Leonardo D. Gilbert

Reproducibility of visual acuity measurements in patients with retinitis pigmentosa.

PURPOSE To establish the normal short-term range of variation in the measurement of visual acuity in patients with retinitis pigmentosa. METHODS Sixteen patients (31 eyes) with retinitis pigmentosa, whose visual acuity ranged from 20/25 to 20/200, participated in this prospective clinical study. The best-corrected visual acuity in undilated and in dilated conditions was recorded independently by two masked observers on two visits of each patient within a 2-week interval by means of the Early Treatment Diabetic Retinopathy Study charts (The Lighthouse, Long Island City, NY). RESULTS Using mixed-model analysis, a reasonable upperbound for intervisit (intraobserver) variability of 6.0 letters for the visual acuity of patients with undilated pupils and 6.3 letters for the visual acuity of patients with dilated pupils and the corresponding maximum interobserver variability of visual acuity of 5.7 letters in patients with either undilated or dilated pupils on the Early Treatment Diabetic Retinopathy Study charts were computed. The overall average interobserver and intraobserver variability in visual acuity ranged from 1.3-2.3 letters. CONCLUSIONS A change in visual acuity of seven letters or more on the standardized Early Treatment Diabetic Retinopathy Study charts may be considered important in patients with retinitis pigmentosa. For these patients with minor lens opacity, visual acuity measurements obtained with undilated and dilated pupils were similar. These findings help to establish guidelines for monitoring the response of visual acuity during any future therapeutic intervention trials or for determining substantial changes in visual acuity over time when the course of visual acuity loss in such patients is monitored.

Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy.

PURPOSE To evaluate the clinical and electrophysiologic findings in a family with two heterozygous sequence changes in the peripherin-retinal degeneration slow (RDS) gene. METHODS A family study was done of a pedigree obtained by screening for rhodopsin, peripherin/RDS, or rom-1 gene mutations in probands from families with hereditary retinal diseases. The patients consisted of three affected and four unaffected members from a family with cone dystrophy. Ophthalmoscopy, visual field testing, electroretinography, and DNA analysis were performed. RESULTS Denaturing gradient gel electrophoresis showed the presence of two different sequence changes in the RDS genes of this family. In three members with a retinal disease, the authors observed the substitution of phenylalanine for serine in codon 27 (serine-27-phenylalanine). The clinical and functional findings in these three patients were most consistent with autosomal-dominant cone dystrophy. Three other family members, unaffected with retinal disease, were found to show a substitution of serine for cysteine in codon 72 of the peripherin protein. CONCLUSION A peripherin/RDS sequence change may produce a cone dystrophy with minimal ophthalmoscopic changes in the macula and limited peripheral degenerative changes. Caution is warranted to avoid ascribing nondisease-causing sequence polymorphisms in candidate genes as responsible for determining the development of a retinal disease phenotype.

Clinical Features of a Previously Undescribed Codon 216 (proline to serine) Mutation in the Peripherin/Retinal Degeneration Slow Gene in Autosomal Dominant Retinitis Pigmentosa

BACKGROUND Mutations in the human peripherin/retinal degeneration slow (rds) gene have been found in patients with macular dystrophies as well as in those with autosomal dominant retinitis pigmentosa. The authors studied the clinical features in members of two families with autosomal dominant retinitis pigmentosa and a previously unreported mutation in the peripherin/rds gene. METHODS Affected family members underwent a clinical ophthalmic examination and electrophysiologic and psychophysical testing. Available family members were evaluated for a mutation in the peripherin/rds gene. RESULTS A mutation in codon 216 of the peripherin/rds gene, resulting in a substitution of the amino acid serine for proline, was found to segregate with retinitis pigmentosa in these two families. Ocular features of this mutation include a later onset of more notable ophthalmoscopic, electrophysiologic, and psychophysical abnormalities of the retina, an atrophic-appearing foveal lesion, and extrafoveal atrophic and hyperpigmented degenerative retinal changes, which were found more posteriorly than usually seen in patients with retinitis pigmentosa. Visual field testing showed a partial ring scotoma or pear-shaped configuration of the remaining portions of the peripheral fields. CONCLUSION A previously undescribed mutation in the peripherin/rds gene is responsible for an autosomal dominant retinitis pigmentosa phenotype. This phenotype tends to be associated with the development of an atrophic-appearing foveal lesion, more posterior distribution of pigmentary changes involving the vascular arcades, the presence of a partial ring scotoma or a pear-shaped configuration of the peripheral visual field, and a later onset of more extensive retinal structural and functional impairment.

Effect of vitamin A treatment on the prolongation of dark adaptation in Stargardt's dystrophy.

Background Prolongation in recovery of rod thresholds has been demonstrated in Stargardts dystrophy. One possible explanation for this finding includes an impairment of vitamin A transport by the retinal pigment epithelium (RPE). By delivering an increased amount of vitamin A to the RPE, it might be possible to overcome a relative deficiency of vitamin A utilization or transport, and thus improve rod dark adaptation. Methods Baseline dark-adapted rod final thresholds were measured for five patients with Stargardts dystrophy after 60 minutes of dark adaptation. A full dark-adaptation curve was then measured after exposure to a bleaching light for 5 minutes. Time of recovery to within 0.2 log units of the prebleach dark-adapted rod threshold was determined. Each subject then took a 14-to 18-day course of oral vitamin A, 50,000 IU daily. Dark adaptation was then reassessed using the same pretreatment protocol. Results Before treatment, all five patients had a prolongation of their rod recovery curve. There was no statistically significant difference between subjects in mean time taken to reach prebleach rod baseline thresholds before and after vitamin A treatment. Conclusions These findings do not rule out the posssiblity that a delay in rod dark adaptation in Stargardts dystrophy results from an inability to transport vitamin A from the RPE to photoreceptor cells. Nevertheless, a high dose of oral vitamin A taken for at least 14 days did not provide any objective improvement in dark-adaptation function in five such patients.

Prolonged Rod Dark Adaptation in Patients With Cone-rod Dystrophy

Thirteen patients with cone-rod dystrophy were assigned into one of four previously described category subtypes according to clinical, electrophysiologic, and psychophysical criteria. The time course of rod dark adaptation was determined for each patient by means of a Goldmann-Weekers dark adaptometer. Nine of the 13 patients showed a normal time to return to their dark-adapted thresholds before bleaching, while four patients showed a prolonged recovery time. The four patients with a prolonged rod-recovery time were all from the same clinical subtype and showed a similar fundus appearance as well as similar electrophysiologic and psychophysical findings.