Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase. OBJECTIVE: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION. DESIGN AND SETTING: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212). MAIN OUTCOMES MEASURES: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out ("off-drug") period; and safety. STUDY POPULATION: Twenty-two participants aged 18 years or older with previous NAION. INTERVENTION(S): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site. RESULTS: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values. CONCLUSIONS: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.

The spectrum of iatrogenic intraocular injuries caused by inadvertent cannula release during anterior segment surgery.

OBJECTIVE: To evaluate the causes of inadvertent intraocular injuries resulting from the use of cannulas during anterior segment surgery. Method Retrospective review of all cases with inadvertent release of irrigation and viscoelastic cannulas during anterior segment surgery in 15 years. RESULTS: Inadvertent release of cannulas occurred in 9 of 10 230 cases of anterior segment surgery during a 15-year period. The incidence of cannula release was 0.88 per 1000 procedures per year. Twenty percent of the surgeons who performed anterior segment surgery in this period were involved in this unfortunate event. Six cases occurred during cataract extraction and 3 during penetrating keratoplasty or replacement of corneal graft. The latter 3 cases included posterior capsule rupture and vitreous loss. Macular scar in 2 (22%) of the 9 cases was associated with poor visual outcome of counting fingers at 2.1 to 3.0 m (P = .03). In all other surgeries, the cannula caused iris or anterior chamber angle injury without consequences. CONCLUSIONS: Inadvertent release of cannulas during anterior segment surgery is a rare, memorable, and unfortunate event. The severity of the injury may be related to the type of the surgical wound. In most cases, visual outcome is not compromised unless the cannula causes retinal disruption.

Intraoperative enoxaparin minimizes inflammatory reaction after pediatric cataract surgery.

PURPOSE: To evaluate the effect of intraocular infusion of enoxaparin, a low-molecular-weight heparin, on postoperative inflammatory response in pediatric cataract surgery. DESIGN: Prospective, comparative, consecutive interventional case series. METHODS: Seventeen consecutive eyes (11 patients) underwent pediatric cataract surgery in two tertiary medical centers. During the procedure, balanced salt solution with enoxaparin (40 mg in 500 ml) was infused into the anterior chamber. Eleven consecutive eyes (eight patients) received balanced salt solution without enoxaparin in the infusion bottle. The inflammatory response in the anterior chamber was compared between the two groups by semiquantification with slit-lamp biomicroscopy. Postoperative inflammatory complications, including fibrin formation, intraocular lens precipitates, anterior and posterior synechiae, cyclitic and pupillary membrane formation, and anterior subluxation of the intraocular lens, were also compared. The follow-up period after surgery was between 3 and 36 months (average 12.3 months). RESULTS: The number of cells and the degree of flare were minimal in the group with enoxaparin in the infusion bottle (P < .001). The total number of postoperative inflammation-related complications was also lower in the enoxaparin-treated group (P = .007). All corneas remained clear, and the endothelial cell count, which was performed in two patients, did not show substantial decrease in their density or changes in shape and size. No other enoxaparin-related complications were observed. CONCLUSIONS: Infusion of enoxaparin during pediatric cataract surgery may minimize the postoperative inflammatory response and decrease the number of postoperative inflammatory related complications. Enoxaparin should also be evaluated for cataract surgery in other conditions where postoperative inflammation may be exacerbated.