Safety of intravitreal ziv-aflibercept in choroido-retinal vascular diseases: A randomised double-blind intervention study

AIM:To evaluate the safety of 1.25mg and 2mg intravitreal ziv-aflibercept (IVZ) in Ghanaian eyes with choroido-retinal vascular diseases. DESIGN:Prospective, randomised, double blind, interventional study. METHODS:Twenty patients with centre involving macular oedema in diabetic retinopathy, retinal vein occlusion, and neovascular age-related macular degeneration were assigned to 2 groups receiving 3 doses of 1.25mg/0.05ml (group 1) and 2mg/0.08ml IVZ (Group 2) at 4 weekly intervals. Safety data was collected after 30 minutes, 1 and 7 days, and 4, 8 and 12 weeks after injection. Changes in continuous variables were compared using paired t-test and categorical variables were compared using chi-square test of proportions. Repeated-Measures ANOVA with nesting test was used to compare variations in continuous variables by IVZ dose over time. Primary outcome measures were ocular and systemic adverse events at 4 weeks. RESULTS:Eleven females and nine males, with mean age of 63.2± 7.3 years were included. Ocular adverse events included subconjunctival haemorrhage in 1 eye, intraocular pressure (IOP) >21mmHg at 30 minutes in 6 eyes and mild pain in 3 eyes at 1-day. There was no significant difference in IOP rise between the 2 groups at 30 minutes (p = 0.21). No other ocular or systemic adverse events were observed. There was significant improvement in the best corrected visual acuity (LogMAR) from 0.95±0.6 to 0.6±0.4 (p<0.01) and 0.47±0.3 (p<0.01), reduction in central subfield foveal thickness from 405.9±140 um at baseline to 255.6±75 um (p<0.01) and 238±88 um (p<0.01) at 4 and 12 weeks respectively, although no difference was observed between the 2 groups (p = 0.34). CONCLUSION:IVZ at 1.25mg and 2mg had similar safety profiles, and did not have any major unexpected adverse events. Further studies with larger cohorts are required to confirm efficacy

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

International collaboration for the development of clinical guidelines in low and middle-income countries: case study on the development of a national framework and clinical guidelines for diabetic retinopathy in Ghana.

BACKGROUND: Diabetic retinopathy is a leading cause of blindness in many countries across the world. Ghana has seen a rise in diabetic retinopathy and is working on various strategies to prevent blindness. Clinical guidelines are seen as a promising strategy for improving quality and reducing cost of care. Little is known about the processes of collaborative guideline development in the African context. METHODS: This case study discusses the process of developing clinical guidelines for diabetic retinopathy in Ghana via a collaboration with the Kenya team that had previously developed guidelines for Kenya. RESULTS: The main lesson learnt was the ability to overcome challenges. The main output achieved was the draft national framework, guidelines and training slides on the guidelines. CONCLUSION: Horizontal international collaboration can aid development of clinical guidelines