PINNACLE is one of the largest prospective multicentre observational studies evaluating the progression of intermediate age-related macular degeneration (iAMD). This paper aims to provide an optical coherence tomography (OCT)-based qualitative and quantitative characterisation of the cohort's baseline morphology. Based on expert grader readings and artificial intelligence (AI)-based image analysis, we report the prevalence, quantitative measurements, topographic distribution and intercorrelation of characteristic iAMD features including drusen, drusen subtypes, subretinal drusenoid deposits (SDD), hyperreflective foci (HRF), double layer sign and various measurements of outer retinal condition, such as ellipsoid zone (EZ) and outer nuclear layer (ONL) thicknesses, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and a semi-automated atrophic marker including EZ loss and choroidal hypertransmission (EZLHT). Drusen accumulate within the central 3 mm while SDD predominantly occurs in the superior perifoveal quadrant. Whereas higher drusen volume was associated with the presence and volume of HRF, it was inversely correlated with SDD presence. Thickness measurements of the EZ and ONL demonstrate outer retinal thinning, indicating photoreceptor compromise in iAMD, more pronounced in eyes showing atrophic features such as iRORA or EZLHT. This work combines expert grader readings with AI-based image analyses, applied on the largest prospectively, densely OCT-imaged cohort of iAMD reported on so far. The results show feature distribution comparable to previous reports. They substantially contribute to the comprehensive morphological characterisation of iAMD. This data is relevant for the interpretation of longitudinal data, refining inclusion criteria for future clinical trials and for providing a reference to other trials in the field.
To explore the histopathological characteristics in eyes with uveal melanoma (UM) that had secondary enucleation after iodine-125 plaque radiotherapy (PRT). This study included 243 patients with unilateral UM treated at Beijing Tongren Hospital from 2007 to 2020. Of these, 119 initially received PRT, followed by enucleation 2 months-9 years later. We retrospectively examined the histopathological features of enucleated ocular tissues to investigate microscopic differences based on treatment methods and reasons for secondary enucleation. Compared with 124 primary enucleations, eyes after PRT were more likely to show tumour diffuse distribution; had more tumour cell necrosis and more inflammation. In addition, eyes after PRT had a higher frequency of sclera invasion, optic nerve invasion by the tumour and neovascularisation of the iris. Histopathologically, 55 eyes (46%) were removed due to local control failure. Compared with eyes enucleated because of severe radiotherapy complications, eyes enucleated for local control failure had tumours invading the optic disc and ciliary body more frequently, pathological mitosis and the proportion of tumour diffuse distribution were higher. Eyes with radiotherapy complications had more tumour tissue necrosis and more neovascularisation of the iris. By observing the pathological features, we regrouped the patients who underwent secondary enucleation after PRT. These differences in histopathology may represent tissue effects of radiotherapy radiation or features related to tumour progression and growth. Tumour insensitivity and progression after PRT clearly increased the risk of metastasis-related death. Some pathological microscopic features may be important prognostic indicators of patients with UM.
The standard of care for neovascular age-related macular degeneration (nAMD) is repeated intravitreal injection with anti-vascular endothelial growth factor agents. Real world evidence suggests that some patients are undertreated, which might be linked with the retreatment decisions made by physicians. Therefore, this multicentre observational study aimed to investigate the extent to which enrichment of optical coherence tomography (OCT) images with segmentation information could influence and support disease activity assessment (DAA) in patients treated for nAMD. Descriptive statistics were tabulated for the demographic and clinical characteristics and outcome variables. To assess the influence of automated OCT image enrichment with segmentation information on DAA, a generalised linear mixed model was employed. The degree of agreement in classification of disease activity across reviewers was assessed by Krippendorff's alpha. The odds estimate for DAA regarding enriched OCT images was 0.759 and for non-enriched OCT images 0.772. The OR for enriched versus non-enriched OCT images was 1.078 with a p value of 0.229. No difference in the odds of DAA between automated OCT image enrichment with segmentation and DAA was noted. Krippendorff's alpha coefficient was 0.416 for enriched and 0.402 for non-enriched OCT images. Thus, the inter-reviewer reliability/agreement was similarly low between enriched and non-enriched OCT images. OCT image enrichment did not appear to impact the likelihood of adequately detecting disease activity, nor did it have an impact on agreement between reviewers of images in this study. No new safety signals in products involved in the study were detected. NCT04662944.
To investigate the effect of switching to a different type of myopia control spectacles on myopia progression. This retrospective matched-cohort study involved 1012 children or adolescents who were prescribed myopia control spectacles. Participants were divided into two groups: the change-of-type group (n=253), who switched to a different spectacle type, and the type-maintenance group (n=759), who retained the same type, using 1:3 propensity score matching. The primary outcome was the annual rate of spherical equivalent refraction progression (D/year) compared between and within groups before and after the switch. The initial prescription of myopia control spectacles occurred at a mean age of 9.46±2.11 years. Subsequent prescription (renewing the same type or switching to a new type) was provided at a mean age of 10.63±2.16 years. Before switching spectacles, the change-of-type group exhibited a significantly faster myopia progression rate than the type-maintenance group (-0.66±0.40 D/year vs -0.37±0.49 D/year; p<0.001). After switching, the progression rate slowed in the change-of-type group (mean reduction 0.18 D/year, p<0.001), narrowing the intergroup difference from 0.30 D/year to 0.08 D/year (-0.48±0.61 vs -0.40±0.50 D/year; p<0.001). However, the improved effect in the change-of-type group was not sustained, with myopia progression accelerating again with prolonged use (early vs late phase, -0.33 vs -0.53 D/year, p=0.024). Switching to a different type of myopia control spectacle may help slow myopia progression for children exhibiting suboptimal response to their initial spectacles. However, this beneficial effect tends to wane over time with prolonged wear.
To examine trends in corneal transplantation in Europe over an 18-year period from 2007 to 2024 by using data from the annual reports of the European Eye Bank Association (EEBA) regarding transplantation procedure type and quality control parameters in eye banking. Data were extracted from annual EEBA reports, and a longitudinal analysis of the categories-type of transplant, storage methods, issuance and contamination rates was conducted. The analysis included 443 237 corneas issued for transplantation from 116 different eye banks across 25 countries. The total number of keratoplasty procedures grew by 108%. A shift towards lamellar procedures was noted. Penetrating keratoplasties decreased from 85% (2007) to 34% (2017). A significant increase in posterior lamellar grafts was seen, reaching 47% in 2017, which were increasingly produced in eye banks. Issuance rates improved over time, with 59% of procured corneas issued for transplantation in 2024. Contamination rates remained low at 1-2% for bacterial and 0.3 to 0.96% for fungal contamination. Comparison with other international studies confirms the observed trend favouring lamellar procedures, while countries with differing socioeconomic conditions deviate from this trend. This study provides a comprehensive overview of the shifting landscape of corneal transplantation in Europe, reflecting a move towards lamellar procedures and bank-prepared transplants. These findings align with broader international trends, underscoring the importance of continued advancements in surgical techniques and eye banking practices. Low contamination rates are indicative of already successful procedures in eye banking in Europe, and reports of lower rates warrant further investigation and improvement.
To determine whether a progressive reduction in Choroidal Vascularity Index (ΔCVI) is independently associated with unexplained visual loss (UVL) in highly myopic (HM) eyes without pathologic myopia (PM), and to evaluate the predictive utility of baseline CVI as a structural biomarker. This longitudinal study included 126 HM eyes (axial length ≥26.0 mm or SE ≤-6.00 D) without PM and with ≥5 years of optical coherence tomography (OCT) follow-up, including 35 eyes with UVL-defined as ≥0.1 logarithm of the minimum angle of resolution best-corrected visual acuity loss in the absence of new anatomical, refractive or media-related changes- and 91 control eyes with stable vision. A 1:2 propensity score analysis was performed matching 32 eyes from UVL group and 62 control eyes. CVI was computed from subfoveal OCT B-scans acquired with Heidelberg Spectralis at baseline and at 60 months. ΔCVI was defined as the difference between follow-up and baseline. Multivariate logistic regression and ROC analyses were performed on the whole cohort to identify independent predictors of UVL. ΔCVI was significantly greater in UVL eyes (mean -1.87%) than in controls (-0.61%, p < 10⁻¹³). Baseline CVI did not differ significantly after matching (p = 0.12). In multivariate analysis, ΔCVI emerged as the strongest predictor of UVL (OR=10.4 per 1% CVI decrease; p < 0.001), with an area under the curve (AUC) of 0.90 and a Youden index of 0.66. In contrast, baseline CVI had poor predictive power (AUC=0.69) and did not improve model performance when added. Longitudinal reduction in CVI, but not baseline CVI, is strongly associated with UVL in HM eyes without PM. ΔCVI may represent an early biomarker of functional decline before visible macular damage.
Dry age-related macular degeneration (dAMD) is the leading cause of irreversible vision loss in older adults, with no approved treatment to modify progression in early and intermediate stages. Photobiomodulation (PBM), which targets mitochondrial dysfunction and retinal inflammation, has shown promise in early studies. This study aims to evaluate the anatomical and functional efficacy of PBM in eyes with early and intermediate dAMD. In this 12-month, multicentre, randomised double-masked controlled trial, 138 eyes from 78 patients with early or intermediate dAMD were included. The primary outcome was change in mean drusen volume (MDV) from baseline to 12 months. Secondary outcomes included change in best-corrected visual acuity (BCVA) and adverse events. Multilevel mixed-effects regression was used to analyse treatment-time interactions. MDV decreased significantly in the PBM group (-0.03±0.05 mm³) while increased in the sham group (+0.02 ± 0.04 mm³; p<0.001) at 12 months. The PBM group also showed a significant improvement in BCVA (+1.31 ± 6.7 letters) compared with a decline in the sham group (-2.62±7.1 letters), yielding a between-group difference of +3.75 letters (95% CI 1.16 to 6.34; p=0.0001). Female sex and higher Age-Related Eye Disease Study (AREDS) category were associated with MDV increase over time (p=0.030 and p=0.003; respectively), while older age was associated with MDV reduction (p=0.049). Four eyes in the sham group developed macular neovascularisation, compared with none in the PBM group (p=0.044), while one eye in the PBM group developed geographic atrophy (p=1.00). No cases of retinal phototoxicity were observed. PBM significantly reduced drusen burden and improved visual function in early and intermediate dAMD over 12 months, with an excellent safety profile. These findings support PBM as a promising therapeutic option for patients with non-neovascular age-related macular degeneration, despite further studies with longer follow-up are needed to confirm the role of PBM in potentially slowing the natural course of the disease.
To assess prevalence and associations of intraretinal hyperreflective foci (HRFs) in a general population. Participants of the population-based Beijing Eye Study underwent optical coherence tomography and macula photography. The study cohort included 1641 eyes (mean age: 62.8±9.1 years; range: 50-93 years). Prevalence of any HRF or HRFs located only above the ellipsoid zone (EZ) increased from 33/590 (5.6%; 95% CI 4.0 to 7.0) and 22/590 (3.7%; 95% CI 2.2 to 5.2), respectively, in normal eyes to 371/725 (51.2%; 95% CI 47.7 to 54.7) and 246/725 (33.9%; 95% CI 30.4 to 37.4), respectively, in eyes with early age-related macular degeneration (AMD), to 283/314 (90.1%; 95% CI 87.1 to 93.1) and 260/314 (82.8%; 95% CI 78.8 to 86.8), respectively, in eyes with intermediate AMD, and to 12/12 (100%) and 12/12 (100%), respectively, in late AMD. HRFs above the EZ were spatially associated with EZ defects in 298/540 (55.2%) eyes and external limiting membrane (ELM) defects in 203/540 (37.6%) eyes. 52 (96%) of 54 eyes with macular hyperpigmentations showed HRFs above the EZ, and 52 (9.6%) of 540 eyes with HRFs above the EZ had corresponding macular hyperpigmentations. Higher HRF prevalence was associated (multivariable analysis) with higher AMD stage (OR: 1.75; 95% CI 1.36 to 2.26; p<0.001), and higher prevalences of EZ defects (OR: 36.6; 95% CI 8.56 to 157; p<0.001), reticular pseudodrusen (OR: 1.91; 95% CI 1.29 to 2.82; p<0.001), retinal pigment epithelium (RPE) elevations (OR: 34.5; 95% CI 10.4 to 111; p<0.001) and interdigitation zone thinnings (OR: 4.22; 95% CI 1.90 to 9.35; p<0.001). The HRF prevalence was relatively high in early AMD and increased to late AMD. HRF location and shape suggested intraretinally migrated RPE cells as their equivalent. The majority of HRFs were not associated with an ophthalmoscopically detected macular hyperpigmentation. HRFs can also be found in locations with a localised interdigitation zone thinning with spatially corresponding EZ defects and ELM defects.
Lenadogene nolparvovec is an intravitreal gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A MT-ND4 variant. Idebenone, a synthetic coenzyme Q10 analogue, is the only approved treatment for LHON. To estimate the relative effects of both treatments, we performed two matching adjusted indirect comparisons (MAICs) between idebenone aggregated data from the LEROS study and expanded access programme (EAP), and lenadogene nolparvovec individual data from the REFLECT study (bilateral treatment). Matching covariates included age at disease onset, sex, baseline best-corrected visual acuity (BCVA), and time from vision loss to treatment. The outcomes of interest were clinically relevant recovery (CRR) from nadir at 24 months, time to initial CRR and change from baseline BCVA at 24 months. For the MAIC LEROS versus REFLECT (effective sample size (ESS): 77), a statistically higher CRR at 24 months was observed with lenadogene nolparvovec compared with idebenone (60.4% vs 35.4%; OR=2.78, 95% CI 1.53 to 5.06; p=0.001). No statistically significant difference was observed for time to initial CRR and change from baseline BCVA at 24 months. For the MAIC EAP versus REFLECT, there was a low overlap between the two populations related to a difference in the time from vision loss to treatment. In a post hoc sensitivity analysis comparing EAP to RESCUE data (ESS: 33), CRR was 39.0% for idebenone versus 69.5% for lenadogene nolparvovec (OR=3.59, 95% CI 1.42 to 9.06; p=0.011). The two MAICs demonstrated a clinically meaningful higher visual recovery at 24 months with lenadogene nolparvovec than with idebenone in patients with LHON due to the m.11778G>A MT-ND4 variant.
To characterise the distribution of retinal non-perfusion and its relationship with neovascularisation elsewhere (NVE) and visual acuity (VA) in referable diabetic retinopathy (DR) using ultra-widefield fluorescein angiography (UWFA). Eyes with treatment-naïve moderately severe non-proliferative DR (NPDR) to proliferative diabetic retinopathy (PDR) (Diabetic Retinopathy Severity Scale (DRSS) level 43-60) with available UWFA were included in this study. Total and zonal non-perfusion and NVE area were manually delineated across concentric zones (central 1-10 mm, extended posterior >10-20 mm and mid-peripheral >20-30 mm diameter). The Non-Perfusion Index (NPI) was calculated as the ratio of non-perfused area to total area per zone. Associations between NPI, NVE, DR severity and best-recorded VA (BRVA) were assessed. A total of 133 eyes (60.9% NPDR, 39.1% PDR) were analysed. The highest NPI occurred in the mid-periphery (20-30 mm) and posterior pole (15-20 mm) zones, with nasal preponderance. NVE was most frequently observed in the posterior pole (66%) and nasal quadrants. Central and mid-peripheral NPI correlated with NVE area in corresponding zones, showing quadrant-specific associations. Receiver operating characteristic analysis identified a total NPI threshold of 0.23 to differentiate PDR from NPDR (area under the curve=0.798), with the lowest threshold in the superior quadrant. Neither NPI nor NVE area correlated with BRVA. NVE represents a localised response to adjacent ischaemia predominantly affecting the nasal and extended posterior retina. NPI threshold of 0.23 distinguishes proliferative from non-proliferative stages, with the superior quadrant showing greater susceptibility to NVE at lower ischaemic levels. No significant correlation found between NPI, NVE area and visual acuity.
Herpes zoster ophthalmicus (HZO) is a viral infection that affects the ophthalmic branch of the trigeminal nerve. HZO is potentially sight-threatening, affecting 4%-20% of all zoster cases. The reported incidence of zoster has quadrupled in the past 60 years, affecting approximately 1 million people per year in the USA and 12.2 per 1000 population in those aged >85 years in the UK.The incidence and severity of vision-threatening complications are moderated by prompt antiviral therapy. Valaciclovir has numerous advantages over aciclovir, including superior bioavailability, higher blood antiviral activity, a longer half-life and simpler dosing regimen. Suppressive antivirals are commonly used as secondary prophylaxis following an episode of HZO, but the evidence to support this practice is weak.Varicella zoster virus is the only human herpesvirus for which highly effective vaccines are available. The recombinant zoster vaccine (Shingrix, GlaxoSmithKline) is a highly effective vaccine in preventing zoster, HZO and postherpetic neuralgia, with vaccine effectiveness of 70%-86%, 67%-93% and 76%, respectively. In this update, the current evidence for the prophylaxis and management of HZO, including keratitis, is evaluated.
Diabetic retinopathy (DR) is a leading cause of preventable blindness among people with type 2 diabetes mellitus (T2DM). Early detection is essential to prevent vision-threatening complications. This study evaluated the long-term cost-effectiveness of CODMAP (Ophthalmologic Screening for Diabetes Mellitus in Primary Care (Cribado Oftalmológico en Diabetes Mellitus en Atención Primaria)), an optimised screening programme combining two-field non-mydriatic fundus photography (NMFP) and optical coherence tomography versus conventional single-field NMFP in a public healthcare setting. A Markov model simulated DR progression over 50 years in a cohort of 7729 patients with T2DM. Eight health states reflected DR severity, with state-specific costs and quality-adjusted life years (QALYs) accrued annually. Analyses took the perspective of the Spanish National Health Service, applying a 3% annual discount rate. Incremental cost-effectiveness ratios, calculated as a ratio of means (ICERsROM), and net monetary benefits (NMBs) were estimated through 10 000 Monte Carlo simulations, at a €30 000 willingness-to-pay threshold. Deterministic and probabilistic sensitivity analyses, scenario analyses and bootstrap validation were performed. CODMAP accrued higher costs (€206.4 million vs €205.1 million) but more QALYs (128 691.7 vs 118 013.8), resulting in an ICERROM of €124.25/QALY. The probability of cost-effectiveness at €30 000/QALY was 74.3%, remaining stable in scenario analyses (75.7%-78.8%). Mean incremental NMB in the base case was €319.0 million. Cost and QALY variations were the main drivers of uncertainty. CODMAP offers greater long-term health gains at a favourable incremental cost per QALY in the Spanish context. However, the non-definitive probability of cost-effectiveness warrants cautious policy consideration, with attention to local infrastructure, implementation capacity and cost structures.
To investigate the prevalence and determinants of subretinal drusenoid deposits (SDDs; also known as reticular pseudodrusen, RPDs) in the European general population. Altogether 18 931 adults from eight population-based studies were included. SDDs/RPDs were determined on optical coherence tomography and/or infrared photography. The prevalence of SDDs/RPDs and associated ocular and systemic determinants using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis were analysed. Mean age ranged from 58.7±10.6 to 88.4±0.0 years in the different studies and prevalence of SDDs/RPDs ranged from 0.6% to 56.0%. Meta-analyses showed that increasing age (OR 1.09 per year, 95% CI 1.04 to 1.13; p<0.001), prevalent early/intermediate and late age-related macular degeneration (AMD) (OR 10.93, 95% CI 5.55 to 21.51; p<0.001 and OR 11.65, 95% CI 4.78 to 28.40; p<0.001, respectively) and AMD genetic risk score (OR 1.21 per unit, 95% CI 1.05 to 1.39; p=0.008) are associated with prevalent SDDs/RPDs. Sex, smoking, education and cardiovascular disease showed borderline association at some cohort levels but not in the meta-analysis. In sensitivity analyses, only age and AMD genetic risk score remained associated with SDDs/RPDs prevalence among participants without any AMD. This multi-cohort analysis emphasises the wide range of SDDs/RPDs prevalence and determinants. Besides age, presence of AMD and AMD genetic risk variants increase the risk of SDDs/RPDs. These cross-sectional findings are compatible with the hypothesis that SDDs/RPDs may not represent a separate disease entity but be an additional sign of retinal pigment epithelium and photoreceptor stress.
To investigate the association between choroidal vascular hyperpermeability (CVH) and the occurrence of submacular haemorrhage (SMH) in polypoidal choroidal vasculopathy (PCV). This retrospective, cross-sectional study included 189 eyes of 159 patients with treatment-naïve PCV. Eyes were categorised into haemorrhage (n=84) and non-haemorrhage (n=105) groups based on the extent of subretinal or subretinal pigment epithelium haemorrhage. Nine-field indocyanine green angiography (ICGA) was performed to evaluate the presence, number, topographic distribution and area of CVH. Logistic regression and correlation analysis were performed to identify factors associated with SMH. The cohort comprised predominantly male patients (67.3%), with a mean age of 65.4±7.6 years. The haemorrhage group showed significantly lower CVH prevalence (32.1% vs 68.6%; p<0.001) and median CVH count (0 vs 1; p<0.001) compared with the non-haemorrhage group. Multivariate model demonstrated that both the presence (p<0.001) and higher count (p=0.004) of CVH were independently associated with a reduced likelihood of SMH. Topographically, this negative association was most pronounced for CVH located in the posterior pole, central nasal and central superior quadrants (all p<0.05). A weak but significant inverse correlation was also observed between the total area of CVH and the area of haemorrhage (Spearman's r=-0.248). The presence and counts of CVH are inversely associated with the occurrence of SMH in PCV, suggesting CVH may serve as a 'pressure-relief window' to dissipate suddenly elevated choroidal vascular pressure which predisposes to vessel rupture.
Postoperative microbial keratitis (MK) can cause graft failure and vision loss following keratoplasty for corneal endothelial decompensation. Many previous studies found penetrating keratoplasty (PK) to result in a higher incidence of MK than Descemet's membrane endothelial keratoplasty (DMEK) or Descemet's stripping automated endothelial keratoplasty (DSAEK); however, findings vary. Recently, there has been a shift towards selective transplant procedures, with DMEK becoming mainstream over PK for endothelial decompensation globally around 2017. This systematic review therefore aims to determine the incidence of MK following DMEK, DSAEK and PK for endothelial decompensation from 2017 to 2025 and to assess variation by follow-up duration, socioeconomic status, microbe type, patient age, contact lens wear and time after surgery. Multiple databases were systematically searched during 2017-2025. The Newcastle-Ottawa scale evaluated bias. Random-effects meta-analyses with logit transformation were performed; heterogeneity was assessed using the I2 statistic. Sensitivity analyses confirmed robustness. Pooled MK incidence was highest following PK (4.84%; 95% CI 3.25% to 7.15%; I2=97.7%), followed by DMEK (0.71%; 95% CI 0.18% to 2.86%; I2=83.5%), then DSAEK (0.27%; 95% CI 0.19% to 0.38%; I2=0%). Subgroup analyses showed variation but few significant differences. Trends suggested significantly higher MK incidence following PK in studies with longer follow-up. Bacterial keratitis was the most common overall; however, DMEK showed a more even distribution across microbe types. MK incidence was highest following PK. High heterogeneity and limited DMEK/DSAEK data warrant cautious interpretation. CRD420251179122.
To evaluate associations of sociodemographic and functional parameters with vision-related quality of life (VRQoL) in recessive Stargardt disease (STGD1). A total of 71 participants (42 females, 29 males; mean age 44±19 years) with genetically confirmed STGD1 were included in this cohort study. Two validated patient-reported outcome measures (PROMs), namely National Eye Institute Visual Function Questionnaire and Impact of Vision Impairment profile, were administered to the participants. Responses were analysed using latent trait models following psychometrically established dimension structures (functional and emotional subscales). Univariable and linear mixed-effects models were applied to investigate the association of putative determinants with VRQoL. The optimised models could predict the measured VRQoL impairment up to a multicollinearity-corrected adjusted accuracy of 0.558. Functional subscales could more accurately be predicted than emotional subscales. Overall, reading acuity was the most important determinant of VRQoL. Other functional parameters, including visual function of the worse eye, revealed significant impact as well while the influence of sociodemographic parameters on VRQoL was more inconsistent. The robust associations between VRQoL and visual function in STGD1 indicate that both PROM are suitable and construct valid outcome measures for upcoming interventional trials. Future clinical trials and patient assessment focusing on VRQoL might take near vision of both eyes into consideration.
To compare 1-year and 2-year outcomes of eyes with persistent and non-persistent diabetic macular oedema (DME) treated with vascular endothelial growth factor (VEGF) inhibitors. This was a cohort study using the Fight Retinal Blindness! (FRB!) international outcomes registry. Participants had treatment-naïve eyes with centre-involving DME starting intravitreal VEGF inhibitor therapy from 2014 to 2023. Eyes were grouped as those with persistent DME and those with non-persistent DME. Main outcome measures were mean visual acuity (VA) change and central subfoveal thickness change after 1 and 2 years of treatment. This study included 877 eyes, of which 40% had persistent DME. The mean VA change in eyes with persistent DME was less than that in eyes with non-persistent DME at 1 (+3.6 vs. +6.5 letters; p<0.001) and 2 (+3.6 vs. +6.3 letters; p<0.001) years. The persistent group had a lower mean reduction in central subfield thickness at 1 (-74 vs -111 µm; p<0.001) and 2 (-90 vs -114 µm; p<0.001) years and received more mean injections at 1 (7.6 vs 6.5; p<0.001) and 2 (11.8 vs 9.5; p<0.001) years. Eyes with persistent DME had significantly lower improvement in mean VA, lower reduction in CST and more injections 1 and 2 years after the initiation of VEGF inhibitor therapy. Eyes with persistent DME likely had a higher treatment burden because they had more aggressive disease that was more difficult to control. More effective agents would likely deliver better outcomes in this significant group of patients with DME.
Fundus fluorescein angiography (FFA) is an important tool in evaluating retinal vascular disease. In the era of optical coherence tomography angiography (OCTA), however, expert preferences regarding the comparative utility of FFA and OCTA remain unclear. Additionally, despite FFA's widespread use, variability exists in the terminology used to describe angiographic findings. This study aimed to establish expert consensus on clinical indications for FFA versus OCTA and to provide consensus definitions of key angiographic terms. Using a two-round modified Delphi process, 25 retinal subspecialists provided perspectives on the clinical indications for FFA in the assessment of a range of retinal vascular conditions. They also evaluated proposed definitions for FFA findings in retinal vascular diseases. Consensus was defined as ≥80% agreement and near consensus as 70%-79%. Experts agreed that FFA is preferable for the diagnosis of retinal vasculitis, ocular ischaemic syndrome and proliferative diabetic retinopathy, even when OCTA is available. Furthermore, FFA was the favoured imaging modality to guide laser photocoagulation in branch retinal vein occlusion. Conversely, FFA was considered non-essential in evaluating neovascular age-related macular degeneration and mild-to-moderate non-proliferative diabetic retinopathy. Finally, definitions were agreed on for seven FFA terms used in the evaluation of retinal vascular diseases. These were non-perfusion, capillary dropout, window defect, pooling, leakage, neovascularisation and staining. This study presents contemporary perspectives on the clinical indications for FFA in an era in which OCT and OCTA are widely available. It also provides a lexicon for FFA reporting in retinal vascular diseases based on expert consensus.
To evaluate the repeatability of the adaptive optics scanning laser ophthalmoscopy (AO-SLO) system (Mona II) in measuring cone photoreceptor parameters and compare repeatability differences in different retinal regions. A total of 126 healthy adults aged between 18 and 36 years with cycloplegic spherical equivalent refraction ≤+0.50 D and >-6.00 D were enrolled. Retinal images were captured at the macular fovea centre (0°, 0°), the temporal, nasal, superior and inferior regions at 1.5° and 3.0° eccentricity. At each region, multiple 2.4°×2.4° images were sequentially captured with 0.9°×2.4° overlap between adjacent regions, covering the detection area within 4.2° centred on the fovea. Three images with clear cone photoreceptors and image quality scores of 0.8 or above were selected from each region for analysis. All parameters of the cone photoreceptors demonstrated excellent repeatability, with intraclass correlation coefficient (ICC) ranging from 0.967 to 0.994. The cone density exhibited good repeatability, with the fovea and the nasal region at 1.5° eccentricity showing the highest ICC (0.992). For the cone spacing, regularity and dispersion also demonstrated high repeatability across all regions (all ICC >0.90). The Mona II AO-SLO system showed high repeatability in measuring parameters of cone photoreceptors in healthy adults, with consistent performance across retinal area within a 4.2° range. ChiCTR2500114249.
To develop and validate a novel set of ocular-centric diagnostic criteria for Behçet's uveitis (BU). A case-control study was designed to develop the BU-specific diagnostic criteria (BU-SDC). The International Criteria for Behçet's Disease were adopted as the reference standard for diagnostic performance evaluation. The ocular findings of BU-SDC were weighted as two points for vitreous cells or haze and retinal vasculitis identified by fluorescein fundus angiography, respectively, and one point for anterior cell-flare dissociation, sterile hypopyon, diffuse retinal atrophy, optic nerve atrophy, superficial retinal infiltrates, retinal haemorrhages, retinal vascular sheathing and retinal ghost vessels, respectively. The systemic features, including recurrent oral ulceration, multiform skin lesions and genital ulceration were weighted as 4 points, 3 points and 2 points, respectively. Primary assessment was based on ocular features alone. An ocular score ≥5 supported a BU diagnosis in patients without signs of granulomatous uveitis or evidence of sarcoidosis or syphilis. For patients with ocular score <5 but high clinical suspicion (the presence of one or more characteristic ocular signs, including vitreous cells or haze, retinal vasculitis identified by fluorescein fundus angiography, superficial retinal infiltrates or retinal vascular sheathing), a secondary assessment incorporating systemic variables was applied, and a combined score ≥5 supported diagnosis. Validation in the independent cohort showed that the area under the receiver operating characteristic curve for BU-SDC (0.954) significantly outperformed the International Study Group criteria (0.911; p<0.01) and the Standardization of Uveitis Nomenclature (0.881; p<0.01) criteria. The BU-SDC provides a validated ocular-centric diagnostic framework for BU, prioritising ocular signs while retaining flexibility through selective systemic integration.