Ophthalmologic Manifestations of Cicatricial Pemphigoid Treatment & Management

No topical agent is effective in stopping OCP activity. In selected patients, subconjunctival steroid injections or subconjunctival injections of mitomycin C may be used temporarily for slowing disease progression, while systemic therapy takes effect.

Adjuvant treatment with topical lubricants should be used in patients with dry eye symptoms. The use of topical cyclosporine and tacrolimus ointment has also been described in anecdotal reports to aid in the control of surface inflammation.^[6]

• Systemic corticosteroids can control the activity of the disease; however, they are not as effective as other immunosuppressive drugs, and the doses required have been shown to be very toxic. Additionally, tapering of systemic steroids has always been associated with recurrence of disease activity, suggesting the need of high doses for extended periods of time. Because of the toxicity of long-term corticosteroid use (eg, aseptic hip necrosis, pathological fractures, uncontrolled diabetes mellitus, hypertension), it is an unacceptable treatment. Corticosteroids should never be used as a sole agent. Their use should be reserved only for severely inflamed eyes that do not readily respond to immunosuppression alone. When administered, corticosteroids should be used for a limited period of time, preferably not longer than 3 months.^[7]
• Long-term use (>1 y) of systemic immunomodulators is the major therapeutic strategy in treating OCP. The current guidelines for using chemotherapy in treating OCP are as follows:

  • For mild-to-moderate inflammation, diaminodiphenylsulfone (Dapsone) is a first-line agent, provided the patient is not glucose-6-phosphate dehydrogenase deficient. Methotrexate may also be considered first-line therapy. If therapeutic response is not satisfactory, or if the use of Dapsone is contraindicated, or if the patient cannot tolerate the drug, mycophenolate mofetil or azathioprine can be substituted. If inflammation persists, cyclophosphamide can be used sequentially.
  • For severe inflammation, cyclophosphamide should be used initially, and systemic prednisone could be added with rapid taper for a limited period of time (3 mo).
  • Patients with active conjunctival inflammation refractory to chemotherapy or patients who do not tolerate the spectrum of immunosuppressive drugs can be treated with intravenous immunoglobulin (IVIg) or a combination of IVIg and rituximab infusions.^{[8, 9]} Combination IVIg plus rituximab therapy may be the treatment approach with the highest likelihood of induction of durable remission and drug-free cure^[10] ; the cost of such therapy may actually be less than the other therapeutic approaches, although such cost may appear to be the highest.^[11] Additionally, since such therapy is not FDA-approved for labeling for treating OCP, obtaining insurance carrier coverage for such off-label use may require considerable effort.

Ocular surgical procedures should only be performed when the inflammation is completely under control, and systemic corticosteroids should be used perioperatively, when the procedure involves the conjunctiva or the cornea. Once the inflammation is suppressed, such procedures as marginal rotation of the eyelid, mucous membrane grafting, retractor plication, fornix reconstruction, or cataract extraction can be performed without significant danger of excessive postoperative inflammation and cicatrization.

• Epilation

  • Aberrant lash growth that produces damage to the ocular surface is common in OCP. Extraction of these lashes and destruction of the follicles is important not only to prevent further irritation of the ocular surface but also to remove a factor that can mimic immunologically driven conjunctival inflammation, thereby hindering judgment regarding clinical response to chemotherapy and disease activity.
  • Mechanical epilation has only a temporary effect, and the lashes that regrow may be more deleterious than the original lashes. Gas permeable scleral contact lenses can be used to provide protection to the ocular surface from injury by aberrant lashes.
  • In case of trichiasis or distichiasis, permanent destruction of the lash follicles is ideal, although not easy to provide. Cryodestruction of lash follicles requires subsequent epilation in 10% of patients. The recurrences can be retreated.
• Punctual occlusion

  • Treat dry eye syndrome with punctal occlusion and ocular lubricants without preservatives. Ocular hydration also can be increased with the use of twice daily mild steroid and topical cyclosporine.
  • Treat meibomian gland dysfunction with warm compresses and lid massages with eyelid hygiene, with or without systemic tetracycline therapy.
• Lid surgery

  • Entropion surgery usually is avoided in patients with OCP because of the interference with the conjunctiva. Recently, several cases of lower lid entropion have been treated successfully with a retractor plication technique. The procedure is repeatable in case of undercorrection. Moreover, the conjunctiva remains intact during the surgery, which can avoid the exacerbation of conjunctival inflammation.
  • Tarsorrhaphy can be used in case of lagophthalmos, corneal hypoesthesia, or corneal epithelial defects.
• Fornix reconstruction

  • Amniotic membrane transplantation or autologous oral mucosa can be used to reconstruct the conjunctival fornices in patients with OCP.
  • Mucous membrane grafting should not be performed when patients have severe keratoconjunctivitis sicca, advanced OCP, or active conjunctival inflammation. The procedure not only reconstructs the anatomy of fornices but also provides nonkeratinizing epithelium with goblet cells supplying mucous production to the ocular surface.
  • The beneficial long-term effect of this procedure is provided in approximately one third of the patients.^[12]
• Corneal surgery

  • The visual acuity in patients with OCP is impaired mostly by corneal pathology. Unfortunately, the spectrum of procedures on the cornea providing a satisfactory long-term visual outcome is very limited. Corneal transplantation on a dry eye with impaired lid function and limbal stem cell deficiency has a very poor prognosis; therefore, corneal grafting in patients with advanced OCP should be avoided. This procedure should only be performed in case of corneal perforation.
  • In patients with advanced corneal damage from OCP, keratoprosthesis may be the only feasible alternative for visual rehabilitation. Necrosis of the tissue surrounding the prosthesis is the major problem limiting the long-term outcomes. This process can lead to aqueous leak, retinal detachment, infection, and extrusion of the prosthesis. Recent advances in keratoprosthesis along with lifelong use of topical antibiotics have improved the outcome. At one facility, 5-8 patients had considerable improvement of visual acuity over a 5-year period.
• Cataract surgery

  • The need for cataract surgery is common in patients with OCP. Cataract surgery performed on patients with OCP is followed by increased conjunctival inflammation, rapid progression of keratopathy, and conjunctival scarring, if the disease is not medically controlled.
  • The results of one study showed that a worse outcome of cataract surgery was associated with chemotherapy intolerance or the presence of any preoperative conjunctival inflammation. Similar to other surgical procedures for OCP, the use of perioperative systemic steroids is necessary in patients who are on systemic immunosuppressive therapy and in those patients whose inflammation is currently in remission without taking any immunosuppressive agents.^[13]

• Consult an appropriate specialist in case of skin involvement or involvement of other mucous membranes. Patients who have difficulty swallowing or breathing require an immediate endoscopic examination looking for esophageal webs, as these patients are at risk of asphyxiation.
• Patients receiving chemotherapy may require regular consultations with a chemotherapeutist.
• Patients should be referred to an ear, nose, and throat specialist for laryngoscopy in case of recent onset of hoarseness, which may be caused by laryngeal stenosis and tracheal scarring. These patients are in a medical emergency because of the risk of mucous accumulation and subsequent fatal asphyxiation. A statim laryngoscopy is essential, and it may be a life-saving procedure.

Patients may be limited by visual acuity.