title: Assessment of differential pharmacodynamic effects using optical coherence tomography in neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To use novel OCT parameters in assessing the differential pharmacodynamic effects of bevacizumab (Avastin; Genentech, South San Francisco, CA), pegaptanib (Macugen; OSI Pharmaceuticals, New York, NY), and verteporfin photodynamic therapy (PDT; Novartis, Basel, Switzerland) in a recently completed phase III/IV clinical trial.
  
  
  METHODS
  Data from 122 patients participating in the Avastin (Bevacizumab) for Choroidal Neovascularization (ABC) trial, were evaluated. OCT scans were analyzed with custom software. Changes in the volume of the neurosensory retina, amount of subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal tissue (SRT), were calculated over the 54-week trial period.
  
  
  RESULTS
  Reductions in retinal edema were more than twice as great from bevacizumab as from pegaptanib (-0.82 mm³ vs. -0.31 mm³), whereas SRF reduction was more than three times greater (-0.54 mm³ vs. -0.15 mm³. Both bevacizumab and pegaptanib led to rapid reductions in SRT; however, in those receiving pegaptanib, these improvements were not maintained (at week 54, -0.22 mm³ vs. +0.18 mm³). Acute increases in SRF were seen 1 week after PDT (+0.36 mm³) and, across all treatment groups, PED volume tended to remain unchanged or to regress only slowly.
  
  
  CONCLUSIONS
  In clinical trials, quantitative OCT subanalysis increases the amount of clinically useful information that can be obtained from OCT images. In the emerging era of neovascular AMD therapeutics, the capacity of OCT to provide such detailed pharmacodynamic information in a noninvasive manner is likely to attain increased importance. In future comparative studies, evaluation of SRT may highlight differential effects on vascular proliferation, whereas measurement of PED volume may be useful for the estimation of retinal and subretinal pigment epithelium (RPE) therapeutic penetration. (ClinicalTrials.gov number, ISRCTN83325075.).
authors.affiliation: NIHR-National Institute of Health Research, Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS-National Health Service Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom.
authors.forename: Pearse A
authors.initials: PA
authors.lastname: Keane
authors.forename: Florian M
authors.initials: FM
authors.lastname: Heussen
authors.forename: Yanling
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Nils
authors.initials: N
authors.lastname: Mokwa
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Walsh
authors.forename: Adnan
authors.initials: A
authors.lastname: Tufail
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Sadda
authors.forename: Praveen J
authors.initials: PJ
authors.lastname: Patel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence / Q000379:methods*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib; D000068258:Bevacizumab