Documenta Ophthalmologica最新文献

Purpose: In this study, we report a case of a young adult with X-linked juvenile retinoschisis (XLRS) with a rare pathogenic variant in the RS1 gene (c.522 + 2 T > A).

Methods: Ophthalmological evaluation, optical coherence tomography, full-field and multifocal electroretinograms and extensive genetic screening of genes related to visual loss were carried out in the participant.

Results: Clinical ophthalmological exams revealed a mild to moderate impairment of visual acuity. Retinal imaging showed bilateral foveal schisis, as well as normal a-wave, reduction in the b-wave amplitudes in dark- and light- adapted full-field electroretinograms, and abnormal oscillatory potentials. We found also diffuse amplitude reduction in multifocal electroretinogram arrays. A canonical splice variant was identified in the RS1 gene (c.522 + 2 T > A).

Conclusion: A rare pathogenic variant of the RS1 gene was associated with diffuse retinal involvement (central and peripheral retina), probably in inner retina, and mild to moderate visual acuity impairment. The phenotypical characterization of rare mutations is relevant to provide information about the disease.

Purpose: We report diagnostic and therapeutic dilemmas in the difficult case of compressive optic neuropathy with severe visual acuity and visual field loss with subsequent visual recovery in both eyes, in a patient with Graves' orbitopathy (GO) by a combination of experimental antithymocyte therapy, orbital radiotherapy with high-dose steroids.

Methods: A 72-year-old man presented with severe vision loss in both eyes. The visual symptoms had appeared over a year before the GO diagnosis. He was initially misdiagnosed with neuroborreliosis and optic neuritis based on brain and orbital magnetic resonance imaging. There was no exophthalmos. The ophthalmological examination included visual acuity, visual field, tonometry in primary and upgaze eye position, optical coherence tomography (OCT), pattern electroretinogram (PERG), pattern, and flash visual evoked potentials (PVEP and FVEP). The patient received experimental therapy with ATG, followed by high-dose of intravenous steroids and orbital radiotherapy.

Results: Delayed VEP peaks became shorter after treatment. After systemic and local therapy lowering of intraocular pressure was achieved. Abnormal PERG has been found three months before ganglion cells atrophy was detected in OCT. Visual acuity and visual field improvement occurred in both eyes after therapy, despite partial left optic nerve atrophy. The patient regained full decimal visual acuity (1.0 right from as poor as 0.3  to 1.0 in the right eye and from hand movements to 0.9 in the left. Severe visual field loss with advanced absolute scotomata has improved to slight relative scotomata. The duration of follow-up time after the treatment was 4 months.

Conclusions: Intensive treatment of steroid-resistant Graves' orbitopathy (GO) may prevent total optic nerve atrophy. Despite severely advanced optic neuropathy, this report emphasizes the necessity of therapy even with nearly complete visual function loss hence there is always a possibility to regain full visual acuity and visual field. Patients with tense orbital septum may not present with significant exophthalmos, thus delaying the correct diagnosis of orbitopathy. A supporting sign of GO was the difference in intraocular pressure in the primary and upgaze eye positions. Electrophysiological examinations are helpful in the diagnosis and monitoring of GO therapy. To our knowledge, this is the first report of this kind presenting visual function restoration and structural recovery in a patient with advanced optic neuropathy in GO.

Purpose: Both rod and cone-driven signals contribute to the electroretinogram (ERG) elicited by a standard strong flash in the dark. Negative ERGs usually reflect inner retinal dysfunction. However, in diseases where rod photoreceptor function is selectively lost, a negative waveform might represent the response of the dark-adapted cone system. To investigate the dark-adapted cone-driven waveform in healthy individuals, we delivered flashes on a dim blue background, designed to saturate the rods, but minimally adapt the cones.

Methods: ERGs were recorded, using conductive fibre electrodes, in adults from the TwinsUK cohort. Responses to 13 cd m^-2 s white xenon flashes (similar to the standard DA 10 flash), delivered on a blue background, were analysed. Photopic and scotopic strengths of the background were 1.3 and 30 cd m^-2, respectively; through a dilated pupil, this is expected to largely saturate the rods, but adapt the cones much less than the standard ISCEV background.

Results: Mean (SD) participant age was 62.5 (11.3) years (93% female). ERGs from 203 right and 204 left eyes were included, with mean (SD) b/a ratios of 1.22 (0.28) and 1.18 (0.28), respectively (medians, 1.19 and 1.17). Proportions with negative waveforms were 23 and 26%, respectively. Right and left eye b/a ratios were strongly correlated (correlation coefficient 0.74, p < 0.0001). We found no significant correlation of b/a ratio with age.

Conclusions: Over 20% of eyes showed b/a ratios less than 1, consistent with the notion that dark-adapted cone-driven responses to standard bright flashes can have negative waveforms. The majority had ratios greater than 1. Thus, whilst selective loss of rod function can yield a negative waveform (with reduced a-wave) in some, our findings also suggest that loss of rod function can occur without necessarily yielding a negative ERG. One potential limitation is possible mild cone system adaptation by the background.

Purpose: To report a case series of patients with retinal toxicity due to hydroxychloroquine (HCQ) within a short span of treatment.

Methods: A retrospective review of case records of patients with accelerated HCQ toxicity within 1 year of starting the treatment was done. Systemic co-morbidities, details of HCQ treatment, details of ocular examination, and results of multimodal investigations were noted.

Results: Nine patients (1 male, 8 females) with age ranging from 40 to 73 years (mean 54.2 ± 13.4 years) who showed accelerated HCQ toxicity were included. None had systemic conditions or drug history predisposing to early HCQ toxicity. The treatment duration ranged from 2 to 11 months and the cumulative HCQ dose ranged from 18 to 120 g (mean 45.0 ± 33.0 g). The visual acuity was normal in 8 (88.9%) patients and retinal evaluation was normal in 4 (44.4%). Optical coherence tomography was abnormal in 4 (44.4%). Six (66.6%) cases had reduced sensitivity in the parafoveal point on visual field testing. All 9 cases had multifocal electroretinographic changes diagnostic of HCQ toxicity. The HCQ treatment was stopped in 8 and continued with reduced dose in 1 patient. The mean duration of follow-up was 11.2 ± 9.6 months during which 5 patients showed improved mfERG and 1 patient had a stable mfERG. Visual fields improvement was noted in 2 cases.

Conclusions: Patients on HCQ need to be kept on regular monitoring with more frequent follow-ups to detect signs of early onset toxicity and prevent permanent visual impairment. mfERG is an important diagnostic tool for HCQ toxicity.

Purpose: The purpose of this study was to describe and diagnose the difficulty in a long-term follow-up (eleven years) patient with a very early presentation of late-onset retinal degeneration (L-ORD) and the significance of electrophysiological examinations and follow-up in assessing undiagnosed inherited retinal diseases.

Methods: This is an observational case report of a 56-year-old woman, with scattered multiple yellow-white retinal dots firstly diagnosed as fundus albipunctatus. Ten years after presentation, a deterioration in rod and cone responses in ff-ERG was detected, which allowed us to discard the first diagnostic hypothesis and proceed with a genetic testing.

Results: Ten years after presentation, she presented a clear progression of the abnormal photoreceptor response with a cone and rod involvement in ff-ERG, which was not compatible with the previous suspicion of fundus albipunctatus. Six months later, genetic testing results together with the typical progression of atrophic patchy lesions in multimodal imaging allowed a certain diagnosis of L-ORD, caused by an already reported pathogenic variant in the C1QTNF5 gene (c.563C > T; p. Pro188 Leu).

Conclusions: We demonstrate the importance of the ff-ERG examination and the follow-up (or ERG and imaging repetition) in the differential diagnosis of an incipient L-ORD, which can be easily misdiagnosed in the early stages, before the appearance of the characteristic chorioretinal atrophy seen with the progression of this rare disease.

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

Purpose: To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone-rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers.

Methods: Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF).

Results: At first visit, with a mean age of 30 years (range 5-70 years), 12 patients had a BCVA below Australian driving standard (LogMAR ≥ 0.3 bilaterally), and 1 patient was legally blind (LogMAR ≥ 1). Longitudinal analysis demonstrated a deterioration of LogMAR by - 0.019 per year (p < 0.001). This accompanied a reduction in CMT of - 1.4 µm per year (p < 0.0001), lengthened EZ disruption by 42 µm per year (p =  < 0.0001) and increased area of FAF by 0.05 mm² per year (p = 0.027). Similarly, cone function decreased with increasing age, as demonstrated by decreasing b-wave amplitude of the light-adapted 30 Hz flicker and fused flicker (p = 0.005 and p = 0.018, respectively). Reduction in CMT and increased EZ disruption on OCT were associated with functional changes including poorer BCVA and decreased cone function on ERG.

Conclusion: We have described the natural long-term decline in vision and cone function associated with mutations in GUCY2D and identified a set of functional and structural biomarkers that may be useful as outcome parameters for future therapeutic clinical trials.

Purpose: To characterize the genotype and phenotype of a patient with CAPN5-related neovascular inflammatory vitreoretinopathy (NIV) who have undergone surgery for macular holes.

Methods: We observed a patient presenting with retinitis pigmentosa and posterior uveitis who later developed vitreoretinal macular traction and a macular hole. Genetic testing was performed using a targeted gene panel. Fundus photography and spectral-domain optical coherence tomography were also performed.

Results: In a targeted gene panel, a monoallelic pathogenic variant, c.750G > T, p.Lys250Asn, in the CAPN5 gene was identified, and CAPN5-NIV was diagnosed. At the first visit, peripheral retinal degeneration and mild posterior uveitis were observed. At that time, neovascularization, epiretinal or fibrous membranes were not observed. After 5 years, vitreomacular traction developed and progressed to a full-thickness macular hole in both eyes. After pars plana vitrectomy, the macular hole was successfully closed without aggravation of uveitis.

Conclusion: In this case, a pathogenic variant of CAPN5 lead to a distinct phenotype of retinitis pigmentosa, posterior uveitis, vitreomacular traction, and macular hole without typical inflammatory neovascularization or tractional membranes. Therefore, the clinical variability of CAPN5-NIV and genetic diagnosis should be considered in cases of atypical retinitis pigmentosa with bilateral macular hole.

Purpose: To determine the full-field electroretinogram (ffERG) parameters, including the light-adapted (LA) 3 ERG and the photopic negative response (PhNR), in 6- to 12-year-old children.

Methods: ffERG data were obtained from 214 eyes of 214 healthy subjects. The amplitudes and peak time of the ffERG responses were obtained from children divided into 6- to 8-year-old and 9- to 12-year-old groups. Using a skin electrode, electrical signals were measured in response to white stimulating light and white background light (LA 3 ERG). A blue background light and red flashes were then used to elicit the PhNR.

Results: The a-wave amplitude ranged from 0.40 to 9.20 μV, the b-wave ranged from 4.70 to 30.80 μV, and the PhNR ranged from 1.30 to 39.90 μV. The b-wave peak time (33.20 ms) of 6- to 8-year-old groups was slightly shorter than that of the 9- to 12-year-old groups (33.60 ms, P = 0.01), but no differences in amplitudes or in peak time of other components. There were significant correlations between the amplitudes (a-wave and b-wave: r = 0.43, p < 0.001; a-wave and PhNR: r = 0.25, p < 0.001; b-wave and PhNR: r = 0.45, p < 0.001). There was a moderate correlation between the a-wave and b-wave peak time (r = 0.31, P < 0.001).

Conclusions: We determined the largest dataset of the LA 3 ERG and PhNR parameters in a population of healthy children, aged 6-12 years, which may provide a useful reference value when evaluating children with potential retinal defects.

Purpose: To establish the extent of agreement for ISCEV standard reference pattern reversal VEPs (prVEPs) acquired at three European centres, to determine any effect of sex, and to establish reference intervals from birth to adolescence.

Methods: PrVEPs were recorded from healthy reference infants and children, aged 2 weeks to 16 years, from three centres using closely matched but non-identical protocols. Amplitudes and peak times were modelled with orthogonal quadratic and sigmoidal curves, respectively, and two-sided limits, 2.5th and 97.5th centiles, estimated using nonlinear quantile Bayesian regression. Data were compared by centre and by sex using median quantile confidence intervals. The 'critical age', i.e. age at which P100 peak time ceased to shorten, was calculated.

Results: Data from the three centres were adequately comparable. Sex differences were not clinically meaningful. The pooled data showed rapid drops in P100 peak time which stabilised by 27 and by 34 weeks for large and small check widths, respectively. Post-critical-age reference limits were 87-115 ms and 96-131 ms for large and small check widths, respectively. Amplitudes varied markedly and reference limits for all ages were 5-57 μV and 3.5-56 μV for large and small check widths, respectively.

Conclusions: PrVEP reference data could be combined despite some methodology differences within the tolerances of the ISCEV VEP Standard, supporting the clinical benefit of ISCEV Standards. Comparison with historical data is hampered by lack of minimum reporting guidelines. The reference data presented here could be validated or transformed for use elsewhere.