EuroTimes April 2021, Volume 26 Issue 4

Research Education Innovation

ESCRS’s vision is to educate and help our peers excel in our field. Together, we are driving the field of ophthalmology forward.

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Contributing Editors

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Dermot McGrath

Roibeard Ó hÉineacháin

Contributors

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Leigh Spielberg

Gearóid Tuohy

Priscilla Lynch

Soosan Jacob

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Published by the European Society of Cataract and Refractive Surgeons, Temple House, Temple Road, Blackrock, Co Dublin, Ireland. No part of this publication may be reproduced without the permission of the managing editor.

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P.28

and rule out other ocular surface diseases

RETINA

22 A multi-pronged approach for AMD will bring better outcomes for patients

23 Population studies illuminate rare conditions, outcomes and disparities in care

24 Ophthalmologica Highlights

As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between January and December 2020 was 46,748

MEDICAL EDITORS

Experts online

Webinars are useful for keeping specialists updated on hot topics

Iam delighted to be invited to write this editorial for the April issue of EuroTimes, which has a special focus on Paediatric Ophthalmology.

As we continue to work under the restraints of COVID-19 pandemic, WSPOS has put a lot of work into maintaining its online presence with regular webinars keeping paediatric and strabismus specialists updated on the latest hot topics in our profession.

The WSPOS World Wide Webinars are a forum for discussion where we can all come together to learn from the experts. We believe that expertise resides all over the world so make sure that you visit https://www.wspos.org/world-wide-webinar and join us in this exciting initiative.

EuroTimes is also an excellent medium for keeping us up to date and in this issue you can read some excellent insights into paediatric myopia from Dr Soosan Jacob.

I would also draw your attention to a very interesting study from Gilles C. Martin MD, MSc, et al. reviewing data collected by French Poison Control Centres during April through August in 2019 and 2020 which identified a sevenfold increase in ABHS-related ocular exposures in children in 2020, compared to 2019

Another very important development is the establishment European Registry of Childhood Cataract (EuReCCa), which aims to improve surgical outcomes in infants and children with cataract. The data collected in EuReCCa will be analysed to identify risk factors for main surgical and postoperative complications and reasons for reoperations. By comparing outcomes associated with different approaches, EuReCCa will help to define standard surgical procedures.

Telemedicine has become an integral part of healthcare delivery. While there are definite drawbacks in doing telemedicine for ophthalmology, we need to develop applications that will be robust for both visual acuity testing and fundus photography, but the advent of the smartphone means that we need to harness this technology to improve eye healthcare delivery. That said, disparities in healthcare delivery must be addressed and not accentuated by digital medicine.

INTERNATIONAL EDITORIAL BOARD

Noel Alpins (Australia), Bekir Aslan (Turkey), Roberto Bellucci (Italy), Hiroko Bissen-Miyajima (Japan), John Chang (China), Béatrice Cochener-Lamard (France), Oliver Findl (Austria), Nino Hirnschall (Austria), Soosan Jacob (India), Vikentia Katsanevaki (Greece), Daniel Kook (Germany), Boris Malyugin (Russia), Marguerite McDonald (USA), Cyres Mehta (India), Sorcha Ní Dhubhghaill (Ireland)

Rudy Nuijts (The Netherlands), Leigh Spielberg (The Netherlands), Sathish Srinivasan (UK), Robert Stegmann (South Africa), Ulf Stenevi (Sweden), Marie-José Tassignon (Belgium), Manfred Tetz (Germany), Carlo Enrico Traverso (Italy)

Finally, it is good to note that vaccination for COVID-19 is continuing world-wide. Together the world is moving forward. We have seen places where there is a marked reduction in people falling sick and dying. It is very important that the vaccination programme is executed in a fair and equitable way and that vaccines are made freely available to everyone and not just those living in the more prosperous nations.

We are all in this together, so let us hope that by the end of 2021 we will be in a better and safer place.

Dr Ken K Nischal, is Chief of the Division of Paediatric Ophthalmology, Strabismus, and Adult Motility, and Medical Director for Digital Health, at the UPMC Children’s Hospital of Pittsburgh, United States, and founding member of WSPOS

By comparing outcomes associated with different approaches, EuReCCa will help to define standard surgical procedures

Emanuel Rosen Chief Medical Editor

José Güell

Ken K Nischal

Thomas Kohnen

Paul Rosen

World Society of Paediatric Ophthalmology and Strabismus

WSPOS World Wide Webinars

Join us for our upcoming episodes in season 2 of the WSPOS World Wide Webinars, we still have lots of great topics and ideas to discuss over the next few months. We believe that expertise resides ALL over the world and as such, we endeavour to provide a world-wide forum for discussion of all the latest issues and trends in paediatric ophthalmology and strabismus. Your voice matters to us, so please tune in, join in the discussion with your comments and learn from the experts!

Saturday, 3rd April - Allergic Conjunctivitis

Saturday, 17th April - Retinoblastoma

Saturday, 24th April - WSPOS Global Grand Rounds

You can watch all our previous episodes from season 1 & 2 on our YouTube channel https://www.youtube.com/c/WSPOSOfficial/videos

Preventing paediatric myopia

With an ever-growing worldwide burden, prevention and correction of myopia are essential. Soosan Jacob, MS, FRCS, DNB reports

Aworldwide projected 50% incidence of myopia by 2025 makes this epidemic a serious public health burden. What causes myopisation? An interplay of various genetic and environmental factors that are still not fully understood.

Normally, the emmetropisation process of scleral elongation tries to match the optical axis length to corneal and lenticular power. A feedback mechanism for emmetropisation proposes the afferent sensory arm to be located in the midperipheral, retro-equatorial ocular region. Peripheral defocus stimulates axial elongation and this theory is supported by the axial myopia that is seen after laser photocoagulation of the peripheral retina but not after anti-VEGF therapy in infants with retinopathy of prematurity.

PREVENTION OF MYOPIA

Spectacles and contact lenses: Peripheral light focusing behind the retina (peripheral hyperopic defocus) leads to axial length elongation while an anterior focus (peripheral myopic defocus) slows myopic progression. Conventional myopic single-vision lenses and standard contact lenses cause peripheral hyperopic defocus. Spectacles with progressive addition lenses (PAL), peripheral asphericised PAL, defocus incorporated multiple segments and multifocal/ multifocal-like contact lenses are therefore being tried in children between 8 and 12 years of age to slow myopisation by providing peripheral myopic defocus and decreasing hyperopic blur.

Though benefit has been shown in decreasing axial length elongation and myopia progression, the optimum amount of add power required, hours of use per day, number of years of treatment required and the permanency of effect once lens wear is stopped are all questions still needing answers.

Orthokeratology or ortho-k uses rigid contact lenses worn overnight to flatten the cornea while sleeping, thus decreasing the need for corrective lenses during daytime.

The oblate change in corneal shape may also slow myopia progression by keeping the macular image in focus while providing a myopic peripheral defocus.

Topical Atropine: The mechanism of action though yet unknown is not related to accommodation. Low-dose Atropine at 0.01% has been used in children from 5 to 17 years of age to decrease myopia progression. It is better tolerated than higher doses while not differing significantly in efficacy and having less myopic rebound on cessation. Poor responders may be given a stepwise increase in dose. The effect is seen to have geographical variation and ideal concentration and dosing are still being evaluated with more region specific studies required. Rebound myopia on cessation may be decreased by using lower doses, tapering dose once stable and continuing

treatment till more than 12 years age or into late teens.

Other anti-muscarinics as well as dopamine, a major neurotransmitter in the retina are also being studied. Dopamine and/or other unidentified molecules may act as messengers that transfer information from the afferent to the efferent arm of the feedback mechanism for emmetropisation.

Vision training: Accommodative abnormalities seen in myopic patients can cause retinal image degradation and increasing myopia, e.g., an increased lag of accommodation may be myopigenic.

Patients on PAL adapt with time and redevelop accommodation lag. In addition, PAL may cause degradation of extrafoveal image due to inherent design and may also cause myopia at near.

Postoperative topography (A), difference map (B), SMILE corneal cuts (C) and two-year postoperative slit-lamp image (D) showing well-centred correction in a child whose amblyopia reversed after SMILE for myopic anisometropic

Vision training for accommodation may therefore be important.

Custom soft contact lenses are being studied to alter spherical aberration, improve accommodation and reduce accommodation lag. The CAMS study tried to improve accommodative accuracy and dynamics using vision training and alteration of spherical aberration. Lifestyle modifications: Environmental factors including outdoor time, prolonged and intense periods of close work, urbanisation etc have been associated with myopia progression and a multi-pronged approach to prevention gives additive effects.

SURGICAL CORRECTION FOR MYOPIA

Children with unilateral or bilateral high myopia with failed conventional therapy with glasses and contact lenses may need surgery. The question, however, still remains as to the threshold level for refractive surgery. Dr Paysee, at the 3rd World Congress of Paediatric Ophthalmology and Strabismus, Barcelona, suggested ≥4.0D for severe anisometropia and ≥-6.0D for severe isoametropia, though in practice, patients who have failed with glasses and contact lenses tend to have much higher values. Surgery is also beneficial in children unable to wear glasses or contact lenses due to altered facial or ocular anatomy, neurobehavioural or developmental problems, intellectual disabilities etc.

Advantages of surgical correction are many and include improved refraction, vision and stereopsis as also more effective amblyopia therapy less dependent on patient and parental compliance, full-time visual correction, social and psychological improvement and a more alert and involved child.

Challenges are also many and include those of a growing eye, changing refractive status, difficult pre- and postoperative assessment, difficult surgery and difficult recognition and management of postoperative complications. Surgery is generally preferred after 2 years of age because of the large changes with growth in the first two years.

The major indication for surgery is anisometropic amblyopia. As in all paediatric refractive surgeries, the target refractive correction opted for needs to be decided

at the time of surgery. The aim should be to bring the refraction to a point where the child can function visually and amblyopia can be prevented. Perfection may not always be necessary as in adults. The need for follow-up amblyopia therapy cannot be under-stressed. Laser vision correction (LVC): Surface ablation is often preferred in children, because of absent risk for flap-related complications that may occur post-LASIK. Postoperative steroids are important to avoid haze and regression. LASIK may be performed but flap-related complications are an ever-present threat in children. A more recent option is small-incision lenticule extraction (SMILE ®), which avoids many of the risks of LASIK and surface ablation while giving good predictability, efficacy and stability. SMILE is not affected by anaesthetic gases unlike excimer laser. Irreversibility, the need for patient cooperation for centration, inability to fixate under anaesthesia, risk for decentred ablation and induction of aberrations are challenges associated with all LVC techniques. The need for an anaesthesia machine is also a challenge as most refractive suites don’t have the facility.

INTRAOCULAR SURGERY

An untouched cornea, less aberration induction and better retinal image magnification in extreme myopias nearing -20D are advantages of phakic IOLs (PIOLs) and refractive lens exchange (RLE). However, the risk of complications such as retinal tears and detachment secondary to intraocular surgery in such high myopic eyes needs to be kept in mind and thorough pre- and postoperative retinal examinations are a must. PIOLs: Lesueur et al showed good safety, refractive and functional outcomes and improvement in quality of life with posterior chamber PIOLs (Visian ICL, Staar Surgical) for paediatric high myopia at the 2017 WSPOS Paediatric Subspecialty Day meeting. Advantages include small incision and reversibility. Cataractogenesis is reported to be less frequent with the V4c model. Silicone PIOLs have been reported to be associated with vitreous luxation of the IOL either due to intra-operative manipulation or cheese-wiring of zonular fibres.

The ideal age for surgery with PIOLs is controversial, since optimum sizing of

Comment from Dr David Granet

the ICL and thereby the vault changes with growth of the eye. Though anterior chamber PIOLs may also be used, long term endothelial concerns have traditionally limited their use in the paediatric population.

RLE: This may be indicated for children with refractive errors exceeding -20D and with insufficient anterior chamber depth. Standard cataract techniques recommended as per the age of the child are used. The loss of accommodation and increased inflammatory response together with the increased risk for glaucoma and posterior segment complications are the biggest disadvantages of RLE. Multifocal and EDOF IOLs are being tried in children but conclusive results are yet awaited. Bioptics: Sequential refractive surgeries may be employed for very high refractive errors. For example, PIOL may be followed up with LASIK for any residual refractive error needing correction or for any new refractive error developing with growth of the eye. Treatment may be done after 18 years of age once refraction is stabilised.

Dr Soosan Jacob is Director and Chief of Dr Agarwal’s Refractive and Cornea Foundation at Dr Agarwal’s Eye Hospital, Chennai, India and can be reached at dr_soosanj@hotmail.com

Director, Ratner Children’s Eye Center of the Shiley Eye Institute, USA

“While there’s some evidence of bifocal or progressive lenses being helpful in slowing myopia, the new spectacle lenses and contacts that deliver peripheral defocus are more impactful in the right patients. Even older style bifocal contact lenses can be advantageous.

“In my practice it is the COMBINATION of approaches that is most powerful. Low-dose atropine, bifocal or peripheral defocus contacts and getting outside after school work is done, when done together, are my most impactful approaches.”

The ideal age for surgery with PIOLs is controversial, since optimum sizing of the ICL and thereby the vault changes with growth of the eye

Soosan Jacob, MS, FRCS, DNB

BEST OPTIONS for myopia

Expanding the range of treatments for myopia in children. Dermot McGrath reports

Although there is no silver bullet solution for progressive myopia in children, there are some reasonably effective myopia control methods currently available, including atropine eye drops, myopia control glasses, myopia control contact lenses and orthokeratology (ortho-k) contact lenses, experts said at the 38th Congress of the ESCRS Virtual.

“Myopic children need different options and it is therefore important for us to keep abreast of current technology and research to offer the best options to our patients,” said Pauline Cho PhD, of the School of Optometry at The Hong Kong Polytechnic University.

Focusing her presentation on optical methods of myopic control including spectacles, lenses and ortho-k, Dr Cho noted that combination therapy of ortho-k with pharmacological treatments holds promise as an effective means of delaying axial elongation in children. The ultimate goal is to prevent progression to high myopia and its associated range of sight-threatening complications, such as maculopathy and retinal detachment.

Dr Cho presented the preliminary oneyear results from an ongoing randomised controlled study of children aged from 6-to-11 years old with -1.00 to -4.00D myopia and astigmatism less than 2.50D. Patients were randomly assigned to either combined therapy of atropine 0.01% and ortho-k (AOK) or ortho-k alone (OK). Results at one year showed that the combination of single-dose 0.01% atropine with ortho-k lens wear was well tolerated and has an additive effect in slowing axial elongation compared with monotherapy.

“The study is ongoing but the results are certainly very promising after one year. When we compared the AOK group with an earlier control group from the Retardation of Myopia in Orthokeratology (ROMIO) study we have a very impressive 81% myopia control effect with the combination therapy,” she said.

In terms of soft contact lenses, the defocus incorporated soft contact (DISC) lens has been shown to slow myopia progression

in a two-year randomised study (Lam CSY et al. Br J Ophthalmol, 2014; 98:40-45). A total of 128 patients completed the study: 65 with DISC and 63 in the control group of single-vision spectacles (SVS). The axial elongation was 0.36 for the SVS group and 0.25 for the DISC group giving a myopia control effect of 31%.

“The authors also reported that subjects who wore the lenses for over eight hours daily obtained a 60% myopia control effect, but this was for only a small number of patients, so we can’t draw any firm conclusions,” said Dr Cho.

Similar results were also obtained by MiSight, a dual-focus soft contact lens in a two-year randomised trial (Ruiz-Pomeda et al. Graefes Arch Clin Exp Ophthalmol. 2018 May; 256(5):1011-1021.). Seventy-four patients completed the follow-up, with axial elongation of 0.28 for MiSight versus 0.45 for the control group, or a 36% myopic control effect. Another multi-centre study involving MiSight (Chamberlain et al, Optometry and Vision Science: August 2019 – Vol. 96, Issue 8: pp 556-567) reported a 52% myopia control effect as compared to a spectacle control group, with no serious adverse events reported.

For spectacles, the defocus incorporated multiple segments spectacle lenses (DIMS) performed well in a two-year study (Lam et al. British Journal of Ophthalmology 2020;104:363-368) with a 60% myopia control effect, said Dr Cho.

Orthokeratology also has a positive track record for effective myopia control in the scientific literature, said Dr Cho.

“There are a lot of robust studies and the overall effects

vary from 32% to 63% depending on the methodologies and the subjects recruited,” she said.

PHARMACOLOGICAL AGENTS

Looking at the range of pharmacological treatments for myopia control currently available, Audrey Chia FRANZO, PhD, Head of the Paediatric Ophthalmology Service at Singapore National Eye Centre, said that muscarinic receptor antagonists, and particularly atropine, have been shown to be the most effective.

“Atropine is definitely the most well established with the largest number of published studies. However, it is hoped that with better understanding of the myopisation process that new pharmacological agents might prove useful in the future,” she said.

Pharmacological agents are thought to work by disrupting the signal cascade for axial elongation in the eye, with muscarinic antagonists, beta adrenergic antagonists and adenosine antagonists all having been employed to try to inhibit myopia progression, she said

The use of atropine is backed by several randomised controlled studies showing a dose-related effect, with higher doses seeming to have a stronger effect on axial elongation than lower doses, said Dr Chia. Although atropine treatment has been widely adopted in Asia and seems to be safe and effective, there are still remaining areas of uncertainty regarding optimal dosage and targeting population.

Other muscarinic receptor antagonists include tropicamide and cyclopentolate for which there is limited evidence, and 2% pirenzepine, which showed some efficacy in a 2005 study but never really gained traction as an alternative to atropine, she said.

Results of beta adrenergic receptor antagonists such as Timolol and Labetalol have been disappointing overall and have not been pursued.

In the category of adenosine receptor antagonists, a trial of oral 7-Methylxanthine (7-MX) in 2008 found some effect on axial elongation after two years, but further studies are needed to fully assess its safety and effectiveness.

Atropine is definitely the most well established with the largest number of published studies

Pauline Cho PhD

Alcohol-based hand sanitiser eye injuries

Proliferation of hygiene stations in public places putting children at risk. Cheryl Guttman Krader reports

Hygiene stations dispensing alcohol-based hand sanitisers (ABHS) have become ubiquitous in public places because of the COVID-19 pandemic. Recommendations from the World Health Organization note the need to adapt the equipment to encourage use by children while the United States Centers for Disease Control and Prevention warns about keeping ABHS out of the reach of children because of toxicity with ingestion.

Information in articles published January 21, 2021 online in JAMA Ophthalmology underscore that risk of potentially serious eye injury is another reason to keep ABHS away from young children.

In a retrospective study, Gilles C. Martin, MD, MSc, et al. reviewed data collected by French Poison Control Centres during April through August in 2019 and 2020. They identified a sevenfold increase in ABHS-related ocular exposures in children in 2020 compared to 2019. In addition, they found a greater than 300% increase in the number of such cases occurring in public places between May and August 2020. In 2020, the involved children had a mean age of 4.5 years with 63 cases occurring from exposure in public places. Some 13% of children needed surgery.

Data from a tertiary ophthalmologic referral centre showed one child was admitted to the hospital for an ABHS injury in 2019 versus 16 children in 2020. In the latter cohort, eight children had a corneal and/or conjunctival ulcer and two

required amniotic membrane transplantation.

In a separate article, authors from the Grewal Eye Institute in Chandigarh, India reported two cases of ABHS eye injuries in children aged 4 and 5 years, respectively. One child presented with a large central corneal epithelial defect and the other had conjunctival congestion and superficial punctate keratopathy.

REMEDIATING MEASURES

The height of the ABHS dispenser of stations found in public places is often at face level in children, and the risk of serious eye injury is compounded by lack of access to water for flushing the eye. Suggested steps for preventing ABHS paediatric eye injuries include public health messages promoting soap and water as the preferred hand hygiene strategy, teaching children about using ABHS dispensers, providing separate equipment for children, and posting cautionary signs about eye exposure and what to do if it occurs.

In an invited commentary, Kathryn Colby, MD, PhD, Elisabeth J Cohen Professor and Chair of Ophthalmology, NYU Grossman School of Medicine and NYU Langone Health, New York, NY, congratulated the authors for alerting the ophthalmology community to this problem.

She told EuroTimes: “Ophthalmologists can help raise public awareness of this potential problem by reporting eye injuries that they see and by educating paediatricians and family practice providers in their community about the danger.”

2 ESCRS Winter Meeting VIRTUAL 2021 t h 5

In conjunction with the Cataract and Refractive Surgery Section, Polish Ophthalmological Society

Friday

19 – Sunday 21 February

The virtual 25th ESCRS Winter Meeting 2021 held over three days, from 19-21 February, attracted more than 1,800 delegates. A total of 420 presentations, 335 presenters and four main symposia all contributed to a highly successful meeting.

A first-rate scientific programme also included free paper sessions, instructional courses, video sessions, the Young Ophthalmologists Programme and satellite meetings covering a wide range of key topics.

The society also introduced greater opportunities for exchange and interaction at the meeting.

During live sessions delegates were able to post questions to the chairpersons, and a 30-minute live question-andanswer session took place after each main symposium. There was also the opportunity to join a breakout room after these sessions, to take part in further faceto-face discussion.

The “Meet The Experts” sessions also allowed delegates to take part in face-to-face discussions with top experts about a range of hot topics, and a new video chat function

to network with friends and colleagues was also added to the meeting interface.

POSTER AWARDS

The ability to think outside the box and apply new approaches to improving diagnostic and therapeutic applications of existing technologies were rewarded by the judging panel in the Best Poster Awards at the ESCRS Winter Meeting Virtual 2021.

Rifat Rasier MD, PhD, from Turkey won first prize in the Cataract category for his poster entitled “Ablation of monofocal intraocular lenses with femtosecond laser”, while the best Refractive award went to Divya Trivedi MD from India for her poster “Novel collagen imaging using ultra-high resolution polarisation sensitive optical coherence tomography (OCT) in healthy, suspect and keratoconus corneas”.

CLOSING REMARKS

In his closing remarks, Prof. Dr. Rudy MMA Nuijts, President of the ESCRS, thanked the chairpersons, moderators

and everyone who had contributed to the programme. He also thanked ESCRS’s industry partners for their continued support.

He also expressed his gratitude to the Cataract and Refractive Surgery Section of the Polish Ophthalmological Society for their invaluable assistance in organising the meeting.

Prof Nuijts reminded delegates that they would have exclusive access to the virtual meeting platform until 31 March 2021. After that, ESCRS members will be able to access the presentations on ESCRS On Demand.

“The ESCRS Annual Congress is planned to take place from the 27th to 30th August at the RAI, Amsterdam, and we very much hope that as many of you as possible will be able to join us there,” said Prof Nuijts. “I hope you and your families stay safe and well, and hopefully we will see you in Amsterdam.”

For full coverage of the meeting visit www.eurotimes.org

More than 1,800 delegates, 420 presentations, 335 presenters and four main symposia all contributed to a highly successful meeting. Colin Kerr reports

Rudy MMA Nuijts at the XXXV Congress of the ESCRS in Lisbon

The ESCRS Annual Congress is planned to take place from the 27th to 30th August at the RAI, Amsterdam, and we very much hope that as many of you as possible will be able to join us there

Prof. Dr. Rudy MMA Nuijts

Treating +4.0 hyperopia?

For younger patients, LASIK, SMILE are top options. Howard Larkin reports

Consider the case of a 35-yearold female paediatrician with +4.00D hyperopia. In four years, her uncorrected visual acuity declined from 2/20 to 20/100 in both eyes, while her spectacle prescription increased from +2.25D to +3.50D. Looking for a solution that would increase her visual independence, she consulted Fernando Faria-Correia MD, PhD, of CUF Porto, Porto, Portugal.

After careful corneal tomography and biomechanical analysis, and counselling and treatment for slight dry eye, Dr Faria-Correia recommended topography-guided femtoLASIK, he told AAO 2020 Virtual. One month after surgery her uncorrected VA was 20/25 in the right eye and 20/20 in the left. The patient was quite satisfied despite some blurry vision episodes that Dr Faria-Correia said were consistent with corneal epithelial remodelling typical of hyperopic LASIK.

Understanding the difference between facultative hyperopia, which can be overcome by accommodation, and absolute hyperopia, which cannot; as well as manifest hyperopia measured with noncycloplegic refraction and latent hyperopia measured with cycloplegic refraction, were keys to determining the treatment, Dr Faria-Correia said. Ocular surface optimisation and preoperative corneal evaluation helped improve the outcome, while epithelial mapping using segmented topography helped him understand the visual outcome, he added.

But what would other ophthalmologists do? Two other surgeons gave their views on the best treatment for laser corneal correction of a young +4.00D hyperope.

LASIK

Making the case for hyperopic LASIK was Gustavo Tamayo MD, director of Bogota Laser Ocular Surgery Centre,

Bogota, Colombia. He considered three surgical options.

Refractive lens exchange with IOLs is not an option “unless we change the definition of young”, Dr Tamayo said. Phakic lenses are subject to exacting requirements, most significantly a 3.0mm anterior chamber depth that is unusual in small hyperopic eyes, and are subject to severe complications, he said. With corneal additive surgeries having died out, hyperopic LASIK is the most attractive surgical option, he reasoned.

Dr Tamayo listed several critical factors for hyperopic LASIK. Maximum post-op corneal curvature is 50D, so the amount of hyperopia that can be corrected may be limited by pre-op corneal curvature, with one dioptre of hyperopia corrected increasing corneal curvature by the same amount. Cycloplegic refraction and postop lubrication are also essential.

Outcomes are excellent, Dr Tamayo said. In a study of 98 hyperopic eyes treated with LASIK or LASEK in his clinic, 93% had 20/20 uncorrected vision and 98% 20/40 or better and only 2% with worse corrected vision 24 months after surgery – results that echo FDA trial data from 2004 and many studies since. While patients must be made aware that the correction will regress over time, enhancements are easy and complications few and mild compare with phakic IOLs.

“Hyperopic LASIK is the best option for young hyperopes, particularly up to +6.00D,” Dr Tamayo concluded.

SMILE

Making the case for SMILE was Rupal Shah MD, group medical director at the Centre for Sight-NVLC, Vadodara, India. While still a short way from commercial availability and not approved in the USA, SMILE for hyperopia has several advantages over LASIK, she said. These include no flap

or related complications, a smaller incision that affects tear profile less after surgery, no tissue ablation resulting in less scatter and more predictable outcome, and lower overall energy input leading to less inflammation and greater stability after treatment.

An early study Dr Shah conducted on 100 hyperopic eyes in 2010 found results were less stable and predictable than hyperopic LASIK. Alterations to the procedure heave since improved it, she said. These include altering the lenticule geometry, increasing the transition zone to 2.0mm and optimising laser settings. This larger transition zone creates a tapering edge to the lenticule rather than a steep drop off due to the larger amount of tissue removed at the perimeter to flatten the cornea.

Current multi-centre studies are being analysed, though the results are promising, approaching or even exceeding hyperopic LASIK in some cases, Dr Rupal said.

“For younger hyperopes, laser refractive surgery is more appropriate, and SMILE® would be my natural choice.”

CAVEATS

Theo Seiler MD, PhD, founder of Institute for Refractive and Ophthalmic Surgery (IROC) in Zurich, Switzerland, congratulated Dr Tamayo on his excellent LASIK outcomes.

“Our hyperopic results are poor; 30% of complaints I see in my clinic are because of hyperopic LASIK.”

Dr Seiler said the main problem is the optical zone size, which ranges from 6.5mm to 7.0mm with a 1.0mm transition zone. A lack of understanding where to centre the LASIK ablation or SMILE further complicates the procedure, he added. This reduces overall patient satisfaction with corneal hyperopic corrections to about 70%.

However, Dr Shah reported good results with hyperopic SMILE up to +4.0D. Dr Seiler suggested that this may be due to newer procedure guidelines Dr Shah is using, which allow a total lenticule diameter in the 8.5-to-9.0mm range. But the optical zone declines from year to year due to epithelial remodelling, he noted, making long-term results problematic. Dr Shah stated she has not seen such regression in her patients with a larger transition zone.

For younger hyperopes, laser refractive surgery is more appropriate, and SMILE would be my natural choice

Rupal Shah MD

Hunting high and low for accuracy in toric IOL implantations. Dermot McGrath reports

Outcomes after toric IOL implantation are influenced by numerous factors including preoperative patient selection, biometry, intraoperative alignment, surgical technique and postoperative care, according to Bartlomiej Kaluzny MD, PhD at the 25th Virtual ESCRS Winter Meeting.

Rooting out surgical errors 2020 2021

Discussing the options of toric IOL implantation for patients at the extremes of low and high astigmatism, Dr Kaluzny, who is Professor of Ophthalmology and Head of Division of Ophthalmology and Optometry, Department of Ophthalmology, Collegium Medicum of Nicolaus Copernicus University, Bydgoszcz, Poland, said that while glasses or contact lenses are available to treat as little as 0.25D of astigmatism, no such option exists for toric lenses.

“We know that greater than 0.50D of astigmatism can degrade visual performance, including reading speed and contrast sensitivity. We also know that small amounts of residual or untreated astigmatism are a leading cause of patients’ dissatisfaction with multifocal IOLs and monovision. And yet, when we check what is available on the market, the lowest available cylinder power at the IOL plane is 1D, which corresponds to 0.67D at the corneal plane,” he said.

Several sources of error lie behind the difficulty in obtaining predictable and accurate outcomes with toric IOLs, especially low power, noted Dr Kaluzny.

“Keratometry readings from different devices are not always the same and integrated K is significantly more accurate than a value from a single device. Both the anterior and posterior corneal surfaces contribute to refractive power but are not always taken into account in preoperative measurements. Modern corneal tomographers have improved greatly in recent years but individual measurements may still be subject to significant variation,” he said.

Although the use of intraoperative aberrometry has helped to improve accuracy, the technology is still not widely available, said Dr Kaluzny.

Surgically induced astigmatism (SIA) remains the main source of error, he said.

“Even with small incisions and fixed meridians, the SIA is highly variable, especially in more curved corneas. Studies have shown not only a high standard deviation in SIA by different surgeons but also in the results produced by the same surgeon. So, we cannot perform reliable and reproducible SIA even if we use microincision cataract surgery,” he said.

Ensuring correct toric IOL alignment has improved in recent years with the introduction of digital markers, said Dr Kaluzny.

Nevertheless, it is important to remember that the eye evolves over time and that includes corneal astigmatism values.

“Even if we are on target immediately after the surgery and for weeks and months postoperatively, corneal astigmatism continues to change towards against-the-rule astigmatism over at least 20 years after cataract surgery. This change was found to be similar in eyes that did not have surgery, so our results may deteriorate in the future,” he said.

To sum up, “in my opinion industry people think that we are not ready for lower cylinder power IOL”.

Applications are open for the Peter Barry Fellowship 2021. This Fellowship commemorates the immense contribution made by the late Peter Barry to ophthalmology and to the ESCRS.

The Fellowship of €60,000 is to allow a trainee to work abroad at a centre of excellence for clinical experience or research in the field of cataract and refractive surgery, anywhere in the world, for 1 year.

Applicants must be a European trainee ophthalmologist, 40 years of age or under on the closing date for applications and have been an ESCRS trainee member for 3 years by the time of starting the Fellowship.

The Fellowship will be awarded at the ESCRS Annual Congress in 2021, to start in 2022.

To apply, please submit the following:

 A detailed up-to-date CV

 A letter of intent of 1-2 pages, outlining which centre you wish to attend and why

 A letter of recommendation from your current Head of Department

 A letter from your potential host institution, indicating that they will accept you if successful

Closing date for applications is 1 May 2021

Applications and queries should be sent to programme@escrs.org

Intracameral cefuroxime: the debate continues

In this article, originally published in the Journal of Cataract & Refractive Surgery as a guest editorial, David F Chang MD, reflects on the impact of the landmark ESCRS intracameral cefuroxime trial

Published 15 years ago in March 2006, the landmark ESCRS intracameral (IC) cefuroxime trial remains the single most important study of antibiotic prophylaxis for ophthalmic surgery. Encouraged by Swedish national registry studies suggesting the efficacy of IC cefuroxime prophylaxis, ESCRS undertook the bold challenge of conducting a multi-centre, prospective randomised clinical trial. The study objective was to determine whether perioperative antibiotics prevent endophthalmitis and, if so, whether they should be administered topically or through IC injection. The audacious goal was to enrol up to 35,000 cataract surgical patients to demonstrate statistical efficacy of either topical fluoroquinolone or IC cefuroxime. Patients were randomised to one of four treatment groups. The four groups received placebo drops only, topical levofloxacin, IC injection of 1mg cefuroxime and a combination of topical levofloxacin plus IC cefuroxime.

From September 2003 to January 2006, approximately 16,000 patients had been enrolled at 24 sites in nine European countries. When an interim analysis showed clear superiority of one treatment group, the data-monitoring committee recommended unmasking of the study. This revealed such a clear benefit to IC cefuroxime that study recruitment was ended, and the decision was made to publish a preliminary report as quickly as possible. The full study analysis was published one year later and demonstrated a nearly five-fold reduction in the

endophthalmitis rate with IC cefuroxime. Publication and announcement of the preliminary findings was a significant and thought-provoking event in ophthalmology. In 2006, topical antibiotic prophylaxis was the community standard in North America and Europe. However, a small percentage of surgeons were combining intraocular antibiotic administration, either by direct IC injection or adding the antibiotic to the irrigating bottle. For these surgeons, the ESCRS study offered validation of their approach. Others were emboldened to adopt IC antibiotic prophylaxis based on the study results. However, most believed that study weaknesses and the lack of a commercially approved intraocular antibiotic argued against adopting this practice routinely.

To better understand the immediate impact and implications of the ESCRS study, the ASCRS Cataract Clinical Committee surveyed the global membership of ASCRS in January 2007. This was nine months after publication of the preliminary findings but six months prior to publication of the full study analysis. Of the more than 1,300 respondents, 30% were using intraocular antibiotic prophylaxis. Half of them directly injected the antibiotic, and half placed the antibiotic in the irrigation bottle. Vancomycin was preferred by 60% of these surgeons and a cephalosporin by 23%. Sixteen percent of surgeons were already injecting IC antibiotic prior to the ESCRS study, and 7% started or planned to do so because of the study. The 77%

that did not plan on adopting routine IC antibiotic prophylaxis was concerned about the risk for mixing solutions (45%) and felt that more study was needed (89%). However, if a reasonably priced IC antibiotic were to be commercially approved, then 82% were likely to use it. These survey results seemed to indicate that absent an approved intraocular product, most surgeons were not convinced of enough benefit to offset the risks for mixing or compounding antibiotic solutions.

In 2012, based largely on the ESCRS study, the European Medicines Agency (EMA) approved Aprokam (Laboratoires Théa), the first premixed IC cefuroxime formulation for endophthalmitis prophylaxis. Aprokam soon became available in many European countries and was effectively endorsed by ESCRS in their 2013 Guidelines for Prevention and Treatment of Endophthalmitis. In a small ESCRS survey, 74% of 193 respondents reported regularly using IC antibiotics, and its adoption generally reflected whether a commercial formulation was available to them or not. Several large retrospective studies subsequently reported reduced endophthalmitis rates after adoption of IC cefuroxime, adding further support to the 2006 ESCRS study conclusions. This included the first large retrospective study of IC antibiotic prophylaxis in the United States.

When the ASCRS member survey was repeated in 2014, a substantial shift in opinion and practice pattern was revealed according to the 1,147 respondents. The percentage of surgeons using IC antibiotic prophylaxis increased from 30% to 50%, and most were now using direct IC injection compared with placing antibiotic in the irrigating solution (84% vs 16% in 2014; 52% vs 48% in 2007). Antibiotic preference was evenly divided between moxifloxacin (33%), cefuroxime

David F Chang MD

Publication and announcement of the preliminary findings was a significant and thought-provoking event in ophthalmology

David F Chang MD

(26%) and vancomycin (37%); however, vancomycin (52%) was still the leading preference in the United States. Most (75%) believed that it was important to have an approved commercial formulation for IC injection (up from 54% in 2007), and this would increase adoption of IC antibiotic to nearly 84%. Risks for non-commercially prepared solutions were a concern for half of those not using IC antibiotic.

The question of which IC antibiotic is preferable for endophthalmitis prophylaxis was not addressed by the ESCRS study. Large retrospective studies from the Aravind Eye Care System have provided strong support for the safety and efficacy of IC moxifloxacin prophylaxis using a preparation that is commercially available in India. Meanwhile, the emergence of haemorrhagic occlusive retinal vasculitis associated with vancomycin has caused a precipitous decline in its use worldwide.

In the ESCRS trial, the 0.25% endophthalmitis rate in patients receiving topical levofloxacin alone was unusually high compared with historical benchmarks. This and concerns that the trial was terminated prematurely were the most significant criticisms of the study. Largely for these reasons, the ESCRS study does not qualify as a valid efficacy study for the US Food and Drug

Administration (FDA). A manufacturer would, therefore, need to conduct a new prospective randomised trial to obtain FDA approval. Until then, surgeons with endophthalmitis rates much lower than 0.25% while using topical prophylaxis alone are left to ponder whether adding an IC antibiotic would be significantly better. Would the risk for toxicity from mixing or compounding errors outweigh the small, theoretical benefit?

Although the ESCRS study did enable EMA approval of an affordable commercial product, it fell short of leading

to the US FDA approval of intraocular cefuroxime. With inconsistent global availability of commercial intraocular antibiotics, the ESCRS study also failed to establish a definitive standard of care for antibiotic prophylaxis. However, thanks to multiple big data and registry studies, the preponderance of evidence now supports the original conclusions from this groundbreaking study. That no other prospective, randomised trial of this size or quality has since been conducted speaks to the foresight, audacity, and determination of the ESCRS study organisers under Peter Barry’s leadership. In a review and analysis of the published literature, the 2017 Cochrane review concluded that the ESCRS study “provides the best evidence for antibiotic prophylaxis against postcataract surgery endophthalmitis”. It was the only study to be rated “moderate to high-certainty evidence”. For this reason, the 2006 ESCRS clinical trial continues to rank as one of the most important and influential studies of the past two decades in cataract surgery. This article originally appeared in the Journal of Cataract & Refractive Surgery: February 2021 - Volume 47 - Issue 2 - p 150-152 and is reprinted with the permission of the author

References on request.

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The question of which IC antibiotic is preferable for endophthalmitis prophylaxis was not addressed by the ESCRS study

David F Chang MD

CATARACT & REFRACTIVE 14

Tracking

The COVID-19 pandemic has had a significant impact on the number of eye-related ED visits and there is a need better health education, according to Ceren Durmaz Engin MD, Dokuz Eylul University, Izmir, Turkey.

In a presentation at the 25th ESCRS Winter Meeting Virtual 2021, Dr Durmaz Engin said the highest decrease was seen in the frequency of acute conjunctivitis cases, which may be secondary to hand hygiene and social distancing measures.

Dr Durmaz Engin and her research team compared the characteristics of eye-related emergency department (ED) visits with ophthalmology consultation during the COVID-19 pandemic in 2020 against an equivalent period in 2019.

Records of 838 patients who admitted to ED for ophthalmic complaints between 11 March 2020 (date of first COVIDpositive case in the country) to 11 September 2020 (Period 1) and 1,585 patients who admitted to ED at equivalent period in the previous year (Period 2) were examined.

The urgency status of complaint, diagnosis, treatment applied, hospitaliation status of patients and total cost of health expenses by institution were compared. Urgency status of the complaint were classified as likely emergent, not likely emergent and undetermined. Records of first three months (11 March – 3 June) and second three months (3 June – 11 September) in 2020 were also compared to reveal the effect of lockdown.

in P2, the frequency increased to 79.4% during P1 (p<0.001). The type of treatment (p=0.089) and hospitalisation status (p=0.29) were not different between two study periods. There was a 44.3% reduction in health expenses.

Researchers further analysed paediatric and adult populations separately and found 70% and 83% of the complaints were likely emergent during partial lockdown period in paediatric and adult populations, respectively. For the paediatric population, there was a 66% reduction in eye-related ED consultations. Acute conjunctivitis cases were significantly reduced during COVID period, which may be explained by social distancing due to schools being closed and increased emphasis on hand hygiene.

For the adult population, there was a 46% reduction in eyerelated ED consultations. CFB, CA and orbital blow-out fractures were the three most common diagnosis during COVID period. Likely emergent conditions were significantly higher in 2020 compared to 2019 for adults. Flashes and floaters, which need to be evaluated immediately and diagnosed with either posterior vitreous detachment or retinal tear and/or detachment were among the 10 most common diagnoses during the COVID period. The frequency of invasive procedures needed increased to 27% of all cases during the COVID period. As expected, the most common indication for invasive procedures was corneal foreign body in both periods.

“Delayed health-seeking behaviour for subtle or less debilitating symptoms due to fear of contracting the virus by hospital attendance may cause the decrease of ED visits for not likely emergent conditions. Not occupying the ED for non-emergency situations is important both economically and in terms of reducing the workload of healthcare personnel fighting with COVID.

“Taking lessons from the COVID period, more rational use of emergency services can be achieved by health education,” she said.

Cataract and systemic disease

Roibeard Ó hÉineacháin reports

Looking beyond the eye during preoperative assessment can optimise the outcomes of cataract surgery in patients with systemic disease with ocular manifestations, said Betty Lorente Bulnes MD, FEBO, Spain, at the 25th ESCRS Winter Meeting.

“Sometimes we are too focused on the eyes of our patients and we forget that they might have diseases outside of their eyes,” Dr Lorente Bulnes said.

She noted that a thorough preoperative exam is crucial in determining systemic diseases that might affect the patient’s ability to cooperate and collaborate with the surgeon. This would include Down syndrome, Alzheimer’s, Parkinson’s disease and musculoskeletal disorders.

As an example, she described a recent case where due to an arthritis condition the patient could not bring the back of his head on to the operating table and she had to perform the operation while standing up.

Also important is careful questioning of the patient regarding the medical history. For example, in patients with a history of prostatic disease, even a brief regimen of alpha blockers such as tamsulosin can leave its imprint on the iris many years later. In such cases, the surgeon will need to be prepared to deal with intraoperative floppy iris syndrome. Research conducted 10 years ago now shows that intracameral phenylephrine is very effective inducing pupil dilation in these eyes, Dr Lorente Bulnes noted.

“Another aspect that is really frequent in our patients is antithrombotic agents. We should take all of this into account before bringing our patients into the OR, studying the risks and benefits of stopping these drugs in these major diseases,” she added.

Marfan’s syndrome is another condition that requires modifications in cataract procedures. Special instrumentation such

as iris retractors and capsular tension rings should be ready to hand in such cases in order to stabilise the bag, she said. She added that eyes with a history of uveitis, whether it is caused by infection or autoimmunity, also require special consideration.

For example, patients at her centre currently receiving corticosteroids require an adjustment of their regimen in the week prior to surgery. In addition, those receiving biologic treatments undergo surgery between treatments and those with herpetic uveitis or a history of herpetic eye disease receive prophylactic treatment

Dr Lorente Bulnes also noted that in patients with ocular surface disease one should be careful not to rule out pemphigoid, a very aggressive and underdiagnosed disease that can masquerade as less serious conditions such as chronic blepharitis or chronic conjunctivitis.

A thorough preoperative exam is essential to find any disease outside of the eyes.

Betty Lorente Bulnes MD, FEBO

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THOMAS KOHNEN European Editor of JCRS

JCRS HIGHLIGHTS

VOL: 47 ISSUE: 3 MONTH: MARCH 2021

3D SURGERY MAY ENHANCE SAFETY

Innovative 3D visualisation systems could offer an increased margin of safety by reducing microscope light-induced retinal phototoxicity in patients undergoing ophthalmic surgery, a new study suggests. The retrospective study compared outcomes for conventional and 3D visualisation surgery (Alcon’s NGENUITY 3D Visualization System) in 51 eyes undergoing femtosecond laser-assisted cataract surgery. While light exposure was similar in both groups, the intensity of light used in the 3D group was significantly less. The 3D group was significantly more likely to reach a visual acuity one day after surgery that was within two lines of that seen at one month. Digital visualisation systems also offer the advantage that images derived from the analogue microscope and displayed on the 3D flat panel screen can be digitally enhanced, thus allowing for the use of lower illumination levels yet with comparable visualisation. ED Rosenberg et al., “Efficacy of 3D digital visualization in minimizing coaxial illumination and phototoxic potential in cataract surgery: pilot study”, 47(3):291-296.

COST EFFICACY AND PREMED

While the ECRS PREMED (PREvention of Macular EDema after cataract surgery) study has shown that a combination of topical NSAIDs and corticosteroids is most effective in reducing the incidence of CME after cataract surgery compared with either drug alone, cost efficacy data has until now been unavailable. A prospective analysis of the ESCRS PREMED data looked at cost-effectiveness through qualityadjusted life years (QALYs). The study concluded that combination treatment with topical bromfenac and dexamethasone was costeffective in prevention of CME in patients without diabetes compared with treatment with either drug alone. Assuming a cost of € 20,000 per QALY, cost effectiveness probability was 3%, 32% and 65% for bromfenac, dexamethasone, and combination groups respectively. R Simons et al., “Economic evaluation of prevention of cystoid macular oedema after cataract surgery in patients without diabetes: ESCRS PREMED study report 4”, 47(3):331-339.

COSTS OF COVID

The interruption in elective ophthalmic surgeries at hospital outpatient departments seen during COVID-19 pandemic led to hundreds of millions of dollars in lost income per month for US hospitals. The cessation in elective surgeries also reduced opportunities for trainees at academic medical centres. Researchers reached these conclusions by comparing national hospital statistics from before (2017) and after the pandemic. The analysis showed that cataract, strabismus and keratoplasty were performed more often in teaching hospitals than in non-teaching hospitals, indicating an effect on the surgical training of residents and fellows. The study results are probably an underestimate, since the analysis did not include all elective procedures such as glaucoma and oculoplastic surgery. MJ Fliotsos et al., “Impact of reduced elective ophthalmic surgical volume on U.S. hospitals during the early coronavirus disease 2019 pandemic”, 47(3):345-351.

NEW APPROACHES for keratoconus

Intrastromal implantation of bioengineered lenticules can be effective in the treatment of keratoconus and hyperopia suggest preliminary results from recent clinical trials.

“New laboratory-made bioengineered stroma could theoretically provide unlimited tissue for refractive and therapeutic purposes,” Neil Lagali PhD and Professor, Department of Biomedical and Clinical Sciences, Linkoping University, Sweden, told the 38th Congress of the ESCRS.

Bioengineered stromal tissues could in the future provide a means for mass-producing made-to-order stromal lenticules that are customised in thickness and shape for use in refractive, tectonic and keratoconus treatments. Unlike lenticules made from donor tissue, their supply is not limited by the availability of donor corneas from eye banks and tissue preservation is very simple. Moreover, the implants are non-allogeneic, reducing the chance of rejection. Bioengineered stromal tissue may also provide additional functions that human tissue cannot.

Prof Lagali noted that in a meta-analysis of studies of patients undergoing deep anterior lamellar keratoplasty (DALK) procedures for keratoconus, the rejection rate for the stromal transplants was 3-to-24%. However, not enough intrastromal lenticule implantations have been performed to date to determine the technique’s rejection rate. In addition, keratoplasty using allogeneic tissue involves the use of immunosuppressant agents, which carry their own risks of IOP increase, cataract and corneal thinning.

Research into decellularised human corneal stromal has shown promising results. In the first human study, Jorge Alió and his associates implanted decellularised corneal lenticules obtained from eye bank corneas in five advanced keratoconus patients. They decellularised the tissue with 0.1% sodium dodecylsulfate (SDS) and deoxyribonuclease (DNase). The 120µm thick stromal implants maintained their stability within the cornea without complications for at least 12 months (Alió del Barrio IL. et al., Am J Ophthalmol. 2018;186:47-58), Prof Lagali said.

“But decellularisation still requires a source of human donor cornea tissue,” he pointed out.

BIOENGINEERED STROMAL TISSUE

Prof Lagali noted that as an alternative to human corneal tissue, he along with his collaborator Assoc Prof Mehrdad Rafat, Linköping University and their associates have been developing collagen-based bioengineered tissues for intrastromal implantation. They start with the base chemical building block of medical-grade porcine collagen. They then take this material and synthetically cross-link it in the laboratory and make it transparent, mechanically strong and customisable in size, thickness and swelling.

Prof Lagali and his associates have also developed a procedure for implanting the bioengineered lenticules. They call the procedure FLISK, an acronym for femtosecond laser-enabled intrastromal keratoplasty. It involves using the laser to create a

pocket for implantation of a lenticule or replacing diseased or scarred corneal stromal tissue, which can first be removed using the laser, prior to insertion of a stromal replacement.

Positive results of intrastromal implantation of the bioengineered tissue, first in a rabbit model and then in a pig model, have led to the first clinical trial with the material. The ongoing prospective study involves a series of advanced keratoconus patients who underwent implantation of Link Cor® (LinkoCare Life Sciences AB, Sweden) a stromal substitute with thickness ranging from 200-440µm, personalised to the patient’s requirements. Preliminary results of the trial have been very promising.

He noted that in patients with 12-months’ follow-up, corneas have remained stable, with increased thickness, significant flattening and regularity compared to preoperative values. In addition, the patients are now contact lens tolerant and their best-corrected visual acuity has improved significantly. Furthermore, the increased corneal thickness now makes them suitable candidates for refractive surgery. There were no cases of scarring or rejection.

PRESBYOPIC MICROLENTICULE

Clinical trials have also begun with the use of the bioengineered stroma tissue in the form of a specially designed lenticule for the treatment of presbyopia, called CorVision® MicroLens (LinkoCare Life Sciences AB, Sweden). As with the FLISK procedure for keratoconus, the lenticule is implanted into femtosecond laser-created pocket in the central stroma.

Early findings from a phase I trial with the implant procedure, conducted by Pavel Stodulka MD and his associates in the Czech Republic, show that at three months’ follow-up all of the first 10 patients to undergo the treatment achieved an uncorrected near visual acuity (UCNVA) of Jaeger 1 (0.0 logMAR), compared to a mean preoperative UCNVA of 0.64 logMAR.

Bioengineered implants may also have a future role in delivering drugs to the eye. Implants loaded with active substances during fabrication can then release the drug in a slow controlled manner, prolonging its physiological effects. In an in vitro experiment, a bioengineered stromal lenticule loaded with recombinant nerve growth factor released the drug first in an initial burst lasting about 10 days, followed by a linear release curve, so that by two months 25% of the agent had been released (Xeroudaki et al., Sci Rep. 2020;10:16936). That means the implants would release nerve growth factor for over half a year, he said.

“There will continue to be growth in the use of human donor lenticules for additive keratoplasty, but with widespread use we may see an increase in cases of stromal rejection. Decellularisation of lenticules is one promising way of overcoming this. However, use of the thicker donor lenticules required when treating keratoconus is limited by what the eye bank can provide. Bioengineered stroma, in contrast, could in principle provide an unlimited supply of non-allogeneic stromal tissue without any need for donor corneas, or any need for decellularisation,” Prof Lagali concluded.

Bioengineered stromal lenticules are showing promise in the treatment of keratoconus and hyperopia. Roibeard Ó hÉineacháin reports

Potential new treatment

Tackling myopia via scleral cross-linking. Dermot McGrath reports

Scleral cross-linking is a potentially promising new treatment modality for pathological myopia that may in the future help to avoid complications associated with more severe forms of the condition, according to Mor Dickman MD, PhD.

“Studies have shown that cross-linking is effective in stiffening the sclera ex vivo and arresting axial elongation in myopia animal models in vivo, with optimised protocols showing promise with regard to retinal safety,” he said at the online 38th Congress of the ESCRS.

Despite its potential, Dr Dickman, Maastricht University Medical Centre, the Netherlands, acknowledged that scleral cross-linking has several substantial hurdles to overcome if it is ever to be adopted as a viable treatment for myopia.

“Scleral cross-linking may interfere with the development of the eye, especially in children, and may also cause glaucoma if it is not restricted. There is also no back-up procedure available in case of failure, which is the equivalent to a penetrating keratoplasty for corneal cross-linking,” he added.

The rationale for targeting the sclera stems from studies showing that the development of high myopia is associated with thinning of the posterior sclera and changes in the collagen fibrils.

“The total scleral volume remains unchanged and the biomechanically weakened sclera expands even under normal intraocular pressure, enlarging the posterior segment of the eye and further weakening the sclera. The process results in a vicious

circle, which weakens the sclera and increases the myopia,” explained Dr Dickman.

The key challenge is to target the appropriate part of the sclera with any cross-linking treatment, said Dr Dickman.

“When the entire sclera is treated the increased stiffness can cause glaucoma. Restricting scleral stiffness to a localised region can actually decrease the risk of glaucoma and act as a neuroprotective therapy by reducing local biomechanical stress on the optic nerve,” he said.

With this goal in mind, Dr Dickman and colleagues together with the group of Professor Avigdor Scherz and Dr Arie Marcovich from the Weizmann Institute in Israel developed a novel CXL technique combing light-sensitive WST11 (Tookad) and near infrared (NIR) light.

“Together we have shown that this technique results in a safe and effective long-term corneal stiffening in vivo. Upon illumination with near infrared light of 750nm, which has deep tissue penetration and is non-toxic to the retina, WST11 releases free radicals that result in collagen cross-linking. It is possible to deliver the drug via sub-tenon’s injection and activate it in the designated treatment area using NIR that is delivered via the pupil to reach the sclera,” said Dr Dickman.

He added that further studies, such as those being carried out by Dr Craig Boote, Cardiff University, UK, and Prof Sally McFadden, University of Newcastle University, Australia, are needed to determine the long-term in vivo safety and efficacy of the technique.

Promising results with refined technique

Isolated Bowman’s layer transplantation (BLT) appears to offer a promising new treatment modality for a growing range of indications including corneal scarring from herpetic disease, corneal haze after refractive surgery or advanced corneal ectasia from keratoconus, according to Jack Parker MD, PhD.

“For the past decade, Bowman’s layer transplantation has been an important part of how we treat patients with advanced corneal scarring from refractive laser or advanced corneal ectasia from keratoconus. As we refine the technique further as an onlay procedure, it is poised to spread more rapidly as the technique becomes simpler and easier, particularly if the graft can be prepared in a more facile manner,” Dr Parker said at the online 11th EuCornea Congress.

Explaining the background to BLT, Dr Parker, in private practice at Parker Cornea, Birmingham, Alabama, and at NIIOS-USA, San Diego, California, said that while little is known about the function of Bowman’s layer in the eye, there is greater understanding of some of the layer’s descriptive features.

“These descriptive features include the fact that it provides an anatomical separation between the epithelium and the underlying anterior stroma and that this separating barrier tends to be mechanically strong,” he said.

Over a decade ago, Dr Parker and co-workers first noticed that dysfunctional healing after refractive laser occurred in the absence of the ablated Bowman layer in these patients.

“We therefore reasoned that we may be able to treat these scars by replacing Bowman’s layer. We performed an experiment in which an isolated donor Bowman’s layer was harvested from a donor cornea. The patient’s epithelium was debrided and the Bowman’s layer graft was placed into the cornea and allowed to heal. We observed that restoring this barrier between the anterior stroma and the overlying epithelium prevented recurrence of the scar,” he said.

Once the relevance of the separation function of Bowman’s layer had been established, the next step was to try to take advantage of the mechanical strength of Bowman’s layer grafts by implanting them in patients with advanced keratoconus.

Once the graft had been harvested from the donor cornea, the surgery was performed by dissecting a pocket in the mid-stroma of the recipient cornea and then sliding the isolated Bowman’s layer graft inside on top of a surgical glide and unfolding it,” he said.

The results of the first surgeries were better than anyone expected, said Dr Parker.

“What we observed is that these eyes would often experience something like eight or more dioptres of corneal flattening, which is already a huge benefit. But the real virtue of the procedure seemed to be that the corneas would be stiffened, with around 90% of the eyes seeing the progression of their keratoconus arrested with Bowman’s layer implant and dramatic improvements in the corneal curvature,” he said.

The outcomes also appeared to be durable, said Dr Parker. “We followed the original cohorts of Bowman layer recipients for up to 10 years and what we saw is that the graft appears to be well integrated in the mid portion of the recipient stroma, and the shape of the cornea was flatter and stable,” he said.

A recent refinement of the transplantation has been to use a Bowman’s layer onlay graft, explained Dr Parker.

“An inlay graft is placed into the middle of the recipient cornea, whereas an onlay graft is placed on to the surface of the recipient cornea. With the onlay approach, we have observed that we can

debride the patient’s epithelium and place the Bowman’s layer graft on top of the cornea and allow it to dry and fixate without sutures or glue or dissecting a pocket,” he said.

The technique has shown promising results in patients with ectasia and fluctuating vision after radial keratotomy.

“What we observe is a normalisation of the shape of the cornea. The ectatic areas get flatter and the flat, sunken, depressed areas tend to get steeper as the cornea remodels with the presence of the Bowman layer graft,” he said.

Dr Parker said that Bowman layer onlay grafting may also have applications in the treatment of corneal haze as a result of herpetic scarring.

“We noted that debriding the epithelium and then placing a Bowman layer onlay graft over the surface of the cornea allowed a normal healing response to finally occur so that the cornea is clear without the recurrence of corneal scarring,” he said.

Going forward, Dr Parker said further research is needed into Bowman layer onlay procedures which are technically easier to perform than inlay grafts.

“We also need new studies on preparation of the graft tissue itself. The Bowman’s layer graft is typically prepared manually in the eye bank, but it is a tedious and time-consuming process. There have been experiments using a femtosecond laser for dissection, but so far these grafts are much thicker than those prepared by hand, and there is some concern that the extra thickness may optically obscure the effect of the transplant,” he concluded.

Jack Parker: Jack.parker@gmail.com

Bowman layer transplantation can be simpler and easier as an onlay procedure. Dermot McGrath reports

As we refine the technique further as an onlay procedure, it is poised to spread more rapidly as the technique becomes simpler and easier...

Jack Parker MD, PhD

Ruling in dry eye and ruling out other OSDs

Basic steps can help in diagnosis of DED. Roibeard Ó hÉineacháin reports

Incorporating the current guidelines from the Tear Film Ocular Surface Society’s 2017 dry eye workshop report (TFOS DEWS II) for dry eye disease (DED) diagnosis into one’s daily surgical practice does not require special expertise in ocular surface disease or the purchase of new expensive equipment, said Carina Koppen MD, PhD, University of Antwerp, Belgium.

“Actually, the scheme includes a lot of tests that you are already familiar with, and with a bit of organisation it’s very possible to include these tests in the routine of your daily workflow,” Dr Koppen told the 25th ESCRS Winter Meeting.

The guidelines suggest starting with a series of triaging questions to help rule in dry eye and rule out other ocular surface diseases. They include questions regarding not only the typical DED symptoms of discomfort and their triggering factors, but also questions regarding visual acuity and fluctuating vision. Also important is a risk factor analysis, to obtain a fuller picture of the patient’s overall ocular and systemic health, with questions regarding smoking, medications and contact lens wear.

Dr Koppen noted that the initial parts of the investigation can be greatly facilitated by the use of questionnaires, such as the Ocular Surface Disease Index and SANDE questionnaires. They have the advantage that patients can fill them out in the waiting room, reducing chair time.

SLIT-LAMP EXAMINATION

The next step in the TFOS DEWS II scheme is a systematic slit-lamp examination of the ocular surface, including the eyelids,

lashes and margins and the lower and upper conjunctiva. Features to look for include conjunctival folds suggestive of dry eye disease and a frothy aspect of the tears such as occur in the presence of meibomian gland disease.

“You might miss cicatrising conjunctivitis or superior limbic keratoconjunctivitis if you don’t examine the eye in the upward and downward gaze, and epithelial dystrophy, which is actually not so rare if you look for it,” she said.

Following this examination, the clinician needs to determine tear break-up time (TBUT) by instilling a drop of fluorescein. A TBUT of less than 10 seconds is suggestive of tear film instability, a TBUT of less than five seconds is the signature of definitive DED. The residual fluorescein stains areas of epithelial damage and erosions.

“As clinicians we should not forget to systematically examine the eyelid margins and the orifices of the meibomian gland and to squeeze the glands to test their functionality,” she added.

MEASUREMENT OF TEAR OSMOLARITY

Osmolarity is another parameter included in the TFOS DEWS II guidelines. Dr Koppen noted that hyperosmolarity is a hallmark sign of DED. Maximum osmolarity greater than 308mOsmol/L and/ or inter-eye difference of >8mOsmol/L suggest DED. But whether ophthalmic clinicians require an osmolarity metre next to the slit lamp remains a matter of

debate. The tests have high specificity (78to-99%) but a more variable sensitivity (48-to-95%).

“The main problem is that values of osmolarity fluctuate, so it is advised to at least test both eyes. The test would probably be more sensitive if you do several tests per eye but each chip costs money so the test becomes prohibitively expensive if you’re going to test both eyes three times,” Dr Koppen said.

Once it has been ascertained on the basis of these tests that a patient has dry eye disease, the next step is to classify the condition as evaporative or aqueous deficient dry eye. Changes in the tear film lipid layer and the meibomian glands are suggestive of evaporative dry eye, while reductions in the tear meniscus height indicate aqueous deficient dry eye, Dr Koppen said.

“Actually, it is not an either/or situation. Once the patient gets trapped in a vicious circle of dry eye disease then both types will be present in the same patient at a certain point in time,” she added.

Dr Koppen added that multi-functional devices are becoming available for the automation of DED diagnosis with considerable accuracy. They include the Oculus keratograph, a tomographer that also has an inbuilt infrared camera for meibography. It can also perform interferometry of the lipid layer, noninvasive tear film break-up time, tear film meniscus height measurement and lipid layer evaluation. Other dedicated and multifunctional devices have recently been introduced for clinical use.

“If you want to improve your dry eye disease diagnostics, systematically screen for signs and symptoms, listen to the patient’s description of their symptoms of discomfort and fluctuating vision, look at the slit lamp and don’t forget to use a drop of fluorescein for TBUT and staining, which can tell you so much, and don’t forget to inspect and squeeze the meibomian glands,” Dr Koppen concluded.

... it is not an either/or situation. Once the patient gets trapped in a vicious circle of dry eye disease then both types will be present in the same patient at a certain point in time

Carina Koppen MD, PhD

Carina Koppen MD, PhD

Adopting a multi-pronged approach

Technological breakthroughs provide a range of options for the treatment of age-related macular degeneration. Priscilla Lynch reports

Amulti-pronged approach to better prevent, diagnose, monitor and treat agerelated macular degeneration (AMD) using the latest exciting knowledge and technology breakthroughs is on the way, and will bring better outcomes for patients, heard the dedicated AMD session held during the 2020 virtual EURETINA Congress.

Caroline Klaver MD, the Netherlands, discussed new insights in AMD derived from the European Union-funded Eye-Risk research consortium, which, using a systems medicine approach, has identified many new risk factors, molecular mechanisms and therapeutic approaches for AMD.

The creation of the Eye-Risk database (from 20 existing longitudinal epidemiological cohorts and biobanks [1991-2015]) was the first task of the consortium, she explained: “We now have extensive data on 53,000 subjects with data on phenotype, genotype, environmental risk factors and blood biomarkers.”

The next task for Eye-Risk was to develop an AMD genotype pipeline. “The pipeline [assay] allows genotyping of virtually all associated AMD SNPs and genotypes several AMD genes entirely for the rare variants, and genotypes genes of macular dystrophies that mimic AMD to rule out misclassification,” she said.

The entire Eye-Risk cohort has now been genotyped with a summary of all AMD risk variants, creating the ‘genetic risk score’. “It shows that late AMD has higher genetic risk scores overall than intermediate and non-AMD but there is considerable overlap.”

Eye-Risk has also categorised all the genetic risks into pathways. “We also saw that most AMD patients carry genetic risk variants in at least three pathways.”

Further Eye-Risk research has identified numerous AMD metabolic biomarkers from blood; especially lipids, amino acids and citrate. “The next steps are to use genetics and genomics and the lessons learned from systems biology to guide the development of personalised interventions,” Prof Klaver stated.

Discussing approaches to slow

progression of intermediate AMD, Robyn Guymer MD, Australia, highlighted the potential use of laser intervention.

She noted that while trials of prophylactic thermal laser in the 1990s were shelved due to fears around increased risk of choroidal neovascularisation (CNV), and a 2015 Cochrane review found that despite evidence of resolution of drusen there was no difference in rates of advanced AMD from this approach, there is now renewed interest in using new nonthermal continuous wave laser modalities.

The aim is to reduce the thermal damage and potential inflammatory stimulus for CNV but harness any drusen-resolving effects.

“So now the short duration pulsed lasers (micropulse and nanosecond lasers) have been developed to see if they can selectively target the RPE [retinal pigment epithelium] and not cause any collateral damage to neuro retina,” Prof Guymer said, outlining her own subthreshold nanosecond study experiences.

While her randomised controlled study (LEAD) did not find any overall significant difference in progression to late AMD in those receiving laser versus sham treatment; upon further investigation it found a significant treatment effect modification according to the presence of reticular pseudodrusen (RPD) at baseline. “So potentially there is a benefit for those without coexistent RPD. I think the results are intriguing and deserve ongoing investigation.”

Concluding, Prof Guymer stressed that there remains a dearth of randomised controlled trials in intermediate AMD, “but I think the new ways of using multimodal imaging to define the earlier stages of AMD should lead to an increase in clinical trial activity in these earlier stages of AMD”.

Adnan Tufail MD, UK, discussed the impact of artificial intelligence (AI)-based biomarker detection in OCT scans of AMD patients. He said that AI biomarker detection is rapidly evolving and will in the future inform treatment choice and assessment.

Deep learning algorithms can now be used to identify AMD biomarkers of the biological process, such as retinal pigment

epithelium (RPE)/Bruch’s membrane thickness and choroidal thickness, as well as the pathogenic process in neovascular AMD. “The challenge going forward is identifying which patients progress from intermediate to late atrophic AMD,” Prof Tufail said, noting that the detection of features such as reticular pseudodrusen will be important in this regard.

TREATMENT ADHERENCE

Looking at the present, in patients who currently have AMD, Anat Loewenstein MD, Israel, discussed efforts to improve adherence and outcomes in AMD therapy using home monitoring, noting that the COVID-19 pandemic has highlighted the need for more remote patient monitoring.

She showed how information generated by tele-connected self-operated OCT in patients’ homes has the potential to support current retinal disease management and any future evolutions that may occur in monitoring patterns, drug selection and dosing, and patient outcomes. The benefits of home OCT for personalising eAMD management include catching ‘wet’ days as soon as they occur, thus avoiding undertreatment and improving visual acuity outcomes as well as reducing costs and treatment burden, and improving patient satisfaction, with very positive trial data to date, Prof Lowenstein outlined.

LONGER-ACTING TREATMENTS

Also speaking during this session was Jordi Mones MD, Spain, who addressed novel therapeutic approaches for neovascular AMD, highlighting the latest promising intravitreal drugs, intraocular devices and gene therapies in various clinical trials, which will bring longer duration outcome efficacy for AMD patients.

Finally, Carl Regillo MD, USA, also discussed long-acting drug delivery in nAMD, specifically the ARCHWAY phase III results, which found that 98.4% of wet AMD patients using an investigational port delivery system implant were able to go six months without needing additional treatment and achieved visual outcomes equivalent to patients receiving monthly ranibizumab injections.

IRIS Registry update

AAO’s Intelligent Research in Sight IRIS® Registry is living up to its promise of shedding light on low-incidence occurrences and broad population trends. Launched in 2014, the IRIS Registry is the USA’s first comprehensive eye disease registry. It currently includes data from nearly 66 million unique patients and 367 million patient visits.

At AAO 2020 Virtual conference, more than 20 papers, posters and presentations featured IRIS Registry-based research ranging from surgical outcomes in rare conditions to demographic disparities in outcomes for more common conditions.

RARE CONDITIONS

On the rare condition end of the spectrum, an AAO Best Poster winner by Peter J Belin MD and Polly A Quiram MD, PhD, of Minneapolis, USA, examined treatment patterns and outcomes of paediatric retinal detachments (RD) associated with hereditary vitreoretinal degenerative diseases including Stickler and Marfan syndromes. Looking for cases of rhegmatogenous RDs in patients aged 18 or younger from across the USA, from 2013 through 2018 they found a total of 421 eyes of 353 patients with one year or more of follow-up.

Among the findings were that patients underwent a mean 1.98 surgeries per eye in one year, with higher rates of additional surgeries required in eyes that initially underwent complex RD repair at 41% than for pars plana vitrectomy at 26%, or scleral buckle at 15%.

Powered by IRIS Registry, this outcomes study provides insight into the variability of technique in this small population that may not be available examining results from a single centre, the authors said.

In another study of sympathetic ophthalmia, a rare, bilateral granulomatous uveitis resulting from autoimmune reaction to antigen exposure during trauma or surgery, Nathan Eli Hall BS, MS, of Harvard University, found that women are at higher risk than men, accounting for 66.71% of cases. The study identified 817 cases among 70 million records, and determined the most frequent precipitating procedure was cataract surgery at 89.73%, with women at significantly higher risk in this subcategory as well.

LARGE POPULATION STUDIES

On the large population end of the spectrum, a poster by Bret L Fisher MD and colleagues of Panama City, Florida, USA, compared the mean time to posterior capsule opacification (PCO) in different types of IOLs implanted in 43,032 eyes with two years or more of follow-up from 2016 to 2018. Overall. 35.7% of eyes had a diagnosis of PCO after two years or more, with a mean time to diagnosis of 268 days after surgery. Multifocal and extended depth of focus lenses had a shorter time to PCO compared with monofocals, while hydrophobic acrylic lenses by two large manufacturers showed differing mean lengths of time to

PCO, with 269 days for Tecnis (Johnson & Johnson) compared with 300 days for AcrySof (Alcon).

An IRIS Registry study comparing glaucoma patients who received the first-generation iStent trabecular bypass device as a standalone procedure with those who received it combined with cataract surgery was presented by Robert T Chang MD, of Stanford University, Palo Alto, California, USA. It found that standalone patients were more likely to have had previous ocular procedures including cataract surgery, nonfiltering and filtering glaucoma surgery, and laser treatments than combined patients, and had more moderateto-severe disease than the combined group. The study involved 995 standalone and more than 187,000 combined surgery patients operated on from 2013 through early 2020.

Nearly 2.7% of eyes in the USA with pathologic high myopia (PHM) experienced retinal detachments between 2013 and 2018, according to an IRIS-powered study by Danielle Fujino MPH of the California, USA, Department of Public Health, Flora Lum MD, of the Academy and Scott P Kelly of Pfizer Inc. Of 461,281 eyes in 249,381 patients with PHM, 12,402, or 2.69%, had retinal detachments during the period. Eyes with glaucoma prior to myopia or vitreous degeneration prior to myopia were more likely to experience RD, as were patients in the Midwest or western regions.

DEMOGRAPHIC DETERMINANTS

Several studies examined demographic and social determinants of health in eye care. One study involving 203,673 patients looked at baseline and outcomes findings for diabetic macular oedema patients who received at least one anti-VEGF injection. Nisha A Malhotra, Rishi P Singh MD and colleagues at the Cleveland Clinic, USA, found that Hispanic patients had fewer anti-VEGF injections and poorer visual outcomes than non-Hispanic patients, and more patients presented in the southern region of the USA. Those with private insurance had better visual outcomes than those on public insurance regardless of ethnicity or geographic location.

“With a growing pool of aggregated data, the IRIS Registry empowers ophthalmologists to recognise disease patterns, better define risk factors and identify effective treatment options for their patients,” said Dr Lum, Academy’s vice president of Quality and Data Science. “All IRIS Registry studies being presented at AAO 2020 Virtual this year reveal interesting and promising results for a better future in eye care.”

Population studies illuminate rare conditions, outcomes and disparities in care. Howard Larkin reports

...women are at higher risk than men, accounting for 66.71% of cases

Nathan Eli Hall BS, MS

With a growing pool of aggregated data, the IRIS Registry empowers ophthalmologists to recognise disease patterns, better define risk factors and improve prevention and treatment options for their patients

Flora Lum MD

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SEBASTIAN WOLF Editor of Ophthalmologica

OPHTHALMOLOGICA

VOL: 244 ISSUE: 1

SUBFOVEAL CHOROIDAL THINNING A BIOMARKER FOR CARDIOVASCULAR RISK

Prominent reductions in the subfoveal choroidal layer could provide a useful biomarker for predicting cardiovascular (CV) risk in patients of advanced age with subclinical atherosclerosis. The retrospective, non-interventional, cross-sectional study included 193 eyes from 193 subjects whose cardiovascular risk were calculated based coronary artery calcification (CAC) as determined by cardiac-gated computed tomography. Enhanced-depth imaging optical coherence tomography showed that average subfoveal choroidal thickness differed significantly among low, intermediate and high CV risk groups (all p<0.05). In addition, multi-variate regression analyses showed that higher CAC scores were significantly associated with subfoveal choroidal thinning. JH Kim et al, “Relationship between Coronary Artery Calcification and Central Chorioretinal Thickness in Patients with Subclinical Atherosclerosis” Ophthalmologica 2021, Volume 244, Issue 1.

CELL CYCLE DEREGULATION A KEY PROCESS IN RETINOBLASTOMA TUMORIGENESIS

A study comparing using retinal tissues of retinoblastoma (RB) patients with those of normal retinas has revealed six key genes involved in the pathogenesis of the malignancy. The study’s authors performed RNA Sequencing on three RB tissues and three normal retinas to identify differentially expressed genes (DEGs) and used bioinformatic analysis to screen them for tumorigenic relevancy. Function and pathway enrichment and protein-protein interaction analysis showed that the cell cycle was the most prominently upregulated pathway found in RB tissues. Comprehensive bioinformatic analyses indicated that six key genes relevant to cell cycle regulation may be potential key factors in RB tumorigenesis. The authors conclude that their findings may lay the foundation for the development of novel targeted therapies. C Nie et al, “RNA Sequencing and Bioinformatic Analysis on Retinoblastoma Revealing that Cell Cycle Deregulation Is a Key Process in Retinoblastoma Tumorigenesis”, Ophthalmologica 2021, Volume 244, Issue 1.

OCT-A MAY HELP UNLOCK MYSTERIES OF GA

Optical coherence tomography-angiography (OCT-A) is providing a new window into the pathophysiology of geographic atrophy (GA), according to authors of comprehensive review of the current literature regarding the use of the new technology in the degenerative retinal condition. The authors note that recent studies using OCT-A have demonstrated that choriocapillaris flow alterations that are particularly associated with the development of GA, exceed atrophy boundaries spatially, and are a prognostic factor for future GA progression. Furthermore, OCT-A may be helpful to differentiate GA from mimicking diseases. Reports also provide evidence for a potential protective effect of specific forms of choroidal neovascularisation in the context of GA. PL Müller et al, “Optical Coherence Tomography-Angiography in Geographic Atrophy”, Ophthalmologica 2021, Volume 244, Issue 1.

Ophthalmologica

Innovative assessments DURING COVID-19

An innovative ‘drive-through’ clinic in Ireland checks patients’ intraocular pressure. Priscilla Lynch reports

Adrive-through clinic in Ireland is being used to measure the IOP of glaucoma patients during the pandemic.

The emergence of COVID19 has wreaked havoc in almost every aspect of medical practice, but it has also created opportunities for innovation and different ways of doing things, including in the field of ophthalmology.

While initially used in a hasty effort to keep patients safe while maintaining essential care, more advanced telemedicine and low physical contact care has evolved to include new services that will likely continue after the pandemic has ended.

One such project is an innovative ‘drivethrough’ clinic set up by two hospitals in Dublin, Ireland, for patients with previously diagnosed glaucoma, where their intraocular pressure (IOP) is checked and assessed.

HOW IT WORKS

Glaucoma patients are invited for drivethrough testing based on clinical need, and once they arrive to the site at their scheduled appointment time, they remain seated in their cars while clinic staff, wearing PPE, undertake IOP testing using a handheld tonometer.

The patients are also asked four key questions; are they experiencing any problems with their sight; are they using their eye drops; have they started any new medications recently; and have they had any side-effects.

Patient results are recorded on handheld computer tablets and then reviewed by glaucoma specialists. Those with concerning results/raised IOP are invited for in-person review in the hospital, and then given corrective treatment if necessary.

INSPIRATION

Speaking to EuroTimes about the development of the service, project co-lead Dr Aoife Doyle, Consultant Ophthalmic Surgeon and Glaucoma Specialist, Royal Victoria Eye and Ear Hospital (RVEEH) Hospital, Dublin, explained that the RVEEH and the Mater Hospital, Dublin, were inspired by a similar service that was launched in Belfast during the first wave of the pandemic last year, which had received positive feedback.

Routine review waiting times for glaucoma patients had become unacceptably long in the two Dublin hospitals before the pandemic and then worsened during lockdown restrictions. Thus the creation of a drive-through service in Citywest, a large conference/ hotel site on the outskirts of Dublin, being operated by the national health service

during the pandemic, was seen as an innovative way to try to address the issue.

The two hospitals went through their glaucoma patient databases and identified about 2,000 hospital glaucoma patients who were overdue for review appointments: “We looked for people who had previously stable pressure measurements and were in the low-risk category of mild-to-moderate glaucoma, and ocular hypertension,” she explained.

Following careful review of these files, about 1,000 patients with mild-tomoderate glaucoma were deemed suitable to be invited to the drive-through clinic, which was launched last August.

NEW TECHNOLOGY

Given that ophthalmology patient reviews depend heavily on in-person assessment using a range of devices in the clinic, this project was only really possible because of recent technological advancements, noted Dr Doyle.

“Part of the reason this project was possible was because of the existence of portable tonometers that give accurate IOP measurements, which is something that wasn’t available in the past. Goldmann applanation tonometry remains the gold standard for IP measurement, so portable tonometers are not in standard use in all clinics, but they have certainly increased in use over recent years, particularly for paediatric patients and those for whom mobility is a problem.

“They seem to be accurate in measuring a range of pressure from around 10-25mmHg, and a majority of our patients would be in that range, and even outside that, in the range that it becomes less accurate, it will overestimate, rather than underestimate pressure, so you won’t miss anything. So it is a good method of picking up glaucoma patients with high pressure and getting them back for urgent review, even if there is sometimes an overestimation of pressures in the very high range.”

The new portable tonometer devices do not need the use of a slit lamp or eye drops, and the patient doesn’t even have to get out of the car to be assessed. “So it

AUDIT RESULTS

In an audit of 195 RVEEH glaucoma patients whose IOP was assessed under the drive-through clinic, 85% were stable and no intervention was required.

The remaining 15% (29 patients) had IOP measurements that were significantly higher than their last assessment, so they were referred for a follow-up visit at the hospital’s specialist nurse-led clinic.

Of these 29 patients, 41% needed no change in treatment, 24% needed their eye drops changed/added, 10% (three patients) had laser treatment, one patient had glaucoma surgery (trabeculectomy) and one patient had cataract removal for angle closure glaucoma.

Since the drive-through clinic was launched last August, approximately 500 RVEEH glaucoma patients have attended appointments there. Patient feedback has been very positive, and it is seen as quick, convenient and safe, Dr Doyle said.

“It has been great, as all those patients [identified as needing follow-up] would have gotten worse and progressed and had further problems. In addition we didn’t have to bring a high proportion of patients seen back for early follow-up – that would have been pointless – so it was worthwhile.”

Initially the drive-through clinic operated a number of times per week but as numbers have reduced it now operates about once a fortnight. “Already that seems to be yielding a good result. So the model of running it at fixed intervals and maximising attendance seems to be a better approach, and we are being helped by the way that appointments for many of these patients have been considerably delayed as

end of April, but Dr Doyle hopes that it can continue and be rolled out onsite in RVEEH itself, where it would be more convenient for staff managing bookings and local patients. In addition, she is hopeful the drive-through IOP model could be replicated in other ophthalmology units in Ireland, including the new emerging network of community-based public ophthalmic clinics.

INNOVATION

Commenting on the project, leading Italian ophthalmologist and former ESCRS President Dr Roberto Bellucci said it was good example of innovative practice, and addresses the need for field control of glaucoma without relying on in-person ophthalmic visits during the pandemic.

“Rebound tonometers can be used by trained nurses or pharmacists, providing excellent care although with probably a high number of false positives.”

He said few if any such initiatives are currently implemented in Italy. “Italy has a huge number of ophthalmologists (>7,000) as compared with UK: patient access to the care is better, but not easy enough. However, there are campaigns to mitigate the difficulty of the patient to receive glaucoma checks. Commercial opticians usually have air puff tonometers. This was a good service although with false positives, but it was discontinued because of the COVID-19 crisis.”

Dr Bellucci said that many ophthalmologists, including himself, do not charge for simple tonometry and therapy check, to encourage patients to show-up. “However, this is not enough, and an initiative to legally empower pharmacists to

We looked for people who had previously stable pressure measurements and were in the low-risk category of mild-to-moderate glaucoma, and ocular hypertension

Dr Aoife Doyle

Examining children

You need to have him sitting on your lap, his back against your chest. One arm around him, incorporating his arms, and one hand on his forehead, keeping his head back. And clamp his feet between your knees.”

Standard instructions to give to a parent when examining a small child, ones that I had given many times before. But it felt more severe, delivering the instructions to my husband. Michael was squirming on his lap, bouncing with curiosity about the odd hat on his mother’s head, wriggling and squealing.

He was amused until I focused the indirect’s beam on his fundus, when he got upset. His Dad held him more firmly, and I worked quickly, checking one eye and then the other.

“Nerves normal, fundi normal.” I sighed in relief.

The idea of examining Michael came up after talking with a paediatrician family friend. I had spoken to her about our visit with the public health nurse, when Michael’s head circumference had come out as above normal on routine checks. Next thing, we were awaiting a visit to hospital to have him checked over, pondering differential diagnoses. Hydrocephalus seemed very unlikely, given he was well otherwise, but I wanted to minimise the chance that he would need any neuro-imaging to rule out a problem. Normal nerves, despite the large head, was reassuring. Hopefully the paediatrician would agree with me.

At the moment I am making an effort to study more, as exams loom again. Our training includes exams that mark the progression from senior house officer to registrar, giving membership status, and final exit exams, granting fellow status. Coming up for us now are the European Board of Ophthalmology exams, mandatory to complete before we can sit our national exit exam. Compared to other exams we do, there is one distinct positive aspect: the exam normally takes place in Paris. There were registrars working in different cities around Ireland who were all planning to sit the exam, and we formed a WhatsApp group, excited about the upcoming trip.

The group was named “Paris in Maytime”, evoking mental images of suitably French scenes – walking to a boulangerie for breakfast croissants, reading over exam notes while sitting outside a café enjoying the early summer light, and an evening celebration after finishing the exam, meeting up in a bar, enjoying some wine... That was until the exam was

cancelled and postponed last year. We have since found out that it is rescheduled to take place in the summer, virtually. Our WhatsApp group was aptly renamed by one of the registrars; “A Desk at Home in June.” Another COVID casualty.

Studying now is both easier and harder than when I was younger. It is more interesting, as I can read up on any new developments in clinical problems that I see regularly. Even for rare diseases or problems, studying them, reading about them, makes it more likely that I’ll know what to do when I do see a patient presenting with them one day. I have motivation, as I know it will make me a better clinician. But the harder aspect is etching out time to get study done. The day-to-day job is busy, and the evenings and weekends feel like time to relax and spend with family. My solution is to do a little most days, especially at work in the morning before the clinics start, after a coffee to get me going. Question banks are easy to dip in and out of. Playing an ophthalmology podcast is handy when driving, or out grocery shopping. Somehow, I will ramp up my reading as the exam gets closer...

By the time we made it to the hospital appointment with Michael, we had started to get anxious again. The paediatrician examined him, and then turned to me. The measuring tape was out, this time for my head. He looked up the adult female head circumference centiles – it turned out that my head measures pretty big too. I had an inkling about this, from hats often not fitting me well. Then the paediatrician took out some old centile charts, that are out of production, specific for children in Ireland and Britain. On these more localised charts, Michael’s head was trending along a more acceptable centile. It turns out that inhabitants of these islands tend to have larger heads, and it can be inherited in an autosomal dominant pattern. The new WHO charts, including a global population, can place healthy Irish babies off the scales in head circumference.

Next time I was looking after a child in distress was in the emergency department, after a mild chemical injury. I found myself sympathising more with both parent and child at their shared discomfort of the examination, and sharing in their joy when I could discharge them.

Clare Quigley is a resident at the Royal Victoria Eye and Ear Hospital, Dublin, Ireland

Next thing, we were awaiting a visit to hospital to have him checked over, pondering differential diagnoses

Examining a small child can be hard enough; it’s even more difficult when it’s your own. Clare Quigley reports

Illustration by Eoin Coveney

Premium cataract IOL

OPHTEC has integrated a laser marking technology in the production process of its Premium Cataract IOLs. A micro ID matrix code is imprinted in the IOL’s loop junctions by this laser. Using this code, special scanners can identify the IOL during the manufacturing process and enable fast and secure production of 2,000 different optical characteristics in the IOLs, according to OPHTEC. Global marketing director Tiago Guerreiro said: “We all know how important it is to collect data on performance and efficiency. How helpful would it be to understand the IOL’s behaviour in situ over years or even decades? OPHTEC is one step closer to getting these answers.” www.ophtec.com

PRESBYOPIA CORRECTING IOL

AcuFocus has submitted a Premarket Approval (PMA) application to the Food and Drug Administration (FDA) for its IC-8 small aperture IOL.

“The IC-8 IOL is a first-of-its-kind presbyopia-correcting lens that is designed to deliver seamless visual acuity from near to far without the ‘blurry zones’ found in traditional lens designs,” said Magda Michna, PhD, Chief Global Clinical, Medical & Regulatory Affairs Officer, AcuFocus.

“We are incredibly grateful to our investigators, their teams and the patients who participated in the study.” www.acufocus.com.

NEW PROPHYLACTIC TREATMENT

Santen has announced the launch of Ducressa, a fixeddose combination (FDC) of levofloxacin/ dexamethasone eye drops solution that is indicated for the prevention and treatment of inflammation, and the prevention of infection associated with cataract surgery in adults. “With the launch of this new FDC, many ophthalmologists now have a new approach in their practice to prevent infection in their cataract surgery patient,” said Prof Marc Coassin, University of Rome, Italy. www.santen.eu

Pandemic marketing lessons

Optimising online content and ethically adjusting to market changes are keys to success. Howard Larkin reports

Around the world, cataract and refractive surgery clinics that focused on online marketing fundamentals saw patient inquiries –and procedure conversions – rise as the COVID-19 pandemic progressed in 2020. Their experience shows what clinics can do to position themselves to weather a looming global recession and any other downturns, said Rod Solar, director of LiveseySolar Healthcare Marketing, London, UK.

Indeed, recent market research and interviews with surgeons around the world suggest that surgery volumes are returning to pre-pandemic levels and elective procedure volume may even be higher, creating opportunities for practices that can ethically adapt to changing conditions, said Kristine Morrill, president of Medevise Consulting, Strasbourg, France. Solar

and Morrill addressed an international audience of ophthalmologists in the ESCRS Practice Management & Development Webinar “Rebuilding Your Practice in a Challenging Environment”, which took place in January and is available free of charge online.

CATCHING THE ONLINE WAVE

Early in the pandemic, Solar and his associates laid out potential futures as the pandemic progressed, and how the cataract and refractive surgery markets might respond. They correctly projected that after a period of denial and panic, interest in surgery would rebound after the initial shutdown.

At the webinar Solar showed the volume of searches on terms such as “laser eye surgery” and “cataract surgery” throughout 2020. They dipped markedly in the first three months of the pandemic followed

by a gradual rise to close to pre-pandemic levels for refractive surgery that remained steady throughout the year. Cataract searches rebounded to a lesser degree, possibly because the population is older and more likely to limit activities due to pandemic restrictions, he said.

Solar also presented data from 11 refractive and cataract practices around the world that successfully increased online traffic as well as conversions – and a couple that were not successful. He found that the successful clinics all shared three online marketing approaches: new content and website design; search engine optimisation and blogging; and implementation of an online “lead magnet”, which is an interactive self-test along the lines of “which cataract or laser surgery is right for you”. Several also offered online consultations.

“All of these things were done so

they could ride this wave of renewed interest and actually do better than they anticipated,” Solar said. By contrast, practices that hibernated didn’t do as well. Paid traffic, or advertising, also helped generate new leads where it is allowed.

STRATEGIES THAT INCREASE TRAFFIC

Solar expanded on several strategies the successful clinics adopted, and how they drove increased conversions to paid appointments and procedures.

Fresh and fast new website designs. Keeping web content up to date is essential both to keep visitors engaged and to keep your site in search results. Viewer expectations for web content are rising and sites must be redesigned periodically to keep up. Successful clinics “kept [web sites] fast and they kept them current. That’s super important now”, Solar said.

Focusing on video content. On websites and social media, visitors are much more likely to engage with and respond to video content, which, like all content, must be kept up to date and topical. “The more video you put out there the more they get to know you and the more likely they are to convert down the road,” Solar said.

Optimising existing content. Search engine optimisation is critical so that your site shows up high on searches for common terms, such as “laser eye surgery” “Lasik” and “cataract surgery”. This is key to riding any interest wave.

Offering a “lead magnet”. Online interactive self-tests, addressing questions such as “which cataract surgery is right for me”, have worked so well that Solar is seeing up to 15% of conversions to appointments from them. But following through is critical. “On the back of a self-test you must follow up with email,” Solar said. Automated systems are best, he said. On the other hand, cost calculators were of no value. “Don’t do cost calculators, they are useless.”

Offering online bookings. “If you take one thing away from this presentation it is offer online booking,” Solar said. “Many people still call but this has a huge impact. Now I am seeing that most of our leads on web sites are coming from booked-online consultations.” At clinics that adopted online booking, callback forms that ask for patients’ contact information died almost completely, he said. Offering virtual consultations. At some locations, 10-to-15% of face-toface appointments began with online

consultations, Solar said. “It opens the ability to engage with patient who might a little bit scared walking into clinics and being out and about.”

None of these practices did any print, TV or radio advertising, or cut prices to increase business. Yet these online strategies are important not so much because they worked in 2020 but because they will work in future times of adversity, Solar said. “Everything they did will help them succeed thorough the global recession that will follow the global pandemic.”

ETHICALLY BALANCING THE MESSAGE

Medevise’s Morrill noted that the pandemic has two sides for the business of ophthalmology. “In a way it has been a boom. We see consumers with more money and time underscored by the understanding that glasses and face masks are not particularly compatible things.” Because they can’t spend money on holidays and travel some have more to spend on themselves, as well as time to investigate refractive surgery options, she added.

On the other hand, shutdowns, reduced patient numbers in the clinic and the need for PPE, disinfection and COVID19 tests raise costs while reducing facility capacity, Morrill noted. Even so, a survey she conducted in the US and Asia found that surgery volumes are returning to pre-pandemic levels, and there is growing interest in refractive surgery in Europe.

All of which presents an ethical question for marketing messaging: How do you balance encouraging doing elective procedures with the realities of managing the current public health crisis?

Morrill advised making sure that both ideas – “yes we want to help you see better” and “we are doing everything to keep you safe in this environment” – are featured together on your web landing page and elsewhere. Adding details, such as your new office hours and what you are doing to ensure a safe environment, such as requiring or providing masks and limiting companions in the clinic, helps foster confidence. When you are not open for surgery, telling patients you are available for consultation for procedures later helps keep the pipeline flowing.

Morrill emphasised that, because cataract and refractive surgery are elective, consent is more important than ever in today’s environment. Make sure yours is careful, thorough and well-documented, and ask for verbal consent at the beginning of any virtual consultation.

To protect patient privacy and data, Morrill advised leveraging commercial online physician consultation platforms, such as Doctolib in France and Germany, rather than trying to do it yourself. Data security standards are strict, so make sure any portal you use complies with all local laws and regulations.

That said, virtual consultations that include family members can help ensure thorough understanding. Given restrictions on patient numbers in the practice, virtual consults are practical, and can even improve conversion rates, Morrill said.

Share regular updates via your website and social media on your clinic’s COVID management practices, including number of tests and vaccinations administered. “Let patients know you are committed to their safety,” Morrill said.

Rod Solar: rod@liveseysolar.com

Kris Morrill: kris@medevise-consulting.com

Rod Solar speaking at the 36th Congress of the ESCRS, Vienna

In a way it has been a boom. We see consumers with more money and time underscored by the understanding that glasses and face masks are not particularly compatible things

Kristine Morrill

Big issues, big ideas

Since the beginning of the COVID-19 pandemic, I have found myself accessing research material outside of my normal remit as Executive Editor of EuroTimes

In a series of articles in the coming months, I will explore some of the ideas discussed in this material that may impact on how ophthalmologists practice as they attempt to come to terms with their “New Normal”.

An article published recently by BBC Environment Correspondent Helen Briggs reported that the mass of all human-produced materials including concrete, steel and asphalt has now grown to equal the mass of all life on the planet. (www. bbc.com/news/science-environment-55239668)

Briggs’ report was based on a recent study carried out at the Weizmann Institute of Science in Rehovot, Israel. (https:// www.weizmann.ac.il)

The study, published in Nature (Elhacham, E., Ben-Uri, L., Grozovski, J. et al. Global human-made mass exceeds all living biomass. Nature 588, 442–444 (2020) shows that at the beginning of the 20th Century, human-produced “anthropogenic mass” equalled just around 3% of the total biomass. Today, on average, for each person on the planet, a quantity of anthropogenic mass greater than their body weight is produced every week.

Prof Ron Milo of the Plant and Environmental Sciences Department, Emily Elhacham and Liad Ben Uri say that their research can provide a crucial understanding of the future shape of the face of the Earth. It also suggests that human beings as a species, will need to behave more responsibly.

“The significance is symbolic in the sense that it tells us something about the major role that humanity now plays in shaping the world and the state of the Earth around us,” Dr Ron Milo, who led the research, told Briggs. “It is a reason for all of us to ponder our role,

how much consumption we do and how can we try to get a better balance between the living world and humanity.”

This begs the question; how can ophthalmologists help to achieve this balance? Juan José Mura MD, MHA, speaking at the 37th Congress of the ESCRS in Paris, France suggested that a start could be made by looking at the use of new disposable technology. (EuroTimes Vol 25 Issue 5, May 2020, p23). In his presentation to the ESCRS, Dr Mura discussed the economic costs, impact on marine life and adverse health consequences of plastic pollution. In addition, he cited a published study that analysed waste generation and life cycle environmental emissions from cataract surgery via phacoemulsification at the Aravind Eye Care System in India (Thiel CL, et al. J Cataract Refract Surg. 2017;43(11):1391-1398).

CARBON FOOTPRINT

Dr Mura also proposed that a large portion of the carbon footprint created through cataract surgery could be reduced by changes in practice to incorporate readily available resource efficiency measures. They include optimising the use of reusable instruments and supplies, maximising single-use device reprocessing, promoting minimum waste and recycling practices, using energy efficient appliances and air handling systems, investing in low carbon energy sources, and using flash autoclaving (also known as immediate-use sterile supplies).

Returning to the theme of this article, Dr Mura’s proposals may be the first steps to reducing the reducing the anthropogenic mass. These are challenging times and we need big ideas to help us prepare for the journey that lies ahead.

For an excellent visual display of Anthropogenic Mass visit www.anthropogenic.org

Do ophthalmologists want to live in a “concrete jungle” and what role can they play in reducing “anthropogenic mass” on the planet? Colin Kerr reports

Due to the COVID-19 virus, a number of meetings have been cancelled or rescheduled. The information in this calendar is correct at the time of going to print; please check the meeting website or email the conference organisers to confirm all meeting dates.

↙ LAST CALL

APRIL 2021

6th San Raffaele OCT & Retina Forum

Virtual Meeting

9 April: 17.30 – 20.30

23 April: 17.30 – 20.30

30 April: 17.30 – 20.30

https://www.octforum2021.eu/

American Association for Pediatric Ophthalmology and Strabismus 2021 (AAPOS 2021)

Virtual Meeting

9 – 11 April

https://aapos.org/meetings/ annual-meeting

MAY

ARVO 2021

Virtual Meeting

1 – 7 May

https://www.arvo.org/

WEBINAR CHIRURGIA

Virtual Meeting

8 May

https://aiccer.it/congressi/congresso-2021

JUNE

AECOS 2021

European Symposium

3 – 6 June

Florence, Italy

https://aecosurgery.org/ 2021-european-symposium/

46th Meeting of the European Paediatric Ophthalmological Society

– EPOS 2021

Virtual Meeting

18 –19 June

https://epos2021.dk/

JULY

AECOS 2021 Summer Symposium

15 – 18 July

Utah, USA

https://aecosurgery.org/2021-summersymposium/

2021 ASCRS Annual Meeting

23 – 27 July

Las Vegas, Nevada

https://annualmeeting.ascrs.org/

The 2021 ASCRS Annual Meeting will take place in Las Vegas, USA

JULY

33rd APACRS–

SNEC 30th Anniversary

Joint Meeting

Virtual Meeting

30 – 31 July

https://apacrs-snec2020.org/

AUGUST

39th Congress of the ESCRS

27 – 30 August

Amsterdam, The Netherlands

https://www.escrs.org/

SEPTEMBER

49th European Contact

Lens and Ocular Surface Congress (ECLSO)

Virtual Meeting

4 September

https://www.eclso.eu/

EURETINA 2021 Virtual 10 – 12 September

https://www.euretina.org/

OCTOBER

Joint event: 14th National Congress of Bulgarian Society of Ophthalmology and Conference

Innovation in Ophthalmology 2021

14 – 17 October

Borovets, Bulgaria

https://mareamedical.com/en/events/ ophthalmology_oct_2021_english/

NOVEMBER

AAO 2021

12 – 15 November

New Orleans, USA

https://www.aao.org/ annual-meeting

DECEMBER

SOE Congress 2021

2 – 4 December

Prague, Czech Republic

https://soe2021.soevision.org/

Watch

 EyeJC (ESCRS Journal Club)

 Advanced Instructional Courses

 Eye Contact Interviews

 Video of the Month

 Video Journal of Cataract, Refractive & Glaucoma Surgery

 Young Ophthalmologists Videos: “My Early Surgeries”

player.escrs.org

The 39th Congress of the ESCRS will take place in Amsterdam, The Netherlands

The SOE Congress 2021 will take place in Prague, Czech Republic

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