Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Ensuring the strict and accurate adherence to inclusion criteria in clinical trials for AMD is crucial

Eye (2024)Cite this article

Subjects

Age-related macular degeneration (AMD) is a major cause of vision impairment in people aged 50 and older [1, 2], affecting an estimated 196 million individuals worldwide [1,2,3]. AMD can be categorized into different stages: early AMD (i.e., drusen >63 µm), intermediate AMD with large drusen ( > 125 µm) and/or pigmentary abnormalities; and late AMD characterized by the presence of macular neovascularization (MNV) or geographic atrophy (GA) [4].

An escalating number of clinical trials are assessing various drugs that have demonstrated efficacy in treating AMD at various stages or are still under investigation with the potential for effectiveness and approval [5]. The rise in clinical trials has increased the need for patient enrolment. While enhancing diversity is crucial for generalizable results, inclusion criteria are often very restrictive [6]. However, the growing demand for AMD patients and the need for diversity might inadvertently include individuals with conditions mimicking AMD [6].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Friedman DS, O’Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PTVM, et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004; 122: 564–72. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15078675 [Accessed April 22, 2015].

  2. Fleckenstein M, Schmitz-Valckenberg S, Chakravarthy U. Age-related macular degeneration. JAMA. 2024;331:147.

    Article  CAS  PubMed  Google Scholar 

  3. Flores R, Carneiro A, Vieira M, Tenreiro S, Seabra MC. Age-related macular degeneration: pathophysiology, management, and future perspectives. Ophthalmologica. 2021;244:495–511.

    Article  CAS  PubMed  Google Scholar 

  4. Ferris FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013; 120: 844–51. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23332590 [Accessed June 21, 2015].

  5. Sarkar A, Jayesh Sodha S, Junnuthula V, Kolimi P, Dyawanapelly S. Novel and investigational therapies for wet and dry age-related macular degeneration. Drug Discov Today. 2022;27:2322–32.

    Article  CAS  PubMed  Google Scholar 

  6. Kelsey MD, Patrick-Lake B, Abdulai R, Broedl UC, Brown A, Cohn E, et al. Inclusion and diversity in clinical trials: actionable steps to drive lasting change. Contemp Clin Trials. 2022;116:106740.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Vallino V, Berni A, Coletto A, Serafino S, Bandello F, Reibaldi M, et al. Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD. Graefe’s Arch Clin Exp Ophthalmol. 2024. https://doi.org/10.1007/s00417-024-06497-8. Online ahead of print.

  8. Michaelides M, Jenkins SA, Brantley MA, Andrews RM, Waseem N, Luong V, et al. Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction. Investig Opthalmol Vis Sci. 2006;47:3085.

    Article  Google Scholar 

  9. Spaide RF. Disease expression in nonexudative age-related macular degeneration varies with choroidal thickness. Retina. 2018;38:708–16.

    Article  PubMed  Google Scholar 

  10. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013;33:1659–72.

    Article  PubMed  Google Scholar 

  11. Gliem M, Hendig D, Finger RP, Holz FG, Charbel Issa P. Reticular pseudodrusen associated with a diseased bruch membrane in pseudoxanthoma elasticum. JAMA Ophthalmol. 2015;133:581.

    Article  PubMed  Google Scholar 

  12. Giani A, Pellegrini M, Carini E, Peroglio Deiro A, Bottoni F, Staurenghi G. The dark atrophy with indocyanine green angiography in Stargardt disease. Invest Ophthalmol Vis Sci. 2012;53:3999–4004.

    Article  PubMed  Google Scholar 

  13. Li CHZ, Pas JAAH, Corradi Z, Hitti-Malin RJ, Hoogstede A, Runhart EH, et al. Study of late-onset stargardt type 1 disease: characteristics, genetics, and progression. Ophthalmology. 2024;131:87–97.

    Article  PubMed  Google Scholar 

  14. Cremers FPM, Lee W, Collin RWJ, Allikmets R. Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations. Prog Retin Eye Res. 2020;79:100861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Antropoli A, Bianco L, Condroyer C, Antonio A, Navarro J, Dagostinoz D, et al. Extensive macular atrophy with pseudodrusen-like appearance. Ophthalmology. 2024. https://doi.org/10.1016/j.ophtha.2024.04.001. Online ahead of print.

  16. Borrelli E, Bandello F, Boon CJF, Carelli V, Lenaers G, Reibaldi M, et al. Mitochondrial retinopathies and optic neuropathies: The impact of retinal imaging on modern understanding of pathogenesis, diagnosis, and management. Prog Retin Eye Res. 2024;101:101264.

    Article  CAS  PubMed  Google Scholar 

  17. Boon CJF, van Schooneveld MJ, den Hollander AI, van Lith-Verhoeven JJC, Zonneveld-Vrieling MN, Theelen T, et al. Mutations in the peripherin/RDS gene are an important cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus. Br J Ophthalmol. 2007;91:1504–11.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Boon CJF, den Hollander AI, Hoyng CB, Cremers FPM, Klevering BJ, Keunen JEE. The spectrum of retinal dystrophies caused by mutations in the peripherin/RDS gene. Prog Retin Eye Res. 2008;27:213–35.

    Article  CAS  PubMed  Google Scholar 

  19. Boon CJF, Klevering BJ, Cremers FPM, Zonneveld-Vrieling MN, Theelen T, Den Hollander AI, et al. Central areolar choroidal dystrophy. Ophthalmology. 2009;116:771–82.e1.

    Article  PubMed  Google Scholar 

  20. Setzer B, Schlesier M, Walker UA. Effects of didanosine‐related depletion of mtDNA in human T lymphocytes. J Infect Dis. 2005;191:848–55.

    Article  CAS  PubMed  Google Scholar 

  21. Borrelli E, Battista M, Gelormini F, Sacconi R, Querques L, Vella G, et al. Rate of misdiagnosis and clinical usefulness of the correct diagnosis in exudative neovascular maculopathy secondary to AMD versus pachychoroid disease. Sci Rep. 2020;10:20344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Da Pozzo S, Battaglia Parodi M, Toto L, Ravalico G. Occult choroidal neovascularization in adult-onset foveomacular vitelliform dystrophy. Ophthalmologica. 2001;215:412–4.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical Sciences, University of Turin, Turin, Italy

    Enrico Borrelli & Michele Reibaldi

  2. Department of Ophthalmology, “City of Health and Science” Hospital, Turin, Italy

    Enrico Borrelli & Michele Reibaldi

  3. IRCCS San Raffaele Scientific Institute, Milan, Italy

    Francesco Bandello

  4. Vita-Salute San Raffaele University Milan, Milan, Italy

    Francesco Bandello

  5. Department of Medicine-Ophthalmology, University of Udine, Udine, Italy

    Paolo Lanzetta

  6. Istituto Europeo di Microchirurgia Oculare—IEMO, Udine, Milan, Italy

    Paolo Lanzetta

  7. Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Bari, Italy

    Francesco Boscia

Authors
  1. Enrico Borrelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele Reibaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Bandello
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Lanzetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Boscia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the conceptualization, writing, and final review of the manuscript.

Corresponding author

Correspondence to Enrico Borrelli.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Borrelli, E., Reibaldi, M., Bandello, F. et al. Ensuring the strict and accurate adherence to inclusion criteria in clinical trials for AMD is crucial. Eye (2024). https://doi.org/10.1038/s41433-024-03232-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41433-024-03232-9

Search

Advanced search

Quick links