Documenta Ophthalmologica最新文献

Purpose: To assess functional and anatomical impairments in pediatric patients and their affected adult family members with juvenile-onset Best vitelliform macular dystrophy (BVMD).

Methods: Fifteen genetically confirmed BVMD patients (10 pediatric and 5 adults) underwent a comprehensive ophthalmic examination with multimodal imaging and electrophysiological testing. We quantified BVMD lesion volumes using sequential spectral-domain OCT (SD-OCT) scans, facilitating correlation with clinical parameters and electroretinogram (ERG) findings.

Results: Children presented less advanced stages of BVMD than adults, had better visual acuity [Log MAR 0.13 ± 0.17] than adults [Log MAR 0.91 ± 0.52, p < 0.001], and displayed lower lesion volumes [0.93 ± 0.71 mm³] compared to adults [1.80 ± 0.79 mm³, p < 0.001]. Interestingly, in 3 eyes in Stage 3 disease (pseudohypopyon stage), despite a high lesion volume (1.74 ± 0.66 mm³), a good visual acuity was still observed (LogMAR of 0.00 in all 3 eyes). Multifocal ERG (mfERG) revealed macular dysfunction in all patients mostly pronounced in the 3 central rings [% of P1 reduction from control in Ring 1 in children and adults: 51% and 51%, Ring 2: 17% and 36% and Ring 3: 8% and 15%, respectively]. Furthermore, higher lesion volumes showed more affected mfERG responses. Full-field flash ERGs were normal in children, while reduced amplitudes and delayed responses were observed in some adults.

Conclusion: While juvenile presentations of BVMD are less severe and more circumscribed, adult presentations demonstrate more widespread functional abnormalities in both amplitude and implicit times correlated with anatomical progression and clinical progression. Interestingly, mfERG responses in children with 20/20 vision also revealed functional impairment, correlating more strongly with the degree of vitelliform liquefaction on OCT than with visual acuity. Our findings suggest that mfERG may serve as an early, reliable indicator of functional defects in BVMD.

Purpose: This study compared the variability of visual evoked potential (VEP) in response to stimulation of eyes affected by unilateral optic neuritis with that of fellow (non-affected) eyes.

Methods: Pattern-reversal VEP (PVEP) and motion-onset VEP (MVEP) recordings from thirty-six subjects with unilateral optic neuritis at different intervals from disease onset were retrospectively evaluated, and differences in the following parameters were compared: signal‒to‒noise ratio (SRN), interquartile range of the response jitter (jitter IQR), and number of trials corresponding to the average response (corresponding N).

Results: In the PVEP recordings, the P1 peak times of the fellow eyes were significantly shorter than those of the affected eyes (Cohen's d = -1.470, p < 0.001). P1 amplitudes were significantly greater in fellow eyes (d = 1.17, p < 0.001). Significant differences were found in the SNR (d = 0.782, p < 0.001), jitter IQR (d = -0.874, p < 0.001), and corresponding N (d = 0.700, p < 0.001). MVEP presented significantly shorter N2 peak times in fellow eyes than in affected eyes (d = 0.840, p < 0.01) and significantly greater amplitudes (d = 0.494, p = 0.002). There was a significant difference in the SNRs (d = 0.440, p = 0.01) and corresponding N values (d = 0.415, p = 0.01). There was no difference in the jitter IQR (d = 0.143, p = 0.230).

Conclusions: The increased variability in eyes affected by optic neuritis compared with fellow eyes (in particular, in pattern-reversal VEP, which predominantly represents the activity of the macular-papillary fibers of the optic nerves) may represent important pathophysiologic features and may add valuable information to diagnostics via VEP examinations.

Purpose: Incomplete congenital stationary night blindness (icCSNB) is a subtype of inherited, non-progressive retinal diseases. Most cases of icCSNB result from mutations in the X-linked gene CACNA1F. We describe the clinical findings of two male siblings diagnosed with icCSNB, both carrying a novel variant c.4008 + 5G > T in CACNA1F inherited from their mother.

Methods: We carried out a comprehensive ophthalmic assessment, including fundus imaging, optical coherence tomography (OCT) scanning and electroretinography. We performed genetic testing with next generation sequencing, in-silico and functional analyses to further characterise the novel variant.

Results: Two male siblings presented with high myopia and reduced visual acuities  at age three. Examination and OCT demonstrated no significant abnormalities in both siblings. Full-field electroretinogram (ffERG) testing demonstrated markedly reduced amplitude to weak flashes and an electronegative waveform to strong flashes in dark-adapted ERGs, resembling that of icCSNB, leading to its diagnosis in both children. Next generation sequencing in the older sibling identified a novel hemizygous c.4008 + 5G > T variant in CACNA1F. In-silico analysis of this variant predicted that it would disrupt normal splicing of CACNA1F, though it was not possible to confirm this by RNA sequencing. This same variant was found in the younger sibling, as well as in their mother who had normal examination and ffERG findings.

Conclusions: We report a novel CACNA1F variant not previously identified in the literature in three patients. Although functional analyses were unable to confirm pathogenicity of this variant, in-silico tools predicted that its effect is consistent with the pathogenesis of icCSNB. Reporting of this family further widens the genotypic spectrum of icCSNB.

Purpose: Quanz et al. (Sci Rep 14:16797, 2024) reported that participants with nystagmus had higher objective visual evoked potential visual acuity estimates (VA_VEP) by 0.12 logMAR relative compared to standard psychophysical VA (VA_{Psych_Stat}). The cause of this modest, but significant VA_VEP overestimation remains unclear. Here we investigated its association with the pattern-pulse stimulation mode applied for steady state VEP recording for VA_VEP estimation. Specifically, we tested whether psychophysical visual acuity to pulsed optotypes (VA_{Psych_Pulsed}) also exceeds standard optotype VA_{Psych_Stat}.

Methods: Twelve participants with nystagmus were included in this analysis. VA_VEP was determined for pattern-pulse steady-state VEP stimulation (Quanz et al. in Sci Rep 14:16797, 2024) using EP2000, psychophysical VA was determined to stationary (VA_{Psych_Stat}) and to pulsed (VA_{Psych_Pulsed}) Landolt-C optotypes employing a modified version of the Freiburg Vision Test (FrACT). Pulsed stimulus timing was identical for VEP and VA (40 ms on and 93 ms off, i.e. at 7.5 Hz). In a separate measurement, fixation stability within the central 4° was determined using microperimetry (Nidek MP-1), and the eye with the stronger fixation instability was selected for the analysis (12 eyes). LogMAR differences were assessed with a paired t-test and the correlation of fixation stability and VA differences (ΔVA_Psych = VA_{Psych_Pulsed} - VA_{Psych_Stat}) was tested.

Results: VA_{Psych_Stat} (0.43 ± 0.06 logMAR) and VA_{Psych_Pulsed} (0.45 ± 0.06 logMAR, P = 0.15) did not differ from each other, but from VA_VEP (0.26 ± 0.08 logMAR, P = 0.02 and P = 0.01, respectively). There was no correlation of ΔVA_Psych with fixation instability (r² = 0.002, P = 0.89).

Conclusion: Pulsed stimulation appears not to be the reason for the VA_VEP overestimation in nystagmus. Further research should address whether differences in the spatial stimulus properties might be of relevance, as VA_Psych is tested with optotypes, VA_VEP with extended patterns.

Background: Foveoschisis refers to the splitting of retinal layers involving the macula that may have different causes with variable structural-functional natural histories. Idiopathic cases are seen in the absence of inherited or acquired predisposing conditions and referred to as stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR). Our study aimed to clinically and genetically characterize females presenting with foveoschisis (including affected male siblings where present).

Methods: Five patients (3 females and 2 males) from 3 consanguineous families presenting with foveoschisis underwent complete ophthalmological evaluation, multimodal imaging including color, infrared, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), electroretinogram (ERG), and molecular evaluation including Sanger sequencing of the RS1 gene and whole exome sequencing (WES). Main outcome measures were age at first visit, best-corrected visual acuity (BCVA), peripheral retinal changes, FAF pattern, ERG findings, and RS1 variants.

Results: The mean age was 21.8 years. The BCVA ranged from 20/100 to 20/20. Peripheral retinal changes ranged from a tapetal reflex, peripheral retinoschisis, vitreous veils, to vitreoretinal traction. A ring of increased signal was the most common FAF abnormality, while one patient exhibited a double-ring hyperautofluorescence. All patients demonstrated an electronegative ERG. One female was considered to have a molecularly undiagnosed inherited retinal disease (IRD). Another female was considered stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) after exclusion of other causes. Three patients showed a novel nonsense variant in the RS1 gene; homozygous in the female sibling and hemizygous in the male siblings. Familial segregation revealed an unaffected father and a carrier mother. Trio SNP array confirmed maternal segmental uniparental isodisomy (seg UPiD).

Conclusion: This is the first reported X-linked retinoschisis (XLRS) case with seg UPiD. We emphasize the significance of SNP arrays in elucidating non-Mendelian inheritance cases. We report a novel variant, which is the first to be detected in the RS1 domain in a female.

Purpose: This study aimed to optimize dynamic random dot correlogram (DRDC) and stereogram (DRDS) stimuli to evoke steady-state visual evoked potentials (ssVEP) on multiple EEG channels for the objective assessment of stereopsis.

Methods: EEG recordings were conducted on 22 healthy adults (mean age: 30.2 ± 5.8 years) while viewing cyclopean and control stimuli. DRDC and DRDS were presented at three temporal frequencies (0.9375, 1.875, and 3.75 cycles per second, cps) using anaglyphic channel separation. The ssVEP responses were analyzed using T²_circ statistical test to determine the most effective stimulus for eliciting significant cortical activity.

Results: DRDC at 1.875 cps evoked significant ssVEP responses in 93% of participants on at least one occipital electrode (O1, Oz, O2) and in 100% when including parietal-occipital electrodes. DRDS at similar frequencies also produced robust responses but required additional parietal electrode monitoring. Monocular control measurements confirmed that responses were stereo-specific.

Conclusions: DRDC at 1.875 cps was the most effective stimulus for objective electrophysiological assessment of stereopsis, demonstrating high reliability with minimal electrode setups. These findings support the integration of optimized ssVEP protocols into clinical assessments, particularly for non-verbal or pediatric populations.

Purpose: This study assessed the diagnostic potential of chromatic pupil campimetry (CPC) using relative maximal constriction amplitude (relMCA), pupillary light response (PLR) latency, and pupillary escape to differentiate optic neuropathies (ON) from healthy individuals and identify specific ON subtypes.

Methods: CPC testing used red and blue stimuli at central (0°) and peripheral (20°) locations to measure relMCA, latency, and pupillary escape. Patients with various ON etiologies, including glaucoma (n = 20), optic nerve compression by meningioma (n = 18), chiasm compression (n = 4), Leber hereditary optic neuropathy (LHON; n = 4), and autosomal dominant optic atrophy (ADOA; n = 3), were tested. Linear mixed-effects models and post hoc Tukey tests were used to analyze differences across subgroups of ON etiologies and a healthy control group (n = 40), regarding signal eccentricities and locations.

Results: Pupillary escape was significantly higher in ON patients during central red stimulation (p = 0.0007). Glaucoma and meningioma groups showed reduced relMCA and prolonged latency for both stimuli compared to controls (p < 0.0001 to p = 0.0058). RelMCA during blue stimulation was lower in glaucoma patients than in ADOA (p = 0.0183). LHON patients exhibited significantly prolonged PLR latency during blue stimulation compared to healthy (p = 0.0284).

Conclusion: CPC effectively distinguished glaucoma and meningioma from healthy controls but was less reliable for differentiating ON subtypes. Our results indicate, that central pupillary escape is associated with inner retinal dysfunction.

Purpose: To report a 42 year-old male patient with Best vitelliform macular dystrophy (BVMD) complicated by diabetic retinopathy, who harbored a missense variant in the BEST1 gene.

Methods: Comprehensive ophthalmological examinations, including full-field electroretinography (ERG) and electrooculography (EOG), were performed. Whole exome sequencing (WES) was conducted to identify potential disease-causing variant(s), and Sanger sequencing was used for confirmation.

Results: Fundus photography and fluorescein angiography revealed macular degeneration and non-proliferative diabetic retinopathy with macular leakage. Although the light peak/dark trough (Arden) ratio on EOG was relatively preserved, a reduced light rise and attenuated dark trough amplitudes were observed. ERG demonstrated normal rod and cone system function. Based on optical coherence tomography findings, the BVMD stage was classified as a stage between the Vitelliruptive and Atrophic stages in the right eye, and as the Pseudohypopyon stage in the left eye. WES identified a previously unreported BEST1 variant, c.737G > A: p.(Ser246Asn) heterozygously, confirmed by Sanger sequencing.

Conclusions: This case emphasizes the importance of EOG assessment and genetic analysis in establishing an accurate diagnosis of BVMD, particularly in patients with coexisting conditions such as diabetic retinopathy.

Purpose: To optimize latency calculation in chromatic pupillography for a more robust evaluation of pupillary light response (PLR) dynamics in a normative collective.

Methods: The PLR of 150 healthy participants aged 18-79 years (median 46 years, 94 females) measured by L-cone- and rod-favoring stimulation protocols in Chromatic Pupil Campimetry (CPC) was analyzed. Three calculation methods of latency to constriction onset after light stimulus were tested. 1: intersection of mean baseline pupil diameter and linear fit through the descending part of the pupillogram (20 data points) at each stimulus position in the central visual field (30°), 2: intersection of a linear fit through the baseline and linear fit using less (15) data points through the pupillary contraction phase at each stimulus position and 3: mean per eccentricity gained by averaged pupillograms. Equivalence testing (two one-sided t-tests, TOST) was used for comparison of the methods.

Results: The longest mean latencies were found with calculation 1 in both photopic and scotopic stimulation, followed by calculation 2. Latency calculation per eccentricity (3) resulted in the shortest mean latencies. The differences in latency results of the three calculation methods increased with increasing eccentricity in both stimulation protocols. Calculation 2 and 3 were equivalent up to 12° eccentricity in photopic and up to 20° eccentricity in scotopic stimulation.

Conclusions: The use of the intersection of a linear fit through the baseline with a linear fit containing an adjusted number of data points adapted to the characteristics of the pupillary contraction phase appears to be suitable to provide consistent latency calculation, particularly for small constriction amplitudes and noisy data as they may occur in patients with e.g. hereditary retinal degenerations. The evaluation of mean latency per eccentricity is equivalent and may be advantageous in difficult clinical test results with low amplitudes.