11.
DME – The Pathogenesis and which Treatment
May be Effective?
Hermann D. Schubert (New York)
The macula, the central and thickest portion of the retina, features a high concentration of glia
and up to four layers of blood vessels. Based on the mere volume of tissue and dual blood supply
from inner retina and choroid, the macula is particularly sensitive to ischemia and breakdown
of the blood ocular barrier. Whereas capillary closure is mediated by leukostasis and
changes in basement membrane by hyperglycemia, multiple upstream cellular mediators,
cytokines and growth factors (the cascades) have been found to be elevated in the diabetic vitreous.
Among them are VEGEF, interleukin 6, hepatocyte growth factor, and early and advanced
glycation end products. Decrease in visual acuity correlates highly with size of foveal avascular
zone, perifoveal intercapillary area and vitreous fluorophotometry penetration ratios as well
as patient age. The average age of patients in western studies of diabetic macular edema is 61 plus-minus ten years superimposing
the ischemia which is related to age. Swelling in macular edema thus depends on what and which cell has survived
the chronic ischemia related to overall retinopathy grade, disease duration and age of patient. There is alwa ys the possibility
of an edematous atrophy of increased thickness. Poor visual correlation attests to this.
Treatment of diabetic edema consists of control of diabetes, hypertension, and hyperlipidemia to delay ischemia.
Spontaneous improvement of vision and macular thickness has occurred among the placebo treated eyes in recent randomized studies and in eyes assigned to delayed photocoagulation in the ETDRS. Focal laser is the only approved treatment for
DME in the US and is being restudied and compared to newer modalities recruiting large numbers of patients in several trials
(www.DRCR.net). First results of these will be available in late 2008. Vitreous traction can be addressed surgically;
cytokines and growth factors can be downregulated or blocked either with a shot gun approach or by targeting isolated cellular
mediators. There will always be more mediators. Apart from side effects and possibly limited duration of visual benefit,
treatment is cumbersome and often anxiety producing to patients, longterm with uncertain endpoint, and costly to society.
Delaying the symptomatic visual threshold by earlier combined interventions may be the most effective and least invasive
strategy.