The Conjunctiva in Crisis

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REVIEW OF OPTOMETRY ■

Graft-vs.-host Disease: How, Why and What Next, PAGE 66 VOL. 154 NO. 11 ■

November 15, 2017 www.reviewofoptometry.comwww.reviewofoptometry.com NOVEMBER 15, 2017 ■

THE CONJUNCTIVITIS ■ RED EYE Ocular surface anomalies and how to treat them. SCLERITIS/EPISCLERITIS ■

GLAUCOMA THERAPY ■

CONTACT LENSES ■ The Conjunctiva in Crisis: Ocular Irritation Unmasked, PAGE 30 When Dry Eye Compromises Corneal Integrity, PAGE 38 A Red Eye: Scleritis or Episcleritis?, PAGE 44 Glaucoma Therapy: Don’t Forget the Ocular Surface, PAGE 50

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ACUVUE® Brand Contact Lenses are indicated for vision correction. As with any contact lens, eye problems, including corneal ulcers, can develop. Some wearers may experience mild irritation, itching or discomfort. Lenses should not be prescribed if patients have any eye infection, or experience eye discomfort, excessive tearing, vision changes, redness or other eye problems. Consult the package insert for complete information. Complete information is also available by visiting acuvueprofessional.com, or by calling Johnson & Johnson Vision Care, Inc. at 1-800-843-2020. Reference: 1. Suwala M, Glasier MA, Subbaraman LN, et al. Quantity and conformation of lysozyme deposited on conventional and silicone hydrogel contact lens materials using an in vitro model. Eye Contact Lens. 2007;33(3):138-143. ACUVUE®, 1-DAY ACUVUE® MOIST, EYE-INSPIRED™, LACREON®, and INFINITY EDGE™ are trademarks of Johnson & Johnson Vision Care, Inc. © Johnson & Johnson Vision Care, Inc. 2016 10444415E January 2016

RO0417_Vistakon Moist.indd 3 3/23/17 11:07 AM News Review

VOL. 154 NO. 11 ■ NOVEMBER 15, 2017

IN THE NEWS California Relaxes After analyzing medical records of 365 patients with posterior vitreous detach- OD Regulations ment (PVD) symptoms, Swedish researchers found those who sought care New legislation significantly widens scope of practice. on the fi rst day of their symptoms had a statistically signifi cant higher risk By Bill Kekevian, Senior Editor of retinal tears. Those with only fl oaters and long duration of symptoms were ears of efforts by optomet- Past Efforts lower-risk patients, the investigators said, ric advocates have paid off “California optometrists worked emphasizing the importance of prompt Yin California as Governor diligently over fi ve years to advo- referral for those with sudden onset of Jerry Brown recently signed a bill cate for scope of practice changes symptoms. expanding optometry’s scope of that strengthen our profession and practice. The bill permits Califor- our ability to care for Californians’ Bond-Taylor M, Jakobsson G, Zetterberg M. Posterior vitreous detachment - prevalence of and risk factors for nia ODs with proper certifi cation eyes,” said Sage Hider, OD, presi- retinal tears. Clin Ophthalmol. 2017;2017(11):1689-95. to use therapeutic pharmaceutical dent of the California Optometric agents (TPA) in a number of new Association.1 Studying a child’s central inner retinal ways, including expansions on Similar legislation proposed in function may be a future predictive measure for myopia, according to a treating pain, hypotrichosis, glau- the past faced adversity. A 2013 new study. Investigators measured cy- coma and blepharitis. The bill also bill would have expanded the role cloplegic refraction and axial length and permits optometrists to use nonin- of optometrists to diagnose and took a global fl ash multifocal electroret- vasive medical devices and technol- treat common systemic diseases, inogram at baseline for 56 emmetropic ogies FDA indicated for conditions including diabetes, hypertension children ages six to nine. The 43 children optometrists already treat; they can and hypercholesterolemia. It would with myopic changes on follow up also even employ some invasive proce- have also authorized TPA use and had reduced response in the central inner dures that require needles. removed limitations on the types of retina. Because this reduced response diagnostic tests ODs could order. preceded the myopia, the researchers speculate this might be an inducement to Bill Highlights By 2014 the bill merely authorized myopia, not a secondary effect. Specifi cally, the legislation focuses ODs to give limited immuniza- on TPA use in cases of blepharitis tions before ultimately being pulled Li SZ, Yu WY, Choi KY, et al. Subclinical decrease in central inner retinal activity is associated with myopia and hypotrichosis and prescribing altogether. development in children. Invest Ophthalmol Vis Sci. 2017;58(10):4399-4406. Tramadol for up to three days. It also clarifi es that certifi ed ODs are Better Future New research found epithelium-off permitted to prescribe currently al- With this bill’s passage, California 15mW accelerated crosslinking lowable drugs “off-label.” ODs can fi nally expand their scope pulsed-light therapy stabilized It opens up new diagnostic av- of practice and better serve their progression and improved vision in patients with stage two keratoconus. enues for certifi ed ODs, such as the patients. The researchers suggest this treat- ability to use intravenous injection “This important legislation is ment modality reduces treatment time, for angiography, collect blood by a step forward for the optometric increases patient comfort and reduces skin puncture to test for diabetes, profession, empowering doctors of post-op glare, subepithelial nerve plexus perform skin tests to diagnose optometry to more fully utilize our damage and postoperative haze. ocular allergies and administer fl u, extensive training, education and Mazzotta C, Baiocchi S, Bagaglia SA, et al. Accelerated shingles and pneumonia vaccines. experience to help expand eye and 15 mW pulsed-light crosslinking to treat progressive 1 keratoconus: Two-year clinical results. J Cataract Finally, ODs can now use a needle health care access,” Dr. Hider said. Refract Surg. 2017;43(8):1081-8. to remove foreign bodies and treat 1. California Optometric Association. COA champions bill to steroid-induced glaucoma. expand optometric practice in California. October 9, 2017.

4 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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RO0617_Keeler Tono.indd 1 5/30/17 11:07 AM News Review

Eye Dominance May Impact Dyslexia yslexia, a signifi cant had symmetrical blue cone-free nium Eye Care in West Freehold, problem for 5% to 17% of areas, causing an undetermined eye NJ. Generally, “the brain is really Dschool-aged children, may dominance.2 good at suppressing the eye that have an ocular biomarker, accord- Without a dominant eye, the is generating an aberrant image.” ing to new research.1 A recent study researchers speculate the patient’s Thus, according to Dr. Potter, the suggests the blue cone-free area at brain is confused by the two differ- research raises more questions than the center of the fovea is different in ent images, causing the characteris- it answers, such as, “Does dyslexia eyes of patients with dyslexia com- tic blurring and distortion described in a one-eyed patient, or a 20/200 pared with eyes of those without by many dyslexic patients.2 amblyope, differ from that of the the condition.2 While the study authors be- binocular patient? Cause vs. comor- Investigators in France studied lieve these fi ndings suggest eye bidity remains the question.” 30 control patients without dys- dominance as a possible cause for More research is necessary to test lexia and 30 subjects with dyslexia. dyslexia, research has a long way to this new theory—and work through While the controls all had asym- go before its true relationship to the all of the questions it raises, includ- metrical blue cone-free areas— diagnosis is understood. ing possible treatment options. leading to the normal dominant/ “I’d say the fi ndings may repre- 1. Habib M, Giraud K. Dyslexia. Handb Clin Neurol. non-dominant relationship between sent a comorbidity, as opposed to 2013;111:229-35. 2. Le Floch A, Ropars G. Left–right asymmetry of the Maxwell the eyes—the same was not true for cause and effect,” says Bill Pot- spot centroids in adults without and with dyslexia. Proceedings the 30 patients with dyslexia. Each ter, OD, chief of Optometry and of the Royal Society B. October 18, 2017. rspb.royalsocietypub- lishing.org/content/284/1865/20171380. Accessed October of the 30 patients with dyslexia Contact Lens Services at Millen- 20, 2017.

Sight Gags By Scott Lee, OD Drug Patents Under Fire llergan continues the battle to protect its control of the patents for its dry eye drug Restasis, this time in the Eastern District of Texas, where a A 1 federal judge recently invalidated four key patents. In September, the company transferred the patents to the Saint Regis Mohawk Tribe in upstate New York in response to a patent challenge fi led in an administrative proceeding with the United States Patent and Trademark Offi ce. By paying the tribe to take posses- sion of the patents and then leasing them back, the company hopes to capitalize on the tribe’s sovereign immunity to shield the patents from the challenge—a move met by criticism from Congress and consumer groups.1 Although the court case and the administrative patent challenge are separate proceedings, the Texas judge had harsh words for the company’s move to avoid re- percussions of the patent challenge: “Sovereign immunity should not be treated as a monetizable commodity that can be purchased by private entities as part of a scheme to evade their legal responsibilities,” he wrote.1 The patent transfers have no bearing on the legal battle in Texas, where manufacturers continue to fi ght over the validity of the patents.1 If the ruling stands, the

6 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

004_ro1117_news.indd 6 11/3/17 12:11 PM Preserving

patents will be invalidated, regardless of the deal with the Mohawk Patients’ Tears, Tribe.2 This recent push for a generic dry eye treatment option may not Worldwide, necessarily be in the patients’ best interest, however. Cost has always been a barrier to proper prescrib- Since 1997 ing, according to Marc Bloomen- stein, OD, director of optometric services at Schwartz Laser Eye Center in Scottsdale, Ariz., and “the notion that a generic is more cost-effective will defi nitely make clinicians more inclined to reach for a pen and Rx pad. However, the perceived cost benefi t will Parasol® come at the price of choice.” That choice, Dr. Bloomenstein says, is between a branded drug with “the best combination of molecule, strength and vehicle to maximize effi cacy while minimizing side effects” and a generic drug with the same molecule but a different concentration and vehicle that lacks human testing to prove its effi cacy. “Optometry’s interest is centered around providing our patients with safe and effi cacious medications to treat their conditions,” he says. “With this challenging disease, I worry that a The Parasol® Punctual Occluder has been generic market, without proper a top-trusted plug for dry eye treatment for testing in humans, will dilute results and cause huge frustrations over two decades — providing chronic dry for doctors and patients.” eye patients with unparalleled retention, Those wary of a generic op- simple sizing and ease of insertion. tion can rest assured it’s far in the future still. Not only does Allergan plan to appeal the decision, but Happy 20th Anniversary! the Food and Drug Administration has yet to approve generic equiva- lents of Restasis, according to a 866-906-8080 press release.1 [email protected] 1. Thomas K. Patents for Restasis are invalidated, opening door to generics. New York Times. October 16, 2017. www.nytimes. beaver-visitec.com com/2017/10/16/health/allergan-restasis-patent-.html. Ac- cessed October 17, 2017. 2. Thomas K. How to protect a drug patent? Give it to a Native American tribe. New York Times. September 8, 2017. www. nytimes.com/2017/09/08/health/allergan-patent-tribe.html. Accessed October 17, 2017.

004_ro1117_news.indd 7 11/3/17 3:44 PM News Review Potential DR Therapy cientists have identiﬁ ed a Photo: Mohammad Rafieetary, OD possible target for reducing BUSINESS OFFICES 11 CAMPUS BLVD., SUITE 100 Sdysfunctional blood vessel NEWTOWN SQUARE, PA 19073 growth in diabetic retinopathy CEO, INFORMATION SERVICES GROUP (DR). The researchers suspect a re- MARC FERRARA ceptor stimulates glycolysis, which (212) 274-7062 • [email protected] promotes pathological angiogenesis PUBLISHER JAMES HENNE 1,2 in retinopathies. (610) 492-1017 • [email protected]

“If we block the adenosine REGIONAL SALES MANAGER receptor A2a, the blood vessels MICHELE BARRETT will not leak, and not as many (610) 492-1014 • [email protected] new blood vessels will grow,” said Patients with diabetic retinopathy may REGIONAL SALES MANAGER MICHAEL HOSTER Yuqing Huo, MD, PhD, chief of one day have a new therapy option. (610) 492-1028 • [email protected]

the Vascular Inﬂ ammation Program VICE PRESIDENT, OPERATIONS at the Vascular Biology Center at colysis dramatically inhibits blood CASEY FOSTER the Medical College of Georgia at vessel proliferation and sprouting (610) 492-1007 • [email protected] Augusta University.1 of endothelial cells that overexpress VICE PRESIDENT, CLINICAL CONTENT PAUL M. KARPECKI, OD, FAAO 1,2 Adenosine receptor A2a is found the receptor. When oxygen levels [email protected]

on the endothelial cells that line were more normal, deleting adenos- PRODUCTION MANAGER blood vessels. When oxygen levels ine receptor A2a didn’t have that SCOTT TOBIN are good, adenosine A2a receptor much impact on glycolysis, possibly (610) 492-1011 • [email protected] expression is low. But in diabetes, because the receptor’s expression is SENIOR CIRCULATION MANAGER HAMILTON MAHER where oxygen levels go down, their not that high when oxygen levels (212) 219-7870 • [email protected] 1 1,2 expression increases. The increased are normal, the scientists suspect. CLASSIFIED ADVERTISING expression “means repairing exist- Luckily, an adenosine receptor (888) 498-1460

ing blood vessels and growing new A2a inhibitor is already in clinical SUBSCRIPTIONS ones in a process called angiogen- trials for Parkinson’s disease, paving $56 A YEAR, $88 (US) IN CANADA, $209 (US) IN ALL OTHER COUNTRIES. esis,” said Dr. Huo. But when “cells the way for more studies.1 don’t use energy effi ciently or build This is another fascinating sci- SUBSCRIPTION INQUIRIES (877) 529-1746 (US ONLY) blood vessels well, it’s actually entifi c endeavor, says Mohammad OUTSIDE US CALL: (845) 267-3065 1 called ‘pathological angiogenesis.’” Rafi eetary, OD, of Charles Retina CIRCULATION With DR, the blood vessels “grow Institute in Germantown, Tenn. PO BOX 81 CONGERS, NY 10920 too much, too fast,” says Dr. Huo, “Ultimately, diabetic retinopathy’s TEL: (TOLL FREE): (877) 529-1746 leading to bleeding or contraction, complications, which include vi- OUTSIDE US: (845) 267-3065 and then to hemorrhage, retinal sion loss, are primarily the result detachment and blindness.1 of hypoxia or ischemia.” Anything The researchers hypothesize that can lessen this hypoxia-induced CEO, INFORMATION SERVICES GROUP that adenosine, via the A2a recep- demise can help limit the degree and MARC FERRARA

tor, helps endothelial cells in the extent of the disease, which ends SENIOR VICE PRESIDENT, OPERATIONS 2 diabetic eye use glycolysis. The with loss of vision. “I am hopeful JEFF LEVITZ

research shows that blocking gly- to see advancements in the basic VICE PRESIDENT, HUMAN RESOURCES science such as these translate into TAMMY GARCIA

Correction clinical applications.” ■ VICE PRESIDENT, CREATIVE SERVICES & PRODUCTION On page 70 of the October 15, 2017 print edition, MONICA TETTAMANZI 1. Baker T. Likely new treatment target identiﬁ ed for diabetic the ocular motility grading standards mentioned in CORPORATE PRODUCTION DIRECTOR retinopathy. Jagwire News. October 2017. jagwire.augusta. JOHN ANTHONY CAGGIANO “My Five Favorite Binocular Evaulation Tests” were edu/archives/48024. Accessed October 25, 2017. incorrectly identiﬁ ed. They are from Northeastern 2. Liu Z, Yan S, Wang J, et al. Endothelial adenosine A2a VICE PRESIDENT, CIRCULATION State University College of Optometry. receptor-mediated glycolysis is essential for pathological retinal EMELDA BAREA angiogenesis. Nature Comm. 2017;8(1):584.

8 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

004_ro1117_news.indd 8 11/3/17 12:11 PM ZYLET®

“A One-Two Combo”

STEROID-RESPONSIVE INFLAMMATORY OCULAR CONDITIONS WITH RISK OF INFECTION

INDICATIONS AND USAGE IMPORTANT SAFETY INFORMATION (continued) ZYLET® (loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic • Prolonged use of corticosteroids may result in glaucoma with suspension) is a topical anti-infective and corticosteroid combination damage to the optic nerve, and defects in visual acuity and fi elds for steroid-responsive infl ammatory ocular conditions for which a of vision. Steroids should be used with caution in the presence of corticosteroid is indicated and where superfi cial bacterial ocular glaucoma. If this product is used for 10 days or longer, intraocular infection or a risk of bacterial ocular infection exists. pressure should be monitored. Ocular steroids are indicated in infl ammatory conditions of the palpebral • Use of corticosteroids may result in posterior subcapsular and bulbar conjunctiva, cornea and anterior segment of the globe such cataract formation. as allergic conjunctivitis, acne rosacea, superfi cial punctate keratitis, • The use of steroids after cataract surgery may delay healing and herpes zoster keratitis, iritis, cyclitis, and where the inherent risk of increase the incidence of bleb formation. In those diseases causing steroid use in certain infective conjunctivitides is accepted to obtain thinning of the cornea or sclera, perforations have been known to occur a diminution in edema and infl ammation. They are also indicated in with the use of topical steroids. The initial prescription and renewal chronic anterior uveitis and corneal injury from chemical, radiation or of the medication order should be made by a physician only after thermal burns, or penetration of foreign bodies. examination of the patient with the aid of magnifi cation such as a slit lamp biomicroscopy and, where appropriate, fl uorescein staining. The use of a combination drug with an anti-infective component is • Prolonged use of corticosteroids may suppress the host response indicated where the risk of superfi cial ocular infection is high or where and thus increase the hazard of secondary ocular infections. In acute there is an expectation that potentially dangerous numbers of bacteria purulent conditions, steroids may mask infection or enhance existing will be present in the eye. infections. If signs and symptoms fail to improve after 2 days, the patient The particular anti-infective drug in this product (tobramycin) is active should be re-evaluated. against the following common bacterial eye pathogens: Staphylococci, • Employment of corticosteroid medication in the treatment of patients including S. aureus and S. epidermidis (coagulase-positive and coagulase- with a history of herpes simplex requires great caution. Use of ocular negative), including penicillin-resistant strains. Streptococci, including some steroids may prolong the course and exacerbate the severity of many of the Group A-beta-hemolytic species, some nonhemolytic species, and viral infections of the eye (including herpes simplex). some Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia • Fungal infections of the cornea are particularly prone to develop coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, coincidentally with long-term, local steroid application. Fungus invasion Morganella morganii, most Proteus vulgaris strains, Haemophilus infl uenzae, must be considered in any persistent corneal ulceration where a steroid and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and has been used or is in use. some Neisseria species. • Most common adverse reactions reported in patients were injection and superfi cial punctate keratitis, increased intraocular pressure, and IMPORTANT SAFETY INFORMATION burning and stinging upon instillation. • ZYLET® is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic Please see Brief Summary of full Prescribing Information for keratitis), vaccinia, and varicella, and also in mycobacterial infections ZYLET® on adjacent page. of the eye and fungal diseases of ocular structures.

RCCL0517_BL Zylet.indd 1 5/1/17 11:04 AM BRIEF SUMMARY OF PRESCRIBING INFORMATION Secondary Infection: This Brief Summary does not include all the information needed to use Zylet safely The development of secondary infection has occurred after use of combinations containing and effectively. See full prescribing information for Zylet. steroids and antimicrobials. Fungal infections of the cornea are particularly prone to ® develop coincidentally with long-term applications of steroids. Zylet (loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension) The possibility of fungal invasion must be considered in any persistent corneal ulceration Initial U.S. Approval: 2004 where steroid treatment has been used. DOSAGE AND ADMINISTRATION Secondary bacterial ocular infection following suppression of host responses also occurs. 2.1 Recommended Dosing USE IN SPECIFIC POPULATIONS Apply one or two drops of Zylet into the conjunctival sac of the affected eye every four to six 8.1 Pregnancy hours. During the initial 24 to 48 hours, the dosing may be increased, to every one to two hours. Teratogenic effects: Loteprednol etabonate has been shown to be embryotoxic (delayed Frequency should be decreased gradually as warranted by improvement in clinical signs. Care ossification) and teratogenic (increased incidence of meningocele, abnormal left should be taken not to discontinue therapy prematurely. common carotid artery, and limb fixtures) when administered orally to rabbits during 2.2 Prescription Guideline organogenesis at a dose of 3 mg/kg/day (35 times the maximum daily clinical dose), a Not more than 20 mL should be prescribed initially and the prescription should not be dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these refilled without further evaluation [see Warnings and Precautions (5.3)]. effects was 0.5 mg/kg/day (6 times the maximum daily clinical dose). Oral treatment of CONTRAINDICATIONS rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥50 mg/kg/day) and embryo- 4.1 Nonbacterial Etiology toxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body Zylet, as with other steroid anti-infective ophthalmic combination drugs, is contraindicated weight and skeletal ossification with ≥50 mg/kg/day). Treatment of rats at 0.5 mg/kg/- in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex day (6 times the maximum daily clinical dose) during organogenesis did not result in any keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of reproductive toxicity. Loteprednol etabonate was maternally toxic (significantly reduced the eye and fungal diseases of ocular structures. body weight gain during treatment) when administered to pregnant rats during organo- WARNINGS AND PRECAUTIONS genesis at doses of ≥5 mg/kg/day. 5.1 Intraocular Pressure (IOP) Increase Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, of the fetal period through the end of lactation, a maternally toxic treatment regimen defects in visual acuity and fields of vision. Steroids should be used with caution in the (significantly decreased body weight gain), gave rise to decreased growth and survival presence of glaucoma. and retarded development in the offspring during lactation; the NOEL for these effects If this product is used for 10 days or longer, intraocular pressure should be monitored. was 5 mg/kg/day. Loteprednol etabonate had no effect on the duration of gestation or 5.2 Cataracts parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during Use of corticosteroids may result in posterior subcapsular cataract formation. the fetal period. 5.3 Delayed Healing Reproductive studies have been performed in rats and rabbits with tobramycin at doses The use of steroids after cataract surgery may delay healing and increase the incidence up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations harm to the fetus. There are no adequate and well controlled studies in pregnant women. have been known to occur with the use of topical steroids. The initial prescription and Zylet should be used during pregnancy only if the potential benefit justifies the potential renewal of the medication order should be made by a physician only after examination risk to the fetus. of the patient with the aid of magnification such as a slit lamp biomicroscopy and, where 8.3 Nursing Mothers appropriate, fluorescein staining. It is not known whether topical ophthalmic administration of corticosteroids could result in 5.4 Bacterial Infections sufficient systemic absorption to produce detectable quantities in human milk. Systemic Prolonged use of corticosteroids may suppress the host response and thus increase the steroids that appear in human milk could suppress growth, interfere with endogenous hazard of secondary ocular infections. In acute purulent conditions of the eye, steroids may corticosteroid production, or cause other untoward effects. Caution should be exercised mask infection or enhance existing infection. If signs and symptoms fail to improve after when Zylet is administered to a nursing woman. 2 days, the patient should be re-evaluated. 8.4 Pediatric Use ® 5.5 Viral Infections Two trials were conducted to evaluate the safety and efficacy of Zylet (loteprednol Employment of a corticosteroid medication in the treatment of patients with a history of etabonate and tobramycin ophthalmic suspension) in pediatric subjects age zero to six herpes simplex requires great caution. Use of ocular steroids may prolong the course and years; one was in subjects with lid inflammation and the other was in subjects with may exacerbate the severity of many viral infections of the eye (including herpes simplex). blepharoconjunctivitis. 5.6 Fungal Infections In the lid inflammation trial, Zylet with warm compresses did not demonstrate efficacy Fungal infections of the cornea are particularly prone to develop coincidentally with long- compared to vehicle with warm compresses. Patients received warm compress lid term local steroid application. Fungus invasion must be considered in any persistent treatment plus Zylet or vehicle for 14 days. The majority of patients in both treatment corneal ulceration where a steroid has been used or is in use. Fungal cultures should be groups showed reduced lid inflammation. taken when appropriate. In the blepharoconjunctivitis trial, Zylet did not demonstrate efficacy compared to vehicle, 5.7 Aminoglycoside Hypersensitivity loteprednol etabonate ophthalmic suspension, or tobramycin ophthalmic solution. Sensitivity to topically applied aminoglycosides may occur in some patients. If hypersensitivity There was no difference between treatment groups in mean change from baseline develops with this product, discontinue use and institute appropriate therapy. blepharoconjunctivitis score at Day 15. There were no differences in safety assessments between the treatment groups in either trial. ADVERSE REACTIONS 8.5 Geriatric Use Adverse reactions have occurred with steroid/anti-infective combination drugs which can No overall differences in safety and effectiveness have been observed between elderly be attributed to the steroid component, the anti-infective component, or the combination. and younger patients. Zylet: NONCLINICAL TOXICOLOGY In a 42 day safety study comparing Zylet to placebo, ocular adverse reactions included injection (approximately 20%) and superficial punctate keratitis (approximately 15%). Increased 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility intraocular pressure was reported in 10% (Zylet) and 4% (placebo) of subjects. Nine percent Long-term animal studies have not been conducted to evaluate the carcinogenic potential (9%) of Zylet subjects reported burning and stinging upon instillation. of loteprednol etabonate or tobramycin. Ocular reactions reported with an incidence less than 4% include vision disorders, Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma discharge, itching, lacrimation disorder, photophobia, corneal deposits, ocular discomfort, TK assay, a chromosome aberration test in human lymphocytes, or in an in vivo mouse eyelid disorder, and other unspecified eye disorders. micronucleus assay. The incidence of non-ocular reactions reported in approximately 14% of subjects was Oral treatment of male and female rats at 50 mg/kg/day and 25 mg/kg/day of loteprednol headache; all other non-ocular reactions had an incidence of less than 5%. etabonate, respectively, (500 and 250 times the maximum clinical dose, respectively) prior to and during mating did not impair fertility in either gender. No impairment of fertility was Loteprednol etabonate ophthalmic suspension 0.2% - 0.5%: noted in studies of subcutaneous tobramycin in rats at 100 mg/kg/day (1700 times the Reactions associated with ophthalmic steroids include elevated intraocular pressure, maximum daily clinical dose). which may be associated with infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing and secondary PATIENT COUNSELING INFORMATION ocular infection from pathogens including herpes simplex, and perforation of the globe This product is sterile when packaged. Patients should be advised not to allow the dropper where there is thinning of the cornea or sclera. tip to touch any surface, as this may contaminate the suspension. If pain develops, redness, itching or inflammation becomes aggravated, the patient should be advised to In a summation of controlled, randomized studies of individuals treated for 28 days or consult a physician. As with all ophthalmic preparations containing benzalkonium chloride, longer with loteprednol etabonate, the incidence of significant elevation of intraocular patients should be advised not to wear soft contact lenses when using Zylet. pressure (≥10 mm Hg) was 2% (15/901) among patients receiving loteprednol etabonate, 7% (11/164) among patients receiving 1% prednisolone acetate and 0.5% (3/583) among MANUFACTURER INFORMATION patients receiving placebo. Bausch + Lomb, a division of Valeant Pharmaceuticals North America LLC Tobramycin ophthalmic solution 0.3%: Bridgewater, NJ 08807 USA The most frequent adverse reactions to topical tobramycin are hypersensitivity and ©Bausch & Lomb Incorporated localized ocular toxicity, including lid itching and swelling and conjunctival erythema. Zylet is a registered trademark of Bausch & Lomb Incorporated or its affiliates. These reactions occur in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside antibiotics. Based on 9007706-9004406 Revised 08/2016 ZYL.0053.USA.16

RRCCL0517_BLCCL0517_BL ZZyletylet PI.inddPI.indd 1 55/1/17/1/17 11:0611:06 AMAM Contents Review of Optometry November 15, 2017

The Conjunctiva in Crisis: A Red Eye: 30 Ocular Irritation Unmasked 44 Scleritis or Episcleritis? When conjunctival calamities strike, here’s how to identify the Differentiating between the two is crucial to ensure you cause and come up with a plan. By Emily Bruce, OD, initiate the right treatment. By Jim Williamson, OD and Rodney Bendure, OD

When Dry Eye Compromises Glaucoma Therapy: Don’t 38 Corneal Integrity 50 Forget the Ocular Surface Your patients’ blurry vision, keratitis and infections could be Following the mantra “do no harm” can be a challenge when caused by ocular surface disease. By Scott G. Hauswirth, OD prescribing topical glaucoma medications. These tips can help minimize damage. By Leslie O’Dell, OD, and Ben Gaddie, OD

EARN 2 CE CREDITS The Origins and Management of Contact Lens Discomfort Understanding how this irritating nuisance develops is the first step toward fighting its deleterious 58 effects. By Dan Fuller, OD

66 Graft-vs.-host Disease: How, Why and What Next Dry eye is rampant in this population, and other complications abound. By Heather Spampinato, OD, and Matthew Hochwalt, OD

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 11

011_ro1117_toc.indd 11 11/3/17 4:36 PM Departments On The Web ›› Review of Optometry November 15, 2017 and more

4 News Review Check out our multimedia and continuing education online at: 14 Outlook Sugar Rush www.reviewofoptometry.com JACK PERSICO Digital Edition 16 Through My Eyes Left your copy of Red Eyes Mean Optometry Review of Optometry at PAUL M. KARPECKI, OD the office? No problem! 18 Chairside Access Review on your It’s All About the Benjamins computer or mobile device! MONTGOMERY VICKERS, OD Go to www.reviewofoptometry. 16 com and click on the digimag link 20 Clinical Quandaries for the current issue. Red Alert PAUL C. AJAMIAN, OD Facebook and Twitter 22 Coding Connection For daily updates, “Like” Steer Clear of the Coding Rut our page on Facebook or JOHN RUMPAKIS, OD, MBA “Follow” us on Twitter!

24 Neuro Clinic • www.facebook.com/revoptom A Second Helping • http://twitter.com/#!/revoptom MICHAEL TROTTINI, OD, AND MICHAEL DELGIODICE, OD Look for augmented content and 73 The Essentials special offers from Review and Go Deep on Corneal Abrasions our advertisers. Specified pages BISANT A. LABIB, OD 73 work in conjunction with your smartphone or other mobile 77 Review of Systems device to enhance the experience. Jaundice and the Eyes CARLO J. PELINO, OD, AND With Layar, interactive content JOSEPH J. PIZZIMENTI, OD leaps off the page!

80 Ocular Surface Review Could Eyelids Be the Key to DED? PAUL M. KARPECKI, OD

83 Cornea + Contact Lens Q&A Step1: Download the free Layar The Role of Toric Peripheries app for iPhone or Android. JOSEPH P. SHOVLIN, OD 84 Retina Quiz Next Time, Order Well Done FATEN EDRISKHALAF, OD, AND 80 Step 2: Look for pages with the MARK T. DUNBAR, OD Layar Logo. 89 Therapeutic Review INTERACTIVE PRINT Stemming the Tide ALAN G. KABAT, OD, AND JOSEPH W. SOWKA, OD Step 3: Open the Layar app, 90 Advertisers Index hold the phone above the page 92 Product Review and tap to scan it. Hold the phone above the page to view 93 Meetings & Conferences the interactive content. 94 Classifieds The first 150 app downloads and completed forms will be entered into a drawing for a 98 Diagnostic Quiz complimentary registration to one of Review’s Like Sunglasses at Night 98 14-hour CE meetings, valued at $495. ANDREW S. GURWOOD, OD

12 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

011_ro1117_toc.indd 12 11/3/17 4:37 PM CONTRIBUTING EDITORS A. PAUL CHOUS, MA, OD, TACOMA, WASH. PAUL C. AJAMIAN, OD, ATLANTA ROBERT M. COLE, III, OD, BRIDGETON, NJ AARON BRONNER, OD, KENNEWICK, WASH. GLENN S. CORBIN, OD, WYOMISSING, PA. MILE BRUJIC, OD, BOWLING GREEN, OHIO ANTHONY S. DIECIDUE, OD, STROUDSBURG, PA. DEREK N. CUNNINGHAM, OD, AUSTIN, TEXAS S. BARRY EIDEN, OD, DEERFIELD, ILL. MARK T. DUNBAR, OD, MIAMI STEVEN FERRUCCI, OD, SEPULVEDA, CALIF. ARTHUR B. EPSTEIN, OD, PHOENIX MURRAY FINGERET, OD, HEWLETT, NY JAMES L. FANELLI, OD, WILMINGTON, NC IAN BEN GADDIE, OD, LOUISVILLE, KY. FRANK FONTANA, OD, ST. LOUIS PAUL HARRIS, OD, MEMPHIS, TN GARY S. GERBER, OD, HAWTHORNE, NJ MILTON HOM, OD, AZUSA, CALIF. ANDREW S. GURWOOD, OD, PHILADELPHIA BLAIR B. LONSBERRY, MS, OD, MED, PORTLAND, ORE. ALAN G. KABAT, OD, MEMPHIS, TENN. THOMAS L. LEWIS, OD, PHD, PHILADELPHIA DAVID KADING, OD, SEATTLE DOMINICK MAINO, OD, MED, CHICAGO PAUL M. KARPECKI, OD, LEXINGTON, KY. KELLY A. MALLOY, OD, PHILADELPHIA JEROME A. LEGERTON, OD, MBA, SAN DIEGO RICHARD B. MANGAN, OD, LEXINGTON, KY. JASON R. MILLER, OD, MBA, POWELL, OHIO RON MELTON, OD, CHARLOTTE, NC CHERYL G. MURPHY, OD, BABYLON, NY PAMELA J. MILLER, OD, JD, HIGHLAND, CALIF. CARLO J. PELINO, OD, JENKINTOWN, PA. BRUCE MUCHNICK, OD, COATESVILLE, PA. JOSEPH PIZZIMENTI, OD, SAN ANTONIO, TEXAS MARC MYERS, OD, COATESVILLE, PA. JOHN RUMPAKIS, OD, MBA, PORTLAND, ORE. WILLIAM B. POTTER, OD, FREEHOLD, NJ DIANA L. SHECHTMAN, OD, FORT LAUDERDALE, FLA. CHRISTOPHER J. QUINN, OD, ISELIN, NJ JEROME SHERMAN, OD, NEW YORK MICHAEL C. RADOIU, OD, STAUNTON, VA. JOSEPH P. SHOVLIN, OD, SCRANTON, PA. MOHAMMAD RAFIEETARY, OD, MEMPHIS, TN JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. JOHN L. SCHACHET, OD, ENGLEWOOD, COLO. MONTGOMERY VICKERS, OD, LEWISVILLE, TEXAS JACK SCHAEFFER, OD, BIRMINGHAM, ALA. WALTER O. WHITLEY, OD, MBA, VIRGINIA BEACH, VA. LEO P. SEMES, OD, BIRMINGHAM, ALA. LEONID SKORIN, JR., OD, DO, ROCHESTER, MINN. EDITORIAL REVIEW BOARD JOSEPH W. SOWKA, OD, FORT LAUDERDALE, FLA. JEFFREY R. ANSHEL, OD, ENCINITAS, CALIF. SRUTHI SRINIVASAN, PhD, BS OPTOM, WATERLOO, ONT. JILL AUTRY, OD, RPH, HOUSTON BRAD M. SUTTON, OD, INDIANAPOLIS SHERRY J. BASS, OD, NEW YORK LORETTA B. SZCZOTKA, OD, PHD, CLEVELAND EDWARD S. BENNETT, OD, ST. LOUIS MARC TAUB, OD, MEMPHIS, TN MARC R. BLOOMENSTEIN, OD, SCOTTSDALE, ARIZ. TAMMY P. THAN, MS, OD, BIRMINGHAM, ALA. CHRIS J. CAKANAC, OD, MURRYSVILLE, PA. RANDALL THOMAS, OD, CONCORD, NC JERRY CAVALLERANO, OD, PHD, BOSTON SARA WEIDMAYER, OD, ANN ARBOR, MI WALTER L. CHOATE, OD, MADISON, TENN. KATHY C. WILLIAMS, OD, SEATTLE BRIAN CHOU, OD, SAN DIEGO KAREN YEUNG, OD, LOS ANGELES

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011_ro1117_toc.indd 13 11/3/17 4:36 PM Outlook By Jack Persico, Editor-in-Chief PRINTED IN USA

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EDITORIAL OFFICES Sugar Rush 11 CAMPUS BLVD., SUITE 100 NEWTOWN SQUARE, PA 19073 November is Diabetic Eye Disease Awareness Month. So WEBSITE • WWW.REVIEWOFOPTOMETRY.COM

SUBSCRIPTION INQUIRIES put away that leftover Halloween candy already! 1-877-529-1746 CONTINUING EDUCATION INQUIRIES ptometrists are often prod- Americans know diabetes can be 1-800-825-4696 ded—by people like me, on detected in an eye exam, even though EDITOR-IN-CHIEF • JACK PERSICO pages like this—to do more. 72% know that there’s a connection (610) 492-1006 • [email protected] O See more patients, add new services, between diabetes and blindness. MANAGING EDITOR • REBECCA HEPP (610) 492-1005 • [email protected] learn new things, sell more products, Consider that discrepancy a man- SENIOR EDITOR • BILL KEKEVIAN hire more people, buy more stuff. date for eye doctors to speak out (610) 492-1003 • [email protected] It must be wearying. So I thought about diabetes often and unabash- ASSOCIATE EDITOR • MICHAEL RIVIELLO (610) 492-1021 • [email protected] I’d start by complimenting you, for edly. I know some doctors feel ill ASSOCIATE EDITOR • MICHAEL IANNUCCI something you’ve already done. at ease talking with patients about (610) 492-1043 • [email protected] According to the AOA, in 2016 weight, diet and other lifestyle SPECIAL PROJECTS MANAGER • JILL HOFFMAN (610) 492-1037 • [email protected] optometrists diagnosed 320,000 choices that might seem to be beyond ART DIRECTOR • JARED ARAUJO new cases of diabetic eye disease in the purview of optometric practice. (610) 492-1032 • [email protected] patients who otherwise didn’t know But they aren’t. Too many people are DIRECTOR OF CE ADMINISTRATION • REGINA COMBS (212) 274-7160 • [email protected] they had diabetes. That’s impressive at risk to be modest about it.

EDITORIAL BOARD unto itself (an average of eight new Whether you’re just starting out CHIEF CLINICAL EDITOR • PAUL M. KARPECKI, OD diagnoses per OD per year), but con- or already established, diabetes ASSOCIATE CLINICAL EDITORS • JOSEPH P. SHOVLIN, OD; sider that, just two years prior, the is going to be a dominant part of ALAN G. KABAT, OD; CHRISTINE W. SINDT, OD number was 240,000. In a two-year your practice for, well, ever. Prevent DIRECTOR OPTOMETRIC PROGRAMS • ARTHUR EPSTEIN, OD CLINICAL & EDUCATION CONFERENCE ADVISOR span, the optometric community Blindness America (PBA) says eight PAUL M. KARPECKI, OD increased its diagnoses of diabetes by million people have diabetic eye dis- CASE REPORTS COORDINATOR • ANDREW S. GURWOOD, OD 33%. That achievement may have ease right now, and that number will CLINICAL CODING EDITOR • JOHN RUMPAKIS, OD, MBA flown under the radar, especially on grow to 11 million over the next CONSULTING EDITOR • FRANK FONTANA, OD editorial pages that always nag, nag, 15 years. PBA projects the Hispanic COLUMNISTS nag. So, congratulations! population will see the most growth, CHAIRSIDE • MONTGOMERY VICKERS, OD “Expanded scope of practice for with cases nearly doubling by 2050. CLINICAL QUANDARIES • PAUL C. AJAMIAN, OD doctors of optometry has produced If these patients present a language CODING CONNECTION • JOHN RUMPAKIS, OD CORNEA & CONTACT LENS Q+A • JOSEPH P. SHOVLIN, OD historic gains in quality care, deliv- or cultural barrier to non-Hispanic DIAGNOSTIC QUIZ • ANDREW S. GURWOOD, OD ered superior outcomes, improved ODs, try to find other ways to reach THE ESSENTIALS • BISANT A. LABIB, OD the lives of patients and established them, such as Spanish-language edu- FOCUS ON REFRACTION • MARC TAUB, OD; a primary care success story,” says cational videos and handouts, or a PAUL HARRIS, OD GLAUCOMA GRAND ROUNDS • JAMES L. FANELLI, OD AOA president Christopher Quinn, public health resource in your com- NEURO CLINIC • MICHAEL TROTTINI, OD; OD. “It’s not at all surprising that munity that serves this audience. MICHAEL DELGIODICE, OD many people learn of their diabetes It’s for these reasons that PBA has OCULAR SURFACE REVIEW • PAUL M. KARPECKI, OD risk through a dilated, comprehen- declared November to be Diabetic RETINA QUIZ • MARK T. DUNBAR, OD REVIEW OF SYSTEMS • CARLO J. PELINO, OD; sive eye examination from their doc- Eye Disease Awareness Month. JOSEPH J. PIZZIMENTI, OD tor of optometry.” And it “reinforces The AOA is doing its part to help SURGICAL MINUTE • DEREK N. CUNNINGHAM, OD; the importance of regular, in-person by offering educational materials WALTER O. WHITLEY, OD, MBA THERAPEUTIC REVIEW • JOSEPH W. SOWKA, OD; eye care,” he adds. for ODs and their patients. A good ALAN G. KABAT, OD But, if I may, there’s still room for place to start is www.aoa.org/news/ THROUGH MY EYES • PAUL M. KARPECKI, OD improvement. Because the state of clinical-eye-care/diabetes-month-17. URGENT CARE • RICHARD B. MANGAN, OD diabetes awareness and attention is Optometrists have already done a JOBSON MEDICAL INFORMATION LLC still dire. The AOA’s 2016 Eye-Q great job of getting vulnerable dia- survey of public knowledge of eye betes patients diagnosed and treated. diseases found that only 41% of Keep up the good work! ■

14 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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RO1117_Zeiss.indd 1 10/30/17 2:45 PM Through My Eyes By Paul M. Karpecki, OD, Chief Clinical Editor Red Eyes Mean Optometry Patients still head to their primary care provider for this when they should be giving their OD a call. What we find could be far more troubling.

patient who sched- tions we can treat, including every- ules an appointment thing from a common conjunctivitis Afor a red eye could to the most critical and rare find- walk through the door ings. It may be ‘pink eye’ or another with any number of ocular basic issue that brings them in; once issues. This month’s feature they’re in the chair, however, we can articles hit the highlights: truly play a life-changing role. allergy, infection, dry eye, Take a recent 50-year-old patient. scleritis and episcleritis, He presented to a local optometrist to name only a few. But simply because of symptoms related some patients still call their to presbyopia. He measured 20/20+ primary care provider for OD and OS. Because it was his first a red eye, especially if the Although this patient had no complaints, his exam with an optometrist, he was patient is a child. Many optometrists found a large retinal lesion during dilated and received a comprehen- parents aren’t aware of the dilated exam, later diagnosed as malignant sive exam. The OD captured the where to take their children choroidal melanoma. image provided here, and imme- when they have ‘pink eye.’ diately referred him to our retina We must continue to educate Staphylococcus, the pathogens in specialty practice for further evalu- patients—starting with each parent childhood conjunctivitis cause a sig- ation. Fundus exam revealed a large or patient who enters our offices— nificant number of systemic issues, lesion, OCT imaging confirmed the on our services beyond the basic including otitis, preceptal cellulitis presence of serous fluid, autofluo- refraction that once defined us. We and, in rare cases, encephalitis. rescence confirmed lipofuscin over have to directly or indirectly convey The first step when examining a the lesion and ultrasound confirmed to our patients that we manage child with conjunctivitis is checking a diameter of more than 3mm. All anything related to the eyes, includ- their temperature and questioning of this led to a confirmed diagnosis ing “red eyes” and children. In the parents regarding systemic find- of a malignant choroidal melanoma. addition to managing garden-vari- ings. A fever, ear infection, malaise Though he was referred to our ety conjunctivitis most effectively, or upper respiratory infection specialty practice, every one of these we can also ensure that it is not an warrants systemic treatment, and tests could have been conducted by iritis, preceptal cellulitis, episcleritis, only then would a referral to the the primary eye care provider. OCTs keratitis or some other potential pediatrician be best. The presence are commonplace in optometry, differential diagnosis that could be of a reddish sheen around the eyes as are ultra-widefield imagers and more painful and problematic. indicates preceptal cellulitis and dilated fundus exams. Even B-scan Optometrists also know to look requires oral antibiotics in addition ultrasounds are now inexpensive for systemic findings in patients to topical treatment—something and have great image resolution. who present with conjunctivitis. optometrists can handle. This is just one more example of The most common causes of bacte- why it is so important to educate rial conjunctivitis in children, for Beyond the Ocular Surface our patients about our knowledge, example, include Haemophilus Now is a critical time for optometry training and capabilities. Without influenza and Streptococcus pneu- to educate the masses. It is always optometric intervention, this mela- monia. Unlike adult conjunctivitis, in our interest to educate about the noma would surely have resulted in which is most commonly caused by technology we use and the condi- devastating consequences. ■

16 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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ight or wrong, for better or closet. So that’s where all that patients to refer friends, cowork- for worse, the most impor- money went! ers and family members. I find that Rtant word in medicine is 5. Make a donation. You will promising not to key their car if “money.” That’s right! I said it! always be rewarded for giving, they refer seems to work. As the great economist Cyndi especially if it’s your state’s optom- 13. Accept any and all insur- Lauper so beautifully explained etry PAC or DVVF—Dr. Vickers’s ances and vision plans as long as it, “Money Changes Everything.” Vacation Fund is also not tax they require policyholders to pay The Notorious B.I.G. expanded deductible, so what’s the difference? for everything out of pocket. This upon the thesis by wisely reminding 6. Reach out to an old friend gives you more time to binge read us, “Mo Money, Mo Problems.” and remind him about that lunch my column. I could go on, because “Money money you gave him in third grade. 14. Square your shoulders and Makes the World Go Round” Explain compounding interest. stand up straight. Look that waiter (Thanks, Liza Minnelli and Joel 7. Ask your closest colleague/ right in the eye and ask if they have Grey). competitor to check your eyes. You a senior citizen discount. If not, After all, we have to make money can steal their best ideas and get order a kid’s meal. or we go out of business; if we go smug satisfaction they didn’t make out of business, we cannot help our any money while with you. I truly hope this helps. Lucky for patients. Why do they not under- 8. Carry a roll of quarters at all me, when I was a kid, my mom told stand that? times so you can physically tell that me: “Don’t marry for money. Just What should you do to make you have money. hang around rich people until you sure your doors stay open? Many 9. Buy a new piece of equipment fall in love with one of them.” I was sage business consultants can offer that will benefit your patients and married three years before I realized to you, for a hefty fee (so they can add potential income to your office. Renee’s dad was a coal miner, not a stay in business) some very effec- A gumball machine, perhaps? gold miner. Darn. ■ tive advice. Or you could listen to 10. Practice mindfulness, so Cyndi and Biggie. I would urge you when you are stressed and broke, to get good advice before you are in you can be completely stressed and trouble, for sure. Here’s what I do broke right where you are. when worried about money: 11. Make sure patients can always find you easily—except 1. Buy something. There’s noth- when they can’t adapt to their ing like the rush when the checkout progressives. clerk says you just saved $30. 12. Urgently 2. Check the change in your car’s motivate console. The other day, I found your enough for a hot dog. 3. Go out to dinner with your grown children. When the waiter brings the check, head to the bath- room until the bill is settled. They owe you. 4. Count the golf shirts in your

18 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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Red Alert A routine conjunctivitis case could portend serious systemic illness. Edited by Paul C. Ajamian, OD Q A 45-year-old female in good key anatomical and physiological health presents with subepitheli- differences, and mitotic rates and al infiltrates and a red eye. It looks like corneal nerve density differ greatly,” simple epidemic keratoconjunctivitis. he explains. A careful history, However, the patient is lethargic with along with patient symptoms and a labored breathing. Do I just assume detailed examination of the cornea that her eye infection is causing her to and adnexa, are essential in differ- feel bad? entiating a sterile from an infectious A “When this patient presented An ill eye, along with non-specific process. to me, I suspected something systemic complaints, could signal a “Remember that, histologically, else was going on,” says Carlton serious systemic condition is afoot. all infections have infiltration with, Edwards, OD, in private practice or occasionally without, overly- in Douglasville, GA. Both eyes had tation of an underlying systemic ing defects or frank ulceration,” been red for only three days, yet disease, such as the nummular he says. “In this case, the patient there were corneal infiltrates noted infiltrates found in Lyme disease and presents with diffuse subepithelial in both eyes, says Dr. Edwards. “It numerous corneal findings of the infiltrates that may signal a viral didn’t add up, so I made an immedi- herpes family of infections, says Dr. cause. Generally, infiltrates in ate referral to her internist, which Shovlin. He says to monitor patients adenovirus disease present the sec- led to hospital admission.” for any unusual symptoms and fol- ond week and, if vision is affected An obvious ocular condition low closely when indicated. “As my significantly, topical steroid drops in conjunction with non-specific mentor once said, ‘When all else such as loteprednol etabonate are systemic complaints should catch fails, re-examine,’” says Dr. Shovlin. indicated.” your attention, as a potentially It just so happens that in this life-threatening condition could Back to Square One case, the viral cause wasn’t located be at work, says Joseph Shovlin, To unravel the mystery of your in the eye. Rather, it was located in OD, a practitioner at Northeastern patient’s illness, Dr. Shovlin says to the heart. Dr. Edwards spoke to the Eye Institute in Scranton, PA, and start by asking them for all the facts. patient’s internist a week later, and president of the American Academy “A detailed history is always a great “the workup confirmed a systemic of Optometry. “Always gauge the place to start,” says Dr. Shovlin. Ask viral infection, which led to prema- general health of your patient and about timing, onset and the exact ture ventricular contractions. The respond to any symptoms that symptoms, he says, as well as sever- cardiomyopathy that ensued could appear sinister or unexpected,” says ity and frequency. have taken the patient’s life if it had Dr. Shovlin. Although patients are been ignored,” says Dr. Edwards. often very uncomfortable with ade- Investigate the Infiltrate novirus infection, severe malaise or Next, see what the corneal disrup- As medical professionals, optom- a feeling that they are very ill are out tion might suggest. Infiltrates— etrists are responsible for the health of the norm, Dr. Shovlin explains. aggregates of white blood of their patients in every area, “If these symptoms occur, it’s cells—have multiple causes, says across organ systems. The ocular imperative that clinicians evaluate Dr. Shovlin. He explains that the system is often a window into the the patient for additional systemic number, location and level of cor- rest of the body. When practitioners ailments.” neal involvement may provide some remain vigilant and suspicious, they Corneal signs, including infil- clues as to the etiology. “The cen- have the best opportunity to save trates, can certainly be a manifes- tral cornea and the periphery have the life of their patients. ■

20 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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WO0317_Alcon surgical.indd 1 2/27/17 4:54 PM Coding Connection

Steer Clear of the Coding Rut Every patient’s office visit is different and, often, so is the coding. By John Rumpakis, OD, MBA, Clinical Coding Editor s we fine-tune our practices, program; intermediate, established 992XX we often focus so intently on patient. The E/M codes are typically used for Acoding new technologies that 92014. Ophthalmological ser- patients with a medical complaint we forget our practice’s foundation: vices: Medical examination and or a continuation of medical case the office visit. Many ODs get into evaluation, with initiation or contin- management. The five levels of E/M the habit of coding the same type uation of diagnostic and treatment codes are universally applicable of visits, which can leave money on program; comprehensive, established for all medical eye care encoun- the table by undercoding or create patient, one or more visits. ters; however, out of the 10 codes undue exposure by overcoding. Comprehensive eye examina- within this subset, only six are used Eye exams can be coded at least tion codes (92004, 92014). These routinely: 99201, 99202, 99203, 16 ways in an optometric practice. describe a general evaluation of the 99212, 99213 and 99214. The 16 codes are comprised of four complete visual system. According These codes have more specific ophthalmic visit codes (920XX), to the CPT definition, it “includes requirements regarding case his- 10 E/M codes (992XX) and two history, general medical observa- tory, elements of exam and medical HCPCS “S” codes (S062X). Because tion, external and ophthalmoscopic decision-making. The higher level S codes are not used for the medical examinations, gross visual fields and codes for a new patient, 99204 and management of a patient, we will basic sensorimotor examination. It 99205, require a comprehensive his- eliminate them from consideration. often includes, as indicated: biomi- tory, for which it is difficult, but not croscopy, examination with cyclo- impossible, for ODs to qualify. 920XX plegia or mydriasis and tonometry. One of the most common mis- Ophthalmic office visits are either It always includes initiation of diag- understandings is scoring the his- comprehensive or intermediate for nostic and treatment programs.” tory. Properly scoring the review of both new and established patients. Gross visual fields and a basic systems, for example, includes only Remember, a new patient is one who sensorimotor exam are also required the systems pertinent to the patient has not received professional services for a comprehensive eye exam, while encounter on that specific day. Too from a physician of the exact same dilation is not; however, as part of often, clinicians count all 14 systems specialty and subspecialty in the the definition of each code, dilation toward their history score, when same group practice in three years. is not a separately billable procedure only a few are pertinent. When 92002. Ophthalmological ser- should you choose to perform it. scored correctly, the highest E/M vices: Medical examination and Intermediate codes (92002, code achievable would generally be evaluation with initiation of diag- 92012). These are defined as: “an 99203 for a new patient and 99214 nostic treatment program; interme- evaluation of a new or existing con- for an established patient. diate, new patient. dition complicated with a new diag- Understanding office visit codes 92004. Ophthalmological ser- nostic or management problem not is critical to coding the proper type vices: Medical examination and necessarily relating to the primary and level of examination. Don’t get evaluation with initiation of diag- diagnosis, including history, general into a rut by performing a particular nostic treatment program; compre- medical observation, external ocular type and level of exam out of habit. hensive, new patient, one or more and adnexal examination and other Instead, be cognizant of the type and visits. diagnostic procedures as indicated; level of care your patients need and 92012. Ophthalmological ser- may include the use of mydriasis for strengthen your practice’s founda- vices: Medical examination and ophthalmoscopy.” Some inappropri- tion for the future. ■ evaluation, with initiation or contin- ately use these codes to reduce the Send questions and comments to uation of diagnostic and treatment exam cost to a non-insured patient. [email protected].

22 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

022_ro1117_coding.indd 22 11/3/17 12:16 PM 8.4 base curve now available!

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RO0817_Menicon.indd 1 7/27/17 10:57 AM Neuro Clinic

A Second Helping Idiopathic intracranial hypertension sometimes returns. When it does, here’s what to do. By Michael DelGiodice, OD, and Michael Trottini, OD

24-year-old Hispanic female hypertension (IIH)—also called presented in consultation from pseudotumor cerebri—a diagnosis Aher neurologist for intractable of exclusion. headache lasting three weeks, with a Consequently, she was sent to normal neurologic exam and blood the emergency department for pressure. Her history was positive for emergent head computed tomogra- neck pain and transient “blackouts” in phy (CT) to discount intracranial both eyes lasting less than 30 seconds. pathologies such as hemorrhage, She was taking Avonex (interferon infection and mass lesion; her CT beta-1a, Biogen) for her MS. Her past scan was unremarkable. She then ocular, family and social histories were underwent lumbar puncture (LP), unremarkable. which revealed an opening pres-

Her best-corrected acuities were sure of 550mm H2O and normal 20/25 OU. Ocular motilities were cerebrospinal fluid (CSF). Because

full with no limitation. Pupil evalu- a reading above 250mm H2O with ation showed no afferent pupillary Two years after an IIH bout, this patient normal CSF is consistent with intra- defect, and she was orthophoric returned with grade four papilledema. cranial hypertension secondary to in primary and lateral gaze in IIH, she was diagnosed with IIH.1 both eyes. She noted 10/10 color plates in each eye. After the patient was discharged from the hospital, Intraocular pressure (IOP) measured 18mm Hg OD we reviewed the laboratory tests to confirm there was and 16mm Hg OS. The anterior segment exam was no contraindication to starting her on acetazolamide; unremarkable. Fundus exam showed bilateral blurring her potassium was within normal range between of the optic disc margins, peripapillary hemorrhages, 3.5mEq/L to 5.0 mEq/L.2 We started her on acetazol- absent venous pulsations and venous engorgement and amide 250mg twice daily and slowly titrated up to tortuosity. 500mg twice daily and discussed a low-sodium weight loss plan of one pound per week for 12 weeks. First Encounter The patient was monitored monthly, and over the Because of her symptoms of transient visual obscura- next six months she lost 10 pounds. The headaches, tions, intractable headaches and neck pain, and in disc edema and visual field testing improved dramati- accordance with the findings of bilateral disc edema, cally. However, she was lost to follow up for the next we were concerned she was suffering from an intracra- two years. nial process. We ordered fundus photography, spectral- domain optical coherence tomography (SD-OCT) and Back for More visual fields (VF). SD-OCT showed significant bilateral She recently returned with complaints of severe head- elevation of the retinal nerve fiber layer, and VF testing ache, pulsatile synchronous tinnitus and bilateral tran- showed an enlargement of the physiologic blindspot sient vision loss despite taking 250mg of acetazolamide and central-inferior hemifield defects OU. daily and a net loss of 20 pounds since her last visit. Given her history and demographics, we formed a Ophthalmologic examination revealed recurrent, differential diagnosis of conditions that may result in grade four papilledema. We ordered a metabolic panel elevated intracranial pressure (ICP): malignant hyper- to evaluate her potassium before increasing the dose tension, space-occupying mass, hemorrhage, infec- of acetazolamide. The potassium level was 3.3mEq/L, tion, inflammation and, lastly, idiopathic intracranial which was slightly lower than the 3.5mEq/L cutoff

24 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

024_ro1117_Neuro Clinic.indd 24 11/3/17 12:21 PM WHAT SETS THE ACTIVEFOCUS™ DESIGN APART? THE DIFFERENCE IS IN THE DISTANCE.

RO1117_Alcon Active.indd 1 10/30/17 2:28 PM Neuro Clinic

value. She was instructed to follow up with her pri- involves axoplasmic stasis with swelling of axons and mary care physician for clearance. Once cleared, we leakage.3 The increased pressure is transmitted along increased her dosage to 500mg of acetazolamide twice the subarachnoid space, leading to increased pressure daily. within the optic nerve tissues and clinical disc edema. She returned four weeks later with no improvement Histopathology of papilledema shows displacement of in symptoms. We then ordered magnetic resonance the retina away from the optic disc with serous sensory venography (MRV) due to the recurrent nature and detachment within the peripapillary area.3 severity of the papilledema. The MRV revealed narrow The most common general symptoms of pseu- dural venous sinuses without frank stenosis or throm- dotumor cerebri include headaches in the morning bosis. Given the recurrent, aggressive nature of the that intensify with movement, projectile vomiting, condition and her lack of proper follow up, we alerted neck pain, tinnitus (whooshing or ringing in the ears) her neurologist and admitted her to the hospital for and loss of consciousness. Ocular symptoms include electrolytes, therapeutic LP and intravenous mannitol. blurred vision, transient visual obscuration, vision loss, Neurosurgery then evaluated her for an intracranial retro-orbital pain and horizontal diplopia.4 Optic nerve shunt. findings include elevation of the disc with hyperemia, blurring of the disc margins, superficial retinal hem- Pseudo Tumor, Genuine Concerns orrhages, edema of the peripapillary region, loss of Even optometrists who see it infrequently know that venous pulsations, concentric retinal or chorioretinal papilledema is defined as bilateral disc edema sec- folds around the optic nerve and macular exudates.4 ondary to increased ICP, and identification is often Other findings include retinal vascular tortuosity and straightforward. To a clinician, the bigger challenge hemorrhages within the posterior pole and retinal is determining what it signifies. Its pathophysiology periphery.4 Diagnostic criteria. IIH is diagnosed based on the modified Dandy criteria, which include: signs and symptoms of increased ICP, no localized neurologic IMPORTANT PRODUCT INFORMATION FOR THE ACRYSOF® IQ RESTOR® FAMILY OF IOLs findings, normal neuroimaging with the exception of CAUTION: Federal (USA) law restricts this device to the sale by or on the order an empty sella (dark appearance of the sella tursica of a physician. on T1-weighted MRI from increased CSF), opening INDICATIONS: The AcrySof® IQ ReSTOR® Posterior Chamber Intraocular Multi- focal IOLs include AcrySof® IQ ReSTOR® and AcrySof® IQ ReSTOR® Toric and are LP pressure of greater than 250mm H2O with normal intended for primary implantation for the visual correction of aphakia secondary CSF and no other causes of increased ICP.5 to removal of a cataractous lens in adult patients with and without presbyopia, who desire near, intermediate and distance vision with increased spectacle Grading. During clinical examination, it is impor- independence. In addition, the AcrySof® IQ ReSTOR® Toric IOL is intended to tant to initially grade the severity of papilledema to correct pre-existing astigmatism. The lenses are intended to be placed in the capsular bag. monitor the effects of therapy:6 WARNINGS/PRECAUTIONS: Careful preoperative evaluation and sound Grade I: C-shaped halo of nerve fiber layer edema clinical judgment should be used by the surgeon to decide the risk/benefit ratio before implanting a lens in a patient with any of the conditions described in the and blurred disc margins with a temporal gap. Directions for Use labeling for each IOL. Physicians should target emmetropia, Grade II: progressive circumferential edema and and ensure that IOL centration is achieved. Care should be taken to remove viscoelastic from the eye at the close of surgery. margin obscuration with blurring of the capillaries. The ReSTOR Toric IOL should not be implanted if the posterior capsule is Grade III: Expanded nerve fiber layer edema and ruptured, if the zonules are damaged, or if a primary posterior capsulotomy is planned. Rotation can reduce astigmatic correction; if necessary lens reposition- obscured major blood vessels as they leave the disc. ing should occur as early as possible prior to lens encapsulation. Grade IV: loss of major vessels on the disc. Some patients may experience visual disturbances and/or discomfort due to Grade V: characteristics of grade IV plus partial or multifocality, especially under dim light conditions. A reduction in contrast sensitivity may occur in low light conditions. Visual symptoms may be significant total obscuration of all vessels of the disc.6 enough that the patient will request explant of the multifocal IOL. Spectacle independence rates vary; some patients may need glasses when reading small Testing. Taking visual fields is necessary to monitor print or looking at small objects. functional vision. According to research, over 90% of Posterior capsule opacification (PCO), when present, may develop earlier into patients with papilledema had visual loss documented clinically significant PCO with multifocal IOLs. Prior to surgery, physicians should 7 provide prospective patients with a copy of the Patient Information Brochure by perimetry. The most common visual field deficits available from Alcon informing them of possible risks and benefits associated with the AcrySof® IQ ReSTOR® IOLs. include enlargement of the blind spot, inferior nasal 8 Do not resterilize; do not store over 45° C; use only sterile irrigating solutions depressions and peripheral constriction. such as BSS® or BSS PLUS® Sterile Intraocular Irrigating Solutions. After diagnosing bilateral disc edema, it is impor- ATTENTION: Reference the Directions for Use labeling for each IOL for a com- tant to check the blood pressure to discount primary plete listing of indications, warnings and precautions. malignant hypertension or secondary hypertension

0024_ro1117_Neuro24_ro1117_Neuro CClinic.inddlinic.indd 2266 111/3/171/3/17 12:2312:23 PMPM from increased ICP. The next step amide, divided into four doses, was is to send the patient to the local administered and then increased emergency department with the by 250mg per week to a maximum diagnosis and your recommenda- dosage of 4g/d until the papill- tion for stat head CT, as well as edema grade was less than one in LP—in the absence of intracranial both eyes and the mean deviation pathology on neuroimaging—to on VF testing improved to equal to record the opening pressure and or better than -1dB in each eye.12 check the CSF for pathology. CT A low-sodium weight management is preferred over MRI in the emer- plan should be implemented. Stud- gency setting because it is readily ies show as little as 6% weight loss available and quickly assesses for is effective in improving signs and intracranial pathologies such as symptoms of ICP.13 hemorrhages, space-occupying During medical therapy, clini- lesions, obstructive hydrocephalus cians should measure the visual and cerebral edema, all of which acuities, test the VFs and perform are neurologic emergencies. Significant bilateral elevation of the nerve fundus photography, OCT and In our case, we ordered MRV fiber layer can be seen on the patient’s OCT. FA. Patients who do not show because the patient continued to improvement in papilledema or show signs of intractable papilledema, headaches and systemic symptoms despite medical therapy and weight tinnitus despite significant weight loss and long-term loss should be referred for neurosurgical consultation. acetazolamide use. The MRV allowed us to discount Surgical treatment includes therapeutic LP, optic nerve abnormalities within the venous drainage system, decompression and intracranial shunting. identify potential additional causes for the recalcitrant nature of the condition, better establish a prognosis In IIH, medical management is necessary to pre- and determine whether surgical intervention was neces- serve visual function and decrease systemic symptoms. sary. According to a recent study, MRV reveals bilat- Monthly follow up is recommended to test visual acu- eral narrowing of lateral sinuses in IIH, which is rarely ities, perform formal perimetry and record the grad- seen in controls.9 ing of disc edema. In recurrent and refractory cases, OCT and fluorescein angiography (FA), in addition consider MRV to discount venous sinus pathologies to recording the stage of papilledema, can be used to and better gauge prognosis. Patients who show nar- monitor the status of the disc during treatment. FA rowing of the venous system may follow a prolonged findings of the early phase of papilledema includes treatment course and require closer observation for disc capillary dilation and leakage within the disc. Late surgery. ■ findings show leakage beyond and pooling around the 10 1. Corbett JJ, Mehta MP. Cerebrospinal fluid pressure in normal obese subjects and patients disc. On OCT, papilledema causes a hyporeflective with pseudotumor cerebri. Neurology. 1983;33(10):1386-8. space above the retinal pigment epithelium within the 2. Kupersmith MJ, Gamell L, Turbin R, et al. Effects of weight loss on the course of idiopathic intracranial hypertension in women. Neurology. 1998;50(4):1094-8. papillary space, representing serous sensory retinal 3. Wang JK, Kardon RH, Ledolter J, et al. Peripapillary retinal pigment epithelium layer shape detachment.11 changes from acetazolamide treatment in the idiopathic intracranial hypertension treatment trial. Invest Ophthalmol Vis Sci. 2017;58(5):2554-65. Treatment. The key goal is to decrease ICP to help 4. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010;28(3):593-617. preserve vision and eliminate intractable headaches. 5. Dandy WE. Intracranial pressure without brain tumor. Ann Surg. 1937;106:492–513. 6. Frisén LJ. Swelling of the optic nerve head: a staging scheme. Neurol Neurosurg Psychiatry. Medical therapies include acetazolamide, oral glycerol, 1982;45(1):13-8. IV mannitol and weight reduction. 7. Wall M, George D. Idiopathic intracranial hypertension. A prospective study of 50 patients. Brain. 1991;114:155-80. Acetazolamide is the treatment of choice to man- 8. Wall M, George D. Visual loss in pseudotumor cerebri. Incidence and defects related to age IIH.2 It reduces CSF production and flow from the visual field strategy. Arch Neurol. 1987;44:170-5. 9. JNP Higgins, JH Gillard, BK, Owler et al. MR venography in idiopathic intracranial hyperten- choroid plexus. Prior to beginning therapy, a complete sion: unappreciated and misunderstood. Neurol Neurosurg Psychiatry. 2004;75:621-5. metabolic panel should be ordered to establish a base- 10. Cartlidge NE, Ng RC, Tilley PJ. Dilemma of the swollen optic disc: a fluorescein retinal angiography study. Br J Ophthalmol. 1977;6:385-89. line level of electrolytes and, if the results are concern- 11. Hoye VJ, Berrocal AM, Hedges TR, Amaro-Quireza ML. Optical coherence tomog- ing, consult with the patient’s primary care physician raphy demonstrates subretinal macular edema from papilledema. Arch Ophthalmol. 2001;119:1287-90. before administering the drug. 12. Newborg B. Pseudotumor cerebri treated by rice reduction diet. Arch Intern Med. In one study, treatment with 250mg of acetazol- 1974;133:802-7.

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 27

024_ro1117_Neuro Clinic.indd 27 11/3/17 12:22 PM NEW STUDY EFFECTIVENESS OF ROHTO® DRY-AID™ VS. WIDELY USED ARTIFICIAL TEAR ROHTO® DRY-AID™ Provides All-Day Dry Eye Symptom Relief

Dry Eye Disease (DED) is the most prevalent ĨŽƌŵŽĨŽĐƵůĂƌĚŝƐĐŽŵĨŽƌƚĂŶĚŝƌƌŝƚĂƟŽŶ͕ǁŝƚŚ ĞƐƟŵĂƚĞƐŽĨĂīĞĐƚĞĚŝŶĚŝǀŝĚƵĂůƐƌĂŶŐŝŶŐĨƌŽŵ ϭŝŶϮϬƚŽĂƐŚŝŐŚĂƐϭŝŶĞǀĞƌǇϱĂĚƵůƚƐŝŶƚŚĞ hŶŝƚĞĚ ^ƚĂƚĞƐ ĞǆƉĞƌŝĞŶĐŝŶŐ ƐŽŵĞ ĚĞŐƌĞĞ ŽĨ mild to moderate dry eye1͕ĂŶĚŝƐŽŶĞŽĨƚŚĞ ůĞĂĚŝŶŐ ĐĂƵƐĞƐ ŽĨ ƉĂƟĞŶƚ ǀŝƐŝƚƐ ƚŽ ĞǇĞ ĐĂƌĞ * ƉƌĂĐƟƟŽŶĞƌƐŝŶƚŚĞhŶŝƚĞĚ^ƚĂƚĞƐ2.

KǀĞƌͲƚŚĞͲĐŽƵŶƚĞƌĂƌƟĮĐŝĂůƚĞĂƌƐĂƌĞŽŌĞŶƚŚĞ ĮƌƐƚůŝŶĞŽĨƚŚĞƌĂƉǇƚŽŵŝŶŝŵŝǌĞĚƌǇŶĞƐƐĂŶĚ ƌĞůĂƚĞĚ ĚŝƐĐŽŵĨŽƌƚ ŽĨ ƉĂƟĞŶƚƐ ǁŚŽ ƉƌĞƐĞŶƚ ǁŝƚŚĚƌǇĞǇĞ͘dŚĞƌĞĂƌĞĨĞǁƉƵďůŝƐŚĞĚƐƚƵĚŝĞƐ ƚŚĂƚ ĚŝƌĞĐƚůǇ ĐŽŵƉĂƌĞ ƚŚĞ ĞīĞĐƟǀĞŶĞƐƐ ŽĨ ĚŝīĞƌĞŶƚ ĚƌŽƉ ƉƌĞƉĂƌĂƟŽŶƐ͕ ĞƐƉĞĐŝĂůůǇ ƚŚŽƐĞ formulated for dry eye.

Ύ^ŽƵƌĐĞƵƌŽŵŽŶŝƚŽƌ/ŶŶƚĞƌŶĂƟŽŶĂů>ŝŵŝƚĞĚ͗ ŽŶƐ ƵŵĞƌƌ,ĞĞĂůƚŚǇĞĂƌĞĚĞĮŶŝƟŽŶ͕ƌĞƚĂŝůǀĂůƵƵĞƐŚĂƌĞ͕ϮϬϭϲĚĂƚĂ͘

ROHTO® DRY-AID™ - BREAKTHROUGH to mimic a natural, healthy tear. It “A key to the study design was that it DRY EYE SYMPTOM RELIEF ĚĞůŝǀĞƌƐ ŝŵŵĞĚŝĂƚĞ ĂŶĚ ůŽŶŐͲůĂƐƟŶŐ represented an assessment conducted According to a study recently published dry eye symptom relief by enhancing ŝŶ Ă ƌĞĂůͲůŝĨĞ͕ ƌĞĂůͲƟŵĞ ƐĞƫŶŐ ƌĂƚŚĞƌ in the peer-reviewed journal Clinical tear adhesion to the surface of the than a strictly clinic-based trial,” says Ophthalmology3 ROHTO® DRY-AID™, eye, providing uniform moisture study co-author Parag A. Majmudar, a new, breakthrough, non-blurring to the aqueous layer, and slowing MD, President and Chief Medical lubricant eye drop, was found to show ĞǀĂƉŽƌĂƟŽŶ ďǇƌĞƉůŝĐĂƟŶŐ ĂŶ ĞǀĞŶ KĸĐĞƌ͕ ŚŝĐĂŐŽ ŽƌŶĞĂ ŽŶƐƵůƚĂŶƚƐ͘ superior relief of discomfort associated lipid layer without blur. (see image 1) “For this reason, it may provide a ǁŝƚŚǀŝƐƵĂůƚĂƐŬŝŶŐĂĐƟǀŝƟĞƐ͕ĂŶĚĚĂŝůǇ ŵŽƌĞƌĞĂůŝƐƟĐƉŝĐƚƵƌĞĂƐƚŽŝƚƐƌĞůĂƟǀĞ diaries indicate that it may provide a ABOUT THE STUDY ĞīĞĐƟǀĞŶĞƐƐĐŽŵƉĂƌĞĚƚŽƚƌĂĚŝƟŽŶĂů ůŽŶŐĞƌĚƵƌĂƟŽŶŽĨƐǇŵƉƚŽŵĂƟĐƌĞůŝĞĨ In a single center, parallel group study, dry eye therapies.” over the course of a day versus one of ƚŚĞĞīĞĐƚƐŽĨZK,dKΠZzͲ/ΡǁĞƌĞ the most widely-used ocular lubricants ĐŽŵƉĂƌĞĚ ǀĞƌƐƵƐ Ă ůĞĂĚŝŶŐ ĂƌƟĮĐŝĂů ALL-DAY RELIEF in the United States. ƚĞĂƌďƌĂŶĚŝŶƉĂƟĞŶƚƐϭϴǇĞĂƌƐŽĨĂŐĞ KĐƵůĂƌĐŽŵĨŽƌƚƐĐŽƌĞƐĐŽŶĮƌŵĞĚƚŚĂƚ Žƌ ŽůĚĞƌ ;ŶсϴϬͿ ĚŝĂŐŶŽƐĞĚ ǁŝƚŚ ŵŝůĚ both products provide an immediate, ROHTO® DRY-AID™ features a unique to moderate DED over approximately ƐŝŐŶŝĮĐĂŶƚ ŝŵƉƌŽǀĞŵĞŶƚ ŝŶ ŽĐƵůĂƌ formula that provides all-day relief ϯϬĚĂǇƐŝŶĂƌĞĂůͲůŝĨĞ͕ƌĞĂůͲƟŵĞƐĞƫŶŐ͘ comfort that was sustained for at least from key symptoms of Dry Eye Disease. Subjects were assigned to one of the ŽŶĞ ŚŽƵƌ ĂŌĞƌ ŝŶƐƟůůĂƟŽŶ͘ ,ŽǁĞǀĞƌ͕ Unlike most eye drops that only work two products, and were monitored at ƉĂƟĞŶƚƐ ƵƐŝŶŐ ZK,dKΠ ZzͲ/Ρ ŽŶƚŚĞĂƋƵĞŽƵƐůĂǇĞƌŽĨƚŚĞƚĞĂƌĮůŵ͕ two and four weeks during the course ;ŶсϰϬͿƌĞƉŽƌƚĞĚůŽŶŐĞƌůĂƐƟŶŐƌĞůŝĞĨŽĨ ROHTO® DRY-AID™ is formulated to of the study. All subjects completed the ocular signs, symptoms, and visual ŚĞůƉ ƌĞƐƚŽƌĞ ŵŽŝƐƚƵƌĞ ƚŽ ƚŚĞ ĞŶƟƌĞ ƚŚĞĞŶƟƌĞϯϬͲĚĂǇĚƵƌĂƟŽŶ͘ ĨƵŶĐƟŽŶ ŝƐƐƵĞƐ ĂƐƐŽĐŝĂƚĞĚ ǁŝƚŚ ƚĞĂƌĮůŵďǇǁŽƌŬŝŶŐŽŶĂůůƚŚƌĞĞůĂǇĞƌƐ versus the comparator product.

RO1117_Mentholatum adv.indd 2 11/6/17 11:54 AM THREE LAYERS OF THE TEAR FILM M LIPIDL TEAR FIL 3 LAYER AQUEOUSA 2 LAYER MUCINM 1 LAYER CORNEA Slows LAYER Enhances Provides evaporation tear adhesion uniform with a to the surface moisture uniform of the eye outer layer

(im(imagee 1)

“One of the most intriguing ŚĞ ĂĚĚƐ͘ ͞ƌƟĮĐŝĂů ƚĞĂƌƐ ƐŚŽƵůĚ ŚĞůƉ ƌĞƉŽƌƚĞĚ ƐŝŐŶŝĮĐĂŶƚ ŝŵƉƌŽǀĞŵĞŶƚƐ ŝŶ ĚŝƐƟŶĐƟŽŶƐďĞƚǁĞĞŶƚŚĞƚǁŽƉƌŽĚƵĐƚƐ ŵĂŝŶƚĂŝŶ ƉƌŽƚĞĐƟŽŶ ŽĨ ƚŚĞ ŽĐƵůĂƌ comfort scores during visual tasking was observed in diary data that ƐƵƌĨĂĐĞ͘ WĂƟĞŶƚͲƌĞƉŽƌƚĞĚ ƐǇŵƉƚŽŵƐ ĂĐƟǀŝƟĞƐ ƐƵĐŚ ĂƐ ƚĞůĞǀŝƐŝŽŶ Žƌ ŵŽǀŝĞ showed ROHTO® DRY-AID™ mean from this study suggest that ROHTO® viewing and driving at night. (see image 2) scores for ocular discomfort and DRY-AID™ balances the ocular surface dryness remained approximately the throughout the day, which may help “Studies consistently show that DED same from morning to evening while ƌĞĚƵĐĞƉĂƟĞŶƚƐ͛ŶĞĞĚĨŽƌĐŽŶƟŶƵŽƵƐ has a measureable impact on several the comparator product mean scores dosing and allow for improved quality ĂƐƉĞĐƚƐ ŽĨ ƉĂƟĞŶƚƐ͛ YƵĂůŝƚǇ ŽĨ >ŝĨĞ͕ in these two areas trended upward of life and visual measures.” including their ability to perform from morning to evening,” notes study ĐĞƌƚĂŝŶ ĂĐƟǀŝƟĞƐ ƌĞƋƵŝƌŝŶŐ ƐƵƐƚĂŝŶĞĚ co-author Michael S. Cooper, OD, IMPROVEMENT IN COMFORT SCORES ǀŝƐƵĂů ĂƩĞŶƟŽŶ ;Ğ͘Ő͘ ƌĞĂĚŝŶŐ͕ tŝŶĚŚĂŵǇĞ'ƌŽƵƉ͕W͕͘͘tŝůůŝŵĂŶƟĐ͕ At each study visit, subjects were also ĚƌŝǀŝŶŐͿ͕͟ ƐĂǇƐ ƌ͘ DĂũŵƵĚĂƌ͘ ͞ĂƚĂ Conn. queried using the Ora Calibra™ Quality from this study suggests that ROHTO® ŽĨ >ŝĨĞ YƵĞƐƟŽŶŶĂŝƌĞ͕ ǁŚŝĐŚ ŝŶĐůƵĚĞƐ DRY-AID™ provides superior relief ͞dŚĞĞīĞĐƚƐŽĨĂƌƟĮĐŝĂůƚĞĂƌƐĂƌĞŽŌĞŶ ƋƵĞƐƟŽŶƐĂĚĚƌĞƐƐŝŶŐǀŝƐƵĂůĨƵŶĐƟŽŶĂƐ of discomfort associated with visual short-lived, providing temporary relief well as other symptom assessments. ƚĂƐŬŝŶŐĂĐƟǀŝƟĞƐ͘͟ ĂŶĚ ƌĞƋƵŝƌĞ ƌĞƉĞĂƚĞĚ ŝŶƐƟůůĂƟŽŶƐ͕͟ Only the ROHTO® DRY-AID™ group

LEARN MORE ROHTO® DRY-AID™ To receive the full report, please contact: IMPROVEMENT IN DISCOMFORT SCORES [email protected] or use the following link: ŚƩƉƐ͗ͬͬŐŽŽ͘ŐůͬǁĚ'Ăϭƌ 33% ROHTO® DRY-AID™ Lubricant Eye Drops are available in a Reduction ƐŝŶŐůĞϭϬͲŵ>ŵƵůƟͲĚŽƐĞďŽƩůĞĂŶĚĐĂŶďĞĨŽƵŶĚĂƚĂůůƌĞƚĂŝů in patient ůŽĐĂƟŽŶƐǁŚĞƌĞŽǀĞƌͲƚŚĞͲĐŽƵŶƚĞƌĞǇĞĚƌŽƉƐĂƌĞƐŽůĚ͘ discomfort

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The study was sponsored by The Mentholatum Company, ZŽŚƚŽΠƌǇͲŝĚΡŝƐĂƚƌĂĚĞŵĂƌŬŽĨdŚĞDĞŶƚŚŽůĂƚƵŵŽŵƉĂŶǇ KƌĂĂůŝďƌĂΡYƵĂůŝƚǇŽĨ>ŝĨĞYƵĞƐƟŽŶŶĂŝƌĞŝƐĂƚƌĂĚĞŵĂƌŬŽĨKƌĂ͕/ŶĐ͘ marketer of ROHTO® DRY-AID™. ƌƐ͘ŽŽƉĞƌĂŶĚDĂũŵƵĚĂƌĂƌĞƉĂŝĚĐŽŶƐƵůƚĂŶƚƐĨŽƌdŚĞDĞŶƚŚŽůĂƚƵŵŽŵƉĂŶǇ

RO1117_Mentholatum adv.indd 3 11/6/17 11:54 AM Conjunctiva

The Conjunctiva in Crisis: Ocular Irritation Unmasked When conjunctival calamities strike, here’s how to identify the cause and come up with a plan. By Emily Bruce, OD, and Rodney Bendure, OD

erhaps no other tear film and hosts ocular ocular structure immune tissues.1 does so much yet The ophthalmic division Preceives such cur- of the trigeminal nerve sory clinical descriptions provides sensation, while as the conjunctiva. ‘Clear autonomic efferents sup- and quiet,’ ‘pinguecula ply the vessels, accessory nasal’ and ‘diffuse injec- lacrimal glands and epi- tion’ dominate the lexicon thelium. Vascular supplies as practitioners evaluate to the bulbar conjunctiva the state of this ocular This patient presented with a unilateral ptosis, edema and and fornices are provided structure. While it doesn’t injection, characteristic of viral conjunctivitis. by the long ciliary arter- catch our attention with ies and peripheral tarsal flashy biochemical processes or pre- minating at the keratinized margin. arcades. The palpebral conjunctiva cisely change shape to focus light, It is composed of cuboidal epithelial is primarily supplied by the terminal the conjunctiva performs a number cells interspersed with Langerhans branches of the ophthalmic artery of essential functions. For instance, cells, melanocytes and lympho- and secondarily by the branches of it acts as a defense of the globe and cytes. Underneath the epithelium the facial artery. Blood drains from eyelids, produces the mucus portion is a richly vascularized substantia the bulbar conjunctiva and fornices of the tear film and facilitates the propria containing lymphatics and via the anterior ciliary and conjunc- globe’s freedom of movement. So, additional immune cells.1 tival veins, while the palpebral con- when the conjunctiva is insulted, it The conjunctiva is typically junctiva drains into the post-tarsal can be a calamity. Here’s a closer divided into three sections: the pal- veins of the eyelids and the deep look at the structure and the con- pebral conjunctiva, the bulbar con- facial branches of the anterior facial ditions that can compromise its junctiva and the fornix. The average vein and the pterygoid plexus. integrity. conjunctiva covers 16cm2—13 times The conjunctiva houses the only greater than the surface of the cor- ocular lymph tissue. Nasal lymphat- Anatomy nea, and 1.3 times greater than the ics drain into the submandibular The conjunctiva is a mucous mem- area of the retina.2 The conjunctiva nodes, while temporal vessels empty brane that extends from the corneo- allows for unencumbered movement into the pre-auricular nodes.1 limbus across the globe, down into of the globe, provides a protective the fornix and then returns back up barrier for the eyeball and orbit, Diagnostic Considerations the inner surface of the eyelid, ter- contributes to production of the When the eye is insulted, whether

30 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

030_ro1117_f1.indd 30 11/3/17 3:25 PM from an allergen, microbe, chemical of adenovirus in existence, 19 are assault, physical trauma or autoim- responsible for 90% of all viral con- mune cause, the local tissue reaction junctivitis.4 Infections can be pres- is an inflammatory response—con- ent in relative isolation, but often junctivitis. When a patient presents occur as epidemics in places such with a red, irritated eye, it can be as schools, hospitals and swimming challenging to determine the cause pools. The virus is capable of surviv- of their conjunctivitis. Each type has ing for weeks, even on dry surfaces. key characteristics, and checking the Patients begin to shed virus particles boxes off on your clinical checklist days prior to the onset of symptoms; can help narrow down the etiologi- therefore, many individuals may be cal culprit (Table 1). affected before preventative mea- Thorough history. It is crucial sures can be employed.5 to ascertain as many details from The adenoviridae infections man- the patient as possible, including ifest in four clinical presentations: onset, duration and laterality. Take non-specific follicular, pharyngocon- note of symptoms, such as pain or junctival fever (PCF), epidemic kera- itching, to further help distinguish toconjunctivitis (EKC) and chronic etiology. For instance, a chief com- adenoviral conjunctivitis. The exact plaint of itching is highly suggestive incidence of each of the adenoviral of an allergic reaction, while severe presentations is unknown. Symp- In the same viral conjunctivitis patient, pain is quite uncommon in isolated toms may be mild to severe, with follicles and injection were present on conjunctivitis and would warrant unilateral redness and serous dis- the palpebral conjunctiva, and sub- a check of the cornea for epithelial charge spreading to the second eye epithelial infiltrates were present in the defects and foreign bodies. one to two days later. cornea. Patient education. Because a Follicular conjunctivitis is the high risk of transmission exists with most common variant and produces Chronic follicular conjunctivitis, bacterial and viral conjunctivitis, a mild bilateral conjunctivitis with the rarest adenoviral conjunctivitis remember to thoroughly educate watery discharge and no corneal variant, is characterized by intermit- patients about rigorous hygiene. involvement.4 It is associated with tent, relapsing episodes of follicular Lab work. In many cases, cultures serotypes 1 through 11 and 19.6 conjunctivitis, though papillae or other laboratory investigations PCF, which is caused by adenoviral may predominate.4 The clinical are helpful to find the cause of the serotypes 3, 4 and 7, can affect the presentation is less severe than in patient’s conjunctivitis. cornea in about 30% of cases.4 It other forms. The condition, though Here we focus on the three most is associated with pharyngitis, high sometimes lasting for years, tends to common types of each conjunctivitis fever and pre-auricular lymphade- resolve spontaneously. Adenoviral etiology—viral, allergic and bacte- nopathy.3 Both follicular conjunc- serotypes 2, 3, 4 and 5 have been rial—and the pearls regarding their tivitis and PCF may be associated isolated from affected individuals.7 diagnosis. with a sore throat and are seen often Coxsackie virus. Acute hem- in children. EKC, adenovirus sero- orrhagic conjunctivitis creates a Viral Conjunctivitis types 8 and 19, is the most severe startling clinical presentation. It is Practitioners often encounter form and involves the cornea about more common in tropical areas and patients with a chief complaint of 80% of the time.4-6 The initial ocu- is usually caused by the enterovirus the dreaded pink eye, and up to lar presentation of EKC and PCF is or coxsackie virus. Infectious out- 80% of infectious cases of acute similar, making differentiation dif- breaks typically occur in underde- red eye are viral in origin.3 When ficult on ocular presentation alone. veloped countries with a prevalence patients present with a red, irritated Therefore, it is helpful to remember of up to 50%.8 Patients are often eye and you suspect a viral etiol- to check for the systemic manifes- worried by the particularly red, ogy, two virus types may be at play: tations of PCF, while corneal sub- bloody appearance of the petechial adenovirus and coxsackie virus.3,4 epithelial infiltrates are much more subconjunctival hemorrhages pres- Adenovirus. Of the 53 subtypes commonly seen with EKC.7 ent with this type of infection.4,5

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 31

030_ro1117_f1.indd 31 11/3/17 3:26 PM Conjunctiva

Table 1. Differential Diagnosis of Viral, Allergic and Bacterial Conjunctivitis Viral Allergic Bacterial Laterality Unilateral, then bilateral Bilateral Unilateral, then bilateral Tissue response Follicles Papillae Papillae Chemosis Chemosis Subepithelial Infiltrates Petechial hemorrhages Corneal scarring, if severe Subepithelial Infiltrates *Note: mixed papillary and follicular response with Chamydia Discharge Serous, mucoserous Serous, mucoserous Mucopurulent, purulent Membrane/pseudomembrane Yes No Yes Lympadenopathy Yes No Only with Neisseria and Chlamydia

Diagnosis. In viral conjunctivitis, (GPC) and atopic keratoconjunctivi- tivitis have a type I hypersensitivity clinical signs often govern the diag- tis (AKC). Some of these conditions response, the cell-mediated type IV nosis. These include eyelid edema, are acute and visually benign, while response typified in these conditions as well as a swollen preauricular others are chronic and pose the is responsible for their sight-threat- node and conjunctival redness, threat of permanent vision loss.1,4,6,11 ening effects.14,15 Risk of permanent follicles, membranes and pseudo- Acute allergic conjunctivitis. vision loss rises sharply with these membranes. Corneal involvement SAC and PAC represent the milder conditions due to the potential for includes superficial punctate kerati- and more common types of ocular secondary conjunctival and corneal tis in mild cases, or discrete whitish allergy, and both are classified as scarring and, although rare, corneal anterior stromal infiltrates, which acute. SAC is the most common perforation. VKC generally presents may persist for months.4,5 form of allergic conjunctivitis, is in males younger than age 30, while Though diagnosis is typically often accompanied by allergic rhi- AKC exhibits a weaker gender pre- made based on clinical presentation, nitis, and its incidence and duration dilection. AKC usually presents after Giemsa stain can reveal multinucle- is tied closely to the arrival of plant- the age of 30, with visual complica- ated giant cells in herpetic infection derived allergens.12 tions in the fourth and fifth decades. and mononuclear cells in adenovi- In PAC, allergens such as dust Ninety-five percent of cases are rus infection. Viral cultures, nucleic mites and pet dander are often trig- associated with a history of atopic acid amplification and, more gers, and though patients often dermatitis.4,6,11 recently, in-office immunochro- notice exacerbations and remissions, GPC, the third form of chronic matography tests such as the Ade- this condition occurs throughout allergic conjunctivitis, is caused noPlus (Quidel), are available for the year. Itching is a hallmark sign by chronic irritation, usually from point-of-care diagnosis. The Adeno- of these conditions, and papillary contact lenses, ocular prostheses, Plus test kit identifies the presence response, watery or stringy dis- exposed surgical sutures, scleral of adenovirus with a sensitivity charge, conjunctival hyperemia and buckles, corneal surface irregular- of 93% and specificity of 98%, mild to moderate conjunctival che- ity and filtering blebs. GPC is a according to research. The in-office mosis are generally present to vari- mechanically induced allergic reac- test results are available within able degrees.1,13 tion and generally resolves when the approximately 10 minutes.9,10 Despite the significant discomfort source of the mechanical irritation for patients, these two entities do is removed. Later in the condition, Allergic Conjunctivitis not pose a significant risk to vision. giant papillae can be greater than Ocular allergy is comprised of sev- Chronic allergic conjunctivitis. 1mm in diameter.4,15,16 eral distinct clinical entities repre- VKC and AKC, chronic forms of CAC occurs when the conjunctiva senting a veritable alphabet soup of allergic conjunctivitis, have pro- exhibits a type IV delayed hypersen- acronyms. These include seasonal longed, complex inflammatory sitivity reaction to ocular medica- allergic conjunctivitis (SAC), peren- reactions involving a number of tions or their preservatives. This nial allergic conjunctivitis (PAC), immune responses, which includes usually presents after patients have vernal keratoconjunctivitis (VKC), T-cells, eosinophils, basophils, neu- been exposed to a medication, solu- contact allergic conjunctivitis trophils and associated cytokines. tion, contact lens material or preser- (CAC), giant papillary conjunctivitis While all types of allergic conjunc- vative for several days.4,6,11

32 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

0030_ro1117_f1.indd30_ro1117_f1.indd 3232 111/3/171/3/17 3:263:26 PMPM RO0815_Lombart.indd 1 7/22/15 2:19 PM Conjunctiva

Diagnosis. All types of allergic Acute bacterial conjunctivitis. conjunctivitis are diagnosed based The most common causes of acute on signs and symptoms. A family bacterial conjunctivitis are Strepto- history of atopic disease or asthma coccal pneumonia, Staphylococcus may support suspicion of ocular aureus, Haemophilis influenzae and allergies. Itching is the hallmark sign Moraxella catarrhalis. Severe pre- of ocular allergy, and its absence sentations should prompt suspicion makes this diagnosis unlikely. In of Neisseria species.4 contrast, conjunctival scrapings may Because S. aureus is ubiquitous in reveal eosinophils, but their absence skin flora, it can present at any time does not rule out ocular allergies. and has no demographic predilec- Conjunctival provocation testing tion. S. pneumoniae infections are with suspected allergens may help more common among children in determine the effectiveness of thera- cooler climates, while H. influenza peutics if a patient has a history of is more commonly seen in children severe allergies. A blood test, the in warmer climates and tends to radioallergosorbent test or ELISA have a more severe presentation.17 testing of tears may be performed to Symptoms include sudden onset identify specific allergens. of redness, burning and discharge occurring in both eyes, though one These images highlight the difference in Bacterial Conjunctivitis may precede the other by one to two appearance between follicles (above) and Last but not least, bacterial conjunc- days. Clinical findings can include papillae (below). tivitis is caused by direct inoculation conjunctival and eyelid edema, with infectious secretions. Three erythema, papillae, mucopurulent Patients who test positive for Neis- presentations of bacterial conjunc- discharge and punctate corneal seria should also be tested for con- tivitis exist: acute, hyperacute and staining. In contrast to viral or aller- current sexually transmitted diseases chronic. gic conjunctivitis, bacterial discharge including syphillus, chlamydia and often has a yellow-green appearance HIV.4,6 along with matting of the eyelids. Chronic bacterial conjunctivitis. Lymphadenopathy typically seen in When the signs and symptoms of viral conjunctivitis is absent, except bacterial conjunctivitis have been in cases of Neisseria infections. In present for more than four weeks, rare cases, the cornea can become there are two likely infectious causes compromised.4,18,19 to consider: a chronic overgrowth Hyperacute conjunctivitis. of normal flora, typically seen as Although they are responsible for blepharitis, and chlamydia.11,20 only a small number of cases of The most common cause of conjunctivitis, Neisseria gonor- blepharitis is Staphylococcus. If rhoaea and meningitides should be ulceration is seen near the lacrimal suspected in cases of severe conjunc- structures and puncta, Moraxella tivitis. Signs include hyperpurulent lacunata should also be considered discharge, severe lid edema, corneal as a causative agent. As practitio- ulceration, lymphadenopathy and ners, we see this every day, and pseudomembranes. If a corneal ulcer we all know the typical signs and is present, aggressive treatment is symptoms: tearing, foreign body In the case of this acute bacterial necessary due to the risk of perfora- sensation, conjunctival hyperemia, blepharoconjunctivitis patient, a culture tion within 24 hours.18,19 thickening of lid margins, telangec- was obtained, which revealed S. aureus In these cases of hyperacute con- tatic vessels, rosettes, collarettes, overgrowth. A pseudomembrane is junctivitis, culture is mandatory. inferior superficial punctate keratitis seen emerging from the upper lid in the Culture media include Giemsa stain, and even sterile infiltrates. Blephari- second picture (bottom). Chocolate agar and Thayer-Martin. tis is easy to diagnose based on the

34 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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RO1117_TelScreen.indd 1 10/20/17 1:58 PM Conjunctiva

clinical picture, but it is extremely Table 2. Conjunctivitis Treatment Options difficult to eradicate due to the Type Severity Treatment always-present skin flora. Mild Allergen avoidance. Chlamydia, caused by Chlamydia Cool compresses. trachomatis, is typically diagnosed Artificial tears. Allergic conjunctivitis in young, sexually active patients Moderate Add dual-acting histamine receptor who present with a red eye that does antagonist and mast cell stabilizer. not respond to other treatments and is present for three to four weeks. Severe Add topical corticosteroid. Chlamydia trachomatis is an intra- Acute Consider laboratory evaluation; treat cellular obligate bacterial species empirically with broad-spectrum ophthalmic antibiotic for seven to 10 and is capable of causing a mild days. unilateral or bilateral chronic con- Hyperacute (purulent) Laboratory evaluation is imperative. junctivitis associated with redness, Ceftriaxone, saline lavage of fornices watering and discharge. Preauricular Q1hr, followed by ophthalmic antibiotic. lymphadenopathy and large follicles Bacterial conjunctivitis Corneal involvement requires primarily of the lower fornix are hospitalization with IV antibiotics. Consider evaluating and treating for common findings. Mild conjuncti- concurrent STDs. val scarring and corneal infiltrates Chronic Warm compresses and eyelid massage in may also be seen. Tarsal conjuncti- addition to eyelid hygiene val scrapings may be obtained for Topical antibiotic; consider an oral laboratory confirmation. Referral tetracycline. to a primary care or genitourinary Mild (PCF and Cold compresses and artificial tears. nonspecific follicular physician is appropriate. Patients Stress hygiene. and their partner(s) should be tested conjunctivitis) Severe (EKC) for other sexually transmitted dis- Viral conjunctivitis Add ophthalmic vasoconstrictor, removal eases.4,5,11 of membranes/pseudomembranes. Diagnosis. This is based on Consider ophthalmic steroid, particularly if corneal involvement is noted. clinical findings, but more specific Ophthalmic Betadine early can decrease information can be obtained with a infectivity of free virus. culture, Giemsa and gram stains. 2. Panda-Jonas S, Jonas JB, Jakobczyk M, Schneider U. 13. Yu CQ, Ta CN. Seasonal and perennial allergic conjunc- Retinal photoreceptor count, retinal surface area, and optic disc tivitis. In: Krachmer JH, Mannis MJ, Holland EJ. Cornea: We strive to provide compre- size in normal human eyes. Ophthalmology. 1994;101(3):519- Fundamentals, Diagnosis and Management. Vol 1, 4th ed. hensive, complete eye care for our 23. Philadelphia: Elsevier; 2017:526-32. 3. Azari AA, Barney NP. Conjunctivitis: a systematic review of 14. Mathys KC, Lee WB. Vernal keratoconjunctivitis. In: Holland patients. By successfully diagnosing diagnosis and treatment. JAMA. 2013;310(16):1721-30. EJ, Mannis MJ, Lee WB. Ocular Surface Disease: Cornea, Con- 4. Kanski JJ, Bowling B, Nischal KK, Pearson A. Clinical junctiva and Tear Film. 1st ed. Elsevier; 2013:97-102. conjunctivitis, you can help to alle- Ophthalmology: A Systematic Approach. 8th ed. Edinburgh, 15. Batta P, Tu EY. Atopic keratoconjunctivitis. In: Holland EJ, England: Elsevier/Saunders; 2016. viate or even eliminate a condition 5. Mandell D. Bennett’s Principles and Practice of Infectious Mannis MJ, Lee WB. Ocular Surface Disease: Cornea, Con- that diminishes quality of life—gar- Diseases. 8th ed. Edinburgh, England: Elsevier/Saunders; junctiva and Tear Film. 1st ed. Elsevier; 2013:103-110. 2015. 16. Tsai JH. Giant Papillary Conjunctivitis. In: Holland EJ, Man- nering increased patient respect and, 6. Yanoff M, Duker JS, eds. Ophthalmology. London, England; nis MJ, Lee WB. Ocular Surface Disease: Cornea, Conjunctiva Elsevier/Saunders; 2013. and Tear Film. 1st ed. Elsevier; 2013:111-115. hopefully, a lifelong patient. ■ 7. Choulakian MY, Mannis MJ, Alvarenga LS. Viral conjunc- 17. Soukiasian SH, Baum J. Bacterial Conjunctivitis. In: tivitis. In: Krachmer JH, Mannis MJ, Holland EJ. Cornea: Krachmer JH, Mannis MJ, Holland EJ. Cornea: Fundamentals, Dr. Bruce is an assistant professor Fundamentals, Diagnosis and Management. Vol 1, 4th ed. Diagnosis and Management. Vol 1, 4th ed. Philadelphia: Else- of optometry at Northeastern State Philadelphia: Elsevier; 2017:493-502. vier; 2017:479-92. 8. Zhang L, Zhao N, Huang X, et al. Molecular epidemiology 18. McElnea E, Stapleton P, Khan S. et al. Challenges in the University’s Oklahoma College of of acute hemorrhagic conjunctivitis caused by coxsackie management of Neisseria gonorrhoeae keratitis. Int Ophthal- Optometry in Tahlequah, Okla. A type 25 variant in China, 2004-2014. Scientific Reports. mol. 2015;35:135. 2017;7:45202. 19. Duke-Elder S. Diseases of the outer eye. In: System Dr. Bendure is an adjunct pro- 9. Sambursky R, Tucker S, Schirra F, et al. The RPS adeno of Ophthalmology. Vol 8, Part 1. St.Louis: CV Mosby Co; detector for diagnosing adenoviral conjunctivitis. Ophthalmol- 1965:167-74. fessor at Northeastern State Uni- ogy. 2006;113:1758-64. 10. Sambursky R, Trattler W, Tauber S, et al. Sensitivity and 20. Lindquist TD, Lindquist TP. Conjunctivitis: An Overview and versity’s Oklahoma College of specificity of the AdenoPlus test for diagnosing adenoviral con- Classification. In: Krachmer JH, Mannis MJ, Holland EJ. Cor- Optometry in Tahlequah, Okla. junctivitis. JAMA Ophthalmol. 2013;131(1):17-22. nea: Fundamentals, Diagnosis and Management. Vol 1, 4th ed. 11. Bagheri N, Wajda B. The Wills Eye Manual. 7th ed. Phila- Philadelphia: Elsevier; 2017:466-78. delphia: Wolters Kluwer; 2017. 21. Kelmenson AT, Rao NK, Raizman MB. Treatment of allergic 1. Holland EJ, Mannis MJ, Barry LW, eds. Ocular Surface 12. Pelikan Z. Seasonal and perennial allergic conjunctivitis: eye disease. In: Holland EJ, Mannis MJ, Lee WB. Ocular Disease: Cornea, Conjunctiva, and Tear Film. Philadelphia: the possible role of nasal allergy. Clin Exper Ophthalmol. 2009; Surface Disease: Cornea, Conjunctiva and Tear Film. 1st ed. Elsevier; 2013. 37:448-57. Elsevier; 2013:117-24.

36 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

0030_ro1117_f1.indd30_ro1117_f1.indd 3636 111/3/171/3/17 3:263:26 PMPM Are dry, itchy eyes a symptom of allergies? It’s not complicated.

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RO1117_Quidel.indd 1 11/6/17 2:08 PM Dry Eye When Dry Eye COMPROMISES Corneal Integrity Your patients’ blurry vision, keratitis and infections could be caused by ocular surface disease. By Scott G. Hauswirth, OD

ry eye disease Apical cells. These are (DED) affects all the outermost cells and are parts of the lac- in direct contact with the rimal functional tear film.1 The apical cells unit—includingD the cornea, contain microvillae and conjunctiva, meibomian microplicae, which extend glands, lacrimal glands and upwards into the tear film the interconnecting innerva- as much as 0.5µm and are tion. As clinicians, we tend coated with a dense glyco- to detect dry eye by listen- calyx. Composed of several ing to patient complaints transmembrane mucins that for DED-related symptoms form a mucoadhesive com- and closely examining the plex, the glycocalyx anchors cornea. This isn’t a mis- the tear film to the apical guided approach, consider- epithelium and defends ing the cornea is crucial to against bacteria.1 vision and is often the first This patient demonstrates diffuse punctate epitheliopathy, The cornea derives structure compromised by and shows decreased barrier function related to dry eye. nutrients and oxygen from DED. two different regions. The This article delves into DED’s basal epithelium, wing cells and peripheral cornea derives its sup- impact on the cornea, including apical cells.1 ply from the limbal region, which what we know about the patho- Basal epithelium. This is in con- contains the vascular loops of the physiology of the condition, the tact with the underlying basement conjunctiva. The central anterior initiating insult and methods of membrane and adheres the epithe- cornea—specifically the corneal progression. lial complex to the structural por- epithelium—obtains most of its tion of the cornea.1 oxygen and nutrients from the tear Corneal Basics Wing cells. These are in the film. The human cornea is an avascular middle section of the epithelium, The epithelial surface is gener- structure comprised of several dis- and represent upwards migration of ated by the stem cell niches at the tinct layers.1 The outermost layer, a portion of the basal epithelium in limbus, which produce transient the corneal epithelium, is composed an intermediary state towards the amplifying cells.1 These migrate of three stratified layers of cells: apical cells.1 across Bowman’s membrane

38 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

038_ro1117_f2.indd 38 11/3/17 2:21 PM towards the central cor- balance or to flush out nea, further from the toxins or irritants. limbus and blood supply. In the dry eye, patients During normal cellular suffer a loss of homeosta- turnover, transient ampli- sis, and the mechanisms fying cell progenies will normally designed to migrate across the cornea defend the eye—such as and differentiate into basal engagement of chronic cells, and then into wing inflammatory response— and apical epithelial cells. may turn against it and As the most richly lead to DED progression. innervated tissue in the Returning to the example body, with receptors that of tearing, it’s common number approximately for mild dry eye patients 6000 sensory terminals to experience tearing as per square millimeter, Corneal staining shows advanced loss of epithelial barrier in a response to stress (e.g., the cornea is designed severe dry eye with loss of the mucoadhesive layer and poor when reading or exposed to monitor and provide wettability of the tear film. to a cold, drafty environ- feedback for changes in ment). In contrast, more the environment, includ- barrier to the environment.5 severe dry eye patients, ing to the protective tear film.2,3 The Several glands on and around particularly those diagnosed with majority of these corneal receptors the ocular surface produce the autoimmune conditions such as are mechanoreceptors, which detect constituent parts of the tear film, Sjögren’s syndrome, may have touch or pain; but approximately primarily the lacrimal and acces- damaged glands and neurosensory 10% to 15% respond to tempera- sory glands, meibomian glands and systems due to chronic inflamma- ture and osmolarity changes, which conjunctival goblet cells. tion, preventing the ocular system may help detect evaporation and Despite all of its important func- from compensating to the stressors provide a means to regulate basal tions, the tear film in a healthy eye of increased evaporative demand.7 secretion.4 is extraordinarily thin, averaging between 2µm and 5.5µm in thick- Corneal Impact Healthy Tear Film ness over the cornea.6 The loss of homeostasis has a In a healthy eye, the tear film is multitude of sequelae on the cor- stable and provides a sufficient Homeostasis nea, including visual complaints, refracting surface for good vision. This entire system is designed to increased risk for infection, kera- It supports the ocular surface by monitor the environment and titis and microerosions and, of providing oxygen and nutrients maintain homeostasis by compen- course, inflammation. and protects it from dessicating sating for alterations in tempera- Blurry vision. Because the cornea environments, such as wind, and ture and humidity and protecting is dependent on the function of the from toxins, microbes and particu- exposed tissue from bacteria and thinnest portion of the tear film, late matter. other offenders. blurry and inconsistent vision may A healthy tear film contains a A normal eye maintains its be one of the earliest clues to a dry variety of constituent parts. It has homeostatic environment via this eye diagnosis. The Progression of a complex set and balanced num- monitoring and compensatory Ocular Findings Study (PROOF), ber of electrolytes.5 It is pH neutral actions. For example, the lacrimal a five year, prospective, multicenter to slightly acidic.5 The tear film functional unit’s ability to com- study, reveals one of the primary contains lysozyme and lacritin as pensate and regulate tear produc- differences between individuals with defense mediators, as well as hun- tion and volume is a hallmark of mild DED and those without dry dreds of proteins and proteolytic a healthy ocular surface system. eye is how they perceive their qual- enzymes that support normal cel- Tearing is a compensatory reflex ity of vision. In both groups, base- lular function of the corneal epi- mechanism designed to increase or line distance best-corrected visual thelium and provide a protective restore volume, to restore osmotic acuity (BCVA) was 20/20. However,

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 39

038_ro1117_f2.indd 39 11/3/17 2:21 PM Dry Eye

58.5% of those who had internal/external osmotic level two dry eye as defined gradient, moving water by the International Task and internal cell ionic Force guidelines expressed content into the extracel- moderate, severe or very lular space. These result severe dissatisfaction with in cell volume losses, their vision, vs. only 13.7% which cause gaps to form of those in the control between adjacent epi- group.8,9 thelial cells, resulting in Inflammation. Hyperos- the appearance of “fine” molarity of the tear film is superficial punctate kera- one of the key mechanisms titis (SPK) and increased that drives inflammation penetration of fluorescein and the progression of into the deeper layers of DED. In addition, evapo- the corneal epithelium rative stress may be at the and then into the anterior center of hyperosmolarity. In this patient, conjunctival epithelial compromise extends onto stroma. Studies examining the cornea in macropunctate erosions, caused by dry eye. Recent measurements osmolarity show that a of SPK lesions seen in difference in the osmolarity levels loproteinases (MMPs). MMPs dry eye patients show that the between the tear menisci and the are substrate-specific proteolytic mean diameters are smaller than precorneal tear film likely exists, enzymes that regulate extracellular a healthy epithelial cell. These are with the precorneal tear film expe- matrix deposition as well as its likely “deflated” or shrunken cells, riencing higher osmolarity.10 In degradation.12 which are in the process of apopto- patients with dry eye, this differ- Keratitis. During periods of sis and have taken up dye.2 ence may be even greater. Math- high evaporative stress, increases In more advanced forms of the ematical models of osmolarity in in tear film osmolarity trigger condition, chronic epithelial com- the precorneal tear film show rapid inflammation, beginning within the promise may also lead to mucin increases due to evaporation and corneal apical cells. Increased tear upregulation and formation of fila- decreased tear break-up time. This film osmolarity alters the normal mentary keratitis, where mucous may drive up the osmolarity of the precorneal tear film to levels that DED Testing are quite high (e.g., 1,900mOsml) Several tests can help you quantify the severity of dry eye, including vital dye staining of the compared with normal (i.e., cornea and conjunctiva, and point-of-care testing for the presence or degree of inflamma- 300mOsml), especially where the tory involvement. Corneal and conjunctival staining is perhaps one of the most accessible 11 tear film separates or collapses. and easily quantifiable methods of assessing damage to the ocular surface. In contrast, the highest readings Grading severity of corneal involvement is a key feature in determining DED severity. in the tear meniscus measure well Several grading systems exist to help classify dry eye, such as the Oxford scheme, the Van below 500mOsml. Bjisterveld system and the NEI/Industry Workshop guidelines.19 On a cellular level, increased Instillation of sodium fluorescein is a helpful diagnostic tool for grading damage to the osmolarity triggers inflammation ocular surface. Fluorescein staining will be present in cells with defective tight junctions, via cell signaling. Cell membrane or a compromised glycocalyx.20 Remember, some mild background uptake of fluorescein receptors such as toll-like recep- dye is considered normal, so there is a weaker correlation between disease severity and tors (TLR) initiate the internal stain uptake in mild forms of dry eye.21 Lissamine green, another vital dye well-tolerated by cell signaling processes, driven patients, will be taken up by epithelial cells with a damaged cell membrane and provides a primarily by NF-kB and mitogen- means of assessing both the cornea and conjunctiva. activated protein kinase (MAPK) While a number of testing options exist to provide a systematic means to assess the 12 activation. These two cytoplas- presence of staining on the cornea, no one particular method seems to have higher accu- mic signaling pathways upregulate racy or better correlation to disease severity, so the testing method is entirely up to the transcription of cytokines (pri- clinician. marily IL-1) and matrix metal-

40 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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adhesions cling to areas of tor that may have an impor- chronic epithelial irregular- tant role in the maintenance ity or compromise. of the corneal epithelial bar- Infections. Dry eye con- rier, increases in proportion tinually arises as one of with MMP-9 levels.18 Stud- the top three risk factors ies show an inverse relation- for bacterial keratitis.13,14 ship between EMMPRIN Corneal integrity is neces- amounts and occludin in the sary as an innate defense cornea. Because occludin against bacteria. Chronic is critical to maintaining breaks in the surface of the the tight junctions between cornea, in conjunction with adjacent epithelial cells, the decreases in lysozyme and overall barrier of the cornea lactoferrin, which provide is compromised. a second defense against Basal secretion, neurologi- bacteria, predispose the dry cal changes and symptoms. eye to a higher risk of cor- In the presence of inflam- neal infection. This becomes mation, damage to corneal even more important for nociceptors and associated contact lens wearers, who neurologic pathways may are exposed to bacterial bio- decrease basal tear secretion films, as well as contact lens as well as contribute to mor- matrices that may become phologic changes in nerve contaminated and populated structure that may lead to over time by a number of sensations of pain or, con- bacteria, fungi and parasites. This patient’s punctate epithelial keratopathy involves the versely, to hypoesthesia and On a cellular level, lym- central cornea in a case of Sjögren’s-related dry eye. neurotrophia despite worsen- phocytic activation, recruit- ing disease.4,7 ment and infiltration of tissues by increased MMP-9 is correlated Mechanical epithelial desquama- T-lymphocytes, all hallmarks of with increased corneal staining tion. In a normal eye, the tear film DED, can ultimately decrease resis- in dry eye patients, but is also provides a cushion and lubrica- tance to infection. Activation and increased in corneal infection, tion to help the lids move over the recruitment of TH1/TH17 via the recurrent erosion and other pathol- ocular surface with minimal fric- nuclear factor kappa beta (Nf-KB) ogies where the corneal epithelial tion. In a dry eye, however, both signaling pathway is a critical part barrier is compromised.17 MMP-9 volume and content of the tear film of the mechanism that drives the is normally found on the ocular is reduced, exposing the glycoca- conversion from an acute response surface in low amounts, below lyx and apical epithelium to the to chronic inflammation and 41ng/mL in healthy corneas. Levels frictional forces of the blink. This seems to play a key role in disease above 41ng/mL are associated with results in increased epithelial des- progression.15,16 Infiltration of the epithelial compromise. MMP-9 quamation compared with normal lacrimal gland leads to damage affects the junctions between epi- eyes. and dysfunction of secretory acini. thelial cells by breaking down the Ultimately, this alters the tear film molecule occludin, a critical com- Dry eye disease has a number of composition. ponent of the tight junctions. negative effects on the ocular sys- Decreased corneal epithe- As concentrations of pro-inflam- tem, beginning with the breakdown lial barrier molecules. While at matory molecules increase, com- of the homeostatic mechanisms least 30 known MMPs exist in pounds that maintain the corneal designed to protect the health of the the human body, MMP-3 and epithelium may decrease. The mol- ocular surface. We can use the cor- -9 appear particularly critical to ecule extracellular matrix metallo- nea as a window to assess the sever- maintaining the epithelial bar- proteinase inducer (EMMPRIN), a ity of DED, and once these systems rier of the cornea. For example, type-1 cornea epithelial cell recep- are compromised, inflammatory

42 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

038_ro1117_f2.indd 42 11/3/17 2:22 PM insult to corneal and conjunctival 1. Nishida T. Cornea. IN Krachmer JH, Mannis MJ, Holland EJ 12. Luo L, Li DQ, Doshi A, Farley W, et al. Experimental dry eye (eds) Cornea. 2nd Edition. Philadelphia, PA. Elsevier Mosby. stimulates production of inflammatory cytokines and MMP-9 tissues make it difficult to return 2005:3-26. and activates MAPK signaling pathways on the ocular surface. to baseline homeostatic function. 2. Courier E, Lepine T, Hor G, et al. Size of the lesions of Invest Ophthalmol Vis Sci. 2004;45:4293-301. superficial punctate keratitis in dry eye syndrome observed 13. Aldebasi YH, Aly SM, Ahmad MI, Khan AA. Incidence and Processes that direct corneal wound with a slit lamp. Cornea. 2016;35(7):1004-7. risk factors of bacteria causing infectious keratitis. Saudi Med healing and tight junction forma- 3. Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the J. 2013;34(11):1156-60. human corneal innervation. Exp Eye Res. 2010;90(4):478-92. 14. Ng AL, To KK, Choi CC, et al. Predisposing factors, micro- tion are compromised. Ongoing 4. Belmonte C, Acosta MC, Gallar J. Neural basis of sen- bial characteristics, and clinical outcome of microbial keratitis injury to the corneal barrier and sation in intact and injured corneas. Exp Eye Res. 2004 in a tertiary centre in Hong Kong: A 10-year experience. J Mar;78(3):513-25. Ophthalmol. 2015;2015:769436. reduced corneal integrity results in 5. Vantaku VR, Gupta G, Rapalli KC, Karnati R. Lacritin salvages 15. Stern ME, Gao J, Siemasko KF, et al. Role of the lacrimal the appearance of reduced wettabil- human corneal epithelial cells from lipopolysaccharide induced functional unit in the pathophysiology of dry eye. Exp Eye Res. cell death. Sci Rep. 2015 Dec 16;5:18362. 2004;78(3):409-16. ity due to glycocalyx disruption or 6.King-Smith PE, Fink BA, Fogt N, Nichols KK, et al. The thick- 16. Guzman M, Keitelman I, Sabbione F, et al. Dessicating loss, punctate keratopathy, micro- ness of the human precorneal tear film: evidence from reflection stress-induced disruption of ocular surface immune tolerance spectra. Invest Ophthalmol Vis Sci. 2000;41:3348-59. drives dry eye disease. Clin Exp Immunol. 2016;184(2):248- erosions, development of filaments 7. Sullivan DA. Possible mechanisms involved in the reduced 56. and increased risk for infection. tear secretion in Sjogren’s syndrome. In: Homma M, Sugai S, 17. Chotivanich S, de Paiva CS. Production and activity of Tojo T, Miyasaka N, Akizuki M, editors. Sjogren’s Syndrome matrix metalloproteinase-9 on the ocular surface increase By identifying issues early, we can State of the Art. Amsterdam:Kugler Press;1994,p. 3-19. in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. make the task of restoring homeo- 8. Behrens A, Doyle JJ, Stern L, Chuck RS, et al. Dysfunctional 2009;50:3203-9. Tear Syndrome: a Delphi approach to treatment recommenda- 18. Huet E, Vallee B, Delbe J, et al. EMMPRIN modulates stasis of the ocular surface and pre- tions. Cornea. 2006 Sep;25(8):900-7. epithelial barrier function through a MMP-mediated occludin venting progression of the disease 9. McDonnel P, Pflugfelder S, Schiffman R, et al. Progression cleavage: implications in dry eye disease. Am J Pathol. of Ocular Findings (PROOF) study of the natural history of dry 2011;179:1278-86. less daunting. ■ eye: study design and baseline patient characteristics. Invest 19. Foulks G. Challenges and pitfalls in clinical trials of treat- Dr. Hauswirth is an assistant Ophthalmol Vis Sci. 2013;54:4338. ments for dry eye. Ocul Surf. 2003 Jan;1(1):20-30. 10. Gaffney EA, Tiffany JM, Yokoi N, Bron AJ. A mass and 20. Bron AJ, Argueso P, Irkec M, Bright FV. Clinical staining professor in the Department of solute balance model for tear volume and osmolarity in the of the ocular surface: mechanisms and interpretations. Prog Ophthalmology at the University normal and dry eye. Prog Retin Eye Res. 2010;29:59-78. Retin Eye Res. 2015;44:36-61. 11. Peng CC, Cerretani C, Braun RJ, Radke CJ. Evaporation- 21. Sullivan BD, Whitmer D, Nichols KK, et al. An objective of Colorado School of Medicine, in driven instability of the precorneal tear film. Adv Colloid Inter- approach to dry eye disease severity. Invest Ophthalmol Vis Denver, CO. face Sci. 2014;206:250-64. Sci. 2010;51:6125-30.

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038_ro1117_f2.indd 43 11/3/17 2:21 PM Inflammation

A Red Eye: Scleritis or Episcleritis? Differentiating between the two is crucial to ensure you initiate the right treatment. By Jim Williamson, OD

hen differentiating fugax, is a benign inflammation episcleritis from scle- of the conjunctival and superficial ritis, clinicians often episcleral vascular plexi.8,9 Simple Wuse the phenylephrine episcleritis is diffuse inflammation, blanching technique: blanch- while nodular episcleritis indicates ing congested conjunctival and a localized process with a well- superficial episcleral blood vessels defined area of elevation.1,11 with either the 2.5% or the 10% Episcleritis is often a self-lim- concentration.1-4 When the deep iting condition with a proposed episcleral plexus does not blanch, incidence of 21.7 per 100,000 per- the diagnosis is usually scleritis. son-years.12-14 While rare in chil- If the redness does disappear, it’s Simple episcleritis is the most common dren, roughly two-thirds of cases episcleritis. presentation.1,11 occur in females with a peak inci- But sometimes the answer is not dence in the fourth decade.1,2,8,15 that simple. For example, overlap- and deep) derived from the anterior ping clinical features or variations ciliary arteries.6 Normally, these ves- Scleritis in perceived patient pain may cloud sels—which run forward from the The sclera consists of a collagen the decision-making process. But insertions of the recti muscles—are scaffold, glycoproteins, proteogly- a prompt and precise diagnosis is not visible because they run deep to cans and protein fibrils.2,9 It is anteri- critical, as treatment and potential the conjunctiva. However, inflam- orly contiguous with the cornea and sequelae differ between the two mation can make them observable, posteriorly with the optic nerve’s clinical presentations.5 Here, we dis- and the superficial plexus anastomo- dural and arachnoid sheaths. The cuss the differences between episcle- ses with the conjunctival and deep sclera is weakened in this area due ritis and scleritis—and how you can episcleral plexus at the limbus. The to perforations by the axons of the identify each of them accurately. superficial vessels are mobile, while optic nerve (lamina cribrosa).9 This the deeper ones are more firmly anatomical relationship explains Episcleritis attached to the sclera.7 why optic nerve edema may occur The episclera, the outermost layer, is Episcleritis, also known as sub- with inflammation of the surround- composed of loose connective tissue conjunctivitis, phlegmatous con- ing posterior sclera. with two vascular plexi (superficial junctivitis and episcleritis periodica Although the sclera is essentially

44 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

044_ro1117_f3.indd 44 11/3/17 1:24 PM avascular, it does have a rich supply Table 1. Systemic Disease Workup of sensory nerves.6 Nutrient delivery Diagnostic Test Remarks comes from the choroid and epi- Complete blood count Elevated white cell count in infections 2,16 scleral vacular complexes. This, Basic metabolic panel Evaluate for vasculitis-related renal disease combined with the sclera’s web-like Erythrocyte sedimentation rate Nonspecific inflammation organization, slows the removal of C-reactive protein Nonspecific inflammation, acute antigens and other materials, provid- 36 ing an ideal environment for persis- HLA B27 Possible posterior scleritis association tent inflammation.2 Antineutrophil cytoplasmic antibodies Granulomatosis with polyangiitis Normally, the fibrous sclera Rheumatoid factor Rheumatoid arthritis appears opaque, but in children Anti-cyclic citrullinated peptide Prognostic indicator for RA severity it may look bluish due to the vis- Antinuclear antibody Systemic lupus erythematosus ibility of the underlying choroid. As Angiotensin-converting enzyme Sarcoidosis patients age, it may appear more yel- Chest x-ray Sarcoidosis low due to fat deposition. The sclera Fluorescent treponemal antibody absorption Syphilis measures roughly 0.45mm at the Rapid plasma reagin Syphilis recti insertions and is thickest at the Tuberculosis testing Mantoux skin or Quantiferon Gold blood posterior pole (1.1mm to 1.3mm), which is important to remember Lyme serology Lyme disease when assessing for posterior scleritis using B-scan ultrasonography.17 remains unclear, as some report a cause overall is the herpes zoster Scleritis is separated into anterior variety of immunopathological find- virus (HZV), which is consistent or posterior, based on the inflam- ings, while others point to granulo- with the greater-than-fourfold mation’s location in relation to matous inflammation and collagen increase in HZV incidence over the the extraocular muscle insertion disruption, which can lead to loss of last 60 years.22,25 Though uncom- sites.3,11,18 Anterior scleritis is further tissue and subsequent thinning.8,9,16,21 mon, scleritis has been reported categorized into diffuse, nodular and Scleritis has a proposed incidence with bisphosphonate use—a class of necrotizing forms.11 Necrotizing scle- of 4.1 cases per 100,000 person- drugs used to treat osteoporosis.12,21 ritis may result in scleral perforation, years and can be idiopathic, associ- Many ocular procedures may trig- which can occur without inflam- ated with a systemic autoimmune ger surgically-induced necrotizing mation and is termed scleromalacia disease, surgically induced or infec- scleritis (SINS)—most commonly perforans.18 tious, although only 4% to 10% of after limbal-incision cataract sur- Most practitioners judge the all cases are deemed infectious.2,14,22 gery—and 75% of patients who severity of scleritis on a numerical Potential pathogens include bacteria, develop SINS have undergone two scale based on their clinical experi- fungi, parasites and viruses. or more procedures.9 ence. However, researchers fostered Ocular surgery and trauma an eight-component, subjective scor- account for almost half of all bacte- Symptoms ing scale to grade scleritis.19 Because rial infectious scleritis, and most oth- Here are the symptoms to look out this scale did not assess inflamma- ers result secondarily from a severe for that can help you differentiate tion, others established a system of corneal infection.21,23 Pterygium between episcleritis and scleritis: standardized images for grading.20 excision and scleral buckling rep- Episcleritis. Generally, this does While helpful, limitations to this resent 75% of surgical causes, and not result in significant pain, and study include the instillation of 10% Pseudomonas aeruginosa is the most usually patients only complain of phenylephrine up to 20 minutes likely causative agent.2,9,24 Research- mild discomfort or irritation.4,12 prior to photography and the docu- ers speculate tissue and blood vessel Episcleritis may present with epiph- mentation of only one quadrant.20 destruction during ophthalmic pro- ora but does not result in decreased Scleritis, however, is considered a cedures may increase susceptibility acuity.2,3,12 chronic inflammatory response that to infection and explain the late Scleritis. This has the potential involves the superficial and deep epi- onset of scleritis.9,24 Fungal and para- for sight-threatening sequelae.26,27 scleral plexus.9,21 The exact mecha- sitic etiologies are rare. Because of the anatomical relation- nism of inflammation in scleritis The most common infectious ship of the optic nerve’s dural and

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 45

0044_ro1117_f3.indd44_ro1117_f3.indd 4545 111/3/171/3/17 1:241:24 PMPM Inflammation

scleritis patients.2,9,21 Less than 10% progress from one type of scleritis to another.3 Vascular congestion and a tender globe follow the insidious onset of diffuse anterior scleritis, the most common and the least severe form.1,3,9,21 A firm, immobile focal area of inflammation denotes nodular anterior scleritis. As with nodular episcleritis, it usually presents within the palpebral fissure and can be single or multiple.1,9,21 Necrotizing anterior scleritis These images show a normal sclera, above, vs. nodular episcleritis, below. Note marks the most severe form and the the increased thickness of the episclera (red arrow) while the scleral thickness is greatest threat to the integrity of the unaffected. The elongated hyporeflective area (blue arrow) could indicate edema in eye.9 Intense vasculitis with closure the presence of a thickened sclera. In this case, it was due to a scleral plaque. of the deep episcleral vascular plexus leads to necrosis, tenderness and arachnoid sheaths, decreased visual Clinical Presentation extreme pain.1,2,9 The translucently acuity may occur with inflamma- Each of these conditions have thin sclera highlights the choroid’s tion around this area. One study slightly different presentations: bluish hue. Necrotizing anterior found that, initially, poor vision was Episcleritis. This is usually dif- scleritis is most likely associated the most important risk factor for fuse or simple with benign, mild with systemic disease and peripheral a negative visual outcome.24 Other inflammation that resolves within ulcerative keratitis.1,3,16,21 symptoms include photophobia and days to weeks.2,4 Nodular episcleri- Although now considered rare increased lacrimation.9 tis, frequently located between the due to improved therapies for RA, Scleritis is a more painful condi- palpebral fissures, is more painful scleromalacia perforans lacks sur- tion than episcleritis, and the pain and lasts longer.1,4 Epiphora may rounding inflammation and stems may appear disproportionate to also be present. Because epislceritis from obliterative arteritis involv- clinical findings.12 Patients describe it involves the conjunctival and super- ing the deep episcleral plexus.9,16 as a deep, boring pain that may radi- ficial episcleral plexi, the affected Necrotic scleral plaques may appear ate to the face, cheek and jaw.2,9,12,16 area appears bright red, unlike the near the limbus, and severe thinning Often, it is worse at night and is characteristic bluish-violet hue asso- yields a brown color, along with a exacerbated with eye movement.2,9,21 ciated with the deep episcleral plexus high amount of astigmatism.1,2,9 Investigators discovered a significant involvement in scleritis.9,21 Addition- increase in pain severity with HZV ally, intraocular pressure (IOP) may Diagnostic Tools scleritis cases vs. those with idio- be elevated due to increased epi- In addition to the clinical exam, pathic etiologies.22 scleral venous pressure (EVP).27 clinicians can use optical coherence Though more agonizing, scleritis Scleritis. This varies depending on tomography (OCT), ultrasound bio- may ironically reduce corneal sensa- the location and nature of involve- microscopy and B-scan ultrasound tion.26 Researchers cite a decrease ment. Uveitis occurs in up to 40% to help differentiate between episcle- in conjunctival sensation in areas of all scleritis patients and is usually ritis and scleritis. OCT, for example, of previous inflammation, with the seen with the necrotizing type.9 Ker- can provide objective cross-sectional exception of HZV scleritis, which atitis is present in 14% to 37% of images and help to describe charac- blunted sensation in both active and scleritis patients and usually targets teristic findings with anterior scle- inactive states. This occurred due to the adjacent peripheral cornea and ritis.19 Using spectral-domain (SD) the cornea and conjunctiva sharing may include thinning, infiltrates and OCT, researchers note consistent the same classes of sensory receptors interstitial keratitis.3,21 Increased IOP findings of hyporeflective spaces sec- and the increased likelihood of cor- from elevated EVP or trabeculitis ondary to edema and blood vessels, neal involvement with HZV.26 leads to glaucoma in 9% to 13% of variations in reflectivity of tissues

46 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

044_ro1117_f3.indd 46 11/3/17 1:24 PM The leading cause of ocular discomfort and contact lens dropout is dryness.

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RO0217_Tear Scient.indd 1 2/2/17 11:12 AM Inflammation

and dilated deep episcleral vessels.19 Treatment mon infectious cause, responds well OCT further shows treatment results Once the proper diagnosis is clear, to oral acyclovir or famciclovir and in normalization of scleral tissue.19 clinicians can initiate the proper should resolve the symptoms within Other researchers noted superfi- treatment for the patient: several weeks or less.22 cial layer involvement in episcleritis, Episcleritis. Because episcleritis Unlike with episcleritis, NSAIDs but dilated vessels in the deeper is usually a self-limiting condition may be a first-line treatment for vascular network with scleritis.7 with a nearly 20% resolution rate diffuse or nodular, idiopathic and Another study found the scleral without treatment, patient educa- non-necrotizing anterior scleritis.3,4,9 thickness in episcleritis and scleritis tion or topical lubricants may suf- If the patient sees no improvement, averages 825µm and 882µm, respec- fice.1,2 Research suggests topical clinicians should prescribe a differ- tively (the normal sclera is roughly non-steroidal anti-inflammatory ent NSAID before advancing to the 750µm with a standard deviation drugs (NSAIDs) provide no benefit next therapeutic level.2 The selective of nearly 70µm).5 Clinicians should over artificial tears.32 Although COX-2 inhibitors such as celecoxib be cautious about basing a diagno- this condition can be self-limiting, are good options when adverse sis solely on thickness, however, as many clinicians initially treat with a gastrointestinal side effects are a nodular cases will skew the measure- topical steroid. If the inflammation concern. While some research sug- ments. The key is looking for pock- continues, the dosing frequency may gests steroids provide no benefits, a ets of edema in the sclera.5 be increased or the patient can be study of a series of non-necrotizing High-frequency ultrasound biomi- switched to a more potent topical anterior scleritis cases showed topi- croscopy can be a useful tool in dis- steroid.1,2,33 Only with the failure of cal steroids resolved nearly half of tinguishing between episcleritis and these regimens should practitioners the cases, but often they require scleritis. Tissue penetration is better resort to oral NSAID therapy, which additional treatment.2-4,34 Durezol with this modality, but it comes at occurs mainly in patients with a (difluprednate, Alcon/Novartis), the the expense of decreased resolution known systemic association.1,33 topical ophthalmic steroid emulsion compared with OCT.5 Early adopt- Scleritis. Before initiating any that exhibits enhanced penetration ers found that episcleral thickening treatment, clinicians should first and bioavailability, has not been could be differentiated from scleral determine if the scleritis is infectious, studied for scleritis use. involvement.28 as drugs such as oral steroids may Oral corticosteroids are the next Unlike with other scleritis forms, worsen the condition. A thorough therapeutic step for refractory cases, the observable eye in posterior dis- history into any ocular surgery those with necrotizing signs or poste- ease may be nonerythematous.18 or trauma should be obtained as rior scleritis.9,33 Typical oral dosages Other dissimilarities include its well. Clinically, a mucopurulent range from 1mg/kg/day to 1.5mg/kg/ twice-as-often unilateral presenta- discharge or scleral abscess may be day until the inflammation is con- tion and pain that does not correlate sufficient signs to signal infection in trolled.1,4 Given the nocturnal pain with the severity of inflamma- the absence of a tissue culture and associated with scleritis, it may be tion.1,2,29,30 Because it is not visible, sensitivity test.23 A complete blood wise to spread the dose over the day clinicians must depend on other count may reveal elevated white vs. a morning-only delivery.1 Taper- procedures when assessing poste- blood cells. HZV, as the most coming depends on dosage, duration of rior scleritis. A dilated fundus exam use and practitioner discretion. Most may reveal choroidal folds, serous practitioners use the lowest pos- retinal detachments, choroidal sible dose for the shortest possible detachments, macular or optic disc time, as long-term steroid treatment edema and vitreous cells.3,21,29 B-scan should be avoided due to the delete- ultrasound demonstrates posterior rious side effects. thickening with fluid collecting in Other routes of steroid introduc- the sub-Tenon’s space, producing the tion include intravenous (IV) and pathognomonic ‘T-sign.’31 Roughly periocular injection. Necrotizing 40% of posterior scleritis patients scleritis, for example, may warrant exhibited this finding and more than This B-scan ultrasound shows a IV methylprednisolone.3,4 Though half had posterior scleral wall thick- thickened posterior sclera (arrows) with not routinely employed, periocular ness greater than 2mm.29 an absent ‘T’ sign. injection of steroids can be effective

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044_ro1117_f3.indd 48 11/3/17 1:25 PM 6. Snell RS, Lemp MA. Clinical Anatomy of the Eye. Cambridge: in controlling inflammation in non- Blackwell Scientific Publications; 1989. necrotizing anterior scleritis without 7. Axmann S, Ebneter A, Zinkernagel MS. Imaging of the sclera 3 in patients with scleritis and episcleritis using anterior seg- the systemic side effects. ment optical coherence tomography. Ocul Immunol Inflamm. 2016;24(1):29-34. Those with an associated systemic 8. Adkinson NF, Bochner BS, Burks AW, et al. Middleton’s condition or the necrotizing type Allergy: Principles and Practice. Philadelphia: Saunders; 2014. 9. Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. typically need immunosuppres- Surv Ophthalmol. 2005;50(4):351-63. sive therapy or biological agents.35 10. Akpek EK, Uy HS, Christen W, et al. Severity of episcleritis and systemic disease association. Ophthalmology. Examples include methotrexate, 1999;106(4):729-31. 11. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Oph- azathioprine, cyclophosphamide, thalmol. 1976;60(3):163 LP-191. mycophenolate mofetil, infliximab This 58-year-old male with diffuse 12. Albert DM, Jakobiec FA. Principles and Practice of Ophthal- mology. Philadelphia: Saunders; 2008. and rituximab. anterior scleritis was placed on naproxen 13. Rajoo SG, Gandhewar J. Recurrent episcleritis in relation to 500mg BID, but continued symptoms menstruation: a case report. Cornea. 2011;30(9):1035-6. There are several concerns to 14. Homayounfar G, Nardone N, Borkar DS, et al. Incidence of remember regarding treatment: warranted an increase to TID. The scleritis and episcleritis: results From the Pacific Ocular Inflam- mation Study Gelareh. Am J Ophthalmol. 2014;156(4):1-12. Recurrence is not uncommon. For inflammation persisted, and we chose to 15. McGavin DD, Williamson J, Forrester JV, et al. Episcle- example, research shows younger change from naproxen to indomethacin ritis and scleritis. A study of their clinical manifestations and association with rheumatoid arthritis. Br J Ophthalmol. patients tend to have recurrence 50mg TID. The patient responded well 1976;60(3):192-226. 29 and the condition resolved. 16. Levin LA, Albert DM. Ocular Disease: Mechanisms and sooner and more frequently. Dif- Management. Philadelphia: Saunders; 2010. fuse anterior scleritis is least likely 17. Hoyt CS, Lambert SR, Lyons CJ, Taylor D. Taylor and Hoyt’s Pediatric Ophthalmology and Strabismus. Elsevier; 2017. to recur, followed by the nodular systemic disease, clinicians should 18. Som PM, Curtin HD. Head and Neck Imaging. 5th ed. Bos- version of the same process.8 Drug consult the proper specialist for ton: Mosby; 2011. 19. Levison AL, Lowder CY, Baynes KM, et al. Anterior segment tapering may initiate recurrence. management. Some state RA is the spectral domain optical coherence tomography imaging of patients with anterior scleritis. Int Ophthalmol. 2016;36(4):499- Immunosuppressive drugs most common systemic condition 508. increase the risk for a secondary associated with scleritis, while others 20. Sen HN, Sangave AA, Goldstein DA, et al. A standardized grading system for scleritis. Ophthalmol. 2012;118(4):768-71. infection. What starts out as an idio- found RA with vasculitis—particu- 21. Krachmer J, Mannis M, Holland E. Cornea. Boston: Mosby; 2011. pathic condition could turn infec- larly granulomatosis with polyan- 22. Gonzalez-Gonzalez LA, Molina-Prat N, Doctor P, et al. tious, which should be considered in giitis (GPA)—was the number one Clinical features and presentation of infectious scleritis 12,33 from herpes viruses: A report of 35 cases. Ophthalmology. patients who respond well initially cause. Still others recorded GPA 2012;119(7):1460-4. but then worsen. and relapsing polychondritis as top 23. Doshi RR, Harocopos GJ, Schwab IR, Cunningham ET. The spectrum of postoperative scleral necrosis. Surv Ophthalmol. Malignancy may mimic treatment- offenders.3 2013;58(6):620-33. 2,18 24. Hodson KL, Galor A, Karp CL, et al. Epidemiology and resistant scleritis. This could visual outcomes in patients with infectious scleritis. Cornea. include intraocular tumors such as A thorough case history, a review 2013;32(4):466-72. 25. Kawai K, Yawn BP, Wollan P, Harpaz R. Increasing incidence melanomas or, rarely, conjunctival of patient symptomatology, com- of herpes zoster over a 60-year period from a population-based 9 study. Clin Infect Dis. 2016;63(2):221-6. tumors and lymphoma. parative clinical findings and further 26. Somkijrungroj T, Pimolrat W, Gonzales JA, et al. Conjunctival The chronic use of NSAIDs is not diagnostic tools are keys to helping sensation in scleritis. Ocul Immunol Inflamm. 2016;24(1):24-8. 27. Pikkel J, Chassid O, Srour W, et al. Is episcleritis associated benign. Clinicians should regularly clinicians successfully differentiate to glaucoma? J Glaucoma. 2015;24(9):669-71. monitor liver and kidney function, between episcleritis and scleritis. The 28. Pavlin C, Easterbrook M, Hurwitz J, et al. Ultrasound biomicroscopy in the assessment of anterior scleral disease. Am J as well as blood pressure in hyper- right diagnosis and prompt treat- Ophthalmol. 1993;116(5):628-35. 2 29. Lavric A, Gonzalez-Lopez JJ, Majumder PD, et al. Posterior tensives. Gastric irritation may ment leads to improved outcomes, as scleritis: analysis of epidemiology, clinical factors, and risk of require additional medications. does adhering to a multidisciplinary recurrence in a cohort of 114 patients. Ocul Immunol Inflamm. 2016;24(1):6-15. Nearly 50% of patients with scle- approach when applicable. ■ 30. McCluskey PJ, Watson PG, Lightman S, et al. Posterior scleritis: clinical features, systemic associations, and outcome in a ritis, and more than 30% of those Dr. Williamson is the residency large series of patients. Ophthalmology. 1999;106(12):2380-6. with episcleritis, have an underlying supervisor at the Memphis VA Medi- 31. Cunningham ET, McCluskey P, Pavesio C, et al. Scleritis. 2,4,9,21,33 Ocul Immunol Inflamm. 2016;24(1):2-5. systemic disease. Therefore, cal Center and is adjunct faculty at 32. Williams CPR, Browning AC, Sleep TJ, et al. A randomised, treatment must include a suitable multiple optometry schools. double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis. Eye (Lond). 2005;19(7):739-42. workup with the understanding that 33. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and 1. Bowling B. Kanski’s Clinical Ophthalmology. Philadelphia: scleritis: clinical features and treatment results. Am J Ophthal- scleritis is the first manifestation Saunders; 2015. mol. 2000;130(4):469-76. of systemic disease in only 15% of 2. Diaz JD, Sobol EK, Gritz DC. Treatment and management of 34. McMullen M, Kovarik G, Hodge WG. Use of topical steroid scleral disorders. Surv Ophthalmol. 2016;61(6):702-17. 3 therapy in the management of nonnecrotizing anterior scleritis. patients (Table 1). Many clinicians 3. Sims J. Scleritis: presentations, disease associations and Can J Ophthalmol. 1999;34(4):217-21. management. Postgrad Med J. 2012;88(1046):713-8. 35. Sainz-de-la-Maza M, Molins B, Mesquida M, et al. Inter- defer this testing in episcleritis cases 4. Yanoff M, Duker JS. Ophthalmology. Boston: Mosby; 2014. leukin-22 serum levels are elevated in active scleritis. Acta unless it is refractory or has a high 5. Shoughy SS, Jaroudi MO, Kozak I, Tabbara KF. Optical coher- Ophthalmol. 2016;94(6):e395-e399. ence tomography in the diagnosis of scleritis and episcleritis. 36. Anshu A, Chee SP. Posterior scleritis and its association with rate of recurrence. Once discovering Am J Ophthalmol. 2015;159(6):1045-1049.e1. HLA B27 haplotype. Ophthalmologica. 2007;221(4):275-8.

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Glaucoma Therapy: Don’t Forget the Ocular Surface Following the mantra “do no harm” can be a challenge when prescribing topical glaucoma medications. These tips can help minimize damage. By Leslie O’Dell, OD, and Ben Gaddie, OD

n estimated 2.2 million Photo: Jacob R. Lang, OD Treatment-related DED Americans have glaucoma Topical intraocular pressure (IOP)- and 20 million have dry lowering medication is often the Aeye disease (DED)—odds first-line treatment for glaucoma are, practitioners are bound to see patients. These agents not only patients diagnosed with both.1,2 contain their active ingredients for Research suggests the comorbidity IOP lowering, but also excipients, of DED in patients treated topically including buffers, preservatives, for ocular hypertension and glau- drug vehicle and viscosity agents— coma could be as high as 20% to all of which may negatively impact 59%.3 But few step back to consider the ocular surface (Table 1). Some the association between these two Fig. 1. Corneal staining in the form of risk factors for iatrogenic DED as a chronic and progressive diseases. punctate epitheliopathy is a diagnostic result of topical glaucoma treatment Often, it’s nearly impossible to finding for DED. Many BAK-containing include the duration of treatment, decipher which disease came first glaucoma medications can cause this concentration of preservatives in the and how much of the DED is iatro- presentation, so ask glaucoma patients medication, the number of medica- genic—caused inadvertently by a about ocular comfort during follow-up, tions being used, a higher baseline medical treatment or procedure. as duration of use and multiple IOP and disease severity.6,9,10 DED may stem from the medi- medication use increases the risk. While randomized clinical trials of cal treatment of glaucoma, for contemporary glaucoma drugs show example. Studies show 38% of and aqueous layers, damage to the decent tolerability, studies fail to glaucoma patients are using a tear goblet cells and neurotoxicity to cor- depict their effects on the ocular sur- substitute, and the mainstay topical neal nerves.4,5 With each additional face because patients at risk for ocu- medications for glaucoma manage- medication involved in the treatment lar surface disease are excluded, the ment come with side effects such as of glaucoma, the risk of an adverse study durations are short and they allergy, toxicity, immuno-inflam- event or possible exacerbation of don’t evaluate the effects of multiple matory effects, punctate keratitis, dry eye multiplies.6-8 Here’s a look at meds on the ocular surface.5 conjunctival inflammation and the ocular surface in patients being Researchers now know the disruption of the tear film.4,5 These treated for glaucoma—and how you negative effects of glaucoma medi- all result in reduction of the lipid can help protect it. cations on the ocular surface are

50 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

050_ro1117_f4.indd 50 11/3/17 3:22 PM dose-dependent.7,8,11 In addition, ing upon awakening.15 For a glau- studies show the prevalence of DED coma medication to be comfortable increases with multiple medication with instillation, the pH should be use.6-8 In one study, 11% of patients between 6 and 8.15 A topical glau- using one medication reported dry coma medication within this range eye symptoms, while 39% on two allows for better drug absorption medications and more than 43% on due to decreased lacrimation from three medications reported symp- discomfort, as well as less risk for toms such as irritation, foreign body tissue damage. sensation, transiently blurred vision Some drugs, such as Trusopt and increased blinking.12 (dorzolamide, Merck), Cosopt The very pharmacokinetics of (dorzolamide hydrochloride-timolol glaucoma medications can cause tear maleate, Akorn) and Zioptan (taflu- film alterations.5 Medication admin- prost ophthalmic solution, Akorn) istration onto the ocular surface for have a lower pH at 5.6, 5.65 and 15 to 20 seconds provides a low 5.5, respectively, making them less Fig. 2. Inflammation is present in all bioavailability of less than 5%, and tolerable with increase symptoms of forms of DED. Conjunctival hyperemia to absorption is affected by the medi- instillation irritation and lacrimation the meibomian gland orifice can be seen cation’s pH level and viscosity.11,13 with instillation (Table 2). clinically, as pictured here. Absorption is also influenced by the Many glaucoma drugs contain drug’s tear solubility and ocular sur- preservatives, namely benzalkonium and damage to goblet cells and cor- face permeability. For example, pros- chloride (BAK). This quaternium neal and conjunctival tissues; if left taglandin analogs (PGAs) require ammonia is necessary to prevent untreated, the cycle perpetutes.16 corneal esterases to convert the drug microbial contamination and pre- One survey of 9,658 glaucoma to the free acid form, which has the vent breakdown of the active ingre- patients found a significant differ- actual therapeutic effect as a pro- dient in multidose formulations. ence in patient experience between drug.14 The retention time is longer While good for bioavailability of the preservative-free and preserved for more viscous solutions, allowing medication, they are not ideal for medications.17 Eliminating preser- for increased absorption. This influ- corneal health. BAK, for example, vatives led to a decrease in dry eye ences the drug’s bioavailability and disrupts tear film homeostasis by sensations from 34.9% to 16%, thus efficacy, but also increases the stripping away the lipid layer, lead- and simply by removing BAK, the risk of an adverse effects (Figure 1) . ing to increased evaporation and clinical finding of corneal staining, The pH of a medication is also entry into the vicious circle of tear a diagnostic criteria for DED, was important for corneal penetration film instability.15 Once in the vicious reduced by 35%.16 Another study and absorption of the therapeutic circle, hyperosmolarity of the tear found switching to preservative-free agent. A healthy tear film has a pH film is followed by inflammation formulations reduced discomfort ranging from 7.3 to 7.7 and is at the to the ocular surface, release of an upon instillation, foreign body sensa- lowest (more acidic) in the morn- inflammatory cascade of cytokines tion, dry eye symptoms, tearing and

Table 1. Known Ocular Side Effects From Glaucoma Medications Medication Ocular Side Effects Carbonic anhydrase inhibitor Allergic reaction, blepharitis, blurred vision, burning/stinging, conjunctival edema, conjunctivitis, discharge, dryness, hyperemia, keratitis, photophobia, tearing Alpha-agonist Burning/stinging, blepharitis, blurred vision, conjunctival blanching, conjunctival follicles, conjunctival hyperemia, conjunctivitis, dry eye, keratitis, eyelid erythema, foreign body sensation, lid edema, pain, photophobia, tearing Beta-blocker Burning/stinging, blurred vision, conjunctivitis, contact dermatitis, eyelid erythema, photophobia, punctate keratitis Prostaglandin analogs Allergic reaction, burning/stinging, blepharitits, blurred vision, cataract, conjunctivitis, cystoid macular edema, dry eye, eyelash growth, eyelid skin darkening, foreign body sensation, hyperemia, iris color changes, iritis, pain, punctate keratitis Cholinergic agents Burning/stinging, blurred vision, conjunctival injection, decreased night vision, decreased vision due to ciliary spasm, myopia and retinal detatchment (rare), keratitis, periorbital headache (brow ache), tearing

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050_ro1117_f4.indd 51 11/3/17 3:22 PM Glaucoma

eyelid itching.18 The newer PGAs to 300mOsms/L. An osmolarity of Protect the Ocular Surface with preservative-free formulations 309mOSms/L to 328mOSms/L is When left undetected or untreated, and alternative preservatives show categorized as mild to moderate, and DED can significantly impact glau- similar improvement of symptoms.19 higher than 328mOsms/L is consid- coma management, as increased Researchers also found ocular sur- ered severe.22 An inter-eye difference symptoms of ocular discomfort face improvement occurred as early of 8mOsms/L or greater also indi- can lead to decreased medication as one month after removing the cates tear film instability and may compliance—a known risk factor for offending agent.20 be more diagnostic of DED than the disease progression.23 level of osmolarity in each eye.23 In addition, tear film disruption Stay Proactive: Evaluate NTBUT measures, as well as can affect the reliability and repro- When examining a patient using at TBUT with fluorescein dye, should ducibility of diagnostic testing such least one glaucoma drug, clinicians always be taken after tear osmolar- as visual fields and OCT. One study should always pay close attention ity. A TBUT reading of 10 or less found artificial tears QID for one to the ocular surface, ask about indicates DED.21 week prior to visual field testing for dry eye symptoms and evaluate for Another point-of-care test cur- patients with DED and glaucoma signs of DED. The five-item Dry Eye rently available in the United States improved test time and results.24 Questionnaire (DEQ-5) or the Ocu- includes the InflammaDry test When it comes to surgical man- lar Surface Disease Index (OSDI) (Quidel) for the detection of elevated agement of glaucoma, a healthy ocu- should be repeated at every patient levels of matrix metalloproteinase lar surface is even more important. encounter, as the effects of topical (MMP-9) in tears (Figure 2). Conjunctival inflammation from glaucoma medications can be prolonged exposure to BAK cumulative. DED is suspected Table 2. Glaucoma Medication pH Values can result in poor surgical if DEQ-5 is greater than six outcomes due to conjuncti- Medication pH Value and if the OSDI staging of val scarring.25 Research also severity is mild (13 to 22), Beta-blockers shows an association between moderate (23 to 32) or severe Betagan (levobunolol 0.25%, 0.5%, Allergan) 5.5 to 7.5 long-term topical glaucoma (greater than 32). To evalu- Betimol (timolol hemihydrate 0.25%, 0.5%, Santen) 6.5 to 7.5 medication use and fibro- ate for clinical signs of DED, Betoptic S (betaxolol 0.5%, Alcon) 7.6 blast proliferation of Tenon’s clinicians can use one of Carteolol 1.0% 6.2 to 7.2 capsule and elevated MMP-9 three TFOS DEWS II recom- Istalol (timolol maleate 0.5%, Bausch + Lomb) 6.5 to 7.5 levels, which can contribute mended tools: noninvasive Timoptic, Timoptic XE (gel) (timolol maleate 0.25%, 7.0 to filtering bleb scarring fol- tear break-up time (NTBUT) lowing trabeculectomy.26 Prostaglandin Analogs or TBUT with fluorescein Another study shows inferior dye; tear film osmolarity; or BAK-free latanoprost 7.0 fornix shortening with topical corneal, conjunctival and lid Lumigan (bimatoprost, Allergan) 6.8 to 7.8 glaucoma therapy for three or staining with fluorescein and Travatan Z (travoprost, Alcon) 5.7 more years.26 lissamine green vital dyes.21 Xalatan (latanoprost, Pfizer) 6.7 The dry eye testing sequence Zioptan (talfluprost, Akorn) 5.5 to 6.7 The Meibomian Glands is important and should be Alpha-agonist While the many adverse events performed from least to most Alphagan P (brimonidine 0.1%, Allergan) 7.4 to 8.0 to the tear film and ocular invasive. surface associated with topi- Alphagan P (brimonidine 0.15%, Allergan) 6.6 to 7.4 Osmolarity provides a cal glaucoma treatments are measure of the tear chemistry Alphagan (brimonidine 0.2%, Allergan) 5.6 to 6.6 well known, the impact on the including tear film stability Carbonic Anhydrase Inhibitors meibomian glands is not. One and homeostasis. TearLab’s Azopt (brinzolamide, Alcon) 7.5 study looked at the effects of osmolarity system collects Trusopt (dorzolamide, Merck) 5.6 beta-blockers and PGAs on and analyzes a 50nL sample Combination Therapy meibomian gland function and of tears obtained from the Combigan (brimolidine/timolol, Allergan) 6.5 to 7.3 morphology and found a posi- inferior lateral meniscus and tive correlation between topi- Cosopt (dorzolamide/timolol, Akorn) 5.65 lid margin. Normal osmolar- cal treatments and decreased Simbrinza (brinzolamide/brimonidine, Alcon) 6.5 ity ranges from 290mOsms/L gland structure and function.27

52 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

0050_ro1117_f4.indd50_ro1117_f4.indd 5252 111/3/171/3/17 3:233:23 PMPM 12HRS CONSISTENT & CONTINUOUS SYMPTOM RELIEF

51% IMPROVEMENT IN TEAR FILM Before using After using STABILITY Rohto® Dry-Aid™ Rohto® Dry-Aid™ From the #1 Global OTC Eye Care Brand†, New Rohto® Dry-Aid™ is clinically shown to help restore and protect the natural tear film. Formulated with Liquidshield™ technology Rohto® Dry-Aid™ works on all three layers of the tear to provide continuous relief all day. 33% For more information visit: REDUCTION IN www.rohtoeyedrops.com/professionals PATIENT © 2017 The Mentholatum Company DISCOMFORT * Clinicaltrials.gov Identifier: NCT03183089. Publication Pending † Euromonitor International Limited: Consumer Health Eye Care definition, retail value share, 2016 data

RP0717_Mentholatum.indd 1 6/20/17 3:10 PM Glaucoma

with autoimmune conditions such as Restore the Tear Film Sjögren’s syndrome, where aqueous Despite rigorous follow up and scru- secretions are already reduced. tiny, glaucoma patients often end up A number of preservative-free with iatrogenic DED from topical and BAK-free glaucoma medica- therapy. When treating the ocular tions exist. Clinicians should surface, the main focus should be on consider starting patients with a restoring homeostasis and reducing BAK-free medication if possible. If the inflammatory response to the a medication with BAK is unavoid- topical medications. Therapies such Fig. 3. MGD is a common cause of able, a medication with the lowest as Restasis (cyclosporine, Allergan) evaporative dry eye. Examining the concentration is the best option to or Xiidra (lifitegrast, Shire) are often lid for structural and functional gland start with. Before adding a second the first choice therapy for DED. changes—such as thickened meibomian medication, clinicians should con- As these add to a patient’s daily list gland secretions, as seen here—should sider changing to a combination of drops, proper education is para- be routine. therapy to reduce the BAK load mount to ensure they wait between on the ocular surface, Cosopt PF is drop for proper clearance of each Another study of meibomian the only combination medication medication. gland epithelial cell survival rates offering combination therapy with Patient education on the side when exposed to pilocarpine and a BAK-free formulation (Table 3). effects of DED therapy, including timolol found a dose-dependent ImprimisRx, a new concept in the burning with instillation, blurred survival rate on cell culture, but not pharmaceutical industry, uses com- vision and dysgeusia, will improve with the drug levels accumulating pounding pharmacies to formulate medication compliance rates. It is near the glands during instillation.28 preservative-free medication options possible that as the ocular surface Much is unknown about the mei- (Table 4). While promising, these heals, some of the side effects could bomain glands and their function, drugs should be used with caution, diminish. Treatments for MGD but clinical practice suggests PGAs as they do not undergo the same include heat with at-home heat have an inflammatory effect on the FDA screening for safety, and con- masks, as well as in-office LipiFlow meibomian glands, evidenced by the tamination is a concern. (TearScience) and manual expres- thickened and red eyelid margin and Alternative therapies such as sion—an often necessary step, tissue surrounding the meibomian selective laser trabeculo- glands (Figure 3). Meibomian gland plasty (SLT) or minimally Table 3. BAK Concentrations in assessment should remain an integral invasive glaucoma surgery Glaucoma Medications part of the comprehensive dry eye (MIGS) may eliminate Medication BAK (%) exam for glaucoma patients. medication-induced effects, Alphagan P (brimonidine, Allergan) BAK-free which should reduce the Cosopt PF (dorzolamide/timolol, Akorn) BAK-free Treatment: Choose Wisely risk for dry eye symptoms. Timoptic XE (timolol maleate, Bausch + Lomb) BAK-free Many choices exist when managing Research shows SLT is Travatan Z (travoprost, Alcon) BAK-free glaucoma patients, and clinicians effective for both primary should try to reduce the risk of iat- and adjunctive glaucoma Zioptan (talfluprost, Akorn) BAK-free rogenic DED whenever possible, treatment with a mean IOP Simbrinza (brinzolamide/brimonidine, Alcon) 0.003 especially in patients with multiple reduction of 3.8mm Hg to Alphagan (brimonidine, Allergan) 0.005 factors associated with dry eye. 8.0mm Hg after six months Betagan (levobunolol, Allergan) 0.005 PGAs are often the first-line choice, to one year and a mean suc- Combigan (brimolidine/timolol, Allergan) 0.005 as they offer great IOP reduction cess rate of 55% to 82 % Lumigan (bimatoprost, Allergan) 0.005 and convenient dosing. However, in the same time frame.29 Cosopt (dorzolamide/timolol, Akorn) 0.0075 PGAs can lead to meibomian gland MIGS surgery can also be Trusopt (dorzolamide, Merck) 0.0075 obstruction, which makes it less than effective at lowering IOP, Azopt (brinzolamide, Alcon) 0.01 ideal for patients with pre-existing and lowers patients’ depen- Betoptic S (betaxolol, Alcon) 0.01 MGD. Topical beta-blockers, how- dency on topical therapies Timoptic (timolol maleate, Bausch + Lomb) 0.01 ever, can reduce aqueous secretions by increasing outflow and may not be ideal for patients through Schlemm’s canal.30 Xalatan (latanoprost, Pfizer) 0.02

54 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

050_ro1117_f4.indd 54 11/3/17 3:23 PM though it adds to your patient’s Table 4. ImprimisRx Glaucoma Combination Drop Therapy treatment burden. Medication Concentration Unit As with all patients, follow up is LAT (latanoprost) 0.005% 5mL key. Patients with DED and glau- TIM-LAT (timolol/latanoprost) 0.5/0.005% 5mL coma are often juggling multiple BRIM-DOR (brimonidine/dorzolamide) 0.15/2% 10mL medications, and return visits are TIM-BRIM-DOR (timolol/brimonidine/dorzolamide) 0.5/0.15/2% 10mL important to continue to monitor the ocular surface to ensure both TIM-DOR-LAT (timolol/dorzolamide/latanoprost) 0.5/2/0.005% 5mL TIM-BRIM-DOR-LAT (timolol/brimonidine/dorzolamide/ 0.5/0.15/2/0.005% 5mL treatments remain effective. latanoprost) Identifying dry eye in patients Triple/quad kit: undergoing glaucoma treatment • TIM-BRIM-DOR (timolol/brimonidine/dorzolamide) 0.5/0.15/2% 10mL is integral to comprehensive care. • TIM-BRIM-DOR-LAT (timolol/brimonidine/dorzolamide/ 0.5/0.15/2/0.005% 5mL Often, we are so busy attending to latanoprost) the first disease that we ignore the ImprimisRx. Compounded ophthalmic formulations. September 2017. www.imprimisrx.com/assets/IMPO0114-Rev6_Fold- fact that its remedy may adversely out-Product-List_pgs.pdf. Accessed October 4, 2017. affect the ocular surface. But identifying DED in our glaucoma patient population may allow for earlier Pitfalls of PGA Treatment intervention, including a chance in Glaucoma patients using PGAs glaucoma management and initia- may be at risk for prostaglandin- tion of DED therapies. ■ associated periorbitopathy, a Dr. O’Dell is the director of the condition that includes: Dry Eye Center of Pennsylvania at • Ptosis This patient has prostaglandin-associated Wheatlyn Eye Care in Manchester, • Relative enophthalmos periorbitopathy with deepened sulci bilaterally Pa. • Inferior scleral show due to periorbital fat atrophy and ptosis. After • Periorbital fat atrophy topical treatment with a PGA for more than 10 Dr. Gaddie is owner and director years, she also has a relative endophthalmos with of Gaddie Eye Centers in Louisville, • Involution of dermatochalasis a sunken globe appearance. Ky. • Hypertrichosis Many of these side effects are irreversible, and clinicians should be cautious when initiating 1. Friedman DS, Wolfs RC, O’Colmain BJ; Eye Diseases treatment with PGA medications, especially for patients treated monocularly. Patients should Prevalence Research Group. Prevalence of open-angle glaucoma in the United States. Arch Ophthalmol. also be educated on the possible cosmetic side effects. 2004;122:532-8. 2. International Dry Eye WorkShop. 2007 report of the Inter- syndrome-related quality of life in glaucoma patients. Eur J www.tearlab.com/pdfs/TearLab%20Clinical%20Utility%20 national Dry Eye WorkShop. Ocul Surf. 2007;5:61-204. Ophthalmol. 2009;19(4):572e9. Guide.pdf. Accessed September 15, 2017. 3. Stewart WC, Stewart JA, Nelson LA. Ocular surface 13. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular 23. Kaštelan S, Tomic M, Metež Soldo K, Salopek-Rabatic disease in patients with ocular hypertension and glaucoma. drug delivery. The AAPS Journal. 2010;12(3):348-360. J. How ocular surface disease impacts the glaucoma Curr Eye Res. 2011;36:391-8. 14. Russo A, Riva I, Pizzolante T, et al. Latanoprost oph- treatment outcome. BioMed Research International. 4. Lemij HG, Hoevenaars JG, van der Windt C, Baudouin C. thalmic solution in the treatment of open angle glaucoma 2013;2013:696328. Patient satisfaction with glaucoma therapy: reality or myth? or raised intraocular pressure: a review. Clin Ophthalmol. 24. Kocabeyoglu S, Mocan MC, Bozkurt B, Irkec M. Effect Clin Ophthalmol. 2015;9:785-93. 2008;2(4):897-905. of artificial tears on automated visual field testing in 5. Gomes JAP, Azar DT, Baudouin C, et al. TFOS DEWS II iat- 15. Chun DK, Shapiro A, Abelson MB. Ocular pharmaco- patients with glaucoma and dry eye. Can J Ophthalmol. rogenic report. The Ocular Surface. 2017;15(3):511-38. kinetics. In: Abelson MB, ed. Principles and Practices of 2013;48(2):110-4. 6. Fechtner RD, Godfrey DG, Budenz D, et al. Prevalence of Ophthalmology. Canada: Elsevier; 2008. 25. Leng F, Liu P, Li H, Zhang J. Long-term topical anti- ocular surface complaints in patients with glaucoma using 16. Baudouin C, Aragona P, Van Setten G, et al. Diagnosing glaucoma medications cause enhanced Tenon’s capsule topical intraocular pressure-lowering medications. Cornea. the severity of dry eye: a clear and practical algorithm. Brit- fibroblastproliferation and abnormal TGF-β and MMP 2010;29(6):618e21. ish J Ophthalmol. 2014;98(9):1168-1176. expressions: potential effects on glaucoma filtering surgery. 7. Lee S, Kim MK, Choi HJ, et al. Comparative cross-sec- 17. Jaenen N, Baudouin C, Pouliquen P, et al. Ocular symp- Curr Eye Res. 2011;36(4):301-9. tional analysis of the effects of topical antiglaucoma drugs toms and signs with preserved and preservative-free glau- 26. Broadway D, Grierson I, Hitchings R. Adverse effects of on the ocular surface. Adv Ther. 2013;30:420-9. coma medications. Eur J Ophthalmol. 2007;17(3):341e9. topical antiglaucomatous medications on the conjunctiva. 8. Saade CE, Lari HB, Berezina TL, et al. Topical glaucoma 18. Pisella PJ, Pouliquen P, Baudouin C. Prevalence of ocular British J Ophthalmol. 1993;77(9):590-6. therapy and ocular surface disease: a prospective, controlled symptoms and signs with preserved and preservative free 27. Arita R, Itoh K, Maeda S, et al. Effects of long-term cohort study. Can J Ophthalmol. 2015;50:132-6. glaucoma medication. Br J Ophthalmol. 2002;86(4):418e23. topical anti-glaucoma medications on meibomian glands. 9. Erb C, UGast, Schremmer D. German register for 19. Uusitalo H, Chen E, Pfeiffer N, et al. Switching from a Graefe’s Arch Clin Exp Ophthalmol. 2012;250(8):1181-5. glaucoma patients with dry eye. I. Basic outcome with preserved to a preservative-free prostaglandin prepara- 28. Zhang Y, Kam WR, Liu Y, et al. Influence of pilocarpine respect to dry eye. Graefe’s Arch Clin Exp Ophthalmol. tion in topical glaucoma medication. Acta Ophthalmol. and timolol on human meibomian gland epithelial cells. 2008;246(11):1593e601. 2010;88(3):329e36. Cornea. 2017;36(6):719-24. 10. Baudouin C, Renard JP, Nordmann JP, et al. Prevalence 20. Zhivov A, Kraak R, Bergter H, et al. Influence of benzal- 29. De Keyser M, De Belder M, De Belder S, De Groot V. and risk factors for ocular surface disease among patients konium chloride on langerhans cells in corneal epithelium Where does selective laser trabeculoplasty stand now? A treated over the long term for glaucoma or ocular hyperten- and development of dry eye in healthy volunteers. Curr Eye review. Eye Vis (Lond). 2016 Apr;3:10. sion. Eur J Ophthalmol. 2013;23(1):47-54. Res. 2010;35(8). 30. Lavia C, Dallorto L, Maule M, et al. Minimally-invasive 11. Ghate D, Edelhauser HF. Ocular drug delivery. Expert 21. Wolffsohn JS, Arita R, Chalmers R. TFOS DEWS II diag- glaucoma surgeries (MIGS) for open angle glaucoma: A Opin Drug Deliv. 2006;3:275-87. nostic methodology report. Ocul Surf. 2017;15(3):539-74. systematic review and meta-analysis. PLoS One. 2017 12. Rossi GC, Tinelli C, Pasinetti GM, et al. Dry eye 22. Tearlab. TearLab osmolarity system: Clinical utility guide. Aug;12(8):e0183142.

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050_ro1117_f4.indd 55 11/3/17 3:23 PM WEST COAST Optometric Glaucoma

2017 Symposium

DECEMBER 15-16, 2017

Join our faculty of renowned ODs and MDs for a highly interactive meeting covering the most up-to-date information in glaucoma care. Up to 12 CE credits for only $295.

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THE ORIGINS AND MANAGEMENT OF CONTACT LENS DISCOMFORT Understanding how this irritating nuisance develops is the first step toward fighting its deleterious effects. By Dan Fuller, OD

ontact lens discomfort (CLD) is a distinctly different entity than dry eye disease (DED), whose prevalence is estimated at 30%.1-4 Numerous studies identify CLD (prevalence 30%) as a major contributing factor to con- Ctact lens dropout rates with best estimates placing it between 12% and 51%.2,5-8 The broad range of values is a function of varying definitions of what constitutes a dropout (e.g., reduced wearing time, temporary or permanent discontinuance). CLD creates significant burdens on patients and dramatically affects industry profitability. Identifying these patients and the factors contributing the condition will inform management decisions. The TFOS Workshop classifies CLD by contributory factors into two large baskets: contact lens-related and environmental etiologies (each with four individual subcategories).1 This article focuses on soft lenses and reviews what we believe we know about Fig. 1. Example of corneal staining representative of contact lens-related factors, the contribution from environmental desiccation while wearing a Group IV lens in patient factors second and offers a rational, evidence-based management with severe ocular surface disease. approach.

Release Date: November 2017 Credit Statement: This course is COPE approved for 2 hours of CE Expiration Date: November 15, 2020 credit. Course ID is 55368-CL. Check with your local state licensing Goal Statement: Contact lens discomfort can develop because of a board to see if this counts toward your CE requirement for relicen- number of issues, including poor lens wettability, low oxygen perme- sure. ability or a host of environmental factors. Optometrists should be Disclosure Statements: skilled at delineating these causes and the available contact lens Author: The author has no relationships to disclose. materials so they can best target treatment and fit patients with the Editorial staff: Jack Persico, Rebecca Hepp, William Kekevian, most approriate option. Michael Riviello and Michael Iannucci all have no relationships to Faculty/Editorial Board: Dan Fuller, OD disclose.

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The Material World Photo: Christina Newman, OD Within the contact lens-related category of CLD are four subcategories: (1) Surface and bulk material differences. (2) Design differences. (3) Fit and wear differences. (4) Lens care factors. Materials vary widely in both surface and bulk properties. Designs vary from rigid to hydrogel to silicone hydrogel and hybrids. Rigid gas permeable lenses represented 7% of all fits worldwide in 2016 while soft lens fits/refits constituted 91% of all fits (55% of which were silicone hydrogels).9 Substantial differences in modulus, wettability Fig. 2. Contact lens-related papillary conjunctivitis while wearing silicone hydrogel. and oxygen permeability prevent direct comfort comparisons between contents lower than 50%, and are contact lens papillary conjunctivitis, silicone hydrogels and data from classified as “low” water content superior arcuate epithelial lesions hydrogel studies.10,11 Lens attributes by the FDA, though at least four (SEAL) and corneal erosions and commonly considered potential silicone hydrogel lenses have water mucin balls (Figures 2 and 3).12,31,33- influences on comfort include poly- contents above this threshold.27 38 Second and third generation mer composition, lubricity, water Increasing water content generally designs reduced the incidence of content and wettability.12-20 increases water and sodium chloride these adverse events by eliminating Various modifications to early permeability more for ionic than plasma coatings in favor of internal hydrogel polymers increased their non-ionic soft lenses.28 This process wetting agents such as polyvinylpy- water content and hydrophilic is an order of magnitude less for rolidone (PVP) and by increasing nature. The objective was to improve silicone hydrogels than hydrogels water contents by altering the con- wettability and oxygen permeabil- since it appears to be more restricted stituent polymers, resulting in more ity in an attempt to improve com- by channels in the polymer.28 The mechanical flexibility.12 Notwith- fort.21 Several studies demonstrate impact of ionicity on comfort has not standing some of the more prevalent increasing water content can lead been demonstrated conclusively.21 adverse events associated with ear- to increased dehydration, corneal Research shows oxygen perme- lier high-modulus, low-water con- desiccation and decreased end-of- ability increases with water content tent designs, the Workshop on CLD day comfort by as much as threefold for hydrogel lenses, but the reverse is concluded little difference in com- in FDA Group II and IV lenses.22-25 true for silicone hydrogel, owing to fort between hydrogels and silicone However, these studies failed to these fundamental differences.21,29,30 hydrogels and when differences consider the contributions from dif- Not long after the introduction have been found, it is highly likely it ferences in lens design, leading to the of modern silicone hydrogels late in resulted from methodological flaws conclusion on-eye bulk dehydration the 1990s, interest in the contribu- in the study.21,39 of materials is likely neither associ- tion of modulus or stiffness to CLD The Workshop on CLD consid- ated or causative of discomfort.21,25 began. “Stiffness” is a function of ered surface properties of contact The higher the water content, the more than the material properties lenses including friction, lubric- more moisture is essentially wicked such as modulus, including water ity and surface wear (collectively away from the ocular surface to content, relative thickness and referred to as tribology) and wetta- replace moisture lost from the lens geometry of the lens.12,31-33 The first bility.21 Studies relating these surface polymer through dehydration, generation silicone hydrogel lenses properties to comfort are similarly resulting in corneal desiccation and were high-modulus, low-water con- plagued by confounding lens char- corneal staining (Figure 1).26 Silicone tent designs with plasma coatings acteristics (e.g., sag and edge pro- hydrogel lenses tend to have water and contributed to higher rates of file) or methodological challenges in

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to matter, with thin knife edges consistently demonstrating better comfort than chisel or rounded edges even though they have a higher association with paralimbal conjunctival staining (Figure 4).57-59 Chisel edge profiles are associated with higher frequencies of conjunctival indentation, which is associated with discomfort (Figure 5).60 Regarding lens designs, prism ballasted toric lenses may be more likely to elicit symptoms of discomfort confused with dryness and may represent lid-lens interactions, but direct comparisons with spherical lenses Fig. 3. Corneal erosions in high modulus silicone hydrogel in superior epithelial are rare to absent.21,61-63 Multifocal arcuate region. contact lens comparisons with spherical lenses are similarly rare but have attempting to model on-eye perfor- eter can be a significant predictor shown no difference in comfort.64 mance.21,40 Notwithstanding, manu- of comfort.52 Most spherical soft facturers have attempted to decrease lenses typically fall within a range Modality and Wear Schedules friction and increase wettability at of 13.8mm to 14.2mm.21 These val- Research does not show that daily the lens surface by incorporating ues are above the largest diameter wear is any more comfortable agents commonly used in over-the- of 13.5mm used to study, which than extended wear (except upon counter wetting agents such as poly- may explain why diameter (corneal waking), but that may be due to a vinyl alcohol (PVA) and hyaluronic coverage by extension) has not been shortage of robust clinical studies.21 acid (HA) into their polymers.41-43 shown to be associated with com- Though duration of lens wearing Some of these are slowly eluted or fort in more recent studies.40,52-55 experience has a role in adapta- activated while blinking and over Lens movement contributes to tion, it is difficult to separate the the wear cycle. More recent designs tear exchange but the contribution impact of duration from frequency such as deleficon A and nesofilcon of lens movement (or lack thereof) of replacement or age.21 Multiple A possess unique surface properties to comfort is somewhat murky. circumstantial studies demonstrate which have either not shown, or Two large retrospective studies improved comfort with increasing not tested, comfort differences over demonstrate “loose” fitting lenses frequency of lens replacement, but it other lenses.44,45 Interest in lid-wiper are associated with discomfort and is difficult to separate out the find- epitheliopathy and lid parallel con- “tighter” lenses are not, but no clear ings from confounding variables of junctival folds is growing as a pos- consensus exists on the minimum differences in lens material or care sible predictor of CLD and may be difference between base curves systems in comparison studies.21 related to studies investigating the which elicit awareness.21,40,55,56 Masked, randomized, controlled role of frictional forces.40,46-51 Centration has not been studied studies are lacking. End-of-day com- in relation to comfort independent fort is clearly differentially worse for Lens Design and Fit of looseness/tightness of fit and all contact lens wearers compared Consideration of comfort must also researchers suggest small amounts with non-wearers, with increasing include a review of fitting character- of decentration (<0.3mm) are symptoms in both groups.65–67 istics and lens design. Fitting charac- unlikely to affect comfort.21,40 A teristics are familiar to all clinicians well-centered lens, with coverage Lens Care and include coverage, movement and minimal amounts of movement It may seem counterintuitive, but and centration. Design attributes (about 0.5mm to 1.0mm) in pri- regardless of the nature of deposits, include edge profile, sphere, toric mary gaze, is associated with better they have not directly been implicat- and multifocal parameters. Studies comfort.40,55 ed in decreasing comfort.21 However, demonstrate a larger lens diam- Additionally, edge profiles appear the subject of lens care solution inter-

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058_ro1117_f5_osc.indd 60 11/3/17 12:27 PM actions and their impact (positive or negative) on comfort is a subject of ongoing debates. It remains very difficult to assess individual impacts of constituent agents due to the confounding influences of their interactions, compliance methods and conflicts between in vitro and in vivo performance differences. Compari- son studies exist, but are limited by the number of possible lens-solution combinations tested. Biocides include hydrogen peroxide-based, polyhexamethylene biguanide PHMB-based, Fig. 4. Example of difference in edge profiles on -3.00D sphrerical lens designs, Polyquad-based, and dual disinfec- demonstrating a rounded, thicker edge in comifilcon A (left) and knife edge in tion systems. The reality is that all senofilcon A (right). FDA-approved systems have met current standards for biocidal effi- Other Factors interval may be related to CLD. cacy against the challenge panel of We have summarized broadly the Seasonal allergies may be associated organisms. evidence supporting contact lens- with CLD. Ethnicity appears not to Peroxide-based systems begin at related factors that may contribute be associated with CLD, with little 3% concentration (30,000 ppm) to CLD. It may be unsatisfying, but evidence supporting a relationship and must be neutralized to 100 nonetheless true, that there is no one between systemic disease and CLD.2 ppm, though threshold sensitivity is factor most responsible for CLD. Modifiable patient factors between 50 to 300 ppm or discomfort Rather, multiple lens and solution included medications, dietary habits, will be reported.21 As previously men- factors contribute to CLD. Factors smoking, cosmetics, compliance and tioned, there are few direct compari- such as discussion of wearing times, psychological factors. Use of oral son studies that control for potential replacement intervals and modal- contraceptives and isotretinoin have confounding variables. Nonetheless, ity must include consideration of been associated with CLD but no there is a “suggestion” peroxide-based environmental factors, controllable other agents are conclusively docu- systems provide better comfort with or uncontrollable. This section will mented as contributing to CLD. the limited data available.68,69 Com- summarize some of the more salient Poor compliance with replacement parisons of comfort using PHMB- take-aways. intervals is associated with CLD. and Polyquad-based systems have Non-modifiable patient factors There is little evidence to support occasionally favored Polyquad- based surveyed in the Workshop on CLD the notion that dietary intake and systems but the majority view is there included sex, age, ethnicity, tear fluids influence CLD. The influence is no difference in comfort.70-75 Pre- film, blink characteristics, comor- of smoking on CLD lacks evidence. servative uptake/release and induc- bidities and allergies.2 The authors Little evidence supports an association of corneal staining with possible found females may have higher rates tion between cosmetic use and CLD. CLD is unique to each lens-solution of CLD, but this does not appear Psychological factors have not been combination, making it relatively to predicative of dropout. Younger found to be associated with CLD.2 unpredictable. Modern multipurpose patients report CLD more often Ocular enviromental factors. Con- solutions incorporate surfactants as than presbyopia patients do, par- tact lens wear alters multiple aspects both detergents and wetting agents. ticularly in hydrogels. Assessments of the ocular anatomy and physiol- There is compelling evidence these of tear film volume and stability ogy, including: thinning and desta- can contribute to patient comfort by including phenol thread test, tear bilization of the tear film; increasing increasing the hydrophilicity of the meniscus, noninvasive TBUT, and tear osmolarity; loss or shortening of lens surface, particularly in silicone pattern of breakup correlate with the meibomian glands; alterations to hydrogels.21 Similar findings exist for CLD. Little evidence exists support- corneal sensitivity; cellular changes the surfactants and wetting agents ing an association between changes in the corneal and conjunctival epi- commonly added to blister pack in blink rate and CLD, but stabil- thelium.2 Among these, the presence solutions. ity of the tear film in the interblink of lid-parallel conjunctival folds,

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conjunctival metaplasia, decreased goblet cell density, meibomian gland dysfunction and lid-wiper epitheliopathy have been shown to be associated with CLD.2 External environmental factors reviewed included relative humidity, temperature, climate, air quality, atmospheric pressure and occupation. Among these, reductions in relative humidity, increased air movement and activities which reduce blink rates such as digital device use may all contribute to CLD.2 The remaining factors lack evidence or are equivocal. Management of CLD History-taking continues to be the foundation of all patient encoun- ters. Certain risk factors help identify wearers at risk for CLD. Younger patients are at increased risk; end-of-day discomfort or dis- Fig. 5. Partial arcuate indentation of the nasal bulbar conjunctiva related to edge comfort upon insertion; specifics profile (yellow arrow). on lens parameters; wearing time; replacement interval; care system; use of adjunctive wetting agents; Table 1. Management Strategies Based on 2013 TFOS Workshop compliance; occupation and vision on Contact Lens Discomfort76 demands; coexisting disease; aller- Treatment strategy Specific intervention gies; and current medications.76 Replacement frequency Increase Strategically manage all underly- No clear rule; switch to from higher to lower ing non-lens factors contributing modulus within silicone hydrogel; switch from to CLD, including diseases that Material silicone hydrogel to hydrogel (or reverse); con- contribute to ocular surface disease. sider lower water content hydrogels Identify instances of inappropriate Consider silicone hydrogels lenses with PVP, Add internal wetting agents medication use, overuse or abuse, PVA, hyaluronic acid. which may destabilize the tear film. Preservative-free rewetting drops; modern MPS Treat coexisting lid, tear film, cor- Add external wetting agents and peroxide disinfection systems offer surfac- nea or conjunctival disease. Manage tants and wetting agents lens-related issues, including condi- Elimination of the care system Daily disposables tion, fit and interactions with the Steeper base curves; aspheric base curves; Change lens parameters larger diameter; knife edge eye. This approach is basic to all contact lens examinations.76 Nutritional supplementation Omega-6 in evening primrose oil When confronted with lens wear- Punctal occlusion Occlude upper and lower ers symptomatic for discomfort, one Topical agents Cyclosporin-A; lifitegrast or more of the recommendations Digital device use and occupational exposure Avoidance from the Workshop on CLD cited Consider changing from GP to soft or vice Consider in relationship to needs in Table 1 may be employed based versa on your clinical assessment of the Reduce wearing time Adjust to find optimum level patient.76 Not all strategies are sup- Other Orthokeratology; refractive surgery; spectacles ported by “level I” evidence and

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058_ro1117_f5_osc.indd 62 11/3/17 12:28 PM a combination approach is often and patient-related factors in contact lens-related dry eye. Optom Vis 42. Peterson RC, Wolffsohn JS, Nick J, et al. Clinical performance of Sci. 2008;85(24):764-72. daily disposable soft contact lenses using sustained release technol- necessary. Implementing too many 16. Tranoudis I, Efron N. Parameter stability of soft contact lenses ogy. Cont Lens Anterior Eye. 2006;29(3):127-34. strategies at once and failing to made from different materials. Cont Lens Anterior Eye. 2004;27:115-31. 43. Ali M, Byrne ME. Controlled release of high molecular weight 17. Wheeler JC, Woods JA, Cox MJ, et al. Evolution of hydrogel hyaluronic acid from molecularly imprinted hydrogel contact lenses. manage underlying conditions may polymers as contact lenses, surface coatings, dressings, and drug Pharm Res. 2009 Mar;26(3):714-26. confuse your management plan. Be delivery systems. J Long Term Eff Med Implants. 1996;6(3-4):207-17. 44. Wolffsohn JS, Hunt OA, Chowdhury A. Objective clinical perfor- 18. Yasuda H. Biocompatibility of Nanofilm-Encapsulated Sili- mance of “comfort-enhanced” daily disposable soft contact lenses. judicious and methodical. cone and Silicone-Hydrogel Contact Lenses. Macromol Biosci. Cont Lens Anterior Eye. 2010;33(2):88–92. CLD is ubiquitous, but we have 2006;6(2):121-38. 45. Schafer J, Steffen R, Reindel W, Chinn J. Evaluation of sur- 19. Ramamoorthy P, Sinnott LT, Nichols JJ. Contact lens material face water characteristics of novel daily disposable contact lens never had more sophisticated characteristics associated with hydrogel lens dehydration. Ophthal- materials, using refractive index shifts after wear. Clin Ophthalmol. lens and solution options. As our mic Physiol Opt. 2010;30(2):160-6. 2015;9:1973-9. 20. Opdahl A, Kim SH, Koffas TS, et al. Surface mechanical proper- 46. Korb D, Greiner J, Herman J, et al. Lid-wiper epitheliopathy and understanding continues to grow ties of pHEMA contact lenses: Viscoelastic and adhesive property dry-eye symptoms in contact lens wearers. CLAO J. 2002;28(4):211-6. so, will our ability to provide wear- changes on exposure to controlled humidity. J Biomed Mater Res. 47. Korb DR, Herman JP, Blackie CA, et al. Prevalence of lid wiper 2003;67(1):350-6. epitheliopathy in subjects with dry eye signs and symptoms. Cornea. ers with lifelong comfortable, clear 21. Jones L, Brennan N, González-Méijome J, et al. The TFOS 2010;29(4):377-83. vision. Identify patients at risk and International Workshop on Contact Lens Discomfort: Report of the 48. Pult H, Purslow C, Berry M, Murphy PJ. Clinical tests for suc- Contact Lens Materials, Design, and Care Subcommittee. Investig cessful contact lens wear: relationship and predictive potential. those with contributory conditions. Opthalmology Vis Sci. 2013;54:TFOS37. 2008;85(10):E924-9. Apply evidence-based management 22. Martin D. Water transport in dehydrating hydrogel contact 49. Berry M, Pult H, Purslow C, Murphy P. Mucins and ocular signs lenses: implications for corneal desiccation. J Biomed Mater Res. in symptomatic and asymptomatic contact lens wear. Optom Vis Sci. strategies in a methodical manner, 1995;29(7):857-65. 2008;85:E930-8. increasing the probability for long- 23. McConville P, Pope J. Diffusion limited evaporation rates in 50. Pult H, Murphy PJ, Purslow C. A novel method to predict the ■ hydrogel contact lenses. CLAO J. 2001;27(4):186-91. dry eye symptoms in new contact lens wearers. Optom Vis Sci. term success. 24. Orsborn GN, Zantos SG. Corneal desiccation staining with thin 2009;86(9):E1042-50. Dr. Fuller is chief of Cornea & high water content contact lenses. CLAO J. 1988;14(2):81-5. 51. Yeniad B, Beginoglu M, Bilgin LK. Lid-wiper epitheliopathy 25. Nichols JJ, Sinnott LT. Tear film, contact lens, and patient-related in contact lens users and patients with dry eye. Eye Contact Lens. Contact Lens Service and founding factors associated with contact lens-related dry eye. Invest Ophthal- 2010;36(3):140–3. supervisor of the Cornea & Contact mol Vis Sci. 2006;47(13):1319-28. 52. McNamara N, Polse K, Brand R, et al. Tear mixing under 26. Fonn D, Peterson R, Woods C. Corneal staining as a response to a soft contact lens: Effects of lens diameter. Am J Ophthalmol. Lens–Refractive Surgery residency at contact lens wear the clinical manifestations. 2010;36(5):318-21. 1999;127(6):659-65. Southern College of Optometry. 27. Tyller Thompson T. FDA Groups. Tyler’s Q Soft Contact Lens 53. Boychev N, Laughton D, Bharwani G, et al. How should initial Param Guid. Available http://tylersq.com. Accsessed: September fit inform soft contact lens prescribing. Contact Lens Anterior Eye. 20, 2017. 2016;39(3):227-33. 1. Nichols J, Willcox M, Bron A, et al. The TFOS international 28. Gavara R, Compañ V. Oxygen, water, and sodium chloride 54. Fedtke C, Bakaraju R, Ehrmann K, et al. Visual performance of workshop on contact lens discomfort: executive summary. Investig transport in soft contact lenses materials. J Biomed Mater Res Part B single vision and multifocal contact lenses in non-presbyopic myo- Opthalmology Vis Sci. 2013;54:TFOS7. Appl Biomater. Available www.ncbi.nlm.nih.gov/pubmed/27441390. pic eyes. Contact Lens Anterior Eye. 2016;39:38-46. 2. Dumbleton K, Caffery B, Dogru M, et al. The TFOS Inter- Accessed September 20, 2017. 55. Truong T, Graham AD, Lin MC. Factors in contact lens national Workshop on Contact Lens Discomfort: Report of the 29. Efron N, Morgan Pb, Cameron Id, et al. Oxygen permeability and symptoms: evidence from a multistudy database. Optom Vis Sci. Subcommittee on Epidemiology. Investig Opthalmology Vis Sci. water content of silicone hydrogel contact lens materials. Optom Vis 2014;91(12):133-41. 2013;54(11):TFOS20-36 Sci. 2007;84(4):E328-37. 56. Young G. Evaluation of soft contact lens fitting characteristics. 3. Craig J, Nichols K, Akpek E, et al. TFOS DEWS II definition and 30. Morgan PB, Efron N. The oxygen performance of contemporary Optom Vis Sci. 1996;73(4):247-54. classification report. The Ocular Surface. 2017;15(3):276–283. hydrogel contact lenses. Contact Lens Anterior Eye. 1998;21(1):3-6. 57. Morgan P, Chamberlain P, Moody K, Maldonado-Codina C. Ocu- 4. Nelson J, Craig J, Akpek E, et al. TFOS DEWS II introduction. The 31. Lin MC, Yeh TN. Mechanical complications induced by sili- lar physiology and comfort in neophyte subjects fitted with daily dis- Ocular Surface. 2017;15(3):269-75. cone hydrogel contact lenses. Eye Contact Lens Sci Clin Pract. posable silicone hydrogel contact lenses. 2013. Jun;36(3):118-25. 5. Young G, Veys J, Pritchard N, Coleman S. A multi-centre 2013;39(1):114-23. 58. Maïssa C, Guillon M, Garofalo RJ. Contact lens-induced circum- study of lapsed contact lens wearers. Ophthalmic Physiol Opt. 32. Tagliaferri A, Love TE, Szczotka-Flynn LB. Risk factors for contact limbal staining in silicone hydrogel contact lenses worn on a daily 2002;22(6):516-27. lens–induced papillary conjunctivitis associated with silicone hydro- wear basis. Eye Contact Lens. 2012;38(1):16-26. 6. Weed K, Fonn D. Discontinuation of contact lens wear. Optom Vis gel contact lens wear. Eye Contact Lens. 2014;40(3):117-22. 59. Maldonado-Codina C, Morgan PB, Schnider CM, Efron N. Sci. 1993;70(suppl 12):140. 33. Holden BA, Stephenson A, Stretton S, et al. Superior epithe- Short-term physiologic response in neophyte subjects fitted with 7. Richdale K, Sinnott LT, Skadahl E, et al. Frequency of and factors lial arcuate lesions with soft contact lens wear. Optom Vis Sci. hydrogel and silicone hydrogel contact lenses. Optom Vis Sci. associated with contact lens dissatisfaction and discontinuation. 2001;78(1):9-12. 2004;81:911-21. Cornea. 2007;26(2):168-74. 34. O’Hare N, Stapleton F, Naduvilath T, et al. Interaction between the 60. Stahl U, Willcox M, Naduvilath T, Stapleton F. Influence of tear 8. Pritchard N, Fonn D, Brazeau D. Discontinuation of contact lens contact lens and the ocular surface in the etiology of superior epithe- film and contact lens osmolality on ocular comfort in contact lens wear: a survey. Int Contact Lens Clin. 1999;26(6):157-62. lial arcuate lesions. Adv Exp Med Biol. 2002;506(Pt. B):973-80. wear. Optom Vis Sci. 2009;86:857-67. 9. Morgan P, Woods C, Tranoudis I, et al. International contact lens 35. Dumbleton K. Adverse events with silicone hydrogel continuous 61. Cho P, Cheung S, Charm J. Visual outcome of Soflens Daily prescribing 2016. Contact Lens Spectr. 2017;32:30-5. wear. Contact Lens Anterior Eye. 2002;25(3):137-46. Disposable and Soflens Daily Disposable for Astigmatism in subjects 10. Diec J, Tilia D, Thomas V. Comparison of silicone hydrogel 36. Dumbleton K. Noninflammatory silicone hydrogel contact lens with low astigmatism. Clin Exp Optom. 2012;95:43-7. and hydrogel daily disposable contact lenses. Eye Contact Lens complications. Eye Contact Lens. 2003;29:S186-9-1, S192-4. 62. Young G, Chalmers R, Napier L, et al. Soft contact lens- Sci Clin Pract. Available journals.lww.com/claojournal/Abstract/ 37. Efron N, Jones L, Bron AJ, et al. The TFOS International Work- related dryness with and without clinical signs. Optom Vis Sci. publishahead/Comparison_of_Silicone_Hydrogel_and_Hydro- shop on Contact Lens Discomfort: Report of the Contact Lens Inter- 2012;89:1125-32. gel_Daily.99381.aspx. Accessed: September 20, 2017. actions With the Ocular Surface and Adnexa Subcommittee. Investig 63. Brennan NA, Efron N. Symptomatology of HEMA contact lens 11. Dumbleton KA, Woods CA, Jones LW, Fonn D. Comfort and Opthalmology Vis Sci. 2013;54:TFOS98. wear. Optom Vis Sci. 1989;66:834-8. adaptation to silicone hydrogel lenses for daily wear. Eye Contact 38. Stapleton F, Marfurt C, Golebiowski B, et al. The TFOS Inter- 64. Richdale K, Mitchell GL, Zadnik K. Comparison of multifocal Lens. 2008;34(4):215-23. national Workshop on Contact Lens Discomfort: Report of the and monovision soft contact lens corrections in patients with low- 12. Jacob JT. Biocompatibility in the development of silicone- subcommittee on neurobiology. Investig Opthalmology Vis Sci. astigmatic presbyopia. Optom Vis Sci. 2006;83:266-73. hydrogel lenses. Eye Contact Lens. 2013;39(1):13-9. 2013;54:TFOS71. 65. Chalmers R, Begley C. Dryness symptoms among an unselected 13. Kim S, Opdahl A, Marmo C, Somorjai G. AFM and SFG studies 39. Guillon M. Are silicone hydrogel contact lenses more comfort- clinical population with and without contact lens wear. Cont Lens of pHEMA-based hydrogel contact lens surfaces in saline solution: able than hydrogel contact lenses? Eye Contact Lens. 2013;39(1):86-92. Anterior Eye. 2006;29:25-30. adhesion, friction, and the presence of non-crosslinked polymer 40. Stapleton F, Tan J. Impact of contact lens material, design and fit- 66. Begley CG, Chalmers RL, Mitchell GL, et al. Characterization chains at the surface. Biomaterials. 2002;23(7):1657-66. ting on discomfort. Eye Contact Lens Sci Clin Pract. 2017;43(3):32-9. of ocular surface symptoms from optometric practices in North 14. Kim S, Marmo C, Somorjai G. Friction studies of hydrogel con- 41. Winterton LC, Lally JM, Sentell KB, Chapoy LL. The elution of America. Cornea. 2001;20:610-8. tact lenses using AFM: non-crosslinked polymers of low friction at poly (vinyl alcohol) from a contact lens: the realization of a time 67. Nichols JJ, Ziegler C, Mitchell GL, Nichols KK. Self-reported dry the surface. Biomaterials. 2001;22(24):3285-94. release moisturizing agent/artificial tear. J Biomed Mater Res B Appl eye disease across refractive modalities. Invest Ophthalmol Vis Sci. 15. Ramamoorthy P, Sinnott L, Nichols J. Treatment, material, care, Biomater. 2007;80(2):424-32. 2005;46:1911-4.

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68. Begley CG, Edrington TB, Chalmers RL. Effect of lens care of “no rub” multi-purpose solutions. Cont Lens Anterior Eye. 74. Lipener C. A randomized clinical comparison of OPTI-FREE systems on corneal fluoresceing staining and subjective comfort in 2004;27:65-74. EXPRESS and ReNu MultiPLUS multipurpose lens care solutions. hydrogel lens wearers. Int Contact Lens Clin. 1994;21:7-12. 72. Santodomingo-Rubido J. The comparative clinical performance Adv Ther. 2009;26:435-46. 69. Keir N, Woods CA, Dumbleton K, Jones L. Clinical performance of a new polyhexamethylene biguanide- vs a polyquad-based contact 75. Epstein AB. Contact lens care products effect on corneal sensitiv- of different care systems with silicone hydrogel contact lenses. lens care regime with two silicone hydrogel contact lenses. Ophthal- ity and patient comfort. Eye Contact Lens. 2006;32:128-32. 70. Sorbara L, Peterson RC, Woods CA, Fonn D. Multipurpose mic Physiol Opt. 2007;27:168-73. 76. Papas E, Ciolino J, Jacobs D, et al. The TFOS international disinfecting solutions and their interactions with a silicone hydrogel 73. Nichols JJ, Mitchell GL, King-Smith PE. Thinning rate of the workshop on contact lens discomfort: Report of the manage- lens. Eye Contact Lens. 2009;35:92-7. precorneal and prelens tear films. Invest Ophthalmol Vis Sci. ment and therapy subcommittee. Investig Opthalmology Vis Sci. 71. Stiegemeier MJ, Cedrone R, Evans D, et al. Clinical performance 2005;46:2353-61. 2013;54:TFOS183.

OSC QUIZ

ou can obtain transcript-quality discomfort? regarding silicone hydrogels? continuing education credit through a. DEWS I and II. a. Most have water contents less than 50%. Ythe Optometric Study Center. Com- b. MGD. b. Permeability to sodium chloride and water plete the test form and return it with the c. CLD. is an order of magnitude less than hydrogels. $35 fee to: Jobson Medical Information, d. Delphi panel. c. Increasing water content in silicone Dept.: Optometric CE, 440 9th Avenue, hydrogels does not increase oxygen 14th Floor, New York, NY 10001. To be 5. ______is NOT a contact lens-related permeability. eligible, please return the card within one factor considered as a contributing factor to d. All the above are true. year of publication. You can also access contact lens discomfort? the test form and submit your answers a. Materials. 11. Which of the following statements and payment via credit card at Review of b. Lens design and fit. regarding comfort comparisons between Optometry online, www.reviewofoptometry. c. Modality and wear schedule. hydrogels and silicone hydrogels is true? com/ce. d. Relative humidity. a. Hydrogels are more comfortable. You must achieve a score of 70 or b. Silicone hydrogels are more comfortable. higher to receive credit. Allow eight to 10 6. Which percentage best represents the c. High water content lenses are most weeks for processing. For each Optomet ric number of soft lens fits worldwide? comfortable. Study Center course you pass, you earn a. 7%. d. The question remains open due to 2 hours of transcript-quality credit from b. 55%. confounding variables. Pennsyl vania College of Optometry and c. 80%. double credit toward the AOA Optom et ric d. 91%. 12. Which of the following adverse events is Recognition Award—Category 1. known to be associated with high modulus, Please check with your state licensing 7. Which figure best represents the number first generation silicone hydrogels? board to see if this approval counts toward of soft lens fits using silicone hydrogels? a. Contact lens papillary conjunctivitis. your CE requirement for relicensure. a. 7%. b. Superior epithelial arcuate lesions. b. 55%. c. Corneal erosions. 1. Which percentage best represents the c. 80%. d. All the above are associated with first number of contact lens wearers affected by d. 91%. generation silicone hydrogels. contact lens discomfort worldwide? a. 25%. 8. Why are direct comparisons between 13. Which of the following is NOT a b. 50%. hydrogels and silicone hydrogels are nearly technique employed in second/third c. 75%. impossible? generation silicone hydrogels to reduce the d. 100%. a. Inherent differences in surface and bulk frequency of adverse events? properties unique to each lens. a. Addition of plasma coatings. 2. Which percentage best represents the b. Difficulty in controlling for differences in b. Inclusion of internal wetting agents. number of patients experiencing dry eye in lens design. c. Increasing water content. the general population? c. Failure to mask investigators and/or d. None of the above reduce adverse events. a. 10%. subjects. b. 20%. d. All the above. 14. Which of the following terms describes c. 30%. the study of friction, lubricity and wettability d. 40%. 9. Which statement regarding water content issues? of hydrogel lenses is FALSE? a. Troglodyteology. 3. Which of the following definitions is a. Higher water content is less likely to be b. Tribology. responsible for the overly broad range of associated with corneal staining. c. Tribbleology. dropout rates? b. Increasing water content increases d. Technology. a. Reduction in wearing time. dehydration rates. b. Temporary discontinuance of lens wear. c. Dehydration has been associated with 15. Which of these clinical signs is LEAST c. Permanent discontinuance of lens wear. corneal desiccation. useful for identifying patients at risk for d. All the above. d. Bulk dehydration is neither associated or contact lens discomfort? causative of discomfort. a. Corneal staining. 4. Which TFOS workshop best summarizes b. Lid-wiper epitheliopathy. what is known about contact lens 10. Which statement is most accurate c. Lid parallel conjunctival folds.

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0058_ro1117_f5_osc.indd58_ro1117_f5_osc.indd 6644 111/3/171/3/17 12:2812:28 PMPM OSC QUIZ Examination Answer Sheet The Origins and Management of Contact Lens Discomfort d. Lens movement in primary gaze greater than 1mm. Valid for credit through November 15, 2020 Online: This exam can be taken online at www.reviewofoptometry.com/ce. Upon passing the exam, you can 16. Which of the following lens design/ view your results immediately and download a real-time CE certificate. You can also view your test history at fitting characteristics is LEAST likely to any time from the website. promote a comfortable fit? Directions: Select one answer for each question in the exam and completely darken the appropriate circle. A a. Decentration less than 0.3mm. minimum score of 70% is required to earn credit. b. Lens diameters greater than 13.5mm. Mail to: Jobson Medical Information, Dept.: Optometric CE, 440 9th Avenue, 14th Floor, New York, NY 10001. c. Lens design with a “knife” edge. Payment: Remit $35 with this exam. Make check payable to Jobson Medical Information LLC. d. Prism ballasted toric designs. Credit: This course is COPE approved for 2 hours of CE credit. Course ID is 55368-CL. Sponsorship: This course is joint-sponsored by the Pennsylvania College of Optometry. 17. Which of the following statements is Processing: There is an eight- to 10-week processing time for this exam. LEAST accurate? a. End-of-day comfort is worse for all Answers to CE exam: individuals, regardless of lens wear. Post-activity evaluation questions: 1. A B C D b. Extended wear is less comfortable than Rate how well the activity supported your achievement of these learning objectives: daily wear at the end of the day. 2. A B C D 1=Poor, 2=Fair, 3=Neutral, 4=Good, 5=Excellent c. More frequent lens replacement may be 3. A B C D 21. Improve my background in the development of contact lens discomfort. 1 2 3 4 5 more comfortable. 4. A B C D 22. Become familiar the oxygen permeability issues d. There is a shortage of masked, 5. A B C D associated with different lens materials. 1 2 3 4 5 randomized, controlled studies comparing 6. A B C D 23. Better understand how to recognize adverse events modalities. 7. A B C D related to contact lens discomfort. 1 2 3 4 5 8. A B C D 24. Teach me to recognize and delineate the different types 18. Which statement is MOST accurate 1 2 3 4 5 9. A B C D of environmental factors. regarding lens solutions? 10. A B C D 25. Better manage patients suffering from contact lens a. Solutions preserved with PHMB are more related discomfort. 1 2 3 4 5 11. A B C D comfortable. 26. Inform me of lens material options for CLD patients. 12. A B C D b. Solutions preserved with Polyquad are 1 2 3 4 5 13. A B C D more comfortable. Rate the quality of the material provided: 14. A B C D c. Peroxide systems are least comfortable. 1=Strongly disagree, 2=Somewhat disagree, 3=Neutral, 4=Somewhat agree, 5=Strongly agree d. Preservative uptake/release and impact 15. A B C D 27. The content was evidence-based. 1 2 3 4 5 on comfort is unique to each lens. 16. A B C D 28. The content was balanced and free of bias. 1 2 3 4 5 17. A B C D 29. The presentation was clear and effective. 1 2 3 4 5 19. Which of the following non-modifiable 18. A B C D 30. Additional comments on this course: factors has been shown to be positively 19. A B C D

associated with contact lens comfort? 20. A B C D a. Male gender. b. Younger age. Please retain a copy for your records. Please print clearly. c. Ethnicity. d. Increased blink rates. First Name Last Name 20. Which of the following modifiable or environmental factors has NOT shown to E-Mail contribute to contact lens discomfort? The following is your: Home Address Business Address a. Oral contraceptive or isotretinoin use. b. High relative humidity. Business Name c. Decreased goblet cell density. Address d. Digital device use. City State

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Graft-vs.-host Disease: How, Why and What Next Dry eye is rampant in this population, and other complications abound. By Heather Spampinato, OD, and Matthew Hochwalt, OD Photo: Christine W. Sindt, OD raft-vs.-host disease plantation, as donor T-cells (GVHD)—an abnor- will view the host’s cells as mal immune response foreign and attack if a large to healthy host tissue enough discrepancy is pres- G 5 following stem cell trans- ent. Other risk factors for plantation for the treatment GVHD include implantation of hematologic diseases—can of donor cells in a recipient of be a complex condition for the opposite gender, advanced eye care practitioners to age of the recipient and signif- manage. It can lead to a host icant damage during the con- of ocular complications, the ditioning process, a necessary most significant of which step that serves to eradicate is dry eye—seen in 40% Keratoconjunctivitis sicca is one manifestation that can the host’s diseased cells and to 76% of patients with help clinicians diagnose chronic GVHD. prevent rejection of the graft.7 GVHD.1 In particular, ocular However, it can also activate GVHD can cause permanent severe HCT most often follows the erad- the host’s antigen presenting cells, aqueous-deficient dry eye (ADDE), ication of malignancies with chemo- in turn stimulating proliferation of as well as other dry eye etiologies, therapy, radiation or both, to replace donor T-cells.8 which can be visually debilitating. It stem cells lost from the blood and is critical that practitioners correctly prevent patient mortality.3 GVHD Forms of GVHD identify dry eye caused by GVHD occurs when the donor immune sys- GVHD can present as either acute and treat accordingly. tem attacks healthy recipient cells as or chronic. Most clinicians classify foreign.2 Incidence of GVHD varies the disease based on the pathologic Disease Presentation from 25% to 80% after allogeneic nature of the inflammation (Table The onset of GVHD typically fol- HCT, although most studies put it 1). Acute GVHD, most commonly lows allogeneic hematopoietic close to 50%.4 seen within the first 100 days after stem cell transplantation (HCT), a Human leukocyte antigen (HLA) transplantation, resembles a toxic- therapy commonly used for patients disparity is by far the most power- like syndrome, which is typically suffering from a range of malignant ful risk factor for the development seen in response to bacterial toxins. and non-malignant hematologic dis- of GVHD.5,6 Matching the donor When acute GVHD affects the eyes, eases such as anemia, leukemia and HLA as close as possible to the it usually responds well to steroids thrombocytopenia.2 recipient is critical before trans- or other immunosuppressants.9,10

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066_ro1117_f6.indd 66 11/3/17 12:38 PM Table 1. Acute vs. Chronic GVHD11,13-15 Acute Chronic Timing Less than 100 days after transplant More than 100 days after transplant Pathophysiology Direct donor T-cell response Loss of regulation of central towards recipient cells tolerance causing indirect activation of the host’s T-cells against self Tissues typically Skin, bile duct and gastrointestinal Skin, lungs and mucous membranes affected system

Chronic GVHD can have more ocular GVHD shows prominent dramatic ocular side effects and can fibrosis and an increase in activated cause significant long-term damage T-cells and stromal fibroblasts in the to the anterior segment of the eye. glandular ducts, while SS shows the It is commonly seen more than 100 fibrosis and inflammation distrib- The days after transplantation and has uted through lesions in the acinar Series 3 a relatively unknown pathophysiol- region of the lacrimal gland.16 ogy. Successfully diagnosing chronic Severe meibomian gland dysfunc- GVHD requires distinguishing from tion (MGD) is also common in RETINOMAX acute GVHD and other possible patients with GVHD. Interferom- diagnoses, as well as identifying at etry confirms a decrease in the tear HAND-HELD least one distinctive manifestation of lipid layer in patients with ocular the disease, such as keratoconjuncti- GVHD.19 However, research has yet vitis sicca, confirmed with diagnostic to determine if the lipids are directly Autorefractor testing such as the Schirmer test.11,12 affected by the GVHD inflamma- More recently, NaFl corneal staining tion or due to the radiation during Precise measurements is the preferred method for diagnos- the conditioning process, which Anywhere - Anytime ing keratoconjunctivitis. can destabilize the lipid layer.20,21 Regardless, it can cause further Ocular Effects evaporation of the already-depleted GVHD can affect many ocular struc- aqueous of the tears. tures, including: Conjunctiva. Researchers estimate Accurate Lacrimal and meibomian glands. 12% of patients with acute GVHD Fast Chronic GVHD can affect several and 11% of patients with chronic tissues of the eyes, the most com- GVHD exhibit some form of con- =\_aNOYR mon and most significant of which junctival involvement.22 Inflamma- are the lacrimal glands. Research tion can result in changes ranging 2SSVPVR[a shows CD4+ and CD8+ T-cells from mild erythema to cicatrizing cause cytotoxic effects on the peri- conjunctivitis similar to ocular cica- ductal epithelial cells of the lacrimal tricial pemphigoid.22 Conjunctival gland.16,17 This damage causes per- inflammation tends to be more sig- manent stenosis of the duct, result- nificant in acute GVHD and is more ing in moderate to severe ADDE commonly hemorrhagic in presenta- similar to Sjögren’s syndrome (SS). tion.23 Investigators have also linked One study found the tear turnover GVHD patients to an increased inci- rate in GVHD patients is similar to dence of conjunctival carcinoma.24 that of patients with SS.18 The same Cornea. Typically, this structure is study found the evaporation rate not directly targeted in this disease was highest in GVHD patients, and process; however, significant sec- their lipid layer was the most unsta- ondary effects from lacrimal gland ble.18 Although the signs of ocular damage and altered tear makeup GVHD are similar to those with SS, are often evident. This manifests as

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066_ro1117_f6.indd 67 11/3/17 12:38 PM Systemic Disease Photo: Christine W. Sindt, OD score of 6mm to 10mm is sufficient can include increased rates of graft for a diagnosis of chronic GVHD if failure, relapse of malignancy and distinctive manifestations are also infection.32 If preventative therapy seen in at least one other organ.11,31,32 fails, systemic immunosuppression In general, dry eye disease is char- is the mainstay for both acute and acterized by hyperosmolarity of the chronic GVHD. However, despite tear film, which can lead to surface adequate systemic therapy, ocular epithelium impairment by activa- complications may still arise. Ocular tion of proinflammatory cytokines GVHD treatment focuses on increas- released into tears.33 Research indi- ing ocular surface moisture and cates a statistically significant corre- decreasing ocular surface inflamma- Corneal neovascularization and scarring lation between tear hyperosmolarity tion.26,31 as a complication of GVHD. and TBUT with osmolarity testing, Lubricants. Treatment typically but the same correlation is not seen begins conservatively with the use of keratoconjunctivitis sicca, which, with Schirmer testing or vital dye preservative-free artificial tears and when severe, can lead to filamentary staining.33 Therefore, TBUT is an ointments, which are less likely to keratitis, corneal ulceration and cor- important measure of dry eye sever- cause epithelial toxicity.35 Research neal perforation.25,26 In rare cases, an ity for patients with GVHD. also suggests hydroxypropyl cellu- immune-mediated limbitis can result Numerous grading systems exist lose ophthalmic inserts can improve in progressive neovascularization.27 to assess the severity of ocular sur- dry eye symptoms and decrease the Lenticular. Cataracts are a com- face disease in these patients. The frequency of artificial tear use.26 mon ocular complication, with one National Institutes of Health (NIH) Punctal Plugs. As lubricants alone study finding lens opacity in 39.4% research group developed one spe- are rarely adequate for the severe of patients with GVHD.28 How- cifically for diagnosing and staging dryness seen in GVHD, punctal ever, researchers note the lenticular GVHD, which takes into consider- plugs may be a useful therapeutic changes were likely secondary to ation the severity of dry eye along option. Patients can show significant steroid use, radiation or both, as with its effect on activities of daily subjective improvement in symptoms opposed to the disease itself.29 living (Table 2).11 However, the NIH and decrease in corneal staining with Posterior segment. When this is scoring system does not take into the use of punctal plugs over the involved, which is rare, researchers account the degree of corneal stain- course of twelve months. Also, there speculate it may be secondary to the ing or other dry eye findings, instead does not appear to be an increase radiation or high-dose steroid treat- focusing on the frequency of topical in ocular inflammation, infection or ments and not a direct complication lubricant use. Because of this, some other adverse events with the use of of ocular GVHD.30 researchers and clinicians use the punctal plugs in patients with ocular Dry Eye Workshop score, which is GVHD.36 Dry Eye Diagnosis based on patient symptomatology, Topical corticosteroids. Local top- In ocular GVHD, performing a Schirmer score, TBUT, corneal and ical treatment with corticosteroids diagnostic evaluation for dry eye is conjunctival involvement, as well as decreases the overall risk associated essential to determine the severity of MGD.34 the disease and monitor for improve- Table 2. NIH Ocular Scoring in Chronic GVHD11 ment. Clinicians should use sodium Ocular Score Definition fluorescein, rose bengal or lissamine Treatment 0 No dry eye symptoms. green staining to determine both Treating GVHD 1 Mild dry eye symptoms not affecting daily activities corneal and conjunctival involve- actually begins (requiring eye drops ≤3x/day) or asymptomatic signs of ment. Additional diagnostic tests with prevention, keratoconjunctivitis sicca. include tear break-up time (TBUT), which is accom- 2 Moderate dry eye symptoms partially affecting daily activities (requiring drops >3x/day or punctal plugs), Schirmer scoring, meibomian gland plished through without vision impairment. evaluation, corneal sensitivity and T-cell depletion. 31,32 3 Severe dry eye symptoms significantly affecting daily tear osmolarity. A Schirmer score Prophylactic treat- activities (special eyewear to relieve pain) or unable to of less than 5mm at five minutes or ment is not with- work because of ocular symptoms or loss of vision caused new-onset dryness with a Schirmer out risks, which by keratoconjunctivitis sicca.

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066_ro1117_f6.indd 68 11/3/17 12:38 PM ELITE

with prolonged and intense systemic activity of proinflammatory cyto- SLIT immunosuppression and more effec- kines in the conjunctiva.38,39 Several tively targets the affected area.26,37 studies indicate statistically signifi- LAMP In particular, ocular corticosteroid cant improvement in Schirmer basal use promotes lymphocytic apoptosis secretion tests, TBUT, corneal fluo- and suppresses cell-mediated inflam- rescein staining and patient symp- mation in the eye more directly toms after twice-daily cyclosporine than does systemic administration.37 0.05% for at least three months.38,39 The +(/,7( Because long-term use of topical For refractory cases, compounding slit lamp features steroids carries the risk of steroid- topical cyclosporine to 1% to 2% an innovative LED induced glaucoma, cataracts, infec- and increasing dosage to six to eight illumination system tious keratitis and corneal thinning, times per day may help promote providing brilliant many clinicians recommend short- healing during the early stages of light spectrum, term use combined with additional ocular GVHD.40 while increasing supportive therapy.26,31,37 Autologous serum. These eye patient comfort. Topical cyclosporine. This agent drops contain epidermal growth is another therapeutic option that factor, vitamin A, cytokines, nerve shows great promise in the treatment growth factors and fibronectin, all of of ocular GVHD. It is an immuno- which are essential for the prolifera- suppressive drug that inhibits T-cell tion, differentiation, maturation and proliferation on the ocular surface, integrity of the corneal and conjunc- increases goblet cell density in the tival epithelial surfaces.32,41-43 Studies $QH[WHQVLYHSRZHU conjunctiva, decreases epithelial cell show autologous serum is effective UDQJHZLWKƬYH apoptosis and interferes with the in treating severe dry eye, and one PDJQLƬFDWLRQVHWWLQJV from 6x to 40x. Standard Photos: Alan Kwok, OD on all ELITE slit lamps. IMAGING The 6237,.+(/,7( slit lamp comes digital ready. Combine with the S4OPTIK all-in-one digital camera to acquire exceptional still and video images.

These images depict a GVHD patient’s eyes before (top) and after scleral lens wear, showing an improved ocular surface, including a reduction in filaments, after just a few hours of wearing time.

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066_ro1117_f6.indd 69 11/3/17 12:39 PM Systemic Disease Photo: C. Kelly Olson, OD, MBA evaporation from the tarsorrhaphy, amniotic membrane inflamed ocular surface.26 transplantation or punctal occlu- In one study, patients were sion.26 Amniotic membranes can aid fit in a monthly extended in epithelialization and prevention wear silicone hydrogel lens of fibrosis and inflammation.50,51 after failing to maintain Research shows using sutureless adequate symptom control amniotic membranes to treat mod- with topical lubricants and erate to severe dry eye significantly punctal plugs after three improves symptoms and ocular months.35,46 Investigators health for up to four months after showed statistically signifi- treatment.51 Extreme poor wetting and lipid deposits in a GVHD cant improvement in patient Patients who do well with punctal patient. symptoms in as little as two plugs but experience recurrent extru- weeks with the use of these sion may be good candidates for demonstrated 20% autologous lenses, but little to no improvement permanent occlusion with punctal serum dosed two to three drops ten in clinical signs of ocular surface cautery. In those with severe dry times a day is effective in improving disease and no significant changes to eye secondary to chronic GVHD, fluorescein and rose bengal staining, the tear film.35,46 Despite the absence researchers found significant TBUT, corneal sensitivity and patient of significant improvements in ocu- improvements in subjective symptom symptoms in ocular GVHD patients lar surface disease, these lenses can scores, Schirmer values, fluorescein resistant to conventional artificial still be considered in patients whose and rose bengal scores and TBUT tear therapy.32,41-43 symptoms are not adequately con- after thermal cauterization.52 Tacrolimus. Another potential trolled with conventional treatment. treatment option in the manage- Patients fit in extended-wear contact Ocular GVHD is a complex and ment of ocular surface inflamma- lenses should be closely monitored challenging condition to diagnose tion from chronic GVHD is topical due to the increased the risk of cor- and manage. Because it can affect 0.03% tacrolimus ointment. This neal edema, infiltrates, neovascular- many ocular tissues, clinicians must medication is FDA approved for the ization and microbial keratitis.47 properly identify all the ocular signs dermatological treatment of atopic Scleral lenses may be the best to determine the best treatment eczema but has been used off-label option for treating ocular GVHD modality. Furthermore, early inter- to treat eczematous eyelid disease, because the liquid reservoir beneath vention is essential to reduce, or even atopic keratoconjunctivitis and other the lens allows for continuous hydra- prevent, the severe complications anterior segment inflammation.44 tion of the ocular surface, protecting often associated with GVHD. A The mechanism of action is thought against evaporation and aiding in multidisciplinary approach is useful to be similar to that of cyclosporine, resurfacing the damaged corneal to determine when systemic, topical though the immunosuppressive epithelium, possibly by reducing the or other therapy options are best. potency of tacrolimus in vitro is 50 hyperosmolarity of the tear film.48,49 These patients rarely return to a fully to 200 times greater than that of The liquid reservoir also helps to normal state due to lacrimal gland cyclosporine.31,45 Although benefi- mask corneal irregularity second- fibrosis and will need long-term cial effects of systemic tacrolimus in ary to dry eye and can significantly treatment and follow up. ■ GVHD have been well documented, improve visual acuity in these Dr. Spampinato is a staff optom- data regarding its use topically is patients. Patients with ocular GVHD etrist at the Cincinnati VA Medical limited.31,32,45 successfully fit in scleral lenses often Center and an adjunct faculty mem- report substantial improvement in ber at The Ohio State University Contact Lens Wear pain and photophobia associated College of Optometry. Several contact lens types are often with the disease.35,48 Dr. Hochwalt is a staff optom- used to treat ocular GVHD, includ- etrist at the Cincinnati VA Medical ing bandage silicone hydrogel lenses Surgical Treatment Center and an adjunct faculty mem- and gas permeable scleral lenses. Patients with severe dry eye refrac- ber at the Ohio State University Col- Research suggests contact lenses tory to other treatment options can lege of Optometry and the Illinois reduce friction pain and control consider surgical management with College of Optometry.

70 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

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1. Tabbara K, AlGhamdi A, Al-Mohareb F, et al. Ocular findings fol- 28. Allen EJ, Flowers ME, Lin MP, et al. Visual acuity and anterior lowing allogenic hematopoietic stem cell transplantation (HSCT). segment findings in chronic graft-versus-host disease. Cornea. Ophthalmology. 2009;116(9):1624-9. 2011;30:1392. 2. Rezvani AR, Storb R. Prevention of graft-vs-host disease. Exper 29. Tichelli A, Gratwohl A, Egger T, et al. Cataract formation after Opin Pharmacother. 2012;13:1737-50. bone marrow transplantation. Ann Intern Med. 1993;119(12): 3. Auw-Haedrich C, Potsch C, Böhringer D, et al. Histological and 1175-80. immunohistochemical characterization of conjunctival graft vs host 30. Kaiserman I, Or R. Laser photocoagulation for central serous disease following haematopoietic stem cell transplantation. Graefe’s retinopathy associated with graft-versus-host disease. Ocul Immun Arch Clin Exp Ophthalmol. 2007;245:1001-7. Inflamm. 2005;13(2-3):249-56. 4. Baird K, Parletic SZ. Chronic graft versus host disease. Curr Opin 31. Espana E, Shah S, Santhiago MR, Singh AD. Graft versus host Hematol. 2006;13:426-35. disease: clinical evaluation, diagnosis, and management. Graefes 5. Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host Arch Clin Exp Ophthalmol. 2013;251(5):1257-66. disease and other late complications of bone marrow transplanta- 32. Shikari H, Antin J, Dana R. Ocular graft-versus-host disease: A tion. Semin Hematol. 1991;28:250-9. review. Surv Ophthalmol. 2013;58(3):233-50. 6. Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis 33. Berchicci L, Iuliano L, Miserocchi E, et al. Tear osmolarity in ocu- of risk factors for acute graft-versus-host disease and for chronic lar graft-versus-host disease. Cornea. 2014;33(12):1252-6. graft-versus-host disease according to National Institutes of Health 34. Tatematsu Y, Ogawa Y, Abe T, et al. Grading criteria for consensus criteria. Blood. 2011;117(11):3214-9. chronic ocular graft-versus-host disease: comparing the NIH eye 7. Clift RA, Buckner CD, Appelbaum FR, et al. Long-term follow up score, Japanese dry eye score, and DEWS 2007 score. Sci Rep. of a randomized trial of two irradiation regimens for patients receiv- 2014;22(4):6680. ing allogeneic marrow transplants during first remission of acute 35. Balasubramaniam S, Raja H, Nau CB, et al. Ocular graft- myeloid leukemia. Blood. 1998;92(4):1455-6. versus-host disease: A review. Eye & Contact Lens. 2015;41(5): 8. Ferrara JLM, Reddy P. Pathophysiology of graft-versus-host 256-61. disease. Semin hematol. 2005;3-10. 36. Sabti S, Halter JP, Braun Frankl BC, et al. Punctal occlusion is Corneal Topography & More! 9. Lew J, Smith JA. Mucosal graft-vs-host disease. Oral Diseases. safe and efficient for the treatment of keratoconjunctivitis sicca in 2007;13:519-29. patients with ocular GVHD. Bone Marrow Trans. 2012;47(7):981-4. 10. Quellmann S, Schwarzer G, Hübel K, et al. Corticosteroids in the 37. Robinson M, Lee S, Rubin BI, et al. Topical corticosteroid prevention of graft-vs-host disease after allogeneic myeloablative therapy for cicatricial conjunctivitis associated with chronic graft stem cell transplantation: a systematic review and meta-analysis. -versus-host-disease. Bone Marrow Trans. 2004;33(10):1031-5. Leukemia. 2008;22(9):1801-3. 38. Rao S, Rao R. Efficacy of topical cyclosporine 0.05% in the 11. Filipovich AH, Weisdorf D, Pavletic S, et al. National institutes of treatment of dry eye associated with graft versus host disease. health consensus development project on criteria for clinic trials in Cornea. 2006;25(6):674-8. chronic graft-versus-host disease: I. Diagnosis and staging working 39. Lelli G, Musch D, Gupta A, et al. Ophthalmic cyclosporine use in group report. Biol Blood Marrow Transplant. 2005;11(12):945-56. ocular GVHD. Cornea. 2006;25(6):635-8. 12. Ogawa Y, Kim S, Dana R, et al. International Chronic Ocular 40. Kiang E, Tesavibul N, Yee R, et al. The use of topical cyclosporine Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed diag- A in ocular graft-versus-host-disease. Bone Marrow Transplantation. nostic criteria for chronic GVHD (part I). Sci Rep. 2013;3:3419. 1998;22(2):147-51. 13. Shulman HM, Kleiner D, Lee SJ, et al. Histopatholgic diagnosis 41. Rocha E, Pelegrino F, de Paiva CS, et al. GVHD dry eyes treated of chronic graft-versus-host disease: National Institutes of Health with autologous serum tears. Bone Marrow Transplantation. consensus development project on criteria for clinic trials in chronic 2000;25(10):1101-3. Meibomian Gland graft-versus-host disease: II. Pathology Working Group report. Biol 42. Ogawa Y, Okamoto S, Mori T, et al. Autologous serum Blood Marrow Transplant. 2006;12:31-47. eye drops for the treatment of severe dry eye in patients with Imaging & Analysis 14. Couriel D, Caldera H, Champlin R, Komanduri K. Acute graft- chronic graft-versus-host disease. Bone Marrow Transplantation. versus-host disease: pathophysiology, clinical manifestations and management. Cancer. 2004;101(9):1936-46. 2003;31(7):579-83. 15. Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft- 43. Tsubota K, Goto E, Fujita H, et al. Treatment of dry eye by autolo- versus-host disease: Association with treatment-related mortality gous serum application in Sjögren’s syndrome. Br J Ophthalmol. and relapse. Blood. 2002;100(2):406-14. 1999;83(4):390-5. 16. Ogawa Y, Kuwana M, Yamazaki K, et al. Periductal area as the 44. Tam P, Young A, Cheng LL, Lam PT. Topical 0.03% tacrolimus primary site for T-cell activation in lacrimal gland chronic graft-ver- ointment in the management of ocular surface inflammation in sus-host disease. Invest Ophthalmol Vis Sci. 2003;44(5):1888-96. chronic GVHD. Bone Marrow Trans. 2010;45(5):957-8. 17. Ogawa Y, Yamazaki K, Kuwana M, et al. A significant role of 45. Ogawa Y, Okamoto S, Kuwana M, et al. Successful treatment stromal fibrogblasts in rapidly progressive dry eye in patients with of dry eye in two patients with chronic graft-versus-host disease chronic GVHD. Invest Ophthalmol Vis Sci. 2001;42:111-19. with systemic administration of FK506 and corticosteroids. Cornea. Non-Invasive Tear Film 18. Khanal S, Tomlinson A. Tear physiology in dry eye associated 2001;20(4):430-4. with chronic GVHD. Bone Marrow Trans. 2012;47(1):115-9. 46. Russo P, Bouchard C, Galasso JM. Extended-wear silicone Break-up Analysis 19. Ban Y, Ogawa Y, Goto E, et al. Tear function and lipid layer altera- hydrogel soft contact lenses in the management of moderate to tions in dry eye patients with chronic graft-vs-host disease. Eye. severe dry eye signs and symptoms secondary to graft-versus-host 2009;23(1):202-8. disease. Eye & Contact Lens. 2007;33(3):144-7. 20. Altinors DD, Akea S, Akova YA, et al. Smoking associated with 47. Inamoto Y, Sun Y, Flowers ME, et al. Bandage soft contact lenses damage to the lipid layer of the ocular surface. Am J Ophthalmol. for ocular graft-versus-host disease. Biol Blood Marrow Transplant. 2006;141(6):1016-21. 2015;21(11):2002-7. 21. Riley PA. Free radicals in biology: oxidative stress and the effects 48. Jacobs D, Rosenthal P. Boston scleral lens prosthetic device for of ionizing radiation. Int J Radiat Biol. 1994;65:27-33. treatment of severe dry eye in chronic graft-versus-host disease. 22. Jabs DA, Wingard J, Green WR, et al. The eye in bone marrow Cornea. 2007;26(10):1195-9. transplantation. III. Conjunctival graft-vs-host disease. Arch Ophthal- 49. Takahide K, Parker P, Wu M, et al. Use of fluid-ventilated, gas- mol. 1989;107(9):1343-8. permeable scleral lens for management of severe keratoconjunctivi- 23. Jack M, Jack G, Sale GE, et al. Ocular manifestations of graft-v- tis sicca secondary to chronic graft-versus-host disease. Biol Blood host disease. Arch Ophthalmol. 1983;101(7):1080-4. Marrow Transplant. 2007;13(9):1016-21. 24. Hon C, Au W, Liang RH. Conjunctival carcinoma as a novel 50. Peris-Martinez C, Menezo J, Díaz-Llopis M, et al. Multilayer post-stem cell transplantation malignancy. Bone Marrow Trans. amniotic membrane transplantation in severe ocular graft versus 2004;34(2):181-2. host disease. European J Ophthalmol. 2001;11(2):183-6. Tear Meniscus Height 25. Yeh P, Hou Y, Lin WC, et al. Recurrent corneal perforation and 51. Cheng A, Zhao D, Chen R, et al. Accelerated restoration of ocu- acute calcareous corneal degeneration in chronic graft-versus-host lar surface health in dry eye disease by self-retained cryopreserved disease. J Formos Med Assoc. 2006;105(4):334-9. amniotic membrane. The Ocular Surface. 2016;14(1):56-63. 26. Nassar A, Tabbara K, Aljurf M. Ocular manifestations of graft 52. Yaguchi S, Ogawa Y, Kamoi M, et al. Surgical management -versus-host disease. Saudi J Ophthalmol. 2013;27(3):215-22. of lacrimal punctal cauterization in chronic GVHD-related dry 27. Mohammadpour M. Progressive corneal vascularization caused eye with recurrent punctal plug extrusion. Bone Marrow Trans. by graft-versus-host disease. Cornea. 2007;26(2):225-6. 2012;47(11):1465-9.

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Go Deep on Corneal Abrasions Understanding the physiology of rupture and repair will improve your management decisions. By Bisant A. Labib, OD

n daily practice, we tend to abrasion site within the basal layer, focus more on clinical signs and where they then differentiate into Isymptoms than pathophysiol- the post-mitotic cells that comprise ogy, especially in corneal abrasion the more superficial epithelial lay- cases—the patient is in pain, infec- ers. Concurrently, epithelial cells tion risk is high and time is tight. also migrate peripherally around The way we treat these patients the limbus until the wound is fully prioritizes pain relief over a more closed.6 These migrating epithelial holistic approach to the cornea’s cells briefly express matrix metallo- status and risk profile. But gaining a proteinase (MMP) and tissue inhibi- greater awareness of how such con- Fluorescein stain under a cobalt blue tor of metalloproteinase (TIMP) ditions progress can help inform our filter depicts a diffuse breakdown of an enzymes, which regulate the adher- treatment choices. This month we otherwise intact corneal epithelium. ence between the injured epithelium do so by looking more deeply at the and underlying basement mem- mechanisms of corneal trauma and mous cells, a wing cell middle layer brane.7 Fibronectin, an extracellular wound repair. and finally the basal cells. In corneal structural protein in the basement abrasion, the basal layer—the only membrane that binds to cells and Why the Cornea is Unique epithelial component capable of collagen, provides a provisional The cornea contains the highest regeneration—begins to prolifer- matrix with which epithelial cells concentration of sensory nerves ate. Basal cells migrate and spread can migrate. Along with collagen I and nociceptors in the body, mak- over the wounded lesion, and then and IV, fibronectin also increases cell ing pain management a primary differentiate into wing cells, which motility and migration.8 Systemic concern.1 Because the cornea is an then differentiate further into the diseases, such as diabetes, may delay avascular and immune-privileged squamous cells that comprise the these metabolic processes and pre- site, wound repair involves several superficial corneal epithelium.5 vent the proper adherence of the epi- unique mechanisms, including epithelium to the basement membrane.2 thelial cell proliferation, differentia- Keys to Corneal Wound Repair Keratocyte release of matrix pro- tion, migration and adhesion to the Following injury, which appears teins. Corneal abrasions induce an basement membrane.2,3 clinically as a defect in the corneal acute inflammatory response and An intact corneal epithelium epithelial surface that stains with flu- also result in the death of underlying plays a vital role as a physical and orescein dye, several processes bring keratocytes.9,10 While diseases that mechanical barrier against infection, the cornea back to its normal state. cause chronic inflammation to the as well as in sustaining the necessary Epithelial cell migration. In cornea are typically detrimental, it biochemical properties required for the early stages of wound heal- is the acute inflammation follow- optical clarity.4 Several mechanisms ing, migration and proliferation ing abrasion that is necessary for can compromise an intact cornea of epithelial cells are necessary for the ocular system to initiate and and manifest clinically as abrasions, closure. The process of epithelial complete the repair process, and, as dystrophies or degenerations, as well cell migration is highly metabolic, such, treatment in this acute phase as refractive problems. depending heavily on glucose from with a topical steroids may delay The corneal epithelium is made the aqueous humor, and occurs in healing time.9 This response is char- up primarily of three distinct cell two ways. First, transient amplifying acterized primarily by neutrophil layers: an outermost layer of squa- cells (TAC) travel centrally to the recruitment and migration from the

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limbal vessels to the wounded area. dage lens also provides lubrication, The accumulation of neutrophils at which aids in healing by providing a the wound site is vital to the repair smooth surface for the migration of effort; studies that investigated the cells, and mitigates pain by shield- effects of reducing neutrophil con- ing the cornea from external forces centrations to the injured area show such as blinking. Its barrier function a significant delay in wound closure also adds microbial protection.13 occurs.11 Lastly, a bandage contact lens allows Corneal keratocytes, found in the antimicrobial drops to remain on stroma, produce extracellular matrix This corneal abrasion with large the corneal surface for an extended components such as collagen, pro- epithelial defect is stained with period, extending the their duration teoglycans and crystallins—all essen- fluorescein dye under cobalt blue light. of action.13 tial in maintaining corneal structure and clarity. Studies have concluded nea advances, so do our protocols. Adjuvant Therapies that keratocytes are depleted for sev- As a result, one historically popular Though a bandage lens will be the eral years following corneal injury, therapy has been phased out and workhorse therapy, other efforts that which may lead to complications another has emerged as the staple can accompany it include: such as ectasia following refractive modality. Artificial Tears. Topical lubri- procedures.9 Pressure patching. Once the cants, such as artificial tears or gels, Platelet build-up. Accumulation mainstay of abrasion treatment, this help accelerate the healing process of these cells at the limbus happens protects the cornea from the shear- by smoothing out ocular surface in concert with neutrophil migra- ing force of the eyelid secondary to abnormalities. The lubrication tion; both are critical for successful blinking. Prior to patching, topical reduces friction from the patient’s corneal wound healing. During antibiotics and a cycloplegic are eyelid and prevents desiccation.11 the first 24 hours following injury, often instilled into the affected eye. Topical NSAIDs. Systematic platelet recruitment aids in epithe- Today, however, pressure patching reviews conclude that topical lial cell division. Platelets attach to is somewhat controversial. It reduces NSAIDs are effective in reducing neutrophils and augment migration. the amount of oxygen reaching the pain, as well as in reducing the need Studies report that platelets also cornea and raises its temperature, for oral analgesic therapy. Due to aid in efficient keratocyte recovery.9 both of which increase the risk of pain control, patients were able Platelets reach copious levels around microbial infection and may even to return to work earlier without the limbal blood vessels approxi- delay healing. As such, exercise cau- jeopardizing the healing process.12 mately 12 hours following injury, tion with this approach.11 Studies Note that long-term use of topical a crucial time when many of the question its value, noting that it NSAIDs may increase the risk of cellular repair processes are under- does not demonstrate a faster heal- corneal melt and toxicity.5 way. Research also shows reducing ing time than observation alone, or Topical Antibiotics. Due to the platelet levels also reduces neutro- even additional pain alleviation. In risk of microbial superinfection phil accumulation, and vice-versa.12 fact, the patch itself was the main from an open epithelial defect, topi- Following the commencement of this cause of pain in 48% of cases.12 The cal antibiotics are frequently used stage, the size of the epithelial defect occlusive effect from patching also as prophylaxis. Studies report a is noticeably diminished or, in some prevents the patient from function- reduced risk of infection or ulcer- instances, completely closed. ing binocularly.11 Cases where pres- ation with, particularly when anti- sure patching may be used include biotic is implemented within the Patches vs. Lenses large abrasions in young children critical period of 12 to 18 hours Since corneal healing mechanisms or special populations where the following injury, a time where the are unique compared to that of other patient may risk rubbing their eye many cellular processes discussed ocular tissues, which carry a blood and worsen the injury. above are in play.12 Gel formulations supply and lack immune privilege, Bandage contact lens. This option of antibiotics offer additional lubri- the treatment approach initiated by supersedes pressure patching in that cation as well. However, patients the practitioner will “make or break it not only alleviates pain, but also must be educated regarding the tran- it.” As our understanding of the cor- promotes wound healing.11 The ban- sient blurring effect due to viscosity.

74 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

073_ro1117_Essentials.indd 74 11/3/17 12:42 PM 11 1. Li Z, Burns AR, Han L, et al. IL-17 and VEGF are neces- Topical antibiotic coverage should coverage. The hyaluronate incites sary for efficient corneal nerve regeneration. Am J Pathol. especially be considered in abra- epithelial migration; studies report 2011;178(3):1106-16. 2. Griffith GL, Kasus-Jacobi A, Lerner MR, Pereira HA. Corneal sions secondary to contact lenses, adequate prophylaxis and faster wound healing, a newly identified function of CAP37, is mediated 11 by protein kinase C delta (PKCdelta). Invest Ophthalmol Vis Sci. foreign body or vegetative matter, resolution of abrasions. It is avail- 2014;55(8):4886-95. 3. Park JH, Kim JY, Kim DJ, et al. Effect of nitric oxide on human as there is an increased risk of infec- able in Europe under the trade name corneal epithelial cell viability and corneal wound healing. Sci Rep. 2017;7(1):8093. tion. Antibiotic-steroid combination Xanternet. 4. Liu, Q, Smith WC, Zhang W, et al. NK cells modulate the inflammatory response to corneal epithelial abrasion and thereby drops should be used with caution, Acacia honey. Honey’s antimicro- support wound healing. Am J Pathol. 2012;181(2):452-62. 5. Wilson SA, Last A. Management of corneal abrasions. Am as the steroidal component may sup- bial, anti-inflammatory and antioxi- Fam Physician. 2004; 70(1):123-8. press the necessary inflammatory dative properties promotes healing 6. Thyagarajan SK, Sharma V, Austin S, et al. An audit of corneal abrasion management following the introduction of local guide- processes and retard wound healing. on the skin surface.15 Epithelial lines in an accident and emergency department. Emerg Med J. 2006;23(7):526-9. These agents are typically used for cell migration was enhanced in a 7. Saika S, Ooshima A, Liu CY, et al. Epithelial repair: roles of extracellular matrix. Cornea. 2002;21(2 Suppl 1): S23-9. 24 hours, or until full resolution of small, in vitro rabbit study, possibly 8. Nishida T. The role of fibronectin in corneal wound heal- 5 ing explored by a physician-scientist. Jap J Ophthalmol. symptoms and signs. because of its high sugar content, 2012;56(5):417-31. 9. Lam FW, Phillips J, Landry P, et al. Platelet recruitment pro- Clycloplegics. While commonly which is necessary for metabolic cell motes keratocyte repopulation following corneal epithelial abrasion in the mouse. PLoS One. 2015;10(3):e0118950. used for pain management because activity. Though it remains far from 10. Gagen D, Laubinger S, Li Z, et al. ICAM-1 mediates surface they minimize ciliary body spasm clinical deployment, its novel mecha- contact between neutrophils and keratocytes following corneal epithelial abrasion in the mouse. Exp Eye Res. 2010;91(5):676-84. and reduce pain, the literature does nism of action makes acacia worthy 11. Faraldi F, Papa V, Santoro D, et al. A new eye gel containing 15 sodium hyaluronate and xanthan gum for the management of post- not suggest a substantial benefit in of future exploration. traumatic corneal abrasions. Clin Ophthalmol. 2012;6:727-31. 14 12. Wilson SA, Last A. Management of corneal abrasions. Am uncomplicated corneal abrasions. Fam Physician. 2004;70(1):123-8. 13. Sun YZ, Guo L, Zhang FS. Curative effect assessment of Topical gel. Though unavail- Corneal wound healing possible bandage contact lens in neurogenic keratitis. Int J Ophthalmol. 2014;7(6):980-3. able in the US, a combination of through a number of complex cel- 14. Joshaghani M, Nazari H, Ghasemi K, et al. Effect of homatro- pine eye drops on pain after photorefractive keratectomy: A pilot xanthan gum, sodium hyaluronate lular processes. Informed treatment study. Saudi J Ophthalmol. 2013;27(2):83-5. and netilmicin may increase heal- choices promote repair and prevent 15. Ker-Woon C, Ghafar NA, Hui CK, et al. The effects of acacia honey on in vitro corneal abrasion wound healing model. BMC ing time and provide antimicrobial delay or complication. ■ Cell Biol. 2015;16:2.

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Jaundice and the Eyes Optometrists may be the first to notice icterus, a harbinger of systemic concerns. By Carlo J. Pelino, OD, and Joseph J. Pizzimenti, OD Photo: CDC/Dr. Thomas F. Sellers n important element of the Jaundice may result from an review of systems (ROS) overproduction of bile or from an Aspecific to the gastrointes- inability of the liver to remove bile tinal system is to investigate for pigments from the blood due to jaundice—a yellowish staining of Hepatitis A may manifest as jaundice of hepatic disease, regurgitation of bili- the skin, conjunctiva/episclera/sclera the conjunctiva and facial skin. rubin back into the bloodstream or (termed icterus), other mucous obstruction of the bile ducts.1-3 membranes and excretions.1 It also contains water, potassium, While not a disease itself, jaundice sodium, copper and other metals.3 Classification is a sign of a number of underly- Bilirubin is a yellow/brownish Clinicians generally describe three ing conditions that cause the bile chemical in bile, formed by the types of jaundice, classified accord- ducts, gallbladder, liver or pancreas breakdown of heme rings, usually ing to what is disrupting the normal to malfunction. The color is caused from metabolized red blood cells. removal of bilirubin from the body:1 by subsequent hyperbilirubinemia, Bilirubin is normally excreted in Prehepatic (hemolytic) jaundice. an excess amount of bilirubin in the bile, giving feces the normal yellow- Here, the disruption happens before blood. Jaundice is often reported brown coloration. As senescent bilirubin has been transported from in infants and newborns, as well as hemoglobin-containing erythrocytes the blood to the liver. It is caused by in children and adults with medical break down, the body builds new conditions such as sickle cell anemia complications (Table 1).1,2 cells to replace them, and the liver and hemolytic anemia. Hemolysis Jaundice is a clinical sign optom- processes the old red blood cells. If is an accelerated breakdown of red etrists should be on the lookout for, the liver cannot handle the blood blood cells, leading to an increase in as it is usually first noticeable in the cells as they break down, bilirubin bilirubin production.1 eyes.1 However, its onset may be so builds up in the body and jaundice Intrahepatic (hepatocellular) gradual that even those in frequent results. Jaundice is detected clinically jaundice. The disruption happens contact with the affected person once the serum bilirubin level rises inside the liver and is caused by con- may not notice it.1 In addition to its above 2.5 mg/dL to 3mg/dL.1,3 ditions such cirrhosis or other liver ocular features for diagnostics, jaun- The amount of bilirubin manu- damage, including injury.1 dice may result from conditions that factured (0.5 to 2.0 grams per day) have significant ocular complica- relates directly to the quantity of tions, such as sarcoidosis, sickle cell red blood cells destroyed. Bilirubin disease and various infections.1 has no known function and can be toxic in the fetal brain. Bilirubin How and Why in the bloodstream is usually in an Bile is produced and released by the unconjugated (free) state. Once liver and stored in the gallbladder. transported to the liver, it is attached Eventually delivered directly to the to the protein albumin and becomes intestinal lumen, it helps with diges- conjugated with glucuronic acid. Bil- tion by breaking down fats into fatty irubin is then concentrated to about acids to be taken into the body by 1,000 times the strength found in the digestive tract. The primary con- blood and transferred to the gall- stituents in bile are cholesterol, acids bladder, where it mixes with other Cholangiography shows dilated bile ducts (also called bile salts) and bilirubin. bile components.1,3 with extensive abscesses and stones.

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 77

077_ro1117_RoS.indd 77 11/6/17 9:31 AM Review of Systems

Post-hepatic (obstructive) jaun- Table 1. Common Causes of Jaundice by Age1,2 dice. With this form, the disruption prevents bile (and thus bilirubin) Age Conditions from draining out of the gallbladder Neonates younger than 2 weeks Neonatal jaundice (physiologic) and into the digestive system. This Neonates older than 2 weeks Hepatitis, biliary atresia, choledochalcyst, obstructive can be caused by conditions such congenital anomalies of the biliary tract, total parenteral as gallstones, biliary tract infection, nutrition, furosemide treatment, phototherapy, pancreatitis or neoplastic disease.1 dehydration, infection, hemolytic anemia and short-gut Gallstones are solid particles syndrome that form from bile cholesterol and Infants and young children (two Cirrhosis, benign strictures and neoplastic disease bilirubin in the gallbladder. They months to four years of age) are known as bile duct stones or Children and adolescents (four to Sickle cell disease, bowel resection, hemolytic anemia choledocholithiasis when located in 18 years of age) and choledochal cyst the bile duct. Certain bacteria can Adults Viral infections (hepatitis A, B and C), chronic alcohol infect the gallbladder and change use, autoimmune disorders, drugs, pregnancy, the conjugated bilirubin back to parenteral nutrition, sarcoidosis, primary biliary free bilirubin and acid. The calcium cirrhosis, primary sclerosing cholangitis, gallstones, from the freed bilirubin can settle surgical strictures, infection (e.g., cytomegalovirus and out as pigment stones, which may Cryptosporidium infection in patients with acquired eventually block the common bile immunodeficiency syndrome), intrahepatic malignancy, duct between the liver, gallbladder cholangiocarcinoma, extrahepatic malignancy and small intestine. When block- (pancreas, lymphoma) and pancreatitis age occurs, conjugated bilirubin is absorbed into the bloodstream and Investigating the Cause must be keenly aware of these signs becomes clinically evident as jaun- Organizing the differential diagnosis and the potential underlying causes. dice and icterus. of jaundice by prehepatic, intrahe- A thorough review of systems and patic and post-hepatic helps make comprehensive history are key, as Jaundice in Infants the workup straightforward. Lab they may point to a specific cause, A healthy newborn may acquire jaundice work should begin with a urine such as cirrhosis or pancreatitis. In because the liver has not fully matured.2 test for bilirubin, which indicates addition to icterus, your ophthalmic Unconjugated hyperbilirubinemia is a that conjugated hyperbilirubinemia workup may uncover such signs as normal physiologic event that occurs in is present. If the complete blood uveitis or metastatic choroidal car- approximately 60% of normal full-term count and initial tests for liver func- cinoma. These ocular complications infants and in 80% of preterm infants.2,3 tion and hepatitis are unrevealing, can guide your lab workup as you The bilirubin level normally increases after the workup typically proceeds rule out various causes of jaundice. two to three days and peaks by five to to abdominal imaging by CT or As always, the patient’s primary care seven days, reaching as high as 12mg/dL ultrasonography.1,3 More invasive physician should be promptly made in normal full-term babies and up to 14mg/ procedures such as cholangiography aware of your findings. dL in normal premature infants by the end or liver biopsy may occasionally be Timely and appropriate testing, of the first week of life.2 Breast-fed babies necessary to arrive at a diagnosis. as well as comanagement with and may normally have an elevated bilirubin referral to the appropriate subspe- level until the end of the second week of Jaundice in Your Chair cialist (e.g., pediatrics, gastroenterol- life. In infants two weeks of age or older, One of the first things an optom- ogy, infectious disease) are typically however, the onset of jaundice within the etrist should do during a patient required. Physicians do not treat first 24 hours of life, rate of rise of serum encounter is to take a step back and jaundice; they treat the condition bilirubin levels greater than 5mg/dL in 24 observe the patient. Whether it is a that causes this telltale sign. ■ hours, direct bilirubin level greater than shuffling gait as a result of advanced 1. Roche SP, Kobos R. Jaundice in the adult patient. Am Fam 1mg/dL at any time, or the persistence or glaucomatous field loss, a head tilt Physician. 2004;69(2):299-304. 2. Gubernick JA, Rosenberg HK, Ilaslan H, Kessler A. US new onset of jaundice may no longer be indicating a high vertical phoria or approach to jaundice in infants and children. Radiographics. physiologic.2,3 2000;20(1):173-95. changes in coloration such as flush- 3. Boyer JL. Bile formation and secretion. Compr Physiol. ing or jaundice, the optometrist 2013;3(3):1035-78.

78 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

0077_ro1117_RoS.indd77_ro1117_RoS.indd 7788 111/6/171/6/17 9:329:32 AMAM Think About Your Eyes Because Life is Worth Seeing!

Motivate the American public to get an annual comprehensive eye exam: that is our one mission at Think About Your Eyes (TAYE) - and now we are now able to do that more effectively. Through the support of our Leadership Partners, the 40 state optometric associations who have signed up every active member, and the individual practices who have purchased a listing on the TAYE locator, TAYE has developed and launched two new television ads and two new radio ads during 2017, all of which celebrate how the gift of sight enhances everyday experiences as well as life’s important moments.

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RO1117_House Taye.indd 1 10/30/17 2:48 PM Ocular Surface Review

Could Eyelids Be the Key to DED? A new theory finds the two linked by a familiar foe: bacterial biofilm. By Paul M. Karpecki, OD

or many years, blepharitis and mation, (3) over-colonization, (4) dry eye disease (DED) were quorum-sensing gene activation, (5) Fconsidered two completely virulence factor production and (6) independent diseases. But the Ryner- inflammation that affects the lash son theory of dry eye blepharitis follicles, meibomian glands and lac- syndrome (DEBS), recently pub- rimal glands.1 To begin the process, lished in Clinical Ophthalmology, bacteria must survive enzymes such suggests dry eye may be the result of as lactoferrin, tear flow, natural decades of chronic blepharitis.1 Let’s cleaning activities of the eyelids take a closer look at what this might with each blink and the protective mean for clinical practice. Expression showing thickened meibum mechanism of mucin secreted by and the ‘volcano’ sign along the lashes. goblet cells.6 When a patient’s blink The Biofilm Bridge rate decreases due to surgery, exten- We’ve heard a lot about biofilms sive digital device use, the use of lately, especially with overused eye drops containing preservatives, contact lens cases, for example. systemic medications that decrease Although a biofilm can accumulate tear volume, presence of various on an inert structure such as a stent comorbidities and a host of multi- or contact lens case, it can also exist factorial contributors, bacteria can on a living structure.2 For instance, survive longer. plaque on your teeth is essentially Next is biofilm formation, biofilm formation.3 described as “the prevailing micro- Depending on the age of the You can see significant biofilm on this bial lifestyle.”7,8 Biofilm formation patient, contact lens use, Demodex patient’s lid margin, a common site for is a survival tactic allowing the bac- and other factors, various manifes- biofilm adherence. teria to avoid desiccation and host tations of blepharitis may demon- responses, produce virulence facts strate various degrees of lid margin tiple similar symptoms, both condi- and communicate with other bacte- “scurf” or debris—biofilm. But the tions can be slowly progressive and rial species (as quorum-sensing). key factor is inflammation, and if chronic with various manifestations Biofilm adherence exists in many it exists, blepharitis is present and depending on the stage of the dis- bacteria, but Staphylococcus in par- should probably be considered as ease.4,5 However, examining the eye- ticular produces a protein known as the underlying disease process.1 lid margins more closely for biofilm adhesin that ensures a tight adher- The diagnosis of blepharitis and formation may serve as a bridge of ence to the surface.9 The lid margin DED has been difficult in the past understanding between these two is a common a site of adherence, because both of these conditions poorly understood diseases. considering one study shows 32 have significant overlap, hence the of the isolates cultured from eyes theory of causation. As an example, From Lid Margin immediately after cataract surgery multiple symptoms of blepharitits Disease to DED had the ability to form biofilms.10 can overlap with those of DED, According to the new theory, Furthermore, although we ranging from dry, gritty, irritated lid margin disease progresses to wash and shower often, we don’t and itching eyes to tearing and inflammation through six steps: (1) naturally wash or clean our eyelid blurred vision.4 In addition to mul- bacterial survival, (2) biofilm for- margins—particularly the inner

80 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

080_ro1117_OSR.indd 80 11/3/17 12:45 PM eyelid margins. In fact, most people inflammation, which can manifest ing on and managing the biofilm tightly close their eyes when wash- clinically as lid laxity, floppy eyelid component of ocular surface dis- ing their face to prevent access to syndrome, ectropion and entropion, ease. Dentistry has mastered this the eyelid margins. This leads to the for example.11,12 important aspect of prevention by slow, progressive, chronic destruc- This DEBS theory may help addressed biofilm formation with tion that occurs via inflammation explain any number of factors, regular cleanings, brushing and over decades, eventually resulting in including how bacteria can survive flossing; this new theory suggests dry eye and even damage to the lid a Betadine prep prior to surgical a similar model that could be even structure itself. procedures, resulting in endophthal- more critical in eye care. ■ mitis—the bacteria is at the stage of Dr. Karpecki is a consultant to The Four Stages of DEBS biofilm formation when it is resis- Blephex, OcuSoft, Bruder Health- The Rynerson theory also suggests tant to an antiseptic.10 care, Paragon Biotech, TearScience stages of DEBS progression. and Akorn. Stage 1 involves the lash follicles, Putting Theory Into Practice 1. Rynerson JM, Perry HD. DEBS–a unification theory for dry where a biofilm can establish itself. I can’t prove or disprove this eye and blepharitis. Clin Ophthalmol. 2016;10: 2455–67. This can often be assessed under theory, but I have seen a significant 2. Artini M, Cellini A, Scoarughi GL, et al. Evaluation of contact lens multipurpose solutions on bacterial biofilm development. high magnification for a ‘volcano positive impact when treating the Eye Contact Lens. 2015;41(3):177-82. sign’ when the base of the lash biofilm mechanically for my DED 3. McSwain BS, Irvine RL, Hausner M, Wilderer PA. Composi- tion and distribution of extracellular polymeric substances in appears edematous. Scurf, or cylin- patients, in addition to anti-inflam- aerobic flocs and granular sludge. Appl Environ Microbiol. drical dandruff in cases of Demodex matory treatment and managing 2005;71(2):1051-7. 4. Bzdrenga J, Daudé D, Rémy B, et al. Biotechnological appli- blepharitis, is a sign of progression; the obstructed meibomian glands. cations of quorum quenching enzymes. Chem Biol Interact. however, these descriptions are Furthermore, mechanical removal May 22, 2016. [Epub]. misnomers and likely represent bio- of the biofilm from the lid margin 5. Ramadhani AM, Derick T, Holland MJ, Burton MJ. Blinding trachoma: systematic review of rates and risk factors for pro- film that has accumulated around shows a profound impact on symp- gressive disease. PLoS Negl Trop Dis. 2016;10(8):e0004859. the lash that pulled off as the lash toms, quality of tears and quality of 6. Guzman-Aranguez A, Argüeso P. Structure and biological roles of mucin-type O-glycans at the ocular surface. Ocul Surf. 1 13 grew. life. 2010;8(1):8-17. Stage 2 DEBS involves both the This theory affects so much of 7. Absalon C, Van Dellen K, Watnick P. A communal bacterial adhesin anchors biofilm and bystander cells to surfaces. PLoS lash follicles and the meibomian the optometric practice from a Pathog. 2011;7(8):e1002210. glands and may explain obvious pathology perspective, including 8. Pickering BS, Smith DR, Watnick PJ. Glucose-specific enzyme IIA has unique binding partners in the Vibrio cholerae vs. non-obvious meibominan gland contact lens wearers who are more biofilm. MBio. 2012;3(6):e00228-12. dysfunction (MGD). Because the prone to early MGD/blepharitis and 9. Edwards AM, Bowden MG, Brown EL, et al. Staphylococcus aureus extracellular adherence protein triggers TNFα release, 14-16 biofilm blocks the large meibomian DED. With this knowledge, we promoting attachment to endothelial cells via protein A. PLoS gland orifices (a combination of bio- may help patients remain in contact One. 2012;7(8):e43046. 10. Kıvanç SA, Kıvanç M, Bayramlar H. Microbiology of film and poor or altered meibum), lenses longer by consciously focus- corneal wounds after cataract surgery: biofilm formation and stage 2 takes longer to antibiotic resistance patterns. J Wound Care. 2016;25(1):12, 14-19. 1 achieve. 11. Baudouin C. Ocular surface and external Stage 3 involves the fol- filtration surgery: mutual relationships. Dev Ophthalmol. 2012;50:64-78. licles, meibomian glands 12. Baudouin C, Messmer EM, Aragona P, and the accessory lacrimal et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of glands of Krause and Wol- meibomian gland dysfunction. Br J Ophthalmol. fring. The distance, narrow 2016;100(3):300-6. 13. Romero JM, Biser SA, Perry HD, et al. Con- ducts and constant tear servative treatment of meibomian gland dys- flushing serve to protect function. Eye Contact Lens. 2004;30(1):14-9. 14. Villani E, Ceresara G, Beretta S. In vivo these glands for decades, confocal microscopy of meibomian glands in making them the last glands contact lens wearers. Invest Ophthalmol Vis Sci. 2011;52(8):5215-9. affected by biofilm forma- 15. Arita R, Fukuoka S, Morishige N. Meibo- tion.1 mian gland dysfunction and contact lens discomfort. Eye Contact Lens. 2017;43(1):17-22. Stage 4 occurs when This 65-year-old woman presented with frequent dryness 16. Vishnubhatla S, Borchman D, Foulks the structural integrity of and irritation, and she reported a “dry eye diagnosis” from a GN. Contact lenses and the rate of evaporation measured in vitro; the influence of wear, the eyelid finally breaks previous practitioner. A closer look at her lid margin suggests squalene and wax. Cont Lens Anterior Eye. down due to the chronic blepharitis is at play here as well. 2012;35(6):277-81.

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 81

080_ro1117_OSR.indd 81 11/3/17 12:45 PM Are you wasting time and money using outdated technology?

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RO1117_House Vision.indd 1 11/3/17 10:03 AM Cornea+Contact Lens Q+A

The Role of Toric Peripheries They provide one last refinement to the fit, improving comfort and vision. Edited by Joseph P. Shovlin, OD Photo: Lynette Johns, OD I just started fitting scleral that comfort, Q lenses but haven’t yet ordered fit and physi- any toric peripheral curve lenses. ologic response My lab consultant mentioned that a is improved majority of the orders she gets are when using for toric peripheries. Most of my sclerals with patients seem happy and I rarely a toric land- see much difference in lens edge ing, Mr. appearance, but am I missing the Kojima says.1-3 point by not ordering toric peripheral “Numerous curve lenses? larger lens Toric sclerals could help improve end-of-day comfort for your “Following the rebirth of designs greater scleral lens patients. A scleral lenses, symmetric than or equal landing of the lenses was the to 16mm in diameter have made a for areas of staining after remov- norm,” says Randy Kojima, a toric back surface standard in their ing the scleral lens, Dr. Barnett research scientist and clinical trial sets.” adds. “Ask patients about their instructor at the Pacific University Also citing scleral shape studies, comfort with sceral lenses, espe- College of Optometry. “Most if Melissa Barnett, OD, immediate cially end-of-day comfort. If any not all designs came as a standard past president of the Scleral Lens aspect of scleral lens wear could be symmetric landing. At the same Education Society, concurs.2-4 improved, consider back surface time, anterior segment OCT was “There may be toricity in the toricity.” being used to better understand sclera, irrespective of corneal “It appears the industry is the shape of the scleral 360 degrees toricity,” she says. “For lens diam- moving from symmetric to toric around.” eters greater than approximately as the lens of first choice in the According to Mr. Kojima, 16mm, back surface toricity may larger diameter,” says Mr. Kojima. numerous studies performed at have certain advantages, including “However, studies show the closer Pacific University have found improved alignment on all merid- to the limbus we land, the more the sclera to exhibit a toricity at ians, reduced post-lens reservoir symmetric the eye surface, so sym- 15mm of approximately 125µm. debris, better centration, less metric landing in scleral lens diam- “When constructing sclerals with movement and improved com- eters of less than or equal to 15mm toricities of between 100µm and fort.” may be advisable.” 150µm, the lenses appear rotation- To get a better idea of whether According to Mr. Kojima, ally stable in most eyes, suggesting toric peripheral curve lenses would researchers should further explore we have improved alignment,” be beneficial for a patient, it may asymmetric scleral lenses, which says Mr. Kojima. “Additionally, help “to evaluate the scleral lens fit may be “the way of the future.” ■ when patients are given the choice outside of the slit lamp and using 1. Schornack MM. Astigmatic correction with scleral lenses: between the symmetric in one eye dim illumination and then with A case series. Poster presented at the 44th Annual American and the toric in the other, they will the slit lamp to look for areas of Optometric Association Meeting; Philadelphia. 2. Visser ES, Visser R, Van Lier HJ. Advantages of toric usually choose the toric as being compression and impingement,” scleral lenses. Optom Vis Sci. 2006;83(4),233-6. 3. Visser ES, Van der Linden BJ, Otten HM, et al. Medical more comfortable.” says Dr. Barnett. At the follow- applications and outcomes of bitangential scleral lenses. Findings from both Europe and up appointment, the cornea and Optom Vis Sci. 2013;90(10):1078–85. 4. Visser ES, Visser R. Case report: Bitorische scleralens bij the United States have suggested conjunctiva should be evaluated keratitis sicca. Visus. 2002;2:92-5.

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083_ro1117_CLQA.indd 83 11/3/17 12:51 PM Retina Quiz

Next Time, Order Well Done A young man returned from an overseas trip with more than just memories. By Faten Edriskhalaf, OD, and Mark T. Dunbar, OD

16-year-old Hispanic male presented with a sud- Aden and painless onset of blurred vision in the right eye for the past two weeks. His social history was remarkable for recent travel to Nicaragua, but his medical history was unremarkable. An examination revealed his best-corrected vision was 20/25 OD and 20/20 OS. His extraocular motility was normal, and confrontation visual fields were full-to-careful finger counting. The pupils were equally round and reactive; there was no afferent pupillary defect. An exam of the anterior segment Fig. 1. Fundus photo of the right eye showing the area of interest. What does this was remarkable for keratic pre- represent? cipitates (KP) on the endothelium in the right eye and 1+ cell in the 2. How would you best character- Diagnosis anterior chamber. The left eye was ize the fundus changes seen in this The lesion superior to the nasal unremarkable. patient? appeared to be a subretinal cyst A dilated fundus exam of the a. Inflammatory. with adjacent subretinal fluid sur- right eye showed 1-2+ vitreous b. Infectious. rounding it. We also observed cells. The optic nerve and macula c. Congenital. chorioretinal scaring and atrophy appeared healthy. Of interest was d. Traumatic. surrounding the cyst. This was an elevated lesion superior to the confirmed on the SD-OCT, which nerve as seen in the fundus photo 3. What is this patient’s most likely shows well delineation of the cystic (Figure 1). A spectral-domain diagnosis? lesion in the subretinal space along optical coherence tomography a. Toxocariasis. with fluid and exudates. (SD-OCT) is available for review b. Toxoplasmosis. The patient admitted to having (Figure 2). c. Cysticercosis. recently traveled to Nicaragua. He d. Treponema pallidum (syphilis). also admitted to eating uncooked Take the Retina Quiz pork. Given this history, the ante- 1. How would you characterize the 4. How should this patient be man- rior chamber and vitreous cells, and OCT image of this patient? aged? OCT findings, we made a tentative a. Intraretinal cyst. a. Placed on Bactrim and moni- diagnosis of cysticercosis. b. Hemorrhagic RPE detachment. tored. c. Sub-retinal pigment epithelium b. Referred for surgical removal. Discussion (RPE) hyperreflective lesion with c. Panretinal photocoagulation. Cysticercosis is the most common fluid. d. Penicillin. parasitic disease of the central ner- d. Exudative retinal detachment. For answers, see page 98. vous system, affecting the eye, mus-

84 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

084_ro1117_RQ.indd 84 11/3/17 12:52 PM cle and subcutaneous tissue.1 It Systemic treatment for neu- is caused by encystment of the rocysticercosis involves anthel- tapeworm Taenia solium from minthic therapy; however, this uncooked pork meat.1,2 It is treatment may be contraindi- believed that the larvae travels cated if an active ocular infec- from the choroid through the tion is present.4 Our patient RPE and either encysts in the underwent magnetic resonance vitreous or subretinal space.2 imaging to rule out neurologi- In the ocular form, it typical- Fig. 2. The above SD-OCT image shows the lesion. cal involvement prior to com- ly presents unilaterally, affects ing in for his retinal exam, and young individuals in the second the results were normal. to fourth decade of life and is Visual prognosis for these endemic in developing coun- patients is good if it does not tries.1 In severe cases, anterior involve the macula, and is typi- and posterior inflammation is cally restored to normal once present and vision is greatly the cyst is removed and the reduced due to exudative reti- patient’s condition is treated nal detachment.2 Rarely, vitre- systemically. Recurrence is ous hemorrhage can occur if uncommon. the cyst migrates through the Proper follow up is warrant- retina into the vitreous.2 Sys- ed postoperatively, as with any temically, neurocysticercosis is surgery. Lastly, the best method the most serious of this condi- of prevention is to thoroughly tion’s sequela.2 Neurological cook pork and use proper findings are most commonly hygiene when handling meat. seizures and hydrocephalus.2 Our patient underwent pars Upon close comparison of plana vitrectomy, removal our high-definition OCT with of the cyst and was treated histopathological slides of for retinal detachment. One cysticercosis, we were able to month post-surgery, his vision definitively characterize that returned to baseline of 20/25 the double-layered cyst wall is without correction. The pathol- evident (Figure 3a). The scolex, Fig. 3. What can this detailed look at the SD-OCT ogy report confirmed the pres- which represents the knoblike image reveal? ence of the cyst in the specimen anterior end of the tapeworm, removed. He did not require can also be seen but is more difficult up for toxocariasis and toxoplas- anthelminthics, as he was not to visualize. We suspect our imaging mosis, as well as a full blood panel affected systemically. ■ captured the outline of the cyst (Fig- to rule out systemic involvement. Dr. Edriskhalaf is a former opto- ure 3b). The honeycomb invagina- Serologic testing for our patient metric resident at the Bascom Palm- tion within the cyst is the intestine was obtained and was negative for er Eye Institute in Miami, FL. of the larvae.(Figure 3c).3,4 active cysticercosis infection and also negative for toxoplasmosis 1. Dhiman R, Devi S, Duraipand K, et al. Cysticercosis of the eye. Int J Ophthalmol. 2017;10(8):1319-24. Treatment infection. The negative testing like- 2. Jain R, Kumar S, et al. Ocular cysticercosis with vitreous The management of ocular cysti- ly indicates the patient may have hemorrhage: a rare complication of a common disease. cercosis consists of prompt referral had this for some time even though Springerplus. 2015;4:217. 3. Amatya B, Kimula Y. Cysticercosis in Nepal: a histo- to a retina specialist for consider- he only recently became symptom- pathologic study of sixty-two cases. Am J Surg Pathol. ation of surgical removal of the atic. Some of the clinical findings 1999 Oct;23(10):1276-9. 4. Karthikeya R, Ravani R, Kakkar P, Kumar A. Intravitreal cyst and treatment of the retinal such as RPE mottling and atrophy cysticercosis with full thickness macular hole: management detachment, if present. All patients also suggest this has been present outcome and intraoperative optical coherence tomography features. BMJ Case Reports. April 21, 2017. casereports. we suspect have this condition longer than his symptoms would bmj.com/content/2017/bcr-2016-218645.abstract. should undergo a serology work have indicated. Accessed October 20, 2017.

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Stemming the Tide Cycloablation lowers IOP at its source: the ciliary body. Once considered a last resort, it may be warranted earlier. By Alan G. Kabat, OD, and Joseph W. Sowka, OD

56-year-old black woman Procedural Process presented for a comprehen- Cyclodestruction procedures aim Asive ocular examination. to decrease IOP by diminishing the Prior to a relocation, her long-time ciliary body’s capacity to produce ophthalmologist had been treat- aqueous. The earliest cyclodestruc- ing her for glaucoma. The patient tive techniques involved the use of reported using latanoprost 0.005% extreme cold (-80° C) applied to the QHS OU, dorzolamide/timolol conjunctival surface circumferen- maleate fixed combination BID tially around the cornea, approxi- OU and brimonidine 0.2% solu- mately 4mm beyond the limbus; tion TID OU. She further reported this procedure is referred to as having had laser treatment for glau- cyclo cryotherapy.1 coma in both eyes (most likely laser Limitations of cyclocryotherapy trabeculoplasty) within the past two include a variable response, in years. which patients may experience no IOP lowering effect or extreme Examination lowering to the point of hypot- Her best-corrected visual acuity was ony.2,3 Moreover, a host of com- 20/20 OD and 20/40-1 OS. Con- plications may be seen, including frontation visual fields were full in intraocular hemorrhage, secondary the right eye but severely constricted cataract, retinal detachment and in the left. Consistently, the left phthisis bulbi, any of which can eye displayed a 3+ relative afferent Fundus photos and OCT images of our lead to further loss of vision and defect on pupil testing. Intraocular 56-year-old glaucoma patient. even enucleation.2,3 Today, cycloc- pressure (IOP) was measured at ryotherapy is rarely used, but 20mm Hg OD and 28mm Hg OS. Gonioscopy revealed similar techniques that employ ophthalmic lasers (col- open angles to the ciliary body in all four quadrants, lectively referred to as cycloablative procedures) remain with moderate pigment and no sign of angle reces- an option for some glaucoma patients. sion in either eye. Central corneal thickness measured Endoscopic cyclophotocoagulation is invasive and 517µm in the right eye and 504µm in left. Upon dilated uses a laser endoscope to allow direct visualization examination, the optic nerves were markedly cupped, and treatment of the ciliary processes by means of a measuring approximately 0.8/0.8 OD and 0.9/0.95 OS. semiconductor diode laser.4 The procedure is typically OCT evaluation showed notable retinal nerve fiber layer performed in conjunction with cataract surgery for (RNFL) damage superiorly in the right eye and extensive patients with moderate to severe glaucoma.5 TS-CPC RNFL damage both superiorly and inferiorly in the left is a noninvasive procedure that uses a diode laser eye. Since the patient was already on maximum toler- attached to a specialized contact probe which is applied able medications and reported excellent compliance, to the conjunctival surface around the limbus. Like we ordered a consultation with a glaucoma specialist. cyclocryotherapy, TS-CPC has been criticized for its After examining her and reviewing the testing, he recom- lack of predictability and propensity toward compli- mended proceeding with transscleral cyclophotocoagula- cations, which include hypotony, early postoperative tion (TS-CPC) in the left eye using the Cyclo G6 system inflammation and pain, cystoid macular edema, persis- (Iridex). tent flare and loss of vision.6

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 89

089_ro1117_TR.indd 89 11/3/17 1:07 PM Advertisers Index Therapeutic Review

For advertising opportunities contact: An Updated Approach Michele Barrett (215) 519-1414 or [email protected] Most glaucoma surgeons today view TS-CPC as an James Henne (610) 492-1017 or [email protected] option only for those patients who have failed more Michael Hoster (610) 492-1028 or [email protected] invasive surgeries (i.e., trabeculectomy or tube shunt procedures) or those who have minimal or no useful Akorn Consumer Health . 19 Mentholatum Company .. 53 vision, but experience chronic pain associated with Phone ...... (800) 579-832 ...... 28-29 uncontrolled IOP.7 The procedure is generally frowned www.akornconsumerhealth. Phone ...... (877) 636-2677 upon for patients with good vision and those who com consumeraffairs@menthola- have only been previously managed with topical meds. However, those attitudes appear to be changing, and tum.com Alcon Laboratories ... 21, 25 some have even suggested that this procedure may be a ...... 26, 100 ...... www.mentholatum.com viable first-line surgical treatment.8,9 Phone ...... (800) 451-3937 This potential paradigm shift can be attributed to Fax ...... (817) 551-4352 Natural Ophthalmics, Inc. 91 new technology and a modified treatment approach. Phone ...... (877) 220-9710 The Cyclo G6, when coupled with the MP3 glaucoma Bausch + Lomb ...... 9. 10, 99 probe, employs micropulse technology; this differs ...... [email protected] Phone ...... (800) 323-0000 substantially from the continuous wave laser that was Fax ...... (813) 975-7762 ...... www.natoph.com used in prior versions of TS-CPC. As its name implies, the micropulse platform produces short bursts of laser Beaver-Visitec NovaBay Pharmaceuticals, energy with intervening rest periods, permitting for International, Inc...... 7 8 Inc...... 41 tissue cooling and rebound. This ensures cellular dis- Phone ...... (866) 906-8080 Phone ...... (800) 890-0329 ruption without total cell destruction, and while the Fax ...... (866) 906-4304 mechanism of action is not completely understood, ...... www.beaver-visitec.com ...... [email protected] researchers theorize that the thermal insult may acti- ...... www.avenova.com vate a cellular biochemical cascade, resulting in an Carl Zeiss Meditec Inc. .... 15 IOP-lowering effect.10 Phone ...... (877) 486-7473 Quidel ...... 37 As experts explain, this unique platform offers Fax ...... (925) 557-4101 Phone ...... (800) 874-1517 some distinct advantages over other surgical techniques. Unlike invasive procedures such as trabecu- [email protected] Eye Designs ...... 13 lectomy or tube-shunt surgery, micropulse TS-CPC is Phone ...... (800) 346-8890 ...... www.quidel.com theoretically repeatable (much like SLT). Moreover, Fax ...... (610) 489-1414 it has the capacity to be performed as an in-office S4OPTIK ...... 67, 69, 71 procedure, although some surgeons still recommend Katena ...... 17 11 Phone ...... (888) 224-6012 it be done in an outpatient facility for greater safety. Phone ...... (800) 225-1195 TS-CPC appears to provide significant results that can ...... www.katena.com be tailored to the patient’s needs. Studies show IOP TearScience ...... 47 reduction ranging from 30% to 45% among popula- Keeler Instruments ...... 5, 88 Phone ...... (919) 459-4891 tions with varied types and severity of glaucoma.12-16 Phone ...... (800) 523-5620 Fax ...... (919) 467-3300 They also show a diminished need for multiple medica- Fax ...... (610) 353-7814 tions following treatment.12-16 In one trial, the average number of glaucoma medications fell from 3.3 down to TelScreen ...... 35 Lombart Instruments ...... 33 1.8 after the procedure.16 Phone ...... (800) 446-8092 ...... www.TelScreen.com Micropulse TS-CPC can be associated with a sig- Fax ...... (757) 855-1232 ...... [email protected] nificant amount of discomfort, to the point that it requires a retrobulbar block, often with the adjunc- Menicon ...... 23 16 Vistakon ...... 2-3 tive use of oral anxiolytics or intravenous sedatives. Phone ...... (800) MENICON Physicians can also anticipate substantial inflam- Phone ...... (800) 874-5278 .... [email protected] mation after the procedure, necessitating the use of ....www.meniconamerica.com Fax ...... (904) 443-1252 strong topical corticosteroids during the immediate This advertiser index is published as a convenience and not as part of the advertising contract. postoperative period. Of course, the greatest concern Every care will be taken to index correctly. No allowance will be made for errors due to spelling, incorrect page number, or failure to insert. with this technique has been the potential for vision

90 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

0089_ro1117_TR.indd89_ro1117_TR.indd 9900 111/6/171/6/17 1:001:00 PMPM Specialty Eye Drops Great with Contacts Professional Quality loss, particularly the “snuffing out” of central fields in Only Available Via Doctors sighted patients with advanced disease. In a 2010 study involving 49 glaucomatous eyes with best-corrected visual acuity of 20/60 or better, 18.3% experienced a loss of greater than or equal to two Snellen lines within 12 months of the procedure.6 After five years, 30.6% of the eyes showed a similar loss of vision.6 The authors found this outcome “con- cerning,” but also concluded that much of the visual deterioration was likely due to the natural course of the disease rather than the intervention itself. They cited a 2007 study in which the same magnitude of vision loss was seen in approximately 33% of eyes Women’s Tear Tear Stimulation undergoing trabeculectomy or tube-shunt surgery Stimulation Forté after one year of follow-up.17 Advocates of this new technology argue that any surgical intervention places the patient at risk for complications and progression, particularly in advanced glaucoma. But they insist micropulse TS-CPC is more predictable and efficacious in the hands of a Allergy Desensitizationon well-trained surgeon than laser trabeculoplasty, mini- Eye Drops mally invasive glaucoma surgery or filtration surgery, while maintaining an acceptable safety profile and the potential for repeatability. Advocates also point to the rising cost of medications, declining insurance coverage and diminishing physician reimbursement for more invasive glaucoma surgeries as a rationale to Ortho-K Thin Ortho-K Thick consider TS-CPC earlier in the disease course.8 ■ -Do not sting 1. De Roetth A. Cryosurgery for the treatment of glaucoma. Trans Am Ophthalmol Soc. 1965;63:189- 204. - Work fast & feel great 2. Gerkowicz K, Toczolowski J. Observations on the use of low temperature in the treatment of glaucoma. Indian J Ophthalmol. 1984 Jul-Aug;32(4):209-11. 3. Benson M, Nelson ME. Cyclocryotherapy: a review of cases over a 10-year period. Br J Ophthalmol. - Preservative free 1990 Feb;74(2):103-5. 4. Uram M. Endoscopic cyclophotocoagulation in glaucoma management. Curr Opin Ophthalmol. 1995 Apr;6(2):19-29. 5. Cohen A, Wong SH, Patel S, Tsai JC. Endoscopic cyclophotocoagulation for the treatment of glau- Rather than sampling lubricants coma. Surv Ophthalmol. 2017 May-Jun;62(3):357-65. 6. Rotchford AP, Jayasawal R, Madhusudhan S, et al. Transscleral diode laser cycloablation in patients with good vision. Br J Ophthalmol. 2010 Sep;94(9):1180-3. and prescribing antihistamines 7. Pastor SA, Singh K, Lee DA, et al. Cyclophotocoagulation: a report by the American Academy of Ophthalmology. Ophthalmology. 2001 Nov;108(11):2130-8. for dry eye or allergy - now you 8. Toyos R. Cyclo G6 glaucoma laser, an alternative to stents for glaucoma. YouTube. March 16, 2017. youtu.be/V-Yhli1I2Vs. Accessed October 1, 2017. 9. Shoham A. Relooking at transscleral cyclophotocoagulation: old and new thoughts 2012. YouTube. can dispense therapeutic March 12, 2014. youtu.be/GDHYaAGLE8g. Accessed October 1, 2017. 10. Fea A, Bosone A, Rolle T, et al. Micropulse diode laser trabeculoplasty (MDLT): A phase II clinical treatments that your patients study with 12 months follow-up. Clin Ophthalmol. 2008 Jun;2(2):247-52. 11. Bendel RE, Patterson MT. Observational report: Improved outcomes of transscleral cyclophotoco- will prefer. agulation for glaucoma patients. Medicine (Baltimore). 2017 Jun;96(23):e6946. 12. Tan A, Chockalingam M, Aquino M, et al. Micropulse transscleral diode laser cyclophotocoagulation in the treatment of refractory glaucoma. Clin Exp Ophthalmol. 2010 Apr;38(3):266-72. 13. Aquino MC, Barton K, Tan AM, et al. Micropulse versus continuous wave transscleral diode cyclophotocoagulation in refractory glaucoma: a randomized exploratory study. Clin Exp Ophthalmol. 2015 Jan-Feb;43(1):40-6. 14. Radcliffe N, Vold S, Kammer J, et al. Micropulse transscleral cyclophotocoagulation (mTSCPC) for the treatment of glaucoma using the MicroPulse P3 device. Presented at: American Glaucoma Society annual meeting; February 26-March 1, 2015; San Diego, CA. 15. Kuchar S, Moster M, Waisbourd M. Treatment outcomes of MicroPulse trans-scleral cyclophotocoagulation in advanced glaucoma. Presented at: American Glaucoma Society annual meeting; February 26-March 1, 2015; San Diego, CA. 16. Toyos M, Toyos R. Clinical outcomes of micropulsed transcleral cyclophotocoagulation in moderate to severe glaucoma. J Clin Exp Ophthalmol. 2016;7(6):620. 17. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. 2007 Jan;143(1):9-22.

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089_ro1117_TR.indd 91 11/3/17 1:08 PM Product Review

Pharmaceuticals device. It enables a 70-degree visual range, wider than Glaucoma Drug Now Approved other low vision devices, the company says. Users can Vyzulta (latanoprostene bunod ophthalmic solution, zoom in and out as needed for different visual tasks and 0.024%), by Bausch + Lomb and Nicox, is now FDA can adjust screen brightness and contrast, interpupillary approved. A prostaglandin analog, it is indicated for distance and magnifier position and shape. Black and open-angle glaucoma and ocular hypertension, and will white and inverted text modes allow for easier reading. be available by the end of year, according to B+L. Visit irisvision.com. The once-daily monotherapy agent metabolizes into latanoprost acid, which primarily works within the In-home Vision Therapy uveoscleral pathway, and butanediol mononitrate, which Vivid Vision has launched a home-use version of its releases nitric oxide to increase outflow through the tra- virtual reality vision therapy system, called Vivid Vision becular meshwork and Schlemm’s canal, B+L says. Home. Patients first see a doctor Visit ir.valeant.com. for an evaluation and prescription, then can use the device (in conjunc- Diagnostic Technology tion with the Oculus Rift, HTC New Ultrasound System Vive or Samsung GearVR) to con- DGH Technology’s Scanmate Flex ultrasound system is duct vision therapy at home. Vivid Vision Home includes notable for the flexibility it gives clinicians, the company tools to assess and track changes in vision, as well as says. The device can be equipped with any combination exercises designed to take advantage of room-scale VR of three probe types: UBM, A-scan and B-scan. Desktop and positional controls, according to the company. or wall-mounted, its internal battery allows it to operate Doctors can track treatment and response remotely. for hours without being plugged in, according to DGH. Visit www.seevividly.com. Visit dghtechnology.com. Scleral Lenses Camera for Retinal Video New Design for Irregular Corneas Heine recently upgraded the imaging resolution of its The Onefit Med scleral lens from Blanchard simplifies Omega 500 BIO. The camera now provides five-mega- fitting for keratoconic patients with nipple and oval pixel resolution with no disturbing picture noise, due to cones, as well as post-RK and post-LASIK patients. the camera’s increased light sensitivity, according to the Practitioners set the parameters for central, mid-periph- company. Practitioners can easily connect to a projector eral, limbal and edge zones, then customize the final to display the video imaging. The company is offering design with an online fitting tool. Multifocal, oblate and institutional discounts for the Omega 500. front toric geometries are possible, the company says, Visit www.heine.com. and the design minimizes lens thickness and tear layer to maximize oxygen transmission. Accutome by Keeler Visit blanchardlab.com. Keeler has acquired the Accutome clinical and diagnostic lines of products. The new “Accutome by Keeler” brand Quadrant-specific Control offers a full complement of clinical pharmaceuticals and BostonSight has introduced a new quadrant-specific supplies, according to the company. Devices for pachym- toric lens design that comes with built-in scleral shape etry, tonometry and ultrasound imaging add to Keeler’s and right- and left-eye anatomical designs. Available in established line of ophthalmic products. 18.0mm, 18.5mm and 19.0mm, the Visit www.accutome.com. BostonSight Scleral is the first of its kind to provide front-surface eccen- Patient-use Devices tricity options for aberration control, Low Vision Aid the company says. BostonSight used Practitioners interested in adding low six years of data from approximately 7,000 eyes to vision have a new device to consider. develop the lens. The incorporated scleral shape allows IrisVision uses Samsung’s Galaxy S7 clinicians to use the same starting point for every patient phone and GearVR virtual reality headset to magnify, regardless of their condition, according to the company. brighten and sharpen text or objects seen through the Visit www.bostonsight.org. ■

92 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

092_ro1117_products.indd 92 11/3/17 1:18 PM Meetings + Conferences

December 2017 [email protected], call (503) 352-2985 or go ■ 1-2. Retina Update 2017. Sheraton Park Hotel, Anaheim, to www.pacificu.edu/future-graduate-professional/colleges/ CA. Hosted by: Review of Optometry. Key faculty: Mohammad college-optometry/continuing-education. Rafieetary, Steven Ferrucci, Leo Semes, Mark Dunbar, Jeff ■ 12-14. AZOA 2018 Bronstein Contact Lens & Cornea Gerson, Rishi Singh. CE hours: 11. For more information, email Seminar. Hilton Scottsdale Resort & Villas, Scottsdale, AZ. [email protected], call (800) 999-0975 or go to Hosted by: Arizona Optometric Association. Key faculty: Melissa www.reviewofoptometry.com/orsretupdate2017. Barnett, Patrick Caroline, Thomas Quinn, Roy Wesley. CE hours: ■ 2-3. 34th Annual Cornea, Contact Lens & Contemporary 15.5. For more information, email Kate Diedrickson at Vision Care Symposium. Westin Memorial City, Houston, TX. [email protected] or go to www.azoa.org/Connect. Hosted by: University of Houston College of Optometry. Key ■ 13-15. Kraskin Invitational Skeffington Symposium on Vision. faculty: Jan Bergmanson. CE hours: 16. For more information, Embassy Suites Hotel at the Chevy Chase Pavilion, Washington email University of Houston College of Optometry at D.C. Hosted by: Optometric Extension Program Foundation [email protected], call (713) 743-1900 or go to and the Institute for Behavioral Optometry. Key faculty: Multiple http://ce.opt.uh.edu. presenters. CE hours: 19. For more information, email Jeffrey ■ 3. Clinical Topics in Optometry. Marshall B. Ketchum Kraskin at [email protected], call (202) 363-4450 or go to University, Fullerton, CA. Hosted by: Marshall B. Ketchum www.skeffingtonsymposium.org. University. CE hours: 8. For more information, email Antoinette ■ 13, 14, 20, 21. Coding and Compliance Seminars. Various Smith at [email protected], call (714) 872-5684 or go to locations, CA. Hosted by: Primary Eyecare Network. Key faculty: www.ketchum.edu/ce. John McGreal. CE hours: 4. For more information, email ■ 7. UABSO Evening of Education. University of Alabama [email protected] or go to www.primaryeye.net. Birmingham School of Optometry, Birmingham, AL. Hosted by: ■ 14-20. 2018 Island Eyes Conference. Ritz-Carlton Kapalua, University of Alabama Birmingham School of Optometry. CE Kapalua (Maui), Hawaii. Hosted by: Pacific University College of hours: 2. For more information, email Katherine Clore at Optometry. Key facutly: Mark Andre, Carlo Pelino, Alan Reichow, [email protected], call (205) 934-5700 or go to Tracy Doll, Walt Whitley, Fraser Horn. CE hours: 29. For more www.uab.edu/optometry/home/uabso-ce. information, email Jeanne Oliver at [email protected], call ■ 7-11. VT/Learning Related Visual Problems. Southern College (503) 352-2740 or go to www.pacificu.edu/future-graduate- of Optometry, Memphis, TN. Hosted by: Optometric Extension professional/colleges/college-optometry/continuing-education/ Program Foundation. Key faculty: Paul Harris. CE hours: 35. For conferences-events/island-eyes-conference. more information, email Karen Ruder at [email protected], ■ 22. Day at the Capitol & Winter CE. Boise Centre, Boise, ID. call (410) 561-3791 or go to www.oepf.org. Hosted by: Idaho Optometric Physicians. CE hours: 4. For more ■ 15-16. West Coast Optometric Glaucoma Symposium. Hilton information, email Randy Andregg at [email protected], call Hotel, Huntington Beach, CA. Hosted by: Review of Optometry. (208) 461-0001 or go to idaho.aoa.org. Key faculty: Murray Fingeret, Robert Weinreb, Ben Gaddie, Alex ■ 25-28. Global Specialty Lens Symposium. Tropicana Hotel, Huang, Richard Madonna, Sameh Mosaed. CE hours: 12. For Las Vegas, NV. Hosted by: Pentavision. Key faculty: Melissa more information, email [email protected], call (800) Barnett, Lyndon Jones, Pauline Cho, Philip Morgan. CE hours: 999-0975 or go to www.reviewofoptometry.com/wcogs2017. 55 total, 19 per OD. For more information, email Maureen Trusky ■ 23-30. Considerations in Ocular Disease Management and at [email protected] or call Treatment. Norwegian Cruise Line’s Norwegian Epic, Western (215) 628-7754. Caribbean Cruise, round-trip Orlando (Port Canaveral), FL. Hosted ■ 28. VOA One-Day CE Conference. Omni Charlottesville, by: Dr. Travel Seminars and the New Jersey Society of Optometric Charlottesville, VA. Hosted by: Virginia Optometric Association. Physicians. Key faculty: Mark Dunbar. CE hours: 16. For more Key faculty: Leo Semes. CE hours: 4. For more information, information, email Dr. Travel Seminars at [email protected], call email Bo Keeney at [email protected], call (804) 643-0309 or go (800) 436-1028 or go to www.drtravel.com. to www.thevoa.org/voa/89-events.

January 2018 To list your meeting, please send the details to: ■ 6. Glaucoma Symposium. Willows Lodge, Woodinville, WA. Michael Iannucci, Associate Editor Hosted by: Pacific University College of Optometry. Key faculty: Email: [email protected] Howard Barnebey, Murray Fingeret. CE hours: 7. For more Phone: (610) 492-1043 information, email Michelena Buckingham at

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 93

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ASSISTANT PROFESSOR POSITIONS: PEDIATRICS ;&ƵůůͲƟŵĞŶŽŶͲƚĞŶƵƌĞƚƌĂĐŬĨĂĐƵůƚǇƉŽƐŝƟŽŶƐĨŽƌƚŚĞŚŝĐĂŐŽŽůůĞŐĞŽĨKƉƚŽŵĞƚƌǇͿ

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ĂŶĚŝĚĂƚĞƐŵƵƐƚďĞǁŝůůŝŶŐƚŽĂĐƟǀĞůǇƉĂƌƟĐŝƉĂƚĞŝŶĐƵƌƌŝĐƵůĂƌĂƐƐĞƐƐŵĞŶƚ͕ƉƌŽĨĞƐƐŝŽŶĂůĚĞǀĞůŽƉŵĞŶƚ͕ƐƚƵĚĞŶƚĐŽƵŶƐĞůŝŶŐĂŶĚƐĞƌǀŝĐĞĂĐƟǀŝƟĞƐǁŝƚŚŝŶƚŚĞĐŽů- ůĞŐĞ͕ƵŶŝǀĞƌƐŝƚǇĂŶĚƚŚĞƐĐŝĞŶƟĮĐĐŽŵŵƵŶŝƚǇ͘^ƵĐĐĞƐƐĨƵůĐĂŶĚŝĚĂƚĞƐĂƌĞĂůƐŽĞǆƉĞĐƚĞĚƚŽďĞŝŶǀŽůǀĞĚŝŶƌĞƐĞĂƌĐŚĂŶĚƐĐŚŽůĂƌůǇĂĐƟǀŝƟĞƐ͕ĂŶĚŚĂǀĞĂƐŝŶĐĞƌĞ ĐŽŵŵŝƚŵĞŶƚƚŽŽƉƚŽŵĞƚƌŝĐĞĚƵĐĂƟŽŶ͕ĐŽŵŵƵŶŝƚǇƐĞƌǀŝĐĞĂŶĚƉĂƟĞŶƚĐĂƌĞ͘WƌŝŵĂƌǇĚƵƟĞƐŝŶĐůƵĚĞ͕ďƵƚĂƌĞŶŽƚůŝŵŝƚĞĚƚŽ͗

a) dĞĂĐŚŝŶŐ b) ^ĞƌǀŝĐĞ • WĂƌƟĐŝƉĂƟŶŐŽŶŽůůĞŐĞĂŶĚhŶŝǀĞƌƐŝƚǇĐŽŵ- • ĞǀĞůŽƉŝŶŐ ĂŶĚ ĚĞůŝǀĞƌŝŶŐ ůĞĐƚƵƌĞƐ ĂŶĚͬŽƌ • ,ĞůƉŝŶŐ ƚŽ ŵĂŝŶƚĂŝŶ ĂŶĚ ŐƌŽǁ ƚŚĞ ƐƚĂƚĞ ŽĨ ŵŝƩĞĞƐ͕ĂƐĂƐƐŝŐŶĞĚ͖ ůĂďŽƌĂƚŽƌŝĞƐ ĨŽƌ ĐŽƌŶĞĂ ĂŶĚ ĐŽŶƚĂĐƚ ůĞŶƐĞƐ ƚŚĞ Ăƌƚ ŽƉƚŽŵĞƚƌǇ ƉƌŽŐƌĂŵ ǁŝƚŚ Ă ƐƚƌŽŶŐ • WĂƌƟĐŝƉĂƟŶŐŝŶŽůůĞŐĞĂŶĚhŶŝǀĞƌƐŝƚǇƐĞƌǀŝĐĞ ĂŶĚƌĞůĂƚĞĚĂƌĞĂƐ͕ĂƐĂƐƐŝŐŶĞĚ͖ ŝŶƚĞƌĚŝƐĐŝƉůŝŶĂƌǇĨŽĐƵƐƚŚĂƚŵĞĞƚƐƚŚĞŶĞĞĚƐ ĂĐƟǀŝƟĞƐ͘ • ŵďƌĂĐŝŶŐ ĂŶĚ ĞŶŚĂŶĐŝŶŐ ƚŚĞ ĚŝĚĂĐƟĐ ƉŚŝ- ŽĨƉĂƟĞŶƚƐŝŶƚŚĞƐƵƌƌŽƵŶĚŝŶŐĐŽŵŵƵŶŝƚǇ͖ŝƐ ůŽƐŽƉŚŝĞƐŝŶƚŚĞK͘͘ƉƌŽŐƌĂŵ͖ ĞĸĐŝĞŶƚ͕ƉĂƟĞŶƚĨƌŝĞŶĚůǇ͕ĂŶĚĐŽƐƚͲĞīĞĐƟǀĞ͖ c) ^ĐŚŽůĂƌůǇĂĐƟǀŝƚǇ • DĂŝŶƚĂŝŶŝŶŐĂŶĚĞǆƉĂŶĚŝŶŐƚŚĞŚŝŐŚƋƵĂůŝƚǇ • tŽƌŬŝŶŐĐůŽƐĞůǇƚŽŐĞƚŚĞƌǁŝƚŚĂůůŽƉƚŽŵĞƚƌǇ ŶŐĂŐŝŶŐŝŶƌĞƐĞĂƌĐŚĂŶĚƐĐŚŽůĂƌůǇĂĐƟǀŝƚǇ͕ŝŶ- ĐůŝŶŝĐĂů ƉƌĂĐƟĐĞ ĞŶǀŝƌŽŶŵĞŶƚ ĨŽƌ ŽƉƚŽŵĞƚƌǇ ĂŶĚŽƉŚƚŚĂůŵŽůŽŐǇĨĂĐƵůƚǇƚŽƉƌŽǀŝĚĞĂĐŽŵ- ĐůƵĚŝŶŐ ƉƌĞƐĞŶƚĂƟŽŶƐ ĂƚƐĐŝĞŶƟĮĐ ŵĞĞƟŶŐƐ͕ ƐƚƵĚĞŶƚƐŽŶƌŽƚĂƟŽŶ͖ ƉůĞƚĞƌĂŶŐĞŽĨĞǇĞĂŶĚǀŝƐŝŽŶĐĂƌĞƐĞƌǀŝĐĞƐ͖ ƌĞƐĞĂƌĐŚ͕ ĂŶĚ ƉƵďůŝĐĂƟŽŶ ŝŶ ƉĞĞƌ ƌĞǀŝĞǁĞĚ • WƌĞĐĞƉƟŶŐƐƚƵĚĞŶƚƐŽŶĐůŝŶŝĐĂůƌŽƚĂƟŽŶĂƚƚŚĞ • WĂƌƟĐŝƉĂƟŶŐŝŶůĞĂĚĞƌƐŚŝƉƌŽůĞƐŝŶƐƚĂƚĞ͕ƌĞ- ũŽƵƌŶĂůƐ ƐƵĸĐŝĞŶƚ ƚŽ ƋƵĂůŝĨǇ ĨŽƌ ĂĐĂĚĞŵŝĐ DŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇǇĞ/ŶƐƟƚƵƚĞ͖ ŐŝŽŶĂů͕ĂŶĚŶĂƟŽŶĂůŽƉƚŽŵĞƚƌǇŽƌŐĂŶŝǌĂƟŽŶƐ͖ ĂĚǀĂŶĐĞŵĞŶƚŝŶĂŶŽŶͲƚĞŶƵƌĞƚƌĂĐŬƉŽƐŝƟŽŶ͘

Yç½®¥®ã®ÊÄÝ͗ĂŶĚŝĚĂƚĞƐŵƵƐƚƉŽƐƐĞƐƐĂŽĐƚŽƌŽĨKƉƚŽŵĞƚƌǇĚĞŐƌĞĞĨƌŽŵĂŶKͲĂĐĐƌĞĚŝƚĞĚŝŶƐƟƚƵƟŽŶ͕ŵƵƐƚŚĂǀĞĐŽŵƉůĞƚĞĚĂŶKͲĂĐĐƌĞĚŝƚĞĚ ƌĞƐŝĚĞŶĐǇ͕ĂŶĚŵƵƐƚďĞĞůŝŐŝďůĞĨŽƌĂŶŽƉƚŽŵĞƚƌŝĐƐƚĂƚĞůŝĐĞŶƐĞŝŶƚŚĞƐƚĂƚĞŝŶǁŚŝĐŚƚŚĞĐŽůůĞŐĞŝƐůŽĐĂƚĞĚ͘WƌŝŵĂƌǇĞǇĞĐĂƌĞĐůŝŶŝĐĂůĞǆƉĞƌƟƐĞŝƐĂůƐŽƌĞƋƵŝƌĞĚ͘

ÊÄãã®Ä¥ÊÙÃã®ÊÄ͗ŽŶƚĂĐƚŝŶĨŽƌŵĂƟŽŶ͗/ŶƚĞƌĞƐƚĞĚĂƉƉůŝĐĂŶƚƐƐŚŽƵůĚĂƉƉůǇŽŶůŝŶĞĂƚǁǁǁ͘ŵŝĚǁĞƐƚĞƌŶ͘ĞĚƵĂŶĚŝŶĐůƵĚĞ ĐƵƌƌŝĐƵůƵŵǀŝƚĂĞĂŶĚůĞƩĞƌŽĨŝŶƚĞƌĞƐƚƐƉĞĐŝĨǇŝŶŐƚŚĞƉŽƐŝƟŽŶĂŶĚĐŽůůĞŐĞƚŚĂƚŚĞͬƐŚĞǁŝƐŚĞƐƚŽďĞĐŽŶƐŝĚĞƌĞĚĨŽƌ͘/ŶƋƵŝƌŝĞƐŵĂǇďĞ ĚŝƌĞĐƚĞĚƚŽƌ͘DĞůŝƐƐĂ^ƵĐŬŽǁ͕ƐƐŽĐŝĂƚĞĞĂŶ͖DŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇ͗ŵƐƵĐŬŽΛŵŝĚǁĞƐƚĞƌŶ͘ĞĚƵ͘

DŝĚǁĞƐƚĞƌŶhŶŝǀĞƌƐŝƚǇŝƐĂŶƋƵĂůKƉƉŽƌƚƵŶŝƚǇͬĸƌŵĂƟǀĞĐƟŽŶĞŵƉůŽǇĞƌƚŚĂƚĚŽĞƐŶŽƚĚŝƐĐƌŝŵŝŶĂƚĞĂŐĂŝŶƐƚĂŶĞŵƉůŽǇĞĞŽƌĂƉƉůŝĐĂŶƚďĂƐĞĚƵƉŽŶƌĂĐĞ͕ ĐŽůŽƌ͕ƌĞůŝŐŝŽŶ͕ŐĞŶĚĞƌ͕ŶĂƟŽŶĂůŽƌŝŐŝŶ͕ĚŝƐĂďŝůŝƚǇ͕ŽƌǀĞƚĞƌĂŶƐƐƚĂƚƵƐ͕ŝŶĂĐĐŽƌĚǁŝƚŚϰϭ͘&͘Z͘ϲϬͲϭ͘ϰ;ĂͿ͕ϮϱϬ͘ϱ;ĂͿ͕ϯϬϬ͘ϱ;ĂͿĂŶĚϳϰϭ͘ϱ;ĂͿ͘

Products and Services Career Opportunities

Staff Optometrist Wanted Bard Optical is a family owned full-service retail optometric practice with 22 offices (and growing) throughout Central Illinois. Bard Optical prides itself on having a progressive optometric staff whose foundation is based on one-on-one patient service. We are currently accepting CV/resumes for Optometrists to join our medical model optometric practice that includes extended testing. The practice includes but is not limited to general optometry, contact lenses and geriatric care. Salaried, full-time positions are available with excellent base compensation and incentive programs and benefits. Some part-time opportunities may also be available.

Current positions are available in Bloomington/Normal, Decatur/Forsyth, Peoria, Sterling and Canton as we continue to grow with new and established offices.

Please email your information to [email protected] or call Mick at 309-693-9540 ext 225. Mailing address if more convenient is: Bard Optical Attn: Mick Hall, Vice President Do you have Merchandise to offer? 8309 N Knoxville Avenue Peoria, IL 61615 Contact us today for classified advertising: Bard Optical is a proud Toll free: 888-498-1460 Associate Member of the Illinois Optometric Association. E-mail: [email protected] www.bardoptical.com

REVIEW OF OPTOMETRY NOVEMBER 15, 2017 97

ROPT1117.indd 97 10/27/17 1:15 PM Diagnostic Quiz

Like Sunglasses at Night By Andrew S. Gurwood, OD

History A 44-year-old Caucasian male reported to the office with a chief complaint of poor night vision. He explained that he had been seen by other eye doctors who had told him he had some “freckles” in his left eye. His systemic and ocular histories were unremarkable and he denied allergies of any kind. Diagnostic Data His best-corrected entering visual Can these fundus images help point to a diagnosis for this 44-year-old patient acuities were 20/20 OU at distance suffering from poor night vision? and near. His external examination was normal with evidence of measuring 15mm Hg OU. The per- you take to manage this patient? sluggish pupil on the left side. His tinent dilated fundus findings are Based on the information pro- peripheral confrontation visual demonstrated in the photographs. vided, what would be your diag- field was distorted and constricted nosis? What do you believe is the in the left eye. The biomicroscopic Your Diagnosis patient’s most likely prognosis? examination of the anterior seg- Does the case presented require To find the answers, please visit ments found normal structures with any additional tests, history or Review of Optometry online at Goldmann applanation pressures information? What steps would www.reviewofoptometry.com. ■

Retina Quiz Answers (from page 84): 1) a; 2) a; 3) c; 4) b.

Next Month in the Mag • Intraocular Lens Choices: How to Find the Best Match For Each Patient Coming in December, Review of Optometry will proudly celebrate its 23rd Annual Surgery Report. • Will SMILE be the Game Changer for Refractive Surgery Has Been Waiting For? Topics include: Also in this issue: • Is it the Lens, Retina or Tear Film? Knowing When to Refer a Cataract Patient • Hey Good Lookin’, It’s Our 2017 Office Design Contest Winners • Postoperative Cataract Care: The Optometrist’s Role in Prescribing NSAIDs, Steroids and Antibiotics • Review of Optometry’s Annual Income Survey Results

REVIEW OF OPTOMETRY (ISSN 0147-7633) IS PUBLISHED MONTHLY, 12 TIMES A YEAR BY JOBSON MEDICAL INFORMATION LLC, 440 9TH AVENUE, 14TH FLOOR, NEW YORK, NY 10013-1678. PERIODICALS POSTAGE PAID AT NEW YORK, NY AND ADDITIONAL MAILING OFFICES. POSTMASTER: SEND ADDRESS CHANGES TO REVIEW OF OPTOMETRY, PO BOX 81, CONGERS, NY 10920-0081. SUBSCRIPTION PRICES: US: ONE YEAR $56; TWO YEARS $97, CANADA: ONE YEAR $88, TWO YEARS $160, INT’L: ONE YEAR $209, TWO YEARS $299. FOR SUBSCRIPTION INFORMATION CALL TOLL-FREE (877) 529-1746 (USA); OUTSIDE USA, CALL (845) 267-3065. OR EMAIL US AT REVOPTOMETRY@CAMBEYWEST. COM. PUBLICATIONS MAIL AGREEMENT NO: 40612608. CANADA RETURNS TO BE SENT TO BLEUCHIP INTERNATIONAL, P.O. BOX 25542, LONDON, ON N6C 6B2.

98 REVIEW OF OPTOMETRY NOVEMBER 15, 2017

098_ro1117_DQ.indd 98 11/3/17 1:20 PM The first sponsored contact lens recycling program from Bausch + Lomb and TerraCycle®

OVER ONE MILLION ITEMS RECYCLED IN JUST ONE YEAR

This America Recycles Day, we’re celebrating the Bausch + Lomb ONE by ONE Recycling Program— a free program in which participating offices and patients work together to collect used blister packs, top foil, and contact lenses for proper recycling.

TerraCycle®, the TerraCycle Logo®, and Brigade® are all trademarks of TerraCycle Inc. used under license, www.terracycle.com, toll-free 866.967.6766. Biotrue is a trademark of Bausch & Lomb Incorporated or its afﬁ liates. ©2017 Bausch & Lomb Incorporated. BOD.0491.USA.17

RO1117_B&L Biotrue.indd 1 10/30/17 2:08 PM YOUR PATIENTS’ EYES TAKE IN A LOT.

Sometimes it’s not all good. SYSTANE ® BALANCE Lubricant Eye Drops are scientiﬁ cally formulated to work on all 3 layers of the tear ﬁ lm, protecting the ocular surface with ingredients that increase lipid layer thickness by 40%.*,1

Recommend SYSTANE® BALANCE to your patients for the temporary relief of dry eye symptoms, and see how science leads to real relief.

*Prospective, randomized, double-masked, single-dose, contralateral eye study, N=40. Lipid layer thickness was measured in nanometers, and baseline measurement was 63.38. The Relief is Real 1. Korb D, et al. Evaluation of extended tear stability by two emulsion based artiﬁ cial tears. Poster presented at: 6th International Conference on the Tear Film and Ocular Surface: Basic Science and Clinical Relevance; September 22-25, 2010; Florence, Italy. © 2016 Novartis 12/16 US-SYS-16-E-5049

RO0517_Alcon Systane.indd 1 4/19/17 11:03 AM