title: Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.
abstract: To compare the enlargement rate of macular atrophy (ERMA) in eyes treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for neovascular age-related macular degeneration (AMD) or fellow control eyes, as well as analyze risk factors for macular atrophy (MA) development and progression.
  
  
  
  Eighteen-month, multicenter, randomized, controlled clinical trial.
  
  
  
  Sixty patients with treatment-naïve neovascular AMD in 1 eye randomized 1:2 to monthly or TREX ranibizumab.
  
  
  
  Patients' study and fellow eyes were followed for 18 months using spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was quantified on FAF images using Heidelberg Region Finder software (Heidelberg Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by SD OCT and infrared reflectance imaging. For eyes without baseline MA yet developed MA by 18 months, intervening visits were assessed to determine the first visit at which MA appeared to define progression rates. Foveal choroidal thickness (FCT), subretinal hyperreflective material (SHRM), and pigment epithelial detachment (PED), were assessed at baseline to determine whether they influenced MA progression.
  
  
  
  Mean ERMA at 18 months. Relationship between visual acuity and MA, and the baseline risk factors for ERMA were also assessed.
  
  
  
  The final analysis cohort included 88 eyes in 3 groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean ERMA over 18 months was 0.39±0.67 (monthly), 1.1±1.9 (TREX), and 0.49±1 mm2(control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline patients with MA was 0.9±1, 1.9±2.2, and 1±1.3 mm2, respectively (P = 0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%, respectively. Mann-Whitney U test revealed a statistically significant association between baseline FCT (127±46 vs. 155±55 μm, P = 0.01) and SHRM thickness (106±131 vs. 50±85 μm, P = 0.02) on MA. In eyes with no baseline MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01, 0.04, 0.004, 0.01, respectively).
  
  
  
  Ranibizumab did not show a statistically significant influence on new MA development in eyes with neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM thickness, and hemorrhage at baseline were all significant predictors of new MA.
authors.affiliation: Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: nizar@ucla.edu.
authors.forename: Nizar S
authors.initials: NS
authors.lastname: Abdelfattah
authors.affiliation: Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Mayss
authors.initials: M
authors.lastname: Al-Sheikh
authors.affiliation: Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California.
authors.forename: Sean
authors.initials: S
authors.lastname: Pitetta
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: SriniVas R
authors.initials: SR
authors.lastname: Sadda
authors.affiliation: Retina Consultants of Houston, Houston, Texas; Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Houston, Texas.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Wykoff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001284:Atrophy / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008266:Macula Lutea / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D000069579:Ranibizumab / Q000627:therapeutic use*; D012307:Risk Factors; D041623:Tomography, Optical Coherence; D014481:United States / Q000453:epidemiology; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*
chemical_list: D020533:Angiogenesis Inhibitors; D000069579:Ranibizumab