Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.

SIGNIFICANCE: Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services. PURPOSE: This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank. METHODS: A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics. RESULTS: The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A 1c , and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03). CONCLUSIONS: In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.

Hyper-reflective dots in optical coherence tomography imaging and inflammation markers in diabetic retinopathy.

The aim of this study is to correlate small dot hyper-reflective foci (HRF) observed in spectral domain optical coherence tomography (SD-OCT) scans of an animal model of hyperglycaemia with focal electroretinography (fERG) response and immunolabelling of retinal markers. The eyes of an animal model of hyperglycaemia showing signs of diabetic retinopathy (DR) were imaged using SD-OCT. Areas showing dot HRF were further evaluated using fERG. Retinal areas enclosing the HRF were dissected and serially sectioned, stained and labelled for glial fibrillary acidic protein (GFAP) and a microglial marker (Iba-1). Small dot HRF were frequently seen in OCT scans in all retinal quadrants in the inner nuclear layer or outer nuclear layer in the DR rat model. Retinal function in the HRF and adjacent areas was reduced compared with normal control rats. Microglial activation was detected by Iba-1 labelling and retinal stress identified by GFAP expression in Müller cells observed in discrete areas around small dot HRF. Small dot HRF seen in OCT images of the retina are associated with a local microglial response. This study provides the first evidence of dot HRF correlating with microglial activation, which may allow clinicians to better evaluate the microglia-mediated inflammatory component of progressive diseases showing HRF.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

PURPOSE: Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS: This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS: We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

Ethnic differences on long term outcomes of polypoidal choroidal vasculopathy after predominantly bevacizumab monotherapy.

BACKGROUND: A 3-year single-centre, retrospective, comparative, non-randomized cohort study to describe the long-term outcomes of treatment-naïve, Caucasian and non-Caucasian eyes with polypoidal choroidal vasculopathy (PCV) after treatment with predominantly Bevacizumab monotherapy or in combination with rescue photodynamic therapy (PDT). METHODS: Demographics, visual outcomes, optical coherence tomography (OCT) and treatment data were collected up to 3 years after the first visit. Stratified analysis according to ethnicity and baseline vision was performed to identify factors predictive of long-term visual improvement and maintenance. RESULTS: A total of 89 eyes with PCV were identified, of which 14 received rescue verteporfin PDT. There was an equal distribution between Caucasian and non-Caucasian individuals. Non-Caucasians present at a younger age (67.3 vs. 76.0 years, p = 0.002), have a higher proportion of foveal involvement (80.9%, vs.54.2% p = 0.007), choroidal hyperpermeability (50% vs 25.8%, p = 0.013) and lower baseline visual acuity (53.1 vs. 63.3 letters, p = 0.008). Mean visual acuity (VA) gain was + 8.9 letters and + 5.0 letters at 1 and 3 years of follow-up, respectively. Non-Caucasian individuals had a lower mean final visual acuity (VA) (54.7 vs. 70.5, respectively; P < 0.001) and net gain in VA (+ 2.0 vs. + 7.6 letters, p = 0.581) compared to Caucasian individuals. The mean total number of injections given over 3 years was 14. CONCLUSIONS: Most patients treated with predominantly Bevacizumab anti-vascular endothelial growth factor (VEGF) monotherapy achieved sustained visual acuity gains out to 3 years. Due to ethnic-specific differences in presenting PCV phenotypes, non-Caucasians presented with lower baseline VA and had poorer long-term visual outcomes.

One-year real-world outcomes of bevacizumab for the treatment of macular oedema secondary to retinal vein occlusion.

BACKGROUND: Bevacizumab is the only agent that many people can afford, yet there are only limited data on whether it improves macular oedema (MO) secondary to retinal vein occlusion (RVO) in real-world clinical practice. Here we studied 12-month real-world treatment outcomes of bevacizumab for RVO-related MO. METHODS: This was a multicentre, observational study analysing 12-month data from the Fight Retinal Blindness! (FRB) database. We studied treatment-naïve eyes with MO secondary to RVO commencing bevacizumab therapy between June 2009 and June 2019. Visual acuity (VA) and central subfield thickness (CST) were measured at baseline, 6 and 12 months. The primary outcome was a change in VA from baseline to 12 months. RESULTS: Two hundred and twenty treatment naive eyes were analyzed. The baseline VA for BRVO was better than CRVO (55.8 vs. 42.6 LogMAR letters) and this gap widened over the 12-month period, with a 12-month VA change of +14.0 (95% CI 11.1, 16.8) letters for BRVO and + 11.9 (95% CI 6.4, 17.4) for CRVO. The mean CST at baseline was 511 µm for BRVO and 627 µm for CRVO, falling at 12 months by -155 µm (-190, -121) in BRVO and -198 µm (-252, -145) in CRVO. The median number of injections for BRVO and CRVO completers was 7 (5, 9). CONCLUSIONS: Bevacizumab can be an effective treatment of RVO-MO in a real-world setting with outcomes approaching those reported by the seminal clinical trials. The functional and anatomical outcomes of intravitreal therapy were better for BRVO than CRVO.

Neovascular age-related macular degeneration at treatment intervals of 14 weeks or greater.

BACKGROUND: We assessed the proportion of eyes with neovascular age-related macular degeneration (nAMD) in routine clinical practice that reach ≥14 week treatment intervals and their outcomes. METHOD: We analysed data from the Fight Retinal Blindness! (FRB!) Project database, a prospectively designed registry of 'real-world' outcomes. Treatment-naive eyes starting vascular endothelial growth factor (VEGF) inhibitors for nAMD from 1st January 2006 were included. Eyes were defined to have reached the ≥14 week treatment interval if they received ≥2 consecutive injections at treatment intervals of ≥14 week but not exceeding 26 weeks. Outcomes were reported in a subgroup of eyes that had 12 months of follow-up from reaching this interval. RESULTS: Of the 3907 treatment-naïve eyes that started treatment during the identified periods on a treat-and-extend regimen and received at least 8 injections over the first 2 years, 402 (10%) eyes received at least 2 consecutive injections at an interval of ≥14 week during their follow-up. Fifty-two percent of these eyes maintained vision to 12 months, however only 40% stayed at this interval and 25% of the lesions reactivated. CONCLUSION: We found that only 10% of eyes with nAMD were extended beyond a 13-week injection interval and that over half had returned to a shorter interval by 12 months. Eyes that stayed at this extended treatment interval maintained stable vision. More data on the outcomes of eyes treated with intervals longer than 3 months are required to establish whether emerging VEGF inhibitors provide a more sustained effect than the currently available drugs.

ASSESSING THE ACCURACY OF A LARGE OBSERVATIONAL REGISTRY OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the accuracy of an observational database that tracks real-world treatment outcomes for neovascular age-related macular degeneration. METHODS: We audited 245 randomly sampled eyes from 189 patients with 3,356 visits from 11 doctors in the Fight Retinal Blindness! DATABASE: Sex, birth year, previous treatments received, treatment, and visual acuity were validated against the clinical notes. Error rates, the proportion of missed visits (the number of visits present in the patient record but not entered into Fight Retinal Blindness!), the level of agreement using Cohen's kappa (κ) and intraclass correlation coefficients, and positive and negative predictive values were calculated. A visual acuity error was defined as an absolute difference of ≥5 letters. RESULTS: The overall error rate was 3.5% (95% confidence interval: 3.1-3.9). The error rate for visual acuity was 5.1% (95% confidence interval: 4.2-5.9) and <5% for the remaining fields. The level of agreement for each field ranged from good to excellent (κ or intraclass correlation ≥ 0.75). The positive predictive value and negative predictive value for visits were 99% and 89%, respectively. The proportion of missed visits was 10.2%. CONCLUSION: Accuracy of the Fight Retinal Blindness! database was good (>95%). The rate of missed visits was high, possibly due to the high burden of retrospective data entry or patients switching practitioners during treatment.

Proof-of-concept calculations to determine the health-adjusted life-year trade-off between intravitreal anti-VEGF injections and transmission of COVID-19.

BACKGROUND: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. METHOD: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. RESULTS: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). CONCLUSION: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.

Outcomes of cataract surgery in eyes with diabetic macular oedema: Data from the Fight Retinal Blindness! Registry.

IMPORTANCE: There are limited data on real-world outcomes of cataract surgery in eyes receiving intravitreal treatments for diabetic macular oedema (DMO). BACKGROUND: Cataract surgery may exacerbate oedema in some eyes with DMO resulting in inferior outcomes. DESIGN: Matched, case-controlled retrospective study of observational data in routine clinical practice. PARTICIPANTS: Eyes receiving intravitreal treatments for DMO tracked in the Fight Retinal Blindness! Registry. METHODS: Eyes that underwent cataract surgery were identified and matched 1:1 with phakic controls also receiving intravitreal injections for DMO. We also assessed potential factors that were associated with better visual acuity (VA) outcomes. MAIN OUTCOME MEASURES: Change in VA 6 months after cataract surgery. RESULTS: Cataract surgery was identified in 208 eyes of 156 patients of which 147 eyes had 6 months of observations before and after surgery. The mean VA 6 months after surgery improved by 10.6 letters and was similar to their matched phakic controls (68.8 vs 69.2 letters; P = 0.8). Mean CST both 6 months before (341 µm) and after (360 µm) surgery were similar (P = 0.08). However, these eyes had thicker maculae and they received more injections than their matched phakic controls both before and after surgery. Eyes with worse VA before surgery and those that had received intravitreal treatment in the 4 weeks preceding surgery were more likely to gain vision. CONCLUSIONS AND RELEVANCE: Visual outcomes of cataract surgery in eyes receiving intravitreal therapy for DMO were reasonably better. Their maculae were thicker and required more injections in the 6 months before and after surgery than their phakic controls.

Cystoid macular oedema following cataract surgery: A review.

Pseudophakic cystoid macular oedema (PCMO) remains a significant cause of compromised postoperative vision in contemporary cataract surgery. Well-established risk factors include intraoperative complications such as posterior capsule rupture and preoperative factors including: diabetes mellitus, uveitis, retinal vein occlusion, epiretinal membrane. The role of topical glaucoma medications in PCMO continues to be debated. Current treatment strategies largely target suppression of inflammation. Topical NSAIDs remain the mainstay in prophylaxis and treatment of PCMO. Topical corticosteroids are commonly used as monotherapy or in combination with NSAIDs. Unfortunately, high-quality trials are notably lacking for other PCMO treatment modalities such as: periocular corticosteroids, orbital floor triamcinolone, intravitreal triamcinolone, corticosteroid implants, intravitreal bevacizumab and pars-plana vitrectomy. A lack of consistency in defining PCMO and resolution of PCMO explains why even large systematic reviews may come to contradictory conclusions. This review explores the varied contemporary evidence-base in relation to the aetiology, diagnosis, prophylaxis and treatment of PCMO.

Validation of neuron activation patterns for artificial intelligence models in oculomics.

Recent advancements in artificial intelligence (AI) have prompted researchers to expand into the field of oculomics; the association between the retina and systemic health. Unlike conventional AI models trained on well-recognized retinal features, the retinal phenotypes that most oculomics models use are more subtle. Consequently, applying conventional tools, such as saliency maps, to understand how oculomics models arrive at their inference is problematic and open to bias. We hypothesized that neuron activation patterns (NAPs) could be an alternative way to interpret oculomics models, but currently, most existing implementations focus on failure diagnosis. In this study, we designed a novel NAP framework to interpret an oculomics model. We then applied our framework to an AI model predicting systolic blood pressure from fundus images in the United Kingdom Biobank dataset. We found that the NAP generated from our framework was correlated to the clinically relevant endpoint of cardiovascular risk. Our NAP was also able to discern two biologically distinct groups among participants who were assigned the same predicted systolic blood pressure. These results demonstrate the feasibility of our proposed NAP framework for gaining deeper insights into the functioning of oculomics models. Further work is required to validate these results on external datasets.

Development and validation of a deep-learning model to predict 10-year atherosclerotic cardiovascular disease risk from retinal images using the UK Biobank and EyePACS 10K datasets.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual's elevated 10-year ASCVD risk score based on retinal images and limited demographic data. Methods: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual's 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%. Results: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%. Conclusion: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. DESIGN: Multicenter, international, BRVO database study. SUBJECTS: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. MAIN OUTCOME MEASURES: Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. RESULTS: Mean adjusted VA change was +11 letters (95% confidence interval 9-13), mean adjusted change in CST was -176 µm (-193, -159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n = 677) and as a monotherapy in 71% (n = 538). Few eyes were switched to steroids (11%, n = 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs. -128 vs. -114 µm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. CONCLUSIONS: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered. DESIGN: Cohort study. PARTICIPANTS: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry. METHODS: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116). MAIN OUTCOME MEASURES: Mean visual acuity (VA) change after 12 months of treatment. RESULTS: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) µm and -85 (-92 to -78) µm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. CONCLUSIONS: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Automation of Macular Degeneration Classification in the AREDS Dataset, Using a Novel Neural Network Design.

Purpose: To create an ensemble of Convolutional Neural Networks (CNNs), capable of detecting and stratifying the risk of progressive age-related macular degeneration (AMD) from retinal photographs. Design: Retrospective cohort study. Methods: Three individual CNNs are trained to accurately detect 1) advanced AMD, 2) drusen size and 3) the presence or otherwise of pigmentary abnormalities, from macular centered retinal images were developed. The CNNs were then arranged in a "cascading" architecture to calculate the Age-related Eye Disease Study (AREDS) Simplified 5-level risk Severity score (Risk Score 0 - Risk Score 4), for test images. The process was repeated creating a simplified binary "low risk" (Scores 0-2) and "high risk" (Risk Score 3-4) classification. Participants: There were a total of 188,006 images, of which 118,254 images were deemed gradable, representing 4591 patients, from the AREDS1 dataset. The gradable images were split into 50%/25%/25% ratios for training, validation and test purposes. Main Outcome Measures: The ability of the ensemble of CNNs using retinal images to predict an individual's risk of experiencing progression of their AMD based on the AREDS 5-step Simplified Severity Scale. Results: When assessed against the 5-step Simplified Severity Scale, the results generated by the ensemble of CNN's achieved an accuracy of 80.43% (quadratic kappa 0.870). When assessed against a simplified binary (Low Risk/High Risk) classification, an accuracy of 98.08%, sensitivity of ≥85% and specificity of ≥99% was achieved. Conclusion: We have created an ensemble of neural networks, trained on the AREDS 1 dataset, that is able to accurately calculate an individual's score on the AREDS 5-step Simplified Severity Scale for AMD. If the results presented were replicated, then this ensemble of CNNs could be used as a screening tool that has the potential to significantly improve health outcomes by identifying asymptomatic individuals who would benefit from AREDS2 macular supplements.

Examination of alternative eGFR definitions on the performance of deep learning models for detection of chronic kidney disease from fundus photographs.

Deep learning (DL) models have shown promise in detecting chronic kidney disease (CKD) from fundus photographs. However, previous studies have utilized a serum creatinine-only estimated glomerular rate (eGFR) equation to measure kidney function despite the development of more up-to-date methods. In this study, we developed two sets of DL models using fundus images from the UK Biobank to ascertain the effects of using a creatinine and cystatin-C eGFR equation over the baseline creatinine-only eGFR equation on fundus image-based DL CKD predictors. Our results show that a creatinine and cystatin-C eGFR significantly improved classification performance over the baseline creatinine-only eGFR when the models were evaluated conventionally. However, these differences were no longer significant when the models were assessed on clinical labels based on ICD10. Furthermore, we also observed variations in model performance and systemic condition incidence between our study and the ones conducted previously. We hypothesize that limitations in existing eGFR equations and the paucity of retinal features uniquely indicative of CKD may contribute to these inconsistencies. These findings emphasize the need for developing more transparent models to facilitate a better understanding of the mechanisms underpinning the ability of DL models to detect CKD from fundus images.

A multi-centre prospective evaluation of THEIA™ to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) in the New Zealand screening program.

PURPOSE: To validate the potential application of THEIA™ as clinical decision making assistant in a national screening program. METHODS: A total of 900 patients were recruited from either an urban large eye hospital, or a semi-rural optometrist led screening provider, as they were attending their appointment as part of New Zealand Diabetic Eye Screening Programme. The de-identified images were independently graded by three senior specialists, and final results were aggregated using New Zealand grading scheme, which was then converted to referable/non-referable and Healthy/mild/more than mild/sight threatening categories. RESULTS: THEIA™ managed to grade all images obtained during the study. Comparing the adjudicated images from the specialist grading team, "ground truth", with the grading by the AI platform in detecting "sight threatening" disease, at the patient level THEIA™ achieved 100% imageability, 100% [98.49-100.00%] sensitivity and [97.02-99.16%] specificity, and negative predictive value of 100%. In other words, THEIA™ did not miss any patients with "more than mild" or "sight threatening" disease. The level of agreement between the clinicians and the aggregated results was (k value: 0.9881, 0.9557, and 0.9175), and the level of agreement between THEIA™ and the aggregated labels was (k value: 0.9515). CONCLUSION: This multi-centre prospective trial showed that THEIA™ did not miss referable disease when screening for diabetic retinopathy and maculopathy. It also had a very high level of granularity in reporting the disease level. As THEIA™ has been tested on a variety of cameras, operating in a range of clinics (rural/urban, ophthalmologist-led\optometrist-led), we believe that it will be a suitable addition to a public diabetic screening program.

Use of public sector diabetes eye services in New Zealand 2006-2019: Analysis of national routinely collected datasets.

OBJECTIVE: To assess diabetes eye service use in New Zealand among people aged ≥15 years by estimating service attendance, biennial screening rate, and disparities in the use of screening and treatment services. METHODS: We obtained Ministry of Health data from the National Non-Admitted Patient Collection on diabetes eye service events between 1 July 2006 and 31 December 2019 and sociodemographic and mortality data from the Virtual Diabetes Register and linked these using a unique patient identifier (encrypted National Health Index). We 1) summarized attendance at retinal screening and ophthalmology services, 2) calculated biennial and triennial screening rate, 3) summarized treatment with laser and anti-VEGF and used log-binomial regression to examine associations of all of these with age group, ethnicity, and area-level deprivation. RESULTS: In total, 245,844 people aged ≥15 years had at least one diabetes eye service appointment attended or scheduled; half of these (n = 125,821, 51.2%) attended only retinal screening, one-sixth attended only ophthalmology (n = 35,883, 14.6%) and one-third attended both (n = 78,300, 31.8%). The biennial retinal screening rate was 62.1%, with large regional variation (73.9% in Southern District to 29.2% in West Coast). Compared with NZ Europeans, Maori were approximately twice as likely to never receive diabetes eye care or to access ophthalmology when referred from retinal screening, 9% relatively less likely to receive biennial screening and received the fewest anti-VEGF injections when treatment was commenced. Disparities in service access were also present for Pacific Peoples compared to NZ Europeans, younger and older age groups compared to those aged 50-59 years and those living in areas with higher deprivation. CONCLUSIONS: Access to diabetes eye care is suboptimal, with substantial disparity between age groups, ethnicity groups, area level deprivation quintile and across districts. Efforts to improve access to and quality of diabetes eye care services must include strengthening data collection and monitoring.

Changes in 12-month outcomes over time for age-related macular degeneration, diabetic macular oedema and retinal vein occlusion.

OBJECTIVES: To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time. METHODS: We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry. RESULTS: The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.3 to +6 letters), DMO (+3.6 to +6.7 letters) and RVO (+10.3 to +11.7 letters for BRVO, +5.9 to +17.7 letters for CRVO and 10.2 to 20.7 letters for HRVO). The median number of VEGF-inhibitor injections in eyes that completed 12-month follow-up also remained stable at 8-9 for nAMD, 6-7 for DMO, 7-9 for RVO. Fewer eyes (