Next-Generation Teleophthalmology: AI-enabled Quality Assessment Aiding Remote Smartphone-based Consultation (preprint)

Blindness and other eye diseases are a global health concern, particularly in low- and middle-income countries like India. In this regard, during the COVID-19 pandemic, teleophthalmology became a lifeline, and the Grabi attachment for smartphone-based eye imaging gained in use. However, quality of user-captured image often remained inadequate, requiring clinician vetting and delays. In this backdrop, we propose an AI-based quality assessment system with instant feedback mimicking clinicians' judgments and tested on patient-captured images. Dividing the complex problem hierarchically, here we tackle a nontrivial part, and demonstrate a proof of the concept.

Mutation of highly conserved residues in loop 2 of the coronavirus macrodomain demonstrates that enhanced ADP-ribose binding is detrimental to infection (preprint)

All coronaviruses (CoVs) encode for a conserved macrodomain (Mac1) located in nonstructural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that binds and hydrolyzes mono-ADP-ribose from target proteins. Previous work has shown that Mac1 is important for virus replication and pathogenesis. Within Mac1, there are several regions that are highly conserved across CoVs, including the GIF (glycine-isoleucine-phenylalanine) motif. To determine how the biochemical activities of these residues impact CoV replication, the isoleucine and the phenylalanine residues were mutated to alanine (I-A/F-A) in both recombinant Mac1 proteins and recombinant CoVs, including murine hepatitis virus (MHV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The F-A mutant proteins had ADP-ribose binding and/or hydrolysis defects that led to attenuated replication and pathogenesis in cell culture and mice. In contrast, the I-A mutations had normal enzyme activity and enhanced ADP-ribose binding. Despite increased ADP-ribose binding, I-A mutant MERS-CoV and SARS-CoV-2 were highly attenuated in both cell culture and mice, indicating that this isoleucine residue acts as a gate that controls ADP-ribose binding for efficient virus replication. These results highlight the function of this highly conserved residue and provide unique insight into how macrodomains control ADP-ribose binding and hydrolysis to promote viral replication and pathogenesis.

Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes. METHODS: Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors. RESULTS: Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown. DISCUSSION: Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020216205.

Relations between the ocular surface and SARS-CoV-2 / Relações entre superfície ocular e SARS-CoV-2

ABSTRACT Introduction: The SARS-CoV-2 pandemic has been a major challenge for the international scientific community. Since its inception, studies aiming to describe pathophysiological aspects and clinical manifestations of the disease have been conducted, raising hypotheses and confirming possible associations. One aspect of this scientific medical production is the role of the ocular surface as a means of transmission and clinical presentation of viral syndrome. Objectives: To analyze the role of the ocular surface in transmission, pathophysiology, and clinical manifestations of SARS-CoV-2, by means of a systematic review. Methods: The search was carried out in three databases: Cochrane, PubMed Central Journals and MEDLINE, using the following descriptors: "COVID-19, ophthalmology". The filters last five years and studies on humans resulted in 32 studies; in that 12 were excluded for not meeting the purpose of the study. Results: There are still few published studies on the relation between SARS-CoV-2 and the ocular route. Most studies showed an association between the presence of nonspecific ocular manifestations and infection by the new coronavirus, with limitations in the number of patients analyzed and the methodology adopted. Hypotheses about the pathophysiological role are largely anchored in the association of SARS-CoV and the ocular surface evaluated in the past. Comments: The results found are still not sufficient to confirm the role of the ocular surface in the pathophysiology of the disease. Most of these preliminary studies are of considerable importance in raising hypotheses based on the medical analysis of the patients studied. However, larger studies with standardized methodology for diagnostic protocol and laboratory analysis of the individuals assessed are required.

RESUMO Introdução: A pandemia da SARS-CoV-2 tem sido um grande desafio para a comunidade científica internacional. Desde seu surgimento, estudos com a intenção de descrever os aspectos fisiopatológicos e as manifestações clínicas da doença vêm sendo conduzidos, levantando hipóteses e confirmando possíveis associações. Um dos temas dessa produção médica científica é o papel da superfície ocular como meio de transmissão e apresentação clínica da síndrome viral. Objetivo: Analisar o papel da superfície ocular na transmissão, na fisiopatologia e nas manifestações clínicas de SARS-CoV-2, através de uma revisão sistemática. Realizou-se a busca em três bancos de dados Cochrane Database, PubMed® e MEDLINE®, utilizando os descritores "COVID-19 e ophthalmology". Foram definidos como filtros o artigo ter sido publicado nos últimos 5 anos e estudo realizado em humanos, tendo sido encontrados 32 artigos. Destes, foram excluídos 12 por não corresponderem ao objetivo do estudo. Resultados: Ainda são poucos os estudos publicados sobre a relação entre o coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2) e a via ocular. A maioria dos estudos mostrou associação entre a presença de manifestações oculares inespecíficas e a infecção pelo novo coronavírus, com limitações no número de pacientes analisados e na metodologia adotada. Hipóteses sobre o papel fisiopatológico se ancoram, em grande parte, na associação estudada entre o SARS-CoV-2 e a superfície ocular no passado. Comentários: Os resultados encontrados ainda não são suficientes para confirmar o papel da superfície ocular na fisiopatologia da doença. Grande parte desses estudos preliminares têm importância considerável ao levantar hipóteses baseadas na análise clínica dos pacientes estudados. No entanto, são necessários estudos maiores e com metodologia padronizada para protocolo diagnóstico e análise laboratorial dos indivíduos avaliados.

History through the eyes of a pandemic.

PURPOSE OF REVIEW: This review provides a historic perspective of the impact that major pandemics have had on human and their relationship with ophthalmology. The novel coronavirus epidemic is also analyzed, highlighting the relevance of the eye as a possible source of transmission, infection, and prognosis for the disease. RESULTS: Smallpox is suspected to be present for more than 12 000 years. However, trachoma seems to be the first recorded ophthalmological infectious disease. The deadliest pandemics include the bubonic plague, smallpox, and Spanish flu. The CoVID-19 epidemic is still developing and measures need to be implemented to prevent further escalation of the crisis. SUMMARY: Understanding the current facts in light of earlier historical evidence may help us prepare better to minimize the spread of infections in the future.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Glaucoma progression due to refraining examination amid the pandemic of COVID-19 (preprint)

Purpose Some patients refrain from seeking an ophthalmologist due to the anxiety and morbidity associated with the coronavirus disease 2019 (COVID-19) pandemic. We investigated progressive visual field defects in patients with glaucoma who refrained from ophthalmological examinations.Methods We retrospectively analyzed data from 886 patients with glaucoma who visited Inouye Eye Hospital in June 2022 and were followed-up prior to January 2020. We examined the number of times patients canceled visits between January 2020 and May 2022 due to coronavirus concerns. We assessed the mean deviation (MD) values of the Humphrey Visual Field Assessment (HFA) program 30 − 2 SITA Standard values after visit interruptions for worsening beyond the MD values predicted by the MD slope. Factors influencing this difference were analyzed using logistic regression analysis.Results The study included 374 men and 512 women. The mean age was 68.7 ± 12.0 years. Visit interruptions occurred in 146 patients (16.5%), with 95 (65.1%) rescheduling once, 27 (18.5%) twice, and 24 (16.4%) three or more times. Among 90 patients who underwent HFA regularly, 50 (55.6%) experienced worse-than-expected MD values and 12 (13.3%) deteriorated by 2 dB or more. Longer interruptions and high intraocular pressure before interruption worsened the MD values by 2 dB or more.Conclusions Patients with glaucoma with visit interruptions due to the pandemic should be monitored for the progression of visual field impairment.

Ophthalmic manifestations in patients recovered from COVID-19 in Mexico.

INTRODUCTION AND OBJECTIVES: Although the ophthalmic manifestations appear to be associated with the coronavirus disease 2019 (COVID-19), there is not enough evidence. Hence, the aim of this study was to determine the various types and frequency of ophthalmic manifestations in patients recovered from SARS-CoV-2 infection in Mexico. MATERIAL AND METHODS: This retrospective, observational and descriptive study included all patients recovered from SARS-CoV-2 infection attending the tertiary level hospital of Mexican Social Security Institute (IMSS) from June 2020 to June 2022. During the hospital admission of patients, the demographic data such age, name, gender was recorded. Ophthalmologic examination was performed under torchlight by an ophthalmologist in the Department of Ophthalmology from IMSS. Data was compiled and statistically analyzed using Fisher's exact test and Spearman correlation. RESULTS: A total of 3081 SARS-CoV-2-positive patients were recorded, of which 318 (10.32%) met the inclusion criteria. Of them, 21 (6.60%) had ophthalmic manifestations and the female-to-male ratio was 1.6:1. The mean age (±SD) was 47.95±15.27 years and the median (interquartile range) time from the diagnosis of COVID-19, as defined by positive SARS-CoV-2 RT-PCR testing, to detection of the ophthalmic manifestation was 31 (142) days. The most common ocular manifestation was orbital mucormycosis (23.80%). Interestingly, the presence of ophthalmic manifestations was not associated with severe COVID-19 (p=0.665). CONCLUSIONS: The ophthalmic manifestations are infrequent in patients recovered from severe COVID-19. Nevertheless, further large sample studies are needed to confirm these findings.

A retrospective clinicopathological analysis of rhino-orbital mucormycosis in second wave of COVID-19.

Background: During the present surge of COVID-19 positive cases, concurrent multifold increase in the incidence of mucormycosis cases has resulted into significant morbidity and mortality. We retrospectively evaluated the clinicopathological features along with microbiological examination findings in histologically diagnosed cases of rhino-orbital mucormycosis. Material and Methods: All the H and E and special stained slides of included mucormycosis cases were retrieved from the records and were evaluated with microbiological findings including screening KOH mount examination and culture results. Results: Out of 16 cases with available details, 10 cases had the previous history of diabetes mellitus. The most frequent single site of involvement was maxillary sinus (7/25) followed by nasal cavity, orbit, ethmoid and sphenoid sinuses. While comparing the histological diagnosis with KOH mount findings and culture results, 15 cases revealed consistent results. Conclusion: A high clinical suspicion, monitoring, early diagnosis, and timely management can improve the morbidity and mortality of this life-threatening complication.

An eye to the future: Acute and long-term neuro-ophthalmological and neurological complications of COVID-19.

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.

Long-Acting Protective Ocular Surface by Instilling Adhesive Dual-Antiviral Nanoparticles.

The eye is susceptible to viral infections, causing severe ocular symptoms or even respiratory diseases. Methods capable of protecting the eye from external viral invasion in a long-term and highly effective way are urgently needed but have been proved to be extremely challenging. Here, a strategy of forming a long-acting protective ocular surface is described by instilling adhesive dual-antiviral nanoparticles. Taking pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a model virus, antiviral agent-loaded nanoparticles are coated with a "double-lock" hybrid cell membrane abundant with integrin-ß1 and angiotensin converting enzyme II (ACE2). After instillation, the presence of integrin-ß1 endows coated nanoparticles with steady adhesion via specific binding to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium, achieving durable retention on the ocular surface. In addition to loaded inhibitors, the exposure of ACE2 can trap SARS-CoV-2 and subsequently neutralize the associated spike protein, playing a dual antiviral effect of the resulting nanoparticles. Adhesive dual-antiviral nanoparticles enabled by coating with a "double-lock" hybrid cell membrane could be a versatile platform for topical long-acting protection against viral infection of the eye.

Assessment of the influence of non-ionizing radiation to the morbidity of MRI and ultrasound diagnostics specialists in Kazakhstan (preprint)

The state of health of healthcare practitioners with occupational exposure to a complex of hazards may differ from the state of health of general population and justify the need to develop a number of preventive measures for healthcare practitioners. The purpose of the study was assessment of the prevalence of morbidity among medical specialists (MRI and ultrasound diagnostics). Design: retrospective (2018-2021), nonrandomized. Participants: MRI and ultrasound diagnostics specialists, ophthalmologists (as control). An analysis of data on healthcare practitioners seeking for medical care was done (diagnosis by ICD-10). Morbidity was also compared with general population of the RK. Higher morbidity of healthcare practitioners of the listed above specialties with genitourinary and musculoskeletal systems diseases, eye diseases and oncopathology was revealed. Comparing with ophthalmologists, ultrasound diagnostic specialists had higher morbidity with malignant and benign neoplasms (RR 2.74 and RR 9.58, respectively), MRI specialists had higher morbidity with malignant neoplasms and blood diseases (RR 4.73 and RR 1.89, respectively). The incidence rates of SARS-COV-2 in MRI and ultrasound diagnostic specialists and ophthalmologists exceeded those in the general population of the RK. Identified features of the morbidity of healthcare practitioners should be taken into account in labor ergonomics and organization of preventive and screening measures for diagnosing diseases.

Seeing Blue Dots After COVID-19 Infection.

A 12-year-old female individual receives a diagnosis of SARS-CoV-2 and reports bilateral blurry vision, large blue paracentral scotomata, and a migraine without a scintillating scotoma. What would you do next?

Effect of COVID-19-Related Interventions on the Incidence of Infectious Eye Diseases: Analysis of Nationwide Infectious Disease Incidence Monitoring Data.

Objective: Social distancing has been confirmed to reduce the incidence of not only the COVID-19, but also the incidence of other diseases. Therefore, this study aimed to investigate the effect of social distancing policies on the incidence of infectious eye diseases by monitoring their nationwide incidence data in all age groups. Methods: In this study, to analyse the impact of COVID-19 policy on IEDSC, the time periods were divided into two interventions. The first intervention was the first COVID-19 patient report in Korea on 19 January 2020. The second intervention was relaxation of the social distancing policy on 6 May 2020. Segmented regression analysis of the interrupted time series was used to assess COVID-19 policies on the IEDSC. Results: After the first incidence of a COVID-19 patient, IEDSCs decreased significantly in all age groups, while the relaxation of the social distancing policy increased IEDSCs significantly, mostly in all groups. Conclusion: In the post-COVID-19 era, we hope that national-level interventions such as reducing air pollution and employing precautionary measures will significantly reduce the financial burden of developing infectious ophthalmic diseases.

Microbiology Profile of COVID-19-Associated Rhino-Orbital Mucormycosis Pathogens in South India.

This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye Institute between May and August 2021. Diagnosed clinically and radiologically, 24 patients with ROM were included in the study. Deep nasal swabs or endoscopically collected nasal swabs or orbital tissues were submitted for microbiological evaluation and in vitro susceptibility testing by microbroth dilution for natamycin, amphotericin B, caspofungin, posaconazole, ketoconazole, and voriconazole. Cultures were processed by 28S ribosomal DNA polymerase chain reaction and molecular sequencing. A portion of orbital tissues was also sent for histopathological evaluation. The age of the patients ranged from 27 to 75 (mean 48.58 ± 14.09) years and the majority (79%) were male. Nineteen patients were known to be diabetic prior to developing ROM and 18 patients had recovered from active COVID-19 infection. Thirteen patients had a history of hospitalization during COVID-19 infection and eight received steroids. Of the 24 samples, microbiological evaluation identified Rhizopus arrhizus in 12, Rhizopus microsporus in 9, Lichtheimia ramosa in 2, and Rhizopus delemar in 1. Twelve isolates were tested for antifungal susceptibility and all were susceptible to natamycin and amphotericin B. The susceptibility to posaconazole was high, with minimum inhibitory concentration (MIC) < 2 µg/mL for 10/12 (84%) isolates, whereas the MIC of other drugs varied. Histopathological examination of tissues showed acute fulminant disease, granuloma formation, and vascular invasion by the fungal pathogens in these specimens. Rhizopus arrhizus was predominantly associated with ROM and most isolates were susceptible to amphotericin B and posaconazole. Further studies are needed to corroborate the findings and explain possible underlying links.