Patient Characteristics
Sixty-five eyes of 65 patients with ME secondary to treatment-naïve BRVO were treated at Aichi Medical University Hospital during the current study. Twenty-eight eyes did not meet the study protocol: over 6 months from BRVO onset (3 eyes), hemicentral RVO (1 eye), epiretinal membrane (3 eyes), low OCT image quality due to dense hemorrhages (3 eyes) or progressed cataract at the initial visit (3 eyes), additional treatments during the study period such as phacoemulsification (3 eyes), laser photocoagulation (3 eyes), treatment with sub-Tenon triamcinolone acetonide injection (4 eyes), and follow-up periods less than 12 months (5 eyes). Thus, 37 eyes of 37 patients (mean age, 71.5 ± 8.1 years; range, 55-88) met the study criteria for analysis. The mean number of anti-VEGF injections/year was 4.1 ± 2.1 (range, 1-9). All 37 (100%) eyes had cystoid spaces in the OPL; 30 (81.1%) eyes had cystoid spaces in both the INL and OPL, and seven (18.9%) eyes only in the OPL. None had cystoid spaces only in the INL. Table 1 shows the clinical characteristics of the 37 patients at the initial visit. The intraclass correlation coefficients (ICCs) of the two observers were high for all measurements of interest (ICC, 0.95, 0.92, 0.92, and 0.97 for the JR, number of INL cystoid spaces, area of the INL, and area of the outer retina, respectively).
Baseline Factors Affecting the Number of Anti-VEGF Injections
We performed univariate and multivariate linear regression analyses using the baseline data to identify the factors directly affecting the number of anti-VEGF injections/year (Table 2). Correlated significantly with the number of anti-VEGF injections/year in the univariate analysis were only three of the parameters at the initial visit: the JR, the number of cystoid spaces in the INL, and the area of the INL (Pearson correlation coefficient, r = 0.721, P < 0.0001; r = 0.348, P = 0.035; and r = 0.388, P = 0.018, respectively). The correlations between the parameters at the initial visit and the number of anti-VEGF injections/year are shown in Fig 1. Among 37 eyes, nine (24.3%) eyes received two or fewer injections/year and their JRs were less than 1.05. Age, duration of symptoms until the initial treatment, VA, central subfield thickness (CST), and area of the outer retina were not correlated significantly with the number of anti-VEGF injections/year (r = 0.0274, P = 0.87; r = 0.285, P = 0.087; r = -0.10, P = 0.55; r = 0.208, P = 0.22; and r = 0.207, P = 0.22, respectively). The results of multivariate linear regression analysis showed that only the JR was correlated significantly with the number of anti-VEGF injections/year (P < 0.0001; coefficient, 22.3) (Table 2).
Correlation between OCT Parameters at the Initial Visit and JR
OCT parameters including the number of cystoid spaces in the INL, area of the INL, CST, and area of the outer retina were evaluated to determine if they were relevant to the JR. The number of cystoid spaces in the INL and area of the INL were correlated significantly with the JR (Pearson correlation coefficient, r = 0.55, P = 0.0005, and r = 0.39, P = 0.016, respectively). The CST and area of the outer retina were not correlated significantly with the JR (r = 0.031, P = 0.86 and r = 0.24, P = 0.16, respectively).
Comparisons of the Locations of Intraretinal Cystoid Spaces Regarding the JR
The mean JR in eyes with cystoid spaces in both the INL and OPL was 1.11 ± 0.01 and that in only the OPL was 1.09 ± 0.03. The JRs did not differ significantly (P = 0.39) between the locations of the cystoid spaces.
Comparisons between Clinical Characteristics at the Initial Visit and BCVA at the 12-Month Visit
The clinical characteristics including age, duration of symptoms until the initial treatment, best-corrected VA (BCVA), CST, and area in the outer retina at the initial visit were correlated significantly with the VA at 12 months in the univariate linear regression analysis (P = 0.0027, P = 0.049, P = 0.0001, P = 0.0088, and P = 0.0094, respectively); other clinical characteristics including the JR were not correlated with the VA at 12 months (Table 3). Multiple linear regression analysis showed that age, duration of symptoms until the initial treatment, and initial BCVA were correlated significantly with the VA at 12 months (P = 0.0045, P = 0.02, and P = 0.0075, respectively).
Case Reports
Case 1 was that of a 77-year-old woman who presented with visual loss due to ME secondary to BRVO. At the initial visit, ME was seen on the OCT images, which showed large cystoid spaces in the OPL and a small amount of subretinal fluid (Fig 2A). The border between the INL and OPL was relatively smooth (Fig 2B). The JR on the OCT image at the initial visit was 1.01. After one anti-VEGF injection, the ME did not recur during the 12-month study period.
Case 2 was that of a 62-year-old woman who presented with visual loss due to ME secondary to BRVO. At the initial visit, ME was seen on the OCT image, which showed small cystoid spaces in the INL and large cystoid spaces in the OPL (Fig 3A). The border between the INL and OPL was not smooth (Fig 3B). The JR on the OCT image at the initial visit was 1.10. The patient was treated with five anti-VEGF injections during the 12-month study period.