Superficial Punctate Keratitis of Thygeson

History

In 1889, Ernst Fuchs first defined the term “keratitis punctata superficialis” or “superficial punctate keratitis” (SPK). He used the term to describe an epidemic keratoconjunctivitis (EKC) that affected patients in the Third Clinic in Vienna. Although the condition was usually bilateral, it began unilaterally and was worse in the first eye to be affected. These patients had an associated follicular conjunctivitis and punctate keratitis. We now believe these patients had EKC and that this epidemic was probably caused by a strain of adenovirus. Subsequently, the term “EKC” was used to describe such epidemics, and the term “SPK” was no longer used.

In 1950, Phillips Thygeson first reported 26 cases of what has become known as superficial punctate keratitis of Thygeson. Some of these patients had been followed in his office for as long as 24 years. In this initial publication, Thygeson discussed the individual lesions in detail. He described individual evanescent opacities that would change position over time. He noted that each opacity comprised a group of smaller intraepithelial opacities. There was little edema and no cellular infiltration. He noted mild conjunctival inflammation accompanying the lesions, with a mild papillary response on the palpebral surface of the upper lid. Despite Thygeson’s detailed description of SPKT, the term “superficial punctate keratitis” has been, and continues to be, used incorrectly to describe many different forms of superficial keratitis.

In 1961, Thygeson added 29 cases and described the five diagnostic features that differentiate SPKT from other epithelial keratopathies: (1) a chronic, bilateral, punctate epithelial keratitis; (2) long duration (months to years) with remissions and exacerbations; (3) eventual healing without scars; (4) lack of response to systemic or topical antibiotics or to the removal of the corneal epithelium; and (5) a striking symptomatic response to topical corticosteroids.

In 1963, Jones reported 27 cases of SPKT and added additional features to the physical findings. He reported a faint opacification of the superficial stroma underlying the epithelial opacity. He believed this stromal change had the gray appearance of lamellar separation caused by edema, rather than the hard or dot-like appearance of cellular infiltration. In addition, in retroillumination this stromal change was transparent or translucent, suggesting edema. Jones also emphasized that the disease should be called SPKT and that SPK should not be used to describe other forms of keratitis.

In 1966, Thygeson described another 27 previously unreported cases and distinguished superior limbic keratoconjunctivitis from SPKT. Thygeson thought that a viral cause of SPKT was strongly suggested by: (1) the absence of bacteria or other microorganisms; (2) the resistance of the disease to antibacterial agents; (3) the scanty mononuclear cell exudate on conjunctival scrapings; and (4) the viral appearance of the epithelial lesions.

In 1968, Quere et al. described three stages in SPKT: (1) the onset, lasting 1–2 weeks, characterized by catarrhal inflammation, photophobia, and tearing; (2) a developmental stage of up to 8 months in which the signs of conjunctival inflammation disappeared, leaving the epithelial lesions; and (3) a stage of regression of several months to years, during which the lesions became fewer in number and smaller until they finally vanished. Quere et al. also suggested that this disease was chronic. The total duration of the disease in these patients ranged from 4 months to 30 years, with an average of 7.5 years and a median of 4 years. The longest reported case of SPKT was 40 years, reported by Tanzer and Smith in 1999.

In 1971, Wakui et al. described the ultrastructural characteristics of the disease. Their electron microscopic findings of the corneal epithelium from patients with SPKT failed to reveal viral particles but did show cell destruction confined to one discrete area, which contrasted with the cell-to-cell spread of herpes simplex keratitis.

In 1974, Lemp et al. isolated varicella-zoster virus (VZV) from a patient with SPKT, but this may have been a laboratory accident or even spontaneous shedding. Current investigators do not believe VZV to be a likely cause.

In 1981, Darrell reviewed the disease and described 36 patients with SPKT in whom there was a significant incidence of the histocompatibility antigen HLA-DR3.

In 1981, Tabbara et al. reported 45 cases. These authors believed that corticosteroids prolonged the course of the disease, based on the natural history of many of these patients compared to the description of the disease by Thygeson before the introduction of corticosteroids.

In 2003, Watson et al. performed confocal microscopy on six patients and found changes not only in the corneal epithelium: irregular nerve fibers and haze in the subepithelial nerve plexus were also found. Generalized haze and areas of high reflectivity, microdots and reflective bodies in the anterior stroma, and keratocytes with reflective nuclei and cell bodies of irregular size and shape were also reported. The images suggested that wound healing and cell death were occurring in the anterior stroma. These findings were related to the duration of SPKT, were not seen in normal fellow eyes, and were also present diffusely in areas without lesions.