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EW FEATURE 48 Microinvasive glaucoma surgery (MIGS) • May 2016 BRIEF SUMMARY OF PRESCRIBING INFORMATION ATION A INDICATIONS AND USAGE ATIONS AND USAGE A TRAV AV A AT VAT V AN Z ATAN Z AT ® (travoprost ophthalmic solution) 0.004% is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. DOSAGE AND ADMINISTRATION ATION A The recommended dosage is one drop in the affected eye(s) once daily in the evening. TRAV AV A AT VAT V AN Z ATAN Z AT ® (travoprost ophthalmic solution) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 2 hours after the first administration with maximum effect reached after 12 hours. TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. CONTRAINDICATIONS ATIONS A None WARNINGS AND PRE WARNINGS AND PRE W CAUTIONS Pigmentation Tr Tr T avoprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Pigmentation is expected to increase as long as travoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of travoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typicall Typicall T y, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with TRAV AV A A VA V T AT A AN Z TAN Z T ® (travoprost ophthalmic solution) 0.004% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. Eyelash Changes TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment. Intraocular Inflammation TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated. Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. TRA TRA TR V AV A AT VAT V AN ATAN AT Z ® Solution should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Angle-closure, Inflammatory or N r N r eovascular Glaucoma TRA TRA TR V AV A AT VAT V AN ATAN AT Z ® Solution has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma. Bacterial Keratitis There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. Use with Contact Lenses Contact lenses should be removed prior to instillation of TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution and may be reinserted 15 minutes following its administration. ADVERSE REACTIONS Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The most common adverse reaction observed in controlled clinical studies with TRA RA R V AV A AT VAT V A ATA AT N ® (travoprost ophthalmic solution) 0.004% and TRA TRA TR V AV A AT VAT V AN ATAN AT Z ® (tr (tr ( avoprost ophthalmic solution) 0.004% was ocular hyperemia which was reported in 30 to 50% of patients. Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions reported at an incidence of 5 to 10% in these clinical studies included decreased visual acuity, eye discomfort, foreign body sensation, pain and pruritus. Ocular adverse reactions reported at an incidence of 1 to 4% in clinical studies with TRA TRA TR V AV A AT VAT V A ATA AT N ® or TRA RA R V AV A AT VAT V A ATA AT N Z ® Solutions included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage and tearing. Nonocular adverse reactions reported at an incidence of 1 to 5% in these clinical studies were allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence and urinary tract infections. In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed. USE IN SPECIFIC POPULATIONS ATIONS A Pregnancy Pregnancy Category C Ter Ter T atogenic effects: Tr Tr T avoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 mcg/kg/day (250 times the maximal recommended human ocular dose (MRHOD), evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, such as fused sternebrae, domed head and hydrocephaly. Tr Tr T avoprost was not teratogenic in rats at IV doses up to 3 mcg/kg/day (75 times the MRHOD), or in mice at subcutaneous doses up to 1 mcg/kg/day (25 times the MRHOD). Tr Tr T avoprost produced an increase in post-implantation losses and a decrease in fetal viability in rats at IV doses > 3 mcg/kg/day (75 times the MRHOD) and in mice at subcutaneous doses > 0.3 mcg/kg/day (7.5 times the MRHOD). In the offspring of female rats that received travoprost subcutaneously from Day 7 of pregnancy to lactation Day 21 at doses of ≥ 0.12 mcg/kg/day (3 times the MRHOD), the incidence of postnatal mortality was increased, and neonatal body weight gain was decreased. Neonatal development was also affected, evidenced by delayed eye opening, pinna detachment and preputial separation, and by decreased motor activity ty t . There are no adequate and well-controlled studies of TRA RA R V AV A AT VAT V A ATA AT N Z ® Z ® Z (tr (tr ( avoprost ophthalmic solution) 0.004% administration in pregnant women. Because animal reproductive studies are not always predictive of human response, TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers A study in lactating rats demonstrated that radiolabeled travoprost and/or its metabolites were excreted in milk. It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TRAV AV A A VA V T AT A AN Z TAN Z T ® Solution is administered to a nursing woman. Pediatric Use Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients. Hepatic and Renal Impairment Tr Tr T avoprost ophthalmic solution 0.004% has been studied in patients with hepatic impairment and also in patients with renal impairment. No clinically relevant changes in hematology, blood chemistry, or urinalysis laboratory data were observed in these patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Tw Tw T o-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 mcg/kg/day did not show any evidence of carcinogenic potential. However, r, r at 100 mcg/kg/day, male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in the mouse study. The high dose (100 mcg/kg) corresponds to exposure levels over 400 times the human exposure at the maximum recommended human ocular dose (MRHOD) of 0.04 mcg/kg, based on plasma active drug levels. Tr Tr T avoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome aberration assay. A slight increase in the mutant frequency was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes. Tr Tr T avoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses up to 10 mcg/kg/day [250 times the maximum recommended human ocular dose of 0.04 mcg/kg/day on a mcg/kg basis (MRHOD)]. At At A 10 mcg/kg/day, the mean number of corpora lutea was reduced, and the post-implantation losses were increased. These effects were not observed at 3 mcg/kg/day (75 times the MRHOD). PATIENT COUNSELING INFORM PATIENT COUNSELING INFORM PA ATION ATION A Potential for Pigmentation Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of TRAV AV A AT VAT V AN Z ATAN Z AT ® (travoprost ophthalmic solution) 0.004%. Potential for Eyelash Changes Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment. Handling the Container Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. When to Seek Physician Advice Patients should also be advised that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician's advice concerning the continued use of TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution. Use with Contact Lenses Contact lenses should be removed prior to instillation of TRAV AV A AT VAT V AN Z ATAN Z AT ® Solution and may be reinserted 15 minutes following its administration. Use with Other Ophthalmic Drugs If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes between applications. Rx Only U.S. Patent Nos. 5,631,287; 5,889,052, 6,011,062; 6,235,781; 6,503,497; and 6,849,253 ALCON LABORATORIES ATORIES A , INC. Fort Worth, Texas 7 Texas 7 T 6134 USA © 2006, 2010, 2011, 2012 Novartis 10/15 US-TRZ-15-E-0278 93398 EW 5/1/16 by Maxine Lipner EyeWorld Senior Contributing Writer P erforming angle surgery is becoming more common, with the iStent (Glaukos, Laguna Hills, California) increasing in popularity, Tools and techniques to find the canal every time Tips for angle surgery a situation where it's like trying to do a coronary stent without angiog- raphy," Dr. Brown said. Dr. Brown pointed out that go- nioscopy, which is pivotal for angle surgery, is a critical skill that requires a real commitment to master. "Visi- bility is a challenge because there are incisions that we try to repressurize with viscoelastic, but the viscoelastic leaks out, so the pressure in the eye is sometimes not what we would like it to be," Dr. Brown said. "There are a series of things that can be improved." Ronald Fellman, MD, Glau- coma Associates of Texas, Dallas, concurs. He said that operating in the angle is totally different from the training received in residency for ab externo work like a trabeculec- tomy. "The training in residency for ab interno glaucoma surgery is probably close to nil," Dr. Fellman said. "That's a big stumbling block right there." Goniolens guidance Learning to use a goniolens in the operating room can take some time. "The difficulty is that with one hand you're balancing a gonioprism on the cornea, and in the other you're manipulating an instrument and potentially hooked up to a device in the anterior chamber, and in between you're looking through the microscope, and there's a foot pedal or two as well that you might be using," Dr. Fellman said. "You might as well be an organist." One of the most common mistakes Dr. Fellman sees is the application of too much pressure to the goniolens. "Instead of just balancing the gonioprism on the cornea, you put a little pressure on it and get corneal folds," he said. "Then all of a sudden the view is compromised." When that happens, practitioners tend to get a little tense and press down more. Dr. Fellman finds this is less of an issue with practice. "When you see [experi- enced physicians doing the proce- dure], you notice that they don't push at all, and that makes it 100 times easier because the view is a lot better," he said. He prefers a Swan Jacob goni- olens for performing angle surgery. A goniolens offers a direct view of the eye versus a gonioprism, where light is reflected off a mirror to the according to Reay Brown, MD, Atlanta Ophthalmology Associates, Atlanta. The issue for some, howev- er, may be that it's not always easy to find the requisite angle. "We're in

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