Publications

2021

Ting DSJ, Foo VH, Yang LWY, Sia JT, Ang M, Lin H, Chodosh J, Mehta J, Ting DSW. Artificial intelligence for anterior segment diseases: Emerging applications in ophthalmology. Br J Ophthalmol. 2021;105(2):158–168.
With the advancement of computational power, refinement of learning algorithms and architectures, and availability of big data, artificial intelligence (AI) technology, particularly with machine learning and deep learning, is paving the way for 'intelligent' healthcare systems. AI-related research in ophthalmology previously focused on the screening and diagnosis of posterior segment diseases, particularly diabetic retinopathy, age-related macular degeneration and glaucoma. There is now emerging evidence demonstrating the application of AI to the diagnosis and management of a variety of anterior segment conditions. In this review, we provide an overview of AI applications to the anterior segment addressing keratoconus, infectious keratitis, refractive surgery, corneal transplant, adult and paediatric cataracts, angle-closure glaucoma and iris tumour, and highlight important clinical considerations for adoption of AI technologies, potential integration with telemedicine and future directions.
Agrawal R, Testi I, Lee C, Tsui E, Blazes M, Thorne J, Okada A, Smith J, McCluskey P, Kempen J, Tappeiner C, Agarwal M, Bodaghi B, Nguyen QD, Gupta V, De Smet M, Zierhut M, Pavesio C, COVID-19 IMT Study Group. Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic. Br J Ophthalmol. 2021;105(5):639–647.
BACKGROUND: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. METHODS: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. RESULTS: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. CONCLUSION: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.
Thng ZX, De Smet M, Lee C, Gupta V, Smith J, McCluskey P, Thorne J, Kempen J, Zierhut M, Nguyen QD, Pavesio C, Agrawal R. COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs. Br J Ophthalmol. 2021;105(3):306–310.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.
Olsen M, Lyngstadaas A, Bair J, Hodges R, Utheim T, Serhan C, Dartt DA. Maresin 1, a specialized proresolving mediator, stimulates intracellular [Ca ] and secretion in conjunctival goblet cells. J Cell Physiol. 2021;236(1):340–353.
Mucin secretion from conjunctival goblet cells forms the tear film mucin layer and requires regulation to function properly. Maresin 1 (MaR1) is a specialized proresolving mediator produced during the resolution of inflammation. We determined if MaR1 stimulates mucin secretion and signaling pathways used. Cultured rat conjunctival goblet cells were used to measure the increase in intracellular Ca ([Ca ] ) concentration and mucin secretion. MaR1-increased [Ca ] and secretion were blocked by inhibitors of phospholipase C, protein kinase C, Ca /calmodulin-dependent protein kinase II, and extracellular-regulated kinase 1/2. MaR1 added before addition of histamine counterregulated histamine-stimulated increase in [Ca ] and secretion. We conclude that MaR1 likely has two actions in conjunctival goblet cells: first, maintaining optimal tear film mucin levels by increasing [Ca ] and stimulating mucin secretion in health and, second, attenuating the increase in [Ca ] and overproduction of mucin secretion by counterregulating the effect of histamine as occurs in ocular allergy.
Cui Y, Zhu Y, Wang J, Lu Y, Zeng R, Katz R, Vingopoulos F, Le R, Laíns I, Wu D, Eliott D, Vavvas D, Husain D, Miller J, Kim L, Miller J. Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield colour fundus photography and fluorescein angiography for detection of lesions in diabetic retinopathy. Br J Ophthalmol. 2021;105(4):577–581.
AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS: This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15×15 mm scan. UWF CFP and UWF FA were taken by a 200°, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS: One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p<0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p>0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p>0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION: WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.
Pivodic A, Nilsson S, Stahl A, Smith L, Hellström A. Validation of the Retinopathy of Prematurity Activity Scale (ROP-ActS) using retrospective clinical data. Acta Ophthalmol. 2021;99(2):201–206.
PURPOSE: The International Neonatal Consortium recently published a proposed retinopathy of prematurity (ROP) activity scale intended for use in clinical trials after validation. The aim of this study was to validate the ROP activity scale (ROP-ActS) in a ROP screened cohort with protocol based collected data by evaluating the ability of the ROP-Act scores to predict ROP treatment. In addition, we aimed to evaluate the scale's sensitivity characteristic of disease severity by studying association with gestational age (GA) in comparison with conventionally used ROP stage and zone. METHODS: A cohort of 535 preterm infants with 3324 ROP examinations with an end-point of ROP treatment or end of screening in Gothenburg, Sweden, was included. Median GA was 28.1 weeks, 47.5% were girls, and 74 (13.8%) infants were treated for ROP. The validation was performed by estimating probabilities for ROP treatment, and by applying logistic and linear regression. RESULTS: The original ROP-ActS was overall well-ordered with respect to ability to predict ROP treatment but could be improved by re-ordering score 3 (zone II stage 1) and 5 (zone III stage 3) based on our clinical cohort data. The modified ROP-ActS was superior to ROP stage and zone in the prediction analysis of ROP treatment. Modified ROP-ActS was more strongly related to GA than currently used ROP stage, but not zone. CONCLUSION: In the studied cohort, the modified ROP-ActS could better predict ROP treatment compared to ROP stage and zone. Retinopathy of Prematurity Activity Scale (ROP-ActS) had a superior sensitivity characteristic studied through association to GA than conventionally used ROP stage.
Baumal C, Sarraf D, Bryant T, Gui W, Muakkassa N, Pichi F, Querques G, Choudhry N, Teke MY, Govetto A, Invernizzi A, Eliott D, Gaudric A, Cunha de Souza E, Naysan J, Lembo A, Lee G, Freund B. Henle fibre layer haemorrhage: clinical features and pathogenesis. Br J Ophthalmol. 2021;105(3):374–380.
BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.