To explore discrepancies on fundus autofluorescence (FAF) obtained with two widely used devices in patients with CNGB3-associated achromatopsia, with respect to the central foveal signal. Secondly, to explore continuity of the foveal ellipsoid zone (EZ) in these patients. Patients who had undergone blue (488 nm; Heidelberg Spectralis) and green (532 nm; Optos) FAF imaging during the same visit were included. The central foveal signal was graded qualitatively as brighter or darker compared to the wider foveal/parafoveal region. Optical coherence tomography images from the same visit were also graded (masked to FAF grading) with respect to foveal EZ continuity. Forty-one patients (24 females; mean age, 32 ± 19 years) were included. For blue FAF, the central foveal signal was graded darker in all cases. For green FAF, the central fovea was brighter in 11 patients (27%), indicating discordance with blue FAF. The discordant group were significantly younger (P = 0.022). The EZ line was gradable in 40 patients: 22 (55%) had continuous foveal EZ in both eyes; these were younger than those with an interrupted EZ in one or both eyes (P < 0.0001). All patients discordant for FAF images had continuous foveal EZ. Discordance occurred between the FAF modalities in more than one-quarter of patients; these patients were significantly younger, and all had a continuous EZ line. Investigating mechanisms of discordance could yield pathophysiological insights. FAF platforms are not interchangeable; these findings could inform the design of natural history studies and therapeutic trials for this condition.

The aim of this study was to compare the near add power of glaucoma patients and controls between the ages of 40 and 79years. This was a cross-sectional study of 2724 bilateral phakic participants aged between 40 and 79years, which included 1615 controls and 1109 patients with primary open-angle glaucoma who were using prostaglandin F (FP) receptor agonists. Participants were classified into eight age groups: 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79years of age. We compared the near add power and other ocular parameters between glaucoma patients and controls by age group. There was a significant difference between glaucoma patients and controls and in spherical equivalent, intraocular pressure, cup/disc ratio, ganglion cell complex thickness, peripapillary retinal nerve fiber layer thickness, and use of dry eye eyedrops across all or many of the age groups studied. The near add power of glaucoma patients was comparable to controls of the immediately older age group until 65-69years, indicating that the advancement of near add power of glaucoma patients was approximately five years earlier than in controls until that age range. There was an earlier progression of presbyopia determined by near add power in glaucoma patients treated with FP receptor agonists compared with controls. Between ages 40 and 79years, glaucoma patients treated with prostaglandin F receptor agonists had higher near add power than controls. This knowledge could contribute to informing better management of glaucoma patients with presbyopia.

The mechanistic target of rapamycin (mTOR) signaling pathway is essential for the onset and progression of diabetic retinopathy (DR). Nevertheless, the impact of mTORC1 downstream proteins in DR remains uncertain. Therefore, we performed a Mendelian randomization (MR) research to assess the causal effect of downstream mTORC1 proteins on DR risk. Summary statistics on mTORC1 downstream proteins and DR were obtained from the INTERVAL and FinnGen studies (14,584 patients and 176,010 controls), respectively. We used various MR techniques, including inverse-variance-weighted, weighted median, and MR-Egger. Possible pleiotropy and heterogeneity were identified through sensitivity analysis. Genetically predicted eIF4E was positively correlated to DR risk (odds ratio = 1.057; 95% confidence interval, 1.008-1.109; P = 0.022]. No relationship has been shown for circulating RP-S6K, eIF4G, eIF4A, eIF4E-BP and eIF4B levels with DR formation. There was no heterogeneity or unbalanced level pleiotropy identified. Higher levels of serum eIF4E promote the progression of DR, proposing that pharmacological inhibition of eIF4E activity may be a prospective DR therapeutic strategy. The present study has highlighted the role of eIF4E in the development of DR, establishing the foundation for basic research into DR targets.

The shape and characteristics of the velocity fields around vitrectomy probes are unknown, resulting in an incomplete understanding of their surgical effects and behavior. The primary aim of this study was to define and measure with high spatial and temporal resolution the field of fluidic effect induced by vitrectomy probes, with assessment of both convective and temporal acceleration in a range of surgically relevant settings with an optimized particle image velocimetry (PIV) methodology. This was a laboratory-based investigation using in vitro testing carried out at Newcastle University. Testing was conducted using a DORC EVA Nexus vitrectomy system with dual cutting action vitrectomy probes in three gauge sizes (23G, 25G and 27G). With the use of balanced salt solution (BSS), PIV measurements were conducted for various flow, vacuum, and cut rates. Experiments were conducted in a range of different probe orientations to reconstruct a three-dimensional representation of the flow fields. Using a variety of improvements in the PIV setup, including choosing an optimal time delay (dt) between the image pairs, the field of fluidic effect was measured with high spatial resolution up to the probe port. Fluid acceleration in the vicinity of the cutter was accurately resolved with values significantly higher than previously reported values. Two clinically relevant zones, high-flow and low-flow, were identified and defined. The high-flow zone (HFZ) had an acceleration of up to 400 m/s2 and reached velocities of up to 1 m/s close to the port for the maximum aspiration setting. The low-flow zone (LFZ) extended approximately 2 to 2.5mm from the port, or 3.5 to 4 times the diameter of the cutter (during maximum aspiration), with the mean velocity at the edge of the zone reaching 0.01 m/s. The extent of the HFZ was relatively constant with respect to gauge size and increased only marginally with both increased flow and vacuum settings. The LFZ increased in extent with both flow and vacuum. It varied in extent by gauge size with vacuum but was relatively unaltered by gauge size with fixed flow. Cut rate had no clinically relevant effect on the HFZ and LFZ extents and velocity fields. Using optimized PIV measurements on an experimental in vitro vitrectomy setup, two clearly defined flow zones could be identified around the vitrectomy port. The study defined the shape of the two flow zones in BSS, outlined influencing factors, and correlated fluctuations with gauge, flow, and cut rates. These parameters enhance surgical understanding and provide a benchmark for future design evaluations. Further study using non-Newtonian fluids would be of interest to outline the differences in flow fields. Understanding the flow patterns around the probe and the effect of key surgical parameters on their extent could assist in optimizing vitrectomy and reducing the risk of iatrogenic retinal trauma.

To investigate the impact of several allergic diseases on the development of keratoconus (KC) from a genetic perspective. Data from multiple genome-wide association studies involving European ancestry individuals were used. Ultimately, 613 allergic conjunctivitis (AC) cases and 474,657 controls, 4387 allergic rhinitis (AR) cases and 471,273 controls, 4859 allergic asthma cases and 135,449 controls, 1169 allergic urticaria cases and 212,464 controls, 22,474 atopic dermatitis cases and 774,187 controls, and 311 KC cases and 209,287 controls were included. Then inverse-variance weighted (IVW) method, potential pleiotropy, heterogeneity, and leave-one-out analyses were assessed to investigate the causal effects of those allergic diseases on KC. IVW estimates indicated that allergic asthma promoted the development of KC (IVW odds ratio [OR] = 2.18; 95% confidence interval [CI], 1.007-4.707; P = 0.048). However, the IVW estimates show that AC (IVW OR = 1.02; 95% CI, 0.960-1.086; P = 0.513), AR (OR = 0.26; 95% CI, 0.037-1.754; P = 0.165), atopic dermatitis (IVW OR = 1.50; 95% CI, 0.942-2.395; P = 0.088), allergic urticaria (IVW OR = 1.11; 95% CI, 0.822-1.511; P = 0.485) are not significantly causally associated with KC. Allergic asthma may promote KC by increasing allergy-related ocular inflammation. The possibility of increased KC in patients with allergic asthma should be considered.

PurposeThe purpose of this study was to develop models that predict which patients with glaucoma will progress to require surgery, combining structured data from electronic health records (EHRs) and retinal fiber layer optical coherence tomography (RNFL OCT) scans.MethodsEHR data (demographics and clinical eye examinations) and RNFL OCT scans were identified for patients with glaucoma from an academic center (2008–2023). Comparing the novel TabNet deep learning architecture to a baseline XGBoost model, we trained and evaluated single modality models using either EHR or RNFL features, as well as fusion models combining both EHR and RNFL features as inputs, to predict glaucoma surgery within 12 months (binary).ResultsWe had 1472 patients with glaucoma who were included in this study, of which 29.9% (N = 367) progressed to glaucoma surgery. The TabNet fusion model achieved the highest performance on the test set with an area under the receiver operating characteristic curve (AUROC) of 0.832, compared to the XGBoost fusion model (AUROC = 0.747). EHR only models performed with an AUROC of 0.764 and 0.720 for the deep learning model and XGBoost models, respectively. RNFL only models performed with an AUROC of 0.624 and 0.633 for the deep learning and XGBoost models, respectively.ConclusionsFusion models which integrate both RNFL with EHR data outperform models only utilizing one datatype or the other to predict glaucoma progression. The deep learning TabNet architecture demonstrated superior performance to traditional XGBoost models.Translational RelevancePrediction models that utilize the wealth of structured clinical and imaging data to predict glaucoma progression could form the basis of future clinical decision support tools to personalize glaucoma care.

To assess corneal resistance to enzymatic digestion after rose bengal (RB)/green light and RB/green light followed by riboflavin (RF)/ultraviolet A (UV-A) cross-linking (CXL), with or without oxygen. Ex vivo porcine corneal buttons (n = 144) underwent CXL with RB/green or RB/green-RF/UV-A under atmospheric 21% oxygen conditions or in a nitrogen chamber with 0.1% oxygen (hypoxic conditions) to test 10- and 15-J/cm2 fluences. After CXL, corneas were digested with 0.3% collagenase A, and mean digestion times (MDTs) were recorded. For the non-irradiated control group, the MDT was 19.75 ± 1.34 hours. Under atmospheric oxygen conditions, RB/green CXL yielded MDTs of 33.69 ± 1.4 and 34.38 ± 1.31 hours with fluences of 10 and 15 J/cm2, respectively. RB/green + RF/UV-A showed MDTs of 39.56 ± 1.93 and 51.94 ± 4.2 hours for combined fluences of 10 + 10 J/cm2 and 15 + 15 J/cm2, respectively. Hypoxic RB/green MDTs were 33.88 ± 1.02 and 34.06 ± 1.57 hours, and RB/green + RF/UV-A MDTs were 39.62 ± 2.5 and 50.35 ± 1.59 hours for the same respective fluences. No significant differences were observed between the control groups and corresponding intervention groups (all P > 0.05). CXL via RB/green and RB/green-RF/UV-A significantly enhanced corneal collagenase digestion resistance, irrespective of oxygen presence. These findings could help optimize infectious keratitis therapy CXL protocols. Our findings aid the understanding of the molecular mechanisms underlying the therapeutic effect of CXL and may contribute to refining accelerated PACK-CXL protocols and other CXL treatment strategies.

The Ocular Pain Assessment Survey (OPAS) has been used to quantify chronic ocular pain and quality of life (QOL). We aim to investigate the psychometric properties of individual OPAS items with the Rasch analysis in an Asian population of dry eye disease and neuropathic corneal pain (NCP). Question responses were obtained from 196 patients; 138 with dry eye disease (DED) and 58 with NCP, at the Singapore National Eye Centre. Item hierarchy, item fit statistics, item separation, reliability indices, and Yen's Q3 values were calculated. Individual dimensions that quantify eye pain levels in the past 24hours and QOL showed good discriminative ability according to their person separation index values. However, individual dimensions that measured eye pain in the past 2weeks, non-eye pain, as well as aggravating and associated factors showed suboptimal person separation index values. Significant correlations were found between the individual item pairs of the aggravating factors dimension as well as between some of the items in the QOL and associated factors dimensions. Two dimensions of the OPAS questionnaire were validated with the Rasch analysis. Based on these findings, we shorten the number of questions in some dimensions to improve the performance of the tool in similar Asian populations. Our study provides insights to improve the existing OPAS for real-world clinical applications and clinical trials.

This study aimed to explore the potential causal relationship between genetically determined elevated levels of pro-inflammatory cytokines and iridocyclitis, including its subtypes: acute and subacute iridocyclitis (ASIR) and chronic iridocyclitis (CIR). A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) summary data for inflammatory cytokines (cases, n = 14,824), iridocyclitis (IR; cases, n = 7306 and controls, n = 357,814), and its subtypes (ASIR: cases, n = 6166 and controls, n = 357,814; and CIR: cases, n = 1401 and controls, n = 357,814). The inverse variance-weighted (IVW) method served as the primary analysis method. Supplementary analytic methods included MR Egger, Weighted median, Weighted mode, and Simple mode methods. Pleiotropy and heterogeneity were evaluated using the Cochran's Q test, MR Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), Bayesian colocalization analysis, and Linkage disequilibrium score regression (LDSC) analysis. Genetically predicted high levels of eotaxin, fibroblast growth factor 23 (FGF23), TNF-related apoptosis-inducing ligand (TRAIL), and Neurotrophin-3 were associated with an increased risk of IR. On the contrary, a high level of interleukin (IL)-2 was associated with a decreased risk of IR. Meanwhile, the IR subgroup analysis demonstrated that high levels of eotaxin and TRAIL were also associated with an increased risk of ASIR. High levels of cystatin D, tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and caspase 8 were associated with an increased risk of CIR. CCL20 and CDCP1 were associated with a decreased risk of CIR. Heterogeneity and pleiotropy tests demonstrated that our findings were stable and reliable. Inflammatory cytokines are involved in the occurrence of IR and its subtypes. Further studies are warranted to elucidate the precise mechanisms of inflammatory cytokines in IR and its subtypes. The present study highlighted the role of inflammatory cytokines in the development of IR.

We present RetOCTNet, a deep learning tool to segment the retinal nerve fiber layer (RNFL) and total retinal thickness automatically from optical coherence tomography (OCT) scans in rats following retinal ganglion cell (RGC) injury. We created unilateral RGC injury by ocular hypertension (OHT) or optic nerve crush (ONC), and contralateral eyes were not injured. We manually segmented the RNFL and total retina of 3.0-mm radial OCT scans (1000 A-scans per B-scan, 20 frames per B-scan) as ground truth (n = 192 scans). We used these segmentations for training (80%), testing (10%), and validation (10%) to optimize the F1 score. To determine the generalizability of RetOCTNet, we tested it on volumetric scans of a separate cohort at baseline and 4, 8, and 12 weeks post-ONC. RetOCTNet's segmentations achieved high F1 scores relative to the ground-truth segmentations created by human annotators: 0.88 (RNFL) and 0.98 (retinal thickness) for control eyes, 0.84 and 0.98 for OHT eyes, and 0.78 and 0.96 for ONC eyes, respectively. On volumetric scans 12 weeks post-ONC, RetOCTNet calculated thinning of 29.49% and 10.82% in the RNFL and retina at the optic nerve head (ONH) and thinning of 38.34% and 9.85% in the RNFL and retina superior to the ONH. RetOCTNet can segment the RNFL and total retinal thickness of both radial and volume OCT scans. RetOCTNet can be applied to longitudinally monitor RNFL in rodent models of RGC injury. This tool automates RNFL and retinal thickness measurement for rat OCT scans following RGC injury, reducing analysis time and increasing the consistency between studies.