The term ocular surface squamous neoplasia (OSSN) encompasses a spectrum of corneal and conjunctival diseases that includes dysplasia, intraepithelial neoplasia, and invasive squamous cell carcinoma (SCC) [[1], [2], [3]]. OSSNs are thought to arise from limbal stem cells and represent the most common non-pigmented ocular surface malignancy [[4], [5], [6]]. The incidence of OSSN ranges from 0.03 to 1.9 per 100,000 persons/year in the United States and Australia to 1.6–3.4 per 100,000 persons/year in sub-Saharan Africa (SSA) [[7], [8], [9], [10]].

The clinical appearance of OSSN can vary but most commonly presents as a gelatinous, leukoplakic, or papillary conjunctival lesion [4]. These tumors are usually located in the limbal cornea or perilimbal bulbar conjunctiva, can be flat or elevated, and may be accompanied by feeder vessels [4,7].

While often obvious, OSSN lesions may also have a subtle presentation as an opalescent lesion on the cornea, or masquerade as a scar, pannus, or episcleral inflammation. Although histopathologic examination remains the gold standard, high-resolution optical coherence tomography (HR-OCT) has emerged as a pivotal aid in the diagnosis and management of OSSN [[11], [12], [13], [14]]. In particular, HR-OCT can help detect atypical presentations of OSSN through the identification of thickened, hyperreflective epithelium with an abrupt transition between normal and abnormal epithelium [[12], [13], [14]].

The most important environmental risk factor for the development of OSSN is chronic ultraviolet radiation (UV) B exposure [7]. Other risk factors include increasing age, infection with the human immunodeficiency virus (HIV) [15,16], human papilloma virus (HPV) [15,17,18], vitamin A deficiency, ocular surface injury, and exposure to petroleum chemicals [3,19,20]. Additionally, patients with immune deficiency or immunosuppression tend to present with more aggressive tumors [7,16,21,22].

This paper raises the possibility that chronic ocular surface inflammation is a potential risk factor for OSSN. Distinct forms of chronic inflammation have long been established as a predisposing factor to the development of metaplasia and ultimately dysplasia [23] including microbial infections, autoimmune disease, and environmental irritants [24,25]. For example, chronic irritation associated with burns can lead to cutaneous malignancies (classically squamous cell carcinoma) known as Marjolin ulcers just like chronic periodontal disease predisposes individuals to developing head and neck cancer [[26], [27], [28]].

In this paper, we describe how various causes of chronic inflammation can be associated with OSSN. We present sixteen cases of OSSN that occurred co-morbid with chronic ocular surface inflammation from a variety of conditions to illustrate the potential link between ocular surface inflammation and neoplasia. Additionally, we highlight the important role of HR-OCT in cases of clinically ambiguous OSSN.