Table of Contents

EyeLife (EYEL)

Eyelife is one of Lifelines' additional assessments.
This assessment was a collaboration between Lifelines and the UMCG Department of Opthalmology.
The goal of the assessment was to quantify ocular health in the general ageing population, in particular the prevalence of glaucoma, using an extensive eye exam. In addition, the goal was to determine if a population-based screening of early glaucoma will be feasible if performed in people genetically predisposed to develop the disease1)

Background

Glaucoma is an insidious and progressive age-related disorder which can be permanently debilitating if not addressed in time. Due to lack of symptoms in the early stages, screening for early-onset cases could be very helpful to prevent blindness. With current tests (mainly eye pressure measurements and visual field testing) population-based screening is not cost-effective. Preselection based on risk factors could change this, and make screening feasible through only examining those identified as high risk. There are numerous studies that have elucidated candidate genes associated with glaucoma risk, suggesting that a genetic pre-screen could be the way to go in the future. The Lifelines cohort is ideal for the evaluation of such a pre-screen: the participants are genotyped already and, importantly, they were not involved in any of the studies that elucidated candidate genes associated with glaucoma, thus enabling an independent evaluation.

Protocol

EyeLife ran between Q2 of 2019 and Q4 of 2022.
~1800 UGLI-genotyped participants aged 55 years and older, pre-screened to have a high or low genetic risk score for glaucoma, were invited to visit the UMCG Policlinic of Ophthalmology for an eye exam.
A total of ~1000 participants completed the eye exam, in which the following parameters were tested:

Refraction: Visual acuity and refraction were measured for both eyes with an autorefraction device. The participant is seated with their forehead and chin placed on rests on the device. They are asked to focus on an image within the device while the auto-refraction occurs. Next, a letter chart is projected and the visual acuity is determined. The visual acuity threshold for abnormality is defined as <0.5.

Intraocular Pressure: The intraocular pressure (IOP) is measured via non-contact tonometry. The participant is seated with their head resting in front of the device. Once the eye is correctly aligned, there is a small puff of air directed to the eye’s surface which estimates the IOP. Three measurements are taken per eye, and the median of these measurements will be the final estimate of the IOP for each eye at the time of examination. If the highest value of both eyes is above 21 mmHg, then the IOP is considered abnormal.

Visual Field: Visual field is examined with a frequency doubling technology perimeter (FDT). In this non-invasive test the participant is seated placing their forehead onto the visor of the FDT machine with the subject focusing on a central spot within the machine. The visual field (VF) of the subject is phenotyped using the C-20-1 screening test. The participant performs the test one eye at the time, and while their chin is resting in the device they have their uncovered eye focused at the central point of the screen, and respond by clicking a remote when light stimuli appears in the periphery. If the participant does not respond to one or more light stimuli at P<0.01 (the equivalent to the 1st percentile of the threshold in the population), the test is repeated. Only if the same test location(s) is/are abnormal again, the test is considered abnormal.

Structural Layers of the eye (OCT): Participant is seated and asked to place their chin on the device (OCT machine), and is required to focus at a central point within the device. The device scans the structural layers of the eye and assess their thicknesses, including the central cornea thickness (CCT) via pachymetry, and all retinal layers relevant to glaucoma. The OCT machine uses low coherence interferometry (with harmless, low intensity infrared radiation) to generate cross-sectional images of ocular tissue. The participants’ measures are compared to an age and sex-matched normality database within the device, and a report of the scan is created. For defining abnormality, the built-in classification is used.

Fundus Photograph: The fundus photograph is taken to obtain a clear view of the entire posterior pole of the eye, including the optic disc, the retinal blood vessels, and the macula. Within glaucoma there can be pronounced optic disc cupping which is measurable via the fundus photo. With the participant sitting with their chin and forehead resting on the machine, a photo is taken when the eye is adequately positioned.

Eye Dryness Measurement: Eye moisture levels are obtained via the Schirmer’s test. A strip of paper is gently placed on the temporal side of each bottom eyelid. The participant closes their eyes and tear production is observed on the test strip after 5 minutes.

Variables

1)
Neustaeter, A. et al. (2021) Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife); BMC Ophthalmol 21(1):18