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Hyperpigmentary abnormalities in age-related macular degeneration: association with progression and impact on visual sensitivity
  1. Kai Lyn Goh1,2,
  2. Himeesh Kumar1,2,
  3. Xavier Hadoux1,
  4. Maxime Jannaud1,
  5. Carla Abbott1,2,
  6. Lauren Hodgson1,
  7. Luba Robman1,
  8. Galina Makeyeva1,
  9. Peter Van Wijngaarden1,2,
  10. Robyn Guymer1,2,
  11. Zhichao Wu1,2
  1. 1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia
  2. 2Ophthalmology, Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
  1. Correspondence to Dr Zhichao Wu, Centre for Eye Research Australia, East Melbourne, Victoria, Australia; wu.z{at}


Background/aims To investigate the additional prognostic value of quantifying the extent of colour fundus photography (CFP)-defined hyperpigmentary abnormalities (HPAs) compared with their presence alone for predicting progression to late-stage age-related macular degeneration (AMD) and to understand their association with visual sensitivity in individuals with intermediate AMD.

Methods 140 participants with bilateral large drusen underwent multimodal imaging and microperimetry at baseline and then every 6 months for up to 3 years. Baseline CFPs were graded for the presence of HPAs and their extent was quantified. Optical coherence tomography (OCT) scans were used to quantify drusen volume. Predictive models for progression to late AMD (including OCT signs of atrophy) were developed using either HPA presence or extent. The association between HPA extent with mean visual sensitivity (both overall and sector based) was also evaluated. All models were adjusted for the confounders of baseline age and drusen volume.

Results The predictive performance for late AMD development was not significantly different for HPA presence or extent (p=0.92). Increasing HPA extent in each sector, but not its overall extent in an eye, was associated with reduced sector-based visual sensitivity (p<0.001 and p=0.671, respectively).

Conclusion In a cohort with bilateral large drusen, quantifying HPA extent did not improve the prediction of late AMD development compared with presence alone. HPA extent was associated with more local, rather than generalised, reductions in visual sensitivity. These findings suggest that quantification of HPA extent adds little to the prediction of AMD progression, but that it provides an imaging biomarker of visual dysfunction.

  • Degeneration
  • Imaging
  • Macula
  • Retina

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • KLG and HK are joint first authors.

  • Contributors Conception and design: KLG, HK, CA, RG and ZW. Data collection: KLG, HK, LH, LR, GM, RG and ZW. Analysis and interpretation: KLG, HK, XH, MJ, CA, LH, LR, GM, PVW, RG and ZW. Manuscript preparation: KLG, HK, XH, MJ, CA, LH, LR, GM, PVW, RG and ZW. Obtained funding: RG and ZW. Overall responsibility: RG and ZW. ZW is guarantor.

  • Funding This study was supported by National Health & Medical Research Council of Australia (project grant no: APP1027624 (RG), and fellowship grant no: GNT1194667 (RG), #2008382 (ZW)), and grants from the Macular Disease Foundation Australia (no grant number, to RG and ZW), the BrightFocus Foundation (grant no.: M2019073 (ZW)), H&L Hecht Trust (no grant number, to XH, MJ and PVW) and Centre for Eye Research Australia (CERA) Innovation Fund (no grant number, to XH, MJ and PVW). CERA receives operational infrastructure support from the Victorian Government. The sponsor or funding organization had no role in the design or conduct of this research.

  • Competing interests Financial disclosure(s): PVW reports personal fees from Roche/Genentech, Bayer Australia, Novartis and Mylan outside the submitted work. RG reports personal fees from Roche/Genentech, Bayer, Novartis and Apellis outside the submitted work. KLG, HK, XH, MJ, CA, LH, LR, GM and ZW report nothing to disclose.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.