Thygeson's Superficial Punctate I<eratitis

KHALID F. TABBARA, MD, H. BRUCE OSTLER, MD, CHANDLER DAWSON, MD, JANGOH,MD

Abstract: Thygeson's superficial keratitis is a chronic disease of the cornea characterized by focal epithelial lesions. We studied 45 cases of Thygeson's superficial punctate keratitis. Twenty-eight were male and 17 were female patients. The disease had been active in our patients from one month to 24 years. The clinical findings, course, outcome, and re­sponse to therapy were studied. Viral cultures and microscopic studies were performed on the corneal epithelial scrapings from ten cases. The average course of the disease was prolonged in patients who received topical steroid therapy. Subepithelial opacities were seen more fre­quently in patients who had received treatment with idoxuridine (IOU). [Key words: idoxuridine, keratitis, Thygeson's superficial punctate keratitis.] Ophthalmology 88:75-77, 1981

Thygeson's superficial punctate keratitis (Thyge­son's SPK) was first described by Thygeson in 1950. 1

The cause of the disease is unknown. It is characterized by episodes of tearing, irritation, and photophobia. The course of the disease is chronic, and spontaneous or steroid-induced remissions occur. In 1966, Thyge­son2 noted that the disease lasted six months to four years. Although Braley3 isolated a single strain of virus which produced lesions in the corneal epithelium of the rabbit, subsequent attempts to recover the virus from corneal lesions failed. 4•5 Lemp et al, 6 in 1974, were able to recover a varicella-zoster virus from le­sions of a patient with Thygeson's SPK.

We studied 45 previously unreported cases of Thygeson's SPK. Most patients were referred to us for consultation by ophthalmologists in the San Francisco Bay Area.

Exactly 30 years after the original report on this en­tity, we present the clinical findings, course, outcome, and response to therapy of these 45 cases and the re­sults of viral cultures among ten patients with Thyge­son's SPK.

From the Francis I. Proctor Foundation for Research in Ophthalmol­ogy, University of California at San Francisco.

Presented at the Eighty-Fifth Annual Meeting of the American Academy of Ophthalmology, Chicago, November 2-7, 1980.

Supported in part by grants EY-01597 and EY-03436 from the Na­tional Institutes of Health, Bethesda.

Reprint requests to Dr. Khalid F. Tabbara, Proctor Foundation, 315-Science, University of California, San Francisco, CA 94143.

PATIENTS AND METHODS

Forty-five cases of superficial punctate keratitis were included in this study. All patients met the criteria for the diagnosis of Thygeson's SPK as previ­ously outlined. 1 At least one of us had examined each patient. The patients' symptoms and biomicroscopic findings were recorded during each visit and the follow-up period ranged from six months to 24 years.

We anesthetized the corneas in ten patients with 0.5% proparacaine, and obtained corneal epithelium specimens from the active corneal lesions with a sterile platinum spatula. We transferred the material to one ml of a culture medium consisting of Eagle's MEM, 5% heat-inactivated calf serum, 100 units of penicillin and 100 p,g/ml of streptomycin. The medium was fro­zen and kept at -70 C until we inoculated it into pri­mary cultures of human embryonic kidney cells. We placed one ml of the specimen into each of two tubes of cell culture containing one ml of the described medium, incubated the tubes at 36 C at a stationary position, and checked them daily for cytopathic effects (CPE). We passed the culture fluid at least twice into fresh cell-culture tubes. If no CPE appeared in any of the tubes after two blind passages, the culture was considered negative.

RESULTS

Patient age at the time of onset of ocular symptoms ranged from 2.5 years to 70 years, with a mean age of

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OPHTHALMOLOGY • JANUARY 1981 • VOLUME 88 • NUMBER 1

29 years. There were 28 male and 17 female patients with a male to female ratio of 1.6: 1.

TRIGGER MECHANISMS

The data obtained in the patients' histories were negative for any specific trigger mechanism .. There was no clear-cut correlation between upper respiratory tract infection and the onset of ocular symptoms. One child who had never been exposed to chickenpox de­veloped symptoms of Thygeson's SPK six months following exposure to his grandfather who had herpes zoster ophthalmicus. There was no associated sys­temic illness in any of the patients studied.

CORNEAL LESIONS

The corneal lesions observed among the 45 patients consisted of round or oval conglomerates of discrete granular white-gray fine intraepithelial dots. The le­sions occasionally had a stellate pattern and produced symptoms when they were elevated. During exacer­bations of the disease, Thygeson's spots were found to be densely granular with an elevated epithelium that stained in the center with fluorescein and rose bengal. When the patients experienced remissions, the corneal lesions appeared completely flat and did not stai~ with fluorescein. The active lesions were hard and resistant to removal by scraping, suggesting intact basal epithe­lial desmosomes.

Twenty (44%) of the 45 patients studied had sub­epithelial opacities. Eighteen of the 20 patients h_ad received topical idoxuridine (IDU) elsewhere and pnor to our examination. In two others who had apparently not received IDU, we saw several subepithelial ghost-like opacities. These were less distinct, how­ever and probably represented mild transient sub­epithelial edema often in association with subepithelial lesions.

In all patients, the lesions were located predomi­nantly in the visual axis except in the two patients who had their lesions close to the limbus. This may suggest that patients with worse symptoms are usually re­ferred. The number varied between 3 and 40 lesions in each cornea with an average of 12 lesions.

DURATION OF DISEASE

The disease had been active in our 45 patients from one month to 24 years with an average of 3.5 years. The disease is characterized by exacerbations and spontaneous remissions. One of our patients was free of symptoms for three years, but had a series o_f re­currences for a period of six months. All the patients were treated with topical steroids at one time during the course of their illness. No associated conjunctivitis was noted during exacerbations.

LATERALITY

In 43 (96%) of the 45 patients, the disease was bilat­eral and in only 2 (4%) the disease was unilateral. In

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one of the patients with unilateral disease, the patient was under our observation for three and a half years and at no time were there any symptoms suggesting involvement of the other eye. The other patient had had the disease only two months when we first saw her but was under our observation for another eight months. The disease remained consistently unilateral. One eye was predominantly affected in 24 of the 43 bilateral cases.

OUTCOME AND SEQUELAE

Thirty-two patients had 20/30 vision or better in both eyes. Eight patients had visual acuity of 20/50 or better in the worse eye, three had vision of 20/80 or better, and two had visual acuity of 20/100 in the worse eye. Patients who had reduced visual acuity (less than 20/50) had evidence of subepithelial opacities in the visual axis that did interfere with the vision. One patient, who had 20/100 vision in one eye, had in addi­tion to the subepithelial opacities evidence of stromal scarring caused by herpes simplex infection that had been treated with steroids. Most of the subepithelial ghost opacities described were apparently induced by treatment with IDU. No subepithelial scarring was at­tributed to Thygeson's spots. Corneal peripheral vas­cularization developed in three patients whose lesions were near the limbus.

TREATMENT

STEROIDS

Thirty-two patients were treated with some form of topical steroid. Fluorometholone 1% and medrysone 1% were the most frequently used drugs. In approxi­mately 50% of the cases, exacerbations were con­trolled by this form of therapy. We have found that dexamethasone 0.01% or 0.05% was effective in con­trolling exacerbations of the disease.

SOFT CONTACT LENSES

In two patients, therapeutic soft contact lenses were used to relieve the symptoms and improve the visual acuity. Both patients showed improvement in their ac­tive Thygeson's spots.

SCRAPINGS

In all patients in whom scrapings of the epithelia were attempted, the epithelia did not come off easily, suggesting that the basement membrane and its hemidesmosome attachments were intact.

In ten of the 45 patients the epithelium in the area of the active group of lesions was removed for culture or electron microscopy. In two other patients, the epithelium was removed to the limbus; and in another, the diseased epithelium overlying the active lesions was removed and the base touched with 2% iodine.

The lesions did recur in the same place and within

TABBARA, et al • THYGESON'S SPK

one week after scrapings. Scraping the lesions appar­ently had no effect on the course of the disease.

IDU

Both IDU and topical antibiotics had no effect on the course of the disease. Twenty patients were on IDU at the time of referral to us. Patients were still having active lesions on treatment and 18 of the 20 had developed subepithelial opacities.

All the specimens from ten patients failed to yield any virus.

DISCUSSION

The data presented in this study have revealed cer­tain interesting features ofThygeson's SPK. The onset of the disease is frequently during the second and third decades with characteristic corneal lesions but no ac­companying conjunctivitis. The course is chronic and we have found one case that lasted for 24 years. The disease is usually bilateral, has an insidious onset, and is not contagious. The corneal sensation remains in­tact. The disease is characterized by spontaneous re­missions and exacerbations. Since the introduction of steroids, Thygeson's SPK has persisted longer than what was previously reported by Thygeson. In Thyge­son's cases seen prior to the introduction of steroids, no cases persisted longer than six years. In one of our patients who was placed on topical steroids, the dis­ease has lasted for 24 years. Steroids, therefore, may have helped to prolong a protracted course of this otherwise self-limited disease. We therefore would recommend that steroids be used sparingly, if at all, and in as low and as infrequent dosages as possible consistent with the activity of the lesions and symp­tomatology of the patient. Alternative therapeutic measures such as therapeutic soft contact lenses may be considered.

The use of IDU is contraindicated in Thygeson's SPK. In 18 of the 20 patients who received IDU, sub­epithelial ghost opacities were seen. Scrapings and chemical (iodine) microcauterization of the active spots do not help the condition and the lesions recur despite such therapy. The use of therapeutic soft con­tact lenses was successful in abolishing the signs and symptoms in two of our patients. The follow-up on these patients, however, is short. Forstot and Binder7

have noted symptomatic relief, fading of the corneal lesions, and improvement in the visual acuities of three patients with Thygeson's SPK who were treated with soft contact lenses. Similarly Goldberg et al,8 more recently, reported rapid resolution of the epithelial le­sions with symptomatic relief in all four patients with Thygeson's SPK with the use of soft contact lenses. Therapeutic soft contact lenses may improve symp­toms by improving the optical characteristics of the cornea, and cover the elevated corneal lesions and

nerves that are constantly in friction with the con­junctiva during blinking. This effect would break a vicious cycle by decreasing lacrimation that is associated with hypotonic tears that may contribute to localized epithelial edema. In addition, the therapeutic soft contact lenses may prevent exposure of the epithelium overlying the corneal lesions in Thygeson's SPK. This therapeutic modality needs a controlled study, and a long-term follow-up. Nevertheless, therapeutic trials with soft contact lenses should be considered in symptomatic patients.

The visual outcome in patients with Thygeson's SPK is generally good. Patients may develop central ghost subepithelial opacities following IDU therapy. Some patients who develop a secondary ocular viral infection, may have cataracts, or glaucoma. Patients with a prolonged course of the disease may have a higher incidence of complications. One patient re­ported by Abbott and Forster9 had a prolonged course (16 years) of the disease and subepithelial opacities without concomitant antiviral therapy and later devel­oped Salzmann's nodular degeneration.

Braley and Alexander and Lemp et al6 have previ­ously reported the isolation of a virus from the corneal epithelium of active lesions in affected individuals. In the latter report, the virus was identified as varicella zoster. The similarity of the corneal lesions to other lesions of known viral origin, such as measles, the protracted character of the disease, its tendency to recur, and the mononuclear cell response, strongly suggests a latent virus or a defective virion as a causa­tive agent. Co-cultivation studies of the epithelia of active lesions are needed to further elucidate the cause of this disease.

REFERENCES

1. Thygeson P. Superficial punctate keratitis. JAMA 1950; 144:1544-8.

2. Thygeson P. Clinical and laboratory observations on superfi­cial punctate keratitis. Am J Ophthalmol 1966; 61:1344-9.

3. Braley AE, Alexander RC. Superficial punctate keratitis. Arch Ophthal 1953; 50:147-54.

4. Thygeson P. Further observations on superficial punctate keratitis. Arch Ophthalmol 1961; 66:158-62.

5. Jones BR. Thygeson's superficial punctate keratitis. Trans Ophthalmol Soc UK 1963; 83:245-53.

6. Lemp MA, Chambers RW, Lundy J. Viral isolate in superficial punctate keratitis. Arch Ophthalmol 1974; 91:8-10.

7. Forstot SL, Binder PS. Treatment of Thygeson's superficial punctate keratopathy with soft contact lenses. Am J Ophthal­mol 1979; 88:186-9.

8. Goldberg DB, Schanzlin OJ, Bro•vn Sl. Management of Thyge­son's superficial punctate keratitis. Am J Ophthalmol 1980; 89:22-4.

9. Abbott RL, Forster RK. Superficial punctate keratitis of Thyge­son associated with scarring and Salzmann's nodular degen­eration. Am J Ophthalmol 1979; 87:296-8.

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