Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage

PURPOSE: To evaluate the safety of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Pooled efficacy data are presented in a companion article in this issue of The Journal. METHODS: Subjects with vitreous hemorrhage > or = 1 month, severe at entry and best corrected visual acuity (BCVA) worse than 20/200 in the study eye were randomized to 7.5 IU, 55 IU, 75 IU ovine hyaluronidase, saline, or no injection. Assessments occurred on day 1, week 1, months 1, 2, 3, 6, and then every 6 months for as long as 32 months. Assessments included history, ocular symptoms, adverse events, BCVA, intraocular pressure, external eye examination, slit-lamp biomicroscopy, fundus examination, B-scan ultrasonography, and fundus photography. RESULTS: Of 1362 subjects in the safety population, 1344 received hyaluronidase or saline and 18 no treatment. Iritis was the most common ocular adverse event, occurring in 33.3%, 62.1%, 58.9%, and 62.1% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. In eyes with more than mild iritis, a dose response was observed: 8.9%, 20.2%, 33.7%, and 39.7% of saline, 7.5 IU, 55 IU, and 75 IU-treated subjects, respectively, were noted to have moderate or severe iritis. Retinal detachments (RDs) were reported in 9.5% of study eyes: 26 (6.9%), 22 (11.1%), 35 (9.3%), and 45 (11.5%) in the saline, 7.5 IU, 55 IU, and 75 IU-treated subjects. Overall, 1.8% of study eyes had rhegmatogenous RD: 1.1%, 2.5%, 1.6%, and 2.3% of saline, 7.5, 55, and 75 IU treated subjects. Cataracts occurred similarly across treatment groups. No injection-related infectious endophthalmitis was reported. CONCLUSIONS: No serious safety issues were reported after a single intravitreous injection of ovine hyaluronidase. RD incidence was not statistically different between groups. Iritis manifesting as an acute self limited inflammation was the most common adverse event, occurred in a dose response fashion, but was not noted to result in a serious adverse event in any hyaluronidase treated eye