Documenta Ophthalmologica最新文献

Purpose: To establish a clinically applicable dark-adapted 15 Hz flicker electroretinogram (ERG) for sensitive detection of functional changes in the fast and the slow retinal rod pathways.

Methods: The study consisted of two parts. In the first part, the paradigm of the previously demonstrated "null-effect" of stimulus luminance on ERG-amplitudes for 15 Hz flicker stimuli with duration of 2.5 s was reexamined. In the second part an optimized faster protocol designed for routine clinical use was tested and compared with the results from the first part and data published in the past. The 15-Hz flicker ERG protocol included 12 steps with different intensities ranging from 0.00019 scot cd.s/m² to 0.05 scot cd.s/m² and was obtained from 15 normally sighted subjects. Stimulus flashes were presented in blue (448 nm) and white, alternating in each luminance step after 20 min of dark adaptation. A shorter version containing only 7 steps was selected with intensities ranging from 0.00031 scot cd.s/m² to 0.005 scot cd.s/m². Additionally, the stimulus paradigm included noise measurement to properly estimate the signal-to-noise ratio.

Results: The results from the first protocol showed a U-shaped amplitude vs. luminance response curve at 15 Hz, consistent with previously published results. Using the new, shortened protocol, we also obtained similar results, but with a much shorter recording time. Based on the signal-to-noise ratio from these measurements a reliable measurement can be obtained in only 2.5 min which presents a considerable time reduction necessary to record a 15 Hz response curve in a clinical setup.

Conclusion: The new protocol is suitable for integration into a daily clinical environment, offering short and well-balanced protocols to address complex retinal network interactions.

Purpose: To assess the repeatability of the multifocal electroretinogram (mfERG) in the 13-lined ground squirrel (13-LGS).

Methods: 13-LGS (Ictidomys tridecemlineatus, 2 M/4F, n = 12 eyes) were equally divided between 61-segment or 103-segment protocols containing two consecutive mfERG scans per session, and two total sessions performed one week apart per eye. The trough-to-peak amplitudes were analyzed under three conditions: raw, normalized to the optic nerve head (ONH), and normalized to the visual streak (VS). For intrasession repeatability, the two consecutive scans within each session were analyzed. For intersession repeatability analyses, one scan was randomly chosen from each day.

Results: Intrasession repeatability of the mfERG trough-to-peak amplitude data averaged at 63% (Raw), 55% (ONH), and 50% (VS). There was no significant difference in repeatability between each day's intrasession repeatability values for all normalization conditions (Raw: Wilcoxon t-test, p = 0.2334; ONH: Paired t-test, p = 0.7803; VS: Wilcoxon t-test, p = 0.3804). Intersession percent repeatability of mfERG trough-to-peak amplitude data averaged at 72% (Raw), 61% (ONH), and 53% (VS). There was a statistically significant difference between the groups (Friedman test, p = 0.0038). This was evident in the Benjamini-Hochberg method of controlling the false discovery rate (FDR) where there was a significant difference comparing Raw versus VS (p = 0.0130) and ONH versus VS (p = 0.0011). There was no difference comparing Raw versus ONH (p = 0.1076).

Conclusions: Overall intrasession and intersession repeatability of mfERG amplitude was relatively poor in our sample, though not markedly different than that reported in some other species and normalization methods did result in improved repeatability. As animal models are critical for vision research, these repeatability estimates will prove useful in interpreting future data collected following interventions or in longitudinal monitoring of disease models.

Objective: To compare the photopic negative response of the multifocal ERG (mfERG_PhNR) and the multifocal pattern electroretinogram (mfPERG) using DTL electrode (E_DTL) vs skin electrode (E_SKIN) in healthy young and old adults.

Methods: Ten "Young" [20-27 years] and eight "Old" [60-72 years] participants took part in this study. The electrophysiological responses were recorded binocularly using E_DTL and E_SKIN. 5-way ANOVAs were applied to investigate the following factors on mfERG_PhNR: i) ELECTRODE, ii) DILATATION, iii) AGE, iv) EYE, and v) ECCENTRICITY. For mfPERG, the same factors, except dilatation, were investigated applying 4-way ANOVAs. These were conducted for amplitude and peak time of different components as well as signal-to-noise-ratio (SNR).

Results: Amplitudes of mfERG_PhNR [mfPERG]-based E_SKIN recording were reduced to 32-38% [37-38%] compared to E_DTL, $p<0.001$ . This corresponded to SNR reduction to 80% [60%], $p<0.001$ . E_SKIN based responses had shorter peak times, by 0.2-0.5 ms for N1 and P1, $p<0.05$ , [P1: 1.5 ms, $p<0.001$ ]. Both age groups had comparable amplitudes and SNRs, but Young had shorter peak times, by 1.5-2.2 ms for N1 and P1, $p<0.05$ [3.7-4.2 ms for N1, P1, N2, $p<0.05$ ]. Compared to dilated recordings, undilated mfERG_PhNR amplitudes were reduced to 47-87%, $p<0.01$ , and peak times were delayed by 2.0-11.8 ms, $p<0.001$ .

Conclusions: mfPERG & mfERG_PhNR traces were similar for E_DTL and E_SKIN. However, for skin electrodes, amplitudes and SNRs were lower and peak times shorter. E_SKIN thus seem to be a viable alternative in patients in whom the use of corneal electrodes is precluded, e.g., children and disabled patients, but at the expense of SNR and with reference to E_SKIN normative data.

Purpose: To report our flicker electroretinographic (ERG) findings in a patient who developed uveitis after treatment with immune checkpoint inhibitors (ICIs) for a metastatic malignant melanoma.

Methods: ERGs were used to monitor retinal physiology in a patient with ocular complications following systemic ICI administration. Flicker ERGs were recorded using the RETeval system before and after the ICI treatments.

Results: A 45-year-old woman was referred to our ophthalmologic clinic for baseline evaluations prior to initiating nivolumab/ipilimumab therapy. The patient had no ocular or ERG abnormalities at the initial visit, but three weeks after starting nivolumab/ipilimumab, she developed conjunctival hyperemia and tearing. Slit-lamp examination showed anterior chamber inflammation, and the ERGs showed a 40% increase in the amplitude from the baseline. However, optical coherence tomography (OCT) did not show any abnormalities. The anterior segment inflammation and increased ERG amplitude resolved with topical betamethasone. The patient developed significant liver damage after the second administration of nivolumab/ipilimumab, and this therapy was discontinued. Two steroid pulse therapies were followed by tapered oral prednisolone. During the follow-up period, no significant abnormalities were observed in the visual acuity or OCT images, but the ERG amplitudes increased from the first to the eighth month after the liver damage was detected. Five years later, the ERGs and OCT findings were within the normal limits, but she had developed a sunset glow fundus in both eyes.

Conclusion: ERGs may be a useful objective test for posterior inflammation induced by administration of ICIs that is not evident in OCT images.

Purpose: The ciliopathies are a broad category of pleiotropic disease with numerous genes involved in pathogenesis. One of the genes implicated in the ciliopathies is WDR19, which can lead to several syndromic diseases that may manifest with a form of retinal degeneration. There is a lack of reporting on the WDR19-mediated retinal phenotype, and therefore warrants more clinical investigation. With retinal degeneration being the most prevalent symptom among the ciliopathies, phenotypic reporting is needed to enhance understanding of pathogenesis.

Methods: Clinical, imaging, and diagnostic records of patients with two variants in the WDR19 gene and a form of retinal degeneration were retrospectively reviewed. Two different individuals analyzed the variants in the studied patients using SnapGene (Version 4.3.11), employing both the canonical NGG PAM and the NGA PAM prime editors.

Results: Four patients from three families each carrying biallelic variants the WDR19 gene were reviewed. Two of the six unique variants identified among the patients were novel. Two identical twin patients presented with a recessive Stargardt (STGD)-like phenotype while the other two patients presented with a clinical picture more characteristic of retinitis pigmentosa (RP). Three of four patients had thickened external limiting membrane (ELM) on spectral-domain optical coherence tomography (SD-OCT). Full-field electroretinograms (ffERG) performed on two patients with the STGD-like phenotype showed a cone-rod pattern of degeneration. Quantitative short-wave fundus autofluorescence (qAF) performed on the two STGD-like patients was within the 95th percentile of normal eyes.

Conclusions: WDR19-mediated retinal degeneration is heterogenous in presentation, and in some cases can phenocopy STGD. The foveal sparing phenotype was apparent in three of four patients with relatively preserved visual acuity, which may serve as a retinal prognostic factor in patients with pathogenic variants in WDR19. All six variants evaluated are correctable by prime editing, establishing a foundation for future research in therapeutic development.

Purpose: To compare signal-to-noise levels in ERG recordings obtained with contact lens electrodes and adhesive skin electrodes.

Methods: 23 subjects were studied. Full-field ERGs were recorded according to ISCEV standards simultaneously with ERG-jet corneal contact lens electrodes and LKC Technologies Sensor Strip adhesive skin electrodes. B-wave amplitude or peak-to-peak amplitude was used as a measure of signal strength. Noise was estimated using the " ± averaging method." Comparisons between signal strength, absolute noise levels, and signal-to-noise ratios between contact lens and skin electrodes were performed by linear regression.

Results: Comparisons of signal strength for LA 3, 30-Hz, DA 0.01, and DA 3 responses, yielded regression coefficient ß values of 0.37, 0.39, 0.39, and 0.35, respectively. For the entire data set, the regression coefficient ß value was 0.36 (95% confidence limits 0.34 - 0.38). The grand average ERG noise for all ERG stimuli was 13.8 µV for contact lens electrodes and 13.0 µV for skin electrodes (not significant: p = 0.66 for paired t-test). For signal-to-noise ratios, regression ß coefficients for contact lens and adhesive skin electrodes for LA 3, 30-Hz, DA 0.01, and DA 3 stimuli were 0.25, 0.39, 0.50, and 0.36 respectively. The ß coefficient for the amalgamated data set was 0.33 (95% confidence limits 0.30- 0.36).

Conclusions: Overall ERG amplitudes obtained with skin electrodes were 1/3 those obtained with contact lens electrodes. Absolute noise levels were similar. Signal-to-noise levels with skin electrodes were 1/3 those seen with contact lens electrodes. Implications for signal-averaging in clinical applications are discussed.

Purpose: To introduce ERGtools2, an open-source R package for processing, analysing and long-term storing visual electrophysiology data.

Methods: A dataset comprising Electroretinogram (ERG) recordings of C57Bl/6J mice, subjected to standard ISCEV stimuli, was used to present the functionality of ERGtools2. ERGtools2 stores and organizes all recordings, metadata, and measurement information from an individual examination in a single object, maintaining raw data throughout the analysis process.

Results: A standard workflow is presented exemplifying how ERGtools2 can be used to efficiently import, pre-process and analyse ERG data. Following this workflow, basic ERG measurements and visualisation of a single exam as well as group statistics are obtained. Moreover, special use cases are described, including for the handling of noisy data and the storage of data in the HDF5 format to ensure long-term preservation and accessibility.

Conclusions: ERGtools2 provides a comprehensive, flexible, and device-independent solution for visual electrophysiology data analysis. Its emphasis on maintaining raw data integrity, combined with advanced processing and analysis capabilities, makes it a useful tool for preclinical and clinical research applications. The open-source nature and the use of open data formats promote reproducibility and data sharing in visual neurosciences.