Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy.

OBJECTIVE: To provide the first measures of the relative rates of rod and cone functional loss in patients with retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). DESIGN: Five-year, prospective natural history study. PARTICIPANTS: Ninety-six patients (67 with RP and 29 with CRD) retaining measurable rod-mediated visual function and 5 normal subjects were tested at baseline and annually for 4 consecutive years. MAIN OUTCOME MEASURES: Tests of visual function included visual acuity, dark-adaptation thresholds, dark-adapted static perimetry, and rod and cone computer-averaged electroretinograms (ERGs), which were obtained over a range of retinal illuminances. Intervisit variability for each measure was obtained in a subset of patients who were tested twice within a 2-month interval and was used to determine whether an individual patient had shown progression, regression, or no change over a particular study interval. RESULTS: Over a 4-year interval, a significant number of patients with RP (60%) and CRD (62%) showed a decline in cone ERG amplitude. For rod ERG amplitude, the percentage of patients with RP or CRD showing progression was 64% and 45%, respectively. Although visual acuity, dark-adapted threshold, and rod visual field area also declined significantly over the 4-year period, the mean rate of change and the numbers of patients showing progression on these measures were lower than those for ERG measures. On specialized ERG testing, the yearly change in rod ERG threshold in RP was greater than the yearly change in cone ERG threshold, and the rate of progression varied significantly among inheritance types. For patients with CRD, the yearly change in rod threshold was comparable to the yearly change in cone ERG threshold. CONCLUSIONS: This study helps to define the natural progression of rod-mediated and cone-mediated functional loss in patients with RP and CRD.

Reactivation of inflammatory lesions in ocular histoplasmosis.

BACKGROUND: Active inflammation has not been traditionally associated with the ocular histoplasmosis syndrome. OBJECTIVE: To investigate the occurrence of presumed inflammatory chorioretinal lesions in patients with the ocular histoplasmosis syndrome. METHODS: Patients seen with acute symptoms and a clinical picture of ocular histoplasmosis were observed prospectively between August 13, 1993, and December 2, 1997. Symptoms, visual acuity, and fluorescein sodium angiography were used to document changes in inflammatory loci. RESULTS: Twelve patients were seen with active inflammatory lesions. Eleven had resolution of the loci with lessening of symptoms and improvement in acuity and angiographic findings. A typical subretinal neovascular membrane developed in 1 patient 8 months after the onset of symptoms. CONCLUSIONS: Inflammatory chorioretinal lesions can reactivate in the ocular histoplasmosis syndrome. In most of these patients, neovascularization did not develop and visual acuity was preserved.

Age-related changes in the color-match-area effect.

Color matches were measured as a function of field diameter (1, 2, 4 and 8 deg) for 53 normal observers aged 13-80 yr. The difference between match midpoints for the 1 deg diameter and the other diameters decreased throughout adulthood, indicating an age-related change in optical density of cone outer segments in the central 1 deg. For all ages, there were large interobserver differences in the magnitude of the difference scores. These results provide an explanation for contradictions in the literature on the effects of age on cone optical density and on the magnitude of the color-match-area effect.

Color matches in diseased eyes with good acuity: detection of deficits in cone optical density and in chromatic discrimination.

Reduced foveal cone optical density in diseased eyes with normal acuity can affect color matches. Using field diameters of 1 degree, 2 degrees, 4 degrees, and 8 degrees, we measured mean color-match midpoints and match widths in patients who had good acuity and who exhibited three categories of eye disease: hereditary macular degeneration (n = 12), retinitis pigmentosa (n = 19), and glaucoma (n = 18). Results were compared with those for normal observers of comparable ages. Mean color-match midpoints were abnormal only for the population with hereditary macular degeneration, indicating a reduction in cone optical density in the central 4 degrees. Mean color-match widths were enlarged for both hereditary macular degeneration and retinitis pigmentosa, a result consistent with a reduction in the number of foveal cones.

Pattern-reversal electroretinographic follow-up of laser photocoagulation for subfoveal neovascular lesions in age-related macular degeneration.

Pattern-reversal electroretinograms were used as an objective measure of macular integrity in a subset of 42 patients who were randomly assigned at enrollment in the Macular Photocoagulation Study to receive laser photocoagulation or no treatment for a subfoveal neovascular lesion. Pattern-reversal electroretinograms were obtained before randomization, three months and six months after randomization, and at six-month intervals randomization, and at six-month intervals thereafter. Responses were obtained to phase-alternating checkerboards of varying check size. Extrapolation of the best-fit regression line relating log-check size to amplitude was used to determine retinal acuity. At each follow-up period, including three months after laser photocoagulation, treated eyes showed less loss in pattern-reversal electroretinographic acuity than untreated eyes. The decline in pattern-reversal electroretinographic acuity in untreated eyes corresponded to the rapid growth in the area of the subfoveal neovascular lesion. The more gradual decline in treated eyes was consistent with an increase in the area of the treatment scar caused by spreading atrophy.

Limiting applications of cryotherapy for severe retinopathy of prematurity.

In an effort to minimize surgical and visual morbidity of cryotherapy for retinopathy of prematurity (ROP), 18 eyes of 13 patients with 3 to 7 clock hours of stage 3 ROP with "plus" disease were treated by cryotherapy applications limited to the avascular retina adjacent to the areas of stage 3 disease. In 17 of 18 eyes, this limited use of cryotherapy was sufficient to cause regression of ROP without further treatments. After at least 3 months follow-up, ROP outcome showed a normal macular appearance in 16 eyes; two eyes developed macular dragging; no retinal detachments occurred.

Pattern-reversal electroretinographic acuity in untreated eyes with subfoveal neovascular membranes.

To define further the natural history of visual loss in eyes with age-related macular degeneration (ARMD) complicated by a subfoveal neovascular membrane, pattern-reversal electroretinograms (ERGs) were obtained from patients randomized to no treatment at the Dallas center of the Macular Photocoagulation Study (Texas Retina Associates). Study eyes (n = 20) were tested during the initial visit and at 3-, 6-, and 12-month follow-up visits. Responses were obtained to phase-alternating checkerboards of varying check size. Extrapolation of the best-fit regression line relating the logarithm of the check size to amplitude was used to determine "retinal" acuity (log MAR). The pattern-reversal ERG acuity rating (100 - [50 x log MAR]) was derived for each visit. Pattern-reversal ERG acuity ratings for all patients across visits were correlated significantly with visual acuity ratings derived from the Bailey-Lovie chart (r = 0.61, P less than 0.001) and inversely related to neovascular membrane area (r = -0.55, P less than 0.001). During 1 yr of follow-up, pattern-reversal acuity ratings dropped from 53 to 12, corresponding to an average decrease of approximately 0.2 octaves/month. These results suggest that the pattern-reversal ERG, which samples the resolving power of the central 20 degrees, is a sensitive index of visual loss in age-related macular degeneration.

Cataract extraction after brachytherapy for malignant melanoma of the choroid.

Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

Longitudinal measures in children receiving ENCAD for hereditary retinal degeneration.

A hydrolysate of yeast RNA (ENCAD) is used in the Soviet Union for the treatment of hereditary retinal degenerations. We report longitudinal data from three young patients who have made at least two visits to the Soviet Union over a five-year period to receive treatment with ENCAD. Two children were diagnosed with cone-rod degeneration and the third has an isolated (simplex) form of retinitis pigmentosa. Visual function measurements were obtained before and after each visit to Moscow. In the comparison of previsit and postvisit visual acuity, 30 Hz flicker amplitude, and visual fields, ENCAD treatment had no significant short-term effect. Despite treatment with ENCAD, each patient has shown a significant decrease in visual function over the 5-year period. The rate of progression in these patients appears similar to previously published data on the natural history of their retinal degenerative disorders.

Vitrectomy in eyes at risk for macular hole formation.

Fifteen eyes believed to be at increased risk for macular hole formation underwent vitrectomy in an attempt to prevent macular hole formation. Full-thickness macular holes have not developed in 10 of 11 eyes with stage 1 macular holes. Four eyes were noted to have small full-thickness foveal defects (stage 2 macular holes) at the time of vitrectomy. Two of the four eyes have not progressed to macular hole formation and have 20/25 visual acuity. All patients have been followed for a minimum of 13 months (median, 18 months). The 12 eyes that have not experienced macular hole formation have had a significant (P less than 0.001) improvement in vision with seven (58%) attaining visual acuity of 20/25 or better. The postoperative foveal electroretinogram (ERG) amplitude was higher than the preoperative amplitude in five of the six eyes tested.

The focal electroretinogram in the clinical assessment of macular disease.

Focal electroretinograms (ERGs) were obtained from the fovea in 142 eyes with a variety of macular diseases and 50 age-matched eyes with acuity loss in which macular disease was ruled out. Across all eyes, the accuracy rate of discriminating macular disease from other causes of acuity loss was 87%. Among all eyes with macular disease, the sensitivity rate of the focal ERG to the presence of macular disease was 85%. Log focal ERG amplitude was significantly correlated with log Snellen acuity, except in those eyes with macular holes. The sensitivity rate increased to 94% when eyes with 20/40 or greater acuity and eyes with macular holes were excluded.

The focal electroretinogram in fellow eyes of patients with idiopathic macular holes.

In a prospective study of macular hole formation, focal electroretinograms (ERGs) were obtained from both eyes of 35 patients with a unilateral, idiopathic, full-thickness macular hole. Foveal cone ERG amplitude was significantly correlated with hole diameter at the initial visit. Twenty-six patients had normal foveal cone ERGs in the fellow eye at the baseline visit and for the duration of the study (mean follow-up, 35 months; range, 24 to 56 months). None of these eyes developed a macular hole. Seven eyes had significantly reduced foveal cone ERGs in the fellow eye, despite good visual acuity and a normal-appearing macula on the initial visit. Four of these eyes subsequently developed a full-thickness macular hole during follow-up (mean follow-up, 35 months; range, 25 to 46 months). Foveal ERG amplitude was significantly related to subsequent macular hole formation, suggesting that this test can provide an objective measure of macular function to help identify eyes at risk for macular hole formation.

Focal cone electroretinograms: aging and macular disease.

Focal cone electroretinograms were obtained with a 3-degree flickering stimulus from 100 normal eyes and 134 eyes with known macular disease. Responses were obtained during direct visualization of the fundus with a hand-held stimulator-ophthalmoscope. Mean foveal cone amplitude for 100 normal eyes was 0.31 microV, with 95% of all amplitudes greater than 0.18 microV. There was a significant inverse correlation between amplitude and age for responses obtained from the fovea (r = -0.91; p less than 0.001) but not for responses obtained from the parafovea (midway between fovea and disk, r = -0.53; not significant). In eyes with known maculopathy, mean foveal cone amplitude was correlated with Snellen acuity. Even after correcting for normal decreases in amplitude with age, responses were significantly reduced in 88/94 (94%) of all eyes with 20/40 or poorer acuity, suggesting that the focal electroretinogram is a sensitive test for detecting macular disease.

An inexpensive fiberoptic light pipe to aid in placement of episcleral radioactive plaques.

Episcleral plaque placement requires accurate localization of choroidal melanomas. Available fiberoptic light pipes can be fashioned to become scleral markers and transilluminators. The equipment is available wherever posterior segment surgery is performed. Surgical technique and equipment modifications are described.

Rod ERGs in retinitis pigmentosa and cone-rod degeneration.

Rod amplitudes as a function of retinal illuminance were analyzed by determining the parameters of the best fit Naka-Rushton function for 15 normal subjects, 25 patients with rod-cone degeneration, and 10 patients with cone-rod degeneration. Rod b-wave implicit times were analyzed by determining the best linear fit to log retinal illuminance. Retinal illuminances necessary for a criterion b-wave implicit time and for a half-maximum amplitude response (log k) were highly correlated indices of rod sensitivity. Both measures were normal or near normal in patients of all ages with cone-rod degeneration, but significantly elevated in patients with rod-cone degeneration. These results suggest that the underlying mechanisms of rod degeneration are fundamentally different in these two forms of hereditary retinal degeneration.

A comparison of visual function tests in eyes with maculopathy.

Several recently developed tests of visual function, including the Potential Acuity Meter (PAM), laser interferometer (LI), white-light interferometer (WLI), blue field entoptic phenomenon, and focal electroretinogram (ERG) were compared in 81 eyes with clear media and known macular disease. The results indicate that the PAM, the LI, and the WLI overread relative to Snellen acuity. Laser interferometric acuity values differed from Snellen acuity by at least 1.5 octaves in approximately 40% of all eyes, regardless of stimulus size (2, 5, or 8 degrees). Similar results were obtained with the WLI. Agreement with Snellen acuity was better for the PAM, with 91% of eyes falling within 1.5 octaves of Snellen acuity. Blue field and focal ERG results were categorized as normal or abnormal. While not producing Snellen equivalents, abnormal results from the blue field and focal ERG corresponded with poor Snellen acuity (less than 20/40) in 65% and 91% of eyes, respectively. Assuming that media opacities do not prevent adequate retinal stimulation, the present results suggest that the PAM and focal ERG are the most reliable for evaluating macular function when maculopathy is present.

Rod ERGs in children with hereditary retinal degeneration.

Rod ERGs were obtained over a broad range of stimulus intensities from young patients with retinitis pigmentosa and progressive cone-rod degeneration. Intensity-response functions suggest that children with retinitis pigmentosa have reductions in the number of functioning rods and that surviving rods generating the ERG have reduced sensitivity. Children with cone-rod degeneration also have reduced numbers of rods, but the remaining rods have normal sensitivity. These findings suggest that the underlying mechanisms of rod degeneration differ in these two forms of disease and demonstrate that insights into the pathogenesis of hereditary retinal degeneration can be obtained by testing children. The ability to distinguish between retinitis pigmentosa and cone-rod degeneration in children is also important because of differences in the rates of progression between the two classes of progressive retinal degeneration.