AIM:To highlight current and emerging applications of sclerotherapy in orbital and peri-orbital pathology while identifying evidence gaps and future directions. METHODS:Systematic review of 108 studies identified through PubMed, Embase, Scopus, and Web of Science databases from inception to April 2026 with independent dual-reviewer screening. RESULTS:Of the 108 included studies, 82 (75.9%) addressed vascular indications and 26 (24.1%) addressed non-vascular indications. All evidence was low-level (Level 3 or 4), with no randomized trials identified. A pooled analysis of 315 cases managed with intralesional bleomycin achieved a favourable response in 86.2% of evaluable patients (n = 269), with sight-threatening complications in 1.3% (n = 4) cases. Non-vascular indications spanned dermoid cysts, conjunctival, orbitopalpebral, and eyelid cysts, intrascleral cysts, xanthelasma, malar festoons, and lacrimal sac obliteration. Foam sodium tetradecyl sulphate demonstrated the broadest indication profile, while trichloroacetic acid was the most common sclerosant for conjunctival cysts in anophthalmic sockets. Bleomycin showed higher response rates in macrocystic variant than microcystic or previously intervened disease. Routine image-guidance appeared prudent, particularly for deep, complex, or distensible orbital vascular lesions. CONCLUSION:Sclerotherapy is a versatile, minimally invasive modality applicable across a broad spectrum of orbital and peri-orbital pathologies. Prospective registries employing standardized ISSVA-based lesion classification and outcome reporting are warranted to formulate evidence.
PURPOSE:To evaluate ocular surface, corneal sensitivity, subbasal nerve morphology, and dendritic cells (DCs) density in eyes with pterygium using in vivo confocal microscopy (IVCM), and to compare postoperative outcomes between amniotic membrane transplantation (AMT) and conjunctival autografting (CAG). METHODS:This prospective study included 41 patients with unilateral primary pterygium. Baseline and first-month postoperative findings were evaluated. Eyes with pterygium were compared with fellow eyes regarding dry eye parameters, corneal sensitivity and IVCM findings. Postoperative changes in ocular surface parameters, subbasal nerves, and DCs were evaluated following AMT or CAG. RESULTS:Preoperatively, eyes with pterygium had significantly lower tear film break-up time than fellow eyes (p = .036), whereas no significant differences were observed in IVCM parameters. At one month postoperatively, ocular surface disease index scores improved (p < .001), while corneal sensitivity decreased (p = .037). DCs and subbasal nerve tortuosity also decreased significantly (p = .041 and p = .016, respectively). Changes from baseline in ocular surface and IVCM parameters did not differ significantly between the AMT and CAG groups (all p > .05). CONCLUSIONS:Pterygium is associated with ocular surface inflammation and corneal microstructural alterations detectable by IVCM. Surgical treatment improves the health of the ocular surface, and both methods showed favorable anti-inflammatory results in a short follow-up period of one month; however, it would be more beneficial to evaluate this in conjunction with long-term outcomes. IVCM may serve as a valuable tool for assessing postoperative inflammatory changes in pterygium patients.
BACKGROUND:Ophthalmology training requires visual interpretation, procedural skill, and supervised clinical reasoning, but trainee volume, faculty availability, and case mix constrain education. AI-enabled tools may support scalable instruction, assessment, and feedback. OBJECTIVE:To evaluate AI-enabled interventions for improving ophthalmology diagnostic, clinical reasoning, and surgical skills, and summarize knowledge acquisition, AI performance metrics, and learner perceptions. METHODS:This PROSPERO-registered review (CRD420251231199) followed PRISMA guidelines. Embase, Ovid MEDLINE, and Cochrane Library were searched through November 15, 2025. Eligible studies were observational or randomized trials in which trainees or clinicians performed ophthalmic diagnostic, clinical, or surgical tasks using AI-based instruction or assessment. Outcomes included diagnostic accuracy, knowledge, clinical reasoning, surgical skill, usability, satisfaction, and educational value. Risk of bias was assessed using ROBINS-I. Findings were synthesized narratively. RESULTS:Seven studies (200 participants) spanned image-based deep learning for diagnostic training, video-based deep learning for surgical assessment, and large language models for educational simulation. AI-tutored learners showed greater gains than lecture-based instruction in disease recognition and diagnosis (Cohen's d = 0.82, p = .016); an AI myopia system produced large gains in classification and lesion detection (d = 1.3-2.3) where lecture alone showed none (p = .16-0.63). AI-based patient simulation was rated comparably to human actors (p = .48). AI-derived surgical metrics distinguished attending from resident performance (AUC 0.55-0.998). CONCLUSION:AI-enabled interventions show promise as adjuncts to ophthalmology training, particularly for diagnostic learning and objective feedback. Evidence remains limited by small samples and heterogeneity, requiring larger, standardized studies to define AI's role.
OBJECTIVE:To evaluate the utility, rationality, and safety of glaucoma surgery recommendations generated by three prominent large language models (LLMs) - ChatGPT, Microsoft Copilot, and Google Gemini - when applied to real-world clinical scenarios. METHODS:Retrospective records from a tertiary hospital were converted into standardized scenarios and stratified into "primary" and "complex" glaucoma groups. Each LLM was prompted to suggest a single surgical approach and provide a rationale. A blinded team of glaucoma specialists evaluated the outputs based on six criteria: appropriateness, rationale quality, specificity, adherence to guidelines, feasibility, and safety risk, using a normalized 0-100 scale. RESULTS:Median overall quality scores across all cases were 80.7 for ChatGPT, 80.7 for Copilot, and 82.7 for Gemini, showing no statistically significant difference in general performance (p = .367). However, case complexity significantly affected performance. For Gemini, appropriateness and rationale quality scores dropped significantly in complex cases and were accompanied by a statistically significant increase in safety risk (p = .009). Although ChatGPT and Copilot demonstrated more stability across groups, their rationale quality was significantly lower in complex scenarios than in primary ones (p = .014 and <0.001, respectively). Pairwise analyses revealed that ChatGPT offered superior rationale quality compared to Copilot, while Gemini exhibited higher specificity. CONCLUSIONS:LLM-based chatbots can provide acceptable surgical guidance for straightforward primary surgical cases, but their utility is limited in high-risk or complex clinical settings. The observed deficiencies in rationale and increased safety risks in complex cases suggest that LLMs should be integrated as auxiliary decision-support tools under expert supervision rather than used as autonomous decision-makers in glaucoma surgery planning.
TOPIC:To evaluate the visual and refractive outcomes of corneal refractive surgery (PRK, LASIK, and SMILE) for hyperopic and mixed astigmatism. The clinical question addressed was: in adults with hyperopic or mixed astigmatism, how effective and safe are modern corneal refractive procedures, without alternative surgical comparators, in reducing refractive cylinder and improving uncorrected distance visual acuity? CLINICAL RELEVANCE:Hyperopic and mixed astigmatism are less predictable to correct than myopic errors due to biomechanical and ablation-profile complexity. Historically, these treatments showed higher regression and retreatment rates. With advances in excimer and femtosecond platforms, updated evidence is needed to inform clinical decision-making and patient counseling regarding expected efficacy, predictability, and safety. METHODS:A systematic review and meta-analysis were conducted following PRISMA 2020 and Cochrane guidelines. PubMed, Scopus, and Web of Science were searched from January 2010 to March 2025. Eligible studies included prospective, retrospective, or randomized human studies evaluating PRK, LASIK, or SMILE for hyperopic or mixed astigmatism. Case reports, small series (<10 eyes), intraocular procedures, and presbyopia treatments were excluded. Risk of bias was assessed using the NIH Quality Assessment Tool for Case Series Studies. Random-effects meta-analyses were performed, and heterogeneity was quantified with I2 statistics. RESULTS:Twenty-three studies (3,561 eyes) were included. Mean preoperative cylinder was 2.45 ± 1.23 D. Pooled residual astigmatism was 0.47 D (95% CI, 0.04-0.90) for hyperopic and 0.67 D (95% CI, 0.37-0.97) for mixed astigmatism. Approximately 66% (hyperopic) and 50% (mixed) achieved ≤ 0.50 D residual cylinder; 81% and 83%, respectively, were within ≤ 1.00 D. Uncorrected distance visual acuity (UDVA) of 20/20 or better was achieved in 60% (hyperopic) and 63% (mixed). Loss of ≥1 line of corrected distance visual acuity (CDVA) occurred in 6% (95% CI, 0.01-0.14) of hyperopic and 5% (95% CI, 0.03-0.15) of mixed eyes (pooled random-effects estimates). No significant differences were found between groups in comparative meta-analysis. CONCLUSION:Modern corneal refractive surgery provides substantial cylinder reduction, high predictability, and excellent safety in hyperopic and mixed astigmatism. Although heterogeneity and predominantly non-randomized designs limit certainty, current laser technologies achieve clinically meaningful outcomes comparable between groups, supporting their use in appropriately selected patients.
INTRODUCTION:Internal limiting membrane (ILM) peeling is widely used to relieve tangential traction and improve anatomical closure. As the ILM is continuous with Müller cells enstheathing retinal capillaries, peeling may impact the retinal microvasculature. We evaluated whether peeling impacts retinal vessel density as measured by optical coherence tomography angiography. METHODS:A systematic search of PubMed, Scopus, and Cochrane CENTRAL was conducted. Eligible studies included adult patients undergoing vitrectomy with ILM peeling and reported OCT-A vessel densities. Weighted mean differences were calculated for superficial (SCP) and deep capillary plexus (DCP) vessel density (VD) in the parafoveal and perifoveal regions. RESULTS:Ten studies including 260 participants were analyzed for parafoveal outcomes, and five studies including 150 participants for perifoveal outcomes. ILM peeling was not associated with significant changes in any of the examined regions: parafoveal SCP VD (WMD = -0.53%; -1.43 to 0.38; p = .25), parafoveal DCP VD (WMD = 0.92%; -0.41 to 2.24; p = .17), perifoveal SCP VD (WMD = -1.10%; -2.80 to 0.61; p = .21), or perifoveal DCP VD (WMD = 1.37%; -1.39 to 4.14; p = .33). Meta-regression analyses did not identify significant effects. DISCUSSION:ILM peeling does not appear to induce sustained microvascular loss detectable by OCT-A. Any early postoperative changes seem transient and should be interpreted cautiously. From a microvascular perspective, the findings support the safety of ILM peeling. Larger longitudinal studies using standardized OCT-A protocols are needed to confirm these findings and clarify any early VD fluctuations.
Conjunctival lesions in children are nearly always benign. The most common are conjunctival nevi. The rare malignant conjunctival tumors in children are usually larger and appear at an older age. Children with xeroderma pigmentosum are a unique group in whom malignant conjunctival tumors can occur at an early age. In this review, we describe common and rare benign and malignant conjunctival lesions in children, grouped by tissue of origin.
INTRODUCTION:Dry Eye Disease (DED) is a common multifactorial condition exacerbated by cataract surgery. This review explores how each step of cataract surgery may contribute to postoperative DED. METHODS:A narrative review was conducted examining preoperative, intraoperative, and postoperative factors implicated in the development and severity of DED following cataract surgery. RESULTS:Preoperative assessments reveal a high prevalence of pre-existing, often undiagnosed, DED among cataract surgery candidates; the effect of dilating drops on tear film stability warrants further investigation. Intraoperatively, povidone-iodine irrigation, lid speculum use, corneal incision size and location, and prolonged ocular surface exposure disrupt ocular surface homeostasis. Postoperative antibiotics, steroids, and NSAIDs, particularly preserved formulations requiring frequent instillation, may further exacerbate dry eye symptoms. Symptom resolution parallels corneal nerve regeneration and stabilization of corneal aberrations, typically occurring within three months. Sodium hyaluronate improves postoperative tear film parameters, while ophthalmic viscosurgical devices and preservative-free drops may minimize DED risk. DISCUSSIONS:DED following cataract surgery results from cumulative surgical and pharmacologic exposures across the perioperative period. Preoperative screening and preservative-free regimens may reduce its incidence and severity.
PURPOSE:To assess the contralateral intraocular pressure (IOP) lowering effect following 180° selective laser trabeculoplasty (SLT) in the untreated eye and to compare IOP reduction between treated and untreated eyes. METHODS:This prospective, interventional, non-randomized study included 40 treated eyes and 40 fellow eyes with open-angle glaucoma, and insufficient IOP control. Preoperative and postoperative IOP were measured using a Goldmann applanation tonometer. Subjects were treated with 50 non-overlapping laser pulses over 180° of the angle. IOP was measured bilaterally before SLT and at 1 week, 1 month, 3 months, and 6 months thereafter. RESULTS:IOP changes were assessed in both the treated and contralateral eyes, revealing a significant reduction throughout the six-month follow-up. In the treated eye, IOP decreased from 20.23 ± 4.74 mmHg pre-SLT to 15.58 ± 3.13 mmHg (p < .001), while the contralateral eye decreased from 18.28 ± 3.87 mmHg to 15.88 ± 3.89 mmHg (p = .004) at the last follow-up visit. The treated eye consistently showed a greater percentage reduction, with contralateral effects of 65.47%, 68.14%, 60.32%, and 58.64% at 1 week, 1 month, 3 months, and 6 months, respectively. A strong positive correlation was found between IOP reduction in the contralateral eye and the corresponding treated eye (r = 0.718, p < .001), and a moderate correlation with the treated eye's baseline IOP (r = 0.368, p = .020). CONCLUSION:A statistically significant contralateral IOP reduction was observed following 180° SLT.
BACKGROUND:Presbyopia is a prevalent age-related visual disorder affecting approximately 1.8 billion individuals worldwide, with many lacking access to effective correction. Topical pharmacologic therapies such as aceclidine have emerged as potential noninvasive treatments, though their efficacy and safety remain incompletely established. METHODS:A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420261353653). Databases were searched till March 2026. Adults with presbyopia treated with topical aceclidine, alone or in combination, were included. The primary outcome was ≥ 3-line improvement in distance-corrected near visual acuity (DCNVA). Random-effects models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). RESULTS:Five trials involving 883 randomized participants were included. In the primary analysis of parallel-group trials, aceclidine significantly increased the likelihood of achieving a ≥ 3-line improvement in distance-corrected near visual acuity compared with placebo (RR 6.28, 95% CI 4.22-9.35; I2 = 2.4%) and compared with aceclidine plus brimonidine (RR 5.05, 95% CI 3.04-8.38; I2 = 28.2%). Secondary analyses of crossover trials demonstrated similar superiority over placebo (RR 14.92, 95% CI 6.77-32.86; I2 = 0%), whereas no significant difference was observed versus combination therapy (RR 1.11, 95% CI 0.90-1.38; I2 = 24.6%). Aceclidine was associated with a higher incidence of treatment-emergent adverse events than placebo (RR 2.23, 95% CI 1.61-3.09). No significant differences were observed in serious adverse events. CONCLUSIONS:Aceclidine provides significant short-term improvement in near vision with an acceptable safety profile. Monotherapy may offer slight efficacy benefits over combination regimens. However, limited study numbers and short follow-up necessitate further large-scale, long-term trials.
To quantify sectoral corneal epithelial thickness (CET) changes in patients with multiple myeloma treated with belantamab mafodotin using anterior segment optical coherence tomography (AS-OCT), and compare CET measurements with those of normal eyes. This retrospective observational study analyzed eight eyes from four patients with multiple myeloma who received belantamab mafodotin and subsequently discontinued therapy because of keratopathy. Clinical parameters-including best-corrected visual acuity (BCVA), mean keratometry, spherical equivalent, and Keratopathy Visual Acuity (KVA) scale-were assessed at baseline and at treatment discontinuation. CET at discontinuation was measured with using swept-source AS-OCT with a 25-sector mapping protocol: a central zone (0-2 mm) and three concentric annuli-inner (2-5 mm), middle (5-7 mm), and outer (7-10 mm)-each subdivided into eight sectors (S, SN, N, IN, I, IT, T, ST). CET values from the patient group were compared with those from 14 normal eyes of 11 controls. Therapy was discontinued after a mean of 5.5 cycles, approximately 4 months after the first infusion. From baseline to discontinuation, BCVA worsened from logMAR 0.04 to 0.20 (p = .027), and the KVA scale increased from 0.25 to 2.88 (p = .008). Compared with normal eyes, eyes exposed to belantamab mafodotin exhibited significantly thinner epithelium across all 25 sectors-including the central and all annular sectors (all p < .05). Within-patient sectoral analysis revealed greater thinning in the inferior than in the superior sectors of the middle ring (5-7 mm; p = .039). No significant nasal-temporal asymmetry was observed. Patients who discontinued belantamab mafodotin therapy due to keratopathy exhibited diffuse epithelial thinning relative to normal eyes, with disproportionate thinning in inferior mid-peripheral sectors. Sectoral AS-OCT mapping of the corneal epithelium may serve as an objective biomarker for quantifying belantamab mafodotin-associated ocular surface toxicity.
PURPOSE:To evaluate the effect of cataract surgery on selected lamina cribrosa (LC) structural parameters in patients with primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG). METHODS:In this prospective comparative study, 50 eyes of 50 patients (25 PACG, 25 POAG) undergoing cataract surgery were consecutively enrolled. Intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, and LC parameters-including lamina cribrosa thickness (LCT), lamina cribrosa depth (LCD), prelaminar depth (PLD), and prelaminar tissue thickness (PLTT)-were assessed using swept-source optical coherence tomography before and 6 months after surgery. Changes over time and between groups were analyzed using repeated measures analysis or nonparametric equivalents. Analysis of covariance was performed to adjust for postoperative IOP reduction and age. RESULTS:Postoperative IOP decreased significantly in both groups (p = .003 and p = .033), with no significant difference in the magnitude of reduction between groups (p = .174). RNFL thickness did not change significantly in either group. In the PACG group, cataract surgery was associated with a significant increase in LCT (p = .01) and significant decreases in LCD (p = .002) and PLD (p < .001), whereas no significant changes were observed in the POAG group. Significant time ×group interactions were detected for LCT (p = .025), LCD (p = .017), and PLD (p = .001). PLTT did not change significantly in either group, and no significant time ×group interaction was observed (p = .09). These differences remained significant after adjustment for postoperative IOP reduction and age. CONCLUSION:Cataract surgery was associated with measurable structural changes in the lamina cribrosa in PACG but not in POAG. Although the magnitude of IOP reduction and other ocular factors may have contributed to these findings, the structural response of the lamina cribrosa following IOP-lowering interventions may differ between glaucoma subtypes. Further studies are required to clarify the mechanisms and clinical significance of these changes.
INTRODUCTION:Pregnancy induces substantial physiological adaptations that affect the eye. Evidence regarding the effect of normal pregnancy on retinal parameters remains limited and inconsistent. This prospective longitudinal study aimed to evaluate ganglion cell layer (GCL) thickness and macular retinal thickness in healthy women during the third trimester of pregnancy and the postpartum period. METHODS:91 right eyes of 91 pregnant women were consecutively recruited between November 2017 and June 2024. All participants underwent comprehensive ophthalmic examination and spectral-domain optical coherence tomography (OCT) imaging. Third trimester and postpartum measurements were compared. GCL thickness was assessed in six macular EDTRS sectors, and retinal thickness was assessed in nine macular EDTRS sectors. Paired comparisons were performed using the Wilcoxon signed-rank test, with Benjamini-Hochberg correction applied for multiple testing. RESULTS:Postpartum GCL thickness was significantly greater postpartum in all sectors except the inferonasal sector, which nonetheless showed a similar trend. Retinal thickness was also significantly greater postpartum in several parafoveal sectors. Central and perifoveal sectors showed non-significant increases in the same direction. CONCLUSIONS:Normal pregnancy is associated with subtle, region-specific reductions in GCL and macular thickness. These findings support that physiological pregnancy-related changes influence retinal structure even in uncomplicated pregnancies. Larger longitudinal studies are warranted to clarify the mechanisms and clinical significance of these changes.
PURPOSE:To characterize short-term structural and functional progression trajectories in medically uncontrolled primary open-angle glaucoma (POAG) managed with adjunctive netarsudil intensification or immediate surgical escalation. METHODS:This retrospective cohort study included 110 eyes with POAG receiving maximally tolerated medical therapy. Thirty-seven eyes underwent netarsudil intensification and 73 eyes underwent trabeculectomy or tube shunt surgery. Stabilized inverse probability weighting was applied to balance baseline covariates. The primary outcome was the 12-month slope of visual field mean deviation (MD). Secondary outcomes included retinal nerve fiber layer (RNFL) thinning rate and intraocular pressure (IOP) reduction. RESULTS:The estimated MD progression rate was -0.61 ± 0.58 dB/year in the netarsudil group and -0.42 ± 0.55 dB/year in the surgical group (between-group difference -0.17 dB/year; 95% CI, -0.38 to 0.04; p = .112). RNFL thinning rates were -1.8 ± 2.1 µm/year and -1.1 ± 1.9 µm/year, respectively (between-group difference -0.7 µm/year; 95% CI, -1.6 to 0.2; p = .138). Surgical management achieved greater IOP reduction (-12.3 ± 3.8 mmHg vs - 5.4 ± 2.3 mmHg; p < .001). During follow-up, 27% of eyes in the netarsudil group required subsequent surgical escalation. CONCLUSIONS:Although surgery achieved greater IOP reduction, short-term structural and functional trajectories remained similar after treatment escalation over 12 months.
OBJECTIVE:To investigate whether maternal diabetes mellitus during pregnancy is a risk factor for CNLDO in offspring. METHODS:This retrospective cohort study utilized electronic medical records from Clalit Health Services (CHS) in Israel, 2010-2023. Neonates were classified as born to diabetic or non-diabetic mothers. Mixed models assessed and compared demographic characteristics and ocular disorders between groups. Generalized estimating equations regression was applied to calculate odds ratios while adjusting for potential confounders. RESULTS:505,928 births were analyzed. CNLDO prevalence was 4.1% among children born to mother with diabetes, compared to 2.9% among children to non-diabetic mothers (OR-1.44, 95% confidence interval [CI] 1.35-1.54; p < .001). Among children to diabetic mothers receiving pharmacological treatment, CNLDO prevalence was 5.2%, while it was 3.7% when managed by diet (OR-1.44, 95% CI 1.26-1.64; p < .001). CNLDO prevalence was 4.7% in children to mothers with HbA1c levels greater than 6.5%, compared to 2.9% when HbA1c levels were below 6.5% (OR-1.62, 95% CI 1.30-2.03; p < .001). After adjusting for confounders, significant association was found between maternal diabetes during pregnancy and CNLDO prevalence in offspring (OR-1.47, 95% CI 1.37-1.58; p < .001). CONCLUSIONS:Maternal diabetes during pregnancy independently increases CNLDO risk, especially in infants to mothers with more severe diabetes.
PURPOSE:Muscle eye brain (MEB) disease is a rare genetic disorder characterized by congenital muscular dystrophy, structural brain malformations and ocular abnormalities. We review the literature on ophthalmic manifestations and highlight key features that may facilitate the diagnosis of this rare condition. METHODS:A literature search was conducted in the National Centre form Biotechnology Information (NCBI) PubMed, Embase, Web of Science and Scopus databases from inception through April 2026 to identify all relevant studies reporting ocular manifestations in MEB disease. RESULTS:The current literature on ocular manifestations in MEB disease demonstrates phenotypic variability. MEB disease is caused by homozygous or compound heterozygous mutations in the POMGnT1 gene and the clinical presentation varies in terms of age of onset, disease pattern and rate of progression. Patients with a genetically established diagnosis may present with a wide range of ocular findings, ranging from mild to severe abnormalities. The spectrum mainly includes ocular motility disorders, high myopia, glaucoma, cataract, optic nerve hypoplasia and retinal dysplastic and degenerative changes, while retinal detachment and microphthalmia are less commonly reported. CONCLUSION:The variation in phenotype and disease progression, along with the limited number of reported cases highlights the need for further research to guide clinical practice, improve risk assessment and optimize patient management. This review discusses the ocular manifestations of the disorder and emphasizes the importance of reporting additional cases of this rare condition to contribute to future research.
PURPOSE:Retinitis pigmentosa (RP) is a leading cause of irreversible blindness in working-age populations and frequently cooccurs with multiple ocular disorders. As their shared genetic basis remains poorly understood, this study aimed to elucidate the shared genetic architecture underlying RP and relevant ocular comorbidities. METHODS:Using large-scale genome-wide association data, we systematically investigated pleiotropy, genetic correlation, cell-type specificity, and genetically predicted causality between RP and major ophthalmic comorbidities. RESULTS:We observed significant genetic correlations and pleiotropic enrichment between RP and retinal detachments and breaks (RDAB), retinal vascular occlusion (RVO), and age-related macular degeneration (AMD), with notable SNP-level overlap between RP and primary open-angle glaucoma (POAG). RP and RDAB, as well as AMD, shared genetic associations at chr1:196176201-197311241 and chr10:123900764-125869042. Totally, 41, 25, 114, and 397 pleiotropic loci were identified between RP and RDAB, RVO, POAG, and AMD, implicating pathways related to cell division, metabolic regulation, immune activation, and complement activation. A novel causal variant (rs36212731) and four pleiotropic genes (ARMS2, HTRA1, CFH, PLEKHA1) were discovered between RP and RDAB. Ten causal variants and 24 pleiotropic genes were identified between RP and AMD. MR analyses demonstrated a genetically causal effect of RP on an increased risk of RDAB and RVO (P˂0.05), and AMD was associated with an increased risk of RP. Cell-type enrichment analyses highlighted vascular smooth muscle cells and retinal pigment epithelium as key mediators of shared susceptibility between RP and RDAB, and POAG. CONCLUSIONS:This study reveals robust genetic and potential causal links between RP and RDAB, RVO, as well as AMD, along with complex pleiotropic associations with glaucoma. These findings provide novel genetic insights into the shared pathogenic mechanisms and generate hypotheses for future biological, translational, and clinical research.
PURPOSE:The comparative efficacy and safety of ranibizumab Port Delivery System (PDS) vs monthly intravitreal ranibizumab in Vascular Endothelial Growth Factor (VEGF)-driven macular diseases remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PDS vs monthly ranibizumab in neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). METHODS:PubMed, Embase, and Cochrane were searched for randomized controlled trials enrolling adults with neovascular age-related macular degeneration or diabetic macular edema treated with the ranibizumab Port Delivery System (100 mg/mL) versus monthly intravitreal ranibizumab 0.5 mg. This systematic review and meta-analysis was conducted according to a predefined PICOTT framework. Continuous and binary outcomes were pooled with mean differences (MDs) and risk ratios (RRs) with a 95% confidence interval (CI), respectively, with a random-effects model. Statistical analyses were performed using RevMan. RESULTS:Three trials were included, with a total of 1,149 eyes of which 688 (60%) received PDS and 461 (40%) received monthly ranibizumab. No significant differences were observed in BCVA (nAMD: MD - 0.69 letters; 95% CI - 2.52 to 1.14; p = .46; DME: MD 0.20; 95% CI - 1.20 to 1.60; p = .78) or CRT (nAMD: MD 26.67 µm; 95% CI - 16.55 to 69.88; p = .23; DME: MD - 3.80; 95% CI - 17.20 to 9.60; p = .58). Incidence of ocular AEs was significantly higher with PDS (RR 1.80; 95% CI 1.49-2.17; p < .00001; I2=74%). Among specific complications, conjunctival bleb or filtering bleb leak (RR 15.29; 95% CI 2.31-101.35; p = .005), conjunctival erosion (RR 8.87; 95% CI 1.66-47.35; p = .01), vitreous hemorrhage (RR 3.61; 95% CI 1.24-10.49; p = .02), hyphema (RR 5.77; 95% CI 1.03-32.20; p = .05), and conjunctival retraction (RR 5.78; 95% CI 1.04-32.29; p = .05) occurred significantly more often with PDS. Systemic AEs were comparable between treatment arms (RR 1.00; 95% CI 0.89-1.13; p = .98). CONCLUSION:In this systematic review and meta-analysis of three randomized controlled trials, PDS was associated with visual and anatomical results comparable to monthly ranibizumab in patients with nAMD. Evidence in DME was limited to a single trial, and conclusions in this population should be considered exploratory. PDS was associated with a higher incidence of procedure- and device-related ocular complications.
