The findings of two multi-center, double-masked trials that enrolled participants with macular edema (ME) secondary to branch or central retinal vein occlusion (RVO): the RanibizumaB for the Treatment of Macular Edema following B RAnch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) trial or the Central Retinal Vein Occl Us Ion Study: Evaluation of Efficacy and Safety (CRUISE) trial were studied to examine the impact of intravitreal ranibizumab on patient-reported visual function using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) through 6 months in patients with ME secondary to branch or central RVO. There were 397 participants in the BRAVO trial and 392 patients in the CRUISE study.

Patients were randomized 1:1:1 to monthly sham, 0.3-mg, or 0.5-mg injections of ranibizumab for 6 months. Although visual acuity was the main outcome measure for the trials, mean change from baseline in NEI VFQ-25 scores at month 6 was a secondary outcome measure.

It was reported that in BRAVO, among the 132, 134, and 131 patients randomized, respectively, to sham, 0.3 mg ranibizumab, or 0.5 mg ranibizumab, the study eye was the worse-seeing eye in 121 (91.7%), 118 (88.1%), and 125 (95.4%) patients and 123 (93.2%), 128 (95.5%), and 125 (95.4%), respectively, had a 6-month follow-up visit. In CRUISE, among the 130, 132, and 130 patients randomized, respectively, to sham, 0.3 mg ranibizumab, and 0.5 mg ranibizumab, the study eye was the worse-seeing eye in 117 (90.0%), 123 (93.2%), and 120 (92.3%) patients and 115 (88.5%), 129 (97.7%), and 119 (91.5%), respectively, had a 6-month follow-up visit. In both trials, it was noted that patients treated with ranibizumab reported greater mean improvements in visual function, with substantial differences observed as early as month 1, including the NEI VFQ-25 composite score and near and distance activities subscales, compared with sham patients. Additionally, p values for comparisons with sham for the composite score and these 2 subscales were <0.05.

These results from the BRAVO and CRUISE trials indicate that patients with ME from RVOs treated with monthly ranibizumab report greater improvements in vision-related function compared with sham-treated patients through 6 months, even when a majority of patients present with RVOs in the worse-seeing eye.

The authors of the following study to sought to investigate the correlation of genetic, sociodemographic, and behavioral risk factors with second-eye progression to end-stage age-related macular degeneration (AMD).

They included 108 patients with end-stage AMD in one or both eyes in a retrospective time-to-event analysis of the onset of end-stage AMD in the second eye. They also performed Multivariate Cox regression survival analysis for gender, age, smoking, body mass index (BMI), education, and 16 single nucleotide polymorphisms (SNPs) associated with AMD.

Except for education, all analyzed sociodemographic and behavioral risk factors were significantly associated with a more rapid progression toward second eye involvement, the authors reported. They noted that hazard ratios (HRs) were 2.6 (95% confidence interval [CI]), 1.4–5.0) for female gender, 5.0 (95% CI, 2.0–12.5) for age >80, 2.2 (95% CI, 1.1–4.1) for BMI >30, and 4.4 (95% CI, 1.4–14.3) for >40 pack years, compared to the referent groups. They also found that carriers of the Lipoprotein lipase (LPL) (rs12678919) risk alleles were at risk for more rapid progression to end-stage AMD in the second eye compared to the referent wild-type genotype (HR 2.0; 95% CI, 1.0–3.6). For Complement factor 1 (CFI) (rs10033900), homozygous carriers of the risk allele progressed faster than wild-type individuals (HR 2.2; 95% CI, 1.1–4.3).

In conclusion, sociodemographic, behavioral and genetic risk factors are associated with the rate of second-eye progression toward end-stage AMD. The findings of this study underline the importance of lifestyle factors and the complement pathway in AMD progression and suggest a role of the high-density-lipoprotein-metabolism in second-eye progression.

Japanese investigators studied the association of ARMS2 A69S genotype with the development of exudative age-related macular degeneration (AMD) in the unaffected fellow eye and to estimate the duration until the development of AMD in the second eye.

In this retrospective cohort study, they reviewed 326 patients who had exudative AMD in at least one eye, genotyping of ARMS2 A69S, and a minimum follow-up of 2 years. They used survival analysis and Cox proportional hazard regression analysis to examine the association between candidate factors and the duration until the development of AMD in the second eye.

At the initial visit, 119 patients (36.5%) had bilateral exudative AMD, the investigators reported. They also noted that a risk allele of ARMS2 A69S was more frequently seen in patients with bilateral AMD (p=.0270) than in those with unilateral AMD. Of the 207 unilateral AMD patients, 23 (11.1%) had AMD in the fellow eye after a mean duration of 56.3 ± 40.4 months. They associated fellow-eye involvement with ARMS2A69S genotype (hazard ratio [HR], 2.673; p=.0013), age (HR, 1.102; p=.0005), and smoking history (HR, 0.680; p=.3663). According to the investigators, as HRs indicate, correlation of genotype (2.673) was as high as that of 10-year aging (1.102¹⁰=2.641). Survival analysis revealed that patients with risk homozygous (TT) genotype had second-eye involvement significantly earlier than those with other genotypes (p=.0028). When the observation duration reached 120 months, second-eye involvement had developed in 50%, 6.6%, and 11.2% of the TT, GT, and GG cohorts, respectively.

ARMS2 A69S genotype is associated with second-eye involvement of exudative AMD and with the period between first- and second-eye involvements.