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AimTo investigate effect of patient age, gender, comorbidities and surgeon on refractive outcomes following cataract surgery.MethodsStudy population: patients on UK national ophthalmic cataract database on cataract operations undertaken between 1 April 2010 and 31 August 2018. Variables examined included gender, age, diabetic retinopathy, glaucoma, high myopia, inherited retinal disease, optic nerve disease, uveitis, pseudoexfoliation, vitreous opacities, retinal pathology, cataract type, previous surgery and posterior capsular rupture. A multivariate normal cross-classified model was fitted to the refractive outcome using Markov Chain Monte Carlo (MCMC) methods with diffuse priors to approximate maximum likelihood estimation. A MCMC chain was generated with a burn-in of 5000 iterations and a monitoring chain of 50 000 iterations.Results490 987 cataract operations were performed on 351 864 patients by 2567 surgeons. Myopic and astigmatic errors were associated with posterior capsule rupture (−0.38/+0.04×72), glaucoma (−0.10/+0.05×95), previous vitrectomy (−0.049/+0.03×66) and high myopia (−0.07/+0.03×57). Hyperopic and astigmatic errors were associated with diabetic retinopathy (+0.08/+0.03×104), pseudoexfoliation (+0.07/+0.01×158), male gender (+0.12/+0.05×91) and age (−0.01/+0.06×97 per increasing decade). Inherited retinal disease, optic nerve disease, previous trabeculectomy, uveitis, brunescent/white cataract had no significant impact on the error of the refractive outcome. The effect of patient gender and comorbidity was additive. Surgeons only accounted for 4% of the unexplained variance in refractive outcome.ConclusionPatient comorbidities and gender account for small but statistically significant differences in refractive outcome, which are additive. Surgeon effects are very small.

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre.Design: Randomised, double-masked, parallel-group, phase III equivalence study.Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ.Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

In this case study, we explore a case of bilateral acute angle closure (AAC) attack detected in a 52-year-old female patient with no other ophthalmic background or predisposition to angle closure, following an increase of her regular sumatriptan dose used for migraine relief. Even though the initial presentation was misinterpreted as migraine attack, it nevertheless alerted the treating physicians to immediate cessation of the drug, allowing for the pertinent ocular symptomatology to be unveiled. Drug-induced bilateral AAC is a rare occurrence and can lead to significant ocular morbidity if not detected and treated early. Clinicians of emergency care should be aware of this uncommon association, as prompt ophthalmology input is vital. Interestingly, although it would be anticipated that people prone to angle closure attack after sumatriptan intake would exhibit symptoms after initiation of the drug, our patient suffered an attack while on long-term treatment and following dose increase.

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.

AimsTo describe the incidence of postoperative cystoid macular oedema (CMO) after endothelial keratoplasty (EK) and to identify its contributory risk factors.Methods2233 patients undergoing EK at Ospedali Privati Forlì ‘Villa Igea’, between January 2005 to October 2018 for Descemet stripping automated endothelial keratoplasty (DSAEK) and June 2014 to August 2018 for Descemet membrane endothelial keratoplasty (DMEK) with a minimum follow-up of 18 months were evaluated. Univariate and multivariate analyses were conducted to identify and quantify contributory risk factors. Receiver operating characteristic (ROC) curve analysis were performed to determine ideal cut-off points of continuous variables.ResultsCMO was identified in 2.82% (n=63) of the cases. CMO occurred in 2.36% of DSAEK eyes and in 5.56% of DMEK eyes (p=0.001). Average onset of CMO was 4.27±6.63 months (range: 1–34 months) postoperatively. Compared with those who did not develop CMO, a higher proportion of patients in the CMO group had diabetes (24.2% vs 9.8%, p67 years (OR=2.35, 95% CI: 1.30 to 4.26, p=0.005) were more likely to develop CMO. There were no other significant differences between the groups.ConclusionsOlder age (>67 years), diabetes mellitus and DMEK have been identified as independent risk factors for postoperative CMO following EK. Close observation is necessary during the first postoperative year after EK, particularly in patients with risk factors.

Background/AimRecent studies have demonstrated adverse psychosocial and mental health disorders among children with ocular disorders. The mental health burden of children with simple congenital ptosis, however, is unknown. The purpose of this study was to compare the psychosocial and mental health findings of children with simple congenital ptosis with controls.MethodsThe medical records of all children (Results81 children with ptosis were diagnosed at a mean age of 3.2 years (range, 1 month–16 years), 35 (43.2%) of whom were girls. An adverse psychosocial development was diagnosed in 41 (50.6%) patients with simple congenital ptosis monitored to a mean age of 21.4 years, compared with 26 (32.5%) controls (p=0.02). A mental illness was diagnosed in 31 (38.3%) patients with ptosis compared with 16 (20%) controls (p=0.01). Children with ptosis were 2.5 times more likely than controls to develop a mental illness and 2.1 times more likely to develop a psychosocial maladjustment. Patients with ptosis were also significantly more likely to have more mental health disorders (p=0.02) and a longer duration of psychotropic medication use (p=0.005).ConclusionsChildren diagnosed with simple congenital ptosis in this population had significantly greater psychosocial and mental health morbidity compared with controls. Children with ptosis may benefit from early psychosocial intervention.

AimsTo identify the mutation spectrum and genotype–phenotype correlations offibrillin-1(FBN1) mutations in a Chinese cohort with congenital ectopia lentis (EL).MethodsPatients clinically suspected of congenital zonulopathy were screened using panel-based next-generation sequencing followed by multiplex ligation-dependent probe amplification. All the probands were subjected to thorough ocular examinations. Molecular and clinical data were integrated in pursuit of genotype–phenotype correlation.ResultsA total of 131 probands ofFBN1mutations from unrelated families were recruited. Around 65% of the probands were children younger than 9 years old. Overall, 110 distinctFBN1mutations were identified, including 39 novel ones. The most at-risk regions were exons 13, 2, 6, 15, 24 and 33 in descending order of mutation frequency. The most prevalent mutation was c.184C>T (seven, 5.34%) in the coding sequence and c.5788+5G>A (three, 2.29%) in introns. Missense mutations were the most frequent type (103, 78.63%); half of which were distributed in the N-terminal regions (53, 51.46%). The majority of missense mutations were detected in one of the calcium-binding epidermal growth factor-like domains (62, 60.19%), and 39 (62.90%) of them were substitutions of conserved cysteine residues. Microspherophakia (MSP) was found in 15 patients (11.45%). Mutations in the middle region (exons 22–42), especially exon 26, had higher risks of combined MSP (OR, 5.51 (95% CI 1.364 to 22.274), p=0.017).ConclusionsThis study extended the knowledge of theFBN1mutation spectrum and provided novel insights into its clinical correlation regarding EL and MSP in the Chinese population.

Background/aimsTumor necrosis factor alpha (TNF-⍺) inhibitors are increasingly being used to treat scleritis, however, their efficacy has not been compared to older treatments. Additionally, few studies have assessed differences in the course of scleritis among different patient groups. We identify demographic factors, comorbidities and treatments associated with the resolution of acute scleritis.MethodsThe records of patients with non-infectious anterior scleritis who presented between 1 January 2013 and 1 January 2018 were retrospectively reviewed.ResultsA total of 141 patients (169 eyes) with anterior scleritis were identified. 92.9% had diffuse anterior scleritis, 5.0% had nodular anterior scleritis and 2.1% had necrotising scleritis. Topical corticosteroids were used in 66.7% of patients, systemic non-steroidal anti-inflammatory drugs (NSAIDs) in 48.9% and systemic corticosteroids in 37.6%. Non-corticosteroid immunomodulatory therapies were required in 37.6% of patients. In a Cox proportionate hazards model, factors positively associated with the resolution of an episode of scleritis included NSAID use (HR=2.145; 95% CI 1.200 to 3.832), Hispanic race (HR=2.991; 95% CI 1.115 to 7.341) and lupus erythematous (HR=6.175; 95% CI 1.774 to 21.489). Bilateral scleritis was negatively associated with resolution (HR=0.437; 95% CI 0.196 to 0.972). TNF-⍺ inhibitors (HR=3.346; 95% CI 1.277–8.763), NSAID use (HR=2.558; 95% CI 1.383 to 4.729), lupus erythematosus (HR=5.251; 95% CI 1.478 to 18.659) and Hispanic race (HR=3.198; 95% CI 1.022 to 10.005) were significantly positively associated with steroid sparing resolution.ConclusionPatient characteristics including a lupus diagnosis and Hispanic race were associated with faster times to symptom resolution and steroid sparing resolution, as were treatments including systemic NSAIDs and TNF-⍺ inhibitors. Due to limitations in the available data, this analysis did not account for disease severity. Future prospective studies will further elucidate the relationship between these factors and patient outcomes.

BackgroundDespite the increasing use of immersive technology (IT) in ophthalmology, the effectiveness of this approach compared to other teaching practices is unclear. This systematic review aimed to determine the value of IT to teach students ophthalmic skills and whether it can supplement or replace conventional teaching practices.MethodsA systematic search was performed of CENTRAL, MEDLINE, EMBASE, ERIC and PsychINFO databases. Randomised controlled trials comparing IT interventions versus (1) no training, (2) standard training, (3) different types of IT interventions, (4) different doses of IT interventions were eligible for inclusion.ResultsSeven trials involving 177 participants were included. IT offered some benefit compared to standard training as most trials demonstrated evidence of learning represented by composite performance score and performance time. Repetitive training with IT displayed similar results.ConclusionIT appears to improve the ophthalmic skill of healthcare trainees and should be considered as a supplement to training.

PurposeTo investigate the long-term safety and efficacy of implantable collamer lens (ICL) V4c implantation and changes in the anterior lens density (ALD) in patients with myopia ≥40 years of age.MethodsThis prospective study included 104 eyes of 52 patients >40 years of age before ICL V4c implantation. Spherical equivalent (SE), uncorrected distance visual acuity, corrected distance visual acuity (CDVA), intraocular pressure, endothelial cell density, anterior chamber depth, anterior chamber volume and anterior chamber angle preoperatively, at 1 and 3 months, and at 3 years postoperatively were recorded. Pentacam HR was used to analyse ALD changes at a depth of 0.5, 1.0 and 1.5 mm within a 3 mm diameter range around the pupil’s centre.ResultsThe overall follow-up was uneventful at 42±7.1 months; the safety index at last follow-up was 1.26±0.35 and the efficacy index was 0.91±0.41. No eye lost the Snellen line of CDVA, 76% of the eyes had an increase in CDVA for ≥1 line and 62% had an SE within ±0.50 dioptre. The increase in ALD at 0.5, 1 and 1.5 mm was 16.52%±10.46%, 16.72%±9.85% and 17.28%±11.93%, respectively. Preoperative, 1-month and 3-month postoperative ALDs showed correlations with SE and age, and ALD at last follow-up was correlated only with age. There was no correlation between ALD and any other parameters.ConclusionICL V4c shows long-term safety and efficacy in people ≥40 years of age. ALD increased in such patients, which may be related to age and SE.

AimsTo recommend a list of complications of glaucoma surgery to be used in future glaucoma surgery research and reporting by exploring the spectrum of complications’ names, the variety of definitions and time frames used for reporting them in glaucoma surgical trials.MethodsComplications’ names, definitions and time frames identified from a previously conducted systematic review of glaucoma surgery trials (registration number: CRD42019121226) were reviewed. Only postoperative complications were considered. Surgical techniques described in the papers from the previous systematic review were retrieved and grouped according their mechanism of action.Reviewers independently recommended each complication’s inclusion or exclusion in a list to be proposed as a potential standard for reporting in glaucoma interventions. A literature-based definition of a ‘surgical complication’ was used to inform these decisions. Recorded complication’s details were used to inform the development of clinically relevant definitions, a consensus-driven exercise between reviewers resolved disagreements.ResultsWe identified 48/111 (43.2%) of the reported complications as suitable for inclusion, of which 17 were merged into other included complications having a broader meaning making up a final table of 32 postoperative complications. For 25 of them, the authors kept ‘names’ that were previously used in the systematic review, but provided a definition that was not mentioned in these papers. Five included complications were given both ‘names’ and definitions not previously mentioned. The authors maintained the name and definition for one complication. There were 16 complications that were in common to all the procedures retrieved from the previous review.ConclusionsWe propose a table of revised names and comprehensive definitions of postoperative complications, to simplify the process of reporting complications after glaucoma surgery and to improve consistency among surgical trials.

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.

First described in 1991 and introduced into clinical practice in 1996, optical coherence tomography (OCT) now has a very extensive role in many different areas of ophthalmological practice. It is non-invasive, cheap, highly reproducible, widely available and easy to perform. OCT also has a role in managing patients with neurological disorders, particularly idiopathic intracranial hypertension. This review provides an overview of the technology underlying OCT and the information it can provide that is relevant to the practising neurologist. Particular conditions discussed include papilloedema, optic disc drusen, multiple sclerosis and neuromyelitis optica, other optic neuropathies, compression of the anterior visual pathway and various neurodegenerative conditions.

PurposeTo explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma.DesignRetrospective, single centre case-control study.MethodsThe study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter.Results346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients’ age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion.ConclusionsThe OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

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.

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.

BackgroundTo demonstrate the efficacy and safety of intravitreal injections of conbercept versus laser photocoagulation in the treatment of diabetic macular oedema (DME).MethodsA 12-month multicentre, randomised, double-masked, double-sham, parallel controlled, phase III trial (Sailing Study), followed by a 12-month open-label extension study. Patients with centre-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata (PRN) sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Patients who entered the extension study received PRN conbercept treatment. The primary endpoint was the changes in best-corrected visual acuity (BCVA) from baseline.ResultsA total of 248 eyes were included in the full analysis set and 157 eyes continued in the extension study. Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3±12.0 letters). Patients in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.ConclusionThe use of a conbercept PRN intravitreal injection regimen improved the BCVA of patients with DME, and its efficacy was better than that of laser photocoagulations, and the same efficacy was observed when the eyes treated with laser alone were switched to conbercept.Trial registration numberNCT02194634.

BackgroundCurrent melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.MethodsRabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. Patients: retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.ResultsIntravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC90 across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%–79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (pConclusionsTaken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

With the growing popularity of lamellar keratoplasty for selective replacement of diseased corneal tissue, it is important to understand the risk of developing an infection after the procedure. Although lesser than that postpenetrating keratoplasty, the reports on post lamellar keratoplasty infectious keratitis are not negligible. Trends of acute infections arising within 2 months of surgery are a subject of interest. Most of these infections are reported post Descemet’s stripping endothelial keratoplasty with a preponderance of Candida species. A donor to host transmission of infection is not uncommon. Among the Candida cases, about 80% seem to occur due to a donor to host transmission. Infections presenting as or progressing to endophthalmitis lead to a poor visual outcome. Strict aseptic measures and protocols during corneal tissue harvesting, tissue processing, tissue storage and surgery are essential to prevent occurrence of these infections. After the infection has occurred, determining the aetiology and drug susceptibility through microbiological testing is vital. This helps to guide treatment protocols and hence determines final outcome of these cases. Most cases require some form of surgical management for resolution of infection, most often a graft removal and therapeutic keratoplasty. Secondary surgical interventions are performed to restore graft clarity and achieve a good final visual outcome.

PurposeTo compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma.MethodsRetrospective, cohort, two-centre, comparative study. Patients’ data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed.ResultsA total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; pConclusionsIntracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens.Trial registration numberISRCTN93098069.

IntroductionTo evaluate the outcomes of the superior oblique split tendon lengthening (SOSL) procedure for Brown syndrome (BS).MethodsAt a single institution, all patients who underwent SOSL surgery for BS from 2013 to 2019 were reviewed retrospectively. We looked at the surgical outcomes and complications in a total of 20 eyes of 18 patients. The superior oblique (SO) muscle was isolated and then extended. The tendon was then split centrally into equal halves. Two 6–0 polyglactin sutures were then placed on each end of the split tendon 6–10 mm apart. To complete the Z-cut, the split tendon was cut distal to the preplaced sutures. The sutures were then tied to produce the split Z-tendon lengthening.ResultsEleven (55%) out of 20 eyes were female patients. The mean age was 6.6 years (range 2–17 years). The mean follow-up was 26.8 months (range 5–72 months). The mean degree of preoperative limitation of elevation on adduction was −3.6±0.58 preoperatively and −0.75±1.25 postoperatively (p=0.0001). Preoperatively, the mean degree of vertical deviation at near was 3.5±7.62 and at distance was 3.10±7.84 prism diopters (PD), respectively. Postoperatively, the mean vertical deviation was 2.77±4.75 and 2.10±4.08 PD at near and distance, respectively. Postoperative complications included haematoma in one patient (5%), overcorrection in two patients (10%) and one patient required reoperation (5%).ConclusionSOSL is a safe procedure that surgeons can consider in managing patients with BS.

AimWe report two cases of endothelial corneal allograft rejection following immunisation with SARS-CoV-2 messenger RNA (mRNA) vaccine BNT162b2 and describe the implications for management of transplant recipients postvaccination for COVID-19.MethodsA 66-year-old woman with Fuchs endothelial corneal dystrophy (FECD) and a unilateral Descemet’s membrane endothelial keratoplasty (DMEK) transplant received COVID-19 mRNA vaccine BNT162b2 14 days post-transplant. Seven days later, she presented with symptoms and signs of endothelial graft rejection. An 83-year-old woman with bilateral DMEK transplants for FECD 3 and 6 years earlier developed simultaneous acute endothelial rejection in both eyes, 3 weeks post second dose of COVID-19 mRNA vaccine BNT162b2. Rejection in both cases was treated successfully with topical corticosteroids.ConclusionsWe believe this is the first report of temporal association between corneal transplant rejection following immunisation against COVID-19 and the first report of DMEK rejection following any immunisation. We hypothesise that the allogeneic response may have been initiated by the host antibody response following vaccination. Clinicians and patients should be aware of the potential of corneal graft rejection associated with vaccine administration and may wish to consider vaccination in advance of planned non-urgent keratoplasties. Patients should be counselled on the symptoms and signs that require urgent review to allow early treatment of any confirmed rejection episode.

BackgroundAutosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).MethodsTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.ResultsA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.ConclusionTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.

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.

ObjectiveTo investigate the concordance between aqueous and vitreous tap culture results among different types of bacterial endophthalmitis.Methods and analysisThis retrospective cohort analysis included all cases diagnosed with endophthalmitis at Moorfields Eye Hospital between January 2008 and March 2020. Aqueous and vitreous samples obtained simultaneously at presentation. Samples were evaluated for sensitivity, specificity, negative and positive predictive values.ResultsA total of 217 patients (217 eyes) were included in the study. Postsurgical endophthalmitis was the most common type of endophthalmitis and diagnosed in 35.9% of the cases. The rate of positive culture results was 32.2% from vitreous tap and 21.7% from aqueous tap. The culture yield through vitreous sampling was 15.7% when aqueous culture results were negative, and in 5.1%, the aqueous sample was positive when the vitreous tap results were negative. Considering the vitreous tap as the gold standard, aqueous sample culture results showed a statistically significant high specificity and positive predictive values in cases of postsurgical endophthalmitis, late-onset endophthalmitis associated with glaucoma procedures, postintravitreal injection and endophthalmitis associated with bacterial keratitis. Coagulase Negative Staphylococcus was the most common organism isolated from vitreous and aqueous samples.ConclusionsEven though the sensitivity and specificity of aqueous tap are low, our results show that in a few cases it identified important organisms, otherwise missed by vitreous sampling alone. Culture of vitreous sample remains the gold standard for isolation of pathogen in bacterial endophthalmitis, but aqueous samples should also be obtained as an adjunct for the diagnosis.

AimTo characterise clinical outcomes following selective laser trabeculoplasty (SLT) in eyes of Afro-Caribbean patients with open-angle glaucoma (OAG) at high risk for progression.MethodsIn a prospective interventional case series, patients meeting high-risk criteria (advanced disease, unilateral glaucoma blindness, inadequate intraocular pressure (IOP) on >2 medications, recent progression on medications, inability to administer, afford or tolerate medications) underwent bilateral 360° SLT and managed based on their subsequent clinical course. Patient-specific indications for SLT—IOP reduction (IOP group) or reduced reliance on medical therapy (MED group)—were recorded before treatment. IOP and medication use were recorded every 3–4 months through up to 24 months of follow-up. Outcomes were analysed separately in the IOP and MED groups.ResultsAmong 33 right eyes (left eye outcomes were similar) in the IOP group, mean (SD) IOP was significantly reduced from 21.7 (7.5) mm Hg to 16.2–17.1 mm Hg over follow-up (p<0.0177); medication use remained unchanged (p>0.05) at all time points. Among 36 right eyes in the MED group, mean medication use was 1.9 (0.9) at baseline and ranged from 1.2 to 1.4 medications per eye through follow-up (p<0.0033), and mean IOP was significantly reduced at months 1–6 (to 13.1 (2.3) mm Hg, p=0.0013), months 13–18 (to 14.3 (2.8), p=0.0136) and unchanged at other time points. No vision-threatening adverse events occurred.ConclusionsAfro-Caribbean patients with OAG at risk for progression can achieve clinically and statistically significant reductions in IOP or medications through up to 24 months following a single 360° SLT treatment.Trial registration numberNCT02375009.

BackgroundPatient-reported outcome measures (PROMs) are increasingly used in paediatric ophthalmology. However, little is known about the distribution of PROM scores among children and young people with visual impairment.AimTo investigate the distributions and predictors of scores on the VQoL_CYP (measuring vision-related quality of life) and FVQ_CYP (measuring functional vision).MethodsChildren and young people aged 8–18 years, with visual impairment/blindness (logarithm of the minimum angle of resolution (LogMAR) worse than 0.48 in the better eye, and/or eligible visual field restriction) completed the VQoL_CYP and FVQ_CYP at home or Great Ormond Street Hospital, London, UK. Associations between VQoL_CYP and FVQ_CYP scores and sociodemographic and clinical factors were analysed using multiple linear regression models.ResultsAmong 93 participants, VQoL_CYP scores ranged from 36.6 to 78.2 (mean=57.9, SD=8.1). FVQ_CYP scores ranged from 23.5 to 70.3 (mean=48.3, SD=10.1). Only 0.4% of the variation in VQoL_CYP scores was explained, with no associations with the variables of interest. By contrast, 21.6% of the variation in FVQ_CYP scores was explained, with a gradient of worse acuity (pDiscussionSelf-rated vision-related quality of life and functional vision are not readily predicted from sociodemographic or clinical characteristics that ophthalmologists measure/record. Routine use of PROMs in clinical practice can offer important insights. Use in research can provide valuable measures of effectiveness of interventions. The reference values provided will aid interpretation in both settings.

BackgroundChalazia are common inflammatory eyelid lesions, but their epidemiology remains understudied. This retrospective case–control study examined the prevalence, risk factors and geographic distribution of chalazia in a large veteran population.MethodsData on all individuals seen at a Veterans Affairs (VA) clinic between October 2010 and October 2015 were extracted from the VA health database. Subjects were grouped based on International Classification of Diseases, Ninth Revision (ICD-9) code for chalazion. Univariable logistic regression modelling was used to identify clinical and demographic factors associated with chalazion presence, followed by multivariable modelling to examine which factors predicted risk concomitantly. All cases were mapped across the continental US using geographic information systems modelling to examine how prevalence rates varied geographically.ResultsOverall, 208 720 of 3 453 944 (6.04%) subjects were diagnosed with chalazion during the study period. Prevalence was highest in coastal regions. The mean age of the population was 69.32±13.9 years and most patients were male (93.47%), white (77.13%) and non-Hispanic (93.72%). Factors associated with chalazion risk included smoking (OR=1.12, pConclusionPeriocular skin, eyelid margin and tear film abnormalities were most strongly associated with risk for chalazion. The impact of environmental conditions on risk for chalazion represents an area in need of further study.

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.

Background/aimsTo determine if nasolacrimal massage or topical antibiotics are associated with higher rates of resolution compared with observation alone in a population-based cohort of infants with congenital nasolacrimal duct obstruction (CNLDO).MethodsThe medical records of all children ResultsAmong 1958 infants diagnosed and followed for CNLDO, 516 (26.4%) were merely observed, 506 (25.8%) were prescribed massage alone, 485 (24.8%) were prescribed at least one course of topical antibiotics, 397 (20.3%) were prescribed both topical antibiotics and massage, and 54 (2.8%) had no documented therapy. Non-surgical resolution, occurring in 1669 (85.2%) during a median follow-up of 3.1 months (range: 1 week–248 months), was 74.6% for the merely observed, 89.7% for those prescribed digital massage, 87.0% for those prescribed antibiotics and 90.7% for those treated with both. This comparison was significant in unadjusted (pConclusionPrescribing topical antibiotics or digital massage for infants with CNLDO in this cohort, individually or in combination, was associated with a higher rate of spontaneous resolution than observation alone.

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/aimsObesity is a well-known risk factor for diabetes, but its association with diabetic retinopathy (DR) is inconclusive, in particular in Asians. We aimed to assess whether body mass index (BMI) is associated with the presence and severity of DR in Asian populations with diabetes.MethodsPooled analysis of individual-level cross-sectional data from 10 010 adults with diabetes who participated in 12 population-based studies conducted in China, India, Japan, Russia (Asian), Singapore and South Korea that were part of the Asian Eye Epidemiology Consortium (AEEC). BMI was calculated as weight in kilograms divided by height in square metres and categorised into normal (2, reference), overweight (25–29.9 kg/m2) and obese (≥30 kg/m2). Any-DR (n=1669) and vision-threatening DR (VTDR, n=489) were assessed from digital retinal photographs and graded according to standard protocols. Each study was analysed separately using multivariable logistic regression models adjusted for age, sex, haemoglobin A1c%, systolic blood pressure and diabetes duration, and the estimated odds ratios (ORs) and 95% confidence interval (CIs) from all studies were then combined using random-effects models.ResultsIn multivariable models, obesity showed a significant inverse association with any-DR (pooled OR (95% CI) =0.74 (0.59 to 0.91)) and VTDR (0.75 (0.60 to 0.93)). Similarly, in continuous analysis, BMI showed a significant inverse association with both any-DR (0.93 (0.87 to 0.99)) and VTDR (0.79 (0.68 to 0.92) per SD increase). Overweight did not show a significant association with any-DR.ConclusionsAmong Asian adults with diabetes, both BMI and obesity showed an inverse association with DR. These findings warrant confirmation in further longitudinal studies.

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.

BackgroundLimited data are available on glaucoma surgical trends in Australia.MethodsNationwide study of glaucoma surgery in Australia over 17-year period from 2001 to 2018. The Australian Institute of Health, Welfare and Ageing hospitalisation database was used to review age- and gender-specific trends in glaucoma surgeries from 2001 to 2018 in Australian public and private hospitals.ResultsAlthough there was an increase in the absolute number of trabeculectomy procedures from 2926 to 3244 over the 17-year study period, this represented a decline in the age-standardised and gender-standardised number of trabeculectomy procedures from 15.1 to 13.2 procedures per 100 000 persons. However, during this same period, there was a dramatic increase in the number of glaucoma drainage devices (GDD) from 119 to 3262 procedures, representing an age-standardised and gender-standardised increase from 0.6 to 13.3 procedures per 100 000 persons. Negative binomial regression analysis revealed a decrease in trabeculectomy procedures of 1.1% per year, while there was increase in GDD insertions of 16.3% per year (p60 years, compared with stable or increasing rates in younger age groups. GDD insertion rates demonstrated a progressively greater increase in older compared with younger age groups.ConclusionOur findings demonstrate changing trends in the surgical management of advanced glaucoma in Australia, likely reflecting updated evidence regarding the role of GDD surgeries.

BackgroundLargest basal diameter (LBD) appears to have independent prognostic value in uveal melanoma (UM).MethodsAll patients undergoing plaque brachytherapy or enucleation for UM involving the choroid and/or ciliary body between 2012 and 2019.ResultsA total of 348 patients with a mean age of 60±14 years were included and followed for a mean of 40±26 months (3.3±2.2 years). On multivariate analysis, LBD >12 mm remained a significant independent predictor of metastasis for both class 1 (HR 21.90; 95% CI 2.69 to 178.02; p=0.004) and class 2 (HR 2.45; 95% CI, 1.03 to 5.83; p=0.04) tumours. Four prognostic groups were created: group 1 (class 1, LBD ConclusionsCombination of GEP and LBD allows separation of patients into four easy-to-use prognostic groups and was similar to a model combining AJCC stage with GEP.

PurposeTo compare the efficacy of aflibercept using a personalised versus fixed regimen in treatment-naïve participants with polypoidal choroidal vasculopathy (PCV).DesignA 52-week, randomised, open-label, non-inferiority, single-centre study that included participants with symptomatic PCV. Participants were randomised (3:1 ratio) to receive either personalised (n=40) or fixed 8-weekly treatment regimen (n=13). The personalised regimen allowed for either early treat and extend (T&E) after week 12 or late T&E with 3 additional 4-weekly aflibercept injections until week 24 in participants with residual polypoidal lesions (PL) on indocyanine green angiography (ICGA) at week 12.Main outcomes and measuresNon-inferiority of personalised to fixed regimen for mean change in best-corrected visual acuity (BCVA) from baseline to week 52 (non-inferiority margin: −5 letters). The key secondary outcomes include reduction in central subfield thickness (CSFT) on optical coherence tomography and the anatomical closure of PL on ICGA.ResultsOf the 53 participants, the mean (SD) age was 69.2 (8.1) years, 19 (35.8 %) were male. Personalised group was non-inferior to fixed for the primary end point (+8.1 vs +7.9 letters at week 52, respectively; difference 0.16, 95% CI −2.8 to 2.4, p=0.79). There was greater reduction in mean CSFT (SD) in the personalised versus fixed group (−248.8 (169.9) vs −164.8 (148.9) µm, p=0.03). Closure of PL occurred in 21 (55.2%) and 5 (41.6%) of study eyes in personalised and fixed groups, respectively at week 52 (p=0.41).ConclusionsPersonalised regimen achieved non-inferior BCVA gain and numerically higher PL closure compared with fixed regimen.Trial registration numberNCT03117634.

PurposeTo evaluate local and systemic safety of suprachoroidal (SC) triamcinolone acetonide injectable suspension (CLS-TA) injections in subjects with non-infectious uveitis (NIU).DesignOpen-label, prospective multicentre safety study.ParticipantsThirty-eight subjects with NIU, with and without macular oedema (MO).MethodsTreatment consisted of two suprachoroidal injections of CLS-TA 4 mg, 12 weeks apart. Best-corrected visual acuity (BCVA), adverse event (AE) assessment, ophthalmic examinations and optical coherence tomography (OCT) were conducted every 4 weeks for 24 weeks. Blood samples were analysed for plasma triamcinolone acetonide (TA) concentrations.Main outcome measuresThe main outcome measure was frequency of AEs. Other endpoints included plasma TA concentrations, change in signs of inflammation, BCVA and retinal central subfield thickness (CST).ResultsBased on a CST of >300 µm, 20 out of 38 subjects had MO at baseline. Mean intraocular pressure (IOP) was 13.3 mm Hg at baseline and 15.2 mm Hg at week 24 in the study eye. A total of six (15.8%) subjects had an IOP rise >10 mm Hg compared with baseline, in the study eye, and two (5.3%) subjects had IOP >30 mm Hg (maximum 34 mm Hg at week 8 and 38 mm Hg at week 20). Cataract formation AEs were reported in four study eyes; one of which was deemed treatment-related. No serious ocular AEs in the study eye occurred in the study. Quantifiable post-injection TA plasma concentration was ConclusionsSuprachoroidally administered CLS-TA was safe and well tolerated over the 24-week, open-label study in NIU subjects with and without MO.

Background/aimLaser photocoagulation is less invasive than chemotherapy (systemic, intra-arterial or periocular) and brachytherapy. We studied the safety and efficacy of laser as primary monotherapy for discrete retinoblastoma with well-defined borders and attached retina.MethodsA single-institution retrospective non-comparative review (2004–2018) of discrete retinoblastoma tumours managed with primary laser (532 or 810 nm wavelength, 0.5–1 s duration and power titrated until desired tumour whitening). Efficacy was evaluated by tumour long-term stability avoiding non-laser therapies. Safety was evaluated by frequency of laser-related complications and uncontrollable tumour progression.ResultsEligible were 112 tumours in 55 eyes of 44 patients. Laser monotherapy (median 2 sessions) achieved initial remission in 95/112 (85%) tumour. Initial encircling only laser photocoagulation was associated with tumour progression (9/11, one tumour had vitreous seeding) compared with direct or combined photocoagulation techniques (0/94 and 0/7 tumours, respectively, p3 DD achieved long-term stability with laser monotherapy (pConclusionsDiscrete retinoblastoma ≤3 DD can be effectively and safely managed with laser monotherapy, sparing a significant proportion of patients/eyes from more invasive therapies.

Background/aimsTo determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4–11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.MethodsRetrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.ResultsA total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.ConclusionWe found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.

Background/AimGlaucoma accounts for 8% of global blindness and surgery remains an important treatment. We aimed to determine the impact of adding simulation-based surgical education for glaucoma.MethodsWe designed a randomised controlled, parallel-group trial. Those assessing outcomes were masked to group assignment. Fifty-one trainee ophthalmologists from six university training institutions in sub-Saharan Africa were enrolled by inclusion criteria of having performed no surgical trabeculectomies and were randomised. Those randomised to the control group received no placebo intervention, but received the training intervention after the initial 12-month follow-up period. The intervention was an intense simulation-based surgical training course over 1 week. The primary outcome measure was overall simulation surgical competency at 3 months.ResultsTwenty-five were assigned to the intervention group and 26 to the control group, with 2 dropouts from the intervention group. Forty-nine were included in the final intention-to-treat analysis. Surgical competence at baseline was comparable between the arms. This increased to 30.4 (76.1%) and 9.8 (24.4%) for the intervention and the control group, respectively, 3 months after the training intervention for the intervention group, a difference of 20.6 points (95% CI 18.3 to 22.9, pConclusionThese results support the pursuit of financial, advocacy and research investments to establish simulation surgery training units and courses including instruction, feedback, deliberate practice and reflection with outcome measurement to enable trainee glaucoma surgeons to engage in intense simulation training for glaucoma surgery.Trial registration numberPACTR201803002159198.

BackgroundSingleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2.MethodsFamilies underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed.ResultsWe have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin.ConclusionsThese results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.

PurposeWe described the 6-year incidence and changes of retinopathy, and their associated risk factors in a multi-ethnic Asian population without diabetes.MethodsWe included 4374 participants with non-diabetes from a population-based cohort, the Singapore Epidemiology of Eye Disease Study, with gradable retinal photographs at baseline and 6-year follow-up visit. Retinopathy was assessed according to the modified Airlie House classification system.ResultsOver the 6-year period, the cumulative rates were 2.5% (106/4279) for retinopathy incidence, 1.0% (1/95) for retinopathy progression and 68.4% (65/95) for retinopathy regression. In multivariable analysis, higher diastolic blood pressure (DBP) (risk ratio (RR)=1.02; 95% CI: 1.00 to 1.04; per 10 mm Hg increase in DBP) and wider retinal arteriolar calibre (RR=1.36; 95% CI: 1.13 to 1.63; per SD increase in central retinal artery equivalent) were associated with higher risk of incident retinopathy, while higher level of high-density lipoprotein (HDL) was associated with lower risk of incident retinopathy (RR=0.56; 95% CI: 0.32 to 0.99; per mmol/L increase in HDL). Compared with Chinese, Malays were more likely to have retinopathy regression (RR=1.63; 95% CI: 1.20 to 2.22), while overweight (RR=0.47; 95% CI: 0.26 to 0.84) and higher glycosylated haemoglobin (HbA1c) level (RR=0.58; 95% CI: 0.37 to 0.93; per per cent increase in HbA1c) were associated with lower likelihood of retinopathy regression.ConclusionRisk of developing retinopathy in Asians without diabetes is generally low. However, regression of retinopathy over time is common, suggesting that these retinopathy signs may reflect subclinical reversible microvascular dysfunction. Several metabolic risk factors are associated with incidence or regression of retinopathy, suggesting that good metabolic control may still be important in the management of non-diabetic retinopathy.

Background/aimsWe previously reported that the visual field (VF) prediction model using the variational Bayes linear regression (VBLR) is useful for accurately predicting VF progression in glaucoma (Invest Ophthalmol Vis Sci. 2014, 2018). We constructed a VF measurement algorithm using VBLR, and the purpose of this study was to investigate its usefulness.Method122 eyes of 73 patients with open-angle glaucoma were included in the current study. VF measurement was performed using the currently proposed VBLR programme with AP-7700 perimetry (KOWA). VF measurements were also conducted using the Swedish interactive thresholding algorithm (SITA) standard programme with Humphrey field analyser. VF measurements were performed using the 24–2 test grid. Visual sensitivities, test–retest reproducibility and measurement duration were compared between the two algorithms.ResultMean mean deviation (MD) values with SITA standard were −7.9 and −8.7 dB (first and second measurements), whereas those with VBLR-VF were −8.2 and −8.0 dB, respectively. There were no significant differences across these values. The correlation coefficient of MD values between the 2 algorithms was 0.97 or 0.98. Test–retest reproducibility did not differ between the two algorithms. Mean measurement duration with SITA standard was 6 min and 02 s or 6 min and 00 s (first or second measurement), whereas a significantly shorter duration was associated with VBLR-VF (5 min and 23 s or 5 min and 30 s).ConclusionVBLR-VF reduced test duration while maintaining the same accuracy as the SITA-standard.

PurposeTo evaluate the effects of manuka honey eye-drops in the treatment of meibomian gland dysfunction.MethodsThis is an assessor-masked (single-blind), randomised controlled trial comparing conventional treatment group with interventional group using Optimel 16% manuka honey topical eye-drops. 59 patients were recruited to the study and randomised into two groups: one given regular lubricants and the other given Optimel 16% manuka honey eye-drops. The Standard Patient Evaluation of Eye Dryness (SPEED) score was measured at baseline and on follow-up. 4 patients were lost to follow-up. Multiple ocular surface parameters were graded from slit lamp examination by a masked assessor. Results were compared from baseline to follow-up date 3 weeks later.ResultsPatients in the conventional treatment group demonstrated minimal difference in SPEED score at 3-week follow-up (mean difference 1.087, p=0.183), which was not statistically significant. However, measurements of tear film break-up time, corneal surface stain (Oxford), lid margin, conjunctival redness, as well as meibum quality and expressibility showed significant improvements at 3 weeks (pConclusionsOptimel 16% manuka honey eye-drops showed significant improvement in symptoms and objective signs in meibomian gland dysfunction and are an effective alternative treatment for meibomian gland dysfunction.Trial registration numberNCT04457648.

PurposeTo evaluate the refractive accuracy of current intraocular lens (IOL) formulas and propose a modification in calculation of corneal power in eyes undergoing combined cataract extraction and Descemet membrane endothelial keratoplasty (DMEK).DesignRetrospective cohort study.MethodsPatients with Fuchs endothelial corneal dystrophy undergoing uncomplicated combined cataract surgery and DMEK at a single institution were included. The Hoffer Q, SRK/T, Holladay I, Barrett Universal II and Haigis formulas were compared. A modified corneal power was calculated using a thick lens equation based on anterior and posterior corneal radii and corneal thickness from Pentacam imaging. Error calculations were adjusted based on the difference in optical biometry and the modified corneal power. Mean absolute error (MAE) for each formula was compared between the corneal power modification and optical biometry corneal power.ResultsIn 86 eyes, the mean error ranged from 0.90 D for the Barrett Universal II formula to −0.10 D for the Haigis formula, with 4 of 5 formulas resulting in a mean hyperopic error. The corneal power modification resulted in a significantly lower MAE for the Hoffer Q (0.82 D), Holladay I (0.85 D), SRK/T (0.85 D) and Barrett Universal II (0.90 D) formulas compared with optical biometry corneal power for the Hoffer Q (1.02 D; pConclusionsAll formulas except the Haigis formula resulted in a hyperopic error. The corneal power modification significantly reduced error in four out of five IOL formulas.

Background/aimsTo assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP).MethodsA systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated.ResultsA total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (−3.45 (−4.77 to −2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (−0.70 (−1.83 to 0.43)) and tafluoprost (−0.41 (−1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(−1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (−0.17 (−1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%.ConclusionLBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Almost two-thirds of patients with giant cell arteritis (GCA) develop ocular symptoms and up to 30% suffer permanent visual loss. We review the three most common mechanisms for visual loss in GCA, describing the relevant ophthalmic arterial anatomy and emphasising how ophthalmoscopy holds the key to a rapid diagnosis. The short posterior ciliary arteries supply the optic nerve head, while the central retinal artery and its branches supply the inner retina. GCA has a predilection to affect branches of posterior ciliary arteries. The most common mechanism of visual loss in GCA is anterior arteritic optic neuropathy due to vasculitic involvement of short posterior ciliary arteries. The second most common cause of visual loss in GCA is central retinal artery occlusion. When a patient aged over 50 years has both anterior ischaemic optic neuropathy and a central retinal artery occlusion, the diagnosis is GCA until proven otherwise, and they should start treatment without delay. The least common culprit is posterior ischaemic optic neuropathy, resulting from vasculitic involvement of the ophthalmic artery and its pial branches. Here, the ophthalmoscopy is normal acutely, but MR imaging of the orbits usually shows restricted diffusion in the optic nerve.