Can Tear Biomarkers Be A Surrogate Marker For Retinal Pathologies?

Ocular surface conditions has benefitted from the use of tear fluid-based biomarkers in the disease stratification, treatment planning and response due to the proximity of the biomarker sample to the tissue of interest. However, biomarkers from sample obtained from close to the tissues in retinal conditions such as Retinopathy of Prematurity (ROP) and diabetic retinopathy (DR) include invasive strategies. Further, it is also difficult to determine the levels of dopamine (DA) produced in the retina that has impact on the development of myopia. Hence, in the current study, tear fluid-based biomarkers were studied in the ROP, DR and myopia to determine the potential use of tear fluid biomarkers in the management of these conditions.

Narayana Nethralaya (a tertiary eye care teaching hospital), Bengaluru, India.

Tear fluid (TF) were collected from pre-term infants, children with and without myopia and patients with DR using sterile Schirmer’s strips. The levels of proangiogenic factor and inflammatory factors were determined by multiplex ELISA in the TF of (i) preterm infants without ROP at first visit and did not develop ROP thereafter (No-ROP, controls; n=77); (ii) preterm infants with ROP at first visit (ROP; n=75) and (iii) Preterm infants without ROP at first visit but developed ROP in subsequent visits (No-ROP to ROP; NRR; n=23). Similar assessments of these factors were also performed in TF of adult control subjects (n=15) and patients with DR (n=20). TF DA levels were measured by ELISA in emmetropes (n=30) and myopes (n=70).

Levels of angiogenic factors such as VEGF, Angiogenin, Angiopoetin-2 and PDGF-AA; and inflammatory factors such as IFNα2, RANTES, IP-10, MCP1 and MIG were significantly lower in TF of NRR infants compared to controls. Levels of IL-1β, BDNF and β2microglobulin were significantly higher in TF of NRR infants compared to controls. Angiogenin IP-10 and IL-33 were significantly higher in ROP infants compared to controls. Similarly, TF angiogenic and inflammatory factors were observed to be significantly higher in DR compared to controls. Finally, TF DA level was significantly lower in myopes compared to emmetropes.

Significant differences were observed in the levels of TF biomarkers in ROP, DR and myopes. The findings demonstrate the feasibility of using tears-based molecular biomarkers for retinal conditions (ROP, DR) and myopia during routine screening for molecular factors-based risk categorization, prognostication, treatment planning and follow-up.