SJS/TEN: Early Intervention with CAM

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe mucocutaneous disorders, primarily caused by hypersensitivity reactions to certain medications such as allopurinol, antimicrobials, and nonsteroidal anti-inflammatory drugs (NSAIDs) (1, 2). SJS/TEN can have a profound physical and psychological impact on patients, causing devastating mucocutaneous disease and substantially reducing a patient’s quality of life.

The economic burden of SJS/TEN is also significant – both to the healthcare system and to the patient – with prolonged recovery disrupting work and financial stability for sufferers. Despite its rarity, SJS/TEN incurs hundreds of millions of dollars in healthcare costs a year (3), due to the need for extensive patient follow-up care of long-term ocular complications.

While SJS/TEN is often managed in burn units due to its systemic nature, ophthalmologists play a crucial role in addressing its ocular complications, which, to varying degrees of severity, affect approximately 80 percent of patients (4, 5).

Severity, grading, and the need for early intervention

Ophthalmic involvement in SJS/TEN ranges from mild conjunctival hyperemia to complete sloughing of the cornea, conjunctiva, and eyelid margins, resembling a severe chemical burn. Dry eye is the most common symptom, with mild cases presenting with conjunctival hyperemia, discomfort, and ocular surface instability. Moderate to severe cases often involve eyelid margins, where scarring and keratinization in the subacute and chronic phases can accelerate disease progression, leading to persistent ocular surface damage. In advanced cases, persistent epithelial defects, limbal stem cell deficiency, and xerosis increase the risk of corneal opacification and vision loss (6, 7).

Several grading systems are used to classify the severity of ocular involvement in SJS/TEN. In 2015, Sotozono et al. proposed a 0–3 grading scale based on increasing severity, which does not account for eyelid margin involvement, and in 2016, Gregory introduced a grading scale that includes eyelid margin, corneal, and conjunctival involvement (4, 8). Iterating on both of these frameworks, my colleagues and I developed a grade-based management system designed to reflect acute presentation patterns, categorizing ocular involvement into four grades (7):

• Grade 0: no ocular involvement

• Grade 1: conjunctival hyperemia without epithelial defects

• Grade 2: corneal, conjunctival, or eyelid defects without pseudo-membranes

• Grade 3: corneal, conjunctival, and eyelid margin defects with pseudo-membranes

Grades 2 and 3 are associated with more severe chronic disease and require early intervention to minimize long-term complications. While chronic complications cannot be fully prevented, early interventions such as artificial tears, lubrication, inflammation and infection control, and cryopreserved amniotic membrane (CAM) can greatly improve visual outcomes and quality of life.

Treatment regimen

For patients with no ocular involvement (grade 0), preservative-free artificial tears administered every hour are sufficient enough to maintain ocular surface hydration and comfort. However, once a patient progresses, additional interventions are necessary to prevent further ocular surface damage.

In these cases, preservative-free artificial tears continue to be used frequently to avoid toxicity from preservatives. Topical antibiotics – typically fluoroquinolones for broad coverage – are also applied, but other antibiotics may be used. Topical steroid drops should be used to manage inflammation, and topical steroid ointment should be applied to the eyelid margin for prolonged surface contact (7).

Once a patient requires CAM treatment (grade 2 and higher), two forms of CAM are available. Prokera (BioTissue, Inc.) consists of a CAM mounted on a ring and is applied directly to the ocular surface like a contact lens. This device is particularly effective for treating corneal and conjunctival epithelial defects (9), but does not cover the eyelid, eyelid margin, palpebral conjunctiva, or mid-peripheral to peripheral bulbar conjunctiva. In cases necessitating broader coverage, amniotic membrane sheets (AmnioGraft; BioTissue, Inc.) are essential (10). These sheets should be applied to cover all affected areas, including the eyelid margin, in cases with more extensive disease involvement.

Surgical options for SJS/TEN patients are severely limited, and many procedures that successfully treat corneal scarring in non-SJS/TEN patients often fail in this population. As such, prevention and early intervention are especially vital for mitigating long-term ocular damage.

Critical treatment window

The crucial treatment window for SJS/TEN is within five to seven days after onset; beyond this period, irreversible corneal or eyelid damage often occurs, causing permanent vision loss or significant impairment in visual function (7, 8). The biggest barriers to effective acute management are: delay in diagnosis and transfer to a tertiary care center, the availability of an ophthalmologist with the necessary expertise, and the availability of specialized resources – such as CAMs, ophthalmic instruments, and contact lenses – that may be required to care for SJS/TEN patients.

CAM is a proven acute-phase treatment for SJS/TEN, reducing severe ocular complications by providing a protective barrier and promoting healing with its extracellular matrix components. A retrospective study I conducted found that implementing a CAM treatment protocol in acute SJS/TEN significantly improved long-term vision – patients had lower rates of blindness (protocol treated vs no protocol, 67 percent vs 17 percent, respectively) and were more likely to achieve 20/40 vision (33 percent vs 92 percent), enhancing their independence and quality of life (11).

The treatment is most effective when administered within the first week of disease onset, but should really be applied as soon as possible, ideally within 24 hours, to maximize benefits and prevent complications. However, lack of access to prompt ophthalmologic care remains a major barrier to effective acute ocular management of SJS/TEN, which can delay treatment beyond the critical window and reduce therapy effectiveness.

Given the potential for rapid disease progression, continuous monitoring is also essential for ensuring timely intervention. A patient that presents with grade 1 disease – a grade which does not typically require CAM treatment – may progress to grade 2 in a matter of days. Therefore, early identification of disease progression is critical to maximize treatment effectiveness and prevent the occurrence of irreversible damage.

Advancements in CAM application

Traditionally, securing a CAM required suturing three separate sheets of CAM together and then suturing this combined sheet to both the eyelid margin and ocular surface, a labor-intensive process that could take 1.5 to 2 hours under challenging burn unit conditions. The introduction of a larger 5×10 cm CAM sheet somewhat simplified this process, but it remained time-consuming and often required an operating room and general anesthesia (10).

The use of cyanoacrylate glue (Ethicon, Somerville, NJ) has revolutionized CAM application by eliminating the need for sutures, reducing the procedure time from over 30 minutes to just nine minutes. This innovation greatly simplifies the process – the glue secures the membrane to the upper and lower eyelid, avoiding direct contact with the ocular surface to prevent toxicity and discomfort. Additionally, symblepharon rings provide extra support by securing the CAM beneath the eyelids into the fornices (12).

These advancements have improved patient outcomes by making the procedure less invasive and more accessible to ophthalmologists. CAMs secured with cyanoacrylate glue and symblepharon rings have achieved similar long-term visual results as those applied with sutures, while reducing manipulation and bleeding of fragile skin and nearly eliminating the need for general anesthesia (12).

Conclusion

While SJS/TEN can cause severe ocular complications and potential blindness, CAM serves as an effective early intervention to help minimize these risks. Given the rarity of SJS/TEN, ophthalmologists unfamiliar with its management should seek guidance from experienced colleagues at academic centers, where these cases are more frequently treated. With limited treatment options for chronic complications, early acute phase intervention with CAM remains the best strategy for preserving vision and improving outcomes in affected patients. As survival rates increase, ophthalmologists must address both the acute and chronic effects of SJS/TEN, as well as recognizing its broader impact on patients’ quality of life.

Disclosures: Dr. Saeed reports receiving research funding through the National Institutes of Health. She also serves as a paid medical expert in SJS/TEN litigation.