Hemoglobin as a Hidden Risk Factor: Implications for Diabetic Retinopathy Management

Hemoglobin as a Hidden Risk Factor: Implications for Diabetic Retinopathy Management

Hemoglobin and DR Quiz
Hemoglobin and Diabetic Retinopathy: Test Your Knowledge
1 What was the strongest association found between low hemoglobin levels and diabetic retinopathy (DR) in the reviewed study?
Correct. The study found the most potent association was with Proliferative DR, with a hazard ratio of 1.95, indicating nearly double the risk.
2 According to the subgroup analysis, in which patient population was the association between low hemoglobin and DR risk STRONGEST?
Correct. The link was stronger in patients without hypertension (HR: 1.58 vs 1.21), suggesting tissue hypoxia from anemia may be a dominant driver when the damaging effects of high blood pressure are absent.
3 What is a key clinical takeaway from this study for vitreoretinal surgeons?
Correct. The study suggests that reviewing hemoglobin levels should become part of the clinical checklist, especially for patients with unexplained or rapid progression to proliferative disease, as it represents a modifiable systemic risk factor.

As vitreoretinal specialists, we are well-versed in the microvascular battlefield of diabetic retinopathy (DR). We target neovascularization, manage macular edema, and understand the pivotal roles of hyperglycemia and hypertension. But are we overlooking a silent, systemic accomplice in the progression to vision-threatening disease?

A compelling new retrospective cohort study, recently published in Eye, has identified low hemoglobin as a significant, independent, and modifiable risk factor for DR development and progression, with a striking link to proliferative disease.

Let’s break down the key findings and what they mean for our clinical practice.


The Core Finding: Hemoglobin is More Than Just a Number

The study analyzed over 57,000 patients with type 2 diabetes from the TriNetX network. After meticulous propensity score matching to account for confounders like kidney disease and age, the results were clear:

  • Patients with low hemoglobin (8-12 g/dL) had a 33% higher risk of developing any DR compared to those with normal levels.
  • The association was most potent for Proliferative DR (PDR), with nearly double the risk (HR: 1.95).
  • Crucially, even mild anemia in the 10-12 g/dL range significantly increased risk, suggesting the retina is exquisitely sensitive to subtle reductions in oxygen-carrying capacity.

Key Subgroup Insights for Patient Stratification

DR Risk Profiling: Subgroup Clues

Hypertension Status: The link between low Hb and DR was stronger in normotensive patients. In these cases, tissue hypoxia from anemia may be the dominant driver, whereas in hypertensive patients, BP-related damage may overshadow this effect.

Independent of Glycemic Control: The association remained firm regardless of HbA1c levels. Even “well-controlled” patients are at risk if anemia is present, reinforcing the multifactorial nature of DR.

Sex-Aware Assessment: The association was more pronounced in male patients using sex-specific hemoglobin thresholds, suggesting a need for targeted screening protocols.

Why This Matters for the Vitreoretinal Surgeon

This isn’t just an internal medicine finding. It has direct implications for our role in managing diabetic eye disease:

  • Pre-Operative Optimization: For our surgical PDR patients, particularly those with recurrent vitreous hemorrhages or aggressive neovascularization, a pre-operative hemoglobin check may reveal a correctable systemic factor. Collaborating with a primary care physician or hematologist to address underlying anemia could be a key part of the holistic pre-surgical workup.
  • Risk Prediction & Screening Intervals: A diabetic patient referred to us with unexplained or rapidly progressive retinopathy, especially if normotensive, should prompt a question about their hemoglobin level. It may help identify those needing more frequent monitoring.
  • Understanding Treatment Resistance: Could chronic, subclinical tissue hypoxia contribute to suboptimal anti-VEGF response or aggressive neovascular recurrence in some patients? This study opens the door to that mechanistic question.

The Clinical Takeaway: A New Item on the Checklist

While we await interventional studies to prove causality, the evidence is strong enough to change our clinical lens.

Action Point: Consider systematically inquiring about or reviewing hemoglobin levels in your diabetic patients, especially those with:

  • Unexplained progression to PDR.
  • Normotensive status with significant retinopathy.
  • Recurrent neovascular events despite treatment.

Managing diabetic retinopathy is a team sport. This study reminds us that our collaboration with internists, endocrinologists, and nephrologists is crucial. By identifying and co-managing systemic risk factors like anemia, we move beyond treating the retinal complication to protecting the patient’s visual system more fundamentally.

Bottom Line: In the complex pathophysiology of diabetic retinopathy, hemoglobin is not a bystander. It’s a potential lever for prevention and a critical piece of the diagnostic puzzle for the vitreoretinal surgeon.


*Based on: Hung K-C, Chang L-C, et al. “Association between haemoglobin levels and the risk of diabetic retinopathy in adults with type 2 diabetes: a retrospective cohort study using the TriNetX network.” Eye (2025).*

0 0 votes
Article Rating
Subscribe
Notify of
2 Comments
Inline Feedbacks
View all comments

My score was 3/3

Important point:

The link between low Hb and DR was stronger in normotensive patients. In these cases