Myopia is the most common refractive error worldwide. This cannot be explained by genetic factors alone, therefore, environmental factors may play an important role. Hence, the main objective of this study was to analyse whether outdoor exposure could exert a protective effect against the development of myopia in a cohort of young adults and to investigate ultraviolet autofluorescence (CUVAF), as a biomarker of time spent outdoors. A cross-sectional observational study was carried out using two cohorts. A total of 208 participants were recruited, 156 medical students and 52 environmental science students. The data showed that 66.66% of the medical students were myopic, while 50% of the environmental science students were myopic (p = 0.021). Environmental science students spent significantly more hours per week doing outdoor activities than medical students (p < 0.0001), but there was no significant difference with respect to near work activities between them. In both cohorts, the degree of myopia was inversely associated with CUVAF, and a statistically significant positive correlation was observed between spherical equivalent and CUVAF (Pearson's r = 0.248). In conclusion, outdoor activities could reduce the onset and progression of myopia not only in children, but also in young adults. In addition, CUVAF represents an objective, non-invasive biomarker of outdoor exposure that is inversely associated with myopia.

Purpose To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total(R); N) on oxidative stress and inflammation-like induced conditions by H2O2 and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H2O2-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFN gamma in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total(R) protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.

Purpose To study the relationship between macular ganglion cell complex (GCC) thickness and visual field defects (VFD) caused by central nervous system (CNS) lesions in children and evaluate the possibility of predicting VFD according to GCC maps. Methods The GCC maps of a group of children with VFD due to CNS lesions with respect of the vertical meridian in at least one eye (study group), as well as of children with other neuro-ophthalmological problems and healthy children were presented to two masked evaluators, who were asked to predict the patients' VFD on the basis of GCC damage: the evaluators classified VFD as normal, hemianopia (homonymous or heteronymous) or diffuse. Results Seventeen patients were included in the study group, with a median age of 12 years. Fifteen had brain tumours and two epilepsy. The mean MD of the affected hemifields was -26.00 dB (SD 7.89 dB) versus -5.51 dB (SD 3.52 dB) for the nonaffected hemifields,p < 0.001. The mean GCC thickness was of 56.04 mu m (SD 11.95 mu m) in the affected hemiretinas versus 74.31 mu m (SD 10.64 mu m) for the non-affected,p < 0.001. Kappa coefficients between VFD and those estimated by the evaluators were 0.705 and 0.658 (p < 0.001) for evaluators 1 and 2. Conclusions GCC thickness can reflect damage to the visual pathway and GCC maps may be useful to identify chiasmal and retrochiasmal lesions, since GCC atrophy in most of these cases respects the vertical meridian. GCC maps might be used as a surrogate marker for visual damage in patients unable to perform perimetry.

Introduction. Even though ocular refractive state is highly heritable and under strong genetic control, the identification of susceptibility genes remains a challenge. Several HGF (hepatocyte growth factor) gene variants have been associated with ocular refractive errors and corneal pathology. Purpose. Here, we assess the association of an HGF gene variant, previously reported as associated with hyperopia, and ocular biometric parameters in a multicenter Spanish cohort. Methods. An observational prospective multicenter cross-sectional study was designed, including a total of 403 unrelated subjects comprising 188 hyperopic children (5 to 17years) and 2 control groups: 52 emmetropic adolescents (13 to 17years) and 163 emmetropic young adults (18 to 28years). Each individual underwent a comprehensive eye examination including cycloplegic refraction, and topographic and ocular biometric analysis. Genomic DNA was extracted from oral swabs. HGF single nucleotide polymorphism (SNP) rs12536657 was genotyped. Genotypic, allelic, and logistic regression analyses were performed comparing the different groups. A quantitative trait association test analyzing several biometric parameters was also performed using generalized estimating equations (GEEs) adjusting for age and gender. Results. No association between rs12536657 and hyperopia was found through gender-adjusted logistic regression comparing the hyperopic children with either of the two control groups. Significant associations between mean topographic corneal curvature and rs12536657 for G/A (slope=+0.32; CI 95%: 0.04-0.60; p=0.023) and A/A (slope=+0.76; CI 95%: 0.12-1.40; p=0.020) genotypes were observed with the age- and gender-adjusted univariate GEE model. Both flat and steep corneal topographic meridians were also significantly associated with rs12536657 for the G/A and A/A genotypes. No association was found between rs12536657 and any other topographic or biometric measurements. Conclusions. Our results support a possible role for HGF gene variant rs12536657 in corneal curvature in our population. To our knowledge, this is the first multicenter quantitative trait association study of HGF genotypes and ocular biometric parameters comprising a pediatric cohort.

Gillespie syndrome (GS) is characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, and progressive cerebellar atrophy. Trio-based exome sequencing identified de novo mutations in ITPR1 in three unrelated individuals with GS recruited to the Deciphering Developmental Disorders study. Whole-exome or targeted sequence analysis identified plausible disease-causing ITPR1 mutations in 10/10 additional GS-affected individuals. These ultra-rare protein-altering variants affected only three residues in ITPR1: Glu2094 missense (one de novo, one co-segregating), Gly2539 missense (five de novo, one inheritance uncertain), and Lys2596 in-frame deletion (four de novo). No clinical or radiological differences were evident between individuals with different mutations. ITPR1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. The homo-tetrameric structure has been solved by cryoelectron microscopy. Using estimations of the degree of structural change induced by known recessive- and dominant-negative mutations in other disease-associated multimeric channels, we developed a generalizable computational approach to indicate the likely mutational mechanism. This analysis supports a dominant-negative mechanism for GS variants in ITPR1. In GS-derived lymphoblastoid cell lines (LCLs), the proportion of ITPR1-positive cells using immunofluorescence was significantly higher in mutant than control LCLs, consistent with an abnormality of nuclear calcium si

. Purpose: To compile a multicenter normative database of retinal nerve fibre layer (RNFL) and macular thicknesses and macular volume values in healthy Caucasian children 417 years using spectral-domain optical coherence tomography (SD-OCT). To analyse variations in the OCT measurements as a function of age, sex, refraction, and axial length (AL). Methods: An observational, multicenter and cross-sectional study among 301 healthy Caucasian children recruited at three Spanish centres was performed. To compile the database, each child underwent a dilated eye examination and a cycloplegic refraction, five AL measurements (IOL Master; Carl Zeiss Meditec, Dublin, CA, USA), five OCT scans with Cirrus OCT: three peripapillary RNFL scans (Optic Disc Cube 200X200 protocol) and two macular scans (Macular Cube 512X128 protocol). One eye of each subject was selected randomly for analysis. Results: Two hundred eighty-three children (117 boys, 41.34%; 166 girls, 58.66%) were included in this study. The mean age of the children was 9.58 +/- 3.12 years (range, 417). The mean SE was +0.63 +/- 1.65 D; (range, -4.88 to +5.25). The mean AL was 22.94 +/- 1.10 mm (range, 20.1026.27). The mean global RNFL thickness was 97.40 +/- 9.0 mu m (range, 77121.7 mu m). Multivariate analysis showed a positive correlation between the RNFL and spherical equivalent (SE) (p = 0.014). The mean central macular thickness was 253.85 +/- 19.76 mu m, the average thickness 283.62 +/- 14.08 mu m, and the mean macular volume 10.22 +/- 0.49 mu m3. Multivariate analysis showed a positive correlation between central macular thickness and age (p < 0.001). Boys had a significantly thicker central macula than girls (p < 0.001). Conclusions: Normative paediatric SD-OCT data might facilitate use of SD-OCT for assessing childhood ophthalmic diseases. This study provides a multicenter paediatric normative database of SD-OCT peripapillary RNFL and macular data.

Purpose: To evaluate the frequency and characteristics of misalignments (MAs) in the retinal nerve fiber layer (RNFL) analysis protocol of spectral-domain optical coherence tomography (Cirrus) and determine factors associated with MAs. Methods: Three hundred eyes (162 normal and 138 glaucomatous eyes) were included in this cross-sectional study. The MAs were considered limited when they affected only part of the scan line, and complete (CMA) when they were observed in the entire scan line. A subgroup (153 cases) with repeated scans was analyzed to compare the RNFL thicknesses in the scans with and without CMAs. Results: Two hundred ninety-nine limited MAs were found in 140 eyes (46.7%) and 151 CMAs were found in 91 eyes (30.3%). The frequency and number of CMAs were significantly related to age (P<0.05). Seventy-two CMAs were in the measurement ring in 48 eyes, more frequently in the 3 and 9-o'clock positions (P=0.001) and the horizontal quadrants (P=0.001). Among the repeated scans, the number of cases with CMAs was similar to the first scan (P=0.32). No significant differences were found in global or quadrant RNFL thickness between scans with and without CMAs. Conclusions: CMAs were present in the first or second scans in about 30% of cases and were related to older age. CMAs were more frequently in horizontal meridians and quadrants. No differences in RNFL thickness were found between scans with and without CMAs in the same patients. Scans with CMAs in the measurement ring can be considered in the RNFL evaluation.