Treatment options show promise for retinal vein occlusion

Attention is currently focused more on pharmacological than surgical methods because of the new drugs available, surgeon says.

Most of the attention within retinal research today is focused on age-related macular degeneration and diabetic retinopathy, but retinal vein occlusion is a major health problem, one physician said.

Julia A. Haller

“Both branch and central retinal vein occlusion (BRVO and CRVO, respectively) are highly prevalent. They are particularly common in patients 75 years of age and older, a sector of the population which is growing in the developed world. In the U.S. alone, we expect about 130,000 new cases per year, which approaches the rate of exudative AMD,” Julia A. Haller, MD, said at the Euretina meeting in Vienna.

Fortunately, Dr. Haller said, there are now several promising options for the treatment of this condition.

Surgical role still uncertain

There are two main lines along which treatment for vein occlusion has evolved, Dr. Haller said. Surgical decompression therapy includes options such as laser anastomosis, branch vein sheathotomy and optic neurotomy. Recently, attention has focused more on pharmacological therapy because of drugs such as steroids and anti-VEGF agents. Both of these options appear to be more promising than thrombolytics, which were historically the first medications used for vein occlusion.

“When we look at surgical approaches, we are mostly talking about case reports and clinical series, although they are relatively large series. Some more controlled and evidence-based studies are currently ongoing,” Dr. Haller said.

However, results are somewhat inconsistent, with a variable rate of success. Therefore, the role of the surgical approach continues to be uncertain, she said.

Steroid treatment

Clinical reports on steroid treatment of macular edema in retinal vein occlusion go back some years, with a particular interest in 2001 and 2002, when reports on intravenous pulse steroids therapy and intravitreal steroid injection in CRVO were published, Dr. Haller said.

The first prospective, controlled trial on the use of steroids for retinal vein occlusion was focused on the dexamethasone posterior segment drug delivery system Posurdex, developed by Oculex and now produced by Allergan.

“Posurdex is micronized dexamethasone in a biodegradable copolymer of polylactic-glycolic acid matrix and is delivered into the vitreous through an injector. The implant ensures sustained intraocular delivery of the drug over a course of several weeks or months,” Dr. Haller said.

In the phase 3 trial, both the 350 µg and 700 µg doses were used.

The study enrolled a mixed group of patients with persistent macular edema that did not respond to other therapies. The largest number of patients was affected by diabetic retinopathy (161), but there were also a large number of patients with retinal vein occlusion (101), BRVO (59) and CRVO (42).

The overall study efficacy in terms of BCVA showed a highly statistically significant difference between treated patients and controls. There was improvement in contrast sensitivity and in fluorescein leakage. Marked anatomic changes in retinal thickness were visible by optical coherence tomography. The control group gained 11 µm vs. the 142-µm decrease of the high 700-µg dose group and the 61-µm decrease of the low 350-µg group.

“If we look at the total [retinal vein occlusion] group, they gained on average about 36 µm, but when treated with the high 700-µg dose, they lost on average 156 µm. When we look at subgroups, we understand that most of this was driven by the tremendous decrease in the central retinal vein occlusion subset,” Dr. Haller said. “There was also a decrease in the BRVO subset, but it was somewhat offset by the fact that, in BRVO, a number of the patients had a spontaneous improvement, which demonstrates that a control group is indeed important.”

Visual acuity improved, particularly in the BRVO group, but not in a statistically significant way compared with controls. According to Dr. Haller, this may have been at least in part because there were not enough eyes in the study with retinal vein occlusion to detect a significant difference, and the edema was longstanding, chronic and resistant.

“The phase 3 study attempts to correct for this issue by enrolling many more patients, all of whom have shorter duration vein occlusion,” she said.

Anti-VEGF therapy

Dr. Haller participated in a study on anti-VEGF ranibizumab as a treatment for macular edema due to vein occlusion at Johns Hopkins University. The study enrolled two groups of patients — 20 with CRVO and 20 with BRVO. In each group, patients were randomly assigned to receive higher (0.5 mg) or lower (0.3 mg) doses of ranibizumab, for a total of three doses at 1-month intervals.

“In CRVO, after three injections, almost every eye had some improvement, but the individual response was variable. In some eyes, there was an immediate improvement, which persisted over time. In some other eyes, the improvement was more gradual but regular, and in other cases, it had a very irregular, up-and-down pattern. BRVO cases seemed to improve more reliably, although to a lesser extent,” Dr. Haller said.

The mean improvement in visual acuity was 14 to 17 letters in the CRVO group and 10 to 18 letters in the BRVO group.

“In both groups, more than three injections seem to be needed, and the duration of the effect appeared to be longer with the higher 0.5-mg dose,” Dr. Haller said.

Currently, according to www.clinicaltrials.gov, 47 registered clinical trials for retinal vein occlusion are ongoing.

“We are waiting for results that will be coming out this year and next year, which include the standard of care vs. corticosteroid for retinal vein occlusion (SCORE) study, the Posurdex study, the Lucentis (CRUISE, BRAVO) and the Macugen studies, the Retisert implant study and the Alimera implant study, among others. At the same time, different types of surgery are under investigation,” she said. – by Michela Cimberle

References:

• Campochiaro PA, Hafiz G, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther. 2008;16(4):791-799.
• Greenberg PB, Martidis A, et al. Intravitreal triamcinolone acetonide for macular edema due to central retinal vein occlusion. Br J Ophthalmol. 2002;86(2):247-248.
• Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. 2002;240(9):782-783.
• Shaikh S, Blumenkranz MS. Transient improvement in visual acuity and macular edema in central retinal vein occlusion accompanied by inflammatory features after pulse steroid and anti-inflammatory therapy. Retina. 2001;21(2):176-178.

• Julia A. Haller, MD, can be reached at Wills Eye Institute, 840 Walnut St., Philadelphia, PA 19107, U.S.A.; +1-215-928-3073; fax: +1-215-928-3853; e-mail: jhaller@willseye.org.