Pathologic myopia in highly myopic patients with high axial anisomyopia.

PURPOSE: To determine prevalence of anisomyopia (axial length (AL) difference ≥2.5 mm) among high myopes ((HMs), defined by spherical equivalent of ≤6.0 diopters or AL ≥ 26.5 mm). To characterise the shorter anisomyopic eye (SAE) and evaluate if pathologic myopia (PM) in the longer anisomyopic eye (LAE) was associated with increased risk of PM in the SAE. METHODS: 1168 HMs were recruited from Singapore National Eye Centre clinic for this cross-sectional study. Biometry, fundus photography and swept-source optical coherence tomography were performed. Patients with high axial anisomyopia were identified. Structural characteristics and presence of PM were described. Stepwise multivariate regression explored associations between PM in the LAE and pathology in the SAE, controlling for confounding variables. RESULTS: Prevalence of anisomyopia was 15.8% (184 of 1168 patients). Anisomyopic patients (age 65.8±13.5 years) had mean AL of 30.6±2.0 mm and 26.2±2.3 mm in the LAE and SAE, respectively. 52.7% of SAEs had AL < 26.5 mm. Prevalence of myopic macular degeneration, macula-involving posterior staphyloma (PS), myopic traction maculopathy (MTM) and myopic choroidal neovascularisation (mCNV) in the SAE was 52.2%, 36.5%, 13.0% and 8.2%, respectively. Macular hole in the LAE was associated with increased risk of MTM in the SAE (OR=4.88, p=0.01). mCNV in the LAE was associated with mCNV in the SAE (OR=3.57, p=0.02). PS in the LAE was associated with PS in the SAE (OR=4.03, p<0.001). CONCLUSIONS: Even when controlled for AL, PM complications in the LAE predict similar PM complications in the SAE. Patients with high axial anisometropia with PM in the LAE should be monitored carefully for complications in the SAE.

Ultrasound Assessment of Gaze-induced Posterior Eyewall Deformation in Highly Myopic Eyes.

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma. Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed. Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (ß = 0.050, P < 0.001) and absolute value of KMax (ß = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The ß coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L. Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

Quantitative assessment of the choroidal vasculature in myopic macular degeneration with optical coherence tomographic angiography.

Background: To assess and compare choroidal morphometric vascular parameters, using optical coherence tomographic angiography (OCTA), in highly myopic adults with and without myopic macular degeneration (MMD). Methods: This is a clinic-based observational study of 148 eyes with axial length (AL) ≥25mm, enrolled from the high myopia clinic of the Singapore National Eye Centre. MMD was graded from fundus photographs. Swept source OCT (SS-OCT) and OCTA were performed and assessed for choroidal layer thickness (CT) and choroidal vasculature (choroidal vessel density (CVD), choroidal branch area (CBA) and mean choroidal vessel width (MCVW)) in the different choroidal layers (overall choroidal layer (CL), medium-vessel choroidal layer (MVCL), large-vessel choroidal layer (LVCL)). Results: CTCL (r=-0.58, p<0.001), CTMVCL (r=-0.22, p=0.04), MCVWCL (r=-0.58, p<0.001), and CVDCL (r=-0.19, p=0.02) were negatively correlated with AL, while CBACL (r=0.61, p<0.001) was positively correlated. Compared to eyes with no MMD, eyes with MMD2 had lower CTCL (120.37±47.18µm vs 218.33±92.70µm, p<0.001), CTMVCL (70.57±15.28µm vs 85.32±23.71µm, p=0.04), CTLVCL (101.65±25.36µm vs 154.55±68.41µm, p=0.001) and greater CVDCL (71.10±3.97% vs 66.97±3.63%, p<0.001), CVDMVCL (66.96±2.35% vs 65.06±2.69%, p=0.002), CVDLVCL (68.36±2.56% vs 66.58±2.88%, p=0.012), MCVWMVCL (6.14±0.34µm vs 5.90±0.35µm, p=0.007), and CBACL (12.69±1.38% vs 11.34±1.18%, p<0.001). After adjusting for age, thicker CTCL (odds ratio (OR) 0.98, 95% confidence interval (CI) 0.97-0.99, p<0.001), CTMVCL (OR 0.97 (0.94-0.99), p=0.002) and CTLVCL (OR 0.97 (0.96-0.98, p<0.001) were significantly associated with lower odds of MMD2, while increased CVDCL (OR 1.37 (1.20-1.55), p<0.001), CVDMVCL (OR 1.39 (1.12-1.73), p=0.003), CVDLVCL (OR 1.31 (1.07-1.60), p=0.009), CBACL (OR 2.19 (1.55-3.08), p<0.001) and MCVWMVCL (OR 6.97 (1.59-30.51), p=0.01) was significantly associated with higher odds of MMD2. Conclusion: Decrease in choroidal vessel width, density and thickness, and an increase in vascular branching were observed in eyes with long AL. A thinner and denser choroid with greater branching area and vessel width, which may all be signs of hypoxia, were associated with greater odds of MMD2.

Choroidal Thickness in Early Postnatal Guinea Pigs Predicts Subsequent Naturally Occurring and Form-Deprivation Myopia.

Purpose: To identify choroidal characteristics associated with susceptibility to development of naturally occurring and experimentally induced myopia. Methods: We compared choroidal properties between pigmented and albino guinea pig (GP) strains. Biometry, cycloplegic refractive error (RE), and eye wall sublayer thickness were measured from 171 GPs at postnatal day (P)6, 14, and 28. Forty-three P14 GPs underwent two-week monocular form-deprivation myopia (FDM). En face images of choroidal vasculature were obtained with a customized swept-source optical coherence tomography. Multivariate regression analyses were performed, with P28 RE as the outcome and P14 choroidal thickness (ChT) as the main predictor variable. Proteomic analysis was performed on choroidal tissue from P14 albino and pigmented GPs. Results: At P14, RE was correlated with thickness of the choroid (ß = 0.06), sclera (ß = 0.12), and retina (ß = 0.27; all P < 0.001). P14 ChT was correlated with P28 RE both with (ß = 0.06, P = 0.0007) and without FDM (ß = 0.05, P = 0.008). Multivariate regression analysis, taking into account FDM (versus physiological growth) and strain, revealed that for every 10-µm greater ChT at P14, P28 RE was 0.50D more positive (P = 0.005, n = 70). En face images of choroidal sublayers showed that albino choroids were relatively underdeveloped, with frequent avascular regions. Consistent with this finding, proteomic analysis suggested abnormalities of the nitric oxide system in the albino GP choroid. Conclusions: Current results are consistent with the notion that greater ChT could protect from or delay the onset of myopia, while lower ChT is associated with greater susceptibility to myopia development. The underlying mechanism could be related to dysfunction of the choroidal vascular system.

Automated Classification and Detection of Staphyloma with Ultrasound Images in Pathologic Myopia Eyes.

The aim of this study was to develop an eyewall curvature- and axial length (AxL)-based algorithm to automate detection (clinician-free) of staphyloma ridge and apex locations using ultrasound (US). Forty-six individuals (with emmetropia, high myopia or pathologic myopia) were enrolled in this study (AxL range: 22.3-39.3 mm), yielding 130 images in total. An intensity-based segmentation algorithm automatically tracked the posterior eyewall, calculating the posterior eyewall local curvature (K) and distance (L) to the transducer and the location of the staphyloma apex. By use of the area under the receiver operator characteristic (AUROC) curve to evaluate the diagnostic ability of eight local statistics derived from K, L and AxL, the algorithm successfully quantified non-uniformity of eye shape with an AUROC > 0.70 for most K-based parameters. The performance of binary classification (staphyloma absence vs. presence) was assessed with the best classifier (the combination of AxL, standard deviation of K and standard deviation of L) yielding a diagnostic validation performance of 0.897, which was comparable to the diagnostic performance of junior clinicians. The staphyloma apex was localized with an average error of 1.35 ± 1.34 mm. Combined with the real-time data acquisition capabilities of US, this method can be employed as a screening tool for clinician-free in vivo staphyloma detection.

MACULAR SENSITIVITY AND CAPILLARY PERFUSION IN HIGHLY MYOPIC EYES WITH MYOPIC MACULAR DEGENERATION.

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

Association of Aberrant Posterior Vitreous Detachment and Pathologic Tractional Forces With Myopic Macular Degeneration.

Purpose: The purpose of this study was to assess whether the tractional elements of pathologic myopia (PM; e.g. myopic traction maculopathy [MTM], posterior staphyloma [PS], and aberrant posterior vitreous detachment [PVD]) are associated with myopic macular degeneration (MMD) independent of age and axial length, among highly myopic (HM) eyes. Methods: One hundred twenty-nine individuals with 239 HM eyes from the Myopic and Pathologic Eyes in Singapore (MyoPES) cohort underwent ocular biometry, fundus photography, swept-source optical coherence tomography, and ocular B-scan ultrasound. Images were analyzed for PVD grade, and presence of MTM, PS, and MMD. The χ² test was done to determine the difference in prevalence of MMD between eyes with and without PVD, PS, and MTM. Multivariate probit regression analyses were performed to ascertain the relationship between the potential predictors (PVD, PS, and MTM) and outcome variable (MMD), after accounting for possible confounders (e.g. age and axial length). Marginal effects were reported. Results: Controlling for potential confounders, eyes with MTM have a 29.92 percentage point higher likelihood of having MMD (P = 0.003), and eyes with PS have a 25.72 percentage point higher likelihood of having MMD (P = 0.002). The likelihood of MMD increases by 10.61 percentage points per 1 mm increase in axial length (P < 0.001). Subanalysis revealed that eyes with incomplete PVD have a 22.54 percentage point higher likelihood of having MMD than eyes with early PVD (P = 0.04). Conclusions: Our study demonstrated an association between tractional (MTM, PS, and persistently incomplete PVD) and degenerative elements of PM independent of age and axial length. These data provide further insights into the pathogenesis of MMD.

Multimodal Imaging-Based Phenotyping of a Singaporean Hospital-Based Cohort of High Myopia Patients.

Purpose: To assess the effect of axial length (AL) on the prevalence of pathologic myopia (PM) and associated myopic features in a Singaporean hospital-based cohort of patient with high myopia (HM). Methods: In total, 923 HM eyes from 495 individuals were recruited from the Myopic and Pathologic Eyes in Singapore (MyoPES) cohort and underwent ocular biometry, fundus photography, fundus autofluorescence, and swept-source optical coherence tomography (SS-OCT). Images were analyzed for the presence of myopic macular degeneration (MMD), myopic choroidal neovascularization (mCNV), myopic traction maculopathy (MTM), peripapillary atrophy (PPA), myopic tilted disc, posterior staphyloma (PS), dome-shaped macula (DSM), vitremacular adhesions (VMA), and the epiretinal membrane (ERM). Eyes were stratified into quartiles based on ALs to determine cut-off values to perform comparisons between shorter-length and longer-length groups. A χ2-test was done to determine the difference in the prevalence of pathologies between groups. Results: Overall, mean AL was 29.2 ± 2.2 mm (range 25.0-36.7 mm). Myopic macular degeneration, PPA, myopic tilted disc, and ERM have AL threshold of ≥27.5 mm, whereas MTM has an AL threshold of ≥29.0 mm. We found that there was a significantly higher prevalence of MMD (88.2 vs. 49.4%; p < 0.001), PPA (98.1 vs. 80.1%; p < 0.001), myopic tilted disc (72.7 vs. 50.2%; p < 0.001), and ERM (81.4 vs. 17.3%; p = 0.003) in eyes with AL ≥ 27.5 mm vs. eyes without AL <27.5 mm. Prevalence of MTM (34.7 vs. 32.1%; p < 0.001), mCNV (17.4 vs. 12.1%; p = 0.03), PS (43.4 vs. 34.7%; p = 0.012), DSM (21.3 vs. 13.2%; p = 0.002), and VMA (5.9 vs. 2.6%; p = 0.014) in eyes with AL ≥ 29.0 mm compared with AL < 29.0 mm. Conclusion: Our study describes the overall prevalence of PM and related pathologies among patients with HM in our hospital-based cohort. Longer eyes even among HM eyes had a significantly higher prevalence of PM-associated pathologies studied. This supports the premise that eyes with longer AL, even among HM eyes may be at greater risk of vision-threatening changes and therefore merit regular follow-up.