Documenta Ophthalmologica最新文献

Background: Neuronal ceroid lipofuscinosis is a group of neurodegenerative disorders with varying visual dysfunction. CLN3 is a subtype which commonly presents with visual decline. Visual symptomatology can be indistinct making early diagnosis difficult. This study reports ocular biomarkers of CLN3 patients to assist clinicians in early diagnosis, disease monitoring, and future therapy.

Methods: Retrospective review of 5 confirmed CLN3 patients in our eye clinic. Best corrected visual acuity (BCVA), electroretinogram (ERG), ultra-widefield (UWF) fundus photography and fundus autofluorescence (FAF), and optical coherence tomography (OCT) studies were undertaken.

Results: Five unrelated children, 4 females and 1 male, with median age of 6.2 years (4.6-11.7) at first assessment were investigated at the clinic from 2016 to 2021. Four homozygous and one heterozygous pathogenic CLN3 variants were found. Best corrected visual acuities (BCVAs) ranged from 0.18 to 0.88 logMAR at first presentation. Electronegative ERGs were identified in all patients. Bull's eye maculopathies found in all patients. Hyper-autofluorescence ring surrounding hypo-autofluorescence fovea on FAF was found. Foveal ellipsoid zone (EZ) disruptions were found in all patients with additional inner and outer retinal microcystic changes in one patient. Neurological problems noted included autism, anxiety, motor dyspraxia, behavioural issue, and psychomotor regression.

Conclusions: CLN3 patients presented at median age 6.2 years with visual decline. Early onset maculopathy with an electronegative ERG and variable cognitive and motor decline should prompt further investigations including neuropaediatric evaluation and genetic assessment for CLN3 disease. The structural parameters such as EZ and FAF will facilitate ocular monitoring.

Purpose: To describe a case of retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter's syndrome.

Methods: Fundus photography, total field electroretinogram, ultrasound, computerized visual field examination, biochemical examination and genetic testing were obtained.

Results: The fundus exam showed diffuse arteriolar attenuation, optic disc with regular contours, and pigment agglomerates like "bone spicules" in the middle periphery. Ultrasound examination revealed scleral thickening and short axial diameter in both eyes. The total field electroretinogram exam showed a subnormal result with greater impairment of the scotopic phase of the exam. Computerized visual field examination demonstrated a diffuse reduction in retinal sensitivity in the periphery. Biochemical examination showed increased urine glycosaminoglycan excretion and iduronate-2-sulphatase activity (IDS) deficiency in leukocytes, confirming the type II mucopolysaccharidosis. Molecular analysis revealed a novel missense mutation (p.A77D) in the IDS gene.

Conclusion: The case report is about a patient presented an attenuated form of the syndrome, with no cognitive impairment. Ophthalmologic follow-up is still an important part of multidisciplinary treatment for Hunter's syndrome.

Purpose: To infer rod phototransduction activation and deactivation characteristics in diabetics who have mild or no clinically-apparent retinopathy.

Methods: Fifteen non-diabetic controls, 15 diabetics with no clinically-apparent diabetic retinopathy (NDR), and 15 diabetics with mild non-proliferative diabetic retinopathy (MDR) participated. Dark-adapted flash electroretinograms (3.2 to 4.4 log scot td-s) were recorded to assess rod activation. The a-waves were fit with a Gaussian model to derive R_mp3 (maximum photoreceptor response amplitude) and S (phototransduction sensitivity). Rod deactivation was assessed with a paired flash paradigm, in which a-waves were measured for two flashes separated by inter-stimulus intervals (ISIs) of 0.125 to 16 s. The ISI needed for the a-wave amplitude of the second flash to recover to 50% of the first flash (t₅₀) was determined. The effect of stimulus retinal illuminance on activation and deactivation was evaluated in a subset of control subjects.

Results: Analysis of variance indicated that both diabetic groups had significant log S reductions compared to controls (p < 0.001). Mean S was reduced by approximately 49% and 78% for the NDR and MDR groups, respectively. In contrast, log R_mp3 and log t₅₀ did not differ significantly among the groups (both p > 0.08). Reducing stimulus retinal illuminance significantly reduced S, but did not significantly affect R_max or t₅₀.

Conclusions: Only phototransduction sensitivity was abnormal in this sample of diabetic subjects. The normal deactivation kinetics suggests that circulating rod current is normal. These findings begin to constrain possible explanations for abnormal rod function in early diabetic retinal disease.

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023.

Purpose: Frequency-domain measures were applied to characterize neural deficits in individuals with schizophrenia using transient visual evoked potentials (tVEP). These measures were compared with conventional time-domain measures to elucidate underlying neurophysiological mechanisms and examine the value of frequency analysis.

Methods: Four frequency bands of activity identified in previous work were explored with respect to magnitude (spectral power), timing (phase), a combined measure, magnitude-squared coherence (MSC), and compared to amplitudes and times of prominent deflections in the response.

Results: Band 2 power/MSC (14-28 Hz) captured the major deflections in the waveform and its power predicted N75-P100 amplitude for patients and controls. Band 3 power/MSC (30-40 Hz) correlated highly with the earliest deflection (P60-N75), reflecting input to primary visual cortex (V1) and produced the largest magnitude effect. Phase of the 24th harmonic component predicted P100 peak time for patients and controls and yielded the largest group difference. Cluster analyses including time- and frequency-domain measures identified subgroups of patients with differential neurophysiological effects. A small but significant difference in visual acuity was found between groups that appears to be neurally based: Acuity (range 0.63-1.6) was not correlated with any tVEP measures in controls nor with input timing to V1 (P60 peak time) in patients, but was correlated with later tVEP measures in patients. All but two of the patients were on antipsychotic medication: Medication level (chlorpromazine equivalents) was correlated negatively with tVEP time measures and positively with certain magnitude measures yielding responses similar to controls at high levels.

Conclusions: Overall, frequency-domain measures were shown to be objective and recommended as an alternative to conventional, subjective time-domain measures for analyzing tVEPs and in distinguishing between groups (patients vs. controls and patient subgroups). The findings implicated a loss of excitatory input to V1 in schizophrenia. Acuity as measured in the current study reflected disease status, and medication level was associated with improved tVEP responses. These novel tVEP techniques may be useful in revealing neurophysiological processes affected in schizophrenia and as a clinical tool.

Purpose: Alport syndrome comprises a heterogeneous group of inherited kidney diseases that are associated with ocular complications. In this study, we aimed to detail the clinical characteristics of a patient with X-linked Alport syndrome.

Methods: We performed next-generation sequencing (NGS) with hybridization capture to identify the disease-causing variant of Alport syndrome and a comprehensive ophthalmic examination, including full-field electroretinography (FF-ERG).

Results: Genetic testing using NGS with hybridization capture revealed a novel hemizygous variant [c.51_52delGA (p.Trp20GlyfsTer19)] in exon 1 of COL4A5. The patient underwent cataract surgery in both eyes because of decreased visual acuity and photophobia. The best-corrected visual acuity improved from 0.9 and 0.7 in the right and left eyes, respectively, to 1.5 in both eyes. Anterior-segment optical coherence tomography (OCT) revealed anterior and posterior lenticonus. Fundus photographs showed central and peripheral fleck retinopathy. Wide-field fundus autofluorescence (AF) imaging showed mottled hyper- and hypo-AF in the peripheral retina, which was consistent with peripheral fleck retinopathy. Furthermore, OCT revealed thinning of the inner retinal layers, especially at the temporal macular, but the outer retinal layers were preserved. Ganglion cell analysis showed no progression for 5 years. FF-ERG was performed at 41 (phakia) and 46 (pseudophakia) years of age. The amplitudes of dark-adapted (DA) and light-adapted (LA) responses showed selective b-wave abnormalities. The b/a-wave ratios of DA 3.0 were 1.22 and 1.16 in the right and left eyes, respectively. The amplitudes of DA 3.0 oscillatory potentials (OP) were reduced. Five years later, the amplitudes of DA and LA responses revealed no remarkable changes, except for an OP wave of DA 3.0, which was substantially reduced.

Conclusions: Our findings revealed electroretinographic abnormalities in a patient with Alport syndrome, which predominantly indicated impairment of the inner retina. Notably, little short-term progression was observed.

Introduction: Mutations in the peripherin-2 gene (PRPH2) are a common cause of inherited retinal dystrophies well known for their phenotypic diversity. We describe a novel presentation of the c.623G > A; p.(Gly208Asp) variant in association with cone-rod dystrophy and reduced penetrance.

Case description: A 39-year-old man presents with a history of decreased visual acuity, photophobia, and dyschromatopsia. Fundus examination was largely unremarkable while spectral-domain optical coherence tomography (SD-OCT) demonstrated diffuse granularity at the ellipsoid zone. Full-field electroretinogram (ffERG) revealed a cone-rod dystrophy. Genetic testing revealed a heterozygous pathogenic variant, c.623G > A; p.(Gly208Asp), in the PRPH2 gene, also found in an unaffected brother. The 50-year-old brother had no visual symptoms and no findings on fundus examination. SD-OCT showed normal retinal architecture and ffERG was within normal limits bilaterally.

Conclusion: This case report broadens the known phenotypic presentations of PRPH2-associated retinopathy and suggests that the PRPH2 variant c.623G > A; p.(Gly208Asp) may be associated with reduced penetrance.

Purpose: Diopsys® NOVA™ is a novel full-field electroretinography (ffERG) device that can make rapid measurements of retinal electrophysiologic function. Diagnosys® Espion 2™ is a clinical gold-standard ERG device. This study aimed to investigate whether light-adapted Diopsys® NOVA™ fixed-luminance flicker ffERG magnitude and implicit time (converted from phase) measurements correlate with light-adapted Diagnosys® Espion 2™ flicker ffERG amplitude and implicit time measurements, respectively.

Methods: Twelve patients (22 eyes) with various retinal and uveitic diseases underwent light-adapted Diagnosys® Espion 2™ and Diopsys® NOVA™ fixed-luminance flicker testing. Diopsys® magnitude and implicit time (converted from phase) measurements were compared to Diagnosys® amplitude and implicit time measurements, and a Pearson correlation was used to evaluate any existing correlation. Groups were also compared using generalized estimating equations. Bland-Altman plots were utilized to determine agreement between the comparison groups.

Results: Age of patients ranged from 14 to 87 years. 58% (n = 7/12) of patients were female. A significant, positive correlation (r = 0.880, P < 0.001) was observed between magnitude (Diopsys®) and amplitude (Diagnosys®) measurements. Amplitude increases by 6.69 µV for each 1 µV increase in Magnitude (p-value < 0.001). A statistically significant, strong positive correlation was observed between Diopsys® implicit time measurements (converted from phase) and Diagnosys® implicit time measurements (r = 0.814, p-value < 0.001). For each 1 ms increase in Diopsys® implicit time, Diagnosys® implicit time increases by 1.13 ms (p-value < 0.001).

Conclusions: There is a statistically significant positive correlation between light-adapted Diopsys® NOVA™ fixed-luminance flicker amplitude and Diagnosys® flicker magnitude values. Additionally, there is a statistically significant positive correlation between Diopsys® NOVA™ fixed-luminance flicker implicit time (converted from phase) and Diagnosys® flicker implicit time values. These results imply that the Diopsys® NOVA™ module, which utilizes the nonstandard shortened International Society for Clinical Electrophysiology of Vision (ISCEV) ERG protocol, can produce reliable light-adapted flicker ffERG measurements.

Purpose: To determine whether short-latency changes in multifocal electroretinography (mfERG) observed in experimental glaucoma (EG) are secondary solely to retinal ganglion cell (RGC) loss or whether there is a separate contribution from elevated intraocular pressure (IOP).

Methods: Prior to operative procedures, a series of baseline mfERGs were recorded from six rhesus macaques using a 241-element unstretched stimulus. Animals then underwent hemiretinal endodiathermy axotomy (HEA) by placing burns along the inferior 180° of the optic nerve margin in the right eye (OD). mfERG recordings were obtained in each animal at regular intervals following for 3-4 months to allow stabilization of the HEA effects. Laser trabecular meshwork destruction (LTD) to elevate IOP was then performed; first-order kernel (K1) waveform root-mean-square (RMS) amplitudes for the short-latency segment of the mfERG wave (9-35 ms) were computed for two 7-hexagon groupings-the first located within the superior (non-axotomized) macula and the second within the inferior (axotomized) macula. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was done.

Results: By 3 months post HEA, there was marked thinning of the inferior nerve fiber layer as measured by optical coherence tomography. Compared with baseline, no statistically significant changes in 9-35 ms K1 RMS amplitudes were evident in either the axotomized or non-axotomized portions of the macula. Following LTD, mean IOP in HEA eyes rose to 46 ± 9 compared with 20 ± 2 mmHg (SD) in the fellow control eyes. In the HEA + EG eyes, statistically significant increases in K1 RMS amplitude were present in both the axotomized inferior and non-axotomized superior portions of the OD retinas. No changes in K1 RMS amplitude were found in the fellow control eyes from baseline to HEA epoch, but there was a smaller increase from baseline to HEA + EG. Upregulation of GFAP in the Müller cells was evident in both non-axotomized and axotomized retina in eyes with elevated IOP.

Conclusions: The RMS amplitudes of the short-latency mfERG K1 waveforms are not altered following axotomy but undergo marked increases following elevated IOP. This suggests that the increase in mfERG amplitude was not solely a result of RGC loss and may reflect photoreceptor and bipolar cell dysfunction and/or changes in Müller cells.

Purpose: Vitamin A plays a crucial role in rod phototransduction, with deficient levels manifesting as night blindness. Animal models have demonstrated bone dysplasia in the setting of hypovitaminosis A. We present a rare case of bony overgrowth leading to bilateral compressive optic neuropathy, combined with outer retinopathy, in a paediatric patient secondary to isolated vitamin A deficiency.

Methods: A single case report was conducted from Toronto, Canada.

Results: A 12-year-old boy with known autism spectrum disorder presented with a 9-month history of progressive painless vision loss. Vision was 20/300 and hand motion in the right and left eye, respectively. Fundus photography demonstrated bilateral optic atrophy and yellow lesions notably in the right eye far periphery. Optical coherence tomography (OCT) imaging demonstrated thinning of the retinal nerve fibre layer, alterations in the ellipsoid zone, as well as retinal pigment epithelium deposits. Computed tomography imaging demonstrated sphenoid bone thickening with narrow optic canals and moderate optic atrophy bilaterally. Full-field electroretinogram (ERG) demonstrated mildly reduced dark adapted (DA) 0.01 b-wave amplitudes and electronegative configuration of DA 3.0 and DA 10.0 ERG; the light adapted ERGs were normal. The patient was treated with pulse vitamin A therapy. Subsequently, the DA ERG normalized, outer retinal changes reversed and vision stabilised; no surgical intervention was conducted.

Conclusion: This case represents a rare presentation of compressive optic neuropathy with concomitant outer retinopathy secondary to isolated vitamin A deficiency. Despite improvement in outer retinal integrity on OCT imaging and ERG testing results following vitamin A supplementation, no functional improvement was obtained due to severe optic atrophy.