Effect of Protective Measures on the Risk of SARS-CoV-2 Infection among Eye Clinic Staff Members.

BACKGROUND: Switzerland was strongly affected by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a nationwide lockdown in March 2020. Ophthalmologists were at most risk of contracting a SARS-CoV-2 infection due to their close working distance from patients. The aim of the study is to evaluate the overall effectiveness of protective measures on the risk of SARS-CoV-2 infection among employees in a large public eye hospital. MATERIAL AND METHODS: After lifting the lockdown in April 2020, standard precaution measures were taken, such as no handshaking and the use of operating face masks and a protective plastic shield on slit lamps and diagnostic devices. Only patients with no signs of SARS-CoV-2 disease were seen during the study period. Specific anti-SARS-CoV-2 IgG antibody titers were measured in eye clinic employees at the end of April 2020 (1st test phase) and in January 2021 (2nd test phase). The prevalence of SARS-CoV-2 IgG antibody titers among employees with daily patient contact was compared to staff members with no patient contact. RESULTS: The SARS-CoV-2 prevalence in employees with daily patient contact, with 0% in the 1st phase and 7.4% in the 2nd phase, was not significantly higher than the prevalence in the control group with no patient contact (0.9% in the 1st phase, p = 0.4; and 8.6% in the 2nd phase, p = 0.8). Furthermore, physicians were not at a significantly higher risk of SARS-CoV-2 infection compared to technicians, nurses, or office staff. CONCLUSIONS: This study shows that the abovementioned precaution measurements are effective in preventing transmission of SARS-CoV-2 infection in eye hospitals and enable us to resume practicing ophthalmology in a safe manner.

Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3) and central subfield thickness (CST) (µm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA. CONCLUSIONS: We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

Outcomes and costs of Ranibizumab and Aflibercept treatment in a health-service research context.

BACKGROUND: To compare anti-VEGF treatments for macular disease in terms of costs and clinical outcomes. METHODS: We identified patients suffering from macular disease and treated either with aflibercept, ranibizumab or both at the largest public eye clinic in Switzerland between January 1st and December 31st 2016 who were insured in one of the two participating health insurance companies. Clinical data were extracted from the electronic health record system. The health insurers provided the health claim costs for the ophthalmologic care and the total health care costs of each patient in the observation period. Using multivariate regression models, we assessed the monthly ophthalmologic and the monthly total costs of patients with no history of switching (ranibizumab vs. aflibercept), patients with a history of switching from ranibizumab to aflibercept, patients switching during the observation period and a miscellaneous group. We examined baseline differences in age, proportion of males, visual acuity (letters), central retinal thickness (CRT) and treatment history before entering the study. We investigated treatment intensity and compared the changes in letters and CRT. RESULTS: The analysis involved 488 eyes (361 patients), 182 on ranibizumab treatment, and 63 on aflibercept treatment, 160 eyes with a history of switching from ranibizumab to aflibercept, and 45 switchers during follow-up and 38 eyes of the miscellaneous group. Compared to ranibizumab, monthly costs of ophthalmologic treatment were slightly higher for aflibercept treatment + 175.0 CHF (95%CI: 1.5 CHF to 348.3 CHF; p = 0.048) as were the total monthly costs + 581.0 CHF (95%CI: 159.5 CHF to 1002.4 CHF; p = 0.007). Compared to ranibizumab, the monthly treatment intensity with aflibercept was similar (+ 0.057 injections/month (95%CI -0.023 to 0.137; p = 0.162), corresponding to a projected annual number of 5.4 injections for ranibizumab vs. 6.1 injections for aflibercept. During follow-up, visus dropped by 0.7 letters with ranibizumab and increased by 0.6 letters with aflibercept (p = 0.243). CRT dropped by - 14.9 µm with ranibizumab and by - 19.5 µm with aflibercept (p = 0.708). The monthly costs of all other groups examined were higher. CONCLUSION: These real-life data show that aflibercept treatment is equally expensive, and clinical outcomes between the two drugs are similar.

Colour Doppler analysis of ophthalmic vessels in the diagnosis of carotic artery and retinal vein occlusion, diabetic retinopathy and glaucoma: systematic review of test accuracy studies.

BACKGROUND: Colour Doppler analysis of ophthalmic vessels has been proposed as a promising tool in the diagnosis of various eye diseases, but the available diagnostic evidence has not yet been assessed systematically. We performed a comprehensive systematic review of the literature on the diagnostic properties of Colour Doppler imaging (CDI) assessing ophthalmic vessels and provide an inventory of the available evidence. METHODS: Eligible papers were searched electronically in (Pre) Medline, Embase and Scopus, and via cross-checking of reference lists. The minimum requirement to be included was the availability of original data and the possibility to construct a two-by-two table. Study selection, critical appraisal using the QUADAS II instrument and extraction of salient study characteristics was made in duplicate. Sensitivity and specificity was computed for each study. RESULTS: We included 11 studies (15 two-by-two tables) of moderate methodological quality enrolling 820 participants (range 30 to 118). In 44.4% participants were female (range 37-59% in specific subgroups). CDI was assessed for internal carotid stenosis, diabetic retinopathy, glaucoma, and branch or central retinal vein occlusion diagnosis. There was insufficient data to pool the results for specific illnesses. For the assessments of ophthalmic arteries, mean sensitivity was 0.69 (range 0.27-0.96) with a corresponding mean specificity of 0.83 (range 0.70-0.96). Mean sensitivity of the central retinal artery assessments was 0.58 (range 0.31-0.84) and the corresponding mean specificity was 0.82 (range 0.63-0.94). CONCLUSIONS: Robust assessments of the diagnostic value of colour Doppler analysis remain uncommon, limiting the possibilities to extrapolate its true potential for clinical practice. PROSPERO 2014:CRD42014014027.

Phototherapeutic keratectomy (PTK) for treatment of recurrent corneal erosion: Correlation between etiology and prognosis - prospective longitudinal study.

BACKGROUND: To evaluate and compare the efficacy of phototherapeutic keratectomy (PTK) for recurrent corneal erosion (RCE) caused by trauma, map-dot-fingerprint dystrophy (MDF) or instances without an established cause. METHODS: Single center prospective longitudinal study. Between January 2003 and November 2006 we treated 89 eyes of 82 patients with PTK. All patients presented with refractory RCE caused either by trauma, MDF or with no established cause. During follow-up (until May 2013), patients, treating ophthalmologists and/or family doctors were interviewed about the patients' state of health, recurrence of pain, the necessity of further treatments or the occurrence of complications. Five patients died or were lost during follow-up and were thus excluded from the analysis. Freedom of recurrence was estimated using logistic regression analysis using indicator variates for the following three etiologic groups: trauma (55 eyes), MDF (29 eyes) and idiopathic (no established cause; 5 eyes). RESULTS: Overall 89 eyes of 82 patients were followed-up. Average follow-up among failures and non-failures was 51.56 months (standard deviation (SD) 21.22, range 24 to 91) and 95.25 months (SD 15.99, range 35 to 137 months), respectively. Fifty-seven percent were female and the average age at first PTK was 45.3 years (range: 23 to 70 years). During follow-up, there were 25 recurrences and 15 of these patients received a re-PTK. Compared to patients with a traumatic cause of epithelial erosions, the likelihood of experiencing a recurrence was higher in patients with MDF [odds ratio (OR) 5.48; 95 % confidence interval (CI) 1.93 to 15.59; p = 0.001]; the OR was 8.81 (95 % CI 1.27 to 61.32; p = 0.028) for patients with an idiopathic cause. CONCLUSIONS: In view of the available evidence, we want to raise the awareness of those managing patients with MDF and idiopathic causes that, in order to control the disease, recurrent PTK treatments are expected to be necessary more often than in cases of traumatic RCE.

Comparison of Eylea® with Lucentis® as first-line therapy in patients with treatment-naïve neovascular age-related macular degeneration in real-life clinical practice: retrospective case-series analysis.

BACKGROUND: To identify differences between Ranibizumab and Aflibercept in treatment-naïve patients with neovascular age-related macular degeneration (nvAMD) in a real-life clinical setting. METHODS: We compared two groups of patients with a fairly similar prognosis either receiving Aflibercept or Ranibizumab within a pro re nata regimen for 1 year. Changes in visual acuity (letters) and central foveal thickness (CFT) and frequency of injections after completing the loading phase were evaluated using two separate multivariate mixed linear models. RESULTS: When correcting for baseline differences between the Aflibercept (11 eyes) and Ranibizumab (16 eyes) group, there was neither divergence in visual acuity (-0.97 letters (95 % CI. -6.06-4.12); p = 0.709), nor a significant difference in the reduction of CFT (-25.16 µm, 95 % CI; (-78.01-27.68); p = 0.351) between the two groups 1 year after treatment initiation. Also, the number of injection did not differ (0.04 (95 % CI; -0.16-0.09); p = 0.565). CONCLUSION: In contrast to health claims, treatment-naïve nvAMD, Ranibizumab and Aflibercept were equivalent in terms of functional and morphologic outcomes and number of injections when studied in real-life clinical practice.

Optical coherence tomography angiography analysis methods: a systematic review and meta-analysis.

Optical coherence tomography angiography (OCTA) is widely used for non-invasive retinal vascular imaging, but the OCTA methods used to assess retinal perfusion vary. We evaluated the different methods used to assess retinal perfusion between OCTA studies. MEDLINE and Embase were searched from 2014 to August 2021. We included prospective studies including ≥ 50 participants using OCTA to assess retinal perfusion in either global retinal or systemic disorders. Risk of bias was assessed using the National Institute of Health quality assessment tool for observational cohort and cross-sectional studies. Heterogeneity of data was assessed by Q statistics, Chi-square test, and I2 index. Of the 5974 studies identified, 191 studies were included in this evaluation. The selected studies employed seven OCTA devices, six macula volume dimensions, four macula subregions, nine perfusion analyses, and five vessel layer definitions, totalling 197 distinct methods of assessing macula perfusion and over 7000 possible combinations. Meta-analysis was performed on 88 studies reporting vessel density and foveal avascular zone area, showing lower retinal perfusion in patients with diabetes mellitus than in healthy controls, but with high heterogeneity. Heterogeneity was lowest and reported vascular effects strongest in superficial capillary plexus assessments. Systematic review of OCTA studies revealed massive heterogeneity in the methods employed to assess retinal perfusion, supporting calls for standardisation of methodology.

Sight threatening diabetic retinopathy in patients with macular telangiectasia type 2.

PURPOSE: Although diabetes is highly prevalent in patients with MacTel, progression to severe non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR) is rarely reported. We report multimodal imaging features of sight-threatening diabetic retinopathy (STDR) in eyes with macular telangiectasia type 2 (MacTel). METHODS: Retrospective case series of seven participants of the MacTel Study at the Moorfields Eye Hospital NHS Foundation Trust study site and one patient from the Institute of Retina and Vitreous of Londrina, Brazil. Sight threatening diabetic retinopathy was defined as severe NPDR, PDR or diabetic macular edema. RESULTS: We report imaging features of 16 eyes of eight patients (7/8, 87.5% female) with diagnoses of MacTel and type 2 diabetes mellitus with STDR. Mean (SD) age was 56 (8.3) years. Patients were followed-up for a mean time of 9.1 (4.7) years. A total of 10/16 (62.5%) eyes showed PDR and 2/16 (12.5%) eyes presented a macular epiretinal neovascularization. CONCLUSIONS: People with diabetes mellitus and MacTel may not be protected from STDR as previously reported. Although the two diseases rarely co-exist, regular monitoring for diabetic retinopathy progression is recommended according to baseline retinopathy severity grades in line with established international guidelines. The presence of MacTel may not modify extended screening intervals, but there is no current evidence. The limited case series in the literature support treatment for complications and should follow the standard of care for either condition. Due to dual pathology, reactivation may be difficult to diagnose on standard imaging and multimodal imaging is recommended.

Deep Learning Models Used in the Diagnostic Workup of Keratoconus: A Systematic Review and Exploratory Meta-Analysis.

PURPOSE: The prevalence of keratoconus in the general population is reported to be up to 1 of 84. Over the past 2 decades, diagnosis and management evolved rapidly, but keratoconus screening in clinical practice is still challenging and asks for improving the accuracy of keratoconus detection. Deep learning (DL) offers considerable promise for improving the accuracy and speed of medical imaging interpretation. We establish an inventory of studies conducted with DL algorithms that have attempted to diagnose keratoconus. METHODS: This systematic review was conducted according to the recommendations of the PRISMA statement. We searched (Pre-)MEDLINE, Embase, Science Citation Index, Conference Proceedings Citation Index, arXiv document server, and Google Scholar from inception to February 18, 2022. We included studies that evaluated the performance of DL algorithms in the diagnosis of keratoconus. The main outcome was diagnostic performance measured as sensitivity and specificity, and the methodological quality of the included studies was assessed using QUADAS-2. RESULTS: Searches retrieved 4100 nonduplicate records, and we included 19 studies in the qualitative synthesis and 10 studies in the exploratory meta-analysis. The overall study quality was limited because of poor reporting of patient selection and the use of inadequate reference standards. We found a pooled sensitivity of 97.5% (95% confidence interval, 93.6%-99.0%) and a pooled specificity of 97.2% (95% confidence interval, 85.7%-99.5%) for topography images as input. CONCLUSIONS: Our systematic review found that the overall diagnostic performance of DL models to detect keratoconus was good, but the methodological quality of included studies was modest.

Comparison of Endophthalmitis Rates after Alcohol-Based Chlorhexidine and Povidone-Iodine Antisepsis for Intravitreal Injections.

OBJECTIVE: Intravitreal injections (IVIs) are the most frequently performed intraocular procedure in Canada. Povidone-iodine (PI) is the current gold standard for antisepsis for IVI and is widely used; chlorhexidine (CH) is a possible alternative antiseptic agent. This study aims to compare rates of endophthalmitis after IVI with 0.05% chlorhexidine with a 4% alcohol base antisepsis to rates of endophthalmitis after IVI with 10% PI antisepsis. DESIGN: Retrospective cohort study. SUBJECTS: Eyes that received IVI between May 2019 and October 2022 at a group retina practice in Edmonton, Canada. METHODS: Eyes at a single center received focal conjunctival application of either 10% PI antisepsis or 0.05% CH in 4% alcohol antisepsis for 30 seconds before each IVI. MAIN OUTCOME MEASURE: Rates of endophthalmitis between the PI and CH groups. RESULTS: A total of 170 952 IVIs were performed during the study period. A total of 31 135 were performed using CH prophylaxis compared with 139 817 with PI prophylaxis. Among all IVIs there were 49 total cases of endophthalmitis, 29 in the PI group (0.021%) and 20 in the CH group (0.064%). There was a statistically significant difference in the rates of endophthalmitis between the 2 groups (P < 0.001). The odds ratio for developing endophthalmitis with CH antisepsis was 3.1 (95% confidence interval, 1.9-5.2) compared with PI antisepsis. There were increased odds of developing endophthalmitis with aflibercept injection compared with bevacizumab (odds ratio, 3.48; 95% confidence interval, 2.09-7.24). CONCLUSIONS: There is a statistically significant difference in rates of endophthalmitis between alcohol-based CH and PI antisepsis for IVI in our patient population utilizing the methods discussed. In our center, alcohol-based CH is now considered a second-line antiseptic agent. Further studies are warranted to further assess the endophthalmitis rate utilizing these 2 antiseptic agents. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Deep-learning automated quantification of longitudinal OCT scans demonstrates reduced RPE loss rate, preservation of intact macular area and predictive value of isolated photoreceptor degeneration in geographic atrophy patients receiving C3 inhibition treatment.

OBJECTIVE: To evaluate the role of automated optical coherence tomography (OCT) segmentation, using a validated deep-learning model, for assessing the effect of C3 inhibition on the area of geographic atrophy (GA); the constituent features of GA on OCT (photoreceptor degeneration (PRD), retinal pigment epithelium (RPE) loss and hypertransmission); and the area of unaffected healthy macula.To identify OCT predictive biomarkers for GA growth. METHODS: Post hoc analysis of the FILLY trial using a deep-learning model for spectral domain OCT (SD-OCT) autosegmentation. 246 patients were randomised 1:1:1 into pegcetacoplan monthly (PM), pegcetacoplan every other month (PEOM) and sham treatment (pooled) for 12 months of treatment and 6 months of therapy-free monitoring. Only participants with Heidelberg SD-OCT were included (n=197, single eye per participant).The primary efficacy endpoint was the square root transformed change in area of GA as complete RPE and outer retinal atrophy (cRORA) in each treatment arm at 12 months, with secondary endpoints including RPE loss, hypertransmission, PRD and intact macular area. RESULTS: Eyes treated PM showed significantly slower mean change of cRORA progression at 12 and 18 months (0.151 and 0.277 mm, p=0.0039; 0.251 and 0.396 mm, p=0.039, respectively) and RPE loss (0.147 and 0.287 mm, p=0.0008; 0.242 and 0.410 mm, p=0.00809). PEOM showed significantly slower mean change of RPE loss compared with sham at 12 months (p=0.0313). Intact macular areas were preserved in PM compared with sham at 12 and 18 months (p=0.0095 and p=0.044). PRD in isolation and intact macula areas was predictive of reduced cRORA growth at 12 months (coefficient 0.0195, p=0.01 and 0.00752, p=0.02, respectively) CONCLUSION: The OCT evidence suggests that pegcetacoplan slows progression of cRORA overall and RPE loss specifically while protecting the remaining photoreceptors and slowing the progression of healthy retina to iRORA.

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months.

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

System usability, user satisfaction and long-term adherence to mobile hyperacuity home monitoring-prospective follow-up study.

PURPOSE: To evaluate the usability and long-term adherence to the mobile hyperacuity app Alleye in patients with retinal pathology. METHODS: We enroled 72 patients (95 eyes) mainly treated for wet AMD (48/95; 50.5%). We calculated changes of clinical characteristics and the System Usability Score (SUS), and personal ratings of usefulness and number of tests performed per month at a follow-up visit of eighteen months. RESULTS: At baseline, mean best corrected visual acuity (BCVA) was 74.9 letters (SD 14.8), mean age was 69.9 (SD 11.4) and 39/72 (54.2%) were female. Of included patients, 47/72 (65.2%) reported to use mobile devices daily. The retention rate until last follow-up was 73.6 % (53/72). The median SUS score at baseline was 90 (interquartile range (IQR) 82.5-95) and 92.5 (IQR 82.5-95) in the follow-up. No association between changes of SUS and clinical characteristics was seen. At baseline, 76.4% (55/72) stated that they would recommend the app to a friend, 83.3% (60/72) were very satisfied with the app and 58/72 (80.6%) of respondents said they trusted the app. These assessments remained similar among patients remaining on the program until the follow-up. Patients who dropped out of the study (n = 19) did not differ in age, gender, BCVA, and SUS at baseline, but stated that they did not use the mobile device daily (Odds Ratio 7.40 (95%CI: 2.32-23.65); p = 0.001). CONCLUSIONS: The majority of users willing to perform home monitoring with the Alleye app are satisfied with the usability and have a positive attitude towards its trustworthiness and usefulness.

Transforming ophthalmology in the digital century-new care models with added value for patients.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Visual and Anatomical Outcomes of a Single Intravitreal Dexamethasone in Diabetic Macular Edema: An 8 Year Real-World Study.

IMPORTANCE: Diabetic macular edema (DME) is a major cause of vision loss in patients with diabetes mellitus. Intravitreal dexamethasone is a treatment option for patients unsuitable for or non-responsive to anti-angiogenic agents. OBJECTIVE: To quantify visual and anatomical outcomes from an initial intravitreal dexamethasone injection over the expected 6-month period of dexamethasone release by the implant. Design and enrolment: This is a retrospective cohort study using electronic medical records of patients reviewed between 1 January 2012 and 1 April 2022. SETTING: A tertiary eye-care center in London, United Kingdom; Moorfields Eye Hospital National Healthcare System Foundation Trust. PARTICIPANTS: The cohort comprised 418 adult patients with DME who received an initial treatment of 700 µg intravitreal dexamethasone in the study period. Of these, 240 patients met the inclusion criteria of ≥2 hospital visits following initial injection (≥1 beyond 6 months) and no previous ocular corticosteroid treatment or missing assessment at baseline. EXPOSURE(S): Intravitreal dexamethasone implant (700 µg). MAIN OUTCOME(S) AND MEASURE(S): Probability of a positive visual outcome, defined as ≥5 or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS)-letter gain after treatment when compared to baseline (Kaplan-Meier models). RESULTS: From the initial intravitreal dexamethasone injection alone, we observed a >75% chance of gaining ≥5 ETDRS letters and >50% chance of gaining ≥10 ETDRS letters within 6 months. There was less than a 50% chance of sustaining either positive visual outcome beyond 4 months. CONCLUSIONS AND RELEVANCE: Most patients can be expected to have a positive visual outcome following an initial injection of dexamethasone implants that subsides within 4 months. Real-world re-treatment was observed to be delayed until after visual benefits were lost in half of the cohort. Further research will be needed to study the effects of delays in re-treatment.

Evaluating the Effects of C3 Inhibition on Geographic Atrophy Progression from Deep-Learning OCT Quantification: A Split-Person Study.

INTRODUCTION: To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification. METHODS: A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12 months. SD-OCT scans of study and fellow eyes taken at baseline and 12 months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye. RESULTS: Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm2; P = 0.003), PRD (0.739 vs. 1.23 mm2; P = 0.015), RPE-loss (0.789 vs. 1.17 mm2; P = 0.007) and intact macula (- 0.735 vs. - 1.29 mm2; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21). CONCLUSIONS: Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF. TRIAL REGISTRATION: Clinical Trials identifier: NCT02503332.

Development and international validation of custom-engineered and code-free deep-learning models for detection of plus disease in retinopathy of prematurity: a retrospective study.

BACKGROUND: Retinopathy of prematurity (ROP), a leading cause of childhood blindness, is diagnosed through interval screening by paediatric ophthalmologists. However, improved survival of premature neonates coupled with a scarcity of available experts has raised concerns about the sustainability of this approach. We aimed to develop bespoke and code-free deep learning-based classifiers for plus disease, a hallmark of ROP, in an ethnically diverse population in London, UK, and externally validate them in ethnically, geographically, and socioeconomically diverse populations in four countries and three continents. Code-free deep learning is not reliant on the availability of expertly trained data scientists, thus being of particular potential benefit for low resource health-care settings. METHODS: This retrospective cohort study used retinal images from 1370 neonates admitted to a neonatal unit at Homerton University Hospital NHS Foundation Trust, London, UK, between 2008 and 2018. Images were acquired using a Retcam Version 2 device (Natus Medical, Pleasanton, CA, USA) on all babies who were either born at less than 32 weeks gestational age or had a birthweight of less than 1501 g. Each images was graded by two junior ophthalmologists with disagreements adjudicated by a senior paediatric ophthalmologist. Bespoke and code-free deep learning models (CFDL) were developed for the discrimination of healthy, pre-plus disease, and plus disease. Performance was assessed internally on 200 images with the majority vote of three senior paediatric ophthalmologists as the reference standard. External validation was on 338 retinal images from four separate datasets from the USA, Brazil, and Egypt with images derived from Retcam and the 3nethra neo device (Forus Health, Bengaluru, India). FINDINGS: Of the 7414 retinal images in the original dataset, 6141 images were used in the final development dataset. For the discrimination of healthy versus pre-plus or plus disease, the bespoke model had an area under the curve (AUC) of 0·986 (95% CI 0·973-0·996) and the CFDL model had an AUC of 0·989 (0·979-0·997) on the internal test set. Both models generalised well to external validation test sets acquired using the Retcam for discriminating healthy from pre-plus or plus disease (bespoke range was 0·975-1·000 and CFDL range was 0·969-0·995). The CFDL model was inferior to the bespoke model on discriminating pre-plus disease from healthy or plus disease in the USA dataset (CFDL 0·808 [95% CI 0·671-0·909, bespoke 0·942 [0·892-0·982]], p=0·0070). Performance also reduced when tested on the 3nethra neo imaging device (CFDL 0·865 [0·742-0·965] and bespoke 0·891 [0·783-0·977]). INTERPRETATION: Both bespoke and CFDL models conferred similar performance to senior paediatric ophthalmologists for discriminating healthy retinal images from ones with features of pre-plus or plus disease; however, CFDL models might generalise less well when considering minority classes. Care should be taken when testing on data acquired using alternative imaging devices from that used for the development dataset. Our study justifies further validation of plus disease classifiers in ROP screening and supports a potential role for code-free approaches to help prevent blindness in vulnerable neonates. FUNDING: National Institute for Health Research Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and the University College London Institute of Ophthalmology. TRANSLATIONS: For the Portuguese and Arabic translations of the abstract see Supplementary Materials section.

Re-evaluating diabetic papillopathy using optical coherence tomography and inner retinal sublayer analysis.

BACKGROUND/OBJECTIVES: To re-evaluate diabetic papillopathy using optical coherence tomography (OCT) for quantitative analysis of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell layer (mGCL) and inner nuclear layer (mINL) thickness. SUBJECTS/METHODS: In this retrospective observational case series between June 2008 and July 2019 at Moorfields Eye hospital, 24 eyes of 22 patients with diabetes and optic disc swelling with confirmed diagnosis of NAION or diabetic papillopathy by neuro-ophthalmological assessment were included for evaluation of the pRNFL, mGCL and mINL thicknesses after resolution of optic disc swelling. RESULTS: The mean age of included patients was 56.5 (standard deviation (SD) ± 14.85) years with a mean follow-up duration of 216 days. Thinning of pRNFL (mean: 66.26, SD ± 31.80 µm) and mGCL (mean volume: 0.27 mm3, SD ± 0.09) were observed in either group during follow-up, the mINL volume showed no thinning with 0.39 ± 0.05 mm3. The mean decrease in visual acuity was 4.13 (SD ± 14.27) ETDRS letters with a strong correlation between mGCL thickness and visual acuity (rho 0.74, p < 0.001). CONCLUSION: After resolution of acute optic disc swelling, atrophy of pRNFL and mGCL became apparent in all cases of diabetic papillopathy and diabetic NAION, with preservation of mINL volumes. Analysis of OCT did not provide a clear diagnostic distinction between both entities. We suggest a diagnostic overlay with the degree of pRNFL and mGCL atrophy of prognostic relevance for poor visual acuity independent of the semantics of terminology.

Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.