Detection of Malignancy in Ocular Surface Lesions by Inverse Spectroscopic Optical Coherence Tomography and Two-Photon Autofluorescence

Abstract

Purpose Advanced imaging is increasingly important in the diagnosis of ocular surface malignancy. Inverse spectroscopic optical coherence tomography (ISOCT) and two-photon autofluorescence microscopy (2P-AF) are emerging techniques capable of quantifying ultrastructural and metabolic changes, respectively. We aimed to detect malignancy in ocular surface lesions using ISOCT and 2P-AF. Methods Portions of excised specimens from patients undergoing conjunctival biopsy at Boston Medical Center were imaged by ISOCT and/or 2P-AF, and submitted for histologic diagnosis. Lesions were categorized as malignant, premalignant (with dysplasia) or benign. ISOCT and 2P-AF findings were compared between categories. Results Fourteen specimens from 13 patients were collected. The IS-OCT marker D was 2.2-fold higher in combined malignant and premalignant (4.27 ± 0.28, n = 3) versus benign (1.92 ± 0.26, n = 11) lesions ( P = 9 × 10 −4 ). ISOCT markers μ s and μ b were not significantly different. By 2P-AF, the redox ratio was 0.24-fold lower in premalignant (0.11 ± 0.004, n = 2) versus benign (0.45 ± 0.04, n = 9) lesions ( P = 1.08 × 10 −5 ). Conclusions Conjunctival lesions with higher malignant potential had higher D and lower redox ratios. Higher D can correlate with ultrastructural changes associated with malignancy, similar to what has been seen in cancers of the gut mucosa. Lower redox ratios can suggest the presence of the Warburg effect, which is associated with tumorigenesis. Translational Relevance IS-OCT and 2P-AF can potentially be applied to the detection of malignancy or malignant potential in ocular surface lesions. ISOCT allows for the detection of nanoscale ultrastructural changes that are not resolvable by conventional OCT.

A Perspective Review: Analyzing Collagen Alterations in Ovarian Cancer by High-Resolution Optical Microscopy

“…The ability to detect and capture early metastases in these systems via ISOCT shows great potential for improving cancer therapeutics and interventions. Lee et al expanded upon these ideas by utilizing ISOCT and two-photon autofluorescence to quantify nanoscale ultrastructural and metabolic changes, respectively, in ocular surface lesions leading to ocular surface squamous neoplasia (OSSN) [46]. Their results suggested that lesions with increased malignant potential had a higher D (mass density measurement) and a decrease in the optical redox ratio (cancer association via increased cellular proliferation or differentiation), which collectively supported ultrastructural compaction and modifications.…”

“…Their results suggested that lesions with increased malignant potential had a higher D (mass density measurement) and a decrease in the optical redox ratio (cancer association via increased cellular proliferation or differentiation), which collectively supported ultrastructural compaction and modifications. Consequently, they were able to differentiate between normal, premalignant and malignant tissue samples more readily [46].…”

Optical biopsy – Optical coherence tomography guided excision of ocular surface squamous neoplasia

“…Optical coherence tomography (OCT) has been used for numerous indications in the diagnosis and management of ophthalmic disorders. [10][11][12][13] The advantage of OCT is the non-invasive and user friendly method. However, there are limited studies on their use in OSSN excision.…”