Association of Vitamin A Supplementation With Disease Course in Children With Retinitis Pigmentosa.

Importance: While oral vitamin A supplementation is considered to potentially slow loss of retinal function in adults with retinitis pigmentosa and normal liver function, little data from children with this disease are available. Objective: To compare disease courses in children with retinitis pigmentosa taking or not taking vitamin A supplementation. Design, Setting, and Participants: Retrospective, nonrandomized comparison of vitamin A and control cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service of the Massachusetts Eye and Ear Infirmary. The study included children with different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and 25 not taking vitamin A. The dates for patient evaluations ranged from June 1976 to July 2016, and the data analysis occurred in October 2016. Interventions: Age-adjusted dose of oral vitamin A palmitate (≤15 000 IU/d). Main Outcomes and Measures: Mean exponential rates of change of full-field cone electroretinogram amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression without and with adjusting for potential confounders. Results: Of the 55 children in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9] years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the 25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2 [1.7] years; and 25 (100%) were white. The estimated mean rates of change with the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263 loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to ocular safety, the mean exponential rates of change of visual field area and visual acuity and the incidences of falling to a visual field diameter of 20° or less or a visual acuity of 20/200 or less in at least 1 eye did not differ by cohort. Conclusions and Relevance: A vitamin A palmitate supplement was associated with a slower loss of cone electroretinogram amplitude in children with retinitis pigmentosa. Although the relatively small-sample, retrospective, nonrandomized design does not allow a test of causation and is subject to possible biases, these findings support consideration of an age-adjusted dose of vitamin A in the management of most children with the common forms of retinitis pigmentosa.

The association between visual acuity and central retinal thickness in retinitis pigmentosa.

PURPOSE: To determine whether visual acuity is related to central retinal thickness in patients with retinitis pigmentosa. METHODS: Visual acuities were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography (OCT3) was used to calculate retinal thicknesses and grade third high-reflectance bands in 162 patients with the typical forms of retinitis pigmentosa who had Snellen visual acuities of 20/20 to 20/200, minimal to no cataracts, and no visible macular cysts. Sixty-five patients were retested within 2 months to estimate the intervisit variability of retinal thickness measurements. RESULTS: ETDRS acuity was best related to retinal thickness measured at fixation and as the average value over the central 1 mm by a second-order polynomial (r(2) = 0.38 and P < 0.001 in both cases). Acuity was maximal for intermediate retinal thickness and appeared to decline for both lesser and greater retinal thicknesses. By linear regression, the decline in acuity for decreasing retinal thickness was steeper in eyes with an absent third high-reflectance band than for eyes with a partially distinct band. No decline was noted in eyes with an intact band. Assessment of intervisit variability of retinal thickness measurements showed 98% confidence limits of +/-17 microm at fixation and +/-11 microm for the central 1 mm. CONCLUSIONS: Both retinal thinning (due to cell loss) and retinal thickening (due to presumed edema) appear to be associated with lower visual acuity in patients with typical retinitis pigmentosa. The definition of the OCT third high-reflectance band may help to predict which patients are more likely to lose visual acuity as retinal thickness declines. An increase or decrease in retinal thickness of more than 17 microm at fixation or 11 microm over the central 1 mm at follow-up can be considered a significant (P < 0.01) change in these patients.

Disease course of patients with pericentral retinitis pigmentosa.

PURPOSE: To estimate the mean rates of decline of ocular function in patients with an atypical form of retinitis pigmentosa, termed "pericentral retinitis pigmentosa." DESIGN: Retrospective observational study. METHODS: setting: Single-center. patient population: Eighteen patients (ages 32 to 65 years) with pericentral retinitis pigmentosa followed for 3 to 26 years. observational procedures: Snellen visual acuity, Goldmann visual field area (V-4e white test light), and full-field electroretinogram (ERG) amplitudes (0.5 Hz and 30 Hz white flashes). main outcome measures: Mean annual exponential rates of change quantified by repeated-measures longitudinal regression. RESULTS: Estimated mean annual rates of decline of remaining ocular function were 1.2% for visual acuity, 1.9% for visual field area, 2.5% for ERG amplitude to 0.5 Hz flashes, and 2.9% for ERG amplitude to 30 Hz flashes. CONCLUSIONS: The mean rates of loss of remaining ocular function of patients with pericentral retinitis pigmentosa were generally slower than those previously reported for patients with typical forms of retinitis pigmentosa.

Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses.

OBJECTIVE: To determine whether docosahexaenoic acid will slow the course of retinal degeneration in subgroups of patients with retinitis pigmentosa who are receiving vitamin A. DESIGN: A cohort of 208 patients with retinitis pigmentosa, aged 18 to 55 years, were randomly assigned to 1200 mg of docosahexaenoic acid plus 15 000 IU/d of vitamin A given as retinyl palmitate (DHA + A group) or control fatty acid plus 15 000 IU/d of vitamin A (control + A group) and followed up over 4 years. Seventy percent of the patients in each group were taking vitamin A, 15 000 IU/d, prior to entry. We compared rates of decline in ocular function in the DHA + A vs control + A groups among the subgroups defined by use or nonuse of vitamin A prior to entry. We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level, dietary omega-3 fatty acid intake, or duration of vitamin A use. Main outcome measures were Humphrey Field Analyzer visual field sensitivity, 30-Hz electroretinogram amplitude, and visual acuity. RESULTS: Among patients not taking vitamin A prior to entry, those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years (P =.01 and P =.03, respectively); these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry. In the entire cohort, red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years (test for trend, P =.05). This was particularly evident over the first 2 years among those not on vitamin A prior to entry (test for trend, P =.003). In the entire control + A group, dietary omega-3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years (intake, <0.20 vs > or =0.20 g/d; P =.02). The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude (P =.008). CONCLUSIONS: For patients with retinitis pigmentosa beginning vitamin A therapy, addition of docosahexaenoic acid, 1200 mg/d, slowed the course of disease for 2 years. Among patients on vitamin A for at least 2 years, a diet rich in omega-3 fatty acids (> or =0.20 g/d) slowed the decline in visual field sensitivity.

Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment.

OBJECTIVE: To determine whether a therapeutic dose of docosahexaenoic acid (DHA), an omega-3 fatty acid, will slow the course of retinal degeneration in adult patients with retinitis pigmentosa who are also receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 221 patients, aged 18 to 55 years, evaluated over a 4-year interval. Patients were given either 1200 mg/d of docosahexaenoic acid or control capsules. All were given 15 000 IU/d of vitamin A (given as retinyl palmitate). Randomization considered genetic type and baseline dietary omega-3 fatty acid intake. MAIN OUTCOME MEASURES: The primary outcome measure was the total point score for the 30-2 program of the Humphrey field analyzer; secondary outcome measures were the total point score for the 30-2 and 30/60-1 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Rentinopathy Study visual acuity. RESULTS: No significant differences in decline in ocular function were found between the docosahexaenoic acid plus vitamin A (DHA + A) group and control plus vitamin A (control + A) group over a 4-year interval among all 221 randomized patients or among the 208 patients who completed all 4 follow-up visits. The mean annual rate of loss of sensitivity for the Humphrey Field Analyzer 30-2 program was 37 dB for the DHA + A group and 38 dB for the control + A group (P =.88). For the Humphrey Field Analyzer 30-2 and 30/60-1 programs combined, the mean annual rates of loss of field sensitivity were 57 dB for the DHA + A group and 60 dB (P =.73) for control + A group. No toxic adverse effects were observed. No significant differences by treatment group assignment were observed within genetic types or within the category of baseline omega-3 fatty acid intake. CONCLUSION: In patients assigned to receive 15 000 IU/d of vitamin A, this randomized trial showed that 1200 mg/d of docosahexaenoic acid supplementation over a 4-year interval did not, on average, slow the course of disease in patients with retinitis pigmentosa.

Cystoid macular edema associated with ocular hypotensive lipids.

PURPOSE: To report angiographically documented cystoid macula edema associated with the use of each of the three newly available ocular hypotensive lipids: unoprostone, travaprost, and bimatoprost. DESIGN: Observational case series. METHODS: Retrospective review of three patients in a clinical practice who had uncontrolled glaucoma on maximal tolerable therapy except for an ocular hypotensive lipids. All three patients also had previous cataract and filtration surgery, and all had an absent or open posterior lens capsule. The patients were informed of the potential risks of cystoid macula edema associated with the use of an ocular hypotensive lipids versus the risks of repeat filtration surgery. RESULTS: An ocular hypotensive lipids was started in the affected eye in each patient, and the patient was instructed to check visual acuity everyday and report back any change in vision occurred. CONCLUSION: Decreased vision of at least two lines caused by angiographically confirmed cystoid macula edema was noted in each of three patients started, respectively, on unoprostone, travaprost, and bimatoprost. The visual acuity returned to baseline, and the cystoid macula edema was angiographically resolved after discontinuation of the ocular hypotensive lipids and the initiation of a topical steroid and non-steroidal anti-inflammatory eyedrops. Until a causal relationship between cystoid macula edema and ocular hypotensive lipids is proved or disproved, caution in their use in high-risk eyes would be prudent.

Off-axis nonmydriatic photography to evaluate the posterior pole through small pupils.

PURPOSE: The purpose of this study was to improve the clarity of retinal images photographed through small pupils. METHODS: Retinal photographs were taken with a Topcon TRC-NW100 digital nonmydriatic camera centered and decentered about the pupillary axis. Four hundred and twelve consecutive individuals (age, 8-95 years) were screened for eye disease with nonmydriatic retinal photography in the District 33N Lions Eyemobile during a 1-year period. RESULTS: Twenty-nine percent of the eyes photographed had pupillary diameters <4 mm and yielded or would have yielded poor-quality images of the posterior pole with standard, on-axis alignment. In 78% of these eyes with small pupils, photography with off-axis alignment produced images of sufficient clarity for clinical assessment of retinal appearance. CONCLUSION: Off-axis alignment increases the percentage of gradable images of the posterior pole in individuals with small pupils.

Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A.

OBJECTIVE: To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received 12 mg of lutein or a control tablet daily. All were given 15,000 IU/d of vitamin A palmitate. Randomization took into account genetic type and baseline serum lutein level. MAIN OUTCOME MEASURES: The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; prespecified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 programs combined, 30-Hz electroretinogram amplitude, and Early Treatment Diabetic Retinopathy Study acuity. RESULTS: No significant difference in rate of decline was found between the lutein plus vitamin A and control plus vitamin A groups over a 4-year interval for the HFA 30-2 program. For the HFA 60-4 program, a decrease in mean rate of sensitivity loss was observed in the lutein plus vitamin A group (P = .05). Mean decline with the 60-4 program was slower among those with the highest serum lutein level or with the highest increase in macular pigment optical density at follow-up (P = .01 and P = .006, respectively). Those with the highest increase in macular pigment optical density also had the slowest decline in HFA 30-2 and 60-4 combined field sensitivity (P = .005). No significant toxic effects of lutein supplementation were observed. CONCLUSION: Lutein supplementation of 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice Data are presented that support use of 12 mg/d of lutein to slow visual field loss among nonsmoking adults with retinitis pigmentosa taking vitamin A. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00346333.

Visual acuity is related to parafoveal retinal thickness in patients with retinitis pigmentosa and macular cysts.

PURPOSE: To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. METHODS: In 316 patients with typical forms of retinitis pigmentosa, visual acuity was measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, macular cysts were detected with optical coherence tomography (OCT), and retinal thicknesses was quantified by OCT. The FREQ, LOGISTIC, and GENMOD procedures of SAS (SAS Institute, Cary, NC) were used to evaluate possible risk factors for cyst prevalence, and the MIXED procedure was used to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. RESULTS: Macular cysts were found in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (P = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (P = 0.038) and within a parafoveal ring spanning an eccentricity of 5 degrees to 10 degrees from the foveal center (P = 0.004). CONCLUSIONS: Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea.

Reading speed of patients with advanced retinitis pigmentosa or choroideremia.

PURPOSE: To quantify, account for, and enhance the reading speed of patients with generalized retinal degeneration and small central visual fields. METHODS: Thirty-three patients with retinitis pigmentosa or choroideremia and 12 normal controls participated in the study. The patients had visual acuities of 20/200 or better, central visual field diameters of < or =20 degrees, and log10 contrast sensitivities of < or =1.65. Reading speed was measured by having participants silently read timed sentences presented with differing font size, font type (Times vs. Courier), and text polarity (standard black text on a white background vs. reversed white text on a black background) and then recall that text aloud. RESULTS: The patients' mean reading speed for standard polarity text using the Times font and their optimal font size was 43% of normal (P < 0.001). Patient reading speed was significantly related to visual acuity (r = 0.44; P < 0.001) and to contrast sensitivity (r = 0.68; P < 0.001) but not to central visual field diameter. In a multiple regression model, only contrast sensitivity by itself was a strong independent predictor of patient reading speed, although visual acuity and visual field in combination did nearly as well. On average, the patients read significantly faster with the Times font than with the Courier font (P < 0.001). The percentage improvement in reading speed with reverse polarity text was most related to contrast sensitivity (r = 0.47; P < 0.001), and 83% of patients with log10 contrast sensitivity of <1.0 versus 36% with higher contrast sensitivity read faster with reverse polarity text (P = 0.02). CONCLUSION: Patients with retinitis pigmentosa or choroideremia and small central fields have, on average, impaired reading speed associated primarily with reduced contrast sensitivity, and those with very poor contrast sensitivity will most likely benefit from reversing text polarity.