Ocular signs and symptoms and vitamin A status in patients with cystic fibrosis treated with daily vitamin A supplements

BACKGROUND/AIMS: Patients with cystic fibrosis (CF) may have low plasma vitamin A levels from malabsorption, zinc deficiency, liver disease, or poor compliance with prescribed supplements. In view of the increasing number of adults with CF, many of whom drive cars, it is important to assess vitamin A status. In our centre an attempt has been made to achieve normal levels of fat soluble vitamins by annual estimation of plasma levels and appropriate oral supplementation. This study aimed to determine if this approach prevents vitamin A deficiency and the consequent problems with dark adaptation. METHODS: The study was conducted at the regional adult and paediatric cystic fibrosis unit and the patients were recruited from there. Dark adaptation studies were conducted at the department of ophthalmology, St James's University Hospital. All patients are regularly seen in the outpatient department by a CF specialist dietitian and have a comprehensive annual dietary assessment. 28 patients had the following investigations: serum retinol, plasma zinc, serum retinol binding protein, liver function tests, dark adaptation, contrast sensitivity, and anterior ocular surface status. 25 age and sex matched controls without CF or ocular pathology were also recruited for the dark adaptation study. RESULTS: None of the patients had vitamin A deficiency, the median value of serum retinol being 48 microg/dl, range 31-80 microg/dl (normal range 30-80 microg/dl). Dark adaptation was normal in all cases compared with the control group where the mean value was 3.4 log units of threshold luminance (95% confidence interval 2.4-4.0). None of the test group had a value of threshold luminance 2 SD above the mean value for the control group. Eight patients had reduced contrast sensitivity. The median value for serum zinc was 14.2 micromol/ l, range 13-81 micromol/l (normal range 8-23 micromol/l) and the median value for retinol binding protein was 36 mg/l, range 13-81 mg/l (normal range 35-58 mg/l). There was no correlation between dark adaptation and serum retinol, zinc, or retinol binding protein. Two patients had clinical evidence of dry eye. CONCLUSION: Regular estimates of plasma vitamin A together with appropriate supplementation and expert dietetic review can maintain normal dark adaptation in patients with cystic fibrosis. The occurrence of reduced contrast sensitivity function is well documented but remains an unexplained phenomenon and deserves further study.     

ERGs in children with pancreatic enzyme insufficient and pancreatic enzyme sufficient cystic fibrosis

Objectives We recorded scotopic and photopic flash electroretinograms (ERGs) in pediatric subjects with cystic fibrosis, aged 4 to 18 years, who were either pancreatic insufficient (PI) or pancreatic sufficient (PS). The aim of the study was to determine whether vitamin supplementation in the PI group allowed comparable retinal function in these two groups. Methods ERGs were recorded from a mixed-gender group of 41 children and adolescents (4 to 17 years of age) with cystic fibrosis. The subjects were grouped according to pancreatic function into PI (n = 29) and PS (n = 12). Full-field flash ERGs were recorded from one eye using a DTL fiber. The pupil was dilated prior to recording using two drops of 0.5% tropicamide. ISCEV photopic and scotopic stimuli and recording conditions were used. Serum levels of vitamin A, β carotene and retinol binding protein (RBP) were measured on the day of ERG recording. Results There was no significant difference in ERG amplitudes or implicit times between PI and PS groups. Vitamin A, β carotene, and RBP levels were not significantly different across the two groups and were not correlated with implicit times or amplitudes of any of the ERG types recorded here. Conclusion Similarity of ERGs across the PI and PS cystic fibrosis patient populations tested here suggests that the supplementation protocol applied to these populations allows similar levels of retinal function (as indicated by flash ERG parameters) in the two groups.     

Loss of contrast sensitivity in cystic fibrosis

We measured the contrast sensitivity function in a 16-year-old boy with cystic fibrosis, before and during vitamin A supplementation. Before vitamin A supplementation, serum levels of vitamin A were abnormally low, the electroretinogram was reduced, and contrast sensitivity was abnormally low at all spatial frequencies. During vitamin A supplementation (25,000 IU/day), serum levels of vitamin A became low normal, the electroretinogram returned to normal, and the overall contrast sensitivity function improved by 94%. We propose that the contrast sensitivity function may be abnormal in patients with cystic fibrosis who have reduced retinal function secondary to vitamin A deficiency.     

Attempts to define the minimal serum level of vitamin A required for normal visual function in a patient with severe fat malabsorption

A case with severe malabsorption of fat soluble vitamins is described. The malabsorption developed after an intestinal bypass operation due to morbid obesity. Night blindness occurred as the first symptom of vitamin A deficiency. The cone visual sensory threshold was elevated about one log unit and the rod threshold abot two and a half log units. No changes of the a- and b-waves of the electroretinogram (ERG) was observed. However, during the initial phase of very low serum reninol level (0.21 mumol/l) the summed amplitudes of the oscillatory potentials (OPs) were lower. After parenteral therapy with vitamin A the night blindness disappeared and the dark-adapted rod and cone threshold sensitivity recovered to normal. However, the time-course of rod adaptation first reached normal levels after 5 months. The amplitudes of the OPs of the ERG response returned to normal when the serum retinol level had increased close to normal. Serum retinol levels of 0.7 mumol/l or higher were always associated with normal or close to normal dark-adapted rod sensitivity. However, a normal serum retinol level (> 0.95 mumol/l) and a normal dark-adapted rod threshold sensitivity were not always associated with a normal time-course of the rod adaptation. It is concluded, that the maintenance dosage of vitamin A must be individualized and that patients who have undergone jejuno-ilea bypass surgery must be carefully monitored for vitamin A deficiency by both serum levels and dark adaptation measurements.     

Ocular findings in cystic fibrosis patients receiving vitamin A supplementation

Background: Vitamin A deficiency with eye symptoms has been reported in patients with cystic fibrosis who received the recommended daily intake of vitamin A. Methods: We measured serum retinol, dark adaptation, contrast sensitivity, and dry eye status in 35 adult cystic fibrosis patients to ascertain whether they had ocular signs or symptons. Results: Median serum retinol concentration was 1.95 mol/l, range 1.08–4.01 mol/l, with no values indicating vitamin A deficiency. Retinal light sensitivity was normal. Nineteen patients had reduced contrast sensitivity. Conjunctival imprints all showed plenty of goblet cells, but were characteristic of dry eye in 42% of patients (n=14). Decreased tear film stability was found in 49% (n=17), tear production was low in 31% (n=11), and 23% (n=8) showed an increased amount of dying epithelial cells. Nine patients (26%) had keratocon-junctivitis sicca according to the Copenhagen criteria. Conclusion: Our patients had no biochemical or clinical signs of vitamin A deficiency. We speculate that the high incidence of dry eye could be a primary manifestation of cystic fibrosis.     

Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: a potential therapy for treatment of lipofuscin-based retinal diseases

PURPOSE: Excessive accumulation of lipofuscin is observed in numerous degenerative retinal diseases. A toxic vitamin A-based fluorophore (A2E) present within lipofuscin has been implicated in the death of RPE and photoreceptor cells. Here, we used an animal model that manifests accelerated lipofuscin accumulation (ABCA4-/- mutant) to evaluate the efficacy of a therapeutic approach based on reduction of serum retinol. METHODS: N-(4-hydroxyphenyl)retinamide (HPR) potently and reversibly reduces serum retinol. The interaction of HPR with retinol binding protein (RBP) and transthyretin was studied by spectrofluorometry and size-exclusion chromatography. To assess the effects of HPR on visual cycle retinoids and A2E biosynthesis, HPR was chronically administered to ABCA4-/- mice. Mice were evaluated using biochemical, electrophysiological, and morphologic techniques. RESULTS: Administration of HPR to ABCA4-/- mice caused immediate, dose-dependent reductions in serum retinol and RBP. Chronic administration produced commensurate reductions in visual cycle retinoids and arrested accumulation of A2E and lipofuscin autofluorescence in the RPE. Physiologically, HPR treatment caused modest delays in dark adaptation. Chromophore regeneration kinetics, light sensitivity of photoreceptors, and phototransduction processes were normal. Histologic examinations showed no alteration of retinal cytostructure or morphology. CONCLUSIONS: These findings demonstrate the vitamin A-dependent nature of A2E biosynthesis and validate a novel therapeutic approach with potential to halt the accumulation of lipofuscin fluorophores in the eye.     

Total rod ERG suppression with high dose compassionate Fenretinide usage

Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.     

Vitamin A in Stargardt disease—an evidence-based update

Background: High intake of vitamin A is suspected to be a risk factor for the progression of Stargardt disease (STGD1) and many health authorities recommend Stargardt patients not to use oral vitamin A supplements outside that provided naturally in the food. The present study provides the first systematic review of the current level of evidence regarding the role of supplementary vitamin A in STGD1.

Materials and methods: We conducted a systematic scientific literature search in the Pubmed database on studies reporting on the effect of oral vitamin A or serum retinol on visual function.

Results: In animal studies neither high nor low serum retinol in an Abca4 knockout mouse model of Stargardt showed any effect on electroretinography (ERG). In humans, significantly better visual function was reported in a cross-sectional study of patients with a low dietary intake of vitamin A, whereas a prospective study did not find any correlation between vitamin A supplementation and visual acuity. A newly introduced vitamin A substitute (C20-D(3)-vitamin A) has shown promising effects on ERG in a Stargardt mouse model.

Conclusions: There are few studies on the effect of vitamin A in STGD1. The scarcity and inconclusiveness of evidence available impel further research efforts to reach a more confident conclusion. Currently, recommendations to avoid vitamin A dietary supplementation rely mainly on a theoretical background. Animal studies on vitamin A substitute as a possible therapeutic approach in preventing or slowing vision loss in STGD1 seems promising but further clinical trials are needed to verify the results.     

Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

Abstract

Purpose: The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10?mg lutein (L), 2?mg zeaxanthin (Z) and 10?mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2).

Methods: CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10?mg?L, 10?mg MZ and 2?mg Z (n?=?60) or placebo (n?=?60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10?mg?L, 10?mg MZ, 2?mg Z plus 500?mg vitamin C, 400?IU vitamin E, 25?mg zinc and 2?mg copper (Intervention A; n?=?75) or 10?mg?L and 2?mg Z plus 500?mg vitamin C, 400?IU vitamin E, 25?mg zinc and 2?mg copper (Intervention B; n?=?75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded.

Conclusions: CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial.     

Vitamin A deficiency in treated cystic fibrosis: case report.

We describe a patient with cystic fibrosis and hepatic involvement who, although on pancreatic extract, developed vitamin A deficiency, night blindness, and a characteristic fundus picture. All of these abnormalities were reversed by oral vitamin A supplementation.     

Retinal structure in vitamin A deficiency as explored with multimodal imaging

Purpose

To define the retinal structural abnormalities in a patient with vitamin A deficiency.

Methods

The patient had a complete ophthalmic examination, electroretinography (ERG), short-wave fundus autofluorescence (SW-AF) and spectral domain optical coherence tomography (SD-OCT) imaging. Serum vitamin A levels were measured.

Results

A 63-year-old man with alcoholic cirrhosis, sclerosing cholangitis and chronic pancreatitis experienced blurred vision and nyctalopia for over a year. There was no family history of eye disorders or consanguinity. His best-corrected visual acuity was 20/20 in each eye; color vision as determined with Ishihara color plates was normal in each eye. Anterior segment examination was unremarkable. He was pseudophakic in both eyes. Standard ERGs showed non-detectable rod function, a cone-mediated dark-adapted response to the standard flash and borderline reduced cone function. Serum vitamin A levels were below 0.06 mg/L (normal 0.3–1.2 mg/L). Fundus examination revealed numerous round yellow–white lesions along the superior arcade and nasal to the optic nerve in both eyes. These lesions were hypoautofluorescent on SW-AF. SD-OCT cross sections demonstrated that they were focal disruptions distal to the ellipsoid band of the photoreceptors with hyperreflective images bulging up the ellipsoid and region. The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. The retinal lesions remained unchanged.

Conclusions

Imaging of this patient with nyctalopia and severe rod dysfunction suggests that the retinal white lesions known to occur in vitamin A deficiency localize to the photoreceptor layer, particularly the outer segment. On OCT, they are reminiscent of lesions observed in genetic diseases with retinoid cycle dysfunction and of drusenoid subretinal deposits, an abnormality commonly associated with age-related macular degeneration.     

The distribution and proportions of vitamin A compounds during the visual cycle in the rat

Radioisotopes and t.l.c. were used to indirectly determine the distribution and proportions of Vitamin A compounds in the rat eye. In the dark adapted eye there are Vitamin A compounds in the pigment epithelium; these compounds are likely within the rod outer segment discs being digested there. During light adaptation. 11-cis retinal decreases, alltrans retinal increases and is reduced to retinol, and retinol is esterified to fatty acids in the retina and in the pigment epithelium. Essentially the reverse occurs during dark adaptation. It is suggested that the metabolism of Vitamin A compounds in the eye functions to return chromophore to the newly synthesized visual pigment at the base of the rod outer segment.     

Plasma homocysteine, vitamin B12 and folate levels in age-related macular degeneration

Purpose The purpose of this study was to investigate the association of age-related macular degeneration (AMD) with plasma homocysteine, vitamin B12, and folate levels.Methods Sixty patients diagnosed with AMD at our clinic between March 2004 and September 2004 were assessed in a prospective cross-sectional study. Plasma homocysteine, vitamin B12, and folate levels taken after 8 h of fasting from 30 patients with exudative AMD and 30 patients with dry AMD were compared with the results of 30 age- and sex-matched healthy participants.Results Patients with both exudative and dry types of AMD had significantly higher plasma homocysteine levels (mean 14.19±3.11 μmol/l; 13.07±2.90 μmol/l respectively) compared with the controls (mean 10.79±2.56 μmol/l; (p=0.000 and p=0.008 respectively). Homocysteine levels were higher in the exudative AMD group compared with the dry AMD group, but the difference was not statistically significant (p=0.290). Plasma vitamin B12 levels were found to be significantly lower in the exudative AMD group (289.14±113.44 pg/l) compared with the controls (436.17±204.12 pg/l) and dry AMD group (443.47±190.83 pg/l; (p=0.000). Plasma folate levels were comparable among groups (p=0.106).Conclusion This study suggests an association between elevated plasma homocysteine and AMD regardless of the subtype. Further controlled prospective studies are needed to investigate the possible role of homocysteine in AMD and the effect of vitamin B12 and folate supplementation in this process.The study was presented at the 38th National Ophthalmology Congress in Antalya, Turkey     

Visual function and rhodopsin levels in humans with vitamin A deficiency

Details of rod and cone dysfunction in vitamin A deficiency have been studied in two subjects with primary biliary cirrhosis and one with Crohn's disease, all of whom presented with symptoms of night blindness. Visual function in the mid-peripheral retina was monitored with two-color adaptometry and rhodopsin levels were measured by fundus reflectometry. Initially all three subjects had no measurable rod function and delayed cone adaptation. In one case the dark-adapted cone threshold was also elevated. Oral supplementation with vitamin A restored visual function to normal within 8 days in all subjects. During supplementation, cone function was restored more rapidly than that of rods, though the pattern of recovery was similar for each receptor type. Final thresholds improved first, though the rates at which they were reached were abnormally slow. As recovery continued, adaptation kinetics returned to normal. When rod adaptation was delayed, the regeneration of rhodopsin was also abnormally slow. When rod final threshold was 2 log units higher than normal, rhodopsin regeneration was incomplete, reaching about 70% of the normal level. The initial stages of visual dysfunction during onset of vitamin A deficiency were studied in one subject, and were found to mirror the pattern seen during recovery: rod adaptation was initially slower than normal, but reached completion. Cone adaptation remained normal until rod function was almost absent.     

Zinc deficiency and oxidative stress in the retina of pigmented rats

PURPOSE: To determine the effect of moderate zinc deficiency on antioxidant defenses and measures of oxidative stress in the retina and retinal pigment epithelium (RPE) of Brown Norway Rats. METHODS: Twenty-four rats were housed individually and divided into three groups of 8 rats each. Group 1 was fed ad libitum a semipurified control diet formulated to contain 50 parts per million [ppm] total zinc; group 2 was fed ad libitum an identical diet but containing 5 ppm total zinc; and group 3 was pair-fed the control diet but restricted in amount to that consumed by group 2. Food intake was measured daily and the rats weighed weekly. After 6 weeks, the rats were killed and the following measurements were made: serum zinc, serum alkaline phosphatase, retinal zinc, RPE-choroid zinc, RPE-choroid catalase, liver metallothionein (MT), retinal MT, RPE-choroid MT, retinal catalase, and retinal thiobarbituric reactive substances (TBARS). RESULTS: The following showed statistically significant differences between groups 2 and 3, respectively: serum Zn (1216 micro/l versus 1555 microg/l, P < or = 0.01), serum alkaline phosphatase (3.75 U/mg versus 5.10 U/mg, P < or = 0.05), liver MT (4.3 microg/mg protein versus 16.7 microg/mg, P < or = 0.0001), RPE-choroid MT (1.3 microg/mg protein versus 2.2 microg/mg, P < or = 0.02), retinal MT (0.85 microg/mg protein versus 2.8 microg/mg, P < or = 0.05), and retinal TBARS (6.2 nM/mg protein versus 2.2 nM/mg, P < or = 0.05). CONCLUSIONS: The results show that retinal MT and RPE MT concentrations are very sensitive to intake of dietary zinc. The increase in retinal TBARS in group 2 indicates that moderate zinc deficiency increases oxidative stress to the retina. The results also suggest that MT is protective against lipid peroxidation of retinal membranes.     

A randomised, double masked, clinical trial of high dose vitamin A and vitamin E supplementation after photorefractive keratectomy

AIM: To evaluate the effect of a high dose vitamin A and E supplementation on corneal re-epithelialisation time, visual acuity and haze following photorefractive keratectomy (PRK). METHODS: Two groups of 20 patients who underwent myopic PRK were supplemented with either 25 000 IU retinol palmitate and 230 mg alpha tocopheryl nicotinate or a placebo. Clinical outcomes were evaluated up to 360 days. RESULTS: In the vitamin treated group, re-epithelialisation time was significantly faster (p = 0.029) and haze incidence was reduced (p = 0.035), especially for high myopic corrections (p = 0.043). This group also reported a significantly better uncorrected visual acuity (p = 0.043). CONCLUSIONS: High dose vitamin A and E oral supplementation may accelerate re-epithelialisation time and may reduce corneal haze formation after PRK.     

Morphologically functional correlations of macular pathology connected with epiretinal membrane formation in spectral optical coherence tomography (SOCT)

Background Preretinal membrane formation is a frequently diagnosed disease in ophthalmology. Its pathogenesis is unclear. Optical coherence tomography is an important diagnostic tool in patients with epiretinal membranes. In our study we use high-speed and high-resolution spectral OCT. Our goal was to present different forms of ERM and to analyze the influence of some morphological changes on visual acuity. Methods We evaluated 44 cases of preretinal fibrosis. Patients were divided into two groups depending on macula morphology. High-resolution and 3D SOCT scans were acquired from all patients and analyzed. Maximum retinal thickness and retinal thickness in the fovea were measured. Type of ERM, presence of retinal cysts and photoreceptor defects were recorded. We analyzed the influence of those data on visual acuity. Results Globally adherent membranes were the most frequent membrane architecture type in each group. The mean visual acuity in both groups did not significantly differ. Presence of retinal cystic formation had no influence on visual acuity. A statistically significant correlation was observed between central retinal thickness and VA in Group 2 (A = −0.488; p = 0.006). Photoreceptor defect was observed in 4 patients in group 1 and 11 in group 2. Patients with photoreceptor defect had significantly lower visual acuity (P = 0.04 for Group 1 and P = 0.002 for Group 2). Conclusions SOCT pictures of eyes with ERM are diverse. Thanks to high-resolution and 3D scanning protocols, more information can be gathered. Morphological changes in the retina, such as oedema with cystic spaces, lamellar macular holes, macular pseudoholes and photoreceptor defects, were present in patients with ERM. Estimation of those changes may be an important prognostic factor in cases of epiretinal membranes. The authors do not have any financial interest in the reported research. The authors have a full control of all the primary data and agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review them, if requested.     

Xerophthalmia and acquired night blindness in a patient with a history of gastrointestinal neoplasia and normal serum vitamin A levels

A 69-year-old male patient presented to our department with a 3-month history of nyctalopia. Reviewing of his general health revealed a history of gastrointestinal tumor treated with a modified WHIPPLE operation. Ocular findings at presentation included mild xerophthalmic features and nonspecific pigmentary retinal changes. A standard full-field electroretinogram (ERG) was obtained that showed normal photopic function and extinguished scotopic function. The ocular symptoms, the history and the ERG findings suggested vitamin A deficiency as a possible cause for his complaints. Serum vitamin A levels were subsequently requested, but the results were within normal limits. Despite the normal serum vitamin A levels, the patient was instructed to commence treatment with high doses of oral vitamin A supplements. One month after the onset of the treatment, the patient reported that his visual function has significantly improved, while repeat ERG testing revealed that scotopic function has improved to normal levels. This case highlights that in patients with acquired night blindness due to vitamin A deficiency, the ERG responses possibly represent a more sensitive marker compared to the serum levels of vitamin A.     

Vitamin E deficiency and the retina: photoreceptor and pigment epithelial changes.

To investigate the role of normal vitamin E levels and the interrelationships between vitamin E and A in maintaining the visual cells of the retina, weanling female Sprague-Dawley rats were fed vitamin E-free diets differing tenfold in their vitamin A content (0.8 and 8.0 mg of retinol per kilogram of diet). Rats on vitamin E-free diets with the higher vitamin A level exhibited marked disruption of photoreceptor outer segment membranes and a fivefold increase in the number of lipofuscin granules in the pigment epithelial cells which ingest these membranes. Rats on vitamin E-free diets with the lower vitamin A level showed the same retinal damages plus significant loss of photoreceptor cells compared to age-matched rats on control diets. Rods and cones were involved equally, and their pattern of loss was not like that found in vitamin A deficiency. Normal levels of vitamin E probably protect photoreceptor membranes from oxidative damage and retard the accumulation of their remnants and other products of lipid breakdown in the pigment epithelium. The vitamin A status of rats has a significant influence on the extent of damage induced by vitamin E deficiency.     

Fundus albipunctatus: A clinical study of the fundus lesions,the physiologic deficit,and the vitamin a metabolism

Two unrelated patients with fundus albipunctatus, each the product of a consanguinous marriage, were studied with reference to their fundus lesions, their physiologic deficit and their vitamin A metabolism.Both patients showed albipunctate lesions that appeared deep to vessels and either blocked fluorescein or were invisible on angiography. Some of the lesions changed during a 1–2 year observation period. In one patient the lesions showeds a radial arrangement in the fundus. Both patients showed greatly retarded dark adaptation, measured subjectively or with the electroretinogram. Cone as well as rod dysfunction was involved, and subtle abnormalities of the visual fields and of color vision were found. The a- and b-waves of the electroretinogram were both affected by the disease, suggesting an adaptation defect prior to generation of the a-wave. These findings are consistent with the observation of Carr, Ripps & Siegel (1974) that photopigment regeneration is retarded in this disease. Both patients showed normal blood levels of vitamin A, carotene, retinol binding protein, amino acids, proteins and lipoproteins. The administration of therapeutic levels of vitamin A parenterally and orally had no effect on the rate of dark adaptation or the fundus lesions.This study supports the view that fundus albipunctatus is a stationary recessive disorder which can be defined physiologically by a slow rate of dark adaptation and visual pigment regeneration, and which is clinically separable from progressive dystrophies such as retinitis punctata albescens. The significance of the albipunctate fundus lesions remains unclear. If vitamin A metabolism is involved in fundus albipunctatus, the involvement must be at a local level.