Glaucoma is one of the leading causes of blindness due to damage to the optic nerve, commonly from elevated eye pressure. Early diagnosis is key to preventing irreversible damage to the optic nerve.
This article will review advancements in glaucoma diagnostic technology while identifying existing challenges.
Brief overview of existing glaucoma technologies
Early steps in diagnosing glaucoma begin with a funduscopic examination of the optic disc and retinal nerve fiber layer (RNFL). We can monitor and quantify progressive changes associated with glaucoma with the technology currently available.
Current technology for the diagnosis of glaucoma aims to provide information on:
- RNFL
- Ganglion cell complex
- Retinal blood flow
- Intraocular pressure (IOP)
- Visual field
- Corneal hysteresis
Optical coherence tomography (OCT) and OCT angiography (OCT-A)
Optical coherence tomography (OCT) is an imaging technique that utilizes light waves to create cross-sectional images of the retina. With this image, we can visualize the layers of the retina, which helps measure changes in RNFL thickness and detect ganglion cell loss.1
OCT angiography (OCT-A) is a non-invasive technique that does not require the use of dyes to visualize retinal blood flow. It works by utilizing laser technology to reflect light on the surface of red blood cells, allowing for the visualization of vessels supplying the eye and eliminating the need for intravenous dye.
Detecting changes in ocular blood flow is crucial for diagnosing glaucoma, as decreased perfusion can contribute to optic nerve damage and cell loss.1
Tonometry
Tonometry measures intraocular pressure (IOP), with readings above 21mmHg being a key risk factor for glaucoma.2
Current technology offers various accessible tonometry options, such as:
- iCare: A portable rebound tonometer
- Tonopen: Another portable option using contact applanation technology,
- Standard Goldmann applanation tonometer: Considered the gold standard for tonometry
There is also a non-contact method of measuring IOP using air-puff tonometry, where a controlled amount of air is delivered to the cornea then the amount of force required to flatten the cornea is measured.3
Perimetry
Perimetry, or visual field testing, is useful in establishing a baseline and tracking glaucoma progression. The Humphrey Field Analyzer in the 24-2 test pattern is a standard test ordered by professionals to assess for the presence of visual field defects in a routine glaucoma assessment.4
Other visual field tests can be ordered, including a 30-2 or 10-2; the difference between all three is the number of degrees around the fovea the visual field is measuring.
Glaucoma follows the pattern of peripheral vision loss and, as the disease progresses, may affect central vision, making a 24-2 or 30-2 more appropriate first-line may affect central vision as the disease progresses test to evaluate glaucoma. Meanwhile, a 10-2 visual field would be more helpful in detecting changes to central vision.5
Adaptive optics
Adaptive optics optimize the visualization of retinal structures by measuring and correcting for ocular aberrations. Retinal imaging can be disturbed by optical aberrations caused by factors that alter how an image is focused on the retina, such as corneal irregularities, lens imperfections, refractive errors, age-related changes, and tear film instability.
Adaptive optics corrects these aberrations using a deformable mirror that functions as a wavefront corrector.6 This is useful for detecting early glaucomatous changes that may not be able to be detectable with standard imaging
Corneal hysteresis
Corneal hysteresis (CH) measures the corneal biomechanics by its ability to absorb and dissipate energy. Corneal hysteresis is commonly measured with an Ocular Response Analyzer (ORA), which delivers a puff of air to the corneal surface and then measures the IOP when the cornea flattens and returns to its standard configuration.
The difference between the two pressures is the corneal hysteresis. A lower CH is associated with an increased risk of glaucoma progression as the cornea is less able to compensate for changes in pressure.7
Current challenges in glaucoma diagnosis
Early detection
A major challenge in diagnosing glaucoma is early detection, as patients often don't show symptoms until significant damage has already occurred. Current technology also has limitations in early detection; for example, OCT can only reveal RNFL loss after substantial damage, and perimetry depends heavily on patient cooperation to generate accurate results.
Diagnosing normotensive glaucoma
Diagnosing normotensive glaucoma, where IOP remains within the normal range of 12 to 21 mmHg, presents a challenge because the primary risk factor for glaucoma detection—elevated IOP—is not applicable. An emerging technology, the multi-excitation optical coherence elastography system (OCE), aims to address this challenge by assessing corneal biomechanics and providing a true-biomechanically corrected IOP measurement.
OCE induces local tissue displacement through a selected excitation method, such as static, vibration, or transient wave propagation.8 An OCT will then measure the wave propagation to evaluate the corneal elasticity.8
In the setting of normotensive glaucoma, the structure and biomechanics of the cornea can be affected due to the chronic stress and remodeling that is associated with the disease, leading to an elevated corneal stiffness. With the use of OCE along with OCT, these changes can be detected and valuable for diagnosis.9
Standardizing data for deep learning/AI systems
Artificial intelligence (AI)/deep learning (DL) systems are making their way into glaucoma diagnostics; however, standardizing data for these systems remains challenging. Creating standardized datasets for AI systems to diagnose glaucoma is difficult due to inconsistent dataset quality, limited detailed clinical records, and varying image quality.
These issues make establishing a uniform protocol for designing effective AI systems is challenging.10
A look at emerging glaucoma technologies
AI- and DL-based systems for glaucoma screening
AI/DL-based systems are being developed to quantify optic cup, disc, and rim characteristics in fundus images, retinal layers in OCT images, and patterns of VF loss, all factors used in diagnosing glaucoma.11
One AI-based system now available, RETfound, is designed to detect markers of eye disease from OCT images, enhancing the ability to note glaucomatous changes.12
Diffusion tensor imaging (DTI) in glaucoma diagnosis
Diffusion tensor imaging (DTI) is a tool for imaging the white matter of the optic nerve. This imaging method uses magnetic resonance imaging (MRI)-based technology to assess neurological structures related to visual pathways, including the optic nerve, optic chiasm, optic tract, lateral geniculate nucleus, and optic radiations. This is useful in glaucoma as a smaller lateral geniculate nucleus is associated with the disease.13
Research also shows that decreased fractional anisotropy of the optic tract, measured through DTI, can be a biomarker of glaucoma.13 With this noninvasive technology, we can gain more insight into the relationship between neurologic structural changes and optic nerve health.
Flavoprotein fluorescence imaging in POAG patients
Flavoprotein fluorescence (FPF) imaging may improve the ability to detect primary open-angle glaucoma (POAG). Mitochondria release flavoprotein fluorescence when under oxidative stress. Levels of FPF are measured using fluorescence lifetime imaging which quantifies the ratio of oxidized flavoproteins to reduced flavoproteins in mitochondria.14
Research has shown that patients with glaucoma have higher levels of FPF around the optic nerve head, with the levels correlating to the degree of glaucoma severity.15 By detecting FPF changes in retinal ganglion cells, this imaging provides a new approach to glaucoma diagnosis.15
Technology to monitor IOP at home
Patients can now track their IOP at home with current technology, including:
- iCare HOME2: The iCare HOME2 tonometer utilizes the exact rebound tonometry mechanism as the iCare used in the clinical setting. This device has a user-friendly feature where the probe shines red when not held correctly and green when held correctly and is ready to take measurement.16
- Sensimed Triggerfish: The Sensimed Triggerfish contact lens sensor is designed for 24-hour wear and works by detecting changes in the cornea's curvature. Changes in cornea shape are related to changes in IOP, allowing this data to be used to monitor IOP throughout the day.17
- Eyemate System: The Eyemate System, by Implandata, is a sensor implanted in the subchoroidal space to directly measure the hydrostatic pressure of aqueous humor.18
Overall, tracking IOP at home and patterns throughout the day is beneficial for managing glaucoma and provides a way for patients to play an active role in their care.
Images of the iCare HOME2, Sensimed Triggerfish, and Eyemate System, respectively.
Virtual reality perimetry
The current standard visual field test relies heavily on patient compliance, and patients often report difficulties while taking the test, which can make the visual field test less reliable.
Systems, including VisuALL by Olleyes and Re:Vive 2.0 by Heru, offer immersive and engaging ways to assess the visual field using a virtual reality headset which can be more convenient for the patient and improve patient compliance.19
Genetic testing for congenital glaucoma
Genome-wide association studies (GWAS) provide insights into congenital glaucoma's hereditary factors. Identifying the associated genetic markers can allow for screening and treatment of glaucoma to be started early, significantly decreasing the risk of vision loss.20
Conclusion
Overall, current technology has progressed significantly in diagnosing glaucoma, but challenges with early detection remain.
However, advancements in diagnostic technology, from changes in how visual fields are administered to at-home IOP monitoring, show significant potential to enhance how healthcare professionals detect and manage glaucoma.
