Liwen Chen, Chaohua Deng, Xuhui Chen, Xian Zhang, Bo Chen, Huimin Yu, Yuanjun Qin, Ke Xiao, Hong Zhang, Xufang Sun

ObjectiveThe novel coronavirus disease (COVID-19) was first reported in Wuhan, China in December 2019 and is now pandemic all over the world. Previous study has reported several COVID-19 cases with conjunctivitis. However, the complete profiling of COVID-19 related ocular symptoms and diseases are still missing. We aim to investigate the ocular manifestations and clinical characteristics of COVID-19 patients. MethodsA total of five hundred and thirty-four patients were recruited at Mobile Cabin Hospital and Tongji Hospital. We collected information on demographic characteristics, exposure history, ocular symptoms, systemic concomitant symptoms, eye drop medication, eye protections, radiologic findings, and SARS-CoV-2 detection in nasopharyngeal swabs by RT-PCR from questionnaires and electronic medical records. ResultsThe median age of patients was 40 and 50 years at Mobile Cabin Hospital and Tongji Hospital, respectively. Of 534 COVID-19 patients, 25 patients (4.68%) presented with conjunctival congestion and 3 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 4.9 {+/-} 2.6 days (mean [SD]), ranging from 2 to 10 days. Dry eye (112, 20.97%), blurred vision (68, 12.73%), and foreign body sensation (63, 11.80%) ranked as the top three COVID-19 related ocular symptoms. Notably, a total of 332 COVID-19 patients (62%) had a hand-eye contact history. We also found that some COVID-19 patients had a history of eye disease, including conjunctivitis (33, 6.18%), dry eye (24, 4.49%), keratitis (14, 2.62%), cataract (9, 1.69%), and diabetic retinopathy (5, 0.94%). In consistent with previous studies, the most common clinical symptoms were fever, cough, and fatigue. Patients, 60.5% in Mobile Cabin Hospital and 67.5% in Tongji Hospital, respectively were confirmed with positive SARS-CoV-2 detection. ConclusionsConjunctival congestion was one of the COVID-19 related ocular symptoms, which may have clinical diagnostic significance. It is essential to provide eye-care equipment and strengthen education on eye protection, as dirty hand-eye contact might be a high risk factor of COVID-19. Further detailed and comprehensive ophthalmological guidance is needed for COVID-19 control.

Yunyun Zhou, Yuyang Zeng, Yongqing Tong, Changzheng Chen

BackgroundThe emerging 2019 novel coronavirus (2019-nCoV) has pushed several countries into state of emergency all over the world. The possible transmission of 2019-nCoV by conjunctiva is controversial and has substantial public health implications. MethodsA retrospective cohort study was initiated to investigate the possible transmission of 2019-nCoV through aerosol contact with conjunctiva. We enrolled 67 cases of confirmed or suspected cases of novel coronavirus pneumonia (NCP) during 17-28 Jan 2020. Nasopharyngeal and conjunctival swabs were collected for real time RT-PCR analysis to detect 2019-nCoV. Results63 patients were identified as laboratory-confirmed NCP and the remaining four were suspected NCP. Conjunctival swab samples from one NCP patient yielded positive PCR results and two NCP patients yielded probable positive PCR results. None of the three patients had ocular symptoms. The only one NCP patient with conjunctivitis as the first symptom had negative conjunctival sac 2019-nCoV test. Conjunctival swab samples from the four suspected cases of NCIP were negative. Conclusion2019-nCoV can be detected in the conjunctival sac of patients with NCP. Through clinical analysis, viral transmission via the conjunctival route was not supported by the data. Good clinical protection can effectively cut off the transmission path.

Onkar B. Sawant, Sneha Singh, Robert Emery Wright, Kayla M. Jones, Michael S. Titus, Eugene Dennis, Eric Hicks, Parag A. Majmudar, Ashok Kumar, Shahzad I. Mian

BackgroundSARS-CoV-2 is found in conjunctival swabs and tears of COVID-19 patients. However, the presence of SARS-CoV-2 has not been detected in the human eye to date. We undertook this study to analyze the prevalence of SARS-CoV-2 in human post-mortem ocular tissues. MethodsThe expression of SARS-CoV-2 RNA was assessed by RT-PCR in corneal and scleral tissues from 33 surgical-intended donors who were eliminated from a surgical use per Eye Bank Association of America (EBAA) donor screening guidelines or medical director review or positive COVID-19 test. Ocular levels of SARS-CoV-2 RNA (RT-PCR), Envelope and Spike proteins (immunohistochemistry) and anti-SARS-CoV-2 IgG and IgM antibodies (ELISA) in blood were evaluated in 10 COVID-19 donors. FindingsOf 132 ocular tissues from 33 surgical-intended donors, the positivity rate for SARS-CoV-2 RNA was [~]13% (17/132). Of 10 COVID-19 donors, six had PCR positive post-mortem nasopharyngeal swabs whereas eight exhibited positive post-mortem anti-SARS-CoV-2 IgG levels. Among 20 eyes recovered from 10 COVID-19 donors: three conjunctival, one anterior corneal, five posterior corneal, and three vitreous swabs tested positive for SARS-CoV-2 RNA. SARS-CoV-2 spike and envelope proteins were detected in epithelial layer of the corneas that were procured without Povidone-Iodine (PVP-I) disinfection. InterpretationsOur study showed a small but noteworthy prevalence of SARS-CoV-2 in ocular tissues from COVID-19 donors. These findings underscore the criticality of donor screening guidelines, post-mortem nasopharyngeal PCR testing and PVP-I disinfection protocol to eliminate any tissue harboring SARS-CoV-2 being used for corneal transplantation. FundingResearch grant from EBAA and National Institutes of Health.

Flora Hui, Jessica Tang, Pete A Williams, Myra B McGuinness, Xavier Hadoux, Robert J Casson, Michael Coote, Ian A Trounce, Keith R Martin, Peter van Wijngaarden, Jonathan G Crowston

ImportanceRetinal ganglion cells endure significant metabolic stress with ageing and glaucoma-related stressors. Injured cells require increased energy for repair but maintain capacity to recover function despite periods of functional loss. Nicotinamide, a precursor of redox co-factor and metabolite, NAD+, is low in serum of patients with primary open-angle glaucoma and its supplementation provides robust protection of retinal ganglion cells by targeting mitochondrial health in glaucoma models. However, the potential of nicotinamide to improve retinal ganglion cell function in humans with glaucoma is yet unknown. ObjectiveTo determine whether nicotinamide supplementation taken in conjunction with conventional IOP-lowering therapy leads to early improvement in retinal ganglion cell function in people with glaucoma. DesignCrossover, double-masked, randomized clinical trial conducted between October 2017 to January 2019. SettingStudy participants recruited from two tertiary care centers in Melbourne, Australia. ParticipantsAdults diagnosed and treated for primary glaucoma. Ninety-four participants assessed for study eligibility. InterventionParticipants randomized to first receive oral placebo or nicotinamide and reviewed six-weekly. Accelerated dosing method utilized; participants commenced 6-week course of 1.5 grams/day followed by 6 weeks of 3.0 grams/day. After 12 weeks, participants crossed over to other intervention for 12 weeks without washout. At each visit, visual function measured using full-field flash electroretinography and white-on-white perimetry. Main outcome measuresPrimary endpoint was change in inner retinal function determined a-priori as change in photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). ResultsFifty-seven participants (65.5{+/-}10.0 years, 39% female) enrolled. PhNR Vmax improved beyond 95% coefficient of repeatability (COR) in 23% of participants following 12 weeks of nicotinamide versus 9% on placebo. Conversely, PhNR Vmax deteriorated in 9% on placebo and 7% on nicotinamide. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [-4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved on average by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide and 3.6% [-3.4%, 10.5%], (p=0.30) on placebo. A concomitant trend for improved visual field mean deviation was observed with 27% improving [≥]1dB on nicotinamide and fewer deteriorating [≥]1dB (4%) compared to placebo (p=0.02). Moderate correlation was observed between PhNR and visual field change with treatment. Participants demonstrated excellent treatment adherence rates (>94%) and nicotinamide was well tolerated with minimal side effects. Conclusions and RelevanceNicotinamide supplementation can improve inner retinal function in patients receiving concurrent IOP-lowering glaucoma therapy. Further studies are underway to elucidate the effects of long-term nicotinamide supplementation on glaucoma progression. Trial RegistrationANZCTR trial ID: ACTRN12617000809336 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373001

Amit Kumar Saxena

IntroductionSevere Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2) spread mainly through respiratory droplets and contact routes. Long term use of spectacles may prevent repeated touching and rubbing of the eyes. Aim of the study is to compare the risk of COVID-19 in long term spectacles wearers with the risk in persons not using spectacles. ObjectivesTo know the association between infection with SARSCoV-2 and wearing of spectacles. Materials and methodsIn this study, 304 patients of Corona virus disease 2019 (COVID-19) were selected. Their spectacles wearing behaviour was assessed through a questionnaire. Spectacles wearing behaviour of general population was obtained from older studies (for comparison). Risk of COVID-19 was calculated in long term spectacles wearers as well as in persons not using spectacles. Chi-Square test was used for statistical analysis. ResultsIn this study, total 58 patients showed the behavior of using spectacles continuously during day time and always on outdoor activities. The risk of COVID-19 was found 0.48 in spectacles wearing population as compared to 1.35 in population not using spectacles. The calculated risk ratio was 0.36. The protective effectiveness of the spectacles was found statistically significant (p-value .00113). ConclusionThe present study showed that the risk of Covid-19 was about 2-3 times less in spectacles wearing population than the population not wearing those. The nasolacrimal duct may be a route of virus transmission from conjunctival sac to the nasopharynx.

Jacob Sterling, Peiying Hua, Joshua L Dunaief, Qi N Cui, Brian L. VanderBeek

Importance: Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat Type II Diabetes Mellitus. Recent work has shown that treatment with the novel GLP-1R agonist, NLY01, decreased retinal neuroinflammation and glial activation to rescue retinal ganglion cells in an animal model of glaucoma. Objective: In this study, we used an insurance claims database to examine whether GLP-1R agonist exposure impacts glaucoma risk. Design, Setting, and Participants: A retrospective cohort of adult patients who initiated a new GLP-1R agonist (i.e., exenatide, liraglutide, albiglutide, dulaglutide, semaglutide, or lixisenatide) was 1:3 age, gender, race, active diabetes medication classes, and year of index date matched to a cohort of patients who initiated a different class of oral diabetic medication during their time in the database. Exclusion occurred for <2 years in the database, age <18 years old, no visit to an eyecare provider prior to the index date, a prior diagnosis of glaucoma, glaucoma suspect, or ocular hypertension, or prior glaucoma medication, procedure, or surgery. Diabetes severity was assessed using hemoglobin A1c and the Diabetes Complications Severity Index (DCSI), a validated metric based on six categories of diabetic complications. Inverse probability of treatment weighting (IPTW) was used within a multivariable Cox proportional hazard regression model to test the association between GLP-1R agonist exposure and the primary outcome. IPTW was derived from a propensity score model based on the DCSI, HbA1c, demographic factors and other systemic health conditions. Exposure: Glucagon-like peptide 1 receptor agonist. Main Outcomes and Measures: New diagnosis of primary open angle glaucoma, glaucoma suspect, or low tension glaucoma. Results: Cohorts were comprised of 1,961 new users of GLP-1R agonists matched to 4,371 unexposed controls. After IPTW, age was the only covariate imbalanced (SMD >0.1) between cohorts. Ten new diagnoses of glaucoma (0.51%) were present in the GLP-1R agonist cohort compared to 58 (1.33%) in the unexposed controls. After adjustment, GLP-1R exposure conferred a reduced hazard of 0.54 (95%CI: 0.35-0.85, P =0.007), suggesting that GLP-1R agonists reduce the risk for glaucoma. Conclusions and Relevance: GLP-1R agonist use was associated with a statistically significant hazard reduction for a new glaucoma diagnosis. Our findings support further investigations into the use of GLP-1R agonists in glaucoma prevention.

Murat Seçkin Ayhan, Laura Kühlewein, Gulnar Aliyeva, Werner Inhoffen, Focke Ziemssen, Philipp Berens

Deep learning-based systems can achieve a diagnostic performance comparable to physicians in a variety of medical use cases including the diagnosis of diabetic retinopathy. To be useful in clinical practise, it is necessary to have well calibrated measures of the uncertainty with which these systems report their decisions. However, deep neural networks (DNNs) are being often overconfident in their predictions, and are not amenable to a straightforward probabilistic treatment. Here, we describe an intuitive framework based on test-time data augmentation for quantifying the diagnostic uncertainty of a state-of-the-art DNN for diagnosing diabetic retinopathy. We show that the derived measure of uncertainty is well-calibrated and that experienced physicians likewise find cases with uncertain diagnosis difficult to evaluate. This paves the way for an integrated treatment of uncertainty in DNN-based diagnostic systems.

Qi Yan, Daniel E Weeks, Hongyi Xin, Anand Swaroop, Emily Y. Chew, Heng Huang, Ying Ding, Wei Chen

Both genetic and environmental factors influence the etiology of age-related macular degeneration (AMD), a leading cause of blindness. AMD severity is primarily measured by fundus images and recently developed machine learning methods can successfully predict AMD progression using image data. However, none of these methods have utilized both genetic and image data for predicting AMD progression. Here we jointly used genotypes and fundus images to predict an eye as having progressed to late AMD with a modified deep convolutional neural network (CNN). In total, we used 31,262 fundus images and 52 AMD-associated genetic variants from 1,351 subjects from the Age-Related Eye Disease Study (AREDS) with disease severity phenotypes and fundus images available at baseline and follow-up visits over a period of 12 years. Our results showed that fundus images coupled with genotypes could predict late AMD progression with an averaged area under the curve (AUC) value of 0.85 (95%CI: 0.83-0.86). The results using fundus images alone showed an averaged AUC of 0.81 (95%CI: 0.80-0.83). We implemented our model in a cloud-based application for individual risk assessment.

Shengjie Li, Danhui Li, Jianchen Fang, Johannes Vierock, Wenjun Cao, Xinghuai Sun, Gezhi Xu

COVID-19 virus has currently caused major outbreaks worldwide. ACE2 is a major cellular-entry receptor for the COVID-19 virus. Although ACE2 is known to be expressed in many organs, whether it is expressed by the conjunctival tissue is largely unknown. Human conjunctival tissues from 68 subjects were obtained, which included 10 subjects with conjunctival nevi, 20 subjects with conjunctivitis, 9 subjects with conjunctival papilloma, 16 subjects with conjunctival cyst, 7 subjects with conjunctival polyps, and 6 ocular traumas as normal subjects. Expression of ACE2 was evaluated by immunohistochemistry, immunofluorescence, reverse transcriptase-quantitative polymerase chain reaction, and western blot assay. We observed the expression of ACE2 by conjunctival tissues, expecially in conjunctival epithelial cells. ACE2 was significantly (p<0.001) overexpressed in conjunctival cells obtained from subjects with conjunctivitis, conjunctival nevi, conjunctival papilloma, conjunctival cyst, and conjunctival polyps epithelial cells when compared to that in conjunctival epithelial cells obtained from control subjects. Collectively, clinical features of reported COVID-19 patients combined with our results indicate that COVID-19 is likely to be transmitted through the conjunctiva.

Li Xu, Xinyue Zhang, Wei Song, Baijun Sun, Jinping Mu, Bing Wang, Zhiqian Wang, Yehong Cao, Xue Dong

PurposeThe 2019 novel coronavirus(COVID-19) mainly transmitted by person-to-person through inhalation of respiratory droplets. We report the laboratory results of conjunctival PCR-tests and some clinical features of these patients in shenyang China. DesignThis is a cross-sectional non-randomized study SubjectsThe study include 14 confirmly diagnosed cases, 16 suspected cases and some medical observed patients. MethodsAll patients with diagnosed and suspected COVID-19 were admitted to a designated hospital in Shenyang, China. We collected conjunctival samples of these patients to do the laboratory tests by real time RT-PCR. Medical observed patients were enrolled if they had clinical symptoms. Then we analysed the PCR results and clinical data from eletronic medical records in order to find some relationships. Main Outcome MeasuresClinical condition and PCR results. of conjunctival swabs compared with other specimens ResultsOne of the identified case coverted from suspected case without typical clinical symptoms. Twenty-two medical observed cases were removed because none of them converted to identified cases. One of the suspected converted to identified case recently. The included cases in our study are imported cases with less underlying diseases and the severity of their infection was relatively moderate. All the conjunctival results of PCR-test were negative. Two cases had typical clinical symptoms but were finally confirmed by repeated pharynxswabtests. ConclusionConjunctiva may be a transmission way of COVID-19. And ocular conjunctival swabs in combination with PCR test could be a non-invasive, convenient and feasible diagnostic method for identifying the infection of COVID-19. Emphasis on the false-negative results is vital.

Kieren Darcy, Omar Elhaddad, Asaf Achiron, Johannes Keller, Duncan Leadbetter, Derek Tole, Sidath E. Liyanage

Objective: To assess potential methods of reducing visible aerosol generation during clear corneal phacoemulsification surgery in the era of Covid-19. Methods: Aerosol generation during phacoemulsification was assessed using a model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber. Typical phacoemulsification settings were used and visible aerosol production was recorded using high speed 4K camera. Aerosolisation was evaluated under various experimental settings: Two different phacoemulsification tip sizes (2.2mm, 2.75mm), varying levels of corneal moisture, the use of suction and blowing air in the surgical field, the use of hydroxypropyl methylcellulose (HPMC) coating of the cornea with a static and moving tip. Results: This model demonstrates visible aerosol generation during phacoemulsification with a 2.75mm phacoemulsification tip. No visible aerosol was noted with a 2.2mm tip. The presence of visible aerosol is unrelated to corneal wetting. Suction in close proximity to the aerosol plume did not impact on its dispersion. Blowing air redirected the aerosol plume towards the ocular surface. Visible aerosol production was abolished when HPMC was used to coat the cornea. This effect lasted for an average of 67{+/-}8 seconds in the static model. Visible aerosol generation was discerned during movement of the 2.2mm tip towards the corneal wound. Conclusions: We demonstrate visible aerosol production in the setting of a model of a clear cornea phacoemulsification. Visible aerosol can be reduced using a 2.2mm phacoemulsification tip and reapplying HPMC every minute during phacoemulsification.

N. Chirpaz, S. Kerever, A. Gavoille, L. Kodjikian, R. Bernier, M. Gerfaud-Valentin, P. Denis, T. Mathis, Y. Jamilloux, P. Sève

AimTo assess the diagnostic value of brain magnetic resonance imaging (bMRI) for the etiological diagnosis of uveitis and to establish predictive factors associated with its advantageous use. MethodsRetrospective study on all patients with de novo uveitis who were referred to our tertiary hospital and who underwent a bMRI between 2003 and 2018. The bMRI was considered useful if it served to confirm a diagnosis or correct a misdiagnosis. We also collected characteristics of uveitis and associated ophthalmological and neurological clinical signs. ResultsBrain MRI was contributive in 19 out of 402 cases (5%): 10 multiple sclerosis, 5 radiologically isolated syndromes, and 4 oculocerebral lymphomas. A total of 34 (8%) had neurological signs and 13 (38%) of those patients had a contributive bMRI. Meanwhile, in the absence of neurological signs, 1% of bMRIs were contributive, and none of them resulted in specific treatment. Among patients with a contributive bMRI, 68% had neurological signs. Univariate analysis established that neurological signs (p<0.001), granulomatous uveitis (p=0.003), retinal vasculitis (p=0.002), and intermediate uveitis (p<0.001) were all significantly associated with a contributive bMRI. Multivariate analysis confirms the significant association of neurological signs (p<0.001) and intermediate uveitis (p=0.01). Patients with oculocerebral lymphoma were significantly older (p<0.001) and all were above 40 years of age. ConclusionBrain MRI appears to be a relevant and contributive exam, but it should be performed in cases of intermediate/posterior uveitis or panuveitis accompanied by neurological signs, retinal vasculitis, or in patients older than 40, to rule out an oculocerebral lymphoma.

Samir Sayegh

Purpose: To demonstrate that the total loss of astigmatism as a consequence of misalignment or rotation of a toric intraocular lens (tIOL) can occur much earlier than the widely believed and taught 30 degrees. To give a precise surgically useful estimate of that value. To clarify the role of mismatch and misalignment of toric intraocular lenses in cataract surgery beyond what is commonly recognized in the literature and make corresponding surgical recommendations. Setting: Private Practice and Research Center. The EYE Center. Champaign, IL, USA. Design: Formal Analytical Study Methods: The astigmatism addition approach is used in its simplest form along with analytical tools to derive new results concerning mismatch, misalignment and rotation of toric intraocular lenses. Results: The often stated results of total loss of astigmatic correction by 30-degree rotation and 3.3 % loss per degree represent a usually poor approximation to realistic surgical cases. We show how they constitute a very special case in the context of a more general framework relevant to procedures performed by refractive cataract surgeons dealing with the surgical correction of astigmatism with tIOLs. Total loss of astigmatic correction can occur with as little as 20 degrees of misalignment and less than 10 degrees of tIOL rotation. A practical approximation for that angle of doom, {Delta}, in the surgically relevant range can be expressed by {Delta} {approx} 30 - 15 {omega} degrees, where {omega} = (L - A) / A is the fractional overcorrection of L, the cylinder of the tIOL, and A, the astigmatism to be corrected. Similarly for undercorrection we show that {Delta} {approx} 30 + 15 degrees where = (A - L) / A represents the corresponding fractional undercorrection. That is to say the angle of doom is extended beyond the 30 degrees for cases of undercorrection of the astigmatism. We also demonstrate that overcorrection of astigmatism results in a significantly faster decline in astigmatism correction per degree of misalignment/rotation. The significant clinical implications and surgical recommendations, including for optimal degree of overcorrection, are a natural consequence of these novel results. Conclusions: Total loss of astigmatism correction can occur at a significantly smaller angle than commonly believed and overcorrected astigmatism residual rises with tIOL misalignment or rotation significantly faster than undercorrected astigmatism. We provide the methodology and explicit solution for determining this behavior.

Darren S Thomas, Alasdair Warwick, Abraham Olvera-Barrios, Catherine Egan, Roy Schwartz, Sudeshna Patra, Haralabos Eleftheriadis, Anthony P. Khawaja, Andrew Lotery, Philipp L Mueller, Robin Hamilton, Ella Preston, Paul Taylor, Adnan Tufail, UK EMR Users Group

Objectives: To report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at one year. Design: Retrospective clinical audit and simulation model. Setting: Multiple UK NHS ophthalmology centres. Participants: Data on the reduction in new nAMD referrals was obtained from four NHS Trusts in England comparing April 2020 to April 2019. To estimate the potential impact on one-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20,825 nAMD eyes from 27 NHS Trusts. Main outcome measures: Simulated mean visual acuity and proportions of eyes with vision [&le;]6/60, [&le;]6/24 and [&ge;]6/12 at one year under four hypothetical scenarios: no treatment delay, 3, 6 and 9-month treatment delays. Estimated additional number of eyes with vision [&le;]6/60 at one year nationally. Results: The number of nAMD referrals at four major eye treatment hospital groups based in England dropped on average by 72% (range 65 to 87%) in April 2020 compared to April 2019. Simulated one-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision [&le;]6/60 from 15.5% (13.2 to 17.9) to 23.3% (20.7 to25.9), and a decrease in the proportion of eyes with vision [&ge;]6/12 (driving vision) from 35.1% (32.1 to 38.1) to 26.4% (23.8 to29.2). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level at the national level for only one month, these simulated results suggest an additional 186-365 eyes with vision [&le;]6/60 at one-year with even a short treatment delay. Conclusions: We report a large decrease in nAMD referrals during the first month of COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision [&le;]6/60 and 25% relative decrease in the number of eyes with driving vision at one year.

Kathleen Vancleef, Michael J Colwell, Olivia Hewitt, Nele Demeyere

AIMWe aimed to document current clinical practice and needs in screening for visual perception problems after stroke to inform development of new screening tools. METHODSWe interviewed 25 health care professionals (12 occupational therapists, 13 orthoptists) from 16 organisations in England. Interviews were transcribed and coded in NVivo Software. Data were thematically analysed using the Value Proposition Canvas, a model which establishes what people want to achieve, the challenges they face and what facilitates their jobs. RESULTSParticipants understanding of visual perception varied and often included sensory and cognitive deficits. Occupational therapists commonly screened for visual field deficits and hemispatial neglect, while other aspects of visual cognition were rarely assessed. They decided on referrals to orthoptists for further assessment. Screening generally occurred during functional assessments and/or with in-house developed tools. Challenges to practice were: lack of time, lack of training, environmental and stroke survivor factors (e.g. aphasia), insufficient continuation of care, and test characteristics (e.g. not evidence-based). Facilitators to practice were: quick and practical tools, experienced staff or tools with minimal training requirements, a streamlined care pathway between a stroke unit and eye hospital supported by occupational therapists and orthoptists. CONCLUSIONScreening employs non-standardised assessments and rarely covers visual perceptual deficits in higher order perception. Our service evaluation demonstrates the need for a standardised visual perception screen, which should ideally be 15 minutes or less, be portable, and require minimal equipment. The screen should be suitable for bedside testing in noisy environments, inclusive for participants with aphasia and evidence-based.

Guofang Ye, Bo Qu, Wen Shi, Xin Chen, Pengjuan Ma, Yuxin Zhong, Shida Chen, Ecosse Lamoureux, Yingfeng Zheng

ObjectiveTo develop a theoretical framework for assessing knowledge about the possible outcomes of undergoing cataract surgery, and explore the association of knowledge level with psychological status and decision quality among patients with cataract in Southern China. MethodsThe details of the knowledge scale were based on the health education information booklet provided by National Eye Institute, NIH. We used a theory-based approach to assess gist knowledge, which comprises conceptual and numeric questions related to knowledge of the possible surgical outcomes. The scale was then used in a cross-sectional study to assess the association of knowledge score with psychological status and decision quality of cataract patients, including worry, anxiety, attitudes, intentions, decisional conflict, confidence in decision making, anticipated regret and temporal orientation. ResultsA total of 489 participants with age-related cataract were included in this study, and 10.2% (50/489) of them had adequate level of knowledge. The knowledge scale was significantly associated to the levels of worry (Odds Ratio (OR) = 0.36, 95%CI: 0.18, 0.70; P = 0.003), anxiety (beta coefficient = -5.36, 95%CI: -8.88,-1.84; P = 0.003), inaction regret (OR = 0.49, 95%CI : 0.28, 0.88; P = 0.016) and decision conflict (beta coefficient = -7.93, 95%CI: -12.81, -3.04; P = 0.002) in multivariate analyses adjusted for age, sex, education level and literacy level. ConclusionThe level of knowledge adequacy with cataract surgery outcomes is high in China and was associated with psychological status and decision quality. These findings suggest that strategies targeting knowledge of possible surgical outcomes may reduce psychological stress and improve decision quality among patients with age-related cataract.

Laura Gutierrez-Benitez, Yolanda Palomino, Noe Casas, Mouafk Asaad

PurposeTo develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM). MethodsThis cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and twice manually by two independent examiners. ResultsIntrascan intraclass coefficient ranged from 0,948 to 0,993 for manual measurements and was 1 for mKSM method. Interscan intraclass coefficients ranged from 0,925 to 0,973 for manual measurements and from 0,770 to 0,902 for mKSM method. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in intermediate capillary plexus. ConclusionsAutomated determination of the FAZ area in HS-OCTA is feasible and less human- dependent by mKSM even if the image is not perfectly centred or has artefacts. The mKSM processing could contribute to our understanding of the three vascular plexuses.

Zhuoting Zhu, Danli Shi, Guankai Peng, Zachary Tan, Xianwen Shang, Wenyi Hu, Huan Liao, Xueli Zhang, Yu Huang, Honghua Yu, Wei Meng, Wei Wang, Xiaohong Yang, Mingguang He

SummaryO_ST_ABSBackgroundC_ST_ABSAgeing varies substantially, thus an accurate quantification of ageing is important. We developed a deep learning (DL) model that predicted age from fundus images (retinal age). We investigated the association between retinal age gap (retinal age-chronological age) and mortality risk in a population-based sample of middle-aged and elderly adults. MethodsThe DL model was trained, validated and tested on 46,834, 15,612 and 8,212 fundus images respectively from participants of the UK Biobank study alive on 28th February 2018. Retinal age gap was calculated for participants in the test (n=8,212) and death (n=1,117) datasets. Cox regression models were used to assess association between retinal age gap and mortality risk. A restricted cubic spline analyses was conducted to investigate possible non-linear association between retinal age gap and mortality risk. FindingsThe DL model achieved a strong correlation of 0{middle dot}83 (P<0{middle dot}001) between retinal age and chronological age, and an overall mean absolute error of 3{middle dot}50 years. Cox regression models showed that each one-year increase in the retinal age gap was associated with a 2% increase in mortality risk (hazard ratio=1{middle dot}02, 95% confidence interval:1{middle dot}00-1{middle dot}04, P=0{middle dot}021). Restricted cubic spline analyses showed a non-linear relationship between retinal age gap and mortality (Pnon-linear=0{middle dot}001). Higher retinal age gaps were associated with substantially increased risks of mortality, but only if the gap exceeded 3{middle dot}71 years. InterpretationOur findings indicate that retinal age gap is a robust biomarker of ageing that is closely related to risk of mortality. FundingNational Health and Medical Research Council Investigator Grant, Science and Technology Program of Guangzhou. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAgeing at an individual level is heterogeneous. An accurate quantification of the biological ageing process is significant for risk stratification and delivery of tailored interventions. To date, cell-, molecular-, and imaging-based biomarkers have been developed, such as epigenetic clock, brain age and facial age. While the invasiveness of cellular and molecular ageing biomarkers, high cost and time-consuming nature of neuroimaging and facial ages, as well as ethical and privacy concerns of facial imaging, have limited their utilities. The retina is considered a window to the whole body, implying that the retina could provide clues for ageing. Added value of this studyWe developed a deep learning (DL) model that can detect footprints of aging in fundus images and predict age with high accuracy for the UK population between 40 and 69 years old. Further, we have been the first to demonstrate that each one-year increase in retinal age gap (retinal age-chronological age) was significantly associated with a 2% increase in mortality risk. Evidence of a non-linear association between retinal age gap and mortality risk was observed. Higher retinal age gaps were associated with substantially increased risks of mortality, but only if the retinal age gap exceeded 3{middle dot}71 years. Implications of all the available evidenceThis is the first study to link the retinal age gap and mortality risk, implying that retinal age is a clinically significant biomarker of ageing. Our findings show the potential of retinal images as a screening tool for risk stratification and delivery of tailored interventions. Further, the capability to use fundus imaging in predicting ageing may improve the potential health benefits of eye disease screening, beyond the detection of sight-threatening eye diseases.

Vijay K. Jidigam, Rupesh Singh, Julia C. Batoki, Caroline Milliner, Onkar B. Sawant, Vera L. Bonilha, Sujata Rao

PurposeTo assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the SARS-CoV-2 infection. DesignComparative analysis of human eyes. SubjectsEleven donor eyes from COVID-19 positive donors and similar age-matched donor eyes from patients with a negative test for SARS-CoV-2 were assessed. MethodsGlobes were evaluated ex-vivo with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for epon-embedding and immunocytochemistry Main Outcome MeasuresRetinal thickness and histopathology, detection of SARS-CoV-2 Spike protein, changes in vascular density, gliosis, and degree of inflammation. ResultsFundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the control. OCT based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes, however the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples. ConclusionsIn situ analysis of the retinal tissue suggested that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.

Qi Yan, Yale Jiang, Heng Huang, Anand Swaroop, Emily Y. Chew, Daniel E Weeks, Wei Chen, Ying Ding

Numerous independent susceptibility variants have been identified for Age-related macular degeneration (AMD) by genome-wide association studies (GWAS). Since advanced AMD is currently incurable, an accurate prediction of a persons AMD risk using genetic information is desirable for early diagnosis and clinical management. In this study, genotype data of 32,215 Caucasian individuals with age above 50 years from the International AMD Genomics Consortium in dbGAP were used to establish and validate prediction models for AMD risk using four different machine learning approaches: neural network, lasso regression, support vector machine, and random forest. A standard logistic regression model was also considered using a genetic risk score. To identify feature SNPs for AMD prediction models, we selected the genome-wide significant SNPs from GWAS. All methods achieved good performance for predicting normal controls versus advanced AMD cases (AUC=0.81[~]0.82 in a separate test dataset) and normal controls versus any AMD (AUC=0.78[~]0.79). By applying the state-of-art machine learning approaches on the large AMD GWAS data, the predictive models we established can provide an accurate estimation of an individuals AMD risk profile across the persons lifespan based on a comprehensive genetic information.