Next-Generation Diagnostics in Glaucoma

In today’s world, technology is ever-evolving; in eye care, it is being used to advance early diagnosis and treatment. One major area in which next-generation diagnostics are being investigated and applied is glaucoma care. The following article discusses a few ways that advanced technologies, including next-generation OCT imaging, AI, and adaptive optics, are being used in the management of glaucoma.

WIDEFIELD OCT

Traditionally, clinicians managing glaucoma have used separate OCT scans of the optic disc and macula to detect damage and changes within the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC). With advances allowing for 3D widefield (WF) OCT imaging, it is now possible to capture the macula and optic nerve at the same time (Figure). In a recent study, WF OCT scans provided greater diagnostic power than individual ones.¹ The study also showed that AI models were able to diagnose glaucoma most accurately based on the WF OCT scan, followed by the optic disc scan, and then the macula scan. The additional information provided by visualizing the nerve and macula together added value to the glaucoma classification process, according to the researchers.¹

To discern if this modality can be applied widely in clinic despite refractive error, a separate study evaluated both glaucomatous and nonglaucomatous eyes, including patients with high myopic prescriptions.² The results of this study agreed that WF images can be effective for monitoring glaucomatous progression in patients, even in those with high myopia.²

In addition, capturing WF OCT imaging can be a faster and more comfortable process for patients in the clinic.

OCT ANGIOGRAPHY

OCT angiography (OCTA) is a noninvasive, dye-free imaging technology used to assess the vasculature within the retina and optic nerve head. In areas of parapapillary atrophy, the choriocapillaris is also visible. OCTA uses red blood cell movement to distinguish vessels from static tissue; before, fluorescein angiography was the only way to visualize these structures.³

OCTA can be used to diagnose and track the progression of glaucoma by detecting changes in the vasculature. A 2020 study reported OCTA findings in a glaucomatous eye, including a reduction in the superficial vessel density in the peripapillary and macular areas, as well as complete loss of choriocapillaris in localized regions of parapapillary atrophy. These changes strongly correlated with the structural elements noted on OCT (such as RNFL and GCC loss) and the functional damage found on visual field testing. OCTA was found to be repeatable, allowing test trends to be more accurately followed.³

Challenges to OCTA include negative effects on the scan due to excessive patient movement, poor fixation, and vitreous opacities, to name a few. Conversely, a notable benefit of OCTA is that its vessel density reduction reaches a floor at a later stage than traditional OCT measurements, allowing more detailed tracking of progression in severe disease states. These characteristics make OCTA a valuable tool in the detection of subtle, early changes to aid in the diagnosis of glaucoma and monitoring patients with advanced disease.³

AI

AI has recently become a household tool with systems such as ChatGPT, Copilot, and Gemini, but it has been used in glaucoma in some form for years. Early machine-learning models were introduced in the 1990s and used to diagnose glaucoma through visual fields. Since then, various AI technologies have been applied to interpretations of fundus photographs, OCT, and OCTA, with use of deep-learning AI models beginning in the 2010s.⁴

Deep-learning AI is designed to mimic the human brain in the recognition and learning process with the use of artificial neurons. By applying this model to glaucoma testing, AI can detect glaucomatous patterns and help diagnose the condition earlier and more accurately, as well as help forecast disease progression.⁴

While no autonomous AI models have yet to receive regulatory approval in the United States, numerous assistive models have been integrated into imaging and visual field devices and are widely available in research and clinical settings. These models can be helpful in quantifying and interpreting testing for more accurate diagnosis and monitoring in clinic. Research has demonstrated autonomous AI reliability in screening, diagnosis, and forecasting of glaucoma, and the existence of autonomous AI-enabled models already approved for diabetic retinopathy and macular edema suggests one for glaucoma may become available.⁴

Challenges to AI use in glaucoma include a lack of standard reference data for models to “learn” from, lack of standardized evaluation and reporting of the model’s performance, concerns regarding liability, and potential ethical issues.⁴

ADAPTIVE OPTICS

The main benefit of adaptive optics is its ability to enhance an image, such as photoreceptors or details within the RNFL. First, a wavefront measurement is performed, and then aberrations are compensated for using a deformable mirror. After this, software applies a closed-loop algorithm that allows for a corrected output wavefront, which is processed by detectors such as cameras to produce significantly more precise imaging.⁵

While we can detect glaucoma early in its disease course, subtle changes are often difficult, if not impossible, to observe with conventional methods (eg, standard automated perimetry and traditional OCT). To aid in this, adaptive optics is being applied to devices such as scanning light ophthalmoscopy, fundus photography, and OCT to correct for ocular aberrations and, thereby, detect the slightest changes at a cellular level.^6,7

For example, most OCT devices measure with extremely high clarity in the axial direction but are limited in lateral resolution to about 15 μm to 20 μm, which reduces overall scan quality. Adaptive optics combats that limitation, allowing for improved resolution in 3D. Using adaptive optics, clinician can view discrete structures of the posterior segment at the cellular level, including RNFL bundles, the lamina cribosa, and photoreceptors.⁸

Clinical trials have shown that the level of detail provided by adaptive optics better enables the detection of very early glaucoma and/or slight progression.^6,7 However, it is still quite expensive and not widely available; usage is limited to research settings.^6-8

GET READY FOR THE FUTURE

While not all these new technologies are readily available in a clinical setting, advances will continue to become mainstream and affect how we manage our patients.