title: Fixation stability and implication for multifocal electroretinography in patients with neovascular age-related macular degeneration after anti-VEGF treatment.
abstract: OBJECTIVE
  To quantify fixation stability in patients with neovascular age-related macular degeneration (nAMD) at baseline, 3 and 6 months after anti-vascular endothelial growth factor (anti-VEGF) treatment and furthermore asses the implications of an unsteady fixation for multifocal electroretinography (mfERG) measurements.
  
  
  METHODS
  Fifty eyes of 50 nAMD patients receiving intravitreal anti-VEGF treatment with either bevacizumab or ranibizumab and eight eyes of eight control subjects were included. Fixation stability measurements were performed with the Eye-Link eyetracking system and the retinal area in degrees2(deg2) containing the 68 % most frequently used fixation points (RAF68) was calculated. MfERG P1 amplitude and implicit time were analyzed in six concentric rings and as a summed response. Patients were examined at baseline, 3 and 6 months. Four different mfERG recordings were performed for the control subjects to mimic an involuntary unstable fixation: normal central fixation, 2.4°, 4.8°, and 7.1° fixation instability.
  
  
  RESULTS
  For control subjects, a fixation instability of 2.4° (corresponding to the central hexagon) did not reduce mfERG ring amplitudes significantly, whereas 4.8° and 7.1° fixation instability reduced the amplitudes significantly in rings 1 and 2 (p < 0.001) as well as in the peripheral rings in the 7.1° instability condition (p < 0.001). Fixation stability improved non-significantly for patients at 3 and 6 months. The size of the retinal area of fixation was at baseline, 3 and 6 months negatively correlated to visual acuity (VA) (rbaseline= -0.65, r3 months= -0.60, and r6 months= -0.66 respectively, p < 0.001) and mfERG amplitudes of the three innermost rings (rbaseline= -0.29, p = 0.042, r3 months= -0.43, p = 0.003 and r6 months= -0.31, p = 0.042). The VA cutoff for a fixation area less than 5 deg2(approximately the central hexagon) was 65, 77, and 68 ETDRS letters (corresponding a maximal Snellen equivalent of 0.31) at baseline, 3 and 6 months, respectively.
  
  
  CONCLUSIONS
  MfERG amplitudes in recordings of nAMD patients are at substantial risk of being reduced due to poor fixation as a large number of patients may use a fixation area of more than 5 deg2. Fixation monitoring during recording as well as interpretation of results should be performed with care, especially in patients with poor visual acuity.
authors.affiliation: Department of Ophthalmology, Rigshospitalet-Glostrup, Nordre Ringvej 57, 2600, Glostrup, Denmark. karenbjerg@yahoo.dk.
authors.forename: K B
authors.initials: KB
authors.lastname: Pedersen
authors.affiliation: Department of Ophthalmology, Odense University Hospital, 5000, Odense, Denmark.
authors.forename: A K
authors.initials: AK
authors.lastname: Sjølie
authors.affiliation: Department of Ophthalmology, Odense University Hospital, 5000, Odense, Denmark.
authors.forename: A H
authors.initials: AH
authors.lastname: Vestergaard
authors.affiliation: Department of Ophthalmology, Lund University, 221 00, Lund, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Andréasson
authors.affiliation: Department of Ophthalmology, Vejle Hospital, 7100, Vejle, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Møller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D004596:Electroretinography; D005260:Female; D005403:Fixation, Ocular / Q000502:physiology*; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab / Q000627:therapeutic use; D012160:Retina / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab
keywords: Age-related macular degeneration; Anti-VEGF; Electrophysiology; Fixation stability; Multifocal ERG; Retinal area of fixation (RAF68)