Cone System Dysfunction Research Articles

Characteristics of Vitamin A Deficiency Retinopathy at a Tertiary Referral Center in the United States

To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients. Single-center retrospective case series. Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR. Retrospective chart review. Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings. Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions. Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol. The authors have no proprietary or commercial interest in any materials discussed in this article.

Evaluation of fluocinolone acetonide 0.19 mg intravitreal implant in the management of birdshot retinochoroiditis

PurposeTo report treatment outcomes and efficacy of the fluocinolone acetonide 0.19 mg intravitreal implant (Iluvien) in controlling retinal and choroidal inflammation in 11 patients with birdshot retinochoroiditis.MethodsA single-centre, retrospective, interventional...

Autosomal Recessive Bestrophinopathy: Clinical Features, Natural History, and Genetic Findings in Preparation for Clinical Trials

PurposeTo investigate the clinical course, genetic findings, and phenotypic spectrum of autosomal recessive bestrophinopathy (ARB) in a large cohort of children and adults.DesignRetrospective case series.ParticipantsPatients with a detailed clinical phenotype consistent with ARB, biallelic likely disease-causing sequence variants in the BEST1 gene, or both identified at a single tertiary referral center.MethodsReview of case notes, retinal imaging (color fundus photography, fundus autofluorescence, OCT), electrophysiologic assessment, and molecular genetic testing.Main Outcome MeasuresVisual acuity (VA), retinal imaging, and electrophysiologic changes over time.ResultsFifty-six eyes of 28 unrelated patients were included. Compound heterozygous variants were detected in most patients (19/27), with 6 alleles recurring in apparently unrelated individuals, the most common of which was c.422G→A, p.(Arg141His; n = 4 patients). Mean presenting VA was 0.52 ± 0.36 logarithm of the minimum angle of resolution (logMAR), and final VA was 0.81 ± 0.75 logMAR (P = 0.06). The mean rate of change in VA was 0.05 ± 0.13 logMAR/year. A significant change in VA was detected in patients with a follow-up of 5 years or more (n = 18) compared with patients with a follow-up of 5 years or less (n = 10; P = 0.001). Presence of subretinal fluid and vitelliform material were early findings in most patients, and this did not change substantially over time. A reduction in central retinal thickness was detected in most eyes (80.4%) over the course of follow-up. Many patients (10/26) showed evidence of generalized rod and cone system dysfunction. These patients were older (P < 0.001) and had worse VA (P = 0.02) than those with normal full-field electroretinography results.ConclusionsAlthough patients with ARB are presumed to have no functioning bestrophin channels, significant phenotypic heterogeneity is evident. The clinical course is characterized by a progressive loss of vision with a slow rate of decline, providing a wide therapeutic window for anticipated future treatment strategies.

Deep Phenotyping of PDE6C-Associated Achromatopsia.

PurposeTo perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.MethodsEight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, best-corrected visual acuity, fundus autofluorescence, and optical coherence tomography. Six subjects also had confocal and nonconfocal adaptive optics scanning light ophthalmoscopy, axial length, international standard pattern and full-field electroretinography (ERG), short-wavelength flash (S-cone) ERGs, and color vision testing.ResultsAll subjects presented with early-onset nystagmus, decreased best-corrected visual acuity, light sensitivity, and severe color vision loss, and five of them had high myopia. We identified three novel disease-causing variants and provide phenotype data associated with nine variants for the first time. No subjects had foveal hypoplasia or residual ellipsoid zone (EZ) at the foveal center; one had an absent EZ, three had a hyporeflective zone, and four had outer retinal atrophy. The mean width of the central EZ lesion on optical coherence tomography at baseline was 1923 μm. The mean annual increase in EZ lesion size was 48.3 μm. Fundus autofluorescence revealed a central hypoautofluorescence with a surrounding ring of increased signal (n = 5). The mean hypoautofluorescent area at baseline was 3.33 mm2 and increased in size by a mean of 0.13 mm2/year. Nonconfocal adaptive optics scanning light ophthalmoscopy revealed residual foveal cones in only one of two cases. Full-field ERGs were consistent with severe generalized cone system dysfunction but with relative preservation of S-cone sensitivity.ConclusionsPDE6C retinopathy is a severe cone dysfunction syndrome often presenting as typical achromatopsia but without foveal hypoplasia. Myopia and slowly progressive maculopathy are common features. There are few (if any) residual foveal cones for intervention in older adults.

ISCEV extended protocol for the dark-adapted red flash ERG

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the dark-adapted (DA) red flash ERG. The DA red flash ERG can be incorporated conveniently within the ISCEV standard ERG protocol after a minimum of 20-min DA and recorded after the DA 0.01 ERG to a flash strength of 0.3 phot cd s m−2, eliciting a waveform with two positive peaks in healthy individuals. The first positive component is the cone-mediated x-wave with a peak at 30–50 ms; the second is a rod-mediated b-wave with a peak time of approximately 100 ms. Shorter DA times may be desirable to shorten the recording time or to alter the prominence of the early cone-mediated x-wave relative to the rod-mediated b-wave. The DA red flash ERG is used to aid the diagnosis of achromatopsia (rod monochromacy), cone dystrophy and other forms of cone system dysfunction, including “Bradyopsia” (RGS9/R9AP-retinopathy), when the DA red flash ERG x-wave is preserved in the absence of ISCEV standard LA ERGs. The DA red flash ERG can also help determine the origin of residual DA ERGs in cases of severe rod dysfunction, for example in disorders such as vitamin A deficiency, fundus albipunctatus (RDH5-retinopathy), Oguchi disease (SAG- or GRK1-retinopathy) and some rod-cone dystrophies. To shorter DA periods, the x-wave may be elicited without the following rod b-wave, shown to be helpful in abbreviated protocols for children.

Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome

To describe a series of patients with Bardet-Biedl syndrome (BBS) and predominantly retinal cone dysfunction, a previously only rarely reported association. Retrospective observational case series. Seven patients with clinically proven Bardet-Biedl syndrome had undergone detailed ocular phenotyping, which included fundus examination, Goldmann visual fields, fundus autofluorescence imaging (FAF), optical coherence tomography (OCT), and electroretinography (ERG). Mutational screening in the BBS genes was performed either by direct Sanger sequencing or targeted next-generation sequencing. All 7 patients had proven BBS mutations; 1 had a cone dystrophy phenotype on ERG and 6 had a cone-rod pattern of dysfunction. Macular atrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. OCT confirmed loss of outer retinal structure within the atrophic areas. No clear genotype-phenotype relationship was evident. Patients with Bardet-Biedl syndrome usually develop early-onset retinitis pigmentosa. In contrast, the patients described herein, with molecularly confirmed Bardet-Biedl syndrome, developed early cone dysfunction, including the first reported case of a cone dystrophy phenotype associated with the disorder. The findings significantly expand the phenotype associated with Bardet-Biedl syndrome.

A detailed phenotypic description of autosomal dominant cone dystrophy due to a de novo mutation in the GUCY2D gene

The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D. Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene. The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother. Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.

A Longitudinal Study of Stargardt Disease: Clinical and Electrophysiologic Assessment, Progression, and Genotype Correlations

To investigate the clinical and electrophysiologic natural history of Stargardt disease and correlate with the genotype. Cohort study of 59 patients. Clinical history, examination, and electrophysiologic assessment were undertaken in a longitudinal survey. Patients were classified into 3 groups based on electrophysiologic findings, as previously published: Group 1 had dysfunction confined to the macula; Group 2 had macular and generalized cone system dysfunction; and Group 3 had macular and both generalized cone and rod system dysfunction. At baseline, there were 27 patients in Group 1, 17 in Group 2, and 15 in Group 3. Amplitude reduction of >50% in the relevant electroretinogram (ERG) component or a peak time shift of >3ms for the 30Hz flicker ERG or bright flash a-wave was considered clinically significant ERG deterioration. Molecular screening of ABCA4 was undertaken. The mean age at baseline was 31.7 years, with the mean follow-up interval being 10.5 years. A total of 22% of patients from Group 1 showed ERG group transition during follow-up, with 11% progressing to Group 2 and 11% to Group 3. Forty-seven percent of patients in Group 2 progressed to Group 3. There was clinically significant ERG deterioration in 54% of all subjects: 22% of Group 1, 65% of Group 2, and 100% of Group 3. At least 1 disease-causing ABCA4 variant was identified in 47 patients. All patients with initial rod ERG involvement demonstrated clinically significant electrophysiologic deterioration; only 20% of patients with normal full-field ERGs at baseline showed clinically significant progression. Such data assist counseling by providing more accurate prognostic information and are also highly relevant in the design, patient selection, and monitoring of potential therapeutic interventions.

A Phenotype–Genotype Correlation Study of X-Linked Retinoschisis

To compare the clinical phenotype and detailed electroretinographic parameters in X-linked retinoschisis (XLRS). Retrospective, comparative study. Fifty-seven patients (aged 1-67 years) with molecularly confirmed XLRS were clinically ascertained. Pattern electroretinography (PERG) and full-field electroretinography (ERG), incorporating international standard recordings, were performed in 44 cases. Thirteen patients, mostly pediatric, were tested using a simplified ERG protocol. On-Off and S-cone ERGs were performed in most adults. Fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) were available in 17 and 21 cases, respectively. The clinical and electrophysiologic data associated with different types of mutation in the RS1 gene. Forty-three patients had missense changes (group A), and 14 patients had nonsense, splice-site, or frame-shifting mutations in the RS1 gene (group B). The mean best-corrected visual acuity was better in group A than in group B (0.34 and 0.21, respectively). Fundus examination revealed foveal schisis in approximately half of both groups. The bright-flash dark-adapted (DA) ERG (11.0 candela.sec.m(-2)) waveform was electronegative in 62% of group A eyes and 100% of group B eyes. The photopic 30-Hz flicker ERG was delayed in all group B eyes and all except 6 group A eyes. On-Off ERG b-waves were subnormal in 39% of group A and 89% of group B eyes; d-waves were delayed in 14 eyes (group A = 10, group B = 4). S-cone ERGs were abnormal in 50% of both groups. The PERG was abnormal in 88% of group A and 100% of group B eyes. A spoke-wheel pattern of high and low intensity was the most common FAF abnormality observed. The OCT showed intraretinal schitic cavities in the majority of eyes. There is profound phenotypic variability in patients with XLRS. Most patients have DA bright-flash ERGs with a low b:a ratio in keeping with inner retinal dysfunction. Generalized cone system dysfunction is common and associated with an abnormal On-response and less frequent additional Off-response involvement. Nonsense, splice-site, or frame-shifting mutations in RS1 consistently caused electronegative bright-flash ERG, delayed flicker response, and abnormal PERG; missense mutations result in a wider range of ERG abnormalities.

X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development

X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.

Novel Mutations and Electrophysiologic Findings in RGS9- and R9AP-Associated Retinal Dysfunction (Bradyopsia)

To examine the phenotypes of 8 patients with evidence of cone dysfunction and normal color vision (characteristic features of both oligocone trichromacy and bradyopsia), and subsequently to screen RGS9 and R9AP for disease-causing mutations. Retrospective case series. Eight affected individuals from 7 families. Ophthalmologic examination, color vision testing, fundus photography, and detailed electrophysiologic assessment were undertaken. Blood samples were taken for DNA extraction from affected subjects and, where possible, unaffected relatives. Mutation screening of RGS9 and R9AP was performed. Detailed clinical, electrophysiologic, and molecular genetic findings. All 8 patients had normal ocular examination results, with visual acuity ranging from 6/12 to 6/18. Four subjects were found to harbor mutations in RGS9 or R9AP, with 3 of the identified sequence variants being novel. Three subjects, 2 Pakistani sisters and an Afghani female, had mutations in R9AP. A novel homozygous nonsense mutation, p.G205fs, was identified in the simplex case, and a second novel homozygous in-frame deletion, p.D32_Q34del, was found in the 2 sisters. The remaining patient, a British male, had a compound heterozygous mutation in RGS9 (p.R128X/p.W299R). The mutation p.R128X represents the first nonsense mutation reported in RGS9. The 4 mutation-positive subjects had concordant characteristic previously described electrophysiologic findings that were not present in the 4 individuals in whom mutations were not identified. Novel findings associated with these mutation-positive patients included that they all showed electroretinogram evidence of severe cone system dysfunction under photopic conditions but normal cone function to a red flash under scotopic conditions. Such findings seem unique for the disorder. This is the first report describing a nonsense mutation in RGS9. We have established novel electrophysiologic observations associated with RGS9 and R9AP mutations, including those relating to dark-adapted cone function and S-cone function. Patients with either RGS9/R9AP mutations (bradyopsia) or oligocone trichromacy have very similar clinical phenotypes, characterized by stationary cone dysfunction, mild photophobia, normal color vision, lack of nystagmus, and normal fundi. The distinctive electrophysiologic features associated with RGS9 and R9AP mutations enable directed genetic screening. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinicopathological Case Series of Four Patients with Inherited Macular Disease

To correlate the phenotype of four patients with inherited macular disease with the immunohistopathology of retinal tissue collected at the time of retinal pigment epithelium (RPE)-choroidal transplantation. A clinicopathologic case series describing the phenotype of four patients, including confocal immunohistochemistry and electron microscopy (EM), and the results of genetic testing. In Case 1, electrophysiology showed only macular dysfunction. Confocal microscopy revealed minor abnormalities. EM showed abnormal cone inner segments with swollen mitochondria. In case 2 (R172W mutation in RDS), electrophysiology demonstrated generalized cone system dysfunction with severe macular involvement. Peripherin labeling of outer segments was nonuniform, and EM showed discs arranged in whorllike structures. Case 3 showed severe central macular dysfunction on multifocal electroretinogram (ERG). Peripherin staining was irregular and disorganized. EM revealed abnormal inner segment morphology, particularly in rods, and disorganized irregular outer segments. Case 4 had localized central macular dysfunction on multifocal ERG. Confocal microscopy was grossly normal, with evidence of early redistribution of cone opsin to the inner segment. EM showed variable rod morphology and normal cones. RPE transplantation provides a unique opportunity to gain insight into retinal disorders by enabling phenotypic correlation with the immunohistopathology of retinal tissue collected during surgery.

Macular and retinal dysfunction of unknown origin in adults with normal fundi: Evidence for an autoimmune pathophysiology

Here we report the discovery of and phenotypic characterization of a retinal disorder of unknown origin in adults using clinical, electrophysiological and psychophysical techniques, and to seek the presence of circulating retinal autoantibodies in the sera of these patients. Sixteen patients were identified with progressive bilateral visual loss over a period of months. Ten of the patients were male, and the average age was 55.3 years (range from 43 to 76 years). Known causes such as carcinoma-associated retinopathy, acute zonal occult outer retinopathy and hereditary cone dystrophy appeared unlikely. Investigations included electrophysiology, fundus autofluorescence imaging and psychophysical tests. The sera of these patients were analyzed with indirect immunocytochemistry and Western immunoblot analysis on murine (BALB/c) retinal tissue for the presence of retinal autoantibodies. Bilateral visual loss and photophobia progressed over a period of months to years (average 28.7 months, range 3–67) and subsequently stabilized. No abnormality was observed by biomicroscopy, angiography or autofluorescence imaging. Electrophysiology indicated predominant cone-system dysfunction, either macular or generalized, and post-phototransduction involvement in 9 patients (56%). Photopic and scotopic visual fields and dark adaptation kinetics showed both cone and rod system involvement in all cases. Heterogeneous immunohistochemical staining patterns were seen with the sera of these patients as compared with controls. A majority of the affected patients (9/15) stained with an antinuclear pattern. The retinal autoantibodies from the sera of most patients reacted with the retinal proteins of molecular weight between 34 and 40 kDa. The aetiology of this distinctive retinal disorder therefore appears to be mediated through an autoimmune mechanism.

Regional Assessment of Cone System Function Following Uncomplicated Retinal Detachment Surgery

To evaluate regional cone system function after uncomplicated retinal detachment (RD) surgery, by recording focal electroretinograms (FERGs) from the central and paracentral regions of the posterior pole. FERGs in response to either a central (eccentricity: 0-2.25 deg) or a paracentral annular (2.25-9 deg) uniform field, presented on a light adapting background and sinusoidally flickered at 41 Hz (95% modulation depth, 93 cd/m(2) mean luminance) were recorded from 16 eyes (16 patients) 2 weeks to 420 months following uncomplicated RD surgery (encircling procedure with or without scleral buckling). Pre-operatively, 10 out of 16 eyes had a macular RD. Mean time elapsed from onset of symptoms to surgery was 20 days (range: 5-90 days). Post-operatively, visual acuity ranged 0.1 to 1.0. Eight age-matched normal subjects served as controls. Amplitude and phase of the FERG fundamental harmonic were measured. Compared to control eyes, affected eyes' central and paracentral FERGs were on average reduced in amplitude (by 40% and 28%, respectively, p<0.01) and delayed in phase (by 70 and 100 degrees, respectively, p<0.01). Eyes with a macular RD did not differ in FERG amplitude or phase from eyes that had a peripheral RD. In individual affected eyes, central, but not paracentral FERG amplitudes were negatively correlated (p=0.05) with time elapsed from onset of symptoms to surgery. Central and paracentral cone system dysfunction may be detected even at lengthy time intervals from retinal reattachment, independent of the presence of a pre-operative macular RD. The extent of central loss appears to be inversely related to RD duration, in agreement with previous reflectometric findings on foveal cone photopigment density [Liem et al., 1994; Ophthalmology 10: 1945-51].

MORPHOLOGY AND FUNCTIONAL CHARACTERISTICS IN ADULT VITELLIFORM MACULAR DYSTROPHY

Detailed morphologic and functional evaluation of adult vitelliform macular dystrophy (AVMD). The records of 61 consecutive AVMD patients (inclusion criterion: vitelliform lesion smaller than one disk diameter at least in one eye) were evaluated retrospectively regarding visual acuity, color vision, perimetry, retinal pigment epithelium (RPE) autofluorescence, fluorescein angiography, electro-oculography, full-field and multifocal electroretinography, and molecular genetic evaluation of the VMD2 and RDS/peripherin genes. The mean age of subjects was 54.6 years. Visual loss was variable (median, 0.6; range, 1.25-0.05). Color vision and visual field were normal in about half of the patients but presented defects with high variability in the remaining patients. Autofluorescence findings showed increased fluorescence within the foveal yellow lesion in 76%. In the majority of eyes, the amplitude of the 30 Hz flicker response of the full-field electroretinogram (72%) and the central P1 amplitude of the multifocal electroretinogram (63%) were reduced. Mutational analyses revealed a potentially disease-associated mutation in the RDS/peripherin gene in one patient. AVMD is characterized by late onset, slow progression, good prognosis, and high variability of morphologic and functional abnormalities resulting frequently in misdiagnosis. Autofluorescence findings indicate lipofuscin accumulation in the yellow lesion. Electroretinography revealed a generalized cone system dysfunction with increasing severity toward the fovea.

Seeing in the dusk: physiological basis and investigation

Dark adaptation and seeing in the dusk require a complex interaction of the cone and rod system. Whereas the former provides high temporal resolution and colour vision in daylight, temporal resolution of the latter is smaller but sensitivity higher by a factor of 100 to 1,000. The two operational ranges overlap by several decades. Characteristic symptoms of disease may be derived from the systems' physiological function and should be enquired about specifically. Problems due to opacity of the optic media or reduced visual acuity should be differentiated from night vision disorders in the more specific sense. Apart from a routine ophthalmological examination a set of other tests should be used: When rods function normally the second limb of the dark adaptation curve initiates at 5 - 12 min und reaches a normal absolute threshold after 30 - 40 min; dark adapted visual fields are unrestricted apart from a physiological central scotoma, and the dark adapted electroretinogram (ERG) shows normal amplitudes and latencies for low intensity flashes. The influence of glare on mesopic contrast sensitivity may be investigated with a mesoptometer. Night vision disorders may arise from cone system dysfunction, too. Intact cone vision provides high visual acuity, normal colour vision, normal photopic visual fields, a quick regeneration within minutes during the first limb of the dark adaptation curve and normal single flash and oscillatory potentials in the light-adapted ERG. Localised defects may be detected using the multifocal ERG. Interpretation of the results must account for the age-related decay of contrast sensitivity and speed of adaptation.

Multifocal electroretinograms in X-linked retinoschisis.

To study local retinal cone function in patients with X-linked retinoschisis (XLRS) by multifocal ERGs (mfERGs). mfERGs were recorded from seven eyes of seven patients with XLRS (mean age +/- SD, 22.1 +/- 3.2 years; range, 18 to 25 years). Five eyes had microcystic changes in the macula and two eyes had nonspecific macular degeneration. Two eyes had peripheral retinoschisis, and some of the stimuli fell on this area. The stimulus array consisted of 103 hexagons and the total recording time was set at approximately 4 minutes. The amplitudes and implicit times of both focal and summed responses for the first- and second-order kernels were analyzed. The amplitudes of the first-order kernel were markedly reduced in the central retina in all eyes. A large variation was observed in the amplitudes outside the fovea. The amplitudes of the focal cone ERGs at the peripheral retinoschisis did not differ from those recorded from adjacent retinal loci without the retinoschisis. The implicit times of the first-order kernel were significantly delayed, and the amplitudes of the second-order kernels were more affected than the first-order kernels across the whole field in all XLRS eyes. The cone-mediated retinal responses were more impaired in the central than peripheral retina in eyes with XLRS. Delayed implicit times of the first-order kernel and reduced second-order kernel across the whole testing field in all XLRS eyes suggest that there is widespread cone-system dysfunction in XLRS.

The fundamental and second harmonic of the photopic flicker electroretinogram: temporal frequency-dependent abnormalities in retinitis pigmentosa

Objectives: The flicker electroretinogram (FERG) consists mainly of a linear (fundamental, 1F) and a non linear (second harmonic, 2F) component. Previous results indicate that 2F originates more proximally in the retina than 1F, and that retinitis pigmentosa (RP) may affect 2F to a greater extent than 1F. The aim of this study was to evaluate FERG 1F and 2F abnormalities in RP as a function of the stimulus temporal frequency (TF).Methods: Twelve patients with typical RP and 10 age-matched controls were examined. FERGs were recorded in response to uniform fields (18°) presented in the macula on a light-adapting background. Stimuli were flickered sinusoidally at different, closely spaced TFs between 3.7 and 52 Hz. Amplitudes and phases of the Fourier analysed 1F and 2F components were measured. Components, apparent latencies were estimated from the rate at which phase lagged with TF.Results: When compared to controls, mean 1F amplitudes of patients were reduced at both low (3.7–12.6 Hz) and high (14–52 Hz) TFs, with greatest losses (0.5 log units) around the peaks (3.7 and 41 Hz) of the normal TF function. Mean 2F amplitudes were reduced mainly at low TFs, with greatest losses (0.5 log units) at 5–8 Hz. On average, the shape of the 2F, but not 1F amplitude versus TF function, differed between patients and controls, showing a selective attenuation at low TFs. Mean 1F apparent latencies were delayed at both low and high TFs, with greater delays at low (85 ms) than at high (33 ms) TFs. Mean 2F apparent latencies were delayed only at low TFs (58 ms).Conclusions: In RP, 1F and 2F phase delays as well as 2F amplitude losses are dependent on TF, suggesting that FERG generators’ subpopulations in both distal and proximal retina are differentially affected. Analysis of the FERG TF response is potentially useful to characterize cone system dysfunction in different genetic subtypes of RP.

Vigabatrin-associated retinal cone system dysfunction

To the Editor: I read with interest the article Vigabatrin-associated retinal cone system dysfunction by Krauss et al.1 I am a neuro-ophthalmologist and epidemiologist who has served as a paid consultant for Hoechst-Marion-Roussel, the manufacturer of vigabatrin. In this capacity I have reviewed ocular and vision data and adverse event reports on more than 2500 patients treated with vigabatrin in clinical trials, as well as adverse event reports on about 125,000 patients exposed to the drug outside of formal trials. Significant visual deficits have been reported in only a small number of cases. However, over time I have become convinced that severe visual field constriction is a real, although rare, adverse effect of the drug. Having reviewed the visual fields on Dr. Krauss' patients, I believe that the field constriction in Patient 1 is similar to that of the previously reported patients …

Vigabatrin-associated retinal cone system dysfunction

To the Editor: I read with interest the report by Krauss et al.1 on visual and ERG abnormalities in epileptic patients taking vigabatrin. The presence of field constriction as an infrequent complication of vigabatrin therapy has been previously documented2 and is of clinical relevance. It is important to evaluate carefully the evidence for the authors' hypothesis that the visual complications of vigabatrin are due to dysfunction in the inner retinal layers of the cone system. Dysfunction in the cone system is generally characterized by abnormalities in color vision and central scotoma, neither of which are present in …