New therapies could enhance retinal vein occlusion treatment

N/A

Issue: March 2011

ByPaolo Lanzetta, MD

Paolo Lanzetta

Recently, newer diagnostic tools and therapies for the treatment of retinal vein occlusion, or RVO, have been proposed. This condition has been an unmet concern for many years, leading to profound frustration for both physicians and patients.

RVO is a common cause of visual loss in the Western world. Population studies have estimated that there are about 520 cases of RVO per million population. These include 442 per million of branch retinal vein occlusion (BRVO) and 80 per million of central retinal vein occlusion (CRVO).

The natural history of RVO is often unfavorable. Untreated eyes with CRVO generally have poor visual acuity worse than 20/40, which declines further over time. Up to 34% of cases of nonischemic CRVO progressively convert to the ischemic form over a 3-year period. In ischemic CRVO, neovascular glaucoma develops in 23% of cases within 3 years. In nonischemic CRVO, macular edema resolves in 30% of cases, generally leaving permanent anatomic sequelae with visual loss. In BRVO, visual acuity may improve without intervention, although any improvement beyond 20/40 is uncommon. Up to 15% of patients develop macular edema at 1 year. Macular edema may resolve spontaneously in 18% to 41% of patients who present with this condition at baseline. BRVO may be bilateral in 10% of cases.

Guidelines applied before newer therapies became available considered laser photocoagulation as the only approach. Panretinal photocoagulation was considered in cases of iris or retinal neovascularization in ischemic CRVO. However, no proven early treatment altered the visual prognosis in established CRVO, and the main management problem was to differentiate ischemic CRVO from nonischemic CRVO. Grid photocoagulation was recommended in macular edema secondary to BRVO after a period of 3 to 6 months after the initial event. The reason for observation was that some eyes can improve spontaneously, with final visual acuity levels similar to those obtained after laser treatment. Also, laser photocoagulation can be applied only after the resolution of macular hemorrhages, which are a common complication of macular edema.

We are now in a revolutionary era in which newly labeled drugs safely and effectively treat macular edema secondary to both CRVO and BRVO and may possibly be used to induce regression of new iris and retinal vessels in combination with laser scatter photocoagulation. Recent studies on macular edema treated with intravitreal Lucentis (ranibizumab, Novartis/Genentech), such as BRAVO and CRUISE, and Ozurdex (dexamethasone biodegradable implant, Allergan), such as GENEVA, have shown that visual acuity can be improved by two to four lines, and this outcome can be maintained over time. Optical coherence tomography has become a mandatory tool both for assessing the entity and morphology of macular edema and for monitoring it during the course of therapy.

There is also evidence that the earlier we treat macular edema, the better results we can obtain in terms of visual acuity improvement. In a sub-analysis of the GENEVA study on Ozurdex, duration of macular edema was a major factor influencing visual acuity improvement after treatment. Each 1-month duration of macular edema had an effect on the odds ratio for achieving at least a three-line improvement in visual acuity 6 months after treatment. This decrease in odds was about 14%, 36%, 60% and 84% for 1, 3, 6 and 12 additional months, respectively. Similar effects may be expected with other pharmacotherapies.

Such a huge progress has a cost. Ophthalmology has moved from being an inexpensive field to being a specialty that uses considerable resources because new, effective therapies have become available where no therapies were previously available. In the third millennium, the burdens of blindness and low vision, including associated comorbidities such as depression and risk of falls, are far more expensive than the costs and benefits of new drugs for retinal diseases.

References:

Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol. 1984;98(3):271-282.

Brown DM, Campochiaro PA, Singh RP, et al; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1124-1133.

Campochiaro PA, Heier JS, Feiner L, et al; BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1102-1112.

Haller JA, Bandello F, Belfort R Jr, et al; OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-1146.

McIntosh RL, Rogers SL, Lim L, et al. Natural history of central retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010;117(6):1113-1123.

Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol. 1997;115(4):486-491.

Rogers S, McIntosh RL, Cheung N, et al; International Eye Disease Consortium. The prevalence of retinal vein occlusion: Pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010;117(2):313-319.

Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010;117(6):1094-1101.

Paolo Lanzetta, MD, can be reached at University of Udine, Department of Ophthalmology, Piazzale S. Maria della Misericordia; 33100 Udine, Italy; +39-0432-559-905; fax: +39-0432-559-904; e-mail: paolo.lanzetta@uniud.it.

Disclosure: Dr. Lanzetta is a consultant for Allergan and Novartis and is a patent holder with Iridex.