Search

Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options., Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis., Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day)., Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks., Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo., Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial., Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor., Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

Objective: This study examined the long-term outcomes of scleral-sutured fixated intraocular lenses (SSIOLs) in patients with uveitis., Patients and Methods: Retrospective, consecutive review of uveitis patients with SSIOL fixation from January 2017 to December 2020. SSIOL techniques included four-point fixation with the Akreos A060 or enVista MX60 (Bausch + Lomb) lens, or Hoffman's pockets rescue., Results: Thirteen eyes of 13 patients received an SSIOL (9 AO60, 2 MX60, 2 Hoffman's pockets). Diagnoses included pan- (9), anterior (2), and posterior uveitis (2). Average LogMAR best-corrected visual acuity pre- and postoperatively was 1.01 (Snellen ∼20/200) and 0.50 (Snellen ∼20/60), respectively ( P = 0.003). No patients had postoperative SSIOL dislocation or conjunctival suture erosion. Six patients (46%) had uveitis flares postoperatively. Average follow-up was 50.2 months (range = 36.8 to 67.5)., Conclusion: This series demonstrates a 0% dislocation and suture exposure rate. Risks of uveitis flares postoperatively are high despite aggressive perioperative control but are manageable with current treatments; therefore, patients must be continually monitored. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:443-447.] .

Background and Objective: Bacillary layer detachment (BALAD) is a recently described finding on optical coherence tomography (OCT) that has been reported in a variety of uveitic and retinal diseases. To add to the growing literature on conditions associated with this finding, we report on the first cases of BALADs in ocular sarcoidosis., Patients and Methods: Observational, retrospective chart review of patients with BALADs as a feature of sarcoid-associated uveitis., Results: Three patients presented with blurry vision and bacillary layer detachments on OCT who were either known to have or found to have sarcoid-associated uveitis. All three patients had resolution of the BALAD and improvement in visual acuity with a combination of high-dose oral steroids and/or systemic immunosuppression., Conclusions: Patients presenting with BALAD should be assessed for sarcoidosis, if appropriate, given the systemic implications of this diagnosis. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:686-690.] .

Purpose: To investigate the response to Acthar Gel® in patients with moderate to severe sarcoidosis uveitis., Methods: This is a prospective open-label study that enrolled patients with moderate to severe sarcoidosis uveitis to receive 80 units daily of Acthar Gel for ten days followed by maintenance treatment with 80 units twice weekly. The primary outcome was the proportion of patients meeting at least one of the following variables 1) improved visual acuity, 2) resolution of intraocular inflammation, 3) ability to taper ocular or oral steroids by at least 50% or 4) reduction of cystoid macular edema, with no worsening of any single measure and no need for additional sarcoidosis therapies at 24 weeks., Results: A total of nine patients were enrolled in the study. Four patients completed the full 24-week course of Acthar Gel, and three of these met the primary endpoint. Among the five patients who did not complete the 24-week course of treatment, four discontinued the treatment due to worsening ocular inflammation. One patient discontinued treatment due to severe adverse effects. The most common adverse effects were fluid retention (77%), insomnia (44%), hypertension (44%) and hyperglycemia (44%)., Conclusions: We observed a clinical response to Acthar Gel in some patients with moderate to severe sarcoidosis uveitis, but a substantial proportion either failed to respond or did not tolerate the therapy. These observations may serve as preliminary data for controlled trials of Acthar Gel, but they do not support its role prior to failure of other agents., Competing Interests: Declaration of Competing interest None, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To describe the frequency of ocular flares in patients with noninfectious uveitis who were switched from the originator infliximab to a biosimilar infliximab., Design: Retrospective case series., Methods: All patients with noninfectious uveitis who were switched from the originator infliximab to biosimilar infliximab-abda for nonmedical reasons were reviewed. Patients were excluded if they had less than 3 months of follow-up on either drug. Data included patient demographics, infliximab dosage information, additional immunosuppression medications, and numbers of and times to flares. The main study outcome was frequency of flares, defined as new or worsening inflammatory activity on examination or imaging., Results: A total of 17 patients met the inclusion criteria. There were no statistical differences between the duration of follow-up while on the originator and the duration while on the biosimilar infliximab (12.0 vs. 10.1 months, respectively; P = .307). Patients experienced more flares per person-years after switching to infliximab-abda (.92), than on the originator infliximab (0.19; P = .028). Four of the 6 patients (66.7%) who experienced flare after switching to infliximab-abda did so within 90 days. Only 1 patient had flares while on originator infliximab went on to develop a single flare on infliximab-abda. The final normalized dosage for patients who flared and remained on infliximab-abda (1.301 mg/kg/week) was higher than that for those who did not flare (1.186 mg/kg/week) but was not statistically significant (P = .417)., Conclusions: Patients who were switched to biosimilar infliximab-abda experience more flares than when previously treated with the originator infliximab. Providers should closely observe patients who switch to biosimilar infliximab, especially within the first 90 days. Patients who do have flares after switching may achieve quiescence with increased biosimilar dosage., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although a small number of cases of secondary uveitis have been documented in the setting of ibrutinib therapy, panuveitis has not previously been described with this medication. The authors describe a presumed case of panuveitis in a patient on ibrutinib for chronic lymphocytic leukemia. The purpose of this report is to document a case of asymmetric, bilateral panuveitis in the setting of ibrutinib use. Panuveitis may develop in the setting of ibrutinib use, and local steroid therapy can be successfully used for treatment without cessation of systemic cancer therapy. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:160-164.] .

Purpose: To report the spectrum of posterior segment findings in tubulointerstitial nephritis and uveitis syndrome (TINU) and discuss the abnormalities that can be seen on imaging., Design: Retrospective, consecutive case series., Participants: Patients with TINU and posterior segment manifestations on examination or imaging., Methods: Patients with elevated urine beta-2 microglobulin (Uβ2M) and a diagnosis of TINU were included if they were evaluated at the Cole Eye Institute and did not have alternative etiologies for uveitis. Electronic medical records were reviewed for abnormal findings on ultra-widefield fluorescein angiography (UWFFA) and OCT., Main Outcome Measures: Presence of peripheral vascular leakage, optic disc leakage, chorioretinal lesions, or leakage within the macula on UWFFA. For OCT findings, patients were categorized as having intraretinal fluid, epiretinal membrane, or optic nerve edema., Results: Twenty eyes from 10 patients (6 female, 4 male) with a bimodal age distribution (10-46 years and 77-83 years) were included. Eighteen of 20 eyes (90%) underwent UWFFA; 13 eyes demonstrated the presence of peripheral vascular leakage, 5 eyes showed optic disc leakage, and 6 eyes had leakage within the macula. All eyes underwent OCT imaging; 7 eyes demonstrated intraretinal fluid, 4 eyes were found to have an epiretinal membrane, and 1 eye had optic nerve edema. Six eyes lacked anterior uveitis on initial or follow-up examination but had abnormal findings on UWFFA or OCT., Conclusions: Tubulointerstitial nephritis and uveitis syndrome is under-recognized in the clinical setting. It can manifest in patients of all ages, and posterior segment involvement is not uncommon. Abnormalities may be seen on posterior segment examination or imaging in the absence of anterior segment inflammation. Tubulointerstitial nephritis and uveitis syndrome should be considered in the differential diagnosis for patients presenting with bilateral uveitis without evidence of infection or other clear etiology for intraocular inflammation., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Noninfectious uveitis has been treated historically with corticosteroid therapy in varying doses and routes. Triesence, a preservative-free sterile formulation of triamcinolone acetonide, has been used in a wide spectrum of ocular pathologies, but there have been few large studies validating its dosing or detailing long-term side effects in uveitic disease. The primary aim of this study was to describe the relative duration of action and side effects of 2 doses of preservative-free intravitreal triamcinolone acetonide (PF-IVTA) in uveitis., Design: Retrospective, comparative consecutive case series., Methods: Charts of all patients receiving PF-IVTA (2 mg or 4 mg) in a defined time period (2012-2014) at the Cole Eye Institute were examined for patient demographics, time to treatment failure (TTF), use of systemic immunosuppression, use of intraocular pressure-lowering therapies, date of cataract surgery and glaucoma filtration surgery, and adverse events., Results: The final data set examined 514 injections in 214 eyes. Mean duration of follow-up was 1.5 years. There was similar demographic distribution between eyes that received 2 mg PF-IVTA only and eyes that received a combination of 4 + 2 mg PF-IVTA. No statistically significant difference in TTF between injection dosages was observed. There was a higher incidence of glaucoma filtering surgery and cataract surgery in eyes that received 4 + 2 mg PF-IVTA as well as a shorter time to glaucoma surgery, when compared to eyes that received 2 mg PF-IVTA alone., Conclusions: This retrospective study supports that 2 mg PF-IVTA displayed noninferior treatment duration to 4 mg PF-IVTA, and may carry a significantly lower side-effect profile of cataract development and glaucoma filtering surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Since its introduction in the early 1990s, optical coherence tomography (OCT) has evolved in resolution and technological advances, and in recent years its initial application of assessing the morphology of a tissue has been implemented by the study of its functional blood flow, through optical coherence tomography angiography (OCTA). This novel technique details capillary networks by comparing the amount of light returned from static and moving targets without the need for intravenous dye administration. While this imaging modality has been used for various ocular conditions, the application OCTA to uveitis conditions remains sparse. This review aims to establish the basis of OCTA and its current application to ocular inflammatory disorders, with an emphasis on monitoring progression and response to treatment, as well as predicting visual complications. In particular, this review explores the use of OCTA in iris vessel dilation seen in various forms of iritis, as a predictive factor for further episodes of inflammation. OCTA can also depict ischemia in the deep plexus layers of the retina and identify true choroicapillaris ischemia in cases of placoid diseases or masking of the indocyanine green dye, as in multiple evanescent white dot syndrome. In addition, OCTA can depict neovascularization in granulomatous disease of the retina or choroid not previously depicted with previous imaging methods. While OCTA provides several advancements in the imaging, management and prognosis of uveitis diseases, we emphasize that further studies are required to fully understand its application to these conditions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the short-term safety and efficacy of topical difluprednate (0.05%) for the treatment of noninfectious uveitic cystoid macular edema., Methods: Twenty-seven patients (35 eyes) undergoing treatment with difluprednate 4 times daily for 3 weeks for noninfectious uveitic cystoid macular edema were reviewed for visual acuity, intraocular pressure, optical coherence tomography, and fluorescein angiography results. A mixed model analysis was fit with each measure as the outcome, visit as the primary predictor, and patient and eye as random effects., Results: Mean central foveal thickness decreased by 117 μm (P < 0.001) at 30 ± 15 days, 124 μm (P < 0.001) at 60 ± 15 days, and 152 μm (P < 0.001) at 180 ± 30 days. Complete resolution of intraretinal fluid was observed in 15 of 34 (44%) eyes at 30 ± 15 days, 11 of 21 (52%) eyes at 60 ± 15 days, and 9 of 12 (75%) eyes at 180 ± 30 days. Improvement in fluorescein leakage was noted in 7 of 8 eyes (88%). Visual acuity improved by a mean of 5 letters (P = 0.001) at 30 ± 15 days, 5.5 letters (P = 0.007) at 60 ± 15 days, and 7 letters (P = 0.032) at 180 ± 30 days. Mean increase in intraocular pressure was 1.48 mmHg at 30 ± 15 days (P = 0.080), 1.92 mmHg at 60 ± 15 days (P = 0.110), and 6.18 mmHg (P = 0.001) at 180 ± 30 days., Conclusion: Topical difluprednate is a well-tolerated and effective treatment for noninfectious uveitic cystoid macular edema with decreased central foveal thickness, mild improvement in visual acuity, and elevation of intraocular pressure observed in a few patients.

Purpose: Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity., Methods: This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology., Results: Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates., Conclusions: As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

The purpose of this study is to review the results of treatment of juvenile idiopathic arthritis-related uveitis with the use of intravitreal dexamethasone implant. Sixteen eyes with Juvenile idiopathic arthritis (JIA)-associated uveitis received intravitreal dexamethasone implant to treat recalcitrant anterior segment inflammation (43.7 %), chronic macular edema (6.2 %), or a combination of both (50 %). One month after injection, mean visual acuity had improvement to 39.6 ± 11 ETDRS letters (p < 0.001). Mean AC cells measure at 1 month was 0.79 and 0.75 at 3 months. One month after injection, there was a significant reduction of central retinal thickness (CRT) to 342.4 ± 79.3 µm (p < 0.01). One month after the second implant, 11 eyes (91.6 %) achieved improved activity of the anterior uveitis, and mean best-corrected visual acuity improved to 44.6 ± 8.1 ETDRS letters (p < 0.01). At 1 month after the second injection, 4/5 eyes had resolution of macular edema with CRT of 250.4 ± 13.7 µm (p < 0.01). Of the 16 eyes, 12 eyes received a second injection at mean of 7.5 ± 3.1 months after the first treatment, and 5 eyes received a third Ozurdex injection on average 7 ± 4.6 months after the second injection. Of the 16 eyes, five eyes were pseudophakic prior to injection. Of the remaining 11 eyes, 8 (73 %) developed worsening posterior subcapsular cataract at a mean of 7.3 ± 1.2 months after the first injection. After the first injection, only one eye required topical antiglaucoma therapy with maximum pressure of 25 mmHg. In patients with recalcitrant JIA-associated active uveitis, injection of sustained-release dexamethasone can achieve control of anterior inflammation and resolution of macular edema.

Immune-mediated uveitis may be associated with a systemic disease or may be localized to the eye. T-cell-dependent immunological events are increasingly being regarded as extremely important in the pathogenesis of uveitis. Several studies have also shown that macrophages are major effectors of tissue damage in uveitis. Uveitis phenotypes can differ substantially, and most uveitis diseases are considered polygenic with complex inheritance patterns. This review attempts to present the current state of knowledge from in vitro and in vivo research on the role of genetics in the development and clinical course of uveitis. A review of the literature in the PubMed, MEDLINE, and Cochrane databases was conducted to identify clinical trials, comparative studies, case series, and case reports describing host genetic factors as well as immune imbalance which contribute to the development of uveitis. The search was limited to primary reports published in English with human subjects from 1990 to the present, yielding 3590 manuscripts. In addition, referenced articles from the initial searches were hand searched to identify additional relevant reports. After title and abstract selection, duplicate elimination, and manual search, 55 papers were selected for analysis and reviewed by the authors for inclusion in this review. Studies have demonstrated associations between various genetic factors and the development and clinical course of intraocular inflammatory conditions. Genes involved included genes expressing interleukins, chemokines, chemokine receptors, and tumor necrosis factor and genes involved in complement system. When considering the genetics of uveitis, common threads can be identified. Genome-wide scans and other genetic methods are becoming increasingly successful in identifying genetic loci and candidate genes in many inflammatory disorders that have a uveitic component. It will be important to test these findings as uveitis-specific genetic factors. Therefore, the burgeoning understanding of the human genome promises to result in new insight into the pathogenesis of uveitis.

Purpose: To describe the management with intracameral recombinant tissue plasminogen activator (rtPA) of severe fibrin effusion after phacoemulsification, and its prevention with sustained-release dexamethasone intravitreal implant., Methods: A 59-year-old man with chronic HLA-B27-associated uveitis underwent phacoemulsification followed by a sustained-release dexamethasone intravitreal implant., Results: A postoperative severe fibrin reaction was completely resolved after intracameral injection of rtPA. At the time of the phacoemulsification of the fellow eye, a dexamethasone implant was injected 5 days prior to surgery, with no fibrin formation., Conclusions: Intracameral rtPA may be successfully used in the management of severe fibrin reaction. Dexamethasone intravitreal implant to control postoperative inflammation may take several days until it achieves high concentrations in the vitreous.

Purpose: To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants., Methods: Time-domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a reading center. Accuracy of retinal thickness data was confirmed with quality evaluation, and caliper measurement of centerpoint thickness (CPT) was performed when retinal thickness data were unreliable. Morphological evaluation included cysts, subretinal fluid, epiretinal membranes (ERMs), and vitreomacular traction., Results: Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%, and 4% were ungradable. Intraclass correlation was.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240 μm) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 to 82% for morphological features., Conclusion: Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.

Purpose: To assess the prevalence of hypotony in patients with severe forms of uveitis., Methods: The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified., Results: Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01)., Conclusions: Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment.

Objective: To determine the validity and reliability of a novel questionnaire to measure vision-related quality of life (VRQOL) in children ages 8-18 years for use in juvenile idiopathic arthritis (JIA)-associated uveitis: the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q)., Methods: Several steps validated the EYE-Q. We interviewed experts and children on how vision affects a child's activities. We developed new items and selected relevant items from existing instruments. We administered initial versions of the EYE-Q to normal-sighted children and those with JIA-associated uveitis. For this study, children with various (or no) ocular conditions were recruited from a clinical population. Visual acuity and contrast sensitivity were performed, and the EYE-Q and Pediatric Quality of Life Inventory (PedsQL) were administered. The EYE-Q was repeated 10 days later. Patients, parents, and physicians rated vision severity., Results: Of 120 patients, 48% were female, 46.7% had no visual impairment, and 53.3% had bilateral eye involvement. The mean age was 11.3 years. There were significant differences in the measures based on visual acuity (P < 0.001). Children with more severe visual acuity and bilateral eye involvement had worse EYE-Q scores (P < 0.001). There were significant associations between the EYE-Q and PedsQL (r = 0.375), repeat EYE-Q (r = 0.864), and clinical measures of ocular disease (r = -0.620)., Conclusions: Our study provides evidence of the validity and reliability of the EYE-Q in the measurement of VRQOL. The EYE-Q may complement clinical measures of visual impairment and overall QOL and become an important tool in the assessment of QOL in JIA-associated uveitis., (Copyright © 2011 by the American College of Rheumatology.)

Purpose: To compare Reading Center (RC) cup-to-disc ratio (CDR) assessment from stereoscopic photographs with clinician estimation in a uveitis clinical trial., Methods: Clinical estimation of CDR was performed by ophthalmologists via dilated biomicroscopy. Photographic evaluation was performed at an independent RC by masked, certified evaluators. Quality control was performed by repeat grading of 77 randomly selected images., Results: Among 479 eyes with uveitis, 353 eyes had clinical and photographic grades for CDR. Agreement between clinical and RC grading was fair, with exact agreement of 29%. Agreement within 0.1 and 0.2 CDR was 70 and 93%, respectively (weighted κ = .34). Intergrader reproducibility at the RC was better (weighted κ = .59, ICC 0.74)., Conclusion: Morphologic assessment of cup to disc ratio is an important outcome and safety measure for determining glaucomatous damage in clinical trials. Masked RC measurements are more likely to be accurate than biomicroscopic grading in identifying meaningful anatomical change associated with glaucoma.

Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease., Design: Randomized, placebo-controlled, double-masked clinical trial., Participants: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease., Methods: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion., Main Outcome Measures: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy., Results: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median -4.0 vs. -1.0, respectively)., Conclusions: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.

PURPOSE:: Quantitative end points for uveitis are needed. Here we quantify the rate of ellipsoid zone (EZ) recovery on optical coherence tomography (OCT) and correlate it with visual acuity (VA) improvement in patients with acute posterior multifocal placoid pigmented epitheliopathy (APMPPE). We use automated and manually graded EZ area analysis to assess EZ recovery in APMPPE. METHODS:: We performed a retrospective review of 9 APMPPE cases (18 eyes) that had characteristic clinical examination and fluorescein angiography findings, outer retinal disruption on spectral-domain OCT, and treatment with systemic steroids after an unambiguous laboratory workup. The EZ was delineated using custom software to perform automated analysis and manual grading by 2 independent physicians. Quantitation of EZ changes was performed in ImageJ (National Institutes of Health). EZ maps were compared with equivalent findings from EZ en face OCT segmentation. RESULTS:: The 9 cases in our study were followed for an average of 198 days. Symptomatic improvement occurred in all eyes. VA recovery occurred in 83% of eyes and depended on presenting foveal involvement. Positive slopes of EZ area over time demonstrated recovery. EZ recovery profiles determined by manual and automated software demonstrated high Pearson correlation coefficients (0.78-0.94). Slab en face EZ analysis demonstrated moderate agreement. CONCLUSIONS:: EZ recovery correlates with symptomatic and VA recovery. Automated EZ analysis shows strong agreement with manually graded EZ analysis in APMPPE. EZ recovery in patients with APMPPE provides a biomarker for recovery and may be applied to other diseases affecting the outer retina.

Background: Autosomal dominant neovascular inflammatory vitreoretinopathy (NIV), formerly called "ADNIV," is a rare autoinflammatory condition mainly of adulthood caused by mutations in calcium-activated calpain-5 protease (CAPN5). Our aim is to report the treatment and visual outcomes of children newly diagnosed with NIV after systemic treatment. Methods: We reviewed charts of patients ≤18 years old with CAPN5 gene mutation, ocular findings consistent with NIV, and treated with systemic immunosuppression for a minimum of 6 months. Treatment response was based on ophthalmic examination, ultra-widefield fluorescein-angiography (UWFFA), and optical coherence tomography (OCT). Results: Eight children (16 eyes) were diagnosed with NIV at a median age of 14 (Range [R] 9–16) years, with a median follow-up of 18 months (R6–20). At diagnosis, one patient had impaired visual acuity (VA > 0.4), eight had vascular leakage, two had neovascularization, and three had macular edema. All responded to oral or local glucocorticoids but was not sustained. Systemic immunosuppression was started in seven patients with methotrexate and infliximab after a median time from diagnosis of 1.5 months (R0.5–2) and 3.2 months (R2.5–3.1), respectively. Infliximab was discontinued in all after a median time of 7 months (R3.5–10) for ineffectiveness, and 5/7 switched to tocilizumab and 1 to adalimumab. Five failed to respond (4 tocilizumab, 1 adalimumab) and one had a minimal response to tocilizumab Conclusions: We report on the systemic treatment response of seven children with ADNIV treated with methotrexate, infliximab, and tocilizumab. None were able to control disease. Further studies are needed to understand long-term outcomes and the utility of systemic immunosuppression. [ABSTRACT FROM AUTHOR]

Purpose: HLA-B27-associated uveitis is classically thought to be a disease of the young, with a median age of onset in the 30s. There is a paucity of literature reporting on older individuals with HLA-B27 uveitis. Here, we describe cases of HLA-B27 uveitis presenting initially at age ≥70.Methods: Retrospective review of patients with HLA-B27-associated uveitis that presented initially at ≥70 years of age.Results: Three patients were identified. All presented with aggressive inflammation (hypopyon in two cases) and two were treated for suspected endophthalmitis. All cases were controlled sufficiently with prolonged topical anti-inflammatory therapy. One patient who was lost to follow-up demonstrated one recurrence over a 3-year period.Conclusions: This series highlights the aggressive initial presentation of HLA-B27-associated uveitis in the older population, and demonstrates the favorable response, and limitation of recurrences, with topical immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

The fluocinolone acetonide (Retisert™™) implant is an approved therapy for chronic, posterior, non-infectious uveitis. Continued episodes of inflammation can occur in patients after device implantation and suspected Retisert™™ malfunction has been previously reported. We report a case of a patient who continued to have inflammation after Retisert™™ implantation, which subsided after device exchange with a normally functioning explant after detailed manufacturer analysis. [ABSTRACT FROM AUTHOR]

Purpose To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). Design Randomized, double-masked, placebo-controlled, phase 2 study. Participants Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. Methods Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. Main Outcome Measures The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. Results At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (−2.1 [n = 11] vs. −1.7 [n = 3], respectively; P = 0.0255) or investigator (−2.5 [n = 19] vs. −1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were −46.8 vs. +2.6 μm (P = 0.0683) in the overall population and −112.5 [n = 13] vs. −1.8 [n = 6] μm (P = 0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). Conclusions Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema. [ABSTRACT FROM AUTHOR]

Purpose This study was designed to determine the feasibility of anterior segment optical coherence tomography (AS-OCT) to objectively image and quantify the degree of AC inflammation. Design Prospective evaluation of a diagnostic test. Participants Patients with anterior segment involving uveitis. Methods Observational case series of patients with uveitis. Single-line and 3-dimensional (3D) volume AS-OCT scans were manually graded to evaluate for the presence or absence of cells in the AC. Clinical grading scores were correlated to the number of cells seen in each line scan. An automated algorithm was developed to measure the number of cells seen in the 3D volume scan and compared with manual measurements and clinical grading scores. Main Outcome Measures Degree of anterior segment inflammation. Results A total of 114 eyes from 76 patients were imaged, 83 eyes with line scans and 31 eyes with volume scans. The average number of cells on line scans was 0.13 for grade 0, 1.2 for grade 1/2+, 2.6 for grade 1+, 5.7 for grade 2+, 15.5 for grade 3+, and 41.2 for grade 4+. Spearman correlation coefficient comparing clinical grade with the individual AS-OCT line scans was 0.967 ( P < 0.0001). The range of cells in the automated cell count of 3D volume scans was 13.60 to 1222; the range for manual cell counts was from 9.2 to 2245. The Spearman correlation coefficients were r = 0.7765 ( P < 0.0001) and r = 0.7484 ( P < 0.0001) comparing the manual and automated cell counts with the clinical grade, respectively. Spearman correlation coefficient comparing the automatic cell counts with manual cell count in the 3D volume scan was 0.997 ( P < 0.0001). Conclusions Anterior segment OCT can be used to image and grade the degree of AC inflammation. Clinical grading strongly correlates with the number of cells on AS-OCT line scans and volume scans. The automated algorithm to measure cell count had a high correlation to manual measurement of cells in the 3D volume scans. This modality could be used to objectively grade response to treatment. [ABSTRACT FROM AUTHOR]