August 15, 2012 — Significantly more patients who received ocriplasmin experienced resolution of vitreomacular adhesions and closure of macular holes than patients who received placebo, according to results from a study published in the August 16 issue of the New England Journal of Medicine. Despite the statistical significance of the results, only a small percentage of patients stand to benefit. Just 13.4% of the patients receiving ocriplasmin achieved nonsurgical resolution of vitreomacular adhesion at day 28.
Peter Stalmans, MD, PhD, an ophthalmologist from the Department of Ophthalmology at Universitaire Ziekenhuizen Leuven in Belgium, and colleagues conducted 2 multicenter, randomized, double-blind, phase 3 clinical trials in which they compared a single intravitreal injection of ocriplasmin (125 μg) with a single placebo injection in patients with symptomatic vitreomacular adhesion.
"[O]ur study shows that enzymatic vitreolysis represents a means to resolve vitreomacular traction and to close macular holes. Intravitreal injection of ocriplasmin was superior to injection of placebo in altering the vitreoretinal interface of affected eyes, although it was accompanied by some, mainly transient, ocular adverse events," the authors write.
Both studies were conducted between December 2008 and September 2009. The primary end point was the percentage of eyes that on day 28 experienced nonsurgical resolution of vitreomacular adhesion.
Secondary end points included the percentage of eyes that experienced total posterior vitreous detachment and nonsurgical macular hole closure at day 28, whether or not the patient required a vitrectomy, and improvement in best-corrected visual acuity (BCVA).
A total of 652 patients were enrolled in the study; 464 were randomly assigned to receive a single intravitreal injection of ocriplasmin 125 μg, and 188 were assigned to receive a placebo injection. Patients were assessed at baseline, on injection day, and on days 7, 14, 28, 90, and 180 after the injection. Investigators could recommend vitrectomy at any point if they felt the patient's condition was deteriorating or if it had not improved at week 4.
The percentage of patients who experienced nonsurgical resolution of the vitreomacular adhesion at day 28 was significantly higher in the ocriplasmin group (13.4%) compared with the placebo group (3.7%; odds ratio [OR], 4.27; 95% CI, 1.89 - 11.32; P < .001).
Among patients without an epiretinal membrane, 37.4% of those who received ocriplasmin experienced nonsurgical resolution of vitreomacular adhesion compared with 14.3% of patients who received the placebo (OR, 3.79; 95% CI, 2.09 - 7.22; P < .001)
Among patients with an epiretinal membrane 8.7% of those who received ocriplasmin experienced nonsurgical resolution of vitreomacular adhesion compared with 1.5% of patients who received placebo (OR, 6.20; 95% CI, 0.93 - 265.068; P = .046).
The percentage of eyes that experienced nonsurgical closure of macular holes at day 28 was higher in the ocriplasmin group (40.6%) than in the group that received the placebo (10.6%; OR, 5.94; 95% CI, 20.9 - 21.01; P < .001). The percentage was still higher in the ocriplasmin group at the end of the study (40.6% vs 17.0% with placebo; odds ratio, 3.45; 95% CI, 1.40 - 9.49; P = .004).
The percentage of patients who experienced total posterior vitreous detachment at day 28 was higher in the ocriplasmin group (13.4%) than the placebo group (3.7%; OR, 4.27; 95% CI, 1.89 - 11.32; P < .001).
The percentage of patients who underwent vitrectomy was lower in the ocriplasmin group (17.7%) than in the placebo group (26.6%; OR, 0.61; 95% CI, 0.40 - 0.94; P = .02). The corresponding values for patients who did not undergo vitrectomy were 9.7% compared with 3.7%.
Overall, BCVA acuity improvement of 3 or more lines on the eye chart was attained in a higher percentage of patients who received ocriplasmin (12.3%) than in patients who received placebo (6.4%; OR, 2.09; 95% CI, 1.08 - 4.41; P = .02).
More patients in the ocriplasmin group (68.4%) experienced ocular adverse events compared with patients in the placebo group (53.5%; P < .001). Ocular adverse events included conjunctival hemorrhage and reports of vitreous floaters, photopsia, or injection-related eye pain. The incidence of serious ocular adverse events including retinal tear or detachment was 7.7% in the group given ocriplasmin compared with 10.7% in the group given the placebo (P = .26).
"This New England Journal of Medicine paper highlights data showing ocriplasmin's potential to become the first pharmacological option for the treatment of symptomatic [vitreomacular adhesions] and macular holes," coauthor Julia Haller, MD, told Medscape Medical News. "An in-office injection would be a new and possibly earlier alternative treatment for the vitreoretinal surgeon to offer to patients with these sight threatening disorders. Ocriplasmin represents a potential new treatment paradigm for the retina community and for our patients with [vitreomacular adhesions] and macular holes.” Dr. Haller is ophthalmologist-in-chief of the Wills Eye Institute in Philadelphia, Pennsylvania.
K. Bailey Freund, MD, a clinical correspondent for the American Academy of Ophthalmology, commented on the study in a telephone interview with Medscape Medical News. Dr. Freund is a retina specialist with Vitreous-Retina-Macula Consultants of New York and a clinical associate professor of ophthalmology at New York University School of Medicine in New York City.
"I'm very anxious that this gets approved.... I think it's something that will benefit patients that might otherwise need to have a more invasive surgical procedure," said Dr. Freund, noting that he sees several patients per week that might benefit from ocriplasmin.
Dr. Freund said that it is disappointing that ocriplasmin does not work in most patients, and that patients should be made aware of this when discussing treatment options.
"This seems to work best when the holes are very small and when patients do not have...epiretinal membrane," Dr. Freund said. "Once an epiretinal membrane has formed, and once the hole has gotten rather large, you've probably missed the opportunity for this to benefit the patient, and then...they're much more likely to need vitrectomy," Dr. Freund explained.
The studies were funded by Thrombogenics. The authors report a variety of relationships with Thrombogenics and other companies involved with ophthalmologic drugs. Two authors are employed by Thrombogenics and hold stock or stock options in Thrombogenics as part of an employee stock option plan. Complete information can be found on the journal's Web site. Dr. Freund disclosed no relevant financial relationships.
N Engl J Med. 2012;367:606-615.
Medscape Medical News © 2012 WebMD, LLC
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Cite this: Ocriplasmin Useful for Vitreomacular Adhesions, Macular Holes - Medscape - Aug 15, 2012.
