Commentary: Oral management of diabetic retinopathy

Diabetic retinopathy (DR) ranks fifth among leading global causes of moderate to severe vision impairment and blindness in adults aged 50 years and older.[1] The disease has been observed to show 1-step and 2-step progressions over four years from baseline in 30.2% and 12.6% of patients, respectively.[2] Chronic inflammation is known to play a role in the pathophysiology of type 1 and 2 diabetes mellitus (DM).[3] There also seems to be role of inflammatory processes in the development and progression of DR.[4] Intravitreal anti-vascular endothelial growth factors (VEGF), corticosteroids, and tumor necrosis factor (TNF); alpha inhibitors are known to reduce vascular permeability and suppress inflammation and thereby regress diabetic macular edema (DME).[5,6,7] Recently, intravitreal anti-VEGF treatment has also been shown to delay the progression of non-proliferative DR to proliferative DR.[8] In diabetic animals, control of inflammation by systemic therapy was found to be associated with amelioration of DR.[9] However, this has not been evaluated in humans. This could be attributed to the requirement of long-term administration of immune-based anti-inflammatory drugs which are associated with unwarranted side effects.

In the current issue of the Indian Journal of Ophthalmology, a prospective observational case-control study has evaluated the role of systemic anti-inflammatory drugs (immunosuppressants) for effect on DR progression.[10] They have utilized the opportunity of evaluating it in diabetic patients who needed immunosuppression for comorbidities such as rheumatoid arthritis and post-renal transplant (PRT) and compared it with matching diabetic patients not requiring immunosuppression. At 1-year follow-up, one-step progression of DR from baseline was seen in 33.3% of patients in the control group only. This small, well-documented study provides initial evidence about the role of systemic anti-inflammatory in the management of DR. The difference in glycemic control between the two groups was 0.4% (worse in the control group) at baseline, which increased to 0.6% at end of the study. This could be a confounding factor and needs to be addressed in future studies. Again, in PRT cases, previous studies have shown that DR status stabilizes in the majority of patients following transplant and in the current study also, PRT cases did not show DR progression.[11] Whether it is related to metabolic control or the effect of prolonged immunosuppressants post-transplant is debatable and needs to be addressed in future studies.

Unlike other anti-diabetic drugs, oral sodium-glucose co-transporter 2 inhibitors (SGLT2i) have a positive effect on cardiorenal functions as well as on vascular endothelium. This also holds promise for delaying the progression of DR.[12] Preliminary data suggests SGLT2i is associated with reduction in central retinal thickness in eyes with chronic DME.[13]

Larger studies are needed for clinical validation of oral therapies for preventing the progression of DR.