Diabetic Retinopathy: A Team Approach
The management of diabetic retinopathy requires an understanding of the importance of general medical management and when to consider laser therapies, intravitreal injection of medications, and vitrectomy.
Control of cardiovascular risk factors is central to slowing the progression of diabetic retinopathy. Maintaining near-normal glucose levels and blood pressure reduces the risk for development and progression of diabetic retinopathy.
The DCCT showed that development and progression of diabetic retinopathy in patients with type 1 diabetes can be delayed by maintaining glucose concentrations in the near-normal range. After 3 years of intensive treatments to reduce glucose levels in patients without retinopathy, the development of any diabetic retinopathy was reduced by 75% over the 9-year duration of the study. Strict glucose control also resulted in a 50% reduction in the rate of progression of retinopathy in patients with existing diabetic retinopathy. Similar data indicating a reduction in risk for progression of diabetic retinopathy in type 2 diabetes was demonstrated in the UKPDS. Furthermore, improved control of hypertension in the UKPDS reduced progression of diabetic retinopathy by 34%.
Some medications may contribute to DME. In particular, glitazone antihyperglycemic agents have been associated with DME. If a patient with DME is taking a glitazone antihyperglycemic agent, the eye doctor and the doctor prescribing the glitazone agent should consider alternative medications if possible.
Laser photocoagulation (panretinal or focal) has been a standard technique for treating diabetic retinopathy since 2 landmark prospective trials: the Diabetic Retinopathy Study and Early Treatment of Diabetic Retinopathy Study (ETDRS).
Panretinal photocoagulation is used to treat PDR, and it indirectly treats neovascularization of the optic nerve, retinal surface, or anterior chamber angle by placing burns throughout the peripheral fundus. Appropriate panretinal photocoagulation reduces the risk for severe vision loss (tripling of the visual angle -- eg, a decrease of visual acuity from 20/40 to 20/120) by 50%.
Focal photocoagulation is used to treat DME and involves applying light, small-sized burns to areas of leaking microaneurysms in the macula. The ETDRS demonstrated that moderate vision loss (doubling of the visual angle -- eg, a decrease of visual acuity from 20/50 to 20/100) can be reduced by more than 50% by performing appropriate focal laser photocoagulation. The primary goal of treatment is to stabilize visual acuity, because vision improves for only a minority of patients.
More recent research has identified VEGF as a key player in the pathogenesis of DME by mediating vascular permeability and accumulation of intracellular and extracellular fluid. Because DME is the major cause of visual impairment in patients with diabetes, VEGFs are appealing as a target of therapy for the treatment of DME. Multiple anti-VEGF drugs, including pegaptanib, ranibizumab, bevacizumab, and aflibercept, are currently available for routine clinical use.
Two recent phase 3 randomized controlled trials (the RISE and RIDE studies) demonstrated good efficacy of ranibizumab in the treatment of DME. These studies randomly assigned patients with DME to undergo standard focal photocoagulation or receive monthly intravitreal injections of ranibizumab. The primary endpoint was the percentage of patients with substantial improvement of vision (able to read at least 15 additional letters [3 lines] on the eye chart). After 24 months, 33.6%-45.7% of patients treated with ranibizumab met the primary endpoint, compared with 12.3%-18.1% of patients treated with standard photocoagulation alone. The use of anti-VEGF medications for the long-term management of DME holds great promise.
Vitrectomy plays an important role in the management of patients with diabetic retinopathy and has been shown to increase vision-related quality of life in specific patients. In PDR, the neovascular vessels are fragile and often accompanied by damaging scar tissue. These vessels can bleed into the vitreous cavity of the eye, causing vitreous hemorrhage and obscuring the visual axis. Alternatively, the associated scar tissues can distort and detach the retina, causing tractional retinal detachment. These are the primary indications for surgical intervention.
Treatments and Prognosis
The management of diabetic retinopathy requires an understanding of the importance of general medical management and when to consider laser therapies, intravitreal injection of medications, and vitrectomy.
Medical Management of Diabetic Retinopathy
Control of cardiovascular risk factors is central to slowing the progression of diabetic retinopathy. Maintaining near-normal glucose levels and blood pressure reduces the risk for development and progression of diabetic retinopathy.
The DCCT showed that development and progression of diabetic retinopathy in patients with type 1 diabetes can be delayed by maintaining glucose concentrations in the near-normal range. After 3 years of intensive treatments to reduce glucose levels in patients without retinopathy, the development of any diabetic retinopathy was reduced by 75% over the 9-year duration of the study. Strict glucose control also resulted in a 50% reduction in the rate of progression of retinopathy in patients with existing diabetic retinopathy. Similar data indicating a reduction in risk for progression of diabetic retinopathy in type 2 diabetes was demonstrated in the UKPDS. Furthermore, improved control of hypertension in the UKPDS reduced progression of diabetic retinopathy by 34%.
Some medications may contribute to DME. In particular, glitazone antihyperglycemic agents have been associated with DME. If a patient with DME is taking a glitazone antihyperglycemic agent, the eye doctor and the doctor prescribing the glitazone agent should consider alternative medications if possible.
Laser-Based Therapies
Laser photocoagulation (panretinal or focal) has been a standard technique for treating diabetic retinopathy since 2 landmark prospective trials: the Diabetic Retinopathy Study and Early Treatment of Diabetic Retinopathy Study (ETDRS).
Panretinal photocoagulation is used to treat PDR, and it indirectly treats neovascularization of the optic nerve, retinal surface, or anterior chamber angle by placing burns throughout the peripheral fundus. Appropriate panretinal photocoagulation reduces the risk for severe vision loss (tripling of the visual angle -- eg, a decrease of visual acuity from 20/40 to 20/120) by 50%.
Focal photocoagulation is used to treat DME and involves applying light, small-sized burns to areas of leaking microaneurysms in the macula. The ETDRS demonstrated that moderate vision loss (doubling of the visual angle -- eg, a decrease of visual acuity from 20/50 to 20/100) can be reduced by more than 50% by performing appropriate focal laser photocoagulation. The primary goal of treatment is to stabilize visual acuity, because vision improves for only a minority of patients.
Intravitreal Injections
More recent research has identified VEGF as a key player in the pathogenesis of DME by mediating vascular permeability and accumulation of intracellular and extracellular fluid. Because DME is the major cause of visual impairment in patients with diabetes, VEGFs are appealing as a target of therapy for the treatment of DME. Multiple anti-VEGF drugs, including pegaptanib, ranibizumab, bevacizumab, and aflibercept, are currently available for routine clinical use.
Two recent phase 3 randomized controlled trials (the RISE and RIDE studies) demonstrated good efficacy of ranibizumab in the treatment of DME. These studies randomly assigned patients with DME to undergo standard focal photocoagulation or receive monthly intravitreal injections of ranibizumab. The primary endpoint was the percentage of patients with substantial improvement of vision (able to read at least 15 additional letters [3 lines] on the eye chart). After 24 months, 33.6%-45.7% of patients treated with ranibizumab met the primary endpoint, compared with 12.3%-18.1% of patients treated with standard photocoagulation alone. The use of anti-VEGF medications for the long-term management of DME holds great promise.
Vitrectomy
Vitrectomy plays an important role in the management of patients with diabetic retinopathy and has been shown to increase vision-related quality of life in specific patients. In PDR, the neovascular vessels are fragile and often accompanied by damaging scar tissue. These vessels can bleed into the vitreous cavity of the eye, causing vitreous hemorrhage and obscuring the visual axis. Alternatively, the associated scar tissues can distort and detach the retina, causing tractional retinal detachment. These are the primary indications for surgical intervention.
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