Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON)

PURPOSE: Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD. METHODS: EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed. CONCLUSION: The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD

A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1

Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies. In this multicentre study, we trained a multi-modal artificial intelligence (AI) system to identify suboptimal responders to the loading-phase of the anti-VEGF agent aflibercept from baseline characteristics. We collected clinical features and optical coherence tomography scans from 1720 eyes of 1612 patients between 2019 and 2021. We evaluated our AI system as a patient selection method by emulating hypothetical clinical trials of different sizes based on our test set. Our method detected up to 57.6% more suboptimal responders than random selection, and up to 24.2% more than any alternative selection criteria tested. Applying this method to the entry process of candidates into randomised controlled trials may contribute to the success of such trials and further inform personalised care

Characterization of the Structural and Functional Alteration in Eyes with Diabetic Macular Ischemia

OBJECTIVE: To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI). DESIGN: Prospective cross-sectional observational study. PARTICIPANTS: Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye. METHODS: Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used. MAIN OUTCOME MEASURES: The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated. RESULTS: A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], −9.92 to −3.41; P < 0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, −18.85 to −7.59; P < 0.001). CONCLUSIONS: In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only

Correlation of Optical Coherence Tomography Angiography Characteristics with Visual Function to Define Vision-Threatening Diabetic Macular Ischemia

The thresholds of macular microvasculature parameters associated with mild visual impairment in diabetic macular ischemia (DMI) patients are unclear. Therefore, this prospective observational study is aimed at demonstrating the optical coherence tomography angiography parameters that best correlate with mild visual impairment (&lt;70 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, Snellen equivalent 20/40) in DMI. The study was completed at the Moorfields Eye Hospital from December 2019 to August 2021. A total of 123 eyes of 87 patients with stable-treated proliferative diabetic retinopathy following panretinal photocoagulation were recruited. DMI was defined as an irregular foveal avascular zone (FAZ) area &ge; 0.5 mm2 or a smaller FAZ area with parafoveal capillary dropout in at least one quadrant. The analysis showed that the whole image deep vascular complex vessel density (DVC VD) in the 3 &times; 3 mm area had the best discriminatory ability to identify participants with mild visual impairment at 41.9% (area under the curve = 0.77, sensitivity 94%, specificity 54%, likelihood ratio [LR] = 2.04), and the FAZ area had the greatest post-test LR = 4.21 at 0.64 mm2. The 3 &times; 3 mm whole image DVC VD and FAZ area cutoffs are useful for screening vision-threatening DMI, but DVC VD has low specificity

The Natural History of Retinal Sensitivity Loss in Diabetic Macular Ischemia over One Year Evaluated by Microperimetry

Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI

Study protocol on prevalence of non-exudative macular neovascularisation and its contribution to prediction of exudation in fellow eyes with unilateral exudative AMD (EYE-NEON)

Abstract Purpose Fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) are at risk of developing macular neovascularisation (MNV). These eyes may first develop subclinical non-exudative MNV (neMNV) before they leak to form exudative MNV (eMNV). The EYE NEON study is a 2-year study aimed at estimating the prevalence and incidence of neMNV and evaluating its role as a predictor for conversion to neovascular AMD. Methods EYE NEON is a multicentre study that will run in retinal clinics across 25 National Health Service with the aim to recruit 800 patients with new onset nAMD in the first eye. The fellow-eye with no evidence of nAMD at baseline will be the study eye. All study eyes will have OCT and OCTA done at first and second year following first anti-VEGF treatment to the first eye (non-study eye), with new onset nAMD. We will estimate the prevalence and incidence of neMNV over 2 years, rate of conversion from neMNV to eMNV and numbers initiated on treatment for neovascular AMD in the study eye will be reported. Predictive models of conversion including neMNV with other demographic and imaging parameters will be developed. Conclusion The study design with proposed target sample size is sufficient to evaluate the retinal imaging characteristics of the study eyes with and without neMNV and develop predictive models to inform risk of conversion to nAMD. </jats:sec