Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia

Abstract

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development.

Keywords: 5-FU; 5-Fluorouracil; AS-OCT; Anterior segment optical coherence tomography; FD-OCT; Fourier-domain OCT; Fourier-domain optical coherence tomography; HIV; HR-OCT; High-resolution optical coherence tomography; Human immunodeficiency virus; IFN; Interferon; LASIK; LSCD; Laser in situ keratomileusis; Limbal stem cell deficiency; MMC; Mitomycin C; OCT; OSSN; Ocular surface squamous neoplasia; Optical coherence tomography; SD-OCT; SL-OCT; SLE; SS-OCT; Slit lamp examination; Slit lamp optical coherence tomography; Spectral domain optical coherence tomography; Swept-source optical coherence tomography; TD-OCT; Time-domain optical coherence tomography; UBM; UHR-OCT; Ultra high-resolution optical coherence tomography; Ultrasound biomicroscopy; anterior segment OCT; high-resolution OCT; ocular surface squamous neoplasia; optical coherence tomography (OCT); slit lamp OCT; spectral domain OCT; swept-source OCT; time-domain OCT; ultra high-resolution OCT.

Figure 1

Photograph of the custom-built UHR-OCT device employed at Bascom Palmer Eye Institute, Miami, FL, USA.

Figure 2

A. Clinical appearance of ocular surface squamous neoplasia (OSSN) in a patient who presented with an elevated lesion, accompanied by feeder blood vessels, located at the corneoscleral limbus. B. Ultra high-resolution ocular coherence tomography (UHR-OCT) image of the same OSSN lesion, demonstrating a thickened, hyper-reflective epithelium (marked with asterisk) and an abrupt transition zone from normal to abnormal epithelium (arrow). C. Slit lamp photo of the same location after medical therapy for OSSN, showing clinical resolution of the lesion. D. Followup UHR-OCT image of the same eye after medical therapy for OSSN, showing a return of normal-appearing, thin epithelium after resolution of the OSSN.

Figure 3

UHR-OCT image of a pterygium, demonstrating an epithelial layer of normal thickness (arrows) overlying thickened, hyper-reflective subepithelial tissue (marked with asterisk).

Figure 4

A 77-year-old male with a history of corneal scarring was referred due to concern for OSSN. A. Clinical examination revealed a white elevated papillary lesion of the cornea with a prominent feeder vessel. B. UHR-OCT revealed a thin, normal hyporeflective epithelium (arrow) and dense subepithelial lesion (marked with asterisk), consistent with subepithelial corneal scarring or lipid. There was no evidence of OSSN by OCT. The patient was followed closely without progressive lesion change and was able to forego excisional procedures of the ocular surface.

Figure 5

A 61-year-old male presented for a second opinion regarding a lesion thought to be OSSN. A. Clinical examination revealed a temporal, nodular conjunctival lesion abutting the corneal limbus, which appeared highly vascular with numerous feeder vessels. There were a few adjacent areas of mild pigmentation in the conjunctiva that the patient stated had been present for many years. B. UHR-OCT of the lesion revealed normal-thickness, mildly hyper-reflective epithelium (arrows) overlying a dense subepithelial lesion (marked with asterisk). The finding of a thin epithelium was inconsistent with OSSN. C. Subsequent excisional biopsy (shown in the hematoxylin and eosin (H&E) stain, 20x magnification) revealed non-thickened conjunctival epithelium (arrows) overlying a dense, subepithelial melanocytic lesion (marked with asterisk) that also stained positive for melan A, consistent with melanoma.

Figure 6

A 34-year-old HIV-positive male with a history of limbal stem cell deficiency, severe vernal keratoconjunctivitis, and OSSN was referred for changes in corneal and conjunctival appearance, suspicious for OSSN. A. Clinical examination revealed diffuse corneal scarring and neovascularization, making the clinical diagnosis difficult. B. UHR-OCT revealed sudden transition from normal to abnormal epithelium (arrow) as well as a thickened, hyper-reflective epithelium (white arrowheads to mark deep margin of epithelium), findings consistent with OSSN. Subepithelial scarring was also present. C. Histopathology (H&E, 20x magnification) revealed nests of dysplastic epithelial cells with faulty maturation sequences consistent with OSSN. D. After a course of primary medical therapy with interferon (IFN) alfa-2B eyedrops, the areas of disease showed significant improvement, but the patient’s baseline ocular surface disease remained, complicating the clinical monitoring of his OSSN to resolution. E. Serial UHR-OCT monitoring demonstrated the return of normal-appearing, non-thickened epithelium (arrow) overlying the patient’s corneal scarring, helping to confirm resolution of neoplastic disease.

Figure 7

A. A 76-year-old male with a history of Salzmann’s nodular degeneration presented with a change in nodule appearance of a previously-documented nasal nodule with associated corneal haziness (arrow). B. UHR-OCT revealed a focus of subepithelial fibrosis consistent with Salzmann’s nodular degeneration (a). Adjacent to this, there was hyper-reflective epithelium (b) with an abrupt transitional from normal to abnormal, consistent with OSSN. White arrowheads indicate the deep margin of the epithelium. C. Histopathologic examination (H&E, 40x magnification) of the epithelial scrapings taken during surgical excision disclosed foci of cellular atypia consistent with OSSN (a), associated with fibrotic material (b). D. Two years after surgical excision, examination showed no evidence of OSSN. E. UHR-OCT two years after excision revealed normal, thin dark epithelium (arrow). There was subepithelial scarring present from the excision and the prior Salzmann’s nodule and no evidence of OSSN.

Figure 8

A 27-year-old male with a history of LSCD and corneal scarring, presumed to be band keratopathy, presented for evaluation of his corneal lesions. A. The appearance was largely consistent with a diagnosis of corneal scarring, but certain areas of the corneal surface appeared slightly elevated (arrow). B. UHR-OCT to evaluate the area of presumed scarring and calcification revealed thickened, hyper-reflective epithelium consistent with OSSN (arrow). C. Subsequent histopathology (H&E, 20x magnification) confirmed the presence of diffusely thickened, dysplastic epithelium with faulty maturation sequences (arrow), consistent with OSSN.

Figure 9

A. An 83-year-old male with no prior history of ocular surface squamous neoplasia (OSSN) presented with a suspicious conjunctival lesion of the left eye (marked by arrow). B. Initial UHR-OCT imaging revealed a hyper-reflective thickened epithelium (a) and a sudden transition from normal to abnormal tissue (b). C. One month after starting treatment with topical recombinant IFN alfa-2B, the area of previously-affected conjunctiva appeared clinically to be free of tumor. D. UHR-OCT, however, demonstrated a focus of persistently hyper-reflective and thickened conjunctival epithelium (arrow), consistent with OSSN. E. Topical therapy was continued accordingly, and at 3-month follow-up, slit lamp examination continued to demonstrate clinical resolution. F. UHR-OCT confirmed normal epithelial appearance, with resolution of prior hyper-reflectivity and with normalization of epithelial thickness (arrow).