Immunology and Uveitis

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Belanger NL, Barbero R, Barclay R, Lepene B, Sobrin L, Bispo PJM. Improved Detection of Herpesviruses from Diluted Vitreous Specimens Using Hydrogel Particles. Diagnostics (Basel) 2022;12(12)Abstract
Infectious uveitis is a sight-threatening infection commonly caused by herpesviruses. Vitreous humor is often collected for molecular confirmation of the causative agent during vitrectomy and mixed in large volumes of buffered saline, diluting the pathogen load. Here, we explore affinity-capture hydrogel particles (Nanotrap®) to concentrate low abundant herpesviruses from diluted vitreous. Simulated samples were prepared using porcine vitreous spiked with HSV-1, HSV-2, VZV and CMV at 105 copies/mL. Pure undiluted samples were used to test capturing capability of three custom Nanotrap particles (red, white and blue) in a vitreous matrix. We found that all particles demonstrated affinity to the herpesviruses, with the Red Particles having both good capture capability and ease of handling for all herpesviruses. To mimic diluted vitrectomy specimens, simulated-infected vitreous were then serially diluted in 7 mL TE buffer. Diluted samples were subjected to an enrichment protocol using the Nanotrap Red particles. Sensitivity of pathogen detection by qPCR in diluted vitreous increased anywhere between 2.3 to 26.5 times compared to non-enriched specimens. This resulted in a 10-fold increase in the limit of detection for HSV-1, HSV-2 and VZV. These data demonstrated that Nanotrap particles can capture and concentrate HSV-1, HSV-2, VZV and CMV in a vitreous matrix.
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.
Betzler BK, Putera I, Testi I, Distia Nora RL, Kempen J, Kon OM, Pavesio C, Gupta V, Agrawal R. Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis. Surv Ophthalmol 2023;68(2):241-256.Abstract
We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness.
Bleicher ID, Brill D, Wu F, Sobrin L, Patel N. Acute Idiopathic Maculopathy Following SARS-CoV-2 Vaccination. Ocul Immunol Inflamm 2023;31(6):1232-1235.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.
Boonsopon S, Maghsoudlou A, Kombo NE, Foster SC. A therapeutic trial of valganciclovir in patients with uveitis and positive Epstein-Barr virus early antigen D IgG titers. Eur J Ophthalmol 2015;26(1):30-5.Abstract

PURPOSE: To evaluate the effectiveness of a therapeutic trial of valganciclovir in patients with uveitis with positive Epstein-Barr virus early antigen D immunoglobulin G titers (EBV EA-D). METHODS: We performed a retrospective chart review of 14 patients at the Massachusetts Eye Research and Surgery Institution who had uveitis with positive EBV EA-D but negative studies for all other causes of uveitis and were treated with valganciclovir 450 mg twice a day or valganciclovir 900 mg twice a day between January 2010 and August 2014. RESULTS: Nine of 14 patients, who had presumed EBV reactivation with associated intraocular inflammation, were successfully treated with valganciclovir: 3 of these were treated with valganciclovir 450 mg twice a day and 6 were treated with valganciclovir 900 mg twice a day. Five of 14 patients failed to respond to valganciclovir with persistent inflammation after at least 2 weeks of valganciclovir therapy, and were subsequently treated with immunomodulatory therapy to control inflammation. CONCLUSIONS: Uveitis can be caused by EBV infection/reactivation. A therapeutic trial with valganciclovir 450 mg twice a day for 1 month in patients with uveitis with positive EBV EA antibody may be beneficial.

Borelli A, Behr J, Ruggeri M, Han M, Zhou Y, Foster SC. Indications for Magnetic Resonance Imaging in Patients With Behcet Uveitis. J Neuroophthalmol 2023;Abstract
BACKGROUND: Behcet disease is a systemic vasculitis, which may involve the eyes and central nervous system. The true prevalence of neurological involvement is not precisely known but may be associated with ocular involvement. This study investigates the association between Behcet uveitis and neuro-Behcet disease. METHODS: A retrospective single-center analysis was conducted for consecutive patients with Behcet uveitis at the Massachusetts Eye Research and Surgery Institution. Uveitis characteristics, neurological symptoms, fluorescein fundus angiography, and MRI results were recorded. RESULTS: Our population included 108 patients with Behcet uveitis, and 26 (24.1%) were found to have neurological involvement associated with Behcet disease. Optic nerve leakage on fundus angiography and neurological symptoms were associated with an increased risk of neurological involvement. Three cases (11.5%) were nonparenchymal, while 23 (88.5%) were parenchymal with lesions in the cortex, subcortical white matter, thalamus, basal ganglia, and brainstem. CONCLUSIONS: There is a high comorbidity between ocular and neurological involvement in Behcet disease. Careful assessment of neurological symptoms and baseline fluorescein fundus angiography are recommended for patients with Behcet disease. MRI has a high diagnostic yield and should be pursued if there is concern for progressive or pre-existing neurological involvement.
Borkar DS, Homayounfar G, Tham VM, Ray KJ, Vinoya AC, Uchida A, Acharya NR. Association Between Thyroid Disease and Uveitis: Results From the Pacific Ocular Inflammation Study. JAMA Ophthalmol 2017;135(6):594-599.Abstract
Importance: Common pathophysiological mechanisms may be responsible for immune dysregulation in both thyroid disease and uveitis. Studies investigating a possible association are limited. Objective: To determine the association between thyroid disease and uveitis. Design, Setting, and Participants: A retrospective, population-based case-control study was conducted from January 1, 2006, to December 31, 2007, among 217 061 members of the Kaiser Permanente Hawaii health system during the study period. A clinical diagnosis of uveitis was determined through a query of the electronic medical record followed by individual medical record review for confirmation by a uveitis specialist. Thyroid disease was determined based on International Classification of Diseases, Ninth Revision, coding. Two control groups were chosen at a 4:1 ratio for comparison with patients with uveitis. A logistic regression analysis was performed with uveitis as the main outcome variable and thyroid disease as the main predictor variable, while adjusting for age, sex, race, smoking status, and history of autoimmune disease. Data analysis was conducted between 2014 and 2016. Main Outcomes and Measures: A diagnosis of thyroid disease among patients with uveitis and respective controls. Results: Of the 224 patients with uveitis (127 women and 97 men; mean [SD] age, 54.1 [17.8] years) identified during the study period, 29 (12.9%) had a diagnosis of thyroid disease, compared with 62 of 896 patients (6.9%) in the control group (P = .01) and 78 of 896 patients (8.7%) in the ophthalmology clinic control group (P = .06). Using the general Kaiser Permanente Hawaii population control group, patients who had thyroid disease had a 1.7-fold (95% CI, 1.03-2.80; P = .04) higher odds of having uveitis compared with patients who did not have thyroid disease when controlling for age, sex, race, smoking status, and autoimmune disease. A similar association was found using the ophthalmology clinic control group (odds ratio, 1.8; 95% CI, 1.1-2.9; P = .02) while adjusting for these factors. Conclusions and Relevance: These findings suggest that a history of thyroid disease has a weak to moderate association with uveitis. Similar autoimmune mechanisms could explain the pathogenesis of both conditions. If future studies corroborate these findings, they may have further clinical implications in the laboratory workup of uveitis.
Brill D, Papaliodis G. Uveitis Specialists Harnessing Disruptive Technology during the COVID-19 Pandemic and Beyond. Semin Ophthalmol 2021;36(4):296-303.Abstract
Spurred by the coronavirus disease pandemic and shortage of eye care providers, telemedicine is transforming the way ophthalmologists care for their patients. Video conferencing, ophthalmic imaging, hybrid visits, intraocular inflammation quantification, and portable technology are evolving areas that may allow more uveitis patients to be evaluated via telemedicine. Despite these promising disruptive technologies, there remain significant technological limitations, legal barriers, variable insurance coverage for virtual visits, and lack of clinical trials for uveitis specialists to embrace telemedicine.
Bui K, Tomaiuolo M, Carter K, Iacob C, Neerukonda V, Stagner A, Sajjadi Z, Escobar KV, Ordoñez Armijos P, Eagle RC, Mehta S, Dunn JP, Hyman L, Milman T, Milman T. Sympathetic Ophthalmia in Patients with Enucleation or Evisceration: Pathology Laboratory and IRIS Registry Experience. Ocul Oncol Pathol 2023;9(5-6):138-151.Abstract
INTRODUCTION: Sympathetic ophthalmia (SO) is a rare bilateral granulomatous panuveitis that can follow surgical or nonsurgical ocular trauma in one eye. Because its diagnosis requires clinical-pathologic correlation, the true incidence of SO is unknown, and there is a need to understand the recent trends in risk factors and frequency of this condition. METHODS: Pathology records of all enucleated or eviscerated (ENEV) eyes at three pathology laboratories were reviewed. Data collected included patient demographics, procedure indication, pathology diagnosis, and clinical history of trauma and uveitis. IRIS® Registry (Intelligent Research in Sight) was searched for all patients with SO, acquired absence of eye (AAE), and/or ENEV. Data obtained included patient demographics, ocular procedures, and preoperative diagnoses within 30 days of AAE/ENEV. RESULTS: In the pathology laboratory setting, the incidence of SO over a 36-year period in patients who underwent ENEV was 0.2% (20/9,092); the 5-year incidence ranged from 0.0 to 0.3%. Among the 20 eyes with SO, the inciting event was surgical trauma in 50% (10/20), nonsurgical trauma in 45% (9/20), and missing/undetermined in 5% (1/20). SO was suspected preoperatively in 7/20 (35%) patients. Clinical concern for SO and ruptured globe were indications for ENEV in 50/9,092 (0.5%) and 872/9,092 (10%) patients, respectively. In the IRIS Registry, 0.7% (199/27,830) of patients with AAE/ENEV had diagnosis of SO. The frequency of SO between 2015 and 2020 was 0.01% (7,371/62,318,249); of these 7,371 cases, 199 (3%) had AAE/ENEV. In 25,975 patients with available data, injury and SO were listed as diagnoses less than 30 days prior to AAE/ENEV in 909 (4%) and 63 (0.2%) cases, respectively. CONCLUSION: The frequency of SO in recent decades has been low. Most cases of SO are not managed with eye removal. In histopathology-confirmed SO, surgical trauma is as frequent as nonsurgical trauma as an inciting etiology of disease.
Butler NJ, Cohen D, Yu Y, Kempen JH, Sobrin L, VanderBeek BL. Dual-Energy X-Ray Absorptiometry Scan Utilization and Skeletal Fragility Among Non-Infectious Uveitis Patients Exposed to Oral Glucocorticoids. Ocul Immunol Inflamm 2023;:1-9.Abstract
INTRODUCTION: Currently, little is known regarding bone health surveillance for glucocorticoid-exposed non-infectious uveitis (NIU) patients or their baseline risks of skeletal fragility outcomes. METHODS: Using claims data, we calculated rates of dual-energy x-ray absorptiometry (DXA) screening for glucocorticoid-exposed NIU and rheumatoid arthritis (RA) patients. Separately, we compared risks of skeletal fragility metrics amongst NIU patients, RA patients, and controls, independent of glucocorticoid use. RESULTS: The adjusted hazard ratio (aHR) of NIU patients to have a DXA scan was 0.64 (95% CI, 0.63-0.65; p < .001) compared to RA patients. The aHR for any skeletal fragility outcome amongst NIU patients was 0.97 (p < .02) compared to normal controls, while RA patients had excess risk (aHR, 1.15; p < .001). CONCLUSIONS: NIU patients are 36% less likely to receive a DXA scan after high-dose glucocorticoid exposure compared with RA patients. No elevated risk of osteoporosis for NIU patients was found compared to normal controls.
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Callaway NF, Gonzalez MA, Yonekawa Y, Faia LJ, Mandelcorn ED, Khurana RN, Saleh MGA, Lin P, Sobrin L, Albini TA. OUTCOMES OF PARS PLANA VITRECTOMY FOR MACULAR HOLE IN PATIENTS WITH UVEITIS. Retina 2018;38 Suppl 1:S41-S48.Abstract
PURPOSE: Inflammatory macular hole is a rare complication of uveitis, and data on surgical outcomes of closure are scarce. The purpose of this study is to evaluate the anatomical and visual outcomes of conventional pars plana vitrectomy for patients with uveitis. METHODS: Noncomparative, interventional, and consecutive case series from 6 vitreoretinal surgical centers from 2007 to 2015. Twenty eyes of 19 patients were included with 4 patients separated as viral retinitis. The primary outcome was change in best-corrected visual acuity at Month 3. Secondary outcomes were closure of the macular hole and postoperative optical coherence tomography characteristics. RESULTS: All eyes underwent conventional three-port pars plana vitrectomy with indocyanine green-assisted internal limiting membrane peeling. Mean Snellen best-corrected visual acuity improved from 20/200 to 20/63 (P = 0.01 for a difference in logarithm of the minimum angle of resolution) at Month 3. Twelve (75%) of patients achieved 2 or more lines of visual acuity improvement by postoperative Month 3. Surgery resulted in decreased epiretinal membrane (P = 0.002), intraretinal fluid (P < 0.001), subretinal fluid (P = 0.029), central subfield thickness (P < 0.001), and central cube volume (P = 0.041). Surgical intervention achieved anatomical success, as measured by macular hole closure, in 13 (81%) of patients at postoperative Month 3. CONCLUSION: Patients with inflammatory macular hole respond well to conventional surgery, with good anatomical and visual acuity outcomes.
Cao JH, Oray M, Cocho L, Foster SC. Rituximab in the Treatment of Refractory Noninfectious Scleritis. Am J Ophthalmol 2016;164:22-8.Abstract

PURPOSE: To describe the outcomes of the use of rituximab in the treatment of refractory noninfectious scleritis. DESIGN: Retrospective case series. METHODS: Review of the medical charts of patients with noninfectious scleritis refractory to conventional immunomodulatory therapy who were seen at the Massachusetts Eye Research and Surgery Institution between 2005 and 2015. The primary outcome measure in this study was steroid-free remission. Secondary outcomes were favorable response (decrease in scleritis activity score) and decrease in steroid dependence. RESULTS: There were 15 patients, with a mean follow-up duration of 34 months. Fourteen patients (93.3%) showed a clinical improvement, with 13 (86.6%) achieving a scleritis activity score of zero at 6 months. To date, 2 patients continue to enjoy durable drug-free remission (28 and 32 months follow-up). There was only 1 adverse effect recorded (infusion hypotension) requiring cessation of rituximab. CONCLUSION: Rituximab can be an effective treatment modality for recalcitrant noninfectious scleritis and, in some, can result in long-term durable drug-free remission.

Chen X, Yao X, Chi Y, Guo C, Zhang J, Li J, Zhang S, Rong X, Pasquale LR, Yang L. A Cross-Sectional Observational Study of Nailfold Capillary Morphology in Uveitis. Curr Eye Res 2018;43(11):1342-1350.Abstract
PURPOSE: We performed nailfold capillary microscopy to explore microvasculature abnormalities in uveitis overall and uveitis stratified in various ways. METHODS: This was a cross-sectional, case-control, observational study. One hundred and seven uveitis patients and 130 control subjects were included. We used a JH-1004 capillaroscope to perform nailfold capillary video microscopy on the fourth and fifth digits of each subject's nondominant hand. Videos were evaluated for hemorrhages, dilated capillary loops > 25 µm, and avascular zones > 200 µm. Univariate analyses were used for the assessment of case-control morphological differences and multivariate analyses were performed to assess the relation between nailfold capillaroscopic findings and uveitis subgroups. RESULTS: In univariate analysis, uveitis patients were more likely to have higher tortuosity ratings and reduced capillary density compared to controls (p < 0.001 for both); furthermore, dilated capillary loops, avascular zone and hemorrhages were more frequent in uveitis versus control subjects (p < 0.001 for all). Among cases, every unit increase in capillary density (vessels/mm) was associated with active uveitis (n = 72 cases) versus inactive disease (n = 35 cases; odds ratio (OR) = 1.7; (95% confidence interval (CI), 1.2-2.5) in multivariate analysis. Furthermore, the presence of any nailfold hemorrhage versus the absence of hemorrhage was more likely to be associated with posterior and panuveitis (n = 41 cases combined) compared to anterior and intermediate uveitis (n = 66 cases combined; OR = 5.8; 95% CI, 2.3-14.2). Moreover, we found a positive correlation between peripheral retinal leakage and nailfold capillaries dilation (r = 0.33; p = 0.015) that was not strictly significant based on the number of comparisons made. CONCLUSIONS: Our study provides support for non-ocular capillary bed abnormalities in uveitis, with interesting correlations based on disease stage and anatomical classification.
Chen X, Lei F, Wang L, Xiong X, Song J. Generation of Tumor Antigen-Specific Cytotoxic T Lymphocytes from Pluripotent Stem Cells. Methods Mol Biol 2019;1884:43-55.Abstract
Immunotherapy is a developing but very promising arsenal to treat cancer. Acquiring a more potent and effective approach in cancer immunotherapy is always the ultimate pursuance. CTL-based therapies are highly acclaimed recently due to its direct killing property. However, difficulty in obtaining adequate number of CTLs is still a major obstacle. In previous studies, it is shown that pluripotent stem cell-derived cytotoxic T lymphocytes (CTL)-especially the genetically engineered tumor antigen-specific CTLs-may serve as a good candidate for this goal. Here we introduce a novel approach in generating tumor antigen-specific CTLs from induced pluripotent stem cells (iPSCs) by using both in vitro and in vivo priming mechanisms for the tumor management in a murine melanoma model.
Cheung CSY, Mireskandari K, Ali A, Silverman E, Tehrani N. Earlier use of systemic immunosuppression is associated with fewer ophthalmic surgeries in paediatric non-infectious uveitis. Br J Ophthalmol 2020;104(7):938-942.Abstract
BACKGROUND/AIMS: There is a paucity of large trials investigating the effect of management strategies for paediatric non-infectious uveitis on complications requiring surgery. The purpose of our study is to investigate whether earlier initiation of systemic immunosuppression in paediatric non-infectious uveitis is associated with fewer ophthalmic surgeries. METHODS: A retrospective review was conducted on 48 children with non-infectious uveitis assessed in 1998-2013. Patients were divided into uveitis diagnosed before December 2008 (group 1) and after January 2009 (group 2). Duration from uveitis onset to methotrexate initiation (U-MTX) and biological addition (U-Biologic) were reviewed. Follow-up visits with topical corticosteroids >3 times daily and active uveitis (≥1+ cells) during 3.5 years were documented. The main outcome measure was the need for ≥1 ophthalmic surgery at 3.5 years. RESULTS: In group 1, 69.5% of patients required ≥1 ophthalmic surgery at 3.5 years versus 26.9% in group 2 (p=0.005). U-MTX was 28.9±11.8 weeks and 14.2±10.0 weeks for groups 1 and 2 (p=0.028). U-Biologic was 134.6±46.0 weeks and 82.3±43.3 weeks for groups 1 and 2 (p=0.0016). Corticosteroid use >3 times daily was 85.9±52.7 weeks and 14.6±11.1 weeks for groups 1 and 2. Multivariate regression showed methotrexate initiation within 6 months of uveitis onset lowered the likelihood of needing ophthalmic surgery at 3.5 years (OR=6.2, 95% CI 1.2 to 33.4; p=0.033). Univariate regression demonstrated biological addition within 18 months of uveitis onset reduced the likelihood of requiring ophthalmic surgery (OR 12.57, 95% CI 1.28 to 123.48; p=0.030). CONCLUSION: Earlier control of uveitis by addition of immunosuppressive therapy reduced the need for ophthalmic surgery.
Cho H, Shin YU, Siegel NH, Yu HG, Sobrin L, Patel A, Durand ML, Miller JW, Husain D. Endogenous Endophthalmitis in the American and Korean Population: An 8-year Retrospective Study. Ocul Immunol Inflamm 2016;:1-8.Abstract

PURPOSE: To study the clinical features of endogenous endophthalmitis (EE) in sample patient populations from the USA and South Korea over an 8-year period. METHODS: We reviewed data from 128 eyes of 60 American and 48 Korean patients diagnosed with EE and compared their clinical characteristics. RESULTS: Fungemia and liver abscess were the most common extraocular infection sources among American (26.7%) and Korean patients (33.3%), respectively. Klebsiella pneumoniae and Candida species were the most common pathogens of EE in the Korean and the American patients, respectively. Endophthalmitis caused by fungi had a better visual prognosis than that caused by bacteria (p = 0.001). Vitrectomy was beneficial for eyes with EE due to virulent bacteria presenting with worse than counting finger vision. CONCLUSIONS: The predisposing conditions and responsible organisms for EE vary in different regions of the world. The visual prognosis was strongly influenced by the underlying pathogen.

Cocho L, Gonzalez-Gonzalez LA, Molina-Prat N, Doctor P, Sainz-de-la-Maza M, Foster SC. Scleritis in patients with granulomatosis with polyangiitis (Wegener). Br J Ophthalmol 2016;100(8):1062-5.Abstract

AIMS: To describe and compare clinical features, complications and outcomes in patients with granulomatosis with polyangiitis (GPA)-associated scleritis with those seen in idiopathic and other autoimmune-associated scleritis, and to further describe the features that may serve as an indicator of life-threatening systemic disease. METHODS: We retrospectively reviewed electronic health records of all patients with scleritis seen at two tertiary care centres. Of 500 patients, 14 had GPA-associated scleritis and were included in this analysis. Measures included were age, gender, laterality, visual acuity and underlying systemic or ocular diseases. Clinical features (location, pain, inflammation) and ocular complications of these patients (decrease of vision, concomitant anterior uveitis and ocular hypertension) were studied and correlated. RESULTS: Fourteen of 500 patients with scleritis were GPA associated. Most of the patients with GPA-associated scleritis presented with sudden onset, bilateral, diffuse anterior scleral inflammation, with moderate-or-severe pain. Vision loss was not significantly different, and pain was more severe in these patients than in those with idiopathic scleritis. When compared with patients with other underlying autoimmune diseases, there were no significant differences found in epidemiological or clinical signs. Necrotising scleritis and corneal involvement were more commonly observed in GPA than in idiopathic scleritis and other autoimmune diseases and are often the presenting feature of the disease. CONCLUSIONS: The presence of necrotising changes or corneal involvement in the setting of scleral inflammation is highly suggestive of an underlying systemic vasculitis, of which GPA is the most common. These features should alert the doctor/optometrist and prompt a thorough diagnostic approach and an aggressive treatment given that it could reveal a life-threatening disease.

Cordero-Coma M, Sobrin L. Anti-tumor necrosis factor-α therapy in uveitis. Surv Ophthalmol 2015;60(6):575-89.Abstract

Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.

Cunningham ET, Sobrin L, Hall AJ, Zierhut M. Vitamin D and Ocular Inflammation. Ocul Immunol Inflamm 2020;28(3):337-340.
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Daniel E, Pistilli M, Kothari S, Khachatryan N, Kaçmaz OR, Gangaputra SS, Sen NH, Suhler EB, Thorne JE, Foster SC, Jabs DA, Nussenblatt RB, Rosenbaum JT, Levy-Clarke GA, Bhatt NP, Kempen JH, for Group SITEDR. Risk of Ocular Hypertension in Adults with Noninfectious Uveitis. Ophthalmology 2017;124(8):1196-1208.Abstract
PURPOSE: To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis. DESIGN: Retrospective, multicenter, cohort study. PARTICIPANTS: Patients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics. METHODS: Demographic, ocular, and treatment data were extracted from medical records of uveitis cases. MAIN OUTCOME MEASURES: Prevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT). RESULTS: Among 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1% (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT. CONCLUSIONS: Ocular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.

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