CRO Volume 26, Number 4, 2015 by MediConcept

CRO

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Clinical & Refractive Optometry Online VOLUME 26, NUMBER 4, 2015

CLICK HERE TO DOWNLOAD AND PRINT THIS ISSUE Monocular Diplopia from a Stage 1a Macular Hole Optometric Co-Management of Multiple Sclerosis Patients Clinical Grading of Nuclear Sclerotic Cataracts Dragged Fovea Diplopia Syndrome

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Clinical&Refractive Optometry: Online Edition Editorial Board • Volume 26, Number 4, 2015

Editor-in-Chief

Associate Editor

Yvon Rhéaume, OD Montreal, Quebec

Richard Maharaj, OD Toronto, Ontario

Leonid Skorin, Jr., OD, DO, MS Albert Lea, Minnesota

Editors Emeriti John Jantzi, OD Vancouver, British Columbia

Brad Almond, OD Calgary, Alberta

Barbara Caffery, OD Toronto, Ontario

Contributing Editors Jean Bélanger, OD Montreal, Quebec

Paul Dame, OD Calgary, Alberta

Gerald Komarnicky, OD Vancouver, British Columbia

Rodger Pace, OD Waterloo, Ontario

Scott D. Brisbin, OD Edmonton, Alberta

Danielle DeGuise, OD Montreal, Quebec

Bart McRoberts, OD Vancouver, British Columbia

Maynard Pohl, OD Bellevue, Washington

Lorance Bumgarner, OD Pinehurst, North Carolina

Pierre Forcier, OD Montreal, Quebec

Ron Melton, OD Charlotte, North Carolina

Barbara Robinson, OD Waterloo, Ontario

Louis Catania, OD Philadelphia, Pennsylvania

Guy Julien, OD Montreal, Quebec

Langis Michaud, OD Montreal, Quebec

Jacob Sivak, OD, PhD Waterloo, Ontario Randall Thomas, OD Concord, North Carolina

Publication Staff Publisher Lawrence Goldstein

Managing Editor Mary Di Lemme

Senior Medical Editor Evra Taylor

Layout Editor Colin MacPherson

Graphics & Design Mediconcept Inc.

Mission Statement Clinical & Refractive Optometry: Online Edition is a peer-reviewed professional journal dedicated to the publishing and disseminating of COPE approved CE credit scientific articles. The contents of each issue are composed of a mixture of original: state-of-the-art/ technical, therapeutic/clinical, or practice management articles which are of particular interest to and use by practicing optometrists. Participants achieving 70% or more on the questionnaires that accompany each of the articles in the journal, will receive a course credit certificate.

About This Issue This online issue of CRO (Clinical & Refractive Optometry) is being sent to you at no charge with the compliments of the CSCRO (Canadian Society of Clinical & Refractive Optometry). Each of the scientific articles contained in this issue have been approved by COPE for 1-hour of CE credit and are available at a cost of $25 per course. To take any of the CE credit courses in this issue, please follow the instructions on the test questionnaire pages. Please note that you can upgrade to a print edition subscription to CRO (Clinical & Refractive Optometry) which includes prepaid CE credit courses in every issue. For more details and to subscribe, please see the subscription upgrade offer on the next page.

Clinical&Refractive Optometry: Online Edition Contents • Volume 26, Number 4, 2015

CE CREDIT ARTICLES 122 Monocular Diplopia from a Stage 1a Macular Hole: A Case Report Michelle J. Steenbakkers, OD ABSTRACT: The incidence of monocular diplopia is unknown and there are very few epidemiological studies published on this topic. Macular holes have been listed anecdotally as a cause of monocular diplopia; however, this report is the first published case of a macular hole (stage 1a) causing monocular diplopia.

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The Journal is made available to all optometrists on www.crojournal.com. Advertising insertion orders and copy must be received before the first day of the preceding month for which the advertising is scheduled.

Recent Developments in the Optometric Co-Management of Multiple Sclerosis Patients Alice Au, OD; Pauline F. Ilsen, OD

While the editorial staff of Clinical & Refractive Optometry: Online Edition exercises great care to ensure accuracy, we suggest that the reader consult the manufacturer’s instructions before using products mentioned in this publication. The views contained in the Journal are those of the respective authors and not of the Publisher.

ABSTRACT: Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system that primarily affect the young adult and middle-aged population. It therefore has a profound impact on society as the disease causes functional disability in the working class typically in their prime. In 2010, the first oral disease modifying medication for MS, fingolimod, was FDA approved to treat relapsing forms of MS. One of the adverse effects of fingolimod found in the clinical trials was macular edema.

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Clinical Grading of Nuclear Sclerotic Cataracts Paul Varner, OD

ABSTRACT: Widespread clinical use of grading scales facilitates patient care. Many cataract classification schema have been proposed, but without universal acceptance. The purpose of the paper is to discern why there is no consensus for grading nuclear sclerotic cataracts.

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Dragged Fovea Diplopia Syndrome After Epiretinal Membrane Peel Surgery Adam T. Gorner, OD; Leonid Skorin Jr., OD

The contents of the publication may not be mechanically or electronically reproduced in whole or in part without the written permission of the publisher. All drug advertisements have been cleared by the Pharmaceutical Advertising Advisory Board.

ABSTRACT: Dragged fovea diplopia syndrome is a condition involving intractable binocular diplopia associated with macular pathology often involving epiretinal membrane and macular pucker. The prevalence of this condition is unknown. There is no known cure for this condition but effective treatment for the symptoms is available. Two cases of intractable central binocular diplopia of 2 to 3 years’ duration that were not correctable with prism are presented.

NEWS & NOTES

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The Eye and Neurodegenerative Diseases; Optometry Giving Sight Helps Establish the First School of Optometry in Mexico; HOYA’s Picture Perfect Campaign

ISSN: 1705-4850; Date of Issue: December 2015

Cover Image: 4+ nuclear sclerotic cataract Courtesy of: Dr. Paul Varner

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Clinical & Refractive Optometry: Online Edition is pleased to present this continuing education (CE) article by Dr. Michelle J. Steenbakkers entitled Monocular Diplopia from a Stage 1a Macular Hole: A Case Report. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 124 for complete instructions.

Monocular Diplopia from a Stage 1a Macular Hole: A Case Report Michelle J. Steenbakkers, BSc (Hons), OD, FAAO

ABSTRACT The incidence of monocular diplopia is unknown and there are very few epidemiological studies published on this topic. Macular holes have been listed anecdotally as a cause of monocular diplopia; however, this report is the first published case of a macular hole (stage 1a) causing monocular diplopia. A 64-year-old Caucasian female presented with a two-week history of left monocular diplopia. The monocular diplopia could not be eliminated with refraction and a subtle macular disturbance with pigment mottling was noted in the left eye. The patient was diagnosed with a stage 1a macular hole which regressed over a one-year period. Monocular diplopia is a visually disturbing symptom for patients and may be the result of a variety of clinical conditions. A systematic differential diagnostic approach will allow the clinician to determine the etiology of monocular diplopia as an acute presenting symptom. Although macular pathologies have been reported to cause monocular diplopia, this is the first published case of a stage 1a macular hole eliciting this symptom.

INTRODUCTION The incidence of monocular diplopia is unknown and there are very few epidemiological studies published on this topic. The following case is the first published report of a macular hole (stage 1a) causing monocular diplopia. The most common causes of monocular diplopia in the literature include refractive error, external irregularities of the eyelid or cornea, multiple pupils from iris injury or iridotomy/ iridectomy, cataract, media opacity, and retinal disease.1-5 Monocular diplopia from macular conditions, such as

M.J. Steenbakkers — Associate Clinical Professor, University of Waterloo, School of Optometry, Waterloo, ON Correspondence to: Dr. Michelle J. Steenbakkers, University of Waterloo, School of Optometry, 200 University Avenue West, Waterloo, ON N2N 3G1; E-mail: mjsteenb@uwaterloo.ca This article has been peer reviewed.

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epiretinal membrane, choroidal neovascular membrane, pigment epithelial detachment and macular edema are less commonly documented.6,7 Macular holes have been listed anecdotally as a cause of monocular diplopia; however, this report is the first published case of a macular hole (stage 1a) causing monocular diplopia.

CASE PRESENTATION A 64-year-old female presented with a two-week history of monocular diplopia in her left eye. The patient described seeing two images that were separated in both the vertical and horizontal direction. Entering spectacle-aided acuities were 6/4.5 (20/15) in the right eye and 6/15 (20/50) in the left eye, reduced from 6/4.5 (20/15) one year prior. There was no improvement with a pinhole and the monocular nature of the diplopia was confirmed: the patient occluded the left eye and a single line of Snellen acuity letters was seen; however, when the patient occluded the right eye, she commented that there the letters were doubled, with a clearer image up to the right and a lower, blurred image on the lower left. The monocular diplopia was not eliminated with refraction. Extraocular motility was full and unrestricted. Amsler grid revealed a doubling of the inferior grid and a central ‘break’ measuring 3x4 degrees. Pupils were equal, round, reactive to light; there was no relative afferent defect. The anterior segment of each eye was unremarkable, no corneal abnormalities or significant cataracts were noted. A dilated fundus examination revealed a macular disturbance with pigment mottling in the left eye. All other ocular findings were unremarkable. Optical coherence tomography (OCT) demonstrated a disruption of the inner and outer photoreceptor segments of the left macula and the patient was diagnosed with a stage 1a macular hole (Fig. 1). Over the following year, the macular hole resolved spontaneously. The visual acuity in the left eye one and two-years after initial presentation was 6/7.5 (20/25) and 6/6 (20/20), respectively, no diplopia was reported and a barely discernible macular disturbance remained.

DISCUSSION The incidence of monocular diplopia is unknown and few epidemiological studies are available. Two retrospective

Fig. 1 Optical coherence tomography of the left macular region at initial presentation (left) and at a 20-week follow-up (right). Note the intrafoveal split and the disruption of the photoreceptor inner segment (IS) and outer segment (OS) at the initial visit. The foveal disruption and the symptoms of monocular diplopia had resolved at the 20-week follow-up visit.

chart reviews of diplopia found that 25.1% of cases in a nine-month period and 11.5% of cases in a 12-month period had monocular diplopia, the cause of which was determined in 90.9%.6,7 The most common causes of monocular diplopia from these studies were lenticular opacities 26.1%, various corneal conditions 25% and refractive and spectacle errors 12.5%.6,7 The differential diagnosis of monocular diplopia includes confirming the monocular nature of the symptom and visual acuity with pinhole assessment as refractive causes of monocular diplopia will normally disappear through a pinhole. A slit lamp examination should include the assessment of eye lid position, tear film, corneal integrity and iris pathology such as polycoria. An assessment for cataract, lens subluxation or intraocular lens implant malposition and examination for vitreal and retinal anomalies should be completed. A macular assessment, especially in the presence of metamorphopsia and decreased acuity, should be performed. OCT assists in

viewing the structural integrity of the macula and central retina. In comparison, binocular diplopia results when mechanical displacement affects the fovea so that the foveae are no longer corresponding retinal points. The assessment and most common causes of binocular diplopia are discussed in depth elsewhere.8 Macular holes can be classified into 4 stages based on clinical examination findings as described by Gass. Briefly, these stages including the impending hole with vitreomacular adhesion and yellowing at the macula (stage 1), a retinal defect +/- operculum (stage 2), central full thickness retinal defect with pre-macular vitreous attached (stage 3) and the detachment of the pre-macular vitreous as well as the presence of a Weiss ring (stage 4).9 Newer classifications are being proposed which include the OCT data, including the assessment of vitreo-macular adhesion and the extent in microns of the macular hole.10 Monocular diplopia is a disturbing symptom for patients and may be the result of a variety of clinical conditions. A systematic diagnostic approach allows the clinician to determine the etiology of monocular diplopia. The most common causes of monocular diplopia are lenticular opacities and corneal conditions. Although macular pathologies have been reported to cause monocular diplopia, this is the first published case of a stage 1a macular hole eliciting this symptom. ❏

REFERENCES 1. 2. 3.

5. 6. 7.

8. 9. 10.

Coffeen P, Guyton DL. Monocular diplopia accompanying ordinary refractive errors. Am J Ophthalmol 1998; 105: 451-459. Brown NA. The morphology of cataract and visual performance. Eye 1993; 7: 63-67. Campbell C. Corneal aberrations, monocular diplopia, and ghost images: analysis using corneal topographical data. Optom Vis Sci 1998; 75: 197-207. Ford JG, Davis RM, Reed JW, Weaver RG, et al. Bilateral monocular diplopia associated with lid position during near work. Cornea 1997; 16: 525-530. Rubin ML. Perspectives in refraction. Survey of Ophthalmology 1980; 24(5): 303-306. Morris RJ. Double vision as a presenting symptom in an ophthalmic casualty department. Eye 1991; 5: 124-129. Comer RM, Dawson E, Plant G, Acheson JF, et al. Causes and outcomes for patients presenting with diplopia to an eye casualty department. Eye 2007; 21: 413-418. Friedman DI. Pearls: diplopia. Seminars in Neurology 2010; 30(1): 54-65. Gass, JD. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol 1995; 119: 752–759. Duker JS, Kaiser, PK, Binder S, et al. The International Vitreomacular Traction Study Group Classification of Vitreomacular Adhesion, Traction, and Macular Hole. Ophthalmology 2013; 120(12): 2611-2619.

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QUESTIONNAIRE Monocular Diplopia from a Stage 1a Macular Hole: A Case Report Michelle J. Steenbakkers, BSc (Hons), OD, FAAO 1. ❑ ❑ ❑ ❑

What is the incidence of monocular diplopia? 5% 10% 15% Unknown

2. ❑ ❑ ❑ ❑

The most common causes of monocular diplopia include all of the following, EXCEPT: Retinal disease Media opacity Cataract Macular edema

3. ❑ ❑ ❑ ❑

In the Case Report presented, what were the patient’s entering spectacle-aided visual acuities? 6/4.5 (20/15) OD; 6/15 (20/50) OS 6/15 (20/50) OD; 6/4.5 (20/15) OS 6/7.5 (20/25) OD; 6/6 (20/20) OS 6/9.5 (20/32) OD; 6/6 (20/20) OS

CRO: Online Edition 26:4, 2015

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In the Case Report presented, the patient had all of the following characteristics, EXCEPT: Pupils were equal, round and reactive to light Anterior segment was unremarkable Extraocular motility was full and unrestricted Monocular diplopia was eliminated with refraction

5. ❑ ❑ ❑ ❑

In the Case Report presented, two years after initial presentation, what was the patient’s visual acuity in the left eye? 6/7.5 (20/25) 6/9.5 (20/32) 6/6 (20/20) 6/4.5 (20/15)

6. ❑ ❑ ❑ ❑

In two retrospective chart reviews of diplopia, the cause was determined in what percentage of cases? 55% 75% 80% 90.9%

7. ❑ ❑ ❑ ❑

The patient in this Case Report was diagnosed with what stage of macular hole? 1a 2 3 4

8. ❑ ❑ ❑ ❑

All of the following statements about monocular diplopia are true, EXCEPT: Slit lamp examination should be performed for differential diagnosis Assessment for cataract should be completed Refractive causes of monocular diplopia will normally disappear through a pinhole OCT should be undertaken

9. ❑ ❑ ❑ ❑

Macular holes can be classified according to how many stages? 1 2 3 4

10. ❑ ❑ ❑ ❑

In two retrospective chart reviews of diplopia, what was the most common cause? Various corneal conditions Lenticular opacities Refractive errors Spectacle errors

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4. ❑ ❑ ❑ ❑

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Clinical & Refractive Optometry: Online Edition is pleased to present this continuing education (CE) article by Dr. Alice Au and Dr. Pauline F. Ilsen entitled Recent Developments in the Optometric Co-Management of Multiple Sclerosis Patients. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 135 for complete instructions.

Recent Developments in the Optometric Co-Management of Multiple Sclerosis Patients Alice Au, OD; Pauline F. Ilsen, OD

ABSTRACT Background: Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system that primarily affects the young adult and middle-aged population. It therefore has a profound impact on society as the disease causes functional disability in the working class typically in their prime. In 2010, the first oral disease modifying medication for MS, fingolimod (Gilenya), was FDA approved to treat relapsing forms of MS. One of the adverse effects of fingolimod found in the clinical trials was macular edema. Optical coherence tomography (OCT) is not only effective in enhancing an optometrist's ability to monitor for macular edema from fingolimod, but it is also proving to be instrumental in following disease progression in MS. In patients with prior episode(s) of optic neuritis, the axonal damage that occurs causes atrophy of the retinal nerve fiber layer (RNFL), which can be detected through thinning of the RNFL on the OCT. Studies have shown that there is RNFL thinning even in the absence of a history of optic neuritis. Thinning of RNFL has been associated with nonocular MS disease activity. Case Report: A 76-year-old patient with multiple sclerosis was referred by his neurologist for a baseline examination prior to initiating treatment with fingolimod. At five month followup, he was found to have very early macular edema, believed to be a side effect of the new medication. The neurologist was notified of the finding; he instructed

A. Au — Resident, West Los Angeles Veterans Affairs Healthcare Center, Los Angeles, CA; P.F. Ilsen — Professor, Marshall B. Ketchum University, West Los Angeles Veterans Affairs Healthcare Center, Los Angeles, CA Correspondence to: Dr. Pauline F. Ilsen, Marshall B. Ketchum University, West Los Angeles Veterans Affairs Healthcare Center, Optometry Clinic (123) Bldg. 304, Room 2-123, 11301 Wilshire Blvd., Los Angeles, CA USA 90073; E-mail: Pauline.Ilsen@va.gov This article has been peer-reviewed.

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the patient to discontinue use of the fingolimod and the macular edema subsequently resolved. Conclusion: OCT may prove to be a useful adjunct or even occasional alternative to MRI for monitoring disease progression in MS. This will especially be helpful in monitoring for therapeutic efficacy in MS clinical trials for new medications. Optometrists may play an important role in the ongoing management of MS patients in the future and should be familiar with the potential value of OCT in monitoring disease activity.

INTRODUCTION Multiple sclerosis is an autoimmune inflammatory disease that affects the central nervous system. It was first formally described in the 1860s by Jean-Martin Charcot as “la sclerose en plaques.”1 It is characterized by injury to the neuronal axons that accumulates and eventually leads to brain atrophy, resulting in the progressive neurological dysfunction.2,3 Approximately 350,000-400,000 people in the United States and 2.5 million people worldwide are affected.2,4 Like most autoimmune diseases, there is a female preponderance of about 2 to 1.2,4 In addition, there is a prevalence of approximately 1 in 1000 in the Caucasian population.4,5 Eighty-five persent of MS patients have the relapsing form of MS at onset, and more than 50% of these patients will progress to secondary progressive MS within 10 to 20 years of diagnosis.3,6,7 Multiple sclerosis is a debilitating disease, causing pain, fatigue, and affecting patients’ mobility. The patient's role in society is significantly impaired; many lose their independence and become a strain for their families. Approximately half the patients will need a cane for assistance within 15 years of onset of the disease if left untreated.6 From a financial perspective, in 2011 the total cost per patient was more than $50,000, taking into account direct medical costs and patient care and the indirect cost of production loss.8 The cost of medical care for patients with MS is estimated to be $14 billion a year.9 The average cost of medications to treat MS alone was estimated to be more $20,000 in 2009.10 Multiple sclerosis has many effects on the eye, ranging from the afferent pathway to the efferent pathways. Commonly seen ocular manifestations of MS include

Fig. 1 The baseline spectral domain OCT demonstrated normal maculas.

optic neuritis, internuclear ophthalmoplegia, and cranial nerve palsies.2,11 More rarely encountered manifestations include retinal periphlebitis, pars planitis, and nystagmus.11 In 2010, an FDA drug approved to treat MS, fingolimod, was found to have an ocular side effect. In addition, studies in recent years have shown retinal nerve fiber layer analysis to be promising in monitoring disease process in MS.

CASE PRESENTATION A 76-year-old Caucasian male was referred from his neurologist for a baseline eye examination prior to initiating fingolimod, an oral medication used to treat multiple sclerosis. The patient had no visual complaints. His ocular history was significant for prior retrobulbar optic neuritis in both eyes, a longstanding right exotropia, and he was a glaucoma suspect. The patient's medical history was significant for multiple sclerosis, partial epilepsy, hypertension, hyperlipidemia, and benign prostate hypertrophy. His medications included divalproex, fingolimod, atorvastatin, amlodipine, hydrochlorothiazide, captopril, baclofen, cholecalciferol, docusate, galantamine, omeprazole, sertraline, terazosin, tizanidine, and levetiracetam. Best-corrected visual acuities were 6/12+ (20/40+) and 6/6- (20/20-) in the right and left eyes, respectively. Pupils were equal, round, and reactive to light, no afferent pupil

defect was observed. Extraocular muscles were grossly full in both eyes. No nystagmus was noted, and an approximately 18 prism diopter constant right exotropia was evident on cover test. Slit lamp biomicroscopy revealed mild meibomian gland dysfunction, mild blepharitis, pingeuculae, clear corneas, flat and avascular irides, and mild nuclear and cortical cataracts in both eyes. Tonometry with Tonopen was OD 17 mmHg, OS 16 mmHg. Dilated fundus examination revealed pale optic nerves OU and flat maculae with no foveal reflex OU. Spectralis optical coherence tomography (OCT) scans of the maculae were also performed for more in-depth examination. The analysis revealed normal retinal thickness and contour with no abnormalities (Fig. 1). The foveal thickness at the initial visit was OD 290 microns and OS 281 microns. The patient was advised to return for a follow-up examination in four months or if he noted any changes to his vision. The patient returned for a follow-up examination five months later due to scheduling mishaps, reporting no changes to his vision. Visual acuities were pinholed to 6/21 (20/70) in the right eye and 6/15 (20/50) in the left eye. A macular OCT was performed again (Fig. 2A,B). A mild amount of intraretinal cystic spaces was seen nasal to the fovea in the right eye, consistent with the appearance of cystoid macular edema (CME). Abnormalities could

Optometric Co-Management of Multiple Sclerosis Patients â&#x20AC;&#x201D; Au, Ilsen

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A C

Fig. 2 (A) At the five-month follow up, the right eye OCT demonstrated intraretinal cysts and increased thickness compared to baseline. (B) At the fivemonth follow up, the left eye OCT demonstrated increased thickness compared to baseline. (C) The macular thickness maps at the five-month follow-up.

not be appreciated in the macular OCT of the left eye. All other exam findings were unchanged from the initial visit five months prior. Comparing the foveal thickness of both maculae to the initial visit, the right eye's foveal thickness was 318 microns and the left eye was 326 microns (Fig. 2C), an increase of 28 and 45 microns, respectively. The mild macular thickening in both eyes and the intraretinal cystic spaces seen on the right eye’s OCT was suspected to be an ocular side effect from fingolimod, given that the patient did not have a history of diabetes or uveitis. The patient was advised to return for a follow-up visit in six weeks to repeat the OCT to monitor the macular edema.

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Additionally, the patient’s multiple sclerosis specialist in neurology was notified of the findings. The patient returned for a follow-up visit two months later. However, due to positioning difficulties at the OCT, macular scans were unable to be obtained. Fluorescein angiography was also considered; however, the patient declined the procedure. Fingolimod was subsequently discontinued by the neurologist with a month. The patient was then treated with another MS disease modifying drug. Three months later, the patient returned for examination again. After much effort, macular OCT scan were obtained (Fig. 3A). The macular thickness map showed that the right eye’s foveal thickness was now 283 microns

B OD

Fig. 3 (A) At follow-up visit 6 months after 2nd visit, right eye OCT shows absence of intraretinal cysts. (B) The macular thickness maps after discontinuing fingolimod.

and the left eye was 287 microns (Fig. 3B). Table I summarizes the changes in foveal thickness over the three visits' OCT macular thickness scans. It appears macular thickness has returned to baseline after discontinuing fingolimod for 3 months.

DISCUSSION Fingolimod Fingolimod (Gilenya, Novartis, New York, NY) was approved by the United States Food and Drug

Administration (FDA) in 2010 to treat relapsing forms of MS.4,12 Prior to the development of fingolimod, multiple disease modifying therapies were available, such a glatiramer acetate (Copaxone, Teva, North Wales, PA), intramuscular (IM) interferon beta-1a (Avonex, Biogen, Cambridge, MA), subcutaneous (SC) interferon beta-1a (Rebif), and SC interferon beta-1b (Betaseron, Bayer, Pittsburgh, PA).12,13 However, these therapies were only available in SC, IM, or intravenous (IM) formulations. Fingolimod was the first oral therapeutic option to treat MS,12 making it an advantageous drug to prescribe for MS

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Table I Comparison of central macular thickness over three visits (baseline, during treatment, after discontinuing treatment). OD OS Baseline Follow up on treatment Follow up after discontinuing treatment

290 318 283

281 326 287

due to its ease of administration. In two phase three clinical trials, FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) and TRANSFORMS (Trial Assessing Injectable Intereferon versus FTY720 Oral in Relapsing-Remitting Multiple Sclerosis), various systemic side effects of fingolimod were found, namely cardiac side effects.12 There was also a small percentage of the ocular side effect of macula edema (ME) found (1% to 1.6% with 1.25 mg of fingolimod and 0.4% with 0.5 mg).12 Fingolimod works by downregulating the immune response via the sphingosine-1-phosphate (S1P) receptor.4,12 The S1P receptors are found on the surface of lymphocytes, and when the ligand for this receptor binds, it creates a concentration gradient that allows the lymphocytes in the lymph node to be released into the circulation.4,12 Thus, fingolimod, which is a structural analog of S1P, acts as an antagonist. It binds to the S1P receptors, effectively blocking the egress of the lymphocytes from the lymph nodes.4,12 Among other functions, the S1P receptor also regulates vascular permeability via promoting the adhesion between the endothelial cells.12,14 Therefore, as an antagonist of S1P, fingolimod potentially decreases endothelial cell barrier integrity, which can lead to the development of macular edema.14 In a small study of 60 patients, Nolan et al showed that “74% of eyes in the fingolimod-treated group exhibited an increase in macular volume vs 37% of eyes in the comparison group.”15 In FREEDOMS II, a phase three clinical trial that took a more in-depth look at the side effect of ME via serial OCT and intravenous fluorescein angiography, 1.5% of patients treated with 0.5 mg fingolimod developed ME.14 The diagnosis of ME was typically made within the first three to four months of treatment initiation.4,14,16 Treatment options include discontinuing fingolimod or starting the patient on topical anti-inflammatory medications.16-18 In the majority of cases, ME resolved after the discontinuation of the drug.16 A case series by Ashfar et al and a case by Chiu et al demonstrated successful treatment of ME with a topical NSAID TID or QID and steroid BID (dosing may vary depending on how the patient responds).17,18 However, in Chiu et al’s case report, ME returned once the patient tapered off the anti-inflammatory drops and permanent resolution was achieved with fingolimod treatment cessation.18 The optometrist’s role in the management of patients on fingolimod treatment includes a baseline eye examination

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before or at the start of treatment, with a thorough dilated fundus examination as well as a macular OCT (spectral domain highly preferred). Thereafter, a follow up examination at three to four months after treatment initiation should be performed, or earlier if the patient has any visual symptoms.4,14 A repeat dilated fundus examination and macular OCT are warranted at the follow up exam, and treatment and consultation with neurology as indicated. A history of uveitis or diabetes may put the patient at greater risk of developing macular edema from fingolimod treatment, though they would not constitute an absolute contraindication.14 However, initiation of fingolimod treatment in a patient who currently has macular edema should be deferred.14 Although the incidence of fingolimod-associated ME is low (1.5%),14 it is important for the eye care provider to recognize the potential ocular side effect of this MS treatment drug. It offers optometrists the opportunity to participate in the interdisciplinary care of the patient, which will have a positive impact on the role of optometry in health care in the near future. As alluded to by the above case presentation, positioning difficulties at the OCT can become a challenge to monitoring macular edema for MS patients who are being treated with fingolimod. In that case, a careful dilated fundus examination, subjective visual acuity findings, and patient symptoms are the main factors to consider in suspecting macula edema. OCT in Multiple Sclerosis The analysis of the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis was first reported in 1974 by Frisen and Hoyt, who were able to subjectively analyze RNFL thinning through evaluation with a hand-held ophthalmoscope.19,20 Decades later, the advancement in technology enabled the OCT to be of immense value in objectively quantifying RNFL loss in multiple sclerosis patients,21-24 Optic neuritis is a common ocular manifestations of multiple sclerosis; it is often the first manifestation of the disease (in 20% of patients).11,25 Studies on RNFL analysis of MS patient with history of optic neuritis agree that there is temporal rim tissue thinning, which may help differentiate between other optic neuropathies, such as glaucoma and ischemic optic neuropathies.26-28 Early studies of RNFL in multiple sclerosis utilized earlier models (time domain) of OCT, such as the Zeiss Stratus. In 2005, Trip et al compared the RNFL thickness using Stratus OCT in patients' eyes that had a history of optic neuritis (MSON) and control patients.29 Though the sample size was small (n=40), MSON eyes were found to have statistically significantly thinner RNFL compared to controls (33% reduction).29 Even in the comparison between MSON eyes and the patients' unaffected fellow eyes, the RNFL was statistically significantly thinner in MSON eyes (27% reduction).29 In an earlier study in 1999

by Parisi et al with a first generation OCT, the results followed the same trends.30 Additionally, Trip et al looked at macular volume and found that there was a persistent lower macular volume in MS patients when analyzed against controls.29 Burkholder et al conducted a study between MS patients and controls, also analyzing the differences between the two groups in macular volume and RNFL thickness with Stratus OCT.31 The same conclusions were drawn from the study: the RNFL and macular volume was thinner and reduced, respectively, in MS patients compared to controls. It is a growing consensus among the studies that the retinal nerve fiber layer from the ganglion cells are measurably affected in the MS disease process. Furthermore, the measurable differences correlated with measures of visual dysfunction. Burkholder et al assessed visual function through testing low-contrast visual acuity and high-contrast visual acuity.31 Lower visual function was found to be associated with reduced macular volume, which is supported over different studies.31-33 Finding similar correlation of visual function to RNFL thickness, Fisher et al argues that it “support[s] validity for these visual function tests as secondary clinical outcome measures for MS trials.”32 Villoslada et al also illustrates that alterations in color vision is associated significantly with thinner RNFL.34 Since the spectral-domain OCT (SD-OCT) became commercially available in 2006, higher resolution retinal images could be obtained. Fjeldstad et al conducted a study comparing the RNFL and macular thickness with SD-OCT in patients with MS without a history of optic neuritis and healthy controls.35 Similar to the previous studies, RNFL and macular thickness were significantly decreased in MS patients.35 Ratchford et al utilized analyzed SD-OCT in their study and looked at ganglion cell layer/inner plexiform layer (GCIP) in additional to RNFL thickness.36 It was found that GCIP, which was measured from the macular cube scans, was a better predictor of MS activity than RNFL thinning.36 The study proposed that RNFL thickness may not be a good measurement of MS disease activity because it may be swollen in subclinical optic nerve inflammation; therefore, the RNFL thickness would be misinterpreted as normal.36 In fact, the researchers found that RNFL thickness was not significantly difference between MS patients' eyes and control eyes.36 The rate of MS activity was also not associated with RNFL thickness.36 On the other hand, GCIP thinning was accelerated in MS patients with disease activity.36 MS disease activity was measured by new T2 lesions, new gadolinium enhancing lesions, and non-optic neuritis relapses.36 Similarly, Saida et al found GCIP to be thinner in all forms of MS compared to healthy controls, with the secondary progressive form of MS having the thinnest GCIP.37 Similarly, RNFL and macular volume were also lower in the progressive form of MS.38 In addition, the study illustrated that GCIP thinning correlated with

various measures of reduced visual function and subjective disability.37 Analyzing the ganglion cells at the macula may be more reliable in detecting the degree of neurodegeneration in MS eyes.36,37,39,40 The implication of the previous studies mentioned is that OCT RNFL and macula analysis may become a possible alternative and/or adjunct to magnetic resonance imaging (MRI) to monitor disease activity in MS patients. Typically, an MRI that displays new gadolinium enhancing lesions and/or changes in T2/FLAIR (fluid attenuated inversion recovery) is a biomarker of MS activity.41 Grazioli et al demonstrated that "T2-lesion volume and NWMV (normalized white matter volumes) were significantly associated with average RNFL thickness."42 There is a definite correlation between RNFL and disease activity in MS, as measured by MRI.36,42,43 OCT is noninvasive, fast, and less expensive than MRI, making it an attractive alternative option. Furthermore, if the RNFL thickness and/or macular analysis are confirmed to be a reliable biomarker of MS activity, it may be useful in tracking the therapeutic efficacy of new treatments in MS clinical trials.44-47 Limitations would include any concurrent optic neuropathies and/or maculopathies that the patient could have as well as positioning difficulties at the machine.

CONCLUSION With the advent of OCT, the optometrist can have an increasingly important role in the management of patients with significant systemic diseases, such as in the case of patients with multiple sclerosis. Specifically, in this case, it allows more opportunities to co-manage patients with neurologists. Patients who are on fingolimod treatment should have a baseline eye exam with macular OCT and subsequent follow up examination in three-four months. OCT can also potentially be used to track neurodegeneration and even neuroprotection for MS. Furthermore, OCT may be applicable for other neurodegenerative diseases such as Alzheimer’s disease48 and Parkinson’s disease.49 ❏

REFERENCES 1. 2. 3. 4. 5. 6.

Kumar DR, Aslinia F, Yale SH, Mazza JJ. Jean-Martin Charcot: the father of neurology. Clin Med Res 2011; 9(1): 46-49. Jacobs DA, Galetta SL. Multiple sclerosis and the visual system. Ophthalmol Clin North Am 2004; 17(3): 265-273. Confavreux C, Vukusic S. The clinical course of multiple sclerosis. Handb Clin Neurol 2014; 122: 343-369. Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med 2012; 366(4): 339-347. Goodin DS. The epidemiology of multiple sclerosis: insights to disease pathogenesis. Handb Clin Neurol 2014; 122: 231-266. Weinshenker BG, Bass B, Rice GP, et al. The natural history of multiple sclerosis: a geographically based study. I. Clinical course and disability. Brain 1989; 112 (Pt 1): 133-146. Koch M, Kingwell E, Rieckmann P, Tremlett H. The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatr 2010; 81(9): 1039-1043. Adelman G, Rane SG, Villa KF. The cost burden of multiple sclerosis in the United States: a systematic review of the literature. J Med Econ 2013; 16(5): 639-647.

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9. 10.

11. 12. 13. 14. 15. 16. 17. 18. 19.

20. 21. 22.

23. 24. 25. 26.

27. 28. 29. 30.

Kobelt G, Berg J, Atherly D, Hadjimichael O. Costs and quality of life in multiple sclerosis: a cross-sectional study in the United States. Neurology 2006; 66(11): 1696-1702. Owens GM, Olvey EL, Skrepnek GH, Pill MW. Perspectives for managed care organizations on the burden of multiple sclerosis and the cost-benefits of disease-modifying therapies. J Manag Care Pharm 2013; 19(1 Suppl A): S41-S53. Chen L, Gordon LK. Ocular manifestations of multiple sclerosis. Curr Opin Ophthalmol 2005; 16(5): 315-320. Yeh EA, Weinstock-Guttman B. Fingolimod: an oral diseasemodifying therapy for relapsing multiple sclerosis. Adv Ther 2011; 28(4): 270-278. O'connor PW, Oh J. Disease-modifying agents in multiple sclerosis. Handb Clin Neurol 2014; 122: 465-501. Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology 2012; 78(9): 672-680. Nolan R, Gelfand JM, Green AJ. Fingolimod treatment in multiple sclerosis leads to increased macular volume. Neurology 2013; 80(2): 139-144. Zarbin MA, Jampol LM, Jager RD, et al. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology 2013; 120(7): 1432-1439. Afshar AR, Fernandes JK, Patel RD, et al. Cystoid macular edema associated with fingolimod use for multiple sclerosis. JAMA Ophthalmol 2013; 131(1): 103-107. Chui J, Herkes GK, Chang A. Management of fingolimodassociated macular edema. JAMA Ophthalmol 2013; 131(5): 694-696. Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter G, Balcer LJ. Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol 2008; 4(12): 664-675. Oliveira C, Cestari DM, Rizzo JF. The use of fourth-generation optical coherence tomography in multiple sclerosis: a review. Semin Ophthalmol 2012; 27(5-6): 187-191. Frohman E, Costello F, Zivadinov R, et al. Optical coherence tomography in multiple sclerosis. Lancet Neurol 2006; 5(10): 853-863. Costello FE, Klistorner A, Kardon R. Optical coherence tomography in the diagnosis and management of optic neuritis and multiple sclerosis. Ophthalmic Surg Lasers Imaging 2011; 42(Suppl): S28-S40. Petzold A, De boer JF, Schippling S, et al. Optical coherence tomography in multiple sclerosis: a systematic review and metaanalysis. Lancet Neurol 2010; 9(9): 921-932. Kallenbach K, Frederiksen J. Optical coherence tomography in optic neuritis and multiple sclerosis: a review. Eur J Neurol 2007; 14(8): 841-849. Sørensen TL, Frederiksen JL, Brønnum-Hansen H, Petersen HC. Optic neuritis as onset manifestation of multiple sclerosis: a nationwide, long-term survey. Neurology 1999; 53(3): 473-478. Bock M, Brandt AU, Dörr J, et al. Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 2010; 112(8): 647-652. Costello F. Evaluating the use of optical coherence tomography in optic neuritis. Mult Scler Int 2011; 2011: 148394. doi: 10.1155/2011/148394. Epub 2011 Mar 22. Pasol J. Neuro-ophthalmic disease and optical coherence tomography: glaucoma look-alikes. Curr Opin Ophthalmol 2011; 22(2): 124-132. Trip SA, Schlottmann PG, Jones SJ, et al. Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 2005; 58(3): 383-391. Parisi V, Manni G, Spadaro M, et al. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999; 40(11): 2520-2527.

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31. Burkholder BM, Osborne B, Loguidice MJ, et al. Macular volume determined by optical coherence tomography as a measure of neuronal loss in multiple sclerosis. Arch Neurol 2009; 66(11): 1366-1372. 32. Fisher JB, Jacobs DA, Markowitz CE, et al. Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006; 113(2): 324-332. 33. Bock M, Brandt AU, Kuchenbecker J, et al. Impairment of contrast visual acuity as a functional correlate of retinal nerve fibre layer thinning and total macular volume reduction in multiple sclerosis. Br J Ophthalmol 2012; 96(1): 62-67. 34. Villoslada P, Cuneo A, Gelfand J, Hauser SL, Green A. Color vision is strongly associated with retinal thinning in multiple sclerosis. Mult Scler 2012; 18(7): 991-999. 35. Fjeldstad C, Bemben M, Pardo G. Reduced retinal nerve fiber layer and macular thickness in patients with multiple sclerosis with no history of optic neuritis identified by the use of spectral domain high-definition optical coherence tomography. J Clin Neurosci 2011; 18(11): 1469-1472. 36. Ratchford JN, Saidha S, Sotirchos ES, et al. Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning. Neurology 2013; 80(1): 47-54. 37. Saidha S, Syc SB, Durbin MK, et al. Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness. Mult Scler 2011; 17(12): 1449-1463. 38. Pulicken M, Gordon-lipkin E, Balcer LJ, Frohman E, Cutter G, Calabresi PA. Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007; 69(22): 2085-2092. 39. Warner CV, Syc SB, Stankiewicz AM, et al. The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials. PLoS ONE 2011; 6(8): e22947. 40. Serbecic N, Aboul-enein F, Beutelspacher SC, et al. HighResolution Spectral Domain-Optical Coherence Tomography in Multiple Sclerosis, Part II - the Total Macular Volume. The First Follow-Up Study over 2 Years. Front Neurol 2014; 5: 20. 41. Sicotte NL. Neuroimaging in multiple sclerosis: neurotherapeutic implications. Neurotherapeutics 2011; 8(1): 54-62. 42. Grazioli E, Zivadinov R, Weinstock-guttman B, et al. Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis. J Neurol Sci 2008; 268(1-2): 12-17. 43. Siger M, Dziegielewski K, Jasek L, et al. Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy. J Neurol 2008; 255(10): 1555-1560. 44. Sergott RC, Frohman E, Glanzman R, Al-sabbagh A. The role of optical coherence tomography in multiple sclerosis: expert panel consensus. J Neurol Sci 2007; 263(1-2): 3-14. 45. Green AJ. Getting beyond the ganglion cell: morphometric adjustments for retinal optical coherence tomography in multiple sclerosis. JAMA Neurol 2013; 70(1): 13-15. 46. Costello F, Van stavern GP. Should optical coherence tomography be used to manage patients with multiple sclerosis? J Neuroophthalmol 2012; 32(4): 363-371. 47. Lidster K, Baker D. Optical coherence tomography detection of neurodegeneration in multiple sclerosis. CNS Neurol Disord Drug Targets 2012; 11(5): 518-527. 48. Paquet C, Boissonnot M, Roger F, Dighiero P, Gil R, Hugon J. Abnormal retinal thickness in patients with mild cognitive impairment and Alzheimer's disease. Neurosci Lett 2007; 420(2): 97-99. 49. Satue M, Seral M, Otin S, et al. Retinal thinning and correlation with functional disability in patients with Parkinson's disease. Br J Ophthalmol 2014; 98(3): 350-355.

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COPE-APPROVED CE CREDIT APPLICATION FORM

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QUESTIONNAIRE Recent Developments in the Optometric Co-Management of Multiple Sclerosis Patients Alice Au, OD; Pauline F. Ilsen, OD, FAAO 1. ❑ ❑ ❑ ❑

What percentage of multiple sclerosis patients have the relapsing form of the condition at onset? 25% 50% 75% 85%

2. ❑ ❑ ❑ ❑

In the Case Report presented, the patient’s medical history was significant for all the following conditions, EXCEPT: Multiple sclerosis Osteoarthritis Hypertension Hyperlipidemia

3. ❑ ❑ ❑ ❑

All of the following clinical findings describe the patient at initial presentation, EXCEPT: Nystagmus OD No afferent pupil defect Pupils were equal, round and reactive to light Mild meibomian gland dysfunction

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What were the patient’s visual acuities at five-month follow-up? 6/12+ (20/40+) OD; 6/6- (20/20-) OS 6/15 (20/50) OD; 6/6 (20/20) OS 6/21 (20/70) OD; 6/15 (20/50) OS 6/24 (20/80) OD; 6/19 (20/63) OS

In the FREEDOM and TRANSFORMS trials, what was the incidence of side effects found with fingolimod 0.5 mg? 0.2% 0.4% 0.5% 0.6%

❑ ❑ ❑ ❑ 6. ❑ ❑ ❑ ❑ 7.

According to Nolan et al, what percentage of eyes in the fingolimod-treated group exhibited an increase in macular volume vs. 37% of eyes in the comparison group? 28% 52% 65% 74%

❑ ❑ ❑ ❑

For patients on fingolimod treatment, in the absence of visual symptoms, at what point should the first follow-up after treatment initiation occur? One to two months Three to four months Five months Six months

8. ❑ ❑ ❑ ❑

Optic neuritis is the first manifestation of multiple sclerosis in what percentage of patients? 10% 20% 25% 30%

In FREEDOMS II, what percentage of patients treated with 0.5 mg fingolimod developed macular edema? 0.2% 1.2% 1.5% 2.3%

❑ ❑ ❑ ❑

10. Approximately what percentage of multiple sclerosis patients will need a cane for assistance within 15 years of onset, if left untreated? ❑ 25% ❑ 30% ❑ 40% ❑ 50%

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Clinical & Refractive Optometry: Online Edition is pleased to present this continuing education (CE) article by Dr. Paul Varner entitled Clinical Grading of Nuclear Sclerotic Cataracts. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 144 for complete instructions.

Clinical Grading of Nuclear Sclerotic Cataracts Paul Varner, OD, MPH

ABSTRACT Importance: Widespread clinical use of grading scales facilitates patient care. Many cataract classification schema have been proposed, but without universal acceptance. Purpose: To discern why there is no consensus for grading nuclear sclerotic cataracts (NSC). Method: A NSC grading method involving anterior and posterior segment correlation was developed for clinical use. Results: This correlation method for grading NSC failed initial standardization testing. Conclusion: Current macroscopic, NSC grading scales appear unable to account for microscopic, lenticular variations, and are not useful clinically. Relevance: Newer technology will be required to achieve objective assessment for NSC.

CLINICAL GRADING OF NUCLEAR SCLEROTIC CATARACTS Cataract remains the leading ophthalmic disease in the 21st century. Worldwide it is still the foremost cause of blindness.1 Lens and cataract procedures are the most common surgeries performed globally2 and in the US,3 and are some of the leading surgical procedures undertaken in Canada.4 Yet for such a ubiquitous ophthalmic finding, there continues to be a lack of clinical consensus regarding how to grade or classify this common entity. The need for a common ground becomes apparent on a daily basis as patients’ descriptions of “cataracts” often do not agree with those of clinicians, who in turn do not agree among themselves. P. Varner — John J. Pershing VA Medical Center, Poplar Bluff, MO Correspondence to: Dr. Paul Varner, John J. Pershing VA Medical Center, 1500 N. Westwood Blvd., Poplar Bluff, MO USA 63901; E-mail: paul.varner@va.gov Dr. Varner reports no financial conflicts of interest. The views expressed in this article are those of the author and do not necessarily represent the position of the US Department of Veterans Affairs. This article has been peer-reviewed.

The importance of objective clinical grading in medicine includes: allowance for determination of progression in clinical and pharmaceutical trials, professional concurrence in cases of litigious or disability claims, improved patient education (especially for those who move between multiple clinicians), and clearer communication between providers regarding clinical findings. This final point is especially important in the ophthalmic world where optometrists often identify patients with cataracts and then refer cases to comprehensive ophthalmologists for surgical correction. It is therefore incumbent upon optometrists and noncomprehensive ophthalmologists to correctly differentiate surgical lenses from non-surgical ones and to succinctly communicate these findings to the operating surgeons in order to streamline the referral process and to ensure that surgical procedures are obtained in the most timeeffective fashion. This is even more critical in parts of the world where access to health care is limited and surgical resources are limited. Visual acuities are the most widely-used test for visual function,5 but do not wholly assess visual disability related to cataracts,6,7 and — as a subjective test — can be tempered by depression, mood and anxiety.8,9 Ideally, a quantitative system would be used to control for subjective influence of both patients and examiners, and to remove qualitative interpretation from this process. In fact many grading systems have been developed in an attempt to standardize descriptions of the various types of cataracts, both in vitro10-13 and in vivo. For the latter case there are several subjective and objective methods described for assessment in the clinic (Table I14-34). To date, no “preferred” grading system has emerged from the ophthalmic community regarding usage of any of these scales. Description of mixed lenticular opacities as N02/NC3/C2 according to LOCS III criteria, for example, is not part of the lingua franca of the ophthalmic world outside research settings.

WHY IS THERE NO CONSENSUS? The answer to this seemingly innocuous question is surely multifactorial and involves any or all of the following components.

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Table I Cataract grading scales Subjective Methods

Date

Via

Oxford Clinical Cataract Classification and Grading System Johns Hopkins (Wilmer) Grading System Color Matching Technique New Dehli Cataract Classification Lens Opacity Rating System Japanese Cooperative Cataract Epidemiology Study Group Wisconsin System for Classification of Cataracts Lens Opacities Classification System (LOCS) III Age-Related Eye Disease Study (AREDS) System World Health Organization (WHO) Simplified Cataract Grading System

1986 1988 1988 1989 1989 1989 1990 1993 2001 2002

Slit lamp & diagrams14 Slit lamp & photographs15 Slit lamp & color samples16 Slit lamp & direct ophthalmoscope17 Slit lamp & photographs18 Slit lamp & photographs19,20 Photograph & standard photos21 Slit lamp & standard photos22 Photographs & standard photos (AREDS)23 Slit lamp & standard photographs24

National Eye Institute (NEI) Scheimpflug Cataract Imaging System Lens Opacity Meter Oxford Modular Cataract Image Analysis System (Case 2000 CCD Method)

1987 1990 1990

Digital Analyzer Lens Absorption Monitor Modified NEI Scheimpflug Cataract Imaging System Laser Slit Lamp Method Anterior Segment Optical Coherence Tomography Computer-Aided Nuclear Cataract Diagnosis System Optical Quality Analysis System

1991 1993 1993 1999 2009 2010 2011

Lens densitometry25 Modulated light source26 Slit lamp & retro-illuminated photos, computer-graded lenticular auto-fluorescence images27 Anterior segment camera/computer28 Video-based images29 Lens densitometry30 Laser slit lamp digital images31 Lens density measurement32 Computer-graded slit lamp images33 Double-pass measure of optical aberrations and light scatter34

Objective Methods

No cataract grading scale has proven to be generalizable. Providers seem unable to agree on the clinical grading of cataract. Inter-observer reliability for grading cataracts has been studied, but found to be poor.35,36 This is unfortunate, considering that confirming inter-observer reliability for cataract evaluation is expensive and time-consuming.37 Head-to-head comparison of subjective grading methods has found both correlation38,39 and poor agreement40 between various scales in the clinical setting. Adequate agreement between subjective and objective classification systems has also been reported in clinical setting,41 although has not translated into widespread professional consensus.

Cataractogenesis remains enigmatic and inevitable. Currently, the exact nature of cataractogenesis remains poorly understood.42 The eye’s lens thickens and turns yellow with age, eventually progressing to opacification (i.e., cataractogenesis).43,44 Cataract development is an unavoidable part of “aging” and will eventually develop in all humans whose longevity permits the natural course of events to unfold. As such perhaps there is little financial impetus to study the natural course of the disease.

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There is no prophylactic treatment against cataract formation, and the only treatment that is available is very successful. There is no prophylactic intervention proved to deter cataract development.44,45 Unlike many other ophthalmic conditions, there is currently only one treatment available for cataracts: surgical removal with prosthetic lens implantation.46 This highly-successful procedure has a 95% success rate, with a 0.001% risk of permanent vision loss.47 With such successful outcomes, cataract surgery is being performed at earlier stages in the disease,7,48 even for “clear-lens” extractions. It is possible that clinicians feel that this situation precludes the wide-spread need for accurate clinical assessment by formalized grading systems (i.e., it’s not a 6/6 (20/20) lens, it can be fixed surgically, end of story).

Cataract is not difficult to understand — no need to complicate the matter. Perhaps cataracts are so ubiquitous and conceptually easy to understand that that the topic is overlooked in the interest of teaching complexities of cornea, glaucoma, uveitis and retinal disease to trainees within the constraint of curricular demands. It is not unexpected that more time is

while some individuals with better vision/moreobvious cataract show little subjective visual improvement following lens extraction/implantation procedures. After a review of the above confounders surrounding cataract evaluation, it should not be surprising that clinical grading scales are not widely used. There is no easy answer to the initial question of why consensus has not been achieved for grading cataracts, and this conundrum has not been specifically addressed in the ophthalmic literature to date.

BACK TO BASICS Fig. 1 White nuclear sclerotic cataract (NSC)

devoted to refraction and contact lens fitting techniques than objective grading scales for cataract. 5.

Unavailability of technology for grading systems. Some objective grading systems rely on photographic or ancillary technology that is not widely available. Unlike automated perimeters or ocular coherence tomographs, Scheimpflug (algorithm for correcting distortions in photographs) and other computer-based technologies used in cataract research are not widely available or used in clinical settings.

Psychometric effects of grading scales. Perhaps proposed grading scales are too coarse for accurate interpretation by clinicians. In the absence of evenlyspaced benchmarks, finer scaling may be required to attain meaningful clinical grading of cataracts.49

Clinical non-correlation of lenticular opacities to visual acuity. Or is non-consensus in grading cataracts due to inconsistencies apparent in correlating lenticular opacities with best-corrected visual acuities? All clinicians have seen best visual acuities that do not correlate well with lenticular opacities (in the absence of other ophthalmic pathology). Occasional patients with advanced lenticular opacities still retain moderately “good” vision, while others with minimal cataract have unexpectedly-poor visual acuity — even considering the psychological state of the patient8,9 — regardless of the grading scale used to evaluate these subjects. It is a frustration to all clinicians when patients with poorer visual acuity/minimal lenticular opacities are found to have greatly improved vision following cataract surgery;

Although seemingly trivial, it is important to remember what a cataract is and is not. A cataract is an opacity of the lens.43,44,50 There are several types of lens opacities, with nuclear sclerotic, posterior subcapsular and cortical varieties being the most common clinically.24 In general, posterior subcapsular and cortical cataracts do not seem clinically difficult to describe — either the opacities are on-axis and visually-significant (symptomatic to patients) or off-axis and visually-insignificant (asymptomatic to patients). Subjective patient symptoms, best-corrected visual acuities and the degree of lens opacities correlate well enough clinically as to prevent frequent miscommunication between patients and providers for the management of these types of lenticular opacities. However, the continuum of nuclear sclerosis and nuclear sclerotic cataracts (NSC) is not so clear-cut. Nuclear sclerosis (i.e., hardening and loss of pliability of lens fibers) is a senescent process that is very commonly associated with yellow discoloration of the lens. The appearance of yellowing of the lens nucleus is readily apparent long before there is an effect on visual acuity or other measures of visual function: binocularity, contrast sensitivity, color desaturation, motion threshold, visual field, etc. It should be emphasized that varying degrees of nuclear sclerospresence of 6/6 (20/20) visual acuity (VA) should not be termed a “cataract.”44 The term cataract is only appropriate when opacification of the lens precludes 6/6 (20/20) VA, the most commonly used clinical measure of visual function. When not accompanied by opacification, nuclear sclerosis is simply an incidental, normal, age-related exam finding. (Advising patients with 6/6 (20/20) VA and nuclear sclerosis that they have “cataracts” — and the psychological implications of this practice for patients — is beyond the scope of this discussion, but is encountered on a daily basis in some patient populations.) It is equally important to recall that nuclear sclerosis is not always associated with yellowing of the lens. “White cataracts” (Fig. 1) occur with opacification of the lens nucleus in the absence of lens discoloration, and, in

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NS Cataract Grading Scale 6/6 (20/20)

6/12 (20/40)

6/24 (20/80)

Clear Pseudophkic, or trace NS

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6/48 (~20/150)

6/120 (~20/400)

>6/120 (>20/400)

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3+ NSC

4+ NSC

Mature Cataract

Fig. 2 Correlated anterior/posterior segment grading scale (representative views from right eyes purposely rotated 180 degrees to maintain consistent views for grading purposes)

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Fig. 3 Paradoxical correlation between lenticular opacity and fundus view

early stages, can be easily overlooked when evaluating a patient with subjective visual symptoms, decreased visual acuities, and a seemingly normal ocular health examination. Conversely, lens brunescence is more readily clinically apparent as a brown-colored appearance of the lens — an atypical form of nuclear sclerosis. The extreme presentations of white, yellow or brunescent lenticular opacities are often described as a “mature cataract.” Early stages of these variant clinical presentations may offer paradoxical challenges to clinicians accustomed to the clinical picture of typical lenticular yellowing and nuclear sclerotic opacification.

IS THERE A BETTER CLINICAL SOLUTION? Non-use of available subjective or objective cataract grading scales suggests an unanswered clinical problem, and opens the possibility of development a new clinicallyrelevant grading scale. Perhaps the answer is a grading scale that includes the appearance of lenticular opacities within the context of ocular fundus views. Figure 2 provides a chart correlating visual acuities, anterior segment photos of different degrees of nuclear sclerotic opacities, the corresponding fundus views taken through those same lenticular opacities, and an equivalent grade. For these images, all eyes either had 6/6 (20/20) VA prior to the development of lens opacities or attained 6/6 (20/20) VA postoperatively following cataract extraction procedures. All vertical columns are intended to be interchangeable: that is, a grade of 2+ NSC should correspond to approximately 6/24 (20/80) VA and the depicted view of the fundus; or a patient with roughly 6/24 (20/80) VA and the associated fundus view would be expected to have lenticular opacities consistent with the picture of grade 2+ NSC. (Incidentally, grades of “2” or “2-” (“two minus”) are not routinely used in medicine. The reasons may be lost to time, but it could be surmised that use of the + superscript was a quick way to distinguish handwritten

numbers from letters, and to prevent errors related to poor penmanship.) The gradations (e.g., 1+ to 2+) are intended to reflect a doubling of the visual angle [e.g., 6/12 (20/40) to 6/24 (20/80)]. It should be emphasized, based on this algorithm, that if there is no direct correlation between best-corrected visual acuity (BCVA) and the degree of lenticular opacity, then the cause for decreased VA should not be solely ascribed to “cataract.” The aim is to create a consistent measure of lens opacity and its effect on visual acuity. Thus a provider should be able to predict BCVA based on lenticular or fundus appearance and vice versa, and the matching grade assigned to a case would provide a standard for communication. Ultimately, this anterior segment-posterior segment, correlated grading scale failed to provide a consistent evaluation of nuclear cataracts during preliminary use. Many exceptions to these gradations were immediately revealed during initial applications of the scale, and it was quickly discovered that many lenticular opacities remain inconsistent with reported visual acuities. Figure 3 provides an example of a case with what should be a 3+ NSC lens, but with reasonable fundus view and visual acuity of 6/12 (20/40). Because lens grading and fundus views did not show a consistent relationship with best-corrected visual acuity, this grading scale also failed to provide a useful clinical tool, and must, too, be relegated to the growing pool of ineffective cataract grading scales.

DISCUSSION It may be inferred that the reason for the discrepancies found for this cataract grading method rests in the microscopic variations found within the lens matrices. Microscopic morphological features such as waterclefts, vacuoles and retrodot opacities have the potential to degrade vision,51 although they may not be readily apparent via biomicroscopy. Higher-order optical aberrations are not directly “observable” during clinical examination, but their presence may also explain non-correlation of subjective, “poorer” visual acuities with clinical examination of the lens.52-54 As lens opacification develops, it is likely an irregular process on the microscopic level of the lens proteins. It may be conjectured that tiny, clear areas remain juxtaposed to opaque ones, resulting in localized pinhole effects that are unobservable by direct examination. Thus, random irregularities within the opacified lens proteins may create optical pinhole effects, which account for visual acuities that are “better” than would be predicted based strictly on biomicroscopic observation of the lenses themselves. Conversely, mildly opacities directly obscuring the eye’s nodal points may result in a VA “worse” than

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might be predicted by direct lens and fundus observations. In the final analysis, it may be surmised that the lack of clinical consensus on existing cataract grading scales is a culmination of lenticular factors at the microscopic level, and may serve to answer the question “why aren’t published grading scales used widely in clinical settings?” Surely future grading systems may redefine cataract in terms of events at the microscopic — rather than macroscopic — level.

CONCLUSION Perhaps a re-formulation of the question at hand is indicated: Are reliable cataract grading scales achievable for clinical use? Given the limits of current cataract grading scales, it appears that clinicians will require newer technology to objectively quantify lens opacification. Recently, use of an Objective Scatter Index was reported to correlate with severity of cataract and visual acuity.7 This technology quantifies optical aberration and light scatter in an objective way. Future study will determine if this method provides sound clinically-useful data. Scanning laser algorithms, aberrometry, and optical coherence tomographs, or a combination of these technologies, are possible avenues for future exploration, although there currently seems to be little incentive to drive these research questions. As such, at least for the present, it appears that reliable quantification of NSC will remain elusive due to higher-order aberrations and localized pinhole effects within lens protein matrices. Ultimately, we are left with a clinical challenge. Clinicians should be aware of these shortcomings in their attempts to quantify and communicate severity of nuclear sclerotic cataracts. Providers must continue to critically view lenticular opacities, but must still consider subjective reports of visual disability to guide decisions of ophthalmic surgical care. ❏ Acknowledgements: The author would like to thank Antonia Varner for the preparation of the Figures and Table.

REFERENCES 1.

World Health Organization. Visual impairment and blindness. 2013. http://www.who.int/mediacentre/ factsheets/ fs282/en/. Accessed 01 Jul 2014. Kohnen T, Baumeister M, Kook D, et al. Cataract surgery with implantation of an artificial lens. Dtsch Arzteblt Int 2009; 106: 695-702. US Department of Health & Human Services, Agency for Healthcare Research and Quality (AHRQ). Ambulatory surgery in US hospitals, 2003. http://www.ahrq.gov/data/ hcup/factbk9/factbk9b.htm. Accessed 01 Jul 2014. Canadian Institute for Health Information. Waiting for health care in Canada: what we know and what we don't know. 2006. http://secure.cihi.ca/cihiweb/products/ WaitTimesReport_06_e.pdf. Accessed 07 Feb 2014.

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Arditi A, Cagenello R. On the statistical reliability of letterchart visual acuity measurements. Invest Ophthalmol Vis Sci 1993; 34: 120-129. Phelps Brown NA. The morphology of cataract and visual performance. Eye 1993; 7: 63-67. Cabot F, Saad A, Mcalinden C, et al. Objective assessment of crystalline lens opacity level by measuring ocular light scattering with a double pass system. Am J Ophthalmol 2013; 155: 629-635. Brody BL, Gamst AC, Wliliams RA, et al. Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration. Ophthalmology 2011; 108: 1893-1901. Eramudugolla R1, Wood J, Anstey KJ. Co-morbidity of depression and anxiety in common age-related eye diseases: a population-based study of 662 adults. Front Aging Neurosci 2013 Oct 2; 5: Article 56. Pirie A. Color and solubility of the proteins of human cataracts. Invest Ophthalmol 1968; 7: 634-650. Chylack LT. Classification of human cataracts. Arch Ophthalmol 1978; 96: 888-892. Marcantonio JM, Duncan G, Davies PD, Bushnell AR. Classification of human senile cataracts by nuclear colour and sodium content. Exp Eye Res 1980; 31: 227-237. Duncan G. On classifying human cataractous lenses. In: Mechanisms of cataract formation in the human lens. Duncan G, ed. London: Academic Press, 1981: 1-5. Sparrow JM, Bron AJ, Brown NA, et al. The Oxford clinical cataract classification and grading system. Int Ophthalmol 1986; 9: 207-225. Taylor HR, West SK. A simple system for the clinical grading of lens opacities. Lens Res 1988; 5: 175. Sparrow JM, Hill AR, Ayliffe W, et al. Human lens nuclear colour matching and brunescence grading in vivo. Int Ophthalmol 1988; 11: 139-149. Sharma YR, Vajpayee RB, Bhatnagar R, et al. A simple accurate method of cataract classification: Cataract I. Indian J Ophthalmol 1989; 37: 112-117. Laties A, Keates E, Lippa E, et al. Field test reliability of a new lens opacity rating system utilizing slit-lamp examination. Lens Eye Toxic Res 1989; 6: 443-464. Sasaki K, Shibata T, Obazawa H, et al. [A cataract classification and grading system]. Nihon Ganka Gakkai Zasshi 1989; 93: 796-800. Sasaki K, Shibata T, Obazawa H, et al. Classification system for cataracts: application by the Japanese Cooperative Cataract Epidemiology Study Group. Ophthalmic Res 1990; 22 Suppl 1: 46-50. Klein BEK, Magli YL, Neider MW, Klein R. Wisconsin System for Classification of Cataracts from Photographs. Madison, WI: University of Wisconsin-Madison; 1990:1-30. Available from National Technical Information Service, Springfield, VA; NTIS Accession No. PB 90-138306. Sponsored by the US Department of Commerce. Chylack LT, Wolfe JK, Singer DM, et al. The lens opacities classification system III. Arch Ophthalmol 1993; 111: 831-836. Age-Related Eye Disease Study Group. The Age-Related Disease Study (AREDS) system for classifying cataracts from photographs: AREDS report no. 4. Am J Ophthalmol 2001; 131: 167-175. Thylefors B, Chylack LT Jr, Konyama K, et al. A simplified cataract grading system. Ophthalmic Epidemiol 2002; 9: 83-95.

25. Datiles MB, Edwards PA, Trus BL, Green SB. In vivo studies on cataracts using the Scheimpflug slit lamp camera. Invest Ophthalmol Vis Sci 1987; 28: 1707-1710. 26. Flammer J, Bebie H. Lens opacity meter: a new instrument to quantify lens opacity. Ophthalmologica 1987; 195: 69-72. 27. Sparrow JM, Phelps Brown NA, Shun-Shin GA, Bron AJ. The Oxford modular cataract image analysis system. Eye 1990; 4: 638-648. 28. Adamsons I, Taylor KI, Enger C, Taylor HR. A new method for documenting lens opacities. Am J Ophthalmol 1991; 111: 65-70. 29. Johnson CA, Howard DL, Marshall D, Shu H. A noninvasive video-based method for measuring lens transmission properties of the human eye. Optom Vis Sci 1993; 70: 944-955. 30. Vivino MA, Chintalagiri S, Trus B, Datiles M. Development of a Scheimpflug slit lamp camera system for quantitative densitometric analysis. Eye 1993; 7: 791-798. 31. Hall NF, Lempert P, Shier RP, et al. Grading nuclear cataract: reproducibility and validity of a new method. Br J Ophthalmol 1999; 83: 1159-1163. 32. Wong AL, Leung CK-S, Weinreb RN, et al. Quantitative assessment of lens opacities with anterior segment optical coherence tomography. Br J Ophthalmol 2009; 93: 61-65. 33. Li H, Lim JH, Mitchell P, et al. A computer-aided diagnosis system of nuclear cataract. IEEE Trans Biomed Eng 2010; 57: 1690-1698. 34. Vilaseca M, Romero MJ, Arjona M, et al. Grading nuclear, cortical and posterior subcapsular cataracts using an objective scatter index measured with a double-pass system. Br J Ophthalmol 2012; 96: 1204-1210. 35. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham eye study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration and visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol 1980; 24(Suppl): 335-610. 36. West S, Rosenthal F, Newland HS, Taylor HR. A comparison of methods for typing and grading lens opacities for field surveys. ARVO Abstracts. Invest Ophthalmol Vis Sci 1985; 26: 119. 37. West SK, Rosenthal F, Newland HS, Taylor HR. Use of photographic techniques to grade nuclear cataracts. Invest Ophthalmol Vis Sci 1988; 29: 73-77. 38. Taylor HR, Lee JA, Wang F, Muñoz B. A comparison of two photographic system for grading cataract. Invest Ophthalmol Vis Sci 1991; 32: 529-532. 39. Hall AB, Thompson JR, Deane JS, Rosenthal AR. LOCS III versus the Oxford Clinical Cataract Classification and Grading System for the assessment of nuclear, cortical and posterior subcapsular cataract. Ophthalmic Epidemiol 1997; 4: 179-194.

40. Tan ACS, Wang JJ, Lamoureux EL, et al. Cataract prevalence varies substantially with assessment systems: comparison of clinical and photographic grading in a population-based study. Ophthalmic Epidemiol 2011; 18: 164-170. 41. Robman LD, McCarty CA, Garrett SKM, et al. Comparison of clinical and digital assessment of nuclear optical density. Ophthalmic Res 1999; 31: 119-126. 42. Andjeli S, Hawlina M. Cataractogenesis. Zdrav Vestn Suppl (Slovenian Medical Journal) 2012; 1: I122-I132. 43. Hart WM, ed. Adler’s Physiology of the Eye. St Louis: Mosby-Year Book, Inc, 1992: 348. 44. Snell RS, Lemp MA. Clinical Anatomy of the Eye. Boston: Blackwell Scientific Publications, 1989: 184. 45. Robin AL, Thulasirag RD. Cataract blindness. Arch Ophthalmol 2012; 130: 1452-1455. 46. de Silva SR, Riaz Y, Evans JR. Phacoemulsification with posterior chamber intraocular lens versus extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens for age-related cataract. Cochrane Database Syst Rev. 2014, Issue 1. Art. No.: CD008812. DOI: 10.1002/ 14651858. CD008812.pub2. 47. National Health Service. Cataract surgery. 2013. http://www.nhs.uk/Conditions/Cataract-surgery/Pages/ Results.aspx. Accessed 07 Feb 2014. 48. Klein BEK, Howard KP, Lee KE, Klein R. Changing incidence of lens extraction over 20 years. Ophthalmology 2014; 121: 5-9. 49. Bailey IL, Bullimore MA, Raasch TW, Taylor HR. Clinical grading and the effects of scaling. Invest Ophthalmol Vis Sci 1991; 32: 422-432. 50. Duke-Elder, S. System of Ophthalmology, Vol XI. St Louis: The CV Mosby Company, 1969: 63. 51. Holden R, Hesler J, Forbes J, Phelps Brown NA. Visual performance and objectively measured grades of cataract. A correlation of methods designed for use in longitudinal trials. Optom Vis Sci 1993; 70: 982-985. 52. Donnelly WJ 3rd, Pesudovs K, Marsack JD, et al. Quantifying scatter in Shack-Hartmann images to evaluate nuclear cataract. J Refract Surg 2004; 20: S515-S522.53. Rocha KM, Nosé W, Bottós K, et al. Higher-order aberrations of age-related cataract. J Cataract Refract Surg 2007; 33: 1442-1446.54. Lee J, Kim MJ, Tchah H. Higher-order aberrations induced by nuclear cataract. J Cataract Refract Surg 2008; 34: 2104-2109. 53. Rocha KM, Nosé W, Bottós K, et al. Higher-order aberrations of age-related cataract. J Cataract Refract Surg 2007; 33: 1442-1446. 54. Lee J, Kim MJ, Tchah H. Higher-order aberrations induced by nuclear cataract. J Cataract Refract Surg 2008; 34: 21042109.

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QUESTIONNAIRE Clinical Grading of Nuclear Sclerotic Cataracts Paul Varner, OD, MPH 1. ❑ ❑ ❑ ❑

What is the foremost cause of blindness worldwide? Glaucoma Cataract Macular edema Stroke

2. ❑ ❑ ❑ ❑

All of the following statements are true, EXCEPT: Cataract is an unavoidable part of “aging” A recently-developed grading scale for cataracts has proved to be generalizable There is no prophylactic treatment against cataract formation Visual acuities are the most widely-used test for visual function

Surgical cataract removal with prosthetic lens implantation has been successful in what percentage of patients? 60% 75% 80% 95%

❑ ❑ ❑ ❑

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❑ ❑ ❑ ❑

What is the risk of permanent vision loss with surgical cataract removal with prosthetic lens implantation? 0.001% 0.003% 0.05% 0.5%

5. ❑ ❑ ❑ ❑

All of the following statements about cataract are true, EXCEPT: Yellowing of the lens nucleus is apparent long before visual acuity is affected Nuclear sclerosis is associated with yellowing of the lens in 100% of cases Nuclear sclerosis is not always associated with yellowing of the lens “Mature cataracts” may have extreme presentations of white lenticular opacities

6. ❑ ❑ ❑ ❑

All of the following are evidence of cataract, EXCEPT: Family history of the condition Best-corrected visual acuities Subjective patient symptoms The degree of lens opacities

7. ❑ ❑ ❑ ❑

All of the following objective methods for assessment in the clinic used lens densitometry or lens density measurement, EXCEPT: National Eye Institute (NEI) Scheimpflug Cataract Imaging System Modified NEI Scheimpflug Cataract Imaging System Digital Analyzer Anterior Segment Optical Coherence Tomography

8. ❑ ❑ ❑ ❑

What are the most common surgeries performed globally? Coronary bypass Hip replacement Coronary stents Lens and cataract procedures

9. ❑ ❑ ❑ ❑

All of the following statements about cataract are true, EXCEPT: Agreement between subjective and objective classification systems has been inadequate Inter-observer reliability for grading cataracts has been found to be poor Visual acuities do not wholly assess visual disability related to cataracts Unavailability of technology for grading systems has been an impediment

10. According to the paper, visual acuities can be tempered by all of the following, EXCEPT: ❑ Depression ❑ Medication ❑ Anxiety ❑ Mood

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Clinical & Refractive Optometry: Online Edition is pleased to present this continuing education (CE) article by Dr. Adam T. Gorner and Dr. Leonid Skorin Jr. entitled Dragged Fovea Diplopia Syndrome After Epiretinal Membrane Peel Surgery. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 152 for complete instructions.

Dragged Fovea Diplopia Syndrome After Epiretinal Membrane Peel Surgery Adam T. Gorner, OD; Leonid Skorin Jr., OD, DO, MS

ABSTRACT Background: Dragged fovea diplopia syndrome is a condition involving intractable binocular diplopia associated with macular pathology often involving epiretinal membrane and macular pucker. The prevalence of this condition is unknown. There is no known cure for this condition but effective treatment for the symptoms is available. Case Reports: Two cases of intractable central binocular diplopia of 2 to 3 years’ duration that were not correctable with prism are presented. Both patients had a history of epiretinal membrane and had undergone membrane peel with vitrectomy. No extraocular muscle dysfunction or paresis was evident in either patient. Both responded favorably to partial monocular occlusion with semitransparent tape. Conclusion: Dragged fovea diplopia can be extremely frustrating for both patients and doctors. An understanding of this condition will allow practitioners to detect it and treat the symptoms in order to allow patients to function normally.

INTRODUCTION Binocular diplopia is most often due to a defect of the ocular motor system, involving the muscles, nerves or supranuclear pathways.1 Less commonly, binocular diplopia can be caused by retinal pathology at or near the macula. Some of the reported retinal pathologies known to cause diplopia are epiretinal membrane (ERM), choroidal neovascular membrane, and central serous retinopathy.2 In the case of ERM, diplopia can occur due to wrinkling of the macula1 or following surgical intervention such as vitrectomy and

A.T. Gorner — Private Practice, Dawson Creek, BC; L. Skorin, Jr. — Senior Staff Ophthalmologist, Mayo Clinic Health System, Albert Lea, MN Correspondence to: Dr. Adam T. Gorner, Kadziolka & Smart, 1100 103rd Avenue, Dawson Creek, BC, V1G 2G7; E-mail: manotheredearth@ gmail.com This article has been peer-reviewed.

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membrane peel.3 Dragged fovea diplopia syndrome is a con-

dition in which the fovea in one or both eyes is displaced causing a loss of correspondence between foveas and thus diplopia which is not correctable with prism.2 We present two cases of intractable diplopia following vitrectomy and epiretinal membrane peel along with their treatment. We also propose ocular coherence tomography as a means of visualizing the dragged fovea and suggest that further investigation into this technique is warranted.

CASE REPORTS Case 1 EN is an 83yearold white male. He presented to our clinic after seeing numerous doctors in the past 4 to 5 years. He claimed to be experiencing double vision that was worse in the distance and none of the treatments he had received involving prism provided any lasting relief. EN had been suffering from intractable binocular diplopia since his first epiretinal membrane peel surgery on the right eye 5 years earlier. He had since undergone the same surgery on the left eye as well but the diplopia persisted despite many variations of prism correction. He denied any dizziness, pain, or monocular diplopia but was having trouble judging distances. He was not taking any ocular medications or culpable systemic medications. He denied any allergies and had not endured injury to either eye. He had a history of cataract extraction with posterior chamber intraocular lens (PCIOL) implantation on both eyes. Family history was unremarkable but EN had a history of hypertension. Distance visual acuity was 6/121 (20/401) in the right eye (OD) and 6/15+2 (20/50+2) in the left eye (OS) with habitual correction of pl1.00 x 060 2 base down OD, and 0.751.00 x 094 3 base up OS. Pinhole acuities over habitual spectacles were 6/91 (20/301) OD and 6/92 (20/302) OS. Near acuity was 6/61 (20/201) OD and 6/9+1 (20/30+1) OS through a near add of +3.50 in both eyes (OU). Pupils were round and reactive without relative afferent pupillary defect, motilities were full and unrestricted OU, and confrontation fields were full to finger counting. Cover test with habitual correction revealed a 4 prism diopter (PD) exophoria and a 3 PD intermittent left hypertropia at distance and a 14 PD

De Pool et al3 by shining a target from a direct ophthalmoscope onto a black background and comparing fusion ability with the lights on and off. While wearing his habitual glasses EN was unable to fuse while looking at the target with the lights on but when the lights were turned off he reported that the targets would come closer together and he would almost see singly but then they would break further apart. We concluded that his habitual spectacles contained enough prism power to make fusion impossible. We performed a few trials of differing prism strengths but none of the variations produced acceptable results. We tried monovision in spectacles with a +2.50 D addition over the left eye and the distance correction in the right eye but this was not comfortable for EN. Finally, we placed a piece of semitransparent plastic tape on the center of the left spectacle lens and EN reported single vision. He elected to keep the tape on his glasses lens as the form of treatment for his condition.

Fig. 1 Ocular coherence tomography scan of the left macula in Case 1 possibly showing foveal displacement.

exophoria at near. The vertical prism in his spectacles appeared to be too strong since the patient’s left hypertropia with correction converted to a left hypotropia when tested without correction. On Amsler grid, EN reported a missing area on the far nasal field of the right eye but no metamorphopsia or scotoma on the left eye’s field. Manifest refraction was +0.751.00 x 162 6/9 (20/30) OD and 0.251.25 x 098 6/9 (20/30) OS.

External appearance and adnexa were unremarkable. Biomicroscopy revealed corneal arcus OU, normal conjunctiva, deep and quiet anterior chambers with flat irides and stable PCIOLs OU with clear or opened posterior capsule. Intraocular pressures were 13 mmHg OD and 8 mmHg OS by applanation. Both optic nerve heads exhibited deep cups with visible lamina and cup to disc ratios of 0.6 and 0.5 OD and OS respectively with healthy pink neuroretinal rim. An epiretinal membrane was present in each eye with a slightly darker area over the macula that resembled a pseudohole. WatzkeAllen sign was negative in both eyes. Otherwise the maculae were flat. Retinal periphery was flat without holes, tears, or retinal detachments OU. Optical coherence tomography (Stratus OCT, Carl Zeiss Meditec, Inc.) was performed on both maculae. The scan for the right eye showed a normal flat macula, but the scan of the left macula appeared displaced with areas of thickening and thinning (Fig. 1). We also performed a modified version of the lights onoff test as described by

Case 2 JS is a 64yearold white male. He first presented complaining of a blurred crescent shape obstructing his vision in the right eye for 6 or 7 months and that he would drive with his right eye closed. Bestcorrected visual acuity was 6/12+2 (20/40+2) OD and 6/6 (20/20) OS. He had a history of a retinal bleed and a posterior vitreous detachment in the right eye. Amsler grid testing showed central metamorphopsia OD and normal OS. Wrinkling of the right macula was evident on ophthalmoscopy and he was diagnosed with an epiretinal membrane for which he underwent a vitrectomy and a membrane peel. Following the surgery he reported some residual blur as well as double vision with images separated vertically. Vertical diplopia was caused by a phoria which over time became an intermittent tropia. He received a prescription with vertical prism which would be altered numerous times over the next year without providing lasting relief from diplopia. His symptoms decreased for a short time after each change to the prism but would soon return. He reported that his peripheral vision appeared single but his central vision was double and still distorted, despite the surgery. One year after the vitrectomy he had a cataract removed from the right eye with implantation of a PCIOL. Following the surgery his bestcorrected visual acuity was 6/7.5 (20/25) OD. He still noted metamorphopsia on Amsler grid testing OD and residual macular wrinkling could be observed on ophthalmoscopy. After a number of visits he was referred back to the surgeon who performed the membrane peel. The retinal surgeon assured JS that the surgery was a success, but she found that one of his spectacle lenses was decentered and tilted. She recommended that a new refraction be performed and his frames adjusted. Changes were again made to his glasses

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Fig. 3 White illumination 6/21 (20/70) Snellen optotype on background used to perform the lights on-off test.

Fig. 2 Optical coherence tomography scan of the right macula in Case 2 possibly showing foveal displacement.

including altered vertical prism without improvement. Finally, he was sent to a strabismus specialist who diagnosed him with dragged fovea diplopia and placed a piece of semitransparent tape on the center of his right lens to partially occlude the eye and eliminate his central diplopia. When he returned to our clinic in followup about 3 years after the initial presentation he was relieved to have single vision. We gave him a new prescription without prism and he continues to wear tape on his right lens. Both maculae appear normal without obvious wrinkling. OCT of the right eye showed a displaced fovea with normal thickness (Fig. 2). We performed the lights onoff test as described by De Pool et al.3 We presented an illuminated white 6/21 (20/70) optotype on a black background (Fig. 3) with the room lights on and JS reported central diplopia with single vision in the periphery. The room lights were then extinguished and a single white optotype was reported within 1 to 2 seconds.

DISCUSSION Binocular diplopia in association with central retinal pathology has been reported in the past.4,5 The dragged fovea diplopia syndrome was coined by De Pool et al3 to describe a condition in which a person experiences central double vision that is not correctable with prism. Often when a patient with this condition is given prism in their glasses they will initially respond favorably but ultimately the diplopia will return. Sometimes the diplopia returns almost immediately, or it may take hours to days for symptoms to appear again.3 Usually a comitant, smallangle hyper-

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deviation is present without evidence of extraocular muscle dysfunction or paresis. The explanation for this intractable diplopia is a mechanical displacement of the fovea in one or both eyes disrupting the normal foveal correspondence and creating rivalry between central and peripheral fusional 2,4-6 mechanisms. A small correcting movement of one or both eyes is made to allow central fusion, thus placing the peripheral retina of each eye in conflict. It is thought that the peripheral drive for fusion overrides the central drive because Panumâ&#x20AC;&#x2122;s fusional area is greater peripherally than 7,8 centrally. Thus, central diplopia is manifest and since prism cannot exclusively influence the central retina, the diplopia remains despite prism treatment. Another possible contributing factor to diplopia, either solely or in conjunction with foveal displacement, is aniseikonia. Benegas et al6 proposed that separation or compression of the photoreceptors from macular disease may produce a difference in retinal image size significant enough to cause diplopia. This is another reason why prism does not relieve symptoms in these patients. We did not perform any tests to detect aniseikonia in our patients.

Some of the reported causes of binocular diplopia from macular pathology are: epiretinal membrane, choroidal neovascularization, central serous retinopathy, paramacular scars, and localized macular detachments.2-5 Both of our patients had a history of epiretinal membrane with subsequent vitrectomy and membrane peel. Diplopia did not ensue until after the surgery was performed. Silverberg et al2 also found this to be the case in 4 out of 7 patients they reviewed and attributed it to improved vision in the operated eye which previously was reduced enough to preclude diplopia. The prevalence of this condition is not known but epiretinal membrane appears to be one of the more common causes. De Pool et al3 reported it as the cause in more than half of the 87 patients they reviewed with dragged fovea diplopia.

Fig. 4 (A) Epiretinal membrane with macular pucker. (B) Note the radial striations from contraction of the membrane.

PATHOPHYSIOLOGY OF EPIRETINAL MEMBRANES Epiretinal membranes (ERMs) are most commonly found in individuals over the age of 50 and are usually bilateral but often asymmetrical.9,10 ERMs are sometimes found in children, although this is rare. If an ERM is present in a child, it is commonly associated with trauma.11 Populationbased studies of different demographics show an overall prevalence ranging from 2.2% to 18.5% and agerelated prevalence of 2% in the 6th decade and up to 35% in the 8th decade.9,10,12-16 They can be classified clinically into an early, usually asymptomatic type called cellophane maculopathy caused purely by glial cell proliferation along the internal limiting membrane (ILM). There is also a more advanced type called preretinal macular fibrosis or macular pucker (Fig. 4A,B). The advanced type is usually more severe and is also caused by glial cells but with a fibrous component that causes traction and wrinkling of the retina.9,15 These membranes can also be classified as either primary or secondary depending on their underlying cause. Primary epiretinal membranes occur idiopathically or following posterior vitreous detachment (PVD). Secondary epiretinal membranes are associated with some kind of pathology or intraocular surgery; usually proliferative diabetic retinopathy, retinal tears or holes, macular holes, retinal detachment, or after cataract surgery.17 The histocytology of epiretinal membranes differs depending on the underlying pathology. Simple primary epiretinal membranes are formed when glial cells migrate through breaks in the ILM of the retina and begin to proliferate along the retinal surface. 18 Snead et al classified ERMs into three types: simple laminocyte ERMs, tissue repair ERMs, and neovascular ERMs. Simple ERMs form after PVD or idiopathically.

Snead et al described the glial cells in a simple ERM as laminocytes because they form a monolayer on the ILM as they proliferate and migrate along the vitreoretinal junction. The ILM in these membranes may become hyperconvoluted as the ERM contracts causing distortion of the retina and subsequent metamorphopsia and reduced visual acuity. Tissue repair ERMs develop after retinal tear, trauma, infection, or blunt injury. This membrane differs slightly from the simple type in that it also contains retinal pigment epithelial 18,19 (RPE) cells, fibroblasts, and macrophages. RPE cells may be liberated when a retinal tear or break occurs, forming the characteristic tobacco dust in the anterior vitreous. Over time these cells settle onto the retina to cause a pigmented 19 epiretinal membrane. Neovascular ERMs develop as a consequence of proliferative diabetic retinopathy, radiotherapy, or vasoformative tumors. This type of membrane is very different because it contains capillaries and acellular 18 20 stromal tissue. Kampik et al found that ERMs also contained collagen and myofibroblasts and concluded that these features may account for the contractile properties of the membranes. Epiretinal membrane can be treated by surgical removal. Vitrectomy and membrane peel can achieve an increase in visual acuity of 2 Snellen lines or more in up to 90% of 21,22 patients and can significantly reduce metamorphopsia. This reduction in metamorphopsia may be an important benefit even 23 if visual acuity is not noticeably improved.

DIAGNOSIS AND TREATMENT ERMs can be seen as a glistening sheen on the surface of the retina different from that seen in a healthy young fundus. This sheen appears less regular, like sunlight reflecting off disturbed water. The membrane may be clear or may have a greenishgrey appearance depending

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on the etiology. If macular pucker is present, radiating folds from one or more retinal contraction foci may be visible (Fig. 4A,B).24 After a membrane peel is performed, some residual retinal wrinkling may be evident and/or an apparent pseudohole may be seen. Alternatively, the retina may appear normal with no evidence of macular pathology on funduscopic examination. Case 1 had a visible remnant of epiretinal membrane and a pseudohole over the macula in each eye with a negative WatzkeAllen sign. In Case 2 some residual wrinkling was apparent in the operated eye. It is not possible to visualize the displacement of the fovea on funduscopy so this condition must be confirmed in other ways. The lights onoff test described by De Pool et al3 is a simple test that we have found very useful. A white illuminated optotype of about 6/21 (20/70) Snellen equivalent is presented on a black background (Fig. 3). In a positive result the patient reports central diplopia with the lights on but when the lights are extinguished and all peripheral cues to fusion are eliminated a single object is reported. Both of our patients responded positively to this test. When we attempted this test in Case 1, we did not have the setup exactly as described but we arranged a modified version with an illuminated target from an ophthalmoscope on a black background. Case 1 reported that the objects came closer together and almost became single but then broke further apart. We attribute this to his glasses which contained vertical prism of sufficient quantity to prevent fusion. In Case 2 we had an LCD screen with a black background and a white optotype as described which produced a definitive positive result. The synoptophore has been used in the past to confirm the disparity between central and peripheral fusion, but the lights onoff test seems to be a valid substitute.2 With the increasing availability of computerized visual acuity charts, the lights onoff test may be more readily available than the synoptophore. We performed OCT (Stratus OCT, Carl Zeiss Meditec, Inc.) of the macula on both patients with interesting results. The image showed the foveal area displaced from the center of the reference lines (Figs. 1, 2). This was instructive because such a displacement is not generally seen when performing macular scans. We wondered if the image produced by the OCT was actually showing the displaced fovea. We recognize that there are inherent flaws in this assumption since fixation cannot be accurately monitored while performing the scans. Gupta et al24 were able to visualize the foci of contraction on the retina with macular pucker using OCT with scanning laser ophthalmoscopy (SLO). This instrument allowed coronal plane images from the OCT to be superimposed on the SLO image with point to point registration. This combined image revealed multiple centers of retinal contraction with retinal folds and areas of thickening easily referenced with

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the anatomical location on the retina. One wonders if it would be possible to measure the displacement of the fovea with this method in dragged fovea diplopia syndrome. There is no known cure for dragged fovea diplopia, only palliative treatment. There is no way to align the foveas without causing peripheral diplopia or vice versa. Others have reported on the success of placing Bangerter foils of different densities over the affected eye in order to degrade the image for that eye and eliminate diplopia.2,3 The foil is cut down so it only affects the central vision and can be placed on the inside center of the spectacle lens. This allows the patient to fixate with the other eye and use peripheral retina to maintain fusion. Patients tend to find this acceptable. Another option described by De Pool et al3 is Scotch Satin tape (3M Co., St. Paul, MN). They found that this was more cosmetically appealing than the more opaque Scotch Magic tape (3M Co., St. Paul, MN) and less expensive than Bangerter foil. Both our patients responded very favorably to tape placed on the center of one lens. The patient in Case 2 has been wearing this tape for almost 2 years. We also attempted monovision in the patient in Case 1; however, he found this uncomfortable and was not able to tolerate it.

CONCLUSION Dragged fovea diplopia syndrome may be more common than we currently realize. It can be very frustrating for both patients and doctors to encounter this condition if it is not understood. There is a simple subjective way to test for it using the lights onoff test. As technology advances perhaps an objective means of detecting this condition will become available. We suggest that further testing should be done with OCT to determine if the actual foveal displacement can be objectively quantified. This condition cannot be cured but the symptoms can be treated very inexpensively and with relatively good success by partially occluding one eye with semitransparent tape or Bangerter foil. ❏

REFERENCES 1. 2.

Barton JJ. “Retinal diplopia” associated with macular wrinkling. Neurology 2004; 63: 925927. Silverberg M, Schuler E, VeronneauTroutman S, Wald K, et al. Nonsurgical management of binocular diplopia induced by macular pathology. Arch Ophthalmol 1999; De Pool ME, Campbell JP, Broome SO, Guyton DL. The draggedfovea diplopia syndrome: clinical characteristics, diagnosis, and treatment. Ophthalmology 2005; 112: 14551462. Bixenman WW, Joffe L. Binocular diplopia associated with retinal wrinkling. J Pediatr Ophthalmol Strabismus 1984; 21: 215219. Burgess D, RoperHall G, Burde RM. Binocular diplopia associated with subretinal neovascular membranes. Arch Ophthalmol 1980; 98: 311317.

Benegas NM, Egbert J, Engel WK, Kushner BJ. Diplopia secondary to aniseikonia associated with macular disease. Arch Ophthalmol 1999; 117: 896899. 7. Burian HM. Fusional movements in permanent strabismus: a study of the role of the central and peripheral retinal regions in the act of binocular vision in squint. Arch Ophthalmol 1941; 26: 626652. 8. Burian HM. Fusional movements: role of peripheral retinal stimuli. Arch Ophthalmol 1939; 21: 486491. 9. FraserBell S, YingLai M, Klein R, Varma R, Los Angeles Latino Eye Study. Prevalence and associations of epiretinal membranes in latinos: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci 2004; 45: 17321736. 10. McCarty DJ, Mukesh BN, Chikani V, Wang JJ, et al. Prevalence and associations of epiretinal membranes in the visual impairment project. Am J Ophthalmol 2005; 140: 288294. 11. Khaja HA, McCannel CA, Diehl NN, Mohney BG. Incidence and clinical characteristics of epiretinal membranes in children. Arch Ophthalmol 2008; 126: 632636. 12. Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, et al. Prevalence and risk factors for epiretinal membranes in a Japanese population: the Hisayama study. Graefes Arch Clin Exp Ophthalmol 2003; 241: 642646. 13. Mitchell P, Smith W, Chey T, Wang JJ, et al. Prevalence and associations of epiretinal membranes. The Blue Mountains Eye Study, Australia. Ophthalmology 1997; 104: 10331040.

14. Kawasaki R, Wang JJ, Sato H, Mitchell P, et al. Prevalence and associations of epiretinal membranes in an adult Japanese population: the Funagata study. Eye 2009; 23: 10451051. 15. Klein R, Klein BE, Wang Q, Moss SE. The epidemiology of epiretinal membranes. Trans Am Ophthalmol Soc 1994 Discussion 425430; 92: 403425. 16. You Q, Xu L, Jonas JB. Prevalence and associations of epiretinal membranes in adult Chinese: The Beijing Eye Study. Eye 2008; 22: 874879. 17. Kanski JJ. Clinical Ophthalmology. 6th ed. New York: Butterworth Heinemann; 2007: 653. 18. Snead DR, James S, Snead MP. Pathological changes in the vitreoretinal junction 1: epiretinal membrane formation. Eye 2008; 22: 13101317. 19. Meyer CH, Mennel S, Schmidt JC, Kroll P. Secondary pigmented macular pucker on optical coherence tomography. Acta Ophthalmol (Oxf) 2008; 86: 579581. 20. Kampik A, Kenyon KR, Michels RG, Green WR, et al. Epiretinal and vitreous membranes: comparative study of 56 cases. 1981. Retina 2005; 25: 14451454. 21. Michels RG. Vitrectomy for macular pucker. Ophthalmology 1984; 91: 13841388. 22. Michels RG. Vitreous surgery for macular pucker. Am J Ophthalmol 1981; 92: 628639. 23. GhaziNouri SM, Tranos PG, Rubin GS, Adams ZC, et al. Visual function and quality of life following vitrectomy and epiretinal membrane peel surgery. Br J Ophthalmol 2006; 90: 559562. 24. Gupta P, Sadun AA, Sebag J. Multifocal retinal contraction in macular pucker analyzed by combined optical coherence tomography/scanning laser ophthalmoscopy. Retina 2008; 28: 447452.

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QUESTIONNAIRE Dragged Fovea Diplopia Syndrome After Epiretinal Membrane Peel Surgery Adam T. Gorner, OD, and Leonid Skorin Jr., OD, DO, MS 1. ❑ ❑ ❑ ❑

The patient in Case 1 had an absence of the following clinical signs and symptoms, EXCEPT: Ocular pain Difficulty judging distances Dizziness Sudden loss of visual acuity

2. ❑ ❑ ❑ ❑

The patient in Case 2 presented with which of the following signs or symptoms? Decreased left-sided visual field A floater Blurred shape obstructing his vision in the right eye Reduced vision at night

3. ❑ ❑ ❑ ❑

All of the following statements about dragged fovea diplopia syndrome are true, EXCEPT: Diplopia may disappear and appear again It is not correctable by prism OCT is effective in determining if the foveal displacement can be objectively quantified Prism is usually effective in curing the condition

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Which of the following best describes an individual with epiretinal membranes (ERMs)? 55-year-old female 60-year-old Caucasian male 65-year-old African-American male 76-year-old Asian female

5. ❑ ❑ ❑ ❑

What is the prevalence of ERMs according to population-basic studies? 1.2% to 4.5% 2.2% to 18.5% 5.3% to 9.4% 3.6% to 20.5%

6. ❑ ❑ ❑ ❑

Secondary epiretinal membranes are associated with all of the following, EXCEPT: Cystoid macular degeneration Macular holes Retinal tears Retinal detachment

7. ❑ ❑ ❑ ❑

Surgery is effective in achieving an increase of visual acuity of 2 Snellen lines in what percentage of patients? 60% 75% 90% 95%

8. ❑ ❑ ❑ ❑

Which of the following is the most likely cause of dragged fovea diplopia syndrome? Cataract extraction Vitreous detachment Membrane peel Family history of the condition

9. ❑ ❑ ❑ ❑

In what number of patients did diplopia occur after vitrectomy and membrane peel? 2 out of 3 4 out of 7 6 out of 9 8 out of 10

10. ❑ ❑ ❑ ❑

Which of the following treatments was effective in the two Case Reports presented in the paper? Partial monocular occlusion with semitransparent tape Care and regular patient monitoring Prism correction Monovision in spectacles

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News and Notes The Eye and Neurodegenerative Diseases Professor Chris Hudson, of the University of Waterloo School of Optometry and Vision Science, is co-lead of ocular diagnosis for an ongoing study of Parkinson’s disease, amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia, stroke-induced vascular cognitive impairment, and Alzheimer’s disease, currently being conducted by the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Using eight assessments, which include tracking eye movement and comparing changes in the retina, the team hopes to develop a method for early detection, followed by a method for monitoring neurodegenerative disease progression. As a scientist and optometrist by training, but also a Parkinson’s patient himself, Hudson is hopeful that early detection and monitoring of these diseases will provide a basis for new treatment options. For additional information, visit http://uwaterloo.ca/optometry-vision-science/news/. Optometry Giving Sight Helps Establish the First School of Optometry in Oaxaca, Mexico Optometry Giving Sight hosted the official signing of a Memorandum of Understanding to establish the first school of Optometry in the state of Oaxaca in Mexico. “Despite the existence of 14 optometry schools in Mexico at a university level, none of these are located in the south or southeastern parts of the country,” said Dr. Juan Carlos Aragon, Chairman of Optometry Giving Sight. “With a combined population of 20 million people, the provision of optometric services is very weak, resulting in a disproportionate percentage of the population being functionally blind or vision impaired due to uncorrected refractive errors.” The goal of the collaboration is to develop a program that will locally produce degree trained optometrists. The School hopes to recruit 50 students per annum commencing in 2016, in what will be a 4-year degree. For more information, visit www.givingsight.org. HOYA’s Picture Perfect Campaign HOYA Vision Care Canada recently launched a new marketing campaign: Picture Perfect with HOYA Lenses. When a dispensing team places an order for one of the eligible HOYA lenses or lens coatings, the job will be delivered with a special gift for the patient, a bluetooth-enabled HOYA selfie stick. The patient will then take a selfie wearing her or his new glasses and post it to social media using #HoyaPicturePerfect. The Picture Perfect with HOYA Lenses campaign will provide independent practices with a fun tool to reward and engage patients and gain an unprecedented opportunity to advertise their practice in many different social media outlets. Every time a patient posts a selfie wearing their new HOYA lenses, hundreds of their social media followers will be instantly connected to the Eye Care Professional – endorsing their practice instantaneously. For additional information, visit www.hoyavision.ca; or contact your Hoya Vision Care representative at tel.: 888-258-4692.s

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