At present, there are no randomized, controlled clinical trial data describing the efficacy and safety of intravitreal triamcinolone for macular edema associated with retinal vein occlusion.29,30
The SCORE Study was initiated to provide data from a randomized, controlled clinical trial regarding this treatment for vision loss associated with macular edema secondary to retinal vein occlusion. The SCORE Study consists of a CRVO clinical trial and a BRVO clinical trial.
The two cohorts enrolled into the SCORE Study are similar in many respects. Demographic characteristics such as gender, race, ethnicity, age, history of coronary artery disease, hypertension and history of cancer were similar between both cohorts and were balanced within cohort with respect to the 3 treatment groups. The main difference was the (non-significant) higher frequency of a history of diabetes mellitus in participants in the SCORE CRVO trial compared with participants in the SCORE BRVO trial. This is consistent with other clinical trials that have evaluated retinal vein occlusion.1,5,22,23
Ophthalmic characteristics were similar at baseline for both cohorts with respect to intraocular pressure, lens status, duration of macular edema and history of prior sector or panretinal photocoagulation. However, the 2 cohorts differed, at baseline, with respect to several important ophthalmic characteristics such as mean visual acuity letter score, mean OCT-measured center point thickness, proportion of eyes with large cystoid spaces (>400 microns) at the center point as detected on OCT, mean area of retinal thickening as measured on color fundus photography and mean area of fluorescein leakage. All of these differences were in the direction of worse visual function and worse anatomy in CRVO participants compared with BRVO participants. Given the similar duration of macular edema in the two groups, these data suggest that CRVO is a disease that affects both anatomy and visual function more adversely than BRVO. One exception is the finding that the mean area of capillary non-perfusion measured greater among BRVO than CRVO participants ( [available at http://aaojournal.org
]); this may be due to the larger mean area of retinal hemorrhage (which may obscure visualization of capillary nonperfusion) in CRVO participants compared with BRVO participants.
These differences between the two cohorts with respect to demographics and ophthalmic characteristics are consistent with what has been reported previously among patients with retinal vein occlusion. For example, in the Eye Disease Case-control Study (EDCCS) (CRVO, N=258; BRVO, N=270), diabetes mellitus was found to be a risk factor for CRVO, but not BRVO.22,23
The CVOS group M (eyes with CRVO and macular edema) included 155 eyes with a median baseline visual acuity of 20/160 in treated eyes and 20/125 in control eyes.5
In the BVOS (group III study – eyes with macular edema, N=139), 56 (79%) treated eyes and 54 (79%) control eyes had a baseline visual acuity between 20/40 and 20/100.1
It is, therefore, not surprising that eyes in the CRVO trial had a lower mean baseline visual acuity letter score, a higher mean OCT-measured center point thickness, a larger mean area of retinal thickening measured on fundus photographs, and a larger mean area of fluorescein leakage compared with eyes in the BRVO trial. The difference in severity of disease between CRVO and BRVO supports the SCORE Study statistical plan to analyze the CRVO and BRVO cohorts as separate trials rather than combining them both into one cohort for analysis.
To examine the comparability of the SCORE Study results to those of prior clinical trials, we compared the baseline characteristics of the SCORE Study participants with baseline characteristics from other studies that have evaluated participants with retinal vein occlusion. The comparison below includes participants from the CVOS (group M study)5
, BVOS (group III study)1
and the Eye Disease Case-control Study.22,23
With respect to race, 91% of participants in the SCORE CRVO trial and 88% of participants in the SCORE BRVO trial were white. In the EDCCS, 72% of participants with CRVO and 73% of participants with BRVO were white. The CVOS group M cohort was 94% white. Racial demographics were not reported for the BVOS group III cohort. The mean age of participants was 68 years in the SCORE CRVO trial and 67 years in the SCORE BRVO trial. Sixty percent of the CRVO cohort and 71% of the BRVO cohort in the EDCCS were between the ages of 55-74 (inclusive) at baseline. The mean age of participants in the CVOS group M cohort was 67 years. In the BVOS, 71% of participants were between the ages of 60-79 years (inclusive).
In the SCORE Study, 71% of CRVO participants and 70% of BRVO participants had a self-reported history of hypertension. In the EDCCS, 65% of participants with CRVO had a history of hypertension and 75% of participants with BRVO had a history of hypertension. In the CVOS, 57% of participants were reported to be taking medication for hypertension or had elevated blood pressure at baseline. In the BVOS, 44% of participants had a history of hypertension defined as taking medication for hypertension before study entry.
In the SCORE Study, 22% of CRVO participants and 14% of BRVO participants had a history of diabetes mellitus. In the EDCCS, 17% of participants with CRVO and 15% of participants with BRVO had a history of diabetes mellitus. In the CVOS, 7% of participants had a history of diabetes mellitus and in the BVOS, 4% of participants had a history of diabetes mellitus.
With regard to ophthalmic characteristics, a comparison of the SCORE CRVO cohort to the CVOS demonstrates that the SCORE CRVO cohort had a shorter mean disease duration and larger areas of retinal thickening on color fundus photography than the cohort in the CVOS, but the cohorts were generally similar. In the CVOS group M, 3% of eyes had <2 disc areas of macular edema, 36% of eyes had 2 to <5 disc areas of macular edema and 61% of eyes had 5 or more disc areas of macular edema. The SCORE CRVO participants had a mean area of retinal thickening of 12.3 disc areas in the grid on color fundus photography and the categorical breakdown for the SCORE CRVO trial shows larger areas of retinal thickening compared with the CVOS group M (data not shown). In terms of disease duration, 97% of CRVO participants in the SCORE Study had a duration of 12 months or less compared with 60% of CVOS group M participants with this duration of disease. The distribution of visual acuity at baseline between the 2 studies was similar; 78% of participants in the SCORE CRVO trial and 82% of participants in the CVOS had a baseline visual acuity of between 20/50-20/200 (inclusive).
A comparison of the BRVO cohort in the SCORE Study to the BVOS also demonstrates a number of similarities between the cohorts with regard to ophthalmic characteristics. In the SCORE BRVO trial, 59% of participants had a disease duration of between 3 and 12 months (inclusive). Fifty-seven percent of participants in the BVOS had this disease duration. The distribution of visual acuity at baseline was similar for the SCORE BRVO cohort and the BVOS group III cohort: nearly half of the participants presented with a visual acuity between 20/40-20/50 and one-third of participants had a visual acuity between 20/70 and 20/100 in both cohorts.
Thus, the baseline demographic and ophthalmic characteristics of the SCORE Study participants are similar to those of participants in other clinical trials that have evaluated retinal vein occlusion. The CVOS and EDCCS were performed a decade ago and the BVOS was performed more than 2 decades ago. The similarities in baseline characteristics across all of these studies are remarkable given the improvement in diagnosis and management of systemic diseases, such as hypertension and diabetes mellitus, that have occurred in the years since the CVOS, BVOS and EDCCS were conducted.
The literature supports that the incidence and prevalence of diabetes mellitus31,32
have increased in the last few decades in the United States. An increased prevalence of diabetes mellitus and hypertension in the general population should, all other things being equal, result in a higher prevalence of diabetes mellitus and hypertension in patients with CRVO and BRVO. We did not observe this phenomenon in the participant population in the SCORE Study, possibly implying that the risk of developing CRVO or BRVO secondary to diabetes mellitus and hypertension has declined. Two possible explanations for this declining risk are (1) improved medical management of diabetes mellitus and hypertension causes the risk to decline (2) more aggressive diagnosis of diabetes mellitus and hypertension means that healthier people are counted as having these diseases, but it is less likely that these healthier patients develop CRVO or BRVO.
The similarities between the different cohorts recruited over various geographic regions from a multitude of clinical sites, over different time periods and across different clinical trials (each with a different purpose and slightly different inclusion and exclusion criteria) suggest that the SCORE Study results, when available, will be applicable to a well characterized patient population with retinal vein occlusion. Additionally, differences, with respect to baseline ophthalmic characteristics, between cohorts with CRVO and BRVO in the CVOS, BVOS and the SCORE Study suggest that future clinical trials for retinal vein occlusion should continue to evaluate CRVO and BRVO as separate entities.