Eyeworld

EW REFRACTIVE SURGERY 94 March 2015 by Maxine Lipner EyeWorld Senior Contributing Writer I t can be par for the course— patients who are dissatisfied with their vision coming in for refractive surgery evaluation often have an underlying dry eye problem, according to William Trattler, MD, Center for Excellence in Eye Care, Miami. "They may have some contact lens intolerance or are just not hap- py with their vision and are hoping that LASIK would solve their prob- lem," Dr. Trattler said. "We therefore see a high percentage of patients that come in for refractive surgery consults who have preexisting dry eye." He finds that this is especially true of contact lens patients. "Con- tact lens wearers often notice that their vision is not as crisp as they would like and they're hoping that LASIK can solve their problem," Dr. Trattler said. Computer use can also be a factor because individuals do not blink as much while using one, he said. "Also, as we get older we have a little more dry eye and as a result, patients commonly expe- rience reduced quality of vision," he explained. In addition, patients who use oral medications like oral antihistamines for allergies often experience dry eye. Uday Devgan, MD, chief of ophthalmology, Olive View-UCLA Medical Center, and Devgan Eye Surgery, Los Angeles, also finds that allergy medications can play a role. "The surface can be affected by a lot of these allergy drops," Dr. Devgan said. "Patients who have seasonal allergies or rhinitis may be taking an antihistamine, which of- ten has pseudoephedrine to dry out their mucous membranes but dries the eyes out, too." For a potential corneal refractive patient, knowing about existing dry eye is even more important, he said. "LASIK or even PRK is going to make everyone's eyes drier since we are interrupting those corneal nerves," Dr. Devgan said, adding that even normal eyes are going to be dry for at least a couple of months post- LASIK. Dr. Trattler said it is important to identify dry eye and optimize the ocular surface for PRK patients be- cause the condition can increase the risk for delays in epithelial healing. "Typically with PRK we expect visual recovery in 3–5 days, but it could take longer if dry eyes are not identified and treated preoperative- ly," he said. Dr. Devgan urges restraint in working with dry eye patients, regardless of the method of refrac- tive surgery. "Let's be careful when operating on dry eye patients during the driest, hottest summer months particularly in arid climates like Southern California," he said. He may recommend that patients use tears to optimize their ocular surface and return in a few months. Preop work With any potential refractive pa- tient, the first step for Dr. Trattler is to determine whether dry eye is present. Usually in younger patients he finds that dry eyes are a form of aqueous deficiency. So preoper- atively he will place punctal plugs, begin topical steroid therapy for 1–3 weeks, and start the patient on Restasis (cyclosporine, Allergan, Ir- vine, Calif.) to enhance the produc- tion of tears. Eric D. Donnenfeld, MD, clini- cal professor of ophthalmology, New York University Medical Center, New York, likewise stresses the impor- tance of vigilance. Preoperatively he tests LASIK patients using the TearLab Osmolarity System (TearLab, San Diego). "We look for anything more than 308 (milliosmoles) or a differ- ence of 8 milliosmoles or greater between the 2 eyes," Dr. Donnenfeld said. He added that they also con- sider MMP-9 readings looking for inflammatory cytokines. If the patient does have pre- existing dry eye, Dr. Donnenfeld is aggressive about appropriate treatment. For those with meibo- mian gland disease, he recommends use of hot compresses, stepping up lid hygiene, use of oral reesterified omega-3 supplements, and adminis- tration of artificial tears. In addition, he suggests instituting LipiFlow (TearScience, Morrisville, N.C.) to heat the lids from the inside and massage out the blocked oil glands. Meanwhile if the patient has aqueous deficient dry eye, Dr. Donnenfeld uses pulse steroid therapy with loteprednol 4 times a day for 2 weeks and then decreases Buffing up refractive results in dry eyes Putting a new shine on the ocular surface RESTASIS ® (Cyclosporine Ophthalmic Emulsion) 0.05% BRIEF SUMMARY—PLEASE SEE THE RESTASIS ® PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION. INDICATION AND USAGE RESTASIS ® ophthalmic emulsion is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular infl ammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-infl ammatory drugs or using punctal plugs. CONTRAINDICATIONS RESTASIS ® is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation. WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination To avoid the potential for eye injury and contamination, be careful not to touch the vial tip to your eye or other surfaces. Use with Contact Lenses RESTASIS ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® ophthalmic emulsion. ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not refl ect the rates observed in practice. In clinical trials, the most common adverse reaction following the use of RESTASIS ® was ocular burning (17%). Other reactions reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring). Post-marketing Experience The following adverse reactions have been identifi ed during post approval use of RESTASIS ® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Reported reactions have included: hypersensitivity (including eye swelling, urticaria, rare cases of severe angioedema, face swelling, tongue swelling, pharyngeal edema, and dyspnea); and superfi cial injury of the eye (from the vial tip touching the eye during administration). USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects: Pregnancy Category C Adverse effects were seen in reproduction studies in rats and rabbits only at dose levels toxic to dams. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), cyclosporine oral solution, USP, was embryo- and fetotoxic as indicated by increased pre- and postnatal mortality and reduced fetal weight together with related skeletal retardations. These doses are 5,000 and 32,000 times greater (normalized to body surface area), respectively, than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS ® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively, during organogenesis. These doses in rats and rabbits are approximately 3,000 and 10,000 times greater (normalized to body surface area), respectively, than the daily human dose. Offspring of rats receiving a 45 mg/kg/day oral dose of cyclosporine from Day 15 of pregnancy until Day 21 postpartum, a maternally toxic level, exhibited an increase in postnatal mortality; this dose is 7,000 times greater than the daily human topical dose (0.001 mg/kg/day) normalized to body surface area assuming that the entire dose is absorbed. No adverse events were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the daily human dose). There are no adequate and well-controlled studies of RESTASIS ® in pregnant women. RESTASIS ® should be administered to a pregnant woman only if clearly needed. Nursing Mothers Cyclosporine is known to be excreted in human milk following systemic administration, but excretion in human milk after topical treatment has not been investigated. Although blood concentrations are undetectable after topical administration of RESTASIS ® ophthalmic emulsion, caution should be exercised when RESTASIS ® is administered to a nursing woman. Pediatric Use The safety and effi cacy of RESTASIS ® ophthalmic emulsion have not been established in pediatric patients below the age of 16. Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: Systemic carcinogenicity studies were carried out in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically signifi cant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males signifi cantly exceeded the control value. In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas signifi cantly exceeded the control rate in the low-dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 80 times greater (normalized to body surface area) than the daily human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS ® twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. Mutagenesis: Cyclosporine has not been found to be mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA- repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE). Impairment of Fertility: No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day (approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating. PATIENT COUNSELING INFORMATION Handling the Container Advise patients to not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion. To avoid the potential for injury to the eye, advise patients to not touch the vial tip to their eye. Use with Contact Lenses RESTASIS ® should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. Advise patients that if contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS ® ophthalmic emulsion. Administration Advise patients that the emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration. Rx Only Based on package insert 71876US18 © 2014 Allergan, Inc. Irvine, CA 92612, U.S.A. ® marks owned by Allergan, Inc. APC21XT14 Patented. See www.allergan.com/products/patent_notices Made in the U.S.A. Live: w 4.36" x h 9.25" NOTES: File is sized to Live Area. Bleed: Pharmaceutical focus

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