Could Tears Hold the Key to Earlier Detection of Brain Tumors?

Early diagnosis of brain tumors is critical for survival and treatment success. Although MRI is currently the gold standard, limited access and unnecessary referrals burden the healthcare system. Noninvasive, low-cost, rapid biomarker tests are therefore needed. As a plasma ultrafiltrate with a wide variety of proteins, tears are a biologically attractive matrix for this purpose.

The main aim of these studies is to use tear biomarkers for early detection of brain tumors and develop the method, before MRI referral in primary care, as a triage tool . They also aim to investigate whether specific metabolites in glioma subtypes (e.g., IDH-mutant), such as D-2-hydroxyglutarate, D-2HG, can be detected in tears, testing the clinical value of subtype-specific biomarkers (Brain Research UK project).

• Sample Collection: Tear collection using Schirmer strips; a low-cost method readily applicable in routine clinical practice.
• Analysis: Quantitative proteomics based on ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS).
• Standardization: A 2025 methods publication (Comito et al.) validated reliable extraction and measurement from Schirmer strips.
• Internal Standards: Nonhuman proteins (e.g., bovine albumin) compensated for extraction/digestion losses.
• Subtype-Specific Biomarker: In IDH-mutant gliomas, sensor development for tear D-2HG is under investigation (Brain Research UK).

• In the pilot study: Patients with brain tumors and controls could be distinguished with ≈95% accuracy.
• In the methodology study: Albumin, lysozyme and lactoferrin were quantified from Schirmer strips with 84–95% recovery.
• In real samples: No significant difference between direct tear analysis and analysis via Schirmer strips; bias <8%.

Tear biomarkers show promise for noninvasive, rapid, cost-effective brain tumor screening. Potentially usable in primary-care triage before MRI, this approach could both improve patient flow through the healthcare system and accelerate early diagnosis. Measuring subtype-specific metabolites could also enable personalized diagnosis and monitoring.

• INFORM and similar large-scale, multicenter validations should continue.
• Tear biomarker panels should be standardized and clinical test kits developed.
• For use in GP practice, rapid sensor-based devices should be made suitable for clinical integration.
• Tear biomarkers could be evaluated not only for diagnosis, but also for treatment response and tumor progression monitoring .