Eyes are more than “windows to the soul” in oculomics.

By examining associations between ophthalmic biomarkers and systemic health vs disease states, they can be the “window to overall health,” Joseph J. Pizzimenti, OD, FAAO, FORS, described in his presentation on oculomics at Optometry’s Meeting 2026, hosted by the American Optometric Association in Phoenix from June 17 to June 20. The terminology and the technology may be new, he said, but the concept is not: Links between the eye and systemic disease were made with simple naked-eye observations even before the introduction of the ophthalmoscope in 1851. The idea has evolved through digital retinal photography, OCT, and semiautomated image analysis, and is now advancing further with multimodal imaging, large datasets in health care informatics, and AI-driven analysis toward precision medicine.

Dr. Pizzimenti also pointed out a fundamental physiologic advantage of ocular examination: The eye remains the only location in the body where neurologic and vascular tissues can be viewed directly, simultaneously, and noninvasively.

In his presentation, he defined biomarkers as objective biological indicators that signal disease risk, presence, or progression. Examples in oculomics include retinal and choroidal thickness, vessel caliber, vessel tortuosity, and optic nerve changes, and have been associated with systemic diseases such as Alzheimer disease, Parkinson disease, cardiovascular disease, and diabetes.

Dr. Pizzimenti said the ideal biomarker is cost-effective, noninvasive, reproducible, and capable of real-time systemic health screening through ocular evaluation.

Current oculomic evaluation incorporates both invasive and noninvasive imaging modalities, he explained. Invasive approaches include fluorescein angiography and indocyanine green angiography, while noninvasive platforms include OCT and OCTA, fundus photography, widefield and ultrawidefield imaging, fundus autofluorescence, ultrasonography, and near-infrared and multicolor imaging.

Retina

In age-related macular degeneration, the presence of reticular pseudodrusen (RPD) is a consistent risk factor for progression to both geographic atrophy and macular neovascularization, Dr. Pizzimenti said. He added that multimodal imaging that combines fundus autofluorescence and OCT offers a “new perspective” on structure-function relationships within the retina, particularly in assessments of ellipsoid zone integrity and RPD. He showed images of these biomarkers, as well as pachychoroid findings in central serous chorioretinopathy, including subretinal fluid and “shaggy photoreceptors” as visualized on OCT.

Hypertensive retinopathy and diabetic retinal disease remain central examples of ocular-systemic overlap. OCT and OCTA findings in diabetes include microaneurysms, foveal avascular zone changes, and neovascularization of the disc and elsewhere. Dr. Pizzimenti demonstrated how proper segmentation on OCTA can highlight neovascular complexes.

Neuro-ophthalmology

Neuro-ophthalmic manifestations associated with systemic disease include cranial nerve palsies, nonarteritic anterior ischemic optic neuropathy, internuclear ophthalmoplegia, and nystagmus. In hypertensive patients, he explained, internuclear ophthalmoplegia and bilateral internuclear ophthalmoplegia were identified as stroke risk factors. Dr. Pizzimenti listed several systemic conditions that are commonly associated with neuro-eye disease:

• hypertension,

• diabetes,

• carotid disease,

• giant cell arteritis,

• multiple sclerosis,

• Alzheimer disease,

• Parkinson disease,

• thyroid disease,

• sarcoidosis,

• lupus, and

• neoplastic disease.

Sickle Cell

Dr. Pizzimenti also showed one case of an African American woman in her late 40s with hemoglobin SS disease who presented asymptomatically with visual acuities of 20/30 OD and 20/20 OS. Although dilated fundus examination appeared normal, SD-OCT demonstrated macular splaying and central macular thinning in the right eye. The findings were attributed to macular ischemia from nonperfusion or prior paracentral acute middle maculopathy (PAMM).

Giant Cell Arteritis

PAMM may function as a highly specific marker for temporal artery biopsy positivity in suspected giant cell arteritis cases, he continued. Evidence suggests this finding could support earlier therapeutic decision-making using a noninvasive approach. Clinical features strongly suggestive of giant cell arteritis included jaw claudication, CRP greater than 2.45 mg/dL, neck and scalp pain, and ESR greater than 47 mm/hr.

Multiple Sclerosis

Dr. Pizzimenti described optic neuritis as a focal inflammatory or demyelinating event that may occur idiopathically or in association with systemic illness, particularly MS. In fact, he said, citing several studies, 90% of optic neuritis cases are associated with multiple sclerosis: Retrobulbar optic neuritis accounts for approximately 65% of cases, while anterior optic neuritis accounts for 35%. Retinal biomarkers in MS include retinal nerve fiber layer (RNFL) thinning and ganglion cell layer plus inner plexiform layer (GCL+IPL) thinning. Acute optic neuritis is associated with 20% to 40% thinning within 3 months.

Even in the absence of optic neuritis, MS patients have demonstrated approximately 12% thinning over time. Study findings showed the greatest RNFL thinning in temporal and inferotemporal regions. They also showed increased visual evoked potential latencies as another biomarker, as well as a correlation between RNFL thinning and reduced quality-of-life scores.

Dr. Pizzimenti noted that OCT biomarkers, low-contrast visual acuity testing, and vision-specific quality-of-life metrics are now incorporated into MS clinical trials.

What's Next

Despite rapid progress, several barriers to implementation remain, including standardization across OCT platforms, data privacy and security, development of sufficiently large datasets for AI training, infrastructure limitations, workflow integration, and reimbursement and cost-effectiveness issues. Retinal measurements also continue to be affected by image quality variability, artifacts, and technical differences between devices.

Dr. Pizzimenti suggested that future advances will likely depend on improved automation, multimodal data integration, adaptive optics imaging, and stronger collaboration among health care professionals. “Oculomics holds immense promise for the future of health care,” he said. “It is a novel, noninvasive tool to assess vital organ health, and allows for early diagnosis of major systemic diseases. It could replace invasive and expensive tests.”

Optometrists are among the health care professionals who will be expected to participate directly in the expansion of oculomics, he said, alongside ophthalmologists, neurologists, cardiologists, nephrologists, diabetologists, and primary care physicians.

Dr. Pizzimenti highlighted efficient prescreening for clinical trials as a particular future research opportunity. He added that further research could also address expanding the scope of disease prediction, exploring adaptive optics and other imaging modalities, and evidence-based validation for oculomics in health care.

"It is my hope to clarify terms like 'oculomics' and 'biomarkers,’” Dr. Pizzimenti told Optometric Management. “These are not new concepts but rather new terminology that describes much of what we are already doing in optometry. Oculomics describes the intersection of retinal imaging, health care informatics, and AI, and it has the potential to forever change health care for the better!"OM