Documenta Ophthalmologica最新文献

Purpose: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the retina acts as a dopaminergic extension of the central nervous system. This study aimed to evaluate the effects of dopaminergic therapy on retinal electrophysiological responses in newly diagnosed, treatment-naïve PD patients and to compare these findings with those of healthy controls.

Methods: Forty eyes from 20 PD patients underwent full-field electroretinography (ffERG). Photopic a-wave, b-wave, and photopic negative response (PhNR) wave amplitudes and implicit times were recorded before and after one month of dopaminergic therapy. For comparison, one randomly selected eye from each of 20 age- and sex-matched healthy control subjects also underwent the same ffERG protocol.

Results: Following dopaminergic treatment, a-wave (- 6.6 ± 1.4 µV, p < 0.001), b-wave (20.0 ± 4.8 µV, p = 0.001), and PhNR wave amplitudes (- 7.9 ± 1.8 µV, p < 0.001) significantly increased. Pre-treatment, a-wave (- 8.9 ± 3.5 µV, p = 0.014), b-wave (38.3 ± 9.8 µV, p < 0.001), and PhNR-wave (- 17.6 ± 2.8 µV, p < 0.001) amplitudes were significantly lower in the PD group compared with controls. Post-treatment, a- and b-wave amplitudes became comparable to those of the control group (p > 0.05), while PhNR-wave amplitude remained significantly reduced (- 9.7 ± 4.1 µV, p = 0.023).

Conclusion: Dopaminergic therapy significantly improved retinal electrophysiological responses in treatment-naïve PD patients. After treatment, the a- and b-wave amplitudes approached control levels, whereas the PhNR amplitude remained significantly reduced. These findings suggest that retinal dopaminergic dysfunction in PD may be partially reversible, and ffERG parameters can serve as sensitive biomarkers for monitoring treatment response.

Purpose: To describe a case of High-altitude retinopathy (HAR) and associated imaging and multimodal assessment.

Methods: The patient was evaluated at Columbia University Irving Medical Center using a comprehensive multimodal imaging protocol that included color fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (OCT). Functional assessments were conducted using full-field electroretinography (ERG), following the ISCEV standard protocols to ensure consistent and reproducible measurements of photoreceptor activity.

Results: A 44-year-old woman with stable RP and previously remitted cystoid macular edema presented with acute bilateral blurry and distorted vision after climbing Mt. Kilimanjaro. OCT revealed new bilateral foveal EZ loss with preserved peripheral retina. OCT-A demonstrated intact retinal and choroidal perfusion, excluding ischemic injury. Dilated fundus examination (DFE) and autofluorescence were unchanged from baseline. Methazolamide was discontinued, and N-acetylcysteine (1800 mg BID) was initiated. At 3-month follow-up, visual acuity improved, and OCT showed partial EZ recovery, consistent with a metabolic or hypoxic insult.

Conclusions: This case highlights a previously undescribed manifestation of HAR: isolated central photoreceptor damage without vascular involvement presenting as EZ line loss. The findings suggest that the high metabolic demand of foveal cones may predispose to hypoxia-induced injury, especially in patients with pre-existing retinal degeneration. Ophthalmologists should consider non-vascular mechanisms of high-altitude retinal injury, particularly in individuals with underlying retinal disease.

Purpose: To report a case of non-hereditary bilateral foveomacular and peripheral retinoschisis in a young female, with electrophysiological abnormalities in the absence of high myopia.

Methods: A 25-year-old female with recent-onset diminution of vision in the left eye (LE) underwent comprehensive ophthalmic evaluation including best-corrected visual acuity (BCVA), slit lamp biomicroscopy, indirect ophthalmoscopy, optical coherence tomography (OCT), full field electroretinography (ERG) and genetic evaluation.

Results: BCVA at presentation was 6/6, N6 in the right eye(RE) and 6/9, N8 in the LE. The patient had a prior history of laser refractive surgery for moderate myopia. Anterior segment examination was unremarkable. Fundus evaluation revealed bilateral foveoschisis and peripheral retinal schisis. OCT showed retinoschisis predominantly involving outer plexiform and outer nuclear layer, along with mild vitreoschisis. Foveal detachment was noted in the LE. ERG demonstrated rod and cone system dysfunction, severe rod bipolar cell dysfunction in both eyes, and a borderline electronegative waveform in the LE. There was no family history, and clinical exome sequencing did not reveal any pathogenic variants associated with the phenotype.

Conclusion: Electrophysiological abnormalities with bipolar cell dysfunction, similar to those seen in hereditary retinoschisis, can also occur in non-hereditary retinoschisis. Genetic evaluation is recommended to differentiate between the two, as ERG may show abnormalities in both.

Purpose: To provide a conceptual understanding of the continuous and discrete wavelet transforms (CWT, DWT) for clinical electroretinography (ERG) analysis, and how these methods uncover time-frequency features that complement traditional time-domain analysis.

Methods: A technical overview without the use of mathematical formula describing the basics of CWT and DWT and implementation considerations. We also review an example of four standard ISCEV full-field ERG (ffERG) recordings from a healthy 32-year-old male.

Results: Wavelet analysis uncovered time-frequency signatures absent in raw traces. In DA 0.01 cd s/m² DWT scalogram, energy localized in the 2-5 Hz range, with CWT scalograms corroborating these findings. In DA 3.0 cd s/m², a broader frequency response is seen across 10, 20 and 40 Hz center frequencies. A similar progression was found in the LA 3.0 cd s/m², with additional low energy indices at 80 and 160 Hz. For the LA 30 Hz flicker, all frequency and time-frequency profiles effectively replicated the 30 Hz response of the cone system.

Conclusions: CWT and DWT provide complementary and objective insight into ERG responses. Open-source MATLAB toolkit and step-by-step tutorial provided herein lower technical barriers and enable use by the broader community.

Purpose: To describe multimodal imaging and electrophysiology features of CTNNA1-associated retinal dystrophy in a family with p.(Leu318Ser) substitution.

Methods: Three family members including a 48-year-old male proband, his 52-year-old sister, and their 67-year-old mother, were evaluated with multimodal imaging and electrophysiology. The proband, referred with suspected Best's disease, underwent a retinal dystrophy panel and two affected family members were target sequenced for the familial variant.

Results: The NM_001903.5:c.953T > C variant in CTNNA1 segregated with affected family members. They maintained a visual acuity of 20/25 or better throughout 2-4 years of follow-up. The proband exhibited butterfly-shaped pigment dystrophy whilst his sister had no macular lesions, and their mother had foveal pigmentary changes. All three displayed peripheral retinal reticular pigmentation with variable atrophy. Microperimetry demonstrated enlarging paracentral scotoma in the proband whilst Esterman binocular suprathreshold test showed reproducible peripheral loss in the proband's sister. Multifocal electroretinography (ERG) confirmed central macular dysfunction in the proband. In all three, full-field ERG showed mildly delayed dark-adapted (DA) 0.01 b-wave and DA3.0 a-wave, and a light-rise of < 1.7 in one or both eyes on electro-oculography (EOG).

Conclusions: CTNNA1-associated retinal dystrophy due to p.(Leu318Ser) has a unique peripheral retinal phenotype despite variable macular involvement. Reduced EOG light-rise and peripheral reticular pigmentation should raise suspicion of CTNNA1 in butterfly-shaped pigment dystrophy.

Purpose: The photopic negative response (PhNR) and pattern ERG, both established electrophysiological measures of retinal ganglion cell (RGC) function, are recorded under photopic conditions. The purpose of this study was to describe the mesopic negative response (MeNR), a novel marker of RGC function within the rod pathway.

Methods: Ten visually-normal controls (mean age ± SD 54.6 ± 5.6 years) and 12 patients with severe primary open-angle glaucoma (mean age ± SD 58.4 ± 4.9 years) participated. Light-adapted, full-field ERGs were elicited by a rod-isolating pulse generated on the principle of silent substitution (0.46 scot. cd/m²; 55% contrast; 40 ms) presented against a steady background (0.30 scot. cd/m²). In addition, (1) the PhNR was recorded; (2) subjects were dark-adapted for 20 min and the ISCEV DA 0.01 was recorded.

Results: The normal rod-isolated pulse response was characterized by a positive potential at 85 ms followed by a slow negative potential (MeNR) at 175 ms following the pulse. The mean (± SEM) amplitude of the positive potential was similar for the control (13.4 ± 1.2 µV) and glaucoma (11.6 ± 1.35 µV) groups (p = 0.33), and was correlated with the DA 0.01 amplitude (r = 0.71, p < 0.001). The amplitude of the MeNR was significantly (p < 0.001) attenuated for the glaucoma group (4.5 ± 0.7 µV) compared to the controls (9.7 ± 1.25 µV), and was correlated with the PhNR amplitude (r = 0.86, p < 0.001).

Conclusions: Rod-isolated ERGs can be obtained without dark-adaptation using silent-substitution. The positive potential and MeNR of the rod-isolated response appear to be generated by rod bipolar cells and RGCs, respectively. In severe glaucoma, the positive (bipolar cell) potential was not significantly affected, whereas the MeNR was significantly reduced. MeNR analysis may be useful for studying RGC function within the rod pathway.

Purpose: To report a rare case of bilateral idiopathic multifocal retinal pigment epithelial detachments (imfPEDs) and to describe the long-term morphological and functional changes observed over a 16-year follow-up period.

Methods: A 49-year-old woman was diagnosed with imfPEDs based on multimodal imaging, including optical coherence tomography (OCT), fluorescein angiography (FA), and fundus photography. Full-field electroretinograms (ffERGs) and multifocal ERGs (mfERGs) were recorded to assess retinal function. The patient voluntarily discontinued follow-up but returned 16 years later due to cataract progression. Retinal morphology and function were re-evaluated using comparable multimodal imaging and electrophysiological methods.

Results: At the initial visit, multiple bilateral pigment epithelial detachments (PEDs) were identified. OCT showed hyporeflective, dome-shaped PEDs with smooth borders, and ERG responses were within normal limits. Sixteen years later, some PEDs had resolved, others had newly developed or fused, and geographic atrophy was observed, particularly in the peripheral retina. Fundus autofluorescence (FAF), performed in place of FA, revealed hyperautofluorescent PEDs and numerous peripheral hypofluorescent spots. ffERGs remained normal, while mfERGs showed localized attenuation with relatively preserved macular function. These findings were consistent with large colloid drusen and cuticular drusen.

Conclusion: This case demonstrates the slow morphological progression and relative functional preservation in bilateral imfPEDs over 16 years. Comparable multimodal imaging and electrophysiological testing were valuable in monitoring the long-term clinical course and support the classification of this phenotype as a variant of large colloid or cuticular drusen.

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.