CROQ Vol 1 Number 6

CROQ ONLINE EDITION

Clinical Refractive & Optometry Quebec EDITION

VOLUME 1, NUMÉRO 6, 2016

CLIQUEZ ICI POUR TÉLÉCHARGER ET IMPRIMER CE NUMÉRO

Tous les articles sont accrédités par l’OOQ pour des crédits UFC de catégorie A

Complications of Silicone Oil in Reparative Retinal Surgery Advances in the Treatment of Central Serous Chorioretinopathy The Science of Dry Eye Hyperosmolarity Diagnosis and Treatment of Ocular Surface Conditions: Focus on Dry Eye

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Clinical

&Refractive Optometry Quebec

Comité de rédaction • volume 1, numéro 6, 2016 Rédacteur en chef

Rédacteur en chef adjoint

Rédacteur en chef adjoint

Dr Yvon Rhéaume Montréal, Québec

Dr Richard Maharaj Toronto, Ontario

Dr Leonid Skorin, Jr. Albert Lea, Minnesota

Collaborateurs à la rédaction Dr Brad Almond Calgary, Alberta

Dre Danielle DeGuise Montréal, Québec

Dr Langis Michaud Montréal, Québec

Dr Jean Bélanger Montréal, Québec

Dr Pierre Forcier Montréal, Québec

Dr Rodger Pace Waterloo, Ontario

Dr Scott D. Brisbin Edmonton, Alberta

Dr John Jantzi Vancouver, Colombie-Britannique

Dr Maynard Pohl Bellevue, Washington

Dr Lorance Bumgarner Pinehurst, Caroline du Nord

Dr Geral Komarnicky Vancouver, Colombie-Britannique

Dre Barbara Robinson Waterloo, Ontario

Dre Barbara Caffery Toronto, Ontario

Dr Bart McRoberts Vancouver, Colombie-Britannique

Dr Jacob Sivak Waterloo, Ontario

Dr Louis Catania Philadelphie, Pennsylvanie

Dr Ron Melton Charlotte, Caroline du Nord

Dr Randall Thomas Concord, Caroline du Nord

Équipe éditoriale Éditeur Lawrence Goldstein

Directrice gérante Mary Di Lemme

Éditrice médicale Evra Taylor

Mise en page Colin MacPherson

Graphisme et design Mediconcept Inc.

Notre énoncé de mission Clinical & Refractive Optometry Quebec est une revue d’optométrie évaluée par les pairs produite en éditions imprimée et en ligne. La revue a pour mandat de publier des articles cliniques et scientifiques approuvés par COPE qui ont été accrédités par l’Ordre des optométristes du Québec (OOQ) et sont offerts comme cours donnant droit à des crédits UFC de catégorie A. Le contenu de cette publication est composé d’articles qui présentent une utilité ou un intérêt particuliers pour les praticiens professionnels des soins de la vue au Québec. Les participants qui répondent aux tests-questionnaires UFC contenus dans la revue et qui obtiennent une note de 50 % ou plus recevront un certificat de crédit UFC personnalisé par courriel.

Pourquoi la revue est-elle publiée en anglais ?

Les règles concernant les crédits d’éducation permanente au Québec ont été amendées. Dorénavant, les articles de revue donnant droit à des crédits UFC qui ont été approuvés par COPE, le conseil créé par The American Regulatory Board of Optometry (ARBO), peuvent être offerts en version imprimée et en ligne aux optométristes du Québec pour des crédits UFC de catégorie A. Il est important de rappeler cependant que tous ces articles ont été à l’origine rédigés, approuvés et accrédités en anglais et ne peuvent être traduits ou reproduits dans une autre langue. Pour cette raison, tous les cours donnant droit à des crédits UFC de catégorie A offerts dans cette publication sont présentés en anglais avec l’approbation de l’Ordre des optométristes du Québec (OOQ).

Clinical

&Refractive Optometry Quebec

Contenu • volume 1, numéro 6, 2016 ARTICLES DE CRÉDITS UFC

216

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 sightthreatening implications for patients.

224

233

La revue est accessible à tous les optométristes praticiens du Québec à www.crojournal.com.

Les commandes d’annonces et les textes doivent être reçus avant le premier jour du mois qui précède la date de publication.

L’équipe éditoriale de Clinical & Refractive Optometry Quebec prend un grand soin pour assurer l’exactitude du contenu, mais nous recommandons toujours aux lecteurs de consulter les directives du fabricant avant d’utiliser les produits mentionnés dans nos pages. Les vues exprimées dans la revue sont celles des auteurs respectifs et non de l’éditeur.

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.

Veuillez faire parvenir toute correspondance à : Mediconcept Rédaction et service des ventes 3484, boul. des Sources, bureau 518 Dollard-des-Ormeaux, Québec Canada H9B 1Z9 Tél. bureau : (514) 245-9717 Courriel : info@mediconcept.ca

The Science of Dry Eye Hyperosmolarity Benjamin J. Barrus, OD

Imprimé au Canada. Tous droits réservés. Copyright © 2016 Mediconcept.

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

INTRODUCTION: Dr. Barrus began his presentation by pointing out that dry eye is a common disease in Calgary, where his practice is located, which has a significant negative impact on patients’ quality of life. An important role for optometrists, he said, is to “own” patients’ dry eye problem and provide the best available options for relief. He treats every dry eye patient differently because every individual case is different and requires its own careful workup and differential diagnosis. On average, he sees about four dry eye patients per day.

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Clinical & Refractive Optometry Quebec est publié six fois par année par Mediconcept.

Le contenu de cette publication ne peut être reproduit par voie mécanique ou électronique en tout ou en partie sans l’autorisation écrite de l’éditeur.

Toutes les publicités de médicaments ont été approuvées par le Conseil consultatif de publicité pharmaceutique.

Diagnosis and Treatment of Ocular Surface Conditions: Focus on Dry Eye Paul Karpecki, OD INTRODUCTION: Dr. Karpecki began his presentation on dry eye disease (DED) by noting that, according to the most recent study on prevalence, 29% of the Canadian population has dry eye. Allergies represent approximately 20% and glaucoma is roughly 2.2%, so this is an enormous opportunity; dry eye is the future of optometry.

ISSN: 2369-498X; Date de ce numéro : Décembre 2016

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Image de Couverture : Peripheral iridectomy in the inferior position of the iris in order to prevent pupillary block.

Gracieuseté de : Dr. Tam Nguyen

CLIQUEZ ICI POUR IMPRIMER CET ARTICLE ET LE TEST DE CRÉDIT UFC

Clinical & Refractive Optometry Quebec is pleased to present this continuing education (CE) article by Dr. Tam Nguyen et al, VA Connecticut Healthcare System, West Haven, CT. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optométristes du Québec. In order to obtain your credit, please refer to page 222 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 Krukenberg’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. ❏

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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.

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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 & Refractive Optometry Quebec 1:6, 2016

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4. ❑ ❑ ❑ ❑

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

9.

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 Quebec is pleased to present this continuing education (CE) article by Dr. Euri Chi et al, Sepulveda VA Medical Center, North Hills, CA. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optométristes du Québec. In order to obtain your credit, please refer to page 231 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

A

B

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 patient’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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A

B

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.

A

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

B

C

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??

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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.

FORMULAIRE DE DEMANDE DE CRÉDIT UFC DE CATÉGORIE A

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DIRECTIVES POUR UN CRÉDIT UFC DE CATÉGORIE A Ce cours a été approuvé pour 1 crédit UFC de catégorie A en santé oculaire par l’Ordre des optométristes du Québec. Veuillez répondre à ce questionnaire et le soumettre pour notation avant le 31 mars 2018.

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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

3.

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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4. ❑ ❑ ❑ ❑

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

5.

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.

Clinical & Refractive Optometry Quebec 1:6, 2016

CLIQUEZ ICI POUR IMPRIMER CET ARTICLE ET LE TEST DE CRÉDIT UFC

Clinical & Refractive Optometry Quebec is pleased to present this continuing education (CE) article by Dr. Benjamin Barrus, IRIS Chinook Centre, Calgary, AB. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optométristes du Québec. In order to obtain your credit, please refer to page 238 for complete instructions.

The Science of Dry Eye Hyperosmolarity Benjamin J. Barrus, BSc, BOptom (Hons), OD

INTRODUCTION Dr. Barrus began his presentation by pointing out that dry eye is a common disease in Calgary, where his practice is located, which has a significant negative impact on patients’ quality of life. An important role for optometrists, he said, is to “own” patients’ dry eye problem and provide the best available options for relief. He treats every dry eye patient differently because every individual case is different and requires its own careful workup and differential diagnosis.

On average, he sees about four dry eye patients per day.

Dr. Barrus recommended that dry eye symptoms be assessed in a follow-up appointment rather than as a component of a standard eye exam. This ensures there will be enough time to conduct a proper assessment and educate the patient about the pathology of the condition.

He often uses images to help patients understand the condition, including images he takes himself while expressing their meibomian glands, so patients can better understand gross meibomian gland dysfunction (MGD).

He also takes images of keratitis he identifies in contact lens wearers to show to patients. He finds that allowing patients to visualize what is happening in their eyes improves both understanding and compliance.

SELECTING TESTS AND EQUIPMENT Many clinical definitions of dry eye and “cookbooks” on its diagnosis and treatment are available, said Dr. Barrus, but to really learn how to manage the condition, optometrists require direct clinical experience. He recommended that optometrists new to the management of dry eye disease wait before investing in expensive diagnostic equipment. Rather, they should take a few months to decide if they want to focus on dry eye and consider what tests, tools, and equipment they have available already before making a large investment. Consider carefully what each test is measuring and diagnosing, he said.

B.J. Barrus — IRIS The Visual Group, Calgary, AB Correspondence to: Dr. Benjamin J. Barrus, Chinook Centre, 148A - 6455 Macleod Trail South, Calgary, AB T2H 0K9; E-mail: drbenbarrus@gmail.com Dr. Barrus has no financial interests in any businesses or products mentioned in this meeting report.

This article has been peer reviewed.

A battery of tests is needed to thoroughly benchmark the different components of tear film, said Dr. Barrus.

“Paint yourself a good picture,” he recommended. Tear film breakup time (TFBUT) testing identifies the presence of a problem but does not pinpoint precisely what the problem is or even its severity. Let patient presentation guide test selection, he advised. Overall, he performs about five to seven tests on each new dry eye patient to create a diagnostic differential list and determine with which clinical component to move forward.

Testing mucin layer can be particularly challenging because good, definitive tests are lacking in this area now that rose bengal staining is no longer available, said Dr. Barrus. He pointed out that rose bengal staining devitalizes cells in the absence of a functional mucin layer rather than simply identifying dry eye damaged cells, as many have been taught. In fact, both sodium fluorescein and rose bengal devitalize epithelial cells. He recommended using lissamine green instead, since it does not kill epithelial cells. He explained that it can be obtained from compounding pharmacies but it is expensive, costing upward of $90 for a 15 mL bottle. Fortunately, only onehalf drop is required for testing.

When developing a consistent practice, said Dr. Barrus, try to choose tests that themselves offer consistency, including both intra- and inter-operator repeatability.

Lack of both intra- and inter-operability, for example, are why Dr. Barrus avoids the Maddox rod test — two different operators performing the test or even the same operator performing the test twice on the same patient at two different time points often obtain two different results.

Dr. Barrus uses the lid expression test, but he acknowledged it also has poor repeatability because there is no standard for grading it. Fluorescein staining has the same limitation if grading systems are not incorporated in practice. This is one reason why new dry eye practitioners should wait before investing in expensive equipment. It is better to take a few months to learn about available tests and what their strong and weak points are before investing in them.

Valuable tests, according to Dr. Barrus, include meibography, meibum expression, tear interferometry, and Schirmer’s test. Dr. Barrus gives every patient undergoing an initial assessment for dry eyes a Schirmer II

The Science of Dry Eye Hyperosmolarity — Barrus

233

Tear Osmolarity “The most accurate way to test for DED” • salt (by far biggest driver) = ~ 95% • proteins < 2% • sugars < 2%

• lipids < 2% • mucins < 2%

Main concentration of electrolytes in the tear film Concentration in mmol/kg Na+

K+

120-170

6-42

Ca2+

µmol/kg Mg2+

Zn2+

0.3-2.0 0.3-1.1 50-100

Mn2+

mmol/kg CI–

0.2-0.9 106-135

HCO3–

PO43–

26

0.07

Fig. 1 Compounds that contribute to tear osmolarity. (Tomlinson A et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci 2006; 47(10): 4309-4315. Lemp MA et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol 2011; 151(5): 792-798. Stahl U et al. Osmolality and tear film dynamics. Clin Exp Optom 2012; 95(1): 3-11.)

(not Schirmer I) test, with anesthetic, to identify potential autoimmune dysfunction aqueous deficiency. This effectively narrows down the potential pathology and provides a framework for moving forward. He said that he recommends Schirmer’s tests to optometrists across the country because of its high validity in diagnosing aqueous deficient variants of dry eye.

For meibography, Dr. Barrus said he usually refers patients to an ophthalmologist because the equipment is so expensive for most clinics. “Pick your easy options, and upgrade your clinic as you go along,” he recommended.

Focus on simple, clinical tests over spending money.

DEVELOPING CONSISTENT PROCESSES FOR DRY EYE MANAGEMENT Optometrists should develop their own processes or “cookbooks” for managing dry eyes, recommended Dr. Barrus. He emphasized the creation of repeatable habits and processes based on evidence. “When you start doing the same thing over and over and over, you get an intuitive sense of normal vs. abnormal,” he explained.

This involves developing automatic systems while also actively considering differential diagnoses rather than just functioning in “robot mode.” It is important to complete every step, every time, without skipping anything to develop an instinct, he said. It is also important to understand the underlying rationale for each step.

PATHOLOGIES OF DRY EYE Some dry eye pathologies, said Dr. Barrus, will repair themselves when other pathologies are addressed. For instance, a patient with a poor TFBUT, elevated high tear osmolarity (e.g., 310 to 315 mOsm/L), and MGD should first be treated with the easiest to manage aspect of the pathology, which in this case is MGD. Getting the gland to express cleanly and giving patients omega-3’s will frequently also improve tear osmolarity because the pathologies overlap.

Thus, it is possible to synergistically treat patients by understanding their underlying pathologies.

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Dr. Barrus pointed out that there are multiple interlinked components to dry eyes, and both patients and optometrists must understand the components as a whole in order to create a “pattern of understanding” of the pathology. This understanding helps patients recognize, for instance, the importance of yearly follow-up visits. He used the analogy of good dental care to explain that treating dry eyes involves both good maintenance (i.e., teeth brushing) and repairing pathologies as they arise (i.e., filling cavities). While there is no cure for dry eyes, the condition can be managed effectively with this approach.

PATIENT EDUCATION The ongoing inflammatory cycle creates a negative feedback loop that can worsen and result in severe pathology, warned Dr. Barrus. Patients may have extremely short TFBUT but insist they do not have dry eyes because they have no symptoms. In such cases, optometrists must explain to them that the pathology is present in a severe form and must be treated. Patient education is paramount.

He emphasized that patients must be educated about early symptoms of dry eyes, such as blurry vision, the need to blink more often, red eyes at the end of the day, and eye strain so they can return for an appointment when needed.

TEAR OSMOLARITY Dr. Barrus explained that osmolality is defined as the number of osmoles in a solute by mass of solvent, while osmolarity is the number of osmoles in a solute by volume of solvent. They both reflect the same concept, but one is expressed by mass and the other by volume. For practical purposes, he said, the difference is not important.

Tear osmolarity refers essentially to the salt content of tears, he said. An eductational analogy he often uses in clinic is the saltiness of sea water. Increasing salt (i.e., Atlantic/ Mediteranean/Red Sea/Dead Sea) changes the properties of the water, causing it to increase buoyancy as well as burn the eyes. Similarily, as tear salt concentration increases, so do burning symptoms and damage to cellular structures in the eye.

Salts present in tears include sodium chloride (NaCl), potassium chloride, and bicarbonate. Other compounds, including proteins, sugars, lipids, and mucins, are also present but in such low concentrations as to be clinically irrelevant because they do not contribute to osmotic pressure difference (Fig. 1).

When a salt comes into contact with water, it breaks into its component electrolytes (e.g., NaCl breaks up into Na+ and Cl–). This means a single molecule of a salt actually creates the pressure of two within the eye.

It is important to explain this concept to patients, using layman’s terms, said Dr. Barrus.

Osmolarity All Studies 1978-2005

Probability

Normal eyes Mean = 302.2 SD = 9.7

Dry eyes Mean = 326.9 SD = 22.1

260

280

300

320

340

360

380

400

Osmolarity (mOsm/L) Fig. 2 Normal distribution of tear osmolarity across studies conducted from 1978-2006 – normal eyes vs. dry eyes. (Baudouin C, et al. Role of hyperosmolarity in the pathogenesis and management of dry eye disease. Ocul Surf 2013; 11: 246-258.)

MEASURING TEAR OSMOLARITY Historically, said Dr. Barrus, tear osmolarity has been tested using freezing point depression and vapor pressure depression, but this requires massive machinery. In the past five years, newer technologies using electrical conductivity to determine differential and osmotic balance have become available. Osmolarity can be measured using osmometers that use electroconductivity to charge particles in tears and determine their concentration based on the degree of resistance to an electric charge. The TearLabTM Osmolarity System (San Diego, CA) works in this manner. For this device, tears must be placed into the device. Another osmometer is the i-Pen® (I-MED Pharma, Montreal, QC), which tests tears in situ.

The National Dry Eye Disease Guidelines for Canadian Optometrists, published in the Canadian Journal of Optometry is a definitive, easy-to-follow guide to the management of dry eye disease, said Dr. Barrus. It states that tear film osmolarity is the most accurate single test for dry eye disease. As a result, a tear osmolarity machine is an important investment for every dry eye clinic, he added.

TEAR OSMOLARITY LEVELS Christophe Baudouin has conducted several studies on tear osmolarity testing, reported Dr. Barrus. His work has demonstrated that optimum osmolarity varies from study to study, depending on how it was tested (Fig. 2). Conductivity osmometers, for instance, generally produce lower readings than freezing point or vapor pressure osmometers because there is a lower limit to what they can read. Normal osmolarity is estimated to be approximately 300 mOsm/L. For dry eye patients, osmolarity is an average of about 326 mOsm, with a standard deviation of 22.

The osmolarity of blood is approximately 290 to 295 mOsm, so that is the ideal osmolarity of tears. The fact that the average tear osmolarity is closer to 300 mOsm/L reflects the fact that tears are an open system and that everyone experiences at least some evaporative dry eye, said Dr. Barrus. This varies from region to region depending on ambient humidity levels. An individual’s tear osmolarity will also fluctuate during the day depending on their environment. Dry office air, for instance, can increase osmolarity. This means tear osmolarity values will vary depending on the time of day patients are tested and what they were doing beforehand. It is possible to obtain normal tear osmolarity results first thing in the morning for a patient who experiences dry eye symptoms toward the end of the workday. In such cases, it is important to educate the patient and book appointments for the time of day when symptoms are in evidence. Dr. Barrus said he finds it particularly important to see nurses and doctors at the end of their shifts because the nature of their work and the dry hospital air is particularly conducive to severe dry eye symptoms.

It is important to “think outside the box” when treating dry eye patients, said Dr. Barrus. For instance, he said he finds he is only able to manage nurses’ dry eye symptoms using bandage contact lenses or scleral lenses. He tells dry eye patients not to sleep with a fan at night, as this can contribute to dry eye symptoms. Using a cool (not hot) mist humidifier instead can be helpful.

TEARLAB VS. i-PEN Dr. Barrus uses both the TearLab and the i-Pen devices in his practice. The TearLab has been available since about 2002 and thus has a long history of published evidence supporting its use, but the in situ testing is an advantage of the i-Pen because it tests hydrated porous tissue, not just an aliquot of tears. Both instruments have been approved by Health Canada.

For both devices, proper technique is essential to obtaining proper results. To use the i-Pen, explained Dr. Barrus, the operator must tip the eyelid down and test against the tarsal conjunctiva on the inferior lid. Conversely, the TearLab draws straight out of the tear prism on the temporal aspect. It is important to train staff to use the devices properly and provide ample opportunity for practice. Expect that the first batch of tears collected by a novice operator will not provide valid results, he said.

Accidentally rubbing against the edge of the eyelid margin with the TearLab will liberate dried salt resting there, producing falsely high results. Similarily, placing the i-Pen without the metal contacts having equal pressure on the palpebral conjunctiva will produce an error message.

Since the two devices use different testing mechanisms, one cannot assume they will provide identical results.

Dr. Barrus described his ongoing aftermarket clinical

The Science of Dry Eye Hyperosmolarity — Barrus

235

Fig. 3 The appearance of a dry eye right after fluorescein instillation.

(Abelson M.B. The pros and cons of dry-eye tests; August 2011; http://www.reviewofophthalmology.com/article/the-pros-and-cons-of-dry-eye-tests-29630)

correlation study of the TearLab vs. the i-Pen. So far, he has recruited about 80 patients. They are being tested using the TearLab first, followed by the i-Pen, because touching the inside of the eyelid with the i-Pen would disrupt the tear index, skewing the readings from a subsequent TearLab test. So far, results of the trial indicate that the two devices produce very similar results, with the i-Pen giving values marginally lower than those of TearLab.

IMPACT OF TEAR OSMOLARITY Tear osmolarity said Dr. Barrus, provides an indicator of where water is being stored within the eye. Only water and oxygen move freely through the tissues and membranes of the eye. Water is always drawn through membranes from areas of lower to higher salt concentration, he explained.

Thus, an osmotic shift results in water loss within the cell, altering cell structures and reducing the ability of the cell to function properly.

Unlike water, salts require an active pump for movement through cell membranes. Cells pump molecules through membranes to protect their cellular metabolites, enzymes, proteins, and DNA. Cell vacuoles draw nutrients from the bloodstream into the cells. Ideally, the osmolarity of interstitial fluid within the cells of the eye match that of the blood, at about 290 mOsm/L. When pathologies such as diabetes or kidney disease affect tear osmolarity, the cells of the eye are no longer able to draw the nutrients they need from the blood.

The lacrimal gland stimulates tear production by secreting salt and other molecules into the central lumen.

This in turn draws out fluid, producing a tear with an osmolarity of about 290 mOsm/L. Accessory glands in the conjunctiva stimulate that same tear production. Tears are

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Clinical & Refractive Optometry Quebec 1:6, 2016

continuously produced to replace fluid lost to evaporation, creating an ongoing cascade. Mucin layer helps control local evaporation rate across the cornea by stabilizing aqueous adhesion to the ocular surface. Lipid layer further reduces general evaporation and improves consistency of the aqueous layer.

A malfunction in any of these processes can disrupt tear osmolarity, explained Dr. Barrus. For instance, a poor mucin layer, small corneal defect, missing epithelial cell, or advanced MGD will all disrupt TFBUT. With evaporative dry eye, tears at the cornea can reach osmolarity levels of almost 600 mOsm/L during an inter-blink phase. This sectoral drying results in portions of the eye that are profoundly more irritated and damaged than other areas. Once the eye begins to lose epithelial cells from that irritation, it produces a vicious cycle of continued TFBUT disruption and further increased osmolarity and irritation. As a result, said Dr. Barrus, small areas of punctate staining in the nasal canthus on the conjunctiva can be a sign of the beginning of a degenerative process that will cascade across the cornea without intervention.

Dr. Barrus said that research on tear osmolarity reveals that an imbalance in intracellular and extracellular osmolarity caused by tear osmolarity â&#x2030;Ľ 320 mOsm/L produces an inflammatory cascade, causing massive damage that impairs the ability of the epithelial cells to migrate across the cornea and re-epithelialize. It upregulates immune modulators (MMP-9s) and cytokines, damaging the structural framework of cells so that microtubules that provide cell structure stop functioning properly and may even disrupt DNA function. Without intervention, this process eventually leads to cell apoptosis, identified by diffuse punctate staining.

Cells have the intrinsic ability to regulate their osmolarity, so why does this damage occur? asked Dr. Barrus. Studies show that massive epithelial loss occurs only with osmolarity < 270 msOm/L. Placing high osmolarity saline solution on the eye does not produce cell apoptosis. Thus, there remains much to be learned about the pathology of dry eyes, concluded Dr. Barrus.

The condition requires further study.

EVALUATING DRY EYES Typically, patients in the early stages of dry eye have more pain than those in the later stages, and younger patients have more severe symptoms than older patients, said Dr. Barrus. When studying tears, it is important to take the necessary time to prepare the eye properly and look closely, he advised. The best staining analysis can be performed only after fluorescein dye has been in the eye for three to five minutes (Fig. 3). Avoid using too much fluorescein. Proper staining allows for the visualization of epithelial edema.

Most dry eye clinics have patients who complain of dry eye symptoms, but testing does not reveal any abnormalities. It is important to take a second look at those patients because their symptoms indicate there is pathology present, recommended Dr. Barrus. Do not dismiss their symptoms or recommend use of drops with preservatives for relief, he warned. Ongoing exposure of the eye to preservatives causes almost as much stress to the cells as poor osmolarity.

It is important not only to diagnose dry eyes but also to eliminate other pathologies, said Dr. Barrus. Symptomatic patients should have their tear osmolarity measured. He also tests how patients respond to Restasis® (cyclosporine ophthalmic emulsion 0.05%, Allergan Inc.) plus twice daily Lotemax® (loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb, Vaughan, ON) for one month, followed by Restasis® alone. After completing a 9 or 12 month Restasis protocol, patients may return complaining of eye pain as soon as they discontinue treatment, which provides insight into their underlying pathology.

NEURORECEPTORS Neuroreceptors are often overlooked in dry eye, said Dr. Barrus, but the cornea contains a high concentration of sensory nerve fibers. Mechano-nociceptors are preferentially activated by mechanical forces. Polymodal nociceptors respond to heat, exogenous irritant chemicals, and endogenous inflammatory mediators, and thermoreceptors are primarily activated by small reductions of the ocular surface temperature. All of these nerve fibers are disrupted by increased tear osmolarity, creating ongoing neuropathies that can persist even after the tear osmolarity is regulated. Damaged nerve fibers require time to heal. It takes about one year for nerve regeneration following ablation of corneal nerve fibers from laser treatment, for instance.

DRY EYE-LIKE PAIN Dry eye-like pain (DELP) is a new concept developed on by ophthalmologists in the United States, said Dr. Barrus.

For patients with DELP, osmoprotectants help manage osmolarity, creating an iso-osmolarity environment, with 290 mOsm/L as the benchmark. Dr. Barrus warned against using eye drops which have an osmolarity < 290

mOsm/L because these will force water into cells and stimulate cell apoptosis.

Currently available osmoprotectants include sodium hyaluronate, which has been shown in studies to reduce immune responses. HYLO™DUAL (0.5 mg/ml sodium hyaluronate, 20 mg/ml ectoine, CandorVision, Montreal, QC) contains both hyaluronic and another osmoprotectants, ectoine. Other options are i-drop® Pur Gel (0.3% sodium hyaluronate and glycerin, I-MED Pharma, Montreal, QC) and Thealoz® (trehalose 3%, Labtician Ophthalmics, Inc., Oakville, ON).

Can-C™ (glycerine 1%, carboxymethylcellulose sodium 0.3%, N-acetylcarnosine 1%, Profound Products) will soon be available on the market, said Dr. Barrus.

N-acetylcarnosine is an antioxidant that has been studied in mice. The mice were placed in an environment with 12% ambient humidity and a temperature of 22ºC, which produced an upregulation of immune modulators in the eyes, including tumor necrosis factor (TNF)-a. Drops containing N-acetylcarnosine prevented this immune cascade. There have also been claims the product can cure cataracts, but Dr. Barrus recommended against using it for this indication until its efficacy has been proven. When sales representatives visit with products, he said, it is important to pay attention to the science behind the product and to vet the research presented. Ask to see the studies that they cite as their evidence so that you can review the literature yourself, he recommended Dr. Barrus added that dry eyes can also be treated with several alternative methods. These include heat packs and omega-3s, which reduce inflammation and promote nerve healing. Lubricants and autologous serums are also helpful. Dr. Barrus said he finds autologous serums to be very effective even for severe cases, but it is important to have them compounded by a pharmacist who knows how to do it correctly. It should be a 20% to 30% autologous serum that is pH matched with an osmolarity of 290 mOsm/L. Serum drops can promote increased healing of the underlying dry eye pathology.

CONCLUSION Dr. Barrus concluded by re-stating the importance of considering and investigating the underlying pathology of dry eyes and aiming to treat it, rather than just masking the disease with moisture drops. ❏

The Science of Dry Eye Hyperosmolarity — Barrus

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QUESTIONNAIRE The Science of Dry Eye Hyperosmolarity Benjamin J. Barrus, BSc, BOptom (Hons), OD 1. ❑ ❑ ❑ ❑

Dry eye symptoms are BEST evaluated: When patients first complain of symptoms that suggest dry eye disease During a follow-up appointment dedicated to evaluating dry eye disease As one component of an overall eye exam First thing in the morning

2.

Based on the clinical experience of Dr. Barrus, approximately how many tests are typically required to accurately diagnose dry eye disease?

1-3 3-5 5-7 7-9

❑ ❑ ❑ ❑ 3. ❑ ❑ ❑ ❑

Which of the following tests are recommended for evaluating dry eye disease without risk of devitalizing epithelial cells?

Rose bengal Maddox rod test Lissamine green Sodium fluorescein

Clinical & Refractive Optometry Quebec 1:6, 2016

FORMULAIRE DE DEMANDE DE CRÉDIT UFC DE CATÉGORIE A

1:5, 16

4. ❑ ❑ ❑ ❑

Which of the following is a limitation of the lid expression test?

Poor repeatability Poor validity Lack of relevance for dry eye disease Widespread poor technique

5.

A patient who presents with poor tear film breakup time, elevated high tear osmolarity, and meibomian gland dysfunction should FIRST be treated: With an approach that addresses all these concerns at once For tear film breakup time For elevated tear osmolarity For meibomian gland dysfunction

❑ ❑ ❑ ❑ 6. ❑ ❑ ❑ ❑

According to The National Dry Eye Disease Guidelines for Canadian Optometrists, which of the following is the most accurate single test for dry eye disease?

Tear film osmolarity Tear film breakup time Lissamine green Schirmer’s test

7. ❑ ❑ ❑ ❑

Based on research by Dr. Baudouin, normal tear osmolarity is estimated to be approximately: 280 milliosmoles per liter 290 milliosmoles per liter 300 milliosmoles per liter 310 milliosmoles per liter

8. ❑ ❑ ❑ ❑

Ideally, osmolarity of the interstitial fluid within the cells of the eye matches that of the blood, at: 280 milliosmoles per liter 290 milliosmoles per liter 300 milliosmoles per liter 310 milliosmoles per liter

9. ❑ ❑ ❑ ❑

Patients with dry eye disease typically have more severe symptoms: If they are older If they are male When they first wake in the morning When they are in the earlier stages of the disease

10. ❑ ❑ ❑ ❑

All of the following are recommended alternative methods of treating dry eye disease EXCEPT: hHeat packs Artificial tears with preservatives Omega 3-s Lubricants

The Science of Dry Eye Hyperosmolarity — Barrus

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Clinical & Refractive Optometry Quebec is pleased to present this continuing education (CE) article by Dr. Paul M. Karpecki, Kentucky Eye Institute, Lexington, KY. This article has been approved for 1 Category A, UFC credit in Ocular Health by the Ordre des Optométristes du Québec. In order to obtain your credit, please refer to page 246 for complete instructions.

Diagnosis and Treatment of Ocular Surface Conditions: Focus on Dry Eye Paul Karpecki, OD, FAAO

INTRODUCTION Dr. Karpecki began his presentation on dry eye disease (DED) by noting that, according to the most recent study on prevalence, 29% of the Canadian population has dry eye. Allergies represent approximately 20% and glaucoma is roughly 2.2%, so this is an enormous opportunity; dry eye is the future of optometry.

The reason for this high rate of DED is digital devices, namely, smart phones, tablets and computers.

The average blink rate is about 15 to 20 times a minute.

Studies have been done analyzing people on digital devices, and the average blink rate or the number of blinks per minute was 4.4 times. In one study, it was as low as 1.8 blinks per minute with a plus or minus 4 standard deviation. One just can't sustain good oil production, good tears with that kind of blink rate and there are people who spend 8 to 10 hours a day at work on a computer.

Eventually, said Dr. Karpecki, they show up in his clinic with few meibomian glands left and they wonder if anything could be done; his answer is that it could have been prevented, but all of this research and insight is only recently known.

In fact, an International Task Force (ITF) comprising a group of 25 of the top experts in the world, including Dr. Karpecki, got together at Johns Hopkins in 2003.

There was an effort to change the name from dry eye to dysfunctional tear syndrome. The stance at the time was to look at the lid margin as the most important area. The task force said that the majority of dry eye was non-lid margin involved. In the end, the top 25 experts were technically 180 degrees wrong. Today, it’s known that 86% of all dry eye does involve the meibomian glands.

That paper was published in 2006 in Cornea.

P.M. Karpecki — Director of Corneal Services and the Advanced OSD Clinic, Kentucky Eye Institute, Lexington, KY Correspondence to: Dr. Paul M. Karpecki, Kentucky Eye Institute, 601 Perimeter Drive, Suite 100, Lexington, KY 40517; E-mail: paul@karpecki.com This article has been peer-reviewed

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PREVALENCE OF DRY EYE Roughly 4 to 5 forms of dry eye involve the lipid layer.

There are a lot of risk factors, including contact lens wear, age and gender, but the major factor is digital devices such as computer use. The Beaver Dam study showed that 14% of the population in the U.S. over age 40, have dry eye.

Last year, they decided to do a study called the BOSS (Beaver Dam Offspring Study), as an offshoot. They analyzed the children of those 11,000 people they had been studying for the last 20 years with regard to dry eye.

The incidence of dry eye between the age of 21 and 40 was as high as that of their parents — likely as a result of these technology devices. Even more interesting was that men and women had equal levels of DED, likely again, due to the use of digital devices. It's only after age 40 that women have more dry eye because of hormonal changes.

In terms of contact lens wear, the dropout rate 20 years ago was approximately 16.5%. People said, “We didn't have silicone hydrogels, daily disposables and hydrogen peroxide solutions that neutralized to preservative-free in 4 hours,” etc. Last year, according to JMI (Jobson Medical Information) data, the dropout rate was 16.4% — it hadn’t changed. Actually, it may have been 30% or higher because of smartphones, tablets and computers, had these new contact lens technologies not been available; but it also says we must treat the dry eye.

Naturally, Dr. Karpecki noted, environmental factors play a role, but the biggest factors in this whole group are digital device use, smoking and diet. He stated that the ratio of omega-6 fatty acids to omega-3 was far too disproportionate — and systemic medications — for example, a study authored by Ousler showed that antihistamines had a 34% drying effect.

There are other medications that also cause excessive drying, including diuretics, beta blockers and antidepressants which cannot be discontinued like oral antihistamines, but patients should be educated about them and how they contribute to the condition. The incidence of dry eye in patients with diabetes in North America has been reported to be above 50% in five different studies, which showed that all levels of diabetes were involved, ranging from borderline diabetes mellitus studied by Dr. Hom to those with severe retinopathy. The incidence was between 50% and 54% in all five studies, which were completely independent, with none of the same authors or researchers.

Rheumatoid arthritis is, of course, a contributing factor; and rosacea can affect the sebaceous glands, which are holocrine oil secreting glands. The meibomian glands are also holocrine oil secreting glands, so there's no way to not affect both in patients with rosacea. The three other major conditions Dr. Karpecki monitors are diabetes, arthritis and thyroid disease. In his experience, when he has a patient for whom he has tried every treatment and nothing seems to work, there's usually a systemic cause.

Eighty-six percent of all Sjögren’s syndrome patients are women, so it’s clear that androgen hormones play a role in this disease. One out of 12 patients with Sjögren's syndrome will develop B-cell non-Hodgkin's lymphoma, which has a much better prognosis if caught early, and optometrists have a role in helping make that diagnosis. In fact, Dr. Karpecki tells every one of his Sjögren's patients, “Every year you need to have your blood work checked for lymphoma.”

CLINICAL SIGNS AND SYMPTOMS OF DRY EYE Carlos Belmonte, a true expert in the understanding of corneal pain, has noted that pain and a lot of other symptoms associated with dry eye actually down regulate when the disease progresses, meaning that the symptoms can lessen as signs worsen, which is very confusing for patients and doctors. This is often termed neurotrophic dry eye, especially if related to previous viral conditions such as herpes simplex virus or herpes zoster ophthalmicus. In neuropathic dry eye, the patients develop what is termed “pain without stain,” where the pain is disproportionate to the signs. As the result of long-standing disease, the corneal nerves can form branches or dendritic nerves that are sensitive to elements they shouldn't be sensitive to, such as air flow and temperature. In these patients, it seems like they don’t respond to therapy, but in time improvement can occur. They may require oral pain medications and scleral lenses.

If symptoms lessen when the disease worsens, how does one diagnose it? The only symptom that's present across all stages of dry eye is blurred vision. However, the problem with this is that blurred vision is also the number one reason people consult optometrists, so it has to be differentiated. In the early stages, it’s transient. When there's superficial punctate keratitis, it's a little more permanent and when there's desiccation, much further along, it's consistently blurred.

The other thing to keep in mind is that corneal staining is not a very good early indicator of dry eye. By the time corneal staining is present, there is desiccation and by that stage patients are at least stage 3 out of 4 in accordance with the ITF classification for DED. Stage 4 is severe and includes conditions such as graph versus host disease, filamentary keratitis, persistent epithelial defects and corneal melts. So, in fact, it’s a scale of 1 to 3 that’s

typically managed in the primary care setting and by the time there’s macropunctate or central corneal staining, it’s level 3, the furthest advanced the patient is ever going to be for most clinics. It's analogous to a visual field defect in glaucoma patients; it only shows up when they’ve lost 30% to 50% of their nerve fiber layer or have advanced glaucoma.

Dr. Karpecki advised practitioners to examine patients’ skin for rosacea, the eyelids for blepharitis, cranial nerve function, and their hands. Rosacea will provide a good indication for which direction to proceed in. Arthritic hands may show an ulnar shift. Check if they're not blinking on one side from a stroke or a cranial nerve function or Bell’s palsy, and definitely look at their eyelids closely.

DIAGNOSIS One of the most important tests is expression of the lower eyelid; approximately 80% of the oils in the tear film come from the lower eyelid, in the nasal to central area.

Dr. Karpecki advised use of a Mastrota paddle, wet Q-tip or one’s fingers to squeeze the glands and see what comes out. It should resemble olive oil. If it’s discolored or turbid, that's level 1 of meibomian gland dysfunction (MGD). If it's thickened or gel-like, it’s level 2. If it's like toothpaste, which is thinner and discolored, that's level 3; and if the gland won’t express, that's level 4.

Dr. Karpecki stated that there are numerous diagnostic tests, the most common at least in the U.S., being the Schirmer's test (including phenol thread tests), which he finds surprising. Schirmer's might be accurate on Sjögren's patients who have no tear flow; a non-anesthetized Schirmer's works in that group, but that's a rare, small population of 0.4% prevalence. He related that he wasn’t able to get lissamine green in Kentucky for the longest time which is a more sensitive test than fluorescein.

Fluorescein dye is a great latent disease indicator; a practitioner can examine tear breakup time, but it has low sensitivity unless you consider a non-invasive tear breakup time, which involves more expensive topographical and wavefront technology. Tear meniscus height is important; it actually predicts dry eye approximately 70% of the time by looking at the height of the meniscus.

However, if too much of a drop of fluorescein is used, it can also be inaccurate.

If practitioners used symptoms alone to make a diagnosis of DED, they’re likely to be wrong as much as 40% of the time. It's similar to glaucoma. With tonometry alone, the result would be wrong 80% of the time. However, adding in tonometry and hysteresis (or pachymetry), along with OCT, careful examination of the optic nerve, visual fields testing; and a repeat on the IOP, the result would be 96% specificity with all of those elements combined.

Dr. Karpecki stated that he still relies on symptoms to

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Osmolarity in Diagnosis and Grading of Dry Eye

Fig. 1 The osmolarity severity scale allows the clinician to plot severity and monitor therapeutic progress.

diagnose DED, however not alone, and favors the following validated questionnaires: Standard Patient Evaluation of Eye Dryness (SPEED), or Dry Eye Questionnaire (DEQ), or 5-item Dry Eye Questionnaire (DEQ-5).

THE IMPORTANCE OF OSMOLARITY Dr. Karpecki uses NaFl dye to observe the tear breakup time (TBUT), the tear meniscus height, and if there's any central or inferior staining. He considers osmolarity testing the most valuable, definitive tool, by far in diagnosing dry eye because of its greater sensitivity to mild or moderate dry eye disease.

Blood osmolarity is between 280 and 295 and tears are made from serum in the blood; that's how the lacrimal glands work, especially the accessory lacrimal glands, so the tear osmolarity should be in the same range (Fig. 1).

Dr. Karpecki discussed the phenomenon of patients who have significant symptoms but very few signs or patients whose signs have been treated and resolved but not their symptoms. Most doctors would treat a patient with symptoms of dryness, grittiness, burning, and redness, worse on the computer and late in the day, with dry eye medications. However, he reviewed the data on a colleague’s group of patients with this profile; they had normal osmolarity, but were complaining of a dry, gritty, burning sensation, with redness and stinging, late in the day and on the computer. He found that over 90% of these patients actually did not have dry eye disease.

He measured the eye alignment of a group of ten patients, and conducted cover tests, looked for Von Graefe fixation, fixation disparity, convergence insufficiency, vertical imbalance between the two eyes, put prism in some, and sent one to a local VT specialist he knew. Nine out of ten had eye misalignment and all nine were solved with prism or VT. People who have fixation disparity,

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exophoria at distance, convergence insufficiency, proprioceptive disparities etc. will, because of rapid eye movements, have an overstimulation of the trigeminal nerve. The result of overstimulation of the ophthalmic branch of the trigeminal nerve is a dry eye sensation of the cornea, often described as gritty, burning and irritated and it would definitely be worse when on a computer or digital device. That's why they had dry eye symptoms, but didn't have dry eye, and without osmolarity testing, these patients are often treated for months or years with no resolutions of symptoms.

Dr. Karpecki noted that he realizes that if he has a patient who has normal osmolarity, meaning both eyes under 295 and 5 units (mOsm/L) of each other, the problem has to be something other than dry eye in about 90% of the cases. The appropriate tests, when combined with osmolarity, provide further specificity and sensitivity.

These tests include expression of meibomian glands, vital dye staining, TBUT, meniscus height and validated questionnaires. That is not to say osmolarity alone isn’t accurate enough because it is actually more accurate than cholesterol or diabetes testing for blood glucose.

Osmolarity has a variation of 1.5%, meaning the variation of osmolarity is only 4 milliosmoles per litre. That's the most accurate test in medicine. However, even then, it's going to be wrong approximately 13% of the time, according to the research. When you combine it with expressing the meibomian glands, checking their blink and meibography, plus the testing listed above, it will provide roughly 98% sensitivity. Now, the right diagnosis can easily be reached. It's like glaucoma, where one combines multiple tests to know what to do, rather than relying on any one test alone.

SCREENING TOOLS AND DIFFERENTIAL DIAGNOSIS With regard to screening questions, Dr. Karpecki cited the Canadian Optometric Dry Eye Disease Guideline questions: 1. Do your eyes feel uncomfortable?

2. Do you have watery eyes?

3. Does your vision fluctuate, especially in a dry environment?

4. Do you use eye drops?

These are an excellent starting points, in addition to “Do you have dry mouth?” to know if it might be Sjögren’s syndrome. Osmolarity is a very valuable screening test.

This has to be priced into the exam, but if a practitioner has a very high level dry eye practice, they should definitely be concentrating on this and patients should be paying for it; they're going to be grateful. Twenty-nine percent of the Canadian population has dry eye disease.

You could establish one of the best clinics in North America by focusing on dry eye disease.

What differentiates an optometrist in this field is knowing when dry eye symptoms are present but it’s not dry eye; and when it is dry eye to make the differential

ITF Dry Eye Guideline Recommendations LEVEL 1

If no improvement, add level 2 treatments

Patient education Environmental modifications Control systemic medications Preserved tears Allergy control

LEVEL 2

If no improvement, add level 3 treatments

Unpreserved tears Gels/nighttime ointments Nutritional support

LEVEL 3

If no improvement, add level 4 treatments

Tetracyclines Punctal plugs (control inflammation first)

LEVEL 4

Cyclosporine A Topical corticosteroids Secretagogues

Systemic anti-inflammatory therapy Acetylcysteine Moisture goggles Surgery (punctal cautery) Behrens A et al. Cornea. 2006; 25(8):900-907.

Fig. 2 Stepwise treatment build for dry eye.

diagnosis between evaporative and aqueous. Dr. Karpecki stated that one of the biggest changes that affected his clinic, besides knowing that asthenopia could cause dry eye symptoms, is the understanding of MGD. With evaporative dry eye, it isn’t enough to just treat the meibomian gland obstruction, or to just use artificial tears such as hyaluronic acid, or manage the biofilm or just the inflammation associated with all forms of dry eye disease; it’s important to treat all four components at the same time: obstruction, inflammation, biofilm development, and tear instability.

TREATMENT OPTIONS Dr. Karpecki uses BlephEx® (Lake Worth, FL) on patients with biofilm issues, to get rid of the keratin on the surface that is blocking the glands; for tear film instability, he prefers treatment with hyaluronic acid. Gauging the various levels of dry eye disease determines the treatment.

For example, in mild cases, he typically does not include a steroid but simply cyclosporine or lifitegrast treatment alone, unless installation results in burning or other side effects. At the moderate stage, which is the most common presentation, he includes a steroid short term; and cyclosporine or lifitegrast and omega fatty acids long term.

In severe cases, he would prescribe steroids and oral treatment for the inflammation such as doxycycline (Fig. 2).

His steroid of preference is loteprednol gel 0.5% because of its relative safety profile, the fact that it has 70% less BAK and it contains known tear film moisturizers.

With mild MGD/mild evaporative dry eye, a hydrating warm compress every night for 10 minutes would usually be fully effective. Hydration penetrates tissue so a hydrating mask is probably the only option that could get the back surface of the eyelid temperature above 40 degrees, stated

Dr. Karpecki. The TheraPearl® Eye Mask (Bausch + Lomb, Vaughan, ON) would be another good option for the price. It doesn't hydrate so it's not quite as effective, but it's better than not using a compress at all.

For mild cases of tear film instability in mild MGD, Dr. Karpecki recommends Liposic® (Bausch + Lomb, Vaughan, ON), Refresh Optive® Advanced (Allergan, Unionville, ON), Systane® Balance (Alcon, Mississauga, ON), or Refresh Ultra® (Allergan, Unionville, ON). In moderate to advanced MGD he prefers HYLO™ (CandorVision, Montreal, QC).

Currently, Restasis® (cyclosporine, Allergan, Unionville, ON) is the only approved drug in its category and Dr. Karpecki feels that it's excellent long term. However, the key to Restasis is using it long enough. Twelve-month use will produce a 191% increase in goblet cells. In comparison, the use of Refresh Ultra alone showed only a 13% improvement in goblet cell density. It takes roughly 3 to 4 months for cyclosporine to work on symptoms, which is why a steroid should be prescribed first. In terms of long-term use of cyclosporine, such as the 1- or 2-year point, a patient may feel great and want to discontinue the medication. Four months later, though, the T-cells start returning, there is ICAM-1 up-regulation and inflammation, and symptoms increase again. Additionally, there is stinging in 17% of cases and combining it with a steroid has been shown to decrease the irritation of Restasis by 75% in this population.

Non-MGD patients have inflammation and need extensive lubrication. Dr. Karpecki cited a study showing that the arm on artificial tears still increased in terms of inflammation count by 40% at 12 months. Therefore, the days of treating any true dry eye without an antiinflammatory medication should be over.

He described a case of severe evaporative dry eye; meibography revealed only five glands remaining, nothing was expressing, and there was scalloping of the lid margin. In moderate to advanced cases he would treat the obstruction with LipiFlow® (TearScience, Morrisville, NC) and a hydrating mask long term. For inflammation, he would definitely start patients on steroids and oral tetracycline derivatives or a 5-day Zithromax® Z-Pak (azithromycin, Pfizer, Montreal, QC) for systemic issues, side effects or contraindications to taking tetracycline medication. His approach for each of these scenarios is very aggressive.

Oral doxycycline is a very good treatment for the more severe forms. In Canada, one can prescribe a hyclate form of 100 milligrams and consider its use once a day or use a pill splitter to allow for b.i.d. dosing. There are a lot less side effects taking one half in the morning and one half in the evening. The medication is dosed twice a day until the expression of the glands starts to improve, which is typically 2 or 3 months; although some patients require

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Fig. 3 Corticosteroids quickly and thoroughly suppress ocular surface inflammation.

Fig. 4 Efficacy of loteprednol etabonate ophthalmic suspension 0.5% versus placebo for the treatment of keratoconjunctivitis sicca.

longer treatment. Once there is improvement, never go from twice a day to zero as this can produce a rebound of inflammation. Oral doxycycline is actually very comparable as an anti-inflammatory to prednisone, which is odd, because it's classified as an antibiotic; taper down to once a day when the condition improves.

Long term, Dr. Karpecki still prefers omega fatty acids. It’s important to keep in mind that the average human being with mild dry eye needs about 1,000 to 1,500 milligrams of EPA/DHA, but some patients require more. There are three factors that dictate how much fish oil someone should take for dry eye. First, how severe the dry eye is; second, how large the person is. A body index above 30 requires more medication than someone who's small, that's just kinetics. However, there are also studies showing that people who are obese, or a BMI in excess of 30, cannot metabolize as much fish oil. The third factor is the current state of nutrition. For example, a patient who eats fish two times a week is not likely to require as much fish oil as someone who never eats fish; or an obese individual who has terrible eating habits and severe dry eye needs 3 to 4 grams of fish oil per day to achieve an effect. On contrast, for a petite female who watches her weight, who eats leafy vegetables, fruits and fish, and has mild dry eye, 1 gram is sufficient. The average fish oil is somewhere between 1.5 and 2 grams per day.

If gamma-linolenic acid (GLA) is added, the amount can be lowered; it's just difficult to get GLA in a combination in Canada. In the States, HydroEye® (ScienceBased Health, Houston, TX) is available and Dr. Karpecki has found it to be extremely effective. It contains high levels of GLA combined with fish oil. Flax works well in women; they can absorb more flax than men although the

percentage in general is low compared to EPA/DHA. However, men do not absorb more than about 5% of flax.

Furthermore, if they themselves or if they have a family history of prostate issues, flax should be avoided.

Basically, the combination of flaxseed oil and fish oil may be a good recommendation for female patients with dry eye.

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STEROID TREATMENT FOR INFLAMMATION Inflammation is the key to dry eye. It perpetuates the disease, it breaks down the epithelial surface and, more importantly, it exposes immature epithelial cells to a very hyperosmolar environment, producing even further inflammation and further breakdown. In patients who are symptomatic, steroids help significantly (Fig. 3). In fact, Dr. Karpecki noted, the best treatment for dry eye inflammation today is steroids. However, dry eye is a chronic condition and steroids are not a good choice for a chronic treatment. As a result, practitioners should use them for only a short term (e.g., 6 to 8 weeks) and in cases of a flare-up where they can be pulse-dosed. Ester steroids are a much safer form of corticosteroid. In fact, there has never been a cataract reported in 10 years of use and over 40 million scripts. What’s more, a significant IOP elevations risk (>10 mmHg) occurs in less than 2% of patients, and the risk of infection seems to be lower as well.

For dry eye or even the MGD type of dry eye where there's enough inflammation, at least a moderate level, Dr. Karpecki uses Lotemax® Gel (loteprednol etabonate 0.5%, Bausch + Lomb, Vaughn, ON) q.i.d. for 2 weeks, then lowers it to twice a day for 6 weeks. He then adds cyclosporine twice a day at the point when he lowers the loteprednol to b.i.d. For severe cases, he prescribes 0.5% more frequent for flare-ups but still prefers to do this on a

pulse-dosed basis meaning for 1 to 2 weeks at a time during a flare-up. The Lotemax drops are on-label, while Lotemax Gel was studied for anterior chamber inflammation suppression post cataract surgery. The gel formulation provides far more advantages because it has significantly less BAK, a neutral pH, the addition of moisturizers, and it does not require shaking like other steroids (Fig. 4).

Dr. Karpecki recommended a follow-up in 3 to 4 weeks to check pressures in any case involving the use of a corticosteroid. Lotemax can be continued for 4 weeks at twice a day if their pressures are normal. Cyclosporine has to be maintained a lot longer. Instruct patients to use Lotemax q.i.d. for 2 weeks, followed by Restasis when Lotemax goes to twice a day; see them again in a month.

At that point, if their pressures are high, discontinue the steroid; it's typically already helped the patient get control of the inflammation associated with dry eye disease and you can now just keep them on cyclosporine. If their pressures are normal, have them stay on it twice a day for another 2 to 4 weeks, depending on what they need. See them back in 3 months, and if necessary 6 months or a year, again depending on how well they're doing at each visit. The key to gaining patient confidence, stated Dr. Karpecki, is topical steroid treatment directly on the ocular surface (as opposed to oral medications, which he also recommends) for the first 1 to 2 months. Studies have demonstrated that one cannot treat dry eye on artificial tears alone. In fact, in one study of people on artificial tears alone, after 6 months they had a 40% increase in T-cells (CD4) and thus one could generally state a 40% increase in inflammation. In episodic dry eye, it would be fine to simply use artificial tears but once the disease process is in place (e.g., elevated osmolarity) then therapeutics that target inflammation are a necessity. Punctal occlusion can be performed at 3 months if the patient hasn’t completely improved. At this point, all the inflammation is controlled and you are simply elevating better quality tears.

A short-term steroid, followed by omega fatty acids and cyclosporine (Restasis) is an effective treatment for inflammation. For biofilm development, Dr. Karpecki suggests lid scrubs such as TheraLid® (TheraTears, Ann Arbor, MI).

Most people respond to steroids in the first 3 to 5 weeks, so it makes sense to check them between 3 and 4 weeks. That being said, if they have glaucoma or a family history of glaucoma, they will often get an IOP

response earlier. If a patient’s pressure was 32 at 3 or 4 weeks, Dr. Karpecki doesn’t think there is any significant risk in such a short-term treatment, but he would discontinue the steroids and note in the chart that the patient is a steroid-responder. In patients with normal pressure at 1 month, he recommends a 2- or 3-month follow-up, with a check every 6 months if they're a severe disease patient on long-term steroids. He tries to get patients off steroids in the first 2 months, if possible, but some are not able to control the disease without them.

Ideally, he would rather get them off of it and leave them on cyclosporine and omega fatty acids long term, but if he cannot, he’ll consider loteprednol 0.2% longer term and monitor the patients regularly.

Even surface regularity improves on steroids, more than any other medication. For patients who say that when they wake up their symptoms are worse, and they have a lot of MGD, the best treatment he has found is Lotemax Ointment overnight. This allows them to start the day at a much higher comfort level. It should not be used if patients have a lot of dense or focal superficial punctate keratitis, an epithelial defect, corneal infiltrates or, of course, an abrasion. He tends to reserve ointments for overnight use and in patients who wake up with significant dry eye symptoms, not the more common dry eye patients with symptoms later in the day. While the safety profile for Lotemax Ointment is excellent, these patients still need to be monitored. Dr. Karpecki favors the fact that it is 100% preservative-free.

When asked about Lotemax Gel versus suspension he noted that the gel formulation has five new improvements.

It has better mucoadhesive consistency. It does not have to be shaken. In addition, it has 70% less BAK than its previous suspension version and less BAK than any other steroid on the market. It contains two moisturizers, glycerin and propylene glycol, two of the most commonly used products as artificial tears. Moreover, it’s closer to the body’s natural physiological pH, which is beneficial for osmolarity and the ocular surface.

CONCLUSION Dr. Karpecki emphasized that the management of dry eye has evolved over the course of time, and all of the available treatment options have a place. They all seem to work now.

This new understanding will have a major impact on how practitioners continue to manage their dry eye patients. ❏

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DIRECTIVES POUR UN CRÉDIT UFC DE CATÉGORIE A

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Ce cours a été approuvé pour 1 crédit UFC de catégorie A en santé oculaire par l’Ordre des optométristes du Québec. Veuillez répondre à ce questionnaire et le soumettre pour notation avant le 31 mars 2018.

Afin d’obtenir un crédit UFC de catégorie A, veuillez suivre les étapes suivantes : • Remplissez la section d’identification et répondez aux dix questions à choix multiple dans ce formulaire de demande de crédit UFC. • Faites un chèque de 25,00 $ à l’ordre de Mediconcept.

• Postez votre formulaire de demande de crédit UFC ainsi que votre chèque à : CROQ, 3484, boul. des Sources, bureau 518, Dollard-des-Ormeaux, Québec H9B 1Z9.

Si vous obtenez une note de 50 % ou plus, un certificat de crédit UFC approuvé par l’Ordre des optométristes du Québec vous sera envoyé pour vos dossiers.

CLIQUEZ ICI POUR IMPRIMER CE TEST DE CRÉDIT UFC ET L’ARTICLE

Prénom :____________________________ Nom :______________________________________ Adresse :_______________________________________________________________________ Numéro

Rue

Bureau

_______________________________________________________________________________ Ville

Tél. bureau : (

Province

Code postal

) _________________ Courriel : _____________________________________

No de permis professionnel :________________________________________________________

QUESTIONNAIRE Diagnosis and Treatment of Ocular Surface Conditions: Focus on Dry Eye Paul Karpecki, OD, FAAO 1. ❑ ❑ ❑ ❑

According to the most recent study on prevalence, what percentage of the Canadian population has dry eye?

15% 29% 32% 45%

2. ❑ ❑ ❑ ❑

What percentage of dry eye involves the meibomian glands?

25% 29% 82% 86%

3. ❑ ❑ ❑ ❑

According to Jobson Medical Information data, what is the dropout rate for contact lens wear in 2015?

14.4% 14.5% 16.4% 16.5%

Clinical & Refractive Optometry Quebec 1:6, 2016

FORMULAIRE DE DEMANDE DE CRÉDIT UFC DE CATÉGORIE A

1:6, 16

4. ❑ ❑ ❑ ❑

All of the following factors play a role in the development of dry eye, EXCEPT: Diet Digital device use Heredity Smoking

5. ❑ ❑ ❑ ❑

All of the following conditions contribute to the development of dry eye, EXCEPT: Rheumatoid arthritis Low IgG levels Rosacea Diabetes

6. ❑ ❑ ❑ ❑

Tear meniscus height predicts dry eye approximately _____ percent of the time.

40 50 70 80

7. ❑ ❑ ❑ ❑

What is the variation rate of osmolarity testing?

1.5% 1.6% 1.7% 1.8%

8. ❑ ❑ ❑ ❑

Twelve-month use of Restasis will produce a _______ increase in goblet cells?

163% 178% 180% 191%

9. ❑ ❑ ❑ ❑

An obese individual who has terrible eating habits and severe dry eye needs how much fish oil per day to achieve an effect?

1 to 2 grams per day 2 to 3 grams per day 3 to 4 grams per day 4 to 5 grams per day

10. ❑ ❑ ❑ ❑

After six months, one study showed that people on artificial tears alone had a ______ increase in T-cells.

20% 30% 40% 50%

Diagnosis and Treatment of Ocular Surface Conditions: Focus on Dry Eye — Karpecki

247

s Relevant warnings and precautions: • LOTEMAX® Ointment is indicated for short-term treatment only (up to 14 days).

If LOTEMAX® Ointment 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.

• 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/Portals/87/Files/ Monograph/Pharma/Lotemax-MonographConsumer-English.pdf for complete dosing instructions, warnings, precautions, adverse events and patient selection criteria. The Product Monograph is also available by calling 1-888-459-5000.

Bausch & Lomb Canada, Vaughan, Ontario L4K 4B4 © Valeant Canada LP ®/TM are trademarks of Bausch & Lomb Incorporated or its affiliates.

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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.

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Indications and clinical use: LOTEMAX® Ointment (loteprednol etabonate ophthalmic ointment 0.5% w/w) is indicated for the treatment of post-operative inflammation n following cataract surgery. and pain • The( safety and efficacy of LOTEMAX® have noti been studied in pediatric patients (<18 years of age) and should not be used in these populations.

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See additional safety information on page 248