Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia

Summary

Anterior segment high-resolution optical coherence tomography (HR-OCT) is a promising non-invasive modality for the diagnosis and therapeutic evaluation of ocular surface squamous neoplasia (OSSN). Here, the system setup, scanning technique, and representative diagnostic results are presented.

Abstract

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. Traditionally, the diagnosis of OSSN relies on histopathological confirmation followed by a full-thickness biopsy. However, in the past two decades, the therapeutic approach to OSSN has shifted from surgical intervention to topical chemotherapy regimens in clinical settings. This shift emphasizes the need for less invasive or non-invasive methods to diagnose ocular surface pathologies. Among various imaging devices, commercially available high-resolution optical coherence tomography (HR-OCT) has emerged as a powerful tool for the characterization of OSSN. HR-OCT provides an in vivo, cross-sectional view of ocular surface lesions, offering an “optical biopsy” for OSSN with high sensitivity and specificity. It provides valuable information in differentiating intraepithelial or invasive OSSN from other benign lesions. Additionally, HR-OCT can be used to monitor the response to topical chemotherapy and to detect subclinical OSSN during follow-up visits. In this article, the scanning protocol for image acquisition is presented, and image interpretation for OSSN is outlined. This standardized, practical, and reproducible approach is recommended in clinical workflows and is expected to assist clinicians in the management of OSSN.

Introduction

Ocular surface squamous neoplasia (OSSN) is the most common non-pigmented tumor of the conjunctiva and cornea. The term OSSN encompasses a broad spectrum of squamous neoplastic changes, including dysplasia (graded I-III), intraepithelial neoplasia (i.e., carcinoma in situ, CIS), and invasive squamous cell carcinoma (SCC)¹. The diagnosis of OSSN can be made clinically by slit lamp examination by detecting the typical appearance of elevated, leukoplakic or papilliform mass, often presented at limbus straddling conjunctiva to the cornea with feeder vessels². Sometimes, they may present less distinctively. The gold standard for the diagnosis of OSSN remains histopathologic confirmation followed by incisional or excisional biopsy^1,3.

Recently, the therapeutic pattern of OSSN has shifted from surgical management to the use of topical chemotherapy. This has greatly promoted the adoption of biopsy to less or non-invasive modalities⁴. Various imaging devices have been studied for the characterization of OSSN, namely HR-OCT, in vivo confocal microscopy (IVCM)⁵, impression cytology (IC)⁶, ultrasound biomicroscopy (UBM)⁷, and methylene blue stain⁴. Currently, several studies have provided insights into the characterization of OSSN using anterior segment HR-OCT. Commercially available HR-OCT devices using spectral-domain technology can attain an axial resolution of approximately 5 µm. These images provide in vivo, cross-sectional views of ocular surface lesions and display distinct features of OSSN that parallel the changes seen in histopathology. Hence, HR-OCT enables clinicians to obtain an “optical biopsy” to expediently diagnose and monitor OSSN in clinics.

To promote the application of HR-OCT in the management of OSSN, a standardized, practical, and reproducible guidance for image acquisition is presented in detail to ensure good quality for clinical use. Also, characteristics of OSSN and other common benign lesions on HR-OCT are elucidated for better image interpretation.

Protocol

All the protocols described below follow the guidelines of the Human Research Ethics Committee of the First Affiliated Hospital of Harbin Medical University and adhere to the tenets of the Declaration of Helsinki. The approval number is 2023IIT008. Written, informed consent was obtained from all study participants. The study included participants who presented with conjunctival masses. Exclusion criteria for enrollment included females who were pregnant or breastfeeding and conditions that prevented performing study inve…

Representative Results

Figure 1A,B illustrate HR-OCT images of OSSN, revealing three key characteristics: (1) Significantly thickened hyper-reflective epithelium; (2) An abrupt shift from normal to abnormal epithelium, marked by a sudden rise in both brightness and thickness of the epithelium; (3) Occasionally, a division plane is visible between the epithelium and underlying tissue. However, in very thick lesions, the lower edge of the lesion may be somewhat obscured by shadowing. <p class="j…

Discussion

Anterior segment OCT (AS-OCT) is a promising diagnostic tool for surveying the ocular surface. It obtains an optical section of the ocular surface following the principle of Michelson's interferometry⁹. The systematic interpretation of AS-OCT begins with the outmost tissue of the ocular surface, namely the epithelium of the cornea, limbal, and conjunctival complex.A recent study by Vempuluru et al. showed that AS-OCT is very useful in confirming epithelial involvement where most ocular surface…

Materials

70% Ethanol	Any make
Fourier-domain optical coherence tomography (OCT) system	Optuvue Inc., Fremont, CA, USA	RTVue XR
RTVue software	Optuvue Inc., Fremont, CA, USA