Molecular medicine in ophthalmic care.
BACKGROUND
Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators.


METHODS
An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 degrees fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function-Contrast Sensitivity Function, 6.5 degrees large field tritan threshold, 10 degrees threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later.


RESULTS
The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin.


CONCLUSIONS
To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention.
Richer
Stuart
S
Eye Clinic, Department of Veterans Affairs Medical Center, North Chicago, Illinois, USA. Stuart.Richer1@VA.Gov
Stiles
William
W
Thomas
Carla
C
D000284:Administration, Oral; D000369:Aged, 80 and over; D001334:Automobile Driving; D004338:Drug Combinations; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D008062:Lipofuscin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008603:Mental Health; D009755:Night Blindness / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D009885:Ophthalmology / Q000379:methods*; D010636:Phenols / Q000008:administration & dosage*; D059808:Polyphenols; D020127:Recovery of Function; D000077185:Resveratrol; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D013267:Stilbenes / Q000008:administration & dosage*; D014785:Vision, Ocular / Q000187:drug effects
D004338:Drug Combinations; D005419:Flavonoids; D008062:Lipofuscin; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; D000077185:Resveratrol