Report of a case of perforating nodular scleritis developed after hospitalisation for COVID-19 pneumonia (preprint)

Introduction: Conjunctivitis, keratoconjunctivitis, and episcleritis are known ocular surface manifestations of coronavirus disease. Case presentation: A 56-year-old male patient experienced red eye two days after being released from the COVID department. Two weeks later developed nodular scleritis. Ultrasound biomicroscopy raised the possibility of a foreign body or helminth; however, this was not confirmed during the surgical exploration. From an intraoperatively obtained sample, methicillin-resistant Staphylococcus aureus grew, while coronavirus could not be detected. Systemic work-up yielded negative results except for the Quantiferon gold test, but as histology showed granulation tissue, not granulomatous inflammation, it was unlikely that Mycobacterium pneumoniae had a role in ocular inflammation. After targeted local antibiotic therapy, the inflammation resolved slowly over the next five months. Conclusions: Thorough systematic workup, surgical exploration, and sample collection were necessary to determine the exact etiology, where only an indirect connection came to light with the COVID infection itself. To the best of our knowledge, there have been no previously published attempts to detect SARS-CoV-2 in scleral inflammatory tissue.

Posterior Scleritis Following COVID-19 Vaccination or Infection Simulating Uveal Melanoma in 8 Consecutive Patients (preprint)

Objectives To determine clinical features and outcomes of posterior scleritis masquerading as uveal melanoma following vaccination against COVID-19 and/or COVID-19 infection.Subjects/Methods: All patients with posterior scleritis referred to our service to rule out intraocular tumor between February 2021 and June 2022, who previously had COVID-19 vaccination and/or infection (n = 8). A retrospective detailed review of patient charts and imaging was carried out.Results Previous COVID-19 vaccination was documented in 6 patients (75%) and previous COVID-19 infection and vaccination in 2 patients (25%). Demographic features included mean age of 59 years (median 68, range 5–86 years), white race (n = 7, 87%), and male sex (n = 5, 63%). Mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70). The main presenting symptom was blurred vision with pain (n = 5, 63%). Features that suggested scleritis and not uveal melanoma included pain (n = 6, 75%), anterior scleritis (n = 3, 38%), disc edema (n = 1, 13%), choroidal detachment (n = 3, 38%), choroidal folds (n = 3, 38%), diffusely thickened scleral wall on ultrasonography (n = 2, 25%), Tenon’s edema (n = 5, 63%), and scleral nodule with medium/high internal reflectivity on ultrasonography (n = 4, 50%). Follow-up information at mean of 2 months (range 0.25-7 months) revealed visual acuity at date last seen was mean 0.30 LogMAR (median 0.29, range 0.0-0.54). By 2 months, resolution of “tumor” was noted in 5/6 (83%) patients with follow-up.Conclusions Posterior scleritis following COVID-19 vaccination and/or infection can masquerade as choroidal melanoma. At 2 months duration, partial or complete resolution of features with minimal visual consequence was noted.

Peripheral Ulcerative Keratitis in a Young Lady with Systemic Lupus Erythematosus Post Rituximab Infusion-A Case Report.

AIM: We report a new ocular finding of episcleritis (OD) and peripheral ulcerative keratitis (OS) in a 40-year-old lady with a 13-year history of systemic lupus erythematosus (SLE), 3 weeks post-rituximab infusion. MATERIALS & METHODS: Retrospective case report. RESULTS: A 40-year-old lady with a history of SLE and 3 weeks post rituximab infusion developed a new onset episcleritis (OD) and peripheral ulcerative keratitis (OS). As the PUK continued to advance with a leading edge, intravenous methyl prednisolone 1 gm/day was given for 3 days followed by a slow tapering course of oral prednisolone 50 mg/day. Though her ocular inflammation resolved, she developed pneumonia 6 weeks later. At 10 months follow-up, there were no ocular recurrences. She is currently on mycophenolate mofetil 2 gm/day along with oral prednisolone of 10 mg/day. CONCLUSION: This case highlights the new occurrence of episcleritis and PUK in SLE post-rituximab infusion.

Atypical immunologic manifestations of COVID-19: A case report and a comprehensive review (preprint)

Introduction: COVID-19 usually presents with classic signs and symptoms, but it can involve multiple systems in atypical cases. SARS-CoV-2 has a complex interaction with the host immune system leading to atypical manifestations.  Case Presentation: In our case, a 32-year-old male patient presented with fatigue, sores on hands and feet, headache, productive cough with blood-tinged mucus, conjunctival hyperemia, purpuric rash on hands and feet, and splinter hemorrhages of fingernails for two weeks. The patient’s SARS-CoV-2 antigen and PCR test were positive. Chest x-ray showed mixed density perihilar opacities in both lungs. Computed tomography of the chest showed extensive airspace opacities in both lungs, suggesting COVID-19 multifocal, multilobar pneumonitis. A renal biopsy indicated limited thrombotic microangiopathy and tubulointerstitial nephritis, for which he was started on steroids, and his renal functions gradually improved. He tested positive for C-ANCA during an immune workup. He was discharged with a steroid taper for nephritis. Once the taper reached less than 10 mg/day, he developed acute scleritis and a new pulmonary cavitary lesion of 6 centimeters. The biopsy via bronchoscopy revealed acute inflammatory cells with hemosiderin-laden macrophages. He was restarted on systemic steroids for scleritis after failing topical steroids, which incidentally also reduced the size of the cavitary lesion, indicating an immune component.  Conclusions: Our case demonstrates the involvement of kidneys and vasculitis of the skin, sclera, and lungs by COVID-19. The patient’s symptoms were not explained by any diseases other than COVID-19. Atypical cases of COVID-19 disease with multifocal systemic symptoms involving the skin, sclera, lungs, and kidneys should be high on differentials. Early recognition and intervention may decrease hospital stays and morbidity.

Colombian Ocular Inflammatory Diseases Epidemiology Study (COIDES): Prevalence, Incidence, and Sociodemographic Characterization of Scleritis in Colombia, 2015-2020 (preprint)

ABSTRACT Objective To describe the epidemiological and demographic characteristics of scleritis in Colombia. Methods and Analysis Population-based study using the national database from the Colombian Ministry of Health, using the ICD-10 code for Scleritis (H150) to estimate the prevalence and incidence from 2015 to 2019. Additionally, we evaluated the impact of the COVID-19 pandemic lockdown on the epidemiology of the disease during 2020, using the Gaussian Random Markov Field model (CAR model). Finally, a standardized morbidity rate map was made to assess the geographic distribution of scleritis in the country. Results The five-year average incidence and prevalence of scleritis in Colombia were 0.6 (95% CI 0.59-0.6) and 0.65 (95% CI 0.64-0.64) cases per 100,000 inhabitants, respectively. We found 1,429 registers of scleritis throughout the country between 2015 and 2019. Women represented 64.3%. The age groups with most cases were between 40 and 69 years in both sexes. However, women between 30-39 years and men between 20-29 years presented the highest number of new cases. In 2020, the pandemic reduced approximately 0.23 points the incidence of scleritis. Bogotá, Valle del Cauca, and Antioquia had most of the cases, the latter two with an increased risk over time. Conclusion Colombia has a lower incidence of scleritis than the reported in other latitudes, with a pattern of presentation at younger ages. Furthermore, the lockdown derived from the CODIV-19 pandemic affected the follow-up and diagnosis of patients with scleritis. This is the first epidemiological description of scleritis in a developing country and South America. Key messages What is already known about this subject? Scleritis epidemiology has been described in developed countries. Its prevalence has been calculated between 1.7 and 93.62 cases per 100,000 inhabitants, and its incidence between 1.0 and 5.54 cases per 100,000 inhabitants per year. What are the new findings? This study describes the epidemiological characteristics of scleritis in a developing country in South America for the first time, finding that the incidence and prevalence of scleritis in Colombia are 0.6 (95% CI: 0.59-0.6) and 0.65 (95% CI: 0.64-0.64) cases per 100,000 inhabitants, respectively. With a high number of new cases in the young population. Also, the pandemic’s negative impact on the diagnosis and follow-up of patients with scleritis was evidenced. How might these results change the focus of research or clinical practice? This article will promote the generation of new research questions in a population that did not have previous studies on this topic. Also, the data highlight that younger people present more new cases and may need more attention from ophthalmologists. This might be due to a lower incidence of scleritis in the elderly population with autoimmune diseases owing to the treatment with immunomodulatory medications.

Recurrent Anterior Non-necrotizing Scleritis as an Adverse Event of ChAdOx1 nCoV-19 (Vaxzevria) Vaccine.

PURPOSE: To describe a case of anterior scleritis related to SARS-CoV-2 vaccine. SARS-CoV-2 vaccines appear safe; however vaccination has triggered thromboembolic events in predisposed patients. METHODS: A retrospective case report of anterior scleritis in a woman following administration of both ChAdOx1nCoV-19 vaccine doses was studied by complete ophthalmologic examination and complementary tests. RESULTS: The patient has overcome SARS-CoV-2 infection a year prior. Ancillary tests including autoimmune and infectious diseases were negative. The chronology between ChAdOx1nCoV-19 vaccine and the sequential episodes of scleritis may have a cause-and-effect relationship. CONCLUSION: Ophthalmologists may be aware of scleritis as an ocular manifestation following ChAdOx1nCoV-19 vaccine, in otherwise healthy patients.

Coronavirus Disease 2019, Eye Pain, Headache, and Beyond.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), emerged in December 2019 and became a devastating pandemic. Although its respiratory effects can be deadly and debilitating, it can lead to other systemic disorders, such as those causing eye pain and headache. This literature review aims to describe presentations of eye pain and headache in relation to COVID-19, with an emphasis on how these disorders help us to understand the pathophysiology of COVID-19. EVIDENCE ACQUISITION: Literature was mined from the PubMed database using the key terms: "eye pain," "conjunctivitis," "episcleritis," "optic neuritis," "migraine," and "headache" in conjunction with "COVID-19" and "SARS-CoV-2." With the exception of general background pathology, articles that predated 2006 were excluded. Case reports, literature reviews, and meta-analyses were all included. Where SARS-CoV-2 research was deficient, pathology of other known viruses was considered. Reports of ocular manifestations of vision loss in the absence of eye pain were excluded. The primary search was conducted in June 2021. RESULTS: The literature search led to a focused review of COVID-19 associated with conjunctivitis, episcleritis, scleritis, optic neuritis, and myelin oligodendrocyte glycoprotein-associated optic neuritis. Four distinct COVID-19-related headache phenotypes were identified and discussed. CONCLUSIONS: Eye pain in the setting of COVID-19 presents as conjunctivitis, episcleritis, scleritis, or optic neuritis. These presentations add to a more complete picture of SARS-CoV-2 viral transmission and mechanism of host infection. Furthermore, eye pain during COVID-19 may provide evidence of hypersensitivity-type reactions, neurovirulence, and incitement of either novel or subclinical autoimmune processes. In addition, investigation of headaches associated with COVID-19 demonstrated 4 distinct phenotypes that follow third edition of the International Classification of Headache Disorders categories: headaches associated with personal protective equipment, migraine, tension-type headaches, and COVID-19-specific headache. Early identification of headache class could assist in predicting the clinical course of disease. Finally, investigation into the COVID-19-associated headache phenotype of those with a history of migraine may have broader implications, adding to a more general understanding of migraine pathology.

Ocular inflammatory events following COVID-19 vaccination: a multinational case series (preprint)

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19-84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1-14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤ 3 lines and > 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome.

Association of Ocular Adverse Events With Inactivated COVID-19 Vaccination in Patients in Abu Dhabi.

Importance: As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective: To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, Setting, and Participants: This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main Outcomes and Measures: Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results: Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and Relevance: In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.

Anterior Scleritis Manifesting After Coronavirus Disease 2019: A Report of Two Cases.

PURPOSE: The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19). METHODS: The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated. RESULTS: Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment. CONCLUSIONS: These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.

COVID-19 ocular findings in paediatric population (preprint)

Purpose To investigate and describe ocular findings in COVID-19 paediatric patients. Methods A total of 17 COVID-19 patients aged between 0 and 17 years old were recruited at the Paediatric Hospital of La Paz University Hospital (Madrid, Spain). A complete ophthalmological examination was performed in all patients.  Results Of 17 patients, 50% had a known COVID-19 previous exposure. PCR from nasopharyngeal swabs was positive in 35.29%, whereas IgM and/or IgG serology tests were positive in 81%. Clinical manifestations were: 6 COVID-19associated Paediatric Inflammatory Multisystem Syndrome (PIMS), 7 pneumonias and 2 cutaneous purpura and/or chilblains. Ocular findings were ocular hyperaemia (5 patients), as bilateral acute conjunctivitis (3 patients) or unilateral episcleritis (2 patients). Mean best corrected visual acuity was 1/1 in all tested cases. Only one patient, presenting unilateral optic neuritis, had visual symptoms as unilateral inferior temporal quadrantanopsy. Retinal involvement was found in one patient, where ocular fundus exam showed unilateral retinal vasculitis. Conclusion SARS-CoV-2 infection could produce ocular pathology in children, frequently presented weeks after the acute phase of the disease. We should take into account COVID-19 when performing differential diagnosis of children presenting with conjunctivitis, episcleritis, retinal vasculitis and/or optic neuritis, meanwhile this world-wide pandemic lasts.   

Ocular manifestations of coronavirus disease 2019.

PURPOSE: Coronavirus disease 2019 (COVID-19) is an ongoing global public health problem, and most of the COVID-19 research is focused mainly on the respiratory system because of life-threatening results. However, manifestations in other organs should not be ignored since they can also be a mode of transmission. We sought to describe the ocular manifestations of COVID-19 and investigate the association between ocular involvement and clinical presentation and laboratory outcomes. METHODS: This cross-sectional study was conducted between March 1, 2020, and April 30, 2020. Ninety-three sequentially hospitalized and clinically confirmed COVID-19 patients were included in the study. The systemic and ocular symptoms, clinical findings, and laboratory outcomes were recorded. RESULTS: Of the 93 COVID-19 patients, 54 (58.1%) were male, and 39 (41.9%) were female. Mean age of the patients was 39.4 ± 21.9 (min 7, max 88) years. Twenty patients (n 21.5%) had at least one ocular abnormality. Most common findings included hyperemia (n = 20), epiphora (n = 9), increased secretion (n = 6), chemosis (n = 3), follicular conjunctivitis (n = 2), and episcleritis (n = 2). The most common symptom was photophobia (n 15). Patients with ocular involvement were more likely to have higher neutrophil counts (p = 0.001), and increased CRP (p < 0.001), PCT (p = 0.001), and ESR levels (p < 0.001). Mean lymphocyte count was statistically lower in patients with ocular manifestations (p = 0.001). Mean age and number of patients with fever over 37.3 °C in the ocular involvement group was found to be higher (p < 0.001, p = 0.006, respectively). CONCLUSION: Older age, high fever, increased neutrophil/lymphocyte ratio, and high levels of acute phase reactants seemed to be risk factors for ocular involvement.