Pterygium Pathology: A Prospective Case-Control Study on Tear Film Cytokines

Abstract

Purpose : To investigate interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF) levels in the tear film as potential biomarkers in pterygium.

Methods : Our study included 38 eyes of 19 patients (primary pterygium (PPt), n=15; recurrent pterygium (RPt), n=8; pinguecula (Pi), n=5; and unaffected contralateral eyes (PHC), n=10) and 37 eyes of 19 age- and gender-matched healthy controls (HC). Pterygia were graded according to the Johnston, Williams & Sheppard's classification. Ocular photographs and tear film samples were collected pre-operatively, at 2 weeks, 3 months and 1 year post-operatively. Tear film levels of IL-6, IL-8 and VEGF were determined through cytometric bead array analysis. Overall vascularized area (%) and pterygium size (%) were calculated using a matlab-based, in-house processing software (figure 1A) and ImageJ (figure 1B/C), respectively. Surgically resected tissues were processed for haematoxylin-eosin staining and immunohistochemistry.

Results : Tear samples taken before surgery from affected eyes (AE) with PPt (n=14) and RPt (n=7), show a mild, non-significant increase in IL-6, IL-8 and VEGF levels compared to healthy eyes (n=37); mean levels (± SEM) of IL-6 [HC=17.51 ± 2.11, AE=31.81 ± 6.93], IL-8 [HC=101.71 ± 27.19, AE=122.91 ± 40.19] and VEGF [HC=80.25 ± 11.06, AE=80.25 ± 11.06] pg/mL. The cytokine levels in the unilateral AE (n=8,PPt+RPt) show a spike 2-weeks post-surgical resection, followed by a drop to match baseline levels as seen in healthy individuals (figure 2A). However, the AE subgroup analysis (n=17) showed significantly higher levels of VEGF in PHC compared to HC (figure 2B). A positive correlation was detected between (I) IL-6 and VEGF secretion and (II) the corneal vascularized area (%) and size of pterygium (%). Age, gender and lesion grade were non-confounding factors. Histologically, pterygium samples displayed tumour-like characteristics such as epithelial-to-mesenchymal transition and loss-of-polarity, supporting the possibility that pterygium is a neoplastic-like growth disorder.

Conclusions : There was no overall significant difference between the AE group and the healthy control group for the three cytokines measured. However, it might be more relevant to consider the individual patients' cytokine level shifts from baseline over time as markers of disease resolution and/or recurrence. Further study and larger patient groups are needed to draw concrete conclusions.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.