Summary: Researchers have developed a new ophthalmological device that can detect degenerative visual problems such as age-related macular degeneration long before the onset of the first symptoms.
Researchers at an EPFL lab have developed an ophthalmological device that can be used to diagnose some degenerative eye disorders long before the onset of the first symptoms. In early clinical trials, the prototype was shown to produce images with a sufficient degree of precision in just five seconds.
Research into treatments to stop or limit the progression of degenerative eye disorders that can lead to blindness is moving ahead apace. But, at present, there is no device that can reliably diagnose these conditions before the first symptoms appear.
These disorders, the best-known of which is age-related macular degeneration (AMD), involve changes to the eye’s photoreceptors. And they all have the same root cause: the deterioration of the retinal pigmentary epithelium (RPE), a layer of cells that sits behind the photoreceptors.
The device developed at EPFL’s Laboratory of Applied Photonics Devices (LAPD) observes changes in the RPE before the onset of symptoms, providing researchers with the first-ever in vivo images in which cells can be differentiated. Armed with this early detection capability, clinicians will be able to diagnose these disorders before irreversible symptoms occur.
The results of the first clinical trial have been published in a paper in the journal Ophthalmology Science.
Observing changes in the cells behind the photoreceptors
In addition to causing AMD, the deterioration of the RPE is behind a number of other eye disorders, including retinitis pigmentosa and diabetic retinopathy.
Located between the photoreceptors and the choroid (a thin layer of tissue containing the vessels that carry blood to the retina), the RPE plays an important role in maintaining visual function and preserving the health of the eye’s rods and cones.
Several research groups have studied these cells under the microscope—in vitro—to determine their properties and to observe the morphological changes that occur with aging but also with the onset and progression of retinal disorders such as AMD and retinitis pigmentosa.
Until now, however, there has been no simple and reliable method for observing the RPE in a live patient—in vivo—for early detection and ongoing monitoring of these conditions.
Oblique light beams hold the key
Various attempts have been made to design a device that allows clinicians to examine the RPE. But each has so far failed on the grounds of inadequate resolution, patient safety concerns or excessively long exposure times.
The team at EPFL developed a retinal camera that features two oblique beams, trained on the white of the eye, coupled with an adaptive optical system that corrects distortions in the light waves to produce a clear image.
This technology, dubbed Transscleral Optical Imaging, is similar to existing retinal imaging systems in its use of infrared light beams.
But, according to Christophe Moser, who heads the LAPD at the School of Engineering, it has one key difference: “The beams focus obliquely through the white of the eye, which circumvents the problem of excess light caused by the highly reflective cone photoreceptor cells, located in the center of the eye, when you illuminate the retina via the pupil.”
Armed with this early detection capability, clinicians will be able to diagnose these disorders before irreversible symptoms occur. Image is in the public domain
The light waves are then captured by the camera as they exit the eye through the pupil. The team had something of a eureka moment when they saw the first clear image on screen, since it was the first time anyone had observed this part of the human body using a clinically compatible imaging camera.
A first clinical trial involving 29 participants
The researchers developed a clinical prototype in partnership with EarlySight, a spin-off from the same EPFL lab. With an exposure time of less than five seconds—a key speed advantage for potential diagnostic use—the camera is capable of capturing 100 raw images. Algorithms then align and aggregate the raw footage to produce a single, high-quality image on screen.
The interface features five buttons, each corresponding to a predefined area of the eye, allowing the desired image to be selected. Users can also click anywhere on the diagram of the back of the eye to select the precise area they want to image.
The prototype device, known as Cellularis, was developed as part of the European Union’s EIT Health ASSESS project, in partnership with Francine Behar-Cohen’s research team at the French National Health and Medical Research Institute (INSERM) in Paris, and with the clinical research center at Jules-Gonin Eye Hospital in Lausanne.
The camera was then assessed in a clinical trial—led by Irmela Mantel, a physician associate at the Medical Retina Unit of Jules-Gonin Eye Hospital—designed to evaluate the device’s ability to produce clear RPE images in 29 healthy volunteers. In each case, the images generated by the camera were precise enough to quantify the morphological characteristics of the participants’ RPE cells. They were stored in a database for future contribution to medical research.
“The morphology of these cells, which play an essential role in retinal function, is a strong indicator of their health,” says Laura Kowalczuk, a scientist at EPFL and at Jules-Gonin Eye Hospital, and the paper’s lead author.
“The ability to precisely detect RPE cells and observe morphological changes occurring in them is vital to the early detection of degenerative retinal disorders and to monitoring the efficacy of new treatments.”
About this age-related macular degeneration research news
Author: Press Office
Contact: Press Office – EPFL
Image: The image is in the public domain
Original Research: Open access.
“in vivo Retinal Pigment Epithelium Imaging using Transscleral OPtical Imaging in healthy eyes” by Laura Kowalczuk et al. Ophthalmology Science
in vivo Retinal Pigment Epithelium Imaging using Transscleral OPtical Imaging in healthy eyes
To image healthy retinal pigment epithelial cells (RPE) in vivo using Transscleral OPtical Imaging (TOPI) and to analyze statistics of macular RPE cell features as a function of age, axial length (AL) and eccentricity.
Single-center, exploratory, prospective, and descriptive clinical study.
49 eyes (AL: 24.03±0.93 mm; range: 21.88 – 26.7 mm) from 29 participants aged 21 to 70 years (37.1±13.3 years; 19 males, 10 females)
Retinal images, including ultra-wide field fundus photography and spectral-domain optical coherence tomography, AL and refractive error measurements were collected at baseline. For each eye, 6 high resolution RPE images were acquired using TOPI at different locations, one of them being imaged 5 times to evaluate the repeatability of the method. Follow-up ophthalmic examination was repeated 1 to 3 weeks after TOPI to assess safety. RPE images were analyzed with a custom automated software to extract cell parameters. Statistical analysis on the selected high-contrast images included calculation of coefficient of variation (CoV) for each feature at each repetition, Spearman and Mann-Whitney tests to investigate the relationship between cell features and eye and/or subject characteristics.
Main Outcome Measures.
RPE cell features such as density, area, center-to-center spacing, number of neighbors, circularity, elongation, solidity and border distance CoV.
Macular RPE cell features were extracted from TOPI images at an eccentricity of 1.6° to 16.3° from the fovea. For each feature, the mean CoV was under 4%. Spearman’s test showed correlation within RPE cell features. In the perifovea, the region in which images were selected for all participants, longer AL significantly correlated with decreased RPE cell density (R Spearman, Rs=-0.746; p<0.0001) and increased cell area (Rs=0.668; p<0.0001), without morphological change. Aging also significantly correlated with decreased RPE density (Rs=-0.391; p=0.036) and increased cell area (Rs=0.454; p=0.013). Lower circular, less symmetric, more elongated and larger cells were observed over 50 years.
The TOPI technology imaged RPE cells in vivo with repeatability of less than 4% for the CoV and was used to analyze the influence of physiological factors on RPE cell morphometry in the perifovea of healthy volunteers.