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Imaging geographic atrophy: integrating structure and function to better understand the effects of new treatments
  1. Stela Vujosevic1,2,
  2. Anat Loewenstein3,
  3. Louise O'Toole4,
  4. Ursula Margarethe Schmidt-Erfurth5,
  5. Dinah Zur6,
  6. Usha Chakravarthy7
  1. 1 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
  2. 2 Eye Clinic, IRCCS MultiMedica, Milan, Italy
  3. 3 Ophthalmology Division, Tel Aviv Medical Center, Tel Aviv, Israel
  4. 4 University College Dublin, Dublin, Ireland
  5. 5 Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
  6. 6 Ophthalmology Division, Tel Aviv University, Tel Aviv, Israel
  7. 7 Centre for Public Health, Queen's University Belfast, Belfast, UK
  1. Correspondence to Dr Stela Vujosevic, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; stela.vujosevic{at}


Geographic atrophy (GA) is an advanced and irreversible form of age-related macular degeneration (AMD). Chronic low grade inflammation is thought to act as an initiator of this degenerative process, resulting in loss of photoreceptors (PRs), retinal pigment epithelium (RPE) and the underlying choriocapillaris. This review examined the challenges of clinical trials to date which have sought to treat GA, with particular reference to the successful outcome of C3 complement inhibition. Currently, optical coherence tomography (OCT) seems to be the most suitable method to detect GA and monitor the effect of treatment. In addition, the merits of using novel anatomical endpoints in detecting GA expansion are discussed. Although best-corrected visual acuity is commonly used to monitor disease in GA, other tests to determine visual function are explored. Although not widely available, microperimetry enables quantification of retinal sensitivity (RS) and macular fixation behaviour related to fundus characteristics. There is a spatial correlation between OCT/fundus autofluorescence evaluation of PR damage outside the area of RPE loss and RS on microperimetry, showing important associations with visual function. Standardisation of testing by microperimetry is necessary to enable this modality to detect AMD progression. Artificial intelligence (AI) analysis has shown PR layers integrity precedes and exceeds GA loss. Loss of the ellipsoid zone has been recognised as a primary outcome parameter in therapeutic trials for GA. The integrity of the PR layers imaged by OCT at baseline has been shown to be an important prognostic indicator. AI has the potential to be invaluable in personalising care and justifying treatment intervention.

  • Drugs
  • Imaging
  • Macula
  • Retina
  • Treatment other

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

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Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

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  • Contributors SV and UC: drafting the manuscript, literature review, revision of the manuscript and final approval. AL: drafting the manuscript and final approval. LO’T, UMS-E and DZ: drafting the manuscript, literature review and final approval.

  • 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 SV: consultant to AbbVie, Apellis, Bayer, Novartis, Hoffman La Roche and Zeiss. AL: consultant to Allergan, Bayer, Beyeonics, ForSight Labs, Notal Vision, Novartis and Roche. LO’T: consultant to Novartis and Bayer. UMS-E: contract research for Roche, Novartis, Apellis, RetInSight. Scientific consultancy for Boehringer, AbbVie, Novartis, Roche, RetInSight, Heidelberg Engineering and Stealth Bio Therapeutics. DZ: Consultant to AbbVie, Bayer, Novartis and Hoffman La Roche. UC: consultant to Apellis, Boehringer Ingelheim, Iveric and Hoffman La Roche.

  • 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.