Artificial intelligence–assisted quantification of fundus tessellation in early-onset high myopia

PurposeThe purpose of our study was to evaluate the interocular symmetry and distribution of peripapillary vessel density in young myopic eyes.MethodsA cross-sectional observational study was designed. A total of 174 eyes of 87 young myopic patients were recruited in this study. According to spherical equivalent (SE), 48 eyes were classified as mild myopia with a mean SE of − 2.12D (SD 0.66D), 66 as moderate myopia with a mean SE of − 4.50D (SD 0.87D), and 60 as high myopia with a mean SE of − 7.39D (SD 1.30D). Optical coherence tomography angiography (OCTA) was used to measure the vessel density. The distribution and interocular symmetry of peripapillary vessel densities were analyzed.ResultsThe vessel densities in the whole image, peripapillary, superior and inferior sectors were significantly lower in the high myopia group than in the mild or moderate myopia group (All P < 0.001), and the density in the nasal sector was significantly lower in the high myopia group than in the mild group. And most interesting, the vessel densities in the inside disc and temporal sector showed no difference among the three myopic groups (All P > 0.05). By Pearson correlation analysis, the vessel densities in the whole image, peripapillary, superior, inferior and nasal sectors were negatively correlated with axial length (AL) and SE (All P < 0.001), but vessel densities in the inside disc and temporal sector did not show this correlation (All P > 0.05). Interocular symmetry was observed in all the vascular parameters through paired-samples t-tests (All P > 0.05), intraclass correlation coefficient (ICC) and Pearson correlation analysis (All P < 0.001).ConclusionThe density of radial peripapillary capillaries decreased in the myopic eye with axial elongation, and optical vascular parameters showed significant interocular symmetry among young myopic eyes.

BackgroundAxial length is determined by genetic and environmental influences. Disorders of axial length encompass both myopia and microphthalmia, accounting for significant visual impairment and blindness worldwide. Despite the ocular morbidity,...

We investigated changes in refraction and ocular biometrics in preschool children with early-onset high myopia. Sixty eyes of 60 children with a mean follow-up time of 58.5 months were included in this study. At baseline, mean age of children was 55.6 ± 13.1 months, mean spherical equivalent (SE) was − 8.59 ± 2.66 D, and 25.64 ± 1.16 mm for axial length (AL). The total annual rate of myopic progression and axial elongation were − 0.37 ± 0.39 D/year and 0.33 ± 0.18 mm/year, respectively. During follow-up period, there was a trend toward less myopic progression and axial elongation over time. Of the total participants, 24 children (40%) were in the myopia progression group and the remaining 36 children (60%) were in the myopia stability group. In multiple linear regression analysis, baseline SE and AL were independently associated with myopic progression, while age, sex, and baseline AL-to-CR ratio were not related to myopic progression. According to the model, more myopic SE (β = − 0.186, P = 0.035) and longer AL (β = − 0.391, P = 0.008) at baseline were significantly associated with myopic progression. Myopia progression in preschoolers with high myopia tended to be relatively modest, with 60% of subjects exhibited myopic stability. Higher myopic SE, and longer AL at baseline were associated with myopic progression in preschool children with high myopia.

To detect variants in 17 known potentially causative genes for non-syndromic myopia in 67 Tujia Chinese patients with early-onset high myopia (eo-HM). DNA from 67 unrelated patients with early onset (<7years old) high myopia (refraction error≤-6.00D or axial length>26mm) were subjected to whole-exome sequencing (WES). Variants in 17 candidate genes were analysed by multistep bioinformatics analysis. Subsequently, Sanger sequencing was used to verify identified candidate mutations and to assess available family members for co-segregation with myopia. A multistep systematic analysis of variants in 17 potentially causative genes for eo-HM revealed four novel pathogenic mutations and three potential pathogenic mutations in 4 of 17 genes in 7 of 67 (10.4%) probands. The pathogenic group included one missense mutation (c.100G>C, p.Asp34His) and one splice donor mutation (c.989+1G>A) in ARR3, one missense mutation (c.995C>A, p.Thr332Lys) in NDUFAF7 and one novel frameshift mutation (c.726dupA, p.Arg243fs*140) in SLC39A5. The potential pathogenic group included two missense mutations (c.3266A>G, p.Tyr1089Cys; c.913G>A, p.Glu305Lys) in ZNF644 and one missense mutation (c.960T>A, p.His320Gln) in NDUFAF7. Sequence changes were confirmed by Sanger sequencing; all had an allele frequency <0.01 in the 1000G, EVS, ExAC and gnomAD databases. Additionally, both the pathogenic and potentially pathogenic mutations were predicted to be damaging by SIFT, Polyphen-2, PROVEAN, MutationTaster2, CADD and REVEL except the p.Tyr1089Cys and p.Glu305Lys changes were predicted to be neutral by PROVEAN. Our research provides more evidence to support the hypothesis that mutations in ARR3, SLC39A5 and NDUFAF7 are disease-causing genes for eo-HM and broadens the eo-HM mutation spectrum among different ethnic groups. It also deepens understanding of the contributions of ARR3, SLC39A5, and NDUFAF7 to eo-HM.

Introduction: High myopia, defined by a spherical equivalent ≥ -6 diopters or an axial length ≥ 26 mm, can increase the risk of degenerative changes. The aim of this study was to correlate central choroidal thickness (CCT) and macular retinal sensitivity (MRS) in pseudophakic patients with high myopia.Material and Methods: Cross-sectional observational study in which high myopic eyes were included. CCT and MRS were analyzed by sector and correlated by semi-automatic segmentation. We used Topcon® DRI OCT and MP-3® Microperimeter for image acquisition.Results: 29 eyes from 20 patients were analyzed. CCT demonstrated increasing thickness from the nasal, inferior, central, temporal to the superior sector. MRS showed increasing sensibilities from the central sector, followed by the inferior, nasal, superior and temporal sector. The linear regression adjusted for gender and age verified correlation between the central MRS and the subfoveal CCT with p = 0.002 (R=0,551); between the central MRS and the mean CCT, in horizontal section with p = 0.006 (R=0.510) and in vertical section with p = 0.005 (R=0,513); between the MRS at the 6o inferior sector and the CCT at 1.5mm from the inferior sector with p = 0.018 (R=0.442), and finally, between the MRS at the 6o nasal sector and the CCT at 1.5mm from the nasal sector with p = 0.032 (R=0.407).Conclusion: After adjusting for gender and age, CCT is correlated with MRS in high myopic patients, and there was a statistically significant correlation (p<0.05) between the variables of interest in all sectors evaluated.

Genetic aetiology is suspected in the development of early-onset high myopia (spherical equivalent refractive error [SER] ≤-6.00 D at ≤6 years of age), considering that the role of environmental factors in inducing high myopia is improbable at an early age. Therefore, we aimed to understand if early-onset high myopia is associated with parental myopia in a clinical setting. A retrospective study was conducted in which information about demographics, age of apparent onset of myopia, refractive error, axial length, number of myopic parents, time spent outdoors and time spent on near-work was obtained from electronic medical records (EMR). It included 195 myopic individuals categorised into (1) Early-onset high myopes (EOHM): SER ≤ -6.00 D with age of presentation ≤6 years, (2) Early-onset low myopes (EOLM): SER > -6.00 D with age of apparent onset ≤6 years, (3) Late-onset high myopes (LOHM): SER ≤ -6.00 D with age of presentation and age of apparent onset >6 years and (4) Late-onset low myopes (LOLM): SER > -6.00 D with age of apparent onset >6 years. Overall, 63% of individuals were found to have parental myopia. The proportion of individuals with EOHM, EOLM, LOHM and LOLM with parental myopia was 57%, 74%, 53% and 64%, respectively. After adjustment for age, gender and environmental factors, the odds of development of EOHM (Odds ratio: 0.78, 95% confidence interval: 0.25-2.48), EOLM (1.54, 0.65-3.67) or LOHM (0.70, 0.30-1.65) were similar in the presence of myopic parents, when compared with LOLM. The SER and axial length did not differ based on the number of myopic parents in any of these categories. This retrospective analysis reveals that the presence of parental myopia, which was self-reported, did not induce additional risk for early-onset high myopia.

To evaluate the refractive differences among school-aged children with macular or peripapillary fundus tessellation (FT) distribution patterns, using fundus tessellation density (FTD) quantified by deep learning (DL) technology. The cross-sectional study included 1942 school children aged six to 15 years, undergoing ocular biometric parameters, cycloplegic refraction, and fundus photography. FTD was quantified for both the macular (6 mm) and peripapillary (4 mm) regions, using DL-based image processing applied to 45° color fundus photographs. Eyes exhibiting tessellation were classified into two groups: the macular distribution group had greater FTD in the macular area, while the peripapillary distribution group had higher FTD in the peripapillary area, allowing for a comparative analysis of axial length (AL), corneal radius, and refraction. Participants had a median age of 13years and a median spherical equivalent (SE) of -0.75 D. The macular distribution group exhibited significantly larger AL (24.13mm vs. 23.93mm, P < 0.001) and more myopic refraction (-1.13 D vs. -0.75 D, P < 0.001) compared to the peripapillary group. A higher prevalence of macular-distributed FT was noted in the myopic groups (χ2 = 131.675, P < 0.001). SE negatively correlated with macular (r = -0.238) and peripapillary FTD (r = -0.195), while AL positively correlated with FTD in both regions (r = 0.308; r = 0.265) (all P < 0.001). The macular FT distribution pattern is significantly associated with larger AL and greater myopic refraction in school-aged children, suggesting its potential as a marker for identifying children at risk of progressing myopia. DL analysis precisely identifies FT distribution patterns, potentially enhancing early detection of high-risk myopia in populations.

This study investigated the relationship between higher-order aberrations (HOAs) and myopia progression as well as axial elongation in schoolchildren. We examined cycloplegic refraction, axial length, and wavefront aberrations prospectively in 71 myopic children. Changes in cycloplegic refraction and axial length during a 2-year study period were assessed, and their correlations with HOA components were analyzed. Sixty-four subjects ([mean ± SD] 9.2 ± 1.6 years) completed the 2-year examinations. Cycloplegic refraction was significantly changed after 2 years (P < 0.0001), and the average change (myopia progression) was −1.60 ± 1.04 D. Axial length also increased significantly (P < 0.0001), and the average increase (axial elongation) was 0.77 ± 0.40 mm. Myopia progression and axial elongation showed significant correlations with many components of corneal HOA (P < 0.0001 to P = 0.0270). Multivariate analysis showed that the total HOA of the cornea was the most relevant variable to myopia progression and axial elongation (P < 0.0001). Eyes with larger amounts of corneal HOAs showed less myopia progression and smaller axial elongation, suggesting that corneal HOAs play a role in the refractive and ocular developments in children.

To determine the nature of hyperopia in children with accommodative refractive esotropia (ARE) by evaluating the relationships between corneal radius (CR), axial length (AL), age and equivalent spherical refraction (SEQ). A total of 112 children with ARE were included in the study. The children underwent an overall ophthalmic examination including cycloplegic refraction, keratometry and ultrasonic AL measurement. Statistical analysis revealed a strong relationship between AL and SEQ (p < 0.001). A significant correlation was also found between AL and CR (p < 0.001). The relationship between AL and age was weak but statistically significant (p = 0.02). Multiple regression analysis, using SEQ as the dependent variable and CR, AL and age as independent variables, revealed that AL accounts for 43.5% of the variance, and the combination of CR and AL accounts for 60.9% of the variance. Hyperopia is predominantly axial in nature in children with ARE. However, other refractive components are also involved in producing hyperopic refractive errors.

Ocular Axial Length and Choroidal Thickness in Newly Hatched Chicks and One-year-old Chickens Fluctuate in a Diurnal Pattern that is Influenced by Visual Experience and Intraocular Pressure Changes

To evaluate macular shape in normal eyes using swept-source optical coherence tomography (SS-OCT). Retrospective cross-sectional study. We retrospectively evaluated 77 normal eyes of 48 subjects. Curvature of retinal pitment epithelium (RPE) and choroid/scleral interface (CSI) was measured in vertical and horizontal SS-OCT 16-mm scanned images. After correcting the optical distortion of OCT images, curvatures of superior, central, and inferior sectors in the vertical scan, and temporal, central, and nasal sectors in the horizontal scan (each 4-mm length) were compared. Factors associated with overall RPE and CSI curvatures were investigated. RPE and CSI curvatures of superior, central, and inferior sectors in the vertical scan were 16.6±3.1, 13.8±2.1, 17.7±3.2 and 17.8±3.0, 13.8±3.3, 18.4±3.3 (×10-5 μm-1), respectively. Central curvature was significantly flatter than superior and inferior curvatures in both RPE and CSI (all P<0.001). The RPE and CSI curvatures of temporal, central, and nasal sectors in the horizontal scan were 17.2±2.3, 15.2±2.5, 18.8±2.7 and 18.3±2.7, 16.7±2.9,14.4±2.9 (×10-5 μm-1), respectively. While central curvature was significantly flatter than nasal and temporal curvatures in RPE (P<0.001 and P=0.025), nasal curvature was significantly flatter than central and temporal curvatures (P=0.027 and P<0.001) in CSI. Overall CSI curvature was significantly associated with axial length (AL) (P<0.001), whereas overall RPE curvature was significantly associated with overall CSI curvature (P<0.001), choroidal thickness (P<0.001), and AL (P=0.038) CONCLUSIONS: This study revealed that RPE curvature is associated with CSI curvature, choroidal thickness, and AL, suggesting that choroidal and scleral structures affect macular RPE curvature.

Associations of Peripapillary Atrophy and Fundus Tessellation with Diabetic Retinopathy

Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci. Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample. Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = -0.83; SE, 0.04; p = 1.95 × 10-89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10-55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04). Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk.

Myopia Control Effect of Repeated Low-Level Red-Light Therapy in Chinese Children: A Randomized, Double-Blind, Controlled Clinical Trial

PurposeTo investigate the dependence of the ciliary body length (CBL) on the axial length (AL) and to draw conclusions on implications regarding safe pars plana access for intravitreal injections and vitreoretinal surgery.MethodsA total of 200 individuals (mean age 42 years, SD ± 15.4) were enrolled in the study. Objective refraction and AL were obtained. Spherical equivalent (SE) was calculated. Anterior segment optical coherence tomography (ASOCT) was used to image and measure the CBL.ResultsThe mean SE was − 1.64 diopters (SD ± 3.15, range − 14.5 to + 9 diopters) and the mean AL was 24.19 mm (SD ± 1.65, range 19.8–32.2 mm). There was a significant correlation between SE and AL (r2 = 0.62, p < 0.0001). Mean CBL correlated significantly with age (r2 = 0.11, p < 0.0001), AL (r2 = 0.23, p < 0.0001) and SE (r2 = 0.25, p < 0.0001). The mean CBL was 3351 μm (SD ± 459, range 2184–4451 μm). Three separate groups were defined by their AL with a normal AL group (AL 22.5 to 25 mm), a short AL group (AL < 22.5 mm) and a long AL group (AL > 25 mm). The mean CBL in the normal AL group was 3311 μm (SD ± 427), in the short AL group 2936 μm (SD ± 335) and in the long AL group 3715 μm (SD ± 365), and differed significantly (p < 0.0001) when compared.ConclusionFor interventions requiring pars plana access (as an intravitreal injection or vitreoretinal surgery), an incision distance of 3.5–4.0 mm posterior to the limbus is recommended. In our research, however, a difference of 0.77 mm in mean CBL between the group with short AL and the group with long AL is demonstrated, implying that the mean CBL in very short and very long eyes differs significantly. These findings suggest that the AL should be taken into account for pars plana access and that it would be advisable to prefer the shorter or longer recommended distance (3.5 and 4.0 mm, respectively) from the limbus, which correlates with the AL. If AL is > 25 mm, a distance of 4.0 mm from the limbus should be chosen; and if AL is < 22.5 mm, a distance of 3.5 mm seems adequate.Trial registration number and dateNCT00564291, 27 Nov 2007