

UNDESIRABLE EFFECTS: Common (1 to 10%): Visual acuity reduced, retinal haemorrhage, uveitis, iritis, vitreous detachment, retinal tear, cataract, conjunctival haemorrhage, vitreous floaters, eye pain, intraocular pressure increase, conjunctivitis, retinal pigment epithelial tear, vision blurred, corneal abrasion, punctate keratitis, hypersensitivity.

Uncommon (<1%): Endophthalmitis, blindness, retinal artery occlusion, retinal detachment, conjunctival hyperaemia, lacrimation increased, abnormal sensation in eye, detachment of retinal pigment epithelium, vitritis, anterior chamber inflammation, irirodyclitis, anterior chamber flare, corneal oedema, vitreous haemorrhage.

Frequency not known: Retinal vasculitis, retinal vascular occlusion.

NATURE AND CONTENTS OF CONTAINER: 0,230 ml sterile solution in a glass vial with a coated rubber stopper sealed with an aluminium cap with a purple plastic flip-off disk. Pack size of 1 vial and 1 blunt filter needle (18 G x 1½″, 1,2 mm x 40 mm, 5 μm).

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This BSS is for use on promotional material linked to SAHPRA-approved professional information dated 06 October 2020.

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48

Opht halmolog y and philately

Ibn al-Haytham was the first to explain that vision occurs when light reflects from an object and then passes to one’s eyes. He was also the first to demonstrate that vision occurs in the brain, rather than in the eyes.

He is called the Father of Optics for his writings on and experiments with lenses, mirrors, refraction and reflection. He correctly stated that vision results from light that is reflected in the eye by an object, not emitted by the eye itself, and then reflected, as Aristotle believed.

Hulusi Bechet (1889–1948) Hulusi Bechet was born in Istanbul during the Ottoman Empire. He graduated from Gülhane Military Medical Academy in Istanbul. At the age of 21 years, in 1910, he became a physician specialising in dermatology and syphilis. He did his postgraduate study in Berlin and Budapest during the First World War. The disease that bears his name and is characterised by mouth ulcer, genital ulcer and eye inflammation, was described by him in 1937. Ocular inflammation with retina involvement is a major cause of blindness in such patients. There is not a specific blood test for the condition and the diagnosis depends on the clinical signs. The disease is common in the Mediterranean area and Japan.

Bechet also published extensively on syphilis, and was the editor of the Turkish Periodical of Dermatology. He died in 1948 at the age of 59 years from myocardial infarction.

Hulusi Bechet stamps issued by (above) Turkey (1980) and (below) Tunisia (1986)

Blacks after the eighth grade. Advised against pursuing a graduate education because of his race, Julian went to Fisk University to teach chemistry.

His synthesis reduced the price of cortisone from hundreds of dollars Percy Lavon Julian per drop for natural cortisone to a few cents stamp issued by the USA in 1993 per gram.

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

was in his 20s, he was an important figure in the blossoming of 18th-century German literature, famous for fiction works like Faust.

But Goethe explored diverse creative paths.

He published his ideas about colour in 1810, as Theory of Colours. By this time, people were familiar with the colour theories of Sir Isaac Newton, the English scientist and mathematician. Newton had published Opticks, the results of his experiments on light and colour, in 1704. In it, he stated that colour came from light and was the result of physics. Most people accepted this idea – except Goethe.

Ragnar Granit (1900–1991) Finnish-Swedish physiologist Ragnar Arthur Granit shared the 1967 Nobel Prize for Physiology or Medicine with two American scientists, George Wald (1906–1997) and Halden K Hartline (1903–1983).

They received the award ‘for their discoveries concerning the primary physiological and chemical visual processes in the eye’. Specifically, Granit analysed the external electrical changes that occur when the eye is exposed to light.

Biochemical proof of Granit’s theory of the spectral sensitivities of the three types of cone cells (blue, green and red) was provided in the 1950s when Wald isolated the three cone pigments.

In the early 1930s, Granit was the first person to observe inhibition in the retina of the eye. His book, titled Sensory Mechanisms of Retina (1947), became a classic work in the field of retinal electrophysiology. He used electrophysiologic methods to demonstrate the presence of three kinds of colour receptor elements in the retina and to show the importance of inhibition among nerve cells in retinal function and in the nervous system in general.

Granit died on 12 March 1991.

Ragnar Granit stamps issued by (right) Grenada (1995) and (below) Sweden (1996)

Johann Wolfgang von Goethe stamps issued by (above) Italy (1999); (below left) Moldova (1999) and below right) West Germany (1949)

Unlike Newton, Goethe argued that colour needed darkness, and some colours were made with elements of darkness. Scientifically, Newton was right. But Goethe’s theories were more art and philosophy than pure science. And, if you think about it, there are differences between how colour is created via the visible spectrum (where white is the combination of all colours) versus with pigments (where the more colours you mix, the darker a colour you get). In a way, it was pigments, or colours in paint, that led to Goethe’s colour experiments, so it is not surprising his ideas differed from those of Newton. 

Percy Lavon Julian (1899–1975) Percy Lavon Julian synthesised physostigmine for the treatment of glaucoma, and cortisone for the treatment of rheumatoid arthritis.

Born in Alabama, the grandson of a former slave, Julian had limited schooling because Montgomery provided no public education for

Johann Wolfgang von Goethe (1749–1832) Goethe was a multi-talented individual. A celebrity in his native country by the time he

Prof J Surka MBBS, DOMS, MS(Ophth), FCS(Ophth)SA

Email: jsurka@gmail.com

50

Vol 16 | No 2 • Autumn 2021 SA Ophthalmology Journal

B o ok re vie w

The Boy Who Never Gave Up Author: Dr Emmanuel Taban Publisher: Jonathan Ball Year of publication: 2021 Number of pages: 245 Reviewer: Clive Novis (clivenovis@mweb.co.za)

E

very doctor has struggled through years of hardship: blood, sweat and tears (literally). Struggled all their young lives to be able to get into med school. Struggled through med school. Struggled to get into a speciality programme. Struggled through that. Some have struggled more than others. Some have prevailed against all odds. This is one such story. And it must surely be the ultimate ‘against all odds’ story.

Emmanuel Taban was born in 1977 in Juba, which is the capital of south Sudan.

He was born into a poor family who lived in one of the poorest countries on Earth.

Not only a poor country but a war-torn country. Shocking violence and barbarity was commonplace. Young Emmanuel had one driving ambition: to educate himself, rise out of poverty, and then help his family, community and country to do the same.

He was only 16 years old when he ran away after being unfairly threatened by police. He was penniless, paperless, with absolutely nothing to his name. Not even food or water.

He did not even have time to say goodbye to his beloved mother and siblings (his father had left his mother before he was born).

He walked alone for hundreds of kilometres. At any time he could have been kidnapped by rebel forces and forced to become a soldier. Most of these young

soldiers would be slaughtered in battle or emotionally or physically scarred for life. He spent months getting from Sudan to Eritrea, to Ethiopia, to Kenya. Then onto Mozambique, Zimbabwe, and eventually, South Africa.

With help from several very kind and generous people, Emmanuel managed to get his matric. He was then accepted to study medicine at Medunsa. He graduated as a medical doctor in December 2004, commenting ‘it felt like the greatest achievement imaginable’.

He did his internship at Kalafong Hospital earning a monthly salary of R6 540 which enabled him to buy his first (old second-hand) car. He did his community service in Bethal, Mpumalanga. During this time, his brother in Sudan died. He flew back to Sudan to see his mother and family for the first time in ten years! The reunion was a surreal occasion as many of his family had given him up for dead.

Dr Taban then went onto specialise in Internal Medicine at the University of Pretoria. He spent four years at Steve Biko Academic Hospital. It was at this time that he developed his three principles for success: passion, determination and consistency.

He also met his future wife there at the library. Her name was Motheo and she was a physiotherapy student.

In 2011 he started practising at the

Highveld Mediclinic in Trichardt, Mpumulanga. He did very well in private practice but yearned to continue studying.

So he went back to academia and superspecialised in Pulmonology at Wits. He officially qualified as a pulmonologist in October 2018.

Dr Taban became famous during the Covid pandemic in 2020 when he discovered that sucking out mucus plugs from the small airways could allow respiration to function again. He developed a bronchoscopy technique for doing this. At the time of writing of this, trials are ongoing to determine the safety and efficacy of his technique.

Dr Taban was disillusioned when he went back to Sudan a decade later to find that hardly any improvements had been made.

He blames the sad state of affairs on misuse of political power. He states: ‘Power should not be an end in itself. Leaders should be able to support themselves on their legitimate salaries without plundering national resources that would be better spent building schools and hospitals and laying water pipes and electricity cables.’

Dr Emmanuel Taban is a true African hero. I hope he becomes our next Minister of Health and maybe even President of South Africa! 

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References: 1. Miljanovic B, et al. Impact of Dry Eye Syndrome on Vison Related Quality of Life. Am J Ophthalmol 2007; 143(3): 409-415. 2. OPTIVE OMEGA™ UD DFU. 3. Stapleton F, et al. TFOS DEWS II Epidemiology Report. The Ocul Surf 2017; 15: 334-365. OPTIVE OMEGA™ Unit Dose Eye Drops. Contains carboxymethylcellulose sodium 5 mg/ml, glycerine 10 mg/ml, polysorbate 80 5 mg/ml, linseed oil and castor oil. For full prescribing information refer to the Instructions for use. Allergan Pharmaceuticals (Pty) Ltd, PO Box 6024, Halfway House, 1685, South Africa (Co. Reg. no. 1984/005576/07) Telephone: +27 (0) 11 545 6600, Facsimile: +27 (0) 11 315 6008. www.allergan.co.za © 2021. ®/TM Registered Trademark/ Trademark of Allergan. Date of Preparation: January 2021. SA-OPT-2150003