Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE
- Conditions
- Age-related Macular Degeneration
- Registration Number
- NCT04269304
- Lead Sponsor
- University of Southampton
- Brief Summary
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 a minimum of 1 year to specifically investigate the morphological sequence of events preceding the conversion towards late AMD. All patients will be followed by Optical Coherence Tomography (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 Vienna Reading Center (VRC), a targeted follow-up schedule will be triggered to investigate the events at that area of change in a targeted manner.
- Detailed Description
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 United Kingdom who will each enrol and follow 25 study patients by Spectral Domain Optical Coherence Tomography (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 a minimum of 1 year. Blood will be taken within the first year for DNA analysis.
200 patients (main cohort) will undergo dense retinal phenotyping at a minimum of 4 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 429
- 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.
- 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 Retinal Pigment Epithelium (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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Sensitivity / specificity of OCT and autofluorescence parameters. 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.
- Secondary Outcome Measures
Name Time Method Sensitivity / specificity of novel imaging characteristics 3 years For example, Adaptive Optics OCT (AO-OCT), OCT-A, at predicting disease progression; Receiver Operating Characteristic (ROC) curves; time from development of imaging change to development of these end-points; structure-function correlation; structure-genotype correlation; predictive risk models.
Trial Locations
- Locations (12)
University Hospital Southampton
🇬🇧Southampton, Hampshire, United Kingdom
University Hospitals Bristol and Weston Nhs Foundation Trust
🇬🇧Bristol, United Kingdom
Medical University of Vienna
🇦🇹Vienna, Austria
St Mary's Hospital
🇬🇧Newport, Isle Of Wight, United Kingdom
Moorfields Eye Hospital
🇬🇧London, United Kingdom
University Hospital Basel
🇨🇭Basel, Switzerland
The Princess Alexandra Hospital Nhs Foundation Trust
🇬🇧Harlow, Essex, United Kingdom
Guy'S and St Thomas' Nhs Ft
🇬🇧London, United Kingdom
Frimley Health Nhs Foundation Trust
🇬🇧Frimley, Surrey, United Kingdom
Salisbury Nhs Foundation Trust
🇬🇧Salisbury, Wiltshire, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
St Mary's Hospital, Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom