Translational Vision Science & Technology

Purpose: To develop an interpretable automated pipeline for dome-shaped macula (DSM) detection and measurement from optical coherence tomography (OCT) B-scans. Methods: We analyzed one eye from each of 300 children aged 4-18 years in the Shanghai Child and Adolescent Large-scale Eye Study High Myopia (SCALE-HM) cohort (50 DSM-positive; 100 test eyes). A U-Net pretrained on OCTA-500 and fine-tuned on the development set segmented the retinal pigment epithelium (RPE) boundary. A geometric module located the apex, fitted a tangent-line baseline, and computed perpendicular height in physical coordinates. An eye was DSM-positive if any gradable B-scan had height >= 50 um. Two masked graders evaluated the test set; a third adjudicated disagreements. Results: The area under the receiver operating characteristic curve was 0.927 (95% confidence interval [CI], 0.850-0.986), sensitivity was 82.1% (95% CI, 64.4%-92.1%), and specificity was 100% (95% CI, 94.9%-100%) against the adjudicated reference. In concordant-positive eyes, automated height agreed with manual measurements (intraclass correlation coefficient, 0.949; mean absolute error, 6.9 um; bias, -5.7 um, versus Doctor A). Mean RPE-boundary error on pediatric test scans was 1.54 um. Conclusions: The pipeline may be considered a reliable and reproducible tool for automated DSM detection and height measurement on radial OCT, with each value traceable to landmarks on the source B-scan. External validation across populations, devices, and acquisition protocols is needed. Translational Relevance: The pipeline provides an objective and reproducible method to detect DSM and quantify dome height, width, and orientation across OCT meridians. Because each measurement can be verified on the source B-scan, it enables standardized DSM assessment.

Purpose: To evaluate the associations of the numerical AI-CO center index and visually classified central dark-area extent with Humphrey 10-2 mean deviation (MD). Methods: This single-center retrospective study included 320 eyes of 169 patients with AI-CO imaging, broad-field 24-2F or 30-2 testing, and 10-2 testing. Both visual field examinations were performed within 365 days before or after AI-CO imaging. Two ophthalmologists independently classified central dark-area extent into five Levels (0-4). Analyses assessed Spearman correlations, areas under the receiver operating characteristic curve (AUCs), distributions across final central dark-area Levels, and interrater reliability. Patient-cluster bootstrap confidence intervals and a one-eye-per-patient sensitivity analysis addressed inclusion of both eyes. Results: AI-CO center correlated with 10-2 MD (rho=0.829; 95% CI, 0.773-0.873). AUCs for 10-2 MD below -2, -6, and -12 dB were 0.902, 0.939, and 0.961, respectively. The numbers of eyes in Levels 0-4 were 66, 57, 94, 53, and 50; median 10-2 MD values were -0.59, -1.48, -3.54, -6.24, and -18.15 dB, respectively. Quadratic-weighted kappa was 0.970 (95% CI, 0.958-0.981). Sensitivity analyses yielded broadly similar findings. Conclusions: The numerical AI-CO center index and visually classified central dark-area extent were associated with central visual field damage. Assessing the extent of dark regions in the central image alongside the numerical index may provide useful information for interpreting central visual field status from the AI-CO display.

Purpose: To externally evaluate the real-world performance of a commercially implemented artificial intelligence system that analyzes OCT image data and provides numerical and grayscale reference outputs, by characterizing the association and numerical relationship between AI-CO output and Humphrey visual field mean deviation (MD) in routine clinical practice. Study Design: Retrospective, single-center observational study. Methods: This study included 819 eyes of 424 patients who underwent AI-CO analysis and Humphrey 24-2F or 30-2 visual field testing within 1 year. The 24-2F and 30-2 groups comprised 343 and 476 eyes, respectively. Because the AI-CO all value, corresponding to the index labeled "peripheral" in the Japanese user interface, is a unitless index, its numerical relationship with Humphrey MD was explored using Pearson correlation, Bland-Altman analysis, and Passing-Bablok regression. Linearity was assessed using the original cumulative sum (CUSUM) procedure described by Passing and Bablok. Results: The AI-CO all value was strongly correlated with Humphrey MD in both the 24-2F (r = 0.836) and 30-2 (r = 0.854) groups (both P < 0.001). In Bland-Altman analysis, the mean difference (AI-CO all minus Humphrey MD) and 95% limits of agreement were -1.23 (-7.23 to 4.77) in the 24-2F group and -1.44 (-7.96 to 5.08) in the 30-2 group. In both groups, the 95% confidence interval for the Passing-Bablok slope included 1, whereas that for the intercept excluded 0. The original CUSUM procedure did not reject linearity in the overall cohort, the 24-2F group, or the 30-2 group (P = 0.086, 0.091, and 0.145, respectively). Conclusions: In this independent real-world external evaluation of a clinically implemented system, AI-CO all was strongly correlated with Humphrey MD, and linearity of their numerical relationship was not rejected. However, its unitless output was lower on average and showed substantial eye-level variability. AI-CO may therefore provide complementary structural-functional information in routine care but should not be interpreted as interchangeable with standard automated perimetry.

PurposeTo evaluate associations between green autofluorescence (GAF) and structural and functional measures relevant to retinal and optic neuropathies, and to establish normative GAF values across the optic nerve head (ONH), macula, and papillofoveal bundle (PFB) in rhesus macaques. MethodsEighty-two macaques with normal ONH morphology by spectral-domain optical coherence tomography (SD-OCT) were included with a mean {+/-} SD age of 12.76 {+/-} 7.18 (range 0.11-29.39) years. The GAF images were acquired in the ONH, macula and PFB with the OcuMet Beacon. In a subset of macaques (n=19), pattern electroretinogram (PERG) and photopic full-field ERG including the photopic negative response (PhNR) were recorded. ResultsThe GAF significantly increased with age in the ONH, macula and PFB. After adjusting by age, there were no sex differences, but IOP showed a positive association with macular GAF. At the ONH, higher GAF correlated with thinner retinal nerve fiber layer, inner and outer segment complex, and total retinal thickness. In the macula, inner nuclear layer thickness was positively associated with GAF, whereas outer plexiform layer and inner and outer segment complex were inversely associated. The PERG amplitudes inversely tracked ONH GAF. ConclusionsGAF rises with age and IOP, couples to retinal structure, and at the ONH, aligns with inner-retinal functional indices. This study provides a regional reference for GAF in rhesus macaques. Translational RelevanceNormative GAF data in healthy rhesus macaques provide a framework for interpreting this noninvasive signal in translational studies of retinal and optic nerve disease.

Purpose Device-specific field-of-view (FOV) may affect quantitative optical coherence tomography angiography (OCTA) metrics. This study quantifies inter-device FOV scale differences across four commonly used clinical OCTA devices. Methods Four devices were evaluated under a nominal 6 by 6 mm (or 20 degrees by 20 degrees) scanning protocol: Zeiss Cirrus, Heidelberg Spectralis, Topcon Triton, and Topcon Maestro2. Device-specific spatial scale was assessed by (1) phantom calibration using a model eye with a 1 by 1 mm checkerboard, computing scale factors relative to Zeiss Cirrus; and (2) in vivo validation, registering same-eye, same-visit retinal images from the three devices to those of Zeiss Cirrus and extracting scale factors from the transformation matrices. Correlation between DICOM-implied FOV and spherical equivalent (SE) was assessed, where DICOM-implied FOV equals pixel-spacing mutiply by image-dimension. Results Phantom measurements showed that Spectralis, Triton, and Maestro2 each captured a systematically smaller FOV than Cirrus, with geometric mean scale factors of 0.933, 0.954, and 0.967. The same pattern was observed across 801 eyes from 556 participants, giving geometric mean scale factors of 0.939, 0.943, and 0.960, agreeing with phantom estimates within 1.2%. DICOM-implied FOV was fixed at 6.000 by 6.000 mm for three devices but varied from 5.212 by 5.209 to 6.743 by 6.739 mm for Spectralis, correlating with SE (P < 0.001). Conclusion Systematic FOV discrepancies exist across clinical OCTA devices despite nominally identical protocols, and DICOM pixel-spacing should be interpreted with caution as a spatial measure. Translational Relevance The reported device-specific scale factors could serve as magnification corrections for quantitative OCTA metrics, addressing the systematic spatial inter-device discrepancies.

Purpose: To investigate the association between mitochondrial DNA (mtDNA) copy number (CN) and the rate of visual field progression in patients with primary open-angle glaucoma. Design: Retrospective cohort study Participants: 200 patients with primary open-angle glaucoma (POAG) with a mean of 11 years of longitudinal clinical data and DNA extracted from peripheral blood. Methods: DNA extraction was performed on peripheral blood leukocytes collected from 200 POAG patients who had an average follow-up of 11 years. Mitochondrial CN was quantified by multiplex quantitative TaqMan PCR using custom primers and probes against cytochrome b and beta-2 microglobulin as measures of mitochondrial and nuclear genes, respectively. Univariable and multivariable linear regression models were used to evaluate the association between mtDNA CN and rates of visual field progression, quantified by the slope of standard automated perimetry (SAP) mean deviation (MD) over time. Main Outcome Measures: Association of mtDNA CN with MD slope. Results: Mean mtDNA CN was 107.6 copies per cell (interquartile range, 70.5 to 126.7). Higher ln(mtDNA CN) was associated with slower rates of MD loss in both univariable (beta = 0.29, p < 0.001) and multivariable analyses (beta = 0.25, p = 0.003). Higher peak IOP was independently associated with faster visual field progression in both analyses. A significant interaction was observed between mtDNA CN and peak IOP (beta = -0.054, p < 0.001), with the association between lower mtDNA CN and faster SAP progression being more pronounced at lower levels of peak IOP. Conclusion: Lower mtDNA CN was associated with faster SAP progression, with the association being most pronounced at lower levels of peak IOP. These findings support mtDNA CN as a potential systemic biomarker of mitochondrial genomic reserve and susceptibility to visual field loss.

Purpose: To characterize the biomechanical response of the optic nerve head (ONH) in myopic versus non-myopic individuals with normal-tension glaucoma (NTG), and to evaluate the association between ONH strains and the rate of visual field (VF) progression. Design: Retrospective clinical cohort study. Participants: A total of 118 NTG eyes from 77 patients with [&ge;] 2 years of follow-up and 5 VF tests were enrolled, including 66 eyes with myopia and 52 eyes without. Methods: Each participant underwent three-dimensional (3D) optical coherence tomography (OCT) imaging of the ONH under three mechanical loading conditions: 20{degrees} adduction, 30{degrees} abduction and acute intraocular pressure (IOP) elevation by applying a 0.80 N force to the lower eyelid. Effective strains across the global ONH complex and within specific segmented tissues (pre-lamina, lamina cribrosa, choroid, and sclera) were quantified using a validated 3D strain-mapping algorithm. Results: Myopic NTG eyes exhibited significantly higher ONH strains compared to non-myopic eyes under acute IOP elevation (10.1{+/-}2.7% vs. 9.3{+/-}1.8%, P = 0.044) and abduction (9.2{+/-}2.3% vs. 8.4{+/-}2.1%, P = 0.048). In the non-myopic group, ONH strains varied significantly across conditions (P < 0.001), with adduction (9.9{+/-}2.0%) and acute IOP elevation (9.3{+/-}1.8%) eliciting greater strains than abduction (8.4{+/-}2.1%). These condition-dependent variations were less pronounced in the myopic group (10.1{+/-}2.7% vs. 9.8{+/-}2.7% vs. 9.2{+/-}2.3%, P = 0.07). Multivariable linear mixed-effects analysis revealed that in myopic NTG, higher ONH strains induced by adduction were significantly associated with faster MD decline (estimate: -0.139 dB/year per 1% increase, P = 0.03, adjusted for age, spherical equivalent and baseline perimetric mean defect). Conversely, larger strains during acute IOP elevation were associated with slower progression (estimate: 0.184 dB/year per 1% increase, P = 0.004). Tissue-specific analysis confirmed that adduction-induced strains in the choroid and pre-lamina tissue as well as IOP-induced strains across all ONH tissues were significantly correlated with the rate of perimetric progression in myopic eyes (all P < 0.05). Conclusions: In this cohort, greater adduction-induced ONH strain was associated with faster perimetric deterioration in myopic NTG. These findings support further investigation of gaze-related optic nerve traction as a potential non-IOP-related biomechanical factor in myopic NTG. Keywords: Normal tension glaucoma, Myopia, Optic nerve head, Ocular biomechanics, Visual field Progression, adduction.

Purpose: To evaluate the safety, procedural performance, sample recovery, and surgeon preference of an ophthalmic needle designed specifically for anterior chamber (AC) paracentesis. Methods: In this multicenter study, AC paracentesis was performed in clinic and operating-room settings using a 32-gauge x 4-mm needle with low dead space. The procedure was evaluated using a standardized physician survey. Prespecified outcomes included procedure-related adverse events (primary outcome), needle entry and handling, aspiration and sample recovery, comparative performance versus a 30-gauge needle, and physician preference for future use. Results: A total of 110 needle uses by eight surgeons were included. No ocular complications occurred, including lens or iris injury, hyphema, AC collapse, wound leak, hypotony, infection, or retinal complication, and no procedure required needle exchange or conversion to another device. Two technical events without ocular sequelae were noted, in which needle entry was partial thickness and did not reach the AC (1.8%; exact 95% CI, 0.2%-6.4%). Physicians rated needle entry, handling and sample recovery as good or excellent. Compared with a 30-gauge needle, the study needle was rated as at least comparable across all assessed domains. All surgeons rated it better or much better for intra-procedural safety and preferred it for future AC taps. Conclusions and Relevance: This short, 32-gauge low-dead-space ophthalmic needle demonstrated a favorable safety profile and was preferred over a 30-gauge needle by all surgeons. As aqueous humor liquid biopsy expands in clinical diagnostics and trials, an ophthalmic-specific needle design may help improve the consistency and safety of aqueous humor collection for molecular analysis and broader clinical use. Keywords: Anterior chamber paracentesis; Aqueous humor; Liquid biopsy; Low dead space; Ophthalmic needle

Purpose: To validate an automated pipeline to detect and quantify focal retinal and choroidal pulsation areas that are synchronous with the cardiac cycle in video indocyanine green angiography (ICGA). Design: Retrospective, observational, hypothesis-generating validation study Subjects, Participants: Consecutive patients with a diagnosis of central serous chorioretinopathy (CSCR) in one or both eyes. Methods: Videos were acquired on Heidelberg HRA+OCT. The pipeline consisted of three steps: signal extraction, foci detection, and quantification. After registration of the constituent frames, each pixel's intensity signal was analyzed at the presumed cardiac frequency (tested from a sample of three detectable frequencies). A synchrony score combining local phase coherence with oscillation amplitude was then derived and computed using a standard deviation ({sigma}) above each video's background oscillation value. Two masked graders marked the retinal and choroidal pulsation areas twice. We compared detection of the pulsation areas against grader consensus using a receiver operating characteristic curve (using multiple grid sizes to divide the scan area) and, separately, using a signal-based area-reduction method to obtain an optimum {sigma} value. Main Outcome Measures: Agreement between the automated algorithm and human graders in detection of pulsation foci, and the optimum threshold multiplier ({sigma}). Results: We studied 20 ICGA videos from 20 eyes. At the 16-pixel grid size, the pipeline achieved a mean area under the curve (AUC) of 0.914, sensitivity of 0.86, and specificity of 0.80. Grader agreement improved with larger grid size, reaching substantial-to-strong levels for choroidal annotations. The two independent validation methods demonstrated similar {sigma} values that differed by 0.62{sigma}, supporting {sigma}=4.0 as the optimum value. Conclusions: We report the first automated method to quantify retinal and choroidal vascular pulsation on video ICGA. It measures pixels that oscillate over time with the presumed cardiac cycle and works reliably at the spatial scale (grid level) where experts agree. Pulsatile hemodynamics may add a new vascular biomarker for glaucoma, diabetes, hypertension, and pachychoroid diseases.

Background: Low vision is a significant cause of visual morbidity in India, yet information on the demographic profile, disease patterns, and assistive technology (AT) utilisation among individuals seeking rehabilitation services remains limited. This study assessed the socio-demographic characteristics, morbidity profile, prior healthcare pathways, and awareness and use of AT among individuals attending a vision rehabilitation clinic. Methods: A cross-sectional analysis was conducted among 1,067 patients attending a tertiary care vision rehabilitation centre. Data were collected on demographics, socioeconomic status, visual acuity, morbidity patterns, prior health system contact, and awareness, usage, and unmet need for assistive products (APs). Results: Males comprised 68.7% of participants, with most (45.1%) aged 18 to 29 years. A majority were unemployed (88.6%), from joint families (75.3%), and economically weaker (95% earning <3 lakh/year). Optic atrophy (13.2%), retinitis pigmentosa (20.8%), rod-cone dystrophy (9.9%), and Stargardts disease (9.8%) were among the leading causes of visual impairment. Most participants had severe visual loss, with 94.8% having <1/60 vision. Only 20.4% possessed a disability card (UDID) despite being eligible. Nearly all patients (99%) had visited multiple health centres before reaching rehabilitation. Conclusion: The study highlights a predominantly young, unemployed population with hereditary ocular diseases and profound visual loss. Awareness and utilisation of assistive technologies remain critically low, underscoring the need for early referral pathways, improved AT training, financial support, and UDID uptake to enhance functional rehabilitation.

Digital photography remains the gold standard for dermatological assessment, but reliance on standardized stationary image-capture systems limits trial scalability, whereas smartphones combined with computer vision artificial intelligence (AI) could enable hybrid and decentralized clinical trials (DCTs). This study assessed the facial feature grading of an AI-based system against expert panel consensus across three settings with decreasing acquisition control: Standard Studio Imaging (SSI), Clinic Smartphone Imaging (CSI), and Home Smartphone Imaging (HSI). Expert inter-rater reliability was good to excellent (median ICC 0.84-0.90), and the system showed high operator-independent test-retest repeatability across independently captured images (median ICC 0.97-0.98). Agreement with experts was maintained across all settings for macro-geometric features (ptosis {rho} = 0.74-0.81, nasolabial fold {rho} = 0.68-0.79) and for discrete pigmentation and inflammatory lesions (pigmented spot density {rho} = 0.62-0.76), declined for fine-texture features under uncontrolled acquisition (forehead wrinkles {rho} = 0.76 to 0.48), and remained limited for color-dependent features irrespective of setting. These findings support the AI-based system as an objective grading tool for a defined subset of facial endpoints in hybrid and DCTs in dermatology.

Purpose: Pupil examination is a routine examination of patients presenting with ophthalmological or neurological symptoms. Our purpose was to determine the sensitivity of pupillometry using HP Reverb G2 Omnicept virtual reality (VR) headset for detecting anisocoria and relative afferent pupillary defect (RAPD). Methods: Twenty-nine patients were included; Group I with asymmetric optic neuropathy (N=21) and Group II with suspected pathological anisocoria (N=8); alongside 19 controls. VR pupillometry consisted of Pupil symmetry test and Swinging light test. Pathological thresholds were established using upper limits of controls. Results were compared with routine pupil exam. Correlations with functional ophthalmological test results were analyzed. Results: RAPD was detected in 16/21 Group 1 patients using both VR pupillometry and standard exam. Remaining 5 had relative afferent pupillary asymmetry (RAPA) within the control range (0.1-0.2 mm). Significant correlation was found between RAPA/RAPD and inter-eye difference in visual acuity and visual field defect (MD) (R=0.58 and 0.68, p<0.01). All patients with >5,8 dB inter-eye MD difference had RAPD. In Group II, pathological anisocoria (>0.8 mm) was detected using VR pupillometry and 1/8 on standard exam. Qualitative differences in pupillary constriction were observed. In control group anisocoria (0.4-0.8 mm) was detected in 37% (7/19); in all greater in the dark (mean 0.2 mm). Conclusion: In comparison to conventional exam VR pupillometry matched detection rate of RAPD and surpassed detection rate of pathological anisocoria. Longitudinal data on pupillary constriction characteristics could significantly contribute to patient diagnosis and monitoring in clinical studies as well as understanding physiological variability.

Published artificial intelligence for keratoconus is unproven in fellow eyes that topography and tomography call normal, the eyes where surgical decisions are made, although it reports near-perfect accuracy for early disease. In a registered systematic review of 573 studies (PROSPERO CRD420261441197), none of 2,035 claim-by-stratum units from 212 adjudicated studies established discrimination in these eyes. Most units (90.0%) answered a different question, never constructed the target population or certified its normality; external validation did not test label generation, and five systematic reviews did not assess it. In a public cohort, a frozen score yielded an area under the receiver operating characteristic curve of 0.996 against a same-eye index label and 0.549 against a contralateral proxy; its inputs reconstructed the label-generating index (r = 0.991), so accuracy there measured agreement with the index. Anchor-gap evaluation measures accuracy in these eyes against the contralateral clinical diagnosis.

Background/Aims: Neovascular glaucoma (NVG) is a severe, secondary glaucoma. This study aimed to identify factors associated with vision, intraocular pressure (IOP), and ocular pain outcomes. Methods: The cohort included all patients diagnosed with NVG during 2008-2024 at Helsinki University Hospital, Finland. Linear mixed-effects models used pre-specified covariates, whereas machine learning was given the full longitudinal data with biomicroscopic findings as an exploratory approach. Results: 626 patients were analysed. Worse baseline vision and a closed angle were associated with worse follow-up vision. Treatments were associated with lower IOP and less pain rather than better vision. Age, sex and comorbidity were largely not associated with the outcomes. Glaucoma drainage devices showed the greatest initial IOP reduction (-10.2 mmHg, 95% confidence interval, CI -11.9 to -8.6 mmHg), followed by transscleral cyclophotocoagulation (TSCPC, -4.7 mmHg, 95% CI -5.8 to -3.7 mmHg) and peripheral retinal cryotherapy (-2.2 mmHg, 95% CI -3.1 to -1.4 mmHg). TSCPC and cryotherapy were also associated with reduced pain (odds ratio 0.51 and 0.46). Pan-retinal photocoagulation and anti-VEGF showed smaller IOP reductions, with a pain reduction for pan-retinal photocoagulation only. Both methods agreed, and machine learning added no novel clinical findings. Conclusions: Vision in this cohort was largely set by the state of the eye at diagnosis. IOP control and pain relief therefore remain realistic goals even when sight cannot be saved. Peripheral retinal cryotherapy stood out, linked to both lower IOP and less pain, seldom reported in NVG. These associations from a large, unselected cohort identify treatments worth comparing prospectively.

Purpose: To understand the functional impact of macular atrophy (MA) and fibrosis in eyes with treated neovascular age-related macular degeneration (nAMD) based on deep visual sensitivity losses. Design: Cross-sectional study. Participants: One-hundred and nine eyes from 97 individuals with nAMD that had been treated for >=12 months without significant retinal fluid. Methods: All participants underwent defect-mapping microperimetry (DMP) testing - a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single 10 decibel stimuli presentations - where 208 locations were sampled in the central 8 degrees radius region. Participants also underwent color fundus photography, fundus autofluorescence and OCT imaging, which were co-registered and manually annotated for MA and fibrosis to determine their two-dimensional pointwise extent at individual test locations, and global extent in the corresponding region where DMP was performed. Main Outcome Measures: Pointwise association between the presence of MA and fibrosis with missing a stimulus on DMP and global association between the extent of MA and fibrosis with the proportion of locations missed (PLM) on DMP. Results: At a pointwise level, the presence of MA and fibrosis were independently associated with an increased likelihood of missing a stimulus on DMP (odds ratio = 42.5 and 2.5 respectively; P < 0.001 for both). However, at a global level, only an increasing extent of MA was associated with a significantly higher PLM on DMP (P < 0.001), but not fibrosis (P <= 0.227). MA extent explained a substantial proportion of the variance in the PLM (R2 = 0.97) and there was a very strong correlation between the two parameters ({rho} = 0.93). Conclusions: This study confirmed the expected functional impact of MA and fibrosis on DMP testing at a pointwise level. However, it showed at the global level that only the extent of MA, and not fibrosis, was independently associated with functional loss on DMP, and that there was a very strong structure-function correlation based on MA. These findings thus suggest that evaluating MA alone may be sufficient for capturing structural changes strongly associated with the global extent of deep visual sensitivity losses in those with treated nAMD.

Purpose: To compare continuous wavelet transform (CWT) and short-time Fourier transform (STFT) analyses of the oscillatory potentials (OPs) of the dark-adapted full-field electroretinogram (FFERG). Methods: FFERG recordings from Royal College of Surgeons (RCS) and healthy Brown Norway (BN) rats, wild-type and Atoh7 enhancer-knockout (KO) mice, and patients with diabetic retinopathy and healthy controls were analyzed with STFT and with CWT employing the real Morlet wavelet, after 60 Hz high-pass and sharp 60 Hz notch filtering. Time- and frequency-localized OP features were quantified and the methods compared on detection of transient OP signals. Both were additionally validated using synthetic OP-like bursts of known frequency embedded in each cohort's recorded noise. Results: CWT revealed distinct time-frequency patterns and disease-specific OP alterations across all rat, mouse, and human cohorts, with improved temporal localization and frequency resolution, whereas STFT merged transient features and was more susceptible to noise. CWT-derived dominant-frequency differences reached significance in all three models; the corresponding STFT difference reached significance only in rats (separate tests; methods not directly compared). In synthetic bursts, both methods recovered injected frequencies to within 1-2.5 Hz, but only CWT resolved two bursts separated by 15 ms. Conclusions: CWT employing the real Morlet wavelet provides a robust, physiologically relevant evaluation of OPs, with improved temporal localization and reduced spectral dispersion relative to STFT in clinical and experimental settings. Translational Relevance: CWT analysis may improve the characterization of inner retinal dysfunction by preserving transient OP time-frequency structure, as illustrated in preclinical rodent models and diabetic retinopathy patients.

Purpose: To test whether juvenile open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG) are polygenically continuous with primary open-angle glaucoma (POAG), using a multi-trait POAG polygenic risk score (PRS). Design: Retrospective cohort study. Participants: 3,102 open-angle glaucoma index cases, of whom 2,836 had a recorded age at diagnosis (52 PCG, 226 JOAG, and 2,558 POAG) and 999 European-ancestry controls from a glaucoma disease registry and a population-based cohort. Two replication cohorts comprised 70 JOAG and 31 PCG probands with 230 controls (Mass Eye and Ear, MEE), and 9 PCG and 120 POAG cases (Genetics of Glaucoma Study, GOGS). Methods: One index case per family was analysed. PRS were calculated from weighted SNPs and adjusted for ancestry. Cases were stratified by age at diagnosis (PCG <=3 years, JOAG >=4 and <40 years, POAG >=40 years) and presence of pathogenic/likely pathogenic variants ("Mendelian"). Groups were compared by Kruskal-Wallis test, with logistic regression and area under the curve for per-SD effects. Main Outcome Measures: PRS centile values compared across glaucoma subtypes and Mendelian and non-Mendelian subgroups. Results: Mean PRS was highest in cases diagnosed in the fourth decade of life. Among subgroups, it was highest in non-Mendelian JOAG (84.1%), exceeding controls (53.3%), Mendelian JOAG (68.9%), and non-Mendelian POAG (79.3%) (all P <= 0.003). Non-Mendelian JOAG was also the best discriminated from controls (OR 3.66 per SD increase, 95% CI 3.02-4.49; AUC 0.814, 95% CI 0.782-0.845). Neither PCG subgroup differed from controls. Among Mendelian cases, only MYOC p.Gln368Ter showed significantly elevated PRS (OR 2.49 per SD, 95% CI 1.89-3.34). In the MEE replication cohort, JOAG was associated with higher PRS (OR 2.12 per SD, 95% CI 1.50-3.07) while PCG was not (OR 0.90, P = 0.73). In GOGS, mean PRS was higher in POAG than PCG (84.8 vs 59.7 centile; P = 0.026). Conclusions: A POAG PRS predicts JOAG risk with discrimination comparable to or greater than POAG itself, supporting a shared polygenic architecture across juvenile and adult open-angle glaucoma. PCG showed no PRS elevation regardless of Mendelian status, indicating a distinct architecture for which rare-variant sequencing remains appropriate.

Introduction: Contact lens (CL) use is increasing globally, yet epidemiological data on CL wearers remain limited in Southeast Asia, including Indonesia. This study aimed to describe the demographic characteristics of CL users, the distribution of CL types, and the factors associated with CL wear patterns and correction status in Indonesia. Methods: This cross-sectional study used convenience sampling to recruit current CL users aged 18-40 years through online advertisements and an ophthalmology clinic in Indonesia. Participants self-reported demographic data, CL type, reasons for use, and refractive correction details. Associations between categorical variables were assessed using chi-square or Fisher's exact tests. Agreement between recommended and actual CL spherical power was evaluated using the Wilcoxon signed-rank test, and factors associated with correction status were analyzed using multinomial logistic regression. Results: Among 350 participants, the majority were female (95.4%), aged 18-30 years (54.0%), held a bachelor's degree (66.6%), and earned [&ge;]Rp5,000,000 monthly (64.9%). Soft colored lenses were the most commonly used type (60.1%), and practicality was the most frequently cited reason for use (38.1%), followed by cosmetic purposes (31.1%) and refractive correction (30.8%). Mild myopia was the most prevalent refractive error (40.0%). Undercorrection was the most common CL correction status (44.4% OD, 44.8% OS), with actual CL power significantly less negative than the recommended power in both eyes (OD: -0.18 D, p=0.015; OS: -0.24 D, p=0.001). Greater myopia severity was significantly associated with both undercorrection (OR 3.63-5.01) and overcorrection (OR 4.22-5.83) in both eyes (all p<0.001), while age, wear duration, and sex showed no significant association. Conclusion: This first nationwide demographic study of CL wearers in Indonesia found a predominance of colored soft lenses and a substantial tendency toward undercorrection linked to myopia severity. These findings highlight the need for public education on professional CL fitting, prescribing, and safe use practices.

Abstract Purpose To apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration. Methods Permeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess. Results In the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69 - 286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13 - 14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization. Conclusion Lesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.

Purpose To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD). Design Phase 1/2a, open-label, dose-escalation clinical trial. Participants Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-naive subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses. Methods Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection. Main Outcome Measures Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection. Results Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 eyes (01-04 and 01-05) completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 eye (02-04) first received protocol-specified rescue at week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained[&ge;]5 letters, 3 gained[&ge;]10 letters, and 1 gained[&ge;]15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-naive 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort. Conclusions In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.