Mucous membrane pemphigoid is characterized by the presence of linear deposits of C3, IgG, IgA, or IgM along the epithelial basement membranes. More than 10 target antigens have been identified in mucous membrane pemphigoid, and these are all components of the epithelial basement membrane.³ Autoantibodies against these basement membrane components include Bullous pemphigoid antigen 1 and 2, Laminin 5 and 6, and type VII collagen. These probably play a role in the pathogenesis of this group of diseases,³ and in the case of OCP, in particular, one antigen, the β4 subunit of α6β4 integrin, has been identified as the target conjunctival basement membrane autoantigen.⁴ When the circulating autoantibodies bind to antigens within the basement membrane, they activate the complement cascade with complement deposition at the level of the lamina lucida with release of inflammatory cytokines and hydrolytic enzymes.⁴

Conventional histopathologic examination is not usually conclusive in OCP, but there are some suggestive findings including the predominance of T cells, neutrophils, and histiocytes; a decrease in goblet cell density; and a mild capillary proliferation.⁴,⁵ The predominance of T cells has led some authors to hypothesize a model for the pathogenesis of OCP. This model postulates a shift away from T suppressor cells to T helper cells that allow the B cells, which are normally prevented by T suppressor cells from releasing autoantibodies against basement membrane components, to escape this surveillance mechanism and promote the activation or release of rogue clones of B lymphocytes, which synthesize these autoantibodies.⁴ It must be underscored that the gold standard for diagnosis of OCP is with the use of immunofluorescence and not conventional histology.⁴ Although the demonstration of linear deposits of IgA, IgG, IgM, or C3 along epithelial basement membranes is one of the essential criteria for the diagnosis of mucous membrane pemphigoid,³ the situation with OCP is more complicated,³,⁴,⁷ and the range of positive biopsies vary from 20% to 67% only. Therefore, although a positive biopsy establishes the diagnosis, a negative one does not exclude OCP.³,⁴,⁷,⁹ It should be noted that demonstration of linear IgG alone is nonspecific as it can be demonstrated in any inflammatory eye condition.⁴ Certain precautions, however, may improve the diagnostic yield: (1) the biopsy specimen should be obtained from conjunctival tissue immediately adjacent to the inflamed tissue and not from the inflamed tissue itself, let alone scarred tissue; (2) if there is multiorgan involvement, a nonocular site should be chosen; (3) fresh tissue should be immediately submitted for immunofluorescence; and (4) the routine use of immunoperoxidase staining in addition to immunofluorescence significantly increases the diagnostic yield.³,⁴,⁷

The age of onset of OCP peaks during the 7th and 8th decades, but this may be partially attributable to a delay in presentation rather than just a delay in onset.⁵,⁹ The ocular, as well as the palpebral findings of OCP, are all attributable to subepithelial fibrosis,⁴,⁷ which usually manifests initially with unilateral or less commonly bilateral chronic conjunctivitis, and nonspecific symptoms of tearing, redness, and foreign body sensation. This is followed by progressive shortening of the conjunctival fornix and symblepharon formation, which usually starts in the lower followed by the upper eyelid (Figure 98.2). Progressive fibrosis results in deformed eyelids with loss of normal architecture, ankyloblepharon with lagophthalmos, keratinization of the mucocutaneous junction, trichiasis, distichiasis, or frank cicatricial entropion (Figure 98.3). The process is progressive and ultimately results in complete bilateral occlusion of the fornices (Figure 98.4). An important clinical finding that is rarely discussed in the literature is that the palpebral, as well as the conjunctival, findings usually start medially. Trichiasis and distichiasis are not uncommon medially and may extend to the lacrimal portion of the eyelids, which is normally devoid of lashes. Ankyloblepharon also starts medially with effacement of the plica semilunaris before advancing laterally as the disease progresses. Additional ocular findings include punctal and canalicular fibrosis, which typically precede occlusion of the ducts of the main and accessory lacrimal glands. Thus, patients with OCP initially present with tearing followed years later by symptoms of severe dry eyes that may also be exacerbated by progressive destruction of the goblet cells.⁷ It is always important to rule out OCP in all patients presenting with tearing and punctal/canalicular fibrosis before rushing to lacrimal surgery that could exacerbate
dry eyes in the future. This vicious cycle of entropion, trichiasis, dry eyes, and lagophthalmos eventually leads to corneal scarring and even corneal perforation.⁷ The clinical manifestations of OCP might not always conform to a strict classification scheme, so it is necessary to keep a broad categorization in mind to serve as a framework for therapeutic decision making. Several classification schemes have been proposed over the years, but the most accepted staging system is the Foster staging system, which classifies ocular/periocular changes in OCP into four stages: Stage I findings include conjunctivitis with discharge and conjunctival subepithelial fibrosis, stage II is characterized by inferior fornix foreshortening, stage III is defined by the appearance of a symblepharon, and stage 4 is an end-stage disease with marked ocular surface keratinization and ankyloblepharon (Figure 98.2B).⁵,⁸ Foster stages II and III are further classified into four subcategories (a-d) according to the degree of fornix shortening.¹⁰