Racial disparities in visual outcomes of ranibizumab-treated DME

(Image credit: Rawpixel.com/AdobeStock)

A newly published meta-analysis of 5 clinical trials found that patient race is not a factor in the visual outcomes of patients with diabetic macular edema (DME) treated with ranibizumab (Lucentis, Genentech),¹ reported M. Ali Khan, MD, first study author, from the Department of Research, Wills Eye Hospital, Philadelphia, and the Department of Research, Kaiser Permanente, Roseville, CA. Senior author Julia A. Haller, MD, is from the Department of Research, Wills Eye Hospital.

However, no conclusive results could be reached because, the research team explained, racial subgroups are underrepresented in clinical trials, a factor that should be addressed in future clinical trials.

Khan and colleagues explained that racial and ethnic differences in the prevalence of ophthalmic diseases have been reported,^2,3 and they cited both that the prevalence rates of diabetic retinopathy and DME were found to be higher in US Black and Hispanic participants,³ and the likelihood of developing DME may be higher in Black patients.^2,1 In addition, the risk of sustained blindness may be greater in Black and Asian patients than in White patients.⁴

Despite efforts^5,4 to equalize the enrollment of patients in non-White racial and ethnic subgroups to study the efficacy and safety of treatments, they are still underrepresented in clinical trials.^6-9 This can result in a lack of clarity about treatment effectiveness across racial subgroups.

To clarify how race affects visuals outcomes in clinical trial participants with DME treated with ranibizumab, Khan and associates analyzed the results of the 5 following randomized clinical trials: the RIDE and RISE trials (Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus); Protocol I (Intravitreal Ranibizumab or Triamcinolone Acetonide in Combination With Laser Photocoagulation for Diabetic Macular Edema), Protocol S (Prompt Panretinal Photocoagulation Versus Intravitreal Ranibizumab With Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy), and Protocol T (A Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and Ranibizumab for Diabetic Macular Edema).^10-13

Meta-analysis factors and results

The authors explained that the total enrollment numbers facilitated a comparison of Black and White participants with DME who were treated with 0.3 or 0.5 mg ranibizumab and who had baseline and month 24 BCVA data available. All ranibizumab-treated arms were pooled. Differences in vision outcomes between Black and White participants were evaluated, with adjustment for the baseline vision. Propensity score–matched models for participants in the RIDE/RISE studies were used to control for differences in baseline and on-study characteristics. The main outcomes were the mean BCVA over time and the mean change from baseline at month 24 by race (Black and White).

A total of 1,109 study patients (mean age, 60.0 years) were included; of these, 181 were Black and 928 were White.

The investigators reported, “The BCVA was better at baseline in Black vs White participants (mean Early Treatment Diabetic Retinopathy Study [ETDRS] letter score, 66.7; 95% confidence interval [CI], 65.0-68.4 vs. 62.0; 95% CI, 61.1-62.8, respectively) but similar at month 24 (mean ETDRS letter score, 72.8; 95% CI, 70.2-75.4 vs. 72.2; 95% CI, 71.2-73.1). The mean BCVA change from baseline at month 24 was lower in Black vs White participants (6.1 ETDRS letters; 95% CI, 3.6-8.6 vs. 10.2 ETDRS letters; 95% CI, 9.3-11.1) and after adjusting for differences in the baseline BCVA (7.7 ETDRS letters; 95% CI, 5.8-9.7 vs. 9.9 ETDRS letters; 95% CI, 9.0-10.7).

When groups were propensity score–matched in the RIDE/RISE studies, the investigators found that the mean BCVA change from baseline appeared similar between Black and White participants (10.6 ETDRS letters; 95% CI, 7.1-14.1 vs. 10.1 ETDRS letters; 95% CI, 7.3-12.9; P = 0.83).

Based on the main findings, the investigators concluded, “As these data cannot conclusively assess the impact of race on treatment outcomes with ranibizumab alone, they provide yet another argument for increased enrollment of underrepresented racial subgroups in future clinical trials. Moreover, additional information regarding social determinants of health and greater characterization of race and ethnicity beyond traditional categories will be important. These steps will better allow for comprehensive evaluation of the effects of race on treatment outcomes.”

References

1. Khan MA, Hill L, Stoilov I, Haller JA. Race and vision outcomes in ranibizumab-treated participants with diabetic macular edema. A meta-analysis. JAMA Ophthalmol. Published online April 10, 2025. doi:10.1001/jamaophthalmol.2024.6371

2. Varma R, Bressler NM, Doan QV, et al. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2014;132:1334-1340. doi:10.1001/jamaophthalmol.2014.2854

3. Wong TY, Klein R, Islam FMA, et al. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol. 2006;141:446-455. doi:10.1016/j.ajo.2005.08.063

4. Wykoff CC, Khurana RN, Nguyen QD, et al. Risk of blindness among patients with diabetes and newly diagnosed diabetic retinopathy. Diabetes Care. 2021;44:748-756. doi:10.2337/dc20-0413

5. Oh SS, Galanter J, Thakur N, et al. Diversity in clinical and biomedical research: a promise yet to be fulfilled. PLoS Med. 2015;12:e1001918. doi:10.1371/journal.pmed.1001918

6. Berkowitz ST, Groth SL, Gangaputra S, Patel S. Racial/ethnic disparities in ophthalmology clinical trials resulting in US Food and Drug Administration drug approvals from 2000 to 2020. JAMA Ophthalmol. 2021;139:629-637. doi:10.1001/jamaophthalmol.2021.0857

7. Yu AJ, Masalkhi M, Brown R, Chen B, Chhablani J. Racial and ethnic distribution in diabetic macular edema clinical trials in the United States (2002-2021). Ophthalmol Retina. 2023;7:1035-1041. doi:10.1016/j.oret.2023.07.015

8. Kaakour AH, Hua HU, Rachitskaya A. Representation of race and ethnicity in randomized clinical trials of diabetic macular edema and retinal vein occlusion compared to 2010 US Census data. JAMA Ophthalmol. 2022;140:1096-1102. doi:10.1001/jamaophthalmol.2022.3929

9. Nguyen QD, Brown DM, Marcus DM, et al; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789-801. doi:10.1016/j.ophtha.2011.12.039

10. Wells JA, Glassman AR, Ayala AR, et al; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372:1193-1203. doi:10.1056/NEJMoa1414264

11. Gross JG, Glassman AR, Jampol LM, et al; Writing Committee for the Diabetic Retinopathy Clinical Research Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314:2137-2146. doi:10.1001/jama.2015.15217

12. Elman MJ, Aiello LP, Beck RW, et al; Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064-1077.e35. doi:10.1016/j.ophtha.2010.02.031

13. Bowe T, Salabati M, Soares RR, et al. Racial, ethnic, and gender disparities in diabetic macular edema clinical trials. Ophthalmol Retina. 2022;6:531-533. doi:10.1016/j.oret.2022.01.018