Clinical and Experimental Approach to the Benefits and Risks of Laser Treatment for Diabetic Macular Edema
Abstract: Diabetic retinopathy is an ophthalmic complication of diabetes that currently affects 93 million people worldwide. Diabetic macular edema is a subtype of diabetic retinopathy that is characterized by leaking blood vessels in the central part of the retina, and it is a major cause of vision loss in individuals with diabetes. Screening for retinopathy is performed at regular intervals to identify subjects in need of treatment. In Sweden, the recommended screening interval for type 2 diabetic subjects with no diabetic retinopathy is 3 years. Laser treatment for diabetic macular edema has been used for decades, but studies have reported conflicting results regarding possible clinical complications following such therapy. Furthermore, the molecular events involved in the clinical benefits of laser treatment have not been fully explored. To determine the safety of the current screening interval, the 3-year incidence of diabetic retinopathy and macular edema was monitored in type 2 diabetic subjects with no retinopathy (Study I). To identify the long-term effects of laser treatment, the retinal sensitivity in 29 consecutively recruited subjects with diabetic macular edema was assessed by visual fields before and after laser treatment every 6 months during a period of 2 years (Study II). To investigate the cellular and molecular events that may be involved in the clinical benefits of laser treatment, a model of in vitro laser coagulation of the retinal pigment epithelium was established and used to evaluate cell death and cell repair (Study III). The same model was also used to explore the effects of laser treatment on mRNA and protein levels by analysis of microarray and proteomics data (Study IV). Study I demonstrated a very low incidence of sight-threatening diabetic retinopathy, which supports the current use of a 3-year retinal screening interval for the subgroup in question. Study II showed no change in retinal sensitivity following laser treatment for diabetic macular edema during the 2-year follow-up compared to baseline. Study III revealed that laser-induced damage involved both necrosis and apoptosis, and the repair process entailed both proliferation and migration. In study IV, the downregulation of the protein Carbonic anhydrase 9 and the upregulation of heat shock proteins 1A and 1B were the most interesting findings and might explain some of the beneficial effects of laser treatment for diabetic macular edema.
CLICK HERE TO DOWNLOAD THE WHOLE DISSERTATION. (in PDF format)