Jeffrey S Heier1, Dante Pieramici2, Usha Chakravarthy3, Sunil S Patel4, Sunil Gupta5, Andrew Lotery6, Eleonora M Lad7, David Silverman8, Erin C Henry9, Majid Anderesi8, Elizabeth A Tschosik9, Sarah Gray9, Daniela Ferrara10, Robyn Guymer11. 1. Ophthalmic Consultants of Boston, Boston, Massachusetts. 2. California Retina Consultants, Santa Barbara, California. 3. Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom. 4. Ophthalmology Specialists of Texas, PLLC, and Integrated Clinical Research, LLC, Abilene, Texas. 5. Retina Specialty Institute, Pensacola, Florida. 6. Faculty of Medicine, University of Southampton, Southampton, United Kingdom. 7. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. 8. Roche Products Limited, Welwyn Garden City, United Kingdom. 9. Genentech, Inc., South San Francisco, California. 10. Genentech, Inc., South San Francisco, California. Electronic address: ferrara.daniela@gene.com. 11. Centre for Eye Research Australia, Department of Surgery, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
Abstract
PURPOSE: To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area. DESIGN: The Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA. PARTICIPANTS: Eligible patients were 50 years of age or older with well-demarcated bilateral GA (lesion size, 1-7 disc areas) without evidence of or previous treatment for choroidal neovascularization in either eye and best-corrected visual acuity (BCVA) letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters). METHODS:Patients (pooled n = 1881) were randomized 2:1:2:1 to lampalizumab every 4 weeks, sham every 4 weeks, lampalizumab every 6 weeks, or sham every 6 weeks. Sham arms were pooled for analysis. MAIN OUTCOME MEASURES: Functional end points included change in BCVA from baseline to week 48, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular and monocular maximum reading speed, and 2 validated patient-reported outcome measures: Functional Reading Independence Index and 25-item National Eye Institute Visual Function Questionnaire. RESULTS: Enlargement of GA area, approximately 2 mm2/year on average across all treatment groups in each study, was accompanied by overall deterioration in all functional end points. No statistically significant differences were found between lampalizumab or sham arms for changes from baseline in functional assessment scores. Of visual function tests, only microperimetry outcomes were correlated moderately with GA lesion area when assessed cross-sectionally at baseline and week 48. CONCLUSIONS: Chroma and Spectri provide a unique data set of functional end points in GA that are relevant for future clinical trials. Patients with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function were not correlated strongly with GA lesion area. It is not possible to predict visual function outcomes from GA lesion size.
RCT Entities:
PURPOSE: To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area. DESIGN: The Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA. PARTICIPANTS: Eligible patients were 50 years of age or older with well-demarcated bilateral GA (lesion size, 1-7 disc areas) without evidence of or previous treatment for choroidal neovascularization in either eye and best-corrected visual acuity (BCVA) letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters). METHODS:Patients (pooled n = 1881) were randomized 2:1:2:1 to lampalizumab every 4 weeks, sham every 4 weeks, lampalizumab every 6 weeks, or sham every 6 weeks. Sham arms were pooled for analysis. MAIN OUTCOME MEASURES: Functional end points included change in BCVA from baseline to week 48, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular and monocular maximum reading speed, and 2 validated patient-reported outcome measures: Functional Reading Independence Index and 25-item National Eye Institute Visual Function Questionnaire. RESULTS: Enlargement of GA area, approximately 2 mm2/year on average across all treatment groups in each study, was accompanied by overall deterioration in all functional end points. No statistically significant differences were found between lampalizumab or sham arms for changes from baseline in functional assessment scores. Of visual function tests, only microperimetry outcomes were correlated moderately with GA lesion area when assessed cross-sectionally at baseline and week 48. CONCLUSIONS: Chroma and Spectri provide a unique data set of functional end points in GA that are relevant for future clinical trials. Patients with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function were not correlated strongly with GA lesion area. It is not possible to predict visual function outcomes from GA lesion size.
Authors: Aneesha Ahluwalia; Liangbo L Shen; Yihan Bao; Mengyuan Sun; Benjamin K Young; Michael M Park; Lucian V Del Priore Journal: Graefes Arch Clin Exp Ophthalmol Date: 2022-10-21 Impact factor: 3.535
Authors: Liangbo L Shen; Mengyuan Sun; Aneesha Ahluwalia; Michael M Park; Benjamin K Young; Eleonora M Lad; Cynthia Toth; Lucian V Del Priore Journal: Br J Ophthalmol Date: 2020-12-23 Impact factor: 5.908