POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells.

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON-OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2-/- mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Associations between corneal curvature and other anterior segment biometrics in young myopic adults.

To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.

MiR-204-5p may regulate oxidative stress in myopia.

The mechanisms underlying myopia remain not fully understood. We proposed to examine the function and underlying mechanisms of miR-204-5p in myopia development. The miR-204-5p expression level was assessed in the vitreous humor (VH) of a cohort consisting of 11 patients with high myopia (HM) and 16 control patients undergoing vitrectomy. Then the functional implications of miR-204-5p in ARPE-19 cells were assessed. Thioredoxin-interacting protein (TXNIP) was found as a possible target of miR-204-5p through mRNA sequencing, and its interaction with miR-204-5p was confirmed employing luciferase assay and western blotting. Furthermore, the miR-204-5p function in regulating oxidative stress was examined by measuring reactive oxygen species (ROS) accumulation. The results indicated a significant reduction of miR-204-5p in the VH of HM patients. Overexpression of miR-204-5p suppressed cell proliferation, migration, invasion, and apoptosis in ARPE-19 cells. The direct targeting of miR-204-5p on TXNIP has been confirmed, and its downregulation mediated the miR-204-5p impacts on ARPE-19 cells. Moreover, miR-204-5p overexpression significantly reduced ROS accumulation by targeting TXNIP. Our findings revealed the possible contribution of the miR-204-5p/TXNIP axis in myopia development by regulating oxidative stress, which may provide new targets to combat this prevalent and debilitating condition.

A new segmentation algorithm for peripapillary atrophy and optic disk from ultra-widefield Photographs1.

BACKGROUND AND OBJECTIVE: The prevalence of myopia and high myopia is increasing globally, underscoring the growing importance of diagnosing high myopia-related pathologies. While existing image segmentation models, such as U-Net, UNet++, ResU-Net, and TransUNet, have achieved significant success in medical image segmentation, they still face challenges when dealing with ultra-widefield (UWF) fundus images. This study introduces a novel automatic segmentation algorithm for the optic disc and peripapillary atrophy (PPA) based on UWF fundus images, aimed at assisting ophthalmologists in more accurately diagnosing high myopia-related diseases. METHODS: In this study, we developed a segmentation model leveraging a Transformer-based network structure, complemented by atrous convolution and selective boundary aggregation modules, to elevate the accuracy of segmenting the optic disc and PPA in UWF photography. The atrous convolution module adeptly manages multi-scale features, catering to the variances in target sizes and expanding the deep network's receptive field. Concurrently, the incorporation of the selective boundary aggregation module in the skip connections of the model significantly improves the differentiation of boundary information between segmentation targets. Moreover, the comparison of our proposed algorithm with classical segmentation models like U-Net, UNet++, ResU-Net, and TransUNet highlights its considerable advantages in processing UWF photographs. RESULTS: The experimental results show that, compared to the other four models, our algorithm demonstrates substantial improvements in segmenting the optic disc and PPA in UWF photographs. In PPA segmentation, our algorithm improves by 0.8% in Dice, 1.8% in sensitivity, and 1.3% in intersection over union (IOU). In optic disc segmentation, our algorithm improves by 0.3% in Dice, 0.6% in precision, and 0.4% in IOU. CONCLUSION: Our proposed method improves the segmentation accuracy of PPA and optic disks based on UWF photographs, which is valuable for diagnosing high myopia-related diseases in ophthalmology clinics.

3D printed fibroblast-loaded hydrogel for scleral remodeling to prevent the progression of myopia.

Pathologic myopia has seriously jeopardized the visual health of adolescents in the past decades. The progression of high myopia is associated with a decrease in collagen aggregation and thinning of the sclera, which ultimately leads to longer eye axis length and image formation in front of the retina. Herein, we report a fibroblast-loaded hydrogel as a posterior scleral reinforcement (PSR) surgery implant for the prevention of myopia progression. The fibroblast-loaded gelatin methacrylate (GelMA)-poly(ethylene glycol) diacrylate (PEGDA) hydrogel was prepared through bioprinting with digital light processing (DLP). The introduction of the PEGDA component endowed the GelMA-PEGDA hydrogel with a high compression modulus for PRS surgery. The encapsulated fibroblasts could consistently maintain a high survival rate during 7 days of in vitro incubation, and could normally secrete collagen type I. Eventually, both the hydrogel and fibroblast-loaded hydrogel demonstrated an effective shortening of the myopic eye axis length in a guinea pig model of visual deprivation over three weeks after implantation, and the sclera thickness of myopic guinea pigs became significantly thicker after 4 weeks, verifying the success of sclera remodeling and showing that myopic progression was effectively controlled. In particular, the fibroblast-loaded hydrogel demonstrated the best therapeutic effect through the synergistic effect of cell therapy and PSR surgery.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Quantifying refractive error in companion dogs with and without nuclear sclerosis: 229 eyes from 118 dogs.

OBJECTIVE: To evaluate the relationship between nuclear sclerosis (NS) and refractive error in companion dogs. ANIMALS STUDIED: One hundred and eighteen companion dogs. PROCEDURES: Dogs were examined and found to be free of significant ocular abnormalities aside from NS. NS was graded from 0 (absent) to 3 (severe) using a scale developed by the investigators. Manual refraction was performed. The effect of NS grade on refractive error was measured using a linear mixed effects analysis adjusted for age. The proportion of eyes with >1.5 D myopia in each NS grade was evaluated using a chi-square test. Visual impairment score (VIS) was obtained for a subset of dogs and compared against age, refractive error, and NS grade. RESULTS: Age was strongly correlated with NS grade (p < .0001). Age-adjusted analysis of NS grade relative to refraction showed a mild but not statistically significant increase in myopia with increasing NS grade, with eyes with grade 3 NS averaging 0.58-0.88 D greater myopia than eyes without NS. However, the myopia of >1.5 D was documented in 4/58 (6.9%) eyes with grade 0 NS, 12/91 (13.2%) eyes with grade 1 NS, 13/57 (22.8%) eyes with grade 2 NS, and 7/23 (30.4%) eyes with grade 3 NS. Risk of myopia >1.5 D was significantly associated with increasing NS grade (p = .02). VIS was associated weakly with refractive error, moderately with age, and significantly with NS grade. CONCLUSIONS: NS is associated with visual deficits in some dogs but is only weakly associated with myopia. More work is needed to characterize vision in aging dogs.

Association between inflammatory cytokines and oxidative stress levels in aqueous humor with axial length in human myopia.

This study investigated the content of inflammatory cytokines and oxidative stress levels in the aqueous humor (AH) of patients with high myopia (HM) and explored the relationship between these factors and the axial length (AL) of the eye, to explore the roles of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia. AH samples from 40 patients (70 eyes) were collected during implantable collamer lens (ICL-V4c) surgery. The subjects were divided into three groups according to AL: group A (AL ≤ 26 mm), group B (26 < AL ≤ 28 mm), and group C (AL ≥ 28 mm). The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and interleukin-1ß (IL-1ß) in the AH of the three groups were measured using the Luminex system. Oxidative stress levels were measured using reagent kits targeting total antioxidant capacity (T-AOC), catalase (CAT), and nitric oxide (NO) and malonaldehyde (MDA) content. The results showed compared with group A, IL-1ß, MMP-2, and IL-6 concentrations were significantly higher and T-AOC levels were significantly lower in group C. There were no significant differences in CAT, NO, MDA, or TNF-α levels among the groups. The concentrations of IL-6 (r = 0.379, p = 0.016), MMP-2 (r = 0.469, p = 0.002), and MDA (r = 0.354, p = 0.025) in AH were positively correlated with the AL, whereas T-AOC (r = -0.678, p = 0.000) was negatively correlated with AL. These results suggest that mild intraocular inflammation and oxidative stress imbalance may be associated with myopia. Further experiments are needed to confirm the role of mild intraocular inflammation and oxidative stress imbalance in the occurrence and development of myopia.

Effects of inflammation on myopia: evidence and potential mechanisms.

As the most common type of refractive error, myopia has become one of the leading causes of visual impairment. With the increasing prevalence of myopia, there is a growing need to better understand the factors involved in its development. Inflammation, one of the most fundamental pathophysiological processes in humans, is a rapid response triggered by harmful stimuli and conditions. Although controlled inflammatory responses are necessary, over-activated inflammation is the common soil for many diseases. The impact of inflammation on myopia has received rising attention in recent years. Elevated inflammation may contribute to myopia progression either directly or indirectly by inducing scleral remodeling, and myopia development may also increase ocular inflammation. This article provides a comprehensive review of the interplay between inflammation and myopia and the potential biological mechanisms, which may present new targets for understanding the pathology of myopia and developing myopia therapies.

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

PURPOSE: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

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.

Performance of neuroretinal rim thickness measurement by Cirrus high-definition optical coherence tomography in myopic eyes.

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.

Pathogenesis of myopic choroidal neovascularization: A systematic review and meta-analysis.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV.

The Mechanosensitive Piezo1 Channel Mediates Mechanochemical Transmission in Myopic Eyes.

Purpose: To identify the expression of the mechanosensitive ion channel Piezo1 in the retina of guinea pigs with form deprivation myopia (FDM) and to investigate mechanisms by which Piezo1 channels might regulate myopia. Method: Sixty 3-week-old guinea pigs were divided into four groups randomly: normal control, FDM, FDM + vehicle control (DMSO), and FDM + Piezo1 inhibitor (GsMTx4). Measurements of spherical equivalent (SE) and axial length (AL) of the guinea pig were taken using retinoscopy and A-scan ultrasound examination, respectively. Location of Piezo1 protein was determined using immunohistochemistry. The histological structure and thickness changes of the guinea pig retina were observed by hematoxylin and eosin. Expression of Piezo1 in the retina was detected using quantitative RT-PCR and Western blot. Reactive oxygen species (ROS) levels in the retina were measured using flow cytometry. Result: After 4 weeks of form deprivation, the FDM group exhibited a significantly increased myopic degree and axial length compared with the normal control group (all P < 0.001), and had higher expression levels of Piezo1 and ROS than the normal control group (P < 0.001 and P = 0.002, respectively). Piezo1 protein expression was down-regulated in guinea pigs given GsMTx4 compared with the DMSO group (P = 0.037). Additionally, the GsMTx4 group showed lower myopic degree (P < 0.001) and lower ROS levels (P = 0.019) compared with the DMSO group. Conclusions: The Piezo1 channel may be activated in the retinas of FDM guinea pigs and be involved in the development of myopia by regulating intraocular ROS levels.

Choroidal Circulation in 8- to 30-Year-Old Chinese, Measured by SS-OCT/OCTA: Relations to Age, Axial Length, and Choroidal Thickness.

Purpose: The purpose of this study was to evaluate and explore the determinants of choroidal vascularity and choriocapillaris perfusion in a Chinese population aged 8 to 30 years old. Methods: Three hundred eighty eyes from 380 subjects aged 8 to 30 years were included in this cross-sectional study. Submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and choriocapillaris flow deficit (CcFD) were estimated using images obtained from optical coherence tomography (OCT). Results: In this population, the mean ChT was 260.4 ± 63.3 µm, TCA was 1.56 ± 0.38 mm2, LA was 0.94 ± 0.25 mm2, and SA was 0.62 ± 0.15 mm2. The mean CVI was 60.25 ± 3.21% and CcFD was 11.95 ± 1.98%. Multivariable analyses showed that higher CVI and LA was associated with older age, thicker ChT, and shorter AL; and lower CcFD was associated with shorter AL. However, the associations were not uniformly rectilinear between CcFD and age. Specifically, CcFD was positively associated with age in subjects ≤19 years old and negatively associated with age in subjects >19 years old. Conclusions: Development of the choroidal medium- and large-sized vascular layers and choriocapillaris was different across patients aged 8 to 30 years old. Greater axial length was associated with attenuated choroidal circulation. Choroidal thickness correlated well with choroidal vascularity, but not with choriocapillaris perfusion. Further comprehensive and longitudinal assessment of choroidal vasculature and choriocapillaris perfusion will help greatly to understand the physiological and pathological mechanisms responsible for myopia.

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.

Myopic Versus Glaucomatous Parapapillary Beta Zone in Myopic Eyes Versus Eyes With Secondary Angle-Closure Glaucoma.

Purpose: To search for histologic differences in the beta zone between myopic eyes versus eyes with secondary angle-closure glaucoma. Methods: The histomorphometric study consisted of human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. Results: The study included 100 eyes (age: 62.1 ± 15.1 years; axial length: 25.6 ± 3.1 mm; range: 20.0-35.0 mm). In non-highly myopic glaucomatous eyes compared with non-highly myopic nonglaucomatous eyes, the parapapillary alpha zone was longer (223 ± 168 µm vs. 125 ± 128 µm; P = 0.03), beta zone prevalence (15/20 vs. 6/41; P < 0.001) and length (277 ± 245 µm vs. 44 ± 150 µm; P = 0.001) were higher, and RPE cell density in the alpha zone and alpha zone border was lower (all P < 0.05). In highly myopic nonglaucomatous eyes compared with non-highly myopic glaucomatous eyes, parapapillary RPE drusen prevalence (2/19 vs. 10/10; P = 0.01) and alpha zone prevalence (2/19 vs. 16/20; P < 0.001) and length (23 ± 68 µm vs. 223 ± 168 µm; P < 0.001) were lower. In non-highly myopic glaucomatous eyes, Bruch's membrane (BM) thickness decreased (P < 0.001) from the beta zone (6.0 ± 3.1 µm) to the alpha zone (5.1 ± 4.3 µm) and peripheral to it (3.0 ± 0.9 µm). In highly myopic nonglaucomatous eyes, BM thickness did not differ (P > 0.10) between all three regions. In the total study population, RPE cell density in the alpha zone (24.5 ± 9.3 cells/240 µm) was higher than at the alpha zone border (19.2 ± 4.8 cells/240 µm; P < 0.001) or peripheral to it (19.0 ± 3.6 cells/240 µm; P < 0.001). Conclusions: The glaucomatous beta zone in eyes with chronic angle-closure glaucoma (with the alpha zone, parapapillary RPE drusen, thickened BM, and higher RPE cell count in the adjacent alpha zone) differs histologically from the myopic beta zone (characterized by the absence of the alpha zone and parapapillary RPE drusen, unremarkable BM thickness, and unremarkable parapapillary RPE). The differences suggest different etiologies of the glaucomatous versus myopic beta zone.

IMI-Nonpathological Human Ocular Tissue Changes With Axial Myopia.

Purpose: To describe nonpathological myopia-related characteristics of the human eye. Methods: Based on histomorphometric and clinical studies, qualitative and quantitative findings associated with myopic axial elongation are presented. Results: In axial myopia, the eye changes from a spherical shape to a prolate ellipsoid, photoreceptor, and retinal pigment epithelium cell density and total retinal thickness decrease, most marked in the retroequatorial region, followed by the equator. The choroid and sclera are thin, most markedly at the posterior pole and least markedly at the ora serrata. The sclera undergoes alterations in fibroblast activity, changes in extracellular matrix content, and remodeling. Bruch's membrane (BM) thickness is unrelated to axial length, although the BM volume increases. In moderate myopia, the BM opening shifts, usually toward the fovea, leading to the BM overhanging into the nasal intrapapillary compartment. Subsequently, the BM is absent in the temporal region (such as parapapillary gamma zone), the optic disc takes on a vertically oval shape, the fovea-optic disc distance elongates without macular BM elongation, the angle kappa reduces, and the papillomacular retinal vessels and nerve fibers straighten and stretch. In high myopia, the BM opening and the optic disc enlarge, the lamina cribrosa, the peripapillary scleral flange (such as parapapillary delta zone) and the peripapillary choroidal border tissue lengthen and thin, and a circular gamma and delta zone develop. Conclusions: A thorough characterization of ocular changes in nonpathological myopia are of importance to better understand the mechanisms of myopic axial elongation, pathological structural changes, and psychophysical sequelae of myopia on visual function.