We will conduct a prospective non-interventional study including 400 early AMD patients (=600 untreated early AMD eyes, including both unilateral (AREDS IV) and bilateral (≥AREDS II)) over 3 years to specifically investigate the morphological sequence of events preceding the conversion towards late AMD. All patients will be followed by OCT imaging every 4 months to detect the earliest focal sites of disease progression. As soon as focal areas of change are observed by the VRC, a targeted follow-up schedule will be triggered to investigate the events at that area of change in a targeted manner.
Full Title of Study: “Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study – PINNACLE”
- Study Type: Observational
- Study Design
- Time Perspective: Prospective
- Study Primary Completion Date: December 2023
We will recruit patients with 1) intermediate AMD in one eye and advanced AMD in the non-study eye or 2) patients with bilateral intermediate AMD (where both eyes will be included). As some participants are symptomless at the stage of intermediate AMD, we will recruit from hospital databases including imaging databases and ophthalmology and optometry practices and engagement with Patient Societies e.g. the Macular Society and patient public involvement meetings. There will be four clinical sites performing detailed assessments on 50 patients each and, to increase sample size, an additional eight referral sites in the UK who will each enrol and follow 25 study patients by SD-OCT every 4 months. The acquired images from these referral sites will be sent to the Vienna Reading Centre for morphological identification of focal events. If a focal event is detected, participants will then be referred for a detailed, targeted assessment at either the University of Southampton or Moorfields Eye Hospital as detailed below. After consent, patients will undergo visual function tests (ETDRS visual acuity, microperimetry) and multimodal imaging including fundus photographs, OCT scans, OCT angiography, autofluorescence and adaptive optics imaging. The visual function tests will be repeated annually and the multimodal imaging will be done at 4 monthly intervals for 3 years. Blood will be taken at the first visit for DNA analysis. 200 patients (main cohort) will undergo dense retinal phenotyping at 10 visits. Medical and smoking history, genotype and body mass index will also be included in the analysis as has been done previously. As well as structural tests, functional tests will be performed at baseline and end of the study using both microperimetry (a type of visual field test to create a "retinal sensitivity map" of the quantity of light perceived in specific parts of the retina) to identify focal changes and low luminance visual acuity to assess global changes. To increase sample size but make the study feasible an additional 200 patients at UK referral sites will undergo 4 monthly OCT and be referred to Southampton / Moorfields for dense phenotyping only if a focal event is detected by OCT.
Arms, Groups and Cohorts
- Intermediate Age-Related Macular Degeneration Patients
Clinical Trial Outcome Measures
- Sensitivity / specificity of OCT and autofluorescence parameters.
- Time Frame: 3 years
- Identified by machine learning (ML) at predicting disease progression defined as focal conversion towards advanced AMD e.g. change in drusen volume, development of new geographic atrophy / choroidal neovascularisation.
- Sensitivity / specificity of novel imaging characteristics
- Time Frame: 3 years
- For example, AO-OCT, OCT-A, at predicting disease progression; ROC curves; time from development of imaging change to development of these end-points; structure-function correlation; structure-genotype correlation; predictive risk models.
Participating in This Clinical Trial
- Subjects ≥ 55 years with either intermediate AMD (as defined by Ferris et al PMID: 23332590) in both eyes, i.e. large drusen > 125 um and/or any definite hyper- or hypopigmentary abnormalities associated with medium or large drusen; or intermediate AMD as defined above in one eye (study eye) and advanced AMD (geographic atrophy or choroidal neovascularization secondary to AMD) in the other eye. – Subjects should have media clarity and pupillary dilation for adequate imaging and functional tests. Exclusion Criteria:
- Co-existent ocular disease, which might affect visual function or retinal morphology – Established glaucoma in either study eye or fellow eye with evidence of visual field loss or retinal nerve fibre loss (ocular hypertension is not an exclusion criterion unless associated with visual field loss or retinal nerve fibre loss in either eye). – Cataract sufficient to affect retinal imaging – Myopia > minus 6 diopters or a history of myopia > minus 6 diopters if patient has had cataract / refractive surgery. – Major ocular surgery 3 months prior or anticipated within the next 6 months following enrolment. – Taking drugs known to cause retinal toxicity such as hydroxychloroquine or tamoxifen – OCT evidence of geographic atrophy (or complete RPE and outer retinal atrophy (cRORA). This is (1) a region of hypertransmission of at least 250 mm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 mm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. – OCT evidence of choroidal neovascularization e.g sub-retinal scar tissue, sub-retinal fluid or intra-retinal fluid associated with a pigment epithelial detachment
Gender Eligibility: All
Minimum Age: 55 Years
Maximum Age: 90 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- University of Southampton
- University College, London
- Provider of Information About this Clinical Study
- Overall Official(s)
- Andrew J Lotery, Prof, Principal Investigator, University of Southampton
- Overall Contact(s)
- Andrew J Lotery, Prof, 023 8120 5049, A.J.Lotery@soton.ac.uk
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