Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

Tubulointerstitial nephritis and uveitis in children during the COVID-19 pandemic: report of four cases.

Tubulointerstitial nephritis and uveitis (TINU) is a rare autoimmune disorder often triggered by drugs and infections. Since the onset of the COVID-19 pandemic, we have observed an unusual cluster of paediatric cases. Four children (3 females) were diagnosed with TINU (median age 13 years) following a kidney biopsy and ophthalmologic assessment. Presenting symptoms included abdominal pain (3 cases), fatigue, weight loss and vomiting (2 cases). At presentation, median eGFR was 50.3 ml/min/1.73m2 (range 19.2-69.3). Anaemia was common (3 cases) with median haemoglobin of 10.45 g/dL (range 8.4-12.1). Two patients were hypokalaemic and 3 had non-hyperglycaemic glycosuria. Median urine protein:creatinine ratio was 117 mg/mmol (range 68-167). SARS-CoV-2 antibodies were detected in 3 cases at presentation. All were asymptomatic for COVID-19 with a negative PCR. Kidney function improved following high-dose steroids. However, disease relapse was observed during steroid tapering (2 cases) and upon discontinuation (2 cases). All patients responded well to further high dose steroids. Mycophenolate mofetil was introduced as a steroid-sparing agent. At latest follow up (range 11-16 months), median eGFR was 109.8 ml/min/1.73m2. All four patients continue on mycophenolate mofetil, with 2 patients applying topical steroids for uveitis. Our data suggest that SARS-CoV-2 infection might be a trigger for TINU.

RARE COMPLICATION OF COVID -19 DISEASE TINU SYNDROME IN A 11-YEAR-OLD BOY, FEATURES AND MANAGMENT.

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare disease defined by a combination of different abnormalities, tubulointerstitial nephritis and uveitis. We describe an 11-year-old boy who got sick with the Covid-19 disease with positive outcome and after 2 weeks developed a complication - tubulointerstitial nephritis with pain in the abdominal cavity, loss of appetite, weakness and low-grade fever with further subsequent attachment of anterior uveitis. Laboratory indicators corresponded to renal insufficiency of tubular origin. Ophthalmological examination conducted against the background of redness of both eyes, photophobia, pain in the eyeball area and decreased vision confirmed bilateral uveitis. Analysis showed high levels of La/SS-B, anti-SARS-CoV-2 IgG with confirmed the suspicion of post-covid TINU syndrome. This case showed a good response to steroid therapy with long-term remission of nephritis and less clinical efficacy in the treatment of uveitis. Special attention should be paid to the occurrence of such a rare syndrome at an early stage after recovery from the Covid-19 disease.

Association between Immunosuppressive Drugs and Coronavirus Disease 2019 Outcomes in Patients with Noninfectious Uveitis in a Large US Claims Database.

PURPOSE: To determine the dose-dependent risk of systemic corticosteroids (SCs) and the risk of other immunosuppressive therapies on coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in patients with noninfectious uveitis (NIU). DESIGN: A retrospective cohort study from January 20, 2020, to December 31, 2020 (an era before widespread COVID-19 vaccination), using the Optum Labs Data Warehouse, a US national de-identified claims database. PARTICIPANTS: Patients who had at least 1 NIU diagnosis from January 1, 2017. METHODS: Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models, with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of SC exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models as a continuous variable, in addition to the dichotomous variable. MAIN OUTCOME MEASURES: Incidence rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death. RESULTS: This study included 52 286 NIU patients of whom 12 000 (23.0%) were exposed to immunosuppressive medications during the risk period. In adjusted models, exposure to SCs was associated with increased risk of COVID-19 infection (HR, 2.66; 95% confidence interval [CI], 2.19-3.24; P < 0.001), hospitalization (HR, 3.26; 95% CI, 2.46-4.33; P < 0.001), and in-hospital death (HR, 1.99; 95% CI, 0.93-4.27; P = 0.08). Furthermore, incremental increases in the dosage of SCs were associated with a greater risk for these outcomes. Although tumor necrosis factor-α (TNF-α) inhibitors were associated with an increased risk of infection (HR, 1.48; 95% CI, 1.08-2.04; P = 0.02), other immunosuppressive treatments did not increase the risk of COVID-19 infection, hospitalization, or death. CONCLUSIONS: This study from an era before widespread COVID-19 vaccination demonstrates that outpatient SC exposure is associated with greater risk of COVID-19 infection and severe outcomes in patients with NIU. Future studies should evaluate the impact of immunosuppression in vaccinated NIU patients. Limiting exposure to SCs and use of alternative therapies may be warranted.

Herpes Simplex Virus 1 Anterior Uveitis following Coronavirus Disease 2019 (COVID-19) Vaccination in an Asian Indian Female.

PURPOSE: To describe a case of herpes simplex virus 1 (HSV 1) infection following coronavirus disease 2019 (COVID-19) vaccination in an Asian Indian female. METHODS: Retrospective case report. RESULT: A 40-year-old female presented with decreased vision, pain, and photophobia of 2 weeks duration. She reported receiving the second dose of COVISHIELDTM (ChAdOx1-S [recombinant]) 1 week prior to the onset of ocular symptoms. Left eye examination revealed granulomatous anterior uveitis. Aqueous sample from the left eye tested positive for HSV1 by polymerase chain reaction(PCR) method. She was managed with oral antiviral therapy, topical steroids, and cycloplegic agent and showed significant improvement of inflammation within 1 week and resolved within 3 weeks. CONCLUSION: This report demonstrates a potential association of HSV 1 anterior uveitis with COVID-19 vaccination. A high index of suspicion of viral etiology is warranted when uveitis presents with reduced corneal sensations and pigmented keratic precipitates, following a recent history of COVID-19 vaccination.

An analysis of the clinical profile of patients with uveitis following COVID-19 infection.

Purpose: To describe the clinical profile of patients presenting with uveitis following COVID-19 infection at a tertiary care eye hospital in South India. Methods: In this retrospective chart review, all consecutive cases presenting with an acute episode of intraocular inflammation and a history of COVID-19 infection diagnosed within the preceding 6 weeks, between March 2020 and September 2021, were included. Data retrieved and analyzed included age, sex, laterality of uveitis, and site of inflammation. The diagnosis was categorized based on the SUN working group classification criteria for uveitis. Details regarding clinical features, investigations, ophthalmic treatment given, response to treatment, ocular complications, and status at last visit were also accessed. Statistical analysis of demographical data was done using Microsoft Excel 2019. Results: Twenty-one eyes of 13 patients were included in this hospital-based retrospective observational study. The study included six male and seven female patients. The mean age was 38 ± 16.8 years. Eight patients had bilateral involvement. Seven patients were diagnosed with anterior uveitis, three with intermediate uveitis, one with posterior uveitis, and two with panuveitis. All patients responded well to treatment and were doing well at their last visit. Two patients had complications that necessitated surgical treatment, following which they recovered good visual outcomes. Conclusion: With prompt diagnosis and appropriate management, all the patients with uveitis post-COVID-19 infection recovered with good visual outcomes. Thus, ophthalmologists must be aware of the possible uveitic manifestations following even uneventful COVID-19 infection.

Vogt-Koyanagi-Harada Relapse after COVID-19 Vaccination.

PURPOSE: To report a relapse of Vogt-Koyanagi-Harada (VKH) disease in a patient after COVID-19 vaccination. CASE REPORT: A VKH disease patient, well controlled on azathioprine therapy, presented a uveitis relapse eleven days after the first vaccination for COVID-19. She received an induction high-dose intravenous corticosteroid therapy, followed by oral therapy, which led to a complete recovery from the uveitis in two weeks. No relapses occurred in the following five months of follow-up. Despite high-dose corticosteroid therapy and azathioprine, and one dose only of vaccination, the patient resulted positive for anti-RBD spike COV19 antibody. CONCLUSION: Relapse of VKH disease can occur after COVID-19 vaccination, despite an appropriate immunosuppressive therapy is ongoing. It responds to the classic therapy for VKH, and a serological response to an incomplete COVID-19 vaccination can also be found.

The Association between Noninfectious Uveitis and Coronavirus Disease 2019 Outcomes: An Analysis of United States Claims-Based Data.

PURPOSE: To identify if noninfectious uveitis (NIU) is associated with a greater risk of Coronavirus Disease 2019 (COVID-19) infection, hospitalization, and death. DESIGN: A retrospective cohort study from January 20, 2020 to December 31, 2020, using a national claims-based database. PARTICIPANTS: Enrollees who had continuous enrollment with both medical and pharmacy coverage for 3 years before January 20, 2020. Patients with an NIU diagnosis within 3 years of the start of the study were included in the NIU cohort. Those with infectious uveitis codes or new NIU diagnoses during the risk period were excluded. METHODS: Cox proportional hazard models were used to identify unadjusted hazard ratios (HRs) and adjusted HRs for all covariates for each outcome measure. Adjusted models accounted for patient demographics, health status, and immunosuppressive medication use during the risk period. MAIN OUTCOME MEASURES: Rates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death identified with International Classification of Disease 10th revision codes. RESULTS: This study included 5 806 227 patients, of whom 29 869 (0.5%) had a diagnosis of NIU. On unadjusted analysis, patients with NIU had a higher rate of COVID-19 infection (5.7% vs. 4.5%, P < 0.001), COVID-19-related hospitalization (1.2% vs. 0.6%, P < 0.001), and COVID-19-related death (0.3% vs. 0.1%, P < 0.001). However, in adjusted models, NIU was not associated with a greater risk of COVID-19 infection (HR, 1.05; 95% confidence interval [CI], 1.00-1.10; P = 0.04), hospitalization (HR, 0.98; 95% CI, 0.88-1.09; P = 0.67), or death (HR, 0.90, 95% CI, 0.72-1.13, P = 0.37). Use of systemic corticosteroids was significantly associated with a higher risk of COVID-19 infection, hospitalization, and death. CONCLUSIONS: Patients with NIU were significantly more likely to be infected with COVID-19 and experience severe disease outcomes. However, this association was due to the demographics, comorbidities, and medications of patients with NIU, rather than NIU alone. Patients using systemic corticosteroids were significantly more likely to be infected with COVID-19 and were at greater risk of hospitalization and in-hospital death. Additional investigation is necessary to identify the impact of corticosteroid exposure on COVID-19-related outcomes.

Bilateral uveitis after inoculation with COVID-19 vaccine: A case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly infectious and pathogenic respiratory disease. To date, there is no effective treatment, and there is an urgent need to develop vaccines against the virus. Five coronavirus COVID-19 vaccines have been approved for inoculation in China, with good safety and few adverse reactions. CASE PRESENTATION: A 50-year-old woman complained of bilateral blurred vision and visual distortion 5 days after vaccination with the inactivated COVID-19 vaccine. Physical and auxiliary examination showed that she developed bilateral posterior uveitis. The patient was administered local and systemic steroids, and the symptoms were appreciably improved 5 weeks later. CONCLUSIONS: A case of bilateral uveitis after COVID-19 vaccination was reported and indicated that uveitis after vaccination appears transient and responds well to steroids.

COVID-19 and the Use of Immunomodulatory Agents in Ophthalmology

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.

Implications of COVID-19 infection on patients with uveitis under biologic treatment.

BACKGROUND/AIMS: To investigate the incidence, severity of COVID-19 infection and the outcomes in patients with uveitis treated with biologic agents during COVID-19 pandemic. METHODS: In this prospective study, we included all patients with uveitis treated with biologic agents and tested for COVID-19 infection between May 2020 and October 2020. RESULTS: A total of 59 patients were identified. Behçet's disease was the most common diagnosis (64.4%). Infliximab was the most frequent biologic agent used (61%). Nine (15.3%) patients were tested positive for COVID-19. None of the patients with positive COVID-19 test developed any COVID-19-related symptoms during follow-up. Of the nine patients with positive COVID-19 test, only two patients had uveitis flare-up after the biologic suspension. CONCLUSION: Uveitis patients under biologic therapy can be silent carriers for COVID-19.

Rapid Resolution of Non-Effusive Feline Infectious Peritonitis Uveitis with an Oral Adenosine Nucleoside Analogue and Feline Interferon Omega.

This is the first report of a successful treatment of a non-effusive feline infectious peritonitis (FIP) uveitis case using an oral adenosine nucleoside analogue drug and feline interferon omega, and alpha-1 acid glycoprotein (AGP) as an indicator of recovery. A 2-year-old male neutered Norwegian Forest Cat presented with uveitis, keratic precipitates, mesenteric lymphadenopathy and weight loss. The cat was hypergammaglobulinaemic and had a non-regenerative anaemia. Feline coronavirus (FCoV) RNA was detected in a mesenteric lymph node fine-needle aspirate by a reverse-transcriptase polymerase chain reaction-non-effusive FIP was diagnosed. Prednisolone acetate eye drops were administered three times daily for 2 weeks. Oral adenosine nucleoside analogue (Mutian) treatment started. Within 50 days of Mutian treatment, the cat had gained over one kilogram in weight, his globulin level reduced from 77 to 51 g/L and his haematocrit increased from 22 to 35%; his uveitis resolved and his sight improved. Serum AGP level reduced from 3100 to 400 µg/mL (within normal limits). Symmetric dimethylarginine (SDMA) was above normal at 28 µg/dL, reducing to 14 µg/dL on the cessation of treatment; whether the SDMA increase was due to FIP lesions in the kidney or Mutian is unknown. Mutian treatment stopped and low-dose oral recombinant feline interferon omega begun-the cat's recovery continued.

Impact of COVID-19 pandemic on uveitis patients receiving immunomodulatory and biological therapies (COPE STUDY).

PURPOSE: To evaluate the change in the ongoing immunomodulatory (IMT) and biological therapies among patients with non-infectious uveitis (NIU), and determine the number of uveitis relapses during the COVID-19 pandemic. METHODS: In this national multicentric prospective case series, data of subjects with NIU receiving corticosteroids, systemic IMT and/or biological agents were analysed. The data collection was performed from 1 March 2020 to 25 June 2020. Main outcome measures included change in the ongoing treatments with corticosteroids, IMT and biological agents, use of alternate therapies and rates of uveitis relapse. RESULTS: In this study, 176 patients (284 eyes) with NIU (mean age: 33±17.1 years; males: 68) were included. A total of 121 eyes (90 patients) were deemed to have active NIU. Of these, seven subjects (7.8%) did not receive intravenous methylprednisolone despite need felt by the treating uveitis experts. In addition, 35 subjects (57.4%) received a rapid tapering dosage of oral corticosteroids despite active disease. A total of 161 (91.5%) subjects were receiving systemic IMT and 25 (14.2%) were on biological therapies. Overall, IMT was altered in 29/161 (18.0%) subjects. Twenty-two eyes were treated with intravitreal therapies in the study period. Fifty-three eyes (32.5%, 29 subjects) developed relapse of NIU, of which 25 subjects (86.2%) were deemed to have reactivation related to altered systemic IMT. No patient developed COVID-19 during follow-up. CONCLUSIONS: During the ongoing COVID-19 pandemic, uveitis specialists may tend to reduce the ongoing systemic IMT, or prefer less aggressive treatment strategies for NIU. These subjects may be at high risk of relapse of uveitis.

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak.

INTRODUCTION: Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED: This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION: Management should proceed as usual when access to health care possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection, and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.

Evolving consensus for immunomodulatory therapy in non-infectious uveitis during the COVID-19 pandemic.

BACKGROUND: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. METHODS: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. RESULTS: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. CONCLUSION: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.