Performing an “Optical Biopsy” With HR-OCT
AT A GLANCE
- Eye care providers have relied on clinical examination and invasive procedures, such as biopsies, as a means of performing histopathology to diagnose ocular surface lesions. Anterior segment high-resolution OCT (AS HR-OCT) has emerged as an adjunctive diagnostic tool for differentiating benign from malignant ocular surface lesions, providing a form of optical biopsy.
- When assessing an AS HR-OCT scan, a systematic approach can help aid diagnosis.
- HR-OCT does not replace the gold standard of histopathologic analysis to diagnose ocular surface malignancies, but it can help narrow differential diagnoses, distinguish benign lesions from those that are malignant, and provide timely management and treatment.
As optometrists, we have likely encountered ambiguous ocular surface lesions or overlapping clinical features acting as masqueraders, leading to a diagnostic dilemma. Recognizing and distinguishing between benign and malignant lesions early on is crucial to guiding appropriate intervention, as some lesions can pose a significant risk to a patient’s health.
Traditionally, the diagnosis of ocular surface lesions has been accomplished via clinical exam and invasive procedures, such as biopsies for histopathology. Anterior segment high-resolution OCT (AS HR-OCT) has emerged recently as an adjunctive diagnostic tool for differentiating benign from malignant ocular surface lesions, providing a form of optical biopsy and, consequently, enabling us to refer patients promptly.1
AS HR-OCT
A study by Nanji et al concluded that the HR Optovue RTVue Fourier-Domain SD-OCT System (Optovue) effectively differentiated various ocular surface pathologies and replicated previously published OCT findings obtained with an ultra-HR (UHR) custom-built OCT device. (UHR = < 5 µm of resolution; HR = 5-7 µm of resolution.2) This axial resolution elucidates enough detail to allow reliable assessment of ocular surface lesions, especially ocular surface squamous neoplasia.3
The following AS HR-OCT systematic approach and cases illustrate how to differentiate benign lesions from malignant lesions.
A SYSTEMATIC APPROACH TO EVALUATING AS HR-OCT SCANS
When looking at an HR-OCT scan, we see the morphology, thickness, and reflectivity of the epithelial and subepithelial layers.4 Increased whiteness of the involved tissue compared with normal tissue is described as hyperreflectivity. Darkening of the tissue within the lesion is described as hyporeflectivity.4
A normal HR-OCT scan (Figure 1) shows a bright, hyperreflective tear film layer overlying the cornea and conjunctiva. The corneal epithelium is thin and hyporeflective, while the limbus and conjunctiva are thin and mildly hyperreflective.2 Normal corneal and conjunctival epithelial thickness range from 50 µm to 70 µm.2,5 The normal subepithelial tissue of the cornea is seen in a regular, linear pattern. The conjunctival subepithelial region, namely the substantia propria, is hyperreflective.5 Beneath it, a thick band of moderate, hyperreflective tissue is the normal scleral tissue.
When assessing an AS HR-OCT scan, use the following systematic approach.
1. Find the normal epithelium.
2. Find the base of the epithelium.
3. Assess the main lesion. Is it epithelial or subepithelial?
4. Determine whether an abrupt transition exists.
5. Assess the epithelium. Is it hyperreflective and thickened?
CASE NO. 1: OCULAR SURFACE SQUAMOUS NEOPLASIA MIMICKING PTERYGIUM
A 56-year-old female presented for evaluation of dryness associated with a persistently injected pterygium. Examination revealed suspicious features, including a mild gelatinous papillary appearance and a feeder vessel. I performed HR-OCT to better evaluate the lesion. The systematic approach aided with diagnosis (Figure 2).
1. Find the base of the epithelium.
2. Assess the main lesion. Is it epithelial or subepithelial? (Epithelial.)
3. Determine whether an abrupt transition exists. (Yes, there is an abrupt transition from normal to abnormal epithelium.)
4. Is the epithelium hyperreflective? Thickened? (Hyperreflective, and the epithelium appears thickened.)
The answers to these questions corresponded with the three classic features of conjunctival ocular surface squamous neoplasia (OSSN) seen on HR-OCT2,4: 1) Thickened epithelium, 2) strongly hyperreflective epithelium, 3) usually with an abrupt transition from normal to abnormal epithelium. The subepithelial layer is usually not involved. The main difference between OSSN and pterygium is the location of the lesion (epithelial for OSSN, subepithelial for pterygium), and other morphologic features (Table). In studies using the commercially available RTVue, an epithelial thickness of 120 µm to 140 µm was considered highly sensitive and specific for OSSN.5 However, the optimal numeric epithelial thickness cutoff for each device remains unknown, and all data should be considered within the clinical scenario.2
Because the pathology report confirmed OSSN, this patient underwent successful treatment with interferon alpha-2b (Figure 3). In cases of OSSN, these HR-OCT features resolve completely with normalization of the epithelium after successful medical treatment or surgical intervention.5
OSSN includes a spectrum of conjunctival and corneal lesions ranging from conjunctival intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma (SCC).5 Clinically, OSSN typically presents as an elevated lesion with a leukoplakic, gelatinous, or papilliform appearance and can have abnormal blood vessel patterns. The lesions most commonly occur at the limbus. Although OSSN is often clinically easy to identify, its coexistence with other ocular surface diseases can make diagnosis difficult. OSSN can occur with corneal ulcers, chronic blepharoconjunctivitis, pterygium, and superior limbic keratoconjunctivitis.3 A study by Theotoka et al found that HR-OCT could identify the lesion’s location (epithelial, subepithelial, or combined) in 100% of cases.4
On HR-OCT, corneal OSSN features a hyperreflective epithelium with an abrupt transition from normal to abnormal epithelium (Figure 4). These lesions are usually thicker than the surrounding epithelium.5 Epithelial findings in SCC are sometimes not as classic as those in noninvasive OSSN, with variable hyperreflectivity and often an absence of an abrupt transition. In addition, a connection between the abnormal hyperreflective epithelium and the subepithelial is not always present.4
CASE NO. 2: CONJUNCTIVAL LYMPHOMA
A 67-year-old male was referred to my clinic for chronic dry eyes and persistent conjunctival injection. The clinical examination revealed a salmon patch lesion. I performed HR-OCT. I again used the systematic approach to help aid diagnosis (Figure 5).
1. Find the base of the epithelium.
2. Assess the main lesion. Is it epithelial or subepithelial? (Subepithelial.)
3. Determine whether an abrupt transition exists. (No.)
4. Is the epithelium hyperreflective? Thickened? (No, there is a hyporeflective, homogenous subepithelial mass.)
Features of lymphoma viewed on AS HR-OCT include:
1. Normal epithelial appearance and thickness.
2. Hyporeflective, homogenous subepithelial mass.
3. Hyperreflective, uninvolved, substantia propia surrounding the lesion.
HR-OCT findings were thus consistent with conjunctival lymphoma. Clinically, conjunctival lymphoma can present as focal salmon-patch masses, subconjunctival mobile masses or nodules, or chronic follicular conjunctivitis.5 However, for both melanomas and lymphomas, HR-OCT images do not always help the clinician obtain a definitive diagnosis, as they do for OSSN, but can help guide the differential. Histopathologic analysis of tissue is always needed for final confirmation.5
CASE NO. 3: AMELANOTIC MELANOMA MIMICKING AN INFLAMED PINGUECULA
A 65-year-old male with a history of longstanding UV exposure was referred for an inflamed pinguecula that was unresponsive to steroid treatment. A slit-lamp examination revealed an elevated gelatinous and papillary conjunctival lesion with a feeder vessel. The lesion encroached on the cornea from the 2 to 5 clock hours, with pigment extending throughout the edge of the lesion. An HR-OCT was performed to better evaluate the lesion. Let’s review the steps of the systematic approach to assist with diagnosis (Figure 6).
1. Find the base of the epithelium.
2. Assess the main lesion. Is it epithelial or subepithelial? (Subepithelial.)
3. Determine whether an abrupt transition exists. (Yes.)
4. Is the epithelium hyperreflective? Thickened? (Slightly thick to normal epithelium. The subepithelial space is hyperreflective, and there is shadowing.)
HR-OCT revealed a subepithelial, hyperreflective mass inconsistent with OSSN, and the shadowing inconsistent with a pinguecula. This patient underwent wide surgical excision and cryotherapy. The histopathologic analysis revealed a conjunctival melanoma. Classic clinical features of melanoma include feeder vessels, elevation, immobility, pigmentation, and melanosis. About 20% of conjunctival malignant melanomas are amelanotic,6 and this presentation can be confused with OSSN, lymphoma, or a benign process, such as episcleritis or pyogenic granuloma. Misdiagnosis can lead to a delay in treatment, with local spread or distant metastasis, or to an incorrect treatment, as incisional biopsy can precipitate tumor seeding.4
Features of amelanotic melanoma viewed on AS HR-OCT include:
1. Normal thickness to somewhat thickened epithelium.
2. Mildly hyperreflective, but often with strong reflectivity of basal epithelium.
3. Hyperreflective subepithelial mass with obscuration of the underlying tissue (due to shadowing). Rarely cysts.
TAKE-HOME POINTS
During the examination and differentiation of ocular surface lesions, it’s essential to assess the lesion location (epithelial vs subepithelial), followed by characteristics of the lesion (thickness and type of reflectivity). CIN lesions involve only the epithelium, and increased epithelial thickness is the most sensitive feature viewable via HR-OCT to help diagnose them.5 Corneal OSSN and corneal pannus can present as a corneal opalescent lesion. However, an abrupt transition at a 90˚ angle perpendicular to the Bowman layer indicates OSSN, whereas pannus appears as an angled transition around 45˚.7 Furthermore, to differentiate pterygium cases from OSSN lesions, an epithelial thickness of 120 µm to 140 µm is considered highly sensitive and specific for OSSN.
Most ocular surface lesions, including lymphoma, pinguecula, melanoma, pterygium, and nevus, involve the subepithelial space. Melanoma lesions are dense and elevated; therefore, the HR-OCT scan shows a hyperreflective subepithelial mass with shadowing. When comparing melanoma with nevus, the nevus HR-OCT may demonstrate the presence of cysts, which is suggestive of a chronic, benign lesion.5
Although HR-OCT as an “optical biopsy” does not replace the gold standard of histopathologic analysis to diagnose ocular surface malignancies, it can help narrow differential diagnoses, differentiate benign lesions from those that are malignant, and provide timely management and treatment. HR-OCT technology is noninvasive and does not require technical expertise for scanning, and clinicians of all levels should be able to perform image interpretation after appropriate training.8
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