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Anti-VEGF and Other Therapies for Macular Edema due to Central Retinal Vein Occlusions

Jonas, Jost B. MD

The Asia-Pacific Journal of Ophthalmology: May 2019 - Volume 8 - Issue 3 - p 195–196
doi: 10.22608/APO.2019112

From the Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University, Mannheim, Germany.

Submitted May 20, 2019; accepted May 31, 2019.

The author has no funding or conflicts of interest to declare.

Reprints: Jost B. Jonas, Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University, Mannheim, Germany. Email:

In their meta-analysis of the current outcomes of anti-vascular endothelial growth factor (VEGF) therapy in the treatment of macular edema secondary to central retinal vein occlusions (CRVOs), Spooner et al1 reported that the anti-VEGF therapy is effective for improving the vision prognosis of CRVO with a good safety record. The results of this meta-analysis agree with previous multicenter randomized controlled trials, recent surveys of the current literature, and other investigations.2-15

Apart from the conclusion of Spooner et al that further larger prospective studies are warranted to investigate the potential impact of anti-VEGF therapy on ischemia in the long term, other aspects in the etiology and therapy of cystoid macular edema may worth to be discussed.

First, the conventional term “central retinal vein occlusion” may be a misnomer since it is not an occlusion but just a retinal venous outflow impediment. In almost all patients with a CRVO, there is still considerable blood flow through the retinal circulatory blood system including the central retinal vein. In the case of a vein occlusion, the lack of outflow would prevent an inflow of blood into the eye, hence a secondary blockade of the central retinal artery would occur.

Second, care has to be taken in the interpretation of some previous trials, which concluded that an early therapy as compared with a late therapy had better outcomes. This conclusion might have partially been due to a bias caused by the possibility of a spontaneous improvement of the disorder.16,17 Not all patients who were included in the control group and who experienced a marked spontaneous improvement of vision might have attended the follow-up visits. Since a spontaneous improvement of macular edema in retinal vein occlusions occurs more often in the early course of the disease than later, the risk of losing control patients with a spontaneous improvement in the early-therapy group will be higher than that in the late-therapy group. As losing patients with a good outcome in the control group worsens their overall mean outcome, the difference between the control group and the study group increases in favor of the study group. This might have influenced the conclusion that early therapy was better than late therapy. This has clinical importance because Hayreh et al18 found that in eyes with an initial visual acuity of 20/70 or worse, visual acuity improved in 47% of the eyes with non-ischemic CRVO, and in 23% of the eyes with ischemic CRVO. These figures may illustrate that a substantial number of eyes would be treated (and exposed to the side-effects) unnecessarily if all eyes with retinal vein occlusion underwent early intravitreal medication.

Third, when reviewing the actual therapy of retinal vein occlusions, one may remember that it was Prof. Sohan Hayreh who, against the strong opinion of the former scientific mainstream, showed that panretinal laser coagulation was not the best of all available options for the therapy of CRVO.18

Finally, although the release of VEGF and interleukin-6 leading to elevated vascular permeability and vasodilation may be pathogenetically important steps for the development of macular edema in eyes with CRVO, one might have neglected the potential role of an increased cerebrospinal fluid pressure, in association with and induced by, an elevated arterial blood pressure that may play in the etiology of the disease.19

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© 2019 by Asia Pacific Academy of Ophthalmology