Current issues of ACP Journal Club are published in Annals of Internal Medicine


Aspirin did not affect the progression of retinopathy in patients with nonproliferative or early diabetic retinopathy

ACP J Club. 1992 Mar-April;116:49. doi:10.7326/ACPJC-1992-116-2-049

Source Citation

Early Treatment Diabetic Retinopathy Study Research Group. Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Ophthalmology. 1991 May;98:757-65.



To evaluate the safety and efficacy of aspirin in patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy.


Randomized, placebo-controlled, multicenter trial of 9 years duration.


22 eye institutes across the United States. (Data obtained from a previous report.)


3711 diabetic patients {aged 18 to 70 years},* with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were included in the study {56% were men}.* Patients were followed for between 3 and 8 years; 2807 patients (93%) attended the final annual examination. (*Data obtained from a previous report.)


Patients were assigned to 650 mg of aspirin daily (n = 1856) or to 2 similar placebo tablets (n = 1855). Other platelet-affecting drugs were not permitted. Each patient had 1 eye assigned randomly to early photocoagulation and the other eye to deferred photocoagulation, done only if "high-risk proliferative diabetic retinopathy" developed (i.e., new vessels on or within 1 disc diameter of the optic disc, with or without vitreous or preretinal hemorrhage).

Main outcome measures

The development of high-risk proliferative retinopathy was identified at scheduled visits by ophthalmoscopic examination and fundus photography. Secondary outcomes were change in visual acuity, development of macular edema, and occurrence of vitreous or preretinal hemorrhage.

Main results

The relative risk (RR) for development of high-risk proliferative retinopathy for eyes assigned to deferred photocoagulation in patients assigned to aspirin compared with patients assigned to placebo was 0.97 (99% CI 0.85 to 1.11). RR was 0.77 (CI 0.45 to 1.31) for eyes with the least severe retinopathy (microaneurysms with exudates, moderate retinal hemorrhages, or macular edema). There was no excess of vitreous or preretinal hemorrhage among patients assigned to aspirin (RR 1.05, CI 0.81 to 1.36) or of development or progression of visual loss or clinically significant macular edema. Risks for these outcomes among the eyes assigned to early photocoagulation did not differ by medication assignment. 340 patients assigned to aspirin died compared with 366 patients assigned to placebo (P > 0.2). Compliance with the study medication measured by urine salicylate or pill count was 80%.


Aspirin did not affect the progression of retinopathy. It also did not increase the risk for vitreous or retinal hemorrhage in diabetic patients with nonproliferative or early proliferative retinopathy.

Source of funding: National Eye Institute.

Address for article reprint: Biometry and Epidemiology Program, National Eye Institute, Building 31, Room 6A-24, 9000 Rockville Pike, Bethesda, MD 20892, USA.


In this, the most recent article from the Early Treatment Diabetic Retinopathy Study Research Group, the authors address both parts of the important question, "Are there harmful or beneficial effects of aspirin on the natural history of diabetic retinopathy?" The population studied is diabetic patients with mild-to-severe nonproliferative or early proliferative retinopathy—a heterogeneous group. Clinical and demographic factors that may affect the prognosis for this disorder (1) did not, however, differ between the randomized groups (2).

The potential benefits of aspirin in diabetic eye disease are suggested in articles describing decreased microaneurysm and cataract formation (3, 4), but still require more controlled clinical trials. The present investigation enrolled enough subjects initially, but fewer than half the patients were in the study for more than 5 years. Because the progression of diabetic retinopathy has a prolonged and somewhat controversial natural history, interpretations of the long-term effects of aspirin on retinopathy from these data remain questionable.

From our understanding of the pharmacologic effects of aspirin and the pathophysiology of diabetic retinopathy, it is enticing to conjecture that cyclo-oxygenase or aldose reductase inhibition or decreased thromboxane synthesis due to aspirin may be beneficial (5). In any case, invoking the words of Hippocrates, " no harm," in considering the results of the present study, it appears that cardiovascular protective doses of this medication are not harmful in patients with diabetic retinopathy when the aspirin is taken for several years.

Carolyn Pedley, MD
Robert Bloomfield, MDBowman Gray School of MedicineWinston-Salem, North Carolina, USA


1. Benson WE, Brown GC, Tasman W. Diabetes and Its Ocular Complications. Philadelphia: W.B. Saunders Co.; 1988:1-5.

2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98:741-56.

3. The DAMAD Study Group. Diabetes. 1989;38:491-8.

4. Cotlier E. Can J Ophthalmol. 1981;16:113-8.

5. Hoojendijk EM, Ten Cate CW. Lancet. 1980;1:93-4.