Eyeworld

3 EW NEWS & OPINION by David F. Chang, MD, and Andre Witkin, MD Joint ASCRS/ASRS Task Force issues findings and recommendations regarding HORV July 2016 were often very poor. Twenty-two of 36 eyes (61%) were 20/200 or worse, and 8 of 36 eyes (22%) were NLP. T he first 2 cases of bilater- al hemorrhagic occlusive retinal vasculitis (HORV) were published in 2014. 1 An additional 4 cases (3 bilater- al and 1 unilateral) were reported in 2015. 2 All 11 of the reported eyes in those 6 cases had undergone other- wise uncomplicated cataract surgery with prophylactic intracameral vancomycin (1 mg/0.1 cc), and there was a delay of 1–14 days before the onset of the severe ischemic retinal vasculitis. The visual outcomes were poor. The authors postulated a de- layed immune response to a surgical adjuvant, with vancomycin as the leading candidate. Because of the popularity of in- tracameral vancomycin for endoph- thalmitis prophylaxis, the American Society of Cataract & Refractive Surgery (ASCRS) and the American Society of Retina Specialists (ASRS) expeditiously formed a joint Task Force to further analyze the prev- alence, potential etiology, treat- ment, and outcomes of this newly described complication associated with intraocular surgery. The Task Force includes ASRS members Steve Charles, MD, Dean Eliott, MD, J. Michael Jumper, MD, Andre J. Witkin, MD, and Charles C. Wykoff, MD, and ASCRS Cataract Clinical Committee members David F. Chang, MD, Richard S. Hoffman, MD, Nick Mamalis, MD, and Kevin M. Miller, MD. Drs. Charles, Jumper, and Miller also serve on the ASCRS Retina Clinical Committee. To better define the clinical characteristics of HORV, an online case registry was set up on the ASRS website for members to report new cases. Information about all surgi- cal medications and adjuvants was requested with a particular goal of uncovering other associations in addition to (or besides) vancomycin. Retinal images including OCT, FA, and fundus photos were reviewed for each case by retina specialist members of the Task Force. In addi- tion, to better understand the preva- lence of this complication, an online "surveillance" survey was emailed to all ASCRS members soliciting any cases of suspected HORV. Positive respondents were sent additional queries for information that were followed up by Task Force retina specialists. Through these methods, a complete data set was compiled on 36 eyes of 22 patients with HORV. All of these eyes received intraocu- lar vancomycin, either 1 mg/0.1 ml intracameral, 1 mg/0.1 intravitreal, or in the infusion bottle (10 mg into the balanced salt solution bottle). Despite intraocular anti-VEGF and steroid treatments, visual results BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE ILEVRO® (nepafenac ophthalmic suspension) 0.3% is associated with cataract surgery. DOSAGE AND ADMINISTRATION Recommended Dosing One drop of ILEVRO® Suspension should be applied to to cataract surgery, continued on the day of surgery period. An additional drop should be administered 30 to 120 minutes prior to surgery. Use with Other Topical Ophthalmic Medications ILEVRO® Suspension may be administered in conjunction with other topical ophthalmic medications such as beta-blockers, carbonic anhydrase inhibitors, alpha-agonists, cycloplegics, and mydriatics. If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. CONTRAINDICATIONS ILEVRO® Suspension is contraindicated in patients with previously demonstrated hypersensitivity to any of the ingredients in the formula or to other NSAIDs. WARNINGS AND PRECAUTIONS Increased Bleeding Time including ILEVRO® Suspension, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal of ocular tissues (including hyphemas) in conjunction with ocular surgery. It is recommended that ILEVRO® Suspension be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time. Delayed Healing including ILEVRO® Suspension, may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems. Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs including ILEVRO® Suspension and should be closely monitored for corneal health. Post marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients. Post marketing experience with topical NSAIDs also suggests that use more than 1 day prior to surgery or use beyond 14 days post-surgery may increase patient risk and severity of corneal adverse events. Contact Lens Wear ILEVRO® Suspension should not be administered while using contact lenses. ADVERSE REACTIONS 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 the rates in the clinical studies of another Serious and Otherwise Important Adverse Reactions The following adverse reactions are discussed in greater detail in other sections of labeling: • Increased Bleeding Time (Warnings and Precautions) • Delayed Healing (Warnings and Precautions) Ocular Adverse Reactions The most frequently reported ocular adverse reactions following cataract surgery were capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These reactions occurred in approximately 5 to 10% of patients. Other ocular adverse reactions occurring at an incidence of approximately 1 to 5% included conjunctival edema, corneal edema, dry eye, lid margin crusting, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment. Some of these reactions may be the consequence of the cataract surgical procedure. Non-Ocular Adverse Reactions Non-ocular adverse reactions reported at an incidence of 1 to 4% included headache, hypertension, nausea/ vomiting, and sinusitis. USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C: Reproduction studies performed with nepafenac in rabbits and rats at oral doses up to 10 mg/kg/day have revealed no evidence of teratogenicity due to nepafenac, despite the induction of maternal toxicity. At this dose, the animal plasma exposure to nepafenac and amfenac was approximately 70 and 630 times human plasma exposure at the recommended human topical ophthalmic dose for rats and 20 and 180 times human plasma exposure for rabbits, respectively. In rats, maternally toxic doses ≥10 mg/kg were associated with dystocia, increased postimplantation loss, reduced fetal weights and growth, and reduced fetal survival. Nepafenac has been shown to cross the placental barrier in rats. There are no adequate and well- controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ILEVRO® Suspension should be used the potential risk to the fetus. biosynthesis inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of ILEVRO® Suspension during late pregnancy should be avoided. Nursing Mothers ILEVRO® Suspension is excreted in the milk of lactating rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ILEVRO® Suspension is administered to a nursing woman. Pediatric Use pediatric patients below the age of 10 years have not been established. Geriatric Use been observed between elderly and younger patients. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Nepafenac has not been evaluated in long-term carcinogenicity studies. Increased chromosomal aberrations were observed in Chinese hamster ovary cells exposed in vitro to nepafenac suspension. Nepafenac was not mutagenic in the Ames assay or in the mouse lymphoma forward mutation assay. Oral doses up to 5,000 mg/kg did not result in an increase in the formation of micronucleated polychromatic erythrocytes in vivo in the mouse micronucleus assay in the bone marrow of mice. Nepafenac did not impair fertility when administered orally to male and female rats at 3 mg/kg. PATIENT COUNSELING INFORMATION Slow or Delayed Healing Patients should be informed of the possibility that slow or delayed healing may occur while using nonsteroidal Avoiding Contamination of the Product Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery. Contact Lens Wear ILEVRO® Suspension should not be administered while wearing contact lens. Intercurrent Ocular Conditions Patients should be advised that if they develop an intercurrent ocular condition (e.g., trauma, or infection) or have ocular surgery, they should immediately seek their physician's advice concerning the continued use of the multi-dose container. Concomitant Topical Ocular Therapy If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. Shake Well Before Use Patients should be instructed to shake well before each use. Released: February 2014 U.S. Patent Nos. 5,475,034; 6,403,609; and 7,169,767. ©2016 Novartis 2/16 US-ILV-16-E-0334 continued on page 8

• Cover