To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation.
Retrospective cohort study.
Patients with noninfectious ocular inflammation managed at 4 tertiary ocular ...inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive.
Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers.
Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy.
Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for >or=28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone <or=10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (<or=10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment.
Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment.
To evaluate the benefits and complications of periocular depot corticosteroid injections in patients with ocular inflammatory disorders.
Multicenter, retrospective cohort study.
A total of 914 ...patients (1192 eyes) who had received ≥ 1 periocular corticosteroid injection at 5 tertiary uveitis clinics in the United States.
Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained at every visit via medical record review by trained reviewers.
Control of inflammation, improvement of visual acuity (VA) to ≥ 20/40, improvement of VA loss attributed to macular edema (ME), incident cataract affecting VA, cataract surgery, ocular hypertension, and glaucoma surgery.
Among 914 patients (1192 eyes) who received ≥ 1 periocular injection during follow-up, 286 (31.3%) were classified as having anterior uveitis, 303 (33.3%) as intermediate uveitis, and 324 (35.4%) as posterior or panuveitis. Cumulatively by ≤ 6 months, 72.7% (95% CI, 69.1-76.3) of the eyes achieved complete control of inflammation and 49.7% (95% CI, 45.5-54.1) showed an improvement in VA from <20/40 to ≥ 20/40. Among the subset with VA <20/40 attributed to ME, 33.1% (95% CI, 25.2-42.7) improved to ≥ 20/40. By 12 months, the cumulative incidence of ≥ 1 visits with an intraocular pressure of ≥ 24 mmHg and ≥ 30 mmHg was 34.0% (95% CI, 24.8-45.4) and 15.0% (95% CI, 11.8-19.1) respectively; glaucoma surgery was performed in 2.4% of eyes (95% CI, 1.4-3.9). Within 12 months, among phakic eyes initially ≥ 20/40, the incidence of a reduction in VA to <20/40 attributed to cataract was 20.2% (95% CI, 15.9-25.6); cataract surgery was performed within 12 months in 13.8% of the initially phakic eyes (95% CI, 11.1-17.2).
Periocular injections were effective in treating active intraocular inflammation and in improving reduced VA attributed to ME in a majority of patients. The response pattern was similar across anatomic locations of uveitis. Overall, VA improved in one half of the patients at some point within 6 months. However, cataract and ocular hypertension occurred in a substantial minority.
This study aims to understand the practice patterns among ophthalmologists in North America who manage patients with acute, non-infectious anterior uveitis.
An eight-question survey was designed to ...elucidate the practice patterns of ophthalmologists across various geographic locations and practice settings regarding the management of anterior uveitis. This survey was distributed via the American Uveitis Society and Young Uveitis Specialists email listserv to ophthalmologists who self-identify as uveitis specialists and have a patient population that is at least 30% uveitis.
A total of 102 responses were received and analyzed (37% response rate). Respondents practiced predominantly in North America, and 40% had received subspecialty training in uveitis. All respondents chose topical corticosteroid therapy as first-line treatment for acute, unilateral, or bilateral non-infectious idiopathic anterior uveitis. The most common initial frequency for prednisolone acetate administration was six times/day while the patient was awake (29.7%) and patients are typically seen in follow-up within a week (75% of respondents). If there is a lack of treatment response within 2-3 weeks with the initial topical treatment, 42 respondents (41.2%) chose to switch to difluprednate eye drops and 29 (28.4%) recommended switching to oral prednisone.
Our results show that topical corticosteroid, most frequently prednisolone acetate 1%, is the treatment of choice for patients with acute noninfectious anterior uveitis. Reported initial medication dosing and follow-up care approaches are highly variable, which suggests heterogeneity in practice patterns. Further research on the optimal initial dosing is needed.
To describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis.
Retrospective, multicenter, cohort study.
Patients aged ≥18 years with noninfectious uveitis ...seen between 1979 and 2007 at 5 tertiary uveitis clinics.
Demographic, ocular, and treatment data were extracted from medical records of uveitis cases.
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).
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.
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.
To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies.
...Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy.
Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs.
We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.
Among cases of visually significant uveitic macular edema (ME), to estimate the incidence of visual improvement and identify predictive factors.
Retrospective cohort study.
Eyes with uveitis, seen at ...5 academic ocular inflammation centers in the United States, for which ME was documented to be currently present and the principal cause of reduced visual acuity (<20/40).
Data were obtained by standardized chart review.
Decrease of ≥ 0.2 base 10 logarithm of visual acuity decimal fraction-equivalent; risk factors for such visual improvement.
We identified 1510 eyes (of 1077 patients) with visual impairment to a level <20/40 attributed to ME. Most patients were female (67%) and white (76%), and had bilateral uveitis (82%). The estimated 6-month incidence of ≥ 2 lines of visual acuity improvement in affected eyes was 52% (95% confidence interval CI, 49%-55%). Vision reduced by ME was more likely to improve by 2 lines in eyes initially with poor visual acuity (≤ 20/200; adjusted hazard ratio HR 1.5; 95% CI, 1.3-1.7), active uveitis (HR, 1.3; 95% CI, 1.1-1.5), and anterior uveitis as opposed to intermediate (HR, 1.2), posterior (HR, 1.3), or panuveitis (HR, 1.4; overall P = 0.02). During follow-up, reductions in anterior chamber or vitreous cellular activity or in vitreous haze each led to significant improvements in visual outcome (P <0.001 for each). Conversely, snowbanking (HR, 0.7; 95% CI, 0.4-0.99), posterior synechiae (HR, 0.8; 95% CI, 0.6-0.9), and hypotony (HR, 0.2; 95% CI, 0.06-0.5) each were associated with lower incidence of visual improvement with respect to eyes lacking each of these attributes at a given visit.
These results suggest that many, but not all, patients with ME causing low vision in a tertiary care setting will enjoy meaningful visual recovery in response to treatment. Evidence of significant ocular damage from inflammation (posterior synechiae and hypotony) portends a lower incidence of visual recovery. Better control of anterior chamber or vitreous activity is associated with a greater incidence of visual improvement, supporting an aggressive anti-inflammatory treatment approach for ME cases with active inflammation.
To describe a case of acute macular neuroretinopathy (AMN) in a patient immediately following administration of the Pfizer-BioNTech COVID-19 vaccine.
The patient complained of paracentral scotoma ...supported by paracentral visual field loss on multiple Humphrey visual fields that corresponded to outer retinal pathology on optical coherence tomography. The patient's symptoms resolved without treatment.
We conclude that the clinical testing demonstrated findings consistent with AMN. AMN may be an exceedingly rare adverse ocular effect of a novel vaccine and likely only in the setting of multiple other risk factors. Despite this, we strongly recommend vaccination against COVID-19.
To estimate the incidence/risk factors for cataract in noninfectious anterior uveitis.
Retrospective multicenter cohort study (6 US tertiary uveitis sites, 1978-2010).
Data were harvested by trained ...expert reviewers, using protocol-driven review of experts’ charts. We studied cataract incidence—newly reduced visual acuity worse than 20/40 attributed to cataract; or incident cataract surgery—in 3923 eyes of 2567 patients with anterior uveitis.
Cataract developed in 507 eyes (54/1000 eye-years, 95% CI 49-59). Time-updated risk factors associated with cataract included older age (≥65 vs <18 years: adjusted hazard ratio aHR 5.04, 95% CI 3.04-8.33), higher anterior chamber cell grade (P(trend)=0.001), prior incisional glaucoma surgery (aHR 1.86, 95% CI 1.10-3.14), band keratopathy (aHR 2.23, 95% CI 1.47-3.37), posterior synechiae (aHR 3.71, 95% CI 2.83-4.87), and elevated intraocular pressure ≥30 vs 6-20 mm Hg (aHR 2.57, 95% CI 1.38-4.77). Primary acute (aHR 0.59, 95% CI 0.30-1.15) and recurrent acute (aHR 0.74, 95% CI 0.55-0.98) had lower cataract risk than chronic anterior uveitis. Higher-dose prednisolone acetate 1%-equivalent use (≥2 drops/day) was associated with >2-fold higher cataract risk in eyes with anterior chamber cell grades 0.5+ or lower but was not associated with higher cataract risk in the presence of anterior chamber cells of grade 1+ or higher.
Cataract complicates anterior uveitis in ∼5.4/100 eye-years. Several fixed and modifiable risk factors were identified, yielding a point system to guide cataract risk minimization. Topical corticosteroids only were associated with increased cataract risk when anterior chamber cells were absent or minimally present, suggesting their use to treat active inflammation (which itself is cataractogenic) does not cause a net increase in cataract incidence.
To compare mycophenolate mofetil (MMF) to methotrexate (MTX) as corticosteroid-sparing therapy for ocular inflammatory diseases.
Retrospective analysis of cohort study data.
Participants were ...identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics were obtained via medical record review. The study included 352 patients who were taking single-agent immunosuppression with MTX or MMF at 4 tertiary uveitis clinics. Marginal structural models (MSM)-derived statistical weighting created a virtual population with covariates and censoring patterns balanced across alternative treatments. With this methodological approach, the results estimate what would have happened had none of the patients stopped their treatment. Survival analysis with stabilized MSM-derived weights simulated a clinical trial comparing MMF vs MTX for noninfectious inflammatory eye disorders. The primary outcome was complete control of inflammation on prednisone ≤10 mg/day, sustained for ≥30 days.
The time to success was shorter (more favorable) for MMF than MTX (hazard ratio = 0.68, 95% confidence interval: 0.46-0.99). Adjusting for covariates, the proportion achieving success was higher at every point in time for MMF than MTX from 2 to 8 months, then converges at 9 months. The onset of corticosteroid-sparing success took more than 3 months for most patients in both groups. Outcomes of treatment (MMF vs MTX) were similar across all anatomic sites of inflammation. The incidence of stopping therapy for toxicity was similar in both groups.
Our results suggest that, on average, MMF may be faster than MTX in achieving corticosteroid-sparing success in ocular inflammatory diseases.
PDF
