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.

Open Fundus Photograph Dataset with Pathologic Myopia Recognition and Anatomical Structure Annotation.

Pathologic myopia (PM) is a common blinding retinal degeneration suffered by highly myopic population. Early screening of this condition can reduce the damage caused by the associated fundus lesions and therefore prevent vision loss. Automated diagnostic tools based on artificial intelligence methods can benefit this process by aiding clinicians to identify disease signs or to screen mass populations using color fundus photographs as inputs. This paper provides insights about PALM, our open fundus imaging dataset for pathological myopia recognition and anatomical structure annotation. Our databases comprises 1200 images with associated labels for the pathologic myopia category and manual annotations of the optic disc, the position of the fovea and delineations of lesions such as patchy retinal atrophy (including peripapillary atrophy) and retinal detachment. In addition, this paper elaborates on other details such as the labeling process used to construct the database, the quality and characteristics of the samples and provides other relevant usage notes.

Scleral collagen cross linkage in progressive myopia.

High myopia is often associated with local ectasia and scleral thinning. The progression of myopia depends upon scleral biochemical and biomechanical properties. Scleral thinning is associated with decreased collagen fiber diameter, defective collagen fibrillogenesis, and collagen cross-linking. Reversing these abnormalities may make the sclera tougher and might serve as a treatment option for myopic progression. Collagen cross-linking is a natural process in the cornea and sclera, which makes the structure stiff. Exogenous collagen cross-linkage is artificially induced with the help of external mediators by using light and dark methods. In this systematic review, we discussed existing literature available on the internet on current evidence-based applications of scleral collagen cross-linking (SXL) by using different interventions. In addition, we compared them in tabular form in terms of their technique, mechanisms, cytotoxicity, and the stage of transition from preclinical to clinical development. Furthermore, we discussed the in-vivo technique to evaluate the post-SXL scleral biomechanical property and outcome in the human eye.

Effects of posterior staphyloma on choroidal structure in myopic adults: a retrospective study.

BACKGROUND: Studies on the choroid of myopic eyes with posterior staphyloma have shown that choroidal thickness decreased. This retrospective study further analysed the effects of posterior scleral staphyloma on choroidal blood vessels and matrix components compared to non-pathological myopia. METHODS: In this cross-sectional study, ninety-one eyes were divided into pathological (posterior staphyloma) and non-pathological myopia. The latter was further divided into three groups (Group 1: 26 mm ≤ axial length; Group 2: 24 mm ≤ axial length < 26 mm; Group 3: 22 mm ≤ axial length < 24 mm). Choroidal thickness, total choroidal area, luminal area, stromal area, and choroidal vascularity index were calculated. RESULTS: The CVI in N1, N2, I1, S2 of the posterior staphyloma group were lower than those of group 1 (both P < 0.05). The mean height of posterior staphyloma was associated with mean CT (Pearson correlation: r = -0.578, P = 0.039) but not with the mean CVI in posterior staphyloma group. In all groups, the mean choroidal thickness, total choroidal area, luminal area, and stromal area were significantly associated with axial length (P < 0.001), and the mean choroidal vascularity index was significantly associated with the mean choroidal thickness (P < 0.001). CONCLUSION: The choroidal structure of pathological myopia with posterior staphyloma and non-pathological myopia with longer axial length demonstrates alterations in which choroidal vessels are more impaired than the stroma. A lower choroidal vascularity index should be alert to pathological changes for myopia with axial length > 26 mm.

Using a combination of peripapillary atrophy area and choroidal thickness for the prediction of different types of myopic maculopathy.

PURPOSE: To analyse the topographic characteristics in macular choroidal thickness (mChT) and ocular biometry in myopic maculopathy and to explore the potential cut-off value for prediction of myopic maculopathy (MM). METHODS: All participants underwent detailed ocular examinations. MM was subdivided into thin choroid, Bruch's membrane (BM) defects, choroidal neovascularization (CNV), and myopic tractional maculopathy (MTM) according to OCT-based classification system. Peripapillary atrophy area (PPA), tilt ratio, torsion, and mChT were individually measured. RESULTS: A total of 1947 participants were included. In multivariate logistics models, older age, longer axial length, larger PPA area, and thinner average mChT were more likely to have MM and different type of MM. Female participants were more likely to have MM and BM defects. A lower tilt ratio was more likely to be associated with CNV and MTM. The area under the curve (AUC) of single tilt ratio, PPA area, torsion, and topographic of mChT for MM, thin choroid, BM Defects, CNV, and MTM were 0.6581 to 0.9423, 0.6564 to 0.9335, 0.6120 to 0.9554, 0.5734 to 0.9312, 0.6415 to 0.9382, respectively. After combining PPA area and average mChT for predicting MM, thin choroid, BM defects, CNV, and MTM, the AUC of the combination were 0.9678, 0.9279, 0.9531, 0.9213, 0.9317, respectively. CONCLUSION: Progressive and continuous PPA area expanding and thin choroid play a role in the development of myopic maculopathy. The present study showed that a combination of peripapillary atrophy area and the choroidal thickness could be used to predict MM and each type of MM.

Posterior Staphyloma as Determining Factor for Myopic Maculopathy.

PURPOSE: The aim of this study was to determine the influence of posterior staphyloma (PS) on the development of myopic maculopathy. DESIGN: Cross-sectional study. METHODS: A total of 467 highly myopic eyes (axial length [AL] ≥26 mm) of 246 patients were included. Patients underwent a complete ophthalmological examination, including multimodal imaging. Presence of PS was defined as the main variable analyzed between groups (PS vs non-PS): age, AL, best-corrected visual acuity (BCVA), atrophy/traction/neovascularization (ATN) components, and presence of severe pathologic myopia (PM). Two different cohorts were studied (age-matched and AL-matched) comparing PS vs non-PS eyes. RESULTS: In all, 325 eyes (69.59%) presented with PS. Eyes without PS were younger and had lower AL, ATN components, and prevalence of severe PM than those with PS (P < .001). Moreover, non-PS eyes had better BCVA (P < .001). Analyzing the age-matched cohort (P = .96); mean AL, A, and T components, and severe PM were significantly higher in the PS group (P < .001), as well as the N component (P < .005), showing worse BCVA (P < .001). Regarding the AL-matched cohort (P = .93), the PS group showed worse BCVA (P < .01), older age (P < .001), A (P < .001), and T components (P < .01), and severe PM (P < .01). The risk of PS increased by 10% per year of age (odds ratio = 1.109, P < .001) and by 132% per each millimeter of growth of AL (odds ratio = 2.318, P < .001). CONCLUSIONS: Posterior staphyloma is associated with myopic maculopathy, worse visual acuity, and higher prevalence of severe PM. AL and age, in this order, constitute the main factors associated with the onset of PS.

A physical sign of pathological myopia: myopic scleral pit.

PURPOSE: Myopic scleral pit (MSP) is a rare physical sign of pathological myopia (PM). The aim of this study was to summarize the clinical characteristics of MSP and analyze its correlation with PM. METHODS: Eight cases with PM and MSP were enrolled in this study. Comprehensive ophthalmic examinations, including subjective refraction, slit-lamp biomicroscope, intraocular pressure, fundus photographs, A- and B-scan ultrasonography and spectral-domain optical coherence tomography, were performed. RESULTS: All the patients had a long history of PM with visual impairment, long axial length, and myopia-related fundus degeneration. Mean axial length was 31.48 ± 2.17 mm. Mean size of MSP was 0.69 ± 0.29 optic disc diameter (PD). Mean logMAR BCVA was 1.21 ± 0.88 logMAR. Spearman correlation analysis showed that the logMAR BCVA had no correlation with the size of pits (P = 0.34). Fundus examination revealed a focal pale concave located in the sclera exposed area of retinal choroid atrophy was found in all cases. OCT showed a deep scleral pit where the retinal choroid was thin or absent, without retinal sensory detachment or sensory defect. CONCLUSIONS: This study identified a rare scleral lesion in all eight individuals with PM, which was termed "myopic scleral pit". This phenomenon is different from focal choroidal excavation and posterior staphyloma.

Assessment of changes in macular structural retinal layers in patients with pathological myopia.

Background/aim: This study aimed to examine changes in the thickness of individual macular retinal layers in eyes with pathological myopia (PM) and to compare the thickness of each retinal layer between the PM and control groups to gain insights into retinal perfusion. Materials and methods: The study included 51 eyes in the PM group and 51 eyes in the control group. Optical coherence tomography (OCT) was used to measure the thickness of each retinal layer in the central fovea, parafoveal, and perifoveal regions. Optical coherence tomography angiography (OCT-A) was used to evaluate the retinal capillary density. Results: In the PM group, the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL) were thicker than in the control group (p = 0.004, p = 0.027, p = 0.020, and p < 0.001, respectively), whereas the outer nuclear layer (ONL) and photoreceptor layer (PRL) were thinner (p = 0.001 and p = 0.003, respectively). In other regions, the RNFL was thicker in the myopic group, whereas the GCL, IPL, INL, and ONL were thinner. OCT-A did not reveal any significant difference between the groups in terms of radial capillary plexus density (p = 0.381); however, the densities of the other plexuses were lower in the PM group. Conclusions: The results showed alterations in the thickness of retinal layers and capillary plexus density in PM. Thus, assessment of the thickness of individual retinal layers may serve as an indicator of vascular diseases that affect the circulation of the retina and choroid.

Inner limiting membrane bridges within Bruch's membrane defects in pathological myopia.

The purpose of the study was to examine peculiarities of the inner limiting membrane (ILM) in axially elongated eyes. The histomorphometric study included human globes enucleated due to reasons such as painful secondary angle-closure glaucoma or malignant uveal melanomas. Using light microscopy, we searched for regions with ILM-specific features in association with a marked axial elongation. Out of 279 eyes (279 patients) (mean age: 61.8 ± 13.9 years; axial length: 25.5 ± 3.1 mm (range: 20.0-37.0 mm)), two eyes (axial length: 30 mm and 34 mm, respectively) showed one region and two regions, respectively, characterized by ILM presence and absence of all other retinal layers, retinal pigment epithelium, Bruch´s membrane (BM) and choroid. The length of these regions, called ILM-bridges, was 1.06 mm, 0.73 mm, and 0.62 mm, respectively. All ILM-bridges were spatially associated with a larger, underlying BM defect and with localized scleral thinning without a staphylomatous scleral configuration. The distance between the ILM-bridges and the optic disc ranged between 1.92 mm and 4.21 mm. In univariable analysis, ILM-bridge number increased with longer axial length (beta: 0.19; P = 0.002) and higher BM defect prevalence (beta: 0.21; P = 0.001), while in multivariable analysis, the ILM-bridges number remained to be significantly correlated only with a higher prevalence of BM defect (beta: 0.15; P = 0.048). ILM-bridges occur in eyes with pathologic myopia in spatial association with underlying, larger BM defects. They may be due to an axial elongation-associated local stretching and rupture of all other retinal layers, caused by the BM defect-related enlargement of the retinal undersurface. Future studies may explore whether these histologic observations support the notion of the ILM having a relatively high biomechanical strength against myopic stretching-associated forces.

Vascular Changes of the Choroid and Their Correlations With Visual Acuity in Pathological Myopia.

Purpose: Photoreceptor loss plays a role in visual impairment in pathological myopia. As the nutrition and oxygen demands of photoreceptors are mainly supported by the choroidal vessels, we aimed to investigate changes in the choroidal vasculature and their correlations with visual acuity in pathological myopia. Methods: The cohort was composed of 136 eyes from 80 participants, including 42 eyes from 21 participants with emmetropia/low myopia, 48 eyes from 26 participants with simple high myopia, and 46 eyes from 33 participants with pathological myopia. Swept-source optical coherence tomography (OCT) was used to image the eyes with a 12-mm radial line scan protocol. The parameters for 6-mm diameters of macula area centered on the fovea were analyzed. A custom deep learning algorithm based on a modified residual U-Net architecture was used to segment the choroidal boundaries. Then, the distance between the two boundaries was determined and choroidal thickness (CT), luminal area (LA), and stromal area (SA) were demarcated based on Niblack's auto-local threshold algorithm after binarization of the OCT images. Finally, the ratio of LA and total choroidal area was defined as the choroidal vascularity index (CVI). The choroidal parameters in three groups were compared, and correlations of the choroidal parameters with age, gender, axial length, and best-corrected visual acuity (BCVA) were analyzed. Results: The CVI, CT, LA, and SA values were lower in pathological myopia than in emmetropia/low myopia and simple high myopia (P < 0.05). The CT, LA, and SA values were lower in simple high myopia than in emmetropia/low myopia (P < 0.05), whereas there was no difference between the CVIs in the emmetropia/low myopia and high myopia groups (P > 0.05). The CVI was nonlinear with increases in axial length (AL), and there was a critical AL flexion point, approximately 27.26 mm; however, the CT, LA, and SA were negatively correlated with AL. Further analysis showed that only younger subjects (40 years old or less) showed significant AL flexion points. Simple and multiple regression models showed that the CVI was correlated with BCVA (P < 0.05). Conclusions: Choroidal vascular alterations, especially decreased CVI, occurred in patients with pathological myopia. The CVI decreased with axial elongation beyond the flexion point and was correlated with visual impairment, indicating that the CVI might be a reliable imaging biomarker to monitor the progression of pathological myopia.

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.

Quantitative Evaluations of Posterior Staphylomas in Highly Myopic Eyes by Ultra-Widefield Optical Coherence Tomography.

Purpose: To determine the shape of posterior staphylomas using ultra-widefield optical coherence tomographic (UWF-OCT) images and to identify the factors contributing to the shape and grade of the staphylomas in eyes with pathologic myopia. Methods: This was an observational case series study. Highly myopic patients who were ≥40 years old with wide or narrow type of macular staphylomas were studied. High myopia was defined as a myopic refractive error (spherical equivalent) greater than -8.0 diopters (D) or an axial length (AL) > 26.5 mm. The maximum diameter and depth of the staphylomas were measured in the 12 radial scans of UWF-OCT images by ImageJ software and were compared between the two types of staphylomas. Results: We studied 197 eyes of 138 patients with a mean age of 64.7 ± 10.4 years and mean AL of 30.0 ± 1.9 mm. The AL was significantly longer in the eyes with the narrow type than the wide type of staphyloma (P = 0.036). Multiple regression analyses showed that age was significantly correlated with the maximum depth/maximum diameter ratio (wide type, P < 0.001; narrow type, P = 0.003) of both types of staphylomas. The AL was significantly correlated with the depth/diameter ratio of only the narrow type of staphylomas (P = 0.005). Conclusions: The significant correlations of age and AL with the wide and narrow types of posterior staphylomas indicate that the factors for their formations may be distinctly different. Quantitative analyses of UWF-OCT images are helpful in determining the shape of the staphylomas.

Choriocapillaris Changes in Myopic Macular Degeneration.

PURPOSE: Myopic macular degeneration (MMD) can cause irreversible vision loss. Thinner choroid is associated with increased MMD severity. This cross-sectional study analyzed choriocapillaris (CC) alterations in MMD. METHODS: Axial length (AL), best-corrected visual acuity (BCVA), fundus photography, and swept-source optical coherence tomography angiography (SS-OCTA) were assessed in controls and high myopes (spherical equivalent ≤ -6 diopters). Myopic patients with grade 2 MMD (macular diffuse chorioretinal atrophy [MDCA]), high axial myopia (AL ≥ 26.5 mm), and BCVA ≥ 20/40 were compared with controls without MMD. CC mean thickness was measured from 3 × 3-mm SS-OCTA scans by identifying CC peaks in A-scan intensity profiles. CC flow deficit percent (CC FD%) was quantified using a fuzzy C-mean local thresholding method on en face OCTA images. Multivariate regressions compared CC thickness and CC FD% between myopic patients and controls, correcting for age and other confounders. RESULTS: Sixteen eyes with MDCA (AL, 26.96-33.93 mm; ages, 40-78 years) were compared with 51 control eyes (AL, 21.65-25.84 mm; ages, 19-88 years). CC thickness in patients with MDCA was 66% lower than that in controls (5.23 ± 0.68 µm [mean ± SD] vs. 15.46 ± 1.82 µm; P < 0.001). CC FD% in patients with MDCA was 237% greater than in controls (26.5 ± 4.3 vs. 11.2 ± 4.6; P < 0.001). CONCLUSIONS: Patients with MDCA with good visual acuity had thinner CC and increased CC FD%, or reduced CC flow, compared with controls. Patients with grade 2 MMD and good visual acuity demonstrated significant choriocapillaris alterations, suggesting that choriocapillaris perfusion defects contribute to the pathogenesis of MMD. TRANSLATIONAL RELEVANCE: Given the potential vascular etiology for MMD, current research about revascularization of ischemic retina likely has implications for the treatment of MMD.

Results with Posterior Scleral Reinforcement for Progressive Highly Myopic Children in Hungary.

PURPOSE: We have been performing posterior scleral reinforcement in our ophthalmological department since 1992 on progressive highly myopic eyes. Here, we report on our results with this technique in the foregoing 7 years in a retrospective comparative design. METHODS: Thirty-eight eyes of 32 patients, operated according to Snyder-Thompson's method, were enrolled in this study, and a control group of 9 age- and myopia-matched children's 14 eyes was built for comparison. Pre- and postoperative best-corrected visual acuity, subjective refractive error (spherical equivalent of spectacle dioptres), and axial length were recorded. Changes within groups were calculated, as well as baseline parameters and their changes during follow-up, and compared between the groups. Correlation analysis was performed to identify factors that could influence myopia progression. RESULTS: Myopic progression was significantly lower in the operated than in the nonoperated group, both in terms of mean annual axial length as well as refractive error changes (0.21 ± 0.08 mm versus 0.49 ± 0.19 mm and 0.18 ± 0.29 D versus 0.6 ± 0.33 D, respectively). Mean overall visual improvement was more explicit in operated eyes as compared to those left untreated (0.15 ± 0.09 versus 0.01 ± 0.1). No association of any factor with myopia progression could be identified. We encountered no serious or lasting complications. CONCLUSION: In our clinical practice, posterior scleral reinforcement according to Snyder-Thompson proved to be a safely applicable and effective surgical method to stop or significantly retard pathological increases in axial length and dioptres, and thus can help prevent the onset of myopic degenerative lesions, and irreversible visual impairment in the long run.

Role of Ultra-widefield Imaging in the evaluation of Long-term change of highly myopic fundus.

PURPOSE: To evaluate the impact of posterior staphyloma identified using ultra-widefield fundus imaging on the long-term progression of myopic maculopathy in highly myopic patients. METHODS: In this observational cohort study, highly myopic patients who were followed up for at least 5 years using ultra-widefield fundus imaging were analysed for fundus abnormalities and the progression of myopic maculopathy based on the International Meta-analysis of Pathologic Myopia classification. RESULTS: This study included 390 eyes (210 patients) with the mean follow-up period of 69.2 ± 7.5 months (range, 60-88). Posterior staphyloma was identified in 198 eyes (50.8%) in the baseline ultra-widefield fundus images. The border of staphyloma was not identified within 50° view circle corresponding to conventional fundus photography in 42 eyes (21.2%) with staphyloma, most of that were wide macular type. Progression of myopic maculopathy during follow-up was observed in 202 eyes (51.8%), and eyes with staphyloma were more likely to show progression compared to those without (142/198 [71.7%] versus 60/192 [31.3%]; p < 0.001). In multivariable regression analysis, the presence of posterior staphyloma was an independent risk factor for the progression of myopic maculopathy (p = 0.005). One or more peripheral retinal lesions were observed in 302 eyes (77.4%) and 321 eyes (82.3%) in the baseline and final ultra-widefield fundus images, respectively. CONCLUSION: Posterior staphyloma was associated with the long-term progression of myopic maculopathy. With a wider field of view, ultra-widefield fundus imaging is useful for identifying the posterior staphyloma and monitoring the progression of myopic maculopathy in highly myopic patients.

Validation of Soft Labels in Developing Deep Learning Algorithms for Detecting Lesions of Myopic Maculopathy From Optical Coherence Tomographic Images.

PURPOSE: It is common for physicians to be uncertain when examining some images. Models trained with human uncertainty could be a help for physicians in diagnosing pathologic myopia. DESIGN: This is a hospital-based study that included 9176 images from 1327 patients that were collected between October 2015 and March 2019. METHODS: All collected images were graded by 21 myopia specialists according to the presence of myopic neovascularization (MNV), myopic traction maculopathy (MTM), and dome-shaped macula (DSM). Hard labels were made by the rule of major wins, while soft labels were possibilities calculated by whole grading results from the different graders. The area under the curve (AUC) of the receiver operating characteristics curve, the area under precision-recall (AUPR) curve, F-score, and least square errors were used to evaluate the performance of the models. RESULTS: The AUC values of models trained by soft labels in MNV, MTM, and DSM models were 0.985, 0.946, and 0.978; and the AUPR values were 0.908, 0.876, and 0.653 respectively. However, 0.56% of MNV "negative" cases were answered as "positive" with high certainty by the hard label model, whereas no case was graded with extreme errors by the soft label model. The same results were found for the MTM (0.95% vs none) and DSM (0.43% vs 0.09%) models. CONCLUSIONS: The predicted possibilities from the models trained by soft labels were close to the results made by myopia specialists. These findings could inspire the novel use of deep learning models in the medical field.

31†Setting up a bank of primary cells lines of pediatric and adolescent sclera and choroid to study post-natal eye growth.

Twice as many teenagers in the UK are becoming short-sighted now, compared with the 1960s; many develop a dangerously high degree of short-sightedness ("progressive myopia") with a risk of sight-threatening conditions in adulthood, such as retinal detachment and glaucoma. The rise in short-sightedness is even more dramatic in the Far East, where over 95% of young men are now shortsighted. One crucial feature in short-sightedness is that the eyeball becomes longer, as the white coat of the eye (sclera) is becoming softer and stretchable. We do not know how exactly this happens, but it must involve the cells that make the collagen in the sclera. At the moment lengthening of the eyeball cannot be reversed and the few existing treatments can only slow myopia progression, not stop it. New and better treatments are needed but a clear understanding of the molecular mechanisms of post-natal eye growth in humans is lacking. Critically, because myopia develops in childhood at a physiological location prohibiting biopsies, we are lacking an understanding of the cellular components involved in human eye growth and myopia, and especially how the tissues that build the eye structurally, the sclera and the choroid, are modulated during normal eye growth. We have recently begun to establish a biobank of primary fibroblasts from the sclera and choroid of pediatric, adolescent and adult tissue, to better understand how the cell populations change in those tissue as the eye grows and settles at its final adult size and shape. We have already been able to demonstrate significant differences in the cells from young and old eyes, as well as regional differences between the posterior and the anterior sections of the eye. We plan to analyse in detail the cellular profiles of the sclera during postnatal eye growth to identify markers of the different stages of eye growth (from infant to elderly). This will allow us to better understand normal eye growth and identify potential markers and new drug targets to prevent and treat myopia. Because pediatric donor tissue is so rare, our unique cell bank will be critical to the development of future studies.

Histology of neovascular myopic macular degeneration.

To assess the histological correlate of neovascular or exudative myopic macular degeneration (nMMD) in highly myopic human eyes, we examined histomorphometrically histologic sections of enucleated eyes of Caucasian patients. The study included 284 eyes (age: 61.9 ± 13.7 years; range: 24-89 years; axial length: 25.5 ± 3.1 mm; range: 20-37 mm). An nMMD was detected in 5 eyes (axial length: 29.6 ± 2.6 mm; range: 26.0-31.0 mm). All these eyes showed within or close to the nMMD a macular Bruch's membrane (BM) defect, fibrous tissue with erythrocyte-filled blood vessels, and proliferations of irregularly pigmented and irregularly piled-up retinal pigment epithelium (RPE) cells each of which was connected with a curled-up, PAS (Periodic-Acid-Shiff)-positive membrane. The nMMD lesions were covered by proliferated RPE cells. RPE cells were not detected within the retina. In binary regression analysis, a higher nMMD prevalence was associated with a higher prevalence of macular BM defects (odds ratio: > 1000; P < 0.001), while the association with axial length was not significant (P = 0.43) in that model. After adjustment for the presence of macular BM defects, the nMMD prevalence was not associated with BM thickness (measured at the posterior pole, equator-posterior pole midpoint, equator and shortly posterior to the ora serrata) (P = 0.10; P = 0.87; P = 0.40; and P = 0.36, respectively), RPE cell layer thickness (P = 0.83; P = 0.79; P = 0.31; P = 0.38, resp.), RPE cell density (P = 0.56; P = 0.91; P = 0.47; P = 0.87, resp.), choriocapillaris thickness (P = 0.47; P = 0.93; P = 0.41; P = 0.75, resp.), and choriocapillaris density (P = 0.99; P = 0.94; P = 0.17; P = 0.97, resp.). The results suggest that nMMD is characterized by a fibrous pseudo-metaplasia of the RPE and is strongly associated with macular BM defects, without other detected histomorphometric differences in thickness or density of the RPE, BM, and choriocapillaris.

Development of deep learning-based detecting systems for pathologic myopia using retinal fundus images.

Globally, cases of myopia have reached epidemic levels. High myopia and pathological myopia (PM) are the leading cause of visual impairment and blindness in China, demanding a large volume of myopia screening tasks to control the rapid growing myopic prevalence. It is desirable to develop the automatically intelligent system to facilitate these time- and labor- consuming tasks. In this study, we designed a series of deep learning systems to detect PM and myopic macular lesions according to a recent international photographic classification system (META-PM) classification based on color fundus images. Notably, our systems recorded robust performance both in the test and external validation dataset. The performance was comparable to the general ophthalmologist and retinal specialist. With the extensive adoption of this technology, effective mass screening for myopic population will become feasible on a national scale.