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Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging
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  • Published on:
    The Controversial Role of Inhibitory Complement Factors in Age-Related Macular Degeneration
    • Anne Lynch, Director of Ophthalmic Epidemiology University of Colorado Denver School of Medicine
    Article Title: Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging BMJ Open Ophthalmology Jan 2020, 5 (1) e000361; DOI: 10.1136/bmjophth-2019-000361
    E-letter sender: Anne M Lynch, Brandie D Wagner, Alan G Palestine, Jennifer L Patnaik, Ashley A Frazier-Abel, Marc T Mathias, Frank S Siringo, V. Michael Holers, Naresh Mandava
    E-Letter Title: Response to letter entitled “The Controversial Role of Inhibitory Complement Factors in Age-Related Macular Degeneration”
    February 12, 2020
     
     
    Dear Editor,
     
    We appreciate the comments from Shiwani et al. regarding our manuscript entitled “Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging.” As reported in the manuscript, (1) we found significantly elevated levels of C3a, Ba, C5a and C2 in cases with the intermediate phenotype of age-related macular degeneration (AMD) compared with cataract controls without AMD. We also found significantly lower levels of Factor B, Factor H, Factor I, C1q, iC3b/C3b, and C5 in the AMD cases compare...
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    Conflict of Interest:
    None declared.
  • Published on:
    The Controversial Role of Inhibitory Complement Factors in Age-Related Macular Degeneration
    • Haaris A Shiwani, Junior Doctor Royal Lancaster Infirmary, University Hospitals of Morecambe Bay NHS Foundation Trust, United Kingdom
    • Other Contributors:
      • Muhammad S Aziz, Junior Doctor

    Dear Editor,

    We read with interest the role of complement in age-related macular degeneration (AMD) explored by Lynch and colleagues1. The authors have expertly examined the numerous components of the complement system and provided much novel data, particularly in the context of intermediate AMD.

    Their results are congruent with that of the literature, especially with regard to lower levels of C3a, C5a and Ba in the setting of AMD2. Furthermore, the results of the FILLY trial have shown positive effects of the inhibition of C3 in limiting geographic atrophy and thus lend an element of support to the conclusions of this study3. We hope that the subsequent phase 3 trials – DERBY and OAKS – will lend further support and allow research such as this to translate to clinical benefit for patients4.

    However, we do feel that there may be an element of multiple hypothesis testing evident in this study that increases the risk of generating some erroneous results. We feel a Bonferroni statistical correction would have been an appropriate tool to add further robustness to the positive findings that have been demonstrated. We especially feel that the results relating to the inhibitory factors of the complement system do not tend to correlate with some of the findings in the literature. Although Lynch et al have identified lower levels of Factor B, Factor H and Factor I in the AMD arm of the study, there are numerous reports in the literature reporting the opposite...

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    Conflict of Interest:
    None declared.