Retinal Vein Occlusion (RVO) Study

Retinal vein occlusion (RVO) trails only diabetic retinopathy as the most common retinal vascular disease, with an estimated prevalence of 0.8% for patients older than 40 years. Depending on the location of the occlusion, RVO can be divided into central RVO, branch RVO, and hemi-RVO. Because occlusions tend to occur in the more proximal region of the vessel, involvement of the macula is common, often resulting in macular edema and compromised vision in the affected eye.

Anti–vascular endothelial growth factor (VEGF) has been shown to have a beneficial effect in the management of macular edema secondary to RVO. However, there remains a subset of eyes that demonstrate an incomplete response to anti-VEGF therapy with persistent edema, despite frequent intravitreous injections. A recent pilot study explored the use of topical dorzolamide hydrochloride–timolol maleate, a potent aqueous suppressant, as an adjunct therapy in patients with neovascular age-related macular degeneration (AMD) who were incomplete responders to anti-VEGF injections. Combining the topical therapy with anti-VEGF seemed to have a beneficial anatomical effect.

This study hypothesized that similar benefits could potentially be seen in eyes with persistent macular edema secondary to RVO, despite frequent anti-VEGF therapy.

Study Design

This single-arm prospective interventional study took place at the Retina Service of Wills Eye Hospital and the associated satellite offices of Mid Atlantic Retina from April 4, 2016, to June 4, 2017. Eyes with either central or branch RVO that were incomplete responders to intravitreous anti-VEGF therapy were prospectively identified. Three major measurements were obtained and included central foveal thickness (CFT), thickest macular cut, and central subfield thickness (CST).

Anatomical Outcomes

• A significant decrease in CFT was observed at the final study visit when compared with the enrollment visit.
• There was also a significant decrease in CFT from the first visit after enrollment to the final visit (P = 0.02).
• There was a significant decrease in mean thickest macular cut observed at the final visit when compared with the enrollment visit.

Visual Acuity and Intraocular Pressure Outcomes

• There was no significant change in visual acuity from the preenrollment visit to the enrollment visit (P = 0.92).
• There was an improvement in visual acuity, which trended toward significance in the two study visits when compared with the enrollment visit.
• There was no significant decrease in mean IOP at the final visit when compared with the enrollment visit.

This pilot study suggests a potentially beneficial effect of dorzolamide–timolol in eyes with RVO resistant to anti-VEGF therapy. The implications of such findings are relevant because more than 10% of eyes may be resistant to anti-VEGF therapy. The underlying cause of this resistance is believed to be a result of anti-VEGF receptor upregulation, which is caused by both the anti-VEGF agent itself and the ischemic state of the retina.

How aqueous suppressants may benefit these eyes is not well understood. It is possible that it could be related to how the anti-VEGF agent is cleared from the eye. There is some evidence that anti-VEGF agents may in part be cleared from the vitreous humor via outflow through the anterior chamber. Consequently, suppression of aqueous production might decrease not only aqueous outflow but also the rate of anti-VEGF removal from the vitreous humor, effectively increasing the half-life.

In addition to the hypothesized decreased clearance of anti-VEGF, there is also the possibility that dorzolamide–timolol has direct beneficial effects through the underlying mechanism of the two chemical agents. Studies have shown that b-receptor blockade could suppress VEGF upregulation.

This pilot study has several limitations, most notably the small sample size. Larger prospective trials will be required to verify the potential influence of topical aqueous suppressants in cases of RVO resistant to anti-VEGF therapy. The results obtained in this small pilot study, coupled with previous results in eyes with neovascular AMD, warrant larger clinical trials to assess the true effect of topical aqueous suppressants as an adjunct to anti-VEGF therapy in incomplete responders.

DOI: 10.1097/ICB.0000000000000752