Search Results (27)

Background and Clinical Significance: Biallelic pathogenic variants in the PCARE gene (photoreceptor cilium actin regulator), also known as C2orf71 (chromosome 2 open reading frame 71), are typically associated with retinitis pigmentosa type 54 (RP54) and, less frequently, with cone–rod dystrophy (CORD23). Case Presentation: A 52-year-old man presented with an eight-year history of progressive visual loss, without photophobia or nyctalopia. He underwent a comprehensive ophthalmological evaluation, including multimodal retinal imaging, automated perimetry, and full electrophysiological testing, in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV)’s standards. Genetic testing was performed using next-generation sequencing (NGS) with an inherited retinal dystrophy gene panel, and findings were confirmed by Sanger sequencing. Clinical examination revealed bilateral macular atrophy with minimal foveal sparing and a central scotoma. Optical coherence tomography (OCT) showed disruption of the outer retinal layers and retinal pigment epithelium (RPE) abnormalities. Fundus autofluorescence (FAF) demonstrated central hypoautofluorescence surrounded by a hyperautofluorescent ring. Electrophysiological testing revealed severely reduced rod- and cone- mediated responses on full-field electroretinography (ERG), absent pattern ERG responses, and markedly reduced multifocal ERG responses, indicating widespread retinal dysfunction with significant macular involvement. Genetic analysis identified a homozygous pathogenic nonsense variant in PCARE [c.3289C>T; p.(Gln1097*)], confirming the diagnosis of an autosomal recessive inherited retinal dystrophy. Conclusions: Biallelic PCARE variants can cause late-onset severe retinal dystrophy, with predominant macular involvement and cone–rod dysfunction. Given its phenotypic overlap with other inherited retinal diseases, accurate diagnosis requires the integration of multimodal retinal imaging, electrophysiological testing, and comprehensive genetic analysis. Full article

Background/Objectives: Posterior vitreous detachment (PVD), which is closely related to epiretinal membrane (ERM) formation, can affect macular microstructure and function through persistent tractional forces. The aim of this study was to evaluate whether PVD status influences preoperative characteristics and long-term functional and morphological retinal outcomes after ERM surgery. Methods: Ninety patients who underwent idiopathic ERM removal were included and divided into two groups on the basis of intraoperative vitreous status: incomplete or complete PVD. Visual function, retinal imaging, microperimetry, and multifocal electroretinography (mfERG) data were assessed preoperatively and at 1, 4, and 12 months postoperatively. Results: At baseline, compared with the incomplete PVD group, the complete PVD group demonstrated greater fixation stability and lower variability, along with smaller foveal avascular zone (FAZ) areas in both superficial and deep vascular complexes. In terms of absolute postoperative values, the complete PVD group exhibited superior functional outcomes, including higher macular sensitivity and improved fixation variability parameters at 12 months. Morphologically, the incomplete PVD group showed consistently larger FAZ areas in both superficial and deep vascular complexes. In terms of changes from baseline, best-corrected visual acuity (BCVA) gain was greater in the complete PVD group at 1 and 4 months, with no difference at 12 months, whereas no significant between-group differences were observed for other functional or morphological parameters at any time point. Conclusions: Complete PVD is associated with faster visual recovery. Incomplete PVD may induce alterations at the retinal microcirculation level that persist postoperatively and influence microperimetric scores. Full article

Introduction: Although anterior non-infectious uveitis affects the structures of the anterior segment of the eye, (inflammatory) disruption of the hemato–ocular barrier may lead to changes in the structures of the posterior segment of the eye. Objective: To evaluate functional retinal changes using multifocal electroretinography (mfERG) and their relationship with structural optical coherence tomography (OCT) parameters in patients with acute anterior non-infectious uveitis (AANU). Methods: This prospective study included 38 eyes of 19 patients diagnosed with unilateral AANU and age-matched healthy fellow eyes as controls. All subjects underwent comprehensive ophthalmological examination, including best-corrected visual acuity (BCVA), spectral-domain OCT, and mfERG testing at baseline, 3 months, and 6 months. mfERG parameters (amplitude and implicit times) were analyzed alongside central field thickness (CFT), macular volume (MV), and average macular thickness (AMT). Results: Eyes affected by AANU demonstrated a significant reduction in mfERG response amplitude in the central retinal region compared with control eyes, particularly during the acute phase. Although OCT parameters showed partial structural normalization during follow-up, functional recovery was less pronounced in selected retinal regions. Latency values showed minimal variation over time. These findings indicate a potential dissociation between electrophysiological function and structural morphology during disease resolution. Conclusions: Acute anterior uveitis is associated with measurable macular functional impairment detectable by mfERG, even when structural OCT parameters appear relatively stable. These results suggest that inflammatory processes in AAU may extend beyond the anterior segment and transiently affect retinal function. mfERG may therefore serve as a sensitive adjunct tool for detecting and monitoring subclinical macular dysfunction in AANU. Clinical Relevance: Functional retinal impairment may persist despite apparent structural recovery in acute anterior uveitis. Incorporating mfERG into clinical evaluation may improve the detection of subtle macular involvement and enhance understanding of disease dynamics beyond conventional imaging findings. Full article

Background: Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the GBA1 gene. Traditionally, GD is classified into three subtypes based on the severity of neurological involvement; however, overlapping clinical features increasingly suggest a continuum of phenotypes rather than distinct categories. In this prospective observational cohort study, we conducted a multidisciplinary assessment of patients with GD to identify and monitor neurological, cognitive, auditory, and visual impairments. Materials and Methods: A comprehensive clinical and instrumental evaluation was performed at baseline and repeated at follow-up, with a median interval of 37 months (IQR 36–38). Neurological assessments included physical examination, clinical rating scales, video-EEG, and brain MRI. Cognitive status was assessed using a standardized battery of neuropsychological tests. Detailed audiological and ophthalmological evaluations were also conducted. Paired parametric or non-parametric tests were applied as appropriate, with Bonferroni correction for cognitive outcomes (p < 0.05). Results: Of the 22 patients assessed at baseline, 18 completed the follow-up evaluation. Neurological assessments showed a worsening of subtle parkinsonian signs, with significant increases in Movement Disorder Society–Unified Parkinson’s Disease Rating Scale Part III scores (p = 0.04) and non-motor symptom scores (p = 0.01). Two of the eighteen patients developed epilepsy during follow-up. A high prevalence of sleep disturbances was confirmed, with 27.8% exhibiting excessive daytime sleepiness and 16.7% reporting REM sleep behaviour disorder on standardized questionnaires. Compared with baseline, cognitive assessments revealed a higher proportion of patients with performance below normative population scores in at least one cognitive domain, particularly memory. Sensorineural hearing loss was confirmed in 11 of 15 patients (73.3%) who underwent audiological evaluation, with progressive worsening of audiometric thresholds observed in 7 of 11 (64%). Ophthalmological evaluations showed no changes in visual acuity or OCT findings; however, multifocal electroretinography abnormalities were detected in 12 of 13 patients. Conclusions: Through in-depth phenotyping, this study identifies measurable neurological, cognitive, and sensory progressive changes in patients with GD over time, supporting the value of tailored, multidisciplinary long-term care strategies to monitor and address emerging clinical needs in this rare disease. Full article

Background: This study evaluated morphological and functional differences among eyes with retinitis pigmentosa (RP) classified according to fundus autofluorescence (FAF) patterns. Methods: A total of 146 eyes from 73 patients with RP were analysed. Based on FAF imaging, eyes were classified as having regular hyperautofluorescent rings (n = 23), irregular rings (n = 76), or absent rings (n = 47). Participants underwent best-corrected visual acuity (BCVA), contrast sensitivity, 10–2 and 30–2 static perimetry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). FAF morphometrics included ring diameters and area. Results: Eyes with a regular FAF ring demonstrated significantly better visual function than those with irregular or absent rings, including higher BCVA (p < 0.001 and p = 0.001) and greater contrast sensitivity (both p < 0.001). The mfERG amplitude density in the first ring was higher in regular than irregular FAF patterns (p = 0.034). Eyes with irregular FAF showed more advanced visual field loss, with lower mean deviation on 10–2 (p = 0.042) and 30–2 perimetry (p = 0.027). In the regular-ring group, the ellipsoid zone was predominantly intact (p = 0.012). The hyperautofluorescent ring area correlated positively with mfERG amplitude density in the first and second rings (Rs = +0.573, p = 0.016; Rs = +0.736, p = 0.001) and with macular volume (Rs = +0.667, p = 0.003). Conclusions: FAF patterns reflect central retinal functional and structural impairment in RP. Therefore, incorporating FAF imaging into the diagnostic algorithm is valuable for monitoring disease progression. Full article

Background/Objectives: Epiretinal membrane (ERM) is often associated with macular thickening and foveal intraretinal fluid. The aim of this study was to evaluate the efficacy of early postoperative SMLT (577 nm) in preventing persistent macular oedema and to assess its impact on selected functional and morphometric retinal parameters after ERM peeling. Methods: A total of 68 pseudophakic patients with ERMs were enrolled and randomly assigned (1:1) to a laser group or a nonlaser control group. SMLT was performed one month after PPV. The functional and morphometric retinal parameters were assessed preoperatively and at one and four months postoperatively via optical coherence tomography (OCT), OCT angiography (OCTA), multifocal electroretinography (mfERG), and microperimetry. Results: The reduction in total retinal volume between the first and fourth postoperative months was significantly greater in the SMLT group than in the control group (p = 0.02). No significant differences in functional parameters were found between the groups. A more substantial reduction in total retinal volume post-SMLT was associated with greater baseline macular thickness, a more advanced ERM stage, worse baseline visual acuity, greater fixation stability, lower initial macular sensitivity and lower preoperative p-wave amplitude in ring R1 on mfERG. Conclusions: SMLT may be considered a therapeutic option in patients with advanced ERM stages and low preoperative visual acuity. Full article

Retinitis Pigmentosa (RP) is a progressive retinal disorder that leads to vision loss and blindness. Accurate staging of RP is crucial for effective treatment planning and disease management. This study aims to develop an objective and reliable method for RP staging by integrating handcrafted features extracted from visual field (VF) grayscale and multifocal electroretinography (mfERG) P1 wave amplitude maps using machine-learning models. Four machine-learning models were evaluated using features derived from VF grayscale maps (GLCM and gray tone features) and mfERG P1 amplitude maps (RGB and HSV features). Additionally, feature selection was performed using the Random Forest (RF) algorithm to identify the most relevant features. The experimental results showed that the Support Vector Machine (SVM) model achieved the highest classification performance with 98.39% accuracy, 98.26% precision, 98.55% recall, 98.41% F1 score, and 99.17% specificity using the seven most important features: RGB Entropy_R, GLCM Contrast_90°, RGB Std_R, GLCM Homogeneity_90°, RGB Energy_R, Histogram Kurtosis, and GLCM Energy_90°. These findings demonstrate that fusing grayscale and amplitude maps provides an effective approach for RP staging. The proposed method may serve as an objective, automated decision-support tool for ophthalmologists, enhancing clinical evaluations and enabling personalized treatment strategies for RP patients. 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

Electroretinography (ERG) is a non-invasive technique for evaluating the retinal function in various ocular diseases. Its results are useful for diagnosing ocular disorders and assessing disease progression or treatment effectiveness. Since numerous studies are based on animal models, validating the ERG results from animals is pivotal. The first part of this paper presents basic information on the types of ERG tests used on rodents, and the second part describes the recorded functional changes in rodents’ retinas when various antioxidant treatments for diabetic retinopathy were used. Our study showed that among the tests for diabetic retinopathy diagnosis in rodents, full-field ERG is accurate and the most commonly used, and pattern ERG and the photopic negative response of the flash ERG tests are rarely chosen. Furthermore, antioxidants generally protect retinas from functional losses. Their beneficial influence is expressed in the preserved amplitudes of the a- and b-waves and the oscillatory potentials. However, prolonging the drug exposure showed that the antioxidants could delay the onset of adverse changes but did not stop them. Future studies should concentrate on how long-term antioxidant supplementation affects the retinal function. Full article

Background/Objectives: Although hydroxychloroquine (HCQ) is used to treat systemic lupus erythematosus (SLE), it is associated with retinal toxicity. Early diagnosis can prevent the further progression of HCQ-associated retinopathy by discontinuing HCQ treatments. This study aimed to evaluate the early diagnostic parameters in patients with SLE treated with HCQ and identify the best approach using multifocal electroretinography (mfERG) and swept-source optical coherence tomography (SS-OCT) to reflect subclinical retinal toxicity. Methods: Thirty-eight patients with SLE (76 eyes) and 18 healthy controls (36 eyes) were enrolled. They were referred for HCQ retinopathy screening without visual field defects. The patients were tested using a standard 61-hexagon mfERG stimulus and SS-OCT. Ten groups of the mfERG responses from the sectors were averaged to compare the quadrants, hemiretinal areas, consecutive ring amplitudes, and ring ratios (R1/R2–R5) from the center to the periphery. Additionally, the ganglion cell complex (GCC) analyses were performed using SS-OCT. Results: No difference was observed in GCC thickness on the OCT images, in the P1 amplitudes, and in the implicit time of mfERG. However, the R1/Rx ring ratios, except the R1/R2 ratio, showed significant differences among the three groups (p = 0.759, 0.018, 0.029, and 0.029, respectively). The R1/R3, R1/R4, and R1/R5 ring ratios demonstrated a correlation with the duration of HCQ therapy (r = −0.303, −0.279, and −0.266; p = 0.003, 0.006, and 0.009). The areas under the receiver operating characteristic curve of the ring ratios R1/R3–R5 were 0.730, 0.702, and 0.724, respectively (p = 0.004, 0.012, and 0.006), indicating the likelihood of being categorized as a high-risk group for subclinical HCQ retinopathy. Conclusions: The ring ratio of mfERG reflects the subclinical electrophysiological alterations induced by HCQ and can become more clinically useful by simplifying screening examinations. Full article

The smaller-incision new-generation implantable miniature telescope (SING IMT) represents an advancement over the previous model, WA-IMT, serving as a unilateral prosthetic device for patients with late-stage age-related macular degeneration (AMD). Purpose: This study aims to report changes in multifocal electroretinography (mfERG) 6 months post–SING IMT implantation. Methods: In this case series, we prospectively evaluated a cohort of phakic patients with late-stage AMD who underwent SING IMT implantation at the Ophthalmology Unit, University of Bari Aldo Moro, Italy. We assessed best-corrected distance visual acuity (BCDVA) and best-corrected near visual acuity (BCNVA) preoperatively and at 6 months postoperatively. Additionally, mfERGs were conducted using Retimax (CSO, Florence, Italy). Results: All four treated patients showed an increase in both BCDVA and BCNVA at the 6-month follow-up. Additionally, all eyes demonstrated increased P1 density at this time point, with the greatest augmentation observed at the central fixation point, gradually diminishing across the five concentric rings. While all patients displayed a general increase in P1 amplitude, the third patient exhibited a slight decrease in the foveal region. Conclusions: In this case series with four cases, the new generation implantable miniature telescope, SING IMT, demonstrates promising results in enhancing mfERG parameters in patients with late-stage AMD. Six months post-surgery, we observed an augmentation in both P1 density and amplitude, predominantly at the fixation point and gradually tapering in the surrounding concentric rings. Full article

Background: This study aimed to analyze the potential pathogenic connection between metabolic factors, photoreceptor cell rearrangements, retinal microvascular perfusion, and functional parameters through multifocal electroretinography (mfERG) in type 1 diabetes mellitus (DM1). Methods: This prospective observational cohort study enrolled DM1 patients (40.5 ± 9.1 years) with mild nonproliferative diabetic retinopathy followed for 4 years. Patients were subjected to multimodal imaging, which included color fundus photography, optical coherence tomography (OCT), OCT angiography, adaptive optics (AO), and mfERG. OCTA slabs were analyzed using ImageJ software (software version 2.3.0/1.53f) to calculate perfusion density (PD) at both superficial (SCP) and deep (DCP) capillary plexuses, as well as flow deficit percentage (FD%) at the choriocapillaris (CC). To calculate cone metrics on AO at the parafovea, including cone density (CD), linear dispersion index (LDi), and heterogeneity packing index (Hpi%) in the parafovea, the images were post-processed using a MATLAB algorithm. The mfERG P1 implicit time (IT) and N1-P1 response amplitude density (RAD) from R1 (foveal area), R2 (parafoveal area), and the unified rings R1 + R2 were evaluated. Results: A total of 22 patients (22 eyes) were enrolled. No significant differences were noted in central mfERG amplitude and implicit time-averaged values (p > 0.05, all). The main factor influencing R1 IT was HbA1c, while R1 RAD was affected by Hpi and CC FD%. R1 + R2 IT was influenced by Hpi, LDi (p > 0.001, all), and modifications in the perfusion density in the SCP (p < 0.001) and DCP (p = 0.03) at the parafovea. In contrast, R1 + R2 RAD were associated with HbA1c (p = 0.02) and Hpi (p < 0.001). Conclusions: Microvascular changes and glucometabolic factors are key elements influencing the long-term morphofunctional alterations at the photoreceptor level in DM1. Full article

Background/Objectives: The objective of this study was to determine the treatment effect of foselutoclax in neovascular age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in AMD studies. Methods: A total of five subjects were included in the study who had active choroidal neovascularization and a history of at least two anti-vascular endothelial growth factor (VEGF) injections in the last 6 months. Subjects received a 50 µL intravitreal injection of foselutoclax at the baseline visit and Weeks 4, 24, and 28 of the study period. Results: After foselutoclax treatment, the largest improvement in the mfERG N1-P1 response density occurred at Week 8 as three of five subjects achieved a ≥20% gain. In addition, three of five subjects demonstrated a BCVA improvement of ≥5 ETDRS letters over baseline at Weeks 4, 8, and 24. The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Conclusions: Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment. Full article

Purtscher retinopathy is a rare but severe sight-threatening eye condition that mostly occurs in middle-aged men after chest compression or head injury. In cases such as acute pancreatitis, connective tissue disorders, kidney failure or COVID-19 infection with similar ocular findings but no history of trauma, a diagnosis of Purtscher-like retinopathy is made. We present a case of a 72-year-old female with typical symptoms of Purtscher retinopathy in both eyes after a car crash accident. Although the pathophysiology of the disease is not fully understood, the main cause of Purtscher retinopathy seems to be an embolic occlusion of the precapillary arterioles which supply the superficial peripapillary capillaries. Activation of the C5a component of the complement predisposes the leukocytes to aggregation, which obstructs blood flow. The main symptom of Purtscher retinopathy is sudden, painless deterioration of vision which occurs up to 48 h after the injury. In most patients, the changes observed in the fundus of the eye resolve within several months, and visual acuity slowly improves, sometimes even returning to the state from before the injury. However, risk factors such as older age, high hyperopia, and late treatment implementation can make the prognosis less favorable. Full article

Diabetic retinopathy (DR), a vision-threatening microvascular complication of diabetes mellitus (DM), is a leading cause of blindness worldwide that requires early detection and intervention. However, diagnosing DR early remains challenging due to the subtle nature of initial pathological changes. This review explores developments in multimodal imaging and functional tests for early DR detection. Where conventional color fundus photography is limited in the field of view and resolution, advanced quantitative analysis of retinal vessel traits such as retinal microvascular caliber, tortuosity, and fractal dimension (FD) can provide additional prognostic value. Optical coherence tomography (OCT) has also emerged as a reliable structural imaging tool for assessing retinal and choroidal neurodegenerative changes, which show potential as early DR biomarkers. Optical coherence tomography angiography (OCTA) enables the evaluation of vascular perfusion and the contours of the foveal avascular zone (FAZ), providing valuable insights into early retinal and choroidal vascular changes. Functional tests, including multifocal electroretinography (mfERG), visual evoked potential (VEP), multifocal pupillographic objective perimetry (mfPOP), microperimetry, and contrast sensitivity (CS), offer complementary data on early functional deficits in DR. More importantly, combining structural and functional imaging data may facilitate earlier detection of DR and targeted management strategies based on disease progression. Artificial intelligence (AI) techniques show promise for automated lesion detection, risk stratification, and biomarker discovery from various imaging data. Additionally, hematological parameters, such as neutrophil–lymphocyte ratio (NLR) and neutrophil extracellular traps (NETs), may be useful in predicting DR risk and progression. Although current methods can detect early DR, there is still a need for further research and development of reliable, cost-effective methods for large-scale screening and monitoring of individuals with DM. Full article