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Objective: To delineate the clinical characteristics of infantile nephropathic cystinosis in adult patients who have undergone renal transplantation.Design: Case series.Setting: Clinical research unit.Patients: All 36 adult patients with nephropathic cystinosis referred to the National Institutes of Health.Outcome Measures: Longevity, growth, renal allograft survival, visual acuity, endocrine insufficiency, myopathy and swallowing dysfunction, cerebral calcifications, and occupational status.Results: Of the 36 patients, seven were dead, five with functioning allografts. The 1-year and 5-year graft survival rates for 30 cadaveric allografts were 90% and 75%, respectively. The patients' mean height and weight were severely retarded. Five patients were legally blind, and three others had severely impaired vision in one eye. Thirty-one (86%) of 36 patients required thyroid hormone replacement therapy. One third had a distal myopathy, and 21 had moderate to severe swallowing abnormalities. Eight patients had cerebral calcifications on computed tomographic scan. Despite these complications, the sighted patients engaged in a normal variety of occupations. Only 11 patients were receiving adequate cystine-depleting therapy with cysteamine (mercaptamine) or phosphocysteamine.Conclusions: Adult patients with nephropathic cystinosis suffer serious complications of the disease. [ABSTRACT FROM AUTHOR]

Objective: To quantify the effect of long-term reduction of plasma ornithine levels through adherence to an arginine-restricted diet on visual function in patients of all ages with gyrate atrophy of the retina and choroid., Methods: A long-term observational study was conducted on 27 patients with gyrate atrophy, 17 of whom elected to comply with the arginine-restricted diet and 10 who were unable to comply. The mean rates of change in the electroretinogram combined response, electroretinogram flicker response, and kinetic and static perimetry were determined., Results: After mean follow-up of 13.9 years for the patients on the diet and 14.1 years for those not on the diet, the mean rates of change for the diet group compared with those of the no-diet group were statistically significantly slower for all outcome measures (age-adjusted P<.05) except for static perimetry (P =.06)., Conclusions: Adhering to an arginine-restricted diet so as to lower the plasma ornithine level below an average of 5.29 to 6.61 mg/dL (400-500 micromol/L) will slow the loss of function as measured by sequential electroretinography and visual field examinations.

Objective: To determine whether the long-term reduction of plasma ornithine levels by way of an arginine-restricted diet in patients with gyrate atrophy will slow the progression of this chorioretinal degeneration., Design: Natural history study of 2 pairs of siblings with gyrate atrophy treated with an arginine-restricted diet., Main Outcome Measures: Fundus photography and electrophysical and psychophysical retinal function tests., Results: After 16 to 17 years of receiving an arginine-restricted diet, the younger sibling in each pair, who was prescribed the diet at an earlier age than the older sibling, demonstrated a slower progression of lesions compared with the older sibling., Conclusions: If started at an early age, long-term substantial reduction of plasma ornithine levels may appreciably slow the progression of the chorioretinal lesions and, to a lesser extent, the progressive loss of retinal function in patients with gyrate atrophy.

Objective: To assess the course of change of visual function outcome variables in 5 patients with gyrate atrophy before a gene replacement therapy clinical trial., Methods: The outcome variables selected were visual field sensitivity and electroretinogram amplitude. The course of change of these outcome variables was determined by calculation of their half-lives., Results: In the 4 to 6 years during which each patient was followed up for this study, median visual field half-lives were 17.0 years (static perimetry) and 11.4 years (kinetic perimetry). Median electroretinogram half-lives were 16.0 years (maximal response) and 10.7 years (flicker response)., Conclusions: The course of the decline of visual function outcome variables is frequently slow. Thus, a long-term clinical trial would be required to assess the efficacy of the intervention in the preservation of visual function.

Objectives: To assess the alterations in dark adaptation induced by low (200 mg/d) doses of fenretinide (4-HPR), to assess whether these effects were cumulative and whether they were reversible, and to attempt to elucidate the mechanism underlying the changes in night vision., Design: Case series., Setting: Outpatient eye clinic., Patients: Twenty-two women enrolled in a breast cancer chemoprevention trial, and 18 normal control subjects., Intervention: Measurements of absolute luminance thresholds during dark adaptation., Main Outcome Measures: Parameters of an exponential model of the dark-adaptation function before, during, and after administration of fenretinide., Results: The most conspicuous effect of fenretinide on dark adaptation was a significant delay in the timing of the rod-cone break (P<.001). A minimal elevation of the final cone threshold was also observed. These effects were reversible after fenretinide therapy was discontinued and did not seem to be cumulative. An inverse relationship between delay of the rod-cone break and plasma retinol concentration was found., Conclusion: The dose of fenretinide used in this study produced clearly measurable, but not severe, changes in night vision, which were rarely symptomatic.

Objective: To assess the association of visual field, vertical cup-disc (VC/D) ratio, and vertical height of optic chiasm., Design: Case series., Setting: Outpatient eye clinic., Patients: Eighteen patients with low, normal, or elevated intraocular pressure, with or without visual field defects., Intervention: Measurement of visual field, VC/D ratio, and vertical height of optic chiasm., Main Outcome Measures: Association between VC/D ratio and visual field defects compared with association between vertical height of optic chiasm and visual field defects., Results: Visual field defects were graded as 0, 1 to 10, and 11 to 20 (from least to most severe). Group mean VC/D ratios were 0.47 (0), 0.55 (1-10), and 0.69 (11-20) for right eyes and 0.48 (0), 0.57 (1-10), and 0.75 (11-20) for left eyes. The significance level for trend was P = .02 for right eyes and P = .006 for left eyes. Group mean chiasm heights were 3.5 (0), 2.9 (1-10), and 2.2 (11-20) mm for right eyes and 3.5 (0), 2.8 (1-10), and 2.2 (11-20) mm for left eyes. The significance level for trend was P < .001 for right eyes and P = .002 for left eyes. To assess the simultaneous effects of VC/D ratio and chiasm height on the visual field defects groups, we used ordinal logistic regression models. Models with both variables implied that chiasm height was a stronger predictor of visual field defects group than VC/D ratio (for right eyes, P = .04 [VC/D ratio], P = .001 [chiasm height]; for left eyes, P = .11 [VC/D ratio], P = .005 [chiasm height])., Conclusions: When chiasm and VC/D ratio were analyzed in the same model, chiasm height was a stronger predictor of visual field defects. In advanced visual field defects, the optic chiasm is atrophic.

Objective: To examine the potential association of central serous chorioretinopathy with endogenous hypercortisolism (Cushing's syndrome)., Design: Ophthalmologic survey of consecutively admitted patients with endogenous Cushing's syndrome., Setting: An eye clinic of a research center (National Eye Institute, Bethesda, Md)., Patients: Sixty consecutive patients with confirmed endogenous Cushing's syndrome., Main Outcome Measures: Findings from complete ophthalmologic evaluation., Results: Three (5%) of 60 patients had one or more episodes of appropriately documented central serous chorioretinopathy. In all cases, the episodes occurred during the period of hypercortisolism., Conclusions: Central serous chorioretinopathy is an uncommon manifestation of endogenous Cushing's syndrome. Since central serous chorioretinopathy has been associated with other hypercortisolemic states, we suggest that glucocorticoids may play a role in the development of this disease.

Spatial contrast sensitivity and lens density were measured in 30 subjects (18 patients with pure nuclear cataracts and 12 age-matched controls). Contrast sensitivity was assessed using two techniques: a conventional monitor method in which gratings were viewed through the cataract (overall spatial contrast sensitivity) and a laser interferometer method in which gratings were formed directly on the retina (interferometric spatial contrast sensitivity), thus reducing the effect of an opaque lens on grating contrast. The degree of lens nuclear opacity was measured by assessing the density of Zeiss Scheimpflug slit-lamp video camera images. A contrast sensitivity loss was found by using both methods; this reduction reached statistical significance only when monitor stimuli were used. There was a significant correlation between lens nuclear density and sensitivity loss at spatial frequencies from 4 to 16 cycles/degree (r = .56 to .79 and P less than .05 to less than .001). A correlation coefficient of .82 (P less than .001) characterized the relationship between visual acuity (log of the minimal angle of resolution) and lens density. Nuclear lens opacity significantly affects contrast sensitivity; pure nuclear cataracts produce spatial visual losses at intermediate and high spatial frequencies.

Gyrate atrophy of the choroid and retina is an autosomal recessive, chorioretinal dystrophy that begins in childhood and leads to blindness in the fourth to seventh decade of life. The primary defect is deficiency of ornithine-delta-amino-transferase, which results in accumulation of ornithine. We examined six pairs of affected siblings to determine if intrafamilial variability in the phenotype was less than interfamilial, and to determine if long-term (5- to 7-year) reduction of ornithine with an arginine-restricted diet had an effect on the progression of the chorioretinal degeneration. All but one set of siblings underwent periodic ophthalmologic examinations. The clinical diagnosis was confirmed with the demonstration of hyperornithinemia and deficiency of ornithine-delta-aminotransferase. The molecular defects in their ornithine-delta-amino-transferase genes also were determined. The two younger pairs of siblings were given an arginine-restricted diet and followed up for 5 to 7 years. We found strikingly similar phenotypes in affected members of the same pair of siblings. In the young patients receiving the diet, there was substantial reduction of ornithine levels. These children had only modest progression of their ocular disease during this period. Furthermore, a comparison of the outcome of the younger with their older siblings at an equivalent age showed that the younger siblings, who started receiving the diet at an earlier age, had much less ocular disease. We conclude that intrafamilial phenotypic variation in gyrate atrophy is less than interfamilial and, therefore, that genetic heterogeneity plays a role in the phenotypic variability of gyrate atrophy. Furthermore, we conclude that chronic reduction of ornithine with an arginine-restricted diet dramatically slows the progression of the chorioretinal dystrophy.

Eighteen patients with nephropathic cystinosis who were younger than 42 months and 11 patients 4 to 31 years of age were entered into a double-masked, randomized, placebo-controlled trial of topical cysteamine eye drops between November 1985 and September 1989. Eight of the younger patients and 2 of the older patients showed marked clearing of corneal crystals in one eye compared with the fellow eye. When the code was broken, all 10 patients were found to have received cysteamine eye drops in the improved eye. Of the remaining 19 patients 4 were unavailable for follow-up. In 15 patients no marked difference was noted between the two eyes. Eight have presumably been in the protocol for too short a time and several have been poor compliers with the therapy. These results not only demonstrate the potential for primary prevention of corneal crystal deposition but also, for the first time, offer the possibility of reversing the corneal complications of cystinosis in older patients.

Eight nephropathic-cystinotic patients having undergone renal transplantation seven to 14 years previously were studied. Serious ocular complications were noted in four of the eight cases not previously reported. These included posterior synechiae, deposition of crystals on the anterior lens surface, and decreased visual acuity accompanied by impaired visual function, as measured by psychophysical and electrodiagnostic tests when possible.

This study of 47 patients from 11 families with neurofibromatosis type 2 (NF 2) confirms our previously reported association between posterior capsular cataract and NF 2. A highly significant statistical association was found between the presence of posterior capsular lens opacities and the presence of NF 2 as determined by magnetic resonance imaging or pathologic diagnosis. This association was not present for other types of lens opacities that could be the result of age-related or nonspecific changes. When considering the diagnosis of NF 2, this finding now makes it essential to use a careful dilated biomicroscopic examination of the lens to evaluate known, suspected, or at-risk individuals for this potentially early associated manifestation.

Neurologic and cognitive function in neurofibromatosis type 1 (NF1) were assessed in a controlled pilot study of 13 pairs of siblings aged 6 to 27 years. One subject in each pair was affected with NF1, and the other, the control subject, was unaffected. Subjects with evidence of focal central nervous system disease were excluded. The 13 subjects with NF1 had no excess of mental retardation, attention-deficit disorder, or specific learning disorders (using Wilcoxon's Signed Rank Test and McNemar's Test for Symmetry). These subjects, however, had significantly higher scores for subtle neurologic abnormalities (21 vs 6) and significantly lower full-scale IQ scores (94 vs 105) than their unaffected siblings. The IQ scores of the affected subjects were not clustered at the lower end of the scale but showed a slight downward shift in distribution compared with those of their siblings. In addition, a visual-spatial orientation deficit was present in eight of nine affected subjects so evaluated. The findings suggest that subjects with NF1 have a widespread alteration of the brain during development that manifests as one or more specific types of neuropsychologic deficits.

Five patients with basal cell carcinoma received fenretinide. Two patients while receiving the drug had evidence of abnormal rod photoreceptor function that reversed rapidly on cessation of therapy. We speculate that fenretinide may interfere with the binding of vitamin A to opsin or with the transport of vitamin A.