title: The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration.
abstract: OBJECTIVE
  To compare the effect of ranibizumab treatment versus photodynamic therapy (PDT) on single-stranded DNA damage in circulating leukocytes in patients with exudative age-related macular degeneration (AMD).
  
  
  METHODS
  A comparative quantification of single-stranded DNA breaks was performed in circulating leukocytes of AMD patients before and 30 min, 45 min, 60 min, and 24 h after two different modes of therapy: a) PDT; and b) intravitreal ranibizumab injection. DNA breaks lead to smaller pieces of DNA, which in an electrical field, migrate out of the nucleus forming a tail. Damage of an individual cell was quantified as a comet tail moment. The proportion of non-zero values compared to the total number of observations was referred to as "amount of DNA damage" expressed in arbitrary units (AU). Comparisons between time points and study groups were assessed using a linear mixed-effect model.
  
  
  RESULTS
  PDT induced an increase in the amount of single-stranded DNA damage in the circulating leukocytes from 0.2 AU (before treatment) to 0.53 AU (30 min after treatment). This increase was significant (p=0.004). In contrast, after ranibizumab treatment, the DNA damage in the circulating leukocytes remained unchanged.
  
  
  CONCLUSIONS
  PDT purposely induces a local oxidative stress to damage the newly formed vessels. Our results indicate an additional systemic oxidative stress, apparent as amount of single-stranded DNA damage in the circulating leukocytes, for at least 30 min after treatment.
authors.affiliation: University Eye Clinic, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Mozaffarieh
authors.forename: A
authors.initials: A
authors.lastname: Schötzau
authors.forename: T
authors.initials: T
authors.lastname: Josifova
authors.forename: Josef
authors.initials: J
authors.lastname: Flammer
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D020552:Comet Assay; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008268:Macular Degeneration / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000009:adverse effects*; D011166:Porphyrins / Q000008:administration & dosage / Q000009:adverse effects*; D000069579:Ranibizumab; D000077362:Verteporfin
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011166:Porphyrins; D000077362:Verteporfin; D000069579:Ranibizumab