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. 2024 Mar-Apr;69(2):165-172.
doi: 10.1016/j.survophthal.2023.10.010. Epub 2023 Oct 27.

Systematic review of prognostic factors associated with progression to late age-related macular degeneration: Pinnacle study report 2

Ahmed M Hagag  1 , Rebecca Kaye  2 , Vy Hoang  2 , Sophie Riedl  3 , Philipp Anders  4 , Beth Stuart  2 , Ghislaine Traber  5 , Christian Appenzeller-Herzog  6 , Ursula Schmidt-Erfurth  3 , Hrvoje Bogunovic  3 , Hendrik P Scholl  5 , Toby Prevost  7 , Lars Fritsche  8 , Daniel Rueckert  9 , Sobha Sivaprasad  10 , Andrew J Lotery  11
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Free article

Systematic review of prognostic factors associated with progression to late age-related macular degeneration: Pinnacle study report 2

Ahmed M Hagag et al. Surv Ophthalmol. 2024 Mar-Apr.
Free article

Abstract

There is a need to identify accurately prognostic factors that determine the progression of intermediate to late-stage age-related macular degeneration (AMD). Currently, clinicians cannot provide individualised prognoses of disease progression. Moreover, enriching clinical trials with rapid progressors may facilitate delivery of shorter intervention trials aimed at delaying or preventing progression to late AMD. Thus, we performed a systematic review to outline and assess the accuracy of reporting prognostic factors for the progression of intermediate to late AMD. A meta-analysis was originally planned. Synonyms of AMD and disease progression were used to search Medline and EMBASE for articles investigating AMD progression published between 1991 and 2021. Initial search results included 3229 articles. Predetermined eligibility criteria were employed to systematically screen papers by two reviewers working independently and in duplicate. Quality appraisal and data extraction were performed by a team of reviewers. Only 6 studies met the eligibility criteria. Based on these articles, exploratory prognostic factors for progression of intermediate to late AMD included phenotypic features (e.g. location and size of drusen), age, smoking status, ocular and systemic co-morbidities, race, and genotype. Overall, study heterogeneity precluded reporting by forest plots and meta-analysis. The most commonly reported prognostic factors were baseline drusen volume/size, which was associated with progression to neovascular AMD, and outer retinal thinning linked to progression to geographic atrophy. In conclusion, poor methodological quality of included studies warrants cautious interpretation of our findings. Rigorous studies are warranted to provide robust evidence in the future.

Keywords: Age-related macular degeneration; Geographic atrophy; Macular neovascularization; PINNACLE study; Prognostic factors; Systematic review.

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Conflict of interest statement

Declaration of Competing Interest Philipp Anders is supported by the “Freiwillige Akademische Gesellschaft Basel” and “OPOS zugunsten von Wahrnehmungsbehinderten” foundations. Ursula Schmidt-Erfurth receives grant support from Genentech, Kodiak, Novartis, RetInSight and Roche and is a consultant for Apellis. Hendrick Scholl is a member of the Scientific Advisory Board of: Astellas, Boehringer Ingelheim, Gyroscope/Novartis, Janssen, Okuvision, and Third Rock Ventures. He is a consultant of Gerson Lehrman Group, Guidepoint Global, and Tenpoint Therapeutics. He is a member of a Data Monitoring and Safety Board/Committee for Belite Bio, ReNeuron Group Plc/Ora Inc., Roche, and member of a Steering Committee for Novo Nordisk. He is a co-director of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) which receives funding from the University of Basel, the University Hospital Basel, Novartis, and the government of Basel-Stadt. Daniel Rueckert is a co-founder and shareholder of IXICO Plc. Sobha Sivaprasad has received funding/fees from Bayer, Novartis, AbbVie, Roche, Boehringer Ingelheim, Optos, EyeBiotech, Biogen, and Apellis. She is a member of a Data Monitoring and Safety Board/Committee for Bayer and a member of a Steering Committee for Novo Nordisk. Andrew Lotery is a consultant for Gyroscope/Novartis, Eyebio, Complement Therapeutics, Allergan, Apellis and Tarsus Pharmaceuticals. No other disclosures were reported. No conflicts related to this project.

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