CRO Vol 27 Number 4 by MediConcept

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Clinical & Refractive Optometry VOLUME 27, NUMBER 4, 2016

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Principles of Dry Eye Disease Tear Dysfunction and Osmolarity Complications of Silicone Oil in Reparative Retinal Surgery Advances in the Treatment of Central Serous Chorioretinopathy

Clinical &Refractive Optometry

Editorial Board â&#x20AC;˘ Volume 27, Number 4, 2016 Editor-in-Chief

Associate Editor

Richard Maharaj, OD, FAAO Toronto, Ontario

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

Editors Emeriti Brad Almond, OD Calgary, Alberta

Barbara Caffery, OD Toronto, Ontario

John Jantzi, OD Vancouver, British Columbia

Yvon RhĂŠaume, 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.

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Clinical & Refractive Optometry is published 6 times per year by Mediconcept.

Contents • Volume 27, Number 4, 2016

CE CREDIT ARTICLES

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Principles of Dry Eye Disease: Diagnosis, Treatment and Management Pavan Avinashi, OD INTRODUCTION: Dr. Avinashi began his presentation by highlighting that dry eye disease certainly represents a major opportunity in optometric practice. Since 2007, when the Delphi panel issued a true definition of dry eye disease, it’s been a constant and continual evolving paradigm shift in the approach to treating dry eye. It’s no longer simply about giving a sample of an artificial tear and instructing the patient to use a hot compress at home with a towel and some warm water, which was and still is, common practice.

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Tear Dysfunction and Osmolarity: Tales from the Trenches Richard Maharaj, OD Introduction: Dr. Maharaj began his presentation by stating that he would be discussing new treatment options for dry eye, also referred to as tear dysfunction, comprising three areas: 1) Clinical approaches to diagnostics in terms of the ocular surface in tear dysfunction; 2) Several case studies revolving around treatment options; and 3) How to apply tear osmolarity testing in the primary eye care arena. He noted that he feels the concept of osmolarity is going to be gaining momentum with new diagnostics coming onto the market and may even differentiate how we traditionally have looked at tear film osmolarity.

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Hyperoleon: Complications of Silicone Oil in Reparative Retinal Surgery Tam Nguyen, OD; Nancy N. Wong, OD; Terry Luk, OD; David M. Galeoto, OD; Karen Wadhams, OD ABSTRACT: Silicone oil injection is associated with many postoperative complications in the eye. The emulsification and forward migration of silicone oil into the anterior chamber is regarded as an invariable phenomenon that will eventually occur following a given in situ period. Emulsification of silicone oil can manifest as an “inverted hypopyon” or “hyperoleon,” filling up space in the superior portion of the anterior chamber. This can cause damage to a variety of structures, posing potential sight-threatening implications for patients.

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The Journal is made available to all optometrists on www.crojournal.com. Advertising insertion orders and copy must be received before the first day of the preceding month for which the advertising is scheduled. 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: Mediconcept Editorial & Sales Office 3484 Sources Blvd., Suite 518 Dollard-des-Ormeaux, Quebec Canada H9B 1Z9 Tel.: (514) 245-9717 E-mail: info@mediconcept.ca Printed in Canada. All rights reserved. Copyright © 2016 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.

Advances in the Treatment of Central Serous Chorioretinopathy Euri Chi, OD; Steven Ferrucci, OD; Brenda Yeh, OD ABSTRACT: Central serous chorioretinopathy is a commonly encountered macular disorder. Most cases of acute serous chorioretinopathy resolve on their own, with a favorable visual outcome within three to six months from onset. For those cases that do not resolve, new treatment modalities are being investigated that may be of help.

NEWS & NOTES 164 New Lens Coating Technologies from NIKON Transitions Innovation Awards Program

ISSN: 1705-4850; Date of Issue: September 2016

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Cover Image: Scleral contact lenses have been proven effective in severe dry eye disease. Courtesy of: Dr. Pavan Avinashi

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article based on a presentation given by Dr. Pavan Avinashi at the CRO 2016 Meeting in Vancouver, BC in which he discussed the diagnosis, treatment and management of dry eye disease. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to the page 133 for complete instructions

Principles of Dry Eye Disease: Diagnosis, Treatment and Management Pavan Avinashi, OD

INTRODUCTION Dr. Avinashi began his presentation by highlighting that dry eye disease certainly represents a major opportunity in optometric practice. Since 2007, when the Delphi panel issued a true definition of dry eye disease, it’s been a constant and continual evolving paradigm shift in the approach to treating dry eye. It’s no longer simply about giving a sample of an artificial tear and instructing the patient to use a hot compress at home with a towel and some warm water, which was and still is, common practice. First, he noted, that’s very mild superficial palliative care; and second, it’s not really treating or managing the problem. When patients are shown that something can be done above and beyond that, with a willingness to investigate things further, and that there are a lot of options in managing dry eye disease, they’re a lot more committed to the practitioner, with a greater degree of trust which will increase their retention and referral rates, as well.

PATIENT COMMUNICATION ABOUT DRY EYE DISEASE

inflammation. It’s not somebody stating that in the past few days they’ve had slight dryness in their eyes. Rather, these are patients who have tried various drops and have been suffering for years, with fluctuating vision as a result. When Dr. Avinashi diagnoses someone with episodic, chronic or recalcitrant dry eye disease, he feels it’s essential to tell them three things. Number one, that dry eye is a disease. If it’s not labelled as such, it’s not given the importance that it deserves. Number two, it’s crucial to mention that dry eye disease is chronic and progressive; it’s not something that will go away forever. It may go away for a while, it may be suppressed or managed, but it’s going to be there persistently. If these factors aren’t stressed, patients may not be on board for compliance for what is being managed or recommended. Number three, he always emphasizes to them that the underlying problem with dry eye disease is inflammation. He does this because the treatment modality of introducing oral omega-3 topical steroids, cyclosporine or anything else of that nature is justified by trying to manage the inflammation as well. In addition, sometimes patients associate the inflammation more with chronic conditions so this way at least there’s a correlation.

TEAR FILM MATRIX COMPOSITION

According to the literature, ocular surface disease occurs in as low as 10% of the general patient population to as much as 70% according to one Japanese publication. A common rule of thumb, said Dr. Avinashi, is that it occurs in almost one third of people who consult with an optometrist. The salient question, though relates to how many are being recognized and managed. Dry eye is a multi-factorial disease affecting people’s comfort, lifestyle and visual stability. Dr. Avinashi explains to his patients that the condition is associated with increased osmolarity, which is the tear composition, and that the underlying problem with dry eye disease is P. Avinashi — Hollyburn Eye Clinic, Vancouver, BC Correspondence to: Dr. Pavan Avinashi, Hollyburn Eye Clinic, 1516 Marine Drive, West Vancouver, BC V7V 1H8 E-mail visualperformance@hotmail.com Dr. Avinashi has no direct financial or proprietary interest in any companies, products or services mentioned in this article. This article has been peer reviewed.

In terms of the tear film, Dr. Avinashi stated, it’s essential to remember that the mucous layer has glycocalyx which act as a type of “cotton candy” to the corneal film. This is extremely important because with dry eye disease, when that gets compromised it also leads to apoptosis of the epithelial tissue and constant chronic conditions. Additionally, it’s where osmolarity can have a huge effect on stabilizing tear film at that level of the cornea and tear film. Dr. Avinashi explains to his patients that the tear film has many purposes but it’s a complex composition of many different elements that have to be addressed. Hence, when we’re mentioning things such as osmolarity nowadays, it’s an index of the composition of the tear film in the eyes. Regarding symptoms, one aspect that is always undermined is visual stability. One study showed that tear instability can constitute up to 20% of visual variability. When a patient complains of visual instability, dry eye disease can’t be ruled out. Risk factors include age,

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Table I Systemic diseases associated with dry eye Inflammatory – Fibromyalgia, RA, SLE, Scleroderma, Osteoarthritis – Sarcoidosis, Raynaud’s, OCP – Thyroid Disease, Sjögren’s Neural – Bell’s Palsy, Compressive Lesions – IIIrd or Vth Nerve Damage/Disorders Hormonal – Post Menopause, Pregnancy – Rosacea

Infectious – Chlamydia, HZ, Viral URI Metabolic – Diabetes Mellitus, Amyloidosis – Vitamin A Deficiency Developmental – Ectodermal Dysplasia – Ichthyosis, Alacrima Medical/Therapeutic – Antihistamines, Decongestants – Sedatives, Anti-depressants – Beta Blockers, Diuretics – OCB, HRT Fig. 1 Tear film instability: a key underlying cause of dry eye disease.

female gender, contact lenses, medications, and autoimmune disease. Regarding medications, Dr. Avinashi noted that many medications have dry eye symptoms as a side effect, for instance, antihistamines.

SYSTEMIC DISEASES AND DRY EYE DISEASE While there are many systemic diseases associated with dry eye disease (Table I), Dr. Avinashi highlighted one that is often overlooked: diabetes. Depending on the studies being considered, 54% to 60% of all diabetics have some level of ocular surface disease. With these patients, cataracts and retinopathy are the main concern, rather than the ocular surface.

TEAR FILM AND OSMOLARITY There are two different categories of dry eye disease: aqueous deficient dry eye and evaporative dry eye. The proportion of patients with a level of evaporative dry eye as a component is close to 100%. While Dr. Avinashi has seen the reported figure as low as 60%, it’s generally considered to be 80%; however, he has read and believes that it’s close to 100%. It may not be in the earlier stages but at some point it’s going to develop into that. So the question that remains is whether or not optometrists are managing their patients correctly in light of this. By sending them home with the aqueous supplement tear and nothing else, are these patients being managed properly? The tear film is a causative mechanism of ocular surface disease. When the tear film becomes unstable, the epithelial tissue is breached and the layers are adversely effected which in turn causes a chronic cycle of inflammation (Fig. 1). This leads to local drying or hyperosmolarity of the exposed surface. This leads to a discussion of the second kind of causative mechanism. Osmolarity testing has been in existence for some time; however,

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there is controversy about how valid the index is. Just in the last five years, more and more studies have been conclusive in the fact that this is actually a big parameter that has to be addressed, or at least looked at from the diagnostic perspective or a patient education perspective. The bottom line, noted Dr. Avinashi, is that a hyperosmolar tear film is an indication of an inflammatory environment. With an aqueous deficient tear flow and an unstable tear film, this leads to a hyperosmolar environment, which leads to cellular death, which leads to inflammation and it becomes a vicious cycle. Tear osmolarity on the ocular surface causes a decrease in aqueous production, so a hyperosmolar condition or environment innately decreases the aqueous and lipid production, evaporation is increased, and this causes an upregulation of inflammatory mediators. This accelerates the entire cycle of disease and it becomes an overall toxic environment for the tear film.

DIAGNOSTIC AND SCREENING TOOLS Dr. Avinashi stated that it’s critical to have a classification system for dry eye disease because that’s going to be the basis on which a treatment plan is developed. Furthermore, a comparison is needed when treating these patients six months or 12 months down the line. Screening for dry eye disease should comprise symptoms as well as signs. One of the best tools is a formalized questionnaire for dry eye disease, examples of which are the Ocular Surface Disease Index (OSDI) and the Dry Eye Questionnaire (DEQ). Another widely used questionnaire is the Canadian Dry Eye Assessment Guide (CDEA). Dr. Avinashi strongly suggests these as an introduction to dry eye management. While it may seem rudimentary and tedious, if the staff become involved and are educated

on administering these questionnaires, they can provide a plethora of information. For example, the CDEA a numeric value that helps guide the level of dryness, the severity of what the patient is experiencing from a personal perspective. This type of index with objective numbers is extremely valuable; whether it’s 3 months, 6 months or 12 months down the line, the questionnaire can be revisited and the number has a comparative value. Patients would return six months later asking what their number was and wanted to repeat the questionnaire to see if their situation had improved over the last visit. As a result, Dr. Avinashi came to the realization that its value was more for the patients as much as anything else. Furthermore, he emphasized that practitioners should look at more than tear breakup time. Everting the eyelids and expressing the meibomian glands should be standard tests done when managing dry eye disease patients. There are a lot of diagnostic tools and methods that can be used simply and inexpensively. Tear breakup time is the most commonly used test, measured with fluorescein. The use of fluorescein also helps give an indication of any type of epitheliopathy or punctate erosion of the cornea. However, with more practice, Dr. Avinashi also recommends using lissamine green. It greatly helps with further understanding the level of devitalized and desquamatized tissue of both the cornea and conjunctiva. He posed the question, “Knowing that essentially 80% if not 100% of ocular surface disease is evaporative, are optometrists currently doing a good job in evaluating meibomian glands?” The diagnostic approach has vastly changed in the last few years with the introduction of the Oculus Keratograph® (Arlington, WA). Regarding meibography, Dr. Avinashi mentioned that Innova (Laval, QC) has an excellent machine; and Topcon (Boisbriand, QC) has a great attachment. These imaging tests indicate the level of congestion through a black and white composite; they non-invasively measure tear breakup time and blink rate. The degree of meibomian gland atrophy can now be measured in terms of stages 1, 2 and 3. InflammaDry®, manufactured by Rapid Pathogen Screening Inc. (Sarasota, FL), is distributed by two companies in Canada. It’s an MMP-9 inflammatory marker test and it recently received FDA approval. It is another easy-toadminister, in-office diagnostic tool to help with the management of dry eye disease patients. One of its drawbacks, though, is that it produces a lot of false negatives.

TEAR OSMOLARITY As a key diagnostic tool, osmolarity testing provides a single biophysical measurement that denotes the balance of inputs and outputs. It’s now becoming increasingly accepted by many key opinion-makers and researchers across North America as being critical in the diagnosis of ocular surface disease management. Osmolarity has a

greater sensitivity and specificity than other diagnostic tests and its objective number is critical in deciding on the treatment approach. A systematic review of 164 peer-reviewed articles related to the diagnostic value of tear osmolarity found that 72% were favourable and supported tear osmolarity as a diagnostic tool for DED. Numerous additional publications have underscored it as an excellent tool to use. Now, after many years, said Dr. Avinashi, there is another viable resource to use, a testing device produced by I-MED, a Canadian company. This testing device is so economical that if a practitioner is thinking even remotely to try getting into dry eye disease management, it’s almost a necessity to have in one’s practice. Even in the National Dry Eye Disease Guidelines for Canadian Optometrists (published in the Canadian Journal of Optometry, Vol. 76, Suppl 1, 2014), it actually says on the subject, “Tear film osmolarity is the most accurate single test for dry eye disease, but should not be used in isolation,” of course. It’s similar to the importance of tracking and setting goals in IOPs in glaucoma. Anytime Dr. Avinashi has a new patient for cataract surgery or a LASIK consultation, he measures osmolarity preoperatively and postoperatively. With any patient going into contact lenses, he uses this measure as part of his workup and assessment as it may guide in how he recommends contact lenses, as well. Osmolarity is measured in milliosmoles per litre and the statistical mean high normal value is 300 mOSm/L. Another element to consider is if there’s a variance in the osmolarity reading. Sometimes a reading in one eye is 290 and the other one is 302, which is still within normal and healthy range, but with that degree of variance between the two eyes, inflammation is producing the result. There are two major osmolarity testing devices on the market: The TearLab Osmolarity System® (TearLab Corporation, San Diego, CA) and i-Pen® (I-MED Pharma, Montreal, QC) a small hand-held device which Dr. Avinashi has used in his practice and has found to be very convenient and easy to use. He reported that he has found it a lot easier to use than TearLab and it has recently been made available to Canadian optometrists. With its favorable cost, he considers it a valuable asset. The difference between the two tests is that TearLab utilizes temperature controlled impedance measurements to provide indirect assessment of osmolarity, whereas i-Pen uses impedance measurements, but these are based on the extracellular fluid in the tear film. Dr. Avinashi stated that his staff uses this measurement process as part of the pre-test and the readings are very quick, especially with the i-Pen.

MANAGEMENT OF DRY EYE DISEASE As per the Canadian Optometry Guidelines, the goals are to reduce symptomology, return the tear film to a healthier state, and decrease the frequency of symptoms. While

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Table II Comparative chart of artificial tears Preserved Tears

Gels/Ointments

Non-Preserved

Various Preservatives

Refresh Optive Advanced Refresh Optive Fusion Refresh Tears Refresh Ultra Tears Naturale Systane Ultra Systane Balance GenTeal HypoTears Liposic TheraTears Isopto Tears

Refresh Liquigel Tear-Gel GenTeal Gel Systane Gel Lacri-Lube Liposic Gel Tears Naturale PM HypoTears Ointment DuoLube Ointment

Refresh Plus Refresh Celluvisc Refresh Endura Refresh Unit Dose Bion Tears TheraTears Tears Naturale Free Systane Ultra Preservative Free i-drop HYLO Drops / Gel i-drop Pur

Purite BAK Polyquad Cetrimide Sodium Perborate

Certain artificial tears specifically address lipid tear film deficiencies – emulsion formula. Some have wound healing properties. Gentle, more acceptable preservatives with least disruption to the corneal surface are available.

practitioners may not be able to wholly fix a patient, but they can reduce the symptomology and definitely reduce the progression. With episodic cases, said Dr. Avinashi, this is where palliative care is standard. Using artificial tears and hot compresses is very important. Non-ocular considerations are sometimes overlooked for the sake of brevity, to get the patient out of the chair, or to encourage them to buy glasses, versus actually managing their disease. Patients’ medications, diet, level of alcohol consumption, whether or not they smoke, and environmental factors play an enormous role as well. In Vancouver, particularly, there are frequent climate changes, and Dr. Avinashi finds that with the higher pollen count he has a lot more patients with dry eye disease visiting his clinic.

ARTIFICIAL TEARS Dr. Avinashi is an avid advocate for tear supplementation. One of his maxims with any product in the realm of dry eye disease treatment is that practitioners should recommend what they sell and sell what they recommend. If optometrists are recommending a product but aren’t selling it, they’re encouraging the concept of patients going elsewhere for what they need and what has been recommended to them. It’s essential to get the staff on board, and to find products that are unique and above the average grade. He recommends first, selling items that patients can’t find in other practices; and second, creating more loyalty to one’s practice so that patients aren’t simply seeking out the lowest-cost products at big box stores. The practitioner’s responsibility is not to be cost sensitive to patients, but to provide them the best recommendations, whether it’s an artificial tear, a heat compress mask, a progressive lens, or a contact lens. In his view, optometry is far too conservative in terms of what the patient can and can’t spend. They need to be provided options, but should always be given the best one first.

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There is a plethora of artificial tears (Table II), Dr. Avinashi noted that his view of artificial tears has greatly changed over the last few years. Most patients, roughly 80%, have evaporative dry eye disease, therefore, optometrists should be recommending lipid-based artificial tears. These patients are often consulting with their GPs and pharmacists for recommendations, and they’re using such products as Tears Naturale® 2 (Alcon, Mississauga, ON) and GenTeal® (Novartis, Dorval, QC). Dr. Avinashi regards these as antiquated given that there has been such an evolution in artificial tears and newer, more advanced products are available. When a patient consults with an optometrist, they may not even mention that they have dry eyes, yet they use a small amount of artificial tears. He advises that practitioners take the time to find out what patients are using because sometimes they become complacent about their drops. They aren’t even aware of which product it is and if it’s appropriate for their situation. Inform them that a customized drop is what they need, more than anything else. Sodium Hyaluronate Dr. Avinashi is a proponent of preservative-free artificial tears. For aqueous deficient dry eyes for which he doesn’t wish to use a lipid-based agent, he opined that if a practitioner isn’t prescribing a product containing sodium hyaluronate, they’re underserving their patient population. In the European market, said Dr. Avinashi, if someone took a poll of every artificial tear that was being offered, 70% of these would contain sodium hyaluronate. A few years ago in Canada, there were only one or two products; now there are perhaps eight, and in the next year or two there are going to be a lot more in the pipeline. Sodium hyaluronate is a polymer that is found in the body’s synovial joints, aqueous humor, many collagen cells, and in the corneal tissue, as well. It’s a natural lubricant and the reason it’s so effective is that it has

viscoelastic properties with hypo-osmolar stability. Sodium hyaluronate increases corneal surface binding which is extremely beneficial to a dry eye patient. It enhances tear film stability, corneal wettability and corneal epithelial healing. Various studies have shown that it actually promotes corneal epithelialization, and in turn decreases the overall toxic environment of the ocular surface. It’s also has a positive effect on lid wiper epitheliopathy, a condition which a lot of optometrists don’t diagnose or manage. There are numerous preservative-free hyaluronate sodium products on the market, including those from I-MED Pharma, as well as HYLO™ (CandorVision, Montreal, QC) and others coming down the product pipeline. In addition, there are an increasing number of dermatology products incorporating it for its ability to create a more youthful appearance to the skin as the result of epithelial tissue healing. Hot Compresses Dr. Avinashi stated that hot compresses are another type of treatment that is not being properly managed by the profession. Whether acute or mildly chronic MGD, optometrists are telling patients about hot compress treatment, but aren’t going to the extent of educating patients regarding their proper application. Several studies have alluded to hot compresses as having some clinical effect on the meibomian glands. However, first, the compresses have to reach a certain temperature − between 41° and 43° Celsius; and second, they must be applied at that temperature for a minimum of 5-10 minutes. The Bruder® moist heat mask (Bruder Healthcare Company, Alpharetta, GA) and the dry heat TheraPearl® mask, distributed by Bausch + Lomb in Canada, are two masks Dr. Avinashi uses. He favors the Bruder version because it contains a moisture bead component, and provides enhanced comfort and durability. An additional consideration is that a moisture release hot mask will provide the meibomian glands increased heat. Lid Hygiene To ensure good lid hygiene, stated Dr. Avinashi, there are a variety of products available, such as i-Lid ‘n Lash™ (I-MED Pharma, Montreal, QC) which has sodium hyaluronate embedded in it. Patients with chronic eczema and irritation find this product very soothing to their skin.

CHRONIC DRY EYE DISEASE Dr. Avinashi is of the opinion that for chronic dry eye disease, optometrists shouldn’t be reticent to prescribe steroids, cyclosporine and anti-inflammatory prescription drops in order to properly manage and treat ocular surface disease. He feels that current treatment exists on a very

superficial palliative level of care, rather than concentrating on long-term treatment that addresses the progression of the condition. Current short-term management of moderate to severe dry eye disease involves a steroid, whether it’s ketone- or ester-based. He prefers Lotemax® (loteprednol etabonate ophthalmic suspension, Bausch + Lomb, Vaughan, ON) not only because it has a high safety profile, but also because it has recently been launched in gel form in Canada, in a formula that contains 70% less BAK. This translates to substantially less stinging, extensive corneal interface time and improved results. In fact, the gel form of Lotemax has become the gold standard in the U.S. All of Dr. Avinashi’s patients are currently using the gel form; he uses the ointment only in certain cases. The duration of steroid use depends on the patient’s history, however, generally prescribes it q.i.d. for two weeks. Naturally, follow-ups are necessary to monitor IOP changes. He recommends Restasis® (cyclosporine ophthalmic emulsion 0.05%, Allergan, Unionville, ON) for long-term treatment. Studies have proven that practitioners don’t have to wait until a patient’s dry eye disease is at Stage 3 or a severe state to use Restasis, he said. Several studies have demonstrated that the patients who benefit most from a long-term anti-inflammatory such as cyclosporine are actually chronic mild and moderate cases. Essential Fatty Acids Dr. Avinashi explained that when he recommends omega-3 fatty acids, it’s critical to educate patients as to why he’s doing so, also noting the difference between properly formuated omega-3s and the generic forms. The 2014 Canadian Guidelines, as well as the U.S. Guidelines, are now recommending an omega-3 even in mild patients; they should be one of optometrists’ first lines of treatment. Especially in Vancouver, where there is strong interest in managing conditions more naturally, this is an important management modality to consider before prescribing any therapeutics. He always recommends omega-3s with a triglyceride base versus an ethyl ester base. Many omega-3 products have various ratios of EPA to DHA, but a high ratio of EPA to DHA 3:1 or 4:1 is needed to better target the ocular surface. GLA is a derivative of the fatty chain of omega-6, which may be counterproductive; however, in the proper ration with EPA/DHA it has been shown to have significant antiinflammatory properties effective in the inflammatory cycle of dry eye disease. This is also outlined in the Canadian Dry Eye Guidelines. The effective dose is typically 2,000 mg per day, and they should be taken with a meal for higher absorption. Several studies have outlined that it can take upwards of two months for any omega-3 to have a proper clinical effect.

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MGD patients. He finds that it has some limited effectiveness for his MGD patients, but not nearly enough to rationalize spending $200 per treatment. Other new therapies on the market and in the product pipeline include those by Oculeve (San Francisco, CA), as well as Intense Pulse Light (IPL) treatment which works on the exterior of the dermis. It uses heat and intense light to act on meibomian gland atrophy. The initial results Dr. Avinashi has heard are that it’s extremely effective.

CONCLUSION Dr. Avinashi concluded his talk by presenting several key points for building a dry eye practice:

Fig. 2 Scleral contact lenses have been proven effective in severe dry eye disease.

Punctal Occlusion Dr. Avinashi feels that this technique has a role to play in dry eye disease management, but that it’s not as widely used in optometric circles. Ten or fifteen years ago, punctal plugs were routinely used whereas now practitioners use it at the end of the treatment process. When a plug is inserted it maintains the inflammatory mediators on the tear film which simply propagates the disease cycle. Scleral Lenses Dr. Avinashi began using scleral lenses two years ago because there were some patients in whom no matter what the treatment, the ocular surface symptomatology was still quite severe (Fig. 2). In patients with severe dry eye disease mini scleral lens have been proven successful. LipiFlow The debate concerning LipiFlow® (TearScience, Morrisville, NC), thermal pulsating treatment for the meibomian glands, isn’t about whether or not it works clinically, but rather, the duration of its efficacy and whether or not it is an end solution. In Dr. Avinashi’s view, the fee is high, at $1,500 per eye or per treatment, and is a prohibitive factor to many patients. Blephex The Blephex® concept is based on microblepharoexfoliation. It removes the biofilm plaque that builds up on lid orifices. While Dr. Avinashi thinks that it has a large part to play in optometric practice, he reserves it for his chronic anterior blepharitis patients, not necessarily his

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Number one: Make a commitment to do so. For example, when using the slit lamp, make an active effort to look at things beyond simply the cornea and eyelids. Number two: Create protocols for treatment. Describe it in writing which always makes it official and, more importantly, involve and educate the staff. Treatment of dry eye is a constantly evolving technology. Whether it’s progressive lenses, contact lenses or therapeutics, if the staff isn’t being educated and updated, they’re not on board with the practitioner’s efforts and it’s difficult to build a practice without employee involvement. Number three: Refer to the National Dry Eye Disease Guidelines for Canadian Optometrists (CJO, Vol. 76, Suppl. 1, 2014), an excellent piece of literature that comprises everything concerning dry eye disease and provides a template for developing a dry eye disease practice. Number four: With the latest advancements in diagnostic testing such as the i-Pen from I-MED Pharma, focus on delivering customized therapeutics, and have in hand their osmolarity readings and tear breakup times. So when they return in six-months, or for their postoperative follow-up, or after treatment with cyclosporine, a comparison can be made. While these tests provide good information, practitioners should still customize a patient’s treatment and explain to them why this particular drop, lid wipe or hot mask is being recommended. Provide them information founded on science-based evidence that supports the treatment plan. Number five: Dr. Avinashi is a strong advocate of properly informing and educating patients. In his practice, if he admits someone to his dry eye clinic, he spends the time required to dialogue with them. If this isn’t being done, they’re not going to be compliant with the treatment plan being proposed. Number six: Don’t be afraid to aggressively treat inflammation in particular and Dry Eye Disease in general.

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QUESTIONNAIRE Principles of Dry Eye Disease: Diagnosis, Treatment and Management Pavan Avinashi, OD 1. ❑ ❑ ❑ ❑

According to the literature, what is the incidence of ocular surface disease in the general population? 10% to 70% 15% to 60% 25% to 50% 30% to 80%

2. ❑ ❑ ❑ ❑

One study showed that tear instability can constitute up to ______ percent of visual variability? 5 10 20 25

3. ❑ ❑ ❑ ❑

All of the following statements about Dry Eye Disease (DED) are true, EXCEPT: Osmolarity has a greater sensitivity and specificity than other diagnostic tests It’s progressive in some cases Lotemax® (loteprednol etabonate) has a high safety profile Level of alcohol consumption plays a role

Principles of Dry Eye Disease: Diagnosis, Treatment and Management — Avinashi

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COPE-APPROVED CE CREDIT APPLICATION FORM

What percentage of diabetics have some level of ocular surface disease as reported in the literature? 23% to 43% 38% to 50% 49% to 52% 54% to 60%

5. ❑ ❑ ❑ ❑

What is the high normal level of tear film osmolarity? 300 mOsm/L 302 mOsm/L 303 mOsm/L 305 mOsm/L

6. ❑ ❑ ❑ ❑

All of the following can have an impact on DED, EXCEPT: Environment Smoking Diet Genetics

7. ❑ ❑ ❑ ❑

What percentage of artificial tears contain sodium hyaluronate? 50% 60% 70% 80%

8. ❑ ❑ ❑ ❑

What is the appropriate ratio of EPS/DHA to GLA in omega-3 supplements? 1:1 or 2:1 2:1 or 3:1 3:1 or 4:1 4:1 or 5:1

9. ❑ ❑ ❑ ❑

All of the following are recommended treatments for DED, EXCEPT: Long-term steroids Hot compresses Cyclosporine Preservative-free artificial tears

10. ❑ ❑ ❑ ❑

Approximately what percentage of patients have evaporative DED? 65% 70% 75% 80%

27:4, 16

4. ❑ ❑ ❑ ❑

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Clinical and Refractive Optometry 27:4, 2016

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article based on a presentation given by Dr. Richard Maharaj at the CRO 2016 Meeting in Toronto, ON in which he discussed new treatment options for dry eye. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to the page 144 for complete instructions.

Tear Dysfunction and Osmolarity: Tales from the Trenches Richard Maharaj, OD, FAAO

INTRODUCTION Dr. Maharaj began his presentation by stating that he would be discussing new treatment options for dry eye, also referred to as tear dysfunction, comprising three areas: 1) Clinical approaches to diagnostics in terms of the ocular surface in tear dysfunction; 2) Several case studies revolving around treatment options; and 3) How to apply tear osmolarity testing in the primary eye care arena. He noted that he feels the concept of osmolarity is going to be gaining momentum with new diagnostics coming onto the market and may even differentiate how we traditionally have looked at tear film osmolarity. On the anatomical side, he reviewed that tears are made up of three layers, the aqueous, mucin and lipid, all coming from the lacrimal glands goblet cells and meibomian glands, respectively. There is also a sensory motor component where the eyelids start to play a role. In the way patients blink and the way their eyelids close, the aperture seal is extremely important. The combination of neurosensory and anatomical components is really the crux of a healthy ocular surface and a stable tear film.

TEAR OSMOLARITY AND THE INFLAMMATION CASCADE Dr. Maharaj stated that the basic concept is whether a patient has an isotonic, hypertonic or hyperosmolar tear film; in other words, a salty or non-salty tear (Fig. 1). Most practitioners have experience with Muro 128® (sodium chloride hypertonicity ophthalmic ointment, 5%, Bausch + Lomb, Vaughan, ON) which is a hypertonic solution that draws water out in order to dehydrate the tissue R. Maharaj — Clinic Director, eyeLABS, Brampton, ON; Staff Optometrist, Humber River Regional Hospital - York/Finch Eye Associates, Toronto, ON; Clinical Adjunct Associate, University of Waterloo, School of Optometry, Waterloo, ON Correspondence to: Dr. Richard Maharaj, 7900 Hurontario, Suite 406, Brampton, ON L6Y 0P6; E-mail: rmaharaj@eyelabs.ca Dr. Maharaj has no direct financial or proprietary interest in any companies or products mentioned in this article. This article has been peer-reviewed.

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it’s in contact with, for example, to treat corneal edema. If the patient’s eyes are being bathed in a hypertonic solution, the water will be drawn out of the tissue leaving it in a dehydrated state. What ends up happening as a result of the dehydration is a type of insult that starts the inflammatory process, with epithelial breakdown and an inflammatory cascade. It is therefore crucial to properly identify hyperosmolar patients early on because many times, hyperosmolarity precedes dry eye symptoms. Dr. Maharaj stated that there are various components to dry eye, namely anatomical impact, environmental impact and age-related changes. Any dysfunction in these areas will result in insult to the ocular surface. On the physiological side, there is activation of inflammation, as well as an immune response involving the T-cells. Restasis® (cyclosporine ophthalmic emulsion 0.05%, Allergan, Unionville, ON) which, Dr. Maharaj noted, targets the T-cell pathway, working on immunomodulation. The question is, at what point do optometrists address the inflammatory cascade equation as the primary eye care doctors? How can they enter this equation a bit earlier? With any disease, whether it is glaucoma, meibomian dysfunction or diabetic eye disease, for example, early intervention or risk reduction has always led to better prognosis. All of the factors mentioned above contribute to friction, which is actually what brings a patient to optometry offices. No patient comes for a consultation and says, “I feel wonderful, my eyes feel like butter and I think I have dry eye.” Until they feel it, until there is insult that they can actually describe, they’re not going to say anything. This leads to the issue of diagnostic criteria: How can practitioners identify risk factors for this friction? When considering the chronology of tear dysfunction, osmolarity tends to be an early indicator. Patients don’t start to feel anything until well after osmolarity has begun to peak and then their symptoms start to worsen. Longterm unmanaged hyperosmolarity can contribute to neuroinflammation which will inevitably lead to corneal hypoesthesia. Subsequently, the patient feels better as if to say, “It’s magic, I’m cured.” The question is not what the practitioner has done but what has the patient done? The natural history of untreated hyperosmolarity has led them to neuropathy and hypoesthesia, and in some cases dysesthesia, referred to as pain without stain by Dr. Perry Rosenthal of the Boston Eye Pain Foundation. The objective is to avoid them arriving at this point through

Concept of Hyperosmolarity Isotonic

Hypertonic

(no net exchange of water)

(net loss of water from ocular cells)

Tear Film

H2O

Surface of the eye

H2O

H2O Epithelial cells

Fig. 2 Reducing surface friction: Identifying the cause of friction is essential. electrolytes

Epithelial cells

electrolytes

Fig. 1 Tear hyperosmolarity triggers an inflammatory cascade.

Table I Role of the tear film 7 major functions of the tear film 1. 2. 3. 4. 5. 6. 7.

Maintains hydration of the eye Lubricates the ocular surface Nourishes the cornea Cleanses the ocular surface Defends against bacterial invasion Buffers the pH of the ocular surface Refracts light for visual clarity

early intervention; and on this point, measuring osmolarity is the key. Figure 2 depicts a patient with damaged corneas or bilateral epitheliopathy, before and after treatment, who is planning on having cataract surgery. Identifying the source of friction requires an understanding of the tear film function, including seven major points listed in Table I, some of which the patient highlighted. The main objective is to maintain hydration. Second is to lubricate the ocular surface as lubrication leads to decreased friction which translates to less inflammation. The tear film is antibacterial as well. Finally, and again this is where patients may become symptomatic, the tear film actually helps the visual pathways so it transmits and refracts light. If a patient has a transient visual complaint, it’s important not to dismiss the tear film as a culprit in the differential diagnosis. A healthy tear film contains a complicated cascade of chemicals, including cytokines, proteins, mucin-related factors, and potassium, to name a few. Dr. Maharaj stated that it’s possible in the future there may be panel testing for these constituents because the tear film is actually very similar to blood in terms of the constituents. This panel testing is only as useful as existing targeted therapies to treat the specific components of a dysfunctional tear film. In comparison to blood, the water content of the human tear is similar and, in fact, the osmolarity overall is quite similar. If there is a wealth of information in the vascular

system, that same wealth of information resides in the tear film as well. For example, Google has already designed a contact lens that will measure a patient’s fasting glucose levels. Industry is looking at different ways to do this through the tear film because it’s more accessible than blood. Dr. Maharaj highlighted that it’s critical to understand that there are similarities and therefore, very likely, there are some answers that lie in the tears that may not have already been thought of. Regarding the proportion of dry eye patients in the average practice, some studies show that it has the highest prevalence of the major eye disease categories in general practices; because of this high prevalence, it makes sense to identify these patients and help them in a more meaningful way than we are currently. Dr. Maharaj remarked that early in his training and career, the treatment of mild corneal fluorescein staining would be one of a bag of various artificial tears, and the practitioner would advise the patient to use them as needed. That was, and perhaps still is in some cases, acceptable patient management. The report from the International Dry Eye Workshop (DEWS) in 2007 did an excellent job at raising awareness in both the academic circuit and in general in the eye care world, on the etiology and classification of dry eye. There are evaporative patients who are affected primarily by environmental factors, lid inflammation and surface anomalies; and there are aqueous deficient patients. Years ago it was thought that the majority of dry eye disease (DED) patients were aqueous deficient and treatment involved artificial tearing every single patient. The followup to the Dry Eye Workshop was the International Workshop on Meibomian Gland Dysfunction (MGD) in 2011 sponsored by the Tear Film & Ocular Surface Society (TFOS). The summary of that entire meeting pointed to MGD being perhaps one of the leading causes of dry eye around the world; we know now that evaporative and aqueous causes may not exist in mutually exclusive pools. In fact, noted Dr. Maharaj, they likely exist together on a spectrum, however, with aqueous patients specifically, it’s important to think about these various categories. The

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Fig. 3 A 52-year-old Asian female with moderate dry eye.

Sjögren’s cases, which probably represent an underdiagnosed population just because historical testing has demonstrated poor specificity and sensitivity for diagnosis. There is now a blood smear test available in the United States called Sjö which may help to increase identification of these patients. Additionally, there are medically induced cases resulting from certain medications such as antidepressants and antihistamines, among others. All of these categories affect aqueous production.

MEASURING OSMOLARITY For the purpose of tear film metric, osmolality and osmolarity are synonymous. Osmolality refers to measures in a solid state, while osmolarity is in a liquid state. It’s the concentration of osmoles or moles of a solute per liter of a solution. There are three main measuring methods, one of which is familiar to most practitioners. Freezing point depression uses the temperature at which a solution freezes below its normal temperature that can be calculated to an osmolarity value. It does require a rather large sample (0.2 µL) and it is not something that is amenable to a clinical setting. It is, however, a very accurate way of measuring osmolarity and is commonly used in academic settings. The converse to that is vapor pressure, the temperature above which a solution will vaporize. The difference between the temperature at which it vaporizes is calculated into an osmolarity value. The sample size required, 5 µL, sounds small, however, it is actually an extremely large sample for the average tear film of 7 µL. Collecting that amount is actually nearly impossible. The electrical impedance model is employed in glucose measuring systems, with which all optometrists are familiar. It measures the electrical impedance of a solution which is proportionate to solute concentration. TearLabTM

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(San Diego, CA), for instance, uses this process. Tears have an ionic content and will alter its conductivity which is then calculated to yield an osmolarity value. Tear osmolarity actually came into the dry eye conversation in the 1970s. The late Jeff Gilbard, MD, an ophthalmologist, discussed and wrote extensively on osmolarity at that time. In the late 1980s, he wrote a paper on how it related to MGD, which was well ahead of his time. The paper discussed the relationship between osmolarity and meibomian gland obstruction, and it wasn’t until the 2011 MGD Workshop (TFOS) that there was actually a consensus about that relationship. In 2007 at the DEWS workshop, tear osmolarity was finally incorporated into the clinical definition of DED. It is a very strong indicator so it has the higher positive predictive value when compared to other metrics such as tear breakup, Schirmer, staining and tear meniscus height according to Lemp et al, 2009. Dr. Maharaj highlighted that one of his educational objectives for practitioners is to have a common language with which to speak intraprofessionally. Osmolarity is a concept that is agreed upon in both ophthalmology and optometry, so it’s an effective bridge when discussing patients.

CASE STUDIES Case #1 Dr. Maharaj presented several cases from his clinical practice, some of which are still in progress. The first is a 52-year-old Asian female who had had LASIK surgery two years prior (Fig. 3). She reported to the clinic with moderate symptoms. Dr. Maharaj quantifies his patients’ symptoms using the SPEEDTM (Standard Patient Evaluation of Eye Dryness score, TearScience, Morrisville, NC). It’s a very quick questionnaire that takes his technician five

Fig. 4 A case of progressive dry eye with meibomian gland atrophy.

minutes to complete and it provides a validated number from a measure of 28. This patient had a score of 16. Symptom scores are very helpful in the identification and management of patients’ symptoms because they provide the patient and practitioner a measurement to quantify their condition. This patient’s symptoms were consistent with moderate dry eye. Shortly after her LASIK she was put on Restasis OU b.i.d., so she had been on it for roughly one-and-a-half years. Dr. Maharaj noted that it typically takes a minimum of three months to appreciate clinical improvement. She was previously a monthly contact lens wearer who disliked wearing her lenses, which was part of her motivation for LASIK. Dr. Maharaj uses an Oculus Keratograph® 5M (Arlington, WA) for meibography, an infrared lighting system that examines the meibomian glands. In this case, it showed gland truncation, which signals gland atrophy measured on a Heiko Pult scale. It also showed the meibomian gland ductules were dilated, which is a sign of obstruction that can lead to meibomian gland atrophy. This is very telling of progressive evaporative dry eye. The patient presented with significant gland atrophy in both eyes, more so in the right than the left. Her osmolarity was 315 mOsm/L in the right eye and 327 mOsm/L in her left (Fig. 4). Additionally, Dr. Maharaj uses an MMP-9 indicator which measures the concentration of an inflammatory marker in the tear film and provides a positive or a negative result, similar to a home pregnancy test. Testing positive for MMP-9 generally signifies surface inflammation. MMP — matrix metallaproteinase — are proteolytic enzymes in the tear film that are produced by surface epithelium when under duress. This patient was MMP-9 negative (InflammaDry®, RPS Inc., Sarasota, FL) which would lead to the conclusion that she doesn’t have inflammation on her

ocular surface, despite her having a hyperosmolar tear film. Dr. Maharaj subsequently consulted with the patient’s optometrist who had done a tear analysis prior to her having LASIK. Her pre-LASIK osmolarity was 299 and 301; for reference, generally a number of 300 mOSm/L or below is considered “normal.” Even before the patient had LASIK, she was on the borderline between normal and mild dry eye. Now that she wasn’t wearing contacts anymore and her eyes were essentially naked to the air, she was becoming symptomatic. Then two years later, her osmolarity had increased. But why was her MMP-9 negative? Dr. Maharaj diagnosed the patient with untreated CLIDE, contact lens induced dry eye, even though she was a post-LASIK patient. Her tear breakup time at this particular visit was markedly reduced in both right and left. MGYLS is a meibomian gland yielding liquid secretion score, a standardized way to measure gland function by diagnostic expression to uncover glands secreting fluid. Dr. Maharaj measured 15 in a row, 5 nasal, 5 central and 5 temporal. This patient had MGYLS of 3 in her right eye and 1 in her left, and they were severely inspissated. She had evaporative dry eye which was exacerbated by her incomplete blinking which is very common in this population. At home she was diligent about using warm compresses with a microwavable heat mask. Dr. Maharaj explained that he tends to be conservative in his treatment, but in this case it was obvious that the patient needed more help than simply a hot compress at home. He used LipiFlow® (TearScience, Morrisville, NC) thermal pulsation which consists of in-clinic vectored heat therapy applied to the posterior gland surface combined with pulsatile pressure. It does a very good job of clearing out all the meibom and aims to leave behind a patent meibomian gland with which the patient can function. Dr. Maharaj then stopped administration of preservative tears and replaced them with i-drop® Pur Gel (I-MED

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Normal mOsm/L + irritation complaint Epithelial basement membrane dystrophy (EBMD) Conjunctival chalasis Demodex blepharitis Non-obvious meibomian gland dysfunction (MGD) Contact lens/solution toxicity Lagophthalmos

Tear Prism Solute Gradient

Hyperosmolar Meibomian gland dysfunction (MGD) Contact lens induced dry eye (CLIDE) Androgen deficiency Peri-surgical Sjögren’s syndrome

Low volume high solute

High volume low solute

+ + +++ +++ ++

Solute gradient towards low solute

++ + + ++ + + + + ++ + + ++ + +

Osmotic pressure

Table II Analysis of dry eye patient symptoms in consideration of osmolarity.

This is why normal mOsm/L with symptoms should not be assumed to resolve with cyclosporine A alone.

Fig. 5 Proposed pathway for measuring tear prism solute gradient.

Pharma, Montreal, QC), a non-preserved hyaluronic acid derivative which works very well in such cases. After one month, the patient’s SPEED score was reduced from 16 to 4. At this point she reported feeling “normal.” The take-home from this is that there was some information gathered preoperatively that was missed. When looking at her history and taking the reference mark of her osmolarity into account, suddenly the picture became a lot clearer. She could have been identified earlier and actually been pre-treated for her ocular surface disease, in which case, Dr. Maharaj opined, she would have done better. Dr. Maharaj questioned whether optometrists are doing enough for their contact lens patients and “insulating their contact lens practice.” He stated that the contact lens industry in general and the impact of competing forces are concerning to some practitioners in terms of possibly losing market share to retail environments with greater buying power. Dr. Maharaj has a differing point of view, namely that practitioners actually have an opportunity to really improve their contact lens healthcare. By identifying patients who are at risk for developing CLIDE, practitioners can build a care model around that to ensure that their contact lens patients are diagnostically screened, using a healthy product contact lens modality. Perhaps a reusable contact lens wasn’t the best idea for this patient; maybe she should have been on a one-day lens. He posed the question, “Can tear osmolarity help increase compliance; to get the patient who is paying two hundred dollars for a year’s supply of a monthly lens and stretching it to a two month lens, to understand why a one-day lens may be more suitable?” He feels that it’s very possible and suggested that a contact lens practice is a dry eye practice that can be enhanced for prevention of ocular surface related conditions. In 2011, Dr. Michael Lemp published a paper in Cornea that established the hallmark of what is now known as the defining number, with 308 mOsm/L as the cutoff point between normal and clinical dry eye disease. In his study of 146 patients, he showed that specificity of

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tear osmolarity testing climbs when the osmolarity increases higher than 308. He also demonstrated that tear osmolarity (tOsm) as a measure had a very high positive predictive value, for people who have the disease. If a patient’s osmolarity is 327, there is a 95% chance the patient has dry eye disease. Dr. Lemp compared osmolarity to Schirmer, tear breakup time and Ocular Surface Disease Index. Osmolarity was the strongest predictor of DED among all measures. Marguerite McDonald, an ophthalmologist in the U.S., presented her work at 2013 ASCRS, examining the prevalence of dry eye in a large sequential cohort. They put patients through a very simple assessment including, demographic, history, and a yes or no series of questions, and then cross-referenced that against osmolarity. The study population was n=9,067. What they found was that of the patients were actually reporting dry eye symptoms, half did not meet the clinical criteria of 308 mOsm/L for dry eye, which is a very interesting finding. What is equally intriguing, said Dr. Maharaj, in fact more troubling, is that almost 50% of patients who were considered asymptomatic by the definition of the study, were hyperosmolar. These were patients who had a hyperosmolar tear film but were not reporting any significant symptoms. These are silent sufferers who are eventually going to develop this condition and are slipping through the cracks of treatment. These are LASIK and premium cataract patients who are possibly remaining underdiagnosed and this is where Dr. Maharaj feels practitioners can improve in identifying that patient base. The question is why do these patients have three or more symptoms if their osmolarity is “normal”? Table II explains this. A patient can have discomfort on the ocular surface without having a hyperosmolar tear film, depending on the stage of the condition. There is an entire host of conditions with which patients may in fact exhibit normal

Table III Tear osmolarity and MMP-9 categorization of OSD (Maharaj Ocular Surface Classification Model). Category 1

Category 2

Category 3

Category 4

Tear Osmolarity

Normal

High

Normal

MMP-9

Negative

Positive

Diagnostic Status

Non-DED

Early DED or on current MMP-9 targeted therapy Treat other aspects of tear dysfunction (MGD)

Moderate to severe DED

Postoperative CCh, EBMD, other etiology (diagnostically may not be tear dysfunction)

Fig. 6 A 69-year-old female patient, one-month post-surgery.

osmolarity. These include epithelial basement membrane disorders, conjunctival chalasis and non-obvious MGD. What is important to understand is that osmolarity isn’t there to classify the patient having one condition or the other, it’s actually meant to signal a practitioner to look more closely into the true etiology of the patient’s discontent.

MEIBOMIAN GLAND DYSFUNCTION One of the questions frequently asked of Dr. Maharaj is, “How does this tie in to meibomian gland dysfunction (MGD)? What do osmolarity and tear film have to do with the glands?” Dr. Anthony Bron in the UK published a paper that described the solute gradient (Fig. 5). Within the tear prism, there is a high concentration at the apex of the tear film and a very dilute concentration at the base; therefore, there is osmotic pressure being applied to the surface of the lid. The osmotic gradient actually forces solutes to the epithelial surface, contributing to the inflammatory process and eventual apoptosis. The epithelial cells, the meibomian gland surface, the orifice and then therefore the glands posterior to them, are being subjected to

insult, namely, inflammation and injury. This gradient is another reason to measure and ensure that osmolarity is being identified. The use of MMP-9 measures complements the use of osmolarity measurement similar to using both OCT and the visual field in a glaucoma patient. He stated that there are four possible scenarios, as shown in Table III. Category 1: The patient shows normal osmolarity and negative MMP-9, in which case they are considered normal. They don’t have or at least don’t meet existing clinical diagnostic criteria at this point to be considered having DED. Category 2: The patient may be hyperosmolar, but have a negative MMP-9. Recalling the case study previously outlined, the patient was on Restasis and it has been demonstrated in several papers that the drug inhibits the presence of MMP-9 on the surface. Therefore, generally speaking, this combination of findings is going to indicate either a patient who has early dry eye disease or a condition that is being pharmacologically managed. Category 3: The patient has a hyperosmolar tear film and has a positive MMP-9 measure. This patient most likely has moderate to severe dry eye and may require more

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pharmacological attention to control the inflammation. Category 4: Osmolarity is normal, however, the patient has a positive MMP-9. Dr. Maharaj pointed out that these four categories can help guide practitioners in their diagnosis and treatment of dry eye. The demographic of a dry eye patient is more consistent with being female than male and over the age of 50, who also tend to be decision-makers in their families. This profile represents the target for an optometrist’s primary care practice, and is certainly in a demographic that should be identified well in advance. In addition, in terms of pre- and post-surgical care, it’s vital to see these patients before they have surgery. It’s crucial to manage their osmolarity and tear dysfunction, or at least identify it and mitigate their risk of postoperative dryness, as demonstrated in the case below. Case #2 A 69-year-old female, one-month post cataract surgery OD, was referred to Dr. Maharaj by her eye surgeon. Her left eye was yet to be done and the difference in ocular surface staining is clear (Fig. 6). In fact, Dr. Maharaj saw this patient preoperatively after being referred initially for preoperative ocular surface optimization. He was asked to pre-treat her dry OS cornea preoperatively. The patient opted to have only one eye pre-treated. At this time OS was scheduled for surgery prior to OD, which eventually was changed. At this second presentation, OD showed that tear and ocular surface metrics were extremely poor. In addition, the patient had blink dysfunction — she wasn’t having full aperture closure due to floppy eyelid syndrome (FES) — and her tear breakup time was low. In terms of osmolarity and MMP-9, though, she was negative on MMP-9 and she did present with a hyperosmolar tear film 331 mOsm/L and 301 mOsm/L OD and OS, respectively. As a result, she fell into Category 2 (Table III). Did the patient have early dry eye disease or was she an MMP-9 targeted therapy? The fact that she was on postoperative Lotemax® (loteprednol etabonate 0.5% ophthalmic suspension, Bausch + Lomb, Vaughan, ON) which downregulates and decreases MMP-9 at the surface, it explains her negative MMP-9 result. Naturally, the patient was very uncomfortable with a severely compromised cornea and multiple sources of friction. Dr. Maharaj used a bandage contact lens (senofilcon A, Johnson & Johnson Vision Care, Markham, ON) which, he said, works very well for these cases. He also prescribed non-preserved hyaluronate and had the patient return for a follow-up. The purpose of the bandage contact lens was to decrease friction because the patient’s lid wiper was rubbing against her cornea and abrading it repeatedly, every time she blinked. He also continued her on loteprednol b.i.d. for another two weeks. In addition, he used his “triad treatment” which is a non-surgical meibomian gland treatment, which consists of eye lid scaling, meibomian gland expression and tear film neutralization with a basic mineral oil solution.

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The patient responded well to the combination of anti-inflammation with meibomian gland optimization via the triad treatment in follow-up care. Physiologically, the improvement in both signs and symptoms happens by managing the obstructive component to her MGD. The obstruction leads to a build-up of biofilm at the lid margin, which contributes to the inflammatory state at the surface. Gland clearance and removal of devitalized epithelium reduce the chemical burden of the surface and allow for more efficient epithelial repair. MMP-9 metrics were misleading in this case because her post-surgical topical regimen included loteprednol 0.5%. This case led into a review of William Trattler’s PHACO study (Prospective Health Assessment of Cataract Patients Ocular Surface Study) which was a prospective multi-centre observational pilot study of 143 patients scheduled to undergo cataract surgery. Key findings of the study suggested that the prevalence of DED signs is more common than frequently reported, with as much as 76.8% of patients testing positive for fluorescein corneal staining of which 50% had significant central staining. Dr. Maharaj opined that with the changing landscape of “premium” cataract and refractive surgery, it’s becoming more and more necessary to optimize the ocular surface. Failing to do so may impact the quality of surgical outcomes and therefore confidence in predicting refractive outcomes. He briefly discussed the study by Alice Epitropoulos, MD et al, in which pre-surgical patients with hyperosmolarity had a statistically significant greater variability in average K readings which impacted IOL power difference by more the 0.5 D. Of note, this difference was not observed when the same patients were grouped by self-reported dry eye, which highlights the value of tOsm as a significant preoperative measure. In a broader sense it further stands to reason that the ocular surface or the peri-surgical patient truly requires primary eye care by optometrists because the complications related to postoperative dry eye will inevitably fall into the hands of optometry long term. Case #3 Dr. Maharaj discussed a 27-year-old female patient, 2 months post-LASIK, who had chronic eye pain and peri-ocular discomfort as her chief complaint. She was a previous compliant contact lens wearer who did not report discomfort prior to surgery. She was prescribed Restasis b.i.d. OU by her surgeon, in addition to non-preserved hyaluronate q3-4h and larci-lube q.h.s. She was also using lid wipes for ocular hygiene. Despite having maximal symptom scores (SPEED=28), her pain was disproportionate to her clinical findings as noted on the incoming referral, as well as during presentation to the dry eye clinic. Oxford staining was <1 OD and OS, TBUT 6s OD, 7s OS, and tOsm 289 and 285 mOsm/L OD and OS, respectively. MMP-9 was negative and tear volume was normal. When referencing Dr. Maharaj’s categorization of

ocular surface disease by MMP-9 and tOsm, this patient falls into Category 1 – Non-DED. An increasing diagnostic entity that both parallels and intersects with DED is neuropathic pain. These cases can be particularly frustrating and often get lumped together by clinicians as the “crazy patient” who cannot seem to be pleased. However, Dr. Maharaj noted, it’s in fact a real entity, but due to diagnostic limitations can only be confirmed by exclusion and careful examination of clinical history and presentation. Managing neuropathic pain can be treated by managing the cyclo-oxygenase (COX) pathways (1 and 2) via COX inhibition, by use of human autologous serum (ranging in 20% to 40% concentrations), and some evidence has pointed to amniotic tissue transfer having some impact on nerve repair. Amniotic tissue in both cryopreserved and dehydrated options has demonstrated efficacy anecdotally with rapid reduction in pain with healing corneas, with cryopreserved possibly having superior impact on nerve repair. Although this list isn’t exhaustive, it represents a cursory review of current literature on pharmacological options for this group of patients. On discussion with the patient and her surgeon, she was initially managed with topical NSAID Prolensa® (bromfenac 0.07%, Bausch + Lomb, Vaughan, ON) q.d. for 1 month with the option of human autologous serum vs. amnion membrane transfer to be considered after 1 month. At the time of this lecture, the patient had sought out ocular surface reconstruction by a U.S. surgeon in addition to meibomian gland intraductal probing and was currently receiving that care. This prompted a short discussion on another commonly dry eye masquerader known as conjunctival chalasis, which is noted by conjunctival redundancy due to loss of Tenon’s fascia causing displaced tear fluid from the ocular surface and mechanical rubbing. Again, in review of Dr. Maharaj’s categorization, these patients may likely fall into Category 4. Case #4 A 63-year-old female presented to the dry eye clinic with a large OS central corneal abrasion. What made the treatment of this case more complicated was that the patient had previously arranged same day travel to Calgary. Although it was her first visit to the clinic, the patient noted a long history of recurrent corneal erosions (RCE) occurring almost monthly. Dr. Maharaj noted that the diagnostic difficulty of this case was low, however he highlighted that the long-term treatment would become more relevant as an educational tool. She was fitted with a bandage contact lens (senofilcon A, Johnson & Johnson Vision Care, Markham, ON) and started on topical Vigamox® (moxifloxacin hydrochloride 0.5%, Alcon, Mississauga, ON) t.i.d., and Muro 128. Arrangements were made for her to follow up with a colleague in Calgary the next day so as not to disrupt her travel. She responded well to therapy and the bandage lens was removed in Calgary 3 days later, with complete visual recovery.

At her two-week follow up back at the dry eye clinic, she received a full ocular surface work-up due to her frequency of RCEs. InflammaDry testing showed positive for MMP-9 which, along with clinical history, resulted in this patient being put on a two-month course of oral doxycycline 50 mg, in addition to loteprednol 0.5% b.i.d. in the affected OS. She was also started on non-preserved 0.3% hyaluronate (i-drop® Pur Gel, I-MED Pharma, Montreal, QC) for the duration. The choice of this combination was based on multiple studies relating MMP-9 inhibition to reduced RCE episodes. Dr. Maharaj reviewed the literature demonstrating oral doxycycline’s efficacy at reducing MMP-9 activity in corneal epithelial cultures, in addition to the benefits of low dose (20 mg) doxycycline when compared to anti-infective doses (200 mg b.i.d.). Whenever prescribing this combination however, patients should always be warned of the potential gastrointestinal discomfort and UV skin sensitivity when taking oral doxycycline, and this medicine should be avoided in patients who are pregnant, nursing or under the age of 13. Finally, Dr. Maharaj concluded the presentation by reviewing the current osmolarity system, with TearLab as the only device available for clinical use. He also introduced the i-Pen® osmolarity meter (I-MED Pharma, Montreal, QC) which will be launched in June 2016. Dr. Maharaj remarked that he has been beta-testing the system since July of 2015 and has been involved in some clinical studies using the i-Pen in a DED prevalence study that is yet to be completed. He reminded the audience of his disclosures, particularly his consultancy with the manufacturer, but stated that he isn’t financially benefiting from this product.

SUMMARY Tear osmolarity represents the single-most defining metric of DED and based on current literature can uncover up to 50% of silent dry eye sufferers in primary eye care practices. Optometry’s role in contact lens care and peri-surgical care is growing rapidly, therefore Dr. Maharaj reminded the audience to identify these patients early and pre-treat surgical cases so as to optimize outcomes. Lastly, tear chemistry represents one of the most interesting areas of DED from both a diagnostic and therapeutic perspective. Using the Maharaj Ocular Surface Classification Model (Table III) as outlined in the cases discussed, the combination of tear osmolarity and MMP-9 may provide clinicians with a tear panel to better classify patients and therefore improve targeted treatment outcomes. He finished by articulating his passion for this area of care and emphasized that optometry’s growing role in managing anterior segment diseases will only grow, so keeping abreast of current literature and treatment options is vital to the growth of the profession. ❏

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QUESTIONNAIRE Tear Dysfunction and Osmolarity: Tales from the Trenches Richard Maharaj, OD, FAAO 1. ❑ ❑ ❑ ❑

Which of the following conditions has the highest prevalence of the major eye disease categories in general practices? Diplopia Blepharitis Open-angle glaucoma Dry eye

2. ❑ ❑ ❑ ❑

At what level of tear osmolarity will a patient be suspected of having dry eye disease? 290 mOsm/L or more 300 mOsm/L or more 305 mOsm/L or more 310 mOsm/L or more

3. ❑ ❑ ❑ ❑

All of the following statements accurately describe the patient in Case #1, EXCEPT: She had a SPEED score of 14 Her symptoms were consistent with moderate dry eye She was previously a monthly contact lens wearer She had previously had LASIK surgery

Clinical and Refractive Optometry 27:4, 2016

❑ ❑ ❑ ❑

According to the literature, approximately ______ percent of patients who were considered asymptomatic were hyperosmolar? 30 40 50 60

5. ❑ ❑ ❑ ❑

All of the following statements accurately describe the patient in Case #2, EXCEPT: She had blink dysfunction Her tear breakup time was normal She was negative on MMP-9 She had hyperosmolar tear film

6. ❑ ❑ ❑ ❑

According to William Trattler’s PHACO study, approximately what percentage of patients tested positive for fluorescein corneal staining? 50% 58% 67% 77%

7. ❑ ❑ ❑ ❑

The following statement regarding the patient in Case #3 is TRUE: Her chief complaint was peri-ocular discomfort Her SPEED score was 26 Her MMP-9 was positive Her tear volume was low

8. ❑ ❑ ❑ ❑

All of the following statements accurately describe the patient in Case #4, EXCEPT: At her initial presentation to the clinic, she showed no history of corneal erosions At her initial presentation to the clinic, she was fitted with a senofilcon A bandage contact lens At her two-week follow-up at the dry eye clinic, she showed positive for MMP-9 At her two-week follow-up at the dry eye clinic, she was prescribed oral doxycycline 50 mg

9. ❑ ❑ ❑ ❑

All of the following are components of dry eye, EXCEPT: Anatomical impact Genetic impact Environmental impact Age-related changes

10. ❑ ❑ ❑ ❑

All of the following statements about MMP-9 are true, EXCEPT: A patient can show normal osmolarity and negative MMP-9, in which case they are considered normal A patient may be hyperosmolar, but have a negative MMP-9 Hyperosmolar patients treated with cyclosporine will have a positive MMP-9 Lotemax® (loteprednol etabonate) down-regulates and decreases MMP-9 at the surface

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Tam Nguyen et al entitled Hyperoleon: Complications of Silicone Oil in Reparative Retinal Surgery. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 152 for complete instructions.

Hyperoleon: Complications of Silicone Oil in Reparative Retinal Surgery Tam Nguyen, OD, MS, FAAO; Nancy N. Wong, OD, PhD, FAAO; Terry Luk, OD, FAAO; David M. Galeoto, OD, FAAO; Karen Wadhams, OD, FAAO

ABSTRACT Silicone oil injection is associated with many postoperative complications in the eye. The emulsification and forward migration of silicone oil into the anterior chamber is regarded as an invariable phenomenon that will eventually occur following a given in situ period. Emulsification of silicone oil can manifest as an “inverted hypopyon” or “hyperoleon,” filling up space in the superior portion of the anterior chamber. This can cause damage to a variety of structures, posing potential sight-threatening implications for patients. It is imperative for the clinician to be familiar with these potential complications so that timely identification and proper management can be initiated. Treatment modalities for secondary glaucoma include conventional topical glaucoma therapies, silicone oil removal (SOR), inferior peripheral iridectomy, and glaucoma surgeries for the control of IOP. In general, treatment and management is case-specific and risk factors need to be modified according to individual clinical presentation.

INTRODUCTION The advent of vitreoretinal surgical techniques in the past 30 years has dramatically altered the management of retinal conditions such as macular and retinal holes or tears, epiretinal membranes and retinal detachments. T. Nguyen — VA Connecticut Healthcare System, West Haven Campus, West Haven, CT; N.N. Wong — VA Hudson Valley Healthcare System, Wappingers Falls, NY; T. Luk — James J. Peters VA Medical Center, Bronx, NY; D.M. Galeoto — James J. Peters VA Medical Center, Bronx, NY; K. Wadhams — VA Portland Healthcare System, Portland, OR Correspondence to: Dr. Tam Nguyen, VA Connecticut Healthcare System, West Haven Campus 950 Campbell Ave. Building 2, Floor 4, West Haven, CT 06516; E-mail: drtamitsu@gmail.com and Tam.Nguyen5@va.gov This article has been peer reviewed.

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Many advances have further expanded the repertoire of treatment modalities such as the introduction of vitreous substitutes as long-acting gases1 and the use of silicone oil in vitreous surgery.2 In particular, silicone oil has been used with increasing frequency.2,3 However, the administration of silicone oil is not devoid of side effects or the potential for complications. Moreover, complications have been well-documented in the literature and include elevated intraocular pressure, refractive change, cataract formation,4 emulsification of oil, silicone oil keratopathy, peri-oil fibrosis,4 re-detachment of the retina4 as well as the development of secondary glaucoma.5-7 Silicone (polymethysiloxane) oil is often used as an intraocular retinal tamponade following reparative retinal detachment surgery. For intraocular applications, silicone oil demonstrates a low density when compared with aqueous. The density disparity easily displaces aqueous downward. Silicone oil has the advantage of being optically transparent, allowing for visualization of the posterior segment surgical fields. Often, silicone is selected over gas for complicated cases because silicone provides permanent or extended retinal tamponade and is not absorbed by ocular tissues like the long-acting gases. Currently, indications for the use of silicone oil in the eye include: internal tamponade in giant retinal tears, tamponade in traumatic or complex retinal detachments, dissection of epiretinal membranes with flattening of the retina, macular holes, and closure of breaks which are complicated by proliferative diabetic retinopathy4 and proliferative vitreoretinopathy.4 The intraocular use of silicone oil may result in adverse complications to multiple structures in the eye. At the posterior surface, silicone oil migration into subretinal spaces has been shown to occur in the presence of breaks in the retina.8 In addition, peri-oil fibrosis can occur at the pre-retinal surface resulting in adherent membranes4 that pose potential threats for retinal detachment. Pupillary block or iris bombé can occur if the silicone oil advances forward towards the anterior segment. Contact between the oil and the lenticular structures may result in refractive error shifts8 and induce cataract formation. Further migration anteriorly may cause interference with the outflow processes of the eye causing elevation in intraocular

tensions.9,10 If silicone oil remains in direct contact with the trabecular meshwork, ultra-structural damage may occur9,10 which may further reduce outflow. Silicone oil contact with the corneal endothelium causes a characteristic keratopathy9,11-13 resembling band keratopathy. The use of silicone oil in the eye may result in multiple iatrogenic complications which may be sight-threatening. With the increased application of silicone oil in retinal repair surgeries, recognition of the postoperative complications represents significant clinical importance in the management of retinal diseases. These complications are unique to its use and often present a straightforward clinical profile. In patients with a history of vitreoretinal surgery with silicone oil administration, proper assessment of postoperative complications with sight-threatening effects is important for disease co-management.

CASE REPORT A 51-year-old African-American male presented to the Eye Clinic with complaints of a mild, dull, periorbital ache and pain in the left eye. The pain was graded as a 4 on a scale of 10. The intermittent pain had been ongoing for the past several weeks. The patient also had complaints of subsequent decreased vision in the left eye. He reported that he felt the reduced vision correlated temporally to when his antihypertension medications were taken. The patient denied symptoms of photophobia, photopsia, headache, and discharge. His last eye exam was approximately 3 months prior. Moreover, the patient had been receiving ongoing care over the course of three years and was co-managed by a local, private retina specialist for an inferior retinal detachment secondary to lattice degeneration. The patient’s ocular history was significant for retinal reparative surgery including pneumatic retinopexy, scleral buckling, pars plana vitrectomy with silicone substitution, phaco-extracapsular cataract extraction, and YAG capsulotomy in the left eye. Following reparative retinal surgery, the left eye had developed cystoid macular edema resulting in subsequent poor vision. Despite prompt treatment, visual acuity was never fully restored to better than counting fingers. The patient’s medical history was significant for type 2 diabetes mellitus, hypertension and benign prostrate hypertrophy, all of which were controlled with oral medical therapy. The patient’s blood pressure measured 115/83 mmHg. Review of laboratory findings indicated a glycosylated hemoglobin level of 7.8%, and a fasting blood glucose level of 117 mg/dL. The patient denied any history of allergies and was alert and oriented to time, person and place. On clinical examination, the patient’s visual acuity was 6/6- (20/20-) and counting fingers at 5 feet with best spectacle correction of -4.50 -1.50 x 077 and -3.00 -1.50 x 071 for the right and left eyes, respectively. The patient’s visual acuity was unchanged with pinhole. A

grade 2 relative afferent pupillary defect OS was again noted on examination. Extraocular muscles were unrestricted in all fields of gaze and cover testing demonstrated orthophoria at distance and a slight exotropia at near. On external examination, there was an OS upper lid ptosis which impinged on the visual axis. Palpebral apertures were 11 mm on the right and 5 mm on the left. Anterior segment evaluation by slit lamp biomicroscopy was remarkable for mild endothelial guttatta, stromal scarring OD>OS and inferior punctuate epithelial erosions OD>OS. Temporal endothelial incision scars were visualized in the peripheral cornea of the left eye. The bulbar and palpebral conjunctiva were quiet OD and trace perilimbal injection was observed in the OS. Further examination of the iris OS demonstrated tiny crystalline-like structures localized to the crypts of the iris furrows. An opaque crystalline-substance occupied the top half of the anterior chamber. A demarcation line was evident 3.5 mm from the superior-most cornea in the left eye. The demarcation line in the anterior chamber separated the white crystalline opacity superiorly from the clear aqueous fluid inferiorly. Applanation tonometry was OD: 20 and OS: 38 mmHg. The anterior chamber appeared clear without cells or flare. In both eyes, angle estimation demonstrated grade 4 open angles by Van Herick technique. Gonioscopy of the left eye demonstrated open angles to ciliary body band in all quadrants except the superior portion where a thick, white, crystalline substance filled the angle. Intraocular pressure (IOP) OS was reduced to 27 mmHg following in-office topical instillation of brimonidine 0.2% and timolol maleate 0.5%. The dilated fundus examination revealed trace nuclear sclerotic and cortical cataracts in the right eye. The posterior chamber intraocular lens implant in the left eye was centered and clear of opacities. The vitreous in the right eye was unremarkable. Silicone oil was evident in the hyaloid space of the left eye. Fundus assessment revealed healthy optic nerves with a cup-to-disc ratio of 0.5 in both eyes. The neuroretinal rim was healthy and intact in the right eye. Pallor and peripapillary atrophy was noticed in the left eye. The macula was clear and flat in both eyes. The left eye demonstrated a foveal reflex. All vasculature was normal for course and caliber OU. The left eye demonstrated an inferior scleral buckle with an old hilar-shaped demarcation line that terminated 4 disc diameters from the macula. Extensive overlying retinal pigment epithelial hyperplasia and disruption were noticed along the demarcation line. The peripheral retina was flat and intact in both eyes. The patient was diagnosed with hyperoleon or emulsified silicone migration into the anterior chamber resulting in subsequent elevation of intraocular pressure in the left eye. The patient was referred back for retinology evaluation. Retinology evaluation was elicited to consider

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and left eyes, respectively. No silicone oil was evident in the anterior and posterior chamber of the left eye. The patient was instructed to taper the topical steroid drops, and complete the antibiotic and non-steroidal anti-inflammatory drops for a 13-day course. He was maintained on the topical beta-blocker to control IOP.

Fig. 1 Inverted or reverse hypopyon as a result of emulsification into the anterior chamber. Migration of silicone oil into the anterior chamber displaces aqueous inferiorly and results in a density gradient demarcation line. (This image was originally published in the ASRS Retina Image Bank. Michael Lambert, MD. Inverted Hypopyon – Silicone Oil Complication. Retina Image Bank, 2016, Image Number 24099. © The American Society of Retina Specialists.)

Follow-up #2 A follow-up examination was performed one month following surgical silicone oil removal. The patient reported resolution of the aching sensation in the left eye and maintenance of stable vision. The patient confirmed compliance with timolol maleate 0.5% ophthalmic solution. Visual acuities remained stable at 6/6- (20/20-) and counting fingers at 5 feet, in the right and left eyes, respectively. The intraocular pressures were 19 mmHg OD and 28 mmHg OS. No silicone oil was evident in the anterior or posterior chamber of the left eye. The patient was maintained on timolol maleate 0.5% b.i.d. OS for the control of pressure. Follow-up management included continued observation of glaucoma status.

DISCUSSION the risks, benefits and alternatives of either partial silicone oil removal from the anterior chamber or complete intraocular silicone oil extraction. The patient was maintained on timolol maleate 0.5% in the left eye to control intraocular pressure. At the retinal evaluation, the patient was counselled on risks and benefits of further surgical procedures for silicone oil removal. The patient elected to undergo complete silicone oil removal. Silicone oil removal from the posterior cavity was completed via vacuum pump. The remaining silicone oil in the anterior chamber was removed by paracentesis and sodium hyaluronate. A washout procedure for the anterior chamber was also performed. The patient underwent the operative procedure without complications. Follow-up #1 A follow-up examination was performed one day following surgical silicone oil removal surgery. The patient reported post-surgical soreness but denied pain or photophobia. Postoperative medications included: moxifloxacin 0.5% (Viagamox®, Alcon Canada, Mississauga, ON), prednisolone 1% (Pred Forte®, Allergan Canada, Unionville, ON), and ketorolac tromethamine 0.5% (Acular®, Allergan Canada, Unionville, ON). In addition, the patient was maintained on timolol maleate 0.5% (Timoptic®, Merck Canada, Kirkland, QC) in the left eye to control intraocular pressure. Visual acuities remained stable at 6/6(20/20-) and counting fingers at 5 feet, in the right and left eyes, respectively. Slit lamp biomicroscopy was significant for trace diffuse injection in the left eye. The ocular tensions were 19 mmHg and 30 mmHg in the right

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The term “emulsification” refers to the breaking up of silicone into small intraocular fragments. The incidence of emulsification into the anterior chamber has been reported from as low as 0.7%9 to as high as 56%.4 Emulsification and migration of silicone oil into the anterior chamber displaces aqueous inferiorly and results in a density gradient demarcation line. The characteristic appearance has also been termed “inverted” or “reverse hypopyon” or “hyperoleon” (Fig. 1). Discrepancies exist in the literature as to whether or not the presence of silicone in the anterior chamber is directly responsible for elevated ocular tension. The emulsification of silicone with subsequent migration into the anterior chamber is a rare complication in phakic or pseudophakic eyes.2,14-16 The natural or pseudophakic lens acts as a barrier to prevent migration16,17 of the silicone oil into the anterior chamber. The incidence of migration is much higher in aphakes.15 The current case represents an uncommon complication of emulsification with migration of silicone into the anterior chamber despite the presence of a pseudophakic implant. Alternative theories suggest partial zonulysis following extracapsular cataract extraction enabling the oil to migrate around the implanted lens.15,16 In the current case, the surgical history is positive for extracapsular cataract extraction. The resultant disturbance of the lens zonules may have contributed to migration of the emulsified silicone oil into the anterior chamber. The incidence of emulsification was thought to decrease with the development of higher viscosity oils. Lower-viscosity oil had a tendency to emulsify more than higher viscosity laboratory grade silicone.9 Despite new innovations in vitreous substitutes, the problem of emulsification has not been eliminated. In particular, for cases in

Fig. 2 Peripheral iridectomy in the inferior position of the iris in order to prevent pupillary block.

which prolonged internal tamponade is desired, 5000 centistokes (cs) of highly purified silicone oil is recommended.9 The current patient received 5000 cs silicone oil, which is characterized as one of the highest viscosity oils currently available for medical use. Despite such precautions, emulsification of silicone still resulted and IOP rise was observed. In the current case, inverse hypopyon was readily visualized when the left eyelid was manipulated superiorly. However, the emulsification of silicone and the deposition in the anterior chamber can also be subclinical.4 The droplet dimensions are smaller than a wavelength of light, therefore, slit lamp biomicroscopy and gonioscopy techniques may not facilitate visualization of the subclinical emulsified particles.4 Ultrasound biomicroscopy, however, has been shown to be more sensitive than the aforementioned techniques.18 Emulsification of oil droplets has been readily identified on ultrasound biomicroscopy as highly reflective images with a typical morphologic appearance.15,18,19 Moreover, ultrasound biomicroscopy should be performed in all cases where emulsification and migration is suspected and a hyperoleon cannot be visualized. The incidence of IOP elevation secondary to silicone oil has been reported to range from 5.9% to 56% of treated eyes.20 The cause of elevated intraocular pressure may be either direct blockage of the trabecular meshwork or inflammation and damage to the trabecular meshwork cells.21 Elevation in IOP is a common finding following vitreoretinal surgery with silicone oil injection.15 However, elevated IOP should prompt consideration of possible surgical complications. In aphakes receiving silicone oil substitutes, elevated ocular tensions can occur immediately following the postoperative period as a result of pupillary block. Pupillary block glaucoma occurs if the silicone oil creates a barrier at the pupillary space and

prevents flow of aqueous into the anterior chamber. Resultant anterior chamber narrowing and elevated intraocular pressure is evident from the misdirection of the aqueous. Pupillary block complications are circumvented by creation of a peripheral iridectomy (PI) in the inferior position of the iris, which allows for communication between the anterior and posterior chambers (Fig. 2). The incidence of elevated tensions in the aphakic individual immediately following surgery has decreased in patients that have received prophylactic treatment with a PI. Similarly, blockage of the iridectomy by blood, fibrin or oil in the postoperative course may be another mechanism for raised intraocular tensions. In phakic or pseudophakic individuals, the mechanism for acutely elevated IOP is likely to be true overfill with silicone oil.4 Elevated IOP in such cases typically demonstrates acute onset following surgery.13 If the intraocular pressure is as a result from true silicone overfill, surgical intervention to remove excess silicone generally has favorable results.13 Additionally, raised IOP may be a late-onset complication. Late-onset elevated pressure is caused by emulsification of silicone, pre-existing glaucoma, steroid induced glaucoma and uveitis.4 Not all patients with a hyperoleon have raised IOP. Many risk factors have been identified that may predispose the patient to an elevation of IOP following pars plana vitrectomy with silicone oil injection.5,7,22 Posner-Schlossman Syndrome generally presents with marked unilateral elevation (40 to 60 mmHg), with minimal conjunctival injection. This syndrome typically presents in young-to-middle-aged patients and is often accompanied with a history of recurrent episodes. In addition, this condition is responsive to steroid treatment. A retrobulbar hemorrhage generally appears in patients with an extensive history of recent blunt ocular trauma or head injury. Accompanying signs on external examination would include subconjunctival hemorrhage, occasionally chemosis and proptosis of the globe. In patients with pigmentary glaucoma, a Krukenbergâ&#x20AC;&#x2122;s spindle may be visualized on the cornea, and patients are typically young males with intact accommodative systems. With inflammatory open-angle glaucoma, a moderate to severe anterior chamber reaction would be evident on slit lamp biomicroscopy. Medications can be responsible for inducing unilateral elevated intraocular pressures (e.g., steroid, topiramate). If the etiology lies in the structure of the lens, this can easily be visualized on slit lamp biomicroscopy. Pupillary block would be evident as a result of a phakomorphic lens. Choroidal detachments and posterior segment tumors will be evident on B-scan ultrasonography of the anterior and posterior segment, respectively (Table I). The presence of an inverted hypopyon or silicone droplets are pathognomonic for emulsification and migration of silicone oil into the anterior chamber. A history of retinal detachment repair with silicone injection

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Table I The differential diagnosis in unilateral elevated intraocular tensions • Glaucomatocyclitic crisis (Posner-Schlossman Syndrome) • Retrobulbar hemorrhage • Pigmentary glaucoma • Inflammatory open-angle glaucoma • Medication-induced • Lens-induced • Choroidal detachment • Posterior segment tumor

is further supportive of the etiology of increased IOP. Isolation of the particular mechanism responsible for the postoperative rise in ocular tensions facilitates timely treatment and management. The causes of hyperoleon and unilateral elevated intraocular pressure in the immediate postoperative period include pupillary block and silicone overfill. Pupillary block generally appears in the aphakic individual and may be accompanied by a mid-dilated pupil. An overlying exudative membrane in pupillary block may be evident in patients with existing PI’s. A lack of an oil/aqueous interface in the pupillary plane is evident, as well as an absence of flare in the anterior chamber. Silicone overfill generally appears in the pseudophake or phakic patient. The condition may be accompanied by signs of shallowing in the anterior chamber, as well as the presence of herniation of oil between the pupil and lens. The causes of hypopyon and unilateral elevated intraocular pressure during the late postoperative period include steroid-induced glaucoma, pre-existing glaucoma, uveitis and emulsification of silicone. Topical steroids are frequently given following surgical intervention. In the present case, the patient was placed on a topical steroid but the steroid response elevation in IOP will often resolve following discontinuation of therapy. This mechanism is a diagnosis of exclusion. Pre-existing glaucoma may aggravate in IOP following re-attachment of the retina because repair reduces the uveal-scleral outflow afforded by the retinal detachment. Elevated intraocular pressure has also been shown to occur secondary to complex vitreal detachments. The condition is evidenced by the presence of cells and flare in the anterior chamber but such constituents should not be mistaken for fine silicone droplets which may mimic the clinical entity. Finally, the presence of silicone in the anterior chamber leads to the diagnosis of emulsification, as described in the current case. Elevated Intraocular Tension and Considerations for Glaucoma Silicone oil use has been associated with emulsification of oil into the anterior chamber, subsequent elevated intraocular pressure, and secondary glaucoma.23-25 Silicone oil emulsification and glaucoma often are coexisting entities; however patients with emulsified silicone may never develop glaucoma, even after long term testing.8,14 The

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pathogenesis remains obscure but generally, the hyperoleon is thought to be a contributor to ocular hypertension or glaucoma in some patients.13-15,26 In patients with emulsification and raised intraocular pressure, removal of the oil is recommended. Some investigators have showed minimal effect on IOP following silicone oil removal.27 Other investigators have demonstrated that removal affords for better control of ocular tensions.6 In general, secondary glaucoma is one of the most serious complications for patients with emulsification of silicone and increased IOP. Individuals with such indications should be followed closely for the development of secondary glaucomas.

CONCLUSION The use of silicone oil in the eye is becoming more prevalent with more advances in vitreoretinal surgery. Silicone oil in the eye can lead to serious complications that have a specific clinical profile. Recognition of specific vitreous substitutes in retinal surgery allow for prompt diagnosis. Isolation of the mechanism for IOP-rise facilitate targeted treatment and management. In general, treatment and management is case-specific so risk factors need to be balanced and subsequently modified according to individual clinical presentation. ❏

REFERENCES 1.

Stern WH, Blumenkranz MS. Fluid-gas exchange after vitrectomy. Am J Ophthalmol 1983; 96: 400-401. 2. Lucke KH, Foster MH, Laqua H. Long-term results of vitrectomy and silicone in 500 cases of complicated retinal detachments. Am J Ophthalmol 1987; 104: 624-633. 3. Scott JD. A rationale for the use of liquid silicone. Trans Ophthalmol Soc UK 1977; 97: 235-237. 4. Chignell AH, Wong D. Management of vitreo-retinal disease: a surgical approach. London: Singer Press, 1999. 5. Honavar SG, Goyal M, Majji AB, Sen PK, Naduvilath T, Dandona L. Glaucoma after pars plana vitrectomy and silicone oil injection for complicated retinal detachments. Ophthalmology 1999; 106: 169-176; discussion 177. 6. Nguyen QH. Lloyd MA, Heuer DK, et al. Incidence and management of glaucoma after intravitreal silicone oil injection for complicated retinal detachment. Ophthalmology 1992; 99: 1520-1526. 7. Henderer JD, Budenz DL, Flynn HW, et al. Elevated intraocular pressure and hypotony following silicone oil retinal tamponade for complex retinal detachment: incidence and risk factors. Arch Ophthalmol 1999; 117: 189-195. 8. Leaver PK, Grey RH, Garner A. Silicone oil injection in the treatment of massive preretinal retraction: late complications in 93 eyes. Br J Ophthalmol 1979; 63: 361-367. 9. Scott JD. Surgery for Retinal and Vitreous Disease. Oxford: Butterworth Heinemann. 1998. 10. McCuen BW, de Juan E Jr, Landers MB 3rd, Machemer R. Silicone oil in vitreoretinal surgery. Part 2: Results and complications. Retina 1985; 5: 195-205.

11. Cockerham WD. Schepens CL, Freeman HM. Silicone injection in retinal detachment. Arch Ophthalmol 1970; 83: 704-712. 12. Grey RH, Leaver PK. Results of silicone oil injection in the treatment of massive preretinal retraction. Trans Ophthalmol Soc U K 1977; 97: 238-241. 13. Kim RW, Baumal C. Anterior segment complications related to vitreous substitutes. Ophthalmol Clin North Am 2004; 17: 569-576. 14. Federman JL, Schubert HD. Complications associated with the use of silicone oil in 150 eyes after retina-vitreous surgery. Ophthalmology 1988; 85: 870-876. 15. Avitabile T, Bonfiglio V, Circero A, et al. Correlation between quantity of silicone oil emulsified in the anterior chamber and high pressure in vitrectomized eyes. Retina 2002; 22: 443-448. 16. Riedel KG, Gabel VP, Neubauer L, et al. Intravitreal silicone oil injection: complications and treatment in 415 consecutive patients. Graefes Arch Clin Exp Ophthalmol 1990; 228: 19-23. 17. Ardjomand N, El-Shabrawi Y. Pupillary block after silicone implantation in a phakic eye. Eye 2001; 15: 331. 18. Genovesi-Ebert F, Rizzo S, Chiellini S, et al. Ultrasound biomicroscopy in the assessment of secondary glaucoma after vitreoretinal surgery and silicone oil injection. Ophthalmologica 1998; 212: 4-5.

19. Azzolini C. Pierro L. Codenotti M, et al. Ultrasound biomicroscopy following the intraocular use of silicone oil. Int Ophthalmol 1995; 19: 191-195. 20. Gedde SJ. Management of glaucoma after retinal detachment surgery. Curr Opin Opthalmol 2002; 13: 103-109. 21. Champion R, Faulborn J, Bowald S, Erb P. Peritoneal reaction to liquid silicone: an experimental study. Graefes Arch Clin Exp Ophthalmol 1987; 225: 141-145. 22. Budenz DL, Taba KE, Feuer WJ, et al. Surgical management of secondary glaucoma after pars plan vitrectomy and silicone oil injection for complex retinal detachment. Ophthalmology 2001; 108: 1628-1632. 23. Chan C, Okun E. The question of ocular tolerance to intravitreal liquid silicone: a long term analysis. Ophthalmology 1986; 93: 651-660. 24. Nakamura K, Refojo MF, Crabtree DV. Factors contributing to the emulsification of intraocular silicone and fluorosilicone oils. Invest Ophthalmol Vis Sci 1990; 31: 647-656. 25. Valone J Jr, McCarthy M. Emulsified anterior chamber silicone oil and glaucoma. Ophthalmology 1994; 101: 1908-1912. 26. Gao RL, Neubauer L, Tang S, Kampik A. Silicone oil in the anterior chamber. Graefes Arch Clin Exp Ophthalmol 1989; 227: 106-109. 27. Moisseiev J, Barak A, Manaim T, Treister G. Removal of silicone in the management of glaucoma in eyes with emulsified silicone. Retina 1993; 13: 290-295.

Management of Ocular Emergencies 6th Revised Edition

ISBN 978-1-896825-33-5

SU FRE SE BSC E W I E PA RIPT TH GE IO 12 N 5

6 chapters 96 pages 53 color plates 16 figures 12 tables 13 Appendices and a Subject Index This Book Contains: Descriptions, Workups and Treatment Options for Managing the Following Ocular Emergencies:

Contributors Raymond Stein, MD, FRCSC Associate Professor, University of Toronto

Harold Stein, MD, FRCSC Professor, University of Toronto

Rebecca Stein, MD Ophthalmology Residency Program, University of Toronto

Nontraumatic Red Eye Traumatic Red Eye Pre-Septal Cellulitis Corneal Abrasions Chalazion Contact Lenses Acute Dacryocystitis Ultraviolet Keratitis Blepharitis Chemical Injuries Dry Eye Corneal Foreign Bodies Allergic Conjunctivitis Intraocular Foreign Bodies Adenoviral Conjunctivitis Blow-Out Fracture Bacterial Conjunctivitis Hyphema Chlamydia Blunt Trauma Injury Herpes Simplex Lacerations and Perforations Herpes Zoster Toxic Conjunctivitis Decreased Vision Recurrent Corneal Erosions in a White Eye Subconjunctival Hemorrhage Vein Occlusion Phlyctenule Artery Occlusion Episcleritis Retinal Detachment Scleritis Maculopathy Corneal Ulcers Vitreous Hemorrhage Iritis Optic Neuritis Acute Angle Closure Glaucoma Ischemic Optic Neuropathy

Decreased Vision in a White Eye (contâ&#x20AC;&#x2122;d) Cortical Blindness Understanding Glaucoma: An Overview Diplopia Third Nerve Palsy Fourth Nerve Palsy Sixth Nerve Palsy Myasthenia Gravis Orbital Disease

Hyperoleon: Complications of Silicone Oil in Reparative Retinal Surgery â&#x20AC;&#x201D; Nguyen

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QUESTIONNAIRE Hyperoleon: Complications of Silicone Oil in Reparative Retinal Surgery Tam Nguyen, OD, MS, FAAO; Nancy N. Wong, OD, PhD, FAAO; Terry Luk, OD, FAAO; David M. Galeoto, OD, FAAO; Karen Wadhams, OD, FAAO 1. ❑ ❑ ❑ ❑

In the Case Report presented, what degree of pain did the patient report at initial presentation? Grade 1 Grade 2 Grade 3 Grade 4

2. ❑ ❑ ❑ ❑

All of the following statements are true, EXCEPT: In the Case Report presented, the patient’s ocular history was significant for scleral buckling In the Case Report presented, the patient’s visual acuity was fully restored to better than counting fingers For intraocular applications, silicone oil has a low density when compared with aqueous The use of silicone oil in the eye may result in complications which may be sight-threatening

3. ❑ ❑ ❑ ❑

In the Case Report presented, what was the patient’s initial visual acuity? 6/6- (20/20-) 6/7.5- (20/25-) 6/9- (20/30-) 6/12- (20/40-)

Clinical and Refractive Optometry 27:4, 2016

All of the following statements describe the patient at follow-up #1, EXCEPT: He denied photophobia Visual acuities remained stable at 6/6- (20/20-) He reported Grade 2 pain Ocular tensions were 19 mmHg and 30 mmHg in the right and left eyes, respectively

5. ❑ ❑ ❑ ❑

What is the reported incidence of IOP elevation secondary to silicone oil? 2.4% to 56% of treated eyes 3.9% to 56% of treated eyes 4.8% to 56% of treated eyes 5.9% to 56% of treated eyes

6. ❑ ❑ ❑ ❑

All of the following statements accurately describe Posner-Schlossman Syndrome, EXCEPT: It typically presents in elderly women It is often accompanied with a history of recurrent episodes It responds to steroid treatment A retrobulbar hemorrhage generally appears in patients with an extensive history of recent ocular trauma or head injury

7. ❑ ❑ ❑ ❑

In the Case Report presented, all of the following clinical signs describe the patient at initial presentation, EXCEPT: The patient’s visual acuity was unchanged with pinhole Extraocular muscles were restricted in some fields of gaze On external examination, there was an OS upper lid ptosis which impinged on the visual axis The bulbar and palpebral conjunctiva were quiet OD

8. ❑ ❑ ❑ ❑

All of the following statements about use of silicone oil are true, EXCEPT: Its use has been associated with secondary glaucoma Silicone oil emulsification and glaucoma often are coexisting entities The majority of patients with emulsified silicone develop glaucoma Hyperoleon is thought to be a contributor to ocular hypertension in some patients

In the Case Report presented, following in-office topical instillation of brimonidine 0.2% and timolol maleate 0.5%, the patient’s IOP OS was reduced to which of the following? 22 mmHg 25 mmHg 26 mmHg 27 mmHg

❑ ❑ ❑ ❑

10. All of the following statements about the incidence of IOP elevation following vitreoretinal surgery with silicone oil injection are false, EXCEPT: ❑ It’s rare ❑ It rises with increased age ❑ It’s common ❑ Steroid response elevation in IOP typically continues despite discontinuation of therapy

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Drs. Euri Chi, Steven Ferrucci, and Brenda Yeh entitled Advances in the Treatment of Central Serous Chorioretinopathy. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 161 for complete instructions.

Advances in the Treatment of Central Serous Chorioretinopathy Euri Chi, OD; Steven Ferrucci, OD, FAAO; Brenda Yeh, OD, FAAO

ABSTRACT Central serous chorioretinopathy (CSC) is a commonly encountered macular disorder. Most cases of acute serous chorioretinopathy resolve on their own, with a favorable visual outcome within three to six months from onset. For those cases that do not resolve, new treatment modalities are being investigated that may be of help.

INTRODUCTION Central serous chorioretinopathy (CSC) is characterized as an idiopathic neurosensory retinal detachment at that macula secondary to abnormal leakage from the retinal pigment epithelium (RPE).1 The exact etiology of CSC is still unclear however the pathogenesis is believed to be due to increased hyperpermeability of choroidal vasculature leading to mechanical disruption of the RPE barrier and ultimately subretinal fluid accumulation and neurosensory detachment.2 Males are six times more likely to get CSC than females.3 It is reported that males account for 72% to 88% of cases.4 It is often associated with Type A personalities, stress, use of exogenous steroids, Cushing’s syndrome, systemic lupus erythematosus, and pregnancy.5-7 CSC has a variety of signs and symptoms. Patients with CSC will often complain of an acute onset central scotoma, metamorphopsia, micropsia, decreased contrast sensitivity, and decreased vision.1 Fundus examination will show a round or oval shaped neurosensory retinal detachment at the macula, a retinal pigment epithelium detachment (PED), or a combination of both8 (Fig. 1A,B). E. Chi — Sepulveda VA Medical Center, North Hills, CA; S. Ferrucci, B. Yeh — Sepulveda VA Medical Center, North Hills, CA; Marshall B. Ketchum University/Southern California College of Optometry, Fullerton, CA Correspondence to: Dr. Steven Ferrucci, Chief of Optometry, Sepulveda Ambulatory Care Center, 16111 Plummer Street, #112e, Sepulveda, CA, 91343; E-mail: Steven.Ferrucci@va.gov This article was peer-reviewed.

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RPE atrophy or hyperpigmentation can indicate areas of previous episodes of CSC. Workup for CSC includes dilated fundus examination (DFE), amsler grid (AG), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICGA). OCT demonstrates a neurosensory retinal detachment, PEDs, chronic exudates, and intraretinal cystic spaces (Fig. 2). Further, it has been identified through enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT) that patients with CSC have increased choroidal thickness compared to normal eyes without history of CSC (Fig. 3A,B). This is believed to be due to increased choroidal vasculature and hyperpermeability causing a thickened choroid. A normal healthy choroid has been reported to have an average subfoveal choroidal thickness of 287 µm ± 76 µm with an annual decline of 15.6 mm per decade of life due to normal age related choroidal atrophy.9 However eyes affected with CSC have been found to have an average subfoveal choroidal thickness of 505 µm ± 124 µm10 in one study and an average subfoveal choroidal thickness of 367.81 µm ± 105.56 µm in another study.11 Fluorescein angiography (FA) may show the hallmark “smokestack” appearance. The smokestack appearance is described to show a hyperfluorescent spot during the early phase that changes into a linear column during the late phase. However, FA more commonly shows what is known as an “ink blot” stain, which is described as a round hyperfluorescent spot that gradually enlarges with time (Fig. 4). Fundus autofluorescence (FAF) is a newer diagnostic tool, which detects the presence of lipofuscin in the RPE. FAF will exhibit hyperfluorescence in acute CSC, which likely indicates increased metabolic activity of the RPE. However, in chronic CSC hypofluorescence is evident, which likely indicates photoreceptor loss and consequently loss of RPE and lipofuscin.12 ICGA is a procedure that uses indocyanine green dye to evaluate choroidal vasculature and is often used in conjunction with FA. With CSC, ICGA will show multifocal areas of dilated choroidal vessels at the posterior pole that will be hyperfluorescent due to choroidal hyperpermeability.13 ICGA has been found to be more sensitive at identifying choroidal hyperpermeability and leakage than fluorescein angiography.14

Fig. 1 (A) Color and (B) red-free photo of a patient with an active central serous chorioretinopathy OS with 6/15 (20/50) acuity OS.

Fig. 2 SD-OCT (spectral domain OCT) of a patient with acute central serous chorioretinopathy OS. Note small pigment epithelium detachment within the lesion.

TREATMENT Careful observation and monitoring is the initial standard of management with CSC. Recommendations to modifying risk factors are suggested, such as inhibiting exogenous corticosteroid use and lifestyle changes to reduce environment stresses. One study found resolution of subretinal fluid in 90% of its patients after the discontinuation of steroids.15 The patientâ&#x20AC;&#x2122;s primary doctor who prescribed the oral corticosteroid should be consulted to discuss plans on discontinuing or tapering the medication. Some practitioners have also suggested yoga and meditation to

patient with CSC, although there are no clinical studies to support these methods. New treatments for CSC are now being examined. Due to the high rate of spontaneous resolution, these treatments are generally considered for chronic CSC, recurrent CSC, a CSC event lasting longer than three months, or cases in which the fellow eye has suffered permanent loss from a previous CSC event. Laser Photocoagulation Focal laser photocoagulation was previously used as the main treatment method for CSC. Laser is applied to areas

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Fig. 3 (A) Choroidal thickness on enhanced depth enhanced imaging shown as 462 Âľm in patient with turbid central serous chorioretinopathy vs. (B) choroidal thickness of 248 Âľm in a control patient.

of leakage that are identified from FA. The mechanism of how focal laser photocoagulation actually works in resolving subretinal fluid is still unknown. It is believed to cause the destruction and scarring of dysfunctional RPE cells that leads to the migration of healthy RPE cells to the treatment area and therefore aid in the resolution of subretinal fluid. Focal laser photocoagulation does help speed up resolution of subretinal fluid; however studies show that it does not help improve final visual acuity versus no laser treatment. It also carries a risk of forming a secondary choroidal neovascularization and permanent scotomas. Therefore, it is no longer considered to be the primary method of treatment.16 Photodynamic Therapy Photodynamic therapy (PDT) is widely recognized in the treatment of wet age-related macular degeneration. However, it has also gained favor in the treatment of CSC. Standard PDT involves an intravenous injection of a photosensitizing drug, verteporfin, which is activated by a laser. A verteporfin dose of 6 mg/m2 over 10 minutes is injected and five minutes later, a 689 nm diode laser at an energy of 50 mJ/cm2 over 83 seconds, and an output of 600 mW, is applied to the areas of leakage in the affected eye. It is believed that PDT works by causing endothelial degeneration of the choriocapillaris and subsequent thinning of the treated choroid.17 One study reported complete resolution of subretinal fluid in 60% of treated eyes who had CSC for greater than 6 months. Treated eyes had stable or improved vision during 6.8 months of follow-up.14 The majority of treated eyes had visual acuities that remained stable, while some had their visual acuity improve by 2 or more lines.

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Reduced-Fluence PDT Due to the risks associated with standard- or full-fluence PDT, such as choroidal ischemia, RPE atrophy, permanent scotomas, and secondary choroidal neovascular membrane (CNVM),18,19 reduced-fluence PDT has been more recently investigated as a method for treating CSC. Essentially, reduced-fluence PDT reduces laser treatment time, administers a smaller verteporfin dosage, uses a lower energy output, or changes the time interval between drug infusion and laser treatment. It is thought that a smaller dose of verteporfin is enough in reducing choroidal hyperpermeability as evident in CSC. Shortening the time between verteporfin infusion and laser application is believed to reduce collateral damage of adjacent retinal structures near the treatment area. One study evaluated the use of reduced-fluence PDT versus placebo in the treatment of CSC. The primary outcome measure was the complete resolution of subretinal fluid within 12 months following treatment. There was a statistically significant percentage of eyes that had complete resolution of subretinal fluid in the reduced-fluence PDT group versus the placebo group. Also, reabsorption of subretinal fluid was faster in the reduced-fluence PDT group versus the placebo group. Lastly, all subjects in the reduced-fluence PDT group experienced improved or stable final visual acuity versus 78.9% of the placebo group. The study showed that reduced-fluence PDT may be more beneficial over monitoring in cases of acute CSC.20 Reduced-fluence PDT has also been shown to be as effective as standard PDT therapy with potentially less risks and ocular complications. Multiple studies concluded similar visual outcomes and rate of subretinal fluid reabsorption between treatments with reduced-fluence PDT

modality over standard-fluence PDT in the treatment of acute as well as chronic CSC.

Micropulse Laser Subthreshold micropulse (STMP) laser has been investigated to treat patients with CSC. Conventional lasers use a continuous stream of energy that cause photocoagulation and scarring of tissue. They carry a risk of causing permanent scotomas, long-term expansion of focal scars, iatrogenic choroidal neovascularization, and potential new areas of leakage due to the thermal burn applied to the retina.22 STMP lasers minimize these risks by reducing the amount of thermal heat exposure to tissue, using a series of short 810 nm micropulses of laser instead a continuous stream, and therefore reducing permanent damage caused by thermal heat to the areas surrounding the treatment area.23 STMP lasers are usually aided by ICGA to look for focal areas of leakage. One case report showed treatment of chronic CSC by ICGA-guided STMP laser was safe and effective. Almost complete resolution of subretinal fluid was noted after 8 weeks following treatment.24

Fig. 4 (A) Fluorescein angiography of a patient with central serous chorioretinopathy demonstrating the “ink-blot” stain, (B, C) gradually getting larger with time

versus standard PDT. However, greater risks of complications, such as choroidal neovascularization, were associated with treating chronic CSC with standard PDT.21 Therefore, reduced-fluence PDT has become the favored treatment

Intravitreal Antivascular Endothelial Growth Factor (VEGF) A few studies have investigated treating CSC with intravitreal anti-VEGF agents, such as bevacizumab or ranibizumab. Although it is unclear how anti-VEGF agents work on resolving subretinal fluid, it is believed that because of choroidal hyperpermeability, choroidal ischemia, as well as choroidal venous congestion, there is a release of VEGF properties into the aqueous.25 Studies have proposed that by decreasing the level of VEGF properties, it would likely lead to a decrease in choroidal hyperpermeability and resolution of subretinal fluid. One study evaluated a single dose of bevacizumab (1.25 mg/0.05 mL) in patients with CSC versus a control group. Overall, both groups had complete resolution of subretinal fluid within six months and there was no statistical difference in final visual acuity.26 Another study looked at the treatment of CSC with intravitreal ranibizumab versus reduced-fluence PDT. Eyes in the ranibizumab group received a 0.5 mg dose every month for 3 months. Eyes in the reduced-fluence PDT group had a single session of reduced-fluence PDT. Visual acuity did improve slightly in both groups, however 75% had complete resolution of sub-retinal fluid and decreased choroidal hyperper meability in the reduced-fluence PDT group versus 25% in the ranibizumab group.27 The role of intravitreal injections have proven to be beneficial in the treatment of choroidal neovascular membranes in age-related macular degeneration, but it has yet to be proven effective in the treatment of CSC.

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Anti-Corticosteroids Increased levels of glucocorticoids, endogenous or exogenous glucocorticoids, have been linked to CSC. Therefore, discontinuation of exogenous corticosteroids is recommended for patients taking them. Further, this has led to several trials evaluating anti-corticosteroids as treatment for CSC Rifampin, a bactericidal antibiotic drug prescribed for treating tuberculosis, has been found to have properties that increase the metabolism of endogenous glucocorticoids. A very small study looked at the treatment of CSC with oral rifampin. One patient with bilateral CSC for 2 years was prescribed 300 mg of oral rifampin twice daily for 1 month. At the 1-month follow-up, the patient noted a subjective improvement in vision. Visual acuity had improved from 6/60 (20/200) to 6/21 (20/70) in the right eye and 6/15 (20/50) to 6/12 (20/40) in the left eye. Complete resolution of subretinal fluid was also evident on SD-OCT.28 A second more recent case study examined three patients with chronic CSC treated with 600 mg of oral rifampin daily. All three responded positively to the rifampin, with increased visual acuity and resolution of subretinal fluid within the first month.29 Mifepristone, another anti-glucocorticoid, has been tested for its potential efficacy in the treatment of CSC. Mifepristone, otherwise known as RU-486, is an antiabortifacient used to terminate a pregnancy within the first month. A small study compared the use of oral mifepristone (200 mg daily for 12 weeks) versus a placebo group. Overall, the results were inconclusive. Seven out of 16 subjects had improvement in visual acuity of 5 or more letters and 7 subjects had improved anatomical findings on SD-OCT from baseline.30 Ketoconazole is a synthetic imidazole, used to treat a variety of fungal infections. Besides anti-fungal properties, ketoconazole also has anti-glucocorticoid effects. A study evaluating five chronic CSC patients receiving 600 mg of ketoconazole did not show any change in acuity or OCT findings at 8 weeks, despite documented decrease in endogenous cortisol levels.31 A second non-randomized study of 15 patients treated for four weeks did not show any better outcomes versus the control group.32 Spironolactone and eplerenone are aldosterone antagonists used primarily for the treatment of heart failure. Resolution in subretinal fluid and reduction in central macular thickness was demonstrated in more than one case series. Additional studies are needed before it is clear if this is a viable treatment option.33-35 A more recent study evaluating spironolactone 25 mg twice daily in 18 patients with CSC revealed central retinal thickness decreased from 405 µm on average pretreatment to 287 µm after treatment for 12 months, with a modest increase in visual acuity.36

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Finasteride is a medication used for the treatment of benign prostatic hyperplasia, as well as male pattern baldness. It is a type II 5-a-reductase inhibitor which limits the amount of testosterone converted to dihydrotestosterone. One study evaluated 5 cases of chronic CSC treated with 5 mg daily dose or oral finasteride for 3 months. Subretinal fluid and central retinal thickness was improved in all 5 patients. Upon cessation of the trial, 4 of the 5 patients had re-appearance of the fluid and subsequent increase in retina thickness.37 Acetazolamide Small studies have investigated the use of acetazolamide, a systemic carbonic anhydrase inhibitor (CAI) in the treatment of CSC. It is believed that acetazolamide speeds up the reabsorption of subretinal fluid by stimulating retinal adhesion and re-establishing RPE polarity.38 In one study, participants were given 500 mg of oral acetazolamide three times daily for 2 weeks, then twice daily for 2 weeks, and finally once daily for an additional 2 weeks. The average time for full anatomical resolution was 3.3 ± 1.1 weeks in the study group and 7.7 ± 1.5 weeks in the control group. There was no statistically significant difference in final visual acuity or rate of recurrence. Participants did note a faster subjective improvement in visual acuity versus those in the control group, 14.7 ± 5.7 days versus 31.3 ± 4.5 days, respectively.39 Treatment with acetazolamide may be a viable option for patients in need of faster recovery of CSC, but may not have an effect on overall acuity. Aspirin Aspirin has also been investigated as a treatment modality of CSC. Increased levels of plasminogen activator inhibitor 1 have been identified in patients with CSC. It is hypothesized that increased levels of plasminogen activator inhibitor 1 cause a decrease in the fibrinolysis leading to thrombotic occlusion of choroidal veins and overall choroidal hyperpermeability as shown in CSC. Aspirin works by reducing the levels of plasminogen activator inhibitor 1.40 One study prescribed 100 mg of aspirin daily for one month followed by 100 mg on alternate days for 5 months on 109 compared to historic controls. Aspirin was shown to be effective in speeding up recovery and decreasing the rate of recurrence, with no effect on overall visual acuity versus no treatment.41 Metoprolol It was noted in a preliminary study that patients with acute CSC started on metoprolol, a beta blocker for the treatment of systemic hypertension, had improved symptoms. Further, the CSC recurred when the metoprolol was discontinued.42 However, a study comparing 23 patients received 10 mg of metoprolol for 45 weeks demonstrated no improvement at 45 weeks compared to the placebo group.43

Helicobacter Pylori Treatment Helicobacter pylori, a bacteria which infects the stomach and has been linked to peptic ulcers, has also been linked to possible CSC. One study indicated that antiHelicobacter pylori treatment in CSC patients quickened the resolution of subretinal fluid.44 However, a second larger randomized study did not show any positive results in the clinical course of CSC patients.45 Additional studies are warranted before any conclusion can be drawn. Methotrexate Methotrexate is an antimetabolite medication used for treating certain cancers, autoimmune rheumatologic disease, vasculitis, as well as for scleritis treatment in eye care. One study found that the mean central retinal thickness and visual acuity improved in 11 patients treated with oral methotrexate for 12 weeks. Further, 9 out of 11 (83%) remained dry even after discontinuation of the medication.46

CONCLUSION Central serous chorioretinopathy generally has a favorable outcome of spontaneous resolution within 3 to 6 months from onset. Therefore, careful monitoring and patient reassurance is often the best treatment. However, reducedfluence PDT has gained favor amongst many physicians as a method for treating CSC when indicated. Small studies have shown mixed reviews on the treatment of CSC with intravitreal injections and oral medications and therefore more studies need to be done to evaluate their effectiveness. Knowing the treatment options for patients with chronic or non-resolving CSC provides better management and increased options for our patients. â??

REFERENCES 1. 2.

4. 5.

6. 7.

8. 9.

Kanski J, et al. Clinical Ophthalmology: A Systemic Approach. Oxford, UK: Elsevier, 2011: 632. Field MG, Elner VM, Park S, et al. Detection of retinal metabolism stress resulting from central serous retinopathy. Retina 2009; 29: 1162-1166. Liew G, Quin G, Gillies M. Central serous chorioretinopathy: a review of epidemiology and pathophysiology. Clin Experiment Ophthalmol 2013; 41: 201-214. Wang M, Munch IC, Hasler PW, et al. Central serous chorioretinopathy. Acta Ophthalmol 2008; 86: 126-145. Carvalho-Recchia CA, Yannuzzi LA, Negrao S. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002; 109: 1834-1837. Wang M, Munch IC, Hasler PW, et al. Central serous chorioretinopathy. Acta Ophthalmol 2008; 86: 126-145. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc 1986; 84: 799-845. Klais CM, et al. Central serous chorioretinopathy. Retina Vol 2. Philadelphia, PA: Elsevier, 2006: 1135-1161. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol 2009; 147(5): 811-815.

10. Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina 2009; 29: 1469-1473. 11. Kim SW, Oh J, Kwon SS, et al. Comparison of choroidal thickness among patients with healthy eyes, early age-related maculolpathy, neovascular age-related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vascuolpathy. Retina 2011; 31(9): 1904-1911. 12. Von Ruckmann A, Fitzke FW, Fan J, et al. Abnormalities of fundus autofluorescence in central serous retinopathy. Am J Ophthalmol 2002; 133(6): 780-786. 13. Nicholson B, Noble J, Forooghian F, et al. Central serous chorioretinopathy: update on pathophysiology and treatment. Surv Ophthalmol 2013; 58(2): 103-126. 14. Yannuzzi LA, Slakter JS, Gross NE, et al. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. Retina 2003; 23: 288-298. 15. Sharma T, Shah N, Rao M, et al. Visual outcome after discontinuation of corticosteroids in atypical severe central serous chorioretinopathy. Ophthalmology 2004; 111: 1708-1714. 16. Leaver P, Williams C. Argon laser photocoagulation in the treatment of central serous retinopathy. Br J Ophthalmol 1979; 63: 674-677. 17. Maruko I, Iida T, Sugano Y, et al. Subfoveal retinal and choroidal thickness after verteporfin photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol 2011; 151: 594. 18. Koytak A, Kazim E, Coskun E, et al. Fluorescein angiography-guided photodynamic therapy with half-dose verteporfin for chronic central serous chorioretinopathy. Retina 2010; 30(10): 1698-1703. 19. Ober MD, Yannuzzi LA, Do DV, et al. Photodynamic therapy for focal retinal pigment epithelial leaks secondary to central serous chorioretinopathy. Ophthalmology 2005; 112: 2088-2094. 20. Chan WM, Lai TYY, Lai RYK, et al. Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial. Ophthalmology 2008; 115: 1756-1765. 21. Reibaldi M, Cardascia N, Longo A, et al. Standard-fluence versus low-fluence photodynamic therapy in chronic central serous chorioretinopathy: a nonrandomized clinical trial. Am J Ophthalmol 2010; 149(2): 307-315. 22. Yadav NK, et al. Subthreshold micropulse yellow laser (577 nm) in chronic central serous chorioretinopathy: safety profile and treatment outcome. Eye 2015; 29: 258-265. 23. Sivaprasad S, Elagouz M, McHugh D, et al. Micropulse diode laser therapy: evolution and clinical applications. Surv Ophthalmol 2010; 55: 516-530. 24. Ricci F, Missiroli F, Cerulli L. Indocyanine green dyeenhanced micropulse diode laser: a novel approach to subthreshold RPE treatment in a case of central serous chorioretinopathy. Eur J Ophthalmol 2004; 14(1): 74-82. 25. Lim JW, Kim MU, Shin MC. Aqueous humor and plasma levels of vascular endothelial growth factor and interleukin-8 in patients with central serous chorioretinopathy. Retina 2010; 30: 1465-1471. 26. Lim JW, Ryu SJ, Shin MC. The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy. Korean J Ophthalmol 2010; 24:155-158

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27. Bae SH, Heo JW, Kim C, et al. A randomized pilot study of low-fluence photodynamic therapy versus intravitreal ranibizumab for chronic central serous chorioretinopathy. Am J Ophthalmol 2011; 152(5): 784-792. 28. Steinle NC, Gupta N, Yuan A, et al. Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. Br J Ophthalmol 2012; 96: 10-13. 29. Nattis A. Josephberg R. Rifampin as an Efficacious Therapy for Chronic CSC. Retinal Physician 2015; 12(3): 52-57. 30. Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina 2011; 31: 1928-1936. 31. Meyerle CB, Freund KB, Bhatnagar P, et al. Ketoconazole in the treatment of chronic idiopathic central serous chorioretinopathy. Retina 2007; 27(7): 943-946. 32. Goshahi A, Klingmuller D, Holtz FG. Eter N. Ketoconazole in the treatment of chronic idiopathic central serous chorioretinopathy: a pilot study. Acta Ophthalmol 2011; 88(5); 576-581. 33. Bousquet E, Beydoun T, Zhao M, et al. Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: a pilot study. Retina 2013; 33(10): 2096-2102. 34. Breukink MB, den Hollander AI, Keunen JE, et al. The use of eplerenone in therapy-resistant chronic central serous chorioretinopathy. Acta Ophthalmol 2014 92(6): e488-e490. 35. Gruska A. Potential involvement of mineralocorticoid receptor activation in the pathogenesis of chronic central serous chorioretinopathy: case report. Eur Rev Med Pharmacol Sci 2013; 17(10): 1369-1373. 36. Herold TR, Prause K, Wolf A, et al. Spironolactone in the treatment of central serous chorioretinopathy-a case series. Graefes Arch Clin Exp Ophthalmol 2014; 252(12): 1985-1991.

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37. Forooghian F, Meleth AD, Cukras C, et al. Finasteride for chronic central serous chorioretinopathy. Retina 2011; 31(4): 766-771. 38. Cox SN, Hay E, Bird AC. Treatment of chronic macular edema with acetazolamide. Arch Ophthalmol 1988; 106: 1190-1195. 39. Pikkel J, Beiran I, Ophir A, Miller B. Acetazolamide for central serous retinopathy. Ophthalmology 2002; 109(9): 1723-1725. 40. Iijima H, Iida T, Murayama K, et al. Plasminogen activator inhibitor 1 in central serous chorioretinopathy. Am J Ophthalmol 1999; 127: 477-478. 41. Caccavale A, Romanazzi F, Imparato M, et al. Low-dose aspirin as treatment for central serous chorioretinopathy. Clin Ophthalmol 2010; 4: 899-903. 42. Avci R, Deutman AF. Chrapek O, et al. Treatment of central serous chorioretinopathy with the beta-blocker metoprolol (prelimary results) Klin Mobl Augenheilkd 1993: 202(3): 199-205. 43. Chrapek O, et al. Treatment of central serous chorioretinopathy with beta-blocker metoprolol. Biomed Pap Med Fac Univ Palcky Olomouc Czech Repub 2013: 3-6. 44. Rahbani-Nobar MB, Javadzadeh A, Ghojazadeh L, et al. The effect of Helicobacter pylori treatment on remission of idiopathic central serous chorioretinopathy. Mol Vis 2011; 17(January): 99-103. 45. Dang Y, Mu Y, Zhao M, et al. The effect of eradicating Helicobacter pylori on idiopathic central serous chorioretinopathy patients. Ther Clin Risk Manage 2013; 9: 355-360. 46. Kurup SK, Oliver A, Emanuelli A, et al. Low-dose methotrexate for the treatment of chronic central serous chorioretinopathy: a retrospective analysis. Retina 2012; 32(10): 2096-2101.

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QUESTIONNAIRE Advances in the Treatment of Central Serous Chorioretinopathy Euri Chi, OD; Steven Ferrucci, OD, FAAO, Brenda Yeh, OD, FAAO 1. ❑ ❑ ❑ ❑

All of the following statements about central serous chorioretinopathy (CSC) are false, EXCEPT: Females are three times more likely to develop it than males Males are twice as likely to develop it as females Males and females show equal incidence of the condition Males are six times more likely to develop than females

2. ❑ ❑ ❑ ❑

All of the following are signs and symptoms of CSC, EXCEPT: Acute onset central scotoma Decreased night vision Metamorphopsia Micropsia

In one study, the discontinuation of steroids resulted in resolution of subretinal fluid in what percentage of patients? 60% 70% 80% 90%

❑ ❑ ❑ ❑

Advances in the Treatment of Central Serous Chorioretinopathy— Chi et al

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All of the following statements about CSC are true, EXCEPT: It has a high rate of spontaneous resolution Patients have increased choroidal thickness compared to normal eyes without a history of CSC It has a hereditary component Fundus examination will show retinal detachment at the macula

In one study, eyes treated with photodynamic therapy (PDT) had stable or improved vision during what period of follow-up? 2.8 months 3.8 months 6.8 months 7.8 months

❑ ❑ ❑ ❑ 6. ❑ ❑ ❑ ❑

In one study, what percentage of the placebo group experienced improved or stable final visual acuity versus the 100% in the reduced-fluence PDT group? 68.2% 78.9% 79.8% 82.4%

7. ❑ ❑ ❑ ❑

In a study of oral rifampin, what was one patient’s visual acuity in the left eye at 1-month follow-up? 6/12 (20/40) 6/15 (20/50) 6/21 (20/70) There was no improvement

8. ❑ ❑ ❑ ❑

In a study of oral methotrexate, what percentage of patients remained dry even after discontinuation of the medication? 42% 60% 75% 83%

9. ❑ ❑ ❑ ❑

What were the results of a study of oral mifepristone versus the placebo group? The results were inconclusive The majority of subjects had improved anatomical findings on SD-OCT from baseline The majority of subjects had improvements in visual acuity The results of the study were controversial due to its small sample size

10. ❑ ❑ ❑ ❑

All of the following statements about CSC are true, EXCEPT: A normal healthy choroid has an annual decline of 10.6 µm per decade of life The exact etiology remains unclear Fluorescein angiography may show a “smokestack” appearance ICGA is more sensitive at identifying choroidal hyperpermeability and leakage than fluorescein angiography.

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4. ❑ ❑ ❑ ❑

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News and Notes New Lens Coating Technologies from NIKON Nikon recently introduced a new, proprietary and innovative coating: SeeCoat Bright. This is a functional coating that delivers brighter, more vivid colour perception in dim light conditions and improves contrast for wearers who experience reduced light transmission. Colour transmission changes according to the intensity of light. Under dim lighting, the eye’s perception of the red colour spectrum diminishes. As a result, colours may appear dull. This loss of colour sensitivity in dim lighting becomes even more notable after the age of 40 as the crystalline lens ages. SeeCoat Bright is the one and only solution to this phenomenon. SeeCoat Bright supplements the transmission of red wavelengths, resulting in more natural colour perception and increased contrast. Adding to its list of innovations, Nikon also presents SeeCoat Blue Premium, an enhanced version of SeeCoat Blue UV that reflects and absorbs blue light. SeeCoat Blue Premium improves blue light cut by 11%, resulting in less eye strain and visual fatigue, as well as better contrast perception. It reduces glare on the lenses by 25%, resulting in only a very subtle hue on the lenses. Furthermore, ghost images are reduced by 64%, providing natural and comfortable vision. SeeCoat Blue Premium can be applied on any type of lens – even those intended for daily use. For additional information, contact your Nikon Territory Manager, Nikon customer services department at 1-800-6638654, or visit www.nikonlenswear.ca. Transitions Innovation Awards Program Industry professionals can begin submitting nominations for the 2016 Transitions Innovation Awards Program. Through the program, Transitions Optical, Inc. recognizes loyal partners and individual optical industry professionals from the U.S. and Canada for their commitment to growing their businesses by supporting the Transitions® brand over the past year. Open to independent eye care professionals and practices; optical industry professionals and educators; national and regional retailers; and optical laboratories, the five Transitions Innovation Awards categories include: • 2016 Transitions Brand Ambassador (Individual-only award) • Best in Growth Achievement • Best in Training • Best in Marketing • Best in Patient Experience. Nominations for all Transitions Innovation Awards will be accepted online from October 1-31, 2016. All finalists in each category will receive a trip for two to the 2017 Transitions Academy, January 29-February 1, 2017 in Orlando, Florida, where the winners will be announced. Award finalists will be notified no later than December 5, 2016 to secure travel plans. For additional information or to enter, visit TransitionsCanadaPRO.ca/Awards.

Indications and clinical use: LOTEMAX® Gel (loteprednol etabonate ophthalmic gel 0.5% w/w) is indicated for the treatment of postoperative inflammation and pain following cataract surgery. • The safety and efficacy of LOTEMAX® have not been studied in pediatric patients (<18 years of age) and the product should not be used in these populations. Contraindications: • Suspected or confirmed infection of the eye: viral diseases of the cornea and conjunctiva including epithelial herpes, simplex keratitis (dendritic keratitis), vaccinia, and varicella; untreated ocular infection of the eye; mycobacterial infection of the eye and fungal diseases of ocular structures. • Hypersensitivity to LOTEMAX® or any ingredient in the formulation or container, or to other corticosteroids. Relevant warnings and precautions: • LOTEMAX® Gel is indicated for short-term treatment only (up to 14 days). If LOTEMAX® Gel is used for 10 days or longer, intraocular pressure (IOP) should be closely monitored. • The use of steroids after cataract surgery may delay wound healing. • Prolonged use of corticosteroids may result in cataract and/or glaucoma formation. Should not be used in the presence of glaucoma or elevated IOP, unless absolutely necessary and close ophthalmologic monitoring is undertaken. • LOTEMAX® Gel includes benzalkonium chloride. • Should not be used in pregnant or lactating women unless the benefit to the mother clearly outweighs the risk to the infant/child. For more information: Please consult the Product Monograph at http://www.bausch.ca/en-ca/our-products/ rx-pharmaceuticals/lotemax-gel-loteprednoletabonate-ophthalmic-gel-05-w-w for complete dosing instructions, warnings, precautions, adverse events and patient selection criteria. The Product Monograph is also available by calling 1-888-459-5000.

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