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Clinical & Refractive Optometry

VOLUME 28, NUMBER 3, 2017

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Performance of an In Vivo Tear Film Osmometer in Normal Ocular Surface Conditions Ocular Findings in a Case of Pseudoxanthoma Elasticum Adult-Onset Foveomacular Vitelliform Dystrophy Cat Scratch Neuroretinitis Orbital Vascular Malformations

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Clinical&Refractive Optometry

Editorial Board • Volume 28, Number 3, 2017 Editor

Associate Editor

Richard Maharaj, OD Toronto, Ontario

Henry Reis, MD Burnaby, British Columbia

François Piuze, OD Quebec City, Quebec

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

Editors Emeriti Brad Almond, OD Calgary, Alberta

Barbara Caffery, OD Toronto, Ontario

John Jantzi, OD Vancouver, British Columbia

Yvon Rhéaume, OD Montreal, Quebec

Contributing Editors Scott D. Brisbin, OD Edmonton, Alberta

Gerald Komarnicky, OD Vancouver, British Columbia

Langis Michaud, OD Montreal, Quebec

Barbara Robinson, OD Waterloo, Ontario

Lorance Bumgarner, OD Pinehurst, North Carolina

Bart McRoberts, OD Vancouver, British Columbia

Rodger Pace, OD Waterloo, Ontario

Jacob Sivak, OD, PhD Waterloo, Ontario

Louis Catania, OD Philadelphia, Pennsylvania

Ron Melton, OD Charlotte, North Carolina

Maynard Pohl, OD Bellevue, Washington

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 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.

WE’VE IMPROVED THE CE TEST SUBMISSION PROCESS In addition to completing the CE-Credit test questionnaires in this issue by hand and then submitting them by regular mail, you now have the option of completing and submitting the test questionnaires completely online and receiving your COPE CE Certificate literally seconds later by return email. For more detailed instructions, please refer to the Instruction Page of each test questionnaire in this issue.

Clinical&Refractive Optometry Contents • Volume 28, Number 3, 2017

PUBLISHER’S PAGE

SCIENTIFIC STUDY 84 Performance of an In Vivo Tear Film Osmometer in Normal Ocular Surface Conditions Henry Reis, MD; Stefanie Grenier, BSc; Daniela Albuquerque, MD CE CREDIT ARTICLES 87 The Streak Marks the Spot: Ocular Findings in a Case of Pseudoxanthoma Elasticum Leonid Skorin Jr., DO, OD; Brittany Schauer, OD ABSTRACT: Pseudoxanthoma elasticum is a progressive calcification disease. It affects the connective tissue of the eyes, skin, and cardiovascular system. Ocular manifestations include angioid streaks, diffuse retinal mottling, retinal pigmented epithelium atrophy, and choroidal neovascularization. We present a classic case of PXE to review the condition and its associated ocular signs.

Adult-Onset Foveomacular Vitelliform Dystrophy Masquerading as Age-Related Macular Degeneration Akilia Hang Nguyen, OD; Tam Nguyen, OD Theresa Zerilli-Zavgorodni, OD; Nancy Shenouda-Awad, OD ABSTRACT: The purpose of this case report is to demonstrate the clinical presentation and work-up needed to diagnose adult-onset foveomacular vitelliform dystrophy. This is a rare macular pattern dystrophy which may cause gradual vision loss.

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Cat Scratch Neuroretinitis Nicky R. Holdeman, OD, MD; Liang Ma, PhD, OD; Rosa A. Tang, MD ABSTRACT: Cat scratch disease (CSD) is caused by a gram-negative bacterium, Bartonella henselae. This uncommon disease is believed to be transmitted by a cat scratch or bite, when the bacterium is present on the cat’s claw or resides in the oral cavity. Neuroretinitis, which occurs in 1% to 2% of CSD cases, is characterized by acute vision loss, optic disc edema, and a macular star. The following case describes a dramatic presentation of a 13-year-old Hispanic female diagnosed with cat scratch neuroretinitis.

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Orbital Vascular Malformations Allison Pierce, OD; Pauline F. Ilsen, OD

Clinical & Refractive Optometry is published 6 times per year by Mediconcept. 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. While the editorial staff of Clinical & Refractive Optometry 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. Please direct all correspondence to: Clinical & Refractive Optometry Editorial & Sales Office 3484 Sources Blvd., Suite 518 Dollard-des-Ormeaux, Quebec Canada H9B 1Z9 Tel.: (514) 245-9717 E-mail: mdilemme@mediconcept.ca Printed in Canada. All rights reserved. Copyright © 2017 Mediconcept. 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: Orbital vascular malformations derive embryologically either from the arterial system, venous system, or both. Classification of the lesion defines appropriate management and is important in preventing potential mistreatment. Two case reports of orbital vascular malformations are presented.

CASE CONSULTATIONS 124 Diagnostic Test Recommendations for a Challenging Dry Eye Case Presented by: Henry Reis, MD Responses from: Pavan Avinashi, OD; Ben Barrus, OD; Francis Gaudreault, OD; Toby Mandelman, OD; Jules Plante, OD 128

NEWS & NOTES

ISSN: 2371-7017; Date of Issue: July / August 2017

Courtesy of: Dr. Nicky R. Holdeman Fundus photograph OS showing reduced swelling of the optic nerve with residual macular exudates.

Clinical&Refractive Optometry

Publisher’s Page • Volume 28, Number 3, 2017

What You Should Know About Predatory Publishing

here is a term that not every optometrist may be aware of, but they should be. The term is, Predatory Publishing. It was first coined by the University of Colorado Denver librarian and researcher Jeffrey Beall, when he compiled and released a list of predatory publishers and journals in 2012. Today, this list is referred to as the Beall List, and it includes literally hundreds of open access clinical and scholarly publications from around the world. What all these publications have in common is that their publisher will accept an original article for publication based solely on payment of an excessive fee by the author or funder of the paper paid in advance, and without the publisher applying any of the expected standards for peer review. The results of this practice can have many implications, but arguably the most injurious of these is the legitimization of statements and conclusions which by definition become part of the global medical literature pool. And very much like toothpaste after it is squeezed from the tube, these statements and conclusions can never really be put back in the tube again. We have just seen an example of this type of publishing. Recently, an open access journal in New Zealand published an article from Canada in which a study was designed and performed to compare the performance of two diagnostic tests. The stated purpose of this comparative study was to assess their precision and accuracy. However, the way that the study was designed, one of these two tests was not performed in accordance with its directions for use. This is a key detail that would have been immediately flagged in any normal peer review process. Not surprisingly then, this study went on to conclude that the test in question demonstrated insufficient performance to accurately and precisely delineate physiologic levels within its reported test range. The reason that this conclusion, and indeed the entire study, is being called into question is that even the most basic peer review by the publisher would have uncovered this flaw in the study’s design. This in turn prompts the question: who is the publisher? As it turns out, this publisher and their journal (no names) had been among the very first to be placed on Mr. Beall’s list of Predatory Publishers and Journals; although they were eventually delisted in 2015, after promises to revise their editorial standards and peer review practices. However, the article that I’ve just described to you was published this year, by the same publisher in the same journal. Please note that not all open access journals operate this way, and in fact many do not. For example, this journal, which is an open access all COPE CE-accredited publication, regularly employs three independent rounds of review. The first is a structured, internal peer review process, the second is an independent review done by Pacific University (Oregon) in their capacity as our COPE sponsoring institution, and a third review is done by ARBO (Missouri) themselves as part of their COPE accreditation process. The point that I am trying to make is that in optometry, like in politics, we all need to be aware of the sources of the information that are being directed to us; and at the end of the day, we all need to become our own peer reviewer. Lawrence Goldstein Publisher

Publisher’s Page

Scientific Study Performance of an In Vivo Tear Film Osmometer in Normal Ocular Surface Conditions Henry Reis, MD; Stefanie Grenier, BSc; Daniela Albuquerque, MD

ABSTRACT

INTRODUCTION

Purpose: To assess the performance of an in vivo osmometer in a clinical setting using the i-Pen® (I-MED Pharma) osmometer in patients who scored within normal limits on the SPEED questionnaire. Methods: A total of 28 patients (ages 26-87) underwent comprehensive ocular surface assessment at an accredited dry eye center in Burnaby, BC, Canada. Patients were screened for ocular surface disease (OSD) with the SPEED questionnaire and the in vivo osmometer i-Pen, and included in the study if all eligibility criteria were met. Results: The mean tear osmolarity encountered in this study was 295 mOsm/L, with an average of 300.85 mOsm/L. Exam values ranged from 276 to 336 mOsm/L, with a statistically higher upper reference limit (URL) when compared to the URL published by the manufacturer. Because of this discrepancy, one might claim that most symptoms of OSD have no defined, sudden onset, leading to a proportionally small group of those patients being classified as normal. OSD symptoms might be initially masked or subclinical, leading to artificially low questionnaire scores in patients that would otherwise be classified as positive for ocular surface disease. The results of an analysis of the tear osmolarity in different ethnical groups revealed a statistically significant variance, with patients of African-American descent presenting with the lowest average value (287 mOsm/L), followed by Mixed (292 mOsm/L), Caucasians (298.36 mOsm/L), Hispanic (302.22 mOsm/L), and lastly, Asians (312.8 mOsm/L). No statistical significance was observed when analyzing the distribution of tear osmolarity by age or time of testing. The i-Pen True Negative Rate (TNR), also known as Specificity (SPC), was calculated as 91.7%. Conclusions: The test has proved to have high specificity, allowing OSD to be excluded where osmolarity testing is negative. It is also important to consider the statistically significant correlation between ethnicity and ocular surface osmolarity, and be conscientious when analyzing dry eye questionnaires, as some patients might neglect to report symptoms in early stages of the condition.

Ocular surface disease (OSD) has been objectively correlated to elevated tear osmolarity, and most progressive diagnostic algorithms currently include osmometers. Eye care practitioners must rely on objective testing to better evaluate patients with dry eye disease, whose gamut of symptoms covers a wide range of presentations from mild ocular pruritus to severe ocular pain. A fundamental concern in OSD investigation is that the performance of osmometers could be influenced by a variety of factors. Among those that could lead to osmolarity underestimation are the administration of non-contact tonometry, retinal photography and topical medication up to two hours prior to OSD screening. Other factors lead to osmolarity overestimation, such as the use of eye makeup and/or contact lenses, or even the excessive use of handheld electronic devices on the day of the examination. It is paramount to understand that a test with high specificity allows eye care practitioners to rule out a condition when encountering a negative result. Several studies have been conducted to assess the validity of osmolarity testing, but most study designs include patients with mild, moderate or severe disease, with emphasis in test sensitivity. Contrary to that approach, the authors intended to evaluate the true negative rate (TNR), also known as test specificity (SPC) of the commercially available in vivo osmometer, I-MED Pharma’s i-Pen, in patients with normal ocular surface. S TN TNR = condition negative S

H. Reis; S. Grenier; D. Albuquerque — Focus Eyecare Centre, Burnaby, BC Correspondence: Dr. Henry Reis, Focus Eyecare Centre, 104-7188 Kingsway, Burnaby, BC V5E 1G3; E-mail: focus@myoptometrist.ca This article has been peer reviewed and accepted for publication in June 2017.

Clinical and Refractive Optometry 28:3, 2017

METHODS The study included 56 eyes, initially screened with the SPEED questionnaire. Patients who failed to meet eligibility criteria were excluded from the study. Inclusion criteria included: patient age greater than 18 years, negative history of makeup or topical ocular medication within 24 hours from the exam, negative history of ocular disease, and SPEED score equal or inferior to 8. Patients were then subcategorized by SPEED score, age, ethnicity and time of osmolarity measurement. Osmolarity measurements with the i-Pen were acquired by CCOA (Canadian Certified Optometric Assistant) personnel strictly following the manufacturer’s manual, with proper patient consent.

Distribution of mOsm/L values 340 330 320 310 300 290 280 270

mOsm/L Fig. 1 Distribution of tear osmolarity in patients with normal ocular surface conditions

Average mOsm/L x Ethnicity 315 312 309 306 303 300 297 294 291 288 285 282 279 276 273 AfricanAmerican

Mixed

Caucasian

Hispanic

Asian

Fig. 2 Analysis of tear osmolarity versus ethnicity

RESULTS According to the i-Pen user manual, the mean osmolarity value in normal patients was 300 mOsm/L and a range from 275 to 316 mOsm/L was documented.

The mean tear osmolarity encountered in this study was 295 mOsm/L, with an average of 300.85 mOsm/L. Exam values ranged from 276 to 336 mOsm/L (Fig. 1), with a statistically higher upper reference limit (URL)

Performance of an In Vivo Tear Film Osmometer in Normal Ocular Surface Conditions â&#x20AC;&#x201D; Reis et al

Patient Age and Osmolarity 340 330 320 310 300 290 280 270 20

Fig. 3 Analysis of tear osmolarity versus patient age yielded no statistical significance.

when compared to the URL published by the manufacturer. In view of that discrepancy, one might claim that most symptoms of OSD have no defined, sudden onset, leading to a proportionally small group of those patients being classified as normal. OSD symptoms might be initially masked or subclinical, leading to artificially low questionnaire scores in patients that would otherwise be classified as positive for ocular surface disease. The analysis of tear osmolarity in different ethnical groups unveiled a statistically significant variance (Fig. 2), with patients of African-American descent presenting with the lowest average value (287 mOsm/L), followed by Mixed (292 mOsm/L), Caucasians (298.36 mOsm/L), Hispanic (302.22 mOsm/L), and lastly, Asians (312.8 mOsm/L). No statistical significance was observed when analyzing the distribution of tear osmolarity by age or time of testing (Fig. 3). The i-Pen True Negative Rate (TNR), also known as Specificity (SPC), was calculated as 91.7%. This is considered clinically significant, as most tests that present SPC values over 90% are considered reliable; despite the fact that a quintessential gold standard test would display both sensitivity and specificity of 100%. Furthermore, a direct TNR comparison between the two commercially available osmometers, TearLab® (TearLab Corp, San Diego, CA) and i-Pen® (I-MED Pharma, Montreal, QC) indicates that both options have similar test specificity, with 88% for the former and 91.7% for the latter.

between ethnicity and ocular surface osmolarity, and be conscientious when analyzing dry eye questionnaires, as some patients might neglect to report symptoms in early stages of the condition. ❏

ADDITIONAL READING 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.

CONCLUSION The inclusion of tear osmolarity in ocular surface disease diagnostic algorithms is strongly encouraged by the authors. The test has proved to have high specificity, allowing eye care practitioners to exclude OSD in most cases where osmolarity testing is negative. It is also important to consider the statistically significant correlation

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13. 14. 15. 16.

Karpecki PM. Diagnosis and treatment of ocular surface conditions: focus on dry eye. Clinical and Refractive Optometry 2016; 27(6): 236-241. Definition and Classification of Dry Eye. Report of the Diagnosis and Classification Subcommittee of the Dry Eye Workshop (DEWS). The Ocular Surface 2007; 5(2): 75-92. Lemp MA, Foulks GN. The Definition & Classification of Dry Eye Disease Guidelines from the 2007 International Dry Eye Workshop. Ophthalmology Management, April 2008. Tomlinson A, Khanal S, Ramaesh K, et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006; 47(10): 4309-4315. Rocha G, Gulliver R, Borovik A, Chan CC. Randomized, masked, in vitro comparison of three commercially available tear film osmometers. Clinical Ophthalmology 2017; 11: 243-248. Versura P, Profazio V, Campos EC. Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases. Curr Eye Res 2010; 35(7): 553-564. Keir N, Ngo W, Situ P, Korb D, et al. Evaluation of the standard patient evaluation of eye dryness (SPEED) questionnaire. Invest Ophthalmol Vis Sci 2013; 54: 6028. Ngo W, Srinivasan S, Keech A, Keir N, et al. Self versus examiner administration of the ocular surface disease index. J Optom 2017; 10(1): 34-42. Narayanan S. Osmolarity: a diagnostic test for dry eye. Review of Optometry, February 2011. Tauber S. Treating and managing dry eye. Clinical and Refractive Optometry 2016; 27(1): 14-17. Avinashi P. Principles of dry eye disease: diagnosis, treatment and management. Clinical and Refractive Optometry 2016; 27(4): 127-132. Barrus BJ. The science of dry eye hyperosmolarity. Clinical and Refractive Optometry 2016; 27(5): 202-206. Maharaj RL. In vivo ocular surface osmolarity in a dry eye population. Clinical and Refractive Optometry 2017; 28(1): 3-6. Baudouin C, et al. Role of hyperosmolarity in the pathogenesis and management of dry eye disease. The Ocular Surface 2013; 11: 246-258. Keech A, Jones L, Senchyna M. TearLab Osmometer Validation Protocol. Centre for Contact Lens Research. University of Waterloo School of Optometry, March 2009. i-Pen Osmolarity System User Manual. I-MED Pharma Inc, 2016.

CLICK HERE TO PRINT THIS CE CREDIT ARTICLE AND TEST

Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Leonid Skorin Jr. and Dr. Brittany Schauer entitled The Streak Marks the Spot: Ocular Findings in a Case of Pseudoxanthoma Elasticum. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 92 for complete instructions.

The Streak Marks the Spot: Ocular Findings in a Case of Pseudoxanthoma Elasticum Leonid Skorin Jr., DO, OD, MS, FAAO, FAOCO Brittany Schauer, OD

ABSTRACT Pseudoxanthoma elasticum (PXE) is a progressive calcification disease. It affects the connective tissue of the eyes, skin, and cardiovascular system. Ocular manifestations include angioid streaks, diffuse retinal mottling, retinal pigmented epithelium (RPE) atrophy, and choroidal neovascularization (CNV). The eyes are also extremely fragile to trauma and can experience choroidal rupture and subretinal hemorrhage. There is no treatment for PXE. Most patients experience a poor visual prognosis, especially later in life. We present a classic case of PXE to review the condition and its associated ocular signs. A calcified Bruch’s membrane can be blamed for angioid streaks and subsequent retinal complications. This case illustrates the importance of routine examinations to monitor and manage threats to vision. If left untreated, these retinal defects can be devastating to one’s eyesight.

INTRODUCTION Pseudoxanthoma elasticum (PXE) is also known as Grönblad-Strandberg syndrome.1 It is a progressive connective tissue disorder that results in calcification, fragmentation, and degeneration of the elastic fibers of the skin, eye, and cardiovascular system.2 PXE has been found to be related to mutations in the ABCC6 gene that is responsible for encoding cellular transport proteins.3,4 Without this mechanism, elastic fibers will calcify. Inherited in an autosomal recessive fashion, PXE affects approximately one in 25,000 to 100,000 people worldL. Skorin, Jr. — Consultant, Community Division of Ophthalmology, Mayo Clinic Health System, Albert Lea, MN; Assistant Professor of Ophthalmology, Mayo Clinic College of Medicine, Rochester, MN; B. Schauer — Optometrist, Vision Source - Mandan, Mandan, ND Correspondence to: Dr. Leonid Skorin, Jr., Mayo Clinic Health System, 404 West Fountain Street, Albert Lea, MN 56007; E-mail: skorin.leonid@mayo.edu The authors have no financial or proprietary interest in any material or method mentioned in this article. This article has been peer reviewed.

wide with higher prevalence in South Africa.4 Women are affected twice as often as men.4 PXE usually develops in childhood around age thirteen.4 Patients will exhibit “plucked chicken” skin distinguished by small yellowish macules, papules, or plaques that are most easily seen in the neck, axillae, antecubital fossa, groin, and paraumbilical areas. The skin becomes progressively loose, thin, and delicate.2,3 Most people are diagnosed through a skin biopsy around the age of 22 that exemplifies fragmented and clustered calcific elastic tissue in the middle to lower dermis.4 Cardiac involvement typically presents in the third to fourth decade with calcification of the elastic media and intima of arteries and heart valves.4 This can result in renal artery stenosis, intermittent claudication, mitral valve prolapse, atherosclerosis, systemic hypertension, and myocardial infarction.1,2,5,6 Internal hemorrhaging can occasionally be found in the urinary tract or cerebrovascular system, but the vast majority of hemorrhaging is localized gastrointestionally due to fragile calcified submucosal vessels.3 Ocular signs occur in 60% to 80% of PXE patients, most often in the second to third decade of life.3 The most common ocular manifestation is angioid streaks. PXE is responsible for 50% of angioid streak cases.2,3 Angioid streaks are full-thickness crack-like dehiscences in Bruch’s membrane. They appear as sharp, linear, irregular, deep, dark red-brown streaks with overlying retinal pigmented epithelium atrophy and underlying choriocapillaris infiltration.1 Bruch’s membrane is brittle, thickened, and calcified which allows the streaks to slowly increase in width and extent over time. Angioid streaks can disappear if pressure is placed on the globe.3 They often expand outward from the optic disc in a spoke-like fashion with pigmentation developing around the streak edges.1 The angioid streaks can often resemble a “spider web” pattern.3 These breaks in Bruch’s membrane are visible with optical coherence tomography (OCT) imaging.7 Angioid streaks are usually bilateral but asymmetric between the eyes.

CASE REPORT A 62-year-old white female came to our clinic for a comprehensive diabetic eye examination. Her chief complaint was that her vision was decreasing, especially

Ocular Findings in a Case of Pseudoxanthoma Elasticum — Skorin Jr., Schauer

Right Eye

Left Eye

Fig. 1 (A) Visual field of the right eye. (B) Visual field of the left eye.

in the left eye. She also complained of diplopia, flashes, and floaters. Ocular history included focal laser photocoagulation OD for treatment of PXE-induced choroidal neovascularization (CNV) with resultant macular scarring and angioid streaks OU. Also bevacizumab (Avastin, Genentech, San Francisco, CA) intravitreal injections OS for treatment of PXE-induced CNV. Medical history included thyroid disease, hypertension, elevated cholesterol, and type II diabetes mellitus (DM). Her most recent glycosylated hemoglobin A1c value was 7.9% in addition to a fasting glucose level of 184 mg/dL. Family history included her father having age-related macular degeneration (ARMD) and her mother having type II DM. The patient is taking glipizide 10 mg daily, hydrochlorothiazide 25 mg daily, levothyroxine 0.05 mg daily, simvastatin 20 mg daily, in addition to taking pseudoephedrine and acetaminophen as needed for pain. She reported being allergic to non-steroidal anti-inflammatory drugs (NSAIDs), codeine, pyrazoles, and salicylates. Best-corrected distance visual acuity (VA) was 6/30-1 (20/100-1) OD and 6/15-1+1 (20/50-1+1) OS. Through a manifest refraction, the patient was slow to call out each letter. Best-corrected near VA was 6/36+1 (20/120+1) OU. Pupils were equally round and reactive to light with no afferent pupil defect. Kinetic visual field testing with a III3e target revealed horizontal ranges of 40° nasal and 64° temporal OD, and 52° nasal and 72° temporal horizontally OS (Fig. 1A, 1B). Extraocular muscles were full and unrestricted in all gazes. Cover test revealed orthophoria at distance and near with poor fixation of the right eye. Color testing 14 out of 16 plates correct. The

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patient appeared to have more difficulty with the visual acuity demand of the test rather than color discrimination. She was unable to appreciate stereopsis with the Stereo Fly Test. Amsler grid testing revealed a large temporal scotoma OD with inferior and superotemporal scotoma OS (Fig. 2). There was no metamorphopsia on Amlser grid testing. Intraocular pressure was 21 mmHg OD and 20 mmHg OS. Slit lamp examination revealed unremarkable lids/lashes, cornea, and a quiet anterior chamber. There was a grade 1+ nuclear sclerosis OU with trace inferior and posterior cortical spoking OD. Funduscopy revealed a cup-to-disc ratio of 0.3/0.3 with pink and distinct neuroretinal tissue margins OU, reduced retinal artery/ vein ratio of 1/3 OU, normal arterial light reflex of 1/4 OU, grade 2+ arteriovenous nicking OU, and angioid streaks OU. The macula showed geographic atrophy OU, retinal pigment epithelium dropout OU, disciform scar OU, and a large central area of pigmentation OD (Fig. 3A, 3B). The patient had a negative WatskeAllen sign OU. The peripheral retina was flat with no holes or tears in all quadrants. There was no retinal neovascularization. OCT revealed macular thickening without edema (Fig. 4A, 4B).

DISCUSSION Patients with PXE commonly exhibit mottled retinal pigmentation known as “peau d’orange.” This often is the first ocular sign seen in PXE, preceding the appearance of angioid streaks by 1 to 8 years.4 This pigmentation can

Fig. 2 Amsler grid testing. The patient indicated inferior and superotemporal scotomas in the left eye and a large temporal scotoma in the right eye.

Fig. 3 (A) Fundus photo of the right eye demonstrated grade 2+ arteriovenous nicking, widespread angioid streaks with associated geographic atrophy, and extensive disciform scarring with pigmentation. (B) Fundus photo of the left eye showed grade 2+ arteriovenous nicking, angioid streaks with associated geographic atrophy, and macular scarring.

sometimes cause angioid streaks to be overlooked. Additional non-specific retinal findings in PXE also include disc drusen, “histo-like” scars, and peripheral salmon patches.3,4 Fluorescein angiography (FA) may show either a hyperfluorescent window defect over the angioid streaks due to retinal pigmented epithelium (RPE) atrophy or hypofluorescence due to RPE hyperplasia.4,7 Angioid streaks are sometimes able to exhibit autofluorescence

due to RPE cell death and lipofuscin accumulation which is best viewed with a confocal scanning laser ophthalmoscope.8 FA is not indicated unless CNV is suspected.3 Indocyanine green angiography (ICGA) will show the streaks as hyperfluorescent bands with pinpoints of even brighter hyperfluorescence.3 ICGA may be superior to FA to detect angioid streaks as it is more sensitive at highlighting small changes.4,9 “Peau d’orange” retinal mottling appears as spotted hyperfluorescence with ICGA.

Ocular Findings in a Case of Pseudoxanthoma Elasticum — Skorin Jr., Schauer

Fig. 4 (A) Macular OCT of the right eye illustrated diffuse irregular macular thickness without associated edema. (B) Macular OCT of the left eye revealed nasal macular thickening and irregularity without associated edema.

Full-field electroretinography (ERG) may serve a role in the ocular evaluation of the PXE patient. In a recent study, generalized retinal dysfunction was found to be more common than originally thought due to abnormal functional phenotype findings: cone-rod dystrophy, rod-cone dystrophy, and severe photoreceptor dystrophy.10,11 Patients with angioid streaks are typically asymptomatic and do not require treatment, but may develop visual impairment in middle adulthood. In 72% to 86% of patients with angioid streaks, CNV can grow through breaks in Bruch’s membrane, with both eyes being affected in 70% of patients.12 Less commonly, visual impairment can be the result of foveal involvement by an angioid streak or by trauma-induced choroidal rupture. Because Bruch’s membrane is extremely brittle, even minor blunt trauma can rupture the choroid and result in a subretinal hemorrhage.2,13 CNV may be treated by conventional thermal laser photocoagulation; but, there is a high risk of recurrence. Treatment can often result in scarring causing visual acuity loss and visual field scotomas. Photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis, Dorval, QC) can decrease or arrest progression of CNV but recurrence and ultimate vision loss is common.3,4,12 Surgical treatments such as macular translocation and

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subfoveal CNV excision have not been successful.4 Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections can stabilize vision; but, CNV can still recur or develop at a new site. However, 85.7% of patients with angioid streak-associated CNV treated with ranibizumab (Lucentis, Genentech, San Francisco, CA) stabilized or improved visual acuity.12 In half of the patients also showed a decrease in retinal thickness via OCT imaging, even though 15% still showed persisting leakage. Ranibizumab is an antigen binding region fragment of humanized monoclonal antibody that is able to neutralize the active form of VEGF factor. It is used for treatment of all types of neovascular “wet” ARMD.7,12 Another study confirmed the positive results of ranibizumab with a mean improvement of 12 letters of reading ability in patients who received monthly injections along with decreased retinal thickness and regressed leakage.7 In addition, most patients involved in a separate study continued to show stable or improved visual acuity after one year.14 Similar long-term optimistic results have been obtained with off-label use of bevacizumab (Avastin) intravitreal injections.15-17 The most success is achieved with early treatment. However, treatment with anti-VEGF agents did not slow RPE atrophy and may possibly expedite it.15 Spectral domain

OCT is a useful tool to evaluate for CNV. Subretinal fluid in patients with PXE is not always indicative of active CNV leakage but instead may be due to abnormal RPE function.11 Subretinal hemorrhage due to choroidal rupture may be treated with a pars-plana vitrectomy and gas-fluid exchange if the hemorrhage does not regress with time. The location of the choroidal rupture strongly affects the visual outcome, especially if the macula is involved. Therefore, injury prevention is paramount.18 Choroidal rupture without hemorrhage that develops CNV in the macular area may be treated with anti-VEGF agents as discussed above.19 There are many other possible systemic causes of angioid streaks to consider. Although PXE is by far the most common association, Paget disease (osteitis deformans) is a progressive chronic metabolic bone disease due to excessive, disorganized resorption and reformation of bone. It results in osteoarthritis, deafness, and vertigo. Angioid streaks appear 8% to 10% of the time with Paget disease when calcium binds to elastin in Bruch’s membrane.3 Hemoglobinopathies, such as sickle-cell, thalassemia, and spherocytosis, can occasionally cause iron deposition into Bruch’s membrane that leads to angioid streaks. Less common causes of angioid streaks include lead poisoning, Marfan syndrome, Ehlers-Danlos syndrome (fibrodysplasia hyperelastica), Sturge-Weber syndrome, tuberous sclerosis, acromegaly, abetalipoproteinemia, thrombocytopenic purpura, and retinitis pigmentosa. Angioid streaks may also be idiopathic.1-3 There is no current treatment for PXE. Patients should be advised to avoid high-risk sports and activities that could cause subretinal hemorrhage.13 They should wear protective polycarbonate safety glasses, avoid smoking, and adapt lifestyle changes to decrease risk of hypertension and atherosclerosis. Anti-coagulant medications may increase the risk of bleeding complications and, when appropriate, should be avoided.2,4 Visual prognosis of patients with PXE is usually poor. The majority of patients over age 50 often manifest a visual acuity of 6/60 (20/200), although total blindness is rare.4 Patients with angioid streaks should be thoroughly evaluated with a complete eye examination with specific attention to visual acuity, dilated fundus evaluation, Amsler grid, and FA. Other important ancillary tests include: sickle cell testing, serum alkaline phosphatase, serum lead levels, phosphorus, urine calcium levels, and skin biopsy. Cardiovascular and gastrointestional evaluations are also indicated.1-3 ❏

10.

11.

12.

13.

14.

15.

16.

17.

18.

REFERENCES 1.

Onofrey BE, Skorin L Jr., Holdeman NR. Ocular Therapeutics Handbook: A Clinical Manual, 3rd edition. Philadelphia, Lippincott Williams & Wilkins, 2011: 493-494. Kaiser PK, Friedman NJ, Pineda R II. The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology, 2nd edition. Philadelphia: Saunders, 2004: 333-335.

19.

Kanski JJ, Bowling B. Clinical Ophthalmology: A Systemic Approach, 7th edition. Philadelphia, Elsevier Health Sciences, 2011: 641-643. Finger RP, Issa PC, Ladewig MS, Götting C, et al. Pseudoxanthoma elasticum: genetics, clinical manifestations, and therapeutic approaches. Surv Ophthalmol 2009; 54(2): 272-285. von Beckerath O, Gaa J, von Mohrenfels CW, von Beckerath N. Intermittent claudication in a 28-year-old man with pseudoxanthoma elasticum. Circulation 2008; 188: 102-104. Kumar G, Ragi K, Pradeep N. Pseudoxanthoma elasticum with cerebrovascular accident. Indian J Dermatol Venereol Leprol 2007; 73(3): 191-193. Finger RP, Issa PC, Hendig D, Scholl HPN, et al. Monthly ranibizumab for choroidal neovascularizations secondary to angioid streaks in pseudoxanthoma elasticum: a one-year prospective study. Am J Ophthalmol 2011; 152(4): 695-703. Finger RP, Issa PC, Ladewig M, Götting C, et al. Fundus autofluorescence in pseudoxanthoma elasticum. Retina 2009; 29(10): 1496-1505. Lee JW, Shin EP, Kim SY. A case of intravitreal bevacizumab injection for the treatment of choroidal neovascularization in angioid streaks. Korean J Ophthalmol 2011; 25(3): 218-221. Audo I, Vanakker OM, Smith A, Leroy BP, et al. Pseudoxanthoma elasticum with generalized retinal dysfunction, a common finding? Invest Ophthalmol Vis Sci 2007; 48(9): 4250-4256. Zweifel SA, Imamura Y, Freund KB, Spaide RF. Mutimodal: Fundus imaging of pseudoxanthoma elasticum. Retina 2011; 31(3): 482-491. Mimoun G, Tilleus J, Leys A, Coscas G, et al. Intravitreal ranibizumab for choroidal neovascularization in angioid streaks. Am J Ophthalmol 2010; 150(5): 692-700. Alpay A, Caliskan S. Subretinal hemorrhage in a soccer player: a case report of angioid streaks. Clin J Sport Med 2010; 20(5): 391-392. Ladas ID, Kotsolis AI, Ladas DS, Niskopoulou M, et al. Intravitreal ranibizumab treatment of macular choroidal neovascularization secondary to angioid streaks: one-year results of a prospective study. Retina 2010; 30(8): 1185-1189. Finger RP, Issa PC, Schmitz-Valckenberg S, Holz FG, et al. Long-term effectiveness of intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks in pseudozanthoma elasticum. Retina 2011; 31(7): 1268-1278. Chang LK, Spaide RF, Brue C, Freund KB, et al. Bevacizumab treatment for subfoveal choroidal neovascularization from causes other than age-related macular degeneration. Arch Ophthalmol 2008; 126(7): 941-945. Bhatnagar P, Freund KB, Spaide RF, Klancnik JM Jr., et al. Intravitreal bevacizumab for the management of choroidal neovascularization in pseudoxanthoma elasticum. Retina 2007; 27(7): 897-902. Horn EP, McDonald HR, Johnson RN, Ai E, et al. Soccer ball-related retinal injuries: a report of 13 cases. Retina 2000; 20(6): 604-609. Francis JH, Freund KB. Photoreceptor reconstitution correlates with visual improvement after intravitreal bevacizumab treatment of choroidal neovascularization secondary to traumatic choroidal rupture. Retina 2011; 31(2): 422-424.

Ocular Findings in a Case of Pseudoxanthoma Elasticum — Skorin Jr., Schauer

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QUESTIONNAIRE The Streak Marks the Spot: Ocular Findings in a Case of Pseudoxanthoma Elasticum Leonid Skorin Jr., DO, OD, MS, FAAO, FAOCO; Brittany Schauer, OD 1. (A) (B) (C) (D)

Pseudoxanthoma Elasticum (PXE) causes calcification, fragmentation and degeneration of the elastic fibers of all of the following, EXCEPT: Central nervous system Skin Eye Cardiovascular system

2. (A) (B) (C) (D)

In cases of PXE, how much more are women affected than men? Women and men are affected equally Women are affected twice as often as men Women are affected three times as often as men Women are affected four times as often as men

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(A) (B) (C) (D)

In the Case Report presented, what was the patient’s best-corrected near visual acuity OU at initial presentation? 6/24+1 (20/80+1) 6/30 (20/100) 6/36+1 (20/120+1) 6/38+1 (20/125+1)

4. (A) (B) (C) (D)

In cases of PXE, when does cardiac involvement typically present? In the second to third decade In the third to fourth decade In the fourth to fifth decade In the fifth to sixth decade

In the Case Report presented, which of the following clinical signs and symptoms did the patient present with at her diabetic eye examination? Decrease in vision Flashes Vertigo A and B are correct

(A) (B) (C) (D) 6. (A) (B) (C) (D)

The Streak Marks the Spot: Ocular Findings in a Case of Pseudoxanthoma Elasticum In the Case Report presented, what was the patient’s intraocular pressure? 18 mmHg OD and 17 mmHg OS 19 mmHg OD and 18 mmHg OS 20 mmHg OD and 19 mmHg OS 21 mmHg OD and 20 mmHg OS

7. (A) (B) (C) (D)

In cases of PXE, the majority of patients over age 50 often manifest a visual acuity of: 6/48 (20/160) 6/60 (20/200) 6/75 (20/250) 6/95 (20/320)

8. (A) (B) (C) (D)

In Paget disease, angioid streaks appear in what percentage of the time? 8%-10% 10%-15% 15%-20% 20%-25%

9. (A) (B) (C) (D)

In the Case Report presented, which of the following medications was the patient taking? Glipizide Metformin-alogliptin Glimepiride Insulin glargine

10. (A) (B) (C) (D)

Which of the following statements accurately describe PXE? Ocular signs occur in 60% to 80% of patients One of the areas “plucked chicken” skin is most easily seen is the neck Bruch’s membrane is brittle, thickened and calcified All of the above

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Ocular Findings in a Case of Pseudoxanthoma Elasticum — Skorin Jr., Schauer

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Akilia Hang Nguyen et al entitled Adult-Onset Foveomacular Vitelliform Dystrophy Masquerading as Age-Related Macular Degeneration. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 102 for complete instructions.

Adult-Onset Foveomacular Vitelliform Dystrophy Masquerading as Age-Related Macular Degeneration Akilia Hang Nguyen, OD; Tam Nguyen, OD, MS, FAAO Theresa Zerilli-Zavgorodni, OD, FAAO Nancy Shenouda-Awad, OD, FAAO

ABSTRACT The purpose of this case report is to demonstrate the clinical presentation and work-up needed to diagnose adult-onset foveomacular vitelliform dystrophy (AFVD). A 72-year-old male presented for a 6-month follow-up to monitor his dry age-related macular degeneration (ARMD) OU. At this visit, the patient had improved visual acuity and visual symptoms from prior visit in both eyes. Dilated fundus examination and optical coherence tomography (OCT) were found to be inconsistent with a previous diagnosis of ARMD. Clinical presentation and repeated OCT exam confirmed a new diagnosis of AFVD. Adult-onset foveomacular vitelliform dystrophy is a rare macular pattern dystrophy which may cause gradual vision loss. Adult-onset foveomacular vitelliform dystrophy is highly variable in clinical appearance, often making it difficult to diagnose; AFVD is often mistaken for dry ARMD or Best’s disease. Knowledge of the clinical presentation, epidemiology and stages of common masqueraders is important for accurate diagnosis of AFVD. This case report discusses diagnostic criteria, clinical evaluation, treatment, and management for AFVD.

A.H. Nguyen — Central Texas Veteran’s Health Care System; T. Nguyen — VA Connecticut Healthcare System, West Haven Campus; T. Zerilli-Zavgorodni — VA Connecticut Healthcare System, West Haven Campus; N. Shenouda-Awad — VA Connecticut Healthcare System, West Haven Campus Correspondence to: Dr. Tam Nguyen, VA Connecticut Healthcare System, West Haven Campus, 950 Campbell Ave. Building 2, Floor 4, West Haven, CT 06516; Email: Tam.Nguyen5@va.gov The authors have no financial or proprietary interest in any material or method mentioned in this article. This article has been peer reviewed.

Clinical and Refractive Optometry 28:3, 2017

INTRODUCTION Adult-onset foveomacular vitelliform dystrophy (AFVD) was first described in 1974 by Gass.1 It is also known as adult vitelliform maculopathy, adult onset Best’s dystrophy, peculiar foveomacular dystrophy, vitelliform macular degeneration or foveomacular vitelliform dystrophy, adult type.2,3,4 It is categorized as one of the five rare pattern dystrophies: adult-onset vitelliform foveamacular dystrophy, butterfly-shaped pigment dystrophy, reticular dystrophy, multifocal pattern dystrophy, and fundus pulverulentus.5 These pattern dystrophies all share a common phenotype, which affects the retinal pigment epithelium (RPE). Genetic studies have revealed an autosomaldominant inherited pattern in the mutations of RDS/ Peripherin, BEST1, IMPG1 (Interphotoreceptor Matrix Proteoglycan 1) or IMPG2 and VMD2 (vitelliform macular dystrophy) link to these five rare pattern dystrophies.3,6,7,8 However, in AFVD, sporadic cases have been reported and most patients with AFVD do not carry these gene mutations.4,6,7 Typically, individuals with mutated genes show heterogeneous, lipofusion-laden cells accumulating between the photoreceptor layer and the RPE.2,8,9,10 As the name suggests, the onset of AFVD is typically between the third and sixth decades of life, but can be highly variable.3,11 Adult-onset foveomacular vitelliform dystrophy does not have a specific racial predilection, but women are at a higher risk than their male counterparts.8 Patients often remain asymptomatic until the fifth decade and some may remain asymptomatic indefinitely.3,11 Symptomatic patients mostly complain of slow, progressive, painless central vision loss. On clinical examination, vitelliform lesions are located in or near the macula. It is characterized by discrete, yellow-grey-white, and slightly elevated lesions. These lesions can have variable patterns, such as a spot, figure or ring with small central pigment clumping.2 In most cases, AFVD is bilateral and asymmetric between the eyes. However, it may also present unilaterally.7,9,12,13 Adult-onset foveomacular vitelliform dystrophy is highly variable in clinical appearance and, oftentimes, mimics Best’s dystrophy or ARMD, leading to an inaccurate diagnosis. The management, course, and prognosis varies for each of these conditions, therefore, arriving at the

correct diagnosis is imperative. Supplemental testing such as fluorescein angiography (FA), OCT, electro-oculogram (EOG), electro-retinogram (ERG), fundus autofluorescence (FAF) are an integral part of the work up. Once the correct diagnosis is made, the patient can be educated about the disease course, prognosis and treatment options. Generally, AFVD has a favorable visual prognosis, however, severe vision loss can occur if the disease progresses to choroidal neovascularization (CNV) formation or geographic atrophy.7,8 If CNV has developed intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is often recommended to reduce macular thickness. However, this does not always correlate to improvement in visual acuity.14 This case report will discuss the clinical presentation, differential diagnosis, treatment options and prognosis of AFVD. Furthermore, it will highlight key characteristics between AFVD and other maculopathies in order to facilitate accurate diagnosis.

CASE REPORT A 72-year-old, white male with a history of ARMD OU presented to the Eye Clinic at West Haven VA Hospital in December 2015 for a 6-month follow-up. He reported no changes in his vision and denied metamorphopsia or scotoma. He was taking AREDS 2 multi-vitamins twice daily as recommended at his last eye exam. His ocular history was remarkable only for dry ARMD in both eyes. His medical history was remarkable for hyperlipidemia and type 2 diabetes mellitus for 30 years without ocular manifestations. His last HbA1c was 6.5%. His medications included simvastatin, Novolin insulin, metformin and glipizide. His social history was negative for alcohol use, recreational drugs, and smoking. He had no known drug or environmental allergies. His family ocular and medical histories were unremarkable. Upon examination best-corrected visual acuity was 6/9 (20/30) OD, and 6/9+1 (20/30+1) OS. The patient’s best corrected visual acuity had improved in his right eye and remained stable in his left eye since his last exam in June 2015. Previously, he was 6/18 (20/60) and 6/9+2 (20/30+2), respectively. On entrance examination, pupils, ocular motilities, and confrontation fields were within normal limits in both eyes. Intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT) was 17 mmHg OD and 16 mmHg OS. The anterior segment was only remarkable for nasal pterygium OD. Dilated fundus examination of the OD revealed four large, discrete, yellow lesions surrounding the foveal center (Fig. 1A). In addition, there was RPE clumping overlying the foveal center OD. In the left eye, there were scattered, paramacular, medium soft drusen and central RPE clumping (Fig. 1B). There were no signs of CNV (Fig. 1A, 1B). At previous dilated examinations, the lesions were noted as one large, soft confluent drusen OU with RPE changes OU.

Macular optical coherence tomography (OCT) showed drusenoid pigment epithelial detachments (PED) in both eyes with good foveal contour, no thickening and no signs of CNV (Fig. 1C, 1D). Macular OCT findings from his last visit in June of 2015 (Fig. 2A, 2B) showed large drusenoid PEDs with multiple subfoveal hyper-reflective lesions disturbing the foveal contour OD (Fig. 2A, arrow). Macular OCT OS showed good foveal contour with small drusenoid PEDs and a few small intra-retinal hyper-reflective lesions (Fig. 2B, arrow). At the June visit, the visual acuity was 6/18 (20/60) OD and 6/9 (20/30) OS and corresponded to the disrupted foveal contour seen on the macular OCT OD. Although the macular OCT findings (Fig. 2A) were suggestive of ARMD or AFVD, the patient was diagnosed with ARMD because demographically it fit the clinical picture. Adult-onset foveomacular vitelliform dystrophy because of its rarity was lower on the list of differentials. Due to the improvement in his visual acuity, and changes in the clinical appearance and macular OCT findings, his diagnosis was changed from ARMD to AFVD OU. He was educated on the prognosis and visual outcome of the disease and was instructed to return in 6 months. At the follow-up examination in March 2016, he again presented with no ocular complaints. His visual acuities, entrance tests and anterior segment findings remained stable. On fundus examination, the left eye was stable in appearance, however, in the right eye, the vitelliform lesions had shifted slightly and decreased in size. Retinal pigment epithelium changes were stable (Fig. 3A, 3B). The macular OCT showed significant improvement OD and remained relatively stable from his initial exam OS (Fig. 3C, 3D). Fundus autofluorescence was obtained and showed no hyper-fluorescence (Fig. 3E, 3F). Resolution of drusenoid PEDs on macular OCT was an unexpected finding. Overall, his ocular examination was stable and he was advised to return every 6 months for dilated fundus examination, or sooner if he became symptomatic for metamorphopsia, vision changes, or scotomas.

DISCUSSION Adult-onset foveomacular vitelliform dystrophy is the most common of the five rare pattern dystrophies.15 Patients are often asymptomatic and rarely complain of visual field loss, metamorphopsia, or scotomas.7,11,16 Patients typically present with a visual acuity range between 6/7.5 (20/25) to 6/120 (20/400), with a mean acuity of 6/15 (20/50).7,16 Adult-onset foveomacular vitelliform dystrophy can easily be mistaken for Best’s disease due to the yellowgrey central lesion, or dry ARMD due to the classic soft drusen.3,4 Given the similarity in clinical appearance, the top two differentials are Best’s dystrophy and ARMD. Correct diagnosis is paramount in order to manage the

Adult-Onset Foveomacular Vitelliform Dystrophy — Nguyen et al

Fig. 1 (From December 2015) (A) Color fundus photo OD showing four large, discrete, yellow vitelliform lesions surrounding the foveal center and central RPE clumping. (B) Color fundus photo OS showing scattered, paramacular, medium soft drusen and central RPE clumping. (C) Macular OCT of OD with good foveal contour, drusenoid PED, disruption of the IS/OS interface (arrow), and no signs of CNV. (D) Macular OCT OS with good foveal contour, drusenoid PED, intra-retinal hyper-reflective lesion (arrow), and no signs of CNV.

condition and be able to properly educate the patient on prognosis and visual outcomes. Diagnostic testing becomes an important tool to aid in correct diagnosis. On clinical examination, AFVD lesions can vary in size, but typically are one-third to one-half disc diameters in size.10 They are often yellow-grey with central pigmentation. The deposits are composed of extracellular photoreceptor outer segment debris, pigment, lipofuscin-laden RPE, and macrophages anterior to the RPE.2,4,12,17 The yellow material is an indicator of advanced damage to the RPE and can fade overtime.1 Adult-onset foveomacular vitelliform dystrophy commonly presents with multiple vitelliform lesions whereas an isolated lesion is often more indicative of Best’s dystrophy.7 Patients with AFVD progress through stages similar to that of Best’s dystrophy. However, most patients do not proceed through all the stages.18 In the earlier stages of AFVD, patients are often asymptomatic or complain of mild visual acuity loss. In the later stages, vision loss can become more significant. Overall, vision loss is a very slow process. Only 5% to 15% of all AFVD patients experience end-stage complications, including subfoveal CNV, full thickness macular hole, or retinal detachment.18

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The four stages of Best’s dystrophy includes previtelliform (stage 1), vitelliform (stage II), pseudohypopyon (stage III), vitelliruptive or “scrambled egg” (stage IV), atrophic (stage Va) and subfoveal CNV (stage Vb). In pre-vitelliform (stage I), patients usually present with normal fundus findings. In the vitelliform stage (stage II), classic “egg-yolk” is observed and visual acuity is still normal. In the pseudohypopyon stage (stage III), the vitelliform liquefies and settles inferiorly. Once it progresses to vitelliruptive (stage IV), vitelliform lesions are absorbed and RPE clumping and migration becomes more apparent. In a retrospective study, CNVs are most commonly detected in the vitelliruptive stage of the lesion rather than the vitelliform stage.3,14,18 Adult-onset foveomacular vitelliform dystrophy advances through similar stages as Best’s dystrophy, however, most AFVD patients do not progress through all of these distinct stages.3,18 In end-stage AFVD, there is usually RPE atrophy, in contrast to the hypertrophic scars in the majority of Best’s dystrophy patients.3,18 In the present case, the patient was most likely in vitelliruptive (stage IV) of the disease. When examining the fundus photos in Figure 1A and 1B compared to fundus

Fig. 2 (From June 2015) (A) Macular OCT of OD, showed hyper-reflective subfoveal lesions with disrupted photoreceptor layer, multiple drusenoid PED and no CNV. Arrow pointing towards disruption in IS/OS interface. (B) Macular OCT OS, showed good foveal contour, small drusenoid PED, small intra-retinal hyper-reflective lesions (arrow), and no CNV.

photo, Figure 3A and 3B, over a 6-month period, the vitelliform lesions shifted and decreased in size as they were being absorbed. This is more noticeable in the right eye than the left eye. In retrospective evaluations of the macular photos, and OCT from June 2015 (Fig. 4A, 4B) compared to December 2015 (Fig. 4C, 4D), definitive changes in the vitelliform lesions were revealed. During the 6-month time period, the right eye (Fig. 4A, 4C) lesions have displaced inferiorly and were in the process of being absorbed. In the left eye, (Fig. 4B, 4D), the vitelliform lesion also showed absorption. Moreover, the most recent photos (Fig. 3A, 3B), revealed central RPE migration OU that is consistent with Stage IV of the disease process. Macular OCT becomes a crucial diagnostic test in patients with maculopathy. Macular OCT will vary depending on the stage of AFVD. The macular OCT OD (Fig. 2A) from June 2015 represents AFVD Stage III. This stage is characterized by a focal, dome-shaped, and hyper-reflective subretinal lesion. The disruption in foveal contour causes a decline in visual acuity. In addition, macular OCT often reveals disruption of the inner segment and outer segment (IS/OS) interface as shown by the arrow in 2A.11,12 In this stage, the similar clinical presentations make it easy for clinicians to misdiagnose this maculopathy for ARMD. Adult-onset foveomacular vitelliform dystrophy Stage IV, is characterized by the absorption of the vitelliform lesions, decreased thickness, and visual acuity improvement.3,11 This was true in our patient. In contrast to ARMD, drusenoid PED’s would increase in size over time and vision would continue to deteriorate. In AFVD, during Stage IV of the disease, the majority of the lipofusion is absorbed. As a result, FAF testing will appear normal (Fig. 3E, 3F). It can be hypothesized that if FAF was performed in June 2015, vitelliform lesions may have been more apparent. The classic hyper-AF surrounded by the hypo-AF ring is usually seen in stages II to III of AFVD. Figure 5A-5F

demonstrates a different patient with late AFVD stage III OD and OS. In the fundus photo, the classic vitelliform lesions are more noticeable in the left eye than the right eye, because the OD lesion is more absorbed. The macular OCT OD and OS reveal the dome-shaped hyper-reflective subfoveal pattern with IS/OS disruption shown by the arrows. Macular OCT OD (Fig. 5C) shows more disruption of the IS/OS junction and the lesion is smaller in size than the lesion in OS which corresponds with later AFVD Stage III. Moreover, fundus autofluorescence OS shows the classic hypo-AF center and hyper-AF ring that is often seen in patients with AFVD (Fig. 5E, 5F). Due to the clinical appearance and staging of the disease after review of past macular OCT images the diagnosis of AFVD was confirmed. FA, EOG, and electroretinogram (ERG) were not performed. FA may be performed later to further confirm diagnosis and rule out a CNV, however, the retinologist agreed that ordering an FA would not add any further diagnostic value. The typical age of onset for Best’s dystrophy is usually between 3 to 15 years of age. It has an autosomal dominant inherent pattern and usually progresses through all stages aforementioned. It is characterized by bilateral, usually symmetric, single and discrete yellow-grey vitelliform lesion on fundus examination. Macular OCT will show large, hyper-reflective subfoveal lesions. Macular OCT and FAF is often similar between Best’s and AFVD. The EOG demonstrates a reduced Arden ratio in Best’s dystrophy compared to AFVD and can be used to differentiate Best from AFVD. End-stage Best’s usually results in hypertrophic scars and decreased visual acuity. In contrast, AFVD does not progress through all of the stages and end stage disease does not result in as severe of a visual decline as noted in Best’s dystrophy.3,11,18 Beside Best’s dystrophy, ARMD is the other most common degeneration often mistaken for AFVD. Agerelated macular degeneration can present with macular drusen, drusenoid PEDs, and disruption of the IS/OS

Adult-Onset Foveomacular Vitelliform Dystrophy — Nguyen et al

Fig. 3 (From March 2016) (A) Color fundus photo of OD showing the vitelliform lesions have shifted inferiorly and decreased in size with central RPE migration. (B) Color fundus photo of OS showing stable appearance. (C and D) Macular OCT of OD and OS, respectively showing improvement in drusenoid PED of OD and relatively stable OS. (E and F) FAF of OD and OS, respectively showing normal hypo-fluorescence of the macula.

interface on macular OCT, which can resemble AFVD clinically. Age-related macular degeneration, however, does not improve as the disease progresses. In this case, the drusen found on initial fundus examination and macular OCT were consistent with ARMD. Given the prevalence of ARMD, OCT findings, and the age of our

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patient, ARMD was the more likely diagnosis at the initial presentation. In two subsequent examinations, macular OCT findings as well as visual acuity significantly improved. OCT showed decreased macular thickness and resorbed subfoveal lipofuscin. These are two critical characteristics that differentiate AFVD from ARMD.

Fig. 4 (From June 2015 vs December 2015) (A) Heidelberg Spectralis OCT taken in June 2015 showing OD with multiple central vitelliform lesions. (B) Photo taken in June 2015 by the Heidelberg Spectralis OCT showing OS with central vitelliform lesion. (C) Photo taken in December 2015 by the Heidelberg Spectralis OCT showing OD with vitelliform lesions displaced inferiorly. (D) Photo taken in December 2015 by the Heidelberg Spectralis OCT showing OS with mostly absorbed vitelliform lesion.

Adult-onset foveomacular vitelliform dystrophy has a more favorable visual prognosis than ARMD, however, severe vision loss can occur if the disease progresses to CNV or geographic atrophy.5,8 Therefore, in patients with AFVD, it is important to monitor patients closely with regular dilated fundus evaluations.2,3,4,12,16,17 If CNV develops,

immediate referral is necessary for consideration of FA and intra-vitreal injection of anti-VEGF treatment to reduce macular thickness. Vision loss may be irreversible in patients with AFVD. The patient can suffer further visual decline should the condition progress to the atrophic stage.14 If this occurs, a low vision rehabilitation referral

Adult-Onset Foveomacular Vitelliform Dystrophy â&#x20AC;&#x201D; Nguyen et al

Fig. 5 (A different patient with AFVD) (A) fundus photo of OD showing minimal macular changes. (B) Fundus photo of OS showing small, yellow, vitelliform lesion overlying the fovea. (C) Macular OCT of OD showing the hyper-reflective lesion with IS/OS disruption. (D) Macular OCT of OS showing the hyper-reflective subfoveal, vitelliform lesion. (E) FAF of OD showing hyper-autofluorescence centrally from the vitelliform lesion. (F) FAF of OS showing the classic AFVD characteristic of hyper-autofluorescence ring with hypo-autofluorescence center.

100

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Table I Adult-onset foveomacular vitelliform dystrophy (AFVD) characteristics on ancillary testing Macular OCT

Focal, dome-shaped, hyper-reflective, subretinal lesion3,7,13 Disruption of the IS/OS junction3 Can vary depending on the stage

Fundus Autofluorescence (FAF)

Central hypo-autofluorescence center with ring of hyper-autofluorescence5,7 Can vary depending on the stage

Fluorescein Angiography (FA)

Central hypo-fluorescence in early frame with ring of hyper-fluorescence7 Can vary depending on the stage

Electro-Oculogram (EOG)

Normal or mildly reduced EOG Arden ratio can be normal or subnormal5,7

Electro-Retinogram (ERG)

Full-field ERG can be normal, or slightly decreased in b-wave amplitude5,7 Often variable

should be considered in order to enhance remaining areas of vision. In addition, it is recommended that family members also have their ocular health examined for early signs of AFVD due to its inheritance pattern. Although AFVD is a rare finding, clinicians should always include it as a possible differential diagnosis for ARMD. This is true especially in cases where patients don’t fit the specific demographic profile or the typical clinical course of ARMD. The clinician should be suspicious of AVFD if there is improvement on visual acuity or OCT findings over the course of time. Because of the similar clinical findings, masqueraders of ARMD should include Best’s dystrophy and AFVD. In addition to a comprehensive dilated fundus exam to evaluate the macula, a variety of diagnostic tools can be used to identify AFVD. Clinicians should consider macular OCT, FAF, FA, EOG, and ERG. Distinct features of AFVD on ancillary testing are included in Table I.

3. 4. 5. 6.

7. 8. 9.

10.

CONCLUSION

11.

Adult-onset foveomacular vitelliform dystrophy is a rare macular pattern dystrophy not often encountered in the primary care setting. Patient can be asymptomatic or have minimal symptoms. It resembles Best’s dystrophy and ARMD due to their similar clinical appearances making it a common masquerader. Clinical tests, such as OCT, FAF, FA, EOG, and ERG become important for differentiation. Although, AFVD often has good visual prognosis and rarely any complications, clinicians should be aware of the dystrophy in order to provide the most accurate diagnosis, and best educate patients on prognosis and management in order to minimize ocular morbidity. ❏

12.

13. 14.

15. 16.

REFERENCES 1. 2.

Gass JD. A clinicopathologic study of a peculiar foveomacular dystrophy. Trans Am Ophthalmol Soc. 1974; 72: 139-156. Arnold JJ, Sarks JP, Killingsworth MC, et al. Adult vitelliform macular degeneration: a clinic pathological study. Eye 2003; 17(6): 717-726.

17. 18.

Chowers I, Tiosano L, Audo I, et al. Adult-onset foveo-macular vitelliform dystrophy: a fresh perspective. Prog Retin Eye Res 2015; 47: 64-85. Tiosano L, Grunin M, Hagbi-Levi S, et al. Characterising the phenotype and progression of sporadic adult-onset foveomacular vitelliform dystrophy. Br J Ophthalmol 2016; 100(11): 1476-1481. Hamilton J, Burke C. Pattern recognition: how to identify and confirm multifocal pattern dystrophy. Review of Optometry, December 2015. Neren A. Acquired vitelliform macular dystrophy. Ophthalmology Grand Rounds, July 2013. SUNY Downstate Department of Ophthalmology, Website Accessed January 22, 2016. <http://www.downstate.edu/ophthalmology/pdf/ GrandRounds-Asher-acquired-md.pdf>. Grob S, Yonekawa Y, Eliott D. Multimodal imaging of adultonset foveomacular vitelliform dystrophy. Saudi J Ophthalmol 2014; 28(2): 104-110. Hodges VM, McGonigal W. Adult vitelliform maculopathy management: from anti-VEGF to low vision. Review of Optometry 2012; 149(6): 84. Coscas F, Puche N, Coscas G, et al. Comparison of macular choroidal thickness in adult onset foveomacular vitelliform dystrophy and age-related macular degeneration. Invest Ophthalmol Vis Sci 2014; 55(1): 64-69. Holz FG, Spaide RF, eds. Medical Retina. Berlin: Springer, 2005. Print. Bhakhri R. Spectral domain optical coherence tomography and autofluorescence findings in adult-onset vitelliform dystrophy. Clin Exp Optom 2015; 98(3): 292-293. Querques B, Forte, R Querques L, et al. Natural course of adultonset foveomacular vitelliform dystrophy: a spectral-domain optical coherence tomography analysis. Am J Ophthalmol 2011; 152(2): 304-313. Parodi MB, Iacono P, Pedio M, et al. Autofluorescence in adultonset foveomacular vitelliform dystrophy. Retina 2008; 28(6); 801-807. Tiosano L, Jaouni T, Averbukh E, et al. Bevacizumab treatment for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Eur J Ophthalmol 2014; 24(6): 890-896. Renner AB, Tillack H, Kraus H, et al. Morphology and functional characteristics in adult vitelliform macular dystrophy. Retina 2004; 24(6): 929-939. Epstein GA, Rabb MF. Adult vitelliform macular degeneration: diagnosis and natural history. Br J Ophthalmol 1980 64(10): 733-740. Burgess DB, Olk RJ, Uniat LM. Macular disease resembling adult foveamacular vitelliform dystrophy in older adults. Ophthalmology 1987; 94(4): 362-366. Do P, Ferrucci S. Adult-onset foveomacular vitelliform dystrophy. Optometry 2006; 77(4): 156-166.

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QUESTIONNAIRE Adult-Onset Foveomacular Vitelliform Dystrophy Masquerading as Age-Related Macular Degeneration Akilia Hang Nguyen, OD; Tam Nguyen, OD, MS, FAAO; Theresa Zerilli-Zavgorodni, OD, FAAO; Nancy Shenouda-Awad, OD, FAAO 1. (A) (B) (C) (D)

At what point does Adult-onset foveomacular vitelliform dystrophy (AFVD) typically appear? Under the age of 18 Between the second and third decades of life Between the third and sixth decades of life Over the age of 75

2. (A) (B) (C) (D)

Which of the following statements about AFVD is TRUE? It does not have a specific racial predilection Women are at higher risk than men Patients may be asymptomatic indefinitely All of the above

Clinical and Refractive Optometry 28:3, 2017

(A) (B) (C) (D)

In the Case Report presented, what was the patient’s best-corrected visual acuity (BCVA) OS at initial presentation? 20/20 (6/6) 20/30+1 (6/9+1) 20/40 (6/12) 20/50 (6/15)

4. (A) (B) (C) (D)

All of the following statements about AFVD are true, EXCEPT: There appears to be no predilection for gender The frequency increases with decreased visual acuities There is a higher occurrence in men There is a higher occurrence in women

5. (A) (B) (C) (D)

Which of the following statements about AFVD is TRUE? It’s the most common of the five rare pattern dystrophies Patients rarely complain of scotomas Vision loss is usually rapid A and B are correct

6. (A) (B) (C) (D)

In the Case Report presented, what was the patient’s previous best-corrected visual acuity (BCVA) OD? 20/40 (6/12) 20/50 (6/15) 20/60 (6/18) 20/63 (6/19)

7. (A) (B) (C) (D)

At what stage of AFVD is lipofusion absorbed? Stage I Stage II Stage III Stage IV

8. (A) (B) (C) (D)

What is the typical age of onset of Best’s dystrophy? 2-10 years of age 3-15 years of age 15-20 years of age 20-25 years of age

9. (A) (B) (C) (D)

What percentage of all AFVD patients experience end-stage complications? 1%-2% 2%-5% 5%-10% 5%-15%

10. (A) (B) (C) (D)

In the Case Report presented, the patient was most likely in what stage of AFVD? Stage I Stage II Stage III Stage IV

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Nicky Holdeman et al entitled Cat Scratch Neuroretinitis. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 110 for complete instructions.

Cat Scratch Neuroretinitis

INTRODUCTION

Nicky R. Holdeman, OD, MD, FAAO; Liang Ma, PhD, OD; Rosa A. Tang, MD, MPH

Neuroretinitis (NR), secondary to cat scratch disease (CSD), is typically a self-limiting condition caused by an infectious and inflammatory reaction of the optic nerve, followed by the formation of a macular star.1,2 The gram-negative bacillus, Bartonella henselae, the primary etiological cause of CSD, is transmitted to humans through scratches, bites or saliva from an infected cat. Direct exposure to Bartonella henselae can cause optic disc inflammation3,4 with infiltration of lipid-rich fluid though the prelaminar optic disc vasculature. Once this fluid migrates into the outer plexiform layer around the macula, the exudates precipitate and form a partial or complete stellate pattern.5,6 Systemic signs and symptoms usually precede the ocular manifestations and may include rashes, regional lymphadenopathy, fever, headache, nausea, anorexia, vomiting, and sore throat. Other ophthalmic signs include reduced visual acuity, mild color defects, and a mild to moderate relative afferent pupillary defect (RAPD). While there is no race predilection for CSD, males are slightly more affected than females (60% vs. 40%), and children and young adults are at an increased risk of infection. A history of exposure to cats, especially kittens, has been reported in over 90% of cases. Ancillary testing for CSD includes serology for Bartonella henselae, optical coherence tomography (OCT), visual fields, and fluorescein angiography.1 Treatment for CSD is controversial due to its self-limiting nature.1,7,8 However, studies have shown that oral antibiotics may shorten the recovery period, especially in moderate to severe cases.9

ABSTRACT Cat scratch disease (CSD) is caused by a gramnegative bacterium, Bartonella henselae. This uncommon disease is believed to be transmitted by a cat scratch or bite, when the bacterium is present on the cat’s claw or resides in the oral cavity. There are approximately 22,000 cases of CSD diagnosed in the United States annually. Neuroretinitis (NR), which occurs in 1% to 2% of CSD cases, is characterized by acute vision loss, optic disc edema, and a macular star. Diagnosis can be aided by fundus examination, optical coherence tomography (OCT), fluorescein angiography (IVFA), and serological testing for Bartonella henselae infection. Cat scratch disease is usually self-limiting; however, oral antibiotics may shorten the duration of the disease. The following case describes a dramatic presentation of a 13-year-old Hispanic female diagnosed with cat scratch neuroretinitis (CSNR). The patient reported an earlier skin rash and lymphadenopathy and presented with monocular vision loss. Examination revealed optic disc edema and a macular star in the left eye. The diagnosis was confirmed by positive serology for Bartonella henselae. She was treated with sulfamethoxazole/ trimethoprim (Bactrim 400 mg/ 80 mg tablets) for three weeks. After six weeks, her systemic signs and symptoms resolved. Her visual acuity recovered but visual distortion remained.

CASE REPORT N.R. Holdeman — University Eye Institute, University of Houston, Houston, TX; L. Ma — Texas Eye and Vision Associates, P.A., Texas City, TX; R.A. Tang — Neuro-Ophthalmology of Texas, Houston, Texas Correspondence to: Dr. Liang Ma, Texas Eye and Vision Associates, P.A., 3528 Palmer Highway, Texas City, TX 77590; Email: lma.2016@alumni.opt.uh.edu The authors have no conflicts of interest in any material or method mentioned and no financial support was received. This article has been peer reviewed.

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A 13-year-old Hispanic female was in her usual state of good health, until she presented with a chief complaint of gradual, but extremely blurry vision in the left eye. The symptoms began one week earlier and the vision had progressively worsened since onset. Five days prior, the patient went to an emergency department (ED), where optic nerve swelling was detected in the left eye. Magnetic resonance imaging (MRI) of the brain, performed at the emergency visit, was within normal limits. The patient

Fig. 1 (A) Fundus photograph OD showing no abnormalities. (B) Fundus photograph OS documents severe swelling of the optic nerve with macular exudates.

Fig. 2 SD-OCT reveals no abnormalities of the right eye but demonstrates extensive macular thickness, due to intraretinal edema and a large serous detachment in the left eye.

was then referred to a neuro-ophthalmologist for further consultation. At the consult visit, the patient denied any associated symptoms or recent travels outside her home town. Her father reported no relevant medical or ocular history and her

family history was non-contributory. She took no medications and had no known drug allergies, including sulfa derivatives. She was a seventh grader doing well in school and had three dogs and one cat in the home. The patient was alert, oriented and in no apparent distress; her vital signs were normal. Her best-corrected visual acuity was OD: 6/6-2 (20/20-2) and OS: 6/60+1 (20/200+1). Extraocular motility and cover testing were within normal limits, with no pain on eye movement. Confrontation visual fields demonstrated superiortemporal and inferior defects in the left eye, which were supported by the findings on Amsler grid testing. A 1.2 log unit relative afferent pupillary defect (RAPD) was found in the left eye. While the color vision in the right eye was normal (14/14 plates), a mild colour vision defect (12/14 plates) was noted in the left eye, using the HardyRand-Rittler (HRR) pseudo-isochromatic test. Both anterior and posterior segments were normal in the right eye (Fig. 1A); however, biomicroscopy revealed 1+ flare in the anterior chamber and 1+ cell in the anterior vitreous of the left eye. Fundus exam of the left eye showed macular edema, a stellate exudative maculopathy, venous tortuosity, and grade IV optic disc edema (ODE), equivalent to a Modified FrisĂŠn Scale of Papilledema (Fig. 1B). Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) of the left eye documented cystoid macular edema (CME) and a serous macular detachment. The central macular region in the left eye (738 um) was three times that of the right eye (243 um) (Fig. 2). Humphrey 30-2 SITA-Fast visual field (Carl Zeiss Meditec, Dublin, CA), with a size III stimulus, showed a nasal hemisphere depression in the right eye, most likely due to low test reliability. Humphrey 30-2 FastPac visual

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Fig. 3 Humphrey visual field of the right eye, while demonstrating a mild nasal depression, was essentially normal, with a visual field index of 97%. The left eye, even with a size V stimulates, had a dense temporal field loss, with an inferior nasal step.

Fig. 4 SD-OCT of the right eye remained stable; the macular contour and thickness in the left eye was much improved.

field (Carl Zeiss Meditec, Dublin, CA), of the left eye, using a size V target, revealed a significantly enlarged blind spot, a superior-temporal quadrantanopia, and a mild to moderate inferior nasal step (Fig. 3). Based on clinical findings, neuroretinitis (NR) was the tentative diagnosis, with optic neuritis and ischemic

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optic neuropathy as differentials. Since the patient reported having multiple dogs and a cat at home, additional history was obtained. The patient stated that the kitten was a new stray and was rescued from the woods one month prior. About a week later, the cat scratched her arms and she subsequently developed a skin rash and a tender anterior cervical lymphadenopathy. Three weeks later, she noted blurry vision in her left eye, which prompted the emergency room visit. Due to the new information, the patient was tested for Bartonella antibodies. The immunoglobulin G (IgG) titer for Bartonella henselae was positive, with a ratio of 1:1280. The serologic tests confirmed the diagnosis of NR secondary to cat scratch disease (CSD), and sulfamethoxazole/ trimethoprim (BactrimÂŽ 400 mg/80 mg tablets, SUN Pharma, Mumbai, India) was prescribed, one tablet every 12 hours for three weeks. She was asked to return in 4 to 6 weeks. The patient returned six weeks later and stated that the vision in the left eye was much better, but that mild visual distortion remained. On testing, the visual acuity in the left eye had improved from 6/60+1 (20/200+1) to 6/6-2 (20/20-2). The macular edema had decreased three fold in comparison to the initial OCT scan â&#x20AC;&#x201D; central macular thickness was reduced from 738 um to 202 um (Fig. 4). Although the sub-retinal fluid had resolved and the macula appeared intact, residual stellate exudates were still present on ophthalmoscopy (Fig. 5A), while the right eye remained unchanged (Fig. 5B). The patient showed improvement on visual field testing, using a size

Fig. 5 (A) Fundus photograph OS showing reduced swelling of the optic nerve with residual macular exudates. (B) Fundus photograph OD demonstrating normal findings.

III target in the left eye. However, an inferior altitudinal defect, with a scattered superior depression was found and a slightly enlarged blind spot remained (Fig. 6). A 0.9 log unit RAPD was measured and color vision testing showed a one plate improvement, compared to the consult exam. Improved, but residual metamorphopsia was confirmed by Amsler grid. Repeat serology continued to show an elevated Bartonella henselae IgG titer (1:2560). Overall, the patient demonstrated considerable improvement; consequently, she was advised to return in two months for a scheduled follow-up, or as needed if any new concerns should manifest.

DISCUSSION Neuroretinitis (NR) secondary to cat scratch disease (CSD), now referred to as cat scratch neuroretinitis (CSNR), is one of the three most common forms of NR (the other being idiopathic NR and recurrent NR).1 There are an estimated 22,000 new cases of CSD reported yearly in the U.S. (6.6 cases per 100,000) and CSNR is the most common form of NR associated with an infectious agent.2,10-12 The primary etiological organism in CSD, Bartonella henselae, can be associated with ocular complications such as NR, Parinaud oculoglandular syndrome (POGS), and focal retinochoroiditis.3 Direct bacterial invasion, or autoimmune response against the optic nerve, may cause optic nerve vascular

inflammation, with a secondary inflammatory reaction in the nerve fiber layer of the retina.1 The first case of NR was reported in 1916 by Theodor Leber, a German ophthalmologist, who described a condition with vision loss, optic disc edema (ODE) and stellate maculopathy.13 However, the term NR was not employed until 1977, when Gass proved the temporal sequence of the leakage sites by using fluorescence angiography (FA).14 The fact that optic nerve edema precedes the macular star (MS) has been confirmed in many case studies by combining FA and OCT imaging.15,16 As OCT is non-invasive, it has become the standard means to provide reliable evaluation and management of CSNR.1,17-22 The diagnosis of CSD or CSNR relies on known cat or flea exposure, lymphadenopathy, and a positive Bartonella henselae titer.3,10 In the patient reported, a skin rash and lymphadenopathy occurred prior to the ocular symptoms and, consequently,6 were not documented by a medical professional. Another common finding in CSD, fever, was not manifest in this case.19 Patients with CSNR can sometimes report ocular discomfort and it is important that other neurological conditions, where pain is more common, such as neuritis and neuromyelitis optica (NMO) be excluded.23,24 Unlike optic neuritis and NMO, pain occurs in only 25% of NR cases and is usually mild in nature.1 In our patient, no pain was reported or associated with eye movement. In addition, the presence of a

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Fig. 6 Reliable Humphrey visual field, 6 weeks after presentation, disclosed a persistent inferior altitudinal defect in the left eye. The right eye remained within normal limits.

macular star was critical in the differential diagnosis, as this finding is atypical in demyelinating conditions. Catch scratch disease is self-limiting,1,2 thus treatment has been controversial.7,8 Oral antibiotics are more likely to speed recovery,9 if specific antigens are identified. It is also recommended to treat complicated cases of CSD, when other organ systems or atypical presentations are involved.7 Although doxycycline and ciprofloxacin have shown efficacy in treating CSNR,1,25,26 they were not prescribed due to the potential adverse effects in a young patient. According to Purvin et al1 sulfamethoxazole/ trimethoprim or azithromycin are suggested to treat young children or adolescents with CSNR; therefore, Bactrim was prescribed in this case. Studies have shown that CSNR has an excellen prognosis. Final visual acuity improved in almost all reported cases, with 93% of patients recovering to 6/12 (20/40) or better, with an average of 7.7 lines gained.1 This patient showed a significant improvement, from 6/60+1 (20/200+1) to 6/6-2 (20/20-2) in six weeks. By contrast, the visual fields showed a slower recovery, with a dense inferior altitudinal scotoma seen at the follow up visit. This defect was probably due to the severe swelling of the optic disc, which will be monitored in follow-up visits.

CONCLUSION With a presentation of optic disc edema and a macular star (ODEMS), combined with a history of a cat scratch or

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contact with cats, CSNR should be considered in the differential diagnoses. Ancillary tests, such as serology, OCT, and visual fields help confirm the etiology, stage the severity of the disease, and assist in following patients with CSNR to resolution. As in the case presented, it is often beneficial for patients with severe symptoms and significant clinical signs to initiate oral antibiotics, and therefore shorten the duration and speed the resolution of the disease. â??

REFERENCES 1. 2. 3. 4. 5. 6. 7.

Purvin V, Sundaram S, Kawasaki A. Neuroretinitis: review of the literature and new observations. J Neuroophthalmol 2011; 31(1): 58-68. Biancardi AL, Curi AL. Cat-scratch disease. Ocul Immunol Inflamm 2014; 22(2): 148-154. Cunningham ET, Koehler JE. Ocular bartonellosis. Am J Ophthalmol 2000; 130(3): 340-349. Accorinti M. Ocular bartonellosis. Int J Med Sci 2009; 6(3): 131-132. Brazis PW, Lee AG. Optic disk edema with a macular star. Mayo Clin Proc 1996; 71(12): 1162-1166. Dreyer RF, Hopen G, Gass JD, Smith JL. Leber's idiopathic stellate neuroretinitis. Arch Ophthalmol 1984; 102(8): 1140-1145. Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004; 48(6): 1921-1933. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and softtissue infections. Clin Infect Dis 2005; 41(10): 1373-1406.

10.

11.

12.

13.

14.

15.

16.

Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J 1998; 17(6): 447-452. Longmuir R. Cat-Scratch neuroretinitis (Ocular bartonellosis): 44-year-old female with non-specific "blurriness" of vision, left eye (OS). EyeRounds.org; March 31, 2005: Available at: http://www.EyeRounds.org/cases/36CatScratchBartonella.htm. Accessed October 10, 2015. Jackson LA, Perkins BA, Wenger JD. Cat scratch disease in the United States: an analysis of three national data-bases. Am J Public Health 1993; 83(12): 1707-1711. Suhler EB, Lauer AK, Rosenbaum JT. Prevalence of serologic evidence of cat scratch disease in patients with neuroretinitis. Ophthalmology 2000; 107(5): 871-876. Leber T. Die pseudonephritischen Netzhauterkrankungen, die Retinitis stellata: Die Purtschersche Netzhautaffektion nack schwerer Schadelverletzung. In: Graefe AC, Saemische T, eds. Graefe-Saemisch Handbuch der Augerheilkunde, 2nd edition Leipzig, Germany: Engelmann 1916: 1319. Gass JD. Diseases of the optic nerve that may simulate macular disease. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 1977; 83(5): 763-770. Stewart MW, Brazis PW, Barrett KM, et al. Optical coherence tomography in a case of bilateral neuroretinitis. J Neuroophthalmol 2005; 25(2): 131-133. Kitamei H, Suzuki Y, Takahashi M, et al. Retinal angiography and optical coherence tomography disclose focal optic disc vascular leakage and lipid-rich fluid accumulation within the retina in a patient with leber idiopathic stellate neuroretinitis. J Neuroophthalmol 2009; 29(3): 203-207.

17. Channa R, Welsbie DS, Patel VR. More than just optic disc swelling. JAMA Ophthalmol 2013; 131(11): 1477-1478. 18. Finger ML, Borruat FX. Dynamics of intraretinal fluid accumulation evidenced by SD-OCT in a case of cat scratch neuroretinitis. Eye (Lond) 2014; 28(6): 770-771. 19. Raihan AR, Zunaina E, Wan-Hazabbah WH, et al. Neuroretinitis in ocular bartonellosis: a case series. Clin Ophthalmol 2014; 8: 1459-1466. 20. Freitas-Neto CA, Orefice F, Costa RA, et al. Multimodal imaging assisting the early diagnosis of cat-scratch neuroretinitis. Semin Ophthalmol 2015: 1-4. 21. Seth A, Raina UK, Thirumalai S, et al. Full-thickness macular hole in Bartonella henselae neuroretinitis in an 11-year-old girl. Oman J Ophthalmol 2015; 8(1): 44-46. 22. Cruzado-Sanchez D, Tobon C, Lujan V, et al. Neuroretinitis caused by Bartonella henselae: a case with follow up through optical coherence tomography. Rev Peru Med Exp Salud Publica 2013; 30(1): 133-136. 23. Perez-Cambrodi RJ, Gomez-Hurtado Cubillana A, MerinoSuarez ML, et al. Optic neuritis in pediatric population: a review in current tendencies of diagnosis and management. J Optom 2014; 7(3): 125-130. 24. Bradl M, Kanamori Y, Nakashima I, et al. Pain in neuromyelitis optica--prevalence, pathogenesis and therapy. Nat Rev Neurol 2014; 10(9): 529-536. 25. Lezrek O, Laghmari M, Jait A, et al. Neuroretinitis in ocular bartonellosis. J Pediatr 2015; 166(2): 496-96.e1. 26. Reed JB, Scales DK, Wong MT, et al. Bartonella henselae neuroretinitis in cat scratch disease. Diagnosis, management, and sequelae. Ophthalmology 1998; 105(3): 459-466.

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QUESTIONNAIRE Cat Scratch Neuroretinitis Nicky R Holdeman, OD, MD, FAAO; Liang Ma, PhD, OD; Rosa A. Tang, MD, MPH 1. (A) (B) (C) (D)

Approximately how many cases of cat scratch disease (CSD) are diagnosed in the United States annually? 15,000 22,000 25,000 30,000

2. (A) (B) (C) (D)

Neuroretinitis (NR) occurs in what percentage of CSD cases? 1%-2% 2%-3% 3%-4% 4%-5%

Clinical and Refractive Optometry 28:3, 2017

Which of the following is NOT characteristic of NR? Acute vision loss A macular star Optic disc edema Severe ocular redness and swelling

4. (A) (B) (C) (D)

All of the following are systemic signs and symptoms of NR, EXCEPT: Rashes Fever Diplopia Regional lymphadenopathy

5. (A) (B) (C) (D)

Which of the following statements about NR is TRUE? Females are slightly more affected than males Asians are at higher risk than other ethnic groups Children and young adults are at an increased risk of infection Individuals over the age of 65 are at an increased risk of infection

6. (A) (B) (C) (D)

In the Case Report presented, what was the patient’s visual acuity OS at the neuroophthalmologist consult visit? 20/125 (6/38) 20/160 (6/48) 20/200+1 (6/60)+1 20/250 (6/75)

7. (A) (B) (C) (D)

In what percentage of patients with NR does pain occur? 10% 15% 25% 35%

Which of the following antibiotics is recommended for the treatment of cat scratch neuroretinitis in a young patient? Azithromycin Ciprofloxacin Sulfamethoxazole/trimethoprim A & C are correct

(A) (B) (C) (D) 9. (A) (B) (C) (D) 10. (A) (B) (C) (D)

In the Case Report presented, how many weeks did it take for the patient’s systemic signs and symptoms to resolve? Four Six Eight Ten In the Case Report presented, all of the following describe the patient’s clinical signs and symptoms at the neuro-ophthalmologist consult visit, EXCEPT: Pain on eye movement Normal vital signs No apparent distress Alert and oriented

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Allison Pierce and Dr. Pauline F. Ilsen entitled Orbital Vascular Malformations. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 121 for complete instructions.

Orbital Vascular Malformations Allison Pierce, OD; Pauline F. Ilsen, OD

ABSTRACT Background: Orbital vascular malformations derive embryologically either from the arterial system, venous system, or both. Classification of the lesion defines appropriate management and is important in preventing potential mistreatment. Case Reports: 1) A 39-year-old male with symptoms of left eye pain, redness, photophobia and diplopia for three weeks was referred for evaluation. Magnetic resonance angiography (MRA) and computed tomography (CT) revealed findings consistent with a left dural arteriovenous carotid-cavernous fistula. The patient underwent coiling intervention five days later. 2) A 48-year-old male presented with the diagnosis of orbital varix of the right upper lid first made at age 25 years. Examination and CT confirmed the diagnosis. No intervention was undertaken as the patient was frail due to extensive squamous cell carcinoma involving the floor of the mouth. Conclusion: Optometrists should be aware of the presentation and classification of orbital vascular malformations as identification is crucial in guiding subsequent management.

INTRODUCTION Vascular malformations have long suffered from conflicting and confusing classification systems, often either based on morphologic grounds or hemodynamic relationships. In 1982, Mulliken and Glowacki proposed a classification separating malformations into two groups, hemangiomas and vascular malformations.1 This differentiation is A. Pierce â&#x20AC;&#x201D; Optometrist, Carlsbad Optometry, Carlsbad, CA; P.F. Ilsen â&#x20AC;&#x201D; Professor, Marshall B. Ketchum University/Southern California College of Optometry, 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 The authors have no financial or proprietary interest in any of the material mentioned in this article. This article has been peer reviewed.

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especially important in the pediatric population in order to distinguish expected outcomes of these lesions.1,2 Hemangiomas were defined by endothelial hyperplasia, rapid growth and angiogenesis. They present at birth or in early childhood, presenting with a proliferative phase followed by a process of gradual involution. Vascular malformations are defined as being present at birth and consisting of abnormal and often combined capillary, arterial, venous, and lymphatic vascular elements. These malformations do not have proliferative properties and grow in proportion with the child.1,3 In 1974, Wright suggested orbital lymphangiomas should be considered primary varices because histological and clinical evidence for lymphatic lineage could not be demonstrated.4 Wright and colleagues went on to later group lymphangiomas and primary varices under the single term orbital venous anomalies, despite variation in venous connections of these lesions.5 Others resisted the unification of lymphangiomas and varices under the common title of orbital venous anomalies, stressing hemodynamic relationships over morphological differences as these are more consistent with their pathophysiologic, clinical, and diagnostic features.6,7 A consensus statement was published by the Orbital Society in 1999 endorsing a classification of orbital vascular malformations on the basis of hemodynamics rather than morphological features, which is more consistent with management.8 Three categories were proposed. Type 1 (no flow) lesions are hemodynamically isolated, showing little connection to the venous system. Lymphangiomas and combined venous lymphatic malformations fall within this category.7-9 Type 2 (venous flow) lesions, or primary varices, are in direct communication with the venous system and therefore can enlarge with venous pressure.7-9 Distensibility varies with the residual thickness and strength of the variceal walls and extent of communication to the venous system.7-9 Changes in venous pressure can be instigated by posture, straining, and Valsalva maneuver.3,7-9 Both distensible venous lesions, which have rich communication with the venous system, and nondistensible lesions, which have minimal communication with the venous system, fall within this category. Type 3 (arterial flow) lesions, or secondary varices, include arteriovenous malformations.7-10 These are

Fig. 1 Orbital T1-weighted magnetic resonance image in the coronal plane revealing marked distention of the left superior ophthalmic vein.

Fig. 2 Computed tomography in the axial plane. Visible is dilation of the left superior ophthalmic vein and slight proptosis of the left globe, indicative of a dural carotid-cavernous fistula.

characterized by direct antigrade high flow through the malformation from the arterial to the venous side, causing normal veins to expand under arterial pressure in the absence of capillary beds to dissipate the force.9,11,12 This classification was later expanded to include anatomical differentiation, establishing four new clinical features based on location.7,9 Superficial lesions are typically visible malformations which involve the conjunctiva or the lids.7,9 Deep lesions are not visible and are restricted to retrobulbar involvement.7,9 Combined lesions have both superficial and deep components.7,9 Complex lesions involve the orbit, the periorbital and intracranial tissues, and may be seen in multifocal sites systemically.7,9 The Barrow classification was proposed to further classify carotid-cavernous sinus fistula arteriovenous malformations based on anatomical-angiographic features.13 Type A lesions are direct high-flow shunts between the internal carotid artery and the cavernous sinus. Type B lesions are dural shunts between meningeal branches of the internal carotid artery and the cavernous sinus. Type C lesions are dural shunts between meningeal branches of the external carotid artery and the cavernous sinus. Type D lesions are dural shunts between meningeal branches of both the internal and external carotid arteries and the cavernous sinus. Type A is considered a direct flow malformation, while Types B, C, and D are indirect.

Types B, C, and D are considered dural arteriovenous malformations.14 Syndromic vascular malformations, such as SturgeWeber syndrome, hereditary hemorrhagic telangiectasias, Wyburn-Mason syndrome, and Klippel-Trengunay syndrome, are beyond the scope of this paper. Two cases of orbital vascular malformations will be presented.

CASE REPORTS Case 1: Fistula A 39-year-old male presented to the Emergency Department (ED) with symptoms of left eye pain, redness, photophobia and diplopia for the previous three weeks. He reported worse symptoms in the mornings with additional trouble raising his eyelid and closing the eyelids completely. He denied any loss of visual acuity or visual field. Before presenting to the ED, the patient was initially seen by an ophthalmologist who had originally diagnosed the condition as conjunctivitis and treated it with topical antibiotics. When symptoms did not resolve a computed tomography (CT) scan was ordered, revealing increased signal of the left ophthalmic vein indicative of a possible arteriovenous dural fistula. The patient was then referred to the ED for neurosurgical evaluation. The emergency department personnel noted left conjunctival and scleral injection, mild proptosis of the left eye,

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Fig. 3 Computed tomography of the sinuses in the coronal plane, showing an orbital varix within the right orbit and metallic fragments.

Fig. 4 Orbital computed tomography in the axial plane. Visible is the orbital varix and one metallic fragment within the right orbit.

and intact extraocular muscle functioning. A magnetic resonance angiogram (MRA) obtained the same day showed findings consistent with a dural arteriovenous fistula to the cavernous sinus with resultant dilation of the left superior ophthalmic vein (Fig. 1). A computed tomography angiography (CTA) and an evaluation at the eye clinic were arranged for the following day (Fig. 2). The presenting complaints at the eye examination were the same as those articulated at the emergency department. The ocular history was negative for surgery or trauma. The patientâ&#x20AC;&#x2122;s medical history was significant for diabetes mellitus type 2 diagnosed three years ago and hyperlipidemia. He was taking glipizide and metformin. His visual acuity was 6/7.5 (20/25) OD and 6/6 (20/20) OS. Pupils were both round and reactive to light with no afferent pupillary defect. The extraocular muscles were full. Visual fields were full to confrontations. Slit lamp biomicroscopy revealed an entirely normal right eye, but the left eye demonstrated decreased depth of upper eyelid crease, conjunctival vessel telangiectasia and tortuosity, a clear cornea with no evidence of exposure, deep and quiet anterior chamber, no iris abnormalities and clear crystalline lenses. The intraocular pressure measured 14 mmHg OD and 28 mmHg OS by Goldmann applanation tonometry. Dilated fundus examination revealed clear macula and vitreous OU, some peripheral pigmentary changes OU, and C/D ratios of 0.4 OU with

peripapillary atrophy. No optic disc edema was noted. Hertel exophthalmometry measured 15 mm OD and 21 mm OS with a base of 105 mm. The patient was started on timolol maleate 0.5% twice daily OS and was advised to return in one week for oculoplastics evaluation. It was noted that coiling intervention was to be arranged by neurosurgery. Four days later the patient returned to the ED with complaints of increasing eye pain OS and blurring of vision OU. The ED personnel noted restricted superior and lateral gaze as well as tenderness of the left globe on palpation. He was sent back to the eye clinic for further evaluation. Eye examination revealed acuities of 6/7.5 (20/25) OD and 6/9 (20/30) OS. The pupils were round and equally reactive to light, with no afferent pupillary defect. Slit lamp examination revealed reduced upper lid crease OS, 2 to 3+ conjunctival chemosis, and telangiectasias; all other biomicroscopy findings were unchanged. Intraocular pressures measured at 18 mmHg OD, 26 mmHg OS. Ophthalmoscopy revealed no evidence of disc edema. Hertel exophthalmometry was 16 mm OD, 23 mm OS with a base of 110. Since there had been no improvement in the intraocular pressure, the medication was changed to timolol-dorzolamide (CosoptÂŽ, Merck Frosst, Kirkland, QC) BID; lubricating ointment and artificial tears were

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also prescribed. He was advised to return to oculoplastics clinic in three days, as originally planned. Because of the progression of symptoms, urgent coiling was recommended. The Emergency Department administered morphine for pain, and ED personnel arranged for the procedure to be performed at another facility on the following day. The patient did not return to the eye clinic until two years later. He reported that his symptoms resolved after the coiling procedure. Visual acuities were 6/6 (20/20) OD and 6/6 (20/20) OS. There was no afferent pupillary defect and extraocular muscles were full. The anterior segment abnormalities OS found on the prior examinations were not evident. Intraocular pressure measured 14 mmHg OD and OS. Hertel exophthalmometry was 16 mm OD, 17 mm OS with a base of 110 mm. On fundoscopy, the discs and maculae were noted to be normal. Relevant findings have remained stable on subsequent eye exams. The patient underwent MRI/MRA three years after his initial presentation. This study revealed that the left superior ophthalmic vein was no longer enlarged. The left cavernous sinus was decreased in size compare with the preoperative scan. There was no significant left proptosis and the extraocular muscles were noted to be normal in appearance. The cavernous carotid arteries were found to be patent. Case 2: Orbital Varix A 48-year-old male presented to the eye clinic with a chief complaint of difficulty reading fine print. His ocular history was significant for an orbital varix involving the right upper lid, first diagnosed at age 25 years. The varix was discovered when the patient went to an emergency room for evaluation after sustaining a serious head injury while playing sports. Exploratory surgery of the varix was done at age 27 years, but no intervention was done. The patient reported enlargement of the lesion with valsalva or exertion, which caused headache, proptosis, and constriction of his inferior temporal visual field OD. He also remarked that the headache and field constriction due to the varix had worsened in recent years. His medical history was significant for squamous cell carcinoma involving the floor of the mouth diagnosed three months earlier. He had undergone surgical dissection two months ago and was being managed by a head and neck clinic. Medications included baby aspirin, butalbital, acetaminophen, cyclobenzaprine, docusate, flunisolide, and hydrocodone. The best corrected visual acuity was 6/6 (20/20) in each eye. The pupils were round and equally reactive to light, with no afferent pupillary defect. Extraocular muscles and confrontation fields were full to finger counting. There was no heterotropia or phoria on cover testing. On biomicroscopy, there was a palpable mass in

the superior nasal recess of the right orbit which enlarged minimally with Valsalva; all other findings were normal. Intraocular pressure measured 18 mmHg OD, OS (Goldmann applanation tonometry). Dilated fundoscopy demonstrated C/D ratios of 0.35 OD, 0.45 OS. No disc edema or pallor was observed, and the retinal background and vasculature were unremarkable. Hertel exophthalmometry was 15 mm OD, 14 mm OS with a base of 92 mm. Since the patient had reported some change in the headache and field defect caused by the varix, an oculoplastics evaluation was arranged, but no surgical intervention was recommended. Observation and annual eye examinations were advised. Three months later, the patient was admitted to the hospital for radiation and chemotherapy for recurrent and metastatic squamous cell carcinoma of the floor of the mouth. He was examined at bedside, at which time he reported five to six episodes over the preceding month of flashing lights in his vision lasting for a few seconds and then resolving. Ocular examination was entirely unchanged from the prior findings three months earlier. A review of a CT scan of the head done two months earlier for evaluation of headache revealed the varix. The CT also demonstrated metallic foreign bodies within the right medial orbit which the neuro-radiologist felt could be post-traumatic (Figs. 3, 4). The patient had no specific recollection of a metallic foreign body trauma to the head. The primary provider recommended that there be no further investigation or management since by that point in time the patient had become gravely ill and his medical prognosis was very poor. He passed away about six months later.

DISCUSSION Orbital vascular malformations are abnormal or weakened segments of the orbital vascular system.7,15,16 they are often made up of a combination of capillary, arterial, venous, and lymphatic vascular elements.7,15,16

VENOUS MALFORMATIONS Venous malformations are composed of thin-walled channels, deficient in smooth muscle, and lined by quiescent endothelium.3,15,17 There continues to be debate in regards to whether venous malformations are congenital or acquired lesions. Many believe these lesions to be congenital, but their size and deep location render them invisible at birth.1,3,9,18 The lesions grow over time in proportion to the individual and may at one point grow large enough to become symptomatic.1,3,9,18 They may also undergo sudden enlargement due to hormonal changes, distention, trauma, infection, thrombosis, hemorrhage or enlargement of preexisting smaller vessels.11

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Risk factors have been attributed to the possibility of an acquired etiology. Sports, yoga, and playing musical instruments have all been linked with a higher incidence of venous abnormalities.18,19 There are case studies, for example, which report varices specifically linked with yoga.18,20 These authors postulated that long-term bending with the head below heart level can cause chronic pooling in the orbital veins, leading to the development of these malformations.18 However, it is difficult to determine whether the varices were congenital and were simply exacerbated by these exercises or whether they were indeed acquired secondary to this process. Orbital varices occur equally in both men and women.21 Studies have shown that the initial manifestation of symptoms can occur at any age. A study of 20 patients by Arat found symptoms manifested at ages ranging from 5 months to 79 years.7 A study of 36 patients by Eivazi revealed that manifestation may occur from birth to age 48 years.22 Deep lesions occurred in 36% of patients, superficial lesions occurred in 27% of patients, and combined lesions occurred in 36% of patients.7 The second case presented is an example of a distensible venous malformation, which is a low-flow venous malformation as characterized by the Orbital Society.8 Orbital venous malformations, as noted previously, may be either distensible or nondistensible. This feature is primarily based on the extent of communication with the venous system, but has also been noted to be related to the strength and thickness of the variceal walls.8,9 Distensible venous malformations constitute the majority of purely venous malformations.9 They are characterized by rich communication with the venous system.8,9 These lesions enlarge upon increased venous pressure, which can be produced by Valsalva maneuver, physical effort, positional changes, coughing, pressing the jugular vein, and forced expiration.9,11,15,18,23 In order to confirm distensibility, these changes can also be documented with radiological imaging, usually with positional changes. In distensible lesions, symptoms are often instigated by lesion enlargement. Clinical manifestation include proptosis (with high venous pressure), pain, diplopia, headache, lagophthalmos, corneal ulceration (secondary to exposure), enophthalmos (with low venous pressure), restricted eye movement, bruising, and optic atrophy.7,9,15,18,21,22 While proptosis is more common, enophthalmos secondary to orbital fat atrophy and/or enlargement of orbital space around the lesion has also been noted, particularly during times of low/normal venous pressure.7,9,15,19 Complications which instigate sudden or acute onset of symptoms, such as thrombosis and hemorrhage, are uncommon in distensible lesions.7-9

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Nondistensible lesions are characterized by few communications with the venous system and stagnant blood flow.7-9 Due to their very low flow hemodynamics, they may blend, from a clinical and management point of view, with lymphangiomas, or no flow lesions. These nondistensible lesions do not respond to changes in venous pressure.9 The malformations will become suddenly and acutely symptomatic in response to a thrombosis or hemorrhage of the lesion, which is promoted by its stagnant blood flow.7,9 Clinical manifestations include sudden pain, proptosis, oculomotor limitation, visual loss, increased IOP, subconjunctival ecchymosis, swelling and disfigurement of superficial structures, lagophthalmos, corneal ulceration (secondary to exposure), diplopia, mydriasis, and optic atrophy.7,9,21

ARTERIOVENOUS MALFORMATIONS Arteriovenous malformations are disorganized tangles of vessels consisting of aberrant arteriovenous shunts.9,11,12 The absence of capillary beds leads to increased venous pressure and resultant antigrade blood flow to the venous side.9,11,12 Arteriovenous lesions must be differentiated between strictly arteriovenous malformations, which include a nidus, or arteriovenous fistulas, which have no nidus and are direct aberrant communication between artery and vein.11 The incidence of intracranial arteriovenous malformations is 50% in the traverse sinus, 16% in the cavernous sinus, 12% in the tentorium cerebella, and 8% in the superior sagittal sinus.24 As with orbital venous malformations, there is a debate regarding whether arteriovenous malformations are acquired or congenital, and the underlying pathophysiology is as of yet unknown.25 Before the 1970s, dural arteriovenous fistulas were thought to be strictly congenital in origin. Castaigne and Djindjian were the first to propose an acquired etiology.24 Vaidya, for example, reports that 50% of lesions are acquired and 50% are congenital.11 Most other authors support an acquired etiology.14,24,26-29 The most common cause is known to be trauma (80%).14 This trauma often occurs in the form of a motor vehicle accident, sports injury, or fall. The theory follows that pre-existing microshunts are broken open and angiogenesis leads to the development of new aberrant shunts.14,24,29 Spontaneous occurrence of these malformations, or occurrence without previous trauma, has led some to believe in a pre-existing lesion, or congenital etiology.30,31 However alternate theories support an acquired etiology for these fistulas. Spontaneous lesions have been attributed to rupture of a pre-existing cavernous sinus aneurysm or rupture of a defective vessel wall. Pre-existing conditions such as hypertension, fibromuscular dysplasia, Ehlers-Danlos syndrome, pseudoxanthoma elasticum, pregnancy, delivery, menopause, and increased systemic thrombotic activity have been

Orbital Vascular Malformation Management

Exposure Keratitis: Aggressive Lubrication

“Watch and See”

Elevated Intraocular Pressure: Pressure-Lowering Agents

Indications for Intervention: Cosmesis, pain, diplopia, optic nerve compression, visual deterioration, proptosis, orbital hemorrhage, thrombosis, elevated intraocular pressure

Managing Venous Malformations

Managing Dural Carotid-Cavernous Fistulas

Endovascular Embolization

Deep lesions

Treatment of choice

Surgical excision Nondistensible and/or Deep Lesions

Carbon Dioxide Laser Ablation Extensive and diffuse superficial or combined lesions

Surgical Resection

Radiation Treatment

Fig. 5 Flowchart of the management of orbital vascular malformations.7,9,11,14,19,22,24,25,35,41-45

petrosal sinuses and inferiorly into the pterygoid plexus.14,33 The aberrant shunt created by the fistula causes increased venous pressure and may cause a reversal of blood flow into tributaries such as the ophthalmic veins, cortical veins, or leptomeningeal veins.25,33 The clinical presentation of dural carotid-cavernous fistulas is highly correlated with the degree of shunting and the route of venous drainage. Drainage most commonly occurs in the superior ophthalmic vein (89%) and this typically causes ocular and neuro-ophthalmological symptoms.34 These symptoms also occur with drainage to the coronary sinus (22%).25 Shunting to the leptomeningeal veins (18.5%) or cortical veins typically causes focal neurological symptoms, such as hemiplegia or aphasia. Manifestation is usually unilateral, but bilateral orbital signs may develop due to portal circulation between two cavernous sinuses.14 The most common clinical symptoms are diplopia (45%), conjunctival injection (41%), chemosis (37%), proptosis (37%) and visual deterioration (30%).25,35 Other symptoms include ophthalmoplegia, orbital pain and headache.28,36,37 Signs seen on examination include bruit (75%), pulsatile exophthalmos, elevated IOP, ocular motility disturbances, optic disc swelling, and venous stasis retinopathy, neovascular glaucoma, angle closure, cranial nerve dysfunction, and optic neuropathy.9,11,14,30,34,35,38-40 Double vision can arise from either extraocular muscle swelling or cranial nerve dysfunction in either the 6th (80%), 3rd (67%), and or 4th nerves (49%).36 If double vision is secondary to extraocular muscle swelling, resolution can be expected one to four weeks after successful treatment of the lesion.36 Facial pain is often secondary to compression of the trigeminal nerve (ophthalmic or maxillary divisions).14

ANCILLARY TESTING considered responsible for the breaking of these microshunts leading to angiogenesis.14,24,27,28,32 Thrombosis of the inferior petrosal or superior petrosal sinus is commonly seen at the time of diagnosis (85%). Whether this thrombosis is a cause or consequence of the fistula is unknown. However, some postulate that this thrombosis leads to increased pressure in the carotid-cavernous sinus and subsequent restructuring of embryonic arteriovenous communications.25 The first case presented here was a dural carotidcavernous fistula (DCCF). This lesion occurs when an aberrant communication is made between meningeal branches of the internal or external carotid arteries and the cavernous sinus.14,25,30,33 Under normal conditions, the cavernous sinus receives drainage anteriorly from the superior and inferior ophthalmic veins and superiorly from the sphenoparietal sinus and cortical veins. Blood then drains posteriorly into the inferior and superior

Radiological imaging is important in orbital vascular malformations for establishing a diagnosis and a treatment plan, which both rely on determining the extent of the lesion, hemodynamics of the lesion, and involvement of surrounding structures.11 Ancillary tests include orbital ultrasound, color Doppler ultrasound, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), and conventional angiography.11,14,16,24 For venous malformations, distensibility can be documented with imaging. Enlargement of the lesion can be seen with MRI, MRA, or CT and is usually done either with dependent positioning or Valsalva maneuver.7,19 These tests can also establish the extent of communication with the venous circulation to verify distensibility, especially if done with contrast enhancement.7 Ultrasound-Doppler examination can be used to document hemodynamics of a lesion, but does not adequately define source of the vascular

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malformation or its relation to surrounding structures.16,19 Flow patterns can be established with conventional angiography or MRA.9

MANAGEMENT Management of orbital vascular malformations (Fig. 5), as noted before, depends on the diagnosis and location of the lesion for both venous malformation and arteriovenous malformations. In the interim time before the lesion itself is treated, secondary symptoms such as exposure keratitis and elevated intraocular pressure must be addressed.11,14,22,24,25,35 Aggressive lubrication with bland ophthalmic ointment and artificial tears is recommended for exposure.11,14,22,24,25,35 Elevated intraocular pressures should be treated with pressure-lowering agents.11,14,22,24,25,35 However, only a modest reduction in intraocular pressure is expected until the lesion is resolved, as raised pressures are often secondary to episcleral venous pressure or blood forced into Schlemmâ&#x20AC;&#x2122;s canal.14,40 Treatment is typically conservative, with a â&#x20AC;&#x153;watch and seeâ&#x20AC;? plan, unless intervention is indicated. Indications for treatment include cosmesis, pain, diplopia, optic nerve compression, visual deterioration, proptosis, orbital hemorrhage, thrombosis, or elevated intraocular pressure.11,14,22,24,25,35 Spontaneous resolution can occur in orbital vascular malformations.25,29,30 This has been occasionally documented in low-flow fistulas shortly after angiography.25,29,30 Nearly all dural carotid-cavernous fistulas require active treatment and rarely resolve spontaneously.14 Treatments include endovascular embolization, surgical resection, a combination of embolization and surgical resection, and radiation treatment.11,24,25,41,42 The preferred and most well established treatment is endovascular embolization.22,43 Halbach et al was the first to use transvenous endovascular embolization, using steel coils and sclerosing liquid injections into the cavernous sinus via the superior ophthalmic vein.44 Since then, many options for embolic agents have become available, including Guglielmi detachable coils, fibered platinum coils, onyx, cyanoacrylate tissue glue, polyvinyl alcohol, and balloon (silicone/latex).11,14,24,42,45 Coils are favored for this procedure.25 Embolization is intended to promote thrombosis of the fistula in order to interrupt flow through the fistula while maintaining the carotid circulation.11,14,22,43 The embolization procedure can be done via a transarterial route or retrograde transvenous route, but the transvenous route has become the mainstay of management.35,46 Theaudin reported a success rate of 87% with transvenous embolization (14 of 16 patients), while only one in four patients who were treated via the transarterial route achieved success (complete occlusion of the fistula).25 Although mainstay treatments are considered safe, eradication of high-flow arteriovenous malformations and fistulas is often difficult and poses a challenge because of

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their complex anatomic and hemorrhagic properties.11,35 Complications include hemorrhage, stroke, vision loss, massive cerebral infarct, pseudoaneurysm formation, ocular motor palsies, venous occlusion, arterial perforation, or pressure breakthrough bleeding.12,14,25 Improper treatment, such as incomplete closure of shunts or incomplete resection of the malformation, can aggravate the lesions by stimulating growth, recanalization or recurrence, making the lesion more difficult to treat.12,22,47 Complication rates vary from 3% to 35% and are higher for higher flow lesions, lesions which require multiple embolizations, or are located close to eloquent cortex.12 Morality is around 1% to 2%.12 Most distensible venous malformations can be followed with conservative treatment until symptoms develop which would make treatment necessary. Most nondistensible lesions, however, due to their propensity for thrombosis, hemorrhage, and acute symptoms require treatment at the time of clinical diagnosis.7 There are a number of options for treatment and management should be based on location, extent, and diagnosis of the lesion. Surgical excision is commonly used for nondistensible and/or deep lesions.7,9,22 Another option for deep lesions is endovascular embolization, which can be done after surgical exposure either with or without surgical excision. When used with surgical excision, emoblization of the lesion can greatly facilitate the complete removal of the lesion and reduce the possibility of hemorrhage.9,19 Embolization is not a good option for superficial lesions as this procedure does not reduce the size of the lesion, and so will not improve cosmesis.7 All of the embolic agents mentioned for use with arteriovenous malformations can also be used with venous malformations. Carbon dioxide laser ablation can be used with extensive and diffuse superficial or combined lesions.7,9 This is done transcutaneously or, if done for deep lesions, after surgical exposure. Sclerotherapy with percutaneous alcohol or sodium tetradecyl sulfate is considered a safe treatment for most craniofacial venous malformations, but is typically avoided in orbital malformations as there is a risk of optic nerve injury if there is leakage into the orbit.3,7,42 Side effects such as local inflammatory reactions and increased intraocular pressure have also be noted.22 This procedure should only be considered with small, defined orbital venous malformations.7 There are a number of potential complications which can occur with the treatment of venous malformations. Surgery can be difficult as these weakened segments of the venous system are very fragile and can be intimately intermixed with normal orbital structure. There is a significant risk of vision loss as a result of hemorrhage or optic nerve damage as these thinned vessels tend to rupture and bleed excessively.9,15 Orbital wall defects are

commonly seen with these malformations and can add difficulty in surgery due to a closer proximity of the lesions to intracranial strucutures.15 Embolization can be effectively done with cyanoacrylate tissue glue, but all of the embolized lesion must be removed from the orbit as there can be a foreign body reaction if the material is not removed. Also, the hard consistency of this embolic agent, while good for complete embolization and to reduce the possibility of hemorrhage, can make surgical dissection difficult.42 Carbon dioxide laser done transcutaneously can sometimes lead to hyperpigmentation (which can resolve), hypopigmentation, atrophic scarring, or hypertrophic scarring.42

CONCLUSION Orbital vascular malformations are rare, but they can be sight threatening in instances where thrombosis or hemorrhage develop. Optometrists should be aware of the presentation of these lesions and how to establish a correct diagnosis based on universally-accepted classification systems. Correct diagnosis is essential in the path towards successful management and, if necessary, referral of these lesions for surgical intervention. â??

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Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg 1982; 69: 412. 2. Trombly R, Sandberg DI, Wolfe SA, Ragheb J. High-flow orbital arteriovenous malformation in a Child: Current Management and Options. J Craniofacial Surg 2006; 17(4): 779-782. 3. Berenguer B, Burrows PE, Zurakowski D, Mulliken J. Sclerotherapy of cranofacial venous malformations: complications and results. Plast Reconstr Surg 1999; 104(1): 1-11. 4. Wright JE. Orbital vascular anomalies. Trans Am Acad Ophthalmol Otolaryngol 1974; 78: 606-616. 5. Wright JE, Sullivan TJ, Garner A, Wulc AE, et al. Orbital venous anomalies. Ophthalmol 1997; 104: 905-13. 6. Harris GJ. Orbital venous anomalies [letter]. Ophthalmol 1998; 105: 388-389. 7. Arat YO, Mawad ME, Boniuk M. Orbital venous malformations: current multidisciplinary treatment approach. Arch Ophthalmol 2004; 122(8): 1151-8. 8. Harris GJ. Orbital vascular malformations: A consensus statement on terminology and its clinical implications. Am J Ophthalmol 1999; 127(4): 453-455. 9. Rootman J. Vascular malformations of the orbit: hemodynamic concepts. Orbit 2003; 22(2): 103-20. 10. Warrier S, Prabhakaran VC, Valenzuela A, Sullivan TJ, et al. Orbital arteriovenous malformations. Arch Ophthalmol 2008; 126(12): 1669-1675. 11. Vaidya S, Cooke D, Kogut M, Stratil PG, et al. Imaging and percutaneous treatment of vascular anomalies. Semin Intervent Radiol 2008; 25(3): 216-233.

12. Renowden S. Interv Radiol Neurol Pract 76 III Sept 2005: iii48-63. 13. Barrow DL, Spector RH, Braun IF, et al. Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg 1985; 62(2): 248-256. 14. Feiner L, Bennet J, Volpe NJ. Cavernous sinus fistulas: carotid cavernous fistulas and dural arteriovenous malformations. Curr Neurol Neurosci Rep 2003; 3: 415-420. 15. Islam N, Mireskandari K, Rose GE. Orbital varices and orbital wall defects. Br J Ophthalmol 2004; 88: 833-834. 16. Leng T, Wang X, Huo R, Cheng Z. The value of threedimensional computed tomographic angiography in the diagnosis and treatment of vascular lesions. Plast Reconstr Surg 2008; 122(5): 1417-1424. 17. Shields JA, Shields CL, Eagle RC, Diniz W. Intravascular papillary endothelial hyperplasia with presumed bilateral orbital varices. Arch Ophthalmol 1999; 117(9): 1247-1249. 18. Cohen JA. Bilateral orbital varices associated with habitual bending. Arch Ophthalmol Nov 1995 1360-1362. 19. Hamedani M, Pournaras JC, Goldblum D. Diagnosis and management of enophthalmos. Surv Ophthalmol 2007; 52(5): 457-473. 20. Margo CE, Rowda J, Barletta J. Bilateral conjunctival varix thromboses associated with habitual headstanding. Am J Ophthalmol 1992; 112: 726-727. 21. Beyer R, Levine MR, Sternberg I. Orbital varicies: A surgical approach. Ophthalmic Plast Reconstr Surg 1985; 1: 205-210. 22. Eivazi B. Orbital and periorbital vascular anomalies - an approach to diagnosis and therapeutic concepts. Acta Oto-Laryngologica 2010: 130: 942-951. 23. Phan IT, Hoyt WF, McCulley TJ, Hwang TN. Blindness from orbital varices: case report. Orbit 2009; 38: 303-305. 24. Gupta AK, Periakaruppan AL. Intracranial dural arteriovenous fistulas: A review. Indian J Radiol Imaging 2009; 19: 43-48. 25. Theaudin M, Saint-Maurice JP, Chapot R, Vahedi K, et al. Diagnosis and treatment of dural carotid-cavernous fistulas: a consecutive series of 27 patients. J Neurol Neurosurg Psych Feb 2007; 78(2): 174-179. 26. Fleishman JA, Garfinkel FA, Beck RW. Advances in the treatment of carotid cavernous fistula. Int Ophthalmol Clin 1986; 26: 301-11. 27. Debrun GM, Vinuela F, Fox AJ, Davis KR, et al. Indications for treatment and classification of 132 carotidcavernous fistulas. Neurosurg 1988; 22: 285-289. 28. Lewis Al, Tomsick TA, Tew JM Jr. Management of 100 consecutive direct carotid-cavernous fistulas: results of treatment with detachable balloons. Neurosurg 1995; 36: 239-244. 29. Yazici B, Yazici Z, Erdogan C, Rootman J. Intraorbital arteriovenous fistula secondary to penetrating Injury. Ophthalmic Plast Reconstr Surg 2007; 23(4): 275-278. 30. Bernini F, Cioffi F, Muras I. Arteriovenous shunts between dural branches of the carotid artery and the cavernous sinus. Surg Neurol 1982 August; 18(2): 102-106. 31. Djindjian R, Manelfe C, Picard L. External carotidcavernous sinus, arteriovenous fistulae: angiographic study of 6 cases and review of the literature. Neurochirurgie 1971 Jan-Feb; 19(1): 91-110.

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32. Chuman H, Trobe JD, Petty EM, Schwarze U, et al. Spontaneous direct carotid-cavernous fistula in Ehlers Danlos syndrome type IV: Two cases of reports and a review of the literature. J Neuro-Ophthalmol 2002; 22(2): 75-80. 33. Ringer AJ, Salud L, Tomsick TA. Carotid cavernous fistulas: anatomy, classification, and treatment. Neurosurg Clin N Am 2005; 16: 279-95. 34. Albuquerque, Felipe, Heinz GW, McDougall CG. Reversal of blindness after transvenous embolization of a carotidcavernous fistula: Case report. Neurosurg 2003; 52(1): 233-237. 35. Caragine LP Jr, Halbach VV, Dowd CF, Higashida RT. Intraorbital arteriovenous fistula of the ophthalmic veins treated by transvenous endovascular occlusion. J Neurosurg 2006; 58(1): ONS-E170. 36. Kupersmith MJ, Berenstein A, Choi I, Warren F, et al. Management of nontraumatic vascular shunts involving the cavernous sinus. Ophthalmology 1988; 95: 121-130. 37. Bussiere M. Direct carotid-cavernous fistula causing brainstem venous congestion. J Neuro-Ophthalmol 2009; 29(1): 21-25. 38. Spencer WH, Thompson HS, Hoyt WF. Ischaemic ocular necrosis from carotid-cavernous fistula: pathology of stagnant anoxic â&#x20AC;&#x153;inflammationâ&#x20AC;? in orbital and ocular tissues. Br J Ophthalmol 1973; 57: 145-152. 39. Liang W, Xiaofeng Y, Weiguo L, Desheng P, et al. Bilateral traumatic carotid cavernous fistula: The manifestations, transvascular embolization and prevention of the vascular complications after therapeutic embolization. J Craniofac Surg 2007; 18(1): 74-77.

40. Leonard TJ, Moseley IF, Sanders MD. Ophthalmoplegia in carotid cavernous sinus fistula. Br J Ophthalmol 1984; 68: 128-134. 41. Jung KH, Kwon BJ, Chu K, Noh Y, et al. Clinical and angiographic factors related to the prognosis of cavernous sinus dural arteriovenous fistula. Neuroradiology 2011; 53(12): 983-992. 42. Garza G, Fay A, Ruben PA. Treatment of pediatric vascular lesions of the eyelid and orbit. Int Ophthalmol Clin 2001; 41(4): 43-55. 43. Guerrero CA, Raja AI, Naranjo N, Krisht AF. Obliteration of carotid-cavernous fistula using direct surgical and coil-assisted embolization. Neurosurg Feb 2006; 58(2): E382. 44. Halbach VV, Higashida RT, Hieshima GB, Reicher M, et al. Dural fistulas involving the cavernous sinus: results of treatment in 30 patients. Radiology 1987; 163: 437-542. 45. Mehrzad H, Alam K, Rennie A. The treatment of dural carotid cavernous fistula using Onyx via a transorbital approach: a technical note. Neuroradiology 2011; 53(11): 895-898. 46. Malek AM, Halbach VV, Higashida RT, Phatouros CC, et al. Treatment of dural arteriovenous malformations and fistulas. Neurosurg Clin N Am 2000; 11: 147-166. 47. Lee BB, Do YS, Yakes W, Kim DI, et al. Management of arteriovenous malformations: a multidisciplinary approach. J Vasc Surg 2004; 39(3): 590-600.

Call for Papers Clinical & Refractive Optometry welcomes original articles based on clinical or basic research, case reports, and review papers related to the practice of optometry. Please submit manuscripts by mail to: Clinical & Refractive Optometry Attn: Mary Di Lemme, Managing Editor 3484 Sources Blvd., Suite 518 Dollard-des-Ormeaux, Quebec H9B 1Z9 or E-mail: mdilemme@mediconcept.ca

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QUESTIONNAIRE Orbital Vascular Malformations Allison Pierce, OD; Pauline F. Ilsen, OD 1. (A) (B) (C) (D)

According to the paper, which of the following can prompt changes in venous pressure? Posture Straining Valsalva maneuver All of the above

2. (A) (B) (C) (D)

Which of the following is a direct flow malformation? Type B Type C Type A Type D

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COPE-APPROVED CE CREDIT APPLICATION FORM

In Case 1, the patient presented in the Emergency Department with symptoms that first began: 6 hours before 24 hours before 1 week before 3 weeks before

4. (A) (B) (C) (D)

Which of the following may cause venous malformations? Head trauma Abrupt changes in pressure Playing musical instruments Extreme fatigue

5. (A) (B) (C) (D)

Which of the following statements about distensible venous malformations are true? They occur more frequently in men They tend to occur more frequently between the ages of 5 and 10 years of age They are always symptomatic for pain None of the above

6. (A) (B) (C) (D)

Which clinical manifestation is not associated with distensible venous malformations? Restricted eye movement Sudden loss of visual acuity Headache Optic atrophy

7. (A) (B) (C) (D)

Which clinical manifestation is not associated with non-distensible lesions? Oculomotor limitation Mydriasis Hemorrhage Increased IOP

8. (A) (B) (C) (D)

According to Vaidya, what percentage of orbital venous malformations is acquired? 20% 30% 50% 70%

9. (A) (B) (C) (D)

All of the following are symptoms of dural carotid-cavernous fistulas, EXCEPT: Conjunctival injection Redness Diplopia Chemosis

10. (A) (B) (C) (D)

Which of the following statements about vascular malformations is true? They are not congenital They proliferate in later life They grow in proportion with the individual They typically develop during the teen years

28.3:17

3. (A) (B) (C) (D)

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Case Consultations CRO is pleased to present a new Feature Department entitled Case Consultations. The first case in this series is presented by Dr. Henry Reis, regarding a patient with a challenging set of dry eye symptoms. We’ve randomly selected five optometrists from across the country to comprise an experts panel. Each panelist was asked to recommend a specific diagnostic testing protocol and treatment plan based entirely on their anecdotal experience. What emerges is a clear picture of their preferred choice of diagnostic tests and followup procedures. Please let us know if their choices match yours.

Refraction/BCVA • OD: -2.25/-1.25x010 (20/20-2) • OS: -3.50/-2.25x170 (20/20-1) • Add: +2.00 (20/20)

Henry Reis, MD Burnaby, BC CASE DESCRIPTION JWR, is a 54-year-old, female, accountant, who was referred by her GP for dry eye investigation and management. JWR complains of bilateral, intermittent foreign body sensation, worse at the end of the day, with insidious onset 6 months. She has discontinued the use of monthly contact lenses one month ago, due to discomfort and distance visual acuity blur. Ocular History • POAG, diagnosed 5 years ago, managed with Lumigan RC 1gtt q.h.s. OU • Floaters, OU, longstanding • Contact lens wear: Air Optix for Astigmatism / Multi-purpose solution (unknown)

Slit Lamp Examination • Capped meibomian glands, collarettes around the base of the lashes. Lid wiper epitheliopathy • Tear prism height 0.2 mm OD; 0.1 mm OS • Mild conjunctival hyperemia OU • Diffuse superficial punctate keratitis 2/4+ OU with limbal neovascularization at 6h OS • NaFl [+] • No crystalline opacities Dilated Fundus Examination • ONH: 0.25x0.30 OD; 0.35x0.30 OS • Vitreous: OD PVD [-] Shaffer; OS floaters • Macula: OU clear • Posterior pole: OU clear • Peripheral retina: OD clear and flat, no holes/breaks; OS clear and flat, no holes/breaks, white without pressure at the inferior temporal mid-periphery

Medical History • Asthma, managed with Symbicort p.r.n. • Anxiety, managed with Citalopram 40 mg p.o. Allergies • Pet dander and pollen • Penicillin

Questions for the Case Consultations Panel 1. What tests (and in what order) would you normally perform on this patient as part of your comprehensive dry eye testing protocol? 2. Based on these test findings how would you manage this patient and what would you recommend for follow up?

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Pavan Avinashi, OD Vancouver, BC MY DIAGNOSTIC TEST PROTOCOL 1. CDEA questionnaire 2. Tear osmolarity – i-Pen in two of our 3 locations and TearLab in the other 3. Inflammadry 4. Case history 5. Slit lamp exam 6. TBUT 7. Lissamine green 8. Meiboscopy and meibography Primary goal: re-habilitate the corneal surface. Begin by starting the patient on preservative-free artificial tears

Ben Barrus, OD Calgary, AB MY DIAGNOSTIC TEST PROTOCOL 1. Visual acuity 2. CDEA questionnaire 3. SM Tube/Schirmer II/Tear meniscus 4. Tear osmolarity with i-Pen 5. LipiView 6. NaFl and/or lissamine green staining 7. TBUT 8. Manual meibomian expression The test results inform the following differentials: 1. Aqueous deficiency – Moderate (based on Schirmer/meniscus/osmolarity) 2. Meibomian gland dysfunction (MGD) – Moderate (based on imaging/expression/osmolarity) 3. Mucin deficiency – Moderate (based on staining/TBUT) To manage aqueous deficiency, I would strive to treat the patient in phases in order to improve compliance. It is my experience that treatment for aqueous deficiency generally starts with copious artificial lubricant drops. The preference to non-preserved drops helps ensure improved outcome and speed of resolution. My preference is for aqueous stabilizing viscosity promoting drops that include the lower percentage hyaluronic acid. If those are not preferred, then standard viscous drops containing methylcellulose or glycol are a second choice. I would

(preferably with sodium hyaluronate, i.e., Hylo, Refresh Fusion or i-drop) q.2h OU along with a liposomal spray (i.e., Calmo) b.i.d.+ OU and moist hot compresses (i.e., Bruder) b.i.d. x 5 minutes; once improved move artificial tears down to b.i.d. to q.i.d. and hot compresses to q.h.s. for maintenance x minimum 30 days. Discontinue contact lens wear until ocular surface has been restored; and thereafter switch her to daily SiHi toric contact lenses (i.e., 1-day Oasys for Astigmatism) ongoing. In view of chronic nature of symptoms; start her on a triglyceride-based Omega-3 (1000 to 2000 mg EPA>DHA) q.d. with GLA additive ongoing (e.g., EPA+) Secondary goal: address MGD/anterior blepharitis/ lid wiper epitheliopathy. Have the patient back in 7 to 10 days for BlephEx treatment. Return to clinic in 1 to 2 months, if symptoms persist and/or MGD/blepharitis is still moderate, consider LipiFlow treatment and/or course of oral doxycycline.

prescribe these drops q.i.d. reassuring the patient that more is better and to strive to use drops in anticipation of periods of worsening comfort i.e., if eyes are dryer at the end of work then drops need to be instilled in the mid-afternoon. To manage the MGD, I would start the patient on approximately 1500 mg EPA in an Omega-3 supplement. This dose is usually achieved in 4000 mg of good quality fish oil. Coaching the patient that this regime is a long-term management approach to dry eye and will minimize the risk of relapse is helpful. The management of MGD is a longer process. If cost is not a factor, then IPL is my preference. An alternative to this is LipiView. If cost or access is prohibitive, then in-office heat treatment followed by manual expression is effective at treating the dry eye. I generally would not attempt expression of the meibomian glands until the patient has been taking Omega-3 consistently for at least 4 weeks to improve the likelihood of successful remission. Mucin deficiency is in my opinion the underserved pathology in chronic dry eye especially in contact lens wearers that show signs of lissamine staining (incl. lid wiper). In order to enable mucin recovery, higher dose viscosity drops used frequently over a sustained period are immensely helpful. To summarize treatment: 1. Hyaluronate drops q.2h 2. Omega-3 4000 mg daily 3. Cease contact lens wear for 4 weeks 4. Return to clinic in 4 weeks

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Jules Plante, OD, MSc, FAAO Montreal, QC MY DIAGNOSTIC TEST PROTOCOL 1. TBUT 2. LipiView/Meibography 3. Phenol red thread test (Zone-Quick) 4. Tear osmolarity with i-Pen

TBUT is of course part of any dry eye evaluation. Additionally, I would definitely recommend a meibography and tear film interferometry (LipiView) to determine the degree of meibomian gland dysfunction (MGD). Considering the reduced tear meniscus on the left eye, I would also perform a phenol red thread test (ZoneQuick) to evaluate the tear volume. Finally, I would measure the in vivo tear film osmolarity (i-Pen).

This patient is obviously affected by a combined evaporative/aqueous deficient ocular dryness aggravated by anterior blepharitis. The inflammatory component can be initially reduced with a soft steroid like Lotemax for a month. The blepharitis can be controlled by daily lid scrubs or microblepharoexfoliation (BlephEx) performed periodically. The MGD has to be controlled by daily warm compresses and massage and/or thermopulsation treatment (LipiFlow). I would also recommend Systane Omega-3 supplements 2000 to 3000 mg daily. An unpreserved lubricant composed of sodium hyaluronate would be my first choice to protect the ocular surface, considering the reduced tear volume and lid wiper epitheliopathy. Finally, I would try to control the IOP with a medication not preserved with benzalkonium chloride (like Travatan Z or Alphagan P), as BAK can be toxic for the corneal surface. A 2-month follow-up would be planned to adjust the long-term therapy. If inflammation is still an issue, cyclosporine A 0.05% (Restasis) could be added. Scleral contact lens fitting could be considered as well, as this can treat the corneal epitheliopathy and correct the refraction simultaneously.

Francis Gaudreault, OD Quebec City, QC MY DIAGNOSTIC TEST PROTOCOL 1. SPEED questionnaire 2. LipiView II 3. Phenol red thread test 4. Tear osmolarity with i-Pen 5. Sodium fluorescein for corneal staining and lissamine green for conjunctival staining 6. TBUT 7. Meibomium gland expression The patient has an aqueous tear deficiency and an evaporative dry eye that cause inflammation. The anti-glaucoma medication probably increases irritation and symptoms.

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First, we should treat the inflammation with corticosteroids. I recommend Lotemax Gel q.i.d. x 14 days and b.i.d. x 14 days. Consider Restasis b.i.d. x 1 year to increase tear production and reduce the inflammation. Use a preservative-free eye drop like i-drop Pur Gel, as needed, in order to hydrate and stabilize the tear film. For the meibomian gland dysfunction and blepharitis, consider using LipiFlow to clear the blocked glands and restore normal function. As an alternative, use warm compresses like the Bruder Moist Heat Eye Compress every day. Also lid hygiene and Omega-3 supplements (Systane Vitamin b.i.d.) would be recommended for every day use. The patient should be followed up in three months.

Toby Mandelman, OD Bedford, NS MY DIAGNOSTIC TEST PROTOCOL 1. LipiView 2. TBUT 3. Phenol red thread test 4. Meibography 5. Test Osmolarity with i-Pen 6. Inflammadry test (optional)

Utilizing LipiView/meibography technology, we would first measure lipid layer thickness, partial blinking rate and perform a meibography scan. We also perform noninvasive TBUT with a corneal topographer and a phenol red thread test to measure aqueous production. Immediately before being assessed by the doctor we also measure in vivo tear osmolarity with i-Pen primarily to confirm if we are dealing with dry eye disease or a case of vertical phoria, allergy or conjunctivochalasis. Inflammadry is performed only if a large degree of inflammation is suspected. Slit lamp examination includes staining with fluorescein and lissamine green and evaluation of the meibomian glands with the TearScience Meibomian Gland Evaluator. Line of Marx is assessed, tear wiper epitheliopathy, lid eversion, tear meniscus height, status of lids and lashes, etc. Korb-Blackie lid light test is also

performed to determine if nocturnal lagophthalmos is present. The patient is also asked to fill out a SPEED questionnaire to determine level of symptomatology. Management, of course will depend on our additional clinical findings, but my treatment plan would likely consist of: • A BlephEx treatment to remove suspected Demodex infestation (as per the collarettes noted) and remove any biofilm present. Patient would also be treated with Cliradex complete and would go home with Cliradex wipes (2x/day for 2 weeks, once/day for 2 weeks). Tobradex b.i.d. x 4 weeks may also be prescribed if inflammation is abundant/severe. • Once the lids look clear in a month, a LipiFlow treatment would be recommended if our testing indicated significant MGD and meibomian gland damage. • Post LipiFlow maintenance involves Lotemax q.i.d. x 2 weeks, b.i.d. x 2 weeks with nightly Bruder mask hot compresses and lid cleansing with a precision Q-tip dipped in mineral oil. A non-preserved lubricant with hyaluronic acid is also used t.i.d. • Additional therapies such as blinking exercises and nocturnal ointment such as Ocunox may be needed depending on testing results. • Patient is evaluated after 3 months. Meibomian glands should be functioning. If aqueous is still low, Restasis may be added. • We would also recommend preservative-free Lumigan and determine if the patient could use an anti-anxiety medication that does not promote dry eyes.

Summary of the Diagnostic Tests Chosen by the Case Consultation Panel Tests chosen by

5 of 5 panelists

Lipiview/ Meibography Tear Breakup Time Tear Osmolarity with i-Pen Phenol Red Thread Test Patient Questionnaires Lissamine Green Inflammadry Slit Lamp Exam Visual Acuity Case History Tear Osmolarity with TearLab

• • •

3 of 5 panelists

• • •

2 of 5 panelists

•

1 of 5 panelists

• • • • Case Consultations

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News and Notes Johnson & Johnson Vision Care Companies Launches ACUVUE OASYS® Brand Contact Lenses 1-Day for ASTIGMATISM Johnson & Johnson Vision Care Companies recently announced the Canadian launch of ACUVUE OASYS® Brand Contact Lenses 1-Day for ASTIGMATISM, a daily disposable contact lens with BLINK STABILIZED® Design and HydraLuxe™ Technology for consistent, clear, stable vision and exceptional comfort. Among people that require vision correction, nearly half have astigmatism in at least one eye and full correction can provide them with improved visual quality of life. ACUVUE OASYS® Brand 1-Day for ASTIGMATISM combines two technologies: • HydraLuxe™ Technology includes tear-like molecules and highly breathable hydrated silicone that integrate with the patient’s own tear film. These tear-like molecules help support a stable tear film and avoid feelings of tired eyes. • BLINK STABILIZED® Design harnesses the natural power of the eyelids, to help keep the lens in the correct position even with head and eye movements. For more information, visit www.acuvueprofessional.ca. Essilor Canada Launches Varilux® RoadPilot™ Now available, Varilux® RoadPilot™ lenses are perfectly adapted for driving with large fields of vision where it matters the most to drivers, allowing presbyopes to fully enjoy the road. Driving requires good intermediate and far vision. With the absence of a near vision zone, the specific fields of vision required for driving are optimized and distortions are reduced. The ergonomic design of Varilux® RoadPilot™ is based on the observation of actual drivers’ visual needs whatever their car and provides them with three main benefits: • A clear panoramic view: Thanks to completely un-obstructed peripheral vision, wearers experience natural eye movements when checking rear-view mirrors and can better anticipate lateral movements and action of other cars. • Easy access to the dashboard and all driving indicators: The intermediate vision zone covers the main portion of the lens, offering direct, natural access to all critical information: speedometer, navigation system and more. • Dynamic vision with no distortion: A small power variation is automatically added to the lenses to ensure functional near vision. This will optimize the fields of vision specific to driving and reduce distortions. Drivers will feel safer behind the wheel and be able to react faster. For additional information, contact your Essilor Lens Consultant; or visit www.essilor.ca.

SEE additional safety information on page 128