The Genetic Determinants of Axial Length: From Microphthalmia to High Myopia in Childhood.

The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is 23.5 mm, but the molecular mechanisms regulating ocular axial length remain poorly understood. Underdevelopment can lead to microphthalmia (defined as a small eye with an axial length of less than 19 mm at 1 year of age or less than 21 mm in adulthood) within the first trimester of pregnancy. However, continued overgrowth can lead to axial high myopia (an enlarged eye with an axial length of 26.5 mm or more) at any age. Both conditions show high genetic and phenotypic heterogeneity associated with significant visual morbidity worldwide. More than 90 genes can contribute to microphthalmia, and several hundred genes are associated with myopia, yet diagnostic yields are low. Crucially, the genetic pathways underpinning the specification of eye size are only now being discovered, with evidence suggesting that shared molecular pathways regulate under- or overgrowth of the eye. Improving our mechanistic understanding of axial length determination will help better inform us of genotype-phenotype correlations in both microphthalmia and myopia, dissect gene-environment interactions in myopia, and develop postnatal therapies that may influence overall eye growth.

Circulating Autoantibody Profiling Identifies LIMS1 as a Potential Target for Pathogenic Autoimmunity in pathologic Myopia.

High myopia is a leading cause of blindness worldwide, among which pathologic myopia, characterized by typical myopic macular degeneration, is the most detrimental. However, its pathogenesis remains largely unknown. Here, using a HuProt array, we first initiated a serological autoantibody profiling of high myopia and identified 18 potential autoantibodies, of which anti-LIMS1 autoantibody was validated by a customized focused microarray. Further subgroup analysis revealed its actual relevance to pathologic myopia, rather than simple high myopia without myopic macular degeneration. Mechanistically, anti-LIMS1 autoantibody predominantly belonged to IgG1/IgG2/IgG3 subclasses. Serum IgG obtained from patients with pathologic myopia could disrupt the barrier function of retinal pigment epithelial cells via cytoskeleton disorganization and tight junction component reduction, and also trigger a pro-inflammatory mediator cascade in retinal pigment epithelial cells, which were all attenuated by depletion of anti-LIMS1 autoantibody. Together, these data uncover a previously unrecognized autoimmune etiology of myopic macular degeneration in pathologic myopia.

Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia.

BACKGROUNDS: Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. METHODS: A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded. Variants were detected by exome sequencing and then analyzed through multiple-step bioinformatic and co-segregation analysis and finally confirmed by Sanger sequencing. Genetic findings were correlated with associated clinical data for analysis. RESULTS: Among the 75 probands with a mean age of 6.21 ± 4.70 years at the presentation, myopic fundus of C1 and C2 was observed in 73 (97.3%) probands. Surprisingly, specific peripheral changes were identified in 63 eyes involving 36 (48.0%) probands after extensive examination, including peripheral retinal avascular zone (74.6%, 47/63 eyes), neovascularization (54.0%), fluorescein leakage (31.7%), peripheral pigmentary changes (31.7%), and others. Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage. CONCLUSIONS: Genetic defects were identified in about one-fourth of simplex uHM patients in which significant consequences may be hidden under a classic myopic fundus in up to half. To our knowledge, this is the first systematic genetic study on simplex uHM to date. In addition to routine care of strabismus and amblyopia, careful examination of the peripheral retina and genetic screening is warranted for patients with uHM in order to identify signs of risk for retinal detachment and other complications and provide meaningful genetic counseling.

Development and validation of predictive models for myopia onset and progression using extensive 15-year refractive data in children and adolescents.

BACKGROUND: Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions. METHODS: We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3-18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models. RESULTS: The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807-0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia. CONCLUSIONS: The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3-18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.

Developing and validating a clinlabomics-based machine-learning model for early detection of retinal detachment in patients with high myopia.

BACKGROUND: Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients. METHODS: We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD. RESULTS: Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322-0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250-0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060-0.8966) and 0.5355 (95%CI = 0.4988-0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340-0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345-0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals. CONCLUSION: GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic.

Positive and Negative Associations of Myopia with Ocular Diseases in Population-Based Studies.

PURPOSE: Prevalence of myopia and vision impairment due to myopic macular degeneration and myopia-related optic neuropathies have markedly increased worldwide. We evaluated whether myopia is associated with other ocular disorders. DESIGN: Population-based studies conducted in Russia, China, and India. PARTICIPANTS: The Russian Ural Eye and Medical Study (UEMS) and the Beijing Eye Study (BES) included 5899 individuals and 4439 individuals (all aged 40+ years), respectively, and the Central India Eye and Medical Study (CIEMS) consisted of 4711 individuals aged 30+ years. The studies were conducted in rural and urban regions in Bashkortostan/Russia, Nagpur/India, and Beijing/China. METHODS: The participants underwent a series of ophthalmological and general medical examinations. MAIN OUTCOME MEASURES: Axial length as a surrogate for myopia and prevalence of diabetic retinopathy (DR), age-related macular degeneration (AMD), angle-closure glaucoma (ACG), and open-angle glaucoma (OAG). RESULTS: In the UEMS, DR prevalence (odds ratio [OR], 0.73), AMD prevalence (OR, 0.85), and ACG prevalence (OR, 0.72) decreased, and OAG prevalence (OR, 1.65) increased with longer axial length in multivariable analyses. In the CIEMS, lower AMD prevalence (OR, 0.81) and lower ACG prevalence (OR, 0.55), and higher OAG prevalence (OR, 1.45) were associated with longer axial length. Diabetic retinopathy prevalence (0.33%) was too low for statistical analysis in the CIEMS. In the BES, prevalence (OR, 0.64) and 10-year incidence of DR (OR, 0.48) and prevalence (OR, 0.83) and 5-year incidence of AMD (OR, 0.996) decreased, and prevalence (OR, 1.35) and 10-year incidence of OAG (OR, 1.40) increased with longer axial length. In all 3 studies, the association between higher OAG prevalence and longer axial length was nonlinear with a slight increase for the moderate myopia range and a steep increase in the highly myopic range. CONCLUSIONS: Myopia is associated with a lower prevalence of DR, AMD, and ACG and a lower incidence of DR and AMD, whereas high myopia more than moderate myopia is associated with a higher prevalence and incidence of OAG. Future studies may assess whether in myopia (in particular, in moderate myopia), the myopia-related advantages, that is, lower prevalence of DR, AMD, and ACG, may outweigh the increased risks for OAG and other myopia-related disorders. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial.

PURPOSE: To assess the effectiveness and safety of repeated low-level red light (RLRL), which is a newly available treatment for myopia control in children and adolescents with high myopia. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (randomized controlled trial; NCT05184621). PARTICIPANTS: Between February 2021 and April 2022, 192 children aged 6 to 16 years were enrolled. Each child had at least 1 eye with myopia of cycloplegic spherical equivalent refraction (SER) at least -4.0 diopters (D), astigmatism of ≤2.0 D, anisometropia of ≤3.0 D, and best-corrected visual acuity (BCVA) of 0.2 logarithm of the minimum angle of resolution or better. Follow-up was completed by April 2023. METHODS: Participants were randomly assigned at a 1:1 ratio to intervention (RLRL treatment plus single-vision spectacles) or control (single-vision spectacles) groups. The RLRL treatment was administered for 3 minutes per session, twice daily with a minimum interval of 4 hours, 7 days per week. MEAN OUTCOME MEASURES: The primary outcome and key secondary outcome were changes in axial length (AL) and cycloplegic SER measured at baseline and the 12-month follow-up visit. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy. RESULTS: Among 192 randomized participants, 188 (97.91%) were included in the analyses (96 in the RLRL group and 92 in the control group). After 12 months, the adjusted mean change in AL was -0.06 mm (95% confidence interval [CI], -0.10 to -0.02 mm) and 0.34 mm (95% CI, 0.30 to 0.39 mm) in the intervention and control groups, respectively. A total of 48 participants (53.3%) in the intervention group were still experiencing axial shortening >0.05 mm at the 12-month follow-up. The mean SER change after 12 months was 0.11 D (95% CI, 0.02to 0.19 D) and -0.75 D (95% CI, -0.88 to -0.62 D) in the intervention and control groups, respectively. CONCLUSIONS: Repeated low-level red light demonstrates stronger treatment efficacy among those with high myopia, with 53.3% experiencing substantial axial shortening. Repeated low-level red light provides an excellent solution for the management of high myopia progression, a significant challenge in ophthalmology practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prevalence and Cause of Loss of Visual Acuity and Visual Field in Highly Myopic Eyes: The Beijing Eye Study.

PURPOSE: To explore the prevalence and causes of loss of visual acuity and visual field in highly myopic eyes. DESIGN: Population-based study. PARTICIPANTS: 4439 subjects of the Beijing Eye Study underwent ophthalmological and systemic examinations including frequency doubling technology perimetry. METHODS: High myopia was defined by a refractive error of ≤-6 diopters (D) or axial length >26.0 mm. MAIN OUTCOME MEASURES: Prevalence of vision impairment causes. RESULTS: 212 highly myopic eyes from 154 participants were included with a mean age of 56.2 ± 9.6 years, a mean refractive error of -9.87 ± 3.70 D and a mean axial length of 27.2 ± 1.3 mm. We observed moderate/severe vision impairment (MSVI) in 40 eyes (18.9%; 95% confidence interval [CI], 13.6-24.2) and blindness in 10 eyes (4.7%; 95% CI, 1.8-7.6). Primary causes for MSVI and blindness were myopic macular degeneration (MMD) (29/50; 58%), age-related macular degeneration (1/50; 2%), and branch macular retinal vein occlusion (1/50; 2%). Secondary causes were MMD (4/50; 8%) and optic nerve atrophy (14/50, 28%), further differentiated into non-glaucomatous optic atrophy (NGOA) (9/50; 18%) and glaucomatous optic atrophy (GOA) (5/50; 10%). Prevalence of MMD as vision impairment cause increased significantly from 1/61 (1.6%) in the refractive error group of -6.00 to ≥-7.00 D, to 16/25 (64%) in the group of <-15.0 D. Higher MMD prevalence correlated with higher myopic refractive error (P < 0.001) and increased likelihood of concomitant optic neuropathy (P < 0.001). Similarly, prevalence of optic neuropathy as vision impairment cause increased from 0/61 (0%) in the refractive error group of -6.00 D to ≥-7.00 D, to 9/25 (36%) in the group of <-15.0 D. Higher optic neuropathy prevalence correlated with more myopic refraction (P < 0.001) and older age (P = 0.02). CONCLUSIONS: In this population-based recruited cohort of highly myopic patients, optic neuropathy accounted for vision impairment in 9.0% eyes, which was lower than the prevalence of MMD as vision impairment cause (18.9%). Notably, optic neuropathy became a significant contributor to vision impairment in more advanced high myopia, reaching 36% in the group with refractive error of <-15.0 D. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Targeting mechanics-induced trabecular meshwork dysfunction through YAP-TGFß Ameliorates high myopia-induced ocular hypertension.

High myopia is a risk factor for primary open angle glaucoma (POAG). The pathological mechanism of high myopia induced POAG occurrence is not fully understood. In this study, we successfully established the guinea pig model of ocular hypertension with high myopia, and demonstrated the susceptibility of high myopia for the occurrence of microbead-induced glaucoma compared with non-myopia group and the effect of YAP/TGF-ß signaling pathway in TM pathogenesis induced by high myopia. Moreover, we performed stretching treatment on primary trabecular meshwork (TM) cells to simulate the mechanical environment of high myopia. It was found that stretching treatment disrupted the cytoskeleton, decreased phagocytic function, enhanced ECM remodeling, and promoted cell apoptosis. The experiments of mechanics-induced human TM cell lines appeared the similar trend. Mechanically, the differential expressed genes of TM cells caused by stretch treatment enriched YAP/TGF-ß signaling pathway. To inhibit YAP/TGF-ß signaling pathway effectively reversed mechanics-induced TM damage. Together, this study enriches mechanistic insights of high myopia induced POAG susceptibility and provides a potential target for the prevention of POAG with high myopia.

Exploration of the pathophysiology of high myopia via proteomic profiling of human corneal stromal lenticules.

This study aimed to investigate the underlying pathophysiology of high myopia by analyzing the proteome of human corneal stromal lenticule samples obtained through small incision lenticule extraction (SMILE). A total of thirty-two patients who underwent SMILE were included in the study. Label-free quantitative proteomic analysis was performed on corneal stromal lenticule samples, equally representing high myopia (n = 10) and low myopia (n = 10) groups. The identified and profiled lenticule proteomes were analyzed using in silico tools to explore biological characteristics of differentially expressed proteins (DEPs). Additionally, LASSO regression and random forest model were employed to identify key proteins associated with the pathophysiology of high myopia. The DEPs were found to be closely linked to immune activation, extracellular matrix, and cell adhesion-related pathways according to gene ontology analysis. Specifically, decreased expression of COL1A1 and increased expression of CDH11 were associated with the pathogenesis of high myopia and validated by western blotting (n = 6) and quantitative real time polymerase chain reaction (n = 6). Overall, this study provides evidence that COL1A1 and CDH11 may contribute to the pathophysiology of high myopia based on comparative proteomic profiling of human corneal stromal lenticules obtained through SMILE.

Intraocular amphiregulin and axial elongation in non-human adolescent primates.

The purpose of the experimental interventional study was to examine the influence of intraocularly applied amphiregulin, a member of the epidermal growth factor (EGF) family, on axial length in young non-human primates. It included three non-human primates (Macaca mulatta), aged 4-6 years. The left eyes received three intravitreal injections of amphiregulin (400ng/50 µl) in intervals of 4 weeks, while the right eyes received three intravitreal injections of phosphate buffered solution (50 µl) at the same time points. Ocular biometry was performed in weekly intervals. At baseline, the left eyes (study eyes) were shorter than the right (control) eyes (20.69 ± 0.21 mm versus 20.79 ± 0.24 mm; P < 0.001), with an inter-eye axial length (AL) difference (left minus right eye) of -0.10 ± 0.23 mm. Inter-eye AL difference increased (P < 0.001) to 0.15 ± 0.18 mm at study end, at 12 weeks after baseline. Axial elongation during the study was higher (P < 0.001) in the left eyes (20.69 ± 0.21 mm to 21.05 ± 0.29 mm or 0.36 ± 0.30 mm) than in the right eyes (20.79 ± 0.24 mm to 20.90 ± 0.31 mm or 0.11 ± 0.17 mm). In a parallel manner, inter-eye difference in vitreous cavity depth combined with lens thickness (left eye minus right eye) increased from -0.04 ± 0.17 mm at baseline to -0.02 ± 0.21 mm (P = 0.02), 0.04 ± 0.10 mm (P = 0.002), and to 0.42 ± 0.67 mm (P < 0.001) at 5, 6, and 12 weeks after baseline, respectively. The results suggest that intravitreally applied amphiregulin as EGF family member led to an increase in axial length in adolescent non-human primates. It supports the hypothesis of amphiregulin as EGF family member being involved in the process of axial elongation.

Heterogenous thinning of peripapillary tissues occurs early during high myopia development in juvenile tree shrews.

Myopia is an independent risk factor for glaucoma, but the link between both conditions remains unknown. Both conditions induce connective tissue remodeling at the optic nerve head (ONH), including the peripapillary tissues. The purpose of this study was to investigate the thickness changes of the peripapillary tissues during experimental high myopia development in juvenile tree shrews. Six juvenile tree shrews experienced binocular normal vision, while nine received monocular -10D lens treatment starting at 24 days of visual experience (DVE) to induce high myopia in one eye and the other eye served as control. Daily refractive and biometric measurements and weekly optical coherence tomography scans of the ONH were obtained for five weeks. Peripapillary sclera (Scl), choroid-retinal pigment epithelium complex (Ch-RPE), retinal nerve fiber layer (RNFL), and remaining retinal layers (RRL) were auto-segmented using a deep learning algorithm after nonlinear distortion correction. Peripapillary thickness values were quantified from 3D reconstructed segmentations. All lens-treated eyes developed high myopia (-9.8 ± 1.5 D), significantly different (P < 0.001) from normal (0.69 ± 0.45 D) and control eyes (0.76 ± 1.44 D). Myopic eyes showed significant thinning of all peripapillary tissues compared to both, normal and control eyes (P < 0.001). At the experimental end point, the relative thinning from baseline was heterogeneous across tissues and significantly more pronounced in the Scl (-8.95 ± 3.1%) and Ch-RPE (-16.8 ± 5.8%) when compared to the RNFL (-5.5 ± 1.6%) and RRL (-6.7 ± 1.8%). Furthermore, while axial length increased significantly throughout the five weeks of lens wear, significant peripapillary tissue thinning occurred only during the first week of the experiment (until a refraction of -2.5 ± 1.9 D was reached) and ceased thereafter. A sectorial analysis revealed no clear pattern. In conclusion, our data show that in juvenile tree shrews, experimental high myopia induces significant and heterogeneous thinning of the peripapillary tissues, where the retina seems to be protected from profound thickness changes as seen in Ch-RPE and Scl. Peripapillary tissue thinning occurs early during high myopia development despite continued progression of axial elongation. The observed heterogeneous thinning may contribute to the increased risk for pathological optic nerve head remodeling and glaucoma later in life.

Distribution and associations of anterior lens zonules lengths in patients with cataract.

PURPOSE: To investigate the characteristics and associations of anterior lens zonules lengths in cataract patients via ultrasound biomicroscope (UBM) measurement. METHODS: Patients with age-related cataracts and high myopic cataracts who planned to undergo cataract surgery were included in the study. After routine ophthalmic examinations, the UBM was performed on both eyes to get images of the anterior lens zonules, and Image J software was used to measure the lengths of the lens zonules. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) diameter of both eyes were obtained by IOL Master 700. Univariate and multivariate regression analyses were used to assess associated factors of anterior lens zonules lengths. RESULTS: Forty-nine patients with age-related cataracts and 33 patients with high myopic cataracts were enrolled. High myopic cataract patients were younger and had longer anterior lens zonules. Multivariate regression analysis showed that anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.036, P = 0.029; nasal location: ß = 0.034, P = 0.011; superior location: ß = 0.046, P = 0.002) and ACD (inferior location: ß = 0.305, P = 0.016) in right eyes. In left eyes, anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.028, P = 0.017; inferior location: ß = 0.026, P = 0.016; nasal location: ß = 0.033, P < 0.001) and ACD (inferior location: ß = 0.215, P = 0.030; superior location: ß = 0.290, P = 0.011). CONCLUSIONS: High myopic cataract patients have longer anterior lens zonules. AL and ACD contributed to the lengths of anterior lens zonules. Thus, for patients with long AL and deeper ACD, lens zonules measurement was crucial. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn identifier is ChiCTR2300071397.

Biological ultrathin amniotic membrane flap to close refractory macular holes associated with high myopia.

PURPOSE: To propose an ultrathin biological amniotic membrane (btAM) thinner than 10 µm as the graft to treat highly myopic macular holes (MH). METHODS: This pilot study included 14 patients affected by refractory macular holes associated with high myopia. btAM was used as a bandage covering the holes. The best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography (OCT) before and after surgery were compared. RESULTS: The mean MH size was 865.93 ± 371.72 µm and all the MHs achieved anatomical closure. The btAM located centrally and fully on MHs from fundus photography yet no obvious visual masking was complained. The average BCVA 1 month, 3, and 6 months after surgery were 0.95 ± 0.24, 0.92 ± 0.23, 0.92 ± 0.23 logMAR, respectively, improved significantly compared to pre-operative BCVA (1.24 ± 0.42 logMAR, all P < 0.05). Ten out of 14 (71.4%) exhibited 2C closure patterns (formally closed and no bare RPE) on OCT. CONCLUSION: The btAM thinner showed a favorable anatomical success with less risk of parafoveal atrophy or iatrogenic injuries and shortened the dissolving time.

Relationship between the structure and microcirculation of the optic disc region and myopic traction maculopathy in highly myopic eyes.

PURPOSE: To explore the characteristics and influencing factors structural and microcirculatory of optic disc and peripapillary tissue in eyes with myopia traction maculopathy (MTM). METHODS: There were 100 eyes from 77 patients in this study. We used 1:1 matching axial length in myopic eyes. Patients were divided into two groups according to the presence or absence of MTM. Fundus structure parameters were obtained by swept source optical coherence tomography (SS-OCT), and the optic disc microcirculation parameters were obtained by OCT angiography (OCTA). RESULTS: MTM group were older (P = 0.001) and had poorer Best-corrected Visual Acuity (BCVA) (P = 0.011), the optic disc-fovea distance (DFD) was longer (P < 0.019), optic disc tilt was greater (P < 0.001), area of peripapillary atrophy (PPA) was larger (P < 0.001), and PPA/optical disc area (ONH) was higher (P < 0.001). The peripapillary scleral thickness (PST) was lower in the MTM group (P < 0.001). The mean peripapillary choroidal thickness (PCT) (P < 0.001) and PCT in the 10 orientations were significantly lower in the MTM group than in the NMTM group (all P < 0.01). Vascular density in the nasosuperior (NS) region of the optic disc was significantly lower in the MTM group (P = 0.037). The generalized estimating equation suggested that PPA area (P = 0.028), mean PCT (P = 0.008), superior PCT (P = 0.027), inferonasal PCT (P = 0.040), temporoinferior PCT (P = 0.013), and PST (P = 0.046) correlated with MTM. Age, axial length, optic disc tilt, PPA area, mean PCT, and optic disc central zone (0-2 mm) vascular density (all P < 0.05) were significantly correlated with PST. CONCLUSIONS: The enlarged PPA area and thinner PCT and PST in eyes with MTM are more significant. Lower PST in high myopia was related to abnormalities of PCT and microcirculation. TRIAL REGISTRATION: Clinical Trial Registration number: ChiCTR2100046590.

Lamellar macular hole in highly myopic eyes and insights into its development, evolution, and treatment: a mini-review.

Lamellar macular holes (LMHs) are a manifestation of myopic tractional maculopathy (MTM). Owing to the complex and multidirectional traction force in the elongated eyeball, the clinical features, development, evolution, and treatment algorithms of LMH in highly myopic eyes may differ from those of idiopathic LMH or MTM in general. This review aimed to specifically explore the LMHs in highly myopic eyes. Several developmental processes of LMH and their association with macular retinoschisis have been demonstrated, with the tractional component identified in all processes. Epiretinal proliferation was more prevalent and more extensive in LMHs in highly myopic eyes than in idiopathic LMHs. LMHs in highly myopic eyes may remain stable or progress to foveal detachment and full-thickness macular hole with or without retinal detachment. The predictive factors associated with disease progression were summarized to facilitate monitoring and guide surgical intervention. The treatment of LMHs in highly myopic eyes was based on an algorithm for treating myopic tractional maculopathy, including gas tamponade, pars plana vitrectomy, macular buckling, and a combination of vitrectomy and macular buckling. New internal limiting membrane (ILM) manipulation techniques such as fovea-sparing ILM peeling or fovea-sparing ILM peeling combined with ILM flap insertion could reduce the risk of developing iatrogenic full-thickness macular holes postoperatively. Further research should focus on the treatment of LMH in highly myopic eyes.

Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia.

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease. CASE PRESENTATION: A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome. CONCLUSIONS: This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.

Inverted flap technique versus internal limiting membrane insertion for macular hole in eyes with extremely high myopia.

BACKGROUND: To compare the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique and ILM insertion for macular hole (MH) without retinal detachment in eyes with extremely high myopia. METHODS: In this retrospective study, we analyzed 22 eyes with an axial length ≥ 30.0 mm that had underwent MH surgery between April 2015 and August 2021. The surgical procedures involved either an inverted ILM flap or ILM insertion. The outcomes were compared between the two techniques. Closure of the MH was confirmed by optical coherence tomography (OCT). The best-corrected visual acuity (BCVA) was measured before and after surgery. Associated complications were documented. RESULTS: The median of axial length was 30.64 mm (range, 30.0-34.42). The MH closed in 100% (22/22) eyes and did not recur with a median follow-up of 12.5 months. For the inverted ILM flap technique, the median BCVA improved significantly from 0.80 logarithm of the minimum angle of resolution (logMAR) (range, 0.40-2.00) before surgery to 0.70 logMAR (range, 0.09-1.52) after surgery (p = 0.002). In addition, the median of final BCVA was better for the inverted ILM flap than ILM insertion (0.7 logMAR V.S. 1.00 logMAR; p = 0.016). CONCLUSIONS: In eyes with extremely high myopia, despite comparable effects on MH closure for both ILM insertion and the inverted ILM flap, the later technique achieved significantly better visual outcomes.

Choroidal vascularity features of fundus tessellation in adults with high myopia.

BACKGROUND: To investigate alterations in choroidal vascularity index among highly myopic adults with fundus tessellation, utilizing optical coherence tomography. METHODS: Total of 143 highly myopic adults (234 eyes) with fundus tessellation were collected in this cross-sectional study, which was stratified into different lesion groups based on the novel tessellated fundus classification. Subfoveal choroidal thickness (SFCT), choroidal luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal vascularity index (CVI) were analyzed utilizing optical coherence tomography (OCT) with enhanced depth imaging (EDI) mode, enabling precise quantification of these parameters. RESULTS: Comparison analysis demonstrated notable distinctions in spherical equivalent (SE), axial length (AL), and SFCT across the four tessellation grades (p < 0.001). Analysis of the choroidal vascularity parameters, including LA, TCA, and CVI, demonstrated notable disparities across the four groups (p < 0.001), while no significant variations were observed in SA when comparing Grade 1 versus Grade 2, as well as Grade 2 versus Grade 3 (p > 0.05). Logistic regression analyses illustrated that the higher grade of tessellated exhibited a positive association with AL (OR = 1.701, p = 0.027), while negatively associated with SFCT (OR = 0.416, p = 0.007), LA (OR = 0.438, p = 0.010) and CVI (OR = 0.529, p = 0.004). Multiple regression analyses demonstrated a significant negative association between CVI and both SE and AL after adjusting for age, while positively associated with SFCT (p < 0.05). CONCLUSION: Subtle choroidal vascularity changes may have a meaningful contribution to the development and progression of fundus tessellation. CVI and LA dramatically decreased during the early stages of tessellation development and maintained a relatively stable status when in the severe tessellated grades.

Analyzing the topological properties of resting-state brain function network connectivity based on graph theoretical methods in patients with high myopia.

AIM: Recent imaging studies have found significant abnormalities in the brain's functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients. METHODS: We conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups. RESULTS: In the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01). CONCLUSION: HM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.