Documenta Ophthalmologica最新文献

Purpose: The electroretinogram (ERG) is the summed response from all levels of the retinal processing of light, and exhibits several profound nonlinearities in the underlying processing pathways. Accurate computational models of the ERG are important, both for understanding the multifold processes of light transduction to ecologically useful signals by the retina, and for their diagnostic capabilities for the identification and characterization of retinal disease mechanisms. There are, however, very few computational models of the ERG waveform, and none that account for the full extent of its features over time.

Methods: This study takes the neuroanalytic approach to modeling the ERG waveform, defined as a computational model based on the main features of the transmitter kinetics of the retinal neurons.

Results: The present neuroanalytic model of the human rod ERG is elaborated from the same general principles as that of Hood and Birch (Vis Neurosci 8(2):107-126, 1992), but incorporates the more recent understanding of the early nonlinear stages of ERG generation by Robson and Frishman (Prog Retinal Eye Res 39:1-22, 2014). As a result, it provides a substantially better match than previous models of rod responses in six different waveform features of the ERG flash intensity series on which the Hood and Birch model was based.

Conclusion: The neuroanalytic approach extends previous models of the component waves of the ERG, and can be structured to provide an accurate characterization of the full timecourse of the ERG waveform. The approach thus holds promise for advancing the theoretical understanding of the retinal kinetics of the light response.

Purpose: The aim of this exploratory study is to investigate the role of S-cones in oscillatory potentials (OPs) generation by individuals with blue-cone monochromacy (BCM), retaining S-cones, and achromatopsia (ACHM), lacking cone functions.

Methods: This retrospective study analyzed data from 39 ACHM patients, 20 BCM patients, and 26 controls. Central foveal thickness was obtained using spectral-domain optical coherence tomography, while amplitude and implicit time (IT) of a- and b-waves were extracted from the ISCEV Standard dark-adapted 3 cd.s.m^-2 full-field ERG (ffERG). Time-frequency analysis of the same measurement enabled the extraction of OPs, providing insights into the dynamic characteristics of the recorded signal.

Results: Both ACHM and BCM groups showed a significant reduction (p < .00001) of a- and b-wave amplitudes and ITs as well as the power of the OPs compared to the control groups. The comparison between ACHM and BCM didn't show any statistically significant differences in the electrophysiological parameters. The analysis of covariance revealed significantly reduced central foveal thickness in the BCM group compared to ACHM and controls (p < .00001), and in ACHM compared to controls (p < .00001), after age correction and Tukey post-hoc analysis.

Conclusions: S-cones do not significantly influence OPs, and the decline in OPs' power is not solely due to a reduced a-wave. This suggests a complex non-linear network influenced by photoreceptor inputs. Morphological changes don't correlate directly with functional alterations, prompting further exploration of OPs' function and physiological role.

Introduction: Infantile nystagmus and foveal hypoplasia associated with AHR gene defects is a newly recognized and rare disorder. Our aim was to present a patient with a novel biallelic AHR pathogenic variant with electrophysiological evidence of chiasmal misrouting.

Materials and methods: Complete ocular examination, fundus imaging, visual evoked potentials (VEP) and full-field electroretinography were performed at initial presentation. Genetic testing was performed by whole exome sequencing.

Results: Female patient of 6 years old presented a reduced best corrected visual acuity, an infantile nystagmus and a grade III typical foveal hypoplasia without ocular hypopigmentation. A crossed asymmetry was discovered on pattern onset/offset VEP. Genetic testing put in evidence a novel homozygous variant in AHR: c.2242del, p. (Gln748Lysfs^*5). During 11-years follow-up period, BCVA gradually improved. There was no evidence of retinal degeneration.

Conclusion: AHR gene defects could be associated with infantile nystagmus, foveal hypoplasia and chiasmal misrouting.

Purpose: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes.

Methods: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification.

Results: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings.

Conclusion: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Purpose: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM.

Case: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy.

Discussion: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential.

Conclusion: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.

Purpose: We evaluate morphological and functional correlations in patients with acute central serous chorioretinopathy (CSC).

Methods: A prospective study was conducted on 50 patients with an acute CSC episode lasting less than 3 months. At baseline, assessments included optical coherence tomography (OCT), best-corrected visual acuity (BCVA), contrast sensitivity (CS), microperimetry (MP), and multifocal electroretinography (mfERG). A correlation analysis between OCT morphological parameters (maximal subretinal fluid height (SRF), central retinal thickness (CRT), and macular volume (MV)) and functional parameters was conducted on the affected eye for each patient.

Results: Among the morphological parameters, SRF showed the strongest correlations with functional parameters (r absolute value range = 0.10-0.70). Weak correlations were observed between BCVA and morphological parameters (r absolute value range = 0.14-0.26). Average retinal sensitivity (MP-A) was the functional parameter displaying the most robust negative correlation with morphological parameters (r absolute value range = 0.61-0.70). In contrast, average contrast sensitivity (CS-A) and mfERG average amplitude density in the first (mfERG-A1) and second (mfERG-A2) ring showed weak to moderate (r absolute value range = 0.35-0.56) yet statistically significantly nonzero correlations.

Conclusions: SRF and CRT could serve as the most representative morphological proxies for visual function deficit in acute CSC patients. Retinal sensitivity, as measured by MP, may be superior to BCVA in clinical research studies or when an in-depth visual function evaluation is needed.

Purpose: Leber hereditary optic neuropathy (LHON) affects retinal ganglion cells causing severe vision loss. Pattern electroretinogram and photopic negative response (PhNR) of the light-adapted (LA) full-field electroretinogram (ERG) are typically affected in LHON. In the present study, we evaluated dark-adapted (DA) and LA oscillatory potentials (OPs) of the flash ERG in genetically characterized LHON patients to dissociate slow from fast components of the response.

Methods: Seven adult patients (mean age = 28.4 ± 5.6) in whom genetic diagnosis confirmed LHON with mtDNA or nuclear DNAJC30 (arLHON) pathogenic variants were compared to 12 healthy volunteers (mean age = 35.0 ± 12.1). Full-field ERGs were recorded from both eyes. Offline digital filters at 50, 75 and 100 Hz low cutoff frequencies were applied to isolate high-frequency components from the original ERG signals.

Results: ERG a-waves and b-waves were comparable between LHON patients and controls, while PhNR was significantly reduced (p = 0.009) in LHON patients compared to controls, as expected. OPs derived from DA signals (75 Hz low cutoff frequency) showed reduced peak amplitude for OP2 (p = 0.019). LA OP differences between LHON and controls became significant (OP2: p = 0.047, OP3: p = 0.039 and OP4: p = 0.013) when the 100 Hz low-cutoff frequency filter was applied.

Conclusions: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.

Background

KCNV2-associated retinopathy causes a phenotype reported as “cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356),” featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR.

Case reports

Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient’s decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a “squaring (trough-flattened)” a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient’s vision gradually worsened, and faint bilateral bull’s eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene.

Patient 2: The second patient was Patient 1’s younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients’ decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene.

Conclusions

The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic “squaring” a-waves in patients with CDSRR.

Purpose

The aim of this neurophysiological study was to retrospectively analyze visual evoked potentials (VEPs) acquired during an examination for diagnosing optic nerve involvement in patients with Lyme neuroborreliosis (LNB). Attention was focused on LNB patients with peripheral facial palsy (PFP) and optic nerve involvement.

Methods

A total of 241 Czech patients were classified as having probable/definite LNB (193/48); of these, 57 were younger than 40 years, with a median age of 26.3 years, and 184 were older than 40 years, with a median age of 58.8 years. All patients underwent pattern-reversal (PVEP) and motion-onset (MVEP) VEP examinations.

Results

Abnormal VEP results were observed in 150/241 patients and were noted more often in patients over 40 years (p = 0.008). Muscle/joint problems and paresthesia were observed to be significantly more common in patients older than 40 years (p = 0.002, p = 0.030), in contrast to headache and decreased visual acuity, which were seen more often in patients younger than 40 years (p = 0.001, p = 0.033). Peripheral facial palsy was diagnosed in 26/241 LNB patients. Among patients with PFP, VEP peak times above the laboratory limit was observed in 22 (84.6%) individuals. Monitoring of patients with PFP and pathological VEP showed that the adjustment of visual system function occurred in half of the patients in one to more years, in contrast to faster recovery from peripheral facial palsy within months in most patients.

Conclusion

In LNB patients, VEP helps to increase sensitivity of an early diagnostic process.

Purpose

To evaluate ERG morphology, in particular the slope between P50 and N95 components of the PERG, as well as between the b-wave and the photopic negative response (PhNR) of the light-adapted (LA) ERG in patients with retinal ganglion cell (RGC) dysfunction due to open-angle glaucoma.

Methods

The PERG and LA-ERG traces of 16 glaucoma patients and 21 age-similar controls were retrospectively analysed. The ERG signal between the peak of the positive component (P50 and b-wave) towards the negative component (N95 and PhNR) was described by a linear regression y = a + bx, where the parameter b indicated the steepness of the P50-N95 and b-PhNR slope.

Results

The P50-N95 slope was less steep in glaucoma patients (−0.079 ± 0.034 vs. −0.166 ± 0.050 in controls, p < 0.001), while the b-PhNR slope was not affected (−4.2 ± 2.1 vs. −4.4 ± 1.2, p = NS). The P50-N95 slope showed strong correlation with PhNR and N95 amplitude (r = −0.68 and −0.92, respectively; p < 0.001), while the b-PhNR slope correlated only with b-wave amplitude (r = −0.66, p < 0.001).

Conclusions

The P50-N95 slope is a sensitive indicator of RGC dysfunction in patients with open-angle glaucoma. A similar component of LA-ERG, the b-PhNR slope, is less affected by glaucomatous RGC dysfunction and probably originates from similar retinal mechanisms as the b-wave.