Treatment Methods

Treatment in the Acute Phase

More serious systemic conditions in the acute phase are more unlikely to attract attention to the eyes, but it is important to check ocular manifestations since the onset of SJS/TEN and suppress the inflammation.

The degree of skin manifestations is not always consistent with that of ocular manifestations. Patients sometimes have severe eye disorders with mild skin eruption, and vice versa. It is difficult to suppress inflammation only with topical treatment in the presence of pseudomembrane formation and ocular surface epithelial erosion, and it is desirable to provide adequate systemic treatment using steroids even when patients only have mild skin eruption.

Ophthalmologic Treatment in the Acute Phase

Extensive keratoconjunctival epithelial defect in the acute phase is likely to lead to loss of corneal epithelial stem cells. Complete loss of the corneal epithelial stem cells will result in coverage of the cornea with conjunctival tissues and lead to a sequela of visual impairment. Suppressing inflammation with steroid instillation and other treatment methods with careful attention to infection will result in the preservation of the corneal epithelial stem cells, that is, prevention of ocular sequelae.

1. Suppressing inflammation

(1) Systemic steroid treatment (steroid pulse therapy)
After steroid pulse therapy (with Solu-Medrol [methylprednisolone sodium succinate] 1000 mg daily by drip infusion for three days), oral or intravenous steroid treatment should be continued while tapering its dose in several weeks. In the presence of serious ocular manifestations, the dose of the steroid should be tapered in consideration of not only skin manifestations but also the degree of inflammation of the ocular surface. However, patients with SJS/TEN are susceptible to infection because of extensive damage to the skin mucosa throughout the body. Therefore, utmost care should be given to complication of infections.

Intravenous immunoglobulin (IVIG) or plasma exchange therapy is recommended in patients who do not respond to steroid treatment or who cannot receive steroids because of serious infections or other reasons.

(2) Topical steroid administration to the eyes
Treatment should be provided 6 to 8 times daily with an ophthalmic solution or an ocular ointment of 0.1% betamethasone or 0.1% dexamethasone according to the degree of inflammation of the ocular surface. In the presence of pseudomembrane formation or epithelial defect, inflammation should be suppressed with the ophthalmic solution and the ocular ointment about 10 times daily in total.

2. Prevention of infections (ocular instillation of antibiotics)

Patients with SJS/TEN often have a high risk of infection in the acute phase because of extensive epithelial defect on the ocular surface. Therefore, efforts need to be made in order to prevent secondary infection. Culture of secretions from the eye or conjunctival scraping should be performed at the initial visit. If any bacterium is detected, an antibiotic should be topically administered in consideration of drug susceptibility. Surveillance culture (culture of conjunctival scraping or eye discharge) should be performed once or more weekly afterwards.

3. Prevention of adhesion

With inadequate suppression of inflammation in the acute phase, adhesion of the bulbar conjunctiva and the palpebral conjunctiva (symblepharon) will progress and result in severe organic adhesion if left untreated.

When adhesion is about to be formed, there is a possibility of inadequate suppression of inflammation. Therefore, treatment regimen should be reviewed. Rapid tapering of the dose of the systemic steroid often causes increased pseudomembrane formation and accelerates progression of adhesion.

Adhesion that has been formed should be broken up mechanically with a glass rod under anesthesia by ocular instillation to prevent or alleviate symblepharon.

The specific guidelines are provided below.

When a patient has any mild or severer manifestation, culture of eye secretion or conjunctival scraping should be performed, and an antibiotic ophthalmic solution (or an ocular ointment) should be administered about four times daily. When any bacteria are revealed, an antibiotic ophthalmic solution should be applied in consideration of drug susceptibility.

In moderate or severe cases, treatment should be provided topically with an ophthalmic solution or an ocular ointment of 0.1% betamethasone or 0.1% dexamethasone 6 to 8 times daily, according to the severity of the manifestations.

In severe cases, treatment should be provided topically with both an ophthalmic solution and an ocular ointment of 0.1% betamethasone or 0.1% dexamethasone about 10 times daily to suppress inflammation.

Ophthalmologic Treatment in the Subchronic Phase

If a patient responds well to the treatment with steroid pulse therapy and topical administration of betamethasone to the eyes in the acute phase, skin eruption will resolve smoothly. On the other hand, in spite of amelioration of the systemic condition, inflammation of the ocular surface may be prolonged. In such cases, the dose of the steroid needs to be reduced in consideration of not only the skin manifestations but also ocular manifestations.

Prolongation of the corneal epithelial defect which develops in the acute phase will result in an intractable condition called “prolonged epithelial defect,” which can easily cause infections and corneal perforation and is highly likely to lead to vision loss. In such a condition, patients often have a better systemic condition and thus are encouraged to be referred to a cornea specialist, if possible.

Cultivated autologous oral mucosal epithelial cell transplantation is helpful for the treatment of prolonged epithelial defect. In some facilities, amniotic membrane transplantation is performed for the treatment of prolonged epithelial defect.

Ophthalmologic Treatment in the Chronic Phase

Management of the ocular surface plays a major role in the treatment in the chronic phase. The sequelae that develop in the chronic phase mainly include serious dry eye, trichiasis, inflammation of the ocular surface, symblepharon and visual impairment.

1. Severe Dry Eyes

Almost all patients with serious ocular complications concomitantly experience serious dry eye in the chronic phase. Treatment should be provided with the methods such as frequent ocular instillation of artificial tears, ocular instillation of hyaluronic acid and punctal plugging.

Diquas® and Mucosta® are the ophthalmic solutions newly developed and approved for the treatment of dry eye. Mucosta® has an anti-inflammatory action and alleviated hyperemia and dryness in a clinical trial conducted in patients with SJS. The drug often alleviates symptoms and dry eye manifestations in patients with severe dry eye with hyperemia and dry eye in the chronic phase. On the other hand, Diquas® is relatively commonly prescribed to patients with dry eye. One of these ophthalmic solutions is prescribed in addition to hyaluronic acid and is continuously used as long as it works.

2. Trichiasis

Eyelashes should be pulled out every two or three weeks. Surgical removal of the roots of eyelashes works well in severe cases.

Patients with districhiasis or entropium ciliarum are encouraged to undergo surgery by an ophthalmoplasty specialist.

3. Bacterial carriage/Inflammation of the ocular surface

Eye discharge is noted in many patients in the chronic phase. Culture of eye discharge should be performed in patients with hyperemia with eye discharge, and treatment should be provided with ocular instillation of an appropriate antibiotic. Inflammation of the ocular surface may be prolonged in patients in whom MRSA or MRSE has been detected.

4. Symblepharon

Symblepharon may develop in spite of adhesion-preventing treatment in the acute phase. Symblepharon cannot be alleviated with conservative treatment, and amniotic membrane transplantation and conjunctival sac reconstruction using a cultivated autologous oral mucosal epithelial cell sheet are helpful.

In severe cases of trichiasis and in patients with constant hyperemia with eye discharge, symblepharon and invasion of the cornea into the conjunctival tissues may progress slowly.

Attention should be paid to slow progression of adhesion even in the chronic phase.

5. Visual Impairment

Cultivated autologous oral mucosal epithelial cell sheet transplantation is currently performed as Advanced Medical Care B for the treatment of severe visual impairment with adhesion on the ocular surface (website of the Department of Ophthalmology, Kyoto Prefectural University of Medicine).

In overseas, there is a method of using scleral-supported special large hard contact lenses for improved visual acuity, which, however, is not appropriate in Asian patients and in patients with severe SJS/TEN with severe adhesion because of a large diameter (approximately 16-23 mm) of the lenses. In that context, there was an advance in development of a limbal-supported hard contact lens as a new medical device for patients with visual impairment due to SJS/TEN, and an investigator-initiated clinical trial was conducted in 2014.