Long-term outcomes of noninfectious uveitis treated with systemic immunomodulatory therapy: a retrospective case series.

OBJECTIVE: To study the clinical characteristics and long-term outcomes of patients with noninfectious uveitis (NIU) who are treated with systemic immunomodulatory therapy (IMT). DESIGN: Retrospective case series. PARTICIPANTS: All consecutive cases of adults with NIU under the care of 5 uveitis subspecialty tertiary care clinics between 2010 to 2021 were included. METHODS: Patient outcomes were assessed at initial presentation and at the latest available follow-up. RESULTS: A total of 418 NIU patients receiving IMT therapy with a median age of 46.0 years and 59.3% female were identified. Each patient required an average of 1.4 agents until achieving an optimal response. Following initial treatment with prednisone, patients were most commonly initiated on methotrexate. The top 3 treatments with the highest proportion of optimal treatment response when taken alone or in combination with other agents were infliximab (79.3%), cyclosporine (75%), and adalimumab (70%). The strongest predictors for requiring a greater number of IMTs trialed were younger age, panuveitis, and a chronic or recurrent disease course. Multivariable linear regression analysis suggested that baseline visual acuity at diagnosis was the only significant predictor of final visual acuity (p < 0.001). CONCLUSIONS: NIU patients on IMT are often trialed on multiple therapeutic agents before achieving an optimal treatment response. Visual acuity at diagnosis is a predictor of final visual outcomes, whereas chronic or recurrent disease course, younger age, and panuveitis are predictors of requiring multiagent treatment regimens.

Characteristics of ocular hypertension and uveitic glaucoma among patients with noninfectious uveitis.

OBJECTIVE: Ocular hypertension and uveitic glaucoma are important downstream sequela of noninfectious uveitis (NIU). Herein, we describe the clinical outcomes of NIU cases with ocular hypertension and uveitic glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: All adults (≥18 years) with NIU under the care of uveitis subspecialty tertiary care clinics between 2010 and 2021 were included. METHODS: The primary outcomes were baseline and final visual acuity. RESULTS: A total of 216 patients out of 914 (23.6%) cases with NIU had ocular hypertension or uveitic glaucoma over the study period. Of all patients with ocular hypertension or uveitic glaucoma, 46% were corticosteroid responders. Baseline and last median visual acuities were better for the ocular hypertension patients compared with patients with uveitic glaucoma (p < 0.001). A higher proportion of patients with uveitic glaucoma than patients with ocular hypertension required glaucoma surgery (p < 0.001). The regression analyses suggested that baseline visual acuity and anatomical classification are significant predictors of last visual acuity, whereas diagnosis of ocular hypertension versus uveitic glaucoma were significant predictors of requirement for glaucoma surgery (p < 0.001). CONCLUSION: A quarter of patients with NIU in this study developed ocular hypertension or uveitic glaucoma. Approximately half of the patients with ocular hypertension or uveitic glaucoma were deemed to be corticosteroid responders. Baseline and last visual acuity outcomes are better amongst ocular hypertension patients compared with those with uveitic glaucoma. Poor baseline visual acuity and panuveitis are predictors of worse vision at last follow-up. Additionally, diagnosis of uveitic glaucoma was a significant predictor of requirement for glaucoma surgery.

ENDOGENOUS FUNGAL ENDOPHTHALMITIS AFTER COVID-19 INFECTION: CASE REPORT AND REVIEW OF LITERATURE.

PURPOSE: The purpose of this study was to describe a case of endogenous endophthalmitis (EE) after severe COVID-19 disease, review patient outcomes with EE after COVID-19 infection, and review evidence regarding risk factors for developing EE. METHODS: This is a review of health records, imaging, intravitreal injection, and pars plana vitrectomy for bilateral fungal EE after severe COVID-19 disease, and is a literature review on outcomes in EE after COVID-19 disease. RESULTS: Sixty-three year-old man with diabetes and hypertension was admitted to hospital for severe COVID-19 disease for 3 months. His stay required intensive care unit admission, intubation, high-dose corticosteroids, tocilizumab, and was complicated by bacteremia, empyema, and fungal esophagitis. He developed floaters and bilateral vision loss (visual acuity 20/40 in the right eye, counting fingers in the left eye) with vitritis 2.5 months into his stay that did not respond to intravitreal voriconazole. Pars plana vitrectomy was performed for both eyes, resulting in visual acuity of 20/40 in the right eye, 20/30 in the left eye. Vitreous cultures were positive for Candida albicans . Endogenous endophthalmitis after COVID-19 disease has been reported in 22 patients to date, and outcomes are poor, with 40%+ of eyes legally blind (20/200 or worse). Although influenced by availability of imaging modalities and degree of training of the evaluating physician, misdiagnosis can affect » of cases, delaying treatment. Age, male sex, and diabetes increase the risk of severe COVID-19, which requires prolonged hospitalization, invasive catheterization, and immunosuppression, which in turn increases the risk of nosocomial infection. CONCLUSION: Low threshold for suspecting EE in patients presenting with floaters and decreased vision after severe COVID-19 disease is necessary to ensure prompt recognition and treatment.

Clinical characteristics of non-infectious uveitis treated with and without systemic immunomodulatory therapy.

OBJECTIVE: To compare the patient characteristics and long-term outcomes for those treated with and without systemic immunomodulatory therapy (IMT) for non-infectious uveitis (NIU). DESIGN: Retrospective cohort study. PARTICIPANTS: All consecutive adults with NIU receiving care at 5 uveitis subspecialty tertiary care clinics between 2010 and 2021. METHODS: Clinical outcomes were evaluated on initial presentation and at the last available follow-up. The main outcome measures were baseline characteristics and final visual acuity. RESULTS: A total of 914 NIU patients (418 IMT, 496 non-IMT) with a median age of 51.0 years and 57.4% female were identified. Over half the patients had bilateral disease, with a significantly higher proportion of bilateral cases in the IMT group compared with the non-IMT group (p < 0.001). The IMT group was more likely to have chronic uveitis (p < 0.001), with a higher proportion of patients experiencing cataracts and cystoid macular edema (p < 0.001 for both). A significantly higher proportion of non-IMT patients had anterior uveitis and an idiopathic etiology (p < 0.001). Overall, visual acuity improved significantly from baseline to last follow-up in the entire cohort (p < 0.001), with a slightly better improvement in the IMT group. Multivariable linear regression analysis suggested that baseline visual acuity and panuveitis were significant predictors of final visual acuity (p < 0.001 for both). CONCLUSIONS: NIU patients on IMT are often younger, suffer from bilateral and chronic uveitis, and are more likely to have ocular complications. Those in the non-IMT group are more likely to have anterior idiopathic NIU. Baseline visual acuity and panuveitis are the main predictors of final vision outcomes among patients with NIU.

Outcomes in PIC-Related CNV: Pooled Analysis of Individual Participant Data.

Choroidal neovascularization (CNV) affects 64-75% of eyes with punctate inner choroidopathy (PIC). Although anti-VEGF agents are considered first-line therapy, there is controversy regarding other modalities, such as immunosuppression. We performed a systematic review of individual participant data (IPD) and generated a dataset of 278 eyes with PIC-related CNV from 45 studies. Forty-two percent presented with moderate visual loss (MVL) or worse. Four different treatment modalities (anti-VEGF, photodynamic therapy, local immunosuppression, and systemic immunosuppression) and most combinations among them were represented. Anti-VEGF injections decreased the likelihood of MVL (Odds Ratio 0.3, p = .027), an effect moderated by presenting visual acuity and patient age. Eyes receiving more than 3 injections were more likely to receive additional therapeutic modalities. Increasing number of modalities was associated with longer follow-up time and did not improve vision. The beneficial effect of anti-VEGF injections persisted when controlling for presenting visual acuity and follow-up time.

OPTICAL COHERENCE TOMOGRAPHY FEATURES IN IDIOPATHIC NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIS.

PURPOSE: To characterize optical coherence tomography features in patients with idiopathic intermediate, posterior, or panuveitis. METHODS: This is a retrospective case series of all consecutive cases of idiopathic intermediate, posterior, or panuveitis at four tertiary care centres between 2010 and 2021. RESULTS: A total of 94 eyes (55 patients) were followed for an average duration of 29.8 (SD 21) months. The median central macular thickness was 284 µ m at baseline and 267 µ m at last follow-up. At baseline and last follow-up, respectively, 24% and 20% of uveitic eyes had intraretinal fluid, 12% and 1% subretinal fluid, and 43% and 54% epiretinal membrane. In addition, ellipsoid zone abnormalities on en-face were noted in 34% and 19% of cases at baseline and last follow-up, respectively. The baseline median visual acuity was significantly lower among cases with ellipsoid zone en-face slab abnormalities compared with those without (0.2 logarithm of minimum angle of resolution [interquartile range: 0-0.6] vs. 0.1 logarithm of minimum angle of resolution [interquartile range: 0-0.3], P = 0.0051). CONCLUSION: With initiation of treatment, the central macular thickness, intraretinal fluid, subretinal fluid, and ellipsoid zone en-face abnormalities improved over time, whereas the number of cases with epiretinal membrane increased among eyes with idiopathic intermediate, posterior, and panuveitis. Presence of ellipsoid zone en-face abnormalities at presentation may be associated with worse visual acuity.

Advancing Early Identification of Axial Spondyloarthritis: An Interobserver Comparison of Extended Role Practitioners and Rheumatologists.

OBJECTIVE: To compare clinical impression and confidence of extended role practitioners (ERP) with those of rheumatologists experienced in axial spondyloarthritis (axSpA) according to (1) evaluation of patients with chronic back pain assessed for axSpA; and (2) magnetic resonance imaging (MRI) recommendation for further investigation of these patients. METHODS: Patients with ≥ 3 months of back pain and age of onset < 45 years were referred for axSpA evaluation. An ERP assessed consecutive patients and recorded standardized clinical information in written form. Three rheumatologists subsequently evaluated each patient based on the recorded information. Patients were classified as having axSpA or mechanical back pain based on clinical and investigative findings. Level of confidence was noted for classification and MRI indication. Agreement between assessors was evaluated using percentage agreement and κ coefficient. RESULTS: Fifty-seven patients were assessed. Interobserver agreement of clinical impression for all raters was moderate (κ = 0.52). Agreement of clinical impression between ERP and rheumatologists ranged between 71.2% (κ = 0.41) and 79.7% (κ = 0.57). Agreement of clinical impression among rheumatologists ranged from 74.1% (κ = 0.49) to 79.7% (κ = 0.58). All rater agreement for MRI indication was fair (κ = 0.37). ERP agreement with rheumatologist for MRI recommendation ranged from 64.2% (κ = 0.32) to 75% (κ = 0.48). Agreement for MRI indication among rheumatologists ranged from 62.9% (κ = 0.27) to 74% (κ = 0.47). Confidence in clinical impression was similar among all practitioners. CONCLUSION: ERP with specialty training in inflammatory arthritis demonstrate clinical impressions comparable with those of rheumatologists in the assessment of axSpA. Incorporation of such roles into existing models of care may assist in early detection of axSpA.

Referral characteristics and wait times for uveitis consultation at academic tertiary care centres in Toronto.

OBJECTIVE: To assess the characteristics of referrals to academic uveitis tertiary care centres in Toronto and identify determinants of wait time for consultation. DESIGN: Retrospective case series. METHODS: Consecutive new uveitis referrals received at 5 University of Toronto-affiliated uveitis tertiary care centres, between February 2016 and November 2016, were included. RESULTS: A total of 159 new uveitis referrals were received from academic (69%) and community (31%) providers. A large proportion of referrals were sent by comprehensive ophthalmologists (33%) and retina specialists (38%). Disease was bilateral in 46% of cases, had an acute onset in 43% of cases, and was classified as posterior uveitis in 38% of cases. Disease etiology at the time of referral was unknown in 55% of cases. Only 43% of all referrals included a basic uveitis workup, and patients who had undergone diagnostic testing had a shorter wait time for consultation (41 ± 43 vs. 59 ± 54 days, p = 0.033). Acute uveitis had a shorter wait time compared with recurrent and chronic uveitis (33 ± 42 vs. 66 ± 44 and 59 ± 58 days, p < 0.001). Referrals triaged as urgent had significantly shorter wait times compared with referrals triaged as semiurgent or elective (7 ± 10 vs. 54 ± 43 and 88 ± 59, p < 0.001). CONCLUSIONS: Referrals to academic uveitis tertiary care centres in Toronto are often acute, bilateral cases affecting the posterior segment without a known etiology. Approximately half of referrals include no diagnostic workup, which may delay diagnosis for patients and lengthen wait times for consultation. We provide a set of recommendations for investigations that should be included in uveitis referrals.

Clinical features of infectious posterior segment uveitis.

OBJECTIVE: To assess the clinical findings and microbiology investigations in patients with suspected infectious posterior segment uveitis (PSU). DESIGN: Retrospective case study. METHODS: Between January and December 2014, medical records of 270 patients with PSU were reviewed. Baseline ocular examination, presumed and final diagnoses, microbiology investigations from aqueous or vitreous fluid, and peripheral blood were reviewed. RESULTS: Infectious PSU was suspected in 28 patients among 270 PSU cases (10.4%, 28/270), and 11 cases were of infectious origin (4.1%, 11/270). Six patients were immunocompromised: 5 patients in the confirmed infectious PSU group (45.5%, 5/11) and 1 in the confirmed noninfectious group (5.9%, 1/17; p = 0.002). Initial visual acuity was 1.8 ± 0.35 logMAR and 0.9 ± 0.23 logMAR for patients with confirmed infectious and noninfectious PSU, respectively (p = 0.04). Anterior chamber reaction was worse in patients with confirmed infectious PSU (1.8 ± 0.49) than confirmed noninfectious cases (0.5 ± 0.1; p = 0.003). The frequency of chorioretinitis among patients with confirmed infectious and noninfectious PSU is 54.5% (6/11) and 11.8% (2/17; p = 0.03), respectively. Onset of confirmed infectious uveitis was more acute (≤6 weeks in duration) than noninfectious cases (p = 0.0015). Among the 11 patients with positive blood culture or serology, 6 had anterior and vitreous chamber fluid analysis. The rate of positive cultures and PCR is 16.7% (1/6) for aqueous humour and 50% (3/6) for vitreous samples. CONCLUSIONS: Clinical features more suggestive of infectious PSU include immunosuppression, worse initial visual acuity, acute onset, worse anterior chamber reaction, and chorioretinitis. Further studies are needed to enhance the diagnostic yields of aqueous and vitreous fluid analyses.

IgG4-related disease in the eye and ocular adnexa.

PURPOSE OF REVIEW: IgG4-related disease is a multi-organ fibro-inflammatory disease with characteristic histopathology showing lymphoplasmacytic infiltration, increased IgG4+ plasma cells and elevated IgG4/IgG ratios (>40%). The lacrimal gland is the most common ocular site of involvement. Scleritis and intraocular involvement in IgG4-related ophthalmic disease (IgG4-ROD) have recently been reported. The purpose of this review is to describe orbital and intraocular IgG4-ROD with a focus on publications since 2016. RECENT FINDINGS: Case reports of scleritis and uveitis in IgG4-ROD have been described since 2012. Systemic prednisone is recommended as the first-line treatment, but immunosuppressive therapy may be required for steroid-sparing or in steroid-resistant cases. High rates of systemic IgG4-RD involvement exist in patients with bilateral IgG4-ROD or if the lacrimal gland is involved. Rituximab is the most specific immune targeted therapy available with high rates of remission. SUMMARY: IgG4-ROD is an emerging cause of scleritis and uveitis and should be considered in any patient with multisystem inflammatory disease. New targeted immune therapies may improve outcomes and lead to clinical remission.

Ten-year retrospective review of outcomes following phacoemulsification with intraocular lens implantation in patients with pre-existing uveitis.

OBJECTIVE: The aim of this study was to evaluate the visual outcome, uveitis control, and complications following cataract surgery for intraocular lens (IOL) implantation in patients with a known diagnosis of uveitis. DESIGN: The study was a retrospective interventional case series. PARTICIPANTS: We reviewed 98 patients (137 eyes) with adult uveitis undergoing cataract surgery with foldable acrylic posterior chamber IOL implantation between 2003 and 2013 in 2 uveitis practices. METHODS: Best-corrected visual acuity (BCVA) and uveitis grade (Standardized Uveitis Nomenclature criteria) were measured at 1 month preoperatively, at postoperative week 1, and at postoperative months 1, 6, and 12. The main outcome measures were mean change in postoperative BCVA, uveitis grade, and complications. RESULTS: Of the eyes studied, 84% had grade 0-0.5 anterior uveitis at postoperative week 1 and maintained uveitis control (77% grade 0; 19% grade 0.5 anterior uveitis) at 1 year postoperatively. None of the patients had active intermediate or posterior uveitis at any time point. Mean BCVA improved from 0.71 ± 0.38 logMAR preoperatively to 0.37 ± 0.36 at 6 months (p < 0.01) and to 0.30 ± 0.25 at 12 months (p = 0.01) postoperatively. Of the study participants, 30% had preoperative complications related to uveitis, including epiretinal membrane (12%), cystoid macular edema (12%), and glaucoma (5.8%); 46% of patients had small pupils as a result of posterior synechiae. Postoperative vision-limiting complications included posterior capsule opacification (18%), epiretinal membrane (9.0%), and cystoid macular edema (8.8%). Of the eyes studied, 5.8% underwent Nd:YAG capsulotomy. CONCLUSIONS: Cataract surgery with acrylic posterior-chamber IOL implantation is effective at improving visual acuity in patients with uveitis. Uveitis was well controlled in the majority of our study patients for 12 months after cataract surgery. The most frequent vision-limiting postoperative complication was posterior capsule opacification, which was treatable with Nd:YAG capsulotomy.

IgG4-related disease presenting as panuveitis without scleral involvement.

BACKGROUND: The following case emphasizes the importance of including IgG4-related disease (RD) in the differential diagnosis of intraocular inflammation and multiple cranial nerve palsies. RESULTS: A 33-year-old man, with a history of idiopathic bilateral panuveitis, presented with a new right pupillary-sparing partial third nerve palsy, which spontaneously resolved in 2 weeks, but was followed 1 month later, by a right sixth nerve palsy, which also resolved within a few weeks. Motility disturbance was accompanied by a decrease in the central acuity in the right eye. Magnetic resonance imaging/angiography (MRI/MRA) demonstrated a densely enhancing osteodestructive skull base process extending through the cavernous sinus and into the right superior orbital fissure. Biopsy of the lesion was consistent with IgG4-related disease (RD). CONCLUSIONS: This is the first reported case of IgG4-RD associated panuveitis without scleral involvement, expanding the list of clinical manifestations of the IgG4-RD.

Prevalence of inflammatory back pain in a cohort of patients with anterior uveitis.

PURPOSE: To determine the prevalence of inflammatory back pain in an anterior uveitis cohort. DESIGN: Retrospective cohort study. METHODS: Patients with anterior uveitis were recruited from the clinic of an ophthalmologist to complete a survey between March and December 2008. Patients were classified with inflammatory back pain if they had ≥2 positive responses to 4 validated inflammatory back pain questions: presence of morning stiffness >30 minutes in duration; improvement in back pain with exercise but not with rest; awakening from back pain during the second half of the night only; and presence of alternating buttock pain. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The impact of disease on quality of life was measured using the EuroQOL (EQ-5D) questionnaire. Twenty-five patients underwent further rheumatologic examination. RESULTS: One hundred forty-one of 167 patients (84.4%) completed the survey. Sixty-six of 141 patients (46.8%) were classified to have inflammatory back pain. Mean BASDAI (4.2, SD 2.41) and EQ-5D scores (0.73, SD 0.21) were lower than patients with no inflammatory back pain (0.82, SD 0.16, P = .0048). In the subgroup that underwent rheumatologic assessment, a classification of inflammatory back pain was 92% sensitive and 67% specific for a diagnosis of inflammatory back pain. CONCLUSIONS: The prevalence of inflammatory back pain in a cohort of anterior uveitis patients was found to be 46.8%. Patients with inflammatory back pain had worse quality of life than those without. Ophthalmologists may use these questions on back pain to select patients classified to have inflammatory back pain to refer for early rheumatologic assessment.

Evaluating the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists.

BACKGROUND: To evaluate the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists and to assess the role of implementing national clinical guidelines for such investigation. METHODS: Based on data extracted from the Canadian National Uveitis Survey (CNUS, 2007 version), the cost of investigating a patient with anterior uveitis, according to current practice patterns of Canadian ophthalmologists, was determined and grouped across 4 clinical scenarios: (i) nongranulomatous anterior uveitis in an adult, (ii) granulomatous anterior uveitis in an adult, (iii) granulomatous anterior uveitis with suspected sarcoidosis in an adult or a child, and (iv) nongranulomatous anterior uveitis in a child. Similarly, the cost of investigating a patient with anterior uveitis as per published evidence-based guidelines was determined and compared with the current practice pattern using a cost-minimization model, sensitivity analyses, and Monte Carlo simulations. RESULTS: Ophthalmologists were found to consistently order more tests than recommended by evidence-based guidelines, across each of the scenarios studied (p < 0.05). Overall, complete blood count, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, and rheumatoid factor were the most commonly ordered extraneous tests that were not included in the evidence-based guidelines for the routine investigation of anterior uveitis. Also, there were significant differences in the cost of investigating a patient with anterior uveitis when compared with those predicted by adhering to evidence-based clinical practice guidelines. Cost minimization and sensitivity analyses revealed that published guidelines imparted cost savings when compared with current practice patterns across the 4 clinical scenarios studied (p < 0.01). The maximum additional cost was associated with investigating nongranulomatous anterior uveitis in an adult, where a minimal additional cost of $75 per patient was spent. For granulomatous anterior uveitis in an adult, the additional cost was approximately $40, whereas the additional cost for investigating an adult or a child with suspected sarcoidosis was $36. Only $11 of additional cost was spent in the workup of a child with nongranulomatous anterior uveitis. When applied to the Canadian population, adherence to the Clinical Practice Guidelines recommended by the CNUS may result in cost savings of $600,000 per year to the Canadian health care system. INTERPRETATION: Adherence to the evidence-based Clinical Practice Guidelines recommended by the CNUS may result in significant cost savings, with virtually no loss of sensitivity in the routine investigation of anterior uveitis in Canada.

Outcome of trabeculectomy with intraoperative mitomycin C for uveitic glaucoma.

BACKGROUND: The purpose of this study was to compare the outcomes of mitomycin C (MMC)-augmented trabeculectomy in glaucoma patients with uveitis to those without uveitis but with other high-risk characteristics. METHODS: A retrospective comparative cohort analysis consisting of 51 eyes of 51 patients (21 uveitic patients and 30 nonuveitic patients) was performed. Two outcome classifications were analyzed: absolute success (intraocular pressure [IOP]

Anterior uveitis investigation by Canadian ophthalmologists: insights from the Canadian National Uveitis Survey.

BACKGROUND: Anterior uveitis can be the result of a number of underlying etiologies and is commonly seen in ophthalmology practice. The clinician must choose from a battery of potential investigations. A nonselective approach to testing is costly and inefficient and can lead to misinterpretation of false positive results. The purpose of this study was to identify investigation patterns of ophthalmologists in Canada for anterior uveitis and to make evidence-based recommendations for appropriate tests that could lead to improved patient care and more cost-effective use of health care resources. METHODS: A cross-sectional survey of practicing ophthalmologists, fellows, and residents in Canada was conducted in September 2004. The survey instrument was an 11-item questionnaire mailed to 1196 physicians in Canada. RESULTS: A total of 498 (42%) physicians responded to the survey. A wide range of tests were chosen when respondents were presented with 5 scenarios for anterior uveitis and asked what investigations they would order. Many of these tests have low diagnostic yields because they lack the sensitivity and specificity to be used as routine investigations in the setting of anterior uveitis. INTERPRETATION: Increased education and awareness could lead to more cost-effective and efficient investigations in the setting of anterior uveitis. On the basis of evidence from a review of the literature, we make recommendations for investigations that should be considered in patients with anterior uveitis.