Visual Acuity Outcomes in CRVO Dependent on Resolution of Macular Edema Profile

Visual acuity outcomes in eyes with central retinal vein occlusion (CRVO) may depend on the resolution profile of macular edema (ME) over time, according to a recent post-hoc analysis.

Led by Sobha Sivaprasad, National Institute of Health Research Biomedical Research Centre, investigators assessed best-corrected visual acuity (BCVA) outcomes at 100 weeks depending on macular fluid resolution patterns by 52 and 100 weeks among patients receiving anti-vascular endothelial growth factor therapy (anti-VEGF) for CRVO-related macular edema.

A post-hoc analysis was performed of the prospective, 3-arm, double-masked, randomized noninferiority trial Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO).

LEAVO evaluated intravitreal aflibercept (2.0 mg/0.05 mL), bevacizumab (1.25-mg/0.05 mL), or ranibizumab (0.05 mg/0.05 mL) in adult patients (≥18 years old) with CRVO-related ME. Patients had a BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 19 to 78 in the study eye (approximate Snellen equivalent, 20/32 to 20/400) and CST 320 μm or greater due to ME secondary to CRVO of ≤12 month duration.

Each was randomized 1:1:1 to 1 of the 3 anti-VEGF agents in the study, with mandated injections at baseline and weeks 4, 8, and 12.

Then, from week 16 - 96, treatment was provided if a patient met 1 or more retreatment criteria, including a decrease in BCVA score of ≥5 between the current and most recent visit attributed to an increase in CST or an increase in BCVA letter score of ≥5 between current and most recent visit.

The study defined participants who achieved CST <320 μm across all milestone visits as having persistently dry macula (no ME), while those who had no visits with CST <320 μm were defined as having persistent ME, and patients who intermittently achieved CST <320 μm at 12, 24, 52, 76, or 100 weeks postbaseline were defined as having recurrent ME. If they were missing CST, the closest intervening visit was moved forward.

The main outcome of the study was defined as BCVA change from baseline to 100 weeks, while categorial VA gains of ≥15 letters and ≥10 letters and those achieving a letter score of ≥70 were additionally assessed.

The post-hoc analysis included a total of 425 participants following exclusions, with a mean age of 69.2 years and 57.2% (n = 243) men.

Data show 117 eyes (28.5%) achieved resolution across all milestone visits by the 100 week marker, while 250 eyes (60.8%) had recurrent ME, and 44 (10.7%) were persistently wet.

The mean visual gains by 100 weeks in ETDRS letters was 16.8 for persistently dry eyes, 13.1 for eyes with recurrent ME, and 6.4 for persistently wet eyes by 100 weeks. The adjusted difference in 100-week BCVA in eyes with persistently wet macula compared with those with recurrent ME was -5.39 ETDRS letters (95% CI, -10.15 to -0.64, P = .03) and those with persistently dry macula was -10.98 ETDRS letters (95% CI, -16.19 to -5.76, P <.001).

Further, the adjusted difference in BCVA at 100 weeks for recurrent ME compared with persistently dry by 52 weeks was -3.47 ETDRS letters (95% CI, -6.60 to -0.33, P = .03). Data show eyes persistently wet by 52 were 7.39 letters (95% CI, 3.05 - 11.72, P <.001) lower than those who remained dry and 3.92 letters (95% CI, 0.2 to 8.05; P = .06) lower than those that were recurrent.

At the 100 week marker, more bevacizumab-treated eyes had persistently wet macular compared to those treated with aflibercept (26 of 140, 18.6% versus 7 of 134, 5.2% difference, 13.3%, 95% CI, 5.9 - 20.8, P <.001) or ranibizumab (26, 18.6% versus 11, 8%; difference, 10.5%, 95% CI, 2.7 - 18.4, P = .01).

“In conclusion, this post hoc analysis showed that VA outcomes in CRVO may be dependent on the ME resolution profile over time, and our 100-week data in a clinical trial setting support the hypothesis that persistent ME across 100 weeks and even 52 weeks should be avoided,” investigators wrote.

The study, “Visual Outcomes Associated With Patterns of Macular Edema Resolution in Central Retinal Vein Occlusion Treated With Anti–Vascular Endothelial Growth Factor Therapy,” was published in JAMA Ophthalmology.