Anterior Chamber Cell Grade Research Articles

The Effect of Adalimumab in Korean Patients with Refractory Noninfectious Uveitis.

We sought to analyze the efficacy of adalimumab in active noninfectious uveitis, and evaluate its efficacy and safety for the management of refractory noninfectious uveitis in Korean patients. A retrospective observational study was conducted. A total of 23 eyes of 14 Korean patients with noninfectious uveitis refractory to conventional treatment, including corticosteroid and immunosuppressive agents, were treated with adalimumab between December 2017 and February 2020. The primary outcomes were vitreous haziness grades, anterior chamber cell grades, and central macular thickness measured prior to injection and at 1, 3, 6, and 12 months after the first adalimumab injection. Among the 23 eyes, 14 eyes (60.9%) were diagnosed with panuveitis and 9 eyes (39.1%) with posterior uveitis [mean follow-up period: 22.3 months (7–27)]. The most common etiologic diagnoses requiring adalimumab injection were Behçet's disease (9 eyes, 39.1%), followed by undifferentiated inflammation (6 eyes, 26.1%), Vogt-Koyanagi-Harada disease (3 eyes, 13.0%), psoriasis (2 eyes, 8.7%), serpiginous chorioretinopathy (2 eyes, 8.7%), and systemic lupus erythematosus (1 eye, 4.3%). At the 1-year follow-up after the first injection, anterior chamber cell grade decreased from 0.5±0.4 to 0.3±0.4, and vitreous haziness grade decreased from 1.1±1.1 to 0.3±0.5 (p<0.05). Central macular thickness improved from 347.2±98.1 µm to 264.3±61.1 µm (p<0.05). Adalimumab injection in patients with refractory noninfectious uveitis decreased the anterior chamber cell grade, vitreous haziness grade, and central macular thickness with no severe side effect. Overall, adalimumab injection may, therefore, be an effective and relatively safe treatment modality for noninfectious uveitis in Korean patients.

Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Open-label, multicenter, phase 3 extension study (VISUAL III). Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or who discontinued the study after meeting treatment failure criteria (active uveitis). Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose. Long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related systemic corticosteroids. At study entry, 67% of patients (283/424) showed active uveitis and 33% (141/424) showed inactive uveitis; 60 patients subsequently met exclusion criteria, and 364 were included in the intention-to-treat analysis. Efficacy variables were analyzed through week 150, when approximately 50% of patients (214/424) remained in the study. Patients showing quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry. Mean daily dose of systemic corticosteroids was reduced from 9.4 ± 17.1 mg/day at week 0 (n= 359) to 1.5 ± 3.9 mg/day at week 150 (n= 181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest were infections (n=275; 79 events/100 patient-years [PY]); AEs and serious AEs occurred at a rate of 396 events/100 PY and 15 events/100 PY, respectively. Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and led to maintenance of quiescence for those with inactive uveitis. AEs were comparable with those reported in the parent trials and consistent with the known safety profile of adalimumab.

Correlation between Subfoveal Choroidal Thickness and Anterior Segment Inflammation in Patients with Chronic Stage of Vogt-Koyanagi-Harada Disease

ABSTRACT Purpose To correlate changes in subfoveal choroidal thickness (SCT) with the degree of anterior inflammatory activity in chronic Vogt-Koyanagi-Harada (VKH) disease. Methods Anterior segment inflammation was assessed using SUN anterior chamber cell grading criteria, and SCT was measured using EDI-OCT in patients with VKH at multiple visits. ANOVA was used to compare the mean SCT for each anterior chamber cell grade. Regression analysis was used to correlate the anterior segment cell grade and the SCT. Results 14 patients were included in the study. A total of 432 data points consisting of SCT and anterior segment cell values were analyzed. ANOVA demonstrated significant difference between the mean SCT for different anterior chamber cell grades (p < .0001). Regression analysis demonstrated significant correlation between SCT and grade of anterior chamber cells (R2 = 0.37, p < .001). Conclusions Chronic VKH is characterized by a dynamic change in SCT that correlates with anterior segment inflammatory activity.

Difluprednate 0.05% versus Prednisolone Acetate Post-Phacoemulsification for Inflammation and Pain: An Efficacy and Safety Clinical Trial.

BackgroundThe purpose of this study was to compare the efficacy and safety of difluprednate 0.05% (PRO-145) versus prednisolone acetate 1% (Prednefrin® SF), for management of postoperative inflammation and pain, after cataract surgery.MethodsThis was a Phase III, multicenter, prospective, double-blind, clinical trial. Intent-to-treat population included 178 post-phacoemulsification patients that were assigned to receive either PRO-145, or prednisolone. One day after unilateral eye surgery, patients instilled a drop 4 times a day for 14 days (then tapering the dose downward for 14 days). The primary efficacy endpoints were anterior chamber (AC) cell grade and flare. Other parameters measured included: retinal central thickness (measured via OCT), conjunctival hyperemia, edema, pain and photophobia. Tolerability and safety were assessed through burning, itching, foreign body sensation, visual acuity (VA), intraocular pressure (IOP) and incidence of adverse events (AE).ResultsA total of 171 subjects were randomized (1:1) and completed the study. Compared to day 1, there was a significant improvement in the AC cell count and flare in both groups by the final visit (80.2% vs 88.4%, p=1.000). Conjunctival hyperemia improved in a similar fashion (81.2% vs 79%, p=0.234) in both PRO-145 and prednisolone groups, without differences between them. This was also observed for edema (82.4% vs 82.5%, p=0.246), pain (15.3% vs 7%, p=0.497) and photophobia (16.4% vs 15.1%, p=0.246), respectively. There was no significant difference between treatments for any tolerability parameter studied. Finally, at the 4-week postoperative visit, there were no significant differences between treatments for VA, IOP and AE results (p-values; 0.095, 0.053 and 0.099, respectively).ConclusionThe results of this study suggest that PRO-145 is as effective and safe as prednisolone acetate in treating postoperative inflammation and pain in patients undergoing phacoemulsification. The study was registered at ClinicalTrials.gov as NCT03693989.

Difluprednate 0.05% vs prednisolone acetate 1% for treatment of endogenous anterior uveitis

Objective The aim was to compare topical difluprednate 0.05% vs prednisolone acetate 1% in the management of acute anterior uveitis (AAU) regarding their efficacy and safety. Patients and methods A prospective clinical trial was conducted on two parallel groups comprising 48 patients who attended the Shebin El-Kom Ophthalmology Outpatient Clinic. All were diagnosed with AAU. Patients in the first group received difluprednate 0.05% eye drops four times daily, whereas patients of the second group received prednisolone acetate 1% eight times per day for 2 weeks. The 14-day treatment period was followed by 14-day tapering dose period. The observation was continued until day 35. Results At day 14, there was no significant difference between the two studied groups regarding anterior chamber cell grading, as all cases were detected to have grade 0 in both groups. Complete clearing of anterior chamber cells at day 3 were seen in eight eyes (8/24; 33.3%) in both groups (P = 0.2). Intraocular pressure change was higher among the prednisolone group at seventh day (P = 0.2) and 14th day (P = 0.03) compared with the difluprednate group, except at day 3, where intraocular pressure change was the same in both groups. The mean IOP values in both groups remained less than 21 mmHg throughout the study. Conclusion Difluprednate 0.05% four times daily is well tolerated and safe compared with prednisolone acetate 1% eight times daily for the treatment of endogenous AU. Difluprednate exhibits better bioavailability, strong efficacy, and low incidence of adverse effects.

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

ABSTRACT Purpose New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66–0.87 and 0.06–0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73–0.97) than in the inferior AC (0.06–0.56). Conclusion AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity.

Intravitreal Dexamethasone Implant for Treatment of Sarcoidosis-Related Uveitis.

To assess the efficacy and safety of intravitreal dexamethasone implant injection in the management of sarcoidosis-related uveitis. A retrospective analysis was performed of the efficacy and safety of intravitreal dexamethasone implant injection for indications such as intractable vitritis, vasculitis, or cystoid macular edema. This study comprised 20 patients with sarcoidosis-related uveitis. A single injection was performed in 13 eyes (65%) and 35% required more than 2 injections during the follow-up period [median 16.5months (range 6-32)]. The best-corrected visual acuity showed significant improvement at 1month (P = 0.004) and 3months (P = 0.001), but there was no significance at 6months after implant injection (P = 0.186). One month after treatment, the central macular thickness decreased to 278.95 ± 52.20μm (P = 0.023). It further decreased to 274.70 ± 55.88μm at 3months (P = 0.027), but there was no significance at 6months (280.65 ± 64.48μm, P = 0.074).The anterior chamber cell grade (P = 0.003) and vitreous haze (P = 0.001) were significantly decreased for up to 6months after a single implant injection. The most common ocular complication was worsening of cataracts during the first 6months. Intravitreal dexamethasone implant injection is efficacious in reducing anterior chamber inflammation, vitreous haze, and cystoid macular edema in patients with sarcoidosis-related uveitis. Considering that sarcoidosis shows a chronic course of disease in a significant proportion of cases, intravitreal dexamethasone implant injection is a possible option to relieve intraocular inflammation.

Comparison of Efficacy of Difluprednate 0.05% and Loteprednol Gel 0.5% After Cataract Surgery.

To compare the outcomes and complications of topical difluprednate 0.05% and loteprednol gel 0.5% after routine cataract surgery. Subjects received either difluprednate emulsion 0.05% (n=30 eyes) or loteprednol gel 0.5% (n=30 eyes) after routine cataract surgery. Topical steroid drops were initiated 3 days before cataract surgery and continued for 2 weeks postoperatively. Anterior chamber (AC) cell grade, corneal edema, corneal pachymetry, visual acuity, ocular surface quality (Oxford scale), and intraocular pressure (IOP) were evaluated at 1 day, 1 week, and 1 month postoperatively. Patients treated with difluprednate or loteprednol had statistically similar resolution of their AC cell grade and corneal edema at 1 day, 1 week, and 1 month postoperatively (P>0.05 at each study visit). Difluprednate-treated and loteprednol-treated eyes achieved a mean best-corrected visual acuity of at least 20/25 by 1 week postoperatively (0.055 and 0.061 logarithm of the minimum angle of resolution, respectively; P=0.82). The nasal ocular surface quality at 1 week had improved in loteprednol-treated eyes compared with difluprednate-treated eyes (1.0 vs. 1.9 Oxford score, respectively; P<0.001), but similar at all other visits. There was no statistical difference between IOP levels between both treatment groups (P>0.05). In the difluprednate-treated group, one patient developed rebound inflammation and two patients developed cystoid macular edema at their 1-month postoperative visit. The anti-inflammatory effect, visual recovery, and IOP of patients using topical difluprednate or loteprednol gel after cataract surgery are equivalent. There may be an additional short-term benefit of loteprednol gel in protecting the ocular surface after cataract surgery.

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III

To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. Phase 3, open-label, multicenter clinical trial extension (VISUAL III). Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through78. Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

Analysis of choroidal and central foveal thicknesses in acute anterior uveitis by enhanced-depth imaging optical coherence tomography

BackgroundCurrently, there are a limited number of reports of structural changes in the retina and choroid in acute anterior uveitis (AAU). The aim of this study was to evaluate choroidal and central foveal thicknesses during episodes of AAU.MethodsThe medical records of 120 patients with AAU and 120 healthy subjects matched for age, sex, and spherical equivalent of refractive error were reviewed. Subjects were divided into group 1 (AAU-affected eyes), 2 (unaffected fellow eyes), and 3 (healthy control eyes).ResultsIn the uveitis group, etiologic diagnoses included human leukocyte antigen (HLA)-B27-associated (n = 71) and idiopathic (n = 49) AAU. The mean subfoveal choroidal thicknesses (SFCTs) in groups 1–3 were 326.7 ± 64.2, 296.1 ± 66.6, and 294.9 ± 41.7 μm, respectively. The corresponding mean central foveal thicknesses (CFTs) were 273.5 ± 29.3, 264.4 ± 24.6, and 263.0 ± 30.8 μm, respectively. The AAU group exhibited a significantly greater SFCT than the control groups (P < .001). Relative to the control group, while eyes with idiopathic AAU exhibited a significantly greater CFT, those with HLA-B27-associated AAU exhibited no such significant difference. Anterior chamber cell grade was not associated with SFCT or CFT.ConclusionsThe SFCT increased significantly during AAU. This indicates the importance of OCT examination for detection of subclinical choroidal and retinal changes in all types of AAU.

Twice-Daily vs. Once-Daily Dosing with 0.075% Bromfenac in DuraSite: Outcomes from a 14-Day Phase 2 Study.

IntroductionBromfenac is a well-known topical ophthalmic nonsteroidal anti-inflammatory drug (NSAID) that is commercialized in the USA and other regions of the world. A new formulation, 0.075% bromfenac in DuraSite®, was developed to treat postoperative inflammation and reduce pain in patients who have undergone cataract surgery. We hypothesized that efficacy and safety would be enhanced with twice-daily (BID) dosing compared to once-daily (QD) dosing.MethodsThis was a multicenter, double-masked, comparative study in which 40 and 45 subjects were randomized to groups receiving BID dosing and QD dosing, respectively. Subjects self-instilled the study drug for 14 days postoperative and were followed for an additional 2-week evaluation phase. The primary efficacy endpoint was the proportion of subjects with an anterior chamber cell (ACC) grade of 0 at day 15.ResultsA total of 45 subjects had cleared ACC (grade “0”) at day 15, of whom 21 were in the BID group (52.5%) and 24 were in the QD group (53.5%). A secondary analysis found 7/40 (17.5%) subjects in the BID group and 10/45 (22.2%) subjects in the QD group achieved an ACC grade of 0 at day 8. There were more adverse events in the QD group (n = 16) than in the BID group (n = 12).ConclusionSimilar outcomes were observed for subjects using Bromfenac 0.075% in DuraSite® in the BID and QD dosing regimens for the treatment of post-cataract surgery inflammation.Trial registrationClinicalTrials.gov identifier, NCT01190878.FundingInSite Vision (now a division of Sun Pharma).

Adalimumab: A Review in Non-Infectious Non-Anterior Uveitis.

Adalimumab (Humira®) is a tumour necrosis factor (TNF)-α inhibitor available in various countries worldwide, including the USA, Japan and those of the EU, for the treatment of non-infectious intermediate, posterior and panuveitis in adults. It is the first biological agent approved for this indication. In two multinational, phase III studies in adults with active and inactive disease, subcutaneous adalimumab significantly reduced the risk of treatment failure relative to placebo following the tapered withdrawal of corticosteroid therapy. Significant differences favouring adalimumab over placebo were seen for each component of treatment failure (vitreous haze, new active inflammatory lesions, anterior chamber cell grade and a worsening of best-corrected visual acuity) in patients with active disease and for the visual acuity component in patients with inactive disease. Adalimumab was also significantly more effective than placebo in improving multiple aspects of uveitic inflammation in patients with active, but not in those with inactive, disease. Adalimumab was generally well tolerated in these patient populations. Its tolerability profile was consistent with the known tolerability profile of the agent in other indications and no new safety signals were identified. Moreover, the incidence of anti-adalimumab antibodies was low. Thus, adalimumab is an effective and generally well tolerated treatment option in adults with non-infectious intermediate, posterior and panuveitis, including those who cannot be treated with corticosteroids.

Development of an activity disease score in patients with uveitis (UVEDAI)

To develop a disease activity index for patients with uveitis (UVEDAI) encompassing the relevant domains of disease activity considered important among experts in this field. The steps for designing UVEDAI were: (a) Defining the construct and establishing the domains through a formal judgment of experts, (b) A two-round Delphi study with a panel of 15 experts to determine the relevant items, (c) Selection of items: A logistic regression model was developed that set ocular inflammatory activity as the dependent variable. The construct “uveitis inflammatory activity” was defined as any intraocular inflammation that included external structures (cornea) in addition to uvea. Seven domains and 15 items were identified: best-corrected visual acuity, inflammation of the anterior chamber (anterior chamber cells, hypopyon, the presence of fibrin, active posterior keratic precipitates and iris nodules), intraocular pressure, inflammation of the vitreous cavity (vitreous haze, snowballs and snowbanks), central macular edema, inflammation of the posterior pole (the presence and number of choroidal/retinal lesions, vascular inflammation and papillitis), and global assessment from both (patient and physician). From all the variables studied in the multivariate model, anterior chamber cell grade, vitreous haze, central macular edema, inflammatory vessel sheathing, papillitis, choroidal/retinal lesions and patient evaluation were included in UVEDAI. UVEDAI is an index designed to assess the global ocular inflammatory activity in patients with uveitis. It might prove worthwhile to motorize the activity of this extraarticular manifestation of some rheumatic diseases.

Adalimumab in Patients with Active Noninfectious Uveitis

BackgroundPatients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.MethodsThis multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported.ResultsThe median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years).ConclusionsIn our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657.)

Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial

Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids. We did this multicentre, double-masked, randomised, placebo-controlled phase 3 trial at 62 study sites in 21 countries in the USA, Canada, Europe, Israel, Australia, and Latin America. Patients (aged ≥18 years) with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by 10-35 mg/day of prednisone were randomly assigned (1:1), via an interactive voice and web response system with a block size of four, to receive either subcutaneous adalimumab (loading dose 80 mg; biweekly dose 40 mg) or placebo, with a mandatory prednisone taper from week 2. Randomisation was stratified by baseline immunosuppressant treatment. Sponsor personnel with direct oversight of the conduct and management of the study, investigators, study site personnel, and patients were masked to treatment allocation. The primary efficacy endpoint was time to treatment failure, a multicomponent endpoint encompassing new active inflammatory chorioretinal or inflammatory retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, and visual acuity. Analysis was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov number NCT01124838. Between Aug 10, 2010, and May 14, 2015, we randomly assigned 229 patients to receive placebo (n=114) or adalimumab (n=115); 226 patients comprised the intention-to-treat population. Median follow-up time was 155 days (IQR 77-357) in the placebo group and 245 days (119-564) in the adalimumab group. Treatment failure occurred in 61 (55%) of 111 patients in the placebo group compared with 45 (39%) of 115 patients in the adalimumab group. Time to treatment failure was significantly improved in the adalimumab group compared with the placebo group (median not estimated [>18 months] vs 8·3 months; hazard ratio 0·57, 95% CI 0·39-0·84; p=0·004). The 40th percentile for time to treatment failure was 4·8 months in the placebo group and 10·2 months in the adalimumab group. No patients in either group had opportunistic infections (excluding oral candidiasis and tuberculosis). No malignancies were reported in the placebo group whereas one (1%) patient in the adalimumab group reported non-serious squamous cell carcinoma. The most common adverse events were arthralgia (12 [11%] patients in the placebo group and 27 [23%] patients in the adalimumab group), nasopharyngitis (16 [17%] and eight [16%] patients, respectively), and headache (17 [15%] patients in each group). Adalimumab significantly lowered the risk of uveitic flare or loss of visual acuity upon corticosteroid withdrawal in patients with inactive, non-infectious intermediate, posterior, or panuveitic uveitis controlled by systemic corticosteroids. No new safety signals were observed and the rate of adverse events was similar between groups. These findings suggest that adalimumab is well tolerated and could be an effective treatment option in this patient population. An open-label extension study (NCT01148225) is ongoing to provide long-term safety data for adalimumab in patients with non-infectious uveitis. AbbVie.

Clinical manifestation of Fuchs uveitis syndrome in childhood.

The aim of this study was to describe clinical signs and complications of Fuchs uveitis syndrome (FUS) with onset in childhood. Ophthalmologic findings and complications in patients with FUS becoming manifest before the age of 16 years were analyzed in a retrospective study at a tertiary referral uveitis center. Inclusion criteria were the presence of pathognomonic FUS findings at any time point and exclusion of any systemic immune-mediated or infectious disease. A total of 23 patients (male = 16, female = 7) with juvenile FUS (unilateral n = 20, bilateral n = 3 patients) were included in the study. Mean ages at uveitis and FUS diagnosis were 12.0 ± 4.2 and 22.7 ± 10.7 years, respectively. In six patients, inflammation was noted at age ≤ 7 years. The following inflammatory signs were observed in a total of 26 eyes: ≤ 1+ anterior chamber cell grade (n = 26), vitreous cells (n = 24), fine keratic precipitates (KPs; n = 23), stellate KPs (n = 11), mutton-fat KPs (n = 23), diffuse (n = 24) or inferior (n = 8) distribution of KPs, Koeppe nodules (n = 10), and iris heterochromia (n = 14). A representative subgroup of patients (n = 5) is shown who presented with non-specific clinical signs in the beginning and in whom typical FUS signs became manifest only at a later stage. Secondary complications such as cataract (n = 19), ocular hypertension (n = 3), or glaucomatous disc damage (n = 2) were found after a mean uveitis duration of 11.6, 19.5, and 20.3 years, respectively. FUS may begin in early childhood, and the characteristic findings may not be present at onset of disease. The diagnosis is often delayed for years, occasionally with the consequence of overtreatment with anti-inflammatory drugs.

Difluprednate 0.05% Versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: A Phase III, Multicenter, Randomized Study

Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (-2.2 vs. -2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate-treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate-treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.).

Comparison of Efficacy and Ocular Surface Toxicity of Topical Preservative-free Methylprednisolone and Preserved Prednisolone in the Treatment of Acute Anterior Uveitis

The aim of this study was to compare the antiinflammatory effect and ocular surface toxicity of topical nonpreserved methylprednisolone sodium succinate 1% and preserved prednisolone acetate suspension 1% for the management of acute anterior uveitis (AAU). In this prospective, randomized, investigator-masked, comparative clinical trial, patients with mild-to-moderate noninfectious AAU were assigned randomly to receive either hourly nonpreserved methylprednisolone 1% (group A) or preserved prednisolone 1% (group B) eye drops followed by a 2-week tapering regimen. Anterior chamber cells and flare were clinically evaluated for the objective comparison of the antiinflammatory effect. The main outcome measure was the percentage of patients with a resolution of inflammation (anterior chamber cells <1+) on day 14. Ocular surface toxicity was assessed by means of the corneal fluorescein staining score, tear breakup time, Schirmer I test, and questionnaire-based grading of ocular discomfort parameters. Seventy-two eyes of 68 patients were studied, of which 38 eyes were enrolled in group A and 34 eyes were enrolled in group B. On day 14, 76.3% of the patients in group A had resolution of inflammation compared with 70.6% of the patients in group B, proving noninferiority (χ = 0.303, P = 0.582). The mean anterior chamber cell grade reduction for patients in group A was similar to that in group B (2.52 vs. 2.86, respectively; P = 0.92). Group A patients showed significantly lower corneal fluorescein staining scores (P < 0.001) and reported milder subjective ocular discomfort (0.55 vs. 1.43, P = 0.01) as compared with group B. Both preparations demonstrated equal antiinflammatory effects for the treatment of AAU. Nonpreserved methylprednisolone eye drops exhibited a significantly lower ocular surface toxicity profile and milder subjective discomfort when compared with that exhibited by preserved prednisolone.

Anterior Chamber Cell Grading by Optical Coherence Tomography

To quantify cells in the ocular anterior chamber (AC) by optical coherence tomography (OCT). A time-domain anterior segment OCT system was used to image latex microsphere suspensions in vitro and the AC of uveitis and normal subjects in vivo. The OCT scan pattern, consisting of 2- and 4-mm-diameter concentric circular scans, was divided into central, superior, and inferior regions. A computer algorithm was developed to automatically identify particles in OCT images. A uveitis specialist used slit-lamp biomicroscopy to grade the AC cells on a scale of 0 to 4+. Latex microspheres and ac cells were visualized as reflective spots in oct images. OCT latex microsphere concentration measurements were highly correlated to known particle concentrations (r = 1.000) and had an efficiency of 0.72. in 30 nongranulomatous and 12 granulomatous eyes, the OCT cell counts correlated well with slit-lamp grades in all three regions (Spearman's rho coefficient: >0.63). The average OCT cell count was 3.7 cells/grade in nongranulomatous eyes and 2.0 cells/grade in granulomatous eyes. OCT revealed significant amounts of inferior AC cells in 5 of 16 quiescent uveitis eyes (mean ± SD: 19.9 ± 7.4 cells). OCT captured rare cells in normal eyes (1.1 ± 1.1 cells centrally). OCT provided quantitative information on AC inflammatory cells. The OCT cell counts correlated well with clinical grading, and particles in the inferior AC that were missed by slit-lamp examination were detected by OCT. OCT could be a valuable tool for the diagnosis and management of anterior uveitis.

Efficacy and safety of loteprednol etabonate 0.5% gel in the treatment of ocular inflammation and pain after cataract surgery

To examine the efficacy and safety of a new gel formulation loteprednol etabonate 0.5% in the treatment of inflammation and pain after cataract surgery. Seventeen United States clinical sites. Prospective double-masked parallel-group study. Patients with anterior chamber cell (ACC) grade 2 or higher after cataract surgery were randomized to loteprednol etabonate 0.5% gel or vehicle 4 times a day for 14 days. Primary outcome measures included the proportion of patients with complete resolution of ACC and grade 0 (no) pain on postoperative day 8. Safety measures included adverse events, intraocular pressure (IOP), visual acuity, biomicroscopy and funduscopy findings, and tolerability (ocular symptoms and drop comfort). The intent-to-treat population included 406 patients (203 per treatment). On day 8, 30.5% of patients in the loteprednol etabonate group and 16.3% of patients in the vehicle group had complete resolution of ACC, whereas 72.9% and 41.9%, respectively, had grade 0 pain (both P<.001). Significant treatment differences for complete resolution of ACC and grade 0 pain favoring loteprednol etabonate were also found on day 15 and day 18. One patient in each treatment group had a significant increase in IOP (≥ 10 mm Hg). Analyses of pain, photophobia, and tearing favored loteprednol etabonate at different time points beginning on day 3. More than 85% of patients in each treatment group reported no discomfort on drop instillation. Loteprednol etabonate gel 0.5% was efficacious and safe in treating postoperative inflammation and pain. Dr. Rajpal is a consultant to Bausch & Lomb, Inc., Allergan, Inc., and Alcon Laboratories, Inc. Dr. Siou-Mermet and Ms. Erb are employees of Bausch & Lomb, Inc. Dr. Roel has no financial or proprietary interest in any material or method mentioned.