Clinical trial NCT04269304: Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE
Official title: Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Age-related Macular Degeneration
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: University of Basel
name: Medical University of Vienna
name: University of Michigan
name: King's College London
name: University College, London
First posted: 2020-02-13
Enrollment: 429
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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 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

Primary outcomes:
measure: Sensitivity / specificity of OCT and autofluorescence parameters.
timeFrame: 3 years
Secondary outcomes:
measure: Sensitivity / specificity of novel imaging characteristics
timeFrame: 3 years
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Harlow
country: United Kingdom
facility: The Princess Alexandra Hospital Nhs Foundation Trust
state: Essex
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
state: Hampshire
city: Newport
country: United Kingdom
facility: St Mary's Hospital
state: Isle Of Wight
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
state: Oxfordshire
city: Frimley
country: United Kingdom
facility: Frimley Health Nhs Foundation Trust
state: Surrey
city: Salisbury
country: United Kingdom
facility: Salisbury Nhs Foundation Trust
state: Wiltshire
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston Nhs Foundation Trust
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: London
country: United Kingdom
facility: Guy'S and St Thomas' Nhs Ft
city: London
country: United Kingdom
facility: St Mary's Hospital, Imperial College Healthcare NHS Trust
Study officials:
affiliation: University of Southampton
name: Andrew J Lotery, Prof
role: PRINCIPAL_INVESTIGATOR
References: