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• Real life visual improvements with anti vascular endothelial growth factor treatment for wet age-related macular degeneration - Absolute or relative?
  Balasubramanian Ramasamy
  Published on: 22 March 2016

• Published on: 22 March 2016

  Real life visual improvements with anti vascular endothelial growth factor treatment for wet age-related macular degeneration - Absolute or relative?

  • Balasubramanian Ramasamy, Consultant Ophthalmologist
  • Other Contributors:
    • Stephanie Tiew, Louis G Clearkin

  Dear Editor

  We congratulate Holz et al.1 on their most important contribution to anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration (n-AMD). We think it is important to note that their main finding "visual acuity improved until about day 120; thereafter visual acuity changes were not maintained" does not contradict the findings of the MARINA2 [Ranibizumab Vs sham in...

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  Dear Editor

  We congratulate Holz et al.1 on their most important contribution to anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration (n-AMD). We think it is important to note that their main finding "visual acuity improved until about day 120; thereafter visual acuity changes were not maintained" does not contradict the findings of the MARINA2 [Ranibizumab Vs sham injection] clinical trial. We have previously re-evaluated3 the published results of the MARINA study to assess the absolute risk reduction (The absolute difference of outcome between experimental - i.e. ranibizumab treated - and control participants in the MARINA trial). This being the approach specified in The ABPI Code of Practice4 Clause 7; Information, Claims and Comparisons "Referring only to relative risk, especially with regard to risk reduction, can make a medicine appear more effective than it actually is. In order to assess the clinical impact of an outcome, the reader also needs to know the absolute risk involved. In that regard relative risk should never be referred to without also referring to the absolute risk. Absolute risk can be referred to in isolation." We set out in the graph below our evaluation of mean letter change from baseline (visual acuity change) derived from MARINA Figure 2 A results page 14262. The published change in letter score is at 3 month intervals rather than for each monthly injection as our efforts to acquire the raw data from the authors of the MARINA study2 have been unsuccessful. The best we can do is to show the letter change for the ranibizumab treated patients (we have confined our analysis to 0.5 mg group) letter score is in green, sham injection is in blue and the difference between the groups is in pink - this being the absolute risk reduction at every time we have data for. Our re-analysis seemingly confirms Holtz's findings1; ranibizumab is apparently most beneficial in the initial stages of treatment of n-AMD and visual gains cease between 3 - 6 months.

  

  Figure 1 - Green line - Ranibizumab treated patients (0.5mg) - change in letters read since last injection. Blue line - Sham-injection treated patients - change in letters read since last injection. Pink line - Absolute risk reduction (The arithmetic difference between the Ranibizumab and sham groups for each 3-monthly time point.)

  We note that Holtz and colleagues presented the mean change in visual acuity score after start of anti-VEGF as their primary endpoints. Our graph demonstrates the change in visual acuity score since previous visit and we note the striking resemblance in that both the analysis plots a very similar graph. While the patient demographics include the various subsets of n-AMD, we could not find any mention of visual acuity outcomes for these subset groups of patients. As MARINA showed visual benefits (stabilization or improvement of letters read) due to Ranibizumab treatment was achieved in only 27.6% of patients, we ask the authors if they are able to predict likely responders based on any base-line characteristics that would distinguish them from non-responders. Also would the authors be able to share if available their analysis of change in visual acuity from the previous visit. This could help in the early identification of those patients unlikely to benefit either prior to treatment or as the treatment progresses and avoid exposing patients unlikely to benefit to the risks of treatment.

  References

  1. Frank G Holz, Ramin Tadayoni, Stephen Beatty et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration.Br J Ophthalmol doi:10.1136/bjophthalmol-2014-305327

  2. Philip J. Rosenfeld, M.D., Ph.D., David M. Brown, M.D., Jeffrey S. Heier, M.D. et al. for the MARINA Study Group. N Engl J Med 2006; 355:1419-1431.

  3. B. Ramasamy, S Tiew, J Wason, L Clearkin . Absolute Risk Reduction and Natural Frequencies of Ranibizumab treatment in neovascular Age-Related Macular Degeneration (nvAMD). Poster and rapid fire presentation, Oxford Ophthalmological Congress ( 7/7/2015)

  4. ABPI Code of Practice for The Pharmaceutical Industry https://www.bsped.org.uk/resources/docs/ABPIguidelines

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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