The Long-term Effects of Laser Photocoagulation Treatment in Patients with Diabetic Retinopathy

Keywords:laser, treatment, medical, fibers,  Time:09-11-2015

The data from the ETDRS suggested that scatter laser photocoagulation should be considered for all eyes with severe nonproliferative diabetic retinopathy or worse and not for those with mild to moderate nonproliferative retinopathy.5 For patients with type 2 diabetes, early treatment at the severe nonproliferative stage rather than waiting for the onset of high-risk proliferative retinopathy is considered, because the rate of severe loss was reduced by more than 50% in such eyes treated with early laser photocoagulation compared with eyes assigned to deferral of laser photocoagulation.6 This beneficial effect of early treatment at the severe nonproliferative stage was not seen in patients with type 1 diabetes. Many factors need to be considered in deciding when to initiate photocoagulation for these patients, but it is apparent from both the DRS and ETDRS that virtually all patients with high-risk proliferative retinopathy should have scatter photocoagulation without delay. Focal laser photocoagulation treatment for diabetic macular edema was also evaluated in the ETDRS. The treatment of eyes with clinically significant macular edema (defined as retinal edema that affects or threatens the center of the macula) with focal laser photocoagulation reduced the risk of moderate vision loss (loss of 3 or more lines on a logarithm of the minimum angle of resolution visual acuity chart) by 50%.4 Focal treatment with laser photocoagulation has become the standard treatment for diabetic macular edema. The results of the Diabetic Retinopathy Vitrectomy Study, a randomized clinical trial of vitrectomy for eyes with dense vitreous hemorrhage and for eyes with very severe proliferative diabetic retinopathy, showed a greater chance of recovering good vision with vitrectomy.7 With the improvement in vitrectomy techniques and instrumentation, the visual results have markedly improved since these early trials.
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Materials and Methods

The ETDRS was designed to assess photocoagulation and aspirin treatment for patients with mild nonproliferative to early proliferative diabetic retinopathy.12 Study patients were randomly assigned to 650 mg of aspirin or placebo daily. One eye of each patient was randomly assigned to early laser scatter and/or focal photocoagulation, whereas the fellow eye was given scatter laser photocoagulation only when high-risk proliferative diabetic retinopathy developed. At baseline, these patients were aged 18 to 69 years with a favorable prognosis for 5-year survival. All patients who were enrolled and followed in the original ETDRS at the Johns Hopkins Medical Institution and who were living at the closeout visit of August 1989 were identified (n
214). Those still living were invited for an eye examination at the National Eye Institute, National Institutes of Health. The institutional review boards for research on human subjects at both the John Hopkins University and the National Eye Institute/National Institutes of Health approved the follow-up study. A total of 3711 patients had been enrolled in 22 ETDRS clinical centers and followed from 5 to 9 years. This follow-up study was conducted from 1997 to 2000 on the patients enrolled at the Johns Hopkins Clinical Center, providing 13 to 19.5 years of follow-up (median, 16.7 years) after the study randomization visit and the initiation of laser photocoagulation. The surviving patients were all invited for an examination at the clinical center at the National Eye Institute/National Institutes of Health. After obtaining signed informed consents, historical information was obtained. Patients received a comprehensive eye examination, which included best-corrected visual acuity, slitlamp biomicroscopy, and dilated ophthalmoscopy. Lens opacities were assessed clinically by slit-lamp biomicroscopy, using the Age-Related Eye Disease Study classification system.13 Stereoscopic fundus photography of seven fields and fluorescein angiography were performed. The Fundus Photograph Reading Center at the University of Wisconsin, in Madison, centrally graded and compared the fundus photographs and fluorescein angiograms obtained at this follow-up visit with those obtained at baseline and during the course of the study. Six patients were willing to be examined but were unable to travel to the National Eye Institute for examination. These patients were examined by collaborating ophthalmologists, most of whom were coinvestigators in the original ETDRS study. They examined these patients in their institutions and private offices using the standardized protocol for examination and fundus photography and completing the data collection forms used at the National Eye Institute.

The names and demographic data of all patients who did not respond to the invitation for a follow-up examination were submitted to the National Death Index. Matches from the National Death Index provided confirmation of the deceased patients. The causes of death were obtained from the death certificates.

Statistical Methods

Comparisons of categorical baseline characteristics between the Johns Hopkins Clinic patients and the ETDRS patients enrolled in the remaining clinical centers were conducted by chi-square test analysis or by permutation testing of the chi-square test statistic if the cell sizes were too small to warrant application of the large sample method. Continuous baseline variables were compared by the t test. Cox proportional hazards regression was applied to assess and adjust for the effects of the following risk factors on mortality in the follow-up group: glycosylated hemoglobin (HBA1c), age, duration of diabetes, proteinuria, blood pressure, visual acuity score, and diabetic retinopathy severity. Because these are secondary analyses, the P value considered to be statistically significant is P0.01.

Results

Mortality

Of the 214 patients who were alive at the end of the original ETDRS study in 1989, 130 (61%) were deceased by the time of the follow-up examination. The causes of death were determined by assessment of the death certificates obtained from the National Death Index report. These consist of cardiovascular disease in 48%, nonspecific diabetic complications in 28%, renal disease in 4%, neurologic causes in 7%, malignancies in 4%, and other causes in 5%. The adjusted analyses (Cox proportional hazards model) of baseline risk factors associated with death for this clinic population included increasing age, proteinuria, and elevated HBA1c (Table 1). In univariate analyses, with or without age adjustment, both poor visual acuity and more severe retinopathy were significantly associated with increased mortality. However, in the final Cox model, these two factors were no longer statistically significant, but the sample size of this study is fairly small. Of the 84 who were still living, 1 patient was hospitalized for Alzheimer’s disease, 1 was confined to a nursing home, 1 had incomplete data from the patient’s ophthalmologist, and 10 could not be contacted. Excluding these 13 patients, 71 (85%) were examined. The duration of follow-up from the beginning of the enrollment in the original ETDRS until the follow-examination was 13 to 15 years for 16 patients (23%), 16 to 17 years for 25 patients (35%), and more than 17 years for 30 patients (42%), with median follow-up of 16.7 years. Table 2 shows a comparison of the baseline characteristics of the patients enrolled in the Johns Hopkins Clinic with the study population enrolled in the remaining ETDRS clinics nationwide. Comparing the patients enrolled at Johns Hopkins with the rest of the ETDRS population, one sees that the patients were similar in age and gender. There were more blacks but fewer Hispanic patients in the Johns Hopkins clinic population than in the general ETDRS population. Patients enrolled in the general ETDRS population were more likely to be cigarette smokers than in the Johns Hopkins clinic population. There were more patients in the Johns Hopkins clinic that had history of congestive heart disease compared with the ETDRS population. Other medical and baseline characteristics were similar in both the Johns Hopkins clinic population and the remaining ETDRS population. The levels of severity of retinopathy at baseline were also similar in the two populations, whereas patients from the Johns Hopkins Clinical Center had somewhat higher intraocular pressures at baseline.