Poor Color Vision Research Articles

Gene Therapy for Achromatopsia.

Achromatopsia is the most common cone dysfunction syndrome, affecting 1 in 30,000 people. It is an autosomal recessive disorder with a heterogeneous genetic background with variants reported in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6. Up to 90% of achromatopsia patients harbour mutations in CNGA3 or CNB3, which encode for the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel in cone-specific phototransduction. The condition presents at birth or early infancy with poor visual acuity, nystagmus, photophobia, and colour vision loss in all axes. Multimodal retinal imaging has provided insightful information to characterise achromatopsia patients based on their genotype. There is no FDA-approved treatment for achromatopsia; however, studies have reported several preclinical gene therapies with anatomical and functional improvements reported in vivo. There are currently five gene therapy clinical trials registered for human patients at the phase I/II stage and for CNGA3 or CNGB3 causing achromatopsia. This review aims to discuss the genetics of achromatopsia, genotypic and phenotypic correlations in multimodal retinal imaging, and the developments and challenges in gene therapy clinical trials.

Quality of Life in Patients with Birdshot Chorioretinitis Aged 80 and Older

ABSTRACT Purpose Birdshot chorioretinitis (BSCR) is an ocular HLA-related disease with variable clinical progression. We examine the quality of life (QOL) of BSCR individuals aged ≥80 years, providing insights into the long-term disease impact. Methods We utilized data from the CO-BIRD cohort (ClinicalTrials.gov Identifier: NCT05153057) conducted at Hôpital Cochin in Paris, France, focusing on BSCR patients aged ≥80. The main outcome was vision-related QOL using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). We used Spearman correlation to explore the impact of better BCVA and MD on the composite score, and the Wilcoxon test to evaluate specific visual symptoms’ effects. Results The study included 35 patients with a mean age of 83.9 ± 3.7 years, 74.3% of whom received systemic immunosuppression. The mean composite score was 58 ± 30, with a median of 75 (23–79). The lowest subscores were driving capacity (38 ± 38), mental health (49 ± 33), and role difficulties (50 ± 35), while the highest were for ocular pain (70 ± 25) and social function (70 ± 38). Decimal BCVA below 0.5 and MD below −6 dB were associated with lower subscores. BCVA and MD were strongly correlated with the composite score (R = 0.67). Symptoms of poor color and blurry vision were significantly associated with lower composite score (p < 0.005). Conclusion Most BSCR patients over 80 in our cohort maintained sufficient vision for daily activities. The high standard deviation and wide range of VFQ-25 results reflect the heterogeneity of visual outcomes among elderly BSCR patients.

LOW VISION IN RETINITIS PIGMENTOSA: HOW TO ENHANCE FUNCTIONAL VISION IN PSEUDOPHAKIC PATIENT

Introduction : Retinitis Pigmentosa (RP) could lead to various visual impairments, including decreased visual acuity, poor dark adaptation, decreased contrast sensitivity, poor color vision, visual field constriction, leading to low vision (LV). LV in RP decreases patient’s quality of life (QoL) and Independence. We aim to report a successful case of LV management in a bilateral pseudophakic patient with RP.&#x0D; Case Illustration : A 33-year-old man came with progressively blurred vision in both eyes (BE) that worsen 6 months ago. Ophthalmologic examination revealed his uncorrected visual acuity for right eye (RE) and left Eye (LE) was 6/60 and 4/60. The patient had cataract surgeries and IOLs implantation on BE in 2021. Funduscopic examination revealed the bone spicule appearance, blood vessel attenuation, and waxy disc pallor on BE. Humphrey's examination showed a peripheral visual field defect. Decreased contrast sensitivity and poor color vision were also found.&#x0D; Discussion : The patient was managed by LV aids and rehabilitation. Spectacle clarified distant and near vision with best corrected visual acuity (BCVA) 6/21 and 0.8 M on BE, photochromic lenses aided in adapting to various lighting levels and as a UV protection, and the addition of illumination and color contrast enhancement improved vision in dim light. A convex mirror to be used as a field- enhancement spotting tool. Rehabilitation enhances his head tracking, scanning, and habitual spotting skills. Improvement of QoL has been recorded using LVQoL questionnaires.&#x0D; Conclusion : LV management are vary based on an individual’s level of functional vision and personal preferences. Optimal LV management could enhance patient QoL and Independence.

Molecular and Clinical Characterization of CNGA3 and CNGB3 Genes in Brazilian Patients Affected with Achromatopsia.

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2) and of the unfolded protein response (ATF6) have been related to ACHM cases, while CNGA3 and CNGB3 alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the CNGA3 and CNGB3 genes. Patients' genotype and phenotype were retrospectively evaluated. The majority of CNGA3 variants were missense, and the most prevalent CNGB3 variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the CNGB3 gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease.

Patients with Ethambutol-Induced Ocular Toxicity Receiving "Directly Observed Treated Short-Course"

Objective: Determine the total number of Category-1 patients with ocular toxicity from Ethambutol after DOTS therapy. Methodology: This study conducted in department of Ophthalmology of abaseen hospital and Khyber medical center Peshawar over the one year, from May 2021 to April 2022 included Category-1 TB patients (both genders) aged 14 and 65 who had normal ocular parameters on an ophthalmological examination when starting DOTS treatment. The frequency of any vision change, optical symptom, including color vision, contrast sensitivity while receiving Ethambutol medication was examined in 240 eyes (120 patients). At the end of the first month and again at the end of the second month of therapy, Each patient's compliance with Ethambutol was examined, and all tests for ocular toxicity were repeated for each chosen patient. The study did not include patients in category-2 with positive sputum smears who had relapsed, had therapy fail, or was getting treatment after a break in treatment. Results: Out of 120 patients (240 eyes), 62 (51.6%) of them were male, and 58 (48.4%) of them were female patients. After a month, there was no sign of ocular toxicity. Ocular toxicity, on the other hand, appeared in 3 (2.5%) of the patients after the second month. Moreover, these three patients showed decreased visual acuity, poor color vision, decreased contrast sensitivity, and optic disc abnormalities. Conclusion: Patients with tuberculosis who use Ethambutol are at risk of developing ocular toxicity. As a result, it is essential to identify visual symptoms and signs as soon as possible to avoid unnecessary diagnostic delays and maybe irreversible vision loss. Keywords: Tuberculosis, Color Vision, Contrast Sensitivity, Optic Disc, Ethambutol-induced ocular toxicity, visual acuity, treatment strategies

Побочное действие психотропных препаратов на орган зрения

Any antipsychotics provoke more or less ocular complications. Some of them are relatively harmless (i.e., dark eyelids, conjunctival and corneal pigmentation, mydriasis, nystagmus, dry eye etc.). These adverse effects are resolved spontaneously after treatment discontinuation, drug switching, or prescribing additional therapy. However, the intake of both typical and atypical neuroleptics, lithium salts, some anticonvulsants (e.g., topiramate) is associated with high risks of vision loss. Moreover, in some patients these medications may result in blindness. The use of psychotropic drugs (e.g., tricyclic antidepressants or serotonin reuptake inhibitors) in patients with higher risk of acute angle closure is of particular concern. The association between phenothiazines and anticonvulsants and retinopathy, chlorpromazine and cataract, anticonvulsants and poor color vision and reduced contrast sensitivity is also important. Psychiatrists and ophthalmologists should consider potential ocular side effects in patients receiving psychotropic drugs. Knowing management algorithm for these conditions is also important. The number of recent publications on this issue is limited. Therefore, articles older than 10 years are sometimes used. Keywords: eye, visual organ, adverse effects, psychotropic drugs, neuroleptics, tricyclic antidepressants, selective serotonin reuptake inhibitors, glaucoma, retinopathy, cataract. For citation: Petukhova A.A., Panov A.A., Malygin Ya.V., Kazanfarova M.A. Side effects of psychotropic drugs on eye. Russian Journal of Clinical Ophthalmology. 2021;21(1):29–33. DOI: 10.32364/2311-7729-2021-21-1-29-33.

The evolution of coloration and opsins in tarantulas.

Tarantulas paradoxically exhibit a diverse palette of vivid coloration despite their crepuscular to nocturnal habits. The evolutionary origin and maintenance of these colours remains mysterious. In this study, we reconstructed the ancestral states of both blue and green coloration in tarantula setae, and tested how these colours correlate with presence of stridulation, urtication and arboreality. Green coloration has probably evolved at least eight times, and blue coloration is probably an ancestral condition that appears to be lost more frequently than gained. While our results indicate that neither colour correlates with the presence of stridulation or urtication, the evolution of green coloration appears to depend upon the presence of arboreality, suggesting that it ptobably originated for and functions in crypsis through substrate matching among leaves. We also constructed a network of opsin homologues across tarantula transcriptomes. Despite their crepuscular tendencies, tarantulas express a considerable diversity of opsin genes-a finding that contradicts current consensus that tarantulas have poor colour vision on the basis of low opsin diversity. Overall, our findings raise the possibility that blue coloration could have ultimately evolved via sexual selection and perhaps proximately be used in mate choice or predation avoidance due to possible sex differences in mate-searching.

Colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration.

Purpose:To generate the first published reference database of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration and to explore this important feature in quality of vision.Background:Quality of vision depends on many factors. Changes in chromatic contrast sensitivity remain largely unexplored in eyes at high risk of neovascular age-related macular degeneration; they may however not only be relevant for quality of life but also an early indicator of the onset of the disease, so it is important to have a means to evaluate any variation in colour contrast sensitivity, especially in view of the likely increase in neovascular age-related macular degeneration as the population ages.Methods:This prospective longitudinal study evaluated colour contrast sensitivity along the protan and tritan colour axes in 145 eyes at high risk of neovascular age-related macular degeneration.Results:Colour contrast sensitivity showed statistically significant correlations with age and visual acuity, but not gender nor laterality (i.e. whether the right or left eye was being tested). There was significant variability among individuals, especially for the tritan axis, with some subjects well within normal limits for age and others with very poor colour contrast sensitivity.Conclusion:This study has generated the first published colour contrast sensitivity reference database for eyes at high risk of neovascular age-related macular degeneration. It has also shown a high inter-individual variability of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration, but the significance of this is unclear. Further work is required to establish if eyes with high colour contrast sensitivity thresholds (i.e. poor colour vision) have a higher risk of developing neovascular age-related macular degeneration over time, and this is the subject of ongoing work.

Visual pathway neurodegeneration winged by mitochondrial dysfunction

ObjectivesTo test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis.MethodsA single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry.ResultsThe visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport.InterpretationThis study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

Optical coherence tomography in the diagnosis of achromatopsia

Case reportThe case of a fifty-five year-old male with nyctalopia, photophobia, poor color vision and nystagmus is presented. The initial suspected diagnoses were achromatopsia and blue-cone monochromatism, since both are clinically indistinguishable. Optical coherence tomography (OCT) showed the characteristic foveal reflectivity pattern of achromatopsia. This diagnosis was subsequently confirmed by genetic study. DiscussionOCT is a non-invasive diagnostic imaging method that allows tissue morphology to be observed with high resolution. Its use might be of great help to distinguish clinically similar diseases.

Examination of colour vision deficiency in different types retinitis pigmentosa

AbstractPurpose Investigation of the colour vision deficiency in different typees of retinitis pigmentosa (RP): autosomal dominant, autosomal recessive, X‐linked recessive, and isolated cases.Methods Colour vision investigation was conducted on 42 patients (18 women, 24 men) with RP using the Farnsworth 28 HUE‐test, anomaloscope –IF‐2 Tomay, flicker threshold test, standard pseudoisochromatic table and Tritan Lantonie album. The age of the patients varied from 5 to 68 years (mean 39 ± 17, SD),Results In 73,3 % of patients with RP we established acquired colour vision deficiency (dyschromatopsy) . Among the patients with aquired colour vision deficiency we found out using the above‐mentioned tests that 67,8% were with tritanopy, 19,3% were with manifested deuteranomaly and 12,9 % were with protanomaly. The type of dyschromatopsy does not show any relation to the age and visual aquity of patients. When no foveal lesion was apparent in patients with visual acuity better than 20/40, patients with autosomal dominant disease showed superior performance on color vision testing when compared to autosomal recessive, X‐linked recessive, and isolated cases. The Farnsworth 28 HUE test was more sensitive in detecting poor color vision performance than the anomaloscope –IF‐2 Tomay.Conclusion We established a great percentile of patients with RP suffer from colour vision deficiency. Our study reveals that colour vision investigation has an important role in PR diagnosis.

Cobalt–chromium toxic retinopathy case study

To report the clinical case of a 65-year-old male who developed retinal dysfunction following cobalt-chromium toxicity. A review of the clinical, haematological, radiological and electrophysiological investigations into a single patient was performed in order to form a case report. A 65-year-old male presented to his ophthalmologist with a 1-year history of worsening vision on the background of a multisystem illness including motor axonopathy, pericardiomyopathy and bulbar palsy. His medical history included hypertension, hypercholesterolaemia and a metallic hip prosthesis. Ocular examination revealed significantly reduced visual acuity bilaterally along with very poor colour vision. Cornea, fundi and optic discs all appeared normal. Bilateral moderate nuclear sclerosis was noted. Basic investigations including mitochondrial studies, auto-immune screen and MRI of brain were unremarkable. Further investigations showed significantly elevated plasma cobalt and chromium levels. Electrophysiological studies revealed an abnormality in all phases of the ERG including a negative b-waveform, suggestive of inner retinal pathology. Following subsequent revision of the hip, cobalt and chromium levels decreased and the patient's vision improved. Further electrophysiological testing indicates a persistent ERG abnormality despite a significant improvement in both the patient's visual acuity and colour vision. These results suggest that cobalt-chromium toxicity can cause inner retinal dysfunction.

Tomografía de coherencia óptica en el diagnóstico de la acromatopsia

Case reportThe case of a fifty five year-old male with nyctalopia, photophobia, poor colour vision and nystagmus, is presented. The initial suspected diagnoses were achromatopsia and blue-cone monochromatism, since both are clinically indistinguishable. Optical coherence tomography (OCT) showed the characteristic foveal reflectivity pattern of achromatopsia. This diagnosis was subsequently confirmed by genetic study. DiscussionOCT is a non-invasive diagnostic imaging method that allows tissue morphology to be observed with high resolution. Its use might be of great help to distinguish clinically similar diseases.

Comparison of photochromic, yellow, and clear intraocular lenses in human eyes under photopic and mesopic lighting conditions

To evaluate the results of the first blue light-filtering photochromic intraocular lens (IOL) and compare them with those of a regular yellow blue light-filtering IOL and a clear ultraviolet-filtering IOL in human eyes under various lighting conditions. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China. Prospective comparative clinical study. This study evaluated eyes that had implantation of 1 of the following 3 IOLs: photochromic Aurium Matrix acrylic, model 400; yellow AF-1 (UY); or clear MC611MI. All eyes were followed for 3 months. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, contrast vision (lighting 400 lux, 30 lux, 5 lux), contrast sensitivity, color vision (Farnsworth-Munsell 100-hue test under 400 lux, 30 lux), and patient questionnaire responses were evaluated. The photochromic IOL group comprised 39 eyes; the yellow IOL group, 41 eyes; and the clear IOL group, 38 eyes. There were no significant differences between the 3 IOLs in UDVA, CDVA, contrast sensitivity, or questionnaire responses. The photochromic group had significantly better color vision than the yellow IOL group at 30 lux and better contrast vision at 5% contrast (P < .05); however, there were no significant differences between the photochromic IOL group and the clear IOL group (P > .05). The photochromic blue light-filtering IOL performed as well as the yellow and clear IOLs under photopic conditions. Under mesopic conditions, the yellow IOL gave poor color vision and contrast sensitivity.

A novel mutation (Cys83Tyr) in the second zinc finger of NR2E3 in enhanced S-cone syndrome

Enhanced S-cone syndrome (ESCS) is an autosomal recessive retinal disorder characterized by an increased number of S-cones over L/M cones and rods. Mutations in the NR2E3 gene, encoding a photoreceptor-specific nuclear receptor, are identified in patients with ESCS. The purpose of this study is to report the ophthalmic features of a 25-year-old Portuguese male with a typical ESCS phenotype and a novel homozygous NR2E3 mutation. The patient underwent a detailed ophthalmic examination including fundus photography, fluorescein angiography (FAF), fundus autofluorescence imaging (FAI), and spectral domain optical coherence tomography (SD-OCT). Full-field electroretinography (ERG), S-cone ERG, and multifocal ERG were performed. Mutation screening of the NR2E3 gene was performed with polymerase chain reaction amplification and direct sequencing. The patient had poor visual acuity but good color vision. Funduscopy showed degenerative changes from the vascular arcades to the midperipheral retina. The SD-OCT revealed macular schisis and cystoid changes that had no fluorescein leakage. The posterior pole showed diffusely increased autofluorescence compared with eccentric areas in both eyes. International-standard full-field ERG showed the typical pathognomonic changes associated with ESCS and the short-wavelength flash ERG was simplified, delayed, and similar to the standard photopic flash ERG. Multifocal ERG showed widespread delay and reduction. Genetic analysis revealed a novel homozygous mutation (p.C83Y), which resides in the second zinc finger of the DNA-binding domain. This homozygous mutation is likely to affect binding to target DNA sites, resulting in a non-functional behavior of NR2E3 protein. It is associated with a typical form of ESCS with a nondetectable rod response and reduced/delayed mfERG responses at all eccentricities.

Chiasmal compression misdiagnosed as normal-tension glaucoma: can we avoid the pitfalls?

Routine neuroimaging for patients with presumed normal-tension glaucoma (NTG) is a contentious issue and it has been suggested that it may be unnecessary due to the low yield for detecting intracranial pathology. However, it has also been reported that 8% of patients diagnosed with NTG have associated compressive lesions of the anterior visual pathways. We present three patients in whom the initial diagnosis of NTG was eventually revealed to be chiasmal compression secondary to a pituitary tumour. Case 1: a 79-year-old woman was treated for NTG for several months before a bitemporal haemianopia developed and imaging showed a pituitary tumour. Case 2: an 83-year-old man was treated for NTG while a magnetic resonance imaging (MRI) scan was requested routinely. This subsequently revealed a pituitary tumour. Case 3: a 52-year-old man with left inferior arcuate visual field loss plus disc pallor was treated for NTG. His visual field deteriorated over 8 years, despite his intraocular pressure (IOP) being well controlled. An MRI was eventually requested, which revealed a pituitary tumour. All of our patients had signs that, with hindsight, should have raised suspicions about the presumptive diagnosis of NTG and initiated neuroimaging at an earlier stage. Whilst compression of the anterior visual pathways is an uncommon finding in patients thought to have NTG, features such as bitemporal field loss, optic disc pallor, poor colour vision and, particularly, poor disc/field correlation should alert the clinician to the possibility of an intracranial mass lesion.

Anterior Ischemic Optic Neuropathy Associated with Pegylated Interferon Therapy for Chronic Hepatitis C

Purpose: To report a case of anterior ischemic optic neuropathy (AION) associated with the combined therapy of pegylated interferon alpha (PEG-IFNα) and ribavirin. Methods: Case report. Results: A 57-year-old male with chronic hepatitis C, treated with PEG-IFNα -2b and ribavirin for 6 months, noted sudden onset of painless blurred vision in his right eye. The initial visual acuity decreased to 20/60 in the right eye. Fundoscopy of right eye revealed optic disc edema with disc hemorrhage. Visual field examination disclosed inferior altitudinal defect. Relative afferent pupillary defect with poor color vision function was also noted in the right eye. Visual evoked potential demonstrated decreased amplitude in the right eye. A marked resolution of disc edema and improvement of visual acuity to 20/20 were noted at 6 weeks follow-up. Conclusions: AION may occur in combined treatment of PEG-IFNα -2b and ribavirin for chronic hepatitis C. Patients who are candidates for this treatment should be informed about its possible occurrence.

Orienteers with poor colour vision require more than cunning running

Background: Highly detailed colour coded maps are used in the sport of orienteering to enable competitors to navigate from one check point to another and to provide guidance on the nature of the terrain to be traversed. The colours are defined by the International Orienteering Foundation (IOF) and are said to have been chosen so they will not be confused by competitors who have abnormal colour vision. However, there are anecdotal reports that individuals with colour vision defects do have problems with the colour coding.Method: A Minolta Spectrophotometer CM‐503i was used to measure the CIE x,y chromaticity co‐ordinates and the reflectances of the standard colours recommended by the IOF for the colour coding of orienteering maps, as well as the colours on two maps used in orienteering events.Results: Four pairs of IOF standard colours are likely to be confused by protan observers and four pairs by deutan observers. There were three pairs of colours likely to be confused by both deutan and protan observers on one of the competition maps and one pair likely to be confused by protan observers on the other map. Some of the colours on the actual competition maps differed noticeably from the standard IOF colours.Discussion: Orienteers with more severe forms of abnormal colour vision are likely to be disadvantaged by their inability to differentiate some colours used on orienteering maps. The IOF should choose different colours that are less likely to be confused or should employ a redundant code (such as a pattern or texture). There is need for better quality control of the colours of competition maps to ensure they do conform to the IOF standard colours.

Technical Note: The effect of refractive blur on colour vision evaluated using the Cambridge Colour Test, the Ishihara Pseudoisochromatic Plates and the Farnsworth Munsell 100 Hue Test

The results of a prospective study examining the effect of refractive blur on colour vision performance in normal subjects measured with three different colour vision tests are reported. The Farnsworth Munsell 100 Hue (FM100) and Cambridge Colour Test (CCT) results were significantly affected at +6 D of spherical refractive blur, whereas those from the Ishihara Pseudoisochromatic Plate (IPP) test were not. In a clinical setting, correction of refractive error up to 3 D for colour vision testing with these tests may not be required. Poor colour vision should not be attributed solely to refractive causes of poor visual acuity (Snellen equivalent: >6/36). Fastest test times were achieved using IPP, followed by CCT.

Clinical and electroretinographic findings of female carriers and affected males in a progressive X-linked cone–rod dystrophy (COD-1) pedigree

Objective To study the clinical and electroretinographic findings of affected males and female carriers in a family with X-linked cone–rod dystrophy (COD-1). Design Observational case series. Participants Twenty-five members of a five-generation pedigree were examined. Methods A history of visual impairment including age at onset, loss of acuity, color vision abnormalities, photophobia, and nyctalopia was obtained. A complete ophthalmologic examination was performed, including kinetic perimetry with a Goldmann perimeter, FM 100-hue testing, and standardized Ganzfeld electroretinography following the ISCEV protocol. Main outcome measures Patients were classified as affected or unaffected on the basis of the clinical examination. All carrier females had affected sons. Results Nine affected males and seven female carriers were identified. Affected males noted decreased visual acuity and poor color vision within the first two decades of life. Early in the disease, macular retinal pigment epithelial (RPE) changes were found that progressed to an atrophic macular scar by the fifth decade. Evidence of progression from macular pigment mottling to an atrophic macular lesion over a 13-year period was identified in one patient. The photopic, single-flash, b-wave amplitude was low in all affected males and declined with age. The 30-Hz flicker b-wave implicit times were abnormally prolonged in all affected males. Female carriers were asymptomatic although three had slightly abnormal color vision and small paracentral field defects and subtle RPE defects were found in three carriers. Carriers demonstrated prolongation of the 30-Hz flicker b-wave implicit time and interocular asymmetry. Five of seven carriers and two affected males demonstrated reduced oscillatory potentials and an abnormal-appearing flattened photopic a-wave. Five men and two women demonstrated a characteristic tapetal-like retinal sheen. Conclusions Affected patients in this pedigree demonstrate early loss of visual acuity and poor cone function with late rod involvement. Female carriers may appear clinically normal or may be identified by subtle color vision defects, fundus abnormalities, prolongation of the 30-Hz flicker implicit time with interocular asymmetry, or an abnormal flattened photopic a-wave. Genetic linkage analysis of this family was recently reported and the disease-causing gene has been mapped to an approximately 1-Mb interval on chromosome Xp11.4.