Dark Adaptation Test Research Articles

Repeatability of Rod-Mediated Dark Adaptation Testing in Normal Aging and Early and Intermediate Age-Related Macular Degeneration

Purpose The vulnerability of rod photoreceptors in aging and early and intermediate age-related macular degeneration (AMD) has been well documented. Rod-mediated dark adaptation (RMDA) is a measure of the recovery of light sensitivity in rod photoreceptors following a bright light. Delays in RMDA during early and intermediate AMD have been widely reported. For RMDA’s promise as an outcome for trials targeted at early and intermediate AMD to be realized, excellent test-retest reliability, its repeatability, must be established. Methods Test-retest performance in a commonly used RMDA test based on the rod intercept time metric (RIT) was evaluated in participants with early and intermediate AMD and with normal retinal aging with testing approximately 2 weeks apart. The test target was placed at 5° eccentricity superior to the foveal center, an area with maximal rod loss in aging and AMD. Disease severity was identified by a trained and masked grader of fundus photographs using both the AREDS 9-step and Beckman classification systems. Bland-Altman plots and intra-class correlation coefficients (ICC) evaluated repeatability. Results The analysis sample consisted of 37 older adults (mean age 76 years, standard deviation 5), with approximately one-third of the sample in each of three groups – normal aging, early AMD, and intermediate AMD. For the total sample, the ICC was 0.98. For individual AMD groups for both AREDS 9-step and Beckman classifications, the ICCs were also very high ranging from 0.82 to 0.99. Conclusion We demonstrated that RMDA testing using the RIT metric has excellent repeatability when target location is at 5° in studying older adults from normal aging to intermediate AMD, suggesting the reliable use of this functional measure in trials.

Development of a cone‐mediated dark adaptation test on a smartphone

Aims/Purpose: Dark adaptometry is considered a useful tool for investigating retinal neurodegenerative diseases. While it has been demonstrated that the loss of rod photoreceptors occurs before the loss of cones, foveal cones are also impacted during the initial stages of age‐related macular degeneration. Our aim was to develop a test to assess cone‐mediated dark adaptation (DA) based on the MOBILE‐DA smartphone app.Methods: The MOBILE‐DA smartphone app for testing rod‐mediated DA was modified to assess cone‐mediated DA. Using an Android smartphone, and a 3° diameter achromatic flashing stimulus centered on the fovea, the measurements were made using an adaptive staircase of 0.007 cd/m2 level up – 0.009 cd/m2 level down. In a dark room, the smartphone was placed 40 cm from the subject, and the luminance thresholds were measured monocularly for 5 min following almost complete photopigment bleaching using a long‐duration light exposure (60 seconds). Luminance Threshold (LT) recovery functions were fitted to an exponential decay model to determine the time constant (τ, seconds) of cone sensitivity recovery and final cone LT.Results: The cone‐mediated DA measured by the smartphone app resulted in τ of 91 ± 15 seconds; final cone LT of −2.29 ± 0.10 log cd/m2, and R2 of 0.96 ± 0.02. The time constant and final threshold values obtained through this app were comparable to those obtained through other established techniques.Conclusions: The smartphone app for evaluating cone‐mediated dark adaptation proved effective in tracking the rapid changes in luminance threshold that take place during this process. These findings suggest that the MOBILE‐DA app is well‐suited for measuring cone‐mediated dark adaptation.

Hyperreflective Foci in Age-Related Macular Degeneration are Associated with Disease Severity and Functional Impairment

To analyze presence of hyperreflective foci (HRF) across different age-related macular degeneration (AMD) severities and examine its correlation with other structural and functional AMD features. Longitudinal, single-center, case-control study. One hundred and fifty-eight participants aged > 50 years old with varying AMD severities (including no AMD). Color fundus imaging was used to assess AMD severity and hyperpigmentation (PGM) presence. Subretinal drusenoid deposits (SDD) and HRF were detected on OCT volumes. The correlations of HRF with additional AMD features were evaluated using linear and logistic mixed-effects models. One study eye per participant underwent dark adaptation (DA) testing to measure rod intercept time (RIT) for structure function associations. Eyes were followed longitudinally and changes in AMD severity and RIT were measured relative to HRF presence. The primary outcome was presence of HRF, which was compared with presence of other AMD features and DA impairment. One hundred and fifty-eight participants (median baseline age of 73.1 [interquartile range (IQR)= 66-79] years) contributing 1277 eye visits were included. Hyperreflective foci (HRF) were detected more frequently in higher AMD severities. Hyperreflective-foci presence was significantly associated with PGM presence (odds ratio 832.9, P < 0.001) and SDD presence (odds ratio 9.42, P= 0.017). Eyes with HRF demonstrated significantly longer DA (median 27.1 [IQR= 16-40] minutes) than those without HRF (13.5 [10-22] minutes) but less than eyes with SDD only (40 [28-40] minutes). Highest RIT values were found in eyes with both HRF and SDD (40.0 [40-40] minutes). Age and HRF explained a similar proportion of RIT variability as age and SDD. Eyes that developed HRF demonstrated baseline RITs closer to eyes with HRF at baseline, compared with eyes that never developed HRF (29.1 [16-40], 38.5 [22-40] versus 13.1 [10-22] minutes; Kruskal-Wallis P < 0.001). The progressively increased presence of HRF in higher AMD severities, and its correlation with previously associated AMD biomarkers, suggests HRF is an important OCT feature adding to the understanding of disease progression. Hyperreflective foci presence was associated with delays in DA, indicating HRF is a marker for visual cycle impairment. Proprietary or commercial disclosure may be found after the references.

Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon.

Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening. Retrospective observational case series of 5 patients who experienced TBVL on awakening seen in the neuro-ophthalmology clinic at the Mayo Clinic between 2016 and 2020. Patients who described generalized blurred vision and those with monocular transient vision loss were excluded. The median age was 81.4 years (range, 68-92 years), and all were male. Every patient described a stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126-728 episodes) before evaluation in the neuro-ophthalmology clinic. All patients had normal optic nerves, and no plaques were noted in the retinal vessels. All 5 had macular drusen, which were predominantly extrafoveal and mild. Two patients underwent electrophysiology testing, which were both normal on full-field electroretinogram (ERG), but there was blunted central wave forms on multifocal ERG. Two patients underwent dark adaptation testing, which showed both prolong and diminished dark adaptation. Neuroimaging and thromboembolic workup were unrevealing. TBVL is a distinct phenomenon from TMVL on awakening, which has a different demographic and symptomology. The etiology is unclear but seems to be a focal macular process in conjunction with an autoregulatory failure resulting in a supply-demand mismatch during low-light conditions.

Evaluation of Cone- and Rod-Mediated Parameters in Dark Adaptation Testing as Outcome Measures in Age-Related Macular Degeneration

To investigate the suitability of 6 rod- or cone-mediated dark adaptation (DA) parameters as outcome measures for clinical trials in age-related macular degeneration (AMD), including their retest reliability, association with age and disease severity, and measurable longitudinal change over time. Prospective, longitudinal study (Clinicaltrials.gov: NCT01352975). A total of 191 patients with AMD and older participants followed longitudinally over 5 years. Dark adaptation testing was performed using the AdaptDx dark adaptometer with a maximum test time of 40 minutes. A 2-part exponential-linear curve was fitted to obtain values for cone decay, cone plateau, time to rod-cone break, rod intercept time (RIT), rod adaptation rate (S2), and area under the curve. Intersession retest reliability was assessed in tests performed within 2 weeks using the Bland-Altman analysis. The relationship of DA parameters with age, AMD severity, and reticular pseudodrusen (RPD) presence was evaluated using linear mixed models. Retest reliability, association with disease severity, and longitudinal change of 6 DA parameters. A total of 1329 DA curves were analyzed. Rod intercept time was the parameter that showed the greatest reliability (intraclass correlation coefficient of 0.88) and greatest association with age, AMD severity, and RPD (marginal R2 of 0.38), followed by the rod-mediated parameters area under the curve and rod-cone break. Cone plateau appeared constant at lower RIT values but increased with progressive rod dysfunction (RIT > 22.8 minutes) with a slope of 0.07 log units per 10 minutes RIT prolongation. Therefore, it might provide additional information in the advanced stages of AMD. Age-related macular degeneration severity and RPD presence are each associated with large differences in multiple DA curve parameters. In addition, substantial differences in some parameters occur with age, even accounting for AMD severity and RPD status. This supports the 2-hit hypothesis of age and disease status on DA (and perhaps AMD pathophysiology itself). Of the DA parameters, RIT has the highest retest reliability, closest correlation with AMD severity and RPD, and largest longitudinal changes. This underscores the suitability of RIT as an outcome measure in clinical trials. The cone plateau increases only in advanced stages of kinetic rod dysfunction, indicating rod dysfunction preceding cone dysfunction and degeneration in the temporal sequence of pathology in AMD.

Retinal Vascular Endothelial Cell Dysfunction and Neuroretinal Degeneration in Diabetic Patients.

Diabetes mellitus (DM) has become a vital societal problem as epidemiological studies demonstrate the increasing incidence of type 1 and type 2 diabetes. Lesions observed in the retina in the course of diabetes, referred to as diabetic retinopathy (DR), are caused by vascular abnormalities and are ischemic in nature. Vascular lesions in diabetes pertain to small vessels (microangiopathy) and involve precapillary arterioles, capillaries and small veins. Pericyte loss, thickening of the basement membrane, and damage and proliferation of endothelial cells are observed. Endothelial cells (monolayer squamous epithelium) form the smooth internal vascular lining indispensable for normal blood flow. Breaking its continuity initiates blood coagulation at that site. The endothelium controls the process of exchange of chemical substances (nutritional, regulatory, waste products) between blood and the retina, and blood cell passing through the vascular wall. Endothelial cells produce biologically active substances involved in blood coagulation, regulating vascular wall tension and stimulating neoangiogenesis. On the other hand, recent studies have demonstrated that diabetic retinopathy may be not only a microvascular disease, but is a result of neuroretinal degeneration. Neuroretinal degeneration appears structurally, as neural apoptosis of amacrine and Muller cells, reactive gliosis, ganglion cell layer/inner plexiform (GCL) thickness, retinal thickness, and retinal nerve fiber layer thickness, and a reduction of the neuroretinal rim in minimum rim width (MRW) and functionally as an abnormal electroretinogram (ERG), dark adaptation, contrast sensitivity, color vision, and microperimetric test. The findings in early stages of diabetic retinopathy may precede microvascular changes of this disease. Furthermore, the article’s objective is to characterize the factors and mechanisms conducive to microvascular changes and neuroretinal apoptosis in diabetic retinopathy. Only when all the measures preventing vascular dysfunction are determined will the risk of complications in the course of diabetes be minimized.

Clinical Findings in Four Siblings with Genetically Proven Oguchi Disease.

Purpose:To assess the clinical findings in normal daylight status and 3 h of dark-adapted status in family members with Oguchi disease (OD).Methods:Four siblings with OD and their parents were included in this case series. The presence of disease was confirmed with genetic analysis and comprehensive clinical evaluation. Corrected distant visual acuity (CDVA), automated visual field analysis (VFA), optical coherence tomography (OCT), OCT angiography (OCTA), colored fundus photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA), electroretinography (ERG), and dark adaptation test (DAT) results were obtained in normal daylight status. On the next day, after 3 h of dark adaptation, the patients were re-evaluated. The findings obtained in normal daylight status and 3 h dark-adapted status were compared.Results:The mean age of the four sibling subjects was 15.25 ± 2.2 years. All subjects had 20/20 CDVA and normal VFA. There was no abnormality in OCT and OCTA in normal daylight status and 3 h of dark-adapted status. Colored fundus photographs showed characteristic golden-yellow colored reflex in the mid-peripheral retina in normal daylight status, and discoloration in 3 h of dark-adapted status. In FAF and FFA, no abnormal pattern was observed in normal daylight status and 3 h of dark-adapted status. ERG showed rod function alterations and normal cone function. DAT showed delayed rod adaptation and normal cone adaptation. ERG and DAT findings remained unchanged after 3 h of dark adaptation.Conclusion:After 3 h of dark adaptation, golden-yellow fundus color returns to normal in patients with OD; however, rod function alterations and normal cone function in ERG, as well as delayed rod adaptation and normal cone adaptation in DAT remain unchanged.

Verifying complaints of difficulties in night vision using electroretinography and dark adaptation tests.

To determine the electroretinographical and psychophysical parameters that can help to verify patients' complaints of reduced night vision. We tested 275 consecutive patients with normal appearing fundi, complaining of visual difficulties at night, using flash electroretinography (ERG) and dark adaptation (DA) test. Two ERG parameters were used to assess a scotopic retinal function: the amplitude of the response to dim blue flash (the rod response) and the b-wave ratio (measured/expected). Dark adaptation was measured with green- and red-light stimuli after exposure to a bright, bleaching light. The psychophysical parameter of night vision was defined as the threshold for detection of the blue-green stimulus that was measured after 40-45min in complete darkness. Fifty-five patients were excluded from the analysis because of a discrepancy between the two ERG parameters in assessment of scotopic retinal function. The remaining 220 patients were divided into 4 groups: (1) normal ERG and normal DA, (2) subnormal ERG and subnormal DA, (3) normal ERG and subnormal DA and (4) subnormal ERG and normal DA. The ERG and DA tests supported the complaint of visual difficulties at night in 67 patients (group 2), while 34 patients were characterized as having normal scotopic visual function (group 1). The other 119 patients (groups 3 and 4) presented a diagnostic dilemma because one test (ERG or dark adaptation) showed normal scotopic function, while the other indicated subnormal scotopic function. Our findings indicate that ERG is an essential, but not sufficient test for verifying patient's complaint on visual difficulties in the dark. We suggest using both electroretinography and psychophysical dark adaptation to test patients complaining of reduced night vision.

Retest Reliability of Mesopic and Dark-Adapted Microperimetry in Patients With Intermediate Age-Related Macular Degeneration and Age-Matched Controls.

To determine the intrasession test-retest reliability of mesopic and dark-adapted fundus-controlled perimetry in patients with intermediate age-related macular degeneration (iAMD). We conducted a cross-sectional study with 23 iAMD patients (67.3 ± 8.2 years; range, 50-85; 78% female) and 24 healthy controls (61.3 ± 5.2 years; range, 50-71; 50% female) using a modified MAIA microperimeter. All patients underwent duplicate mesopic (achromatic stimuli, 400-800 nm) and dark-adapted (red stimuli, 627 nm) microperimetry, using a grid of 33 stimuli over 14° of the central retina. Main outcome measure was the intrasession test-retest reliability for pointwise sensitivity (PWS). PWS test-retest reliability was good among mesopic and dark-adapted testing in both patients and controls (coefficient of repeatability of 4.4, 4.52, 3.96, and 4.56 dB, respectively). Mean mesopic sensitivity in patients was 2.62 dB lower than in controls (P < 0.01); mean dark-adapted sensitivity was 2.49 dB lower than in controls (P < 0.01). The modified MAIA device allows for reliable mesopic and dark-adapted microperimetry in iAMD patients. We found that iAMD is associated with both reduced mesopic and dark-adapted retinal sensitivity.

Decreased Visual Function Scores on a Low Luminance Questionnaire Is Associated with Impaired Dark Adaptation

We investigate whether responses on a Low Luminance Questionnaire (LLQ) in patients with a range of age-related macular degeneration (AMD) severity are associated with their performance on focal dark adaptation (DA) testing and with choroidal thickness. Cross-sectional, single-center, observational study. A total of 113 participants older than 50 years of age with a range of AMD severity. Participants answered the LLQ on the same day they underwent DA testing using a focal dark adaptometer measuring rod intercept time (RIT). We performed univariable and multivariable analyses of the LLQ scores and age, RIT, AMD severity, subfoveal choroidal thickness [SFCT], phakic status, and best-corrected visual acuity. The primary outcome of this study was the score on the 32-question LLQ. Each item in the LLQ is designated to 1 of 6 subscales describing functional problems in low luminance: driving, emotional distress, mobility, extreme lighting, peripheral vision, and general dim lighting. Scores were computed for each subscale, in addition to a weighted total mean score. Responses from 113 participants (mean age, 76.2±9.3 years; 58.4% were female) and 113 study eyes were analyzed. Univariable analysis demonstrated that lower scores on all LLQ subscales were correlated with prolonged DA testing (longer RIT) and decreased choroidal thickness. All associations were statistically significant except for the association of choroidal thickness and "peripheral vision." The strongest association was the LLQ subscale of driving with RIT (r=-0.97, P < 0.001). Multivariable analysis for each of the LLQ subscale outcomes, adjusted for age, included RIT, with total LLQ score, "driving," "extreme lighting," and "mobility" also including choroidal thickness. In all multivariable analyses, RIT had a stronger association than choroidal thickness. This cross-sectional analysis demonstrates associations of patient-reported functional deficits, as assessed on the LLQ, with both reduced DA and reduced choroidal thickness, in a population of older adults with varying degrees of AMD severity and good visual acuity in at least 1 eye. These analyses suggest that local functional measurements of DA testing (RIT) and choroidal thickness are associated with patient-reported functional deficits.

Dominant Cystoid Macular Dystrophy

To describe the clinical characteristics and long-term follow-up in patients with autosomal dominant cystoid macular dystrophy (DCMD). Retrospective case series. Ninety-seven patients with DCMD. Extensive ophthalmic examination, including visual acuity (VA), fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), color vision testing, dark adaptation testing, full-field electroretinography (ERG), and electro-oculography (EOG). Blood samples were obtained for DNA extraction and subsequent haplotype analysis. Age at onset, VA, fundus appearance, and characteristics on FA, FAF, OCT, ERG, and EOG. Cystoid fluid collections (CFCs) were the first retinal abnormalities detectable in DCMD, developing during childhood. At long-term follow-up, the CFCs decreased in size and number, and eventually disappeared with concurrent development of progressive chorioretinal atrophy and hyperpigmented deposits in the posterior pole. Dominant cystoid macular dystrophy could be classified into 3 stages, based on characteristics on ophthalmoscopy, FAF, FA, and OCT, as well as on results of electrophysiologic analysis. The staging system correlated with age and VA. In stage 1 DCMD (20 patients; 22%), patients generally were younger than 20 years and had CFCs with fine folding of the internal limiting membrane and mild pigment changes. In stage 2 DCMD (48 patients; 52%), the CFCs tended to decrease in size, and moderate macular chorioretinal atrophy developed. Patients with stage 3 DCMD (24 patients; 26%) generally were older than 50 years and showed profound chorioretinal atrophy, as well as coarse hyperpigmented deposits in the posterior pole. Most patients were (highly) hyperopic (72 patients; 92%). All DCMD patients shared the disease haplotype at the DCMD locus at 7p15.3. Dominant cystoid macular dystrophy is a progressive retinal dystrophy, characterized primarily by early-onset cystoid fluid collections in the neuroretina, which distinguishes this disorder from other retinal dystrophies. The phenotypic range of DCMD can be classified into 3 stages. The genetic locus for this retinal dystrophy has been mapped to 7p15.3, but the involved gene is currently unknown.

Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven‐year follow‐up of photodynamic treatment of a young boy with choroidal neovascularization

To determine the mutation in a Swedish family with Best disease (vitelliform macular dystrophy; VMD) and to investigate the short- and long-term effects of photodynamic treatment (PDT) on subretinal neovascularization in a young boy. The five members of three generations of a family with VMD underwent a thorough ophthalmological examination, including best-corrected visual acuity (VA), visual field, colour vision, biomicroscopy of the posterior segment (dilated), fundus photography and electro-oculography (EOG). For the proband, an eleven-year-old boy, his father and grandfather, dark adaptation test, angiography and electroretinography (ERG) were also performed. After PCR amplification, the genotype was determined by cleavage with restriction enzyme, specific for the W93C allele. Four family members had an abnormal EOG response. All showed the W93C mutation in the VMD2 gene. Visual acuity ranged from 20/20 to 20/250. The fundus manifestations varied from minor pigmentary changes over egg yolk-like lesions to chorioretinal atrophy, and fluorescein angiography showed corresponding pathology. In the proband, VA decreased during follow-up from 0.5 (20/40) to 0.08 (20/250) due to a subfoveal neovascularization with haemorrhage, and PDT with visudyne was begun. The haemorrhage resolved within 2 months, and after three treatments, VA had increased to 0.25 (20/80). One year later, acuity had improved to 0.5 (20/40), and this result was stable throughout the 7 years of the follow-up. The mutation was determined to be W93C, the most common mutation in VMD in Sweden. In an eleven-year-old boy with subretinal neovascularization, PDT seemed to be beneficial also in a long-term follow-up.

Macular Thickness and Aging in Retinitis Pigmentosa

This study was designed to analyze macular tomography in patients of different ages with retinitis pigmentosa (RP) and correlate their visual function with macular thickness, which was measured by optical coherence tomography. In all, 75 RP patients and 75 controls were stratified into three age groups and macular thickness was measured by optical coherence tomography. The tomography was subdivided into three circular zones, four quadrants, and nine areas for analysis. Ophthalmic examinations, which involved ophthalmoscopic examinations, dark adaptation tests, visual acuities, visual field examinations, electrooculography, and color sense discrimination tests, were performed. Macular thickness of the RP patients decreased in the middle age group (45- to 55-year old), whereas the oldest group showed an increased thickness. The thickness of the outer inferior area remained virtually unchanged, whereas the thickness of the inner temporal area showed the most fluctuation with age. In terms of circular sections, the most dramatic changes in macular thickness were observed in the fovea, and the aging effect decreased outward to the outer ring. Furthermore, the thickness of the fovea was more important than the thickness of the inner ring and the outer ring for electrooculography, visual acuity, and color sense discrimination in RP patients. In middle age RP patients, the macular thickness decreased, whereas an increased thickness was observed in patients older than 55 years. In addition, the inner temporal area was the most fragile, and the outer inferior area was the least affected in patients with RP.

Occurrence and pattern of ocular disease in children with cholestatic disorders

To describe visual function and ocular manifestations in patients with onset of cholestasis during the neonatal period. Patients with neonatal cholestasis, either transitory or chronic, who came for assessment to our tertiary referral centre were included in a cross-sectional study and underwent ophthalmological examinations including fundus photography. A total of 57 patients (24 girls and 33 boys), aged 0.4-18.0 years, were included. Of these, 28 patients had biliary atresia, 11 had Alagille's syndrome, five had progressive familiar intrahepatic cholestasis and nine had different disorders such as pituitary insufficiency, alpha-1-antitrypsin deficiency, mitochondriopathy, congenital infections or cholestasis caused by unknown reasons. Visual dysfunction and/or one or several ocular manifestations occurred in 39 out of 57 patients. Major ocular malformations occurred in five patients. Out of three patients with biliary atresia, one patient had severe visual impairment caused by microphthalmia and chorioretinal coloboma, one patient with Cat Eye syndrome had bilateral uveochorioretinal coloboma and one patient had Rieger's anomaly. Two patients, both with pituitary deficiency and transient cholestasis, had severe unilateral visual impairment caused by optic nerve hypoplasia. The majority (68%) of the patients with cholestasis had ocular manifestations. Although the severity of ocular complications varied with diagnosis, and was most apparent among patients with biliary atresia or pituitary deficiency, no conclusion can be drawn regarding the connections between these conditions from the present study. Nevertheless, ocular assessment is important for diagnostic purposes and for early intervention in patients with cholestasis.

Anatomical and functional impairment of the retina and optic nerve in patients with anorexia nervosa without vision loss

AimThe aim of this cross-sectional study is to evaluate the macular and retinal nerve fibre layer (RNFL) thickness, as well as the electrical activity of the macula in female patients...

Retinitis pigmentosa and punctate cataracts in mevalonic aciduria.

Mevalonic aciduria, caused by deficiency of mevalonate kinase, was the first recognized defect in the biosynthesis of cholesterol and isoprenoids. Ophthalmic features of this potentially blinding disorder include blue sclera, cataract, uveitis, optic atrophy, and, importantly, a retinitis pigmentosa-like retinopathy. To date, ∼30 cases of this rare autosomal recessive disorder have been reported, with no full characterization appearing in the ophthalmic literature. An 11-year-old white girl with mevalonic aciduria presented with decreasing peripheral vision and night blindness. Examination revealed decreased central vision, punctate cataracts, and a retinitis pigmentosa-like retinopathy. Goldmann visual fields confirmed severe constriction in both eyes. A full-field electroretinogram was performed. A-waves, B-waves, and oscillatory potentials were all nonrecordable in both eyes, indicating severe bilateral retinopathy, affecting both cone- and rod-mediated responses. Dark adaptation testing showed severely impaired cone and rod function under dark-adapted (scotopic) conditions. Farnsworth-Munsell hue discrimination (FM-100 hue) testing was abnormal in both eyes. The ocular findings in patients with mevalonic aciduria are heterogeneous and include blue sclerae, cataracts, uveitis, retinopathy, and optic atrophy. Visual prognosis is guarded; several patients surviving to adulthood have progressed to apparent legal blindness caused by cataracts and/or retinopathy.

Diabetes and Obesity

Diabetes and Obesity

Six Patients with Bradyopsia (Slow Vision): Clinical Features and Course of the Disease

Recently, it was discovered that subjects who showed a prolonged response suppression on their electroretinogram (ERG) and had symptoms of photophobia, problems adjusting to bright light, and difficulties seeing moving objects shared a mutation in the RGS9 (regulator of G-protein signaling 9) gene that is involved in the deactivation of photoreceptor responses. The disorder was termed bradyopsia (slow vision). This paper reports the clinical presentation and long-term follow-up of 6 bradyopsia patients. Retrospective observational case series with a follow-up ranging from 6 to 30 years. Six patients with a homozygous mutation in the RGS9 gene. Clinical symptoms and signs were compared between the subjects and between their visits over time. Symptoms, visual acuity (VA), ocular findings, visual fields, dark-adaptation tests, color tests, fluorescein angiography, and ERG findings. Data showed a consistency in the individual symptoms and ERG recordings, but an extreme variation in VA between visits. Beside some irregularities in the macula in some patients, no other related eye abnormalities were seen. The low-to-subnormal VA varied with background luminance and typically increased by 2 to 3 lines when pinholes were used. Dark-adaptation tests, color tests, and fluorescein angiography were normal. Visual field tests showed a minor diffuse sensitivity loss. No progressive changes were seen over time. No signs of progression were noted in the 6 bradyopsia patients. Photophobia, impaired movement perception, variable reduced VA that improved with the use of pinholes and ERG abnormalities were typical for the disease.

Reticular Dystrophy of the Retinal Pigment Epithelium

A laser flare-cell meter was used to examine blood-aqueous barrier function in a 57-year-old male patient who had typical reticular dystrophy of the retinal pigment epithelium with a bilateral hyperpigmented reticular pattern at the posterior pole in both eyes. Fluorescein angiography showed hypofluorescent reticular net resembling a fishing net with knots associated with a central diffuse hyperfluorescence. Dark adaptation test revealed that the final rod threshold was elevated. Laser photometry showed an increase in the aqueous flare intensity in both eyes, as compared to the results in normal subjects. Quantitative measurement of the aqueous flare intensity by a laser flare-cell meter might indicate abnormalities in the blood-aqueous barrier in patients with reticular dystrophy of the retinal pigment epithelium.

Physiologic Indicators of Vitamin A Status

Physiologic indicators reflect the functional consequences of vitamin A deficiency and may be particularly useful for detecting early perturbations in vitamin A status. In conjunctival impression cytology (CIC), epithelial morphology and the presence or absence of mucin spots and goblet cells allow samples, obtained by applying filter paper to the temporal conjunctiva, to be characterized as normal or typical of vitamin A-deficient keratinizing metaplasia. The validity of CIC has been established with reference to other indicators of vitamin A status, and a prevalence of > or =20% abnormal results has been suggested as indicative of a public health problem. However, interpretation of specimens requires considerable training, and nonresponsiveness to supplementation is a frequent problem, which limits the utility of CIC as a method for evaluating the impact of intervention programs. Several simplified field protocols for dark adaptation have been developed, including one in which dark adaptation is assessed by the responsiveness of the pupil to light. Night blind subjects have consistently shown abnormal results on this test, and a significant response to placebo-controlled dosing has been demonstrated for children and pregnant women. Scores have correlated significantly with serum retinol and relative dose response. Pupillary dark adaptation testing is acceptable to most children as young as 2 y old. Limitations of this technique include a time course for recovery after dosing as long as 4-6 wk, a testing time of 20 min, and the need for 1-3 d of training. Given its low cost, noninvasive nature, and lack of the need to transport samples, pupillary dark adaptation offers advantages over other techniques for assessing a population's vitamin A status.