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Are There Clinically Detectable Antecedents To Diabetic Retinopathy?

Can evaluating retinal photoreceptor (rod and cone) distribution and function be used as an indicator of oncoming diabetic retinopathy? Paul Chous, M.A., O.D. Doctor of Optometry evaluates the possibility in his feature Are There Clinically Detectable Antecedents To Diabetic Retinopathy?
Are There Clinically Detectable Antecedents
To Diabetic Retinopathy?
Paul Chous, M.A., O.D. Doctor of Optometry
Type 1 diabetic since 1968

Because diabetic retinopathy is the leading cause of vision loss in working age Americans and a major cause of new blindness in the Western world, considerable clinical and research attention has been devoted to identifying those individuals at highest risk for blindness. All diabetes clinicians are familiar with the ophthalmoscopic signs of diabetic retinopathy, and eye care specialists in particular are trained to detect and stage retinopathy for appropriate management and timely intervention, including diabetes education and, when indicated, laser photocoagulation.

Because tighter glycemic, hypertensive and lipid control have been directly linked to reduced risk of retinopathy incidence and severity, the mantra has become “early detection and early intervention equals improved ocular outcomes.” To this end, ophthalmic researchers have attempted to identify early measures of impaired retinal function that precede the classic ophthalmoscopic signs of retinopathy (i.e. microaneurysms, dot & blot hemorrhages, lipid exudation, cotton wool spot formation, venous irregularities, retinal thickening and/or frank neovascularization.)

One line of inquiry has relied upon the peculiar features of retinal photoreceptor (rod and cone) distribution and function. Retinal cones mediate good central visual acuity and, in addition, perception of color. Cones come in three subtypes: blue (short wavelength or S-cones), green (medium wavelength or M-cones) and red (long wavelength or L-cones). The ratio of stimulation of these three cone subtypes determines color perception. Because there is a relative paucity of S-cones, metabolic insult to retinal photoreceptors will, in theory, selectively affect S-cone function as well as the retinal ganglion cells to which those S-cones are connected.

In fact, there is good evidence that S-cone function is preferentially affected by hyperglycemia. Blue-yellow color vision abnormalities have long been associated with diabetic retinopathy, but their psychophysical precursors are only now becoming easy to assess in the clinic. Blue stimulus on top of yellow background perimetry (short wavelength automated perimetry or SWAP) selectively isolates S-cone activity, and SWAP abnormalities not only accompany diabetic retinopathy but, more recently, have been shown to precede ophthalmoscopically detectable retinopathy in long-term diabetics. SWAP capability is now available in several commercially available perimeters designed for earlier detection of visual field defects due to glaucoma, but may also prove useful in diabetes.

Frequency Doubling Technology (FDT) perimetry uses a low spatial frequency sinusoidal gradient stimulus to selectively isolate non-redundant M (magnocellular) retinal ganglion cells. This technology has been advocated for early detection of glaucoma, but test results now appear to be negatively affected by diabetes as well, even in patients with no ophthalmoscopic evidence of retinopathy. As such, abnormalities due to diabetic retinal dysfunction may confound those caused by glaucoma, but they may also be distinctly predictive of future development of overt retinopathy. The FDT apparatus is faster and less expensive than SWAP, factors that may give it some relative advantage. However, neither SWAP nor FDT abnormalities are necessarily specific for diabetic retinal dysfunction (i.e. glaucoma, neurological and non-diabetic retinal vascular patholologies can all cause visual field defects), so perimetric results always must be considered in light of the patient’s overall clinical profile.

Electrophysiological changes associated with ocular disease typically have been measured only in University settings. Examples include the electroretinogram (designed to measure the photo-electrical response of rods and/or cones and used in diagnosis of retinal degenerative diseases like retinitis pigmentosa) and the electrooculogram (designed to measure electrical activity within the retinal pigment epithelium and useful in the diagnosis of diseases like vitelliform macular dystrophy, AKA Best’s Disease). Development of the multifocal electroretinogram (mfERG) has allowed scientists to identify specific loci of retinal dysfunction, and has led to the formulation of a highly predictive model for sites of future development of diabetic retinopathy. Much work needs to be done, however, to make such sophisticated technology clinically useful and available.
References below:

Lessons from a Diabetic Eye Doctor: How to Avoid Blindness and Get Great Eye Care

Dr. Paul Chous received his undergraduate education at Brown University and the University of California at Irvine, where he was elected to Phi Beta Kappa in 1985. He received his Masters Degree in 1986 and his Doctorate of Optometry in 1991, both with highest honors from the University of California at Berkeley. Dr. Chous was selected as the Outstanding Graduating Optometrist in 1991. He has practiced in Renton, Kent, Auburn and Tacoma, Washington for the last 12 years, emphasizing diabetic eye disease and diabetes education. Dr. Chous has been a Type 1 diabetic since 1968. He lives in Maple Valley, Washington with his wife and son.


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