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Risk factors for development of hyper-reflective foci overlying drusen in eyes with intermediate age-related macular degeneration
  1. Alireza Mahmoudi1,2,
  2. Navid Manafi1,2,
  3. Giulia Corradetti1,2,
  4. Muneeswar Gupta Nittala1,2,
  5. Mehdi Emamverdi1,2,
  6. Stephanie Trejo Corona3,
  7. Charles C Wykoff3,
  8. David Sarraf4,
  9. SriniVas R Sadda1,2
  1. 1Doheny Eye Institute, Pasadena, California, USA
  2. 2Department of Ophthalmology, University of California Los Angeles, Los Angeles, California, USA
  3. 3Retina Consultants of Texas, Houston, Texas, USA
  4. 4Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute,University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
  1. Correspondence to Dr SriniVas R Sadda, Doheny Eye Institute, pasadena, USA; ssadda{at}


Aims The aim of this study is to assess baseline characteristics of drusen preceding the development of intraretinal hyper-reflective foci (IHRF) in eyes with intermediate age-related macular degeneration (AMD).

Methods In this retrospective case-control study, longitudinal optical coherence tomography (OCT) volume data from eyes with intermediate AMD in a retina clinic population were screened. All drusen that developed overlying IHRF were marked. A random number generator was used to select for further grading three drusen that did not develop IHRF.

Results Ninety eyes (from 72 patients), including 140 drusen with overlying IHRF and 270 IHRF− drusen, were analysed. Greater drusen height, basal drusen width and overlying ellipsoid zone (EZ) and external limiting membrane disruption were associated with a significantly greater risk for IHRF development (p≤0.001). Regression analysis revealed EZ disruption increased these odds by 4.1 (p≤0.001). Each 10-µm increase in drusen height and width increased the odds by 34% (p≤0.001) and 3% (p: 0.005), respectively. Each 100-µm increase in distance from the fovea decreased the odds by 10% (p: 0.013).

Conclusions The presence of overlying EZ disruption and a greater drusen height substantially increased the risk for IHRF development, whereas drusen further from the fovea indicated reduced risk. Given the importance of IHRF as a biomarker for AMD progression, these findings may be of value in defining patient populations for future early intervention trials.

  • Macula
  • Retina
  • Degeneration

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors SS, AM and GC conceived of the presented idea. AM, SS, DS and CCW developed the theory and performed the computations. MN and STC verified the analytical methods. AM and SS investigated and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.SS: guarantor

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests SriniVas R. Sadda receives support from 4DMT, Alexion, Allergan, Alnylam Pharmaceuticals, Amgen Inc Apellis Pharmaceuticals, Astellas, Bayer Healthcare Pharmaceuticals, Carl Zeiss Meditec, Catalyst Pharmaceuticals, Centervue, GENENTECH, Gyroscope Therapeutics, Heidelberg Engineering, Iveric Bio, Janssen Pharmaceuticals, Merck & Co., Nanoscope, Nidek Incorporated, Novartis Pharma AG, Optos, Oxurion/ Thrombogenics, Pfizer, Regeneron Pharmaceuticals, Samsung Bioepis, Topcon Medical Systems, Vertex Pharmaceuticals Incorporated. David Sarraf receives support from Amgen, Bayer, Endogena Therapeutics, Genentech, Iveric Bio, Novartis and Optovue/Visionix and receives research grants from Amgen, Boehringer, Genentech, Heidelberg, Optovue/Visionix, Regeneron, and Topcon. Charles C. Wykoff receives support from 4DMT, AbbVie, Adverum, Aerie, AGTC, Alcon, Alimera, Allergan, Allgenesis, Alnylam, Annexon, Apellis, Arrowhead, Bausch + Lomb, Bayer, Bionic Vision, Boehringer Ingelheim, Chengdu Kanghong, Cholgene, Clearside, Curacle, EyePoint, Foresite, Frontera, Genentech, Gyroscope, IACTA, IVERIC Bio, Janssen, Kato, Kiora, Kodiak, Kriya, Merck, Nanoscope, NGM, Notal Vision, Novartis, OccuRx, Ocular Therapeutix, Ocuterra, OliX, ONL, Opthea, Palatin, PerceiveBio, Perfuse, PolyPhotonix, Ray, RecensMedical, Regeneron, RegenXBio, Resonance, Roche, SciNeuro, Stealth, Surrozen, THEA, TissueGen, Valo, Verana, Vitranu. Grants from ongoing relationships as a Principal Investigator with: 4DMT, Adverum, Aerie, AffaMed, Aldeyra, Alexion, Alimera, Alkahest, Allergan, Allgenesis, Amgen, Annexin, Annexon, Apellis, Asclepix, Bayer, Boehringer Ingelheim, Chengdu Kanghong, Clearside, Curacle, EyePoint, Gemini, Genentech, Graybug Vision, Gyroscope, IONIS, iRENIX, IVERIC bio, Kodiak, LMRI, Nanoscope, Neurotech, NGM, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, Opthea, Oxurion, Oxular, Oyster Point, Perceive Biotherapeutics, RecensMedical, Regeneron, RegenXBio, Roche, SamChunDang Pharm, Sandoz, Taiwan Liposome Company, UNITY, Verily, Xbrane. Stock Options (not owner) from ongoing relationships as a Consultant from Private Companies: ONL, PolyPhotonix, RecensMedical, TissueGen, Visgenx, Vitranu. Giulia Corradetti receives support from Nidek. Muneeswar Gupta Nittala receives support from Eyenuk.

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

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