PRECISE Study
Research type
Research Study
Full title
Can deep phenotyping of retinal images predict response to intravitreal aflibercept therapy in Patients with Neovascular Age-Related Macular Degeneration?
IRAS ID
251170
Contact name
Sobha Sivaprasad
Contact email
Duration of Study in the UK
2 years, 3 months, 31 days
Research summary
Wet (neovascular) age related macular degeneration is the most common cause of blindness in the elderly. Anti-vascular endothelial growth factor drugs such as aflibercept are injected into the eye as the standard of care for this condition. Patients require monthly injections for 3 months and then seen and injected every 8 weeks based on a fixed protocol. However, the response rate with the drug is different. Human graders have attempted detailed grading of the retinal image scans (OCT and OCTA) taken as part of their care to identify responders. To date, we have not been able to precisely determine the markers of response. In this project, we aim to consent the 3000 patients across 10 NHS sites to collect their 4 consecutive retinal scans (OCT in 3000 and OCTA in approximately 1000 patients) done at initiation of treatment during their routine care and send these images to computer scientists in UCL as well as IBM, Australia and Europe. IBM has very powerful computers that may give a better idea of treatment response using artificial intelligence. A risk model can then be created to better inform patients of their expected response after 3 loading injections at an individual level.
Lay Summary of Results:
This study enrolled patients with treatment naïve wet age related macular degeneration and evaluated imaging markers to predict treatment response to intravitreal aflibercept on 2000 patients during the monthly loading phase (3 injections) and reviewed up to 10 weeks after the loading phase. In the study the eye scans (OCT and OCTA) of the enrolled patients were assessed using artificial intelligence to identify good, partial and poor responders to intravitreal aflibercept therapy compared to human grading outcome .The imaging markers which predicted excellent and poor responses once identified helped in predicting the visual outcome at an early course and there by facilitates early decision to switch the treatment with a different drug. The study then evaluated baseline characteristics on OCT and OCTA graded by human graders that are associated with vision change and macular improvement. Predictive models were developed to inform new trial design and change clinical practice.
Has the registry been updated to include summary results?: No
If yes - please enter the URL to summary results:
If no – why not?: N/A
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Yes
If yes, describe or provide URLs to disseminated materials: JOURNAL ARTICLES
1. Chorev M, Haderlein J, Chandra S, Menon G, Burton BJL, Pearce I, McKibbin M, Thottarath S, Karatsai E, Chandak S, Kotagiri A, Talks J, Grabowska A, Ghanchi F, Gale R, Hamilton R, Antony B, Garnavi R, Mareels I, Giani A, Chong V, Sivaprasad S. A Multi-Modal AI-Driven Cohort Selection Tool to Predict Suboptimal Non-Responders to Aflibercept Loading-Phase for Neovascular Age-Related Macular Degeneration: PRECISE Study Report 1. J Clin Med. 2023 Apr 20;12(8):3013. doi: 10.3390/jcm12083013. PMID: 37109349; PMCID: PMC10142969.2. Chandra S, Gurudas S, Burton BJL, Menon G, Pearce I, Mckibbin M, Kotagiri A, Talks J, Grabowska A, Ghanchi F, Gale R, Giani A, Chong V, Yamaguchi TCN, Pal B, Thottarath S, Pakeer RM, Chandak S, Montesel A, Sivaprasad S. Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2. Eye (Lond). 2024 Mar;38(4):757-765. doi: 10.1038/s41433-023-02769-5. Epub 2023 Oct 18. PMID: 37853106; PMCID: PMC10920623.
3. Chandra S, Gurudas S, Pearce I, Mckibbin M, Kotagiri A, Menon G, Burton BJL, Talks J, Grabowska A, Ghanchi F, Gale R, Giani A, Chong V, Chen CNT, Nicholson L, Thottarath S, Chandak S, Sivaprasad S. Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3. Eye (Lond). 2024 May;38(7):1301-1307. doi: 10.1038/s41433-023-02886-1. Epub 2023 Dec 15. PMID: 38102473; PMCID: PMC11076629.
4.Montesel A, Pakeer Muhammed R, Chandak S, Kazantzis D, Thottarath S, Chandra S, Chong V, Burton BJL, Menon G, Pearce I, McKibbin M, Kotagiri A, Talks J, Grabowska A, Ghanchi F, Gale R, Giani A, Yamaguchi TCN, Sivaprasad S. Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4. Eye (Lond). 2024 Sep;38(13):2596-2602. doi: 10.1038/s41433-024-03087-0. Epub 2024 Apr 23. PMID: 38653751; PMCID: PMC11385578.
5. Thottarath S, Gurudas S, Chandak S, Patel PJ, Kotagiri A, Pearce I, McKibbin M, Menon G, Burton BJL, Talks J, Grabowska A, Ghanchi F, Gale R, Karatsai E, Chandra S, Sivaprasad S. Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5. Eye (Lond). 2024 Oct;38(14):2737-2743. doi: 10.1038/s41433-024-03110-4. Epub 2024 May 6. PMID: 38710939; PMCID: PMC11427460.
6.Chandak S, Gurudas S, Pakeer Muhammed R, Keskin A, Thottarath S, Ghanchi F, Grabowska A, Talks SJ, Pearce I, McKibbin M, Kotagiri A, Menon G, Burton BJL, Gale R, Sivaprasad S. Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6. Eye (Lond). 2025 Aug;39(11):2194-2203. doi: 10.1038/s41433-025-03797-z. Epub 2025 May 12. PMID: 40355704; PMCID: PMC12274454.
7. Chandak S, Gurudas S, Pakeer RM, Kazantzis D, Ghanchi F, Grabowska A, Talks SJ, Pearce I, McKibbin M, Kotagiri A, Menon G, Burton BJ, Gale R, Sivaprasad S. Factors associated with achieving various visual acuity outcomes during loading doses of aflibercept 2 mg for treatment naïve exudative age-related macular degeneration: PRECISE Study Report 7. Eye (Lond). 2025 Jun;39(8):1553-1561. doi: 10.1038/s41433-025-03687-4. Epub 2025 Feb 21. PMID: 39984700; PMCID: PMC12089498.
CONFERENCE PRESENTATION-POSTERS
1.Prevalence of Bacillary Layer Detachment (BALAD) in Treatment Naive Neovascular Age-Related Macular Degeneration (nAMD) and response to treatment after loading phase of aflibercept 2 mg in the PRECISE study-Kazantzis, Dimitrios; Thottarath, Sridevi P.; Lamanna, Francesca; Keskin, Ayse Merve; Kubravi, Syed; Wijesingha, Naomi; Sivaprasad, Sobha
ARVO 2025, May 4-8 Salt Lake City, Utah, USA.2. Incidence and associations of Retinal pigment epithelial (RPE) tear post-loading phase of aflibercept 2mg in Treatment Naïve Neovascular Age-Related Macular Degeneration (nAMD-Dimitrios Kazantzis, Sarega Gurudas, Sridevi Thottarath, Swati Chandak, Shruti Chandra, Chris Holmes, Ayse Keskin, Naomi Wijesingha, Sobha Sivaprasad
Euretina Barcelona, Spain, 20/SEP/2024.3. Response of subtypes of macular neovascularisation to 2mg aflibercept loading therapy in neovascular age related macular degeneration.-Sridevi Thottarath, Sarega Gurudas, Swati Chandak, Dimitrios Kazantzis, Shruti Chandra, Ayse Merve Keskin, Syed Kubravi, Sobha Sivaprasad
Euretina Barcelona, Spain, 20/SEP/2024.If pending, date when dissemination is expected:
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: Yes
If yes, describe and/or provide URLs to materials shared and how they were shared: Publication of the study outcomes/results were shared with participants
If pending, date when feedback is expected:
If no, explain why they haven't:
Have you enabled sharing of study data with others?: Yes
If yes, describe or provide URLs to how it has been shared: The data (study results) have been shared widely via dissemination at conference meetings and publication of the study results in high quality peer reviewed open access journals (URLs to relevant material below) doi: 10.3390/jcm12083013 doi: 10.1038/s4143
If no, explain why sharing hasn't been enabled:
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: N/A
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London - Stanmore Research Ethics Committee
REC reference
19/LO/1385
Date of REC Opinion
21 Aug 2019
REC opinion
Favourable Opinion