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Blood-Aqueous Barrier Changes After the Use of Prostaglandin Analogues in Patients with Pseudophakia and Aphakia a 6-Month Randomized Trial

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Blood-Aqueous Barrier Changes After the Use of Prostaglandin Analogues in Patients with Pseudophakia and Aphakia a 6-Month Randomized Trial CLINICAL SCIENCES Blood-Aqueous Barrier Changes After the Use of Prostaglandin Analogues in Patients With Pseudophakia and Aphakia A 6-Month Randomized Trial Enyr S. Arcieri, MD; Alessandro Santana, MD; Fabiano N. Rocha, MD; Gustavo L. Guapo, MD; Vital P. Costa, MD Objectives: To investigate the effects of prostaglandin throughout follow-up (P Ͻ .02). Four latanoprost- analogues on the blood-aqueous barrier and to evaluate treated eyes, 1 bimatoprost-treated eye, and 1 travoprost- the occurrence of cystoid macular edema in aphakic or treated eye developed cystoid macular edema; all cases pseudophakic patients with glaucoma. resolved after discontinuation of the prostaglandin ana- logue and treatment with topical diclofenac sodium. Mean Methods: In this randomized, masked-observer, 6-month intraocular pressure reductions after 6 months were higher clinical trial, patients with primary open-angle, pseudo- for the latanoprost (26%), bimatoprost (28%), and tra- phakic, or aphakic glaucoma were treated once daily with voprost (29%) groups than for the control (3%) and uno- bimatoprost (n=16), latanoprost (n=15), or travoprost prostone (14%) groups (PϽ.05). Bimatoprost induced (n=17) or twice daily with unoprostone (n=16) or lu- significantly higher hyperemia scores than latanoprost, bricant drops (control group) (n=16). Blood-aqueous bar- unoprostone, and placebo (PϽ.01). rier status, which was assessed using a laser flare meter; intraocular pressure; the occurrence of angiographic cys- toid macular edema; and conjunctival hyperemia were Conclusion: Bimatoprost, latanoprost, and travoprost use evaluated. may lead to disruption of the blood-aqueous barrier in patients with pseudophakia and aphakia. Results: Mean flare values were significantly higher in the bimatoprost, latanoprost, and travoprost groups Arch Ophthalmol. 2005;123:186-192 EVERAL YEARS AFTER THE OB- CME has also been reported25 in patients servation that prostaglandin with pseudophakic or aphakic glaucoma (PG) F2␣ was a potent ocular being treated with bimatoprost, travo- hypotensive substance,1-5 la- prost, or unoprostone. tanoprost, unoprostone, tra- To the best of our knowledge, there are Svoprost, and bimatoprost were devel- no published clinical studies that com- oped and became widely used in the pare the safety of topical PG analogues in treatment of primary open-angle glau- patients with pseudophakia or aphakia. coma and ocular hypertension.5-7 Al- The primary objectives of this study are though these drugs have structural differ- to investigate the effects of PG analogues ences, they share similar characteristics and on the blood-aqueous barrier and to evalu- Author Affiliations: Glaucoma 5 Service, Department of are often referred to as PG analogues. ate the occurrence of angiographic CME Ophthalmology, University of Many adverse effects have been re- in patients with aphakic or pseudopha- Campinas, Campinas, São ported with PG analogues, including con- kic glaucoma. Paulo, Brazil (Drs Arcieri, junctival hyperemia, iris hyperpigmenta- Santana, Rocha, and Guapo); tion, and eyelash growth.3,8-17 However, METHODS Department of Ophthalmology, among the serious PG-induced adverse ef- School of Medicine, Federal fects are the disruption of the blood- University of Uberlândia, aqueous barrier and the development of This 6-month, randomized, masked-observer Uberlândia, Minas Gerais, Brazil cystoid macular edema (CME).18-25 Al- clinical trial was conducted at the Glaucoma (Dr Arcieri); and Department of though there have been several stud- Service of the University of Campinas. The Ophthalmology, University of 18-23 study was performed in accordance with the São Paulo (Dr Costa). ies of CME and anterior uveitis asso- Declaration of Helsinki after receiving ap- Financial Disclosure: Dr Costa ciated with latanoprost use in patients with proval from the ethics committee of the Uni- has received research grants pseudophakia and aphakia, the inci- versity of Campinas. Written informed con- from Alcon Inc, Novartis, and dence of these adverse effects is un- sent was obtained from each patient before Pfizer in the past. known. Angiographically documented inclusion in the study. (REPRINTED) ARCH OPHTHALMOL / VOL 123, FEB 2005 WWW.ARCHOPHTHALMOL.COM 186 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Patients were eligible for participation if they met the fol- lowing inclusion criteria: age older than 18 years, pseudopha- kia or aphakia, intraocular pressure (IOP) greater than the tar- get level (determined by V.P.C.), and a diagnosis of primary open-angle, pseudophakic, or aphakic glaucoma. Pseudopha- kic and aphakic glaucoma were defined in individuals with pseu- dophakia and aphakia with no history of glaucoma before cata- ract surgery. Patients were excluded from the study if they had Grade 0 (None) Grade 1 (Mild) a history of uveitis or CME, substantial ocular irritation at base- line, or a history of intraocular surgery or a laser procedure within 6 months of baseline. We also excluded individuals who had been treated with PG analogues in the past and those who had undergone other ocular surgery except for cataract or glau- coma. Finally, the presence of systemic disorders that could be associated with uveitis or CME (ie, diabetes mellitus and rheu- matologic diseases), pregnancy, lactation, and inadequate con- Grade 2 (Moderate) Grade 3 (Severe) traception (in females) were also exclusion criteria. If patients were eligible but were using any antiglaucoma Figure 1. Standard photographic chart used to grade conjuctival hyperemia. medications (except PG analogues), hypotensive therapy was discontinued. Required washout periods before the baseline visit were 4 weeks for ␤-adrenergic antagonists, 2 weeks for adren- ments, and ophthalmoscopy. The measurements were per- ergic agonists, and 5 days for cholinergic agonists and car- formed at the same time (10 AM) at all visits by a masked ob- bonic anhydrase inhibitors. A safety check with IOP measure- server. ment was required after 2 weeks for all patients undergoing a A laser flare meter (FM 500; Kowa Co Ltd, Tokyo, Japan) 4-week washout. At that time, patients whose IOPs had risen was used to determine the status of the blood-aqueous barrier to levels deemed to be detrimental were excluded from the study. at all follow-up visits by the same masked investigator (E.S.A.). No other IOP-reducing therapy was permitted during the study. The flare measurements were repeated 7 times, the highest and If both eyes of a patient were eligible for study inclusion, the lowest values were excluded, and the mean of the 5 remaining same medication was prescribed for both eyes, although only values was adopted as a “flare value” for statistical analysis. Ac- 1 eye per patient was included in the analysis. cording to information provided by the manufacturer, flare read- Study medications, packaged in commercially available, la- ings greater than 26 photon counts per millisecond (p/ms) are beled containers, were as follows: 0.005% latanoprost (Xala- indicative of a disruption in the blood-aqueous barrier. tan; Pfizer Inc, New York, NY), 0.03% bimatoprost (Lumigan; The IOP was measured using a Goldmann applanation to- Allergan Inc, Irvine, Calif), 0.004% travoprost (Travatan; Al- nometer by the same investigator (E.S.A.) at all visits. Three con Inc, Ft Worth, Tex), and 0.12% unoprostone (Rescula; measurements were performed in each eye, and the mean of 3 Novartis AG, Basel, Switzerland). Before dispensing, latano- values was used for statistical analysis. At baseline and during prost and unoprostone were stored refrigerated at 2°C to 8°C, follow-up, a masked investigator (A.S.) graded the conjuncti- and patients were instructed to conserve them under refrig- val hyperemia according to a scale. Each eye was compared with eration. Bimatoprost and travoprost were stored at room tem- standard photographs showing conjunctival hyperemia of grades perature. 0, 1, 2, and 3 (none, mild, moderate, and severe, respectively) To investigate the effects of benzalkonium chloride, the pre- (Figure 1); the scale included values of 0, 0.5, 1.0, 1.5, 2.0, servative used in all PG analogues, we included in the study a 2.5, and 3.0. control group of patients with pseudophakic and aphakic glau- Fluorescein angiography (FA) was performed to investi- coma who had reached IOP control after trabeculectomy with- gate the occurrence of CME at baseline and at 1 and 6 months out the need for medication. These patients received a lubri- of follow-up, or if a patient showed decreased visual acuity at cant drop (Tears Naturale; Alcon Inc) containing 0.01% any time during follow-up. If CME was detected, the patient benzalkonium chloride. was instructed to discontinue taking the medication, and a non- To preserve masking, a designated unmasked coordinator steroidal anti-inflammatory drug, diclofenac sodium (Voltaren; (A.S.)—who did not perform any study evaluations or assess- Novartis), was prescribed (4 times a day for 4 weeks). Then, ments—received randomization codes, dispensed the medica- FA was again performed to evaluate whether the CME had re- tions, and instructed the patients on how to use and store the solved. The FAs were analyzed by a single masked retina spe- containers. The Web program Research Randomizer v3.0 (http: cialist, who graded them as normal (no fluorescein leakage) or //www.randomizer.org) was used for random assignment. Pa- abnormal (fluorescein leakage compatible with CME). tients
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