Faculty Bibliography

We studied three members of three successive generations of a family with autosomal dominant congenital stationary night blindness and normal fundi. Psychophysical studies on two members showed normal final cone thresholds and mildly increased rod thresholds. Full-field electroretinograms on all three members showed normal photopic b-wave amplitudes and implicit times. Under scotopic conditions, the rod response was absent, and with a bright flash stimulus, there was a normal a-wave with no b-wave. This electronegative dark-adapted electroretinogram resembled the Schubert-Bornschein type seen in congenital stationary blindness, which has been seen only in autosomal and X-linked recessive pedigrees

We have attempted to determine in this study whether the arterial administration of vincristine produces in cat the functional defects associated with hereditary and vincristine-induced night blindness in man. Using the isolated perfused cat eye, it has been possible to mimic some of the essential features of human night blindness, namely, retention of normal rhodopsin chemistry and normal photoreceptor activity, with marked suppression of the ERG b-wave. In addition, we find that vincristine produces an early, rapid fall in the c-wave, a potential that arises largely in the pigment epithelium. Ultrastructurally, it appears that many classes of retinal neuron are affected by the drug, but the principal changes in cytoarchitecture are seen in the photoreceptors. Except for the outer segments, paracrystalline deposits were found in all parts of the visual cell. The disruption of the normal microtubular organization of these cells suggests that the drug interferes with the functional integrity of the transport system by which synaptic activity is maintained. By reducing the efficacy of communication between visual cells and their second-order neurons, the electrical responses of post-synaptic elements is degraded. The route by which vinca alkaloids reach the neural retina is still uncertain, but our preliminary studies using HRP indicate that the relatively high concentration of vincristine used in this study may be responsible for compromising the blood-retinal barrier.

A 22-year-old man had a three-year history of progressive day blindness, most notably peripherally, and denied difficulty with central vision or color vision. Visual function studies demonstrated a diffuse dysfunction of the photopic system and normal scotopic function. The central cone function, however, was essentially normal. Visual acuity was 20/20 in each eye, results on AO-HRR and Ishihara color plate testing were normal, color naming visual fields demonstrated color discrimination in the central 10 degrees, and foveal adaptation was normal

Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use

Ingestion of the rat poison N-3-pyridylmethyl-N'-p-nitrophenylurea (PNU) produced ocular toxicity in three humans and in an animal model, the Dutch Belted rabbit. The electroretinogram b wave was especially susceptible to the effects of the rodenticide, and the target tissue appeared to be the retinal pigment epithelium. Injection of PNU itself did not produce ocular toxicity. The poison had to be administered orally. Gentamicin administered orally with PNU prevented the ocular toxicity. Presumably this antibiotic killed those gastrointestinal bacteria responsible for PNU's metabolism into an ocular toxin. L-tryptophan, a known antidote for the lethal effects of PNU, was an antidote for the ocular toxicity when administered orally but not when administered parenterally.

Psychophysical, reflectometric, and electrophysiologic studies were done on four members of a dominant pedigree with progressive cone dystrophy. The two youngest individuals were asymptomatic at the initial examination, and none of the subjects complained of problems associated with night vision. Nevertheless, absent or grossly reduced cone-mediated electroretinographic (ERG) responses showed the widespread loss of cone function, and moderate elevations (less than 1 log unit) in absolute threshold together with reductions in rhodopsin levels in the mid-peripheral retina provided evidence of impairment of the rod system. The progressive nature of the disease was apparent from the case histories and the changes in visual performance that occurred on re-test after a 5-year interval. Moreover, the results of increment threshold measurements at several retinal loci suggested that peripheral cones may be affected earlier and more severely than those in the central retina

A healthy, 14-year-old girl presented with nyctalopia, good vision, and multiple, irregular, yellowish lesions of the fundus. Dark adaptometry showed prolonged cone and rod branches, elevated thresholds, and the cone-rod transition occurring after 50 minutes in darkness. Her scotopic electroretinogram (ERG) b-wave attained normal amplitudes after 45 minutes of dark adaptation. The half-time for regeneration of rhodopsin after an extensive bleach was 16 minutes, four times longer than normal, and the maximum density difference measured by fundus reflectometry was at the lower limit of the normal range. Although photopigment kinetics were significantly faster than observed in other reported cases of fundus albipunctatus, it appears likely that there is a wide spectrum of functional and funduscopic abnormalities in this disorder. However, fundus appearance, adaptometric findings, and rhodopsin determinations serve to distinguish fundus albipunctatus from other flecked retina diseases.