Primary and Secondary Interventions for Diabetic Retinopathy Reviewed

August 27, 2007 — A systematic review in the August 22/29 issue of the Journal of the American Medical Association provides an overview of primary and secondary interventions for diabetic retinopathy (DR).
"Diabetic retinopathy (DR) is the leading cause of blindness in the working-aged population in the United States," write Quresh Mohamed, MD, from the Centre for Eye Research Australia, University of Melbourne, and the Royal Victorian Eye and Ear Hospital in Melbourne, and colleagues. "There are many new interventions for DR, but evidence to support their use is uncertain."
To summarize and review the best available evidence for primary and secondary intervention in the management of DR, including diabetic macular edema (DME), the authors performed a systematic review of all pertinent English-language articles. These were identified with a keyword search of MEDLINE from 1966 through May 2007, EMBASE, the Cochrane Collaboration, the Association for Research in Vision and Ophthalmology database, and the National Institutes of Health Clinical Trials Database, as well as manual searches of reference lists of selected major reviews.
Inclusion criteria for the reviewed studies were all English-language randomized controlled trials with more than 12 months of follow-up and meta-analyses. Delphi consensus criteria were used to identify studies with good methodology.
Of 44 studies meeting the inclusion criteria, 3 were meta-analyses. Based on these studies, the study authors concluded that tight glycemic and blood pressure (BP) controls were associated with lower incidence and slower progression of DR.
In patients with severe nonproliferative and proliferative retinopathy, panretinal laser photocoagulation (PRP) was associated with a 50% decrease in the risk for moderate and severe visual loss. In eyes with macular edema, focal laser photocoagulation was associated with a 50% to 70% decrease in the risk for moderate visual loss.
Early vitrectomy was associated with improvement in visual recovery in patients with proliferative retinopathy and severe vitreous hemorrhage. When conventional treatment has failed, intravitreal corticosteroid injections may be an option for eyes with persistent visual loss.
Available evidence is not sufficient for the efficacy or safety of lipid-lowering therapy, medical interventions, or antivascular endothelial growth factors on the incidence or progression of DR.
"Tight glycemic and blood pressure control remains the cornerstone in the primary prevention of DR," the investigators write. "Pan-retinal and focal retinal laser photocoagulation reduces the risk of visual loss in patients with severe DR and macular edema, respectively. There is currently insufficient evidence to recommend routine use of other treatments."
Specific clinical recommendations for primary and secondary interventions for DR are as follows:
For glycemic control, any lowering of levels of hemoglobin A1c (HbA1c) is beneficial in reducing the development of new DR or slowing the progression of existing DR. A target of HbA1c level of less than 7% is ideal in patients with DR (level of evidence, A I).
For BP control, any lowering of systolic and/or diastolic BP is beneficial in reducing the development of new DR or slowing the progression of existing DR. A target systolic BP of less than 130 mm Hg is ideal in patients with DR (level of evidence, A I).
In terms of lipid-lowering therapy, reducing levels of low-density lipoprotein cholesterol is associated with decreased macrovascular complications of diabetes and may be beneficial in DME (level of evidence, A II).
For patients with proliferative DR, early PRP is recommended, especially when there are high-risk features (level of evidence, A I).
Patients with early, less severe proliferative DR, defined as flat, new vessels elsewhere without high-risk features, or those with severe nonproliferative DR may be observed closely. However, treatment is recommended, especially in patients with type 2 diabetes, if there are any signs of progression or any anticipated difficulty or delay in follow-up (level of evidence, A II).
In eyes with DME involving the center of the macula and decreasing visual acuity, focal laser photocoagulation is recommended. For DME threatening the center of the macula, focal laser therapy should be considered. However, patients must be warned of the potential risks of therapy, particularly when their vision is 6/6 or better. Ideally, treatment should be guided by fluorescein angiography, because laser therapy is not likely to be helpful when significant macular ischemia is present (level of evidence, A I).
In patients with type 1 diabetes, severe vitreous hemorrhage, and significant DR, early surgical vitrectomy (within 3 months) is recommended. For eyes with severe proliferative DR refractory to extensive PRP and/or associated with traction involving the macula, vitrectomy should be considered (level of evidence, B, II).
In selected cases of diffuse severe DME refractory to other treatments, vitrectomy may be helpful, especially when vitreomacular traction is present (level of evidence, B, III).
Although intravitreal triamcinolone (IVTA) may be helpful in diffuse DME refractory to focal laser therapy, patients must be warned about the high incidence of secondary intraocular pressure increase, cataract, other potential harms, and the possibility that repeat treatment will be needed (level of evidence, B, II).
There is currently insufficient evidence to recommend the routine use of intravitreal antivascular endothelial growth factor agents (level of evidence, B, II/III) or of protein kinase C inhibitors, growth factor antagonists, and other treatments (level of evidence, C, II/III).
Aspirin does not reduce the risk of developing DR, and it does not increase the incidence of retinal or vitreous hemorrhage (level of evidence, C, I).
"Although DR remains the leading cause of preventable blindness in working adults, there are primary and secondary interventions proven effective in limiting visual loss," the study authors conclude. "The indications, efficacy, and safety of newer medical and surgical treatments, however, require further evaluation."
The National Health and Medical Research Council of Australia funded this study. One of the authors was included as an inventor on patents relating to the formulation of triamcinolone for ocular use. Two authors have disclosed various financial relationships with Pfizer, Novartis, and Allergan.
JAMA. 2007;298:902-916.