Several treatment options have been advocated for the management of macular edema secondary to CRVO, including grid laser photocoagulation and intravitreal injections of corticosteroids and anti-VEGF molecules (14–20). However, RVO in patients aged < 50 years has been poorly investigated.
To date, only two previous studies have addressed the management of macular edema secondary to CRVO in patients aged < 50 years, the first of which concluded that dexamethasone implants could offer significant improvements in half of the patients after a 12-month follow-up. However, dexamethasone drawbacks were evident in approximately one third of the patients who developed intraocular pressure elevation as a treatment complication (18). The other more recent study has adopted intravitreal injection with anti-VEGF (21). The authors investigated the effectiveness of ranibizumab for the management of ME, with no exclusion of cases with ischemic-type CRVO. To our knowledge, this is the first study to assess the effect of intravitreal anti-VEGF injection in patients aged < 50 years with selectively nonischemic CRVO. Furthermore, this study is the first to compare the two approved anti-VEGF injections in such patient categories. This study demonstrated a significant steady elevation of BCVA and reduction of CST from baseline to 12 months.
In our study, the change in BCVA over the study period was approximately + 7.6 and + 4.85 letters in the ranibizumab and aflibercept groups, respectively. Consistent with our findings, the study by Chatziralli et al. (2017) found that ranibizumab was superior to aflibercept in the management of CRVO and showed a higher change in BCVA (20). However, although the authors included cases aged > 50 years and those with ischemic CRVO, our figures of improvement were inferior to their reported figures; they found that the change in BCVA from baseline to 12 months was approximately + 9.0 and + 8.3 letters in the ranibizumab and aflibercept groups, respectively. This may be attributed to their higher baseline figures as their study patients started with mean BCVA values of 66.2 and 61.3 letters compared with 48.3 and 55.9 letters in the present study. When expressing the improvement in terms of percentages, the percentages of improvement were 13.6% and 13.5% in their study compared with 15.7% and 8.7% in ours for the ranibizumab and aflibercept groups, respectively. The worse aflibercept efficacy in our cohort is consistent with that of Lehmann-Clarke et al. (2015) who reported that aflibercept yields better outcomes in ischemic cases (22).
In patients aged < 50 years, Battaglia Parodi et al. (2020) (21) reported approximately 23% BCVA improvement after 1-year ranibizumab treatment. Their superior outcome may be related to the higher number of injection times as they injected their patients up to nine times during the study, whereas in the present study, the maximum number of injection times was six. At the end of the follow-up period, it was found that 40% and 50% of the patients showed macular edema resolution in the ranibizumab and aflibercept groups, respectively. This is comparable to the study of Battaglia Parodi et al. (2020) (21) who found a macular edema resolution rate of 63% when using ranibizumab and Chatziralli et al. (2017) (20) who reported macular edema resolution rates of 55.9% and 50% in the ranibizumab and aflibercept groups, respectively, after a similar period. This may be related to the higher number of injection times since Chatziralli et al. (2017) (20) reported mean values for injection times of 6.8 ± 1.3 and 6.1 ± 2.0 for the two groups compared with 5.40 ± 0.8 and 4.90 ± 1.2 in the present study.
Of note, in this study, both treatment arms did not show significant differences concerning BCVA improvement, CST reduction, macular edema resolution, ellipsoid zone disruption, or the needed injections over the follow-up period. This is consistent with the findings of Chatziralli et al. (2017) (20) and the earlier study conducted by the Diabetic Retinopathy Clinical Research Network (2015) (23) who reported comparable effectiveness of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema.
Our finding is consistent with what was previously presumed that the VEGF load found in RVO is highly exceeding that of diabetic retinopathy or age-related macular degeneration (24), and thus, such greater VEGF load may overcome the variations in the anti-VEGF types (20).
This study has some limitations. It is limited by the absence of a control group, the short follow-up period, and the relatively small sample size, which was attributed to the relative difficulty in including patients aged < 50 years. However, the study is strengthened by its prospective design, selecting a particular category of patients and comparing two FDA-approved treatments.
Conclusion: Ranibizumab and aflibercept showed a comparable promising outcome in the management of macular edema secondary to nonischemic CRVO in patients aged < 50 years.