Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Intraocular Pressure Risk Factors Parekh A, Srivastava S, Bena J, Albini T, Nguyen QD, Goldstein DA. Risk factors associated with intraocular pressure increase in patients with uveitis treated with the fluocinolone acetonide implant. JAMA Ophthalmology. Published online February 26, doi: /jamaophthalmol

Copyright restrictions may apply Introduction The intravitreal fluocinolone acetonide implant (FAI) (Retisert; Bausch & Lomb Inc) is a Food and Drug Administration–approved therapy for the treatment of chronic noninfectious intermediate, posterior, and panuveitis. Elevated intraocular pressure (IOP) is a well-known adverse event secondary to the use of the FAI. Objective –To report risk factors that may predispose patients to elevated IOP after treatment with the FAI.

Copyright restrictions may apply Setting: Multicenter private or institutional practices worldwide. Design: Data from 3 multicenter, 3-year, prospective, randomized, phase 2b/3 clinical trials evaluating the safety and efficacy of the FAI were pooled and analyzed. Participants –No underlying glaucoma. –At least 1 eye with a history of recurrent noninfectious uveitis. –Required ≥1 of the following: Systemic therapy (corticosteroids or other immunosuppressive drugs) for ≥3 months before enrollment. ≥2 sub–Tenon capsule corticosteroid injections for uveitis management during the 6 months before enrollment. Systemic corticosteroid or sub–Tenon capsule corticosteroid injection therapy required for ≥2 separate recurrences within 6 months before enrollment. Methods

Copyright restrictions may apply Data Analysis –Factors evaluated as risk factors for IOP elevation included age, sex, lens status, uveitis severity at enrollment, and location of uveitis. Limitations –Data were pooled from 3 different clinical trials with similar but not identical inclusion criteria, looking at different outcomes. –The definition of glaucomatous damage in this population was dependent on the physician. –No strict criteria were set in terms of who needed intervention and when to perform surgery. Methods

Copyright restrictions may apply Data analyses were based on 641 eyes. 351 eyes did not receive an FAI; 290 eyes had the 0.59-mg FAI placed. An increase in IOP of 10 mm Hg was seen in 17.1% of untreated eyes and 65.1% of treated eyes (P <.001). An absolute IOP of 30 mm Hg was found in 7.7% of untreated eyes vs 50.7% of treated eyes (P <.001). 2% of untreated eyes required surgical intervention for elevated IOP as compared with 32.1% of treated eyes (P <.001). In patients with the FAI, younger age, male sex, and phakic lens status were associated with higher risk of IOP elevation and the need for glaucoma surgery (P =.003, P <.001, and P <.001, respectively). Results

Copyright restrictions may apply Univariable Evaluations of Risk Factors for an IOP Increase of 10 mm Hg or Reaching 30 mm Hg for Eyes Treated With the 0.59-mg Implant Results

Copyright restrictions may apply Results Analysis of Changes in Mean Deviation and Cup-Disc Ratio by Treatment Group With Adjustment for Age, Sex, and Phakic Lens Status

Copyright restrictions may apply Patients receiving the FAI had a higher risk of developing an IOP increase of 10 mm Hg or an absolute IOP of 30 mm Hg when compared with patients without the FAI. Age, sex, and lens status were all independently associated with an increased risk of requiring surgery for IOP after implantation of the FAI. –Increased risk was seen in patients who were male, younger, and phakic. Despite close monitoring, eyes with the FAI developed changes in the cup-disc ratio during the study period. 50% of patients who reached an IOP of ≥30 mm Hg underwent surgical intervention. Comment

Copyright restrictions may apply Even with the high degree of vigilance in clinical trials, therapy for IOP was often performed too late to prevent ocular hypertension from progressing to glaucoma. Close monitoring of IOP is advised to reduce the risk of progression to glaucoma. The data found in this study may be helpful in counseling patients about their risks prior to placement of an FAI. Comment

Copyright restrictions may apply If you have questions, please contact the corresponding author: –Debra A. Goldstein, MD, Department of Ophthalmology, Northwestern University, 675 N St Clair St, Ste , Chicago, IL Funding/Support This study was supported in part by an unrestricted grant from Research to Prevent Blindness (Dr Goldstein). Additional Information Bausch & Lomb Inc paid for the original studies in this article. They had a role in design of original studies as well as collection and management of the original data. However, Bausch & Lomb Inc had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. Contact Information

Copyright restrictions may apply Dr Srivastava reported working as a consultant for Bausch & Lomb Inc and receiving financial support from Bausch & Lomb Inc, Novartis, and Allergan. Dr Albini reported working as a consultant for Bausch & Lomb Inc, Allergan, and Eleven Biotherapeutics and receiving financial support from Genentech. Dr Nguyen reported receiving financial support from Genentech, Regeneron, Lux Biosciences, Abbott, GSK, Santen, Optos, and Heidelberg Engineering and working as a consultant for Santen and Bausch & Lomb Inc. Dr Goldstein reported working as a consultant for Bausch & Lomb Inc, Xoma, Clearside Biomedical, and Abbvie. No other disclosures were reported. Conflict of Interest Disclosures