By Cheryl Guttman Krader,Reviewed by Francísco J. Rodriguez, MD
Results from major clinical trials support anti-VEGF therapy as first-line treatment for macular edema, secondary to retinal vein occlusion (RVO), and indicate that when patients respond, it may be possible to reduce the frequency of injections, particularly after one year.
However, more research is needed to better understand approaches for patients who do not respond optimally to anti-VEGF therapy and the long-term management of this chronic disease, said Francísco J. Rodriguez, MD.
“Loss of visual function in patients with central or branch RVO is mainly caused by macular edema,” said Dr. Rodríguez, scientific director, Fundación Oftalmológica Nacional, and chairman, Department of Ophthalmology, Universidad del Rosario School of Medicine, Bogotá, Columbia. “Treatment for these patients has been transformed with the use of intravitreal injection of anti-VEGF agents. But, RVO is a chronic disease and its management requires a patient-centric individualized approach that should be based on close follow-up.”
Dr. Rodríguez added that the prognosis is improved when there is early intervention and that it is important to continue seeing patients over the long-term. More studies are needed to see how physicians might optimize best-corrected-visual acuity for these patients with regimens that are safe and reduce treatment cost and burden.
Expert panels reviewing the available scientific evidence have developed algorithms that provide step-by-step recommendations for evaluation and management of macular edema secondary to RVO.
Image 1: Right eye of a 70-year-old male with central retinal vein occlusion. The OCT shows increased thickness (CRT 441 um), lost foveal depression, and cystoid macular edema. (Image provided by Francisco J. Rodriguez, MD)
According to algorithms published in 2015 by a group of 11 Canadian retinal specialists [Berger AR, et al. Ophthalmologica. 2015;234(1):6-25], initial treatment for branch retinal vein occlusion (BRVO) is guided by the presence or absence of neovascularization and macular edema, while macular edema is considered for central retinal vein occlusion (CRVO) patients.
The panel recommended initial laser therapy for patients with BRVO and neovascularization with adjunctive use of an anti-VEGF agent if vitreous hemorrhage is also present. Initiating treatment with monthly anti-VEGF injections was recommended for eyes with macular edema and vision loss.
Image 2: OCT of 70-year-old male's right eye following six anti-VEGF monthly injections. The thickness decreased to CRT 259 um, best-corrected visual acuity at last follow-up was 20/30. (Image provided by Francisco J. Rodriguez, MD)
When patients start anti-VEGF therapy, the algorithm recommends evaluating response after three monthly injections. It proposes the use of intravitreal corticosteroids as second-line treatment for suboptimal responders with CRVO and grid laser for BRVO patients.
Freund and colleagues conducted a literature review and consensus recommendations on treat-and-extend regimens with anti-VEGF agents in retinal diseases [Freund KB, et al. Retina. 2015;35(8):1489-1506]. Although they found there were too few published studies using the treat-and-extend approach in eyes with RVO-related macular edema to make specific recommendations, they felt from clinical experience that their proposed algorithm was applicable.
The panel recommended that monthly treatment should be maintained until maximum response was observed as defined by complete resolution of subretinal and intraretinal fluid or no further decrease in subretinal or intraretinal fluid for at least two consecutive visits in the absence of new retinal hemorrhage.
Thereafter, the treat-and-extend approach could be initiated and continued as long as the edema was resolved–or at least stable–and there was no new hemorrhage. The panel recommended increasing the treatment intervals by two-week increments with a maximum extension to 12 weeks. Decisions on adjusting the treatment interval in the event of disease reactivation with deterioration depend on the severity of the relapse.
In a paper published in 2016, Ashraf et al. developed what they termed “a simplified modified” treatment algorithm for CRVO based on review of large published studies of ranibizumab, aflibercept, corticosteroids, and laser therapy [Ashraf M, et al. Eye (Lond). 2016;30(40:505-514]. Their algorithm recommends initiating therapy with three monthly anti-VEGF injections.
Patients then are assessed with optical coherence tomography for changes in macular edema and categorized as early responders if they have fluid resolution, nonresponders, or partial responders. The early responders may be treated on an as-needed basis, but should be followed monthly through the first year. Thereafter, the follow-up interval can be extended gradually, but should not exceed three months.
According to the algorithm, partial responders should receive three more monthly anti-VEGF injections. Switching to another anti-VEGF agent or treatment with the dexamethasone implant (Ozurdex, Allergan) is recommended for partial responders with persistent fluid after six injections and for patients with no response after three injections.
Francísco J. Rodriguez, MD
This article is based on a presentation given by Dr. Rodríguez at the 2017 Retina World Congress. Dr. Rodríguez is a consultant and on the speaker bureau for Novartis/Alcon Laboratories, Allergan, and Bayer. He receives research funds from Novartis, and is on the speaker bureau for Topcon and Nidek.