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PurposeTo quantify retinal and choriocapillaris (CC) microvasculature in highly myopic (HM) eyes with myopic macular degeneration (MMD) using swept-source optical coherence tomography angiography (SS-OCTA).Methods162 HM eyes (spherical equivalent ≤ −6.0 dioptres or axial length (AL) ≥26.5 mm) from 98 participants were enrolled, including 60 eyes (37.0%) with tessellated fundus, 54 eyes (33.3%) with peripapillary diffuse chorioretinal atrophy (PDCA), 27 eyes (16.7%) with macular diffuse chorioretinal atrophy (MDCA) and 21 eyes (13.0%) with patchy or macular atrophy. PLEX Elite 9000 SS-OCTA was performed to obtain perfusion densities (PD) of the superficial and deep retinal capillary plexus, and CC signal voids (number, area and density).ResultsRetinal PD decreased with increasing severity of MMD. Multivariable analysis showed that after adjustment of age and other factors, retinal PD decreased significantly in eyes with longer AL (β≤−0.51, p<0.001) and with an MMD severity of MDCA or worse (β≤−1.63, p<0.001). Reduced retinal PD were significantly associated with worse vision (β≤−0.01, p≤0.04). In terms of CC signal voids, multivariable analysis showed that longer AL (p<0.001), but not MMD severity (p≥0.12) was significantly associated with CC signal void changes in the earliest stage of MMD.ConclusionWe demonstrate significant OCTA alterations in the retina and CC in HM eyes with varying severities of MMD. In eyes with early-stage PDCA, lower retinal PD and more extensive CC signal voids are predominantly associated with increasing AL. In contrast, in eyes with MDCA or worse, MMD itself was associated with sparser retinal and CC circulation.

Purpose To investigate the prevalence and risk factors of posterior staphyloma using wide‐field optical coherence tomography (WF‐OCT) in adults with high myopia in Singapore. Design Population‐based cross‐sectional study. Methods Adults with spherical equivalent (SE) ≤ −5D in either eye at the first visit of Singapore Epidemiology of Eye Diseases study and Singapore Prospective Study Program study were recruited. Posterior staphyloma was diagnosed using WF‐OCT (PLEX®Elite9000, Carl Zeiss Meditec). Myopic macular degeneration (MMD), myopic traction maculopathy (MTM) and vision‐related quality of life (VRQoL) were assessed using fundus photographs, DRI‐Triton OCT (Topcon) and the Impact of Vision Impairment (IVI) questionnaire, respectively. Factors associated with posterior staphyloma were identified with multilevel, multivariable logistic regression. Impact of posterior staphyloma on MMD, MTM and visual function was analysed with multilevel, multivariable logistic regression and linear mixed model, respectively. Results Among the 225 eyes [mean SE = −6.5 ± 2.2 D, mean axial length (AL) = 26.2 ± 1.5 mm] of 117 participants (mean age = 60.3 ± 7.1 years), posterior staphyloma was detected in 47 (20.9%) eyes of 38 (32.5%) participants. Older age [odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10–1.26], more myopic SE (0.63; 0.51–0.77) and increased AL (2.51; 1.69–3.73) were associated with higher prevalence of posterior staphyloma (all p < 0.001). Adults with posterior staphyloma had higher odds of MMD (2.67; 1.23–5.82; p = 0.013), MTM (3.79; 1.13–12.68; p = 0.031) and worse IVI Reading (β = −1.44; −2.31 to 0.58; p = 0.001) scores. Conclusions About one in three adults with high myopia had posterior staphyloma, which was associated with increased odds of having myopic maculopathy and a detrimental impact on VRQoL.

Background/aimsAlthough measurements of the Bruch’s membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) with optical coherence tomography (OCT) have been widely adopted in the diagnostic evaluation of glaucoma, there is no consensus on the diagnostic criteria to define BMO-MRW and RNFLT abnormalities. This study investigated the sensitivities and specificities of different diagnostic criteria based on the OCT classification reports for detection of glaucoma.Methods340 eyes of 137 patients with glaucoma and 87 healthy individuals, all with axial length ≤26mm, had global and sectoral BMO-MRW and RNFLT measured with Spectralis OCT (Heidelberg Engineering). Six diagnostic criteria were examined: global measurement below the fifth or the first percentile; ≥1 sector measurement below the fifth or the first percentile; superotemporal and/or inferotemporal measurement below the fifth or the first percentile. The sensitivities and specificities of BMO-MRW/RNFLT assessment for detection of glaucoma (eyes with visual field (VF) defects) were compared.ResultsAmong the six criteria examined, superotemporal and/or inferotemporal measurement below the fifth percentile showed the highest sensitivities and specificities for glaucoma detection. Abnormal superotemporal and/or inferotemporal RNFLT attained a higher sensitivity than abnormal superotemporal and/or inferotemporal BMO-MRW to detect mild glaucoma (mean VF MD: −3.32±1.59 dB) (97.9% and 88.4%, respectively, p=0.006), and glaucoma (mean VF MD: −9.36±8.31 dB) (98.4% and 93.6%, respectively, p=0.006), at the same specificity (96.1%).ConclusionsSuperotemporal and/or inferotemporal RNFLT/MRW below the fifth percentile yield the best diagnostic performance for glaucoma detection with RNFLT attains higher sensitivities than MRW at the same specificity in eyes without high myopia.

BackgroundMany artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.MethodsThis was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.ResultsOne thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83.ConclusionOphthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

Ophthalmology has been one of the early adopters of artificial intelligence (AI) within the medical field. Deep learning (DL), in particular, has garnered significant attention due to the availability of large amounts of data and digitized ocular images. Currently, AI in Ophthalmology is mainly focused on improving disease classification and supporting decision-making when treating ophthalmic diseases such as diabetic retinopathy, age-related macular degeneration (AMD), glaucoma and retinopathy of prematurity (ROP). However, most of the DL systems (DLSs) developed thus far remain in the research stage and only a handful are able to achieve clinical translation. This phenomenon is due to a combination of factors including concerns over security and privacy, poor generalizability, trust and explainability issues, unfavorable end-user perceptions and uncertain economic value. Overcoming this challenge would require a combination approach. Firstly, emerging techniques such as federated learning (FL), generative adversarial networks (GANs), autonomous AI and blockchain will be playing an increasingly critical role to enhance privacy, collaboration and DLS performance. Next, compliance to reporting and regulatory guidelines, such as CONSORT-AI and STARD-AI, will be required to in order to improve transparency, minimize abuse and ensure reproducibility. Thirdly, frameworks will be required to obtain patient consent, perform ethical assessment and evaluate end-user perception. Lastly, proper health economic assessment (HEA) must be performed to provide financial visibility during the early phases of DLS development. This is necessary to manage resources prudently and guide the development of DLS.

PurposeAlpha-enolase (ENO1), a major glycolytic enzyme, is reported to be over-expressed in various cancer tissues. It has been demonstrated to be regulated by the Hypoxia-inducible factor 1-α (HIF-1α), a crucial transcriptional factor implicated in tumor progression and cancer angiogenesis. Choroidal neovascularization (CNV), which is a leading cause of severe vision loss caused by newly formed blood vessels in the choroid, is also engendered by hypoxic stress. In this report, we investigated the expression of ENO1 and the effects of its down-regulation upon cobalt (II) chloride-induced hypoxia in retinal pigment epithelial cells, identified as the primary source of ocular angiogenic factors.MethodsHIF-1α-diminished retinal pigment epithelial cells were generated by small interfering RNA (siRNA) technology in ARPE-19 cells, a human retinal pigment epithelial cell line. Both normal and HIF-1α-diminished ARPE-19 cells were then subjected to hypoxic challenge using cobalt (II) chloride (CoCl2) or anaerobic chamber. The relation between ENO1 expression and vascular endothelial growth factor (VEGF) secretion by retinal pigment epithelial cells were examined. Protein levels of HIF-1α and ENO1 were analyzed using Western Blot, while VEGF secretion was essayed by enzyme-linked immunosorbent assay (ELISA). Cytotoxicity after hypoxia was detected by Lactate Dehydrogenase (LDH) Assay.ResultsUpon 24 hr of CoCl2-induced hypoxia, the expression levels of ENO1 and VEGF were increased along with HIF-1α in ARPE-19 cells, both of which can in turn be down-regulated by HIF-1α siRNA application. However, knockdown of ENO1 alone or together with HIF-1α did not help suppress VEGF secretion in hypoxic ARPE-19 cells.ConclusionENO1 was demonstrated to be up-regulated by HIF-1α in retinal pigment epithelial cells in response to hypoxia, without influencing VEGF secretion.

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