Proteins found in the tear film are becoming a valuable resource for diagnostic testing, and have already helped researchers identify signals of ocular diseases, most notably dry eye. Osmolarity and MMP-9 testing are becoming routine. Will eye doctors also be screening their patients for neurodegenerative diseases one day? Two papers being presented this week at ARVO 2019 suggest it could happen.

Alzheimer’s

Recent imaging research has repeatedly shown that the retina can reveal some indicators of Alzheimer’s disease (AD). Now it turns out the front of the eye might do the same.

Researchers investigated the diagnostic potential of tears as a source of peripheral biomarkers for AD and presented their findings Monday at ARVO in Vancouver. They found that tear total-tau and amyloid-beta 42 (Aβ42) levels have reasonable discriminatory power for the AD state and could be diagnostic markers. They note, however, that studies with larger sample sizes are required to confirm these results.¹

The team investigated the tear biomarker level of total-tau and Aβ42 in a cohort of 25 patients with AD, mild cognitive impairment (MCI) or subjective cognitive impairment (SCI) and nine healthy controls.¹ The results confirmed that the levels of tear total-tau and Aβ42 changed with increasing AD stage. They discovered a significant increase in total-tau in tears of AD patients compared with SCI patients and MCI patients.¹

“AD is a very complex disease with RNA-splicing defects,” says Joseph Shovlin, OD, of Northeastern Eye Institute in Scranton, PA. “Using the biomarker cascade appears to be a promising frontier in identifying and hopefully eventually curing this dreaded disease.”

Given the pathological heterogeneity of AD and related dementias, future work on biomarkers must be able to characterize a patient’s underlying pathophysiology, the study authors argue in their ARVO abstract. This requires an expansion of the current biomarker panel, a critical move for a broader characterization of pathology in patients with AD by identifying different patient sub-types.¹

Parkinson’s

While the investigation into tear biomarkers for AD is in its early stages, biomarkers for Parkinson’s disease (PD) are already well known. These patients often present with non-motor features and symptoms of cholinergic dysfunction years prior to showing motor symptoms. Tear secretion from the lacrimal gland is greatly stimulated by cholinergic neurons; thus, specific proteins in tears may be altered by changes in the function of nerves regulating lacrimal secretion. Tear proteins are potential biomarkers for PD at different stages of the disease.²

Researchers from the University of Southern California evaluated whether the protein composition of basal and reflex tears differs in patients with PD vs. healthy controls; they presented their results yesterday at ARVO. They found that tear levels of alpha-synuclein (α-Syn) may be able to discriminate between PD patients and healthy controls. They note that reflex tear α-Syn levels demonstrated a greater increase and sensitivity in distinguishing PD patients from healthy controls than basal tears and illuminated differences in lactoferrin (LF) that are not seen in basal tears, offering a more reliable and sensitive source of biomarkers for PD.²

The team collected basal tears from 93 PD patients of varying disease severities and 82 healthy controls with an anesthetized Schirmer’s test. Reflex tears were collected from 84 PD patients and 83 healthy controls with an un-anesthetized Schirmer’s test. They then pooled samples from both eyes to analyze their levels of total α-Syn, oligomeric α-Syn, LF and matrix metallopeptidase-9 (MMP-9).²

They found total α-Syn was significantly decreased in basal tears in PD patients relative to healthy controls. On the other hand, oligomeric α-Syn was significantly increased in basal tears compared with healthy controls. The study findings indicated that there was no difference in LF or MMP-9 between PD patients and healthy controls in basal tears.²

The researchers found oligomeric α-Syn was significantly increased in PD patients compared with healthy controls and that total α-Syn was unchanged. In reflex tears, they note that a significant difference emerged in LF content in PD patients compared with healthy controls but not in MMP-9.²

This works adds to the body of literature documenting the patterns and presentations of PD signals in human tear film samples that may form the basis of future clinical testing protocols.