Ocular cicatricial pemphigoid, also known as mucous membrane pemphigoid (MMP), is an autoimmune disease that can cause scarring in the conjunctiva of your eyes.
The conjunctiva is the inside lining of your eyes that keep a smooth surface when you blink or close your eyes. When there is scarring in your conjunctiva, your eye can become damaged, causing vision loss.
MMP can also cause scarring in other mucous membranes, including your mouth and throat. This disease usually affects people over 60, and more women have MMP than men.
As an autoimmune disease, MMP uses your immune system to cause damage to your body in several areas. Symptoms may include the following; eye redness, mucous discharge in your eyes, ulcers in your conjunctiva, mouth, genitals, and anus hoarseness, and difficulty swallowing.
If left untreated, MMP can cause many problems in your eyes. Over time, symptoms can become worse.
Problems can include the following; chronic tear deficiency causing severe dry eyes, entropion/trichiasis—this happens when your eyelids turn inwards, causing your eyelashes to touch the front surface of your eye.
This in turn causes irritation, infection, and scarring eye pain from damage to the cornea loss of vision in the worst cases.
Patients with severe cases of the ocular surface disease can be some of the most challenging in ophthalmology, and cannot be treated with a “cookbook” approach. Often, these patients require a physician to pull out all the stops in the treatment armamentarium.
The first step is keeping the inflammation under control. Without that control, the patient can slide down a path filled with hurdles to improving their ocular health. The importance of the conjunctiva cannot be overemphasized.
The tissue allows for the monitoring of inflammation. The goblet cells, which secrete the mucin layer of the tears, are a hallmark of healthy conjunctival tissue. When goblet cells are identified on the corneal surface, it is diagnostic of limbal stem cell deficiency (LSCD).
In addition to LSCD, other sequelae of conjunctival inflammation can occur, including goblet cell loss, mucin deficiency, symblephara formation, loss of the fornices, and end-stage surface keratinization.
The salvage options are very difficult once patients have run the gauntlet of these ocular insults. The eyes with chronic conjunctival inflammation and total LSCD have the worst prognosis with any surgical intervention.
The sequelae of LSCD are daunting and include conjunctivalisation, visual loss, chronic pain with persistent epithelial defects, photophobia, red-eye, and corneal transplant failure.
Patients with more than 50% LSCD and active conjunctival inflammation, such as those with Stevens-Johnson syndrome, mucous membrane pemphigoid (MMP), and recent chemical or thermal injury, can expect the worst outcomes.
Following a step-wise approach, as discussed here, can help to give patients with ocular cicatricial disease the best results.
Good history-taking is mandatory for identifying some of the ocular offenders in plain sight that can be overlooked, such as topical formulations with preservatives and glaucoma medications that can damage the ocular surface with chronic use.
Also, a medical history of atopy, graftversus-host disease, and Stevens-Johnson syndrome can create cicatricial changes on the ocular surface. The physician should also be alert to a history of infections, i.e., herpes simplex virus and adenovirus; trauma from chemical/thermal injury or radiation; and inflammation from rosacea and chronically treated refractory blepharitis.
The presence of a disease such as MMP with ocular involvement is not always evident initially and the condition of the ocular surface—the persistence of inflammation—can escape the control of the treating physicians.
Determining the etiology of the inflammation is important to keep it in check. MMP can be misdiagnosed and managed as blepharitis for years (stage 1). With no improvement, a biopsy of the abnormal conjunctiva is performed (stage 2).
Symblephara forms (stage 3) and end-stage keratinization (stage 4) develops with resultant poor prognosis. Patients need systemic immunosuppression to control the inflammation. Patients often need a combination of long- and short-term treatments to optimize the ocular surface.
Examples of such treatments are lubricants, anti-inflammatory drugs, nutritional support, management of lid margin disease, adjunctive therapy such as punctual plugs, environmental changes, elimination of agents that are toxic to the ocular surface, changes in systemic medications, and scleral contact lenses, among others.
STEP 1 in managing patients with cicatricial disease is the optimization of glaucoma with the early placement of a tube shunt and eliminating the toxicities from glaucoma medications.
STEP 2 involves correcting lid abnormalities such as entropion, trichiasis, exposure, keratinized lid margins, and lagophthalmos. If left uncorrected, reconstructive efforts will have a poor prognosis.
STEP 3 calls for suppressing ocular surface inflammation and autoimmune responses. This can be accomplished with topical instillation of treatments or systemic therapies. This can take months or years to achieve.
Patients with chemical burns treated with inflammatory suppressive measures do much better sometimes up to a decade after the insult with this approach. This is the point at which we can stop and not need to go on with other interventions.
Two commonly used scleral contact lenses used in patients are the prosthetic replacement of the ocular surface ecosystem (PROSE, Boston Foundation for Sight) and the impression-molded EyePrintPro (EyePrint Prosthetics), a clear device that is custom-fitted onto the eye surface.
The case of a 21-year-old patient with monocular vision who had Stevens-Johnson syndrome and was fitted with the EyePrintPro and achieved a best-corrected visual acuity of 20/30 in his functioning eye.
STEP 5 involves ocular surface stem cell transplantation in which either the limbal stem cells or the conjunctiva can be transplanted for patients for whom the previous steps failed. Symblepharon and ankyloblepharon lysis can be performed, and the fornix can be reformed to facilitate the wearing of therapeutic contact lenses.
The Boston Keratoprosthesis (Kpro type 1) can be implanted if there are contraindications to systemic immunosuppression. Several types of stem cell transplants are available. Conjunctival limbal allograft or autograft are indicated for mild/ moderate disease.
Keratolimbal allografts use cadaver donors and are reserved for moderate and severe diseases in the absence of a suitable donor. These grafts serve as complete barriers to conjunctivalisation, and are secured with glue and sutures and re-epithelialize between 1 and 3 months postoperatively.
A combination approach, i.e., the Cincinnati Procedure, uses both live and cadaver tissue. This provides greater replenishment of goblet cells as well as a 360-degree limbal stem cell barrier.
STEP 6 is the final step—optical corneal transplantation. The surgical choices are deep anterior lamellar keratoplasty, penetrating keratoplasty, Kpro type 1 if the previous two fail, or Kpro type 2 if Kpro type 1 fails.
The patient must have ongoing surveillance for glaucoma, infection, corneal melt, retinal detachment, sterile vitritis, endophthalmitis, or extrusion.
Symblepharon formation may indicate that much more is going on as in the case of a patient referred for a biopsy to rule out MMP. The biopsy uncovered squamous cell carcinoma. Symblepharon after epidemic keratoconjunctivitis also can be associated with binocular diplopia with side gaze.
After dry eye and inflammation were addressed, the symblephara were freed and an amnion graft placed into the conjunctival defect and fornix.
The key to success is to allow conjunctival reepithelialisation before symblephara re-forms. Keratolimbal allograft segments can be used to treat symblephara that form as the result of mechanical and iatrogenic trauma, such as orbital floor fractures, tree branch injuries, and blepharoplasty gone awry.
Also according to a reported an unusual case in which uneventful cataract surgery was complicated by symblepharon formation to the wound, postoperatively; The patient-reported eye pain, fatigue, severe weakness, abnormal complete blood count, and bone marrow biopsy that resulted in an ultimate diagnosis of leukemia, which was the underlying cause for paraneoplastic pemphigus, which requires treatment of the malignancy and immunosuppressive therapy.
A step-wise approach with a multi-disciplinary team is needed for ocular surface reconstruction in ocular cicatricial diseases. Therapeutic scleral contact lenses can delay or obviate the need for surgery. Biopsy acute symblepharon to rule out squamous cell carcinoma and MMP. MMP can be a paraneoplastic manifestation.