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Pathologic myopia is a severe form of myopia that can lead to permanent visual impairment. The recent global increase in the prevalence of myopia has been projected to lead to a higher incidence of pathologic myopia in the future. Thus, imaging myopic eyes to detect early pathological changes, or predict myopia progression to allow for early intervention, has become a key priority. Recent advances in optical coherence tomography (OCT) have contributed to the new grading system for myopic maculopathy and myopic traction maculopathy, which may improve phenotyping and thus, clinical management. Widefield fundus and OCT imaging has improved the detection of posterior staphyloma. Non-invasive OCT angiography has enabled depth-resolved imaging for myopic choroidal neovascularisation. Artificial intelligence (AI) has shown great performance in detecting pathologic myopia and the identification of myopia-associated complications. These advances in imaging with adjunctive AI analysis may lead to improvements in monitoring disease progression or guiding treatments. In this review, we provide an update on the classification of pathologic myopia, how imaging has improved clinical evaluation and management of myopia-associated complications, and the recent development of AI algorithms to aid the detection and classification of pathologic myopia.

Background/aimsThis study investigated the risk factors for epiretinal membrane (ERM) in eyes with primary rhegmatogenous retinal detachment (RRD) that received silicone oil (SO) tamponade.MethodsThis retrospective analysis included 1140 patients (1140 eyes) with RRD who underwent primary vitrectomy and SO tamponade. The prevalence of ERM was estimated and possible risk factors (eg, type 2 diabetes, proliferative vitreoretinopathy (PVR), SO tamponade time (SOTT), photocoagulation, vitreous haemorrhage, choroidal detachment, cryotherapy and retinal tear size) were analysed via multiple logistic regression.ResultsThe prevalence of ERM was 12.3% (140/1140), and the accuracy of preoperative ERM diagnosis was 40.5%. Multivariate logistic regression analysis showed that risk factors for ERM in eyes with SO tamponade included preoperative PVR (OR=4.336, 95% CI 2.533 to 7.424, pConclusionIn eyes with RRD that received SO tamponade, the prevalence of ERM was 12.3%, while the accuracy of preoperative ERM diagnosis was low. Preoperative PVR, type 2 diabetes, photocoagulation energy and SOTT were the main risk factors for ERM.

AimsTo report the baseline intraocular pressure (IOP) characteristics and its diurnal fluctuation in the Laser in Glaucoma and Ocular Hypertension China cohort.Methods622 primary open-angle glaucoma (POAG) patients and 149 ocular hypertension (OHT) patients were recruited at Zhongshan Ophthalmic Center from 2015 to 2019. Standardised ocular examinations were performed including IOP measurement using the Goldmann applanation tonometer. Daytime phasing IOP was recorded at 8:00, 10:00, 11:30, 14:30, 17:00 hour.ResultsThe mean baseline IOP was 20.2 mm Hg for POAG patients and 24.4 mm Hg for OHT. Multiple regression analysis revealed that thicker central corneal thickness (CCT) was correlated with higher IOP in both POAG and OHT. Male gender and younger age were correlated with higher IOP only for POAG. As for diurnal IOP fluctuation, mean IOP fluctuation was 3.4 mm Hg in POAG eyes and 4.4 mm Hg in OHT. The peak and trough IOP occurred at 8:00 and 14:30 hour in both POAG and OHT eyes.ConclusionsYounger age, male gender and thicker CCT are correlated to higher IOP in POAG patients while only thicker CCT is related to higher IOP in OHT patients. Peak IOP appears mostly at early morning or late afternoon and trough value occurs mostly at early afternoon.

Background/aimsTo describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care.MethodsA database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA—letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits.ResultsAt baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; pConclusionsHRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes.

Background/aimsTo investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD).MethodsPOAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models.ResultsThirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: −0.50 (95% CI −0.83 to –0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively).ConclusionIn POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

BackgroundTo assess the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in uveitic glaucoma (UG).MethodsA retrospective interventional case series in which 33 eyes of 32 patients with UG underwent GATT with or without concomitant cataract extraction and intraocular lens implantation (CE/IOL) at three Canadian treatment centres from October 2015 to 2020. The main outcome measure was surgical success defined as an intraocular pressure (IOP) ≤18 mm Hg and at least one of the following: IOP within one mm Hg of baseline on fewer glaucoma medications as compared with baseline or a 30% IOP reduction from baseline on the same or fewer medications. Secondary outcome measures were IOP, medication usage and surgical complications.ResultsMean patient age (mean±SD) was 49±16 years (range: 18–79) and 44% were female. GATT was performed as a standalone procedure in 52% of cases and the remainder were combined with CE/IOL. Surgical success was achieved in 71.8% (SE: 8.7%) of cases. Mean preoperative IOP (±SD) was 31.4±10.8 mm Hg on a median of 4 medications. 59% of patients were on oral carbonic anhydrase inhibitors (CAIs) prior to surgery. After 1 year, average IOP was 13.8 mm Hg on a median 1 medication, with 6% of patients being on oral CAIs. No sight threatening complications occurred during surgery or follow-up.ConclusionGATT is an effective surgical strategy in the management of UG. This microinvasive conjunctival-sparing procedure should be considered early in these patients.

AimsTo characterise the influence of primary open-angle glaucoma (POAG) and high myopia (HM) on the macular and choroidal capillary density (CD).MethodsTwo hundred and seven eyes were enrolled, including 80 POAG without HM, 50 POAG with HM, 31 HM without POAG and 46 normal controls. A fovea-centred 6×6 mm optical coherence tomography angiography scan was performed to obtain the CD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris. Macular and choroidal CDs were compared among the groups and the association of CDs with visual field mean deviation (MD) was determined using linear regression models.ResultsCompared with normal eyes, SCP CD was decreased in the POAG without HM group (pConclusionsPOAG and HM reduced macular CD in different layers of the retinal capillary plexus and both particularly in the outer ring of the 6×6 mm scans. Furthermore, assessment of the CD in the outer ring of the SCP may facilitate the diagnosis of glaucoma in eyes with HM.

In 2018, a consortium of government bodies in China led by the Ministry of Education released theComprehensive Plan to Prevent Nearsightedness among Children and Teenagers(CPPNCT), aiming to reduce the incidence of myopia and control myopic progression in China. Recommendations span from home-based to school-based interventions, including time outdoors, physical activity, light exposure, near-work activity, screen time, Chinese eye exercises, diet and sleep. To date, the levels of evidence for this suite of interventions have not been thoroughly investigated. This review has summarised the evidence of the interventions recommended by the CPPNCT in myopia prevention and control. Thus, the following statements are supposed by the evidence: (1) Increasing time outdoors and reducing near-work time are effective in lowering incident myopia in school-aged children. (2) All interventions have a limited effect on myopia progression. Ongoing research may lead to a better understanding of the underlying mechanisms of myopia development, the interaction of different interventions and recommendations, confounding variables and their true effect on myopia prevention, and the identification of those most likely to respond to specific interventions. This field may also benefit from longer-term studies of the various interventions or strategies covered within this review article, to better understand the persistence of treatment effects over time and explore more novel approaches to myopia control.

Background/aimTo evaluate the safety and efficacy of ruthenium-106 (Ru-106) plaque brachytherapy in managing invasive ocular surface squamous neoplasia (OSSN).MethodsThis is a retrospective, non-comparative, interventional case series of 42 eyes with OSSN with histopathologically-proven corneal stromal and/or scleral invasion that underwent Ru-106 plaque brachytherapy. Main outcome measures were tumour regression, eye salvage, final visual acuity, treatment complications and metastasis.ResultsAt presentation, the mean tumour basal diameter was 9.3 mm (range 5–26 mm) and thickness 3.1 mm (range 1.5–11 mm). Prior treatment included excision biopsy in two patients (5%), incision biopsy and topical interferon in one each (2%). Following excision with 4 mm clinically clear margins, corneal stromal and/or scleral invasion of OSSN was confirmed in all 42 cases, with the excised base showing invasive squamous cell carcinoma. A total dose of 5000 cGy over a mean duration of 19.7 hours (range 7–41 hours) was provided to an axial depth of 2 mm using Ru-106 surface plaque. Over a mean follow-up of 36.9 months (range 22.3–72 months), complete tumour regression was achieved in all eyes (100%). Two eyes (5%) showed conjunctival tumour growth remote from the site of prior treatment. Visual acuity was maintained at ≥20/200 in 35 eyes (83%), with a loss of >2 Snellen lines in 1 eye (2%). There was no evidence of regional lymph node or systemic metastasis.ConclusionHistopathology-guided use of Ru-106 surface plaque brachytherapy is a safe and an effective adjuvant therapy in the management of corneal stromal and/or scleral invasion of OSSN.

Background/aimsTo compare risk factors for poor visual outcomes in patients undergoing primary rhegmatogenous retinal detachment (RRD) repair and to develop a scoring system.MethodsAnalysis of the Primary Retinal detachment Outcomes (PRO) study, a multicentre interventional cohort of consecutive primary RRD surgeries performed in 2015. The main outcome measure was a poor visual outcome (Snellen VA ≤20/200).ResultsA total of 1178 cases were included. The mean preoperative and postoperative logMARs were 1.1±1.1 (20/250) and 0.5±0.7 (20/63), respectively. Multivariable logistic regression identified preoperative risk factors predictive of poor visual outcomes (≤20/200), including proliferative vitreoretinopathy (PVR) (OR 1.26; 95% CI 1.13 to 1.40), history of antivascular endothelial growth factor (VEGF) injections (1.38; 1.11 to 1.71), >1-week vision loss (1.17; 1.08 to 1.27), ocular comorbidities (1.18; 1.00 to 1.38), poor presenting VA (1.06 per initial logMAR unit; 1.02 to 1.10) and age >70 (1.13; 1.04 to 1.23). The data were split into training (75%) and validation (25%) and a scoring system was developed and validated. The risk for poor visual outcomes was 8% with a total score of 0, 17% with 1, 29% with 2, 47% with 3, and 71% with 4 or higher.ConclusionsIndependent risk factors were compared for poor visual outcomes after RRD surgery, which included PVR, anti-VEGF injections, vision loss >1 week, ocular comorbidities, presenting VA and older age. The PRO score was developed to provide a scoring system that may be useful in clinical practice.

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections.MethodsThis is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid.ResultsThe presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness.Conclusion and relevanceBaseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO.

AimsTo determine the incidence and risk factors of cystoid macular oedema (CMO) following descemet membrane endothelial keratoplasty (DMEK) with or without combined cataract surgery (triple-DMEK).MethodsWe reviewed the records of patients who underwent DMEK surgery alone or triple-DMEK performed at the Rothschild Foundation Hospital (Paris, France) between January 2019 and March 2020. Patients with pre-existing CMO observed on the preoperative macular optical coherence tomography (OCT) were excluded. Spectral-domain OCT was performed in patients with postoperative visual impairment. Data regarding comorbidities, intraoperative characteristics and postoperative treatments or complications were collected and analysed. Univariate and multivariate analyses were performed.ResultsTwenty three of 246 eyes (9.36%) developed clinically significant (cs)-CMO after DMEK. Triple-DMEK was not associated with a higher risk to develop CMO (12.2% in DMEK alone and 6.1% in triple-DMEK). Pseudophakic bullous keratopathy (PBK ; 39.1% vs 9%; OR=3.5 (1.0 to 11.8), p=0.045) and epiretinal membrane (ERM; 39.1% vs 7.7%; OR=10.5 (3.4 to 32.3), pConclusionsWe identified a clinically significant CMO incidence of 9.35% after DMEK. Patients with a history of ERM, PBK and intraoperative hyphaema may be at risk of developing CMO after DMEK surgery and should be monitored.

BackgroundThe etiopathogenesis of vernal keratoconjunctivitis (VKC) is incompletely understood. Bioactive lipids play a key role in allergic disorders. This study focused on the sphingolipid metabolism on the ocular surface of VKC and to explore if it has a contributory role in the refractoriness of the disease.MethodsActive VKC cases, (n=87) (classified as mild/moderate and severe/very severe based on the disease symptoms) and age-matched healthy controls (n=60) were recruited as part of a 2-year prospective study at a tertiary eye care centre in South India. Conjunctival imprint cytology was used to assess gene expression of enzymes of sphingolipids metabolism. Sphingolipids were estimated in the tears by LC-MS/MS analysis. In vitro study was done to assess IgE-induced alterations in sphingosine-1-phosphate (S1P) receptor expression and histone modification in cultured mast cells.ResultsSignificantly altered gene expression of the sphingolipids enzymes and S1P receptor (SIP3R) were observed in conjunctival imprint cells of VKC cases. Pooled tears analysis revealed significantly lowered levels of S1P(d17:0), S1P(d20:1) (pConclusionAltered sphingolipid metabolism in the ocular surface results in low tear ceramide and sphingosine levels in severe/very severe VKC compared with the mild/moderate cases. The novel finding opens up fresh targets for intervention in these refractory cases.

AimsTo characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications.Methods36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: 200 µm, with associated chorioretinal pathology).Results80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043).ConclusionsThe FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

AimsTo report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations.MethodsChinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related macular degeneration (AMD) features and drusen volume was generated using commercially available automated software.ResultsA total of 4172 eyes of 2580 participants (mean age 58.12±9.03 years; 51.12% women) had baseline and 6-year follow-up CFP for grading, of these, 2130 eyes of 1305 participants had gradable SD-OCT images, available for analysis. Based on CFP grading, 136 (3.39%) participants developed incident early AMD and 10 (0.25%) late AMD. Concurrently, retinal pigment epithelial-Bruch’s membrane (RPE-BrC) volumes decreased, remained stable and increased in 6.8%, 78.5% and 14.7%, respectively, over 6 years. In eyes where RPE-BrC volumes were >0 mm3at baseline, this was associated with two-fold higher prevalence rate of any AMD at baseline (pConclusionAMD incidence detected at 6 years on CFP and correlated OCT-derived drusen volume measurement change is low. Older age and some systemic risk factors are associated with drusen volume change, and our data provide new insights into relationship between systemic risk factors and outer retinal morphology in Asian eyes.

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

AimsTo evaluate the rates of keratoconus progression and associated factors in eyes of children and adolescents.MethodsRetrospective, cohort study of individuals ≤18 years old at the time of keratoconus diagnosis and with at least 6 months of follow-up. Corneal tomography was performed using an Orbscan tomographer (Bausch & Lomb, Rochester, New York, USA) to determine whether progression occurred. Tomographic progression of keratoconus was defined as a change in any of the investigated parameters (keratometry values, KMAX, maximum anterior or posterior elevation, central pachymetry, thinnest pachymetry) beyond the limits of repeatability.Results148 eyes of 106 patients with a mean age of 15.2±2.5 years were studied over a mean follow-up period of 2.9±2.2 years. The overall rate of tomographic progression was 77.0% (114/148 eyes). Eyes that progressed had more advanced disease at presentation with higher anterior curvature (KMAX55.4±6.3 vs 52.2±5.4 dioptres; pConclusionsA high rate of progression was identified in keratoconic eyes of children and adolescents. More advanced disease at initial presentation may increase the risk of further keratoconus progression.

BackgroundTo assess prevalence and associated factors of changes in the ophthalmoscopic optic disc size and shape.MethodsThe case–control study included all highly myopic eyes (myopic refractive error ≤−6.0 diopters) and a randomly selected group of non-highly myopic eyes, examined in the population-based Beijing Eye Study 2001 and 2011.ResultsThe study included 89 highly myopic eyes (age:65.0±9.8 years) and 86 non-highly myopic eyes. Reduction in ophthalmoscopic disc size (prevalence, high myopia: 30 (33.7%) eyes; non-high myopia: 7 (8.1%) eyes) was associated with non-circular gamma zone enlargement (OR: 19.4; 95% CI: 6.7 to 56.6; pConclusionsMyopic axial elongation may lead first to a Bruch’s membrane (BM) opening (BMO) shift into the foveal direction leading to BM overhanging into the nasal intrapapillary compartment, development and enlargement of gamma zone at the temporal disc side, reduction in the ophthalmoscopically visible disc area and ovalisation of the ophthalmoscopic disc shape. In a second step, an axial elongation-associated BMO enlargement may lead to a circular gamma zone increase and, due to the retraction of BM at the nasal disc border, to an enlargement of the ophthalmoscopically visible optic disc.

BackgroundTo explore the outcomes and mechanisms of intraocular pressure (IOP) control using low-dose transscleral cyclophotocoagulation (LDTSCP) followed by phacoemulsification in patients with prolonged acute primary angle closure (APAC).MethodsPatients with prolonged APAC refractory to all other treatment modalities were prospectively recruited, and underwent LDTSCP (10 shots, 2 s duration, 120° treatment with the energy starting at 1500 mW and titrated to the level with audible burst but not exceeding 2000 mW) and anterior chamber paracentesis 1 week prior to phacoemulsification with intraocular lens implantation and viscogoniosynechiolysis. Postoperative IOP, vision, anatomic changes on anterior segment optical coherence tomography and complications were recorded.ResultsTwenty eyes with prolonged APAC were recruited. Median follow-up was 12 months (range 9–18), at which point the vision in all eyes had improved and IOP was ≤17 mm Hg on no antiglaucoma medications. Following LDTSCP at postoperative day (POD) 1, IOP decreased in all eyes to a median 15 mm Hg (range: 6–28 mm Hg). Post-LDTSCP supraciliary effusion (SCE) occurred in 90% of eyes on POD1 or POD7 and ciliary body defect (CBD) was detected in 30% of eyes and resolved in all cases by postoperative month 1. Lower post-LDTSCP IOP was associated with more number of bursts (r=−0.558, p=0.011) and higher grade of SCE (r=−0.877, pConclusionsLDTSCP-induced SCE may explain the post-LDTSCP IOP reduction seen in eyes with prolonged APAC. LDTSCP instead of traditional more extensive treatment, was sufficient to provide a relatively safe and effective bridge therapy prior to phacoemulsification.Trial registration numberChinese Clinical Trials Registry (ChiCTR1900023567).

AimTo evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME).MethodsThe open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks.ResultsOf 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and –89.6 µm (pConclusionIn this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME.Trial registration numberNCT02731911.

BackgroundThe BEVORDEX trial compared outcomes of eyes with diabetic macular oedema (DMO) randomised to receive either intravitreal dexamethasone (DEX-) implant or bevacizumab over 2 years. We assessed long-term efficacy and safety outcomes 5 years from enrolment.MethodsPatients received standard clinical care after they finished the study. Their files were reviewed for visual and anatomical outcomes, post-trial treatments and complications.ResultsThree-year and five-year data were available for 82% and 59% of eyes enrolled in the BEVORDEX study, respectively. Visual acuity gains at end of trial were generally lost by both treatment groups at 5 years but the macular thickness did not change from end of trial to 5 years. A similar proportion of eyes from each treatment group gained ≥10 letters at 5 years from enrolment in the BEVORDEX trial.Eyes that were initially randomised to the DEX-implant group had significantly fewer treatments but were more likely to develop proliferative diabetic retinopathy (PDR) over the 5-year period compared with eyes initially randomised to bevacizumab. The proportion of eyes that had cataract surgery by 5 years was similar between initial treatment groups.ConclusionsEyes in the BEVORDEX trial had similar 5-year rates of cataract surgery, however, more eyes converted to PDR in the group initially treated with DEX-implant. Eyes that were initially treated for 2 years with either intravitreal DEX-implant of bevacizumab followed by standard of care had similar visual and anatomical outcomes at 5 years.

Background/aimsTo evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients receiving treatment for unilateral nAMD in a UK National Health Service (NHS) hospital outpatient setting.MethodsA patient-level state transition model was constructed to simulate the onset, detection, and treatment of nAMD in the second eye. Five index tests were compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity from baseline, fundus assessment by clinical examination or colour photography, and spectral domain optical coherence tomography (SD-OCT). Diagnosis of nAMD was confirmed by fundus fluorescein angiography (FFA) before prompt initiation of antivascular endothelial growth factor treatment. Quality-adjusted life-years (QALYs) and costs of health and social care were modelled over a 25-year time horizon.ResultsSD-OCT generated more QALYs (SD-OCT, 5.830; fundus assessment, 5.787; Amsler grid, 5.736, patient’s subjective assessment, 5.630; and visual acuity, 5.600) and lower health and social care costs (SD-OCT, £19 406; fundus assessment, £19 649; Amsler grid, £19 751; patient’s subjective assessment, £20 198 and visual acuity, £20 444) per patient compared with other individual monitoring tests. Probabilistic sensitivity analysis indicated a high probability (97%–99%) of SD-OCT being the preferred test across a range of cost-effectiveness thresholds (£13 000–£30 000) applied in the UK NHS.ConclusionsEarly treatment of the second eye following FFA confirmation of SD-OCT positive findings is expected to maintain better visual acuity and health-related quality of life and may reduce costs of health and social care over the lifetime of patients.

Background/aimsThis study aimed to establish a wide-field optical coherence tomography (OCT) deviation map obtained from swept-source OCT (SS-OCT) scans. Moreover, it also aimed to compare the diagnostic ability of this wide-field deviation map with that of the peripapillary and macular deviation maps currently being used for the detection of early glaucoma (EG).MethodsFour hundred eyes, including 200 healthy eyes and 200 eyes with EG were enrolled in this retrospective observational study. Patients underwent a comprehensive ocular examination, including wide-field SS-OCT (DRI-OCT Triton; Topcon, Tokyo, Japan). The individual wide-field scan was converted into a uniform template using the fovea and optic disc centres as fixed landmarks. Subsequently, the wide-field deviation map was obtained via the comparison between individual wide-field data and a normative wide-field database that had been created by combining images of healthy eyes into a uniform template in a previous study. The ability of the new wide-field deviation map to distinguish between EG and healthy eyes was assessed by comparing it with conventional deviation maps based on the area under the receiver operating characteristic curve (AUC).ResultsThe wide-field deviation map obtained using the normative wide-field database showed the highest diagnostic ability for the diagnosis of EG (AUC=0.980 and 961 for colour-coded pixels presenting ConclusionThe wide-field SS-OCT deviation map exhibited good performance for distinguishing between eyes with EG and healthy eyes. The visualisation of the wider damaged area on the wide-field deviation map could be useful for the diagnosis of EG in clinical settings.

PurposeTo assess the effects of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography (OCTA).MethodsIn this prospective cross-sectional study, one eye each of 36 normal controls and 64 patients with glaucoma underwent 4.5 mm disc-centred and 6 mm macula-centred OCTA scans. The peripapillary nerve fibre layer plexus capillary density (NFLP-CD) and macular superficial vascular complex vessel density (SVC-VD) were measured using both a commercial algorithm (AngioAnalytics) and a custom algorithm (Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART)). The nerve fibre layer and ganglion cell complex thicknesses were measured on structural OCT.ResultsThe overall peripapillary NFLP-CD and macular SVC-VD measured with the two algorithms were highly correlated but poorly agreed. Among the normal controls, the perfusion measurements made by both algorithms were significantly correlated with age. AngioAnalytics measurements were also correlated with signal strength index, while COOL-ART measurements were not. These covariates were adjusted. The diagnostic accuracy, measured as the area under the receiver operating characteristic curve for glaucoma detection, was not significantly different between algorithms, between structural and perfusion parameters and between the peripapillary and macular regions (All p>0.05). The macular SVC-VD in the 6 mm square had a significantly higher diagnostic accuracy than that of the central 3 mm square area (p=0.005).ConclusionsAngioAnalytics and COOL-ART vessel density measurements are not interchangeable but potentially interconvertible. Age and signal strength are significant covariates that need to be considered. Both algorithms and both peripapillary and macular perfusion parameters have similarly good diagnostic accuracy comparable to structural OCT. A larger macular analytic area provides higher diagnostic accuracy.

AimsTo identify morphological characteristics preceding the development of exudative neovascularisation secondary to Macular Telangiectasia type 2 (MacTel) using multimodal retinal imaging.MethodsIn this retrospective study, eyes with a minimum observation period of 6 months prior to the de novo diagnosis of an exudative neovascularisation secondary to MacTel were analysed. Morphological changes preceding the formation of neovascularisation were evaluated using colour fundus photography, infrared imaging, fluorescein angiography, macular pigment measurement and optical coherence tomography (OCT). OCT-angiography (OCT-A) images were additionally available in a subset of patients.ResultsTwenty eyes from 20 patients were examined over a median period of 17 months (range: 6–100 months). Eyes were characterised by an accelerated progression of ellipsoid zone loss (median of 0.013 mm2/month), increased thickness of the temporal parafovea and hyper-reflective lesions on OCT. The latter underwent morphological changes preceding the development of exudative neovascularisation, including an increase in size and density, and expansion to outer retinal layers and the retinal pigment epithelium. All eyes showed a foveal depletion of macular pigment. On OCT-A, a focal increase in blood flow was observed at the level of the outer retina/choriocapillaris, and retinal–retinal and retinal–choroidal anastomoses preceded the formation of exudative neovascularisation.ConclusionsMultimodal imaging allows the identification of prognostic morphological features preceding the formation of exudative neovascularisation in MacTel. Eyes exhibiting these characteristics should be monitored closely and patients should be alert for emergent symptoms in order to detect and treat neovascularisation early and, thereby, prevent irreversible visual loss.

Background/AimsThis study aims to assess the contribution of biallelicCPAMD8variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES).MethodsPotentially pathogenicCPAMD8variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype–phenotype correlation was assessed by a systematic review of biallelicCPAMD8variants that including our data and data from the literature. The expression profile ofCPAMD8in human tissues was determined at the mRNA and protein levels.ResultsBiallelicCPAMD8variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma.CPAMD8mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry.ConclusionsThe data from this study not only provide further evidence to support the association of biallelicCPAMD8variants with JOAG but also suggest that biallelicCPAMD8variants might be associated with POAG and PACG.

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.MethodsClinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in theCFH(rs1061170),HTRA1(rs1200638) andC3(rs2230199) genes were genotyped.ResultsFrom 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (pCFHand/orC3risk alleles carried by the patient (Pearson’s r: −0.608; p=0.003).ConclusionsPatients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.

Background/aimTo evaluate relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration (nAMD).MethodsThis post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg, monthly or as-needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0–50, >50–100 and >100 µm) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography (SD-OCT). Best-corrected visual acuity (BCVA) was assessed. MA was identified using fluorescein angiograms and colour fundus photographs, as well as SD-OCT.ResultsSeven hundred eighty-five of 1097 eyes met analysis criteria. In eyes without baseline MA, residual versus no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1% vs 22.1%) and M24 (13.3% vs 31.2%) (both p0–50 µm, 71.2 letters; >50–100 µm, 71.3 letters; >100 µm, 69.2 letters) versus no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6.ConclusionTR-SRF was not detrimental to vision outcomes over 2 years, regardless of thickness. MA rates were significantly higher without TR-SRF.

PurposeTo optimise the objective diagnosis of dry eye disease (DED), the capabilities of wide corneal epithelial mapping using optical coherence tomography (OCT) were studied and subsequently integrated into a new scoring method.MethodsFifty-nine patients (118 eyes) with DED and 55 control subjects (110 eyes) were included. All patients underwent a complete ocular surface evaluation. Corneal epithelial thickness was collected using OCT for seven zones. DED and the control group were compared using a t-test, and univariate receiver operating characteristic (ROC) curves were calculated to define the diagnostic ability of OCT epithelial mapping. Multivariate analyses were performed using artificial intelligence (random forest) and logistic regression approaches to define the best way to integrate OCT mapping in the diagnosis of DED. Then, a final multivariable model for diagnosing DED was validated through a bootstrapping method.ResultsThe DED group had significant epithelial thinning compared with the controls, regardless of location. Superior intermediate epithelial thickness was the best marker for diagnosing DED using OCT (binormal estimated area under ROC: 0.87; best cut-off value: 50 µm thickness). The difference between the inferior and superior peripheral zones was the best marker for grading the severity of DED (analysis of variance, p=0.009). A multivariate approach identified other significant covariables which were integrated into a multivariate model to improve the sensitivity (86.4%) and specificity (91.7%) of this innovative diagnostic method.ConclusionIncluding OCT corneal epithelial mapping in a new diagnostic tool for DED could allow optimisation of the screening and staging of the disease in current practice as well as for clinical research purposes.

Background/aimsWe aimed to explore the impact of glaucomatous macular damage, specifically retinal ganglion cell (RGC) loss, on macular pattern vision measured by the vanishing optotype (VO) recognition contrast threshold.MethodsSeventy-two patients (mean age, 33.51±7.05 years) with primary open-angle glaucoma and 36 healthy controls (mean age, 30.25±6.70 years) were enrolled. VO recognition contrast thresholds of each participant were measured at the 16 preset test locations covering the central 5° visual field (VF). Macular sensitivity (MS) was tested by macular threshold test of Humphrey Field Analyzer. Macular RGC plus inner plexiform layer (GCIPL) thickness was also measured by spectral domain optical coherence tomography.ResultsThe VO contrast threshold demonstrated weak-to-moderate correlations (rho=−0.275 to −0.653) with MS (pConclusionsGlaucomatous eyes have higher contrast thresholds for VO recognition in fovea-around VF. Stronger structure–function relationships indicate that VO contrast threshold is more vulnerable to RGC damage.

AimsTo examine presentation, management and long-term sequelae of ocular hypertension and uveitic glaucoma.MethodsRetrospective observational study of all subjects with uveitic glaucoma or ocular hypertension seen in Auckland uveitis clinics over the last 10 years.ResultsA total of 188 eyes of 139 subjects with uveitic glaucoma or ocular hypertension were included for analysis. Total follow-up was 1854.5 eye years (mean 9.9 years). The mean age at uveitis diagnosis was 49.3 years. 52.5% of subjects were male. The most common diagnoses were idiopathic uveitis (29.3%), sarcoidosis (13.3%), herpes zoster (6.9%), HLA-B27 uveitis (6.9%), tuberculosis (5.9%) and Posner-Schlossmann or cytomegalovirus (CMV) uveitis (5.3%). Median intraocular pressure (IOP) at diagnosis was 35 mm Hg (IQR 29–45). 144 eyes (77.0%) developed glaucoma during the follow-up period, of whom 41 lost some central vision due to glaucoma. Oral acetazolamide was required for IOP control in 64.5%, 50 eyes underwent trabeculectomy, 18 eyes required a tube and 6 underwent minimally invasive glaucoma surgery.ConclusionRapid progression was observed from ocular hypertension to uveitic glaucoma. Uveitic glaucoma is aggressive, with high likelihood of requiring surgical management and high risk of central vision loss. Close collaboration between uveitis and glaucoma specialists is required to maximise outcomes for these patients.

Background/aimsTo investigate the long-term outcomes of cultivated oral mucosal epithelial transplantation (COMET) for fornix reconstruction in eyes with chronic cicatrising disease.MethodsThis retrospective cohort study involved 16 eyes of 15 patients who underwent COMET for symblepharon release and fornix reconstruction between June 2002 and December 2008. The mean postoperative follow-up period was 102.1±46.0 months (range: 32–183 months). The treated cicatrising disorders included ocular cicatricial pemphigoid (OCP, five eyes), thermal/chemical injury (three eyes) and other chronic diseases (seven eyes; including recurrent pterygium (two eyes), Stevens-Johnson syndrome (one eye) and graft-versus-host disease (one eye)). Ocular-surface appearance was evaluated before surgery, at 1, 4, 12 and 24 weeks postoperative, and then annually based on the previously reported scoring system. Main outcome measures included overall and disease-specific fornix-reconstruction success probabilities analysed by the Kaplan-Meier survival curve. Symblepharon/fornix-shortening recurrence at 24 weeks postoperative, and its relationship to long-term surgical success was also examined.ResultsAt 5 years postoperative, the mean±SD overall fornix-reconstruction success probability was 79.6%±10.7%, and success probability for thermal/chemical injury and OCP was 100% and 53.3%±24.8%, respectively (p=0.53, log-rank test). The 3-year success probability was significantly higher in the no-disease-recurrence group at 24 weeks postoperative (13 eyes) than in the disease-recurrence group (three eyes) (100% and 33.3%±27.2%, respectively) (p=0.0073, log-rank test).ConclusionCOMET was found to be safe and effective for symblepharon release and long-term fornix reconstruction in eyes with chronic cicatrisation. Although the 5-year success probability differed depend on the underlying disease, ocular-surface appearance at 24 weeks postoperative is a factor for predicting long-term outcome.

AimTo estimate the minimally important difference (MID) in change in National Eye Institute Visual Function Questionnaire-25 (VFQ-25) composite score using methods aligned with patient perception.MethodsRetrospective analysis of prospectively collected data from adults with primary angle closure or primary angle closure glaucoma enrolled in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction study. We included data from 335 participants with patient reported visual function (VFQ-25) and health status measured by the EQ-5D-3L over 36 months. We used the recommended anchor-based methods (receiver operating characteristic (ROC), predictive modelling and mean change) to determine the MID of the VFQ-25. EQ-5D-3L anchor change was defined as none (0.075 points).ResultsMean baseline VFQ-25 score was 87.6 (SD 11.8). Estimated MIDs in the change in VFQ-25 scores (95% CI) were 10.5 (1.9 to 19.2); 3.9 (−2.3 to 10.1); 5.8 (1.9 to 7.2) and 8.1 (1.7 to 14.8) for the ‘within-patient’, ‘between-patient’ change, ROC and predictive modelling anchor methods respectively. Excluding estimates from the methodologically weaker ‘within-patient’ method, the MID of a change in VFQ-25 composite score is 5.8 (median value).ConclusionsEstimates of the MID using multiple methods assist in the interpretation of the VFQ scores. In the context of early glaucoma related visual disability, a change score of around six points on the VFQ-25 is likely to be important to patients. Further confirmatory research is required. Studies comparing changes in patient-reported outcome measure scores with a global measure of patients’ perceived change are required.

PurposeTo investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT).DesignRetrospective consecutive observational cohort study.MethodsWe included highly myopic eyes (refractive error ≤−8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis.ResultsTwenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (pConclusionsDecreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

BackgroundTo investigate the longitudinal change of localised retinal nerve fibre layer (RNFL) defects associated with change of ß-zone parapapillary atrophy (PPA) in primary open-angle glaucoma (POAG) eyes.MethodsPOAG patients with a localised RNFL defect and ß-zone PPA who had undergone disc/RNFL photography at 1-year intervals for 10 years or longer were enrolled. The topographic parameters of ß-zone PPA (area, maximal radial extent and angular extent around disc) were measured. Progression of RNFL defect was defined as widening of defect and/or appearance of new defect. The factors associated with progression of RNFL defect were assessed by OR using multivariable logistic regression.ResultsA total of 209 patients (209 eyes) with POAG were included (mean: 54 years old). Over the course of 11.5±2.3-year follow-up period, progression of RNFL defect was detected in 114 eyes (54.5%). Enlargement of PPA parameters (area and angular extent) was significantly more common in patients with RNFL defect progression than in eyes without progression (all pConclusionsProgression of RNFL defect is associated with increment of angular extent of PPA in POAG eyes.

AimsTo characterise the association between visual field (VF) defects and myopic macular degeneration (MMD) in highly myopic adults without glaucoma.MethodsParticipants (n=106; 181 eyes) with high myopia (HM; spherical equivalent ≤−5.0 D or axial length (AL) ≥26 mm), after excluding glaucoma and glaucoma suspects, from the Singapore Epidemiology of Eye Diseases-HM study were included in this cross-sectional study. Humphrey VF (central 24–2 threshold), cup-disc ratio (CDR) and intraocular pressure (IOP) measurements were performed. Mean deviation (MD) and pattern SD (PSD), VF defects (normal or abnormal; pResultsMean age was 55.4±9.9 years and 51.9% were women (AL=26.7±1.1 mm). MMD eyes had lower MD (−3.8±2.9 dB vs −1.1±1.4 dB) and higher PSD (2.8±1.7 dB vs 1.7±0.6 dB). A higher percentage of MMD eyes (n=48) had abnormal VF (62.5% vs 28.6%; pConclusionHighly myopic adults with MMD may have VF loss when compared with highly myopic patients without MMD even in adults without glaucoma.

Background/AimsTo investigate the utility of a data-driven deep learning approach in patients with inherited retinal disorder (IRD) and to predict the causative genes based on fundus photography and fundus autofluorescence (FAF) imaging.MethodsClinical and genetic data from 1302 subjects from 729 genetically confirmed families with IRD registered with the Japan Eye Genetics Consortium were reviewed. Three categories of genetic diagnosis were selected, based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS) and occult macular dystrophy (RP1L1). Fundus photographs and FAF images were cropped in a standardised manner with a macro algorithm. Images for training/testing were selected using a randomised, fourfold cross-validation method. The application program interface was established to reach the learning accuracy of concordance (target: >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1 and normal).ResultsA total of 417 images from 156 Japanese subjects were examined, including 115 genetically confirmed patients caused by the three prevalent causative genes and 41 normal subjects. The mean overall test accuracy for fundus photographs and FAF images was 88.2% and 81.3%, respectively. The mean overall sensitivity/specificity values for fundus photographs and FAF images were 88.3%/97.4% and 81.8%/95.5%, respectively.ConclusionA novel application of deep neural networks in the prediction of the causative IRD genes from fundus photographs and FAF, with a high prediction accuracy of over 80%, was highlighted. These achievements will extensively promote the quality of medical care by facilitating early diagnosis, especially by non-specialists, access to care, reducing the cost of referrals, and preventing unnecessary clinical and genetic testing.

AimsTo validate a deep learning (DL) algorithm (DLA) for 360° angle assessment on swept-source optical coherence tomography (SS-OCT) (CASIA SS-1000, Tomey Corporation, Nagoya, Japan).MethodsThis was a reliability analysis from a cross-sectional study. An independent test set of 39 936 SS-OCT scans from 312 phakic subjects (128 SS-OCT meridional scans per eye) was analysed. Participants above 50 years with no previous history of intraocular surgery were consecutively recruited from glaucoma clinics. Indentation gonioscopy and dark room SS-OCT were performed. Gonioscopic angle closure was defined as non-visibility of the posterior trabecular meshwork in ≥180° of the angle. For each subject, all images were analysed by a DL-based network based on the VGG-16 architecture, for gonioscopic angle-closure detection. Area under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators were calculated for the DLA (index test) against gonioscopy (reference standard).ResultsApproximately 80% of the participants were Chinese, and more than half were women (57.4%). The prevalence of gonioscopic angle closure in this hospital-based sample was 20.2%. After analysing a total of 39 936 SS-OCT scans, the AUC of the DLA was 0.85 (95% CI:0.80 to 0.90, with sensitivity of 83% and a specificity of 87%) to classify gonioscopic angle closure with the optimal cut-off value of >35% of circumferential angle closure.ConclusionsThe DLA exhibited good diagnostic performance for detection of gonioscopic angle closure on 360° SS-OCT scans in a glaucoma clinic setting. Such an algorithm, independent of the identification of the scleral spur, may be the foundation for a non-contact, fast and reproducible ‘automated gonioscopy’ in future.

Background/aimsTo examine the relationship between macular perfusion, as assessed using optical coherence tomography angiography (OCTA), and long-term visual outcome after surgical repair of macula-off rhegmatogenous retinal detachment (RRD).MethodsA prospective study of 29 patients who had undergone successful surgical repair of macula-off RRD. OCTA imaging was performed at month 3 and repeated at months 6 and 12 after surgery. Associations between OCTA parameters including, foveal avascular zone (FAZ) area, vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow deficit features and logMAR best-corrected visual acuity (VA) were assessed using a random intercept hybrid linear mixed model.ResultsOver the 1-year follow-up, VA improved (0.025 logMAR/ month, 95% CI 0.015 to 0.035) and FAZ area decreased (−0.020 mm2/month, 95% CI −0.032 to −0.007). Better VA after surgery was significantly associated with denser superficial VD (β=0.079, 95% CI 0.026 to 0.131), lower number of choriocapillaris flow deficits (β=−0.087, 95% CI −0.154 to −0.021) and larger average size of choriocapillaris flow deficits (β=0.085, 95% CI 0.022 to 0.147), after adjusting for baseline VA, types of surgery and other factors.ConclusionsOCTA measures of vascular perfusion in the macula may provide new pathophysiological insights and prognostic information related to macula-off RRD.

Background/AimTo provide a comprehensive multimodal retinal imaging characterisation of patients with North Carolina macular dystrophy (NCMD).MethodsClinical evaluation and retinal imaging in six families.ResultsTwenty-one subjects showed phenotypic characteristics of NCMD . Small drusen-like deposits were found in all affected individuals, either tightly grouped in the macula, or surrounding atrophic or fibrotic macular alterations. These small subretinal lesions showed an increased fundus autofluorescence and were associated with only mild irregularities on optical coherence tomography imaging. Similar drusen-like deposits were regularly seen in the peripheral fundus, predominantly temporally and often with a radial distribution. Two patients showed a bilateral chorioretinal atrophy and two had a macular neovascularisation (MNV). Findings from follow-up examinations were available from 11 patients. The retinal phenotype remained overall stable, except for two patients: one patient with atrophy showed a distinct growth of the atrophic lesions on longitudinal AF imaging over a review period of 14 years. One patient with MNV showed a unilateral decline of best-corrected visual acuity. Genetic testing identified the single nucleotide variant chr6:100040987G>C upstream of the PRDM13 gene in all family members with NCMD phenotype.ConclusionPatients with NCMD show a characteristic retinal phenotype and distribution of drusen that differ from drusen in patients with age-related macular degeneration. Although the prognosis of this developmental condition is overall better than for other macular diseases with drusen, patients may be at risk of developing MNV or enlargement of pre-existing atrophy.

PurposeTo study the role of two anterior segment optical coherence tomography angiography (AS-OCTA) systems in eyes with acute chemical injury.MethodsProspective study in subjects with unilateral chemical injuries. Sequential slit-lamp assessment with spectral domain (SD) (AngioVue, Optovue, USA) and swept source (SS) (Plex Elite, Zeiss, Carl Zeiss Meditec, Dublin, California, USA) AS-OCTA was performed in both eyes within 24–48 hours of injury. Subjects were managed with a standard clinical protocol and followed-up for 3 months. We assessed limbal disruption (loss of normal limbal vessel architecture), limbal vessel density measurements and agreement (kappa coefficient, κ) between masked assessors of limbal disruption based on AS-OCTA scans and slit-lamp assessment.ResultsTen subjects with median age 31 (25–33) years, 20% women, 60% suffered alkali injuries (Roper-Hall grade 1.5±0.7, Dua grade 2.3±1.2) at presentation. Mean limbal vessel density was lower in quadrants of affected eyes compared with controls detected by SD AS-OCTA (9.4%±2.0% vs 15.5%±1.8%, pConclusionsIn this pilot study, AS-OCTA provided objective, non-contact, rapid assessment of limbal vasculature involvement in eyes with acute chemical injury. Further studies are required to establish the role of AS-OCTA in determining the prognosis of eyes with chemical injury.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The identification of the central role of vascular endothelial growth factor (VEGF) in the pathogenesis of neovascular AMD and the introduction of anti-VEGF agents as gold-standard treatment, have drastically changed its prognosis—something yet to be seen in dry AMD. Several therapeutic avenues with a wide variability of targets are currently being investigated in dry AMD. The approaches being investigated to reduce the rate of disease progression include, (1) drugs with antioxidative properties, (2) inhibitors of the complement cascade, (3) neuroprotective agents, (4) visual cycle inhibitors, (5) gene therapy and (6) cell-based therapies. A number of early phase clinical trials have provided promising results, with many more ongoing and anticipated in the near future. In this review, we aim to provide an update of the interventional trials to date and future prospects for the treatment of dry AMD.

PurposeTo report the long-term outcomes of Boston keratoprosthesis type I (B-KPro type I) implantation in the management of severe ocular surface disorders.MethodsRetrospective case series. Patients who underwent B-KPro type I implantation at the People’s Liberation Army General Hospital were enrolled between March 2011 and September 2019. Data regarding visual acuity (VA), B-KPro type I retention and postoperative complications were recorded and analysed.ResultsA total of 103 eyes of 100 patients who underwent B-KPro type I implantation were included. The main indications were chemical burn (59.2%), ocular trauma (25.2%), herpetic keratitis (11.7%) and autoimmune diseases (3.9%). The percentage of eyes with postoperative VA of 10/200 or better was 82.7% at 6 months, 82.8% at 12 months, 77.9% at 2 years, 72.4% at 3 years, 71.1% at 4 years, 69.4% at 5 years, 58.9% at 6 years, 56.8% at 7 years and 42.9% at 8 years. Preoperatively, 8.7% eyes were diagnosed with new-onset glaucoma. Retroprosthetic membrane formation occurred in 19.4% eye. Corneal melting occurred in 18.4% eyes. Sterile vitritis was diagnosed in 4.9% eyes and infectious endophthalmitis in 2.9% eyes. Retinal detachment occurred in 0.9% eyes.ConclusionsIn a Chinese patient group, B-KPro type I is a viable option for treating severe ocular surface disorders in eyes where conventional keratoplasty would have a poor prognosis, especially in patients with chemical and thermal burns. Improved visual outcomes and high retention rate can be achieved and maintained in most cases.

Background/aimsTo evaluate the time needed for patients with Boston type 1 keratoprosthesis (KPro) to reach their best-corrected visual acuity (BCVA) and all contributing factors.MethodsWe retrospectively reviewed 137 consecutive eyes from 118 patients, measured how long they needed to reach their BCVA and looked at factors that might affect this time duration including patient demographics, ocular comorbidities and postoperative complications.ResultsThe mean follow-up was 5.49 years. The median time to BCVA postoperatively was 6 months, with 47% of patients achieving their BCVA by 3 months. The mean best achieved logMAR visual acuity was 0.71, representing a gain of 6 lines on the Snellen visual acuity chart. Postoperative glaucoma, retroprosthetic membrane (RPM) and endophthalmitis prolonged this duration. We found no correlation between the following factors and time to BCVA: gender, age, indication for KPro surgery, primary versus secondary KPro, number of previous penetrating keratoplasties, previous retinal surgery, intraoperative anterior vitrectomy and preoperative glaucoma.ConclusionIn our retrospective cohort, the majority of subjects reached their BCVA between 3 and 6 months after KPro implantation. This duration was significantly prolonged by the development of postoperative glaucoma, RPM and endophthalmitis.

AimsTo elucidate the influence of age and myopic shift on retinal development.MethodsThis 1-year longitudinal study included 769 participants aged 6–17 years. Cycloplegic refraction, axial length and swept-source optical coherence tomography were examined at baseline and follow-up. The thickness changes in the retina, ganglion cell complex (GCC) and outer retinal layers (ORL) in the macular region were calculated, and their relation with age and myopic shift was analysed with multiple linear regression analysis.ResultsThe thickness of the central foveal retinal layers was increased in children (13 years). The thickness changes in the retina, GCC and ORL decreased with age (r=−0.24,–0.23, −0.15, respectively, all pConclusionsRetinal development and its relation with myopic shift varies from childhood to adolescence. Myopia-related retinal thinning may result from less increase in the RT in childhood rather than a decrease in RT in adolescents. Children under 9 years old could be at a critical age for future myopia-related retinal thinning.

Background/aimsThe primary aim of this study was to describe the causes of de novo uveitis in individuals 60 years and older. Secondary objectives were to determine the incidence of intraocular lymphoma and the clinical predictors of lymphoma.MethodsRetrospective chart review of all subjects presenting to the uveitis service at Auckland District Health Board (Auckland, New Zealand) between January 2006 and October 2020Results686 subjects (900 eyes) were aged ≥60 years at first presentation with uveitis, representing 23.4% of all subjects with uveitis during the study period. Non-infectious aetiology occurred in 631 (70.1%) eyes and infectious etiologies occurred in 269 (29.9%) eyes. The most frequent causes were idiopathic (36.3%), herpes zoster (14.8%), HLAB27 (8.7%) and sarcoidosis (4.8%). Twenty (2.2%) eyes of 13 (1.9%) subjects had a diagnosis of lymphoma. Lymphoma represented 11.2% of all intermediate uveitis. Subjects diagnosed with lymphoma did not develop posterior synechiae, epiretinal membrane, cystoid macular oedema or ocular hypertension.ConclusionsIntraocular lymphoma was uncommon in the overall cohort, but an important cause of intermediate uveitis. A diagnosis of lymphoma needs to be considered in any older subject with de novo intermediate uveitis. The lack of posterior synechiae, cystoid macular oedema, epiretinal membrane and ocular hypertension further increases the suspicion for lymphoma.

Background/ObjectiveAnterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) are two non-invasive imaging techniques used for the measurement of tumour thickness in corneal and bulbar conjunctival tumours. Histopathology (HP), however, remains the gold standard for the measurement of tumour thickness. The aim of this study was to determine whether AS-OCT and UBM are as accurate as HP for measuring tumour thickness.MethodsForty-two corneal and bulbar conjunctival tumours were imaged using AS-OCT and UBM. Images were assessed and tumour thickness was measured. Eleven patients subsequently underwent surgical excision. All specimens were measured during histopathological analysis. The correlation of the thickness measurement on HP to AS-OCT and UBM was then statistically analysed. In cases where the tumour was not excised, thickness measurement comparisons between AS-OCT and UBM were analysed.ResultsAS-OCT and UBM measurements of tumour thickness were found to be significantly positively correlated (p=ConclusionBoth AS-OCT and UBM are useful techniques to image and measure the thickness of corneal and conjunctival bulbar tumours. While AS-OCT provides better details than UBM, it was more limited in visualising the posterior boundary of the tumour, particularly in malignant tumours. While thickness measurements of both methodologies were correlated, neither should yet be considered as replacements to the gold standard of HP.

Background/aimsOptical coherence tomography angiography (OCTA) allows the study of vessel density (VD). We intended to perform a systematic review of studies focusing on longitudinal changes in peripapillary and macular VD measurements in glaucoma.MethodsA search was performed across MEDLINE, Scopus, ISI Web of Science and Google Scholar, using the following query from inception until 20 September 2019: ((“optical coherence tomography angiography”[tiab]) OR (optical coherence tomography angiography[MeSH]) OR (“OCTA”[tiab]) OR (“OCT-A”[tiab]) OR (“angio-OCT”[tiab]) OR (“OCT- angiography”[tiab]) OR (“OCT-angio”[tiab]) OR (“OCT-angiographie”[tiab])) AND (glaucom*[tiab] OR glaucoma[MeSH]). Prospective studies that quantitatively assessed the longitudinal changes in VD in glaucoma with at least 3 months of follow-up were included.ResultsTen out of 4516 studies were included. The rate of VD change in glaucoma varied from 0.036/year to 1.08/year and 1.3% to 3.2% per year, with significantly different rates between glaucoma and healthy controls. Five studies assessed VD change after glaucoma surgery, obtaining variable results, ranging from a temporary VD decrease to increase after 3 months. Meta-analysis was not possible due to a wide variation in methods, measurements and region of VD.ConclusionOCTA is a non-invasive technology, which shows promise in glaucoma. Measures should be taken to increase the quality and standardise the methodology of VD measures in OCTA longitudinal studies, for future meta-analyses.