Surgical Care in Specialist Ophthalmology Departments: Structure and Impact of the COVID-19 Pandemic.

BACKGROUND: Specialist ophthalmology departments contribute to the surgical care of German patients. Outpatient and inpatient surgeries were restricted during the COVID-19 pandemic and led to a sharp decline in the number of cases in ophthalmological care. The aim of this analysis was to improve the understanding of the logistic structures of medical facilities as well as the effects of the pandemic. MATERIAL AND METHOD: Based on reported process data, a sample of the specialist ophthalmological departments were examined based on operation and procedure codes (OPS) and data submitted between 01.01.2017 and 31.05.2021 according to the benchmarking programmes of the Professional Association of German Anaesthetists (BDA), the Professional Association of German Surgeons (BDC), and the Association for Operating Theatre Management (VOPM). RESULTS: Eighteen ophthalmology departments from Germany were analysed. After the decline in the number of cases (by temporarily up to 48%) during the first wave of the pandemic, the case numbers of all interventions assessed as nonurgent continued to be reduced. While intravitreal injections hardly decreased during the first wave (- 16%), significant drops in the coverage of cataract surgery (- 79%), vitrectomies (- 35%), glaucoma surgery (- 59%), strabismus surgery (- 95%), and eyelid surgery (- 52%) were found. One exception was intravitreal injection, which stabilised at a lower level early on during the pandemic. Overall, the number of cases during the later phases of the pandemic were significantly reduced below the level of previous years, despite the maintenance of emergency care. The underuse was variable for different interventions. CONCLUSION: In addition to self-reported figures, the analysed process data demonstrates the effect that various factors had on elective as well as urgent operations within hospital care during the pandemic. Despite partial stabilisation of some services, a relevant supply gap for outpatient and inpatient interventions was identified, with corresponding effects on the eye health of the population, while compensation or performance enhancement have not taken place to date. Facing the growing preload and the demographic development, future structures must therefore allow for an increase in the performance of specialist ophthalmological departments.

A model to quantify the influence of treatment patterns and optimize outcomes in nAMD.

Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that often leads to severe and permanent vision loss. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to preserve vision in nAMD patients. Concurrently, treatment outcomes in real-world are inferior to those reported in clinical trials. The most likely reasons observed are fewer treatment-intensity in routine clinical practice than in clinical trials. The other possibility could be the delay in starting treatment and the re-treatment interval. Although a negative impact of aforementioned parameters seems obvious, quantitative impact measures remain elusive in a real-world setting due to a lack of an 'optimal treatment' control group. To overcome this shortcoming, we developed, validated, and applied a model to assess and quantify the impact of anti-VEGF administration variables on visual acuity development in a prospective nAMD patient cohort. The model was further applied to probe the impact of the COVID-19 pandemic on visual progressions in nAMD patients. The presented model paves the way to systematically explore and evaluate realistic interventions in the current treatment paradigm, that can be adopted in routine clinical care.

Viral S protein histochemistry reveals few potential SARS-CoV-2 entry sites in human ocular tissues.

Despite the reported low expression of the primary SARS-CoV-2 receptor ACE2 in distinct ocular tissues, some clinical evidence suggests that SARS-CoV-2 can infect the eye. In this study, we explored potential entry sites for SARS-CoV-2 by viral S protein histochemistry on various ocular tissues and compared the staining patterns with RNA and protein expression of TMPRSS2 and ACE2. Potential viral entry sites were investigated by histochemistry using tagged recombinant viral S protein on 52 ocular tissue samples including specimens of the cornea, conjunctiva, lid margin, lacrimal gland tissue, retina, choroid, and RPE. In addition, ACE2 and TMPRSS2 immunohistochemistry were performed on the same ocular tissue, each with distinct antibodies binding to different epitopes. Lung tissue samples were used as positive controls. Finally, bulk RNA sequencing (RNA-Seq) was used to determine the expression of ACE2 and its auxiliary factors in the tissues mentioned above. S protein histochemistry revealed a positive staining in lung tissue but absent staining in the cornea, the conjunctiva, eye lid samples, the lacrimal glands, the retina and the optic nerve which was supported by hardly any immunoreactivity for ACE2 and TMPRSS2 and scarce ACE2 and TMPRSS2 RNA expression. Negligible staining with antibodies targeting ACE2 or TMPRSS2 was seen in the main and accessory lacrimal glands. In contrast, ocular staining (S protein, ACE2, TMPRSS2) was distinctly present in pigmented cells of the RPE and choroid, as well as in the ciliary body and the iris stroma. S protein histochemistry revealed hardly any SARS-CoV-2 entry sites in all ocular tissues examined. Similarly, no significant ACE2 or TMPRSS2 expression was found in extra- and intraocular tissue. While this study suggest a rather low risk of ocular infection with SARS-CoV-2, it should be noted, that potential viral entry sites may increase in response to inflammation or in certain disease states.

Expression of the COVID-19 receptor ACE2 in the human conjunctiva.

SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. Recent studies have described conjunctival congestion in 0.8% of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and there has been speculation that SARS-CoV-2 can be transmitted through the conjunctiva. However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctivas, 12 melanomas, seven squamous cell carcinomas, and seven papilloma samples, were analyzed using high-throughput RNA sequencing to assess messenger RNA (mRNA) expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median: 0.0 transcripts per million [TPM], min: 0.0 TPM, max: 1.7 TPM) and protein levels. Similar results were obtained for the transcription of other auxiliary molecules. In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.

What is the significance of the conjunctiva as a potential transmission route for SARS-CoV-2 infections?

Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV­2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV­2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV­2. The current body of evidence indicates that SARS-CoV­2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV­2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.

[What is the importance of the conjunctiva as a potential transmission pathway for SARS-CoV-2 infections?] / Welche Bedeutung hat die Bindehaut als möglicher Übertragungsweg für eine SARS-CoV-2-Infektion?

Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV­2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV­2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV­2. The current body of evidence indicates that SARS-CoV­2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV­2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.