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Ophthalmic manifestations in patients recovered from COVID-19 in Mexico
Abstract
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 3,081 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.
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Due to the COVID-19 pandemic, numerous vaccines have been developed for the disease. However, with large-scale vaccination has come the gradual emergence of immunological phenomena caused by these new vaccines. Herein, we report a 48-year-old female with a sudden onset of inferior visual field defects in the left eye following her first dose of the ChAdOx1 vaccine. Dilated fundus examination combined with optical coherence tomography and fluorescein angiography confirmed the diagnosis of branch retinal artery occlusion. Within 4 weeks following vaccination, symptoms associated with hearing impairment developed, and magnetic resonance imaging revealed leptomeningeal enhancement. The diagnosis of Susac syndrome (SS) was confirmed. The development of SS may be caused by endotheliopathy resulting from the molecular mimicry of the ChAdOx1 vaccine. Clinicians should be aware of the symptoms of SS, which may develop after COVID-19 vaccination. Further experimental surveillance and case–control studies are required to confirm this relationship.
Introduction
Increased risk of thromboembolic events has been associated with SARS-CoV-2 infections and more recently, with COVID-19 vaccination. To date, however, there are no reports of an association between the COVID-19 vaccination and retinal artery occlusions. We report a case of a patient who developed central retinal artery occlusion (CRAO) 2 days following the administration of the AstraZeneca COVID-19 vaccine.
Case description
A 76-year-old woman presented to our Department of Ophthalmology complaining of painless vision loss in her left eye 48 hours after she had received her first dose of the AstraZeneca COVID-19 vaccine. Her best-corrected visual acuity was only hand movement in the left eye. Left eye ophthalmologic examination showed the presence of arterial narrowing and a cherry red spot. Optical coherence tomography showed severe macular swelling of the inner retinal layers in the left eye Fluorescein angiography performed the following day confirmed the diagnosis. The cardiovascular examination including Holter ECG was unremarkable. Complete blood count was within normal limits, without thrombocytopenia. A subsequent cerebral CT and CT-angiography scans did not show any other acute vascular event. Doppler angiography of the carotid artery was performed and showed normal flow without clinically significant plaques, stenoses, occlusions or dissections.
Conclusions
To our knowledge, this is the first case of an isolated CRAO following the administration of the AstraZeneca COVID-19 vaccine. Further studies are needed to evaluate this potential association and identify pathophysiologic relationships between COVID-19 vaccinations and CRAO.
Introduction and aim
Mucormycosis is a lethal opportunistic infection caused by filamentous fungi of the family Mucoraceae (black fungus). There has been a sudden increase in the incidence of these cases during the second wave of the COVID-19 pandemic due to the immunocompromised state caused by the disease and its treatment. Early diagnosis and appropriate medical management are essential to reduce disease morbidity and mortality. Through this study, we aim to study the clinical features, risk factors, laboratory investigations, and radiological findings of patients with mucormycosis as well as evaluate the clinical outcomes in each case.
Methods and materials
This was a prospective study that included only confirmed mucormycosis cases admitted in Tata Main Hospital (TMH) from April 2021 to July 2021. A case of mucormycosis was defined as the one in which clinical and radiological features were consistent with mucormycosis and fungus was demonstrated in the tissue by potassium hydroxide (KOH) mount/culture/histopathological examination (HPE). Data relating to epidemiology, risk factors, clinico-radiological features, and outcomes were analyzed and expressed as a percentage of total cases.
Results
Of the total 15 cases, three patients (33.3%) had active COVID-19 infection, eight (53.3%) were in the post-COVID-19 state, two (13.4%) had COVID-19 like illness and two (13.4%) patients did not have COVID-19 in the recent past. There was male predominance with the male to female ratio being 2.75:1. The commonest associated co-morbid condition was diabetes mellitus (13 patients, 86.7%). Amongst the myriad manifestations, periorbital swelling was the commonest symptom (11 patients, 73.3%). Among neurological manifestations, involvement of cranial nerves was found in nine (60%) patients with the third cranial nerve being the most commonly affected nerve (eight patients, 53.3%). Cavernous sinus thrombosis (CST) was found in one (6.7%) patient. Diagnostic nasal endoscopy (DNE) revealed eschar at various sites in 13 patients (86.7%). Central retinal artery occlusion (CRAO) was found bilaterally in one patient (6.7%) while two patients (13.3%) had CRAO on the left. Radiologically, the most commonly involved sinuses were maxillary and ethmoidal (eight patients, 53.3%). Bilateral sinus involvement was more common (46.7%) than unilateral sinus involvement. The average length of stay (LOS) was 17.5±7.8 days. The overall mortality was 40%. Five (33.3%) patients developed secondary bacterial infections. All patients received medical therapy with intravenous amphotericin B. In addition, seven (46.7%) patients underwent functional endoscopic sinus surgery (FESS) with debridement of which, five (71.4%) patients survived and made a good recovery. One patient (6.7%) with pulmonary mucormycosis underwent lobectomy.
Conclusion
New-onset headache, black nasal discharge, periorbital swelling, retro-orbital pain, visual diminution, restriction of eye movements should prompt an immediate search for mucormycosis especially in the background of history of diabetes mellitus in patient with recent or current COVID-19 disease. Radio-imaging with computerized tomography and magnetic resonance imaging are complementary to clinical evaluation in assessing the disease extent and diagnosis of complications. Prompt diagnosis is essential due to the angio-invasive nature of the mucor and requires aggressive anti-fungal therapy and debridement of the devitalized tissue.
Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine.
To describe the medium-term ophthalmological findings in patients recovering from COVID-19. Patients recovered from the acute phase of COVID-19 underwent a complete ophthalmological evaluation, including presenting and best-corrected visual acuity (BCVA), refractometry, biomicroscopy, tonometry, break-up time and Schirmer tests, indirect ophthalmoscopy, color fundus picture, and retinal architecture evaluation using optical coherence tomography. Socio-demographic data and personal medical history were also collected. According to the severity of systemic manifestations, patients were classified into mild-to-moderate, severe, and critical. Sixty-four patients (128 eyes) were evaluated 82 ± 36.4 days after the onset of COVID’s symptoms. The mean ± SD duration of hospitalization was 15.0 ± 10.7 days. Seven patients (10.9%) had mild-to-moderate, 33 (51.5%) severe, and 24 (37.5%) critical disease. Median [interquartile ranges (IQR)] presenting visual acuity was 0.1 (0–0.2) and BCVA 0 (0–0.1). Anterior segment biomicroscopy was unremarkable, except for dry eye disease, verified in 10.9% of them. The mean ± SD intraocular pressure (IOP) in critical group (14.16 ± 1.88 mmHg) was significantly higher than in severe group (12.51 ± 2.40 mmHg), both in the right ( p 0.02) and left eyes ( p 0.038). Among all, 15.6% had diabetic retinopathy, and two patients presented with discrete white-yellowish dots in the posterior pole, leading to hyporreflective changes at retinal pigment epithelium level, outer segment, and ellipsoid layers. The present study identified higher IOP among critical cases, when compared to severe cases, and discrete outer retina changes 80 days after COVID-19 infection. No sign of uveitis was found.
Introduction:
The symptoms of coronavirus disease-19 (COVID-19) may range from mild to severe. Patients usually present with fever, cough, and other respiratory tract symptoms, but may also be asymptomatic. Some studies have also indicated the ocular involvement by the virus. This study aims to look deeply into all ophthalmic findings seen in COVID-19 patients and their clinical characteristics.
Methods:
This longitudinal study was conducted in the COVID-19 unit of a tertiary care hospital, Pakistan. Data of patients hospitalized with COVID-19 infection between July 2020 and March 2021 were included in the study. Ophthalmological examination was done at the time of admission and was repeated every alternate day to look for any ophthalmological manifestation.
Results:
Out of 441 (n= 441), 61 (13.8%) participants had ophthalmological findings on examination. Patients with ophthalmological findings were significantly younger compared to patients without ophthalmological findings (42 ± 6 years vs. 44 ± 7; p-value, 0.03). C-reactive protein (CRP) was also significantly higher in patients with ophthalmological findings (122.2 ± 16.2 vs. 112.8 ± 19.8; p-value, 0.005). The most common ophthalmological finding was conjunctival irritation (50.8%), followed by diplopia (27.8%) and cotton wool spots (27.8%).
Conclusion:
Ophthalmological findings are prevalent in patients with COVID-19. In this study, patients with higher CRP levels were associated with ophthalmological findings. It is important to conduct ophthalmological examinations in patients with COVID-19, as they may give a clue about other complications associated with COVID-19.
Objective: To determine if there was an increase in the rate of cases presenting with rhino-orbital-cerebral mucormycosis (ROCM) to a tertiary care center during the first wave of the COVID-19 pandemic, and the characteristics of the presenting cases.
Methods: Retrospective observational study reviewing ROCM cases presenting from March 25th till September 25th, 2020. Cases fulfilling the clinical, radiological, and pathological/microbiological criteria for diagnosis with ROCM were included. Number of cases presenting during the designated interval, their COVID-19 status, comorbidities, and clinical presentation were analyzed. Number of cases during the corresponding interval in the previous 3 years was used as reference to detect if there was a recent spike.
Results: Of the 12 ROCM cases identified, 5 had a concurrent positive RT-PCR test result for SARS-CoV-2, 1 had a prior positive result, and 6 did not have concurrent nor prior positive test results. Nine of the 12 cases had poorly controlled diabetes mellitus, and 2 cases had a hematologic malignancy. All cases had orbital invasion and 8 cases had cerebral invasion. The number of cases identified during the interval is much higher than numbers presenting in the prior 3 years during equivalent intervals (range: 1 -2 cases), and than those reported in the literature in different settings in the pre-pandemic era.
Conclusions: There is an increased rate of ROCM cases presenting to our center during the first wave of the COVID-19 pandemic. This is a preliminary report and further studies are needed to corroborate the findings and explain possible underlying links.
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had health implications of unprecedented magnitude. The infection can range from asymptomatic, mild to life threatening respiratory distress. It can affect almost every organ of the body. Ophthalmologists world over are reporting various manifestations of the infection in the eye. This review was undertaken to help ophthalmologists recognize the possible manifestations and the stage of the viral disease when they commonly appear. Literature search was performed for the publications on ophthalmic manifestations of coronavirus disease-19 (COVID-19) between January 1, 2020 and January 31, 2021. 46 case reports, 8 case series, 11 cross sectional/cohort observational studies, 5 prospective interventional studies, 3 animal models/autopsy studies and 6 reviews/meta-analysis were included. Conjunctivitis is the most common manifestation and can develop at any stage of the disease. Direct effect due to virus, immune mediated tissue damage, activation of the coagulation cascade and prothrombotic state induced by the viral infection, the associated comorbidities and drugs used in the management are responsible for the findings in the eye. The viral ribonucleic acid (RNA) has been isolated from ocular tissues but the role of eye as a route for infection is yet to be substantiated. Ophthalmic manifestations may be the presenting feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of the possible associations of ocular diseases with SARS-CoV-2 in order to ask relevant history, look for specific signs, advise appropriate tests and thereby mitigate the spread of infection as well as diagnose and initiate early treatment for life and vision threatening complications.
SARS CoV-2, the causal agent of the Covid- 19 disease, infects the digestive and respiratory mucosa, affecting epithelial cells. The virus enters through the ACE2 membrane receptor causing the disruption of cell homeostasis. Frequent reports indicate the presence of ocular conjunctivitis in patients diagnosed with Covid-19, which has alerted scientists to the potential source of viral infection from lacrimal secretions. The epithelia of the sub-palpebral and corneal ocular conjunctiva are characterized by presenting the receptor for angiotensin-converting enzyme 2 (ACE2) and associated transmembrane protease serine 2 (TMPRSS2), whose interaction activates cytokine release mechanisms, with the ability to start the infectious conjunctivitis process by SARS CoV-2, but not necessarily extend the infection to the digestive and respiratory systems. Although this inflammatory process is more frequent as an expression of the general and more serious infection. However, whatever the route of infection or entry of the SARS CoV-2 virus, it is important to consider the risk of infection of tears and conjunctival secretions in patients. This study aims to draw attention to health care and control measures, incorporating better standards of personal protection and biosafety, especially in the areas of ophthalmology, assuming that the ocular mucosa can be a route of entry for the virus, and at the same time a source of contagion. A further consideration is the potential of viral infection with associated underlying diseases, such as glaucoma and diabetes. It is also suggested to incorporate histological studies of the ocular mucosa to differentiate healthy and infected epithelia.
Aim
The current world has changed in all shapes since the emergence of the novel coronavirus (nCoV-2) also known as COVID-19. Among the extra-pulmonary manifestations of nCoV-2, ophthalmic symptoms have less been systematically studied. The so far existing body of evidence indicates that nCoV-2 has the potential to affect both anterior and posterior chambers of the eye. Albeit, the exact mechanisms which underlie ophthalmic manifestations of nCoV-2 are yet to be elucidated.
Methods
The present brief review is an attempt to put together and highlight the significant yet limited number of studies which have spotlighted ophthalmic issues in nCoV-2 patients using a systematic literature search strategy.
Results
All case series or reports (including both published and preprint articles) which described ocular manifestations of patients with COVID-19 and/or documented testing of SARS-COV-2 in ocular secretions via various sampling or detection methods were sought to be included.
Conclusion
The ophthalmic presentations in SARS-COV-2 are often found to be salient. Raising awareness in this respect may help defining evidencebased protective measures in today’s practice of ophthalmology and allied disciplines.
Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.
The worldwide outbreak of the severe and acute respiratory coronavirus disease (COVID-19) caused by the coronavirus strain SARS-CoV-2 is currently the focal point of discussion due to the suffering this syndrome is causing to humanity. However, the ophthalmological implications of this syndrome has not yet been well described. Both eyes and tears as portals of entry and sources of contagion have been the subject of debate by many authors. The purpose of this review is to summarize the evidence currently available on COVID-19 and its ocular implications and manifestations, in both animals and humans, with the aim to facilitate prevention and educate the ophthalmological community on this subject. A review of the literature revealed that the results of some studies suggest that ocular symptoms commonly appear in patients with severe COVID-19 pneumonia and that it is possible to isolate the virus from the conjunctival sac of these patients. Conjunctivitis is not a common manifestation of the disease, but contact with infected eyes could be one route of transmission. Consequently, ophthalmologists need to have correct prevention strategies in place. Some guidelines regarding the prevention and management of ophthalmology clinics are reviewed. However, well-designed trials should be conducted to rule out other ocular manifestations that may result from COVID-19 infection and to understand the transmission of the virus through the eyes.
Acute invasive fungal rhinosinusitis is a rare, although highly morbid, infection primarily affecting immunosuppressed individuals. The same population is at particularly high risk of complications and mortality in the setting of SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. The authors present a case of acute invasive fungal rhino-orbital mucormycosis in a patient with COVID-19 and discuss the prevalence, diagnosis, and treatment of fungal coinfections in COVID-19. Prompt recognition, initiation of therapy, and consideration of the challenges of rapidly evolving COVID-19 therapy guidelines are important for improving patient survival.
Purpose
The spike proteins of SARS-CoV-2 interact with ACE2 or basigin/CD147 receptors, regulating human-to-human transmissions of COVID-19 together with serine protease TMPRSS2. The expression of these receptors on the ocular surface is unknown.
Material and Methods
Gene expression of SARS-CoV-2 receptors was investigated in conjunctival epithelial cell samples and in ex-vivo cornea samples using microarray or transcriptome sequencing.
Results
ACE2 is expressed in conjunctival samples at a low level, while BSG and TMPRSS2 are expressed at intermediate levels in both conjunctiva and cornea. Other receptors such as ANPEP, AGTR2 are expressed at low level in the conjunctiva. Two RNA editing enzymes involved in antiviral responses, APOBEC3A, and ADAR-1 were also highly expressed.
Conclusions
The ocular surface may represent an entry point for the SARS-CoV-2 in the human body. The conjunctiva and the cornea can adopt antiviral countermeasures which may explain the low prevalence of eye involvement.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.
All components necessary for the formation of angiotensin II, the biologically active product of the renin-angiotensin system (RAS), have been demonstrated in ocular tissue or vitreous and subretinal fluid. The tissue concentrations of renin were too high to be explained by admixture of blood. This raises the possibility of an intraocular RAS, independent of the RAS in the circulation.
In the present study, gene expression of RAS components in different parts of enucleated human eyes was investigated as evidence for tissue specific production.
By using pooled tissue samples renin mRNA could be detected with the RNAse protection assay in retinal pigment epithelium (RPE) choroid, but not in neural retina or sclera. With reverse transcription polymerase chain reaction (RT-PCR), renin mRNA was detected in individual samples of RPE choroid and neural retina, and not anterior uveal tract or sclera. Angiotensinogen and angiotensin converting enzyme (ACE) gene expression could be demonstrated by RT-PCR in individual RPE choroid and neural retina samples and marginally in sclera samples.
These results support the concept of intraocular synthesis of angiotensin II, independent of renin, angiotensin, and ACE in the circulation. Since gene expression was highest in ocular parts, which are highly vascularised, local angiotensin II may be involved in blood supply and/or pathological vascular processes such as neovascularisation in diabetic retinopathy.
Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular renin-angiotensin system
- Wagner
Frequency of ophthalmological findings in hospitalized COVID-19 patients
- Khan