Causal Association between Iritis or Uveitis and Glaucoma: A Two-Sample Mendelian Randomisation Study.

Recent studies have suggested an association between iritis or uveitis and glaucoma. This study investigated the causal relationship between glaucoma and iritis and uveitis as exposures in a multi-ethnic population. Single-nucleotide polymorphisms associated with exposures to iritis and uveitis from the genome-wide association study (GWAS) data of Biobank Japan (BBJ) and the meta-analysis data from BBJ and UK Biobank (UKB) were used as instrumental variables (IVs). The GWAS dataset for glaucoma was extracted from the meta-analysis data (n = 240,302) of Genetic Epidemiology Research in Adult Health and Aging and UKB. The casual estimates were assessed with a two-sample Mendelian randomisation (MR) test using the inverse-variance-weighted (IVW) method, weighted median method, MR-Egger method, and MR-Pleiotropy Residual Sum and Outlier test. The IVW method revealed a significant causal association between iritis and glaucoma using IVs (p < 5.0 × 10-8) from the East Asian population (n = 2) (odds ratio [OR] = 1.01, p = 0.017), a significant association between iritis exposures (p < 5.0 × 10-8) in the multi-ethnic population (n = 11) (OR = 1.04, p = 0.001), and a significant causal association between uveitis exposures (n = 10 with p < 5.0 × 10-8) and glaucoma in the multi-ethnic population (OR = 1.04, p = 0.001). Iritis and uveitis had causal effects on glaucoma risk based on IVs from the multi-ethnic population. These findings imply that the current classifications of uveitic glaucoma and open-angle glaucoma overlap, indicating the need for further investigating these complex relationships.

Understanding COVID-19 Risk in Patients With Immune-Mediated Inflammatory Diseases: A Population-Based Analysis of SARS-CoV-2 Testing.

OBJECTIVE: To investigate the incidence of and factors associated with SARS-CoV-2 testing and infection in immune-mediated inflammatory disease (IMID) patients versus matched non-IMID comparators from the general population. METHODS: We conducted a population-based, matched cohort study among adult residents from Ontario, Canada, from January 2020 to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 patients without IMIDs based on sociodemographic factors. We estimated the incidence of SARS-CoV-2 testing and infection in IMID patients and non-IMID patients. Multivariable logistic regressions assessed odds of SARS-CoV-2 infection. RESULTS: We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least 1 SARS-CoV-2 test versus patients without IMIDs (27.4% versus 22.7%), but the proportion testing positive for SARS-CoV-2 was identical (0.9% in both groups). Overall, IMID patients had 20% higher odds of being tested for SARS-CoV-2 (odds ratio 1.20 [95% confidence interval 1.19-1.21]). The odds of SARS-CoV-2 infection varied across IMID groups but was not significantly elevated for most IMID groups compared with non-IMID comparators. The odds of SARS-CoV-2 infection was lower in IBD and MS and marginally higher in RA and iritis. CONCLUSION: Patients across all IMIDs were more likely to be tested for SARS-CoV-2 versus those without IMIDs. The risk of SARS-CoV-2 infection varied across disease subgroups.

Comparison of postcataract surgery anti-inflammatory regimens on the incidence of cystoid macular edema, iritis, pain, and photophobia.

PURPOSE: To compare postcataract surgery anti-inflammatory regimens of intracanalicular dexamethasone insert and topical bromfenac on the incidence of cystoid macular edema (CME), iritis, pain, and photophobia. SETTING: Eyes of York Cataract & Laser Center, York, Pennsylvania. DESIGN: Retrospective chart review. METHODS: Case records of 647 consecutive patients (1001 eyes) who underwent cataract surgery and received dexamethasone intracanalicular insert 0.4 mg (Group 1; 482 eyes) or topical nonsteroidal anti-inflammatory drug (NSAID) (bromfenac 0.075% 2 times a day) for 4 weeks postoperatively (Group 2; 519 eyes) were included. Both groups received intracameral moxifloxacin and phenylephrine/ketorolac. Patients with prior CME, vitreomacular traction, combined cataract/glaucoma surgery, and medication protocols different from those examined in this study were excluded. RESULTS: Compared with the dexamethasone insert group, the topical NSAID group had a significantly lower incidence of CME (0.4% [2/519] vs 3.9% [19/482], P < .001) and photophobia (1.9% [10/519] vs 4.8% [23/482], P = .012). The incidence of breakthrough iritis (3.5% [18/519] vs 5.6% [27/482], P = .104) and pain also trended lower (4.0% [21/519] vs 5.4% [26/482], P = .314) in the topical NSAID group. CONCLUSIONS: Topical NSAIDs were found to be more effective in controlling CME, pain, iritis, and photophobia after cataract surgery compared with the intracanalicular dexamethasone insert in the presence of intracameral phenylephrine/ketorolac.

Extreme intraocular pressure and steroid-dependent iritis.

A 50-year-old ophthalmic technician was referred by her retina specialist for urgent consultation due to markedly elevated intraocular pressure (IOP) unresponsive to medical therapy. Her history included chronic polyarticular juvenile rheumatoid arthritis and chronic uveitis requiring ongoing topical steroid therapy. She had a sub-Tenon injection of Kenalog (triamcinolone) 18 months prior to referral. Chronic topical anti-inflammatory therapy included nepafenac (Ilevro) and prednisolone acetate 2 times a day. Attempts to discontinue topical steroid resulted in worsening inflammation. The patient was referred when the IOP measured 44 mm Hg in the left eye despite aggressive medical therapy, including acetazolamide. The IOP improved slightly when loteprednol was substituted for prednisolone acetate. Current medications in the left eye include brimonidine 3 times a day, loteprednol 2 times a day, nepafenac 2 times a day, and fixed combination latanoprost + netarsudil at bedtime. Her only medication in the right eye was travoprost. She is intolerant to dorzolamide. She was also taking acetazolamide 500 mg 2 times a day. She was not taking any anticoagulants. Past surgical history included cataract surgery in each eye. She has not had laser trabeculoplasty in either eye. Examination revealed uncorrected visual acuity of J1+ in the right eye (near) and 20/30 in the left eye (mini-monovision). There was no afferent pupillary defect. There was mild band keratopathy in each eye while the central cornea was clear in both eyes without keratic precipitates. Here angles were open to gonioscopy without peripheral anterior synechia. There was mild to moderate flare in each eye with trace cells. The IOP was 17 mm Hg in the right eye and 31 mm Hg in the left. Central corneal thickness measured 560 µm and 559 µm in the right and left eye respectively. There was a well-positioned intraocular lens within each capsule with a patent posterior capsulotomy. There was mild vitreous syneresis but no vitreous cell. The cup to disc ratio was 0.5 in each eye with a symmetrical neural rim. The retina was flat without macular edema. Visual field was normal in both eyes (Figures 1 and 2). Optical coherence tomography of retinal nerve fiber layer (RNFL) is shown in Figure 3 and retinal ganglion cell layer is shown in Supplemental Figure 1 (http://links.lww.com/JRS/A756).JOURNAL/jcrs/04.03/02158034-202301000-00020/figure1/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure2/v/2022-12-26T045736Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202301000-00020/figure3/v/2022-12-26T045736Z/r/image-tiff Please comment on your management of this patient's left eye.

Self-identified Black Race as a Risk Factor for Intraocular Pressure Elevation and Iritis Following Prophylactic Laser Peripheral Iridotomy.

PRCIS: In primary angle closure suspects (PACS), self-identified Black race was a risk factor for intraocular pressure (IOP) elevation and iritis following laser peripheral iridotomy (LPI). Laser type was not associated with either immediate post-LPI IOP elevation or iritis in multivariate analysis. PURPOSE: The aim was to determine the impact of laser type and patient characteristics on the incidence of IOP elevation and iritis after LPI in PACS. MATERIALS AND METHODS: The electronic medical records of 1485 PACS (2407 eyes) who underwent either neodymium-doped yttrium-aluminum-garnet or sequential argon and neodymium-doped yttrium-aluminum-garnet LPI at the University of Pennsylvania between 2010 and 2018 were retrospectively reviewed. Average IOP within 30 days before LPI (baseline IOP), post-LPI IOP within 1 hour, laser type, laser energy, and the incidence of new iritis within 30 days following the procedure were collected. Multivariate logistic regression accounting for intereye correlation was used to assess factors associated with incidence of post-LPI IOP elevation and iritis, adjusted by age, sex, surgeon, and histories of autoimmune disease, diabetes, and hypertension. RESULTS: The incidence of post-LPI IOP elevation and iritis were 9.3% (95% confidence interval: 8.1%-10.5%) and 2.6% (95% CI: 1.9%-3.2%), respectively. In multivariate analysis, self-identified Black race was a risk factor for both IOP elevation [odds ratio (OR): 2.08 compared with White; P=0.002] and iritis (OR: 5.07; P<0.001). Higher baseline IOP was associated with increased risk for post-LPI IOP elevation (OR: 1.19; P<0.001). Laser type and energy were not associated with either post-LPI IOP elevation or iritis (P>0.11 for all). CONCLUSIONS: The incidence of immediate IOP elevation and iritis following prophylactic LPI was higher in Black patients independent of laser type and energy. Heightened vigilance and increased medication management before and after the procedure are suggested to help mitigate these risks.

COVID-19 Hospitalizations, Intensive Care Unit Stays, Ventilation, and Death Among Patients With Immune-mediated Inflammatory Diseases Compared to Controls.

OBJECTIVE: To investigate coronavirus disease 2019 (COVID-19) hospitalization risk in patients with immune-mediated inflammatory diseases (IMIDs) compared with matched non-IMID comparators from the general population. METHODS: We conducted a population-based, matched cohort study using health administrative data from January to July 2020 in Ontario, Canada. Cohorts for each of the following IMIDs were assembled: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), ankylosing spondylitis, systemic autoimmune rheumatic diseases (SARDs), multiple sclerosis (MS), iritis, inflammatory bowel disease, polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 non-IMID comparators based on sociodemographic factors. We compared the cumulative incidence of hospitalizations for COVID-19 and their outcomes between IMID and non-IMID patients. RESULTS: A total of 493,499 patients with IMID (417 hospitalizations) and 2,466,946 non-IMID comparators (1519 hospitalizations) were assessed. The odds of being hospitalized for COVID-19 were significantly higher in patients with IMIDs compared with their matched non-IMID comparators (matched unadjusted odds ratio [OR] 1.37, adjusted OR 1.23). Significantly higher risk of hospitalizations was found in patients with iritis (OR 1.46), MS (OR 1.83), PsA (OR 2.20), RA (OR 1.42), SARDs (OR 1.47), and vasculitis (OR 2.07). COVID-19 hospitalizations were associated with older age, male sex, long-term care residence, multimorbidity, and lower income. The odds of complicated hospitalizations were 21% higher among all IMID vs matched non-IMID patients, but this association was attenuated after adjusting for demographic factors and comorbidities. CONCLUSION: Patients with IMIDs were at higher risk of being hospitalized with COVID-19. This risk was explained in part by their comorbidities.

Diagnosis and Management of Idiopathic Persistent Iritis after Cataract Surgery (IPICS).

PURPOSE: To investigate the diagnosis and management of patients with idiopathic persistent iritis after cataract surgery (IPICS). DESIGN: Retrospective interventional case series. METHODS: Patients diagnosed with IPICS were evaluated for demographic and clinical characteristics and immune blood markers. Those with more than 6 months of follow-up were evaluated for treatment efficacy to achieve remission (ie, absence of inflammation for 3 months), with either exclusive slow tapering of topical steroids or the need for systemic immunosuppression. RESULTS: Forty-five patients presented with IPICS. Most were African American (39, 86.7%) or female (33, 77.3%). Antinuclear antibodies were present in 23 (69.9%) of patients. Main complications were steroid dependency (38,84.4%), glaucoma (24,53.5%), and macular edema (11,37.5%). Thirty two patients presented treatment follow up. On these,the proposed treatment strategy achieved remission in 30 (93.8%) of cases in a mean of 6.1 months via tapering of topical steroids in 15 (46.9%) of patients. However, in 17 (53.1%) of cases, adjuvant anti-inflammatory systemic medication was indicated. Meloxicam use was associated with remission in 11 (64.7%) of these patients and, in a minority with persistent iritis, treatment was escalated to methotrexate, which was successful in 4 (100%) of the cases. CONCLUSIONS: IPICS is a distinct clinical anterior uveitis most common in African American and female patients, characterized by an unexpected onset of iritis after cataract surgery and high rates of steroid dependency, glaucoma, and macular edema. It is best treated with an initial slow taper of topical steroids; although adjuvant systemic anti-inflammatory therapy may be necessary to obtain remission and avoid complications.

The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies.

This post hoc analysis of the UNITI studies found ustekinumab (UST) did not significantly improve overall extraintestinal manifestations (EIMs) of Crohn's disease compared to placebo-treated patients at weeks 6 and 52. BACKGROUND AND AIMS: The UNITI trials demonstrated that UST was effective in inducing and maintaining clinical remission in Crohn's disease (CD). However, limited data exists regarding its effectiveness for treatment of EIMs. This post hoc analysis evaluated the efficacy of UST in treatment of EIMs. METHODS: Data from UNITI-1/2 and IM-UNITI (NCT01369329, NCT01369342, NCT01369355) were obtained from the Yale Open Data Access Project (2019-4104). Nine hundred and fourty-one patients eligible for UST induction and 263 patients eligible for maintenance UST were included. The primary outcome of interest was EIM resolution at Week 6 in UST and placebo-treated patients using the chi-square test. EIM resolution at Week 52 was also assessed. McNemar's test was used to compare the proportion of patients who reported active EIMs at weeks 6 and 52 versus baseline. RESULTS: From 941 UST-treated patients in UNITI-1/2, 504 had 527 EIMs at baseline. Overall, there was no significant difference in EIM resolution observed in UST-treated patients (186/504, 36.9%) compared to placebo (90/230, 39.1%; p = 0.564) at Week 6. Patients treated with continuous UST (91/119, 76.4%) had no significant difference in overall EIMs resolved at Week 52 compared to placebo (72/90, 80.0%; p = 0.542). Although many EIMs demonstrated reduction in prevalence compared to baseline at initiation of UST, only erythema nodosum was more likely to improve at Week 52 on treatment versus placebo. CONCLUSION: Overall, UST did not lead to significant resolution of EIMs for CD compared to placebo at weeks 6 and 52.

Anti-Neutrophil Cytoplasmic Antibody-Associated Ocular Manifestations in Japan: A Review of 18 Patients.

ABSTARCTPurpose: To investigate ocular manifestations in patients positive for serum anti-neutrophil cytoplasmic antibodies (ANCAs) in Japan.Methods: The clinical records of patients who had ocular manifestations and who were serum ANCA positive between 2011-2017 at Tokyo Medical and Dental University Hospital were retrospectively reviewed.Results: Eighteen patients were identified to be positive for serum ANCA and had ocular manifestations, including optic nerve involvement (50%), scleritis (27.8%), iritis (27.8%), retinal vasculitis (16.7%), oculomotor disorder (16.7%), and peripheral ulcerative keratitis (11.1%). Six patients had ANCA-associated vasculitis (AAV), including 5 patients with granulomatosis with polyangiitis and 1 patient with microscopic polyangiitis. Most patients with optic nerve involvement were myeloperoxidase-ANCA positive. Contrastingly, most patients with anterior segment involvement were proteinase-3-ANCA positive.Conclusion: Ocular manifestations were observed in some patients positive for serum ANCAs. Serum ANCA evaluation is useful for identifying the etiology of ocular inflammation and for diagnosing AAV, a life-threatening disease.

Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery.

PURPOSE: To assess the effectiveness of intracameral phenylephrine-ketorolac during cataract surgery compared with postoperative topical steroids in reducing the incidence of postoperative clinical cystoid macular edema (CME) confirmed via optical coherence tomography (OCT), breakthrough iritis, pain, and photophobia. SETTING: Ambulatory surgical center/clinical practice. DESIGN: Retrospective 2-cohort study. METHODS: This study of cataract surgery patients compared the incidence of postoperative CME, breakthrough iritis, pain, and photophobia between patients receiving either intracameral phenylephrine 1.0%-ketorolac 0.3% during surgery or topical loteprednol 0.5% 2 days preoperatively, tapered postoperatively. Patients with prior CME or at high risk for postoperative CME, combined cataract/glaucoma surgery, and medication protocols different from those studied here were excluded. All eyes received bromfenac 2 days preoperatively and 10 weeks postoperatively. RESULTS: The study enrolled 2218 eyes (n = 1402). The phenylephrine/ketorolac treatment group included 1334 eyes (n = 830) and the topical loteprednol control group included 884 eyes (n = 572). The groups were comparable in age, race, gender, and perioperative characteristics. Clinical CME incidence was significantly lower in the phenylephrine-ketorolac group (0.52% vs 1.47%, P = .021). The phenylephrine-ketorolac group also had significantly lower breakthrough iritis (1.72% vs 4.86%, P < .001) and pain (1.27% vs 4.19%, P < .001) than the topical loteprednol group. The incidence of photophobia trended lower for the phenylephrine/ketorolac group relative to the topical loteprednol group (0.90% vs 1.13%, respectively, P = .590) but was not statistically significant. CONCLUSIONS: Intracameral phenylephrine/ketorolac and topical nonsteroidal antiinflammatory drugs (NSAIDs) without postoperative topical steroids significantly reduced postoperative clinical CME, breakthrough iritis, and pain after cataract surgery when compared with conventional perioperative topical steroids and NSAIDs.

Importance of pediatric rheumatologists and transitional care for juvenile idiopathic arthritis-associated uveitis: a retrospective series of 9 cases.

BACKGROUND: Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a serious condition associated with the risk of blindness. However, pediatric rheumatologists rarely encounter cases of blindness, because most patients reach adulthood during the course of follow-up before blindness occurs. Here, we report the progress of 9 patients with JIA-U, including 2 patients who became blind after the transition period. We aimed to highlight the importance of the role of pediatric rheumatologists and transitional care in preventing blindness associated with JIA-U. CASE PRESENTATION: We conducted a retrospective analysis of the case records of 9 JIA-U patients (1 male, 8 female; median age 16.8 years, range 5.5-19.8 years). All patients presented with oligo-juvenile idiopathic arthritis (oligo-JIA) (one presented with extended oligo-JIA); the median age of uveitis onset was 5.0 years (range 3.0-13.0 years), and the onset of uveitis preceded the onset of arthritis in 2 patients. The median disease duration was 12.5 years (range 3.5-24.7 years); 4 patients had anti-nuclear antibody (ANA) positivity (≧1:160) (all with a homogeneous and speckled-pattern subtype). All patients were negative for rheumatoid factor. Eight patients received methotrexate, 7 patients received one or more biologic drugs (etanercept, infliximab, adalimumab, and golimumab), and 6 patients required ophthalmic surgery at an early age (≦ 18 years). Two patients developed blindness after the transition period. Medical examination by pediatric rheumatologists and use of biologics had been delayed in both patients. One patient developed depression after transition and interrupted her own treatment. CONCLUSIONS: The reason for blindness in the 2 patients was thought to be the delay in the commencement of treatment and failure to provide transitional care. Inflammation is difficult to control in JIA-U even with appropriate treatment. Pediatric rheumatologists must be informed about the risk of JIA-U blindness, especially after transition. To ensure a good prognosis, the specialized treatment with the involvement of pediatric rheumatologists is necessary early on, and consideration for transitional medicine is essential. Therefore, this report reaffirms the importance of planned transitional care that has been advocated for globally.

Lassa Virus Targeting of Anterior Uvea and Endothelium of Cornea and Conjunctiva in Eye of Guinea Pig Model.

Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors.

Fracture Prevention with Zoledronate in Older Women with Osteopenia.

BACKGROUND: Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed. METHODS: We conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of -1.0 to -2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. A dietary calcium intake of 1 g per day was advised, but calcium supplements were not provided. Participants who were not already taking vitamin D supplements received cholecalciferol before the trial began (a single dose of 2.5 mg) and during the trial (1.25 mg per month). The primary end point was the time to first occurrence of a nonvertebral or vertebral fragility fracture. RESULTS: At baseline, the mean (±SD) age was 71±5 years, the T score at the femoral neck was -1.6±0.5, and the median 10-year risk of hip fracture was 2.3%. A fragility fracture occurred in 190 women in the placebo group and in 122 women in the zoledronate group (hazard ratio with zoledronate, 0.63; 95% confidence interval, 0.50 to 0.79; P<0.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15. As compared with the placebo group, women who received zoledronate had a lower risk of nonvertebral fragility fractures (hazard ratio, 0.66; P=0.001), symptomatic fractures (hazard ratio, 0.73; P=0.003), vertebral fractures (odds ratio, 0.45; P=0.002), and height loss (P<0.001). CONCLUSIONS: The risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate than in women who received placebo. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12609000593235 .).