Case 1: Fluorescein stain showing quiet bulbar conjunctiva but extensive sloughing of epithelium on the lid margins, tarsal conjunctiva, and cornea
An exam under anesthesia was performed in the operating room on Day 2 of hospitalization. The whitened areas on the lid margins were grasped with toothed forceps and with gentle traction of the entire epithelium on the lid margins, and palpebral conjunctiva is peeled off. AMT was immediately performed on all four eyelids, and a 15 mm Prokera was placed on each eye.
How Do You Decide What Type of Amniotic Membrane to Use and How It Should Be Applied?
The decision to use amniotic membrane is based on the extent and location of epithelial sloughing as highlighted by fluorescein staining (Table 21.1). Small areas of conjunctival sloughing (less than 1 cm in longest dimension) will generally heal without significant scarring if they are not expanding, and there are not multiple such areas adjacent to one another. If enough normal mucosa is retained, it can heal in the small areas of sloughing with normal mucosa. If the areas of staining are extensive, however, the sloughed areas tend to heal in with scar tissue rather than normal mucosa.
Classification of severity of acute SJS/TEN ocular involvement with treatment recommendations
Conjunctival hyperemia with no conjunctival, corneal, or lid margin staining
Medical, with close monitoring
– Small area of conjunctival staining (<1 cm diameter)
Medical, with close monitoring
– Minimal lid margin staining
– No corneal epithelial defect
– Extensive lid margin staining (>1/3 of length)
Urgent AMT to lid margins, palpebral conjunctiva, and ocular surface. May use Prokera on the ocular surface if not multiple areas of bulbar conjunctival stain but must still always cover the lid margins and palpebral conjunctiva with sutured AMT
– Larger, more diffuse conjunctival staining (>1 cm diameter)
– Any corneal epithelial defect
– Same as severe but multiple areas involved [multiple areas of severe involvement on lid margin, conjunctiva (bulbar and palpebral), and cornea]
Same as for severe but more likely to need sutured AMT to ocular surface, rather than just a Prokera. Also more likely to have prolonged inflammation that will need repeat AMT 1 week after the initial AMT
Any sloughing of the corneal epithelium is concerning, as it increases the risk for corneal infection and ulceration. Additionally, intense inflammation and sloughing of the limbal areas may lead to limbal stem cell deficiency in the long term and an inability to maintain a normal corneal epithelium.
Staining of the lid margins is also concerning as it may lead to damage of the meibomian gland orifices and eyelash follicles. In addition to misdirected lashes, there may also be distichiasis in areas that have had severe inflammation along the lid margins. Even if lid margin staining is limited, whitening of the lid margins is concerning. The lid margins may not stain if the dead skin has not yet sloughed off, but whitening suggests that significant necrosis and inflammation are occurring in this area.
Cryopreserved amniotic membrane is the only form of the membrane that has been described in the treatment of acute SJS/TEN [1–4, 6, 7, 9–13, 15]. We begin the AMT procedure by trimming all the eyelashes as close to the skin as possible so that the membranes will be in close contact with the inflamed lid margins. We also debride any necrotic tissue from the lids and conjunctiva. Amniotic membrane is then applied to the lid margins and palpebral conjunctiva. A 3.5 cm square of amniotic membrane (AmnioGraft, Bio-Tissue, Miami, FL) is cut in half and each half is used to treat one eyelid. The membrane is fixated to the external eyelid skin 1–2 mm peripheral to the lash line using an 8–0 nylon running suture. The membrane is oriented with the stromal surface in contact with the epidermal surfaces being treated. Using muscle hooks, the remainder of the amniotic membrane sheet is then tucked over the eyelid margin onto the palpebral conjunctiva and into the fornix. This portion of the membrane is fixated to the posterior lid surface using a double-armed 6–0 polypropylene suture with both ends passed full thickness through the membrane, palpebral conjunctiva, and the eyelid, then tied over bolsters on the external eyelid skin. Generally two separate sets of full-thickness sutures and bolsters are required per eyelid, and all four eyelids are treated in this fashion.
Attention is then turned to the surface of the globe. If the staining involves only a limited area of the bulbar conjunctiva, then a Prokera (Bio-Tissue, Miami, FL) may be used to treat this portion of the eye. A Prokera is a 15 mm diameter symblepharon ring with amniotic membrane stretched across the lumen of the ring. The device is applied in a manner similar to a bandage contact lens (Fig. 21.2). A Prokera only covers the cornea and perilimbal conjunctiva with amniotic membrane, however. If there is extensive staining of the bulbar conjunctiva, it is better to apply a sheet of amniotic membrane that covers the bulk of the ocular surface. A full 3.5 cm square of AmnioGraft is a good size for this step. We prefer to attach the membrane to the bulbar conjunctiva with nylon sutures rather than using fibrin glue. We place a 10–0 nylon running suture circumferentially around the cornea approximately 1–2 mm peripheral to the limbus. We then place a single interrupted suture in each oblique quadrant and at the medial and lateral canthi. Leaving the suture tails long allows them to lie flat and also facilitates finding the sutures for later removal. This suturing may require a trip to the operating room, but we find it is more reliable in this situation than fibrin glue. Fibrin glue will not reliably attach the membrane if there are areas of intact epithelium interspersed among the areas of sloughing. If the ocular surface is treated with sutured AMT rather than a Prokera, we place a separate symblepharon ring on the eye once the membranes have been fixated in place.
Prokera device. Cryopreserved amniotic membrane stretched across the lumen of a symblepharon ring. Amniotic membrane covers only the cornea and perilimbal conjunctiva. In cases with limited bulbar conjunctival sloughing, a Prokera may be used in combination with amniotic membrane sutured to the lids and palpebral conjunctiva but is not an adequate treatment by itself
It needs to be stressed that a Prokera alone, while easy to apply, does not constitute adequate treatment for acute SJS. It is imperative that the tarsal conjunctiva and lid margins be treated with AMT as well. Patients treated with Prokera alone have a higher risk of long-term problems from tarsal and lid margin scarring.
Twelve days after the initial AMT, another exam under anesthesia was performed. The lid sutures and Prokeras were removed. The corneal and conjunctival epithelial defects had resolved, with minimal ongoing inflammation. No further AMT was performed. The patient was discharged after 29 days of hospitalization.
What Is the Follow-Up and Treatment Regimen Following Discharge from the Hospital?
If stable without corneal epithelial defects, patients may be rechecked after 1–2 weeks. We generally continue a topical steroid drop such as fluorometholone 0.1% two to four times per day, cyclosporine 0.05% drops two times per day (Restasis, Allergan, Irvine, CA), and tobramycin 0.3%/dexamethasone 0.1% ointment to the lid margins for 1–2 months depending on the patient’s symptoms and intraocular pressure.
After 9 months of follow-up, the patient had no dry eye symptoms and BCVA was 20/20 in each eye. There was mild scarring of the inferior tarsal conjunctiva in each eye without keratinization ( Fig. 21.3 ). No other ocular surface sequelae had occurred.
Case 1 outcome 6 months after amniotic membrane transplantation for acute Stevens-Johnson syndrome. Minimal scarring and no dry eye problems
A 70-year-old woman with a past medical history of gout had recently been started on allopurinol treatment. She presented to the emergency room with a 1-day history of bilateral eye pain, epiphora, conjunctival injection, and oral mucosal sloughing and was admitted for suspected SJS.
What Is Your Treatment Approach to This Patient?
In patients with acute SJS, ophthalmic involvement can be severe and devastating. Damage wrought to the ocular surface in the acute phase of disease can lead to permanent ocular sequelae, including blindness and debilitating eye pain. Furthermore, ocular involvement can rapidly evolve. Therefore, these patients should be thoroughly examined and followed closely, as described in the previous case. Many reports have shown that aggressively treating inflammation during the acute phase limits long-term damage and ocular sequelae. Treatment with intensive topical anti-inflammatory medications (corticosteroids and possibly cyclosporine) and prophylactic antibiotic drops (especially in the presence of a corneal epithelial defect) may be initiated, and consideration should be given to AMT, depending on the extent of epithelial sloughing on the ocular surface and eyelids (Table 21.1). Additionally, daily eye examinations should be performed to assess for any worsening.
The patient was started on hourly topical fluorometholone ointment (FML 0.1%, Allergan, Irvine, CA) and a broad-spectrum topical antibiotic drop four times a day. Daily eye examinations were performed and included thorough inspection of her eyelids, conjunctivae (bulbar and palpebral), and corneas for fluorescein staining.
Over the next 48 hours, the patient worsened from both an ophthalmic and systemic standpoint, eventually requiring intubation for respiratory distress. Her ophthalmic findings included worsening injection and the development of conjunctival epithelial defects involving both the bulbar conjunctiva and eyelid margins of both eyes.
How Would Your Management Change at This Stage?
In the acute stage of Stevens-Johnson syndrome, progression can occur quickly. Initiating therapy with medical treatments alone is often the first step for patients with similar ophthalmic presentations. Every 24 hours, the patient should be reevaluated to assess the amount of ophthalmic involvement and the response to medical therapy. In this patient, when the ophthalmic picture worsened despite aggressive topical medical treatment, surgical intervention with amniotic membrane was considered.
After a long discussion with the family about the proposed treatment with amniotic membrane, including the risks, benefits, and alternatives, it was decided to initially treat only the left eye with amniotic membrane. Both eyes continued to receive aggressive topical medical therapy.
What Surgical Technique Should Be Used? Where Should the Procedure Be Performed?
The surgical technique for amniotic membrane application in acute SJS/TEN should ensure that all denuded and inflamed surfaces are completely covered with amniotic membrane. We used the technique described by Gregory and covered the lid margins, all conjunctival surfaces (palpebral, forniceal, and bulbar), and the cornea with amniotic membrane [5, 8] For this particular patient, surgery was performed at the bedside based on the recommendation of the primary team. If possible, our preference is to perform surgery in the operating room as this allows for the use of the ophthalmic microscope. However, if the patient is deemed too unstable for transport to the operating room, surgery can safely be performed at the bedside. As is usually the case with the bedside technique, Prokeras were used to cover the cornea and perilimbal bulbar conjunctiva (the bulbar conjunctiva beyond the perilimbal region would require a sheet of sutured amniotic membrane, and suturing to the bulbar surface is difficult without an operating microscope). Four sheets of amniotic membrane were used to cover the lid margins and palpebral conjunctiva of the four eyelids; this can readily be performed without an operating microscope.