Volume 27, Number 3, 2016 by MediConcept

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Clinical & Refractive Optometry VOLUME 27, NUMBER 3, 2016

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Scleral Lenses Fit for Symptomatic Patient with Keratoconus Orbital Mucocele Ocular Signs of Multiple Myeloma Traumatic Choroidal Rupture and Macular Hole

Clinical &Refractive Optometry

Editorial Board â&#x20AC;˘ Volume 27, Number 3, 2016 Editor-in-Chief

Associate Editor

Richard Maharaj, OD, FAAO Toronto, Ontario

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

Editors Emeriti Brad Almond, OD Calgary, Alberta

Barbara Caffery, OD Toronto, Ontario

John Jantzi, OD Vancouver, British Columbia

Yvon RhĂŠaume, OD Montreal, Quebec

Contributing Editors Scott D. Brisbin, OD Edmonton, Alberta

Gerald Komarnicky, OD Vancouver, British Columbia

Langis Michaud, OD Montreal, Quebec

Barbara Robinson, OD Waterloo, Ontario

Lorance Bumgarner, OD Pinehurst, North Carolina

Bart McRoberts, OD Vancouver, British Columbia

Rodger Pace, OD Waterloo, Ontario

Jacob Sivak, OD, PhD Waterloo, Ontario

Louis Catania, OD Philadelphia, Pennsylvania

Ron Melton, OD Charlotte, North Carolina

Maynard Pohl, OD Bellevue, Washington

Randall Thomas, OD Concord, North Carolina

Publication Staff Publisher Lawrence Goldstein

Managing Editor Mary Di Lemme

Senior Medical Editor Evra Taylor

Layout Editor Colin MacPherson

Graphics & Design Mediconcept Inc.

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

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Clinical&Refractive Optometry

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Contents • Volume 27, Number 3, 2016

The Journal is made available to all optometrists on www.crojournal.com.

CE CREDIT ARTICLES 79 Scleral Lenses Fit for Symptomatic Patient with Keratoconus William J. Denton, OD ABSTRACT: Keratoconus is a near central corneal thinning at the layer of the stroma, creating a physical out-pouching, optically irregular astigmatism and other associated aberrations, which can lead to further complications causing decreased vision and possibly surgery.

Orbital Mucocele Hannah Chu Shinoda, OD; Pauline F. Ilsen, OD ABSTRACT: Orbital mucoceles are respiratory epithelial lined sacs of mucin that originate from the paranasal sinuses. Though considered benign lesions, mucoceles can expand beyond the sinuses, cause bone resorption, reformation, and enter the orbit. These lesions produce a mass effect in the orbit and can cause ophthalmological findings and symptoms.

100

Ocular Signs of Multiple Myeloma Steven Mordukowitz, OD ABSTRACT: A healthy 54-year-old male came in to our clinic for a routine exam. He had no ocular complaints but reported a number of systemic symptoms: a constant dry cough for two weeks, intermittent diarrhea with fever over the past 4 to 6 weeks and recurrent painful mouth sores that were slow to resolve. Dilated fundus exam revealed few scattered cotton-wool spots (CWS) and flameshaped hemorrhages in both eyes along with a small Roth spot hemorrhage present in his right eye below the optic nerve head.

113

Traumatic Choroidal Rupture and Macular Hole in a 10-Year-Old Child: Case Report and Review Christopher J. Borgman, OD ABSTRACT: A 10-year-old African-American female presented with decreased vision in her right eye (OD) after failing a school vision screening. Her dilated retinal exam revealed a large choroidal rupture and traumatic macular hole in the right eye presumably from an earlier trauma without a clear timeline.

Advertising insertion orders and copy must be received before the first day of the preceding month for which the advertising is scheduled. While the editorial staff of Clinical & Refractive Optometry exercises great care to ensure accuracy, we suggest that the reader consult the manufacturer’s instructions before using products mentioned in this publication. The views contained in the Journal are those of the respective authors and not of the Publisher. Please direct all correspondence to: Mediconcept Editorial & Sales Office 3484 Sources Blvd., Suite 518 Dollard-des-Ormeaux, Quebec Canada H9B 1Z9 Tel.: (514) 245-9717 E-mail: info@mediconcept.ca Printed in Canada. All rights reserved. Copyright © 2016 Mediconcept. The contents of the publication may not be mechanically or electronically reproduced in whole or in part without the written permission of the publisher. All drug advertisements have been cleared by the Pharmaceutical Advertising Advisory Board.

COMMUNICATION 122 Are Current Sodium Hyaluronate Solutions That Are Buffered in Phosphate Safe for Daily Administration? Jeffrey Lam, BSc (Hons); Faran Vafaie, OD NEWS & NOTES 124 CooperVision Announces Nationwide Availability of Biofinity® XR Toric Contact Lenses; World Economic Forum and EYElliance Release New Report

ISSN: 1705-4850; Date of Issue: July/August 2016

Cover Image: OD fit with NaF to show tear lens Courtesy of: Dr. William J. Denton

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. William J. Denton entitled Scleral Lenses Fit for Symptomatic Patient with Keratoconus. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 87 for complete instructions.

Scleral Lenses Fit for Symptomatic Patient with Keratoconus William J. Denton, OD, FAAO, FSLS

ABSTRACT Introduction: Keratoconus is a near central corneal thinning at the layer of the stroma, creating a physical out-pouching, optically irregular astigmatism and other associated aberrations, which can lead to further complications causing decreased vision and possibly surgery. Case Report: DC is a 56-year-old Caucasian veteran who came to our contact lens clinic with a long history of being managed in our program. Recently, he presented with keratoconus along with chronic complaints ranging from fluctuating blurred vision with his present contact lenses to ocular itching and grittiness. Conclusion: Switching him from his present contact lens system to scleral lenses has dramatically improved his symptoms and quality of life, as confirmed by results from the Ocular Surface Disease Index questionnaire. Eye doctors should become aware of areas to further improve their patients through changing modes of contact lenses and screening with questionnaires.

INTRODUCTION Keratoconus (KCN) is a near central corneal thinning at the layer of the stroma, creating a physical out-pouching, optically irregular astigmatism, and other associated aberrations. The prevalence of KCN is 8.8 to 54.4 per 100,000 with no gender predilection.1 KCN has shown to be the most symptomatic between the second and fifth decades of life.2 Clinically, inferior keratometry or topography readings can both provide a diagnosis and

W.J. Denton — WJB Dorn VA Medical Center, Columbia, SC Correspondence to: Dr. William J. Denton, Wm. Jennings Bryan Dorn VA Medical Center, 6439 Garners Ferry Road, Columbia, SC 29209; E-mail: William.Denton@va.gov There were no grants associated with this paper. The author has no financial interest in any companies mentioned in this paper. This article has been peer reviewed.

determine the severity of the disease, which correlates with visual complaints. Less than 48 D would be considered mild, 48 D to 54 D as moderate, and greater than 54 D as severe.3 Other than visual complaints, it is common for patients with KCN to have symptoms of ocular dryness and itching. Patients with KCN frequently admit to having a history of extreme eye-rubbing.

CASE REPORT DC is a 56-year-old Caucasian veteran who came to the WJB Dorn Veterans Affairs (VA) Medical Center contact lens clinic with a long history of being managed in our program since prior to 1998. He was diagnosed early on with KCN and was managed with many types of rigid gas permeable (RGP) contact lenses (Table I). Each change occurred as newer technology was available and corneal progression was evident. Additionally, DC has some chronic complaints that include blurred vision with his current contact lenses, ocular allergies and dryness. Over the last ten or more years he was given many medications to assist with these complaints (Table II). Recently, the patient also found that herbal Similasan® Allergy #2 eye drops assists his symptoms greatly. His son had been diagnosed with KCN, but no other family ocular history. DC was the first contact lens patient who was fit with scleral contact lenses in our clinic. After proper training of the staff and obtaining trial sets, DC jumped at the opportunity to try anything that may allow for better comfort, improvement in his vision, or at least a decrease of his dryness symptomology. It is important to state that he was cautiously content with his previous contact lens situation, which consisted of ClearKone® hybrid contact lens (SynergEyes, Inc) OD and a piggyback system OS. His chronic symptoms were compromises he was willing to accept. Lens removal and cleaning was necessary every two hours to obtain clear vision. He also had severe dryness symptoms and was currently using Restasis® ophthalmic emulsion (Allergan) b.i.d. OU, Similasan Allergy #2 eye drops q30min OU, lanolin ophthalmic ointment q.h.s. OU and olopatadine ophthalmic solution q.d. OU. The Ocular Surface Disease Index (OSDI) questionnaire is a way to quantify and compare dryness

Scleral Lenses Fit for Symptomatic Patient with Keratoconus — Denton

Table I Patient’s past lens history from oldest to most recent Lens Type

Description

Soper Cone Rose K Dyna Z Intra-Limbal Piggyback Hybrid

Bicurve contact lens where vaulting of the lens is increased as the base curve decreases. Computer-generated lens design where the optic zone diameter is decreased as the base curve steepens Large diameter lens that is fit within the limbus and is comfortable due to the lid attachment technique When RGPs become uncomfortable and/or begin to damage the cornea a hydrogel lens can be placed under the RGP RGP center to maximize the clarity needed for an irregular cornea, with a soft skirt to maximize the comfort.

Table II Patient’s past medication history Medication

Reason

Carboxymethylcellulose opthalmic solution Lanolin ophthalmic ointment Cromolyn sodium ophthalmic solution Ketorolac ophlamic solution Olopatadine ophthalmic solution Gentamicin ophthalmic solution Tobramycin ophthalmic solution Restasis ophthalmic emulsion Rimexolone ophthalmic solution Chlorphenamine tablet Loratadine tablet Punctal plugs

Lubrication during the day Lubrication q.h.s. Ocular allergy – q.i.d. Ocular allergy – b.i.d. Ocular allergy – q.d. VA Emergency Room gave for red eye Optometry Clinic gave for red eye Reduce inflammatory factors Older soft steroid for severe ocular allergic symptoms Older oral anti-histamine Recent oral anti-histamine Apparatus used to assist in ocular dryness

Table III Health problem list matched with medication Problem

Medication/Device

Carpal Tunnel Syndrome

Naproxen

Degenerative Disc Disease

Naproxen

Gastroesophageal Reflux Disorder Omeprazole Gout

Allopurinol

Keratoconus

RGPs

Hyperlipidemia

Gemfibrozil Simvastatin

Sleep Apnea

CPAP machine

Dry Eye Syndrome

Lubricating ophthalmic ointment Refresh artificial tears Similasan Allergy #2 eye drops Restasis ophthalmic emulsion

Seasonal allergies

Loratadine Fluticasone

Asthma

Albuterol

and related symptoms. His results were calculated as a 64.5 result prior to scleral lens fitting. He was asked to quantify his quality of life (scale: 1 worst, 10 best) before fitting with scleral lenses and he stated a score of 3, due to the many drops and cleaning regimens he has accumulated. Despite his enthusiasm to try another contact lens option, he did accept that the outcome may not be any better than his current situation. He was encouraged to be fit with scleral contact lenses in order to improve

Clinical and Refractive Optometry 27:3, 2016

his dryness and allergy symptoms, meanwhile keeping his present level of visual acuity. In Table III, all of DC’s systemic diseases/complications and treatments are listed. Initial Visit With his habitual contact lenses his visual acuity was 6/6 (20/20) OD, and 6/6 (20/20) OS with much patient head maneuvering and blinking throughout the assessment. DC’s most recent contact lens parameters were: Habitual Contact Lens Parameters • OD: ClearKone hybrid lens • Power: +4.50 D • Base Curve*: 2.00 µm vault, medium skirt curve • Diameter: 14.5 mm • Assessment: Very little movement; centered; appropriate edge; good vision. * ClearKone is not measured by base curve, but by vault. It is similar to a scleral lens because it vaults over the cornea. It is different than a scleral lens because it has a soft lens skirt. •

• • • • • •

OS: Piggyback method; Intra-limbal RGP (Lens Dynamics, Inc.) Power: -3.00 D Base Curve: 6.75 mm Diameter: 11.2 mm Focus® Night & Day®** (CIBA Vision Corp.) Power: -0.50 D Base Curve: 8.4 mm

Fig. 1 OD fit with NaF to show tear lens

Fig. 2 OS fit with NaF in tear lens

Diameter: 14.5 mm Assessment: Very little movement; centered; appropriate edge; good vision ** CIBA Vision has since renamed this lens to Air Optix® Night & Day®

• •

Due to extreme anisometropia and aniseikonia, DC admits not wearing his glasses that were prescribed approximately ten years prior. Habitual Glasses Prescription • OD: -9.00-5.00x135 • OS: -4.00-3.50x135; +2.50 Flat top bifocal The anterior segment examination showed the following signs: some corneal thinning (pachymetry: 448 µm OD, 406 µm OS), quite obvious Munson’s sign OU, a trace amount of apical scarring centrally OU with a Fleisher ring, Vogt’s striae OU, trace diffuse conjunctival injection, 1+ pingueculae nasal and temporal OU, <1 mm of neovascularization on the cornea 360° and 1+ central corneal staining OU. His puncta were open and without punctal plugs. His previous dilated examination was 6 months prior and was unremarkable, showing no additional ocular health concerns. His annual dilated fundus exam was scheduled for 6 months later. When fitting scleral lenses from this company, keratometry readings are less important data as the lens

vaults over the cornea. The initial diagnostic lens was chosen based on a quick assessment of the profile of the patient’s cornea. This lens and a few others showed an inadequate fit. When fitting, non-preserved sodium chloride solution is used to fill the lens so that when inserted there are no air bubbles. Upon inserting the fourth lens, it was inserted with staining of the sodium chloride solution with a sodium fluorescein (NaF) strip so the tear lens between the cornea and diagnostic scleral lens would be more prominent for evaluation. The lens was allowed to settle for approximately thirty minutes. The patient was instantly impressed with both the comfort and the visual acuity once the overrefraction was determined. The same lens was used for the initial fit in the OS and also was a successful fit. • • • • • •

• • • • •

OD: Jupiter® (Essilor Contact Lenses) Diameter: 15.6 mm Base Curve: 6.37 mm Power: -13.00 D Over-refraction: +6.25 D providing 6/7.5 (20/25) Assessment: No bubbles with adequate clearance of ~350 µm centrally and no touch peripherally; well centered; no conjunctival blanching. Subjective: Good vision; good comfort. OS: Jupiter Diameter: 15.6 mm Base Curve: 6.37 mm Power: -13.00 D

Scleral Lenses Fit for Symptomatic Patient with Keratoconus — Denton

Table IV Pre- and post-scleral fitting comparisons Pre-Fitting

Post-Fitting 0 9 None

Medications

64.6 3 Dryness Itching Blurred vision Similasan Allergy #2 Eye Drops q30min OU Olopatadine ophthalmic solution b.i.d. OU Lanolin ung. q.h.s OU Restasis ophthalmic emulsion b.i.d. OU

*Max # of Med Instillations/Day *Mechanical Rub Cleaning

29 q2h

5 q6h

OSDI Quality of Life (1-10) Symptoms

Similasan Allergy #2 Eye Drops q.d.-b.i.d. OU Olopatadine ophthalmic solution p.r.n. OU Lanolin ung. q.h.s OU Restasis ophthalmic emulsion q.a.m. OU

*Assuming 12-hour wear

• •

•

Over-refraction: +4.75 D providing 6/7.5 (20/25) Assessment: No bubbles with adequate clearance of ~400 µm central and no touch peripherally; decentered 1 mm nasally; no conjunctival blanching. Subjective: Good vision; good comfort.

Second Visit At the follow-up appointment, the new lenses were inserted with NaF strips coloring the central tear lens and allowed to settle for approximately 30 minutes, OD (Fig. 1); OS (Fig. 2). • • • • • • •

• • • • • • •

OD: Jupiter Diameter: 15.60 mm Base Curve: 6.37 mm Power: -6.75 D Over-refraction: +1.25 D providing 6/7.5 (20/25) Assessment: No conjunctival blanching; good central vault (~350 µm) without touching peripherally; centered. Subjective: Patient extremely pleased with vision and comfort. OS: Jupiter Diameter: 15.6 mm Base Curve: 6.37 mm Power: -8.25 D Over-refraction: +1.25 D providing 6/6 (20/20) Assessment: No conjunctival blanching; good central vault (~350 µm) without touching peripherally; centered. Subjective: Patient extremely pleased with vision and comfort.

insertion. Insertion and removal training was performed with great success. The lenses were given to the patient so he could practice insertion and removal, but was warned that if he wore them that headaches and eye strain, especially at near, would occur due to the improper prescription power. The change in the over-refraction was made and the patient was called for his next appointment when the lenses arrived. Third Visit When DC arrived, he was given the newest lenses to insert, which gave an opportunity to observe his technique. He proved to be quite proficient and it was evident he had been practicing. No NaF strips were used prior to insertion to assure the maximum possible visual acuity can be documented. • • • • • • •

• • • •

The patient was advised to use a peroxide-based cleaning system, which he was already using with great success. A 0.9% sodium chloride inhalation solution in preservative-free 3 mL vials and used off-label, was ordered through the VA pharmacy to fill the lens prior to

Clinical and Refractive Optometry 27:3, 2016

• • •

OD: Jupiter Diameter: 15.60 mm Base Curve: 6.37 mm Power: -5.50 D Over-refraction: Plano providing 6/6 (20/20) Assessment: No conjunctival blanching; good central vault (~350 µm) without touching peripherally; centered. Subjective: Patient extremely pleased with vision and comfort. OS: Jupiter Diameter: 15.60 mm Base Curve: 6.37 mm Power: -7.00 D Over-refraction: Plano providing 6/6 (20/20) Assessment: No conjunctival blanching; good central vault (~350 µm) without touching peripherally; centered. Subjective: Patient extremely pleased with vision and comfort.

After his visual acuity was checked and over-refraction was performed, NaF strips were wet and smeared above each lens on the conjunctiva. He was sent out to the waiting room for thirty minutes. Upon return, DC showed NaF dye throughout the tear lens behind each scleral lens, which indicated there was adequate tear exchange. He agreed to return in 3 months for a follow-up visit. Fourth Visit DC was seen three months later to assess his scleral lenses. He was very pleased with his new lenses and described at length the comfort and consistent, improved vision compared to his old lenses. Additionally, he mentioned he only had to take the lenses out once a day to clean, a large improvement on removing every two hours with his previous lens system. His eye drops now consisted of Similasan q.d.-b.i.d. OU, Patanol® (Alcon) p.r.n. OU, lanolin ophthalmic ointment q.h.s. OU, Restasis q.a.m. OU. The post-fitting OSDI questionnaire results were a 0.00 index score. He was asked to quantify his quality of life (scale: 1 worst, 10 best) after being fit with scleral lenses and reported a 9, due to the fact that “he still had to wear lenses for maximum vision.” Table IV shows the preand post-scleral lens fitting results. As an aside, he left our clinic stating he intended to get his son fit with scleral lenses as soon as possible. Since then his son has been successfully fit, has a restricted driver’s license and is employed.

DISCUSSION The OSDI questionnaire was published in 1997 by the Outcomes Research Group at Allergan, Inc.4 It is a 12-item questionnaire that can be used to assess the symptoms common with ocular surface disease. Initially, DC scored a moderately-severe range, despite using many ocular medication options. After being fit with scleral lenses, DC had a score of 0.00, which indicated that he had zero symptoms. Symptoms that are common for patients with KCN include frequent changes in spectacle prescription, decreased tolerance to contact lens wear, and glare.3 The author has noticed a tendency of many patients with moderate to severe KCN prefer additional minus prescription in their glasses. This can be explained by the expected contrast sensitivity reduction that is common with many ocular diseases. Caution and awareness of this is important not to cause unnecessary eyestrain or headaches. Some researchers and clinicians theorize that KCN is the result of mechanical rubbing of the lens on the central cornea.5 Research has suggested that inflammatory mediators, proteins and enzymes may be in the tears.6,7 Additionally, patients with concomitant autoimmune and allergic immune diseases may point to an immune component in the pathogenesis of KCN.8 With any pubescent patients who rub their eyes or who use antihistamine ophthalmic drops, a screening with a keratometer

or corneal topography should be strongly considered. It is important to compare central keratometry readings with readings with the patient looking up slightly, in order to measure the inferior corneal curvature. On a manual keratometer the target can be the “+” sign, which is about an inch above the usual target. This is important as the inferior corneal curvature is most commonly the steepest in KCN. Many patients who have an early stage of KCN remain subclinical until symptoms are increased from the disease. There are some diagnostic signs that can assist the eye doctor for patients with KCN.3 An “oil droplet” reflex may be seen with the direct ophthalmoscope at a distance, and a “scissor” reflex with retinoscopy can be seen due to irregular astigmatism. While performing biomicroscopy, fine, vertical, central and deep stromal striae can be seen, known as “Vogt lines” or “Vogt striae,” which disappear with external pressure on the globe. A brownish or olive green “Fleisher ring” can be seen surrounding the base of the cone indicating epithelial iron deposits.3,7 Progressive corneal thinning up to one-third of normal thickness centrally or inferocentrally can result in both reduction in vision and steep keratometry readings. A “Munson sign” can be appreciated when the patient looks down and the bulging or out-pouching of the cornea is outlined by the lower lid. Most patients who are diagnosed with KCN will have plenty of questions regarding the disease. It is important to instruct them what to look for and to keep their follow-up appointments. The patient should be given a prognosis or long-term plan of management after being diagnosed. This may encourage them to embrace being fit with various forms of contact lenses earlier. The clinician must also know what to check during each contact lens or annual ocular examination. Complications include acute hydrops, thinning and rarely spontaneous perforation.9 Acute hydrops are caused by a rupture in Descemet’s membrane allowing an influx of aqueous into the cornea and a drop in visual acuity and severe discomfort and tearing. Healing takes weeks to months for the breaks to close and edema to clear. Stromal scarring may develop as a result. Acute episodes are treated with hyperosmotics and a soft bandage contact lens when possible. A paradoxical outcome may result in better vision due to a flattening of the cornea from scarring.3 Prescription glasses are a popular option early in the disease, but with the development of irregular astigmatism and glare in later stages, a type of RGP or scleral lens would be a better option. Whereas a contact RGP lens has at least some mechanical dynamic with the diseased cornea, a scleral lens vaults over and does not fall out. An RGP would demand increased chair time with the need of multiple adjustments as the disease progresses, while a scleral lens could potentially last quite a few years without an adjustment. Hwang et al notes that RGP fitting with

Scleral Lenses Fit for Symptomatic Patient with Keratoconus — Denton

multicurve lenses is not likely to contribute to any progression of KCN, but that it would be beneficial to have a long-term longitudinal study investigating the long-term effects of RGPs.10 The type of contact lenses used varies depending on the severity of KCN. The contact lens modality represents the treatment of choice in 90% of patients with KCN.1,11 Large diameter SynergEyesÂŽ, a 3rd generation hybrid lens, allows for increased comfort and stability of vision;12 however the scleral lens option provides even better comfort, and still allows for great ocular health, while providing excellent vision stability. The goal of contact or scleral lenses is to provide comfort and good vision, and ultimately to delay the need for corneal surgery. Smiddy et al showed that approximately 70% of KCN patients who present for surgical consideration with keratoplasty can be managed successfully with some type of contact lenses.13 Eventually about 12% to 20% of the affected patients may require some sort of surgical procedure involving replacement of at least some corneal layers at a relatively young age.1 Penetrating or deep lamellar keratoplasty, is indicated in patients with a more advanced stage of KCN, especially with significant corneal scarring. Despite clear grafts occurring in over 85% of cases, optical outcomes may be less than ideal by residual astigmatism and anisometropia. After a corneal surgery, these two frequent complications may further need to be fixed with a contact or scleral lens correction for best acuity.3 Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet A (UVA) has been performed for many years, but just recently received approval by the Food and Drug Administration (FDA), and has proven to strengthen the corneal tissue through development of new cross-links within the collagen fibers and is only mildly invasive.2,14,15 McAnena et al showed CXL to be productive and safe for teenagers.16 Additionally, Mazzotta et al used in vivo confocal microscopy findings to confirm that the CXL procedure is safe.17 CXL should be considered to potentially delay the need for lamellar or penetrating keratoplasty, while increasing the strength of the central cornea through modification of the stromal structures.18,19 Recently, accelerated CXL has been proven to stabilize KCN progression and may be best with advanced KCN.20 Accelerated CXL uses higher irradiance to reduce the treatment time, however, conventional CXL showed greater corneal flattening and showed clinical improvement compared to the accelerated CXL.21 At the time of the scleral lens fitting, the VA did not provide CXL as a treatment option. This procedure most likely will be approved for future patients with KCN now that the FDA has approved it as a viable treatment option. Other procedures and surgeries that should be mentioned with KCN management are phakic intraocular lenses (IOLs) and intracorneal ring segments (ICRS). Phakic IOLs are typically used to treat lower-order

Clinical and Refractive Optometry 27:3, 2016

aberrations of KCN not found to improve with contact lenses.22 Due to a progressively steepening cornea, a phakic IOL most likely would not fix the symptoms longterm. After patients with prior contact lens intolerance underwent ICRS implantation, approximately 80% or better became tolerant to wear contact lenses again.23 ICRS prove to flatten the cornea, but have not shown to decrease corneal aberrations consistently.24 The attractiveness of ICRSs, unlike phakic IOLs, is that ICRSs can be removed and different stages can be implemented as the disease progresses. ICRSs can be implanted as long as the central cornea is clear and without scarring, and there is adequate corneal thickness. DC would not be a good candidate for ICRSs as he does not have the minimum 450 Âľm of corneal thickness required. ICRS have been encouraged for mild to moderate stages of KCN. This happens to be the same time frame an optometrist would fit the patient with contact lenses. Furthermore, the ICRS can be implemented prior to a CXL procedure without any loss of effect of either procedure.24 There are several corneal surgical options including PKP or DALK. While a penetrating keratoplasty removes all layers of the cornea and replaces it with a donor cornea, the only portion that is not damaged with lamellar keratoplasty is the endothelium, which is healthy in KCN. Kubaloglu et al showed long-term endothelial cell loss was moderate and lower with deep anterior lamellar keratoplasty than penetrating keratoplasty grafts.25 PKP often produces satisfactory visual outcomes, but it also comes with significant long-term risk of complications, months to years of follow-up exams, and prescription ocular medications.26 Fukuoka et al studied 125 eyes that had PKP and showed improvement of visual acuity after the procedure; however, it decreased 20 years afterwards.27 Kelly et al. showed that a repeated PKP would be more successful if the initial PKP was at least 10 years old, largely due to episodes of inflammation or graft rejection.28 A portion of patients who have undergone PKP or other surgical procedures end up wearing contact lenses to maximize their visual acuity.1 KCN is known to be associated with many multisystem, systemic, ocular and corneal disorders. DC would be considered overweight, was previously diagnosed with obstructive sleep apnea (OSA), and prescribed a continuous positive airway pressure (CPAP) mask to wear while sleeping. Naderan et al stated in their study that patients with KCN have an increased risk of developing OSA. In addition, Naderan et al concluded that patients diagnosed with KCN who are at higher risk of developing OSA, because of weight and age, may have a more severe case of KCN.29 DC was encouraged to continue wearing his CPAP mask and to follow through with monitoring appointments. Further information was given on ways to

lose weight, which in turn can reduce the risk of needing a CPAP machine. Clinicians should educate their patients with KCN of the risk factors of OSA and how they can limit their chance of being diagnosed with it. KCN is also considered a multifactorial disease additionally involving both genetic and environmental factors that add to the disease manifestation. DC has a constant battle with severe allergies, admits to eye-rubbing, and has a son also diagnosed with KCN. In a recent review of literature the author argues that KCN is not a non-inflammatory disease, but an “inflammatory-related” disease. KCN meets some, but not all, the classic inflammatory disease characteristics, so it cannot be categorized as inflammatory.30 Patients with KCN were found to possess higher levels of interleukin-6, tumor necrosis factor-alpha, and matrix metalloproteinase (MMP)-9 in their tears. Reduced protein levels, such as immunoglobulin A and lactoferrin, were also found in their tears.30-32 This may prove to interfere with the immune function of the ocular surface. A new potential predictor of systemic inflammation is the neutrophil-tolymphocyte ratio. When evaluated in patients with KCN, the neutrophil-to-lymphocyte ratio was found to be at higher levels in patients with progressive KCN in comparison to patients with a non-progressive stage of the disease.31 Additionally, Pastori proposed that a contact lens loaded with lactoferrin may be an option to treat ocular surface diseases characterized with high levels of oxidative stress.32 DC admitted having a history of rubbing his eyes vigorously at times. He attributed it to his allergies and dry eyes. Allergies and dry eyes, which have strong connections to KCN and are accepted risk factors. A previous study or previous investigated report that an estimated 50% of KCN patients rub their eyes.33 An interesting study showed that a person without any eye disorders rubs for less than 5 second while someone with an allergic or infective ocular disease typically rubs less than 15 seconds. A KCN patient rubs between 10 to 180 seconds. There can be much variation to how gentle or vigorous this eye rubbing occurs. Corneal micro-trauma from eye rubbing, or potentially a poor contact lens fit, may be the culprit to pro-inflammatory factors to be released and cause the disease to be progressive in nature.33 A patient wearing scleral lenses would be less likely to cause this micro-trauma from eye rubbing as the lens would shield the cornea. It may appear quite unorthodox to not have keratometry reading or a corneal topography on a patient before fitting scleral lenses. In private practice it would be advantageous to charge for a corneal topography and also provide proof to the insurance company of your diagnosis as many insurance companies will reimburse for a specialty contact lens fitting for KCN. DC had a history of wearing

RGP lenses, so a keratometry range could easily be assessed based on an RGP and the staining pattern with the lens on. The scleral lens vaults over the cornea, so these readings are not as important as with other contact lenses. A study by Schornack et al had results that indicated there was no predictive relationship between topographic indices, which would include keratometry readings, and base curve for scleral lenses. It was suggested that a fitting paradigm based on sagittal depth be established.34 Many management options are available for maximizing vision with KCN patients, but it is essential that they are provided the options that would best meet the patient’s expectations. With DC it appears he will be quite content with his new scleral contact lenses for a long time. Management options may have been different if he started showing scarring or other complications earlier. In addition to insertion and removal training, the clinician should provide guidance on what cleaning products to use. With DC a hydrogen-peroxide cleaner was chosen based on his history of allergies. He also had an RGP multipurpose cleaner he used to clean the scleral lenses mid-day. DC was reminded of the warnings and limitations of the hydrogen-peroxide cleaner. The scleral lens needs a preservative-free solution to fill the lens before inserting on the eye. This provides a consistent optical light pathway that starts with the scleral lens, goes through the liquid solution and then into the cornea. A very practical and easy solution is to prescribe 0.9% sodium chloride inhalation solution as an off-label use. It comes in 3 mL or 5 mL vials and would be discreet and easily carried in a pocket, purse or bag. The VA pharmacy was contacted prior to the first order to make sure the process went through seamlessly. In private practice, it is a nice way to get the patient to return to the clinic as refills will be needed. Most prescription plans will cover a portion of this cost since it is a prescribed medication, so it ends up economically better for the patient. A nonpreserved bottle option can be found over-the-counter, however, the expiration date needs to be followed, contamination is more likely, and it is less ideal to carry a bottle around than the vial option. Initially, when DC was practicing removal of his scleral lens, he had difficulty. After observing his technique of using a large diameter plunger, it was suggested to him to use a “can-opener” technique that the author thought up. It involves using a wet plunger and attaching it to the far nasal or temporal portion of the lens while on the eye and twisting the wrist, similar to opening a soda can tab, in an arc. The patient was able to master this technique. During the scleral lens fitting process, the tear lens behind the scleral lens tended to accumulate debris easily that can be explained by the light tissue paper of the NaF strips. Fragments of the light tissue paper break off and

Scleral Lenses Fit for Symptomatic Patient with Keratoconus — Denton

result as debris in the tear lens. It is the author’s experience that this results in at least a half line of visual acuity loss. Using a thicker paper for NaF strips may counteract this problem. As a clinician, it is important to be aware of this in case the visual acuity is not as good as expected. At the time of this patient encounter, the goal was to have between 300 µm to 500 µm of vault between the cornea and the lens. Since then, it has been encouraged to have between a 150-µm to 200-µm vault. This allows for greater oxygen transmission to the cornea.

CONCLUSION This case report represents how a realistically content patient with KCN can still improve ocular allergic and dryness symptoms, along with more consistent quality vision, with a scleral lens fit. This was proven through the decrease in ocular medications, increase in quality of life scale, and a significant improvement in the OSDI when comparing pre- and post-scleral lens fitting. Eye doctors should become aware of areas to further improve their patients through changing modes of contact lenses and screening with questionnaires. ❏

REFERENCES 1. 2. 3.

7. 8.

9. 10.

11.

12. 13.

Jhanji V, Sharma N, Vajpayee RB. Management of keratoconus: current scenario. Br J Ophthalmol 2011; 95(8): 1044-1050. Chang CY, Hersh PS. Corneal collagen cross-linking: a review of 1-year outcomes. Eye Contact Lens 2014; 40(6): 345-352. Kanski J. Clinical ophthalmology: a systematic approach. 6th ed. Edinburgh; New York: Butterworth-Heinemann/ Elsevier; 2007. Walt JG, Rowe MM, Stern KL. Evaluating the functional impact of dry eye: the ocular surface disease Index [abstract]. Drug Inf J 1997; 31: 1436. Mashor RS, Kumar NL, Ritenour RJ, Rootman DS. Keratoconus caused by eye rubbing in patients with Tourette Syndrome. Can J Ophthalmol 2011; 46(1): 83-86. Jun AS, Cope L, Speck C, Feng X, Lee S, Meng H, et al. Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients. PLoS ONE 2011; 6(1): e16437. Pannebaker C, Chandler HL, Nichols JJ. Tear proteomics in keratoconus. Mol Vis 2010; 16: 1949-1957. Nemet AY, Vinker S, Bahar I, Kaiserman I. The association of keratoconus with immune disorders. Cornea 2010; 29(11): 1261-1264. Lam FC, Bhatt PR, Ramaesh K. Spontaneous perforation of the cornea in mild keratoconus. Cornea 2011; 30(1): 103-104. Hwang JS, Lee JH, Wee WR, Kim MK. Effects of multicurve RGP contact lens use on topographic changes in keratoconus. Korean J Ophthalmol 2010; 24(4): 201. Ambekar R, Toussaint Jr. KC, Wagoner Johnson A. The effect of keratoconus on the structural, mechanical, and optical properties of the cornea. J Mech Behav Biomed Materials 2011; 4(3): 223-236. Abdalla YF, Elsahn AF, Hammersmith KM, Cohen EJ. SynergEyes lenses for keratoconus. Cornea 2010; 29(1): 5-8. Smiddy WE, Hamburg TR, Kracher GP, Stark WJ. Keratoconus. Contact lens or keratoplasty? Ophthalmology 1988; 95(4): 487-492.

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14. De Bernardo M, Capasso L, Lanza M, Tortori A, Iaccarino S, Cennamo M, et al. Long-term results of corneal collagen crosslinking for progressive keratoconus. J Optom 2015; 8(3): 180-186. 15. Li J, Ji P, Lin X. Efficacy of corneal collagen cross-linking for treatment of keratoconus: a meta-analysis of randomized controlled trials. PLoS ONE. 2015; 10(5): e0127079. 16. McAnena L, O’Keefe M. Corneal collagen crosslinking in children with keratoconus. J AAPOS. 2015; 19(3): 228-232. 17. Mazzotta C, Hafezi F, Kymionis G, Caragiuli S, Jacob S, Traversi C, et al. In vivo confocal microscopy after corneal collagen cross-linking. Ocul Surf 2015; 13(4): 298-314. 18. Jankov Ii MR, Jovanovic V, Delevic S, Coskunseven E. Corneal collagen cross-linking outcomes: review. Open Ophthalmol J 2011; 5: 19-20. 19. Newman BY. Hope for keratoconus. Optometry 2011; 82(1): 3. 20. Chan TCY, Chow VWS, Jhanji V, Wong VWY. Different topographic response between mild to moderate and advanced keratoconus after accelerated collagen crosslinking. Cornea 2015; 34(8): 922-927. 21. Ng ALK, Chan TC, Cheng AC. Conventional versus accelerated corneal collagen cross-linking in the treatment of keratoconus. Clin Experiment Ophthalmol 2016; 44(1): 8-14. 22. Hamdi IM. Preliminary results of intrastromal corneal ring segment implantation to treat moderate to severe keratoconus. J Cataract Refract Surg 2011; 37(6): 1125-1132. 23. Piñero DP, Alio JL, Tomás J, Maldonado MJ, Teus MA, Barraquer RI. Vector analysis of evolutive corneal astigmatic changes in keratoconus. Invest Ophthalmol Vis Sci 2011; 52(7): 4054-4062. 24. Poulsen DM, Kang JJ. Recent advances in the treatment of corneal ectasia with intrastromal corneal ring segments. Curr Opin Ophthalmol 2015; 26(4): 273-277. 25. Kubaloglu A, Sari ES, Unal M, Koytak A, Kurnaz E, Cinar Y, et al. Long-term results of deep anterior lamellar keratoplasty for the treatment of keratoconus. Am J Ophthalmol 2011; 151(5): 760-767. 26. Kumar NL, Rootman DS. Newer surgical techniques in the management of keratoconus. Int Ophthalmol Clin 2010; 50(3): 77-88. 27. Fukuoka S, Honda N, Ono K, Mimura T, Usui T, Amano S. Extended long-term results of penetrating keratoplasty for keratoconus. Cornea 2010; 29(5): 528-530. 28. Kelly T-L, Coster DJ, Williams KA. Repeat penetrating corneal transplantation in patients with keratoconus. Ophthalmology 2011; 118(8): 1538-1542. 29. Naderan M, Rezagholizadeh F, Zolfaghari M et al. Association between the prevalence of obstructive sleep apnoea and the severity of keratoconus. Br J Ophthalmol 2015; 99(12): 1675-1679. 30. McMonnies CW. Inflammation and keratoconus. Optom Vis Sci 2015; 92(2): e35-41. 31. Karaca EE, Özmen MC, Ekici F, Yüksel E, Türko lu Z. Neutrophil-to-lymphocyte ratio may predict progression in patients with keratoconus. Cornea 2014; 33(11): 1168-1173. 32. Pastori V, Tavazzi S, Lecchi M. Lactoferrin-loaded contact lenses: eye protection against oxidative stress. Cornea 2015; 34(6): 693-697. 33. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int 2015; 2015:795738. doi: 10.1155/2015/795738. Epub 2015 May 17. 34. Schornack MM, Patel SV. Relationship between corneal topographic indices and scleral lens base Curve. Eye Contact Lens 2010; 36(6): 330-333.

27:3, 16

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QUESTIONNAIRE Scleral Lenses Fit for Symptomatic Patient with Keratoconus William J. Denton, OD, FAAO, FSLS 1. ❑ ❑ ❑ ❑

All of the following statements about keratoconus are true, EXCEPT: Ocular dryness is a common symptom Itching is a common symptom There is no gender predilection It has shown to be the most symptomatic between the third and fourth decades of life

2. ❑ ❑ ❑ ❑

In the Case Report presented, the patient had all of the following clinical signs and symptoms, EXCEPT: Blurred vision with his current contact lenses Ocular pain Ocular allergies Ocular dryness

3. ❑ ❑ ❑ ❑

In the Case Report presented, what was the patient’s visual acuity with his habitual contact lenses? 6/4.8 (20/16) OU 6/6 (20/20) OU 6/7.5 (20/25) OU 6/9.5 (20/32) OU

Scleral Lenses Fit for Symptomatic Patient with Keratoconus — Denton

❑ ❑ ❑ ❑ 5. ❑ ❑ ❑ ❑ 6.

According to Smiddy et al, approximately what percentage of keratoconus patients who present for surgical consideration with keratoplasty can be managed successfully with some type of contact lenses? 40% 50% 65% 70% After patients with prior contact lens intolerance underwent ICRS implantation, approximately what percentage became tolerant to wear contact lenses again? 65% 72% 80% 85%

❑ ❑ ❑ ❑

Kelly et al showed that a repeated penetrating keratoplasty (PKP) would be more successful if the initial PKP was at least how old? 5 years old 10 years old 15 years old 20 years old

7. ❑ ❑ ❑ ❑

According to the literature, what is the estimated percentage of keratoconus patients who rub their eyes? 50% 55% 60% 70%

8. ❑ ❑ ❑ ❑

In the Case Report presented, what was the patient’s initial quality of life score? 3 4 5 6

9. ❑ ❑ ❑ ❑

Rigid gas permeable (RGP) lenses are the treatment of choice in what percentage of patients with keratoconus? 60% 70% 80% 90%

10. ❑ ❑ ❑ ❑

In cases of keratoconus, clear grafts occur in what percentage of cases? Over 64% Over 72% Over 80% Over 85%

27:3 16

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Clinical and Refractive Optometry 27:3, 2016

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Hannah Chu Shinoda and Dr. Pauline F. Ilsen entitled Orbital Mucocele. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 98 for complete instructions.

Orbital Mucocele

INTRODUCTION

Hannah Chu Shinoda, OD; Pauline F. Ilsen, OD

Mucoceles have been noted beginning with Lagenback, who first described them in 1819, and Rollet, who first coined the term “mucocele” in 1896.1-6 Paranasal mucoceles are benign lesions that are mucus enclosed in respiratory epithelium that originate in the paranasal sinuses and slowly expand into the orbit and/or cranium.3,7,8 They are the most common expansile lesion in the paranasal sinus and account for 4% to 8.5% of expanding orbital lesions.9,10 A paranasal sinus mucocele is considered an orbital mucocele when there is damage to any of the orbital walls through damage to the lamina papyracea, periorbita, or orbital floor.11 An increasing number of paranasal sinus mucoceles have been reported since computed tomography (CT) scans became more readily available in the 1980s and since the rise of endonasal endoscopic surgical techniques.1,12 We describe a case of orbital mucocele, and discuss the epidemiology, pathophysiology, clinical presentation, diagnostic testing, and management of orbital mucoceles.

ABSTRACT Background: Orbital mucoceles are respiratory epithelial lined sacs of mucin that originate from the paranasal sinuses. Though considered benign lesions, mucoceles can expand beyond the sinuses, cause bone resorption, reformation, and enter the orbit. These lesions produce a mass effect in the orbit and can cause ophthalmological findings and symptoms. Case Report: A 61-year-old African-American male presented to the clinic who had developed an anterior ethmoidal mucocele with orbital extension after a blowout fracture, status post repair in the left eye. Due to multiple traumas, CT scans of the orbit were performed, displaying growth of the mucocele. However, due to early intervention, no ophthalmological manifestations had yet developed. Conclusion: Though orbital mucoceles are slow growing, they can cause proptosis, diplopia, optic atrophy, and even permanent vision loss depending on the location of the mucocele. Imaging through computed tomography is the gold standard for establishing a diagnosis of orbital mucoceles with magnetic resonance imaging as an additive imaging option for complicated cases. Surgical intervention is necessary to either marsupialize the mucocele or completely obliterate the sinus after mucocele removal. Prognosis is good given prompt treatment and clinical detection of the mucocele.

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

CASE REPORT A 61-year-old African-American male presented with a chief complaint of blurry vision since he lost his glasses when an automobile hit him six months ago. Ocular history was significant for a blowout fracture of the left eye from a robbery over 15 years ago; he was status post-repair. The patient was also lost to follow up for three and a half years as a glaucoma suspect secondary to suspicious optic nerve head cupping. Medical history was remarkable for hepatitis C, hepatomegaly, thrombocytopenia, carotid artery disease, psychosis with paranoid features, and a history of cocaine and alcohol abuse. Current medications were: trazadone, risperidone, tramadol, ibuprofen, and gabapentin. Best-corrected visual acuities were 6/7.5 (20/25) OD and 6/12 (20/40) OS, with a manifest refraction of +0.501.25x080 OD and -1.00-1.00x110 OS. Pupils were equal, round and reactive to light with no afferent pupil defect noted. Extraocular motility revealed a longstanding restriction in the upper right gaze with symptomatic diplopia. The intraocular pressures were 11 mmHg OD and 13 mmHg OS by Goldmann applanation tonometry. Anterior segment was unremarkable except for 1+ nuclear

Orbital Mucocele — Chu Shinoda, Ilsen

Fig. 1 Optic nerves demonstrating no rim pallor and distinct margins. ONH cupping is suspicious for glaucoma.

Fig. 2 Humphrey Visual Field using a Sita-Standard strategy with a size III white stimulus. Results have a good reliability. (A) Right eye shows anelongated blind spot with few peripapillary defects and scattered defects superiorly. (B) Left eye shows a scattered superior defects. Both do not demonstrate any defects respecting the midline or any glaucomatous patterns.

sclerosis in both eyes and posterior subcapsular cataracts located superior to the visual axis in the right eye, and more centrally in the left eye, causing more visual significance in the left eye compared to the right. Posterior segment was homogenous with pink and healthy optic nerve head rims, distinct margins, and large cup-to-disc ratios: 0.70 OD, 0.80 OS (Fig. 1). Humphrey Visual Field Central 24-2 Sita Standard revealed mild superior defects from lid defects in both eyes, not respecting the vertical midline (Fig. 2A,B), which were attributed to the eyelids. The patient reported no areas of facial or orbital pain or pressure, and no new diplopia. Hertel exophthalmometry was within norms: 20 mm OD, 21 mm OS with a base of 124 mm though on gross examination there appeared to be proptosis due to facial asymmetry from multiple facial injuries. Palpation of the orbit revealed no resistance to retropulsion.

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A further review of the patient’s history revealed a computed tomography (CT) imaging two years prior after the patient presented to the emergency room for an 8/10 headache and new onset dizziness and headache following head trauma and concussion after he was “punched out.” His CT scan revealed bony loss along the left medial orbital wall with an ovoid, lentiform lesion that was isodense with the brain (Fig. 3A,B). The patient had another CT scan one year later after an automobile accident where the patient was injured as a pedestrian and had undergone multiple reconstructive surgeries. The CT scan revealed an expansion of the lesion from 11 mm in the transverse direction to 15 mm. The lesion was now placing a mass effect on the left medial rectus muscle without optic nerve involvement (Fig. 4A,B). A follow up CT scan was ordered to assess for progression and the lesion was grossly stable,

Fig. 3 CT imaging from 2 years prior. (A) The image on the left is a transverse section that demonstrates the patientâ&#x20AC;&#x2DC;s marked facial asymmetry from prior trauma and the metal wire mesh caudal to the orbit from orbital reconstructive surgery. (B) The image on the right is a transverse section revealing a lentiform lesion medial to the orbit that is isodense with the brain, measuring 11mm in the transverse direction.

Fig. 4 CT imaging from 1 year prior. (A) The image on the left is a transverse section now revealing bony loss of the medial wall of the left orbit and mass effect on the medial rectus muscle. The isodense lesion is now 15 mm in the transverse direction. (B) The image on the right is a coronal section also demonstrating bony loss of the medial wall and mass effect. There is no optic nerve involvement.

now 16 mm in the transverse direction (Fig. 5A,B). The tentative diagnosis was orbital mucocele versus other soft lesion. The patient was referred to head and neck clinic and neuro-ophthalmology to determine if surgical intervention was warranted; however, he repeatedly failed to keep his appointments in both clinics.

DISCUSSION Epidemiology A mucocele can be found in any sinus and is estimated to be unilateral in 90% of cases.13 They can occur at any age but are most commonly reported in the 3rd and 4th

Orbital Mucocele â&#x20AC;&#x201D; Chu Shinoda, Ilsen

Fig. 5 CT imaging following initial consult. (A) The image on the left is a transverse section demonstrating bony loss of the medial wall of the orbit, a lesion isodense with the brain that is causing mass effect on the medial rectus muscle and expansion into the ethmoid sinus and left orbit. (B) The image on the right is a coronal section also demonstrating mass effect on the medial rectus muscle. The optic nerve is not involved.

decade, with a mean of 53.3 years of age, and is rarely reported in the pediatric population.2,3,5,11,14 There is no gender predilection for mucocele formation.3,11,15,16 The etiology of paranasal sinus mucoceles is not well understood, but is generally accepted that there is a blockage of the sinus ostia or a compartment of the septated sinus by means of inflammation, trauma, surgery, polyps, or allergy.16-21 In 30% of the cases, a cause cannot be determined.1 Primary mucoceles are idiopathic, when they occur without any predisposing factors. Secondary mucoceles, on the other hand, are caused by a known factor, such as inflammation, trauma, previous sinus surgery, or any other possible etiologic factors.3,11 Primary and secondary mucoceles display differences in intraorbital extension (IOE) and intracranial extension (ICE). In a study by Fu et al 61.4% of IOE was caused by primary mucoceles compared to 23.9% caused by secondary mucoceles. Intracranial extension was caused by primary mucoceles in 12.3% of the cases compared to 1.8% by secondary mucoceles.11 Trauma has been highlighted as a significant predisposing factor in 9% to 28% of reported cases as the outflow tract of the frontal sinus is particularly susceptible to obstruction.22 Mucoceles in children are commonly linked with cystic fibrosis â&#x20AC;&#x201D; they are found in up to 16% of children with cystic fibrosis.13,18 Nasal polyposis can by nature obstruct a sinus drainage and cause mucocele formation; however, the risk of development is low, 0.6% compared to mucocele development after nasalization, 2.5%.1 The key is that there is damage to the

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ventilation of the sinus, which can be caused by inflammation, polyps, prior sinus surgeries, allergies, trauma, Pagetâ&#x20AC;&#x2122;s disease, fibrous dysplasia, osteoma, or tumors.8,19 Studies detailing the most common etiologies of paranasal mucoceles have conflicting reports. An analysis of four studies helps narrow down more commonly published etiologies of paranasal mucoceles. In Figure 6, the trend demonstrates that paranasal mucoceles occur most frequently post-surgically, in chronic sinusitis, in nasal polyposis, or idiopathically. However, itâ&#x20AC;&#x2122;s important to note that most of the noted surgeries were for patients with chronic sinusitis; thus, chronic sinusitis plays alarger role in predisposing patients to mucocele development than shown.6,16,22,23 Mechanism of Expansion Though mucoceles are considered benign lesions, they behave like space-occupying lesions through inflammation and expansion.1,24 Initially, mucoceles are limited in the bony walls of the sinuses, but then invade the orbit by expansion or erosion of the wall.4,25 Analysis of mucocele tissue reveals inflammatory factors that are responsible for a dynamic process of bone resorption and new bone formation.4 Prostaglandin E2 (PGE2) is found in excess by 40% of what is found in normal tissue when compared to mucosal tissue, which is an important contributor in bone resorption.18,24 In a study by Lund et al specimens from mucoceles were obtained during surgery and subject to immunohistochemical analysis. Through monospecific

Etiology

60%

70%

50% Bockmuhl et. al (185) Sautter et. al (57) Shkoukani et. al (42) Serrano et. al (60)

60% 50%

Bockmuhl et. al (185) Serrano et. al (60) Shkoukani et. al (42) Sautter et. al (57)

30% 20%

40%

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30%

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a da c he s Per ior bit Pre al ssu re/ Na Pai s al n Ob s tr uc t ion Dip lop ia An os m Vis ia ua l Ch a ng CS e s FR hin orr he a Rh ino rrh ea E pi pho ra Pto sis As y mp to m a ti c

20%

40%

Symptoms

Fig. 6 An analysis of the most common causes of paranasal sinuses. Values following the authors are the number of cases in each study. There is variability in reports of most common causes; however this graph demonstrates that the strongest factors in causing a mucocele are chronic sinusitis and post-surgery.

antibodies, the presence of cytokine interleukin-1a (IL-1a ), interleukin-1ß (IL-1ß), Intercellular adhesion molecule (ICAM), and E-selectin was seen only in specimens of mucoceles, and not in normal respiratory lining. Cytokines, such as IL-1, are important in the production of PGE2. ICAM and E-selectin are important adhesion molecules in allowing the migration of cytokines to the site of inflammation along the mucocele lining. Therefore, Lund et al propose that IL-1 and ICAM and E-selectin are responsible for the bone destruction in mucocele expansion.24 Another contributor in mucocele expansion is osmosis: as the mucocele continues to secrete mucin, the increased protein content draws in more fluid, and the hydrostatic pressure within mucoceles rises causing expansion.4,26 Through these dynamic factors, paranasal mucoceles have the potential to cause IOE and ICE and mass effect on neighboring structures. Presentation Mucoceles are slowly expanding lesions that are slow to cause visual symptoms or signs, if any at all. In a 10-year review by Shkoukani et al of 54 mucoceles, it took 4 to 24 years for the lesion to develop, with an average of 15 years.23 They occur most commonly in the anterior paranasal sinuses (61%), which is divided into the frontal, maxillary, and anterior ethmoid sinuses, and less frequently in the posterior paranasal sinuses, which is divided into the posterior ethmoid and sphenoid sinuses (26.8%), and least

Fig. 7 An analysis of the symptoms from paranasal mucoceles. The values following the authors are the number of cases in each study. Given that anterior sinus mucoceles are more common, the symptoms are skewed towards symptoms associated with anterior sinus mucoceles rather than posterior sinus mucoceles.

often in both (12.2%).21 Mucoceles occur in the frontal sinus 54.4% to 65% of the time, and in the ethmoid 20% to 30%, maxillary 5% to 10%, and in the sphenoid 2% to 10% of the time.4,6,18,21 Because of the bias of mucoceles to develop in the anterior sinuses, there is a bias of “anterior sinus symptoms” seen in Figure 7 compared to the symptoms associated with the posterior sinus. Signs/Symptoms Given that the paranasal sinus has extensive recesses through the head and around the orbit, symptoms can vary depending on the location and the extent of the mucocele.23,27 The frontal sinus is adjacent to the orbital roof, the maxillary sinus shares part of the orbital floor, the ethmoid sinus is along the orbital medial wall, and the sphenoid sinus almost circumferences the orbital apex.21 The most common symptoms of orbital mucoceles are: proptosis, orbital displacement, headache, periorbital swelling, blurred vision, diplopia.6,8,10,17,20 There is little agreement in the overall prevalence of symptoms. For example, proptosis is found in 26% to 83.3% of patients, and rhinorrhea in 2.5% to 31% of patients.3,6,20,23 In Figure 7, the variety of symptoms and the spread of the prevalence is demonstrated. Given that mucoceles are more commonly found in the frontal and ethmoid sinuses, the symptoms graphed are skewed towards symptoms caused by mucoceles in those locations.21 If we divide the paranasal sinuses in two, with the anterior sinuses including frontal, maxillary, and anterior ethmoid, and the posterior sinuses including the posterior ethmoid and sphenoid sinuses, we can group the symptoms as being more commonly found in the anterior sinuses versus the posterior sinuses.

Orbital Mucocele — Chu Shinoda, Ilsen

In the anterior sinus, dull pain or headache is more common, as there is inflammation, stretching of the sinus or nasal cavity mucosa, or dura, which is transmitted by the trigeminal nerve.8,21,25 Mass effect directly on the globe is more common in anterior mucoceles where the globe is displaced and proptotic and patients may experience diplopia, and a palpable mass.12,20,27 The palpable mass is non-tender, smooth and partially compressible, and due to the mass it can cause nasal obstruction sensation and rhinorrhea.5,20 Intraocular pressure may also be elevated if there is disturbance of aqueous flow from compression.12,28 Because of the proximity of the sinuses to the extraocular muscles, mucocele expansion can also cause EOM restriction and diplopia.25 Frontal and ethmoidal mucoceles are more likely to cause IOE.11 Posterior paranasal sinus mucoceles have a graver prognosis and can cause optic neuropathy from either compression of the nerve or compromised blood supply to the nerve, or optic neuritis from the spread of suppuration from the sinuses which causes a nerve conduction block.17,21,28,29 It’s important to note the anatomic proximity of the nerve and the posterior sinuses. They are separated by a 40 µm to 60 µm thin ethmoid bone; therefore, posterior sinus mucoceles are much more likely to cause nerve damage than anterior mucoceles that are located further away.28 Secondary to optic atrophy, patients may present with relative afferent pupillary defect, blurred vision, unilateral color defects, and changes in the visual field.21,27,28 Also, mucoceles in the sphenoid sinus have a close proximity to cranial nerves III, IV, V, and VI; thus, they can cause nerve palsies and diplopia.12,25 Mucoceles in the sphenoid sinus are the most likely to develop intracranial extension.11 Given the higher risk of optic nerve damage and extension into the cranium, patients with mucoceles in the posterior sinuses need to be referred promptly to avoid potentially devastating sequela such as meningitis or cerebral spinal fluid leakage.3,12,27 Diagnosis Diagnosis of orbital mucocele is aided by MRI and CT imaging and supported by patient history and symptoms. On imaging, mucoceles have a characteristic appearance: homogenous lesion that is isodense with the brain, defined borders, and causing mass affect with sinus architecture bowing outwards.7,21,26,30,31 Other lesions that can produce a mass effect on the orbit that can be differentiated on MRI are dermoid cysts, histiocytosis, fungal and tuberculosis infections, neoplasms, and granulomas.7 With the combination of MRI and CT imaging, other differentials can be ruled out.19,24 Imaging Imaging is the most crucial piece of information in diagnosis of an orbital mucocele. Thanks to the advent of new technologies, there are a variety of imaging techniques to choose from.

Clinical and Refractive Optometry 27:3, 2016

X-ray is helpful in demonstrating the loss or displacement of the bony walls; however, mucoceles can be missed in the anterior ethmoid or not recognized in the sphenoid sinus.5,32 MRI is useful in ruling out other soft tissue masses with similar presentations, such as brain prolapse, malignant neoplasia, meningocele, rhabdomyosarcoma, hemangioma, and neuroblastoma, and for demonstrating secondary mucocele formation when not apparent on CT.13,20,24 Though the characteristic appearance of mucoceles on MRI is hypointense in T1 imaging and hyperintense in T2 imaging, the appearance can vary depending on the fluid content, dessication and viscosity of the mucocele.3,20,24,31 In T1 imaging, the mucocele is most commonly hypointense because the water content is high, and is hyperintense for the same reason in T2 imaging.20,33 One the pitfalls, however, is that if a mucocele is more dessicated, lacking hydrogen protons, it can appear as an aerated sinus in T1 and T2 images and the mucocele could be missed completely.7,20,31 On CT, a mucocele will appearance as a homogenous mass that is isodense or hypodense with the brain, surrounded by defined borders.3,7,13,17,20,30 Also, there may be patchy osteolysis around the mass with bony reformation, creating a “pseudocapsule” or “eggshell bone” appearance.7,17,25,30,34 The mucocele can slowly change with increased density on CT depending on the age of the mucocele, because the mucocele contents can increase as the mucus becomes thickened.26,31,32 Studies have shown that with gadolinium contrast, the mucocele does not enhance.3,30 CT imaging is best at demonstrating bony details and evaluating the bony expansion/erosion of bone; thus, it’s used preoperatively to outline the extent, location, and size of the mucocele.3,19 CT imaging in the axial/transverse and coronal planes are the optimal views for assessing bony expansion.32 Therefore, CT is the gold standard for the diagnosis of orbital mucocele.3,4,13,16,20 Management Although mucoceles are considered benign expanding lesions, they have a destructive potential to cause vision loss and to become infected.26,27 Furthermore, recovery of visual acuity is dependent on how quickly the patient receives treatment.12 Therefore, the standard of care is to treat patients promptly.11,35 The treatment options for orbital mucoceles have transformed in the last few decades with the availability of better technology. However, there are still a variety of opinions regarding the optimal approach to treatment of mucoceles.16 The unifying thought, despite the variety of opinions, is that each case is unique depending on the location, size, and extent of the mucocele; thus, the approach to removal or drainage of the mucocele is unique and no one surgical method can be applied to all orbital mucoceles.7,22,34 There are many

different surgical approaches for the treatment of orbital mucoceles; we will review the most common, which are two external approaches: the osteoplastic flap obliteration, and the Lynch-Howarth external incision, as well as the endoscopic marsupialization approach. Osteoplastic flap obliteration allows maximum exposure of the mucocele to completely remove it.35 A coronal incision is made posterior to the hairline, creating a flap, and then an incision through the glabella is made to enter the anterior wall of the frontal sinus.27,36 With the maximum exposure, the mucocele capsule is completely removed followed by reconstructive surgery where the intracranial and extracranial separation is reestablished.35,36 This method is superior in allowing visualization of the lesion, and in avoiding visible scars.20,27,35 Facial deformities returned to normal immediately following the surgery.2 However, the incision is large and the dissection of the forehead flap can cause scalp numbness, hair loss, flap hematoma, frontalis palsy, and has a greater risk of surgical morbidity compared to other techniques.20,37 Postoperatively, the radiographic imaging of the sinus can be unreliable and difficult to distinguish between an obliterated sinus and a recurrent mucocele.10,37 Lynch-Howarth external incision takes about 1 to 2 hours and may be chosen over the osteoplastic flap coronal incision, especially if the patient has frontal baldness, to avoid obvious scarring.2,8,38 The patient undergoes general anesthesia and an incision is made over the superomedial orbital rim to enter the medial orbit by completely removing the lateral bony wall to remove the mucocele.22,38 The mucocele is opened and drained, with samples taken for pathological analysis, and the mucocele lining may or may not be stripped from the sinus walls.38 Facial deformities are expected to return to normal immediately following the surgery.2 During the removal of the bone lateral to the frontal recess, there is subsequent soft tissue prolapse and facial scarring, which is a major disadvantage.22,38 Other disadvantages include possible worsening of diplopia from damage to the superior oblique muscle or from scarring of adjacent structures, and disinsertion of the medial canthal tendon.38 Despite the setbacks, this technique is still used when mucoceles are not accessible through other techniques or if there are other complicating factors, such as a mucocele secondary to tumors.8 Endoscopic approach with marsupialization has become the gold standard in treatment of orbital mucoceles.7,8,16 The procedure is 15 to 30 minutes in duration with the option of local anesthesia instead of general anesthesia, and is minimally invasive.2,16,37 Transnasally, an ethmoidectomy is performed to allow drainage of the mucocele, followed by decompression of the mucocele by suctioning out the contents. The contents are sent for culture.37 Then the mucocele is irrigated by saline, leaving

the mucocele lining intact with a marsupialization that is as wide as possible.8,16 If the mucocele marsupialization is not wide enough, the mucocele is prone to recur.7 Facial deformities take 2 to 3 months to return to normal for the endoscopic approach.2 Marsupialization has been advocated as early as the 1920s by Horwath, where the goal is to allow the mucocele to drain into the nasal cavity without recurrence and â&#x20AC;&#x153;by removing the floor of the mucocele, one practically makes the mucocele a part of the roof of the nose.â&#x20AC;?13,14,37 A 0% recurrence rate was first reported by Kennedy et al by exclusively treating ethmoid, frontal, and sphenoid mucoceles with the endoscopic technique.22 A retrospective study by Conboy et al reported the endoscopic group had a 9% recurrence rate compared to 26% in external/combined approach, and the overall recurrence rate was 15%.8 A large study of 108 mucoceles demonstrated a 0.9% recurrent rate at 4.7 years.39 External approach had a 19% recurrence rate.10 More advantages to the endoscopic approach are lower morbidity due to the option of local anesthesia and less invasiveness, the natural sinus drainage pathways are left intact, no visible skin scarring, low rate of recurrence.3,6,16,22,34 Also, histological analysis of the mucocele mucosa six months after marsupialization demonstrates conversion back to normal or near normal respiratory epithelium with transportation capacity, demonstrating no benefit in removing the mucocele lining.10,11,16,37,39 Furthermore, postoperative CT scans show partial or complete osteogenesis of the orbital walls that had been eroded away by the mucocele; the mucosa left intact by marsupialization allows neo-osteogenic osteogenesis to proceed.16 However, there are limitations to the endoscopic approach, as in the case of where the mucocele is not accessible endoscopically, when another lesion needs to be excised, when mucoceles are secondary to malignancy, when there is major sclerosis of the sinus floor, or when there is extensive bone erosion causing orbital or intracranial complications.7,8,22 In such complicated cases, one of the external approaches or a combination with endoscopic approach is performed.2,8,16,22 After treatment of mucoceles, there is no consensus on the timeline for follow up though there is a recommendation for lifetime follow up given the insidious and long period of development of mucoceles after trauma or surgery.19,39 Prognosis The visual prognosis following treatment is heavily dependent on the preoperative vision, duration of symptoms, and onset of symptoms.27,28 In a study by Morita, et al, patients with a visual acuity of better than 6/60 (20/200) showed marked improvement in vision, suggesting that preoperative visual acuity may be prognostic of postoperative outcome.12 Patients with no light perception did not recover their visual acuity.12,27,28 A study by Lee et al showed no visual improvement

Orbital Mucocele â&#x20AC;&#x201D; Chu Shinoda, Ilsen

postoperatively in patients that had visual disturbances longer than six months.40 Visual recovery is better when acuity loss is gradual compared to sudden.4 For patients who experience diplopia, complete recovery is promising if they show improvements in extraocular movement in the initial three months postoperatively.40 Complications Aside from surgical complications, the greatest the complication for mucoceles is infection. Mucoceles are filled with sterile mucin. But in the case where the mucocele becomes infected, it’s a mucopyelocele, which can have potentially lethal complications. The surrounding tissue becomes inflamed, causing fever, leukocytosis, erythema, and pain; it can also spread to cause meningitis, orbital cellulitis, cavernous sinus thrombosis, subdural empyema, orbital abscess, or osteomyelitis.5,15,27,28 Imaging on CT would demonstrate an uneven intrinsic density to the lesion compared to a homogenous lesion for a mucocele.30 The results of an investigation by Brook et al were that the bacteria flora of the mucopyelocele were 19% aerobic or facultative bacteria, 42% anaerobic, and 39% mixed aerobic and anaerobic, which is similar to that found in patients with chronic sinusitis.41 It’s suspected that the high prevalence of anaerobic bacteria is related to the poor drainage and increased intranasal pressure when the sinuses are inflammed.41 Given the aggressive nature of a mucopyelocele, the visual prognosis becomes more guarded, and treatment should be instituted as soon as possible.11,12,27 Furthermore, a mucocele can cause orbital and cranial complications by mass effect as it continues to expand. Mass effect on the orbit can cause proptosis, headache, pressure/pain, diplopia, increased intraocular pressure, choroidal folds, and ultimately vision loss.5,12,17,20,21,25,27-29 Mass effect on the cranium and introduce meningitis, cerebrospinal fluid leak, or a brain abscess and their own corresponding sequela of complications.11

CONCLUSION Though orbital mucoceles are rare, they are an important differential diagnosis for patients presenting with proptosis, orbital pain/pressure, diplopia, and a history of sinus surgery or facial trauma.25 It’s important to recognize signs and symptoms and follow up with the patient’s history in order to determine if CT imaging is appropriate and to make an appropriate referral to an otolaryngologist or neuro ophthalmologist. Prognosis for patients with orbital mucoceles is very promising, but they require prompt treatment due to the risk of conversion to mucopyelocele. ❏

9. 10.

11.

12. 13. 14.

15.

16.

17. 18.

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26.

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Chobillon M, Roger J. Relationship between mucoceles, nasal polyposis and nasalisation. Rhinology 2004; 43: 219-224. Iseh KR. Endoscopic and external surgical approach to paranasal sinus mucocele. J Surg Tech Case Rep 2010; 2(1): 49-53. Lee TJ, Li SP, Fu CH, et.al. Extensive paranasal sinus mucoceles: a 15-year review of 82 cases. Am J Otolaryngol 2009; 30(4): 234-238.

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Prasad KC, Alva B, Prasad SC, Shenoy V. Extensive sphenoethmoid mucocele: an endoscopic management. J Craniofac Surg 2008; 19(3): 766-771. Rajan KV, Santhi T. Frontoethmoidal mucocele with orbital and intracranial extension. Indian J Otolaryngol Head Neck Surg 2007; 59(4): 363-365. Sautter N, Citardi M, Perry J, Batra P. Paranasal sinus mucoceles with skull-base and/or orbital erosion: is the endoscopic approach sufficient? Otolaryngol Head Neck Surg 2008; 139(4): 570-574. Aggarwal S, Bhavana K, Keshri A, et al. Frontal sinus mucocele with orbital complications: management by varied surgical approaches. Asian J Neurosurg 2012; 7(3): 135. Conboy PJ, Jones NS. The place of endoscopic sinus surgery in the treatment of paranasal sinus mucoceles. Clin Otolaryngol 2003; 28: 207-210. Carr RB, Lau RKM, Dalley RW. CT and MRI of sinonasal mass lesions. Contemporary Diagnostic Radiology 2011; 34(4): 1-6. Khong JJ, Malhotra R, Wormald PJ, Selva D. Endoscopic sinus surgery for paranasal sinus mucocele with orbital involvement. Eye 2004; 18; 877-881. Fu C, Chang K, Lee T. The difference in anatomical and invasive characteristics between primary and secondary paranasal sinus mucoceles. Otolaryngol Head Neck Surg 2007; 136(4): 621-625. Morita S, Mizoguchi K, Iizuka K. Paranasal sinus mucoceles with visual disturbance. Auris Nasus Larynx 2010; 37(6): 708-712. Diaz MCG, Schmidt RJ. Ethmoid mucocele presenting as an orbital mass. Pediatr Emerg Care 2008; 24(12): 845-846. Tatla T, East C, Marucci DD, et al. Frontoethmoidal mucocele following pediatric craniofacial surgery. J Craniofac Surg 2014; 25(6): 2008-2012. Herndon M, McMains KC, Kountakis S. Presentation and management of extensive fronto-orbital-ethmoid mucoceles. Am J Otolaryngol Head Neck Med Surg 2007; 28: 145-147. Serrano E, Klossek JM, Percodani J, et.al. Surgical management of paranasal sinus mucoceles: a long-term study of 60 cases. Otolaryngol Head Neck Surg 2004; 131(1): 133-140. Capra GG, Carbone PN, Mullin DP. Paranasal sinus mucocele. Head Neck Pathol 2012; 6(3): 369-372. Obeso S, Llorente JL, Rodrigo JP, et al. Paranasal sinuses mucoceles. Our experience in 72 patients. Acta Otorrinolaringol Esp 2009; 60(5): 332-339. Koudstaa MJ, Van Der Wal KGH, Bijvoet HWC, et al. Post-trauma mucocele formation in the frontal sinus; a rationale of follow-up. Int J Oral Maxillofac Surg 2004; 33(8): 751-754. Rinna C, Cassoni A, Ungari C, et al. Fronto-orbital mucoceles: our experience. J Craniofac Surg 2004; 15(5): 885-889. Tseng CC, Ho CY, Kao SC. Ophthalmic manifestations of paranasal sinus mucoceles. J Chin Med Assoc 2005; 68(6): 260-264. Bockmuhl U, Kratzsch B, Benda K, Draf W. Surgery for paranasal sinus mucoceles: efficacy of endonasal micro-endoscopic management and long-term results of 185 patients. Rhinology 2006; 44(1): 62-67. Shkoukani MA, Caughlin BP, Folbe A, et al. Mucoceles of the paranasal sinuses: a 10-year single institutional review. J Otol Rhinol 2013; 2(1): 1-3. Lund VJ, Henderson B, Song Y. Involvement of cytokines and vascular adhesion receptors in the pathology of front-oethmoidal mucoceles. Acta Otolaryngol 1993; 113: 540-546. Wang TJ, Liao SL, Jou JR, Lin LLK. Clinical manifestations and management of orbital mucoceles: the role of ophthalmologists. Jpn J Ophthalmol 2005; 49: 239-245. Lee JT, Brunworth J, Garg R, et al. Intracranial mucocele formation in the context of longstanding chronic rhino-sinusitis: a clinicopathologic series and literature review. Allergy & Rhinology 2013; 4(3): 166-175. Loo JL, Looi ALG, Seah LL. Visual outcomes in patients with paranasal mucoceles. Am Soc Ophthal Plast Reconstr Surg 2009; 25(2): 126-129. Kim YS, Kim K, Lee JG, et al. Paranasal sinus mucoceles with ophthalmologic manifestations: a 17-year review of 96 cases. Am J Rhinol Allergy 2011; 25(4): 272-275.

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Rothstein J, Maisel RH, Berlinger NT, Wirtschafter JD. Relationship of optic neuritis to disease of the paranasal sinuses. The Laryngoscope 1984; 94(11): 1501-1508. Perugini S, Pasquini U, Menichelli F, et al. Mucoceles in the paranasal sinuses involving the orbit: CT signs in 43 Cases. Neuroradiology 1982; 23(3): 133-139. Tassel PV, Lee YY, Jing BS, De Pena C. Mucoceles of the paranasal sinuses: MR imaging with CT correlation. Am J Roentgenol 1989; 153(2): 407-412. Lloyd G, Lund VJ, Savy L, Howard D. Optimum imaging for mucoceles. J Laryngol Otol 2000; 114(3): 233-236. Morgan MA, Gaillard F. Paranasal sinus mucocele. Radiology Reference Article. Radiopaedia.org. Paranasal Sinus Mucocele (n.d.): n. pag. Radiopaedia.org. Web. 15 Mar. 2015. Shah A, Meyer DR, Parnes S. Management of fronto-ethmoidal mucoceles with orbital extension: is primary orbital reconstruction necessary?" Ophthal Plast Reconstr Surg 2007; 23(4): 267-271.

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Delfini R, Missori P, Iannetti G, et al. Mucoceles of the paranasal sinuses with intracranial and intraorbital extension: report of 28 cases. Neurosurgery 1993; 32(6): 901-906. Weitzel EK, Hollier LH, Calzada G, Manolidis S. Single stage management of complex fronto-orbital mucoceles. J Craniofac Surg 2002; 13(6): 739-745. Harel G, Balwally A, Lucente F. Sinus mucoceles: is marsupialization enough? Otolaryngol Head Neck Surg 1997; 117(6): 633-640. Lai PC, Jou JR, Hou PK. Transcaruncular approach for the management of frontoethmoid mucoceles. Br J Ophthalmol 2003; 87(6): 699-703. Har-El G. Endoscopic management of 108 sinus mucoceles. Laryngoscope 2001; 111(12): 2131-2134. Lee LA, Huang CC, Lee TJ. Prolonged visual disturbance secondary to isolated sphenoid sinus disease. Laryngoscope 2004; 114(6): 986-990. Brook I, Frazier EH. The microbiology of mucopyocele. Laryngoscope 2001; 111(10): 1771-1773.

Management of Ocular Emergencies 6th Revised Edition 6 chapters • 96 pages • 53 color plates • 16 figures • 12 tables • 13 Appendices • Subject Index Nontraumatic Red Eye Pre-Septal Cellulitis Chalazion Acute Dacryocystitis Blepharitis Dry Eye Allergic Conjunctivitis Adenoviral Conjunctivitis Bacterial Conjunctivitis Chlamydia Herpes Simplex Herpes Zoster Toxic Conjunctivitis Recurrent Corneal Erosions Subconjunctival Hemorrhage Phlyctenule Episcleritis Scleritis Corneal Ulcers Iritis Acute Angle Glaucoma

Traumatic Red Eye Corneal Abrasions Contact Lenses Ultraviolet Keratitis Chemical Injuries Corneal Foreign Bodies Intraocular Foreign Bodies Blow-Out Fracture Hyphema Blunt Trauma Injury Lacerations and Perforations

Diplopia Third Nerve Palsy Fourth Nerve Palsy Sixth Nerve Palsy Myasthenia Gravis Orbital Disease

Decreased Vision in a White Eye Vein Occlusion Artery Occlusion Retinal Detachment Maculopathy Vitreous Hemorrhage Optic Neuritis Ischemic Optic Neuropathy Cortical Blindness

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

Harold Stein, MD, FRCSC Professor University of Toronto

Rebecca Stein, MD Ophthalmology Residency Program University of Toronto

✁ Management of Ocular Emergencies: Order Form

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Orbital Mucocele — Chu Shinoda, Ilsen

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QUESTIONNAIRE Orbital Mucocele Hannah Chu Shinoda, OD; Pauline F. Ilsen, OD 1. ❑ ❑ ❑ ❑

Orbital mucoceles cause all of the following clinical signs and symptoms, EXCEPT: Proptosis Diplopia Optic atrophy Severe ocular pain

2. ❑ ❑ ❑ ❑

Paranasal mucoceles account for what proportion of expanding orbital lesions? 2.5-3.4% 4-8.5% 6.2-7.1% 7.4-8.1%

3. ❑ ❑ ❑ ❑

In the Case Report presented, the patient’s medical history include all of the following, EXCEPT: Emphysema Hepatitis C Carotid artery disease Alcohol abuse

Clinical and Refractive Optometry 27:3, 2016

COPE-APPROVED CE CREDIT APPLICATION FORM

In what percentage of mucocele cases does the cause remain undetermined? 10% 15% 30% 35%

5. ❑ ❑ ❑ ❑

What proportion of mucoceles occur in the anterior paranasal sinuses? 25% 45% 55% 61%

6. ❑ ❑ ❑ ❑

In osteoplastic flap obliteration, dissection of the forehead flap can cause all of the following, EXCEPT: Neuralgia Hair loss Frontalis palsy Scalp numbness

7. ❑ ❑ ❑ ❑

According to Conboy et al, what was the recurrence rate for orbital mucoceles 10% 15% 20% 25%

8. ❑ ❑ ❑ ❑

Mass effect on the orbit caused by a mucocele can cause all of the following, EXCEPT: Headache Pressure/pain Hemorrhage Choroidal folds

9. ❑ ❑ ❑ ❑

In which sinus do mucoceles most commonly occur? Frontal sinus Ethmoid Maxillary Sphenoid

10. ❑ ❑ ❑ ❑

All of the following statements about orbital mucoceles are true, EXCEPT: They are rare They are considered to be benign lesions They occur most commonly in people under age 20 They can be caused by head trauma

27:3, 16

4. ❑ ❑ ❑ ❑

Orbital Mucocele — Chu Shinoda, Ilsen

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Steven Mordukowitz entitled Ocular Signs of Multiple Myeloma. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 111 for complete instructions.

Ocular Signs of Multiple Myeloma Steven Mordukowitz, OD, FAAO

ABSTRACT A healthy 54-year-old male came in to our clinic for a routine exam. He had no ocular complaints but reported a number of systemic symptoms: a constant dry cough for two weeks, intermittent diarrhea with fever over the past 4 to 6 weeks and recurrent painful mouth sores that were slow to resolve. Dilated fundus exam revealed few scattered cotton-wool spots (CWS) and flame-shaped hemorrhages in both eyes along with a small Roth spot hemorrhage present in his right eye below the optic nerve head. A complete blood work-up along with a chest X-ray were ordered. Chest X-ray revealed bilateral lower lobe pneumonia. Complete blood count (CBC) indicated anemia while a comprehensive metabolic panel (CMP) revealed elevated serum proteins and globulins. Subsequent blood tests indicated a rapidly progressing anemia, cytopenia and thrombocytopenia which are highly suggestive of some underlying hematologic disorder. Additional blood testing using serum protein electrophoresis (SPEP) and immunofixation illustrated a positive M-spike and elevated IgG lambda monoclonal proteins. Bone marrow biopsy confirmed a diagnosis of multiple myeloma.

INTRODUCTION Multiple myeloma (MM) is the most common plasma cell dyscrasia. Multiple myeloma is caused by abnormal plasma cells that multiply uncontrollably, producing incomplete, non-functional antibodies that are incapable of fighting off invading micro-organisms. This results in more frequent infections. In addition, these abnormal plasma cells can infiltrate into the bone marrow, bones and other tissues, producing anemia/cytopenia, pathologic S. Mordukowitz â&#x20AC;&#x201D; Senior Staff Optometrist, Bronx Veterans Administration Medical Center, Bronx, NY Correspondence to: Dr. Steven Mordukowitz, Bronx VAMC, 130 West Kingsbridge Rd, Bronx, NY 10468; E-mail: steven.mordukowitz@va.gov This article has been peer reviewed.

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fractures and impairment of organ function (i.e., renal failure). Our patientâ&#x20AC;&#x2122;s systemic symptoms suggest that he is probably immunocompromised. The cotton-wool spots (CWS) and retinal hemorrhages (in the absence of elevated blood pressure) are highly indicative of anemic retinopathy caused by some underlying systemic disease process.

CASE REPORT A 54-year-old male in good physical health came in for an eye exam. He reported that a close relative had recently been diagnosed with glaucoma. Patient was 6/6 (20/20) at distance in each eye without correction and required only reading glasses for presbyopia. Our patient reported a number of systemic symptoms: 1) A constant dry cough for the past two weeks; 2) Intermittent bouts of diarrhea with fever over the past 4 to 6 weeks; and 3) Reoccurring, painful canker sores in the mouth which were slow to resolve. Intraocular pressures (IOPs) were 15 mm in each eye. Extraocular muscle function was normal with no strabismus or ophthalmoplegia. There was no afferent pupillary defect or proptosis present in either eye. Anterior chamber angles were deep and quiet with clear corneas and crystalline lenses. Dilated fundus exam revealed C/D ratios of 0.3 with a few CWS and small flame-shaped retinal hemorrhages in the posterior poles of both eyes (Figs. 1-4). A Roth spot hemorrhage was also present in the right eye just below the optic nerve head. A complete blood work-up was ordered which included a complete blood count (CBC) and blood chemistry profile. Patient had an elevated ESR (119) with a blood pressure of 120/70. A chest X-ray was also ordered which revealed pneumonia in both lower lobes. Patient was referred to a pulmonologist for evaluation and treatment. CBC revealed significantly reduced hemoglobin (Hb) levels, red blood cell (RBC), white blood cell (WBC) counts and platelets. Blood chemistry profile illustrated elevated serum proteins and globulins with significantly reduced albumin/globulin (A/G) ratio (Tables I-III). It is unusual for a fairly young, healthy adult to develop pneumonia without some underlying systemic etiology. His systemic symptoms suggest that he is probably immuno-compromised from some underlying disease process. The CWS and retinal hemorrhages are usually indicative of hypertension or an anemic process.

Fig. 1 Cotton wool spot (CWS) in OD post pole.

Fig. 2 Close-up of CWS and flame hemorrhages off superior arcades.

Fig. 3 CWS near ONH in OS post pole.

Fig. 4 OCT of CWS shows increase thickness of retinal nerve fiber layer.

With a diagnosis of anemia it is imperative to perform a full systemic work-up to determine its etiology. Initial CBC results that I ordered revealed reduced hemoglobin (Hb), hematocrit (Hct), RBC count and platelets. Blood chemistry profile showed elevated total serum protein and globulin levels with reduced albumin and albumin/ globulin (A/G) ratio. Subsequent CBC ordered by the pulmonologist and later hematologist showed a rapidly progressive decreased Hb, Hct, RBC, WBC and platelet count within a span of a few weeks. In addition, blood chemistry profile revealed progressively increasing total serum proteins and globulin levels with reduced albumin and A/G ratios also occurring in a few weeksâ&#x20AC;&#x2122; time. The rapid onset of anemia, neutropenia and cytopenia along

with elevation of total serum proteins and gamma globulins indicates the development of a more serious hematologic condition. In addition to the elevated blood proteins and gamma-globulins, a positive M-spike and IgG lambda monoclonal protein was detected. His serum IgG indicated hyperglobulinemia, measuring 10,701 mg/dL. The patient was referred to a hematologist at our hospital who repeated the blood work, performed a bone marrow biopsy, skeletal survey and bone density scan. Results of the skeletal survey on our patient indicated no suspicious lytic lesions or fractures. Bone density scan was also performed to establish a baseline prior to beginning treatment with glucocorticoids and other agents. In

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Table I CBC reveals reduced erythrocytes, hemoglobin (Hb), hematocrit (Hct) and platelets. Test/Profile

Result

CBC with Differential/Platelet Profile WBC RBC Hemoglobin Hematocrit MCV MCH MCHC RDW Platelets Neutrophils Lymphs Monocytes Eos Basos Immature Cells Neutrophils (Absolute) Lymphs (Absolute) Monocytes (Absolute) Eos (Absolute) Baso (Absolute) Immature Granulocytes Immature Granulocytes (Absolute) NRBC Hematology Comments:

7.1 3.53 11.7 35.7 101 33.1 32.8 14.1 122 63 21 15 1 0 DNR 4.4 1.5 1.1 0.1 0.0 0 0.0 DNR DNR

Comp. Metabolic Panel (14) Profile Glucose, Serum BUN Creatinine, Serum eGFR if NonAfrican Am

101 17 1.05 80

our patient, the bone density scan of the appendicular spine was normal. Mild osteopenia of the patient’s left hip and femoral neck was detected. Our patient’s kidney function was normal as indicated by normal creatinine and blood urea nitrogen (BUN) levels. Bone marrow biopsy confirmed a diagnosis of MM with abnormal plasma cells making up 60% to 70% of the plasma cells. Other histologic findings revealed reduced hematopoietic elements with mild neutropenia and eosinophilia. Monoclonal plasma cells making up 10% of cells tested positive for cytoplasmic lambda chains. Congo red stain ruled out the presence of amyloidosis. In spite of the elevated IgG and serum light chain levels, our patient’s prognosis was good since his kidney function was normal and he did not display any lytic lesions on the skeletal survey. Our patient began treatment for MM with lenolidamide (Revlimid®, Celgene) 25 mg daily with initially intravenous bartezomid (Velcade®, Millennium Pharmaceuticals), which lowered his IgG to 5650 mg/dL, and later subcutaneous

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H/L

L L L H H

Range

Units

Test Sit

4.0-10.5 4.14-5.80 12.6-17.7 37.5-51.0 79-97 26.6-33.0 31.5-35.7 12.3-15.4 140-415 40-74 14-46 4-13 0-7 0-3

x10E3/uL x10E6/uL g/dL % fL pg g/dL % x10E3/uL % % % % %

1.8-7.8 0.7-4.5 0.1-1.0 0.0-0.4 0.0-0.2 0-2 0.0-0.1

x10E3/uL x10E3/uL x10E3/uL x10E3u/L x10E3/uL % x10E3/uL

RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN RN

65-99 6-24 0.76-1.27 >59

mg/dL mg/dL mg/dL mL/min/1.73

RN RN RN RN

Velcade; once his elevated blood proteins and abnormal IgGs started to come down. Oral dexamethasone, 40 mg pulse dose (taken on one day) was also prescribed. In addition, once monthly intravenous treatment with zoledronic acid (Zometa®, Novartis) was given along with daily Vitamin D 1000 IU tablets, to protect the patient’s bones from the corticosteroid and the myeloma (Zometa was later reduced to every three months, due to the patient’s relatively healthy physical condition). Due to the potential side effects of uncontrolled clotting from the chemotherapeutic agents, the patient was instructed to take aspirin 81 mg daily. The patient returned for ocular examination two weeks later, after starting treatment for MM. His IOPs were 16 and 13 mmHg. Dilated fundus exam revealed a small flameshaped hemorrhage in his right eye, just below his optic nerve head, where the Roth spot hemorrhage was previously seen. A small flame-shaped hemorrhage was also present in his left eye, below the optic nerve head. There were no signs of any lens opacities in either eye.

Table II Repeat labs illustrated significantly elevated serum proteins and reduction in RBCs, Hb, Hct and platelets. Performing Laboratory Information: TBR Quest Diagnostics One Malcolm Avenue Teterboro NJ 07608 Laboratory Director: Janet Piscitelli, M.D. CLIA No.: 31D0696246 List of Results Printed in the Out of Range Column: Sodium 130 L 135-146 mmol/L 30 L >=40 mg/dL HDL Cholesterol Protein, Total, Serum 12.1 H 6.1-8.1 g/dL Albumin 3.3 L 3.6-5.1 g/dL Globulin, Calculated 8.8 H 1.9-3.7 g/dL A/G Ratio 0.4 L 1.0-2.5 LD 116 L 120-250 U/L Iron, Total 36 L 45-170 mcg/dL TIBC 233 L 250-425 mcg/dL Transferrin Saturation 15 L 20-50 % Protein, Total, Serum 12.1 H 6.1-8.1 g/dL Alpha-1-Globulin 0.42 H 0.10-0.30 g/dL Gamma Globulin 5.77 H 0.60-1.60 g/dL M-Spike 5.24 H Negative g/dL Immunofixation, Serum Detected Not Detected RBC 3.27 L 4.20-5.80 Mill/mcL Hemoglobin 10.7 L 13.2-17.1 g/dL Hematocrit 32.4 L 38.5-50.0 % Platelet Count 109 L 140-400 Thous/mcL ESR Westergren 119 H 0-20 mm/hr Confirmed by repeat analysis

Our patient returned for monthly follow-ups to check his IOPs, anemic retinopathy and any signs of lens opacities secondary to dexamethasone treatment. His anemic retinopathy resolved with his medical treatment. His IOPs remained normal with no change in C/D ratios. He developed only minor peripheral lens vacuoles which did not progress with time. After about six months of treatment, the patient’s hematologist changed his medications to oral pomalidomide (Pomalyst®, Celegene) and intravenous carfilzomib (Kyprolis®, Onyx Pharmaceuticals) due to a plateauing of his IgG levels at the 5466 mg/dL level. Approximately two months later, our patient had another bout of pneumonia. He developed a fever and cough shortly after undergoing intravenous Kyprolis treatment. Our patient had been prone to develop cytopenia, neutropenia, anemia and thrombocytopenia from his oral and intravenous chemotherapeutic agents. For this reason, he had been given periodic infusions of whole blood, subcutaneous injections of darbepoetin (Aranesp®, Amgen), an erythropoietin analogue; and felgastrin (Neupogen®, Amgen), which is granulocyte-colony stimulating factor (G-CSF), when his Hb or WBC count was extremely low. Our myeloma patient was diagnosed with a combination of bacterial and viral pneumonia secondary to influenza and strep pneumonia infection. He was admitted for a four-day hospital stay to treat his pneumonia.

After our patient was released from the hospital he was instructed by his hematologist that he get ready for stem cell harvesting in preparation for a stem cell transplant, which is the most effective treatment for his myeloma. Our patient underwent two more cycles of chemotherapy with Pomalyst and Kyprolis, along with a reduced dose of dexamethasone (16 mg per week), under the direction of a myeloma specialist. This was done to lower his abnormal IgGs and free lambda serum light chains prior to transplant, for more effective results. After the transplant our patient returned to his myeloma specialist for re-evaluation. All chemotherapeutic drugs and corticosteroids were discontinued. The patient was prescribed prophylactic acyclovir (400 mg b.i.d.), to prevent herpes zoster infection, along with vitamin D supplements. His myeloma panel was retested one month later and then again at three months. In addition, at the three-month post-transplant visit, another bone marrow biopsy and a PET Scan (from the base of his skull to his mid-thigh region) was performed. Results of the PET Scan revealed no lytic lesions. However, repeat bone marrow biopsy indicated abnormal plasma cells making up about 30% of the total plasma cell volume. Bone marrow biopsy results indicated reactivation of MM and the need to continue with treatment. Since our patient’s myeloma was getting resistant to the chemotherapy treatment, he was switched to an immunotherapy drug study. Immunotherapy is the newest treatment modality for MM, where it specifically targets the myeloma cells without causing any significant cytotoxicity to the normal host cells. This patient will be returning to our clinic for periodic monthly follow-up exams.

DISCUSSION Epidemiology Multiple myeloma affects mainly older patients with its incidence increasing with age. Multiple myeloma accounts for 10% of all hematologic cancers. It is the most common plasma cell dyscrasia. The median age of patients with this disease is 68 years old for men and 70 years for women. The male to female ratio is about 3:2. The lifetime risk of getting myeloma is 1 in 161 (0.62%). In the United States, African-Americans are twice as likely as whites to have myeloma, with a ratio of 2:1. Myeloma is rare in people of Asian descent with an incidence of 1 to 2 cases per 100,000 people.1,2 Today, due to all of the advances in myeloma research, drugs and treatment, patients are living over 20 years with this disease. Multiple myeloma is now a treatable condition, like diabetes or hypertension, provided it is diagnosed early and treated properly.

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Table III Subsequent blood tests indicated a rapidly progressing anemia, cytopenia and thrombocytopenia over a short period of time. Test Name CBC/PENTRA WBC RBC HGB HCT MCV MCH MCHC PLT RDW MPV LYMPH# LYMPH% MONOS# MONOS% NEU% NEU# EOS% EOS# BASO% BASO# ALY# ALY% LIC% LIC# [A] RETIC COUNT RETIC% RETIC# RETIC LOW RETIIC MED RETIC HIGH MRV IMMATURES COR. RETIC CNT MFI%

Result

Units

Flag

3.9 2.81 9.3 28.5 101 32.9 32.5 86 13.1 6.5 1.56 39.6 0.24 6.2 51 2.02 2.6 0.10 0 0.02 0.1 3.1 1 0.0

10^3/mm^3 10^6/mm^3 g/dL % nm^3 pG/cell g/dL 10^3/mm^3 % nm^3 K/UL % K/UL % % # % # % # # % % #

Low Low Low Low High High

0.87 0.024 95.70 4.3 0.00 107.0 0.05 0.53 7.1

% #

Low

High

um^3 % Low %

Reference Range Run by: RT on 9/11/2013 4.5-10.1 3.40-5.50 10.8-15.5 32.5-47.6 81-99 26.3-32.8 31.2-34.1 155-366 12.6-16.8 6.0-10.0 0.40-4.20 13.0-50.0 0.10-0.70 3.1-9.6 41-75 2.10-6.30 0.0-4.9 0.00-0.40 0-3 0.00-0.12 0.0-0.2 0.0-2.0 0-2 0.0-0.2 Run by: PS on 9/12/2013 0.50-2.50 0.020-0.100 65.00-97.00 0.0-40.0 0.00-10.00 0.0-9999.0 0.00-0.60 0.75-2.30 5.0-30.0

Etiology The cause of MM is unknown and it does not have a genetic etiology. It has been speculated that patients exposed to certain environmental toxins or radiation are more prone to develop the disease.

and urine of all myeloma patients with IgG being the most common immunoglobulin affected, followed by IgA, IgD and IgE.

Pathophysiology In MM, a single plasma cell multiplies uncontrollably; resulting in a group of identical cells (“clones”) producing a large quantity of single chain antibodies (known as monoclonal antibodies [“M-proteins”]), or “free-floating” light or heavy chains. With these monoclonal gammopathies, the antibodies produced are incomplete since they contain only a light or heavy chain (not both). These monoclonal antibodies are totally ineffective in fighting invading pathogens, therefore resulting in more frequent infections in the affected patient (Fig. 5). Hypergammuloglobulinemia along with M-protein is present in serum

Monoclonal Gammopathy: Proliferating plasma cells produce structurally abnormal or incomplete immunoglobulins (M-proteins). Complete immunoglobulin molecules have large molecular weights and are mainly restricted to plasma or extracellular fluid. They are only found in the urine in cases of glomerular damage. Incomplete M-proteins (i.e., free light chains) have a much lower molecular weight and are freely filtered by normal functioning kidneys. In myeloma patients, an accumulation of free light chains in the plasma will occur due to significant over-production of immunoglobulins or renal failure.

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Types of Hypergammagobulinemia

Hypercalcemia (due to destruction of bone and release of calcium) • Infections • Impairment of visceral organ function (rare) •

Signs of Circulating Monoclonal Proteins Include: • Renal failure (due to deposition of light chains [BenceJones Proteins], hypercalcemia or amyloidosis) • Hyperviscosity syndrome (due to large amounts of circulating immunoglobulins [most commonly IgM]) • Bleeding (due to interference of monoclonal proteins with hemostatic system) • Neuropathies (due to nerve compression from vertebral/ skeletal fractures and amyloid or light-chain deposition in perineural and perivascular tissues).

LAB TESTS

Fig. 5 Complete immunoglobulin. Each immunoglobulin contains 2 heavy and 2 light chains, joined by disulfide bonds. [* = antigen binding sites]

Polyclonal Gammopathy: Involves an over-production of all classes of immunoglobulins. This can occur in many conditions due to exaggeration of the normal immune response from exposure to certain antigens. Possible etiologies include: chronic infection, liver disease, connective tissue or hematologic disease. Common Signs of Multiple Myeloma A good abbreviation for the most common signs of MM is the “CRAB” pneumonic: C = elevated serum Calcium, R = Renal failure, A = Anemia, B = Bone lesions. Not all of these signs need to be present to diagnose MM. In the early stages of this disease, like in our patient, only anemia may be present. Both MM and plasmacytomas can result in infiltration of the bone marrow or tissues by malignant clones of plasma cells or elevated amounts of monoclonal proteins. Common symptoms include fatigue, weakness, back pain, muscle aches and recurrent infections. Signs of Plasma Cell Infiltration in the Bone Marrow or Tissues Include: • Anemia and cytopenia • Spinal cord compression (a medical emergency) • Bone pain with pathologic fractures (due to osteolytic destruction of bones, via activation of osteoclasts which resorb bone, get resulting bone breakdown and appearance of “punched-out” lytic lesions)

Serum Protein Electrophoresis (SPEP) Detects abnormal plasma protein in serum by separating plasma proteins into several groups (Fig. 6). Quantifies M-protein but needs to be done with serum Immunofixation to determine the monoclonality and immunoglobulin heavy or light chain class. This test is ordered when the following conditions are present: anemia and cytopenia, hypercalcemia, renal insufficiency or proteinuria, immunoglobulin deficiency, elevated total serum protein or increase albumin-globulin gap.3 Immunofixation Uses antibodies directed against heavy and light chain compounds to differentiate monoclonal vs polyclonal elevation in immunoglobulins and the type of immunoglobulin involved (i.e., IgG-kappa). Determines the type and quantity of abnormal immunoglobulins detected by SPEP. Figure 7 illustrates how this test differentiates: • Elevated monoclonal vs. polyclonal gammaglobulins. • Identifies class of monoclonal protein and light chains. • Gives accurate quantification of monoclonal immunoglobulins. • Other causes of M-bands on SPEP (i.e., hyperfibrinogenemia) Serum Free Light Chains (FLC) This is a sensitive antibody-based system that can detect small amounts of monoclonal free light chains (kappa or lambda) in serum or urine. This test is useful for myeloma patients that produce only free light chains (called BenceJones proteins in the urine) usually in a concentration too low to be detected by immunofixation. Serum FLC assay is a more sensitive test for detecting monoclonal free light chains than urine immunofixation.

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ABNORMAL M-SPIKE: monoclonal immunoglobulin

NORMAL

a1 a2

albumin

POLYCLONAL IMMUNOGLOBULIN Chronic inflammation

a1 a2

albumin

Fig. 6 Serum protein electrophoresis

Fig. 7 Immunofixation: this image represents IgGK monoclonal gammopathy.

24-Hour Urine Protein Secretion and Electrophoresis (UPEP) Uses electrophoresis to separate urine proteins and allows for detection and quantification of M-protein in the urine. Must be done in combination with urine immunofixation to differentiate monoclonal vs. polyclonal elevated immunoglobulins and the type of light-chain involved. Important to detect the presence of nephrotoxic concentrations of urinary light chains and to monitor for progression and response to therapy in patients with urinary monoclonal proteins.

Bone Marrow Aspiration and Biopsy Checks for any cytologic abnormalities. A plasma cell count greater than 10% of the bone marrow is diagnostic of MM.

Urine Immunofixation Uses antibodies directed against the light chain components to differentiate a monoclonal vs. a polyclonal elevation in immunoglobulins and to determine the type of light chain involved. This is the preferred method to identify monoclonal proteins in the urine. More sensitive than UPEP but cannot estimate the size of the monoclonal protein.

Hemoglobin <10 g/dL One must determine if the anemia is normocytic (i.e., composed of normal sized RBCs) or normochromic (i.e., normal concentration of Hb in RBCs) vs macrocytic. Different causes of anemia that need to be ruled out include: bone marrow replacement by abnormal plasma cells, immune hemolysis or bleeding.

Complete Skeletal Survey Checks for lytic lesions in all bones including the skull, axial skeleton, proximal long bones of the upper and lower extremities (Fig. 8).

PET/CT Scan (F-18 FDG Positron Emission Test/CT Imaging) Uses a radioactive drug (tracer) to evaluate tissue or organ function. This tracer (i.e., F-18 fluorodeoxyglucose;

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Fig. 8 Lytic â&#x20AC;&#x153;moth-eatenâ&#x20AC;? appearing skull lesions in a multiple myeloma patient.

Fig. 9 Band keratopathy in a patient with hypercalcemia.

FDG) collects in areas of the body with greater levels of metabolic activity which often corresponds to disease. (“Hot Spots” refers to areas with greater or brighter signal intensity where large amounts of tracer have accumulated, corresponding to areas with higher metabolic activity.) PET Scans are useful in the diagnosis of cancer, heart disease or brain disorders (i.e., tumors, seizures, Alzheimers’ disease or CVA). They are often used in MM patients to evaluate the skeletal system for any lytic lesions or plasmacytomas. Other Tests • CT (for local accumulation of plasma cells in bone or soft tissues) • MRI (detects spinal cord or nerve root compression) • Tissue Biopsy (for suspected plasmacytoma) • Serum Viscosity (for symptoms of hyperviscosity syndrome)

OCULAR SIGNS OF MULTIPLE MYELOMA Multiple myeloma can affect all ocular tissues, including the cornea, conjunctiva, lens, uvea, retina and orbit. It can also cause neuro-ophthalmologic symptoms as well. Cornea Although rare, MM can cause the development of various deposits in different layers of the cornea. Small crystallike, paraprotein deposits (most commonly occurring with elevated IgG) can be observed in Bowman’s membrane or the corneal stroma. In addition, Band keratopathy can also develop from systemic hypercalcemia (Fig. 9). Increase copper deposition in Decemet’s membrane has been known to occur in patients with IgG MM, due to abnormal immunoglobulin binding copper and depositing these

Fig. 10 Close-up of pars plana cyst.

Reprinted with permission from: The ASRS Retina Image Bank. Norman Bryer, MD. The Peripheral Retina in Profile. Retina Image Bank. Nov 2012 (file# 2090). © The American Society of Retina Specialists (ASRS).

precipitates in the cornea or lens capsule. Unlike Wilson’s disease, these deposits generally occur in the central cornea, potentially affecting vision.4 Conjunctiva A crystalline-like material can also deposit in conjunctival connective tissue. Malignant plasmacytomas can also develop in conjunctival tissue. Lens Anterior and posterior deposits on the lens capsule have been observed, including copper in addition to paraproteins. Uvea Aggregates of plasma cells can accumulate on the iris and choroid. Plasma cells can also be observed floating in the anterior chamber or attached to the posterior cornea.5,6 Cysts of the ciliary epithelium have been noted on histologic study in 33% to 50% of myeloma patients.7 These cysts can range in size and number. Pars plana cysts can become confluent and large, while pars plicata cysts tend to remain small and spherical. These cysts tend to be translucent, therefore making them harder to observe on clinical exam. Histologically these cysts are formed by the separation of the pigmented and non-pigmented layers of the ciliary epithelium and are filled with plasma cells, macrophages, melanin granules and protein-like material (i.e., abnormal gamma-globulins; Fig. 10). Retina Myeloma patients with retinopathy generally have significantly reduced hemoglobin and platelet counts. All types of retinal hemorrhages can occur with hemoglobin levels below 8 g/dL or platelets under 50,000/uL. The presence of retinopathy is not associated with a worse prognosis of

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Other signs of orbital involvement include: conjunctival chemosis, choroidal folds, ptosis, orbital swelling and venous engorgement at the optic disc. Diagnosis of orbital invasion can be confirmed by CT scan with coronal imaging of the brain and orbits.

NEURO-OPHTHALMOLOGIC Multiple myeloma can cause a number or neurologic signs including: Papilledema Is the result of elevated intracranial pressure caused by expansion of plasmacytomas in the skull, which can compress brain tissue or cause obstruction of the dural venous sinuses.11

Fig. 11 Roth spot hemorrhages in another patient with anemic retinopathy.

MM. The retinopathy generally improves with systemic treatment. Common signs of retinopathy include: discrete flame and Roth spot hemorrhages, CWS and microaneurisms.8 The Roth spot hemorrhage, a common sign in many blood dyscrasias, is composed of a fibrin-platelet thrombus that arises at the site of retinal capillary damage (Fig. 11).9 Hyperviscosity syndrome, although rare with MM, can occur with signs similar to Waldenstrom macroglobulinemia. Signs of hyperviscosity include: dilated and tortuous retinal veins, superficial and deep retinal hemorrhages along with retinal edema. Central retinal and branch retinal vein occlusions, serous or exudative retinal detachments, subhyaloid and vitreal hemorrhages can also develop. Orbit Orbital signs are usually the first manifestation of ocular involvement in the majority of myeloma patients. The most common orbital sign is a unilateral, slowly progressing proptosis that develops over several weeks or months with symptoms of pain, diplopia and reduced acuity. Restriction of eye movements in all fields of gaze, especially abduction, also occurs due to an infiltration of myeloma plasma cells into the adjacent muscles. Plasmacytomas can also arise in soft tissues or surrounding bones with secondary orbital invasion.10 The orbital roof and frontal bones are often affected, resulting in proptosis and downward displacement of the globe. Myeloma tumors can affect the soft tissues of the orbit (i.e., lacrimal gland) and on rare occasions extend upwards from the orbital floor.

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Ocular Cranial Nerve Palsies Of the cranial nerves palsies, the VI nerve is most commonly affected, due to its proximity to the skull base and its long extradural course. VI nerve palsies can be unilateral or bilateral, with unilateral palsy more common. In addition, VI nerve palsies in combination with other cranial nerve palsies are more prevalent than single isolated palsies, due to compression of the basal skull area by plasma tumors. Optic Nerve Involvement Is the result of optic nerve compression or infiltration of plasma cells into the optic nerve, resulting in optic nerve swelling. This can cause variable visual defects including: central scotomas, marcus-gunn pupils and varying degrees of visual acuity loss. Visual Field Defects An optic chiasmal syndrome can be produced by a plasmacytoma arising from the tuberculum sellae that appears like a pituitary adenoma. Homonymous visual field defects in myeloma can result from compression or infiltration of the post-chiasmal pathway by myeloma cells or from secondary effects of the disease (i.e., occipital infarction or infectious complications).

DIFFERENTIAL DIAGNOSIS OF ROTH SPOT HEMORRHAGES Multiple Myeloma Can cause all types of retinal hemorrhages, including flame-shaped, Roth spots, CWS, and microaneurisms; especially when the CBC reveals hemoglobin levels less than 8 g/dL and platelets under 50,000/uL. Bacterial Endocarditis (Infective Endocarditis) Involves inflammation and infection of the inner surface of the heart (endocardium). It can affect heart valves or mechanically implanted devices (i.e., pacemaker, defibrillator, etc.). Ocular signs can include: retinopathy, uveitis,

vitritis or endophthalmitis secondary to thrombosis or septic emboli. Occlusion of small arterioles can result in CWS, while occlusion of larger retinal arteries can result in CRAO or BRAO. The Roth spot hemorrhage can therefore be an early sign of endogenous endophthalmitis and can result in serious complications, including stroke or death. Leukemia In this condition the retina is involved more than any other ocular tissue. Retinal signs include capillary rupture with hemorrhages and extravascular exudates of leukocytes in all layers of the retina, especially the inner retinal layers. This results from endothelial ischemia secondary to anemia, direct occlusion of capillaries by leukemia cells or plateletfibrin aggregates, or sludging from hyperviscosity.12 Vitamin B12 Deficiency Anemia Can cause megaloblastic anemia* which often requires RBC and platelet transfusions. Vitamin B12 deficiency often results from poor diet or alcohol abuse. Pathophysiology involves destruction of vascular endothelial cells due to anemia along with disturbances in clotting sequence as a result of reduced platelets. Retinal lesions commonly occur when both severe anemia and thrombocytopenia are present.13,14 (*Megaloblastic anemia is a type of macrocystic anemia due to reduced DNA synthesis secondary to Vitamin B12 or folic acid deficiency. It tends to produce oversized, irregular-shaped, more fragile, nucleated RBCs.) Other Causes of Roth Spots • HIV infection • Other blood dyscrasias or metastatic cancers • Severe anemia or anoxia • Carbon monoxide poisoning • prolonged intubation with anesthesia • pre-eclampsia • Intracranial hemorrhages from AV malformations or aneurysms • Acute reduction in IOP after trabeculectomy

DIFFERENTIAL DIAGNOSIS OF PLASMA CELL DISORDERS Monoclonal Gammopathy of Unknown Significance This is the most common monoclonal gammopathy. In this condition the patient is asymptomatic without any cytopenia, lytic lesions, or any organ impairments. Some patients develop MM or related disorders, with median onset within 10 years. This condition is a diagnosis of exclusion after all other possible monoclonal gammopathies have been ruled out. This is generally a benign condition that does not require treatment.

Lab tests: a positive monoclonal gammopathy with bone marrow plasma cells less than 10%. Waldenstrom’s Macroglobulinemia This is a low grade lymphoma with increase plasma cell secretion of IgM monoclonal protein. Being a large immunoglobulin, IgM in large amounts can cause hyperviscosity syndrome. Bone disease and renal failure are uncommon, therefore skeletal surveys and 24 hour urine collections are not required. Typical signs of WM include: a) Bone marrow infiltration: this causes fatigue and weakness, due to anemia; along with reoccurring infections, due to reduced WBCs b) Visceral Organ Infiltration: results in lymphadenopathy, liver and spleen enlargement, as well as cutaneous lesions. Lab tests: SPEP with immunofixation, increase serum viscosity, biopsy of enlarged lymph nodes, CT of chest, abdomen and pelvis, and bone marrow biopsy, revealing elevated IgM. Amyloidosis A rare condition where patient’s organs are infiltrated by fibrillar deposits of amyloid proteins. Most patients do not have coexisting myeloma (only 15% with MM). Prognosis is poor; most patients die within 1 to 2 years of diagnosis. Lab tests: no specific blood test, scan or radiograph available; diagnosed from biopsy of gingival or rectal tissue, subcutaneous fat, kidney or bone marrow. Pathophysiology: Abnormal antibodies are produced by cells in the bone marrow that cannot be broken down, unlike normal antibodies. These abnormal antibodies accumulate in the blood and then deposit in tissues as amyloid, therefore interfering with organ function. Types of Amyloidosis Primary Amyloidosis (Monoclonal light chain amyloidosis) • Causes deposition of whole or fragments of immunoglobulin light chains (produced by clonal plasma cells) into various organs and tissues, leading to damage. • 15% are associated with MM. Can affect many areas of the body Secondary Amyloidosis • Occurs with chronic infection or inflammatory disease. Mainly affects the kidneys, spleen, liver and lymph nodes. Hereditary (Familial) Amyloidosis • Inherited condition that affects the liver, heart, kidneys and nerves. Dialysis-related Amyloidosis (DRA) • Most commonly affects patients on long-term dialysis. Results in proteins from the blood being deposited in joints or tendons.

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CONCLUSION As primary eye care providers, optometrists must be cognizant of patient’s systemic symptoms as possible signs of systemic disease that can affect their visual system. Our patient in this report displayed significant signs and symptoms of immunodeficiency that manifested in the eyes in the form of anemic retinopathy. Systemic work-up and lab testing revealed a potentially lifethreatening hematologic disease. It is imperative that all eye care practitioners followup with MM patients frequently, since MM can affect all ocular tissues; including the orbits, retina, uvea, cornea, lens and neuro-ophthalmologic systems. With newer treatments emerging involving immunotherapy, MM patients are now living longer with their disease and will require constant monitoring of their visual system. It is important that all optometrists become familiar with the interpretation of the various hematologic lab tests (i.e., CBC, CMP, etc.) and imaging procedures, to properly diagnose and co-manage these patients with their hematologists or primary care physicians. ❏

5. 6.

7. 8. 9.

10. 11. 12.

13.

14.

Hettinga YM. Anterior uveitis: a manifestation of graftversus host disease. Ophthalmology 2007; 114(4): 794-797. Westeneng AC. Ocular graft-versus host disease after allogenic stem cell transplantation. Cornea 2010; 29(7): 758-763. Baker TA. Ocular findings in multiple myeloma: a report of two cases. Arch Ophthalmol 1974; 91: 110-113. Pomeranz H. Roth spots. Arch Ophthalmol 2002; 120 (11): 1596. Priluck JC. Spectral-domain optical coherence tomography of Roth spots in multiple myeloma. Eye (London) 2012; 26(12): 1588-1589. Adkins JW. Plasmacytoma of the eye and orbit. Int Ophthalmol 1996-1997; 20(6): 339-343. Biousse V. Anemia and papilledema. Am J Ophthalmol 2003; 135(4): 437-446. Perrone G, Hideshima T. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia 2009; 23(9): 1679-1686. Zehetner C. White centered retinal hemorrhages in Vitamin B12 deficiency anemia. Case Rep Ophthalmol 2011; 2(2): 140-144. Aisen ML. Retinal abnormalities associated with anemia. Arch Ophthalmol 1983; 101(7): 1049-1052.

REFERENCES

ADDITIONAL READING

•

Caers J. Multiple myeloma an update on diagnosis and treatment. Eur J Hematol 2008; 81(5): 329-343. Kyle A. Criterion for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23(1): 3-9. Tripathy S. The role of SPEP in the detection of multiple myeloma: an experience of a corporate hospital. J Clin Diagn Res 2012; 6(9): 1458-1461. Martin NF. Ocular Copper deposition associated with pulmonary carcinoma, immunoglobulin monoclonal gammopathy and hypercupremia. Ophthalmology 1983; 90: 110-116.

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Berenson JR, Yellin O, Woytowitz D, et al. Bortezomid, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and welltolerated frontline regimen. Eur J Haematol 2009; 82(6): 433-439. • Schamier A. Hematology for the Medical Student. Lippincott Williams and Wilkins 2003. • Stewart S. Autologous Stem Cell Transplants: A Handbook for Patients. bmtinfonet.org, 2012. • Zhou Q, Liang J, Lu H. Intravitreal bevacizumab for ocular metastasis of multiple myeloma. Optom Vis Sci 2013; 90(9): e236-e240.

27:3, 16

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QUESTIONNAIRE Ocular Signs of Multiple Myeloma Steven Mordukowitz, OD, FAAO 1. ❑ ❑ ❑ ❑

Diagnosis of anemia requires all of the following tests, EXCEPT: CBC and CMP Bone marrow biopsy Skeletal survey and bone density scan HbA1C

2. ❑ ❑ ❑ ❑

The most common signs of multiple myeloma include all of the following, EXCEPT: Elevated serum calcium with bone lesions Hypertension (HTN) Anemia Renal failure

Retinal signs highly suggestive of anemic retinopathy (in the absence of hypertension), include all of the following, EXCEPT: Cotton-wool spots Flame-shaped hemes with microanneuryms Hollenhorst plaque Roth spot hemorrhages

❑ ❑ ❑ ❑

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Signs of plasma cell infiltration into bone marrow or tissues include all of the following, EXCEPT: Anemia and cytopenia Bone pain with pathologic fractures Hypercalcemia Hyponatremia

5. ❑ ❑ ❑ ❑

Which of the following is NOT a commonly used lab test for the diagnosis of multiple myeloma? Serum protein electrophoresis Immunofixation Prothrombin time Complete skeletal survey

6. ❑ ❑ ❑ ❑

Corneal deposits caused by multiple myeloma include: Filamentary keratitis Band keratopathy Recurrent corneal erosion Corneal guttata

7. ❑ ❑ ❑ ❑

Pars plana cysts can be filled with all of the following, EXCEPT: Plasma cells Erythrocytes Macrophages Melanin granules

8. ❑ ❑ ❑ ❑

The most common orbital sign of myeloma is: Conjunctival chemosis Ptosis Unilateral, slowly progressive proptosis Choriodal folds

9. ❑ ❑ ❑ ❑

Neuro-ophthalmologic signs of multiple myeloma include all of the following, EXCEPT: Papilledema VI cranial nerve palsy Nystagmus Visual Filed defects

10. ❑ ❑ ❑ ❑

All are causes of Roth spot hemorrhages, EXCEPT: Bacterial endocarditis Leukemia Diabetic retinopathy Vitamin B12 deficiency anemia

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4. ❑ ❑ ❑ ❑

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Clinical & Refractive Optometry is pleased to present this continuing education (CE) article by Dr. Christopher J. Borgman entitled Traumatic Choroidal Rupture and Macular Hole in a 10-Year-Old Child: Case Report and Review. In order to obtain a 1-hour Council of Optometric Practitioner Education (COPE) approved CE credit, please refer to page 120 for complete instructions.

Traumatic Choroidal Rupture and Macular Hole in a 10-Year-Old Child: Case Report and Review Christopher J. Borgman, OD, FAAO

ABSTRACT A 10-year-old African-American female presented with decreased vision in her right eye (OD) after failing a school vision screening. Her dilated retinal exam revealed a large choroidal rupture and traumatic macular hole in the right eye presumably from an earlier trauma without a clear timeline. Given the lack of any evidence for choroidal neovascular membrane formation and the lack of a clear timeline of the macular hole formation, the retinal specialist declined surgical intervention on this patient. Although this was a typical case of choroidal rupture and traumatic macular hole formation, it was unusual given the patient’s young age and unknown history of trauma. Long term follow up will be important given risk of potential future ocular complications such as CNVM. A review of choroidal ruptures and traumatic macular holes follows.

INTRODUCTION Ocular trauma among children is the leading cause of non-congenital monocular vision loss and monocular visual disability in children under 20 years of age.1,2 About 50% of children’s ocular injuries are caused by another child inflicting the injury, whereas 32% were self-inflicted, and overall 18% were found to be purely accidental in nature.3 The proportion of children with eye injuries among all eye patients admitted to hospital seems to be

C.J. Borgman — Southern College of Optometry, Memphis, TN Correspondence to: Dr. Christopher J. Borgman, Southern College of Optometry, 1245 Madison Avenue, Memphis, TN 38104; E-mail: cborgman@sco.edu The author has no disclosures to report in regards to anything within this article. This article has been peer reviewed.

stable at 3% to 4% according to Niiranen et al.3 Missiles are the most common cause of injury followed by shot, hit, and sports injury respectively.3 Boys are four times more likely to be involved in an ocular injury compared to girls.3 Girls have equal rates of injuries across all ages, however boys’ risks increase substantially from the age of 8 onwards.3 Trauma can result in numerous injuries to the eyes. This case highlights the effects of choroidal ruptures and macular holes on vision secondary to trauma and the resultant management options. Choroidal ruptures are defined as breaks within the choroid, Bruch’s membrane, and occasionally the retinal pigmented epithelium layers of the retina.4-13 These tissues tend to be more affected because of their relative inelasticity in comparison to the other layers of the retina which are stretched in cases of traumatic events leading to rupture.4-13 Choroidal ruptures are characterized as yellow/ white subretinal streaks that are concentric with the optic nerve and typically occur in the posterior pole.4-13 Choroidal ruptures are caused by blunt trauma to the eye and occur in about 5% of all ocular trauma cases.4-8,11,12 Multiple ruptures within the same eye occur in approximately 25% of all rupture cases.11,13 As with most traumatic events, males are affected more commonly than females due to their more likely involvement in higher risk activities.13 Visual acuity is dependent on the location of the rupture relative to the macula, the length of the rupture, and the presence or absence of a choroidal neovascular membrane (CNVM).4-8,10,14 In the absence of CNVM, patients are monitored with the Amsler grid looking for growth or sudden onset of CNVM.4-8,10,13,14 Accompanying macular holes secondary to trauma can also occur. Raman et al reported 3.1% of choroidal ruptures had an accompanying macular hole in their study.11 Traumatic macular holes have variable responses to therapy depending on the extent of the hole and nature of the traumatic event. Some macular holes spontaneously close, however some need surgery via pars plana vitrectomy (PPV) and gas tamponade to achieve anatomical closure of the hole which historically has very good success rates.15-20 The following represents a case review of the treatment and evaluation of both a traumatic macular hole and choroidal rupture in a 10-year-old AfricanAmerican female.

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Fig. 1 Choroidal rupture and macular hole at initial presentation OD.

CASE REPORT A 10-year-old African-American female presented with her father in September 2010 for her first-ever eye exam. The patient and father denied any visual problems but revealed she had failed a school vision screening earlier that month. The patient denied any asthenopia, headaches, and diplopia. Family ocular history was positive only for the maternal grandmother being a glaucoma suspect. Family medical history was additionally unremarkable. The father denied any patient medical problems and reported the child saw her pediatrician every year on a regular basis. All developmental milestones were reported as normal per the father. The father reported her birth history as a full-term, uncomplicated birth. The father denied the patient was on any medications and also denied any drug or medical allergies. The father reported the patient was doing great in school, receiving mostly As and a few Bs. The patient was also oriented to time, place, and person. Upon examination, uncorrected visual acuities were 6/24- (20/80-) in the right eye (OD) with pinhole showing no improvement (PHNI) in acuity, and 6/6 (20/20) in the left eye (OS). Extraocular motilities demonstrated full range of motion in both eyes (OU) with no restrictions OU. Confrontational visual fields were full to finger count OU. Pupils were equal, round, and reactive, with no signs of afferent pupillary defect OU. Primary gaze alignment at distance and near was orthophoric and 10Î&#x201D; exophoria, respectively. Stereopsis testing revealed that the patient was unable to appreciate the shapes/forms and was found to be suppressing the OD on the suppression check. Colour vision testing with the Ishihara test plates tested normal OD, OS. Objective retinoscopy without cycloplegia was found to be +1.50-1.50x180 OD with 6/24- (20/80-) bestcorrected visual acuity OD, and +0.75 DS OS with 6/6

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Fig. 2 Magnified view of macula OD.

(20/20) best-corrected visual acuity OS. Manifest refraction revealed no changes in spectacle prescription or acuities OU. Her anterior segment exam was unremarkable OU. Intraocular pressures were measured at 20 mmHg OD and 20 mmHg OS via Goldmann applanation. The patient was dilated with one drop each of the following OU: 2.5% phenylephrine, 1% tropicamide, and 1% cyclopentolate. The decision to use cyclopentolate was made in order to rule out any refractive amblyopia secondary to any possible latent hyperopia. Post-dilated/cycloplegic retinoscopy demonstrated the same prescription OU with no changes in measured acuity in either eye. Dilated fundus examination revealed 5 to 6 longitudinal, areas of chorioretinal scarring, concentric with the optic nerve, adjacent and temporal to the macula OD (Fig. 1). Close inspection of the macula revealed a full thickness macular hole OD (Fig. 2). The patient reported a negative Watzke-Allen sign, however she did not seem to clearly understand what was being requested of her during this test so her response was judged to be unreliable. The optic nerve had a cup-to-disc ratio of 0.2H/0.2V, healthy rim tissue, pink in color and had clear, distinct borders OD. Blood vessels were of normal caliber and showed no signs of sheathing OD. Dilated fundus examination of the OS was unremarkable and revealed a healthy optic nerve with a cup-to-disc ratio of 0.2H/0.2V, healthy pink optic nerve rim tissue and clear, distinct optic nerve margins. To assist in diagnosing

time given the lack of evidence of CNVM. Since no timeline could be established with the traumatic event, it was determined that although anatomical macular closure with surgery might be possible, without a clear timeline of the traumatic event itself, visual improvement would likely be poor secondary to the chronicity of the hole, and therefore the specialist determined the best course of action would be to simply monitor the patient on a 6 month basis. A follow-up exam 6 months later confirmed stable findings with the patient doing very well overall.

Fig. 3 High definition ocular coherence tomography (OCT) cross-section scan of the patient’s macular hole OD.

and to document the fundus appearance of the right eye, photos and spectral domain ocular coherence tomography (OCT) of the macula were ordered that day (Figs. 1-3). The OCT scan of the right eye (Fig. 3) revealed a full thickness macular hole involving all the retinal tissues down to the RPE layer of the retina in the center of the macula. Cystic pockets of intraretinal fluid are shown to be accumulating on the nasal side of the macula within the neurosensory retina. The temporal side of the OCT scan shows an atrophic and thinned flap of neurosensory retina. Mild subretinal fluid can be seen both nasally and temporally in the hole which gives the tissues a trapezoid appearance. Scar tissue stemming from the choroidal rupture is shown in the OCT scan as thickening and disruption of the RPE layer temporal to the macular hole underlying choroidal shadowing. Based on the clinical appearance and presentation, the patient was diagnosed with presumed multiple traumatic choroidal ruptures and a traumatic macular hole OD despite the patient nor the father recalling any specific ocular trauma that could have caused the ocular findings. She was referred to a retinal specialist for a second opinion given her young age, reportedly negative history of any trauma, and for any possible surgical treatment options. The patient returned 5 days later as directed for her consult with the retinal specialist. The patient reported no changes since the previous visit in her vision, medical history, and social history. Both the patient and father again denied any history of trauma, even when asked separately. Visual acuities remained unchanged as did all entrance tests, slit lamp examination, dilated examination, and tonometry measurements from the previous visit. Upon repeated dilated examination, the retinal specialist agreed with the previous diagnosis of traumatic macular hole and multiple choroidal ruptures of the OD. He deferred fluorescein angiogram (FANG) testing at the

DISCUSSION Choroidal Ruptures Choroidal ruptures occur in just 5% of all ocular trauma cases.4-8,11,12 There are two types of choroidal ruptures: indirect and direct.4-8,10,12 Direct ruptures usually occur at the site of impact and result in a scar that is parallel with the ora serrata and more anterior in location.4-8,10,12 Indirect ruptures, the classic type of choroidal ruptures, are a result of the contrecoup effect of the traumatic event and are located in the posterior pole.4-8,10,12 The vast majority of choroidal ruptures are indirect (80%) whereas only 20% of ruptures are direct.4-8,10,12 The formation of the classic scar tissue of a rupture is typically fully formed within 3 to 4 weeks post-trauma.13,14 However, acutely, the rupture can be obscured by retinal hemorrhaging or commotio retinae for weeks to months; therefore close follow up of patients after trauma is important to assess the damage in its entirety.4-8,13,14,20 The mechanism of action for the formation of a choroidal rupture stems from the traumatic event itself. The inciting event typically causes antero-posterior compression of the globe.9,13 Since the globe itself is a fixed volume of space, compression in the horizontal meridian causes an elongation/stretching in the opposite vertical meridian. The choroid is anatomically “anchored” to the optic nerve and vortex veins,9 so when the vertical stretching occurs with the traumatic event, the tissue between the optic nerve and vortex veins is torn/pulled apart leading to the formation of the rupture.13 This would also explain why the majority of ruptures are “concentric” to the optic disc in the posterior pole between the two “anchor/tether” points. In fact, during the traumatic event, the choroidal tissue stretches up to 128% its normal length in the vertical meridian and the rebound effect may result in rebound stretching in the horizontal meridian up to 112%.13 This leads to the separation of the underlying, less-elastic tissues of the choroid, Bruch’s membrane, and the retinal pigmented epithelial (RPE) layer of the retina, which in turn causes the rupture.9,13 The most severe complication that can occur with choroidal ruptures is the development of a choroidal neovascular membrane (CNVM) from the release of

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Table I Percentage of subjects with choroidal rupture (CR) with a final visual acuity (VA) of ≥6/12 (≥20/40) after 1.5 years post-trauma and the effect of CR location and the presence of choroidal neovascular membrane (CNVM) on final visual acuity.10 Peripheral CR Subjects (n) Percentage of subjects with ≥6/12 (≥20/40) VA

(-) CNVM

(+) CNVM

59%

22%

38%

vascular endothelial growth factor (VEGF) liberated during the traumatic event from the surrounding damaged tissues.4-13,21 Bruch’s membrane is a physiologic barrier to the choroidal vasculature, however the break in Bruch’s membrane provides the underlying choroidal vasculature/ CNVM a window or space to invade the retinal tissues, which is just anterior to the RPE later in the neurosensory space.8,22 Clinical signs of CNVM typically include sub-RPE hemorrhage or exudation, RPE detachment, serious retinal detachment, and intraretinal hemorrhage or exudation.4-13,21 A patient’s symptoms usually include sudden loss or decrease in vision, metamorphopsia, and/or scotomas.4-13,21 CNVM’s occur in only 5% to 10% of all choroidal ruptures, however they can be visually devastating if they occur within or near the macula.4-10,13,20 In fact, CNVM’s tend to occur more frequently in choroidal ruptures at the end of the rupture closest to the fovea.13 CNVM can occur months to years after the traumatic event.4-8,10,13 Of all CNVM’s associated from a choroidal rupture, 81% occur within the first year after trauma, with most being within 7 to 8 months on average.10,12 However, case reports have reported CNVM onset up to 37 years after the traumatic event.13 FANG and indocyanine green angiography (ICG) are historically the best ways to visualize CNVM.23 With a FANG, the CNVM from a rupture will hyperflouresce in the early stages and will continue to leak dye as the FANG progresses over time.13 FANG’s are very beneficial and advantageous for retinal vasculature, but fluorescein easily leaks from the choriocapallaris and obscures the visualization of the underlying choroid leading to poor clinical assessment of the choroidal vasculature in general, which is a disadvantage of FANG’s with choroidal ruptures.23 However, with ICG, there is a high serum protein binding ratio (98%) which prevents leakage of the dye from the choroidal vasculature leading to a much better assessment of the choroidal circulation.23 One other advantage of ICG versus FANG is in the presence of acute retinal hemorrhage. Fluroescein requires absorption of 500 nm light source, whereas ICG requires absorption of 835 nm light source. Longer wavelengths of light have much better penetration through hemorrhage, serous exudation, and ocular pigments than with a FANG and as a result, ICG results in much better visualization of the underlying vasculature of the choroid.23 One other method

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to consider for monitoring for CNVM is ocular coherence tomography (OCT) imaging. With the recent advances in OCT imaging and spectral domain analysis, OCT has become a very good additional, non-invasive tool to use in a standard clinical setting when monitoring for CNVM in a variety of retinal conditions, including choroidal ruptures.14,24 With OCT, CNVM’s will typically show a mild to severe reflective lesion protruding from the retinal pigmented epithelium with possible subretinal fluid present which indicates leakage from the weaker CNVM blood vessels as the vessels invade the retinal tissues through a ruptured Bruch’s membrane.8 Treatment for choroidal ruptures depends strictly on the presence or absence of CNVM. In the absence of CNVM, there is no treatment available other than self-evaluation with Amsler grids in order to detect the earliest onset of a CNVM. Patients are typically followed every 6 to 12 months in a stable, non-CNVM state. If CNVM develops, treatment options include referral to a retinal specialist/surgeon for laser photocoagulation, photodynamic therapy (PDT), anti-vascular endothelial growth factor agents (VEGF), and/or surgical removal.4-8,13,21 Sometimes, spontaneous regression of the CNVM can occur.19 Which treatment option the surgeon chooses depends on the location of the CNVM in relationship to the macula and the surgeon’s previous surgical experience. Historically, extrafoveal CNVM’s have been treated with laser photo-coagulation, while juxtafoveal and subfoveal CNVM’s are typically treated with either PDT or antiVEGF agents, such as ranibizumab or bevacizumab which target all active VEGF forms, to preserve the macula as much as possible, and consequently to preserve vision at the highest levels.4-13 The anti-VEGF agents are more widely used today than laser photocoagulation or PDT therapies as anti-VEGF agents have been shown to be more effective in halting or stabilizing the progression of CNVM’s for many different conditions and are much less destructive to the surrounding retinal tissues than is the case with laser photocoagulation.8 Surgical removal is not widely practiced secondary to the high invasiveness of the procedure compared to the other treatment options available, but small case studies have reported good outcomes.22 In the latest and largest study of choroidal ruptures in 2006, Ament et al studied 111 indirect choroidal rupture eyes to determine the final visual acuity expected after a

Table II Stages of idiopathic macular hole formation.4 Stage 1A

Impending macular hole with vitreal condensation, foveolar detachment

Stage 1B

Impending macular hole with vitreal condensation, foveal detachment

Stage 2

Small perifoveal dehiscence (<400 µm)

Stage 3

Larger full thickness hole (>400 µm); may be small operculum present, no PVD

Stage 4

Larger full thickness hole (>400 µm); with complete PVD present

minimum of 1.5 years post-rupture. Their expected acuity findings depended on the location of the rupture as well as the presence or absence of CNVM and are listed in Table I.10 They concluded that the probability of CNVM increases with older age, length of rupture (not width), and location of the rupture relative to the macula.10 Those eyes with the poorest prognosis for visual recovery are those with macular rupture location, decreased baseline acuity, and the presence of CNVM.10 However, reasonable visual outcomes can be expected in most non-complicated choroidal ruptures. Traumatic Macular Holes Of the different types of macular holes, traumatic macular holes (TMH) make up 5% to 15%, while idiopathic macular holes (IMH) make up the remaining approximately 83% of all macular holes.16,19 IMH tend to form gradually over weeks to months secondary to tangential vitreomacular traction while TMH typically coincide with the traumatic event resulting in immediate formation.16,19 IMH are typically broken down into four stages (Table II), and are usually extrapolated to include traumatic macular holes as well. Stage 1A is an impending hole, yellow spot, or ring in fovea with foveolar detachment, usually around 100 to 200 μm in diameter.7,16,17,25 Stage 1B is an impending hole with further vitreous condensation resulting in foveal detachment, usually 200 to 300 μm in diameter.7,11,16,25 Stage 2 is a small, full thickness hole/ dehiscence of <400 μm.7,16,17,25 Stage 3 is a full thickness hole/dehiscence with a cuff of subretinal fluid in the absence of a posterior vitreal detachment which is >400 μm and may have a small operculum overlying the macular hole and usually has vision in the range of 6/24 (20/80) to 6/60 (20/200).7,16,17,25 Stage 4 is a full thickness hole with a cuff of subretinal fluid in the presence of a posterior vitreal detachment and are typically large (400 to 700 μm) with vision in the 6/60 (20/200) to 6/120 (20/400) range.7,16,17,25 Surgery, in the form of PPV with gas tamponade, for macular holes is supported by clinical trials for full thickness holes in stages 2, 3, or 4 because most stage 2 holes (67% to 98%) progress to stage 3 or 4.7,15,16,17,25 Surgery is not recommended for stages 1A and

1B holes secondary to a reasonable likelihood (50% to 60%) they may spontaneously close on their own.7,16,17,25 These stages of macular holes are typically designated for IMH, but can be extrapolated by clinicians for TMH. Diagnosis of a macular hole has historically been a clinical diagnosis upon dilated fundus examination and relied on the patient to help differentiate a positive or negative Watzke-Allen sign and/or a positive or negative laser aiming-beam test.16 Recent advancements in OCT imaging has re-shaped the ability to diagnose, follow, and treat macular holes on a much more detailed level. Spectral domain OCT imaging has a resolution of 4 to 6 µm, compared to time domain’s resolution of approximately 10 µm, which has allowed a much better understanding of the forces that create macular holes.16 In 2010, Huang et al used OCT imaging to study full thickness macular holes of traumatic as well as idiopathic origin. They determined that TMH were less circular than IMH and that posterior vitreal detachments were present in just over half of the IMH patients compared to none in the TMH eyes.24 This could mean TMH tend to be only Stage 3 macular holes and thus may have a strong vitreomacular traction component involved in their pathophysiology. Diameters of idiopathic macular holes are important to know as the size of the hole can relate to how likely the hole is to close and how likely vision is to improve. However this does not hold true for traumatic macular holes as in the study by Huang et al none of the measured parameters with OCT correlated with visual acuity in TMH patients, as it does with IMH where the larger the hole, the worse the visual acuity.24 This was hypothesized to be secondary to the photoreceptor inner segment-outer segments (ISOS) junctions where the ISOS junctions were shown to be disrupted beyond the boundary of the macular hole itself with TMH. Therefore, the size of the TMH may not reflect the extent of the actual functional disturbance to the retinal tissue, like it does in IMH.24 The mechanism of action of TMH’s is debatable, but it is hypothesized to be the same as the antero-posterior compression mechanism by which choroidal ruptures are formed. This typically results in an immediate hole formation as the retinal tissues are stretched, however case reports of TMH that took a few weeks post-trauma to form have been reported.24 Yamashita et al hypothesized that there are two types of TMH. One is the immediate rupture of the fovea upon impact as discussed previously. The second is delayed visual loss secondary to persistent/ stronger vitreofoveal adhesion leading to dehiscence of the fovea.20,21 The macula tends to be involved more commonly because the retina is the thinnest/weakest at the fovea, so any stretching of the retinal tissues would tend to cause tearing at the macula for this reason.21 In addition to this, the dynamics of stronger vitreous attachment points and the resultant traction to the optic

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nerve and macular regions during a traumatic ocular event are believed to play a role in TMH formation as well.20,21,24 Treatment for TMH typically requires a three-port pars plana vitrectomy (PPV) surgical procedure with fluid-gas bubble exchange, the same procedure as with idiopathic macular hole repair surgery.20,21,24 However, studies have shown that anywhere from 10% to 67% of traumatic macular holes can have spontaneous anatomical closure of the hole, which is a large range.20,21,24 One of the most recent studies on traumatic macular holes was performed in Japan by Yamashita et al in 2002 and contained two arms of data. One arm looked at the results of monitoring TMH and the second arm looked at the results of PPV surgery outcomes of TMH. The first arm of the study looked at 18 TMH eyes. Of the 18 traumatic macular holes studied, 44% spontaneously closed within 8.4 months on average.20 Yamashita et al sited two different studies out of Japan which reported spontaneously closure rates from 10% to 67%. They found that regardless of whether the macular holes closed spontaneously or were anatomically closed via PPV, the final visual acuity result was the same.20 However, it is impossible to foresee which holes will spontaneously close on their own versus the ones that will need surgery for closure. As a result of this, Yamashita et al suggests monitoring patients with traumatic macular holes for a several months to see if they spontaneously close before referring for PPV surgery.20 The second arm of the Yamashita et al study involved 39 total eyes which combined two previous studies to determine surgical outcomes for traumatic macular holes. They reported a 95% anatomical closure rate with PPV surgery and that 77% of eyes regained better than 6/12 (20/40) visual acuity.20 Again, they determined that surgery resulted in faster closure of macular holes but had no effect on the final visual acuity.20 One aspect that can play a large role in visual outcomes is the chronicity of the macular hole. Typically, the longer the hole has been present the poorer the visual outcome, but what are the established timelines for when surgery is appropriate and when it is not? The literature available has offered differing guidelines, but as the PPV procedure continues to evolve and improve, the timelines are beginning to extend. Alexander reports that macular holes greater than 24 months in duration have a much lower expected visual acuity recovery than holes with less than 24 months duration.7 Chow et al studied 16 TMH eyes and found that the only anatomic failure in their series of patients was one eye that was operated on 2.95 years post onset of the TMH, whereas the 15 other eyes in the study all resulted in anatomical closure however they were operated on in 6 months or less.19 However, in general, macular holes older than 1.5 years, greater than 400 µm in size, and holes secondary to another retinal

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pathology typically make significant visual function restoration more complicated.26 So despite the varying opinions on timelines, each patient’s encounter should be taken into consideration individually and the risks/ benefits of treatment should be thoroughly discussed. In our patient’s case, two factors were mainly considered. One, the surgery would require potentially 7 to 14 days with face-down positioning,20 which could be difficult for a child to reliably do without supervision. Interestingly, recent studies have shown that perhaps only 4 days in the prone position may be all that is needed for macular hole repair.7 And two, the timeline of the traumatic event could not be determined via the father or the patient, therefore the length of time the macular hole had been present was truly unknown. As a result of this, the risks and benefits associated with performing a pars plana vitrectomy could not appropriately be determined and the decision was made by the retinal specialist to just monitor the patient closely for other complications that may arise in the future.

CONCLUSION This case is important, because it serves as an example of a rare pediatric case of choroidal rupture and macular hole formation. It also serves as a good example of prognosis rates and how to treat patients according to the latest research on traumatic macular holes and choroidal ruptures. The case was obviously complicated by the patient’s age, ocular findings, and reportedly negative history of any trauma. However, during follow up of this patient it was reported that she was the youngest of 7 siblings, and the father speculated that perhaps one of her siblings had been responsible for the traumatic event. However, no traumatic event could be elicited in this case. As is standard of care for essentially monocular patients, the patient was prescribed polycarbonate lenses to be worn full time to protect the remaining better-seeing eye which was explained to the father. Also, the patient and father were extensively educated on the nature of the patient’s condition and told to return back to the clinic immediately if any changes in vision are noticed as this may suggest a choroidal neovascular membrane which may result in further visual deterioration. In the event of choroidal ruptures and/or traumatic macular holes, timely recognition and referral by eye care providers to a retinal specialist for treatment of suspected CNVM and/or macular hole closure is important. Given the fact that the longer the duration of the CNVM or macular hole, the lower the rates of successful treatment, timely referral is paramount. In the absence of these treatable entities, simply monitoring the patient on a 6to 12-month basis once proven stable, and prescribing polycarbonate lenses for protection is the standard of care for these conditions. In our patient’s case, in the absence of any vision changes, she will be followed/monitored

every 6 to 12 months with regularly scheduled dilated comprehensive eye exams and will be referred back to a retinal specialist for treatment if the need arises. ❏ Acknowledgements: The author would like the staff at the Illinois Eye Institute in Chicago, IL for their help in this case. Specifically, Dr. Stephanie Klemencic, Dr. Jennifer Harthan, Dr. Sandra Block, and Dr. Leonard Messner.

REFERENCES 1.

Unver YB, Acar N, Kapran Z, Altan T. Visual predictive value of the ocular trauma score in children. Br J Ophthalmol 2008; 92(8): 1122-1124. 2. Sternberg P, De Juan E, Michels RG. Penetrating ocular injuries in young patients: initial injuries and visual results. Retina 1984; 4(1): 5-8. 3. Niiranen M, Raivio I. Eye injuries in children. Br J Ophthalmol 1981; 65(6): 436-438. 4. Ho AC, Brown GC, McNamara JA, et al. Choroidal rupture. Color Atlas & Synopsis of Clinical Ophthalmology (Wills Eye Hospital): Retina. Spain: McGraw-Hill, 2003: 26-29. 5. Gerstenblith AT, Rabinowitz MP. Choroidal Rupture. The Wills Eye Manual: Office and Emergency Room Diagnosis and Treatment of Eye Disease: 6th Ed. Philadelphia: Lippincott, Williams & Wilkens, 2012: 50-51. 6. Friedman NJ, Kaiser PK. Choroidal rupture. The Massachusetts Eye and Ear Infirmary: Illustrated Manual of Ophthalmology: 3rd Ed. China: Saunders Elsevier, 2009: 328. 7. Alexander LJ. Choroidal ruptures and macular holes. Primary Care of the Posterior Segment: 3rd Edition. Spain: McGraw-Hill, 2002: 110-112, 136-146. 8. Liang F, Puche N, Soubrane G, Souied EH. Intravitreal ranibizumab for choroidal neovascularization related to traumatic Bruch’s membrane rupture. Graefes Arch Clin Exp Ophthalmol 2009; 247(9): 1285-1288. 9. Atebara NH. Miscellaneous abnormalities of the fundus: traumatic choroidal rupture. Duane’s Clinical Ophthalmology 2011; 3: 36. Electronic Version. Accessed April 1, 2011. 10. Ament CS, Zacks DN, Lane AM, et al. Predictors of visual outcome and choroidal neovascular membrane formation after traumatic choroidal rupture. Arch Ophthalmol 2006; 124(7): 957-966.

11. Amari F, Ogino N, Matsumura M, et al. Vitreous surgery for traumatic macular holes. Retina 1999; 19(5): 410-413. 12. Secretan M, Sickenburg M, Zografos L, Piguet B. Morphometric characteristics of traumatic choroidal ruptures associated with neovascularization. Retina 1998; 18(1): 62-66. 13. O’Connor J. Choroidal rupture. Optometry Clinics 1993; 3(2): 81-89. 14. Oehrens AM, Stalmans P. Optical coherence tomographic documentation of the formation of a traumatic macular hole. Am J Ophthalmol 2006; 142(5): 866-869. 15. Azevedo S, Ferreira N, Meireles A. Management of pediatric macular holes: case report. Case Rep Ophthalmol 2013; 4(2): 20-27. 16. Wolfe JD, Ho AC. Macular hole. Duane’s Clinical Ophthalmology 2011; 3: 21. Electronic Version. Accessed April 1, 2011. 17. Raman SV, Desai UR, Anderson S, Samuel MA. Visual Prognosis in patients with traumatic choroidal rupture. Can J Ophthalmol 2004; 39(3): 260-266. 18. Garcia-Arumi J, Corcostegui B, Cavero L, Sararols L. The role of vitreoretinal surgery in the treatment of posttraumatic macular hole. Retina 1997; 17(5): 372-377. 19. Chow DR, Williams GA, Trese MT, et al. Successful closure of traumatic macular holes. Retina 1999; 19(5): 405-409. 20. Yamashita T, Uemara A, Uchino E, et al. Spontaneous closure of traumatic macular hole. Am J Ophthalmol 2002; 133(2): 230-235. 21. Johnson RN, McDonald HR, Lewis H, et al. Traumatic macular hole: observations, pathogenesis, and results of vitrectomy surgery. Ophthalmology 2001; 108(5): 853-857. 22. Gross JG, King LP, de Juan Jr E, Powers T. Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture. Ophthalmology 1996; 103(4): 579-585. 23. Akman A, Kadayifcilar S, Oto S, Aydin P. Indocyanine green angiographic features of traumatic choroidal ruptures. Eye 1998; 12(Pt 4): 646-650. 24. Huang J, Liu X, Wu Z, Sadda S. Retinal disorders: comparison of full-thickness traumatic macular holes and idiopathic macular holes by optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2010; 248(8): 1071-1075. 25. Onofrey BE, Skorin L, Holdeman NR. Macular hole. Ocular Therapeuitics Handbook: 3rd Edition. Philadelphia: Lippincott Williams & Wilkins, 2011: 522-525. 26. Gurwood AS. Left eye’s in bad shape. Review of Optometry, February, 7, 2011. Available at: http://www.revoptom.com/ content/c/26539. Accessed March 25, 2014

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QUESTIONNAIRE Traumatic Choroidal Rupture and Macular Hole in a 10-Year-Old Child: Case Report and Review Christopher J. Borgman, OD, FAAO

1. ❑ ❑ ❑ ❑

Choroidal ruptures occur in what percentage of all ocular trauma cases? 1% 5% 15% 25%

2. ❑ ❑ ❑ ❑

What is the most severe complication that can occur with choroidal ruptures? Choroidal neovascular membrane Macular edema Vitreal floaters Traumatic cataract

3. Which of the following is NOT considered a treatment for choroidal neovascular membranes associated with choroidal ruptures? ❑ Laser photocoagulation ❑ Photodynamic therapy ❑ Topical non-steroidal anti-inflammatories ❑ Anti-vascular endothelial growth factors

Clinical and Refractive Optometry 27:3, 2016

❑ ❑ ❑ ❑ 5. ❑ ❑ ❑ ❑ 6. ❑ ❑ ❑ ❑ 7. ❑ ❑ ❑ ❑ 8. ❑ ❑ ❑ ❑ 9. ❑ ❑ ❑ ❑

Per the study by Ament et al in 2006, the probability of choroidal neovascular membrane formation in choroidal ruptures does NOT increase with which of the following? Length of choroidal rupture Width of choroidal rupture Older age Proximity of choroidal rupture to macula Approximately what percentage of choroidal neovascular membranes associated with choroidal ruptures occur in the first year post-trauma? 20% 40% 60% 80% In a 2002 study by Yamashita et al., reported spontaneous closure rates of traumatic macular holes were found in what percentage of cases? 22% 44% 66% 88% In this same 2002 study by Yamashita et al., what did they report was their anatomical closure rate of traumatic macular holes with the surgical combination of pars plana vitrectomy and fluid-gas exchange? 50% 75% 85% 95% What percentage of eyes regained ≥6/12 (≥20/40) visual acuity after surgical closure of traumatic macular holes? 57% 67% 77% 87% What is the mechanism of action believed to be responsible for immediate traumatic choroidal rupture and traumatic macular hole formation? Sudden IOP elevation Antero-posterior compression of globe Residual inflammation Tangential vitreomacular traction

10. In a study by Chow et al. in 1999, they found that when traumatic macular holes were surgically repaired within _________ of the traumatic event/onset, they had approximately a 94% anatomical closure rate. ❑ < 6 months ❑ < 1 year ❑ < 1.5 years ❑ < 2 years

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Communication Following numerous enquiries about the question of the safety and efficacy profile for buffered phosphates when used in commercial tear solutions containing sodium hyaluronate, we forwarded this question to the Center for Ocular Surface Disease at the University of Waterloo School of Optometry for their review and analysis. Clinical & Refractive Optometry is pleased to present the following Communication by Jeffrey Lam and Dr. Faran Vafaie reflecting their findings.

Are Current Sodium Hyaluronate Solutions That Are Buffered in Phosphate Safe for Daily Administration? Jeffrey Lam, BSc (Hons), MRT(R) Faran Vafaie, OD, MSc, BSc

INTRODUCTION The role of phosphates in sodium hyaluronate artificial tears is primarily to act as a buffer system to achieve a pH similar to normal tear film. Phosphate buffers are widely used by the ophthalmic preparation industry because of their high buffering capacity and high solubility in water. However, concentrations of phosphate vary widely amongst available sodium hyaluronate preparations. Recent evidence has suggested that in the presence of epithelial keratopathy, acute intensified treatment with high concentration phosphate containing sodium hyaluronate artificial tears may promote rapid corneal calcification which may lead to sight threatening complications.1 Since most people living with dry eyes rely on chronic use of artificial tears, it is of interest to determine 1) the safety of chronic exposure phosphate buffers, and 2) the maximum toxic concentration (MTC) typical for chronic use. Knowledge of different commercial preparations’ phosphate concentrations and their impacts is thus helpful in determining proper recommendations to avoid corneal complications.

the central stroma2 and can migrate deeper within the stroma, penetrating descemet’s membrane and causingcalcareous degeneration.3 Hydroxyapatite has very low solubility that decreases with alkalinity. Evidence suggests that deposits occur when the epithelium and Bowman’s membrane are compromised in the presence of a high concentration of phosphates. Stromal degradation and inflammation increases local free calcium and increases alkaline pH, respectively.4 Therefore, it is important to note that factors such as increased free calcium level and alkaline pH both promote the precipitation of hydroxyapatite within the deep stroma when exposed to high amounts of phosphate buffer.

PHOSPHATE BUFFER CONCENTRATION In 2006, Bernaurer et al took samples from different sodium hyaluronate formulations on the market and analyzed their concentration of phosphate buffers. The formulation Hylo-Comod® (URSA Pharm) or Hycosan® (Scope Healthcare) was indicated to have the highest concentration of phosphate at 50.9 mmol/L within commercially available sodium hyaluronate artificial tears. Furthermore, the authors provided evidence that the previous formulation of Hylo-Comod or Hycosan favoured the precipitation of calcium phosphate with coexisting epithelial keratopathy due to its high amount of phosphate concentration. Five patient studies showed that the use of Hylo-Comod upwards to 100 times per day with intervals as short as every 10 minutes converted to calcareous corneal degeneration.

CORNEAL CALCIFICATION

BUFFER SUBSTITUTION CONSIDERATIONS

Corneal calcification due to intensified treatment with high phosphate concentration formulations was identified to be extracellular crystal deposits of hydroxyapatite Ca5(PO4)3OH within the cornea.1 Unlike band keratopathy, the hydroxyapatite crystals are radially arranged around

As a result of potential corneal degeneration secondary to contact with high levels of phosphate, phosphate containing sodium hyaluronate preparations have reformulated theirTMsolutions with other buffers such as citrate (i.e., Hylo , CandorVision). It should be noted that although there is no evidence of corneal calcification with citrate buffers, there is evidence which suggests that high concentrations of cytosolic citrate could inhibit the glycolytic pathway.5 Citrates inhibit phosphofructokinase, an enzyme that is required for one of the rate-limiting steps of glycolysis. As a result, energy production is halted within the cell when citrate levels increase and this may lead to cell death.6,7

J. Lam — Candidate for Doctor of Optometry 2017, University of Waterloo School of Optometry, Waterloo, ON; President of the Canadian Association of Optometry Students; F. Vafaie — eyeLABS Optometry and Center for Ocular Surface Disease, Brampton, ON; Supervision Clinician, University of Waterloo School of Optometry, Waterloo, ON

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Furthermore, considerations should be taken when substituting buffers as it will affect pH maintenance. The physiological lacrimal film pH is 7.2 to 7.7.8,9 Buffers that are ideal for biological tissues should have pKa ranges from 6 to 8. Citrate buffers have a pKa of 6.2 making them more ideal for lower pH maintenance, while phosphate buffers have a pKa of 7.2 which is more suitable to maintain the pH of physiological tears.

DECREASED PHOSPHATE CONCENTRATION Although the exact critical concentration of phosphate that leads to corneal calcification in humans has not yet been determined, animal model studies involving rabbits with induced alkali burns found that a phosphate concentration of 148 mmol/L in irrigation solutions led to the development of corneal calcification.10 In addition, we may also use the concentration of 50.9 mmol/L in Hylo-Comod as a starting reference for MTC levels of phosphate which had adverse corneal complications. All other sodium hyaluronate formulations that were compared in the 2006 Bernauer report had phosphate concentrations under 10.9 mmol/L1 suggesting that lower concentrations of phosphate buffers with sodium hyaluronate formulations may not carry the same adverse risks. As such, the European Medicines Agency prepared a report11 which determined that the risk of corneal complications with epithelial keratopathy treated with phosphate buffer formulations was lower than one case for every 10,000 patients treated. They concluded that the benefits of topical treatment with phosphate containing artificial tears were significantly higher than the risk of developing corneal complications. Furthermore, low concentrations of phosphate buffers have been widely used in ophthalmic viscosurgical devices (OVD). Healon® (Abbott Medical Optics) is a sodium hyaluronic OVD that has been used for more than 35 years, becoming the most popular amongst viscoelastic substances for intraocular surgery.12 Formulations of Healon are buffered with 2.2mmol/L of phosphate13 which closely resembles the physiological phosphate concentration in the tear film (1.45 mmol/L).14 Despite there being no direct study to measure the MTC of phosphate that predisposes compromised corneas to calcification, it is assumed that low concentrations of phosphate do not cause adverse events as seen in hyaluronic artificial tears containing high concentrations of phosphate; however, more studies controlling for dosing and frequency of exposure should be established to make comparisons.

include pH, dosing frequency, and severity of epithelial defect.15,16 Moreover, it can be assumed that low and high concentrations of phosphate carry different risk profiles for corneal calcification. In Canada, the only produced phosphate buffered hyaluronic acid formulation is the i-drop® line by I-MED Pharma. This product contains very low concentrations (<2.5 mmol/L) of phosphate buffer and has not had any reports of adverse events. Although there have been no reported cases of rapid calcareous calcification from the use low concentration phosphate formulations of sodium hyaluronate artificial tears, future studies to determine the MTC and evaluate the relative risks of corneal complications are needed to further define safe daily dose. As such, it is important to have an in-depth knowledge about the full composition of artificial tears to mitigate and identify potential adverse effects to those who are at greatest risk. ❏

REFERENCES 1.

2. 3. 4.

10.

11. 12.

13. 14.

CONCLUSION It is evident that high topical phosphate concentrations in sodium hyaluronate artificial tears have potential sight threatening complications due to rapid calcareous degeneration of the cornea in association with ocular surface insult. However there are many variables that determine the risk of such complications. These factors

15.

16.

Bernauer W, Thiel MA, Kurrer M, et al. Corneal calcifiction following intensified treatment with sodium hyaluronate artificial tears. Br J Ophthalmol 2006; 90(3); 285-288. Daly M, Tuft SJ, Munro PMG. Acute corneal calcification following chemical injury. Cornea 2005; 24(6): 761-765. Lavid, FJ, Herreras JM, Calonge M, et al. Calcareous corneal degeneration: report of two cases. Cornea 1995; 14(1): 97-102. McDowell H, Gregory TM, Brown WE. Solubility of Ca5 (P04) 3OH in the System Ca (OH)2-H3PO4-H2O at 5, 15, 25, and 37°C. Journal of Research of the National Bureau of Standards–A. Physics and Chemistry 1977; 81A(2&3): 273-281. Parmeggiani A, Bowman RH. Regulation of phosphofructokinase activity by citrate in normal and diabetic muscle. Biochemical and Biophysical Research Communications 1963; 12(4): 273-281. Berg JM, Tymoczko JL, Stryer L. The glycolytic pathway is tightly controlled. In: Biochemistry, 5th edition. New York: W.H. Freeman, 2002: Section 16.2. Denton RM, Randle PJ. Citrate and the regulation of adipose-tissue phosphofructokinase. Biochemical Journal 1966; 100(2): 420. Fischer FH, Wiederholt M. Human precorneal tear film pH measured by microelectrodes. Graefes Arch Clin Exp Ophthalmol 1982; 218(3): 168-170. Chen FS, Maurice DM. The pH in the precorneal tear film and under a contact lens measured with a fluorescent probe. Exp Eye Res 1990; 50(3): 251-259. Schrage NF, Schlossmacher B, Aschenbernner W, Langefeld S. Phosphate buffer in alkali eye burns as an inducer of experimental corneal calcification. Burns 2001; 27(5): 459-464. European Medicines Agency. Questions and answers on use of phosphates in eye drops. EMA/CHMP/753373/2012. Higashide, Tomomi, and Kazuhisa Sugiyama. "Use of viscoelastic substance in ophthalmic surgery–focus on sodium hyaluronate." Clin Ophthalmol 2008; 2(1): 21-30. Buratto L. Phacoemulsification: principles and techniques. Thorofare, NJ: SLACK, 2003: 228. Print. Tapaszto I. Pathophysiology of human tears. Int Ophthalmology Clin 1973; 13(1): 119-147. de Frutos-Lezaun M, Martinez-Soroa I, Ostra Beldarrain M, et al. Determination of phosphate concentration and pH in artificial tear drops. Arch Soc Esp Oftalmol 2016 Feb 22. pii: S0365-6691(16)00051-4. doi: 10.1016/j.oftal.2016.01. 018. [Epub ahead of print] Bernauer W, Thiel MA, Langenauer UM, Rentsch KM. Phosphate concentration in artificial tears. Graefes Arch Clin Exp

Ophthalmol 2006; 244(8): 1010-1014.

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News and Notes CooperVision Announces Nationwide Availability of Biofinity® XR Toric Contact Lenses CooperVision, Inc. recently announced the expanded availability of Biofinity® XR toric, the latest addition to the Biofinity range of monthly silicone hydrogel contact lenses. Now Biofinity XR toric is available to all eye care practitioners, and their patients, throughout Canada. Biofinity XR toric lenses are available in sphere powers from +10.00D to -10.00D (0.50D steps after +/-6.00D), with cylinder powers from -2.75 to -5.75 (0.50 steps) and an axis of 5 degrees to 180 degrees in 5-degree steps, and +8.50D to +10.00D with cylinder powers from -0.75 to -2.25 (0.50 steps) and axis of 5 degrees to 180 degrees in 5-degree steps. “With nationwide availability of Biofinity XR toric lenses, eye care practitioners across the country can fit a greater number of patients in a leading silicone hydrogel material, keeping pace with the widespread move to this healthier material,” said Jerry Warner, President, North America, CooperVision. Biofinity XR toric is a fully cast molded made to order lens that incorporates the same uniform horizontal ISO thickness and optimized ballast band design as Biofinity toric, making it an easy-to-fit, stable toric lens with excellent visual acuity. Its optimized, continuous surface ensures that the eyelid interacts with a smooth lens surface on every blink, resulting in a more comfortable wearing experience. Like all Biofinity lenses, Biofinity XR toric features Aquaform® Technology, which allows more oxygen to reach the eyes, helping to maintain clear, white eyes and healthier corneal physiology. The lens material is naturally and uniformly wettable, providing a soft and flexible lens. For more information, visit www.coopervision.ca. World Economic Forum and EYElliance Release New Report Essilor has joined new multi-stakeholder coalition EYElliance and contributed to a new report, published recently by the World Economic Forum that highlights the strong case for investment in eyeglasses provision to generate significant socio-economic development gains. Along with new data highlighting the scale of the world's visual divide, and examples of validated, scalable models, including Essilor’s Eye Mitra model in India, the report also publishes a set of recommendations for governments, businesses and development partners that are keen to address this global challenge. “We are excited to partner with EYElliance and to co-sign this important call to action alongside several esteemed personalities from the private and public sectors,” said Jayanth Bhuvaraghan, Chief Mission Officer at Essilor International. In 2015, non-governmental organizations and inclusive businesses collectively distributed less than 8 million pairs of eyeglasses in developing countries. Essilor accounted for 1/5 of these eyeglasses, distributed through its inclusive business division 2.5 New Vision Generation and its strategic giving initiatives in over 30 countries. To read the report, go to https://visionimpactinstitute.org/ research/eyeglasses-global-developmentbridging-visualdivide/.

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

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