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Additional options for treating macular edema secondary to retinal vein occlusion
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Retinal vein occlusion has been a frustrating condition for years because limited therapeutic options were available and possible dramatic evolutions could cause issues such as ocular neovascularization and macular edema.
Laser photocoagulation or observation has been the standard of care since the 1980s for treating macular edema secondary to branch retinal vein occlusion or central retinal vein occlusion, respectively. In most cases, patients were dissatisfied with the approaches because visual acuity did not improve to normal levels. However, notably, 63% of eyes treated with laser improved by three lines of vision or more compared with 36% of control eyes at 3 years. Still, 40% of eyes had visual acuity less than 20/40, and 12% of eyes had visual acuity less than 20/200. On average, visual acuity improved by 1.3 lines at 3 years.
Paolo Lanzetta
Intravitreal drugs showed significantly improved results. For example, in the BRAVO trial, patients treated with Lucentis (ranibizumab, Genentech/Novartis) gained an average of almost four lines at 1 year. This positive outcome was maintained for almost 3 years during the extension phase called HORIZON, although patients tended to lose some gained visual acuity when transitioned to an as-needed regimen after an initial fixed monthly dosing of 6 months.
Similarly, patients with macular edema secondary to CRVO may now experience, for the first time, improved vision when treated with ranibizumab. In the CRUISE study, the average gain after 6 months of monthly injections was about three lines. This outcome slightly decreased to two lines gain during the extension HORIZON phase with an as-needed regimen.
Other options
Ozurdex (dexamethasone intravitreal implant, Allergan) is another available option. In the GENEVA trial, patients treated with this potent steroid showed an early visual acuity improvement with an increase of about two lines 2 months after implantation, with some decrease to about one line at 6 months. Re-treatment with a second exposure to the drug was associated with similar outcomes at an additional 6 months. The rationale for the use of steroids comes from the evidence that inflammation is a key component of macular edema during retinal vein occlusion and correlates with its severity.
Encouraging results are also reported with Eylea (aflibercept, Regeneron/Bayer HealthCare) at 6 months of follow-up for both conditions. This compound is still under evaluation and is not approved by the U.S. Food and Drug Administration or the European Medicines Agency for the treatment of retinal vein occlusion.
With these unique drugs and outcomes available, intravitreal therapy should now be considered the standard approach to patients with macular edema secondary to retinal vein occlusion. However, there are still many questions besides the dilemma of which drug to use for which patient. We should also consider the burden of pharmacotherapy in terms of number of injections and treatment regimen (fixed or as-needed), the type of patient (age, degree of ischemia), the right time to start treatment, and the possible role of laser as either monotherapy or combination therapy.
Among commercially available drugs, ranibizumab seems to provide the best outcomes in terms of visual acuity, but we should consider that different populations were enrolled in the different studies. For example, the average duration of macular edema may be an important factor with respect to chances for visual acuity improvement. In the GENEVA study, only 15% and 17% of patients treated with dexamethasone implant for CRVO or BRVO, respectively, had macular edema duration of less than 90 days, whereas in the CRUISE and BRAVO studies, these figures were 72% and 67%, respectively, for patients treated with ranibizumab. The COMO study is currently ongoing and will compare head-to-head dexamethasone implant and ranibizumab in the same population.
Prompt treatment with pharmacotherapy may significantly influence visual acuity outcomes. In patients enrolled in the GENEVA study, each 1-month increase in macular edema duration was associated with a significantly lower likelihood of achieving a visual acuity improvement of 15 letters or more, and longer macular edema duration at the time of first treatment with dexamethasone implant was associated with a significantly lower likelihood of achieving clinically meaningful improvements in vision.
A specific challenge is seen with younger patients because although they may respond better to intravitreal therapy or even no treatment, the ocular condition is often associated with underlying systemic inflammatory conditions that deserve a careful investigation by dedicated specialists.
No information from the cited studies is available on the role of retinal ischemia associated with macular edema and how treatment with anti-VEGF agents or steroids may influence this specific and threatening condition. However, it has been observed that anti-VEGFs can cause a temporary regression of new retinal and iris vessels.
Laser is the mainstay for eyes that develop neovascularization and may still be an option for specific subtypes of macular edema before intravitreal therapy is eventually started in an attempt to reduce the burden of treatment. Data from the control groups of the cited trials suggest that patients who have been first treated with laser and are then switched to intravitreal therapies show visual acuity improvement, although generally to a lesser extent than those patients who receive anti-VEGF or steroid from the beginning.
Safety
Finally, although intravitreal injection is currently one of the most performed ocular procedures with acknowledged safety, it may be associated with devastating consequences such as endophthalmitis. In a personal review of recent randomized trials on 9,914 eyes, the mean incidence of endophthalmitis per patient and per injection was 0.39% and 0.04%, respectively. Every treating physician should adopt a risk mitigation process in order to limit adverse events to the minimum frequency and severity and to improve outcomes.
Newer therapy options and strategies have expanded the treatment armamentarium of macular edema due to retinal vein occlusion and, more importantly, have provided superior benefits for our patients. Physicians must still improve their diagnostic and therapeutic skills in order to identify which patient may benefit best from which treatment plan.
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.
Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012;119(5):1024-1032.
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.
Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology. 1995;102(10):1425-1433.
Haller JA, Bandello F, Belfort R Jr, et al; Ozurdex GENEVA Study Group, Li J. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology. 2011;118(12):2453-2460.
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.
Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012;119(4):802-809.
Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol. 1997;115(4):486-491.
Noma H, Funatsu H, Mimura T, Harino S, Hori S. Aqueous humor levels of vasoactive molecules correlate with vitreous levels and macular edema in central retinal vein occlusion. Eur J Ophthalmol. 2010;20(2):402-409.
Noma H, Funatsu H, Yamasaki M, et al. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond). 2008;22(1):42-48.
Yeh WS, Haller JA, Lanzetta P, et al. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant. Ophthalmology. 2012;119(6):1190-1198.
For more information:
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; email: paolo.lanzetta@uniud.it.
Disclosure: Lanzetta is a consultant for Allergan, Bayer and Novartis.