Photoreceptor loss in age-related macular degeneration.
OBJECTIVE
The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the fundus. If so, AMD must have a predilection for rods over cones. The authors tested this hypothesis by determining the relative numbers of cones and rods in donor eyes with mid-to late-stage AMD and in age-matched controls.


METHODS
Thirteen eyes (from seven donors) with grossly visible macular drusen and pigmentary disturbances were either wholemounted for photoreceptor counts or sectioned through the fovea for histopathology and carbonic anhydrase histochemistry to label red-green cones. Eyes were assigned to AMD or control groups on the basis of histopathology and clinical history.


RESULTS
Five nonexudative AMD (NE-AMD) eyes from three donors showed sparing of foveal cones and loss of rods and cones in the parafovea. In two donors, rod loss exceeded cone loss at most parafoveal locations, and in one donor, rod density was normal and cone density was reduced. In eight exudative AMD (EX-AMD) eyes from five donors, photoreceptors surviving along the margins of and overlying disciform scars were largely cones.


CONCLUSIONS
Photoreceptors are lost in NE-AMD as well as in the more severe exudative form, consistent with functional and clinical studies. The authors propose that rods die in older eyes without evidence of overt retinal pigment epithelial disease. In persons susceptible to AMD, the retinal pigment epithelium becomes dysfunctional. Secondarily, rod loss continues and cones begin to degenerate. Eventually, only degenerate cones remain; ultimately, all photoreceptors may disappear.
Curcio
C A
CA
Department of Ophthalmology, University of Alabama at Birmingham 35294-0009, USA.
Medeiros
N E
NE
Millican
C L
CL
D000368:Aged; D000369:Aged, 80 and over; D002256:Carbonic Anhydrases / Q000378:metabolism; D002452:Cell Count; D005260:Female; D005451:Fluorescein Angiography; D005584:Fovea Centralis / Q000473:pathology; D005654:Fundus Oculi; D006651:Histocytochemistry; D006801:Humans; D008268:Macular Degeneration / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D010786:Photoreceptor Cells / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D015593:Retinal Drusen / Q000150:complications; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000150:complications
D002256:Carbonic Anhydrases