Documenta Ophthalmologica最新文献

Purpose: To report a case of hereditary spherocytosis (HS) carrying a pathogenic variant in the SPTB gene, presenting with angioid streaks (ASs) and central retinal dysfunction.

Methods: A 63-year-old female patient diagnosed with HS was evaluated using multimodal imaging, full-field and multifocal electroretinograms (ffERGs and MfERGs), and genetic testing with an HS gene panel.

Results: Her best-corrected visual acuity was Snellen equivalent 20/22 in the right eye and 20/20 in the left eye. Fundus examination revealed ASs with chorioretinal atrophy around the optic discs in both eyes (OU). Fundus autofluorescence imaging showed areas of autofluorescence loss corresponding to ASs and chorioretinal atrophy. In the ffERGs, dark-adapted (DA) 0.01 b-wave amplitudes and DA 3.0/10.0 a-wave amplitudes were nearly normal, but b-wave amplitudes were slightly reduced in OU. Meanwhile, light-adapted (LA) 3.0 a- and b-wave amplitudes, as well as the LA 30 Hz flicker amplitudes, were slightly reduced. The mfERG trace arrays showed amplitude reductions, particularly in the central to temporal regions in OU. Genetic testing identified a heterozygous splice-site variant (c.4973 + 5G > A) in SPTB (NM_001355436.2), classified as likely pathogenic.

Conclusions: This is the first reported case of an HS patient with ASs associated with an SPTB variant, exhibiting mild cone system dysfunction accompanied by central retinal dysfunction.

Purpose: To investigate the effects of brief flickering light stimulation (FLS) on retinal electrophysiology and retinal blood flow (RBF) in normal C57BL6J mice.

Methods: RBF and full-field electroretinography (ffERG) were measured before and after a 60 second FLS (12 Hz, 0.1 cd·s/m²) in a cohort of 8-12-weeks old C57BL6J mice (n=10) under anaesthetic and light-adapted conditions. A separate set of age-matched mice (n=9) underwent RBF and ffERG measurements before and after steady light stimulation (SLS) at 1 cd/m² under similar conditions. The changes in RBF (arterial and venous flow) as well as the amplitudes and implicit times of the a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed.

Results: FLS significantly increased both arterial (p=0.003) and venous (p=0.018) blood flow as well as b-wave amplitudes (p=0.017) compared to SLS, which did not have any significant changes in either RBF or ERG. However, no significant differences were found in other ffERG responses (amplitudes and implicit times of a-wave, OPs, and PhNR, as well as b-wave implicit time) between the two groups after light stimulation. An increase in b-wave amplitude was positively associated with an increase in both arterial (r=0.655, p=0.040) and venous blood flow (r=0.638, p=0.047) in the FLS group.

Conclusions: Our results suggest that transient FLS not only increases RBF but also enhances electro-retinal responses of the middle retinal layer, as shown by ffERG, thus demonstrating its substantial effects on both the vascular and neuronal components of retinal neurovascular coupling in mice.

Purpose: Landrace pigs are increasingly used as a large-animal model in ophthalmic research due to their cone-enriched visual streak and anatomical similarity to the human eye. However, they are commonly studied at 16-20 weeks of age, a timeframe in which the animals double their weight and development-related physiological changes may occur. This study aims to characterize retinal function and morphology and establish reference values for future translational studies.

Methods: Landrace pigs (16-20 weeks old) underwent standardized examinations of the left eye at baseline (16 weeks), 18 and 20 weeks. The left eye was examined by optical coherence tomography (OCT), fundus photography, histology, and full-field electroretinography (ffERG) under light- and dark-adapted conditions, using the ISCEV-compliant 6-step Dog, Cat, Nonhuman Primate protocol.

Results: A total of 30 animals were included. Retinal morphology remained stable throughout the study period, with no significant changes in retinal thickness observed by OCT (baseline: 252 ± 24 µm; week 20: 249 ± 11 µm; p = 0.17) or by histology. ffERG revealed increased amplitudes under light- and dark-adapted conditions at 20 weeks compared to baseline at 16 weeks of age (e.g. light-adapted b-wave: + 65 µV, + 18.4%, p < 0.01), while latencies remained stable without clinically relevant changes.

Conclusions: During this phase of rapid development, Landrace pigs undergo significant functional retinal maturation without corresponding morphological changes emphasizing importance of functional testing in retinal assessments. This study provides reference data in a large number of animals.

Purpose: To evaluate subjective and objective macular retinal function and morphology in eyes after autologous retinal transplantation (ART).

Methods: We conducted the study in three patients with large macular holes (MHs) who underwent ART. The examination modalities included optical coherence tomography (OCT), microperimetry (MP-3), and focal macular electroretinography (FMERG) with 10-degree and 5-degree stimulus spots under infrared camera monitoring centered on the treated MHs after ART.

Results: All three patients showed improved visual acuity after the ART; MP-3 showed relatively good sensitivity around the fixation point with a dense scotoma at the center of the graft. All MHs were closed with autologous grafts and the size of MHs was decreased. OCT revealed clearly visible ellipsoid zones of the host retina around the grafted retina, however one transplanted eye showed disorganized outer layer of the host retina near the border of graft-host retina. FMERGs with the 10-degree stimulus were recorded successfully in all three treated eyes with more than half of a- and b-wave amplitudes of the fellow eyes. FMERGs with the 5-degree stimulus were recorded successfully in two of the treated and their fellow eyes.

Conclusions: The FMERGs showed well-maintained macular retinal function after ART. The electrophysiologic and anatomic outcomes suggested that the host retina around the transplanted retina may play an important role in the postoperative macular retinal function with the mechanical support by the graft.

Introduction: Retinal dysfunction associated with CACNA2D4 gene defects is a rare disorder of photoreceptor to bipolar cell signaling. We report two affected siblings presenting a surprising disparity of retinal involvement.

Materials and methods: Patients underwent complete ocular examination, multimodal fundus imaging, and full-field electroretinography (ffERG). Genetic testing was performed by a targeted Next Generation Sequencing panel.

Results: Two siblings presented a reduced visual acuity and light sensitivity. ffERG was specific for CACNA2D4-related retinal dysfunction, but amplitudes of responses were different in the two patients. Additionally, an x-wave to a dim red flash was well preserved, and there was a reduced b/a ratio to a high intensity (30cd/m2) dark-adapted stimulus. Both patients were homozygous for the variant c.2406C > A, p.(Tyr802*) in CACNA2D4. During 17 years of follow-up, vision remained stable in patient 1, with no evidence of retinal degeneration.

Conclusion: Intrafamily clinical and electrophysiological expression of CACNA2D4-associated retinal dysfunction can be variable.

Purpose: This case report aims to describe an atypical presentation of pigmented paravenous chorioretinopathy (PPCRA).

Methods: Detailed clinical ophthalmologic examinations, multimodal imaging and electroretinography of a 33-year-old woman who presented with unilateral PPCRA.

Results: A 33-year-old female who is known to have hypothyroidism and had previous bariatric surgery, referred for retinal evaluation following incidental findings during a refractive surgery consultation. Fundus examination revealed unilateral segmental perivascular hyperpigmentation, vascular sclerosis, and areas of chorioretinal atrophy, raising the differential diagnosis of pigmented paravenous chorioretinopathy (PPCRA) versus resolved retinal vasculitis. The patient reported no significant ocular symptoms apart from decreased night vision in one eye and denied a history of acute visual loss or photophobia. Systemic workup, including autoimmune and infectious serologies, imaging, and a detailed clinical history, was unremarkable. The patient reported consanguinity within the family.

Conclusion: This report underscores the challenge of distinguishing PPCRA, a rare, typically bilateral hereditary condition, from resolved vasculitis, which often presents unilaterally with a history of systemic inflammation. Fluorescein angiography and optical coherence tomography were instrumental in identifying the lack of active inflammation and vascular leakage, favoring the diagnosis of PPCRA.

Purpose: To determine if harmonic components of the 30 Hz flicker ERG are useful for detecting neural dysfunction in diabetics who have mild or no non-proliferative diabetic retinopathy (NPDR).

Methods: Previously reported light-adapted flicker ERG data recorded from 20 diabetics who had no clinically-apparent retinopathy (NDR), 20 who had mild NPDR (MDR), and 20 non-diabetic controls were reanalyzed. From this dataset, the amplitude and phase of the 31.25 Hz flicker ERG fundamental and second harmonic were extracted. The 62.5 Hz flicker ERG fundamental was also extracted. Similar responses were also acquired prospectively from 10 controls, 5 NDR, and 5 MDR subjects, comprising a second dataset.

Results: Analysis of variance indicated that both diabetic groups had normal amplitudes elicited by the 31.25 Hz stimulus (fundamental and second harmonic), whereas the 62.5 Hz amplitude was reduced significantly in both diabetic groups. This pattern was found in both the retrospective and prospective analyses.

Conclusions: The second harmonic of the 31.25 Hz flicker response (equivalent to 62.5 Hz) was normal in early-stage DR, whereas the response to 62.5 Hz flicker stimuli was abnormal. The second harmonic of the ISCEV standard 30 Hz flicker ERG does not appear to be a useful indicator of neural dysfunction in early DR.

Purpose: To investigate the reproducibility of hand-held full-field electroretinogram (ERG) to determine the minimum change required in longitudinal measurements to reach statistical significance.

Methods: The study included 27 healthy volunteers, aged 45-65. Light-adapted (ISCEV standard) full-field ERGs measured with the RETeval device (LKC Technologies, Germantown, MD, USA) were recorded using non-invasive skin electrodes, followed by a second examination 1-14 days later. Intersession variability of the a- and b-waves, the flicker responses (light intensity 85 Td·s, frequency 28.3 Hz) and the photopic negative response (PhNR, 38 Td·s on 380 Td blue) were assessed.

Results: The mean standard deviations were 0.86, 0.83, 0.40 and 3.24 ms for a-wave, b-wave, flicker and PhNR peak times, respectively. Coefficient of variations (CV) were 32%, 22%, 18%, and 19.2% for the amplitudes of the a-wave, b-wave, flicker and PhNR, respectively.

Conclusion: While flicker ERGs had the smallest variability, ISCEV standard a-wave and b-wave times also had variability less than 1 ms, indicating excellent reproducibility. Amplitudes were more variable, with the a-wave amplitude having the most variability. While it depends on disease, longitudinal studies utilizing ERG timing are expected to be more likely to show statistically significant results due to low inter-session variability.

Purpose: The purpose of this study was to evaluate the effect of repeat testing on N1 and P1 amplitudes, signal-to-noise (SNR) ratios, and amplitude ring ratios (RR) in multifocal electroretinography (mfERG).

Methods: This was a retrospective review of mfERG records from 08/2022 to 05/2023. Patients were tested binocularly with the Espion system (Diagnosys LLC). Only records from patients with repeat mfERG tests at the same appointment were included. N1 and P1 amplitudes, signal-to-noise ratio (SNR), and amplitude ring ratios were evaluated for the first recording (run #1), the second recording (run #2), and the combination of run #1 and run #2 (combined run).

Results: Data was collected for 93 eyes from 47 patients (5 males, 42 females) with a mean patient age of 56.1 ± 17.3 years. No change was observed between run #1 and run #2 for N1 or P1 amplitudes, however amplitudes of the combined run decreased significantly (p  <  0.05) compared to run #1 amplitudes for all rings, right and left eyes (except for ring 1 in right eyes). SNR increased significantly from run #1 to run #2 for rings 2-5 (~10%), but not for ring 1. The number of blinks recorded during testing decreased from run #1 to run #2 (p < 0.001). Amplitude ring ratios R5/R4 and R5/R3 did not change significantly from run #1 to run #2, while amplitude R1/R2 ratio decreased significantly (p < 0.05).

Conclusion: The change in signal quality from run #1 to run #2 suggests a superior quality signal in the second run. Furthermore, the decreased P1 amplitude in the combined run compared to run #1 should be considered when a clinician uses the combined run for their final report.

Purpose: Pupillometry is most commonly performed in laboratory settings using specialized, non-portable instruments that require lengthy test protocols. The purpose of this study was to develop and evaluate a rapid, clinically-applicable pupillometry protocol using a commercially available, portable, handheld instrument.

Methods: Thirty-seven healthy individuals (ages 21-61 years) participated in three experiments. In each experiment, the pupillary light reflex (PLR) was elicited by full-field, 500 ms chromatic flashes (470 nm and 621 nm; 12,000 Td). Experiment I evaluated the minimum dark adaptation (DA) time needed to achieve maximum PLRs. Experiment II determined the effect of age. Experiment III estimated PLR test-retest repeatability. For all experiments, baseline pupil size (BL; 1 s before flash onset), maximum pupil constriction (MPC) following the flash, and post-illumination pupillary response (PIPR; median size 6-8 s after flash offset) were quantified.

Results: Experiment I showed that from 1 to 3 min of DA, BL and MPC increased slightly (0.27 mm and 5%, respectively), whereas the PIPR increased considerably (17%). The responses did not change appreciably after 3 min, therefore a 3 min DA period was used for Experiments II and III. Experiment II showed a trend for BL and MPC to decrease with age, but correlations with age were not statistically significant (all p > 0.05). PIPR was independent of age (r = - 0.01; p = 0.96). Experiment III showed test-retest repeatability of approximately 1 mm for BL, and 10% for MPC and PIPR, indicating good repeatability.

Conclusion: The proposed approach is useful for measuring the MPC and PIPR across a broad range of ages and baseline pupil sizes. Given the device portability and short test duration (approximately 5 min including DA), this approach has promising clinical utility.