COVID 19 repercussions in ophthalmology: a narrative review

BACKGROUND: The new coronavirus of 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally and has repercussions within ophthalmological care. It has caused ocular manifestations in some patients, which can spread through eye secretions. OBJECTIVES: The purpose of this review was to summarize the currently available evidence on COVID-19 with regard to its implications for ophthalmology. DESIGN AND SETTING: Narrative review developed by a research group at Universidade Federal de São Paulo (UNIFESP), São Paulo (SP), Brazil, and at Ludwig-Maximilians-Universität, Munich, Germany. METHODS: We searched the literature on the repercussions of COVID-19 within ophthalmological care, using the MEDLINE and LILACS databases, with the keywords “COVID-19”, “ophthalmology” and “coronavirus”, from January 1, 2020, to March 27, 2021. Clinical trials, meta-analysis, randomized controlled trials, reviews and systematic reviews were identified. RESULTS: We retrieved 884 references, of which 42 were considered eligible for intensive review and critical analysis. Most of the studies selected reported the evidence regarding COVID-19 and its implications for ophthalmology. CONCLUSIONS: Knowledge of eye symptoms and ocular transmission of the virus remains incomplete. New clinical trials with larger numbers of patients may answer these questions in the future. Moreover, positively, implementation of innovative changes in medicine such as telemedicine and artificial intelligence may assist in diagnosing eye diseases and in training and education for students.


METHODS
We conducted a review of the literature considering the period from January 1, 2020, to March 27, 2021. We used the MEDLINE database (via PubMed) and LILACS (via Virtual Health Library) to identify relevant articles on the repercussions of COVID-19 within ophthalmological care, without restrictions on languages. Different combinations of keywords and MeSH terms were used as search strategies in order to ensure a broad search strategy: "ophthalmology", "COVID-19" and "coronavirus". The titles and abstracts of citations identified through these search strategies were screened for eligibility. We selected the main articles that reported on ophthalmological manifestations of coronavirus and how the pandemic was impacting ophthalmological care and education. We also selected articles that presented alternative solutions for eye care, such as the use of telemedicine and artificial intelligence. The details of the search strategy are shown in Table 1.

RESULTS
From the search in the databases, two clinical trials, 11 metaanalyses, one randomized controlled trial, 158 reviews and 27 systematic reviews were identified. After screening the titles and abstracts, removing duplicates and screening the citations, 42 studies were considered eligible for critical analysis. The article selection process is detailed in Figure 1.

Ophthalmological manifestations
The main symptom reported by infected patients was viral conjunctivitis (hyperemia, eye pain, photophobia and tearing), which lasted for 2 to 24 days (average of 6 days). The incubation period for this viral infection is 2 to 14 days. 8 In a study conducted among a total of 535 patients with COVID-19, 5.0% had conjunctival congestion, 29.6% had conjunctival discharge, 22.2% had watery eyes and 18.5% had ocular pain. Eye symptoms were usually present in patients with more severe symptoms of the disease. In that study, no viral nucleic acid was detected in the conjunctival swabs taken from the patients. 9 In another study on 1,099 patients, presence of conjunctival congestion was detected in 0.8% of the patients. Conjunctivitis in these patients usually has follicles and mucoid secretion. 10,11 Children can be affected by conjunctivitis, as well as adults, and they may present a picture of eyelid dermatitis. 12 The viral load of conjunctival sac secretions in patients with COVID-19 is relatively low and is usually proportional to the severity of the disease. 13 Xia et al. reported that SARS-CoV-2 existed only in the conjunctival and lacrimal secretions of a patient with conjunctivitis and that patients without ocular manifestations would not be a source of infection via this transmission route. 14 However, another study demonstrated the presence of the virus in the eye secretions of patients without conjunctivitis. 15 Therefore, ophthalmological examinations need to be carried out in a ventilated place and all possible measures should be taken to avoid cross-infection among ophthalmic patients. Patients should be advised not to touch their eyes because of the risk of contamination by the virus. The recommended treatment for viral conjunctivitis is supportive, and most cases are self-limiting. However, some recommendations for decreasing transmission rates should be followed, such as frequent hand washing and avoidance of touching one's eyes.
The coronavirus epidemic has changed the criteria for corneal donation in some countries. In these, exclusion of suspected or confirmed cases has been started. 16 Coronavirus patients may present with hyperreflective lesions at the level of ganglion cells and in the inner plexiform layer. This condition may be associated with hemorrhages and cottony exudates. 17 Cases of changes in ocular motility after coronavirus infection have been described. 18 Clinical findings such as conjunctivitis, retinitis, anterior uveitis and optic neuritis have been recognized in animal models. Thus, awareness of these possible manifestations in humans is needed. 19

Ophthalmological services
Because ophthalmological care is administered close to patients' faces, ophthalmologists are exposed to tears and eye discharges. The examination room needs to be well ventilated, and the ophthalmic devices should be disinfected immediately after use, with 0.1% sodium hypochlorite or 70% ethanol for at least one minute before and after examination of the patient. Use of a non-contact tonometer should be avoided because of the micro-aerosols that are generated. The tips of the Goldman tonometer need to be disinfected. 20,21 Examinations using direct ophthalmoscopy should be avoided due to the proximity to the patient. This can be replaced by retinography, which allows greater distancing from the patient. Acrylic shields need to be installed in the slit lamp, so as to reduce contact with aerosols generated by patients. Ophthalmological examinations should be conducted as soon as possible. Elective procedures should be postponed during this period. Emergency surgery for infected patients should be performed preferably in operating rooms with negative pressure. Moreover, surgery with general anesthesia should be avoided, given that intubation can generate an aerosol.
So far, there is no evidence to contraindicate use of contact lenses by patients. However, because it is known that the virus can be isolated in tears and conjunctiva, it is advisable to avoid adaptation to contact lenses during this period. The main objectives of these measures are to minimize cross-infection between employees and patients, and to ensure a safe working environment.

Telemedicine
The training of ophthalmology students has been greatly affected during the pandemic period, since most appointments and elective surgeries have been canceled. 22 Telemedicine with use of distance training has become an option for training clinical staff during this period. The teleguidance for ophthalmological patients has also been used, with the aims of correctly directing emergencies to hospitals and preventing patients from unnecessarily looking for hospitals, which might increase their risk of contamination. During this period, use of training models and simulators has proven to be useful in training these students for surgery and eye examination. [23][24][25] Patients can also be assisted through teleophthalmology, which can be improved with appropriate training for healthcare professionals. Quality images can be captured and sent to ophthalmologists in other locations. In special pandemic situations, some images can even be captured by patients using smartphones. 26,27 The COVID-19 pandemic has transformed some leading telehealth platforms, which have reported that virtual visits by patients have increased by between 257% and 700%. 28 For evaluation of macular diseases, there are applications and devices to monitor the central 10 degrees of the field of view, such as the hyperacuity perimeter ForSee device (Notal Vision). 29 There are already smartphones capable of capturing images of the retina, but they have not yet been designed for patients to use at home. 30 During this period of global health emergency, rapid communication and international collaboration are essential, in order to achieve better outcomes from the pandemic, and telemedicine has collaborated in this process. Teleophthalmology plays an important role in rural areas and in places with few specialists, but during this pandemic it has become useful even in areas with enough ophthalmologists, in order to promote social isolation and reduce the rate of virus transmission.

Artificial intelligence
In this scenario of difficult access to eye care, artificial intelligence SciSight is an algorithm that uses artificial intelligence to explore associations between concepts that appear in the COVID-19 dataset. It is available at https://SciSight.apps.allenai.org/. 40 [48][49][50][51] Academic medical centers should take this opportunity to modify their curricula, including training in data science, computing, virtual reality and telemedicine. The expectation is that, with increasing levels of vaccination in the population, eye care and the number of surgeries will be able to return to normal within a short time. 52

Strengths and limitations
The articles included in this review generated heterogeneous data because of the diversity in the design of the studies (clinical trials, meta-analysis, randomized controlled trials, reviews and systematic reviews). The main limitation of this review was the lack of tools for methodological assessment of the reviews. This narrative review does not provide quantitative answers to specific questions about the ophthalmic manifestations of coronavirus.
The selection of studies and the interpretation of information may have been influenced by the authors' subjectivity.