Currently submitted to: JMIR Research Protocols
Date Submitted: Oct 13, 2026
Open Peer Review Period: Oct 13, 2026 - Dec 8, 2026
(currently open for review)
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Association Between Hemoglobin Levels and the Severity of Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus: Protocol for a Cross-Sectional Study
ABSTRACT
Background:
Diabetic retinopathy (DR) is a leading microvascular complication of type 2 diabetes mellitus (T2DM). Anemia affects roughly one-third of people with diabetes and has been linked to more severe DR, possibly through retinal hypoxia. Most supporting data come from retrospective or non-Indian cohorts, and the contribution of renal disease to this relationship remains uncertain.
Objective:
To estimate the association between hemoglobin concentration and DR severity in patients with T2DM attending a tertiary care hospital in central India, after adjustment for sex, diabetes duration, and glycemic control.
Methods:
This hospital-based cross-sectional study will recruit 150 consecutive patients with T2DM and any stage of DR at Acharya Vinoba Bhave Rural Hospital, Wardha, Maharashtra. DR will be graded on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale by dilated fundus examination with fundus photography, and 20% of images will be regraded by a masked second grader. Hemoglobin will be measured from a venous sample drawn at the same visit. The primary analysis is a proportional odds ordinal logistic regression of DR severity (mild, moderate, or severe nonproliferative DR, or proliferative DR) on hemoglobin as a continuous variable, adjusted for sex, diabetes duration, and glycated hemoglobin (HbA1c). Secondary analyses include a trend test across World Health Organization anemia grades, Firth penalized logistic regression for proliferative DR, and an exploratory analysis of diabetic macular edema. Prespecified sensitivity analyses will remove HbA1c, add diabetic kidney disease, and exclude previously treated eyes. Secondary, sensitivity, and effect-modification analyses are hypothesis-generating and will not be adjusted for multiplicity. The sample size was derived by simulation; 150 participants give about 86% power to detect an odds ratio of 1.30 per 1 g/dL lower hemoglobin at a 2-sided α of 0.05.
Results:
The Institutional Ethics Committee approved the protocol on June 30, 2025, and the study was registered with the Clinical Trials Registry-India (CTRI/2025/11/097568) on November 17, 2025. Enrollment began on December 1, 2025; 62 participants had been enrolled by October 9, 2026. Enrollment is expected to be completed by November 2027.
Conclusions:
The study will provide prospectively collected data from an Indian tertiary care population on whether lower hemoglobin is associated with more severe DR. Because the design is cross-sectional, any association will be hypothesis-generating and will not establish causation. Clinical Trial: Clinical Trials Registry-India CTRI/2025/11/097568
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