As the prevalence of diabetes mellitus increases worldwide, diabetic retinopathy(DR) has grown in global significance as a major cause of vision loss. Diabetic macular edema(DME) is a common vision threatening form of DR that develops in approximately 20% of diabetic patients within 15 years following the diagnosis of diabetes and when untreated , culminates in progressive central vision loss with time. While pathophysiological processes leading to DME are incompletely understood, it is clear that the pathology extends beyond a pure microvasculopathy to include other factors such as inflammatory mechanisms like inflammasome activation.

Review of literature:

  Lamivudine is a Nucleoside Reverse Transcriptase Inhibitor(NRTI) being used to control disease activity in people living with HIV / AIDS (PLHA). Studies have demonstrated anti-inflammatory as well as anti-angiogenic activity of drugs used to treat HIV, including lamivudine. Lamivudine has been shown in mouse models to have a protective effect against the development of the vascular effects of diabetic retinopathy. Health insurance database analyses have shown that both HIV- negative and HIV - positive patients taking NRTIs have a reduced risk of developing type 2 diabetes. Importantly, the safety profile of Lamivudine is well established in both children and adults , making it a promising candidate for further investigation in this new therapeutic context.

Justification for the study:

  The standard of care for diabetic macular edema is intra-ocular, specifically, intravitreal injection of anti-VEGF agents such as bevacizumab/ ranibizumab/ aflibercept. This procedure needs sterile operation theatre conditions, driving up costs for both the hospital and the patient. Substituting intravitreal injections with oral tablets would reduce costs involved as well as remove attendant risks associated with an invasive procedure such as endophthalmitis. 

Major objective: 

 To test safety and efficacy of oral lamivudine as treatment for diabetic macular edema and compare outcomes with intravitreal bevacizumab(avastin) injected for the same indication.

Study design: 

  Randomized , placebo- controlled, single blinded clinical trial .

Patients will be randomly assigned to one of two groups:

1) Lamivudine group: Patients will receive oral lamivudine at a dose of 150mg twice daily.

2) Placebo group: Patients will receive no treatment

Follow up and intervention:

At the end of weeks 4,8 and 12 , participants from both the groups will receive loading doses of intravitreal Avastin. This phase will continue for the next three months following the initial 12- week period. 

Risk and benefits:

  Most common adverse events include nausea, dizziness, fatigue, malaise, headache, dreams, insomnia and skin rash. Laboratory abnormalities are uncommon with lamivudine. Possible benefits include resolution of macular edema , also, possible approval of lamivudine as an oral drug for controlling diabetic macular edema.