Search Results (22)

Introduction: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a benign proliferation of the melanin-producing retinal pigment epithelium (RPE). Although often a benign and incidental finding, multifocal CHRPE may mimic lesions associated with familial adenomatous polyposis (FAP). Case Description: We describe an 8-year-old girl presenting with optic disc pallor and widespread multifocal bear track CHRPE observed bilaterally on dilated fundoscopy. Fundus autofluorescence (FAF) imaging showed uniform areas of hypoautofluorescence corresponding to the bear track lesions. Spectral domain optical coherence tomography (SD-OCT) demonstrated normal lamination without atrophy. The full-field electroretinogram (ffERG) was within normal limits. Whole-genome sequencing (WGS) revealed a likely pathogenic heterozygous variant in the STAG2 gene (c.3222dup, p.Ser1075IlefsTer12). Conclusions: We present a rare case of bilateral, panretinal bear track CHRPE in a child with a likely pathogenic variant in STAG2. Using multimodal imaging, we contrast bear track lesions of the retina with FAP-associated CHRPE. We also present possible ophthalmic manifestations in carriers of pathogenic STAG2 variants. Full article

To compare the clinical characteristics of inherited retinal diseases (IRDs) caused by biallelic versus monoallelic variants in the RP1, BEST1, and PROM1 genes. A total of 52 patients (26 female) with genetically confirmed IRDs were retrospectively selected from the records of the Harkness Eye Institute Clinical Coordinating Center at Columbia University Irving Medical Center. In RP1, 3 individuals with biallelic variants and 22 patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. In BEST1, eight individuals with biallelic variants and nine individuals with monoallelic variants classified as either pathogenic or likely pathogenic were included. In PROM1, four individuals with biallelic variants and six patients with monoallelic variants classified as pathogenic or likely pathogenic were selected. All patients underwent multimodal retinal imaging and, when available, full-field electroretinography (ffERG). In all three genes, individuals with biallelic variants had markedly earlier disease onset and more severe phenotypes. In RP1, on SD-OCT, foveal involvement was observed in all biallelic cases (3/3, 100%) and in 4/22 (18%) monoallelic cases. In BEST1, the average age of onset in the biallelic cohort was 7.12 years, and the average age was 32.7 years in the monoallelic cohort. Four of eight (50%) patients in the biallelic group were additionally found to have widespread serous lesions outside of the central macula. This finding was not observed in the monoallelic group. Three of eight (38%) biallelic BEST1 patients had moderate reductions in their photopic flicker. All monoallelic BEST1 patients had photopic responses within the normal range. PROM1 biallelic cases showed severe functional impairment on ffERG, while most monoallelic cases retained normal responses. In the biallelic cohort, four of four (100%) of patients had severely attenuated or extinguished photopic responses. In the monoallelic PROM1 group, four of five (80%) monoallelic PROM1 patients had normal photopic responses, and P2-2 had mildly attenuated photopic responses. Individuals with biallelic variants exhibited earlier disease onset, more severe retinal degeneration, and significantly reduced retinal function compared with those with monoallelic variants. These observations highlight the role of loss-of-function mechanisms in more aggressive disease courses and underscore the importance of considering zygosity when determining prognosis and planning gene-based therapies. Full article

This is the studyto investigate the correlation between macular cone density (MCD) and flicker electroretinogram (ERG) response in healthy eyes. In this exploratory study, 23 eyes from 12 healthy subjects were enrolled in this study. The fixed-luminance flicker full-field electroretinogram (ffERG) responses of the retina and MCDs at 24 locations were measured using the Diopsys^® NOVA™ system and the rtx1 adaptive optics retinal camera, respectively. Regression analysis was employed to evaluate the correlations. The mean age of the subjects was 30 ± 3 years. The average magnitudes of the flicker response and phase response were 13.44 ± 4.88 μV and 332.63 ± 22.12°, respectively. The MCDs for all 24 locations were 15,043 ± 3511 cones/mm². Among all locations, regression analysis revealed a significant correlation only at one specific location (0, −4°) between cone density and both the mean magnitude and phase of the flicker response, with p-values of 0.005 and 0.004, respectively.In conclusion, we identified a significant correlation between MCD and ffERG responses at a specific retinal locus (0, −4°). This finding may be attributed to the distribution of different cone types throughout the retina and the possibility that various cone types may contribute differently to ERG. Further studies are required to investigate this finding. Full article

Background: Chronic granulomatous disease (CGD) is a rare genetic disorder that causes primary immunodeficiency. In addition to increasing infection susceptibility in various bodily systems, several ocular manifestations have been described in males. This condition is well described in males, due to its X-linked recessive inheritance. However, here we present, to our knowledge, the first cases of X-linked CGD chorioretinitis in female carriers, possibly due to skewed X-inactivation (lyonization). Methods: Comprehensive multimodal imaging, including color fundus photography, short-wavelength autofluorescence, and spectral domain optical coherence tomography (OCT), was conducted. Functional assessment was completed with full-field electroretinogram (ff-ERG). Results: This report details two sisters with X-linked CGD carrier status, both presenting chorioretinal lesions on fundoscopy. Observed features included punched-out chorioretinal lesions, perivascular atrophy, and peripheral pigment changes. Autofluorescence imaging confirmed hypoautofluorescent areas correlating with chorioretinal atrophy, and OCT revealed retinal collapse and ellipsoid zone loss in one sibling. Despite these structural changes, visual function remained stable with minimal progression over time. Subsequent serial ERGs did not show progression. Conclusions: The findings highlight that skewed X-inactivation may contribute to retinal changes in asymptomatic CGD carriers, underscoring the need for awareness of potential ocular manifestations in X-linked genetic disorders in female carriers. Full article

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography (mfERG), pattern electroretinography (PERG), visual evoked potentials (VEP), and electrooculography (EOG) offer insights into retinal and optic nerve function, often detecting abnormalities before clinical symptoms manifest. In hearing loss syndromes like Refsum disease, Usher syndrome (USH), and Wolfram syndrome (WS), electrophysiology facilitates the detection of early retinal changes that precede the onset of visual symptoms. For mitochondrial disorders such as maternally-inherited diabetes and deafness (MIDD), Kearns–Sayre syndrome (KSS), and neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, these tests can be useful in characterizing retinal degeneration and optic neuropathy. In obesity syndromes, including Bardet-Biedl syndrome (BBS), Alström syndrome, and Cohen syndrome, progressive retinal degeneration is a hallmark feature. Electrophysiological techniques aid in pinpointing retinal dysfunction and tracking disease progression. Other syndromes, such as Alagille syndrome (AGS), abetalipoproteinemia (ABL), Cockayne syndrome (CS), Joubert syndrome (JS), mucopolysaccharidosis (MPS), Neuronal ceroid lipofuscinoses (NCLs), and Senior–Løken syndrome (SLS), exhibit significant ocular involvement that can be evaluated using these methods. This review underscores the role of visual electrophysiology in diagnosing and monitoring visual system abnormalities across a range of syndromes, potentially offering valuable insights for early diagnosis, monitoring of progression, and management. Full article

Purpose: To describe an atypical phenotypic pattern of late-onset retinitis pigmentosa (RP) due to the same specific c.425A>G (p.Tyr142Cys) heterozygous mutation in the cone–rod homeobox gene (CRX gene) in two unrelated Italian patients. Case 1: A 67-year-old woman (P.P.) was incidentally diagnosed with sector RP at the age of 50. The patient was initially asymptomatic and did not have any family history of retinal dystrophy. Fundus examination showed the presence of typical retinal pigmentary deposits with a peculiar pericentral/sector distribution. Genomic sequencing disclosed the missense mutation c.425A>G (p.Tyr142Cys) in the CRX gene. During the follow-up period of 7 years, the patient maintained good visual acuity and complained only of mild symptoms. Case 2: A 76-year-old man (P.E.) presented with nyctalopia and visual field constriction since the age of 50. Fundus examination showed the presence of retinal pigment deposits with a concentric pericentral and perimacular pattern. A full-field electroretinogram (ffERG) showed extinguished scotopic responses and reduced abnormal photopic and flicker cone responses. Genomic sequencing identified the same missense mutation, c.425A>G (p.Tyr142Cys), in the CRX gene. Similarly to the first case, during the whole follow-up of 7 years, the visual acuity remained stable, as did the visual field and the patient’s symptoms. Conclusions: We report the first cases of late-onset retinitis pigmentosa related to a specific heterozygous CRX gene mutation in exon 4. We also report two atypical phenotypic RP patterns related to mutations in the CRX gene. Full article

Aland island eye disease (AIED), an incomplete form of X-linked congenital stationary night blindness (CSNB2A), and X-linked cone-rod dystrophy type 3 (CORDX3) display many overlapping clinical findings. They result from mutations in the CACNA1F gene encoding the α_1F subunit of the Cav1.4 channel, which plays a key role in neurotransmission from rod and cone photoreceptors to bipolar cells. Case report: A 57-year-old Caucasian man who had suffered since his early childhood from nystagmus, nyctalopia, low visual acuity and high myopia in both eyes (OU) presented to expand the diagnostic process, because similar symptoms had occurred in his 2-month-old grandson. Additionally, the patient was diagnosed with protanomalous color vision deficiency, diffuse thinning, and moderate hypopigmentation of the retina. Optical coherence tomography of the macula revealed retinoschisis in the right eye and foveal hypoplasia in the left eye. Dark-adapted (DA) 3.0 flash full-field electroretinography (ffERG) amplitudes of a-waves were attenuated, and the amplitudes of b-waves were abolished, which resulted in a negative pattern of the ERG. Moreover, the light-adapted 3.0 and 3.0 flicker ffERG as well as the DA 0.01 ffERG were consistent with severely reduced responses OU. Genetic testing revealed a hemizygous form of a stop-gained mutation (c.4051C>T) in exon 35 of the CACNA1F gene. This pathogenic variant has so far been described in combination with a phenotype corresponding to CSNB2A and CORDX3. This report contributes to expanding the knowledge of the clinical spectrum of CACNA1F-related disease. Wide variability and the overlapping clinical manifestations observed within AIED and its allelic disorders may not be explained solely by the consequences of different mutations on proteins. The lack of distinct genotype–phenotype correlations indicates the presence of additional, not yet identified, disease-modifying factors. Full article

Inherited retinal dystrophies encompass a diverse group of disorders affecting the structure and function of the retina, leading to progressive visual impairment and, in severe cases, blindness. Electrophysiology testing has emerged as a valuable tool in assessing and diagnosing those conditions, offering insights into the function of different parts of the visual pathway from retina to visual cortex and aiding in disease classification. This review provides an overview of the application of electrophysiology testing in the non-macular inherited retinal dystrophies focusing on both common and rare variants, including retinitis pigmentosa, progressive cone and cone-rod dystrophy, bradyopsia, Bietti crystalline dystrophy, late-onset retinal degeneration, and fundus albipunctatus. The different applications and limitations of electrophysiology techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP), in the diagnosis and management of these distinctive phenotypes are discussed. The potential for electrophysiology testing to allow for further understanding of these diseases and the possibility of using these tests for early detection, prognosis prediction, and therapeutic monitoring in the future is reviewed. Full article

Background: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. Methods: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. Results: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0–18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. Conclusions: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure. Full article

Purpose: The axial elongation in myopia is associated with some structural and functional retinal changes. The purpose of this study was to investigate the effect of a contact lens (CL) intended for myopia control on the choroidal thickness (ChT) and the retinal electrical response. Methods: Ten myopic eyes (10 subjects, 18–35 years of age) with spherical equivalents from −0.75 to −6.00 diopters (D) were enrolled. The ChT at different eccentricities (3 mm temporal, 1.5 mm temporal, sub-foveal ChT, 1.5 mm nasal, and 3 mm nasal), the photopic 3.0 b-wave of ffERG and the PERG were recorded and compared with two material-matched contact lenses following 30 min of wear: a single-vision CL (SV) and a radial power gradient CL with +1.50 D addition (PG). Results: Compared with the SV, the PG increased the ChT at all eccentricities, with statistically significant differences at 3.0 mm temporal (10.30 ± 11.51 µm, p = 0.020), in sub-foveal ChT (17.00 ± 20.01 µm, p = 0.025), and at 1.5 mm nasal (10.70 ± 14.50 µm, p = 0.044). The PG decreased significantly the SV amplitude of the ffERG photopic b-wave (11.80 (30.55) µV, p = 0.047), N35-P50 (0.90 (0.96) µV, p = 0.017), and P50-N95 (0.46 (2.50) µV, p = 0.047). The amplitude of the a-wave was negatively correlated with the ChT at 3.0T (r = −0.606, p = 0.038) and 1.5T (r = −0.748, p = 0.013), and the amplitude of the b-wave showed a negative correlation with the ChT at 1.5T (r = −0.693, p = 0.026). Conclusions: The PG increased the ChT in a similar magnitude observed in previous studies. These CLs attenuated the amplitude of the retinal response, possibly due to the combined effect of the induced peripheral defocus high-order aberrations impacting the central retinal image. The decrease in the response of bipolar and ganglion cells suggests a potential retrograde feedback signaling effect from the inner to outer retinal layers observed in previous studies. Full article

Age-related macular degeneration (AMD) is an eye disease that leads to progressive vision loss. Its prevalence has been increasing due to population aging. Previously, it was commonly believed that the disease affects the central retina, that is, the macula. However, recent studies have shown that it also involves the peripheral retina. Novel imaging techniques revealed various degenerative lesions that extend beyond the central macula. While their prevalence remains unknown, they seem to be more frequent in patients with late AMD. These findings suggest that the term “age-related retinal dysfunction” might be more adequate to describe some cases of AMD. They also raise the question about the role of electroretinography (ERG) as an objective measure of retinal function. The most common types of ERG tests used in AMD are multifocal (mfERG) and full-field ERG (ffERG). mfERG is more sensitive to macular changes, but the test is difficult to perform when fixation is unstable. On the other hand, ffERG reflects the function of the entire retina, not only the macular area. It helps assess the impact of peripheral retinal lesions and overall retinal function in patients with AMD. As ffERG results are normal in early-stage AMD, any abnormalities indicate that the disease is more severe and affects the entire retina. Anti-vascular endothelial growth factor injections improve retinal function in patients with neovascular AMD, as demonstrated by an increase in their ERG responses. More research is needed to assess the association between local and general retinal dysfunction. In this review, ffERG findings in patients with AMD are described and the usefulness of ffERG is discussed based on previous studies and cases from our own clinical practice. Full article

Background: Cone–rod dystrophies (CRDs) are a heterogeneous group of inherited retinal diseases (IRDs) characterized by cone photoreceptor loss, that is followed by subsequent rod photoreceptor impairment. Case presentation: A 49-year-old man complaining of diminution of vision in both eyes (OU) was referred to our outpatient clinic. He reported visual loss for 5 years, but it was most progressive during the last few months. The best-corrected visual acuity (BCVA) at presentation was 0.4 in the right eye (RE) and 1.0 in the left eye (LE). Fundus fluorescein angiography (FFA) revealed granular hyperfluorescence in the macula and concomitant areas of capillary atrophy. Flash full-field electroretinography (ffERG) showed lowering of a and b waves as well as prolonged peak time in light-adapted conditions. However, outcomes of dark-adapted ERGs were within normal limits. Based on the constellation of clinical, angiographic, and electrophysiological tests findings, a diagnosis of IRD was suspected. Genetic testing showed a homozygous, pathogenic c.783G>A mutation in the cadherin-related family member 1 (CDHR1) gene, which confirmed CRD type 15 (CRD15). Conclusions: We demonstrate the clinical characteristics, retinal imaging outcomes, and genetic test results of a patient with CRD15. Our case contributes to expanding our knowledge of the clinical involvement of the pathogenic mutation c.783G>A in CDHR1 variants. Full article

Friedreich’s ataxia (FRDA) is a rare autosomal recessive neurodegenerative disorder due to the homozygous pathological expansion of guanine-adenine-adenine (GAA) triplet repeats in the first intron of the FXN gene, which encodes for the mitochondrial protein frataxin. In the visual system, the typical manifestations are ocular motility abnormality, optic neuropathy, and retinopathy. Despite the evidence of ophthalmological impairment in FRDA patients, there is a lack of information about the morpho-functional condition of the retina and of the optic pathways in healthy heterozygous carriers of Friedreich’s ataxia (C-FRDA). Ten C-FRDA subjects (providing 20 eyes) and thirty-five Controls (providing 70 eyes) underwent a complete neurological and ophthalmological examination comprehensive of functional (full-field Electroretinogram (ffERG), multifocal Electroretinogram (mfERG), Visual Evoked Potential (VEP), and Pattern Reversal Electroretinogram (PERG)) and morphological assessments (Optical Coherence Tomography, OCT) of the retina, macula, retinal ganglion cells, and visual pathways. The groups’ data were compared using a two-sample t-test. Pearson’s test was used to investigate the morpho-functional correlations. Statistically significant differences (p < 0.01) between C-FRDA and Control eyes for the values of the following parameters were found: ffERG b-wave amplitude, mfERG Response Amplitude Densities, PERG P50 implicit time and P50-N95 amplitude, VEP P100 implicit time, Retinal Nerve Fiber Layer (RNFL) Overall, and Nasal thickness. The values of the OCT macular volume were not statistically different (p > 0.01) between the two Groups. Therefore, our data suggest that, in C-FRDA, a dysfunction of retinal elements without morphological macular impairment may occur. In addition, a morphological impairment of RNFL associated with an abnormal neural conduction along the visual pathways can be also detected. Full article

We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers. Full article

It is important for clinicians to consider exposure to toxic substances and nutritional deficiencies when diagnosing and managing cases of vision loss. In these cases, physiologic damage can alter the function of key components of the visual pathway before morphologic changes can be detected by traditional imaging methods. Electrophysiologic tests can aid in the early detection of such functional changes to visual pathway components, including the retina or optic nerve. This review provides an overview of various electrophysiologic techniques, including multifocal electroretinogram (mfERG), full-field ERG (ffERG), electrooculogram (EOG), pattern electroretinogram (PERG), and visual evoked potential (VEP) in monitoring the retinal and optic nerve toxicities of alcohol, amiodarone, cefuroxime, cisplatin, deferoxamine, digoxin, ethambutol, hydroxychloroquine, isotretinoin, ocular siderosis, pentosane, PDE5 inhibitors, phenothiazines (chlorpromazine and thioridazine), quinine, tamoxifen, topiramate, vigabatrin, and vitamin A deficiency. Full article