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: 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.

Purpose: We report the clinical history of two siblings, initially diagnosed with juvenile glaucoma (JG), who were subsequently found to harbor a novel pathogenic OPA1 splicing variant consistent with dominant optic atrophy (DOA).

Methods and results: The male proband presented with elevated intraocular pressure (IOP) at age 11, while his sister had normal IOP values at age 16. Both developed bilateral temporal optic nerve pallor, central visual field defects, and reduced color vision. Optical coherence tomography (OCT) confirmed thinning of the retinal nerve fiber and ganglion cell layers. Whole exome sequencing identified a novel splice-site variant in OPA1 (NM_130837.3:c.611-2A>T) in both siblings and their affected mother, classified as pathogenic according to ACMG/AMP guidelines. During treatment washout, the male proband showed elevated IOP, consistent with concomitant JG and DOA, whereas the sister exhibited DOA only.

Conclusions: This report highlights the importance of considering DOA in young patients with presumed JG, and suggests potential overlapping pathophysiology involving mitochondrial dysfunction and retinal ganglion cells vulnerability.

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: 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.

Objective: To evaluate full-field electroretinogram (ffERG) parameters and evaluate their clinical associations in patients with acute Vogt-Koyanagi-Harada (VKH) disease over a 4-year follow-up.

Methods and analysis: This retrospective cohort study included 21 patients with acute VKH disease followed for 48 months after initiation of systemic corticosteroid therapy, with or without adjunctive immunosuppression. ffERG was performed at 1, 6, 12, and 48 months (M) post-treatment. At M48, eyes were classified into two groups: Group 1 (normal ffERG) and Group 2 (subnormal ffERG), based on whether any ffERG parameters fell below the 5th percentile of age-matched healthy controls. Main outcomes included longitudinal ffERG changes, clinical associations, and the 6-month recovery ratios relative to baseline (M1).

Results: All ffERG parameters improved significantly from baseline to M6 (p < 0.001) and to M12 (p < 0.001) and stabilized thereafter. Group 2 exhibited consistently reduced ffERG amplitudes compared to Group 1 throughout follow-up (p < 0.01 to p < 0.001), despite similar recovery trends. Recovery ratios at M6 ranged from 27%-78% in Group 1 and 26%-175% in Group 2; however, Group 2 remained below normal levels at M48. Sunset glow fundus (SGF) at M12 was significantly more frequent in Group 2 (60.7%) than in Group 1 (21.4%, p = 0.025).

Conclusions: Retinal function improved during the first year and stabilized thereafter, irrespective of treatment type. Persistent subnormal ffERG at 48 months reflected a poorer baseline function and was associated with the development of SGF.

Purpose: To report the clinical phenotype, imaging characteristics, and electrophysiologic findings of a 62-year-old patient with retinitis pigmentosa (RP) harboring a likely pathogenic homozygous KIZ (NM_018474.6) start codon variant (c.3G > A, p.Met1?), only previously reported in the compound heterozygous state.

Methods: The patient underwent clinical evaluation including full medical history, best-corrected visual acuity (BCVA), slit lamp exam, and dilated fundus examination (DFE), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinography (ffERG), following the ISCEV standard protocols. Genetic testing was performed using the Invitae inherited retinal disorders panel of 330 genes.

Results: BCVA was 20/40 in both eyes. Fundus examination revealed mild optic disc pallor, arteriolar attenuation, peripheral pigment migration, and macular hyper-autofluorescence along the arcades. with macular sparing. Outside the arcades, there are hypo-autofluorescence spots corresponding to retinal pigement epithelium atrophy. There is marked peri-papillary atrophy. SD-OCT showed diffuse outer retinal thinning, ellipsoid zone constriction, mild cystoid macular edema, and epiretinal membrane. ffERG was consistent with a rod-cone dystrophy, with extinguished dark-adapted responses and severely attenuated 30 Hz flicker amplitudes. Genetic testing identified a heterozygous variant of uncertain significance in CTNNA1 (c.1486C > T, p.Arg496Cys) and a homozygous KIZ variant (c.3G > A, p.Met1?), previously observed only in compound heterozygosity. The patient was diagnosed with KIZ-associated RP and initiated on topical dorzolamide.

Conclusions: This case expands the clinical spectrum of KIZ-associated RP by describing the phenotype associated with a homozygous start codon variant. Despite the disruptive nature of the mutation, the patient exhibited a relatively mild rod-cone dystrophy with retained cone responses into the seventh decade. These findings support the inclusion of KIZ in diagnostic panels for autosomal recessive RP and contribute valuable genotype-phenotype correlation data for this rare ciliopathy.

Purpose: To compare pupillary responses during two-color light stimulation and the post-illumination pupillary response (PIPR) between patients with Leber hereditary optic neuropathy (LHON) and established optic atrophy and patients with primary open-angle glaucoma (POAG) who have central visual dysfunction with similar magnitude to that of the LHON patients.

Methods: Fourteen normal controls, eight patients with POAG and mean deviation of the Humphrey visual field and circumpapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thickness measured using optical coherence tomography being comparable to those of LHON patients, and nine patients with LHON were included. Using a handheld electronic pupillometer, pupil diameter of the eye contralateral to the stimulation was recorded during a 7 s baseline period, a 10 s red light stimulation followed by a 40-s post-stimulation period, and a 10 s blue light stimulation followed by a 40 s post-stimulation period.

Results: The ratio of pupil diameter at 6 s after blue, but not red, light offset as well as the subtraction of difference between the baseline pupil diameter and the mean pupil diameter during the 30 s post-illumination using red stimulus from the counterpart using blue stimulus was significantly larger in POAG patients than in the other two groups. The maintenance of pupillary constriction during blue light stimulation was significantly reduced in POAG patients compared with the other two groups.

Conclusions: Compared with POAG patients who had comparable macular structural and functional damage, LHON patients showed better pupillary responses during blue light stimulation and PIPR, reflecting preserved ipRGC function.

Purpose: To characterize the clinical phenotype associated with a homozygous start codon-altering complex variant in the ABCA4 gene and evaluate its severity and prognosis in the context of Stargardt disease.

Methods: Patient records were retrospectively reviewed for homozygous ABCA4 start codon variants. Patients underwent ophthalmic exam, multimodal imaging, full-field electroretinography (ffERG), and inherited retinal disease panel testing. Structural and functional retinal assessments were reviewed to determine phenotype severity.

Results: Three brothers of Ashkenazi Jewish descent presented with profound early-onset vision loss beginning at age 7, with best-corrected visual acuity reduced to counting fingers or hand motion by early adulthood. Imaging revealed widespread macular atrophy, extensive intraretinal pigment migration, and near-complete foveal outer nuclear layer loss. ffERG demonstrated extinguished scotopic and photopic responses. The patients were found to be homozygous for a complex ABCA4 allele containing the start codon variant c.[1A > G;6089G > A]. These features were consistent with the rapid-onset chorioretinopathy phenotype, previously associated with null ABCA4 alleles.

Conclusions: This report characterizes the clinical findings in patients homozygous for the c.[1A > G;6089G > A] variant in ABCA4, confirming its association with a severe, rapid-onset chorioretinopathy phenotype. The data support the pathogenic nature of this complex allele and expands the genotype-phenotype correlational spectrum of ABCA4-related disease, with implications for prognosis and genetic counseling.

Purpose: To report a case of α-mannosidosis with intellectual, hearing impairment and progressive retinal degeneration, supported by ten years of ophthalmic follow-up, genetic testing, and leukocyte α-mannosidase enzymatic analysis.

Methods: The patient underwent serial ophthalmic examinations over a ten-year period, including best-corrected visual acuity (BCVA) testing, fundus photography, optical coherence tomography (OCT), and fundus autofluorescence (FAF), to monitor disease progression. Trio-based whole-exome sequencing (WES) was performed on the family. Variant confirmation was conducted via Sanger sequencing. To support the genetic findings, leukocyte α-mannosidase activity was measured using fresh peripheral blood samples.

Results: At first presentation, BCVA was 20/50 OD and 20/40 OS. Over the next decade, vision progressively declined to 20/200 in both eyes. Fundus images showed granular pigment mottling in the posterior pole, and subsequent wide-angle imaging detected bone-spicule pigmentation deposits in peripheral retina. OCT demonstrated progressive retinal thinning, with loss of the ellipsoid zone. FAF revealed expanding areas of retinal atrophy. The patient has presented with bilateral sensorineural hearing loss, delayed speech development, persistent dysarthria, mild cognitive impairment, and coarse facial features since childhood. Genetic analysis identified a novel homozygous MAN2B1 mutation: c.1316_1327delinsTGATG (p.Ala439Valfs*36), inherited from consanguineous parents with the same heterozygous genotypes. The variant was classified as pathogenic based on ACMG criteria. The patient's leukocyte α-mannosidase activity was profoundly decreased, confirming the diagnosis.

Conclusions: This case highlights the progressive nature of retinal degeneration in α-mannosidosis and underscores the diagnostic value of leukocyte enzyme testing alongside genetic and ophthalmic assessments. Early recognition of ophthalmic signs, particularly in patients with syndromic features such as hearing loss and facial dysmorphism, is essential for timely diagnosis and intervention.