Search

AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

BACKGROUND/AIMS: Neonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants. METHODS: We prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models. RESULTS: 83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI -15.9 to -4.9) lower in infants with than without sepsis/NEC in the univariable analysis (p

PurposeTo evaluate the superficial vascular density of the optic nerve head in different stages of pseudoexfoliation disease using optical coherence tomography angiography (OCTA).MethodsIn this cross-sectional study, 57 normal eyes, 41 eyes with pseudoexfoliation syndrome (PXS), 82 eyes with pseudoexfoliation glaucoma (PXG) and 27 non-glaucomatous fellow eyes of PXG (NL-PXG) that had OCTA were included. Circumpapillary RNFL (cpRNFL) thickness and circumpapillary capillary density (cpCD) were compared among the groups after adjusting for confounders using linear-mixed model.ResultsPXG eyes had thinner global RNFL and lower cpCD (74.2±14.3 µm and 36.7±10.0%) than control (103.3±8.6 µm and 52.5±2.3%), PXS (96.8±8.8 µm and 51.5±2.3%), and NL-PXG eyes (96.3±11.1 µm and 50.1±3.9%) (p

Aim: The aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON)., Methods: This study is a multicentre, randomised, parallel-group, double-blind, dose-finding trial on patients aged ≥7 years with a confirmed diagnosis of indirect TON in ≤3 weeks. The trial had a 3-day treatment period and a 3-month follow-up period. Patients were randomly allocated (1:1:1) to receive EPO at doses of 900 IU/kg (300 IU/kg/day), 1800 IU/kg (600 IU/kg/day) or 3600 IU/kg (600 IU/kg/day on presentation and then 1 month later) EPO. The changes in the best-corrected visual acuity (BCVA), colour vision and relative afferent pupillary defect (RAPD) were assessed., Results: Out of 118 eligible patients, 95 were randomised and 93 (31 in each group) completed the follow-ups. Three groups were not different regarding baseline BCVA (p=0.66), colour vision (p=0.25) and RAPD (p=0.79). All three groups showed a significant improvement of BCVA and RAPD with no significant differences among the groups. Colour vision showed a significant improvement only in the group with 3600 IU/kg EPO (p=0.005), even though final colour vision was not significantly different between the groups (p=0.49). Initial vision of no light perception (OR=7.79 (95% CI: 2.98 to 20.36), p<0.001), older age (OR=4.76 (95% CI: 1.92 to 11.76), p<0.001), longer trauma-treatment interval (OR=2.72, 95% CI: 1.16 to 6.33, p=0.02) and posterior orbital fractures (OR=2.63 (95% CI: 1.13 to 6.13), p=0.02) led to a significantly worse visual recovery., Conclusion: Increasing dose of EPO in patients with TON did not result in a better BCVA, colour vision and RAPD improvement., Trial Registration Number: NCT03308448., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To explore the prevalence and associated factors of parapapillary scleral ridges (PSRs)., Methods: Out of the cohort of the population-based Beijing Eye Study (n=3468 participants), the study included all eyes with an axial length of ≥25 mm and a randomised sample of eyes with an axial length of <25 mm. Using optical coherence tomographic (OCT) images and fundus photographs, we examined the presence and height of PSRs, defined as a ridge-like structure located on the OCT scans in the parapapillary region., Results: The study cohort consisted of 366 eyes (314 individuals; mean age: 63.7±9.7 years). PSR prevalence increased from 0% in the non-myopic group to 3.8% (95% CI 0.3%, 7.3%) in moderately myopic group and 29.2% (95% CI 15.7%, 42.5%) in the highly myopic group. All PSRs were located in the temporal parapapillary gamma zone and corresponded to an ophthalmoscopically visible demarcation line running almost parallel to the optic disc border. Higher PRS prevalence correlated with longer axial length (OR 2.98; 95% CI 1.99, 4.46; p<0.001), female sex (OR 6.48; 95% CI 1.56, 27.0; p=0.01) and older age (OR 1.09; 95% CI 1.01, 1.18; p=0.02). Axial length had the strongest influence (beta: 0.48), followed by sex (beta: 0.20) and age (beta: 0.14). If age was dropped from the multivariable model, myopic maculopathy prevalence (OR 10.0; 95% CI 1.41,70.9; p=0.02) and stage (OR 3.57; 95% CI 1.21, 10.6; p=0.02) became significantly correlated with higher PSR prevalence., Conclusions: With a PSR prevalence of >60% in eyes with an axial length of >28 mm, PSRs are a common morphological feature of high myopia, with age and female sex as additional associated factors. PSRs may be due to a biomechanical interplay between the optic nerve and the posterior ocular segment of markedly axially elongated eyes., Competing Interests: Competing interests: JBJ and SP-J: European patent EP 3 271 392, JP 2021-119187 and US 2021 0340237 A1: 'Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia. European patent application 23196899.1 'EGFR Antagonists for the treatment of diseases involving unwanted migration, proliferation and metaplasia of retinal pigment epithelium (RPE) cells'., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Progressive outer retinal necrosis (PORN) is an alphaherpesvirus-caused panuveitis with devastating consequences for the eye. Our study aims to describe new findings in the clinical spectrum and propose a mechanism for the pathogenesis of PORN., Methods: Observational, consecutive case series. Seven eyes from five patients diagnosed with PORN were enrolled. Detailed case histories, ocular examination findings and multimodal images of retina were collected. Optic nerve and brain imaging were obtained by MRI., Results: All eyes were confirmed human alphaherpesviruses positive in ocular fluid by qPCR. Optic nerve oedema was observed on MRI in all eyes. A relative afferent pupillary defect was recorded in the affected eye for the unilateral cases. Two patients with unilateral involvement had a history of viral encephalitis and focal encephalomalacia found in the temporal lobe on brain MRI. The affected eyes were characterised by sensory retinal necrosis sparing retinal pigment epithelium, starting at the end of the retinal nerve fibre (horizontal raphe or peripheral area of the retina) and progressing rapidly along the nerve fibre. The wall of the retinal artery and vein was destroyed, resulting in blood flow interruption on fluorescein angiography and retinal haemorrhages along the large vessels., Conclusions: Combination the neurotropic characteristics of alphaherpesviruses and the signs of PORN, we hypothesised that the reactivated PORN virus originated from the lateral geniculate nucleus, then propagated along the optic nerve and was released at the terminals, causing necrosis of the entire sensory retina rather than just affecting the outer segment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

BackgroundThe time of onset of optic disc swelling in non-arteritic anterior ischaemic optic neuropathy (NAION) is not known, and it is commonly assumed to arise simultaneously with vision loss. Our goal is to report the presence and persistence of optic disc swelling without initial vision loss and its subsequent evolution to typical, symptomatic NAION.MethodsClinical case series of patients with optic disc swelling and normal visual acuity and visual fields at initial presentation who progressed to have vision loss typical of NAION. All subjects underwent automated perimetry, disc photography and optic coherence tomography and/or fluorescein angiography to evaluate optic nerve function and perfusion.ResultsFour patients were found to have sectoral or diffuse optic disc swelling without visual acuity or visual field loss; the fellow eye of all four had either current or prior NAION or a 'disc at risk' configuration. Over several weeks of clinical surveillance, each patient experienced sudden onset of visual field and/or visual acuity loss typical for NAION.ConclusionsCurrent treatment options for NAION once vision loss occurs are limited and may not alter the natural history of the disorder. Subjects with NAION may have disc swelling for 2-10 weeks prior to the occurrence of visual loss, and with the development of new therapeutic agents, treatment at the time of observed disc swelling could prevent vision loss from NAION.

Purpose: To describe the pattern of MRI changes in the pregeniculate visual pathway in Leber hereditary optic neuropathy (LHON)., Method: This retrospective observational study enrolled 60 patients with LHON between January 2015 and December 2021. The abnormal MRI features seen in the pregeniculate visual pathway were investigated, and then correlated with the causative mitochondrial DNA (mtDNA) mutation, the distribution of the MRI lesions and the duration of vision loss., Result: The cohort included 48 (80%) males and 53 (88%) had bilateral vision loss. The median age of onset was 17.0 years (range 4.0-58.0). 28 (47%) patients had the m.11778G>A mutation. 34 (57%) patients had T2 hyperintensity (HS) in the pregeniculate visual pathway and 13 (22%) patients with chiasmal enlargement. 20 patients (71%) carrying the m.11778G>A mutation had T2 HS, significantly more than the 14 patients (44%) with T2 HS in the other LHON mutation groups (p=0.039). Furthermore, significantly more patients in the m.11778G>A group (16 patients (57%)) had T2 HS in optic chiasm (OCh)/optic tract (OTr) than the other LHON mutation groups (7 patients (22%), p=0.005). Optic chiasmal enlargement was more common in patients with vision loss duration <3 months compared with those ≥3 months (p=0.028)., Conclusion: T2 HS in the pregeniculate visual pathway is a frequent finding in LHON. Signal changes in the OCh/OTr and chiasmal enlargement, in particular within the first 3 months of visual loss, were more commonly seen in patients carrying the m.11778G>A mtDNA mutation, which may be of diagnostic significance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the clinical characteristics of Leber hereditary optic neuropathy (LHON) with mtDNA primary mutations to better understand features associated with prognosis., Methods: This study enrolled 1540 LHON patients from 1516 unrelated families genetically confirmed by Sanger or whole-mitochondrial sequencing between 1997 and 2022. The spectrum of variants was summarised and compared in different ethnic groups. Clinical data from outpatients were collected, including onset age, disease course, optic disc categories and the corresponding visual acuity., Results: Of the 1516 LHON families, 13 pathogenic mtDNA variants were detected, in which the proportion of m.11778G>A, m.3460G>A and m.3635G>A was significantly different from non-East Asians (p<0.0001). About 95% (1075/1131) of patients were between 8 and 40 years old at onset, with a median onset age of 16. The eyes of m.14484T>C patients presented with better visual acuity and slower progression across patients with different onset ages and initial severity. Eyes (N=439) with available fundus images were divided into four categories (C1-C4). The progression grades were derived from the category and the corresponding time course, where a higher grade (C3-C4 within 1 year) was associated with greater visual impairment than a lower grade (C1-C2 over 1 year) (p=4.60E-05) . A prognostic matrix showed that later onset and a higher progression grade are associated with higher risk of blindness., Conclusion: Compared with non-East Asians, Chinese LHON patients had higher proportions of m.11778G>A and m.3635G>A and lower m.3460G>A mutations. A novel progression grade derived from optic disc category was proposed. The prognostic matrix indicated that lower grade and younger-onset age are the most favourable prognostic factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study evaluates the predictive power of the critical flicker fusion frequency (CFF) test for visual outcomes in keratoprosthesis (KPro) candidates, comparing its accuracy with B-scan ultrasound, flash visual evoked potentials (fVEP) and endoscopy., Methods: The study included 42 patients (42 eyes) scheduled for KPro surgery with a median follow-up period of 6 months. The receiver operating characteristic curve identified the cut-off threshold for CFF in the model development study (17 eyes). All patients in the comparison study (25 eyes) underwent preoperative assessments including trichromatic CFF (red, green and yellow), B-scan ultrasound, fVEP and perioperative endoscopy. Results were classified as either favourable or unfavourable predictors of visual outcomes based on predefined criteria. Sensitivity and specificity of each assessment were calculated based on postoperative best-corrected visual acuity (BCVA)≥20/200. The Bland-Altman test assessed the consistency between CFF-predicted BCVA and actual BCVA., Results: Among the trichromatic CFF tests, the yellow-CFF (yCFF) exhibited the highest area under the curve value of 0.97 and a cut-off threshold at 10 Hz for predicting postoperative BCVA≥20/200 (p<0.05). yCFF achieved 90% sensitivity and 80% specificity in predicting satisfactory postoperative outcomes. Endoscopy had 80% sensitivity and 80% specificity, B-scan showed 70% sensitivity and 60% specificity, and fVEP had 75% sensitivity and 40% specificity. yCFF showed a mean bias of 0.091 logarithm of the minimum angle of resolution (logMAR) in postoperative prediction., Conclusions: The CFF test provides robust visual function evaluation in KPro candidates. It demonstrates superior predictive accuracy for visual prognosis compared with routine ophthalmologic examinations, such as B-scan ultrasonography, fVEP and endoscopy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: To examine the relationship between baseline blood flow biomarkers and long-term open-angle glaucoma (OAG) progression., Methods: 112 patients with early to moderate OAG (mean age 64.9±11.0 years; 68 female) were evaluated at baseline and every 6 months from 2008 to 2013. Biomarkers of retinal capillary blood flow were assessed by Heidelberg retinal flowmetry. Functional disease progression was monitored via Humphrey visual field examinations, defined as two consecutive visits with a mean deviation decrease ≥2 decibels and/or Advanced Glaucoma Intervention Study score increase ≥2 compared with baseline. Structural progression was monitored with optical coherence tomography and Heidelberg retinal tomograph, defined as two consecutive visits with retinal nerve fibre layer thickness decrease ≥8% and/or horizontal or vertical cup/disk ratio increase ≥0.2 compared with baseline. Mixed-model analysis of covariance was used to test for significant change from baseline to 5-year follow-up. Times to functional and structural progression were analysed using Cox proportional hazards models., Results: Lower HRF retinal capillary blood flow in the superior retina was significantly associated with structural progression (p=0.0009)., Conclusion: In our OAG sample, baseline lower retinal capillary perfusion in the superior retina was predictive of structural progression after 5 years., Trial Registration Number: NCT01145911., Competing Interests: Competing interests: There are no competing interests. Professor Alon Harris would like to disclose that he received remuneration from AdOM, Qlaris, Cipla for serving as a consultant, and he serves on the board of AdOM and Qlaris. Professor Alon Harris holds an ownership interest in AdOM, Oxymap, Qlaris and SlitLed. All relationships listed above are pursuant to Icahn School of Medicine’s policy on outside activities. The contribution of the author Francesco Oddone was supported by Fondazione Roma and by the Italian Ministry of Health. None of the other authors listed have any financial disclosures., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up., Methods: A retrospective analysis of prospectively collected data from the Fight Glaucoma Blindness observational registry. Complete success (CS) was defined as intraocular pressure (IOP) reduction ≥20% from preoperative and an IOP ≤18 mm Hg and ≥6 mm Hg with no secondary procedure at 2 years and without IOP-lowering medications. Qualified success (QS) was defined similarly, allowing the use of IOP-lowering medications., Results: The Xen 45 gel stent implant was implanted in 646 eyes of 515 patients. Preoperative IOP was 21.4±7.6 (mean±SD) mm Hg on 2.7±1.3 IOP-lowering medication and mean deviation was -10.2±8.4 dB. After 24-month follow-up, IOP was 16.8±7.3 mm Hg (mean reduction of 21.7%) on 1.2±1.4 IOP-lowering medications. CS and QS rates at 24 months were 26% and 48%, respectively. CS and QS were higher in the Xen stand-alone group (33% and 52%, respectively) than in the Xen+cataract group (16% and 42%, respectively). Bleb needling was performed in 28.4% of cases, and 18% underwent a secondary procedure., Conclusions: The Xen 45 gel stent implant offers acceptable long-term efficacy for the treatment of open-angle glaucoma. However, there is a significant rate of reoperation and needling, and outcomes are less effective if combined with cataract surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To assess pupillary light responses (PLRs) in eyes with high myopia (HM) and evaluate the ability of handheld chromatic pupillometry (HCP) to identify glaucomatous functional loss in eyes with HM., Methods: This prospective, cross-sectional study included 28 emmetropes (EM), 24 high myopes without glaucoma (HM) and 17 high myopes with confirmed glaucoma (HMG), recruited at the Singapore National Eye Center. Monocular PLRs were evaluated using a custom-built handheld pupillometer that recorded changes in horizontal pupil radius in response to 9 s of exponentially increasing blue (469.1 nm) and red (640.1 nm) lights. Fifteen pupillometric features were compared between groups. A logistic regression model (LRM) was used to distinguish HMG eyes from non-glaucomatous eyes (EM and HM)., Results: All pupillometric features were similar between EM and HM groups. Phasic constriction to blue (p<0.001) and red (p=0.006) lights, and maximum constriction to blue light (p<0.001) were reduced in HMG compared with EM and HM. Pupillometric features of melanopsin function (postillumination pupillary response, PIPR area under the curve (AUC) 0-12 s (p<0.001) and PIPR 6 s (p=0.01) to blue light) were reduced in HMG. Using only three pupillometric features, the LRM could classify glaucomatous from non-glaucomatous eyes with an AUC of 0.89 (95% CI 0.77 to 1.00), sensitivity 94.1% (95% CI 82.4% to 100.0%) and specificity 78.8% (95% CI 67.3% to 90.4%)., Conclusion: PLRs to ramping-up light stimuli are unaltered in highly myopic eyes without other diagnosed ocular conditions. Conversely, HCP can distinguish glaucomatous functional loss in eyes with HM and can be a useful tool to detect/confirm the presence of glaucoma in patients with HM., Competing Interests: Competing interests: RPN, DM and TA have a patent application based on the handheld pupillometer used in this study (PCT/SG2018/050204): Handheld ophthalmic and neurological screening device. The rest of the authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Histological evidence indicates that the earliest structural changes to the optic nerve head (ONH) in glaucoma occur in the lamina cribrosa (LC) and its interface with the sclera. However, clinical imaging of these structures remains challenging. We compared the visibility of deep ONH structures with newer iterations of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT)., Methods: Twelve patients with open-angle glaucoma were imaged with SD-OCT with 24 radial B-scans centred on Bruch's membrane opening (BMO) and SS-OCT with a horizontal and vertical raster scan pattern containing five lines each, centred on the ONH. Single best-matched horizontal and vertical scans from the two modalities were selected and exported. Three independent observers masked to modality determined if BMO, posterior choroid surface, anterior scleral canal opening and anterior and posterior LC insertions into the sclera were detectable in the matched B-scan images. We determined the interobserver agreement and concordance in detecting each structure with the two OCT imaging modalities., Results: There was a high interobserver agreement with both SS-OCT and SD-OCT (inter-item correlations: 0.81-0.93 and 0.77-0.82, respectively). There was a consistent tendency for higher overall detection rates with SS-OCT, however, the differences failed to reach statistical significance. With respect to individual structures, only the posterior LC insertion in the nasal quadrant was statistically different, with a detection rate of 13 and 6 (pooled out of a total of 36 across the three observers) with SS-OCT and SD-OCT, respectively (p=0.04)., Conclusion: Overall, both SS-OCT and SD-OCT showed statistically equivalent visualisation of ONH structures, however, SS-OCT tended to have higher visualisation rates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the surgical outcomes using navigation-guided transcaruncular orbital optic canal decompression (NGTcOCD) and investigate the relationship between visual prognosis. visual evoked potential (VEP), association with DeLano type of optic canal and Onodi cells in patients with indirect traumatic optic neuropathy (TON)., Design: Prospective observational., Methods: Fifty-two consecutive patients with indirect TON unresponsive to steroid therapy were divided into three groups where Group I comprised of cases with optic canal fracture who underwent NGTcOCD, Group II without optic canal fracture who underwent NGTcOCD and Group III, no-decompression group who chose not to undergo NGTcOCD. An improvement in visual acuity (VA) at 1 week, 3 months and 1 year and amplitude and latency of VEP at 1 year were considered as primary and secondary outcomes, respectively., Results: The mean VA improved from 2.55±0.67 and 2.62±0.56 LogMAR at presentation to 2.03±0.96 and 2.33±0.72 LogMAR at final follow-up among Group I and Group II patients, respectively (p<0.001 and p=0.01). Statistically significant improvement observed among both the Groups in VEP amplitude (p=<0.01) and among Group II in VEP latency (p<0.01). Both Group I and Group II patients have better outcomes than patients in no-decompression group. VA at presentation and Type 1 DeLano optic canal were observed as significant prognostic factors., Conclusions: NGTcOCD serves as a minimally invasive transcaruncular route to the optic canal which enables ophthalmologists to perform decompression from the anterior-most orbital end under direct visualisation. Patients with indirect TON with or without optic canal fracture and unresponsive to steroid therapy when managed with NGTcOCD have shown comparable and superior outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Although obesity, tobacco and alcohol consumption were linked to the progression of numerous chronic diseases, an association of these social history aspects with glaucoma progression is not yet determined. This study aims to investigate the effect of body mass index (BMI) and history of tobacco and alcohol use on the rates of retinal nerve fibre layer (RNFL) change over time in glaucoma patients., Methods: 2839 eyes of 1584 patients with glaucoma from the Duke Ophthalmic Registry were included. Patients had at least two spectral-domain optical coherency tomography (SD-OCT) tests over a minimum 6-month follow-up. Self-reported history of alcohol and tobacco consumption was extracted from electronic health records and mean BMI was calculated. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on RNFL change over time., Results: Mean follow-up time was 4.7±2.1 years, with 5.1±2.2 SD-OCT tests per eye. 43% and 54% of eyes had tobacco or alcohol consumption history, respectively, and 34% were classified as obese. Higher BMI had a protective effect on glaucoma progression (0.014 µm/year slower per each 1 kg/m 2 higher; p=0.011). Tobacco and alcohol consumption were not significantly associated with RNFL change rates (p=0.473 and p=0.471, respectively). Underweight subjects presented significantly faster rates of structural loss (-0.768 µm/year; p=0.002) compared with normal weight., Conclusions: In a large clinical population with glaucoma, habits of tobacco and alcohol consumption showed no significant effect on the rates of RNFL change. Higher BMI was significantly associated with slower rates of RNFL loss., Competing Interests: Competing interests: FAM: Aerie Pharmaceuticals (C); Allergan (C, F), Annexon (C); Biogen (C); Carl Zeiss Meditec (C, F), Google (F); Heidelberg Engineering (F), nGoggle (P), Novartis (F); Stealth Biotherapeutics (C); Reichert (C, F)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals., Methods: This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy., Results: Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively., Conclusion: Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG)., Design: Clinic-based cross-sectional study., Methods: The ONH from one eye of 228 subjects (114 subjects with HTG (pre-treatment IOP≥21 mm Hg) and 114 with NTG (pre-treatment IOP<21 mm Hg)) was imaged with optical coherence tomography (OCT) under the following conditions: (1) OCT primary gaze, (2) 20° adduction from OCT primary gaze, (3) 20° abduction from OCT primary gaze and (4) OCT primary gaze with acute IOP elevation (to approximately 33 mm Hg). We then performed digital volume correlation analysis to quantify IOP-induced and gaze-induced ONH tissue deformations and strains., Results: Across all subjects, adduction generated high effective strain (4.4%±2.3%) in the LC tissue with no significant difference (p>0.05) with those induced by IOP elevation (4.5%±2.4%); while abduction generated significantly lower (p=0.01) effective strain (3.1%±1.9%). The lamina cribrosa (LC) of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG: 4.6%±1.7% vs NTG: 4.1%±1.5%, p<0.05). Conversely, the LC of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9%±1.9% vs HTG: 4.0%±1.4%, p<0.05)., Conclusion: We found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects-and that these differences were most pronounced in the LC tissue., Competing Interests: Competing interests: MJAG is the co-founder of the AI start-up company Abyss Processing Pte Ltd., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia., Design: Cross-sectional study., Methods: Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images., Results: Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm 2 vs 0.31 (0.19, 0.42) mm 2 , p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD., Conclusions: MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects., Competing Interests: Competing interests: Financial disclosures: EM: none; NE-N: none; TN: none; SM: none; JR: none; MAF: National Eye Institute (F), Heidelberg Engineering (F), Topcon (F); MHS: none; CB: none; AB: none; MC: none; JBJ: European patent EP 3 271 392, JP 2021-119187 and US 2021 0340237 A1: agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; RW: Abbvie (C), Alcon (C), Amydis (C), Eyenovia (C), Topcon (C), Nicox (C), Topcon (C), Heidelberg Engineering (F), Implandata (C), IOPtic (C), Carl Zeiss Meditec (F), Konan Medical (F), OptoVue (F), Topcon (F), Centervue (F), National Eye Institute (F), National Institute of Minority Health (F); LMZ: National Eye Institute (F), Carl Zeiss Meditec Inc. (F), Heidelberg Engineering GmbH (F), OptoVue Inc. (F, R), Topcon Medical Systems Inc (F, R) and Abbvie (C)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To compare the influence of choroidal microvasculature dropout (cMvD) on progressive retinal nerve fibre layer (RNFL) thinning in glaucomatous eyes with parapapillary β-zones and γ-zones., Methods: 294 eyes with primary open-angle glaucoma (POAG) and parapapillary atrophy (PPA) underwent optical coherence tomography (OCT) to determine the type of PPA and OCT angiography scanning of the optic nerve head to determine the presence of cMvD. Eyes were classified based on the type of PPA (β-zones and γ-zones), and their clinical characteristics were compared. Factors associated with the rate of rapid progressive RNFL thinning were determined in each group, including the presence of cMvD as an independent variable., Results: Of the 294 eyes, 186 and 108 were classified as having β-zones and γ-zones, respectively. The rate of RNFL thinning was slower (p<0.001), axial length was longer (p<0.001) and presence of cMvD was less frequent (57.4% vs 73.1%, p=0.006) in eyes with γ-zone than those with β-zone. Multivariate analyses showed that greater lamina cribrosa curvature (p=0.047) and the presence of cMvD (p=0.010) were associated with a faster rate of RNFL thinning in eyes with β-zone, whereas larger intraocular pressure fluctuation (p<0.001), shorter axial length (p=0.042) and greater baseline RNFL thickness (p<0.001) were associated with a faster rate of RNFL thinning in eyes with γ-zone., Conclusions: The presence of cMvD was significantly associated with a faster rate of RNFL thinning in POAG eyes with β-zone, but not γ-zone. The pathogenic consequences of cMvD in POAG eyes may depend on accompanying peripapillary structures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH to changes in intraocular pressure (IOP)) from a single optical coherence tomography (OCT) volume scan of the ONH without the need for biomechanical testing and (3) identify what critical three-dimensional (3D) structural features dictate ONH robustness., Methods: 316 subjects had their ONHs imaged with OCT before and after acute IOP elevation through ophthalmo-dynamometry. IOP-induced lamina cribrosa (LC) deformations were then mapped in 3D and used to classify ONHs. Those with an average effective LC strain superior to 4% were considered fragile, while those with a strain inferior to 4% robust. Learning from these data, we compared three AI algorithms to predict ONH robustness strictly from a baseline (undeformed) OCT volume: (1) a random forest classifier; (2) an autoencoder and (3) a dynamic graph convolutional neural network (DGCNN). The latter algorithm also allowed us to identify what critical 3D structural features make a given ONH robust., Results: All three methods were able to predict ONH robustness from a single OCT volume scan alone and without the need to perform biomechanical testing. The DGCNN (area under the curve (AUC): 0.76±0.08) outperformed the autoencoder (AUC: 0.72±0.09) and the random forest classifier (AUC: 0.69±0.05). Interestingly, to assess ONH robustness, the DGCNN mainly used information from the scleral canal and the LC insertion sites., Conclusions: We propose an AI-driven approach that can assess the robustness of a given ONH solely from a single OCT volume scan of the ONH, and without the need to perform biomechanical testing. Longitudinal studies should establish whether ONH robustness could help us identify fast visual field loss progressors., Precis: Using geometric deep learning, we can assess optic nerve head robustness (ie, sensitivity to a change in IOP) from a standard OCT scan that might help to identify fast visual field loss progressors., Competing Interests: Competing interests: MJAG and AHT are the co-founders of the AI start-up company Abyss Processing., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants., Methods: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA., Results: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 μm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 μm/week (95% CI: -0.9 to -0.6)., Conclusion: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs., Competing Interests: Competing interests: SFF: Qlaris—consultant; CT: Alcon Laboratories—royalties; EMMES—consultant; Theia Imaging—owner equity and consultant., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To verify whether the area of the ONSAS (ONSASA) obtained by transorbital ultrasonography can be used to accurately evaluate the intracranial pressure (ICP)., Methods: The recorded indexes included the optic nerve diameter, the optic nerve sheath diameter (ONSD), the width of both sides of the ONSAS (ONSASW) at 3 mm from the optic nerve head and the entire ONSASA outlined between 3 and 7 mm. After exploring and comparing five models to describe the relationship between body mass index (BMI), mean arterial blood pressure (MABP), ONSASA and ICP, the best model was determined., Results: In all, 90 patients with neurological diseases undergoing continuous invasive ICP monitoring were included in the study. In the training group, the correlation coefficient for the association between the ICP and ONSASA (Pearson's correlation r=0.953) was higher than that for the association of the ICP with the ONSD (r=0.672; p<0.0001) and ONSASW at 3 mm behind the globe (r=0.691; p<0.0001). In the training group, the weighting function for prediction of the ICP was as follows: non-invasive ICP=2.050×ONSASA-0.051×BMI +0.036*MABP-5.837. With 20 mm Hg as the cut-off point for a high or low ICP, the sensitivity and specificity of ONSASA predicting ICP was 1.00 and 0.92. Receiver operator curve analysis revealed that the calculated cut-off value for predicting elevated ICP was 19.96 (area under curve= 0.960, 95% CI 0.865 to 1.00)., Conclusion: Measurement of the ONSASA using ultrasonography can serve as a practical method for rapid and non-invasive quantification for evaluating ICP through an accurate mathematical formula with the BMI and MABP considered as contributing parameters., Trial Registration Number: The study was registered in the Chinese Clinical Trial Registry (Study no ChiCTR2100045274)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To characterise the ocular manifestations of Williams-Beuren syndrome (WBS) and compare these to patients with isolated elastin mediated supravalvular aortic stenosis (SVAS)., Methods: Fifty-seven patients with a diagnosis of WBS and five with SVAS underwent comprehensive ophthalmic evaluation at the National Institutes of Health from 2017 to 2020, including best-corrected visual acuity, slit-lamp biomicroscopy, optical biometry, dilated fundus examination, optical coherence tomography and colour fundus imaging., Results: Mean age of the 57 WBS patients was 20.3 years (range 3-60 years). Best-corrected visual acuity ranged from 20/20 to 20/400 with mean spherical equivalent near plano OU. Twenty-four eyes (21.8%) had an axial length (AL) less than 20.5 mm and 38 eyes (34.5%) had an AL measuring 20.5-22.0 mm. Stellate iris and retinal arteriolar tortuosity were noted in 30 (52.6%) and 51 (89.5%) WBS patients, respectively. Novel retinal findings in WBS included small hypopigmented retinal deposits (OD 29/57, OS 27/57) and broad foveal pit contour (OD 44/55, OS 42/51). Of the five patients with SVAS, none had stellate iris or broad foveal pit contour while 2/5 had retinal arteriolar tortuosity., Conclusion: WBS is a complex multisystem genetic disorder with diverse ophthalmic findings that differ from those seen in isolated elastin mediated SVAS. These results suggest other genes within the WBS critical region, aside from ELN , may be involved in observed ocular phenotypes and perhaps broader ocular development. Furthermore, retinal arteriolar tortuosity may provide future insight into systemic vascular findings in WBS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Back Ground/aims: To determine whether parapapillary choroidal microvasculature (PPCMv) density, measured by optical coherence tomography angiography, differed between acute primary angle-closure (APAC), primary open-angle glaucoma (POAG) and controls., Methods: This is a prospective, cross-sectional, observational study. Data from 149 eyes from two academic referral centres were analysed. Automated PPCMv density was calculated in inner and outer annuli around the optic nerve region in addition to the peripapillary superficial vasculature, using customised software. A generalised estimating equation was used to compare vessel densities among groups, adjusted for confounders., Results: Data from 40 eyes with APAC, 65 eyes with POAG and 44 eyes in healthy controls were gathered and analysed. Global radial peripapillary capillary densities were reduced in eyes with APAC and POAG compared with controls (p=0.027 and 0.136, respectively). Mean outer annular PPCMv density in the POAG group was lower vs the APAC group by 3.6% (95% CI 0.6% to 6.5%) (p=0.018) in the multivariable model adjusted for confounders. The mean difference in inner and outer superior PPCMv between the POAG and APAC groups was 5.9% and 4.4% (95% CI 1.9% to 9.9% and 1.0% to 7.7%, respectively; both p<0.010). Furthermore, POAG and APAC groups both had significantly lower PPCMv compared with controls (both, p<0.001)., Conclusions: While superficial peripapillary vessels were affected to similar degrees in POAG and APAC, PPCMv drop-out was greater with POAG versus APAC, suggesting that choroidal vessel density may be affected to a lesser extent following an acute increase in intraocular pressure before glaucoma develops., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background/aims: To identify normative values and determinants for Bruch's membrane opening (BMO) and the minimum rim width of BMO (BMO-MRW) among healthy children., Methods: A population-based cross-sectional study from the Hong Kong Children Eye Study, recruiting 1, 226 children aged 6-8 years. Spherical refractive error, axial length (AL), body mass index and intraocular pressure (IOP) were measured. The optic nerve head and the peripapillary retinal nerve fibre layer (p-RNFL) were imaged through spectral domain-optical coherence tomography, using 24 equally spaced radial B-scans. Global and sectoral BMO-MRW values, BMO area and fovea-to-BMO (FoBMO) angle were calculated. Multiple regression analysis was performed to define the determinants of BMO area and BMO-MRW in relation to demographic and ocular parameters., Results: The mean values for global BMO-MRW, BMO area and FoBMO angle among children were 345.76±54.08 µm, 2.34±0.49 mm 2 and -5.45±4.36°, respectively. Global and sectoral values for BMO-MRW correlated with p-RNFL thickness (r=0.11-0.35, p<0.001). After adjusting for demographic and ocular parameters, global BMO-MRW increased with age (β=6.4, p<0.001) and greater global p-RNFL thickness (β=1.41, p<0.001), but decreased with larger BMO area (β=-47.46, p<0.001) and higher IOP (β=-1.73, p<0.001). Global BMO-MRW did not associate with AL, whereas both BMO area and FoBMO angle associated with AL (β=0.04, p=0.02 and β=0.31, p=0.03, respectively), but not with age., Conclusion: We observed that BMO-MRW increases with age among children. Our results provide normative values and the determinants of BMO parameters among Chinese children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: The aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma in the UK National Health Service Hospital Eye Service., Methods: GLAUC-STRAT fast was applied to the LiGHT trial participants by risk-stratifying the worse eye of each patient at baseline and after 3 years of treatment. Metrics of disease severity or treatment intensity used for the validation were: increased number of monitoring visits or treatment escalations; needing a trabeculectomy; a reduction of >2 dB in visual field mean deviation (VF MD) during the monitoring period; identification of rapid VF loss on total (TD) and/or pattern deviation (PD). The proportion of eyes within each baseline stratum for each of the above markers was compared against the other strata, using a χ 2 test for proportions., Results: There was an association between the baseline stratification and the number of treatment escalations needed to maintain the eye-specific target intraocular pressure (p=0.001), the number of visits needed throughout the 3-year follow-up period (p=0.001), the need for trabeculectomy (p<0.001) and absolute loss of MD over the course of the monitoring period (p<0.001). The rate of VF progression was not associated with baseline risk stratification for TD or PD progression (p≥0.007, with Bonferroni correction)., Conclusion: The GLAUC-STRAT fast tool is a useful tool for risk stratifying eyes with ocular hypertension or open angle glaucoma. Further research is needed to confirm and validate its applicability to more advanced glaucomas and generalisability to clinical use., Trial Registration Number: The LiGHT trial is registered at controlled-trials.com (ISRCTN32038223)., Competing Interests: Competing interests: GG is the president-elect of UKEGS. This work was funded by Moorfields Eye Charity (GR001214)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the longitudinal changes of peripapillary retinal nerve fibre layer (RNFL) and choroidal thickness during myopic axial elongation., Methods: Peripapillary RNFL and choroidal thickness were prospectively evaluated by spectral-domain optical coherence tomography (SD-OCT) in 46 eyes of 23 myopic children over the course of 4 years. Using serial OCT images acquired based on a fixed scan circle in the glaucoma progression analysis mode, general and sectoral RNFL thicknesses were acquired at the same position and the angular location of the peak was measured. The peripapillary choroidal thickness likewise was measured at eight positions in serial OCT images., Results: The mean age at the baseline was 9.6±1.7 years. The mean axial length increased from 24.80±1.28 mm to 25.64±1.35 mm. The global peripapillary RNFL thickness was 98.54±12.06 µm at baseline. The global and sectoral RNFL thicknesses did not change during the 4 years. The angular location of RNFL peaks was also stable and was located in the superotemporal (64.18±10.85°) and inferotemporal (293.98±11.62°) sectors. The global peripapillary choroidal thickness was 145.40±28.67 µm at the baseline. The global and sectoral choroidal thicknesses did not change during the 4 years., Conclusions: The peripapillary RNFL and choroidal thicknesses as well as the locations of the RNFL peaks had been preserved, during the 4-year follow-up on myopic children, when traced and measured from the same location., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To examine the normative profile of retinal nerve fibre layer (RNFL) thickness and ocular parameters based on spectral-domain optical coherence tomography (SD-OCT) and its associations with related parameters among the Chinese population., Methods: This population-based cohort Handan Eye Study (HES) recruited participants aged≥30 years. All subjects underwent a standardised ophthalmic examination. Peripapillary RNFL thickness was obtained using SD-OCT. Mixed linear models were adopted to evaluate the correlation of RNFL thickness with ocular parameters as well as systemic factors. R V.3.6.1 software was used for statistical analysis., Results: 3509 subjects (7024 eyes) with the average age of 55.54±10.37 were collected in this analysis. Overall mean RNFL thickness measured was 113.46±10.90 µm, and the thickest quadrant of parapapillary RNFL was the inferior quadrant, followed by the superior quadrant, the nasal quadrant and the temporal quadrant. In the multivariate linear regression model, thinner RNFL thickness was remarkable association with male (p<0.001), older age (p<0.001), increased body mass index (>30, p=0.018), absence of diabetes (p=0.009), history of cataract surgery (p=0.001), higher intraocular pressure (p=0.007), lower spherical equivalent (p<0.001) and increased axial length (p=0.048)., Conclusions: In non-glaucoma individuals, this difference of RNFL thickness in Chinese population should be noted in making disease diagnoses. Meanwhile, multiple ocular and systemic factors are closely related to the thickness of RNFL. Our findings further emphasise the need to demonstrate ethnic differences in RNFL thickness and the specificity of associated ocular and systemic factors, as well as to develop better normative databases worldwide., Trial Registration Number: HES was registered in Chinese Clinical Trial Registry website, and the registry number was ChiCTR-EOC-17013214., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications., Methods: 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression., Results: SNPs rs33912345 (p=7.7×10 -4 ) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10 -4 ) and rs10483727 (p=3.3×10 -4 ). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL., Conclusions: Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Spaceflight associated neuro-ocular syndrome (SANS) refers to a distinct constellation of ocular, neurological and neuroimaging findings observed in astronauts during and following long duration spaceflight. These ocular findings, to include optic disc oedema, posterior globe flattening, chorioretinal folds and hyperopic shifts, were first described by NASA in 2011. SANS is a potential risk to astronaut health and will likely require mitigation prior to planetary travel with prolonged exposures to microgravity. While the exact pathogenesis of SANS is not completely understood, several hypotheses have been proposed to explain this neuro-ocular phenomenon. In this paper, we briefly discuss the current hypotheses and contributing factors underlying SANS pathophysiology as well as analogues used to study SANS on Earth. We also review emerging potential countermeasures for SANS including lower body negative pressure, nutritional supplementation and translaminar pressure gradient modulation. Ongoing investigation within these fields will likely be instrumental in preparing and protecting astronaut vision for future spaceflight missions including deep space exploration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: In Leber's hereditary optic neuropathy (LHON) in children and teenagers, the influence of age on visual prognosis has not yet been investigated., Methods: Patients from the mitoNET registry with LHON onset at age 4-16 years with at least 4 years of follow-up without treatment were included. Visual acuity (VA) at baseline, lowest VA ever recorded (nadir) and VA at end of follow-up were compared between childhood onset (ChO, ≤12 years of age) and early-teenage onset (eTO; 13-16 years)., Results: Out of 231 patients with LHON, 19 met the inclusion criteria (8.2%). There were 11 patients in the ChO and 8 patients in the eTO group. Mean age at onset was 8.6 (SD 2.1) years (ChO) and 15.4 (SD 0.7) years (eTO) (p<0.00001). Follow-up was mean 184 (SD 129) months (ChO) and 119 (SD 78) months (eTO) (p=0.22). Baseline VA was similar between both groups in better (p=0.96) and worse eyes (p=0.54). In worse eyes, both groups deteriorated similarly (p=0.79) until nadir and showed similar recovery until end of follow-up (p=0.38). In better eyes, both groups deteriorated similarly (p=0.16) until nadir. From nadir until end of follow-up, better eyes in the ChO group showed a significantly better recovery (-0.35 (SD 0.36) vs -0.01 (SD 0.06) logMAR; p=0.02) than eTO eyes., Conclusion: Visual prognosis of LHON in children is much more favourable in cases of childhood onset (≤12 years of age) as compared with teenage onset (13-16 years), mostly due to better recovery from nadir in childhood onset., Competing Interests: Competing interests: No author reports any financial interest relevant to this publication. JS has received speaker honoraria, consultancy fees and travel expenses from Novartis Pharma GmbH, Bayer AG, Allergan GmbH, Heidelberg Engineering GmbH, Carl Zeiss Meditec AG and Oculentis OSD Medical GmbH, all unrelated to this publication. BS has received previous speaker fees and travel expenses from Novartis Pharma GmbH and Topcon Corporation. TK has received research support, consultancy fees, speaker honoraria and travel funds from GenSight Biologics and Santhera Pharmaceuticals, as well as consultancy fees and speaker honoraria from Chiesi GmbH, all unrelated to this publication. SP has received speaker honoraria, consultancy fees and travel expenses from Novartis Pharma GmbH, Oertli AG, Bayer AG, Alcon Pharma GmbH, Allergan GmbH and Heidelberg Engineering GmbH, all unrelated to this publication. CP has received speaker honoraria from Novartis Pharma GmbH, all unrelated to this publication., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: Whereas myopic optic disc deformation has been posited as a risk factor for glaucomatous damage, longitudinal studies evaluating their association have been sparse. We investigated whether the optic nerve head (ONH)'s morphological alteration during myopia progression play any role in development of retinal nerve fibre layer defect (RNFLD) in children with a large vertical cup-to-disc ratio (vCDR)., Methods: Sixty-five normotensive eyes of 65 children aged under 8 years with (1) vCDR ≥0.5 but no additional signs of glaucoma and (2) who could be tracked at young adulthood (18-28 years) were included. Children's spherical equivalent (SE), intraocular pressure, vCDR and optic disc tilt ratio were recorded. Rare events logistic regression analysis was employed to identify factors associated with RNFLD-development risk., Results: The study group's mean age was 5.4±1.3 years, its average vCDR was 0.62±0.07, and the average SE was -0.3±1.4 dioptres ((D), range -3.15 to 2.75D) at the baseline. After an average follow-up of 16.1±3.0 years, the mean vCDR was 0.64±0.09, and the mean SE, -3.2±2.2D (range -7.25 to 0.00 D). Among the 65 eyes, 12 (18.5%) developed RNFLD. A greater SE change (OR=1.737, p=0.016) and a greater increase in tilt ratio (OR=2.364, p=0.002) were both significantly associated with higher RNFLD-development risk., Conclusion: In this cohort of Korean children with large vCDR, progressive optic disc tilt in the course of myopia progression was associated with higher RNFLD-development risk. This finding suggests that morphological alterations in the ONH during axial elongation might represent an underlying susceptibility to glaucomatous damage in large-vCDR children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Radiation is a commonly used treatment modality for head and neck as well as CNS tumours, both benign and malignant. As newer oncology treatments such as immunotherapies allow for longer survival, complications from radiation therapy are becoming more common. Radiation-induced optic neuropathy is a feared complication due to rapid onset and potential for severe and bilateral vision loss. Careful monitoring of high-risk patients and early recognition are crucial for initiating treatment to prevent severe vision loss due to a narrow therapeutic window. This review discusses presentation, aetiology, recent advances in diagnosis using innovative MRI techniques and best practice treatment options based on the most recent evidence-based medicine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)