Alexander R. Gaudio

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.

Foveal electroretinograms and choroidal perfusion characteristics in fellow eyes of patients with unilateral neovascular age-related macular degeneration.

AIMS/BACKGROUND--A prolonged choroidal filling phase on fluorescein angiography has been reported to be a common finding and associated with visual function abnormalities in patients with age-related macular degeneration (AMD). This investigation was carried out to determine whether this perfusion defect was related to the slowing of foveal cone electroretinogram (ERG) implicit time seen in patients with AMD. METHODS--Fluorescein angiograms and foveal cone ERGs were evaluated in the fellow eyes of 67 patients with unilateral neovascular AMD. RESULTS--Twenty eight (42%) of the eyes had a choroidal perfusion defect. ERG implicit times averaged 1 ms slower (p = 0.0167) and were more likely to be delayed (p = 0.0078) in eyes with abnormal choroidal perfusion than in eyes with normal choroidal filling; significant relations were found also after controlling for age. ERG implicit time was also inversely related to ETDRS visual acuity and positively related to the extent of macular drusen; and the latter showed a borderline significant tendency to be more prevalent in eyes with prolonged choroidal perfusion. However, an association of a delayed ERG implicit time with prolonged choroidal filling remained after controlling for age, acuity, and the extent of drusen. CONCLUSION--These findings further establish prolonged choroidal perfusion as a common finding in AMD and link it to retinal malfunction.

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.

SLOW PHOTOSTRESS RECOVERY AND DISEASE SEVERITY IN AGE-RELATED MACULAR DEGENERATION

Purpose: To determine whether photostress recovery time varies with severity of disease in age‐related macular degeneration. Methods: Photostress recovery time, visual acuity, and foveal retinal pigment epithelial atrophy were evaluated for the fellow eyes of 133 patients with unilateral neovascular agerelated macular degeneration. Recovery times were measured by a method that flashed letters on a computer screen in random order before and after a 10 second bleach. Results: Recovery times were delayed in 62% of the patients (including 47% of those with normal visual acuity), ranged up to 6 times the normal limit, and increased with advancing age (P < 0.0001). Photostress recovery time was inversely correlated with visual acuity (P < 0.0001) and longer in eyes with visible atrophy than in eyes without atrophy (P = 0.0007). Significant relationships between these two pairs of measures were also found after controlling for age. Conclusion: These findings support previous evidence that the time for visual recovery after exposure to a glare source is commonly slowed in age‐related macular degeneration even among patients with normal visual acuity and further show that it can vary with age and extent of disease.

High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration

OBJECTIVE This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye. DESIGN The study design was a prospective cohort study. PARTICIPANTS One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated. INTERVENTION Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time. MAIN OUTCOME MEASURE The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured. RESULTS On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10-1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06-2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time. CONCLUSIONS A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.

Visual field deficits in early age-related macular degeneration

Patients with early age-related macular degeneration (AMD) may retain good visual acuity but experience distortion and other qualitative visual changes. The purpose of the present study was to determine whether deficits of form recognition, as well as of light sensitivity, were related to retinal pigment epithelial (RPE) atrophy and/or drusen. We assessed form recognition deficits by the Amsler grid and by a perimetric test of letter recognition and sensitivity deficits by the macular threshold test of the Humphrey Field Analyzer in 59 patients with AMD and visual acuities of 20/40 or better. The number of defects on each test was compared with the area of RPE atrophy and with the area of drusen determined from fundus photographs. Multiple regression analyses based on ordinal data revealed that the number of visual field defects by each test was significantly correlated with the area of atrophy, but not with the area of drusen. There was also no significant tendency for a patient with a regional preponderance of drusen to have more impairment in the corresponding visual field. These results suggest that deficits of form recognition, as well as of sensitivity, in patients with early stages of AMD can be attributed to alteration of photoreceptor function associated with RPE atrophy, but not with drusen.

Hyperopia and Neovascularization in Age-related Macular Degeneration

PURPOSE Refractive errors for phakic eyes of patients referred with age-related macular degeneration were reviewed to determine whether some range of refractive error might be a risk factor for the neovascular form. METHODS The authors compared refractive errors of 198 patients with unilateral neovascular disease with refractive errors of 129 patients with bilateral dry disease. These groups had comparable distributions with respect to age, sex, and visual acuity of their better eyes. Students t tests and multiple linear regression analyses were performed to assess group differences in mean refractive error. Contingency table and multiple logistic regression analyses were performed to determine odds ratios for having the neovascular form based on a stratification of refractive error. RESULTS By comparing better eyes of the two groups, patients with the unilateral neovascular form had an average spherical equivalent that was 1.0 diopter (D) more hyperopic than that of patients with the bilateral dry form (P < 0.001). Patients with a refractive error of +0.75 D or greater were more likely to have the neovascular form compared with patients with other refractive errors (odds ratio, 2.40; 95% confidence interval, 1.53-3.78; P < 0.001). Similar relationships between the two groups of patients were found by comparing worse eyes. CONCLUSION These findings suggest that hyperopia is a risk factor for choroidal neovascularization among patients referred with age-related macular degeneration.

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.

Neovascular Glaucoma Following Pars Plana Vitrectomy for Complications of Diabetic Retinopathy

The patient charts of 81 consecutive vitrectomies performed for complications of proliferative diabetic retinopathy were reviewed. Sixty-five preoperative, intraoperative, and postoperative variables were analyzed. In eyes with completed panretinal photocoagulation, only postoperative retinal detachment had a statistically significant correlation with postvitrectomy development of neovascular glaucoma. Eighty-three percent of eyes with detached retinas, as compared with 4% of eyes with attached retinas, developed neovascular glaucoma (P less than .00001). Aphakia alone did not have a statistically significant effect on the development of neovascular glaucoma; however in the presence of retinal detachment the incidence was very high (92%). Our study shows that a completely attached retina and aggressive panretinal photocoagulation are of paramount importance in decreasing the risk of neovascular glaucoma following vitrectomy for complications of proliferative diabetic retinopathy.

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.