Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1.

BACKGROUND: The sodium channel and clathrin linker 1 gene (SCLT1) has been involved in the pathogenesis of various ciliopathy disorders such as Bardet-Biedl syndrome, orofaciodigital syndrome type IX, and Senior-Løken syndrome. Detailed exams are warranted to outline all clinical features. Here, we present a family with a milder phenotype of SCLT1-related disease. MATERIAL AND METHODS: Comprehensive eye examination including fundus images, OCT, color vision, visual fields and electroretinography were performed. Affected individuals were assessed by a pediatrician and a medical geneticist for systemic features of ciliopathy. Investigations included echocardiography, abdominal ultrasonography, blood work-up for diabetes, liver and kidney function. Genetic testing included NGS retinal dystrophy panel, segregation analysis and transcriptome sequencing. RESULTS: Two male children, age 10 and 8 years, were affected with attention deficit hyperactivity disorder (ADHD), obesity and mild photophobia. The ophthalmic exam revealed reduced best-corrected visual acuity (BCVA), strabismus, hyperopia, astigmatism and moderate red-green defects. Milder changes suggesting photoreceptors disease were found on retinal imaging. Electroretinogram confirmed cone photoreceptors dysfunction. Genetic testing revealed a homozygous likely pathogenic, splice-site variant in SCLT1 gene NM_144643.3: c.1439 + 1del in the proband and in the affected brother. The unaffected parents were heterozygous for the SCLT1 variant. Transcriptome sequencing showed retention of intron 16 in the proband. CONCLUSIONS: In this report, we highlight the importance of further extensive diagnostics in patients with unexplained reduced vision, strabismus, refractive errors and ADHD spectrum disorders. SCLT1-related retinal degeneration is very rare and isolated reduced function of cone photoreceptors has not previously been observed.

Retinal nerve fiber layer thickness associates with cognitive impairment and physical disability in multiple sclerosis.

BACKGROUND: Reductions of the peripapillary retinal nerve fiber layer (pRNFL) thickness has been indicated even in early-stages of multiple sclerosis (MS). The aim was to investigate the association between pRNFL thickness, measured with optical coherence tomography (OCT), and physical disability and cognitive impairment in MS. METHODS: 465 MS patients and 168 healthy controls (HCs) were included. MS subjects were divided into subgroups according to disease subtype. All subjects underwent OCT examination of all pRNFL quadrants using Canon OCT-HS100. Associations were tested using linear mixed effect models. Physical disability was assessed with the Expanded Disability Status Scale (EDSS) and cognitive function with the Symbol Digit Modalities Test (SDMT). RESULTS: The average pRNFL, inferior pRNFL and temporal pRNFL thicknesses were significantly correlated to both EDSS (-1.0 µm, p < 0.01; -1.2 µm, p < 0.05; -1.2 µm, p < 0.01) and SDMT (0.1 µm, p < 0.05; 0.2 µm, p < 0.05; 0.2 µm, p < 0.01). A significant thickness loss compared with HCs was seen in the average pRNFL and in all quadrants except for the superior quadrant of primary progressive MS. The largest reduction compared with HCs was seen in the temporal pRNFL of PPMS eyes (-15.8 µm; p < 0.001). CONCLUSION: The reduction of average pRNFL, inferior pRNFL and temporal pRNFL thickness is associated with physical and cognitive disability in MS. We suggest the use of temporal pRNFL as a more sensitive outcome as it showed the strongest association to both EDSS and SDMT.

The Temporal Retinal Nerve Fiber Layer Thickness Is the Most Important Optical Coherence Tomography Estimate in Multiple Sclerosis.

BACKGROUND: Reduced peripapillary retinal nerve fiber layer (pRNFL) and combined ganglion cell and inner plexiform layer (GCIP) thicknesses as measured by optical coherence tomography (OCT) have been observed in multiple sclerosis (MS) patients. The purpose was to determine the most associative OCT measure to level of cognitive and physical disability in MS. METHODS: Data were collected from 546 MS patients and 175 healthy controls (HCs). We compared the average pRNFL, temporal pRNFL (T-pRNFL), overall inner ganglion cell/inner plexiform layer (GCIP), and the overall ganglion cell complex (GCC) including macular RNFL and GCIP thicknesses measurements in differentiating MS subtypes from HCs. The association between OCT measures, Expanded Disability Status Scale (EDSS), and Symbol Digit Modalities Test (SDMT) were assessed using generalized estimating equations models. RESULTS: Both peripapillary and macular OCT measurements could differentiate all MS subtypes from HCs. The SDMT score was significantly associated with reduced thickness of all OCT measures, mostly in average pRNFL (0.14 µm, P = 0.001) and T-pRNFL (0.17 µm, P < 0.001). The EDSS score was significantly associated with reduced inner retinal layer thickness. The largest reduction was seen in T-pRNFL (-1.52 µm, P < 0.001) and inner GCC (-1.78 µm, P < 0.001). CONCLUSION: The T-pRNFL is highly sensitive and associated with level of both cognitive and physical disability.

Objective Assessment of Nuclear and Cortical Cataracts through Scheimpflug Images: Agreement with the LOCS III Scale.

PURPOSE: To assess nuclear and cortical opacities through the objective analysis of Scheimpflug images, and to check the correlation with the Lens Opacity Classification System III (LOCS III). METHODS: Nuclear and cortical opacities were graded according to the LOCS III rules after pupil dilation. The maximum and average pixel intensity values along an elliptical mask within the lens nucleus were taken to analyse nuclear cataracts. A new metric based on the percentage of opaque pixels within a region of interest was used to analyse cortical cataracts. The percentage of opaque pixels was also calculated for half, third and quarter areas from the region of interest's periphery. RESULTS: The maximum and average intensity values along the nucleus were directly proportional to the LOCS III grade: The larger the LOCS III value, the larger maximum and average intensity ones. These metrics showed a positive and significant correlation with the LOCS grade: The larger the LOCS grade, the higher was percentage of opaque pixels along the cortex within the same mask's size. This metric showed a significant correlation to the LOCS grade. CONCLUSION: The metrics used to assess nuclear opacities showed good correlation with the LOCS III. The percentage of opaque pixels showed to be a useful metric to measure objectively the severity of the cortical opacity. These metrics could be implemented in an algorithm to detect and grade lens opacities automatically and objectively.

Repeatability Using Automatic Tracing with Canon OCT- HS100 and Zeiss Cirrus HD-OCT 5000.

BACKGROUND: Optical coherence tomography (OCT), can be used in clinical practice to provide high resolution cross-sectional images of the retina, optic disc and macula structure. These measurements can be useful for early detection, diagnosis, monitoring and treatment guidance for retinal diseases. Therefore, repeatability of measurements in OCT is of great importance. METHODS: Macula and optic disc parameters from the right eye of 30 healthy subjects were obtained twice with the Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. Repeatability was evaluated by use of the coefficient of repeatability (CR) and the coefficient of repeatability as a percentage of the mean (CR%), and the obtained measurements were compared between the instruments. RESULTS: CR% of optic disc parameters ranged between 0.90 and 22.22% and 0.00 and 16.00% with the Canon and Zeiss OCT respectively. For macular parameters CR% ranged between 0.62 and 2.81% and 0.99 and 1.81% with the Canon and Zeiss OCT respectively. No statistical difference could be found when comparing the CR of all macular and disc measurements between the instruments. Compared to our previously published data repeatability has significantly improved with the inclusion of automatic tracking systems with both the Canon and Zeiss OCT. CONCLUSION: Automatic tracking function improves repeatability in both Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. However, measurements generated by the two instruments are still not interchangeable.

Reproducibility of disc and macula optical coherence tomography using the Canon OCT-HS100 as compared with the Zeiss Cirrus HD-OCT.

PURPOSE: In a clinical setting, the usefulness of optical coherence tomography (OCT) is strongly dependent on reproducibility of the measurement. The aim of the present study was to evaluate macula and optic disc measurement reproducibility with the new spectral-domain OCT (SD-OCT) from Canon (Canon OCT-HS100) and to compare reproducibility and obtained measurements with the Zeiss Cirrus HD-OCT. METHODS: Macula and optic disc parameters from the right eyes of 31 subjects were obtained twice with both instruments. Interoperator reproducibility was evaluated by use of the coefficient of repeatability (CR), and the obtained measurements were compared between the instruments. RESULTS: No difference in interoperator reproducibility could be found when comparing the 2 instruments and reproducibility ranged from 3.94% to 12.77% for optic disc parameters and from 1.19% to 3.54% for macula parameters. The lowest reproducibility was found for cup volume and vertical cup/disc ratio with both instruments. For all macula and retinal nerve fiber layer (RNFL) thickness measurements, there was a statistical difference when comparing the 2 instruments, except for RFNL measurements of the superior quadrant, with the Canon OCT-HS100 always evaluating the thickness to be thicker; however, the 2 instruments correlated well. CONCLUSIONS: The Canon OCT-HS100 is a reproducible instrument that matches the Zeiss Cirrus HD-OCT well. It remains to be evaluated how sensitive the Canon OCT-HS100 is to detect small subtle changes in optic disc parameters and macular nerve fiber layer thickness. Furthermore, due to the differences in thickness estimation, it is important to emphasize that SD-OCTs are not interchangeable.