EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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50 EW GLAUCOMA Alternatives continued from page 49 "In ocular devices nothing is ap- proved quickly," said L. Jay Katz, M.D., Wills Eye Hospital, Philadel- phia, on the FDA process. "Every- thing is kind of on a slow path. [Glaukos has] one last hurdle appar- ently and one last question the FDA wants resolved, and that's been re- submitted. If that's resolved I think they are home free." Thomas W. Samuelson, M.D., Minnesota Eye Consultants, Min- neapolis, published a study in March 2011 in Ophthalmology (118:459- 467) assessing the safety and efficacy of the device in combination with cataract surgery in 240 eyes with mild to moderate open-angle glau- coma. Patients had an IOP of ≤24 mm Hg controlled on one to three medications and were randomized for cataract surgery with iStent im- plantation or cataract surgery only. Success was defined as unmedicated IOP ≤21 mm Hg at 1 year. A second- ary success measure was unmed- icated IOP reduction ≥20% at 1 year. "In this study of the iStent, when used in conjunction with cataract surgery in subjects with mild to moderate open-angle glau- coma, we found a statistically and clinically significant treatment effect in favor of the iStent in reducing IOP with less medication use com- pared with cataract surgery alone," the authors concluded. "At 12 months after implantation, there was a 22% treatment difference (72% vs. 50%) in favor of the iStent in the proportion of patients with IOP 21 mm Hg without ocular hy- potensive medications at 12 months." In terms of complications, Dr. LUMIGAN 0.01% AND 0.03% (bimatoprost ophthalmic solution) ® INDICATIONS AND USAGE LUMIGAN® CONTRAINDICATIONS None WARNINGS AND PRECAUTIONS Pigmentation: Bimatoprost 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 bimatoprost 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 bimatoprost, pigmentation of the iris is likely to be permanent, while pigmen- tation 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. Typically, 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 LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. Eyelash Changes: LUMIGAN® 0.01% and 0.03% 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: LUMIGAN® 0.01% and 0.03% should be used with caution in patients with active intraocular inflammation (eg, uveitis) because the inflammation may be exacerbated. Macular Edema: Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution. LUMIGAN® 0.01% and 0.03% should be used with caution in aphakic patients, in pseudo- phakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Angle-closure, Inflammatory, or Neovascular Glaucoma: LUMIGAN® 0.01% and 0.03% has not been evaluated for the treatment of angle-closure, inflam- matory, 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 LUMIGAN® 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. In clinical studies with bimatoprost ophthalmic solutions (0.01% or 0.03%), the most common adverse event was conjunctival hyperemia (range 25%-45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.01% or 0.03% bimatoprost ophthalmic solutions. Other common events (> 10%) included growth of eyelashes and ocular pruritus. Additional ocular adverse events (reported in 1% to 10% of patients) with bimatoprost ophthalmic solutions included ocular dryness, visual disturbance, ocular burning, foreign body sensation, eye pain, pigmentation of the periocular skin, blepharitis, cataract, superficial punctate keratitis, eyelid erythema, ocular irritation, eyelash darkening, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, increases in iris pigmentation, conjunctival edema, conjunctival hemorrhage, and abnormal hair growth. Intraocular inflammation, reported as iritis, was reported in less than 1% of patients. Systemic adverse events reported in approximately 10% of patients with bimatoprost ophthalmic solutions were infections (primarily colds and upper respiratory tract infections). Other systemic adverse events (reported in 1% to 5% of patients) included headaches, abnormal liver function tests, and asthenia. USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category C. 0.01% and 0.03% and may be reinserted 15 minutes following 0.01% and 0.03% (bimatoprost ophthalmic solution) is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost that achieved at least 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels. At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well-controlled studies of LUMIGAN® potential benefit justifies the potential risk to the fetus. Nursing Mothers: It is not known whether LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) administration in pregnant women. Because animal reproductive studies are not always predictive of human response, LUMIGAN® should be administered during pregnancy only if the 0.01% and 0.03% is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when LUMIGAN® 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 pigmen- tation 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 Impairment: In patients with a history of liver disease or abnormal ALT, AST, and/or bilirubin at baseline, bimatoprost 0.03% had no adverse effect on liver function over 48 months. OVERDOSAGE No information is available on overdosage in humans. If overdose with LUMIGAN® 0.01% and 0.03% (bimatoprost ophthalmic solution) occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 than the accidental dose of one bottle of LUMIGAN® is at least 70 times higher 0.03% for a 10-kg child. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility: Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks. Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/ kg/day (at least 103 times the recommended human exposure based on blood AUC levels). PATIENT COUNSELING INFORMATION 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 LUMIGAN® ophthalmic solution). 0.01% and 0.03% (bimatoprost 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 LUMIGAN® 0.01% and 0.03%. 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 LUMIGAN® 0.01% and 0.03%. Use with Contact Lenses: Patients should be advised that LUMIGAN® 0.03% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of LUMIGAN® may be reinserted 15 minutes following its administration. 0.01% and and 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. © 2011 Allergan, Inc., Irvine, CA 92612 ® marks owned by Allergan, Inc APC81RP11 based on 71807US12B. Rx only Katz pointed out that hyphema in the anterior chamber is pretty com- mon. A rare complication is the mis- placement of the device altogether. "The FDA is always concerned when we're putting devices in the eye, what happens to the cornea, but looking at the parameters we've had in the studies, there's no evi- dence of increased corneal injury re- lated to having a stent inside the eye," he said. If a patient needs a lower IOP than a single stent implant will achieve, surgeons can insert multi- ple stents into a single eye. Using multiple stents, said Dr. Katz, does not appear to increase complication rates. "We're trying to create a bridge somewhere between failure with medications and the other surgeries like trabeculectomy and tube shunt," said Dr. Katz. "I think the iStent is a procedure that offers something that might be effective but is safer than going to the big guns. If it doesn't work by the na- ture of what type of surgery it is, meaning it doesn't involve cutting into the conjunctiva, then we haven't jeopardized the success of the big gun surgeries like trabeculec- tomy and tube shunts down the road." EW Editors' note: Dr. Francis has financial interests with Endo Optiks (Little Silver, N.J.). Dr. Katz has financial interests with Glaukos. Dr. Lewis has no finan- cial interests related to this article. Dr. Noecker has financial interests with Endo Optiks. Dr. Salim has financial interests with Alcon. Dr. Vold is founder and chief executive officer of NeoMedix. Contact information Francis: BFrancis@doheny.org Katz: ljaykatz@gmail.com Lewis: rlewiseyemd@yahoo.com Noecker: noeckerrj@gmail.com Salim: sarwat_salim@yahoo.com Vold: svold@cox.net February 2011 January 2012