Ocular cicatricial disease requires a step-wise approach to secure the best results.
This article was reviewed by Clara C. Chan, MD, FRCSC, FACS
Patients with severe cases of 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 of 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.
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According to Clara C. Chan, MD, FRCSC, FACS, assistant professor of ophthalmology, University of Toronto, department of ophthalmology, and medical director, Eye Bank of Canada, Ontario Division, the importance of the conjunctiva cannot be overemphasized.
“The tissue allows for monitoring of inflammation,” she said. “The goblet cells, the 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 are goblet cell loss, mucin deficiency, symblephara formation, loss of the fornices, and end-stage surface keratinization, Dr. Chan pointed out.
The salvage options are very difficult once patients have run the gantlet of these ocular insults.
Dr. Chan explained that eyes with chronic conjunctival inflammation and total LSCD have the worst prognosis with any surgical intervention.
“The sequelae of LSCD are daunting, and include conjunctivalization, visual loss, chronic pain with persistent epithelial defects, photophobia, red eye, and corneal transplant failure,” she said.
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.
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Good history-taking is mandatory for identifying the 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.
In addition, a medical history of atopy, graft-versus-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 clearly is important to keep it in check.
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Dr. Chan pointed out that 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) develop 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 that include lubricants, anti-inflammatory drugs, nutritional support, management of lid margin disease, and adjunctive therapy such as punctal plugs, environmental changes, elimination of agents toxic to the ocular surface, changes in systemic medications, scleral contact lens, among others.
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Steps to success
Step 1 in managing patients with cicatricial disease is optimization of glaucoma with 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, Dr. Chan commented.
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,” she emphasized. Patients with chemical burns treated with inflammatory suppressive measures do much better sometimes up to a decade after the insult with this approach.
Step 4 is a preemptive trial of scleral contact lenses to avoid surgery. If the contact lens fails, ocular surface reconstruction is a consideration. “Scleral contact lenses,” she noted, “have revolutionized how I manage these patients. Often, 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 Dr. Chan’s 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.
Dr. Chan described 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.
“We did not have to do stem cell transplantation, avoided systemic immunosuppressive therapy, and his vision has been maintained for 10 years,” she said.
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 re-formed to facilitate wearing of therapeutic contact lenses. The Boston Keratoprosthesis (Kpro Type 1) can be implanted if there are contraindications to systemic immunosuppression, Dr. Chan noted.
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A number of 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 disease in the absence of suitable donor; these grafts serve as complete barriers to conjunctivalization and are secured with glue and sutures and reepithelialize from between 1 to 3 months postoperatively, according to Dr. Chan.
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,” she explained.
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 I fails. “The patient must have ongoing surveillance for glaucoma, infection, corneal melt, retinal detachment, sterile vitritis, endophthalmitis, or extrusion,” Dr. Chan advised.
According to Dr. Chan, 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.
This article was reviewed by Clara C. Chan, MD, FRCSC, FACS
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 reepithelialization 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.
Dr. Chan described an unusual case in which uneventful cataract surgery was complicated by symblepharon formation to the wound, postoperatively.
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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,” she concluded. “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.
Read more by Lynda Charters
Clara C. Chan, MD, FRCSC, FACS
This article is based onDr. Chan's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Chan has received prior honoraria or research funds from Alcon, Allergan, Bausch + Lomb, Johnson & Johnson, Labtician Thtea, Santen, Shire, Tearlab, and Zeiss.