PURPOSE: To develop a globally applicable, theoretical mathematical construct for predicting altitude-related intraocular pressure (IOP) elevation following pars plana vitrectomy (PPV) with intraocular gas tamponade, ena...PURPOSE: To develop a globally applicable, theoretical mathematical construct for predicting altitude-related intraocular pressure (IOP) elevation following pars plana vitrectomy (PPV) with intraocular gas tamponade, enabling personalized travel risk assessment through route-specific elevation profiling and bedside computational tools. DESIGN: Single-center retrospective observational case series integrated with computational modeling and clinical illustrative scenarios. SUBJECTS: Twelve patients (12 eyes) who underwent standard PPV with 14% C₃F₈ tamponade at Xinhua Hospital (altitude 0 m), failed to follow postoperative travel restrictions, and subsequently developed symptomatic IOP elevation during high-altitude travel (≥1000 m). METHODS: A mathematical model was developed integrating Boyle-Mariotte's law with first-order gas absorption kinetics, incorporating surgical center altitude correction. Clinical application employs a binary safety threshold (ΔIOP ≤6 mm Hg: proceed; >6 mm Hg: defer). The framework was applied to 4 gases (14% C₃F₈, 16% C₂F₆, 20% SF₆, and 100% air). A Google Earth Pro-based elevation profiling protocol and web-based calculator were developed for bedside risk estimation. MAIN OUTCOME MEASURES: Predicted ΔIOP, binary safety determination, and minimum safe air travel intervals by gas type. RESULTS: Theoretical safety intervals varied by half-life: air travel (2400 m cabin) was safe after day 35 for C₃F₈, day 22 for both SF₆ and C₂F₆, and day 13 for air. The 12 cases illustrated clinical utility. CONCLUSIONS: This theoretical construct provides a reproducible, globally applicable binary decision-support tool for post-vitrectomy travel risk assessment. Route-specific elevation profiling and web-based calculation enable personalized bedside risk estimation.
Gumustop SS, Ding X, Zhang YS
… +16 more, Ploumi I, Zhu Y, Wang L, Romano F, Garg I, Chen C, Nodecker KN, Shah SH, Wagner SL, Kim LA, Wu DM, Patel NA, Vavvas DG, Husain D, Miller JW, Miller JB
PURPOSE: To compare non perfusion area (NPA) and the ischemic index (ISI) between 2 fields of view using ultra-widefield optical coherence tomography angiography (UWF-OCTA) and evaluate their correlation with diabetic re...PURPOSE: To compare non perfusion area (NPA) and the ischemic index (ISI) between 2 fields of view using ultra-widefield optical coherence tomography angiography (UWF-OCTA) and evaluate their correlation with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL). DESIGN: Cross-sectional, retrospective study. PARTICIPANTS: Sixty-two patients (101 eyes) with DR without prior pan-photocoagulation (PRP) treatment, imaged with 12 × 12-mm and 21 × 26-mm scans on UWF-OCTA. Forty-nine patients (79 eyes) with same-day ultra-widefield color fundus photography (UWF-CFP) were included in the PPL analysis. METHODS: NPA was calculated from UWF-OCTA scans using a semi-automatic algorithm on FIJI. ISI was determined as NPA divided by total scan area. A subset of eyes with same-day UWF CFP were assessed by 2 graders for the presence and extent of fields with PPLs - defined as >50% of diabetic lesions in extended versus Early Treatment of Diabetic Retinopathy Study (ETDRS) fields. Eyes were classified as having PPLs if ≥ 1 field met this criterion. MAIN OUTCOME MEASURES: NPA and ISI from 12 × 12-mm and 21 × 26-mm scans and their association with DR severity. RESULTS: NPA and ISI were significantly greater in PDR versus NPDR for both scans and the NPA/ISI was significantly higher in the 21 × 26-mm scan (P < .001 for all). Both the 12 × 12-mm (OR: 1.26 [95% CI: 1.07-1.48, P = .006]) and the 21 × 26-mm ISI (OR: 1.20 [95% CI: 1.10-1.29, P < .001]) were significantly associated with increasing DR severity. ROC analysis showed similar performance between both scan ISI at predicting DR severity (AUC: 0.868 vs 0.878, P = .558). In the sub-analysis, presence of PPL was only significantly associated with ISI on the 21 × 26-mm scan (B = 0.43901, P = .009). However, the interaction of both presence (B = 0.16, P = .006) and extent (B = 0.2,5 P = .044) of PPLs with increasing DR severity was positively associated with increasing ISI on the 21 × 26-mm scan. CONCLUSIONS: NPA/ISI on both the 12 × 12-mm and 21 × 26-mm scans is predictive of DR severity, highlighting the importance of OCTA detection of ischemia. The wider scan area of the 21 × 26-mm scan can better assess far peripheral ischemia that correlates with PPLs, supporting its potential role in tracking DR progression.
TOPIC: Depression and anxiety are common in chronic eye diseases, and the psychological implications of symptomatic vitreous opacities (SVO) remain underexplored. This systematic review synthesized current evidence on th...TOPIC: Depression and anxiety are common in chronic eye diseases, and the psychological implications of symptomatic vitreous opacities (SVO) remain underexplored. This systematic review synthesized current evidence on the psychological burden of SVOs and the extent to which interventions confer psychological benefit. CLINICAL RELEVANCE: Although SVOs typically occur with normal visual acuity, many patients with vision-degrading myodesopsia report significant distress, impaired well-being, and measurable degradation of contrast sensitivity. Understanding the magnitude of this burden and the potential psychological benefits of available treatments is important for clinical decision-making and patient counseling. METHODS: In June 2025, Medline, Embase, and the Cochrane Library were searched. Eligible studies assessed outcomes related to mental health, depression, anxiety, personality, quality of life, coping, and/or patient experiences or perceptions of vitreous opacities or their treatment. The protocol was prospectively registered in PROSPERO (CRD420251243887). The primary outcome was psychological burden relative to healthy controls; secondary outcomes included psychological changes following Nd:YAG vitreolysis or pars plana vitrectomy. Given substantial heterogeneity in study design and psychological instruments, findings were synthesized descriptively. RESULTS: Thirteen studies met inclusion criteria, encompassing 635 patients aged 18 to 88 years across Europe, Asia, and the Americas. Across study designs, individuals with SVO reported significantly higher levels of depression, anxiety, and perceived stress than healthy controls, despite preserved visual acuity. Standardized instruments (NEI-VFQ, PHQ-9, CES-D, HADS, Zung SDS, GAD-7, STAI, PSS-10) consistently showed elevated psychological symptom scores and lower mental health-related quality-of-life scores. Personality assessments (BFI) revealed greater neuroticism and lower extraversion in patients with SVO. Interventional studies with Nd:YAG laser vitreolysis and pars plana vitrectomy demonstrated improvements in vision-related QoL and psychological well-being. CONCLUSION: SVOs commonly present with a psychological overlay that affects emotional well-being. Our findings raise the possibility of a visual somatization component in psychologically vulnerable individuals, whereby vitreous changes may contribute to heightened anxiety or distress. Recognizing that traditional clinical metrics such as visual acuity may underestimate functional impairment supports the need for psychological screening, patient-centered counseling, and integration of validated floater-specific outcome measures alongside psychological endpoints.
OBJECTIVE: To evaluate the safety, tolerability, and preliminary efficacy of a single intravitreal injection of UGX-201, an optogenetic therapy utilizing an adeno-associated virus 2 type 7m8 variant to deliver a recombin...OBJECTIVE: To evaluate the safety, tolerability, and preliminary efficacy of a single intravitreal injection of UGX-201, an optogenetic therapy utilizing an adeno-associated virus 2 type 7m8 variant to deliver a recombinant chimeric opsin to retinal ganglion cells, in advanced nonsyndromic retinitis pigmentosa (RP) patients. DESIGN: An investigator-initiated, open-label, nonrandomized, single-center trial (ChiCTR2200062174). PARTICIPANTS: Nine patients with advanced nonsyndromic RP were enrolled and stratified into two cohorts by visual function: six with light perception (LP) cohort and three with no LP (NLP) cohort. METHODS: Single intravitreal injection of UGX-201 at dose of 1.5 × 10 vg/eye was administered in one eye per participant. All participants were followed up for at least 52 weeks and underwent comprehensive ophthalmic and systemic safety assessments along with visual structure and function examinations. MAIN OUTCOME MEASURES: The primary endpoint was safety, including adverse events (AEs), serious AEs, and treatment-related AEs over 52 weeks. Secondary endpoints included changes from baseline in best-corrected visual acuity, full-field stimulus threshold testing, and National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) scores through 52-week follow-up period. RESULTS: No serious ocular or systemic AEs occurred during the 52-week follow-up period. In the LP cohort, mean best-corrected visual acuity in the treated eyes assessed by Freiburg Visual Acuity and Contrast Test showed an improvement of 0.30 logMAR at Week 52. One participant exhibited substantial improvement in full-field stimulus threshold testing. The total composite score of the NEI VFQ-25 in LP cohort increased by 3.72 points at Week 52 from that at baseline. In the NLP cohort, all three participants restored LP in the treated eyes at Week 2, Week 4, and Week 24, respectively. Among them, two still maintained LP at Week 52 (end of study). CONCLUSIONS: UGX-201 exhibited a favorable safety profile and was well-tolerated in patients with advanced nonsyndromic RP. Sustained, meaningful visual acuity gains were observed in both LP and NLP cohorts, irrespective of baseline visual function status. These findings underscore the potential of UGX-201 as a first-in-class mutation-independent treatment option for advanced nonsyndromic RP.
Tribin FE, Durkee H, Alfonso A
… +9 more, Rodriguez Leiva A, Aguilar MC, Merikansky S, Hernandez M, Munoz B, Maestre-Mesa J, Flynn HW, Amescua G, Miller D
PURPOSE: Artificial tears (ATs) are widely used to relieve ocular symptoms of irritation, yet their diverse formulations containing varying viscosity agents, electrolytes, osmoprotectants, oils, and surfactants may diffe...PURPOSE: Artificial tears (ATs) are widely used to relieve ocular symptoms of irritation, yet their diverse formulations containing varying viscosity agents, electrolytes, osmoprotectants, oils, and surfactants may differentially support microbial growth. This study compared the growth of Staphylococcus aureus and Pseudomonas aeruginosa in commercially available ATs to identify formulation-dependent differences in susceptibility to contamination. DESIGN: Laboratory investigation. METHODS: Clinical and reference isolates of methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and P. aeruginosa were recovered from patient sources (conjunctiva [n = 2], contact lens [n = 1], cornea [n = 5], corneal button [n = 1], eyelids [n = 6], lacrimal sac [n = 2], and sclera [n = 1]) and inoculated into ten ATs categorized as preservative-containing multidose bottles (MDBs), preservative-free (PF)- MDBs, or PF single-dose vials (SDVs). Turbidity of the samples was recorded for 24 hours and growth kinetics, lag time (λ), specific growth rate (µ), and area under the curve (AUC), were derived using the Gompertz equation. Samples were cultured to quantify microbial growth. MAIN OUTCOME: Microbial growth. RESULTS: PF ATs supported significantly greater microbial proliferation than preserved formulations across all organisms (P < .001). Among PF ATs, SDVs exhibited the highest AUCs, particularly for P. aeruginosa, which showed delayed but more robust growth compared with S. aureus strains. Preserved ATs demonstrated uniform bactericidal activity irrespective of preservative type, whereas PF formulations were largely bacteriostatic or permissive to growth. Linear mixed-effects modeling indicated that AT formulation explained most AUC variability (57%), exceeding strain-level effects (9%). CONCLUSIONS: Microbial proliferation in ATs is strongly formulation dependent. PF formulations pose the greatest contamination risk, whereas preserved ATs provide broad-spectrum inhibition. These findings emphasize the need for formulation-specific evaluation of ATs and future optimization strategies that balance antimicrobial protection with ocular surface safety.
PURPOSE: To map anterior ocular wall thickness across quadrants and eccentricities in a heterogeneous adult population and to evaluate the anatomical adequacy of fixed-depth suprachoroidal injection strategies currently...PURPOSE: To map anterior ocular wall thickness across quadrants and eccentricities in a heterogeneous adult population and to evaluate the anatomical adequacy of fixed-depth suprachoroidal injection strategies currently used in clinical practice. DESIGN: A cross-sectional observational study. METHODS: A total of 110 eyes from 110 participants (18-75 years; +3.00 to -11.00D) were included. Swept-source anterior segment optical coherence tomography was used to measure central corneal thickness, anterior scleral thickness (AST), conjunctival-tenon capsule thickness, anterior choroidal thickness, anterior conjunctival-scleral thickness, and anterior conjunctival-scleral-choroidal thickness. Measurements were obtained in four quadrants at 0 to 5 mm posterior to the scleral spur at 1-mm intervals. Associations between thickness parameters and demographic, refractive, and anatomical factors were analyzed using mixed-effects models. The frequency of measurements below commonly used suprachoroidal injection depths (900 and 1100 µm) was determined. RESULTS: Anterior ocular wall thickness exhibited marked spatial variability across quadrants (P < .001), decreasing sharply 1 to 2 mm posterior to the scleral spur before stabilizing. At 4 mm posterior to the scleral spur, all eyes exhibited AST values below 900 µm, and anterior conjunctival-scleral-choroidal thickness was below 900 µm in 63.64% of eyes. AST was independently associated with age and central corneal thickness but showed no association with spherical equivalent or axial length. CONCLUSIONS: Anterior ocular wall thickness varies substantially by quadrant and eccentricity. While fixed-depth needles are clinically safe, understanding this anatomical variation may clarify injection mechanics and support anatomically guided approaches to optimize suprachoroidal drug delivery.
PURPOSE: The longitudinal trend of tissue-related adverse events (AEs) from corneal transplant procedures is not well characterized. By identifying corneal transplantation-related AEs over time, eye banks and clinicians...PURPOSE: The longitudinal trend of tissue-related adverse events (AEs) from corneal transplant procedures is not well characterized. By identifying corneal transplantation-related AEs over time, eye banks and clinicians can better understand changes and assess the risks associated with tissue transplantation. DESIGN: Trend study. SUBJECTS: Corneal tissues obtained from individuals who donated to Eversight Eye Bank. METHODS: This study investigated the rates of reported AEs at a large eye bank in the United States. Data was extracted from the eye bank database between May 2007 and December 2024. A longitudinal analysis of AEs in corneal tissue was conducted across AE types and procedural types. MAIN OUTCOME MEASURES: The main outcome measures were surgeon-reported AEs to the eye bank and AEs determined to be tissue-related causes. AE types for tissue-related AEs were assessed. RESULTS: A total of 126,072 donor tissues were included between May 2007 and December 2024. 176 AEs were determined to be tissue-related, representing an estimated prevalence of 0.14% (95% CI: 0.12%-0.16%). For every year, there was an associated 6.7% (95% CI: 3.8%-9.5%) reduction in the odds of AEs (P < .001), an estimated 69.2% reduction over 17 years. Adjusted for year, Descemet stripping automated endothelial keratoplasty (EK) (DSAEK) had 2.3 times (95% CI: 1.6-3.2, P < .001) and Descemet membrane EK (DMEK) had a 2.8 (95% CI: 1.8-4.5, P < .001) odds of AE compared to PKP, but no significant difference in the rate of improvement for PKP to DSAEK (P = .6) or PKP to DMEK (P = .4). Rates of infectious keratitis (OR: 0.91, 95% CI: 0.83-0.99, P = .024) and primary graft failure (OR: 0.90, 95% CI: 0.86-0.94, P < .001) significantly improved year-over-year, while endophthalmitis (P = .13) and early regraft (P = .3) did not significantly improve. CONCLUSIONS: AE rates in corneal transplantation procedures continue to decline year-over-year, highlighting the improving safety and quality in eye banking and corneal transplantation. Rates improved across procedure types (PKP, DMEK, and DSAEK) and AEs (infectious keratitis and graft failure).
PURPOSE: To assess rotational stability and refractive outcomes of a toric hydrophilic acrylic intraocular lens (IOL). DESIGN: Single-center, noncomparative, interventional clinical trial. METHODS: In this study, 120 eye...PURPOSE: To assess rotational stability and refractive outcomes of a toric hydrophilic acrylic intraocular lens (IOL). DESIGN: Single-center, noncomparative, interventional clinical trial. METHODS: In this study, 120 eyes from 80 patients with age-related cataract and preoperative corneal astigmatism greater than 1.0 diopter (D) were enrolled. Patients underwent phacoemulsification with implantation of a RayOne EMV Toric IOL. Rotational stability was evaluated relative to baseline measurements at the end of surgery (EOS) and compared to retroillumination images acquired at 1 hour (1 h), 1 week (1 w), 1 month (1 m), and 6 months (6 m), postoperatively. Subjective manifest refraction was assessed at the 6 m follow-up visit. RESULTS: A total of 114 eyes from 75 patients were available for the final analysis. Mean absolute rotation from EOS to 6 m was 2.44° ± 2.34° (range: 0.04; 10.60). Rotation between follow-up visits was 0.89° ± 1.10° (0.00; 8.37) from EOS to 1 h, 0.58° ± 0.49° (0.00; 2.76) from 1 h to 1 w, 1.19° ± 1.45° (0.02; 7.17) from 1 w to 1 m, and 1.11° ± 1.41° (0.00; 7.96) from 1 m to 6 m. Preoperative corneal astigmatism was 1.68 ± 0.66 D (1.00; 3.99), which was reduced to a postoperative refractive astigmatism of 0.27 ± 0.26 D (0.00; 1.25) at 6 m. CONCLUSIONS: The RayOne EMV Toric IOL demonstrated good rotational stability within the first postoperative week. However, an increased tendency to rotation after 1 w was observed, leading to a total of 19 (16.7%) IOLs rotating more than 5°, including one case exceeding 10° from EOS to 6 m. Refractive outcomes were favorable, with 92% of eyes achieving ≤0.50 D of residual refractive astigmatism.
TOPIC: This systematic review and meta-analysis evaluated whether gene therapy provides safe and clinically meaningful efficacy for patients with neovascular age-related macular degeneration (nAMD). The clinical question...TOPIC: This systematic review and meta-analysis evaluated whether gene therapy provides safe and clinically meaningful efficacy for patients with neovascular age-related macular degeneration (nAMD). The clinical question addressed outcomes in patients with nAMD receiving gene therapy (primarily adeno-associated virus-based anti-vascular endothelial growth factor (anti-VEGF) constructs) compared with baseline or standard care contexts, focusing on visual acuity, anatomical response, treatment burden, and safety. Anti-VEGF intravitreal injections remain the current standard of care but require frequent administration and long-term adherence. CLINICAL RELEVANCE: nAMD is a major cause of irreversible vision loss in older adults and imposes substantial treatment burden due to repeated injections. Gene therapy aims to achieve sustained intraocular therapeutic protein expression after a single or infrequent administration, potentially reducing injection frequency while maintaining disease control. Establishing safety and functional efficacy is critical before translation into routine retinal practice. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases (PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library) were searched from inception to February 1, 2026. Eligible studies were prospective interventional clinical studies evaluating gene therapy in neovascular age-related macular degeneration, including randomized early-phase trials and open-label dose-escalation cohorts. Primary outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), rescue anti-VEGF requirement, mortality, and adverse events (AEs). Risk of bias was assessed using the revised Cochrane Risk of Bias tool version 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. Multilevel random-effects meta-analyses using restricted maximum likelihood (REML) accounted for clustering of multiarm cohorts. RESULTS: Eight prospective interventional studies comprising 203 treated participants were included, including randomized early-phase trials and open-label dose-escalation cohorts. The primary multilevel REML analysis showed no significant pooled BCVA improvement (mean difference (MD) 0.54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; 95% confidence interval (CI), -7.38 to 8.46), despite favorable fixed-effect sensitivity estimates. CST demonstrated significant anatomical reduction (MD 37.13 µm; 95% CI, 26.63-47.62). Approximately 44% of treated eyes required rescue anti-VEGF injections. Safety outcomes showed low-to-moderate cumulative event probabilities, although estimates varied by model, endpoint, and vector platform. Publication bias was detected for BCVA and CST but was minimal for most safety outcomes. CONCLUSION: Gene therapy for neovascular age-related macular degeneration demonstrates encouraging anatomical efficacy and manageable short- to midterm safety signals but lacks consistent functional visual improvement. Current evidence supports a treatment-burden-reducing adjunctive role rather than replacement of conventional anti-VEGF therapy. Evidence strength is limited by early-phase designs, small sample sizes, and clinical heterogeneity; ongoing phase 3 trials are required to define long-term efficacy and clinical positioning.
Yehezkeli V, Parunakian E, Meng Q
… +2 more, Demer JL, Suh SY
Am J Ophthalmol
· 2026 Jul · PMID 41933568
·
Full text
PURPOSE: Undercorrection is common after standard dosing of medial rectus (MR) recession for partially accommodative esotropia (PAET). Our goal was to evaluate motor and sensory outcomes in patients with PAET undergoing...PURPOSE: Undercorrection is common after standard dosing of medial rectus (MR) recession for partially accommodative esotropia (PAET). Our goal was to evaluate motor and sensory outcomes in patients with PAET undergoing augmented MR recession. STUDY DESIGN: Interventional case series. METHODS: We studied patients with PAET who underwent augmented bilateral MR recession targeted to the average distance esotropia with and without hyperopic correction. RESULTS: A total of 110 patients (47% female) with a mean age of 5 ± 3 years were included. Preoperative distance esotropia measured 42 ± 13Δ without spectacle correction and 25 ± 11Δ with full hyperopic spectacle correction. Surgery was performed for target angles based on Parks' tables. Despite using an augmented target angles that exceeded the deviations measured with hyperopic correction, 33 patients (30%) had >5Δ residual esotropia at final follow-up. Consecutive exotropia developed in 9 patients (8%), of whom 8 (89%) were managed with hyperopic undercorrection. Posterior pulley fixation in 23 patients reduced the mean distance-near disparity from 12 ± 5Δ to 1 ± 4Δ. Only 8 patients (7%) underwent reoperation, 7 for persistent esotropia and 1 for consecutive exotropia. CONCLUSIONS: Augmented bimedial rectus recession for PAET, based on a target angle averaging distance esotropia with and without correction, achieved high rates of favorable motor and sensory outcomes. Nevertheless, 30% of patients had residual esotropia, underscoring that even augmented dosing may be insufficient. Rare overcorrections were effectively managed by reducing hyperopic spectacle power.
PURPOSE: To evaluate the association between geography and retinoblastoma care, including treatment modality, stage at diagnosis, and time to treatment in the United States, and whether geography modifies ethnoracial and...PURPOSE: To evaluate the association between geography and retinoblastoma care, including treatment modality, stage at diagnosis, and time to treatment in the United States, and whether geography modifies ethnoracial and socioeconomic disparities in care. DESIGN: Retrospective, population-based cohort study. SUBJECTS: Children aged <15 years diagnosed with retinoblastoma from 2000 to 2021 in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. METHODS: We examined the association between geography and treatment modality, stage at diagnosis, and time to treatment, while accounting for race/ethnicity and county-level median household income. Multinomial and binary logistic regression models were used to evaluate predictors of treatment modality and stage at diagnosis, and multiple linear regression was used to assess time from diagnosis to treatment initiation (days). Interaction terms between geography and race/ethnicity, as well as between geography and income were included to assess effect modification. MAIN OUTCOME MEASURES: Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations with treatment modality, stage at diagnosis, and time to treatment. RESULTS: The cohort included 1375 pediatric patients (1817 eyes). Children residing in metropolitan areas had lower odds of enucleation (aOR: 0.692; 95% CI: 0.451-0.914; P = .002) and reduced receipt of chemotherapy (aOR: 0.629, 95% CI: 0.444-0.891, P = .015). Non-Hispanic White children also had reduced odds of enucleation compared with non-White children (aOR: 0.757; 95% CI: 0.613-0.838; P = .010). Interaction analyses demonstrated that geography modified associations between race/ethnicity and enucleation (P = .018) and receipt of chemotherapy (P = .031). Among patients with staging data, those from lower-income households were more likely to present with regional/distant disease (aOR: 1.342; 95% CI: 1.010-1.794; P = .044), while Non-Hispanic White children were more likely to present with localized disease (aOR: 1.931; 95% CI: 1.303-2.863; P = .001). Geography modified the association between household income and stage at presentation (P = .022). Time to treatment did not differ significantly across patients, regardless of geography. CONCLUSIONS: Geography influences disparities in retinoblastoma care by shaping access to key therapies and modifying the impact of race/ethnicity and socioeconomic status. With no differences in time to treatment after diagnosis, inequities may arise earlier in the care pathway, during disease recognition and referral. Strengthening early detection, referral networks, and access to advanced therapies in non-metropolitan regions may help reduce these disparities.
PURPOSE: To describe the clinical spectrum, novel imaging features, and associations of unilateral retinal pigment epithelium dysgenesis (URPED), expanding its phenotypic and pathogenetic framework. DESIGN: Retrospective...PURPOSE: To describe the clinical spectrum, novel imaging features, and associations of unilateral retinal pigment epithelium dysgenesis (URPED), expanding its phenotypic and pathogenetic framework. DESIGN: Retrospective, longitudinal, multicenter case series. SUBJECTS: Ten eyes of ten patients with URPED and two eyes with combined hamartoma of the retina and retinal pigment epithelium (RPE) exhibiting URPED-like changes, examined between 2011 and 2025 at Luigi Sacco Hospital (Milan, Italy) and Macquarie University Hospital (Sydney, Australia). METHODS: Comprehensive multimodal imaging was performed, including color fundus photography, near-infrared reflectance, short-wavelength fundus autofluorescence (SW-FAF), fluorescein and indocyanine green angiography (FA/ICGA), and spectral-domain optical coherence tomography (SD-OCT). Lesions were classified as overt, when diagnosis was achievable on noninvasive imaging alone, or covert, when ICGA was required. Near-infrared reflectance, SW-FAF, FA, and ICGA patterns were correlated with structural OCT findings. Lesion area was manually measured at baseline on SW-FAF and ICGA, and at last follow-up on SW-FAF. MAIN OUTCOME MEASURES: URPED phenotypic patterns; multimodal imaging characteristics; frequency of associated hamartomatous lesions and other complications. RESULTS: Seven eyes (70%) were classified as overt URPED, displaying scalloped (n = 4), mottled (n = 1), or mixed (n = 2) SW-FAF patterns; three eyes (30%) were categorized as covert URPED, detectable only on ICGA. The classic inverted SW-FAF/FA pattern occurred exclusively in overt scalloped or mixed lesions. SD-OCT consistently demonstrated Bruch membrane-RPE separation with overlying "sawtooth" changes (10/10, 100%). Evidence of iRORA/cRORA was present in six eyes (60%), and choroidal caverns in six eyes (60%). Hamartomatous lesions were identified in four eyes (40%), three retinal capillary hemangiomas, and one choroidal osteoma; all topographically colocalizing with URPED. Choroidal neovascularization developed in four eyes (40%), all responding favorably to anti-VEGF therapy. Lesion size remained largely stable over a median follow-up of 27.5 months, with excellent intergrader reproducibility (intraclass correlation coefficient = 0.98-0.99). CONCLUSIONS: URPED encompasses a broader phenotypic continuum than previously recognized, ranging from overt to covert forms unified by Bruch membrane-RPE dysgenesis. The frequent coexistence with hamartomatous lesions supports a shared developmental origin. Multimodal imaging is essential for diagnosis and phenotypic classification, with ICGA playing a pivotal role in detecting covert forms.