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.

Bi-Gaussian analysis reveals distinct education-related alterations in spherical equivalent and axial length-results from the Gutenberg Health Study.

PURPOSE: The aim of this study is to investigate the distribution of spherical equivalent and axial length in the general population and to analyze the influence of education on spherical equivalent with a focus on ocular biometric parameters. METHODS: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany. Participants underwent comprehensive ophthalmologic examinations as part of the 5-year follow-up examination in 2012-2017 including genotyping. The spherical equivalent and axial length distributions were modeled with gaussian mixture models. Regression analysis (on person-individual level) was performed to analyze associations between biometric parameters and educational factors. Mendelian randomization analysis explored the causal effect between spherical equivalent, axial length, and education. Additionally, effect mediation analysis examined the link between spherical equivalent and education. RESULTS: A total of 8532 study participants were included (median age: 57 years, 49% female). The distribution of spherical equivalent and axial length follows a bi-Gaussian function, partially explained by the length of education (i.e., < 11 years education vs. 11-20 years). Mendelian randomization indicated an effect of education on refractive error using a genetic risk score of education as an instrument variable (- 0.35 diopters per SD increase in the instrument, 95% CI, - 0.64-0.05, p = 0.02) and an effect of education on axial length (0.63 mm per SD increase in the instrument, 95% CI, 0.22-1.04, p = 0.003). Spherical equivalent, axial length and anterior chamber depth were associated with length of education in regression analyses. Mediation analysis revealed that the association between spherical equivalent and education is mainly driven (70%) by alteration in axial length. CONCLUSIONS: The distribution of axial length and spherical equivalent is represented by subgroups of the population (bi-Gaussian). This distribution can be partially explained by length of education. The impact of education on spherical equivalent is mainly driven by alteration in axial length.

Influence of Lens Thickness on Accuracy of Kane, Hill-RBF 3.0, Barrett Universal II, Emmetropia Verifying Optical, and Pearl-DGS Formulas in Eyes with Nonhigh Myopia and High Myopia.

PURPOSE: To investigate the influence of lens thickness (LT) on accuracy of Kane, Hill-RBF 3.0 Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), and Pearl-DGS formulas in eyes with different axial lengths (AL). METHODS: The prospective cohort study was conducted at Eye and ENT Hospital of Fudan University. Patients who had uneventful cataract surgery between March 2021 and July 2023 were recruited. Manifest refraction was conducted two-month post-surgery. Eyes were divided into 4 groups based on AL: short (<22mm), medium (22-24.5 mm), medium long (24.5-26mm) and very long (≥26mm). In each AL group, eyes were then divided into 3 subgroups based on the LT measured with IOLmaster700: thin (<4.5 mm), medium (4.5-5.0 mm), and thick (≥ 5 mm). The influence of LT on accuracy of Kane, Hill-RBF 3.0, BUII, EVO, and Pearl-DGS formulas were investigated in each AL group. RESULTS: A total of 327 eyes from 327 patients were analyzed, with 64, 102, 73 and 88 eyes in each AL group, respectively. In eyes with AL < 24.5 mm, myopic PE was significantly associated with greater LT using all the 5 formulas (all p < 0.05). Backward stepwise multivariate regression analyses revealed that LT was an important influencing factor for PE in all 5 formulas, particularly in eyes with AL <24.5 mm. In eyes with AL <24.5 mm and LT > 5.0 mm, PE of all 5 formulas calculated with the optional parameter LT were more myopic than those calculated without LT. CONCLUSIONS: Thicker LT was associated with more myopic PE among eyes with AL <24.5 mm when using all 5 formulas. Further optimization of current formulas is necessary, especially for eyes with short AL and thick LT.

Association Between Endothelial Cell Density and Corneal Thickness in Medium, Short, and Long Eyes of Han Chinese Cataract Patients.

PURPOSE: To evaluate the association between the endothelial cell density (ECD) and central corneal thickness (CCT) in medium, short, and long eyes of preoperative Han Chinese cataract patients. DESIGN: Retrospective cross-sectional study. METHODS: We consecutively enrolled 410 eyes, namely, 50 short eyes (axial length [AL]<22.0 mm), 150 medium eyes (22.0≤AL<24.0 mm), 120 medium-long eyes (24.0≤AL<26.0 mm), and 90 long eyes (AL≥26.0 mm), of 410 adult patients scheduled for cataract surgery. The ECD and CCT were determined preoperatively with a noncontact specular microscope. The association between the CCT and ECD was identified by using a multivariable regression analysis. A thin cornea was defined as having a CCT less than 500 µm. RESULTS: After adjusting for age, the presence of arterial hypertension, the presence of diabetes mellitus, intraocular pressure, and AL, a positive association between the CCT and ECD was identified in short eyes (linear regression coefficient [B]=3.40; standardized B [ß]=0.52; P = .03), medium eyes (B = 2.33; ß=0.28; P = .002), medium-long eyes (B = 1.84; ß=0.25; P = .02), and long eyes (B = 2.69; ß=0.41; P = .04). In the total group, the multivariable logistic analysis showed a significant link between the presence of a thin cornea and a lower ECD (odds ratio [OR]=0.80 per 100 cells/mm2 increase; P = .001). CONCLUSIONS: For cataract patients of Han ethnicity, a significant association between a thin CCT and a lower ECD was shown across the AL spectrum and was most prominent in short eyes. Eyes with a thin cornea are more likely to have a lower ECD.

Impact of segmented optical axial length on the performance of intraocular lens power calculation formulas.

PURPOSE: To investigate the difference between the segmented axial length (AL) and the composite AL on a swept-source optical coherence tomography biometer and to evaluate the subsequent effects on artificial intelligence intraocular lens (IOL) power calculations: the Kane and Hill-RBF 3.0 formulas compared with established vergence formulas. SETTING: National Hospital Organization, Tokyo Medical Center, Japan. DESIGN: Retrospective case series. METHODS: Consecutive patients undergoing cataract surgery with a single-piece IOL were reviewed. The prediction accuracy of the Barrett Universal II, Haigis, Hill-RBF 3.0, Hoffer Q, Holladay 1, Kane, and SRK/T formulas based on 2 ALs were compared for each formula. The heteroscedastic test was used with the SD of prediction errors as the endpoint for formula performance. RESULTS: The study included 145 eyes of 145 patients. The segmented AL (24.83 ± 1.89) was significantly shorter than the composite AL (24.88 ± 1.96, P < .001). Bland-Altman analysis revealed a negative proportional bias for the differences between the segmented AL and the composite AL. The SD values obtained by Hoffer Q, Holladay 1, and SRK/T formulas based on the segmented AL (0.52 diopters [D], 0.54 D, and 0.50 D, respectively) were significantly lower than those based on the composite AL (0.57 D, 0.60 D, and 0.52 D, respectively, P < .01). CONCLUSIONS: The segmented ALs were longer in short eyes and shorter in long eyes than the composite ALs. The refractive accuracy can be improved in the Hoffer Q, Holladay 1, and SRK/T formulas by changing the composite ALs to the segmented ALs.

The long and short of it: a comprehensive assessment of axial length estimation in myopic eyes from ocular and demographic variables.

BACKGROUND/OBJECTIVES: Axial length, a key measurement in myopia management, is not accessible in many settings. We aimed to develop and assess machine learning models to estimate the axial length of young myopic eyes. SUBJECTS/METHODS: Linear regression, symbolic regression, gradient boosting and multilayer perceptron models were developed using age, sex, cycloplegic spherical equivalent refraction (SER) and corneal curvature. Training data were from 8135 (28% myopic) children and adolescents from Ireland, Northern Ireland and China. Model performance was tested on an additional 300 myopic individuals using traditional metrics alongside the estimated axial length vs age relationship. Linear regression and receiver operator characteristics (ROC) curves were used for statistical analysis. The contribution of the effective crystalline lens power to error in axial length estimation was calculated to define the latter's physiological limits. RESULTS: Axial length estimation models were applicable across all testing regions (p ≥ 0.96 for training by testing region interaction). The linear regression model performed best based on agreement metrics (mean absolute error [MAE] = 0.31 mm, coefficient of repeatability = 0.79 mm) and a smooth, monotonic estimated axial length vs age relationship. This model was better at identifying high-risk eyes (axial length >98th centile) than SER alone (area under the curve 0.89 vs 0.79, respectively). Without knowing lens power, the calculated limits of axial length estimation were 0.30 mm for MAE and 0.75 mm for coefficient of repeatability. CONCLUSIONS: In myopic eyes, we demonstrated superior axial length estimation with a linear regression model utilising age, sex and refractive metrics and showed its clinical utility as a risk stratification tool.

Quantitative analysis of dynamic iris changes in primary angle-closure disease with long axial lengths: the Handan Eye Study.

OBJECTIVE: To investigate dynamic iris changes in patients with primary angle-closure disease (PACD) with long axial length (AL) compared to those with short and medium AL. METHODS: This observational cross-sectional study enrolled participants aged 35 years or older from the Handan Eye Study follow-up examination who were diagnosed with PACD and underwent Visante anterior segment optical coherence tomography (ASOCT) imaging under light and dark conditions. The right eye of each participant was included in the analysis. AL was categorized as short (<22.0 mm), medium (≥22.0 to ≤23.5 mm), or long (>23.5 mm). Anterior segment parameters, including iris dynamic changes, were compared among the three groups with different ALs. RESULTS: Data from 448 patients with PACD were analyzed. We found that 10.9% of included eyes had a long AL with a flatter cornea; larger central anterior chamber depth, angle opening distance, anterior chamber width, anterior chamber area, and volume; and smaller lens thickness and lens vault (LV) (P < 0.05) than those with short AL. No significant difference existed between the three groups in iris thickness, iris cross-sectional area (IA), iris curvature, or pupil diameter (PD) change between light and dark (P > 0.05). The significant associated factors for IA changes were area recess area (ARA) in the dark, LV in the dark, and PD change from light to dark (P < 0.05). CONCLUSIONS: Dynamic and static iris parameters were consistent across patients with PACD with short, medium, or long AL and may contribute to the pathogenesis of angle closure in atypical PACD.

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.

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

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

Guided Trocar Insertion in Highly Myopic Eyes.

PURPOSE: To demonstrate through a diagnostic test used as a new preoperative assessment that trocar insertion for pars plana vitrectomy could be safely placed at a distance >4.0 mm in highly myopic eyes to facilitate the surgical maneuvers. METHODS: Thirty eyes of 30 patients were tested with a biometer for the axial length measurement and with ultrasound biomicroscopy to measure the pars plana length. Pars plana lengths of highly myopic eyes were then compared with those of emmetropic eyes. The surgeon also measured the pars plana of highly myopic eyes intraoperatively and compared it with ultrasound measurements to assess ultrasound biomicroscopy reliability. RESULTS: The mean axial length was 23.81 mm (SD ± 0.30) in the control group and 31.11 mm (SD ± 0.56) in the myopic group. The mean pars plana length was 4.96 mm (SD ± 0.19) in control eyes and 6.65 (SD ± 0.36) in myopic eyes. An extremely significant statistical difference ( P < 0.001) was obtained by comparing the length of pars plana between control eyes and myopic eyes. The results of pars plana measurements were 6.65 mm (SD ± 0.36, ultrasound biomicroscopy) and 6.66 mm (SD ± 0.34, intraoperative measurements) in myopic eyes. The statistical comparison of the measurements in these two groups did not give a statistically significant result ( P = 0.950). CONCLUSION: Ultrasound biomicroscopy is a reliable technique to calculate the length of pars plana in highly myopic eyes, where this parameter is significantly greater than that of emmetropic eyes. Trocars insertion for pars plana vitrectomy may be performed, in eyes with axial length >30 mm, in relative safety at a distance to limbus higher than 4 mm.

Development and validation of a deep learning model to predict axial length from ultra-wide field images.

BACKGROUND: To validate the feasibility of building a deep learning model to predict axial length (AL) for moderate to high myopic patients from ultra-wide field (UWF) images. METHODS: This study included 6174 UWF images from 3134 myopic patients during 2014 to 2020 in Eye and ENT Hospital of Fudan University. Of 6174 images, 4939 were used for training, 617 for validation, and 618 for testing. The coefficient of determination (R2), mean absolute error (MAE), and mean squared error (MSE) were used for model performance evaluation. RESULTS: The model predicted AL with high accuracy. Evaluating performance of R2, MSE and MAE were 0.579, 1.419 and 0.9043, respectively. Prediction bias of 64.88% of the tests was under 1-mm error, 76.90% of tests was within the range of 5% error and 97.57% within 10% error. The prediction bias had a strong negative correlation with true AL values and showed significant difference between male and female (P < 0.001). Generated heatmaps demonstrated that the model focused on posterior atrophy changes in pathological fundus and peri-optic zone in normal fundus. In sex-specific models, R2, MSE, and MAE results of the female AL model were 0.411, 1.357, and 0.911 in female dataset and 0.343, 2.428, and 1.264 in male dataset. The corresponding metrics of male AL models were 0.216, 2.900, and 1.352 in male dataset and 0.083, 2.112, and 1.154 in female dataset. CONCLUSIONS: It is feasible to utilize deep learning models to predict AL for moderate to high myopic patients with UWF images.

Parapapillary ßBM and γ Zones Played Different Roles in Axial Elongation Among Young Adolescents Using Optical Coherence Tomography.

Purpose: To evaluate the influencing factors of parapapillary ßBM and γ zones incidence in young adolescents and to explore their associations with axial length progression. Methods: In this prospective cohort study, 976 seventh-grade students from nine secondary schools in Beijing, China, were enrolled and followed up 1 year later. Parapapillary ßBM zone was defined as retinal pigment epithelium loss while Bruch's membrane was present. Parapapillary γ zone was defined as the absence of retinal pigment epithelium and Bruch's membrane. Logistic regression model was used to analyze the influencing factors of ßBM and γ zone incidence. A linear mixed model was used to analyze the associations between parapapillary zones and axial elongation. Results: Of the 976 participants, 139 (14.2%) had only ßBM zone, 398 (40.8%) had only γ zone, and 171 (17.5%) had both. At follow-up, the incidence of ßBM zone was 11.5% (76/659), and the incidence of γ zone was 9.7% (39/404). Optic disc tilt, thinner subfoveal choroid, and longer axial length at baseline showed a higher risk of γ zone incidence. The absence of γ zone at baseline showed a faster axial length progression. When the baseline axial length was 25 mm or longer, the ßBM zone was also related to the axial elongation. Conclusions: The γ zone was associated with axial length progression, and the ßBM zone was also associated with the axial length progression when the axial length exceeded 25 mm, which was consistent with the notion that excessive axial length growth not only is the extension of the eyeball but also has its own pathologic changes.

Observation of the effect of posterior scleral reinforcement combined with orthokeratology and 0.01% atropine in the treatment of congenital myopia: a case report.

BACKGROUND: Myopia has recently emerged as a significant threat to global public health. The high and pathological myopia in children and adolescents could result in irreversible damage to eye tissues and severe impairment of visual function without timely control. Posterior scleral reinforcement (PSR) can effectively control the progression of high myopia by limiting posterior scleral expansion, improving retrobulbar vascular perfusion, thereby stabilizing the axial length and refraction of the eye. Moreover, orthokeratology and low concentrations of atropine are also effective in slowing myopia progression. CASE PRESENTATION: A female child was diagnosed with binocular congenital myopia and amblyopia at the age of 3 and the patient's vision had never been rectified with spectacles at the first consultation. The patient's ophthalmological findings suggested, high refractive error with low best corrected visual acuity, longer axial length beyond the standard level of her age, and fundus examination suggesting posterior scleral staphyloma with weakened hemodynamics of the posterior ciliary artery. Thereby, PSR was performed to improve fundus health and the combination of orthokeratology and 0.01% atropine were performed to control the development of myopia. Following up to 8 years of clinical treatment and observations, the progression of myopia could be well controlled and fundus health was stable. CONCLUSION: In this report, 8-year of clinical observation indicated that PSR could improve choroidal thickness and hemodynamic parameters of the retrobulbar vessels, postoperative orthokeratology combined with 0.01% atropine treatment strategy may be a good choice for myopia control effectively.

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.

Myopia: Histology, clinical features, and potential implications for the etiology of axial elongation.

Myopic axial elongation is associated with various non-pathological changes. These include a decrease in photoreceptor cell and retinal pigment epithelium (RPE) cell density and retinal layer thickness, mainly in the retro-equatorial to equatorial regions; choroidal and scleral thinning pronounced at the posterior pole and least marked at the ora serrata; and a shift in Bruch's membrane opening (BMO) occurring in moderately myopic eyes and typically in the temporal/inferior direction. The BMO shift leads to an overhang of Bruch's membrane (BM) into the nasal intrapapillary compartment and BM absence in the temporal region (i.e., parapapillary gamma zone), optic disc ovalization due to shortening of the ophthalmoscopically visible horizontal disc diameter, fovea-optic disc distance elongation, reduction in angle kappa, and straightening/stretching of the papillomacular retinal blood vessels and retinal nerve fibers. Highly myopic eyes additionally show an enlargement of all layers of the optic nerve canal, elongation and thinning of the lamina cribrosa, peripapillary scleral flange (i.e., parapapillary delta zone) and peripapillary choroidal border tissue, and development of circular parapapillary beta, gamma, and delta zone. Pathological features of high myopia include development of macular linear RPE defects (lacquer cracks), which widen to round RPE defects (patchy atrophies) with central BM defects, macular neovascularization, myopic macular retinoschisis, and glaucomatous/glaucoma-like and non-glaucomatous optic neuropathy. BM thickness is unrelated to axial length. Including the change in eye shape from a sphere in emmetropia to a prolate (rotational) ellipsoid in myopia, the features may be explained by a primary BM enlargement in the retro-equatorial/equatorial region leading to axial elongation.

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.

Beta zone parapapillary atrophy in elderly Chinese.

PURPOSE: Assess the beta zone parapapillary atrophy in elderly Chinese. PATIENTS AND METHODS: The Beijing Eye Study 2011 is a population-based cross-sectional study, which includes 3468 patients with the average age of 64.5 ± 9.8 years. The beta zone of parapapillary atrophy was captured and analyzed morphometrically by using colour optic disc photographs. RESULTS: The beta zone was found in 1358 (39.9%) eyes, measuring 0.37 ± 0.84 mm2 in size, 203.5 ± 81.8° in circumferential angle, 0.36 ± 0.27 mm in the maximum radial extent, the most often and longest in the temporal peripapillary region, followed by the temporal inferior region and the temporal superior region, the nasal region at least. Beta zone has statistically significant association with male gender (P = 0.001), myopic refractive error (P = 0.003), thinner retinal nerve fiber layer thickness (P<0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P<0.001). The size of beta zone has statistically significant association with longer axial length (P = 0.004)，increasing age (P<0.001), urban (P = 0.025), cardiovascular disease history (P = 0.025), with age related macular degeneration (P = 0.038), myopic ametropia (P<0.001), thinner retinal nerve fiber layer thickness (P = 0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P = 0.001). CONCLUSION: The population prevalence of beta zone was 39.9% in elderly Chinese. The area of the beta zone has statistically significant association with age, urban, the thickness of retinal nerve fiber layer, age related macular degeneration, cardiovascular disease history, axial length, myopic refractive error, size of optic disc size, the thickness of subfoveal choroid.

CHARACTERISTICS AND MANAGEMENT OF MYOPIC TRACTION MACULOPATHY IN MYOPIC EYES WITH AXIAL LENGTH LESS THAN 26.5 mm.

PURPOSE: To explore the characteristics and underlying mechanisms of myopic traction maculopathy (MTM) with axial length less than 26.5 mm and to assess the effectiveness of macular buckling for the treatment of MTM. METHODS: Thirty-eight MTM eyes with axial length less than 26.5 mm were prospectively enrolled. Thirty-one eyes received surgery, and they were followed up for at least 6 months. Characteristics of MTM and surgical outcomes were evaluated. RESULTS: Of the MTM eyes, 92.11% (35/38) showed posterior staphyloma. Narrow macular staphyloma was the most common type (54.29%, 19/35), followed by peripapillary (37.14%, 13/35). Three cases (8.57%) had wide macular staphyloma, and 44.74% of cases (17/38) had vitreoretinal traction. Twenty-two MTM eyes of type T3 underwent macular buckling surgery, and all the cases achieved foveal reattachment after the surgery. The mean best-corrected visual acuity improved significantly at the 6-month follow-up (P < 0.001). Nine MTM eyes of type T4 or T5 received combined surgery, all macular holes recovered, and the best-corrected visual acuity also improved postoperatively (P = 0.008) as of the 6-month visit. CONCLUSION: Posterior staphyloma might serve as the initial force of the pathogenesis of MTM in eyes with axial length ˂26.5 mm. Macular buckling is a productive way to improve the MTM.

Melanopsin modulates refractive development and myopia.

Myopia, or nearsightedness, is the most common form of refractive abnormality and is characterized by excessive ocular elongation in relation to ocular power. Retinal neurotransmitter signaling, including dopamine, is implicated in myopic ocular growth, but the visual pathways that initiate and sustain myopia remain unclear. Melanopsin-expressing retinal ganglion cells (mRGCs), which detect light, are important for visual function, and have connections with retinal dopamine cells. Here, we investigated how mRGCs influence normal and myopic refractive development using two mutant mouse models: Opn4-/- mice that lack functional melanopsin photopigments and intrinsic mRGC responses but still receive other photoreceptor-mediated input to these cells; and Opn4DTA/DTA mice that lack intrinsic and photoreceptor-mediated mRGC responses due to mRGC cell death. In mice with intact vision or form-deprivation, we measured refractive error, ocular properties including axial length and corneal curvature, and the levels of retinal dopamine and its primary metabolite, L-3,4-dihydroxyphenylalanine (DOPAC). Myopia was measured as a myopic shift, or the difference in refractive error between the form-deprived and contralateral eyes. We found that Opn4-/- mice had altered normal refractive development compared to Opn4+/+ wildtype mice, starting ∼4D more myopic but developing ∼2D greater hyperopia by 16 weeks of age. Consistent with hyperopia at older ages, 16 week-old Opn4-/- mice also had shorter eyes compared to Opn4+/+ mice (3.34 vs 3.42 mm). Opn4DTA/DTA mice, however, were more hyperopic than both Opn4+/+ and Opn4-/- mice across development ending with even shorter axial lengths. Despite these differences, both Opn4-/- and Opn4DTA/DTA mice had ∼2D greater myopic shifts in response to form-deprivation compared to Opn4+/+ mice. Furthermore, when vision was intact, dopamine and DOPAC levels were similar between Opn4-/- and Opn4+/+ mice, but higher in Opn4DTA/DTA mice, which differed with age. However, form-deprivation reduced retinal dopamine and DOAPC by ∼20% in Opn4-/- compared to Opn4+/+ mice but did not affect retinal dopamine and DOPAC in Opn4DTA/DTA mice. Lastly, systemically treating Opn4-/- mice with the dopamine precursor L-DOPA reduced their form-deprivation myopia by half compared to non-treated mice. Collectively our findings show that disruption of retinal melanopsin signaling alters the rate and magnitude of normal refractive development, yields greater susceptibility to form-deprivation myopia, and changes dopamine signaling. Our results suggest that mRGCs participate in the eye's response to myopigenic stimuli, acting partly through dopaminergic mechanisms, and provide a potential therapeutic target underling myopia progression. We conclude that proper mRGC function is necessary for correct refractive development and protection from myopia progression.