eMedicine Specialties > Ophthalmology > Cornea
Thygeson Superficial Punctate Keratitis
Updated: Jun 17, 2008
Introduction
Background
In 1950, Phillips Thygeson published case reports on a superficial punctate keratitis that he described as a transient, bilateral disease, having coarse corneal epithelial opacities and no associated stromal involvement1 Today, this condition, now known as Thygeson superficial punctate keratitis (TSPK), is a chronic one, lasting 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 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.
Pathophysiology
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.
Frequency
United States
A review of the literature suggests the frequency of TSPK in the United States is currently unknown.
International
A review of the literature suggests the worldwide frequency of TSPK is unknown.
Mortality/Morbidity
A review of the literature suggests TSPK does not cause mortality and the morbidity of the disease is unknown.
Race
A review of the literature suggests statistics on race for TSPK are currently unknown.
Sex
A review of the literature suggests there is no predilection for sex in TSPK.
Age
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
Clinical
History
Patients with TSPK often report bilateral tearing, burning, photophobia, foreign body sensation, and ocular irritation during exacerbations.
During the inactive stages of the disease, patients may have no complaints.
Physical
TSPK is characterized by a bilateral, recurrent, focal, epithelial keratitis without associated conjunctival or stromal inflammation.2,3,4,5,6 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).7
Corneal sensitivity is typically normal or only slightly decreased, but it is never completely absent as in herpes simplex keratitis.2
Although a conjunctival response is typically not seen, a minimal reaction by way of conjunctival injection may be noted.3,8
Causes
The exact etiology of TSPK is unclear.
Associations with various viral infections, including the adenovirus, herpes simplex virus, and varicella zoster virus, have been made9,10 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.9,10 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 agent11,12
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.3
Differential Diagnoses
Conjunctivitis, Viral
Corneal Erosion, Recurrent
Dry Eye Syndrome
Dystrophy, Map-dot-fingerprint
Keratitis, Herpes Simplex
Other Problems to Be Considered
Sterile corneal infiltrates
Workup
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 the 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 TSPK13,14
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.14
Staging
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).7
Corneal sensitivity is typically normal or only slightly decreased, but it is never completely absent as in herpes simplex keratitis.2
Although a conjunctival response is typically not seen, a minimal reaction by way of conjunctival injection may be noted.3,8
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.4,7 Also, some patients develop subepithelial opacities that occasionally become permanent even in the absence of overlying epithelial disease.3
Attacks may last up to several months and go into remission for up to 3 years.2,7 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.2,15
Treatment
Medical Care
Many therapies for 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 alone16 In addition, there have been multiple observations that idoxuridine causes persistent subepithelial ghost opacities and scarring in individuals with TSPK; therefore, it is contraindicated.2,10
A few successful therapies for TSPK do exist.
Topical lubricants have been shown to be an effective treatment method for relieving clinical symptoms17
Topical corticosteroids are now 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 is prolonged secondary to the introduction of these medications.2,5 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.12,18
Therapeutic soft contact lenses used on an extended-wear basis also offer an alternative treatment, especially for severe cases, although potential complications (eg, microbial keratitis) may exist.18,19 Contact lenses improve symptoms by covering the elevated corneal lesions and nerves, which are constantly in friction with the conjunctiva during blinking.2,20Nagra 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.5 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.15
Surgical Care
There are a few reports of remission and recurrence following laser refractive surgery21,22,23,24
Fite and Chodosh reported that the use of photorefractive keratectomy (PRK) prevented the recurrence of TSPK in the area of the excimer laser treatment.24
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).22
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.2,22
Consultations
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.
Medication
Anti-inflammatory agents
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.
Dosing
Adult
Solution: 1 gtt into conjunctival sac qid for approximately 2 wk, then taper slowly
Pediatric
<2 years: Not established
>2 years: Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity; herpes simplex, keratitis, viral and fungal diseases of the ocular structure
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Prolonged use may result in elevated intraocular pressure or glaucoma
Lubricants, ocular
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.
Dosing
Adult
1-2 gtt into affected eye(s) 2-6 times a day prn
Pediatric
Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Hyperemia, photophobia, stickiness of eyelashes, and ocular discomfort or irritation may occur
Immunomodulators
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.
Dosing
Adult
Instill 1 gtt in each eye q12h, occasionally used more frequently
Pediatric
<16 years: Not established
>16 years: Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity; ocular infection
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Herpes keratitis; do not administer while wearing contact lenses; may cause ocular burning, conjunctival hyperemia, ocular discharge, excessive tearing, eye pain, foreign body sensation, pruritus, stinging, or blurred vision
Follow-up
Further Outpatient Care
Patients 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.
Complications
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.
Prognosis
Regardless of the treatment method selected, the visual prognosis in patients with TSPK is excellent.2,5,6
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.
Miscellaneous
Medicolegal Pitfalls
Patients need to understand the characteristic chronic nature of the disease, with exacerbations and remissions, over time.
Clinicians should be aware that since therapy is aimed at providing patients with comfort, the minimum strength and dosage of topical anti-inflammatory medications necessary to control symptoms should be prescribed.15
Patients on topical steroids need routine follow-up examinations to monitor for steroid side effects, such as glaucoma and cataracts.
Multimedia
Media file 1: The cornea of a 33-year-old African American man with active Thygeson superficial punctate keratitis (TSPK).
References
Thygeson P. Superficial punctate keratitis. J Am Med Assoc. Dec 30 1950;144(18):1544-9. [Medline].
Tabbara KF, Ostler HB, Dawson C, Oh J. Thygeson's superficial punctate keratitis. Ophthalmology. Jan 1981;88(1):75-7. [Medline].
Darrell RW. Thygeson's superficial punctate keratitis: natural history and association with HLA DR3. Trans Am Ophthalmol Soc. 1981;79:486-516. [Medline].
Jones BR. Thygeson's Superficial Punctate Keratitis. Trans Ophthalmol Soc U K. 1963;83:245-53. [Medline].
Nagra PK, Rapuano CJ, Cohen EJ, Laibson PR. Thygeson's superficial punctate keratitis: ten years' experience. Ophthalmology. Jan 2004;111(1):34-7. [Medline].
Thygeson P. Clinical and laboratory observations on superficial punctate keratitis. Am J Ophthalmol. May 1966;61(5 Pt 2):1344-9. [Medline].
Arffa RC. Grayson's Diseases of the Cornea. 4th ed. St. Louis: Mosby-Year Book; 1997.
Tantum LA. Superficial punctate keratitis of Thygeson. J Am Optom Assoc. Dec 1982;53(12):985-6. [Medline].
Lemp MA, Chambers RW Jr, Lundy J. Viral isolate in superficial punctate keratitis. Arch Ophthalmol. Jan 1974;91(1):8-10. [Medline].
Braley AE, Alexander RC. Superficial punctate keratitis; isolation of a virus. AMA Arch Ophthalmol. Aug 1953;50(2):147-54. [Medline].
Reinhard T, Roggendorf M, Fengler I, Sundmacher R. PCR for varicella zoster virus genome negative in corneal epithelial cells of patients with Thygeson's superficial punctate keratitis. Eye. Mar 2004;18(3):304-5. [Medline].
Reinhard T, Sundmacher R. Topical cyclosporin A in Thygeson's superficial punctate keratitis. Graefes Arch Clin Exp Ophthalmol. Feb 1999;237(2):109-12. [Medline].
Cheng LL, Young AL, Wong AK, Law RW, Lam DS. In vivo confocal microscopy of Thygeson's superficial punctate keratitis. Clin Experiment Ophthalmol. Jun 2004;32(3):325-7. [Medline].
Watson SL, Hollingsworth J, Tullo AB. Confocal microscopy of Thygeson's superficial punctate keratopathy. Cornea. May 2003;22(4):294-9. [Medline].
Tanzer DJ, Smith RE. Superficial punctate keratitis of thygeson: the longest course on record?. Cornea. Nov 1999;18(6):729-30. [Medline].
Nesburn AB, Lowe GH 3rd, Lepoff NJ, Maguen E. Effect of topical trifluridine on Thygeson's superficial punctate keratitis. Ophthalmology. Oct 1984;91(10):1188-92. [Medline].
Gock G, Ong K, McClellan K. A classical case of Thygeson's superficial punctate keratitis. Aust N Z J Ophthalmol. Feb 1995;23(1):76-7. [Medline].
Del Castillo JM, Del Castillo JB, Garcia-Sanchez J. Effect of topical cyclosporin A on Thygeson's superficial punctate keratitis. Doc Ophthalmol. 1996-1997;93(3):193-8. [Medline].
Forstot SL, Binder PS. Treatment of Thygeson's superficial punctate keratopathy with soft contact lenses. Am J Ophthalmol. Aug 1979;88(2):186-9. [Medline].
Goldberg DB, Schanzlin DJ, Brown SI. Management of Thygeson's superficial punctate keratitis. Am J Ophthalmol. Jan 1980;89(1):22-4. [Medline].
Jabbur NS, O'Brien TP. Recurrence of keratitis after excimer laser keratectomy. J Cataract Refract Surg. Jan 2003;29(1):198-201. [Medline].
Seo KY, Lee JB, Jun RM, Kim EK. Recurrence of Thygeson's superficial punctate keratitis after photorefractive keratectomy. Cornea. Oct 2002;21(7):736-7; author reply 737. [Medline].
Netto MV, Chalita MR, Krueger RR. Thygeson's superficial punctate keratitis recurrence after laser in situ keratomileusis. Am J Ophthalmol. Sep 2004;138(3):507-8. [Medline].
Fite SW, Chodosh J. Photorefractive keratectomy for myopia in the setting of Thygeson's superficial punctate keratitis. Cornea. May 2001;20(4):425-6. [Medline].
Keywords
Thygeson’s superficial punctate keratitis, TSPK, cornea, corticosteroid, cyclosporine
Contributor Information and Disclosures
Author
Robert S Duszak, OD, FAAO, Co-Director of Residency Program and Consulting Staff, Philadelphia Veterans Affairs Medical Center; Consulting Staff, Nemours Health Clinic & Mayfair Eye Associates; Adjunct Clinical Faculty, Pennsylvania College of Optometry
Robert S Duszak, OD, FAAO is a member of the following medical societies: American Academy of Optometry, American Geriatrics Society, and American Optometric Association
Disclosure: Nothing to disclose.
Medical Editor
Richard W Allinson, MD, Associate Professor, Department of Ophthalmology, Texas A&M University Health Science Center, Scott and White Clinic
Disclosure: Nothing to disclose.
Pharmacy Editor
Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.
Managing Editor
Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Eye Bank Association of America, Pennsylvania Medical Society, and Philadelphia County Medical Society
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other
CME Editor
Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.
Chief Editor
Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)