Retinal Changes From Hyperopia to Myopia: Not All Diopters Are Created Equal.

Purpose: To quantitatively characterize retinal changes across different quantiles of refractive error in 34,414 normal eyes of 23,064 healthy adults in the UK Biobank. Methods: Twelve optic disc (OD), foveal and vascular parameters were derived from color fundus photographs, correcting for ocular magnification as appropriate. Quantile regression was used to test the independent associations between these parameters and spherical equivalent refraction (SER) across 34 refractive quantiles (high hyperopia to high myopia)-controlling for age, sex and corneal radius. Results: More negative SER was nonlinearly associated with greater Euclidian (largely horizontal) OD-fovea distance, larger OD, less circular OD, more obliquely orientated OD (superior pole tilted towards the fovea), brighter fovea, lower vascular complexity, less tortuous vessels, more concave (straightened out towards the fovea) papillomacular arterial/venous arcade and wider central retinal arterioles/venules. In myopia, these parameters varied more strongly with SER as myopia increased. For example, while every standard deviation (SD) decrease in vascular complexity was associated with 0.63 D (right eye: 95% confidence interval [CI], 0.58-0.68) to 0.68 D (left eye: 95% CI, 0.63-0.73) higher myopia in the quantile corresponding to -0.60 D, it was associated with 1.61 D (right eye: 95% CI, 1.40-1.82) to 1.70 D (left eye: 95% CI, 1.56-1.84) higher myopia in the most myopic quantile. OD-fovea angle (degree of vertical separation between OD and fovea) was found to vary linearly with SER, but the magnitude was of little practical importance (less than 0.10 D variation per SD change in angle in almost all refractive quantiles) compared with the changes in OD-fovea distance. Conclusions: Several interrelated retinal changes indicative of an increasing (nonconstant) rate of mechanical stretching are evident at the posterior pole as myopia increases. These changes also suggest that the posterior pole stretches predominantly in the temporal horizontal direction.

PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness.

Purpose: We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (n = 45) and assessed how measurements compared with healthy controls (n = 46). We also developed automatic rejection thresholds and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (ß = -9.81; standard error [SE] = 3.16; P < 0.05), in the temporal inferior zone (ß = -29.78; SE = 8.32; P < 0.01), with the nasal/temporal ratio (ß = 0.88; SE = 0.34; P < 0.05), and in the whole disc (ß = -8.22; SE = 2.92; P < 0.05). Furthermore, pallor was significantly higher in the patient group. Last, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational Relevance: We think our method will be useful for the identification, monitoring, and progression of diseases characterized by disc pallor and optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.

Corneal biomechanics are not exclusively compromised in high myopia.

INTRODUCTION: Research assuming linearity has concluded that corneal biomechanics are compromised in high myopia. We investigated whether this assumption was appropriate and re-examined these associations across different levels of myopia. METHODS: Myopic (spherical equivalent refraction, SER ≤ -0.50 D) eyes of 10,488 adults aged 40-69 years without any history of systemic and ocular conditions were identified in the UK Biobank. Ordinary least squares (OLS) regression was employed to test the linear association between corneal hysteresis (CH) or corneal resistance factor (CRF), separately, and SER while controlling for age, sex, corneal radius and intraocular pressure. Quantile regression (QR) was used to test the same set of associations across 49 equally spaced conditional quantiles of SER. RESULTS: In OLS regression, each standard deviation (SD) decrease in CH and CRF was associated with 0.08 D (95% CI: 0.04-0.12; p < 0.001) and 0.10 D (95% CI: 0.04-0.15; p < 0.001) higher myopia, respectively. However, residual analysis indicated that the linearity assumption was violated. QR revealed no evidence of a significant association between CH/CRF and SER in low myopia, but a significant (p < 0.05) positive association became evident from -2.78 D (0.06 and 0.08 D higher myopia per SD decrease in CH and CRF). The magnitude of association increased exponentially with increasing myopia: in the -5.03 D quantile, every SD decrease in CH and CRF was associated with 0.17 D (95% CI: 0.08-0.25; p < 0.001) and 0.21 D (95% CI: 0.10-0.31; p < 0.001) higher myopia. In the -8.63 D quantile, this further increased to 0.54 D (95% CI: 0.33-0.76; p < 0.001) and 0.67 D (95% CI: 0.41-0.93; p < 0.001) higher myopia per SD decrease in CH and CRF. CONCLUSIONS: Corneal biomechanics appeared compromised from around -3.00 D. These changes were observed to be exponential with increasing myopia.

Factors associated with pathologic myopia onset and progression: A systematic review and meta-analysis.

PURPOSE: To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework. METHODS: Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework. RESULTS: Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21). CONCLUSIONS: Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted.

Higher intraocular pressure is associated with slower axial growth in children with non-pathological high myopia.

OBJECTIVES: To investigate the association between intraocular pressure (IOP) and axial elongation rate in highly myopic children from the ZOC-BHVI High Myopia Cohort Study. METHODS: 162 eyes of 81 healthy children (baseline spherical equivalent: -6.25 D to -15.50 D) aged 7-12 years with non-pathological high myopia were studied over five biennial visits. The mean (SD) follow-up duration was 5.2 (3.3) years. A linear mixed-effects model (LMM) was used to assess the association between IOP (at time point t-1) and axial elongation rate (annual rate of change in AL from t-1 to t), controlling for a pre-defined set of covariates including sex, age, central corneal thickness, anterior chamber depth and lens thickness (at t-1). LMM was also used to assess the contemporaneous association between IOP and axial length (AL) at t, controlling for the same set of covariates (at t) as before. RESULTS: Higher IOP was associated with slower axial growth (ß = -0.01, 95% CI -0.02 to -0.005, p = 0.001). There was a positive contemporaneous association between IOP and AL (ß = 0.03, 95% CI 0.01-0.05, p = 0.004), but this association became progressively less positive with increasing age, as indicated by a negative interaction effect between IOP and age on AL (ß = -0.01, 95% CI -0.01 to -0.003, p = 0.001). CONCLUSIONS: Higher IOP is associated with slower rather than faster axial growth in children with non-pathological high myopia, an association plausibly confounded by the increased influence of ocular compliance on IOP.

A Systematic Review and Meta-Analysis of Applying Deep Learning in the Prediction of the Risk of Cardiovascular Diseases From Retinal Images.

Purpose: The purpose of this study was to perform a systematic review and meta-analysis to synthesize evidence from studies using deep learning (DL) to predict cardiovascular disease (CVD) risk from retinal images. Methods: A systematic literature search was performed in MEDLINE, Scopus, and Web of Science up to June 2022. We extracted data pertaining to predicted outcomes, model development, and validation and model performance metrics. Included studies were graded using the Quality Assessment of Diagnostic Accuracies Studies 2 tool. Model performance was pooled across eligible studies using a random-effects meta-analysis model. Results: A total of 26 studies were included in the analysis. There were 42 CVD risk-related outcomes predicted from retinal images were identified, including 33 CVD risk factors, 4 cardiac imaging biomarkers, 2 CVD risk scores, the presence of CVD, and incident CVD. Three studies that aimed to predict the development of future CVD events reported an area under the receiver operating curve (AUROC) between 0.68 and 0.81. Models that used retinal images as input data had a pooled mean absolute error of 3.19 years (95% confidence interval [CI] = 2.95-3.43) for age prediction; a pooled AUROC of 0.96 (95% CI = 0.95-0.97) for gender classification; a pooled AUROC of 0.80 (95% CI = 0.73-0.86) for diabetes detection; and a pooled AUROC of 0.86 (95% CI = 0.81-0.92) for the detection of chronic kidney disease. We observed a high level of heterogeneity and variation in study designs. Conclusions: Although DL models appear to have reasonably good performance when it comes to predicting CVD risk, further work is necessary to evaluate the real-world applicability and predictive accuracy. Translational Relevance: DL-based CVD risk assessment from retinal images holds great promise to be translated to clinical practice as a novel approach for CVD risk assessment, given its simple, quick, and noninvasive nature.

Emmetropic eye growth in East Asians and non-East Asians.

PURPOSE: To compare axial length (AL) growth curves in East Asian (EA) and non-EA emmetropes. METHODS: A meta-regression of 28 studies with emmetrope-specific AL data (measured with optical biometry) was performed. Emmetropia was defined as spherical equivalent refraction (SER) between -0.50 and +1.25 D, determined under cycloplegia if the mean age was ≤20 years. The AL growth curve (mean AL vs. mean age) was first fitted to the full dataset using a weighted nonlinear mixed-effects model, before refitting the model with ethnicity as a two-level grouping variable (EA vs. non-EA). Ethnic differences in growth curve parameters were tested using the Wald test. RESULTS: A total of 3331 EA and 1071 non-EA emmetropes (mean age: 6.5-23.1 years) were included. There was no evidence of an ethnic difference in either final AL (difference: 0.15 mm, 95% CI: -0.04 to 0.35 mm, p = 0.15) or initial AL, as represented by the amount that the final AL needed to be offset to obtain the y-intercept (difference: -2.77 mm, 95% CI: -10.97 to 5.44, p = 0.51). Likewise, AL growth rate (curve steepness) did not differ between ethnic groups (difference: 0.09, 95% CI: -0.13 to 0.31, p = 0.43). Collectively, AL growth rate decreased from 0.24 mm/year at 6 years of age to around 0.05 mm/year at 11 years of age, after which it dipped below the repeatability of optical biometry (±0.04 mm) and practically plateaued around 16 years of age (final AL: 23.60 mm). CONCLUSIONS: EA and non-EA emmetropes have comparable AL growth curves.