Thygeson Superficial Punctate Keratitis

Updated: Feb 21, 2023
Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD 



In 1950, California ophthalmologist Phillips Thygeson described multiple case reports of an unusual superficial punctate keratitis that he described as a transient, bilateral disease, having coarse corneal epithelial opacities and no associated stromal involvement.[1]

Today, this condition is known as Thygeson superficial punctate keratitis (TSPK). It is a chronic, often bilateral, recurring illness, with relapses over years to decades. Multiple, whitish gray, intraepithelial corneal lesions, with minimal to no conjunctival involvement, are trademark characteristics of the disease.

Although TSPK has a genetic association with HLA-DR3, controversy exists regarding its exact etiology.

Artificial tears, topical corticosteroids, topical cyclosporine, and therapeutic soft contact lenses are the typical treatment methods for the disease, and the success of these treatments varies according to the severity of the disease.

Although vision may be mildly decreased during the active disease, the long-term visual prognosis is excellent.

The cornea of a 33-year-old African American man w The cornea of a 33-year-old African American man with active Thygeson superficial punctate keratitis (TSPK).


A review of the literature suggests the pathophysiology of TSPK remains unclear, although viral and immunogenic components are both likely in the disease's formation.



United States

The frequency of TSPK in the United States is currently unknown.


The worldwide frequency of TSPK is unknown.


TSPK does not cause mortality and the morbidity of the disease is unknown.


A review of the literature suggests statistics on race for TSPK are currently unknown.


TSPK has a slight female predilection.


TSPK can affect individuals of all age groups. Cases of TSPK in patients ranging in age from 2.5 years to 70 years have been reported, with a mean age of 29 years.[2]


Regardless of the treatment method selected, the visual prognosis in patients with TSPK is excellent.[2, 3, 4]  Visual acuity of 20/20 to 20/30 is maintained in the majority of cases.[5]

Patient Education

Due to the chronic nature of the disease, with exacerbations and remissions, patients need to be educated that their symptoms may recur no matter which course of therapy is followed. Patients on topical steroids need routine follow-up examinations.




Patients with Thygeson superficial punctate keratitis (TSPK) often report bilateral tearing, burning, photophobia, foreign body sensation, and ocular irritation during exacerbations. Patients also may experience mild blurring of vision. There usually is minimal or no conjunctival hyperemia and no discharge.

During the inactive stages of the disease, patients may have no complaints.


TSPK is characterized by a bilateral, recurrent, focal, epithelial keratitis without associated conjunctival or stromal inflammation.[2, 3, 4, 6, 7]  The classic corneal lesion in active TSPK is a conglomerate of coarse, oval shaped, slightly raised, whitish gray dots that stain minimally with fluorescein. The lesions tend to accumulate centrally in the cornea, and 1-50 lesions may be present (averaging about 20 lesions per flare-up).[8]

Corneal sensitivity typically is normal or only slightly decreased, but it is never completely absent as in herpes simplex keratitis.[2]

Although a conjunctival response typically is not seen, a minimal reaction by way of conjunctival injection may be noted.[6, 9]


The exact etiology of TSPK is unclear.

Associations with various viral infections, including the adenovirus, herpes simplex virus, and varicella zoster virus, have been made.[10, 11] In 1953, Braley and Alexander provided questionable results suggesting a virus may be responsible for TSPK, and, in 1974, Lemp et al were able to isolate the varicella zoster virus from a corneal surface, albeit a 10-year-old boy.[10, 11] In more recent studies using polymerase chain reactions, the varicella zoster virus was not detected in eyes with TSPK, providing doubts this virus is the causative agent.[12, 13, 14]

HLA-DR3, an antigen associated with immune response genes and multiple autoimmune disorders, has some association with TSPK as well. It has been proposed that this antigen may alter the immune response of individuals with TSPK, yielding the prolonged course of the disease and its hallmark of exacerbations and remissions.[6]


Mild scarring can occur in cases of long-standing TSPK.

Steroid adverse effects can also occur, so appropriate follow-up is important for patients using steroids.





Laboratory Studies

Culturing the flora of the cornea during active inflammation may be helpful in future research, but it is not necessary for the diagnosis, treatment, or management of Thygeson superficial punctate keratitis (TSPK), since it is not an infectious disease.

Imaging Studies

Slit lamp photography may be used to document active inflammation and periods of inactivity, but it is not necessary to successfully diagnose or manage the disease.

Histologic Findings

Intracellular and intercellular edema at the epithelial level are common histological features of TSPK.[15, 16, 17]

Other abnormalities have been observed in the subepithelial nerve plexus, the Bowman membrane, and the anterior stroma. These changes are most severe in eyes with a longer duration of disease and can possibly be reversed with topical steroid therapy.[16]


TSPK is in either the active stage or the inactive stage of the disease.

As mentioned above, the classic corneal lesion in active TSPK is a conglomerate of coarse, oval shaped, slightly raised, whitish gray dots that stain minimally with fluorescein. The lesions tend to accumulate centrally in the cornea, and 1-50 lesions may be present (averaging about 20 lesions per flare-up).[8]

During the inactive stages of the disease, the lesions can disappear, or they can appear as flat gray, stellate shaped, subepithelial opacities that do not stain with fluorescein.[7, 8] Also, some patients develop subepithelial opacities that occasionally become permanent even in the absence of overlying epithelial disease.[6]

Attacks may last up to several months and go into remission for up to 3 years.[2, 8] The disease may continue for an average period of 3.5-7.5 years, although reports of more than 24, 30, and 41 years have been reported, particularly with steroid use.[2, 18]



Medical Care

Many therapies for Thygeson superficial punctate keratitis (TSPK) have been tried and proven unsuccessful over the years.

Antibiotics have been shown to be an ineffective treatment method.[2]

Antivirals have had mixed results; mild improvements have been reported with trifluridine, but it has also been reported to cause the disease to disappear more slowly than when treated with corticosteroids alone.[19] In addition, there have been multiple observations that idoxuridine causes persistent subepithelial ghost opacities and scarring in individuals with TSPK; therefore, it is contraindicated.[2, 11, 20]

A few successful therapies for TSPK do exist.

Topical lubricants have been shown to be an effective treatment method for relieving clinical symptoms.[21]

Topical corticosteroids now are considered to be the mainstream treatment of TSPK, as they have been shown to be very successful in managing both clinical signs and symptoms; however, there is speculation that the natural course of the disease may be prolonged secondary to the introduction of these medications.[2, 3] In addition, topical cyclosporine has been reported to be effective when used as a first-line treatment of patients with TSPK, with the advantage of fewer adverse effects compared with corticosteroids.[13, 22, 23]

Therapeutic soft contact lenses used on an extended-wear basis also offer an alternative or an additive treatment, especially for severe cases, although potential complications (eg, microbial keratitis) may exist.[22, 24] The use of anti-inflammatory topical medications while wearing contact lenses, especially extended-wear lenses, increase the known risks of contact lenses. Contact lenses improve symptoms by covering the elevated corneal lesions and nerves, which are constantly in friction with the conjunctiva during blinking.[2, 25]

Nagra et al have had overwhelming success with topical corticosteroids, and they suggest an initial management of TSPK with fluorometholone 0.1% (FML 0.1%) or a similar low-dose steroid, followed by the use of stronger steroids, and then extended-wear contact lenses or topical cyclosporine in a stepwise approach.[3] They reinforce an important point that steroids must be tapered gradually over the course of months in many patients, with some patients requiring longer term, infrequent, but regular use (ie, weekly, biweekly). Since therapy is aimed at providing patients with comfort, clinicians should be aware that the minimum strength and dosage of topical anti-inflammatory medications necessary to control symptoms should be prescribed.[18]

Surgical Care

There are a few reports of remission and recurrence following laser refractive surgery.[26, 27, 28, 29]

Fite and Chodosh reported that the use of photorefractive keratectomy (PRK) prevented the recurrence of TSPK in the area of the excimer laser treatment.[29]

Seo et al suggested that the recurrence rate of TSPK following refractive laser procedures is lower with PRK than with laser in situ keratomileusis (LASIK).[27]

Other reports have suggested that both PRK and laser subepithelial keratomileusis (LASEK) do not prevent the recurrence of TSPK, and even similar attempts of debridement of the corneal epithelium are insufficient at alleviating the course of inflammation in these patients.[2, 27]


A consultation with a cornea specialist or an anterior segment specialist may be warranted if the diagnosis and the management of a patient with TSPK are confounding or if a patient is not responding to treatment.

Long-Term Monitoring

Patients with Thygeson superficial punctate keratitis (TSPK) should be followed regularly during flare-ups; otherwise, they should be followed periodically for routine eye examinations.

Patients using topical steroids need to be seen routinely to monitor for steroid adverse effects, such as glaucoma and cataracts.



Anti-inflammatory agents

Class Summary

These agents decrease inflammation.

Fluorometholone (FML)

Inhibits edema, fibrin deposition, capillary dilation and phagocytic migration of acute inflammatory response and capillary proliferation, collagen deposition, and scar formation. Decreases inflammation and corneal neovascularization. Suppresses migration of polymorphonuclear leukocytes and reverses capillary permeability. Believed to act by the induction of phospholipase A-2 inhibitory proteins.

Used topically, it can elevate IOP and cause steroid-response glaucoma. In clinical studies of documented steroid responders, fluorometholone demonstrated a significantly longer average time to produce a rise in IOP than dexamethasone phosphate. In a small percentage of individuals, a significant rise in IOP occurred within 1 wk. The ultimate magnitude of the rise was equivalent.

Lubricants, ocular

Class Summary

These agents increase lubrication of the eye.

Artificial tears (Refresh Tears, Optive, Systane, Celluvisc, Murine, Refresh, Tears Naturale, GenTeal, TheraTears)

Used to increase lubrication of the eye. Contains equivalent of 0.9% NaCl and maintains ocular tonicity. Acts to stabilize and thicken precorneal tear film and prolong tear film breakup time, which occurs with dry eye states. Preparations that have hydroxymethylcellulose or dextran are more viscous and, therefore, can last longer before needing to be reapplied. Preservative-free artificial tears are preferred to avoid preservative-associated ocular reactions.


Class Summary

Cyclosporine ophthalmic drops are thought to act as a partial immunomodulator. The exact mechanism of action is not known.

Cyclosporine 0.05% (Restasis)

Used to relieve dry eyes caused by suppressed tear production secondary to ocular inflammation. Thought to act as partial immunomodulator. Exact mechanism of action is not known.