The lesions of TSPK resemble the corneal lesions seen in measles during the convalescent stage of the infection, or in the early stages of epidemic keratoconjunctivitis before the subepithelial infiltrates appear. The morphologic similarity has led many to speculate that a virus may play a role in the etiology of the disease, and in fact Braley and Alexander (3) recovered a virus from one case of TSPK, and later Lemp and associates (4) reported the isolation of a varicella-zoster virus from a patient with this disease. Repeated attempts, by Thygeson and others, have been unsuccessful in isolating a virus through cultures or serologic studies, and epidemiologic studies have not shown a relationship to viral illnesses (5, 6, 7, 8). The favorable response of the lesions to topical steroids also suggests that if the lesions are caused by a virus, they must at least in part represent an immunologic response to the virus.

Thygeson (5) observed that this entity was self-limited, and resolved within 4 years in all patients. More recent studies have demonstrated a more prolonged disease course of decades, with the longest duration reported being 41 years (9). It has been speculated that the duration of the disease is prolonged by treatment with steroids. Topical steroids may have an adverse effect on the natural course of the disease, such as one would expect if it were a “slow virus” (7). Further research is warranted to confirm the role of a virus in this entity.

TSPK is reported to be associated with human leukocyte antigen (HLA)-DR3, suggesting a predisposition to the disease among some of the population (6). In addition, this association may imply an autoimmune component to the disease.

As the cause of TSPK is unknown, one can only speculate on the pathogenesis. As noted above, the lesions are similar to those seen during the convalescent period of measles and the coalescent phase of the corneal changes seen in epidemic keratoconjunctivitis between the first and second weeks of disease onset and before the subepithelial infiltrates appear, which suggests that the etiology may be a slow virus. In many slow viral infections, such as verruca and molluscum contagiosum, epidemiologic studies are unrewarding in explaining the source of the infections. In addition, the time between exposure to the agent and manifested clinical disease is so prolonged that there is little hope of determining the source of the infection. Moreover, serologic studies are unproductive for slow viral infections. The spontaneous healing of the lesions after 2 to 4 years in the early cases when steroids have not been used is also compatible with a slow viral infection, similar to the spontaneous resolution of most verruca and molluscum contagiosum nodules within that time frame. Conversely, the proposed prolongation of disease course with topical steroids may be similar to the prolongation of the duration of infections of verruca and molluscum contagiosum when immunosuppressive agents are used.

If the disease is caused by a slow virus, then the pathogenesis should be similar to other slow viral infections. Following exposure of a healthy or immunosuppressed host, the virus replicates in the epithelial cells of the cornea and gradually converts the cells’ functions to its own use. The viral infection stimulates the cells to divide, and after many months the disease becomes manifest clinically. After a few days to several weeks, the lesions probably cause a nonspecific inflammatory reaction that leads to loss of the grossly infected cells and subsidence of the lesions. Subsequently, the entire process begins anew.

TSPK occurs in all areas of the world, affecting people of all races (10). There is no gender predilection. Patients of all ages have been affected, with the youngest reported patient being 2½ years old, and the oldest reported patient with active symptoms being 85 years old.

At onset, patients note the insidious onset of foreign-body sensation, photophobia, and tearing. Other symptoms include blurred vision, redness, and diplopia. Patients may be asymptomatic, with just one or two spots (11). Typically, the more spots seen, the more symptomatic patients are. The symptoms usually increase for 1 to 2 weeks, and then slowly subside. During a period of remission, the patients remain asymptomatic. Duration of remission can vary, but often lasts for 4 to 6 weeks, followed by the new onset of symptoms. Remissions and exacerbations may occur for years or decades.