Immunology and Uveitis

Immunology and Uveitis Publications

Bleicher ID, Brill D, Wu F, Sobrin L, Patel N. Acute Idiopathic Maculopathy Following SARS-CoV-2 Vaccination. Ocul Immunol Inflamm 2022;:1-4.Abstract
A 49-year-old man presented with acute unilateral blurred vision one week after SARS-CoV-2 vaccination. A unilateral serous detachment of the macula, intraretinal hemorrhages, vitritis, and anterior chamber cell was found. Diagnostic testing was negative for infectious and inflammatory causes, and a diagnosis of acute idiopathic maculopathy (AIM) was made. Symptoms and serous detachment resolved over 12 weeks, with residual retinal pigment epithelial changes consistent with the disease course. AIM is a rare diagnosis that presented in close proximity to SARS-CoV-2 vaccination without evidence of coxsackievirus infection. Further research is necessary to clarify an association between this vaccine and uveitis.
Agarwal A, Singh RB, Erckens RJ, Berendschot TTJM, Webers CAB. Quantitative Analysis of the Choroidal Vascularity in Eyes with Uveitis Using Optical Coherence Tomography Angiography: A Systematic Review. Ocul Immunol Inflamm 2022;:1-12.Abstract
PURPOSE: The purpose of this systematic review is to identify techniques used for quantification of choriocapillaris (CC) flow in eyes with uveitis using optical coherence tomography angiography (OCTA), report reliability and level of correlation with techniques such as indocyanine green angiography (ICGA). METHODS: A systematic search of several databases was done. The studies were analyzed for techniques of measurement, reliability, and correlation with other modalities. Risk of bias assessment was performed. RESULTS: Thirteen studies were included. CC vessel density (7 studies) and flow deficit area (4 studies) were the most used indices. There was significant heterogeneity in the studies due to differences in the scan protocol, thresholding strategy, and analysis. Comparison with ICGA was performed by only one study, and reliability indices were reported by only two studies. CONCLUSION: OCTA is a useful tool to measure the CC vascularity in eyes with uveitis. However, standardized acquisition and analysis protocols are needed.
Valdes L, Cox JT, Yang J, Susarla G, Han S, Papaliodis GN, Sobrin L. Anti-infliximab antibodies and clinical response in noninfectious uveitis and scleritis patients treated with infliximab: A retrospective review. Am J Ophthalmol Case Rep 2022;27:101634.Abstract
Purpose: To investigate the clinical response to infliximab in ocular inflammation patients who develop anti-infliximab antibodies (AIA) vs. those patients who do not develop AIA. Observations: A retrospective review was performed of patients treated with infliximab for noninfectious uveitis (NIU) or scleritis. Clinical response was determined as a composite clinical endpoint and classified as complete, partial, or absent. Nine of 32 infliximab-treated patients (28%) were found to develop AIA. Among the AIA-positive patients, clinical response was complete in 7 patients (78%) and partial in 2 patients (22%). Among the AIA-negative patients, clinical response was complete in 15 patients (65%), partial in 6 patients (26%) and absent in 2 patients (9%). Serum infliximab levels tended to decrease with appearance of AIA but rarely became undetectable. Conclusions and Importance: In this pilot study, AIA-positive patients did not have diminished clinical response to infliximab when compared with AIA-negative patients. There was a high rate of complete clinical response to infliximab in this group of NIU and scleritis patients. Approximately a quarter of patients developed AIA. AIA-positive patients did not have diminished rates of clinical response when compared with AIA-negative patients. This suggests that routine AIA monitoring may not be clinically useful, although validation of this finding in larger cohorts is necessary.
Maleki A, Colombo A, Manhapra A, Foster SC. Authors' response. Surv Ophthalmol 2022;67(3):880-882.
Silpa-Archa S, Sriyuttagrai W, Foster SC. Treatment for Epstein-Barr Virus-associated uveitis confirmed by polymerase chain reaction: Efficacy of Anti-Viral Agents and a literature review. J Clin Virol 2022;147:105079.Abstract
BACKGROUND: There are still many research challenges and unanswered questions in relation to Epstein-Barr virus-associated uveitis. These include the presence of Epstein-Barr virus (EBV) DNA in asymptomatic patients, its pathogenicity in the uveitis eye, and the role of antiviral therapy for EBV-associated intraocular inflammation. METHODS: This was a retrospective review of prospectively collected data from the Ophthalmology Department, Rajavithi Hospital between 2015 and 2020. A qualitative assay using multiplex real-time PCR was performed to detect pathogen genes from specimens obtained from a total of 344 patients. The main outcome measure was treatment success defined by clinical improvement and absence of viral DNA confirmed by PCR. RESULTS: Of the 35 cases, 24 with complete data were enrolled in the study, including 22 with post-treatment PCR results. Sixty-seven percent were HIV-infected, and other plausible causes or coinfection with other pathogens were found in 75% of patients. Cytomegalovirus (38%) was the most common co-infecting pathogen. The most commonly employed regimen was a combination of systemic acyclovir and intravitreal ganciclovir injection (58%). Of the 22 cases who had post-treatment PCR results, absence of detection of the virus by PCR in the intraocular fluid after treatment was demonstrated in 73% of patients. CONCLUSION: Patients with EBV infection can be simultaneously co-infected with other pathogens. Systemic acyclovir and ganciclovir achieved clinical improvement in most cases, and EBV infection was cured in the majority of patients.
Silpa-Archa S, Hoopholerb T, Foster CS. Appraisal of vitreous syphilis antibody as a novel biomarker for the diagnosis of syphilitic uveitis: a prospective case-control study. Eye (Lond) 2022;Abstract
PURPOSE: To determine the sensitivity and specificity of syphilis antibody tests in vitreous samples and to propose an algorithm using vitreous syphilis antibody as a supplementary test to confirm syphilitic uveitis (SU). METHODS: A prospective case-control study was conducted at the Retina and Uveitis Clinic from May 2017 to January 2020. Initially, patients were classified based on syphilis serology into group 1 (positive testing) and group 2 (negative testing). Group 1 was further divided into 2 subgroups (group 1A and 1B) depending on their relevant clinical manifestations and clinical improvement. Group 2 served as a control group. RESULTS: Thirty-eight patients were enrolled in the study: 14 in group 1A, 5 in group 1B, and 19 in group 2B. No patient was assigned to group 2A. All patients in group 1A, representing definite SU, completed syphilis test (rapid plasma reagin [RPR], enzyme immunoassay [EIA], and fluorescent treponemal antibody-absorption [FTA-ABS]) for vitreous, and all vitreous samples yielded positive results. Of the 5 subjects in group 1B, 3 cases were considered to be not SU with different conditions, and 2 were indeterminate for SU. They presented with different features not typical of SU, and they had variable and fewer positive syphilis antibody responses. The most sensitive test for detecting syphilis antibodies in vitreous was EIA (90.9%), followed by RPR (80.0%) and FTA-ABS IgG (78.9%). EIA and FTA-ABS had the highest specificity, detecting 100% of the syphilis antibody. CONCLUSIONS: Vitreous analysis of syphilis antibody can serve as a supplementary test to confirm SU in selected cases as the proposed algorithm.
He B, Tanya SM, Wang C, Kezouh A, Torun N, Ing E. The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis. Am J Ophthalmol 2022;234:117-125.Abstract
PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.
Maleki A, Anesi SD, Look-Why S, Manhapra A, Foster SC. Pediatric uveitis: A comprehensive review. Surv Ophthalmol 2022;67(2):510-529.Abstract
Pediatric uveitis accounts for 5-10% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or noninfectious in etiology. The etiology of noninfectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, its treatment, and its complications on the child and the child's family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications, and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. In this review article, We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.
Sharon Y, Anesi SD, Martinez CE, Huang AJW, Foster CS, Chu DS. Repository Corticotropin Injection as an Alternative Treatment for Refractory Ocular Mucous Membrane Pemphigoid. Cornea 2022;41(1):45-51.Abstract
PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.
Roldan AM, Zebardast N, Pistilli M, Khachatryan N, Payal A, Begum H, Artornsombudh P, Pujari SS, Rosenbaum JT, Sen NH, Suhler EB, Thorne JE, Bhatt NP, Foster SC, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Buchanich JM, Kempen JH, for Group SITED (SITE) CSR. Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors. Am J Ophthalmol 2021;Abstract
PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of corneal endothelial transplantation (CET), including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet Membrane Endothelial Keratoplasty procedures. The incidence of CET was calculated; potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis with a median follow-up 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%-1.53%). Risk factors for CET included age >60 years vs. <40 years (aHR 16.5; 95% CI,4.70-57.9), anterior uveitis and scleritis vs. other types (aHR 2.97; 95% CI, 1.46-6.05 and aHR 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR 5.12; 95% CI, 2.34-11.2), and hypotony (aHR 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, PAS, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing corneal endothelial transplantation; these factors likely are associated with endothelial cell damage.
Betzler BK, Gunasekeran DV, Kempen J, Smith JR, McCluskey P, Nguyen QD, Pavesio C, Gupta V, Agrawal R. The Historical Evolution of Ocular Tuberculosis: Past, Present, and Future. Ocul Immunol Inflamm 2021;:1-7.Abstract
Ocular involvement is a rare manifestation of tuberculosis. Four key issues historically faced by clinicians when diagnosing and treating ocular tuberculosis - diagnostic uncertainty, naturally heterogeneous presentations, limitations of existing laboratory diagnostic tools, and non-uniform treatment guidelines - continue to test today's physicians. Unparalleled scientific and clinical developments over the past century have greatly expanded the knowledge surrounding this challenging ophthalmic condition. Experience with large volumes of cases at tuberculosis-endemic centres has led to recent growth in knowledge and physician experience, perhaps more so in developing countries. Looking forward, the role of diverse new technologies, including artificial intelligence and proteomics, will advance ocular tuberculosis research. Efforts have been made to address the lack of standardized nomenclature, diagnostic uncertainty, and unvalidated, geographically variable treatment guidelines.
McKay MK, Apostolopoulos N, Dahrouj M, Nguyen HV, Reddy A, Blazes M, Lacy M, Pepple KL, Lee AY, Lee CS. Assessing the Uniformity of Uveitis Clinical Concepts and Associated ICD-10 Codes Across Health Care Systems Sharing the Same Electronic Health Records System. JAMA Ophthalmol 2021;Abstract
Importance: Big data studies may allow for the aggregation of patients with rare diseases such as uveitis to answer important clinical questions. Standardization of uveitis-related variables will be necessary, including the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes used to identify patients of interest. There are currently limited data on the uniformity of diagnosis mapping to ICD-10 codes for uveitis diagnoses among different health systems. Objective: To assess the degree of uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same electronic health record (EHR) system. Design, Setting, and Participants: This multicenter survey study was conducted between September 14 and October 9, 2020, at 5 academic health care systems that use the Epic EHR. Researchers from the University of Washington, Harvard University, Stanford University, Yale University, and the University of California, San Francisco queried 54 uveitis-related diagnostic terms and recorded the associated ICD-10 codes. Main Outcomes and Measures: The degree of uniformity for uveitis clinical concepts and associated ICD-10 codes. Results: Fifty-four uveitis-related diagnostic terms were queried within the Epic EHR at 5 different health care systems. There was perfect agreement among all 5 centers for 52 of the 54 diagnostic terms. Two diagnostic terms had differences in ICD-10 coding: juvenile idiopathic arthritis associated chronic uveitis and intermediate uveitis. Intermediate uveitis was associated with codes H20.1x (ICD-10 description: chronic iridocyclitis) or H20.9 (ICD-10 description: unspecified iridocyclitis) in 3 centers while being associated with code H30.2x (ICD-10 description: posterior cyclitis) at the 2 remaining centers. The discrepancies appear to be related to a recent update in diagnostic mapping in the Epic EHR. Conclusions and Relevance: This study suggests that ICD-10 code mapping to uveitis diagnostic terminology appears to be highly uniform at different centers with the Epic EHR. However, temporal changes in diagnosis mapping to ICD-10 codes and a lack of 1-to-1 mapping of diagnosis to ICD-10 code add additional sources of complexity to the interpretation of big data studies in uveitis.

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