Neuro-ophthalmological manifestations of diabetes mellitus during COVID-19-related lockdown in India.

Purpose: The coronavirus disease 19 (COVID-19) pandemic has resulted in a huge impact on the health care system. Diversion of health care workforce toward management of a high number of COVID-19 cases and lockdown restrictions have affected the follow-up of patients. The objective of this study was to analyze the impact of this situation on the control of diabetes, eventually resulting in related neuro-ophthalmological complications. Methods: This retrospective case series included diabetic patients visiting the neuro-ophthalmology clinic at a tertiary care eye center in India from 25 March 2020 to 25 September 2020 during the lockdown. The incidence of diabetes-related neuro-ophthalmological complications, including third, fourth, sixth nerve palsies and non-arteritic anterior ischemic optic neuropathy (NAION) was evaluated and compared with that of the same period during 2019. Results: Overall disease incidence rate was significantly higher in the year 2020 (60.2%) compared to the previous year of 2019 (29.8%). The proportion of third nerve palsy (4.8% vs 16.3%, P < 0.001) and NAION (0.3% vs 14.3%, P < 0.001) had increased. Even though the percentage of sixth nerve palsy was 25% in 2020, this was not significantly different from 2019. There was a reduction in the percentage of fourth nerve palsy cases from the year 2019 to 2020. Conclusion: There was a significant increase in diabetes-related neuro-ophthalmic complications during the COVID-19 lockdown. This can possibly be attributed to worsening of glycemic control in diabetic patients.

Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review.

INTRODUCTION: The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic. METHODS: All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement. RESULTS: We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after. CONCLUSION: Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.

Unveiling COVID-19-associated organ-specific cell types and cell-specific pathway cascade.

The novel coronavirus or COVID-19 has first been found in Wuhan, China, and became pandemic. Angiotensin-converting enzyme 2 (ACE2) plays a key role in the host cells as a receptor of Spike-I Glycoprotein of COVID-19 which causes final infection. ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells. In this study, the single-cell RNAseq data of the five tissues from different humans are curated and cell types with high expressions of ACE2 are identified. Subsequently, the protein-protein interaction networks have been established. From the network, potential biomarkers which can form functional hubs, are selected based on k-means network clustering. It is observed that angiotensin PPAR family proteins show important roles in the functional hubs. To understand the functions of the potential markers, corresponding pathways have been researched thoroughly through the pathway semantic networks. Subsequently, the pathways have been ranked according to their influence and dependency in the network using PageRank algorithm. The outcomes show some important facts in terms of infection. Firstly, renin-angiotensin system and PPAR signaling pathway can play a vital role for enhancing the infection after its intrusion through ACE2. Next, pathway networks consist of few basic metabolic and influential pathways, e.g. insulin resistance. This information corroborate the fact that diabetic patients are more vulnerable to COVID-19 infection. Interestingly, the key regulators of the aforementioned pathways are angiontensin and PPAR family proteins. Hence, angiotensin and PPAR family proteins can be considered as possible therapeutic targets. Contact: sagnik.sen2008@gmail.com, umaulik@cse.jdvu.ac.in Supplementary information: Supplementary data are available online.

Understanding structural malleability of the SARS-CoV-2 proteins and relation to the comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (COVID-19), is a part of the $\beta $-Coronaviridae family. The virus contains five major protein classes viz., four structural proteins [nucleocapsid (N), membrane (M), envelop (E) and spike glycoprotein (S)] and replicase polyproteins (R), synthesized as two polyproteins (ORF1a and ORF1ab). Due to the severity of the pandemic, most of the SARS-CoV-2-related research are focused on finding therapeutic solutions. However, studies on the sequences and structure space throughout the evolutionary time frame of viral proteins are limited. Besides, the structural malleability of viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins. This dysfunctionality may lead to comorbidities during the infection and may continue at the post-infection stage. In this regard, we conduct the evolutionary sequence-structure analysis of the viral proteins to evaluate their malleability. Subsequently, intrinsic disorder propensities of these viral proteins have been studied to confirm that the short intrinsically disordered regions play an important role in enhancing the likelihood of the host proteins interacting with the viral proteins. These interactions may result in molecular dysfunctionality, finally leading to different diseases. Based on the host cell proteins, the diseases are divided in two distinct classes: (i) proteins, directly associated with the set of diseases while showing similar activities, and (ii) cytokine storm-mediated pro-inflammation (e.g. acute respiratory distress syndrome, malignancies) and neuroinflammation (e.g. neurodegenerative and neuropsychiatric diseases). Finally, the study unveils that males and postmenopausal females can be more vulnerable to SARS-CoV-2 infection due to the androgen-mediated protein transmembrane serine protease 2.

Preoperative COVID-19 testing for elective vitreoretinal surgeries: Experience from a major tertiary care institute in South India.

PURPOSE: To study the prevalence of asymptomatic SARS-CoV-2 virus infection (COVID-19) among patients undergoing elective vitreoretinal surgeries at a tertiary care eye hospital. METHODS: This cross-sectional, observational study was performed between July 16, 2020 and August 31, 2020, in the retina clinic of a tertiary care eye hospital in south India. All patients undergoing elective retinal surgical procedures underwent RT-PCR testing for SARS-CoV-2 before being posted for surgery and after obtaining informed consent. Patients planned for surgery under general anesthesia underwent additional computed tomography of the chest. Testing strategies and outcomes were documented. RESULTS: Out of a total of 413 patients who were given appointments for surgery during this period, nine patients (2.2%) were found to have positive RT-PCR for SARS-CoV-2, and their surgeries were postponed. The test positivity (prevalence) rate of asymptomatic COVID-19 infection among all elective vitreoretinal surgical patients in our hospital was 2.2%. None of the patients were symptomatic for COVID-19. CONCLUSION: Our results showed that among patients visiting high volume ophthalmic centers in the near future, approximately 1 in 45 patients may be asymptomatic, SARS-CoV-2 RT-PCR positive. Asymptomatic COVID-19 patients may lead to chances of transmission of the virus inside healthcare facilities among other visiting patients and healthcare workers.

To evaluate the effect of COVID-19 pandemic and national lockdown on patient care at a tertiary-care ophthalmology institute.

PURPOSE: To evaluate the effect of COVID-19 pandemic and national lockdown on patient care at a tertiary-care ophthalmology institute. METHODS: Records of all the patients who presented from March 25th to May 3rd, 2020 were scanned to evaluate the details regarding the presenting complaints, diagnosis, advised treatment and surgical interventions. RESULTS: The number of outpatient department visits, retinal laser procedures, intravitreal injections and cataract surgeries during this lockdown decreased by 96.5%, 96.5%, 98.7% and 99.7% respectively compared from the corresponding time last year. Around 38.8% patients could be triaged as non-emergency cases based on history alone while 59.5% patients could be triaged as non-emergency cases after examination. Only eighty-four patients opted for video-consultation from April 15th to May 3rd, 2020. Nine patients presented with perforated corneal ulcer, but could not undergo penetrating keratoplasty due to the lack to available donor corneal tissue. One of these patients had to undergo evisceration due to disease progression. Two patients with open globe injury presented late after trauma and had to undergo enucleation. Around 9% patients could not undergo the advised urgent procedure due to logistical issues related to the lockdown. CONCLUSION: A significant number of patients could not get adequate treatment during the lockdown period. Hospitals need to build capacity to cater to the expected patient surge post-COVID-19-era, especially those requiring immediate in-person attention. A large number of patients can be classified as non-emergency cases. These patients need to be encouraged to follow-up via video-consultation to carve adequate in-person time for the high-risk patients.