The use of high resolution optical coherence tomography (HR-OCT) in the diagnosis of ocular surface masqueraders

Abstract

Introduction: Ocular surface masqueraders encompass any ocular surface lesion masquerading as another ocular surface lesion. High resolution optical coherence tomography (HR-OCT) has emerged as an adjunctive tool to clinical acumen. This study's purpose is to evaluate the utility of HR-OCT images in guiding the diagnosis and management of those lesions.

Material and methods: 22 individuals with a clinically ambiguous ocular surface lesion with slit lamp photographs (SLP), HR-OCT images, and histopathological examination were included in the study. The presumptive clinical diagnosis based on SLP was compared to the diagnosis suggested by HR-OCT findings and to definitive diagnosis by histopathology. The main outcome of this study was the frequency in which HR-OCT findings guided the clinician to the correct diagnosis.

Results: 7 lesions were epithelial, 3 had an epithelial and a subepithelial component, and 12 were subepithelial. HR-OCT was most effective in discerning lesion location, successfully identifying the location in 100% of cases. Classic HR-OCT findings were detected in 68.2% of cases while suggestive features were detected in 31.8% of cases. The epithelial lesions' mean epithelial thickness was 265.4 ± 140.6 μm, the subepithelial lesions' mean was 58.0 ± 25.0 μm, and the combined lesions' mean was 140.0 ± 70.0 μm. The epithelium was significantly thicker in epithelial lesions compared to subepithelial and combined lesions. By ROC analysis we identified that using a cut off of 156 μm, the sensitivity was 86% and the specificity was 93%.

Discussion: HR-OCT can be a valuable diagnostic tool, assisting in the differentiation of ambiguous ocular surface pathologies by providing a cross-sectional, morphological image of the lesion.

Keywords: Amyloid; Classic; Epithelial; HR-OCT; Lymphoma; Masquerade; Melanoma; Ocular surface; Ocular surface squamous neoplasia; Squamous cell carcinoma; Subepithelial.

Figure 1:. Ocular surface squamous neoplasia (OSSN) masquerading as chronic episcleritis

a. Slit lamp photography of the right eye of a 61-year-old white Hispanic female referred for a 10-month history of episcleritis (white arrow). b. High resolution optical coherence tomography (HR-OCT) demonstrates hyperreflective thickening of the epithelium (asterisk) classic for OSSN. Inset shows scan location. Biopsy confirmed the HR-OCT diagnosis of conjunctival intraepithelial neoplasia, carcinoma in situ. c. Slit lamp photography shows dramatic clinical resolution of the lesion after treatment with 4 one-week cycles of 5-fluorouracil 1% eye drops. d. HR-OCT reveals normalization of the epithelium (white arrows). Inset shows scan location. Post treatment biopsies confirmed the HR-OCT findings of tumor resolution. e. Thickened epithelium (between arrows) that demonstrates faulty maturational sequencing which extends up to full thickness is present. (Hematoxylin and eosin, original magnification x 100).

Figure 2:. Squamous cell carcinoma (SCC) masquerading as infectious sclerokeratitis

a. Slit lamp photograph of the right eye of a 66-year-old black male with diffuse conjunctival injection, midstromal corneal infiltrates & pigmented keratic precipitates (white arrow), 2+ cell in the anterior chamber, a temporal thickening of the conjunctiva (white arrowhead) b. High resolution optical coherence tomography (HR-OCT) reveals a thickened, hyperreflective epithelium (thin white arrows) with a mass invading into the subepithelial space (thick white arrow). Shadowing precludes clear visualization of the scleral tissue. c. Squamous cell carcinoma consisting of glands and cords of malignant epithelial cells located within the substantia propria (thick black arrow). The overlying epithelium contains a mild chronic inflammatory cell infiltrate and is minimally thickened (between small black arrows). (Hematoxylin-eosin, original magnification x 200).

Figure 3:. Squamous cell carcinoma masquerading as sclerokeratitis

a. Slit lamp photography of the left eye of a 68-year-old white Hispanic female with presumptive herpetic sclerokeratitis. Image shows diffuse corneal opacification, injected feeder vessels, lipid keratopathy, and a gelatinous area from 1 to 3 o’clock. Black arrow shows location of high resolution optical coherence tomography (HR-OCT) scan. b. HR-OCT reveals a thickened hyper reflective epithelium (asterisk) along with a diffuse, subepithelial mass (white arrows) without an obvious connection. These features were suggestive of neoplasia. c. Squamous cell carcinoma with foci of dyskeratosis (black arrows) are present within the substantia propria. The overlying epithelium (asterisk) appears unremarkable (hematoxylin-eosin, original magnification x 200).

Figure 4:. Amelanotic CMM masquerading as OSSN/pannus

a. Slit lamp photography of the left eye demonstrating gelatinous lesion encroaching on the cornea from 3:30 to 6 o’clock associated with hairpin loop vessels and trace pigment. b. High resolution optical coherence tomography (HR-OCT) demonstrates a subepithelial hyperreflective mass (white star) with an overlying hyperreflective and essentially normal thickness epithelium (white arrows). Posterior shadowing is seen. Inset shows scan location. c. Atypical melanocytic cells are present within the substantia propria (star). Tumor cells are located within the basal aspect of the epithelium (arrowheads) with minimal overlying acanthosis (between arrows). (Hematoxylin-eosin, original magnification x 200).

Figure 5:. Conjunctival malignant melanoma (CMM) masquerading within a longstanding pinguecula/pterygium

a. Slit lamp photography of the left eye of a 35-year-old white male shows a gelatinous lesion on the conjunctiva and encroaching on the cornea from 2 to 4 clock hours accompanied by a feeder vessel and with a pigmented edge on the corneal margin. Melanosis inferiorly to the lesion was seen. b. High resolution optical coherence tomography (HR-OCT) shows a subepithelial hyporeflective mass (asterisk) with some associated cysts (thin arrow), most likely representing long-standing nevus. Adjacent to this lesion, there is a hyperreflective subepithelial mass (thick arrowheads) and hyperreflective thin epithelium, suggestive of conjunctival melanoma. Inset shows location of the scan. c. A large nest of morphologically benign nevus cells is present within the substantia propria (asterisk). Atypical pleomorphic melanoma cells are present within the epithelium and superficial substantia propria (arrows). (Hematoxylin-eosin, original magnification x 100).

Figure 6:. Lymphoma masquerading as sarcoidosis

a. Slit lamp photography of the right eye of a 23-year-old black female shows diffuse conjunctival thickening and a whitish nodular mass located on the inferior bulbar conjunctiva. b. High resolution optical coherence tomography (HR-OCT) reveals a subepithelial, homogenous, hyporeflective subepithelial mass (asterisk) with monomorphic dot-like infiltrates bordered by a band of hyperreflectivity superiorly (thin arrows) and a thin epithelium. Extensive posterior shadowing is noted. Inset shows scan location. c. A diffuse infiltrate of atypical large basophilic lymphoma cells is present within the substantia propria (arrows). (Hematoxylin-eosin, original magnification x 40).

Figure 7:. Conjunctival amyloidosis masquerading as episcleritis

a. Slit lamp photography of the right eye of a 28-year-old white female shows a hyperemic, elevated area on the inferior bulbar conjunctiva (arrowheads). b. High resolution optical coherence tomography (HR-OCT) reveals thin epithelium overlying a subepithelial heterogeneous, dark lesion with irregular borders. Linear subepithelial, hyperreflective infiltrates were present in the mass(white arrows). Inset shows scan location. c. Congo red positive amyloid is present within the substantia propria (asterisk), (Congo red; original magnification x 100). d. Apple green birefringence is present within the substantia propria (asterisk), (Congo red; original magnification x 400).

Figure 8:

Receiver operating characteristics (ROC) curve and corresponding area under the curve (AUC) for prediction of a lesion as epithelial based on epithelial thickness. Area under the ROC curve=0.914.