Treatment of diabetic retinopathy begins with therapies that prevent the disease from developing, and the two primary preventive approaches are glycemic control and blood pressure control.8,27 Good glycemic control and blood pressure control have been shown to reduce the incidence and progression of diabetic retinopathy in both type 1 and type 2 diabetes,8 and there is evidence that suggests that both treatments together are more effective than if either one is applied alone.8,27
Dyslipidemias are very common in patients who have diabetes, they are considered a risk factor for developing diabetic retinopathy, and lipid-lowering therapy is often prescribed to diabetic patients. Lipid-lowering therapy and treatment with fenofibrate to lower serum triglyceride level may slow the progression of diabetic retinopathy and prevent the need for treatment,28-30 but there is no conclusive evidence that either one prevents diabetic retinopathy.8
The four commonly used and effective therapies for the treatment of diabetic retinopathy and macular edema are intravitreal anti-vascular endothelial growth factor (VEGF) medications, focal photocoagulation therapy with laser, pan-retinal photocoagulation, and vitrectomy. These can be used alone or as adjuncts to each other, and the choice of treatment depends on the type of diabetic retinopathy, the severity of the disease, and whether there is macular damage.
VEGF inhibitors: Vascular endothelial growth factor is a protein that stimulates angiogenesis, the growth of new blood vessels. Production of VEGF is increased when the retinal tissues are hypoxic, and the new blood vessels can cause edema, increase capillary permeability, and they can rupture very easily. The VEGF inhibitors like bevacizumab and ranibizumab are monoclonal antibodies that bind to and inhibit VEGF, thus preventing angiogenesis. The VEGF inhibitors have been successfully used for patients who have non-proliferative and proliferative diabetic retinopathy (the evidence for their use in PDR is less robust), alone or as an adjunct to pan-retinal photocoagulation and/or vitrectomy and they can slow the rate of progression of the disease and may decrease its severity, as well.8,31 The VEGF inhibitors have been proven to be superior to focal laser photocoagulation for treating diabetic macular edema,32-34 at least as effective as pan-retinal photocoagulation at treating proliferative diabetic retinopathy without macular edema,35,36 and they are now considered first-line treatment.32-34
The VEGF inhibitor medications that are commonly used to treat diabetic retinopathy are aflibercept, bevacizumab, pegaptanib, and ranibizumab but only pegaptanib and ranibizumab are FDA-approved for the treatment of diabetic retinopathy, and macular edema,8 and VEGF inhibitors and focal laser photocoagulation are often used together.32 Using a VEGF is done by application of a topical anesthetic and a topical antibiotic, a local injection of an anesthetic is administered, and then the eye is injected with a VEGF. Multiple injections are often needed, and the common side effects include conjunctival hemorrhage, infection, and eye pain.
Focal laser photocoagulation therapy: For many years focal laser photocoagulation therapy has been a standard treatment for diabetic macular edema.8,32 This technique cauterizes retinal blood vessels, reducing areas of ischemia and thus decreasing VEGF production. It can reduce the risk of moderate vision loss and blindness, but it seldom will improve a patient’s vision32 and VEGF inhibitors are now the treatment of choice for diabetic macular edema.32-34 However, focal laser photocoagulation still has an important role as an adjunct to treatment with VEGF inhibitors; the combination provides a synergistic effect and can help reduce adverse effects of both therapies.33
Pan-retinal photocoagulation: Pan-retinal photocoagulation has long been the standard therapy for proliferative diabetic retinopathy without macular edema.8,35,36 Unlike focal photocoagulation, the pan-retinal technique is more extensive, less focused, and treats more areas of the retina and not just the maculae. This technique can be very effective at reducing vision deficits.8
Vitrectomy: Surgery is an option for patients who have diabetic macular edema or proliferative retinopathy, and specific complications like retinal detachment and vitreous hemorrhage,8,37 and the pars plana vitrectomy is the most commonly performed procedure. Pars plana vitrectomy involves removal of vitreous gel through the pars plana, a structure which is part of the ciliary body; this is the basic procedure, and there are several ways it can be done. The pars plana vitrectomy can be used for patients who have not responded to laser photocoagulation, intravitreal steroids, or VEGF inhibitors,37,38 and for certain patients who have proliferative retinopathy, vitrectomy can improve vision.8 The effectiveness of vitrectomy for treating macular edema is less certain. Some researchers have found that the technique improves visual acuity while others have not; vitrectomy may be no more effective for treating macular edema than laser therapy or waiting,8,39,40 and the incidence and seriousness of some of the complications associated with the procedure like retinal detachment and recurrent vitreous hemorrhage are not insignificant.37 These reported differences in effectiveness can be explained in part by the patient selection and vitrectomy may benefit only a small number of patients who have macular edema.8
Intravitreal injections of glucocorticoids have been used to treat macular edema and proliferative retinopathy,8 but they are considered a second-line therapy that is used only if other treatments do not work.8,21,33 Intravitreal glucocorticoids are less effective than other therapies; improvements are relatively short-term. This therapy is associated with a high incidence of serious adverse effects like cataract formation and glaucoma,8,21,33 and a recent 2018 literature review concluded that combining intravitreal glucocorticoids with VEGF inhibitors was no more effective than VEGF inhibitors alone and was associated with a high risk of complications.41