BackgroundGlaucoma causes permanent blindness. Current treatments have limited effectiveness, necessitating novel therapeutic strategies. We aimed to identify potential drug targets for glaucoma by integrating multi-trait and multi-omic analyses.MethodsWe sourced druggable gene expression and protein abundance summary-level data from quantitative trait loci studies, and genetic associations with glaucoma from a large-scale multi-trait analysis. We employed proteome and transcriptome Mendelian randomization (MR) and colocalisation to identify potential therapeutic targets, glaucoma endophenotype MR to explore the potential mechanisms of identified associations, and phenome-wide MR to investigate possible adverse effects of candidate targets.ResultsWe identified CPXM1 and FLT4 as tier 1; INSR as tier 2; and CPZ and PXDN as tier 3 druggable genes. Genetically predicted higher levels of CPXM1 [odds ratio (OR): 0.86, 95% confidence interval (CI): 0.81–0.91, PFDR < 0.001], FLT4 (OR: 0.74, 95% CI: 0.64 − 0.87, PFDR = 0.033), INSR (OR: 0.58, 95% CI: 0.43 − 0.78, PFDR = 0.042), and CPZ (OR: 0.55, 95% CI: 0.40 − 0.74, PFDR = 0.033) were associated with decreased glaucoma risk while those of PXDN (OR: 1.33, 95% CI: 1.15 − 1.54, PFDR = 0.033) with increased risk. The associations for CPXM1 (OR: 0.53, 95% CI: 0.39 − 0.73, P < 0.001) and FLT4 (OR: 0.86, 95% CI: 0.78 − 0.95, P = 0.005) were confirmed transcriptome-wide and colocalisation was confirmed for CPXM1 [posterior probability H4 (PPH4) = 0.940], FLT4 (PPH4 = 0.701), and INSR (PPH4 = 0.706). The protective effects of CPXM1 and CPZ may be attributed to intraocular pressure-lowering activities. The risk associated with PXDN is due to its involvement in glaucomatous neuropathy. No significant adverse effects were identified.ConclusionsThis study provides novel insights into glaucoma pathophysiology and promotes pharmaceutical target innovation.

BackgroundDespite extensive research on keratoconus (KC) detection with traditional machine learning models, stacking ensemble learning approaches remain underexplored. This paper presents a stacking ensemble learning method to enhance automated KC screening.MethodsThis study utilizes a clinical dataset containing detailed corneal data from 2491 cases classified as non-KC (NKC), subclinical KC (SCKC) and clinical KC (CKC). Each cornea is represented by 79 features extracted from Pentacam imaging. Following extensive pre-processing, key corneal features that are strongly correlated with the target diagnosis are identified. These features are the keratometry of the steepest anterior point, surface variance index, vertical asymmetry index, height decentration index, and height asymmetry index. A novel stacking ensemble model is developed using the selected features to improve corneal classification into NKC, SCKC, and CKC by integrating top tree-based classifiers (random forest, gradient boosting, decision trees) with a support vector machine meta-classifier.ResultsThe pre-processing and feature selection techniques reduced the model's parameters to just 6.33% of the original dataset, improving classification performance, and cutting over 85% of the training time. The performance of the developed model was validated and tested on unseen data. Experimental results showed that the model outperforms existing studies, achieving 99.72% accuracy, precision, sensitivity, F1, and F2 scores, with a Matthews correlation coefficient of 0.995. It accurately classified all NKC and CKC cases, with just one misclassification involving an SCKC case. The model also demonstrated consistent performance on 100 additional unseen test cases, underscoring its generalizability and robustness in KC screening.ConclusionsBy combining the strengths of diverse base models and key Pentacam indices, the stacking ensemble approach ensures reliable, accurate KC screening, providing clinicians with an automated tool for early detection and better patient management.

BackgroundA post hoc analysis of the STAR study, which was a 48-week, phase IV, multicenter randomized controlled multicenter clinical trial was performed. This study aims to identify the baseline factors associated with visual and anatomic changes over 48 weeks in the treatment of active polypoidal choroidal vasculopathy (PCV) with conbercept.MethodsIn the STAR study, 249 participants were randomized to either the 3 + Q12W (3 monthly injections followed by injections every 12 weeks) or 3 + TAE (3 monthly injections followed by treat and extend regimen) group. The association of 27 baseline factors with three outcomes—changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and maximum retinal thickness (MRT) from baseline to 48 weeks—was investigated using univariate regression analysis followed by multivariate linear regression analysis.ResultsThe final multivariate model indicated that worse baseline BCVA (P < 0.01), CRT ≤ 400 μm (P < 0.01), fewer polypoidal lesions (P < 0.01), and younger age at baseline (P = 0.04) were associated with greater BCVA gain at week 48. Higher CRT and MRT at baseline were associated with a greater reduction in CRT and MRT at week 48, separately (P < 0.01 and P < 0.01, respectively). Smaller pigment epithelial detachment (PED) volume at baseline was associated with greater reductions in CRT and MRT at week 48 (both P < 0.01). Eyes with relatively good BCVA (> 73 letters) at baseline exhibited lower reductions in CRT and MRT at week 48 (P < 0.01 and P = 0.02, respectively). At week 48, eyes with hemorrhagic PEDs showed greater reductions in CRT and MRT than those with fibrovascular PEDs (P = 0.02 and P = 0.03, respectively). Furthermore, eyes with shallow irregular or sharp-peaked PEDs exhibited greater reductions in CRT (both P < 0.01) and MRT (P = 0.01 and P < 0.01, respectively) than those with multilobular PEDs from baseline to week 48.ConclusionsIn Chinese patients with PCV receiving intravitreal injections of conbercept, baseline characteristics, including age, BCVA, CRT, MRT, number of polypoidal lesions, PED volume, and PED types and morphology, served as predictors of visual and anatomical changes over 48 weeks.

BackgroundPatient expectations for post-cataract surgery outcomes have risen. This study aims to evaluate patient satisfaction after bilateral implantation of enhanced monofocal IOL (RayOne EMV RAO200E) designed with positive spherical aberration, used for monovision with a 1.00 D offset.MethodsProspective, non-comparative, interventional case series. Patients underwent bilateral cataract surgery and implantation of an enhanced monofocal IOL (RayOne EMV IOL RAO200E, Rayner, Worthing, UK) with target refraction of −1.00 D in the non-dominant eye and emmetropia in the dominant eye. Patient-reported outcome measures (PROMs) were assessed 3 months postoperatively using the Spanish version of the Catquest-9SF and a self-administered questionnaire. Other outcome measures included subjective refraction, visual acuity at various distances, and contrast sensitivity.ResultsBoth eyes of 51 patients were included (102 eyes). Three months postoperatively, all patients reported being satisfied or very satisfied with the overall surgical outcomes. The majority of patients reported that their vision during night driving was as good or better than before the surgery (95%); further, there was no difficulty in recognizing faces (93%), navigating uneven terrain (95%), and viewing prices while shopping (81%). The mean subjective spherical equivalent for dominant and non-dominant eyes were −0.24 ± 0.34 D and −0.86 ± 0.33 D, respectively. Binocular UDVA (4 m), UIVA (66 cm), and UNVA (40 cm) were 0.06 ± 0.09, 0.25 ± 0.12, and 0.30 ± 0.11 logMAR, respectively. Contrast sensitivity was within the population norms (CSV-1000).ConclusionMonovision with the RayOne EMV IOL provided high patient satisfaction, with preserved contrast sensitivity, good distance vision, and functional intermediate and near vision.Trial registration: Clinicaltrials.gov, NCT06528678. Registered 22 July 2024—Retrospectively registered, https://clinicaltrials.gov/study/NCT06528678.

BackgroundInterleukin detection is helpful in screening vitreoretinal lymphoma (VRL). However, the levels of interleukin in aqueous humor (AqH) can be abnormally low in some cases, leading to underdiagnosis of VRL merely dependent on AqH. The purpose of this study was to investigate the correlation of interleukins between paired AqH and vitreous humor (VH) samples in VRL cases, and to explore potential factors affecting interleukin levels and diagnostic parameters.MethodsThis was a case series study. Reviewed were consecutive biopsy-proven B-cell VRL cases of which adequate paired AqH and VH samples were obtained for the measurement of interleukin 10 (IL-10) and interleukin 6 (IL-6). The correlations of IL-10 and IL-6 between AqH and VH were analyzed. Influences of clinical manifestations on IL levels and positive rates of IL-related parameters in AqH and VH were evaluated, which included AqH IL-10 > 30 pg/mL, VH IL-10 > 65 pg/mL, IL-10/IL-6 ratio > 1, and Interleukin Score for Intraocular Lymphoma Diagnosis (ISOLD) > 0 in both the AqH and VH.ResultsSeventy-four eyes of 64 patients with VRL were included. IL-10 in VH was significantly higher than in AqH (median: 1159.77 vs. 225.74 pg/mL, P < 0.001). For both IL-10 and IL-6, the AqH concentrations were positively correlated with VH concentrations in the form of power functions (P < 0.001 and P < 0.001, respectively). The positive rate of AqH IL-10/IL-6 > 1 (77%) was lower than that of VH IL-10 > 65 pg/mL (91%), VH IL-10/IL-6 > 1 (89%) and VH ISOLD > 0 (91%). Eyes without intraretinal infiltration tended to have lower IL-10 levels in the AqH and VH (median: 141.08 pg/mL vs. 449.10 pg/mL, 825.48 pg/mL vs. 2285.77 pg/mL; P = 0.001 and P < 0.001, respectively), and lower positive rates of AqH IL-10 > 30 pg/mL (78% vs. 97%, P = 0.018) and AqH ISOLD > 0 (76% vs. 97%, P = 0.033).ConclusionsIL-10/IL-6 in AqH may not be as sensitive as the parameters (including IL-10, IL-10/IL-6 and ISOLD) in VH for VRL screening. Cases without intraretinal involvement were less likely to be positive for IL-10 > 30 pg/mL and ISOLD > 0 in AqH; the possibility of VRL should be ruled out more cautiously in these cases.

BackgroundTransepithelial photorefractive keratectomy (transPRK) can be safely and predictably performed to correct low-to-high astigmatism. This study explored the effects of fixation stability, corneal density (CD), ocular residual astigmatism (ORA), and the surgically-induced change in the epithelial thickness (ΔET) on the efficacy of astigmatism correction by transPRK.MethodsEighty-three consecutive patients who underwent transPRK to correct myopia and myopic astigmatism were divided into two groups according to refractive astigmatism [high refractive astigmatism (RA) group: ≥ 2.0 D, n = 31; low RA group: < 2.0 D, n = 52]. Fixation stability was evaluated by measuring the lateral movement of the pupil center on the eye tracker images. The CD was measured using a Pentacam Scheimpflug imaging system, epithelial thickness mapping was performed using optical coherence tomography, and the ORA was determined using vector analysis. Multiple linear regression analyses were performed to identify factors associated with the correction index (CI) and angle of error (AOE).ResultsAt 6 months postoperatively, the RA was higher in the high RA group (− 0.66 ± 0.44 D) than in the low RA group (− 0.29 ± 0.29 D, P < 0.001), whereas no significant differences were found in CI or AOE between two groups. Multiple linear regression analyses showed that for the low RA group, preoperative anterior CD of the central 2 mm (CD0-2A, β = − 0.482, P = 0.011) and ΔET (β = 0.295, P = 0.041), were associated with CI, whereas the vector length of the pupil center shift (PCVL, β = − 0.404, P = 0.005) and ΔET (β = − 0.293, P = 0.036) were associated with AOE. For the high RA group, ΔET (β = 0.519, P = 0.038) was associated with CI, whereas static cyclotorsion (β = − 0.493, P = 0.040) was associated with AOE. No significant associations were found between ORA and CI or AOE.ConclusionsPostoperative changes in epithelial thickness were associated with the efficacy of transPRK in both the low and high RA groups, whereas the pupil center shift and anterior CD were associated with the efficacy of transPRK in the low RA group.

Vitreoretinal lymphoma (VRL) is often a diffuse large B-cell lymphoma in nature, and patients may have or eventually develop central nervous system lymphoma, which frequently leads to a poor prognosis. Currently, there are no international or domestic clinical guidelines specifically for the diagnosis and treatment of VRL, and no standardized diagnostic procedures or treatment evaluation systems for this disease. VRL is clinically characterized by prominent vitreous opacities, multiple lesions beneath the retinal pigment epithelium or subretinal, and intraretinal infiltration, making it one of the most common masquerade syndromes in ophthalmology. To promote early diagnosis and standardized treatment of VRL, the Ocular Immunology Group of the Chinese Medical Association Ophthalmology Branch has developed "Clinical Guidelines for the Diagnosis and Treatment of Vitreoretinal Lymphoma in Chinese Patients (2024)", based on extensive references to diagnosis, treatment experiences and relevant clinical recommendations. The working group systematically reviewed and comprehensively summarized the latest research evidence from both domestic and international sources. Using the Oxford Evidence Level System, we assessed the quality of evidence and the strength of recommendations. This guideline provides crucial academic references and clinical practice guidance for the diagnosis and treatment of VRL patients. This guideline, including VRL diagnostic methods, processes, and treatment recommendations is suitable for clinical practice in China and is intended to assist ophthalmologists in clinical diagnosis and treatment of VRL.

BackgroundThis study aimed to investigate the combined effects of obstructive sleep apnea (OSA) risk and short sleep duration on glaucoma prevalence and intraocular pressure (IOP) using data from the 2019 to 2021 Korea National Health and Nutrition Examination Survey (KNHANES).MethodsThis cross-sectional study analyzed data from 7,732 KNHANES participants aged ≥ 40 years. OSA risk was assessed using the STOP-BANG questionnaire, with a high risk defined as a score ≥ 3. The diagnosis of glaucoma was based on the criteria of the International Society of Geographical and Epidemiological Ophthalmology. Multivariate logistic regression models were used to evaluate the associations among glaucoma prevalence, OSA risk, and sleep duration, adjusting for demographic and health-related variables. The interaction effects of OSA risk and sleep duration on glaucoma and IOP were also assessed.ResultsAmong the 7,732 participants, 5.28% (n = 408) were diagnosed with glaucoma. Individuals with a high risk of OSA had significantly higher odds of glaucoma compared to those with a low risk (odds ratio: 1.34, 95% confidence interval: 1.02–1.77; P < 0.05), with the STOP-BANG components “snoring”, “pressure”, and “age” being most associated with increased glaucoma risk. No significant association was observed between abnormal sleep duration (< 7 h or ≥ 9 h) alone and glaucoma prevalence (P > 0.05). Individuals with a high risk of OSA with a sleep duration < 9 h showed a significantly higher glaucoma prevalence than those with ≥ 9 h of sleep (P < 0.05), suggesting that sleep duration modifies the association between OSA risk and glaucoma. Similar trends were observed for IOP, with significant interaction effects between OSA risk and sleep duration.ConclusionsOur findings suggest that sleep duration modulates the association between OSA risk and both glaucoma prevalence and higher IOP, highlighting the importance of including sleep duration in glaucoma risk assessments for patients with OSA. Further research is required to clarify the mechanisms underlying the association between OSA, sleep duration, and glaucoma.

BackgroundEarly detection of keratoconus is essential for maximizing the potential of cross-linking treatments designed to halt keratoconus progression, minimizing the risks of iatrogenic ectasia as well as reducing the need for corneal transplantation. This review focuses on the progress that has been made in the early detection of keratoconus using biomechanical and topographical properties derived from three different technologies, namely the ocular response analyser (ORA), corneal visualization Scheimpflug tonometer (Corvis ST) and optical coherence tomography (OCT).MethodA PubMed search was performed using the keywords of ‘early keratoconus’, ‘subclinical keratoconus’, ‘forme fruste keratoconus’, ‘very asymmetric ectasia with normal topography/tomography’ and ‘ocular response analyser’ and/or ‘Corvis ST’/‘corneal visualized Scheimpflug tomographer/tomography’ and/or ‘optical coherence tomography/tomographer’.ResultsThe integration of biomechanical parameters and corneal morphological data from the topography/tomography or OCT, or the assessment of bilateral asymmetry, has demonstrated improvement in the accuracy of diagnosing early-stage keratoconus.ConclusionsAs measurement principles differ depending on the technique used for keratoconus assessment, comprehensive metrics may be needed to reflect subtle anterior or posterior corneal changes and help identify eyes with very early ectasia. Although clinical experts have always, and will most likely, continue to play a pivotal role in decision-making for early keratoconus diagnosis, future developments in technology and AI may lead to enhanced early detection in the future.

BackgroundTo investigate the relationship between obesity and corneal nerve metrics in patients with type 2 diabetes mellitus (DM).MethodsThis cross-sectional study included a total of 385 healthy controls and 663 patients with DM. Metrics for corneal nerve and epithelial cells were evaluated using in-vivo confocal microscopy (IVCM). Corneal nerve and epithelial cell parameters were quantified and compared between patients with and without obesity and across six different body mass index (BMI) categories. Multivariable regression analyses were conducted to determine the association between corneal nerve metrics and BMI in patients with DM.ResultsOf the DM participants, 162 (25.4%) had obesity. Compared to the non-obese group, patients with obesity had significantly lower corneal nerve fiber density (CNFD, P < 0.0001), corneal nerve fiber length (CNFL, P = 0.002), and corneal nerve branch density (CNBD, P = 0.005). Analyses across different BMI categories showed a progressive decline in corneal nerve parameters including CNFD (P < 0.0001), CNFL (P < 0.0001), CNBD (P < 0.0001), corneal nerve fiber total branch density (P = 0.003), corneal nerve fiber area (P = 0.04), and corneal nerve fiber fractal dimension (P = 0.02) with increasing obesity severity. Multivariable regression analyses demonstrated that lower CNFD (β: − 0.21, 95% CI: − 0.29 to − 0.13, P < 0.0001), shorter CNFL (β: − 0.12, 95% CI: − 0.17 to − 0.07, P < 0.0001), and lower CNBD (β: − 0.17, 95% CI: − 0.30 to − 0.04, P = 0.01) were significantly associated with BMI after adjusting for confounders. There were no significant differences in the corneal epithelial parameters between the obese and non-obese groups.ConclusionsGeneral obesity, specifically higher BMI, adversely affects corneal nerve health in individuals with DM. Evaluation of corneal nerves and resultant keratopathy should be considered in patients with DM and concomitant obesity.