Samir R. Tari

Adalimumab in Patients with Active Noninfectious Uveitis.

BACKGROUND Patients 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. METHODS This 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. RESULTS The 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). CONCLUSIONS In 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

BACKGROUND 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. METHODS 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. FINDINGS 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). INTERPRETATION 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. FUNDING AbbVie.

Functional and structural measurements for the assessment of internal limiting membrane peeling in idiopathic macular pucker.

Objective: To investigate the role of structural and functional measurements in the assessment of internal limiting membrane (ILM) peeling for the treatment of eyes with macular pucker. Methods: Ten patients with macular pucker who underwent pars plana vitrectomy with ILM peeling were studied prospectively. Visual acuity measurement, standard automated achromatic perimetry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT) were performed before and 3 months after surgery. Four surgical samples obtained from similar patients were analyzed with electron microscopy. Results: Three months after surgery, mean visual acuity ± SD was significantly improved from 0.4 ± 0.11 logMAR to 0.19 ± 0.13 logMAR (P ≤ 0.002), and mean central retinal thickness ± SD was significantly decreased 428 ± 73 &mgr;m to 326 ± 34 &mgr;m (P ≤ 0.002). The mfERG response amplitudes were slightly decreased in eight patients, and five of these patients also had asymptomatic decreases in visual field sensitivity. The electron micrographs revealed segments of Müller cell footplates on the retinal side of the ILM in all four specimens. Conclusion: In this study, the use of mfERG, OCT, and standard automated achromatic perimetry showed changes in macular function and structure postoperatively. These measures of visual function and structure allow for better evaluation of the surgical outcome and understanding of the changes that may occur after ILM peeling.

Prevalence of Noninfectious Uveitis in the United States: A Claims-Based Analysis

Importance Noninfectious uveitis (NIU) is a collection of intraocular inflammatory disorders that may be associated with significant visual impairment. To our knowledge, few studies have investigated NIU prevalence overall or stratified by inflammation location, severity, presence of systemic conditions, age, or sex. Objective To estimate NIU prevalence using a large, retrospective, administrative claims database. Design, Setting, and Participants This analysis used the OptumHealth Reporting and Insights database to estimate 2012 NIU prevalence. Analysis was conducted in September 2016. The large administrative insurance claims database includes 14 million privately insured individuals in 69 self-insured companies spanning diverse industries. Included in the study were patients with NIU with 2 or more uveitis diagnoses on separate days in 2012 and continuous enrollment in a health plan for all of 2012 and categorized by inflammation site. Main Outcomes and Measures We estimated overall NIU prevalence by inflammation site, severity, sex, and age. Patients with anterior NIU were categorized by the presence of systemic conditions. Results Of the approximately 4 million eligible adult patients, approximately 2.1 million were women, and of the 932 260 children, 475 481 were boys. The adult prevalence of NIU was 121 cases per 100 000 persons (95% CI, 117.5-124.3). The pediatric NIU prevalence was 29 cases per 100 000 (95% CI, 26.1-33.2). Anterior NIU accounted for 81% (3904 cases) of adult NIU cases (98 per 100 000; 95% CI, 94.7-100.9) and 75% (207 cases) of pediatric NIU cases (22 per 100 000; 95% CI, 19.3-25.4). The prevalences of noninfectious intermediate, posterior, and panuveitis were, for adults, 1 (95% CI, 0.8-1.5), 10 (95% CI, 9.4-11.5), and 12 (95% CI, 10.6-12.7) per 100 000, respectively, and for pediatric patients, 0 (95% CI, 0.1-1.1), 3 (95% CI, 1.8-4.1), and 4 (95% CI, 2.9-5.6) per 100 000, respectively. The prevalence of NIU increased with age and was higher among adult females than males. Application of these estimates to the US population suggests that NIU affected approximately 298 801 American adults (95% CI, 290 512-307 324) and 21 879 children (95% CI, 19 360-24 626) in 2015. Conclusions and Relevance The estimated prevalence of NIU was 121 cases per 100 000 for adults (95% CI, 117.5-124.3) and 29 per 100 000 for children (95% CI, 26.1-33.2). Prevalence was estimated using administrative claims from a commercially insured population, which may have a different prevalence than other segments of the US population. A better understanding of the prevalence of NIU will help to determine the number of patients affected.

Effect of Adalimumab on Visual Functioning in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis in the VISUAL-1 and VISUAL-2 Trials

Importance Adalimumab was recently approved for the treatment of noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Objective To assess the effect of adalimumab on the visual functioning and quality of life in patients with corticosteroid-dependent noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Design A post hoc analysis of clinical trials of adults with active (VISUAL-1) and inactive (VISUAL-2) noninfectious intermediate uveitis, posterior uveitis, and panuveitis was conducted in the United States, Canada, Europe, Israel, Australia, Latin America, and Japan. A total of 217 patients (110 adalimumab, 107 placebo) in VISUAL-1 and 226 patients (115 adalimumab, 111 placebo) in VISUAL-2 were studied using intent-to-treat analyses. The clinical trials were conducted between August 10, 2010, and May 14, 2015. Interventions In VISUAL-1 and VISUAL-2, patients were randomized to receive adalimumab, 80-mg, subcutaneous loading dose followed by 40 mg every other week or placebo for 80 weeks. All patients underwent prednisone tapering, with patients in VISUAL-1 receiving an initial prednisone burst. Main Outcomes and Measures The 25-item National Eye Institute Vision Function Questionnaire (NEI VFQ-25) composite score questionnaire assessed the impact of visual impairment from the patient’s perspective; scores on the questionnaire range from 0 to 100, with higher scores indicating better vision-related quality of life. The change in NEI VFQ-25 from best state achieved prior to week 6 (VISUAL-1) and from baseline state (VISUAL-2) to the final or early termination visit was determined in each group and statistically compared using analysis of variance. The temporal effects of adalimumab and placebo on NEI VFQ-25 were investigated using a longitudinal model. Results Of the 217 patients in VISUAL-1, 124 (57.1%) were women; the mean (SD) age was 42.7 (14.9) years. Of the 226 patients in VISUAL-2, 138 (61.1%) were women; the mean (SD) age was 42.5 (13.4). In VISUAL-1, the change from final score to best score in NEI VFQ-25 was −1.30 for adalimumab and −5.50 for placebo—a difference of 4.20 (95% CI, 1.04 to 7.36; P = .01) associated with adalimumab compared with placebo. In VISUAL-2, the change from baseline NEI VFQ-25 was 3.36 for adalimumab and 1.24 for placebo—a difference of 2.12 (95% CI, −0.81 to 5.04; P = .16). In both trials, the longitudinal models showed a significant difference in NEI VFQ-25 between adalimumab and placebo of 3.07 (95% CI, 2.09 to 4.06; P < .001) and 4.66 (95% CI, 0.05 to 9.26; P = .048) in the VISUAL-1 (74.15 vs 71.08) and VISUAL-2 (82.39 vs 77.73) trials, respectively. Conclusions and Relevance This post hoc analysis suggests that adalimumab is associated with statistically significant and clinically meaningful improvements in patient-reported visual functioning for patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Trial Registration clinicaltrials.gov Identifiers: NCT01138657 (VISUAL-1) and NCT01124838 (VISUAL-2)

SAT0523 Adalimumab in Patients with Active, Non-Infectious Uveitis Requiring High-Dose Corticosteroids: the Visual-1 Trial

Background Corticosteroids, currently the mainstay of uveitis treatment, are associated with unwanted side effects, and are not always fully effective. Accordingly, there is a clear unmet need for steroid-sparing treatments. Multiple reports describe the use of biologics, including adalimumab (ADA), in the management of non-infectious uveitis as steroid-sparing agents, but there is a paucity of level 1 evidence to support efficacy of these drugs. Objectives To assess ADA efficacy and safety in patients with active, sight-threatening, non-infectious uveitis despite systemic high-dose corticosteroid therapy. Methods This multinational, double-masked trial included patients aged ≥18 years with active, non-infectious intermediate, posterior, or panuveitis on ≥2 weeks of prednisone (10–60 mg/d). Patients with active uveitis had ≥1 of: active, inflammatory chorioretinal or retinal vascular lesion; anterior chamber (AC) cell grade ≥2+; or vitreous haze (VH) grade ≥2+. Patients were randomized 1:1 to receive placebo or ADA. The ADA group received an 80-mg baseline loading dose and 40 mg every other week for up to 80 weeks; all patients received prednisone 60 mg/d that was tapered to 0 mg by week 15. Primary endpoint was time to treatment failure (TF) in ≥1 eye. TF was defined as ≥1 of: new, active, inflammatory vascular lesions; worsening of BCVA by ≥15 letters at or after week 6; inability to achieve ≤0.5+ AC cell grade or ≤0.5+ VH grade (at week 6); or 2-step increase in AC cell grade or VH grade (after week 6). Ranked secondary endpoints included change in AC cell grade, VH grade, and BCVA from the best state achieved before week 6 to the final visit. Safety was monitored during the trial. Results 217 patients were enrolled (female, 57%; mean age, 42.7 y; mean uveitis duration, 46 mo); 22% had intermediate, 33% had posterior, and 45% had panuveitis. Patients on ADA were less likely to have TF (hazard ratio=0.5; 95% CI, 0.36–0.70; P<0.001) and had fewer causes of TF. Median time to TF was 13 weeks for placebo and 24 weeks for ADA (Figure). Worsening of AC cell grade, VH grade, and BCVA from best state achieved were reduced with ADA compared with placebo (all P<0.05). Adverse event rates were similar in the ADA and placebo groups. Conclusions In patients with active, non-infectious intermediate, posterior, or pan uveitis despite the use of corticosteroids, ADA significantly lowered the risk for uveitic flare or BCVA loss. The safety profile was consistent with the known safety profile across approved ADA indications. Acknowledgements Writing assistance was provided by Jillian Gee and Katherine Groschwitz of Complete Publication Solutions, LLC (CPS), Horsham, PA and Peter Rittenhouse of Complete Healthcare Communications, Inc (CHC), Chadds Ford, PA, on behalf of AbbVie. AbbVie provided funding to CPS and CHC for medical writing assistance. AbbVie funded the study (NCT01138657), contributed to its design and the data analyses, and was involved in the drafting, review, and approval of the abstract. Disclosure of Interest G. Jaffe, MD Consultant for: AbbVie, J. Thorne, MD, PhD Grant/research support from: National Eye Institute and Allergen, Inc., Consultant for: AbbVie, Gilead, and XOMA, D. Scales, MD Consultant for: AbbVie Steering Committee, P. Franco, MD: None declared, S. Tari, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Camez, MD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, A. Song, MD, MPH Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, M. Kron, PhD Shareholder of: May hold AbbVie stock or options, Employee of: AbbVie, T. Barisani-Asenbauer, MD, PhD Consultant for: AbbVie Advisory Board, A. Dick, MBBS, MD, FMedSci Consultant for: AbbVie Advisory Board

THU0565 Clinical Relevance of Treatment Failure as Assessed by The 25-Item Visual Functioning Questionnaire in Patients with Intermediate-, Posterior- and Pan-Uveitis: Results from The Visual-1 Trial

Background Time to treatment failure is the primary endpoint in the VISUAL-1 clinical trial (NCT01138657) of patients with non-infectious intermediate-, posterior- and pan-uveitis (NIIPPU); however, the relationship between the treatment failure (TF) criteria and patient-reported outcome of visual functioning is not well understood. Objectives To examine the relationship between TF and vision-related quality of life (QoL) as assessed by the Visual Functioning Questionnaire 25 (VFQ-25) among patients with NIIPPU. Methods The VISUAL-1 clinical trial was a randomized, placebo-controlled, 80-week study designed to investigate the efficacy and safety of adalimumab in patients with active NIIPPU. Patients were examined at scheduled study visits for TF at and after week 6. TF was assessed using 4 criteria: presence of inflammatory, chorioretinal, and/or inflammatory retinal vascular lesions, anterior chamber (AC) cell grade, vitreous haze (VH) grade, and visual acuity (VA). Patients with TF due to 1, 2, 3, and 4 of these components met 1 of 4 criteria, 2 of 4 criteria, 3 of 4 criteria, and all 4 criteria, respectively. The VFQ-25 measures 12 health domains (11 vision-related; 1 general health–related) and was used to assess the effect of ocular disease on vision-related QoL from the patients perspective. VFQ-25 total score was the mean of 11 vision-related domains. Scores ranged from 0 (worst vision) to 100 (best vision). Analyses were conducted for patients with 1, 2, 3, and 4 components, and for patients with no component (non-failure). Changes in VFQ-25 total and subdomain scores from best state prior to week 6 to final visit were calculated for each component, at least 1 component, and no component (non-failure). Analysis of covariance (adjusting for best state prior to week 6) was used to assess the association between VFQ-25 score and 1, 2, 3, or 4 components. Missing data were imputed using last observation carried forward. Results Data from 203 patients were analyzed. Unadjusted mean change in VFQ 25 total score was -4.92 for at least 1 component compared with 0.19 for non-failure; unadjusted mean change was −3.90, −5.09, −11.1, and −13.88, for 1, 2, 3, and 4 components, respectively. Adjusted change in VFQ-25 score from best state prior to week 6 to final visit was −3.9 (P<.0001) for each additional component. When assessing patients by component, the greatest change in VFQ-25 total score was seen for VA (−7.99) followed by VH grade (−3.29), AC cell grade (−2.8), and retinal vascular lesion (−2.76). In general, results were similar for the VFQ-25 subdomain scores. Conclusions Clinically meaningful decreases in VFQ-25 scores among patients experiencing TF were substantial1 supporting TF as a relevant outcome from the patient perspective. Among causes for TF, the loss of VA had the greatest impact on the QoL, the other causes for TF had a lesser effect. References Naik RK, et al. Qual Life Res. 2013;22:2801–8. Acknowledgement Financial support for the study and medical writing (Joann Hettasch, Arbor Communications, Inc) were provided by AbbVie Inc. AbbVie participated in the interpretation of data, review, and approval of the abstract; all authors contributed to the development of the publication and maintained control over the final content. Disclosure of Interest A. Brézin Consultant for: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, S. Tari Shareholder of: AbbVie, Employee of: AbbVie, M. Skup Shareholder of: AbbVie, Employee of: AbbVie, A. Joshi Shareholder of: AbbVie, Employee of: AbbVie

Polychromatic angiography for the assessment of VEGF-induced BRB dysfunction in the rabbit retina.

PURPOSE To determine the utility of polychromatic angiography (PCA) in the assessment of VEGF-induced blood retinal barrier (BRB) dysfunction in rabbits. METHODS Twenty-six eyes of 24 Dutch Belted rabbits were injected intravitreally with 1.25 μg (group A, n = 5), 10 μg (group C, n = 7), or 4 μg (group B, n = 6; group D, n = 4; and group E, n = 4) of VEGF on day 0. Groups D and E were also injected intravitreally with 1.25 μg and 12.5 μg bevacizumab, respectively, on day 2. On days 0, 2, 4, 7, 11, and 14, PCA was performed using a contrast agent mixture composed of fluorescein sodium, indocyanine green, PCM102, and PCM107 and imaged with a modified fundus camera. PCA scores were based on detected leaking fluorophores. RESULTS On day 7, there was a statistically significant difference between PCA scores of group A (0.6 ± 0.89) and both groups B (2.67 ± 1.37, P = 0.0154) and C (3.33 ± 0.52, P = 0.00085). There was also a statistically significant difference between groups B and E (PCA score 0.75 ± 0.96, P = 0.032) on day 7. On day 11, there was statistically significant difference between group C (1.80 ± 1.1) and both groups A (0, P = 0.021) and B (0.33 ± 0.52, P = 0.037). CONCLUSIONS A differential response to both increasing VEGF dose and administration of bevacizumab could be discerned using the PCA. PCA allowed stratification of VEGF-induced BRB dysfunction and inhibitory effects of bevacizumab therapy in the rabbit retina.

Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials

ABSTRACT Purpose: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. Methods: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). Results: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40–0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37–0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41–3.54]; VISUAL II: HR = 0.45 [0.20–1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). Conclusions: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.

FRI0618 Adalimumab in non-infectious uveitis – efficacy across different etiologies in the visual i and visual ii trials

Background There is increasing interest in understanding the efficacy of adalimumab across different etiologies of uveitis. No prospective analysis has been conducted to date to determine the efficacy of adalimumab among non-infectious uveitis patients with different etiologies. Objectives To assess adalimumab (ADA) efficacy in active and inactive, non-infectious uveitis across different etiologies in patients who were recruited as part of the VISUAL program. Methods Exploratory data analyses from two global phase 3, double-masked trials: VISUAL I (patients with active uveitis despite ≥2 weeks of prednisone 10–60 mg/day) and VISUAL II (patients with inactive disease dependent on 10–35 mg/day of prednisone to maintain inactivity) were performed. Patients received placebo (PBO) or ADA subcutaneously (80 mg week 0, followed by 40 mg every other week from week 1 up to 80 weeks). In VISUAL I, all patients received a prednisone burst followed by taper to 0 mg by week 15. In VISUAL II, prednisone taper to 0 mg was mandatory by week 19. The primary endpoint was time to treatment failure (TF) at or after week 6 for VISUAL I; and at or after week 2 for VISUAL II1,2. For this analysis, patients were categorized into different uveitis etiologies which they presented at study entry. Hazard ratios (HR) for time to TF were obtained for each uveitis etiology. Results The efficacy of ADA was significantly greater than PBO in the largest subgroup of patients with Idiopathic/other uveitis (VISUAL I: 103 and VISUAL II: 90) etiology in both VISUAL I1 and VISUAL II trials. All other subgroups showed a trend in favor of ADA, except for Sarcoidosis subgroup in the VISUAL II trial (Figure). Overall safety for both trials has been previously reported 1,2. Conclusions These exploratory analyses from the VISUAL I and VISUAL II trials show significantly higher efficacy in ADA-treated patients over PBO in “idiopathic/other” diagnoses of patients with both active and inactive non-infectious uveitis. Furthermore, across different uveitis etiologies, these analyses suggest that ADA-treated patients had a prolonged time to treatment failure compared to PBO. References Jaffe GJ, Dick AD, Brezin AP, et al. N Engl J Med (2016); 375:932–43. Nguyen QD, Merrill PT, Jaffe GJ, et al. The Lancet (2016); 388(10050): 1183–92. Acknowledgements AbbVie funded the VISUAL I and VISUAL II studies and provided writing support. All authors contributed to the development of the content. The authors and AbbVie reviewed and approved the abstract. The authors maintained control over the final content. Medical writing assistance was provided by Gaurav Patki, PhD of AbbVie Inc. Disclosure of Interest P. T. Merrill Consultant for: Santen, AbbVie, A. Vitale Consultant for: ACIONT, M. Zierhut Consultant for: AbbVie and Santen, E. Forton Consultant for: AbbVie, Alcon and Allergan, H. Goto Consultant for: AbbVie, M. Kron Shareholder of: AbbVie, Employee of: AbbVie, S. Tari Shareholder of: AbbVie, Employee of: AbbVie, S. Pathai Shareholder of: AbbVie, Employee of: AbbVie