Mendelian Randomization Implicates Bidirectional Association between Myopia and Primary Open-Angle Glaucoma or Intraocular Pressure.

PURPOSE: Observational studies suggest that myopic eyes carry a greater risk of primary open-angle glaucoma (POAG); however, the evidence for this association is inconsistent. This may be the result of confounding factors that arise from myopia that complicate clinical tests for glaucoma. This study used Mendelian randomization (MR) analysis to determine genetic causal associations among myopia, glaucoma, and glaucoma-related traits that overcome the effects of external confounders. DESIGN: Bidirectional genetic associations between myopia and refractive spherical equivalent (RSE), POAG, and POAG endophenotypes were investigated. PARTICIPANTS: Data from the largest publicly available genetic banks (n = 216,257-542,934) were analyzed. METHODS: Multiple MR models and multivariate genomic structural modeling to identify significant mediators for the relationship between myopia and POAG. MAIN OUTCOME MEASURES: Genetic causal associations between myopia and POAG and POAG endophenotypes. RESULTS: We found consistent bidirectional genetic associations between myopia and POAG and between myopia and intraocular pressure (IOP) using multiple MR models at Bonferroni-corrected levels of significance. Intraocular pressure showed the most significant mediation effect on RSE and POAG (Sobel test, 0.13; 95% confidence interval, 0.09-0.17; P = 1.37 × 10-8). CONCLUSIONS: A strong bidirectional genetic causal link exists between myopia and POAG that is mediated mainly by IOP. Our findings suggest that IOP-lowering treatment for glaucoma may be beneficial in myopic eyes, despite the challenges of establishing a clear clinical diagnosis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

High Myopia Normative Database of Peripapillary Retinal Nerve Fiber Layer Thickness to Detect Myopic Glaucoma in a Chinese Population.

PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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 Antihypertensive Medication with Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness.

PURPOSE: To evaluate the association between different classes of antihypertensive medication with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness in a nonglaucomatous multiethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 9144 eyes for RNFL analysis (2668 Malays, 3554 Indians, and 2922 Chinese) and 8549 eyes for GC-IPL analysis (2460 Malays, 3230 Indians, and 2859 Chinese) aged 44 to 86 years. METHODS: Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for collection of data on medication and other variables. Intraocular pressure (IOP) readings were obtained by Goldmann applanation tonometry before pupil dilation for fundoscopy and OCT imaging. Blood pressure (BP) was measured with an automatic BP monitor. Mean arterial pressure (MAP) was defined as diastolic BP plus 1/3 (systolic BP - diastolic BP). Regression models were used to investigate the association of antihypertensive medication with OCT measurements of RNFL and GC-IPL. MAIN OUTCOME MEASURES: Average and sectoral RNFL and GC-IPL thickness. RESULTS: After adjusting for age, gender, ethnicity, MAP, IOP, body mass index (BMI), and presence of diabetes, we found that participants taking any type of antihypertensive medication (ß = -0.83; 95% confidence interval [CI], -1.46 to -0.02; P = 0.01), specifically angiotensin-converting enzyme inhibitors (ACEIs) (ß = -1.66; 95% CI, -2.57 to -0.75; P < 0.001) or diuretics (ß = -1.38; 95% CI, -2.59 to -0.17; P < 0.05), had thinner average RNFL in comparison with participants who were not receiving antihypertensive treatment. Use of a greater number of antihypertensive medications was significantly associated with thinner average RNFL (P for trend = 0.001). This association was most evident in the inferior RNFL quadrant in participants using ACEIs (ß = -2.44; 95% CI, -3.99 to -0.89; P = 0.002) or diuretics (ß = -2.76; 95% CI, -4.76 to -0.76; P = 0.007). A similar trend was noted in our analysis of macular GC-IPL thickness. CONCLUSIONS: Use of 2 or more antihypertensive medications, ACEI, and diuretics were associated with a loss of structural markers of retinal ganglion cell health in a multiethnic Asian population.

Glial cell interactions and glaucoma.

PURPOSE OF REVIEW: The present review describes new advances in our understanding of the role of glial cells in the pathogenesis of glaucoma. It is becoming clear that retinal glia should not be studied in isolation in glaucoma because glia have dynamic and diverse interactions with a range of different cell types that could influence the disease process. RECENT FINDINGS: Microglial activity is modulated by signals from retinal ganglion cells and macroglia that influence RGC survival in various models of injury. New studies suggest that circulating monocytic populations may play a role in mediating the immune response to glaucoma. Astrocytes have been found to develop discrete localized processes that interact with a specific subset of retinal ganglion cells, possibly responding to the expression of phagocytic signals by stressed retinal ganglion cells. SUMMARY: Retinal glia constitute a highly versatile population that interacts with various cells to maintain homeostasis and limit disease. Defining the mechanisms that underlie glial communication could enable the development of more selective therapeutic targets, with great potential clinical applications.

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.

Anatomical compensation of retinal nerve fiber layer improves the detection of glaucoma between ethnicities.

The study aimed to evaluate the impact of compensating retinal nerve fiber layer (RNFL) thickness for demographic and anatomical factors on glaucoma detection in Chinese and Indian adults. A population-based study included 1995 healthy participants (1076 Chinese and 919 Indians) to construct a multivariable linear regression compensation model. This model was applied to 357 Chinese glaucoma patients, 357 healthy Chinese, and 357 healthy Indians using Cirrus spectral-domain optical coherence tomography (OCT). The compensated RNFL thickness considered age, refractive error, optic disc parameters, and retinal vessel density. Results showed that although the average RNFL thickness was significantly higher in Chinese participants compared to Indians, the compensation model reduced this difference to nonsignificance. Moreover, the compensation model significantly improved the area under the receiver operating characteristic curve (0.90 vs. 0.78; p<0.001), sensitivity (75% vs. 51%), and specificity (67% vs. 32%) in distinguishing Chinese glaucoma patients from healthy Indian individuals. The compensation model significantly enhanced the diagnostic accuracy of RNFL thickness in distinguishing glaucoma in the Chinese ethnic group compared to the OCT instrument's default values. These results suggest that modifying RNFL measurements based on individual characteristics can yield substantial benefits for glaucoma detection across ethnicities.

Enhancing the structure-function relationship in glaucoma using anatomical compensation of retinal nerve fibre layer.

BACKGROUND/AIMS: To investigate whether compensating retinal nerve fibre layer (RNFL) thickness measurements for demographic and anatomical ocular factors can strengthen the structure-function relationship in patients with glaucoma. METHODS: 600 eyes from 412 patients with glaucoma (mean deviation of the visual field (MD VF) -6.53±5.55 dB) were included in this cross-sectional study. Participants underwent standard automated perimetry and spectral-domain optical coherence tomography imaging (Cirrus; Carl Zeiss Meditec). Compensated RNFL thickness was computed considering age, refractive error, optic disc parameters and retinal vessel density. The relationship between MD VF and RNFL thickness measurements, with or without demographic and anatomical compensation, was evaluated sectorally and focally. RESULTS: The superior arcuate sector exhibited the highest correlation between measured RNFL and MD VF, with a correlation of 0.49 (95% CI 0.37 to 0.59). Applying the compensated RNFL data increased the correlation substantially to 0.62 (95% CI 0.52 to 0.70; p<0.001). Only 61% of the VF locations showed a significant relationship (Spearman's correlation of at least 0.30) between structural and functional aspects using measured RNFL data, and this increased to 78% with compensated RNFL measurements. In the 10°-20° VF region, the slope below the breakpoint for compensated RNFL thickness demonstrated a more robust correlation (slope=1.66±0.18 µm/dB; p<0.001) than measured RNFL (slope=0.27±0.67 µm/dB; p=0.688). CONCLUSION: Compensated RNFL data improve the correlation between RNFL measurements and VF parameters. This indicates that creating structure-to-function maps that consider anatomical variances may aid in identifying localised structural and functional loss in glaucoma.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults.

BACKGROUND: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. METHODS: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. RESULTS: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001). CONCLUSION: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.

Caveolin-1 in vascular health and glaucoma: A critical vascular regulator and potential therapeutic target.

Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found in most cell types. Cav-1 has been found to contribute significantly to ocular function, with mutations of Cav-1 being associated with a genetic risk of glaucoma development. Raised intraocular pressure (IOP) is a major modifiable risk factor for glaucoma. Cav-1 may be involved in both IOP-dependent and independent mechanisms involving vascular dysregulation. Systemic vascular diseases including hypertension, diabetes and hyperlipidaemia, have been shown to be associated with glaucoma development. Cav-1 is closely interlinked with endothelial nitric oxide synthase pathways that mediate vascular function and prevent cardiovascular diseases. Endothelial nitric oxide synthase and endothelin-1 are key vasoactive molecules expressed in retinal blood vessels that function to autoregulate ocular blood flow (OBF). Disruptions in the homeostasis of OBF have led to a growing concept of impaired neurovascular coupling in glaucoma. The imbalance between perfusion and neuronal stimulation arising from Cav-1 depletion may result in relative ischemia of the optic nerve head and glaucomatous injury. OBF is also governed by circadian variation in IOP and systemic blood pressure (BP). Cav-1 has been shown to influence central BP variability and other circadian rhythms such as the diurnal phagolysosomal digestion of photoreceptor fragments and toxic substrates to maintain ocular health. Overall, the vast implications of Cav-1 on various ocular mechanisms leading to glaucoma suggest a potential for new therapeutics to enhance Cav-1 expression, which has seen success in other neurodegenerative diseases.

Neurovascular segregation of the retinal nerve fiber layer in glaucoma.

The imaging data of one eye from 154 healthy and 143 glaucoma participants were acquired to evaluate the contributions of the neuronal and vascular components within the retinal nerve fiber layer (RNFL) for detecting glaucoma and modeling visual field loss through the use of optical coherence tomography (OCT) and OCT angiography. The neuronal and vascular components within the circumpapillary RNFL were independently evaluated. In healthy eyes, the neuronal component showed a stronger association with age (r = -0.52, p < 0.001) compared to measured RNFL thickness (r = -0.46, p < 0.001). Using the neuronal component alone improved detection of glaucoma (AUC: 0.890 ± 0.020) compared to measured RNFL thickness (AUC: 0.877 ± 0.021; χ2 = 5.54, p = 0.019). Inclusion of the capillary components with the sectoral neuronal component resulted in a significant improvement in glaucoma detection (AUC: 0.927 ± 0.015; χ2 = 15.34, p < 0.001). After adjusting for potential confounders, AUC increased to 0.952 ± 0.011. Results from modeling visual field loss in glaucoma eyes suggest that visual field losses associated with neuronal thinning were moderated in eyes with a larger capillary component. These findings suggest that segregation of the neurovascular components could help improve understanding of disease pathophysiology and affect disease management in glaucoma.

Angle closure extent, anterior segment dimensions and intraocular pressure.

AIM: To investigate the association between the extent of iridotrabecular contact and other quantitative anterior segment dimensions measured by swept-source optical coherence tomography (SS-OCT; CASIA SS-1000, Tomey, Nagoya, Japan) with intraocular pressure (IOP). METHODS: Cross-sectional study. All subjects who were ≥50 years with no history of glaucoma, ocular surgery or trauma, underwent SS-OCT imaging (eight equally spaced radial scans), Goldman applanation tonometry and gonioscopy on the same day. We measured iridotrabecular contact (ITC) index and area, total volume of trabeculo-iris space area and angle opening distance at 500 and 750 from the scleral spur (TISA 500 and 750, AOD 500 and 750, respectively), anterior chamber depth (ACD), volume, area and width, pupil diameter, lens vault and iris volume.Their relationship with IOP (dependent variable) was assessed by locally weighted scatterplot smoothing (Lowess) regression with change-point analysis and generalised additive models adjusted for confounders. RESULTS: 2027 right eyes of mostly Chinese Singaporeans (90%) were analysed. ITC index above a threshold of ~60% (95% CI 34% to 92%) was significantly associated with higher IOP. Independent of the extent of ITC, ACD was also significantly associated with higher IOP below a threshold of 2.5 mm (95% CI 2.33 mm to 2.71 mm). Greater ITC index and shallower ACD had a joint association with IOP. A model including ACD and ITC index was more predictive of IOP than a model considering these variables separately, particularly for women with gonioscopically closed angles (R2 52.7%, p<0.05). CONCLUSIONS: The extent of angle closure and the ACD below a certain threshold had a significant joint association with IOP. These parameters, as biometrical surrogates of mechanical obstruction of the aqueous outflow, may jointly contribute to elevated IOP, particularly in women with gonioscopic angle closure.

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.

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head.

Purpose: The purpose of this study was to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia (PM) alone or PM with staphyloma (PM + S). Methods: We studied 282 eyes, comprising of 99 controls (between +2.75 and -2.75 diopters), 51 HM (< -5 diopters), 35 HMG, 21 PM, and 75 PM + S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degrees adduction, (3) 20 degrees abduction, and (4) primary gaze with acute IOP elevation (to ∼35 mm Hg) achieved through ophthalmodynamometry. We then computed IOP- and gaze-induced ONH displacements and effective strains. Effective strains were compared across groups. Results: Under IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 ± 2.4%) than PM eyes (6.9 ± 5.0%, P < 0.001), HMG eyes (4.7 ± 1.8%, P = 0.04), and PM + S eyes (7.0 ± 5.2%, P < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% ± 2.7%) than PM + S eyes (6.0 ± 3.1%, P = 0.02). We also found that eyes with higher axial length were associated with higher strains. Conclusions: Our study revealed that eyes with HMG experienced significantly greater strains under IOP compared to eyes with HM. Furthermore, eyes with PM + S had the highest strains on the ONH of all groups.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

Early cholecystectomy and ERCP are associated with reduced readmissions for acute biliary pancreatitis: a nationwide, population-based study.

BACKGROUND: Cholecystectomy is recommended during hospitalizations for acute biliary pancreatitis (ABP). OBJECTIVE: We sought to assess the population-based effectiveness of index cholecystectomy by using nationwide data. DESIGN: Retrospective, cohort study. SETTING: All acute-care hospitals in Canada from 2007 to 2010. PATIENTS: This study involved patients admitted for ABP in the Canadian Institutes for Health Information hospital discharge database. INTERVENTION: Cholecystectomy and therapeutic ERCP during the index admission. MAIN OUTCOME MEASUREMENTS: Rate of hospital readmissions for ABP. RESULTS: Among 5646 patients with ABP, 32% underwent cholecystectomy and 22% ERCP during the index admissions. Patients admitted to hospitals in the highest quartile for cholecystectomy volume were more than 10-fold likely to undergo cholecystectomy during the index admission (adjusted odds ratio 11.0; 95% confidence interval [CI], 7.4-16.5). The 12-month readmission rate for ABP was lower with cholecystectomy (5.6% vs 14.0%; P < .0001) and therapeutic ERCP (5.1% vs 13.1%; P < .0001). After multivariate adjustment, lower readmission rates were independently associated with both cholecystectomy (adjusted hazard ratio [HR] 0.39; 95% CI, 0.32-0.48) and ERCP (adjusted HR 0.37; 95% CI, 0.29-0.50). After excluding early readmissions (within 28 days of discharge), the adjusted HR for cholecystectomy was 0.43 (95% CI, 0.34-0.57). The admitting hospital's cholecystectomy volume was inversely associated with 12-month readmission rates for ABP (quartile 1, 15.9%; quartile 2, 13.9%; quartile 3, 11.3%; quartile 4, 10.0%; P < .001). LIMITATIONS: The study was based on hospital administrative data. CONCLUSION: Cholecystectomy and ERCP during the index admission were associated with reduced readmission rates for ABP, providing population-based evidence to support consensus guidelines that recommend early biliary intervention.

Advances in OCT Imaging in Myopia and Pathologic Myopia.

Advances in imaging with optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technology, including the development of swept source OCT/OCTA, widefield or ultra-widefield systems, have greatly improved the understanding, diagnosis, and treatment of myopia and myopia-related complications. Anterior segment OCT is useful for imaging the anterior segment of myopes, providing the basis for implantable collamer lens optimization, or detecting intraocular lens decentration in high myopic patients. OCT has enhanced imaging of vitreous properties, and measurement of choroidal thickness in myopic eyes. Widefield OCT systems have greatly improved the visualization of peripheral retinal lesions and have enabled the evaluation of wide staphyloma and ocular curvature. Based on OCT imaging, a new classification system and guidelines for the management of myopic traction maculopathy have been proposed; different dome-shaped macula morphologies have been described; and myopia-related abnormalities in the optic nerve and peripapillary region have been demonstrated. OCTA can quantitatively evaluate the retinal microvasculature and choriocapillaris, which is useful for the early detection of myopic choroidal neovascularization and the evaluation of anti-vascular endothelial growth factor therapy in these patients. In addition, the application of artificial intelligence in OCT/OCTA imaging in myopia has achieved promising results.

Investigating the macular choriocapillaris in early primary open-angle glaucoma using swept-source optical coherence tomography angiography.

Introduction: There has been a growing interest in the role of vascular factors in glaucoma. Studies have looked at the characteristics of macular choriocapillaris in patients with glaucoma but with conflicting results. Our study aims to use swept-source optical coherence tomography angiography (SS-OCTA) to evaluate macular choriocapillaris metrics in normal participants and compare them with patients with early primary open-angle glaucoma (POAG) (mean deviation better than -6dB). Methods: In this prospective, observational, cross-sectional study, 104 normal controls (157 eyes) and 100 patients with POAG (144 eyes) underwent 3 mm × 3mm imaging of the macula using the Plex Elite 9000 (Zeiss Meditec, Dublin, CA, USA). Choriocapillaris OCTA images were extracted from the device's built-in review software and were subsequently evaluated for the density and size of choriocapillaris flow deficits. Results: After adjusting for confounding factors, the density of flow deficits was independently higher in those aged 53 years and above (P ≤ 0.024) whereas the average flow deficit size was significantly larger in those aged 69 years and above (95% CI = 12.39 to 72.91; P = 0.006) in both normal and POAG patients. There were no significant differences in the density of flow deficits (P = 0.453) and average flow deficit size (P = 0.637) between normal and POAG participants. Conclusion: Our study found that macular choriocapillaris microvasculature on SS-OCTA is unaltered by subjects with POAG. This suggests that OCTA macular choriocapillaris may not be potentially helpful in differentiating early glaucoma from healthy eyes.