Grand Rounds at the New England Eye Center

Elderly woman presents with bilateral symblephara

Both eyes also had mild optic disc pallor with peripapillary atrophy as well as myopic macular degeneration.

A 75-year-old woman was referred to the New England Eye Center for evaluation of 2 months of intermittent burning, tearing and redness of both eyes. Her symptoms initially involved the right eye only, but after 2 to 3 weeks, the left eye became affected as well.

The patient’s ocular history was notable for myopic degeneration of both eyes, a macular hole in the right eye with surgical repair in 2001, retinal detachment in the right eye with surgical repair in 2004 and pseudophakia in both eyes. Her most recent baseline corrected vision was 20/400 in the right eye and 20/30 in the left eye. Her medical history included hypertension, hyperlipidemia, gastroesophageal reflux and type 2 diabetes. Her ophthalmic medications included cyclosporine ophthalmic solution in both eyes, loteprednol etabonate ophthalmic gel in the right eye and artificial tear ointment in the right eye. Her systemic medications included metformin, glyburide, lisinopril, atorvastatin, omeprazole, alprazolam and a multivitamin. She had no known drug allergies. She did not smoke or use any illicit drugs, and she drank alcohol only socially. Family history did not include any eye disease. Her review of systems was otherwise unremarkable; more specifically, the patient denied oral and nasal sores, difficulty swallowing and skin rashes.

Examination

slit lamp exam of the right eye
Figure 1. On slit lamp exam of the right eye, there was subepithelial fibrosis, inferior fornix foreshortening and symblephara centrally and laterally in the lower fornix.

Source: Malgorzata Dymerska, MD, Michael B. Raizman, MD, and Nora M.V. Laver, MD

slit lamp exam of the left eye
Figure 2. On slit lamp exam of the left eye, there was subepithelial fibrosis, inferior fornix foreshortening and symblephara nasally and laterally in the lower fornix.

The patient’s corrected visual acuity in the right eye was count fingers at 3 feet and did not improve with pinhole; in the left eye, the corrected visual acuity was 20/40 and improved to 20/30 with pinhole. The pupil in the right eye was round and minimally reactive; the pupil in the left eye was round and briskly reactive to light. There was a slight right afferent pupillary defect. IOP was 19 mm Hg bilaterally. Motility was full. Confrontation visual field testing was normal in the left eye but showed diffuse constriction in the right eye.

External exam was normal in each eye. Slit lamp exam was notable for upper eyelid madarosis bilaterally that prevented upper eyelid eversion, as well as bilateral inferior fornix foreshortening with conjunctival subepithelial fibrosis. There were symblephara centrally and temporally in the right lower fornix (Figure 1), and in the left lower fornix, there were symblephara nasally and temporally (Figure 2). Examination of the cornea was notable for decreased tear breakup time and diffuse superficial punctate keratitis bilaterally. The anterior chambers were deep and quiet bilaterally. There were well-centered posterior capsule IOLs bilaterally, with a dense posterior capsular opacification in the right eye and an open posterior capsule in the left eye.

Posterior segment exam showed mild optic disc pallor with peripapillary atrophy as well as myopic macular degeneration bilaterally. There was also scarring in the peripheral retina of the right eye.

What is your diagnosis?

See answer on next page.

Bilateral symblephara

The differential diagnosis for bilateral symblephara includes several inflammatory and infectious etiologies. Ocular cicatricial pemphigoid typically presents in elderly patients with conjunctival subepithelial fibrosis, forniceal foreshortening and symblepharon, all of which our patient had. The inferior fornix is usually the initial site of involvement. Stevens-Johnson syndrome with ocular involvement can present with mucopurulent conjunctivitis and can lead to symblepharon formation. This condition was thought to be less likely in our patient, as she did not have mucopurulent discharge and had no known triggers for a systemic inflammatory reaction, such as recent viral illnesses or changes in medications. Conjunctival chemical and thermal burns can result in scarring and lead to symblepharon formation, but our patient did not have a history of such burns. Adenoviral, herpes and other viral infections can also lead to symblepharon. Repeat episodes of active trachoma can lead to conjunctival scarring and symblepharon formation as well, but this was less likely in our patient who did not have documented past episodes of follicular conjunctivitis. Of note, trachoma usually involves the superior conjunctiva before the inferior.

Additional workup

The patient underwent conjunctival biopsy with removal of tissue adjacent to the superior limbus of the right eye. Direct immunofluorescence of the conjunctival specimen showed linear IgM and fibrinogen deposits in the basement membrane of the conjunctival epithelium (Figure 3), consistent with a diagnosis of ocular cicatricial pemphigoid.

Direct immunofluorescence of the conjunctival specimen
Figure 3. Direct immunofluorescence of the conjunctival specimen showed linear IgM and fibrinogen deposits in the basement membrane of the conjunctival epithelium.

Discussion

Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune conjunctivitis that leads to scarring (cicatrization) of the conjunctiva. OCP is estimated to represent about 60% of cicatricial conjunctivitis. Its incidence is between one in 12,000 to one in 60,000. Women are generally affected more frequently than men. The average age of onset is usually between 60 and 80 years, with individuals younger than 30 years of age rarely affected. The exact pathogenesis of the condition is not well known at this time.

OCP typically presents as persistent conjunctivitis that has limited response to topical treatment. In early stages, subepithelial fibrosis of the conjunctiva and shortening of the fornices can be seen. Symblepharon formation can subsequently occur, as well as cicatricial entropion and trichiasis. In severe cases, keratinization of the cornea and ankyloblepharon formation can occur. Vision loss is common if the disease progresses to involve the cornea. Severe dry eye can result from conjunctival damage.

It is important to remember that OCP is the ocular manifestation of mucous membrane pemphigoid, which can cause oral, nasopharyngeal, anal, genital and, less commonly, tracheal and esophageal ulceration. Eye involvement can be isolated or occur along with inflammation of the other mucosal sites.

Diagnosis of OCP requires a conjunctival biopsy that should be submitted unfixed for direct immunofluorescence. Samples are then stained for IgG, IgA, IgM and C3 complement. Positive staining shows a linear pattern of deposition at the level of the basement membrane of the conjunctival epithelium.

Treatment typically requires systemic therapy, with topical therapy as an adjunct for surface disease. Corticosteroids and other systemic immunosuppressive medications are used.

Clinical course continued

Our patient’s condition appeared to be in remission after the biopsy, and her symptoms and surface exam were much improved with treatment of the ocular surface, with more frequent topical treatment with loteprednol etabonate ophthalmic gel and artificial tear ointment bilaterally. Her exam has been stable for more than 5 months, and she has not required initiation of systemic immunosuppressive therapy.

A 75-year-old woman was referred to the New England Eye Center for evaluation of 2 months of intermittent burning, tearing and redness of both eyes. Her symptoms initially involved the right eye only, but after 2 to 3 weeks, the left eye became affected as well.

The patient’s ocular history was notable for myopic degeneration of both eyes, a macular hole in the right eye with surgical repair in 2001, retinal detachment in the right eye with surgical repair in 2004 and pseudophakia in both eyes. Her most recent baseline corrected vision was 20/400 in the right eye and 20/30 in the left eye. Her medical history included hypertension, hyperlipidemia, gastroesophageal reflux and type 2 diabetes. Her ophthalmic medications included cyclosporine ophthalmic solution in both eyes, loteprednol etabonate ophthalmic gel in the right eye and artificial tear ointment in the right eye. Her systemic medications included metformin, glyburide, lisinopril, atorvastatin, omeprazole, alprazolam and a multivitamin. She had no known drug allergies. She did not smoke or use any illicit drugs, and she drank alcohol only socially. Family history did not include any eye disease. Her review of systems was otherwise unremarkable; more specifically, the patient denied oral and nasal sores, difficulty swallowing and skin rashes.

Examination

slit lamp exam of the right eye
Figure 1. On slit lamp exam of the right eye, there was subepithelial fibrosis, inferior fornix foreshortening and symblephara centrally and laterally in the lower fornix.

Source: Malgorzata Dymerska, MD, Michael B. Raizman, MD, and Nora M.V. Laver, MD

slit lamp exam of the left eye
Figure 2. On slit lamp exam of the left eye, there was subepithelial fibrosis, inferior fornix foreshortening and symblephara nasally and laterally in the lower fornix.

The patient’s corrected visual acuity in the right eye was count fingers at 3 feet and did not improve with pinhole; in the left eye, the corrected visual acuity was 20/40 and improved to 20/30 with pinhole. The pupil in the right eye was round and minimally reactive; the pupil in the left eye was round and briskly reactive to light. There was a slight right afferent pupillary defect. IOP was 19 mm Hg bilaterally. Motility was full. Confrontation visual field testing was normal in the left eye but showed diffuse constriction in the right eye.

External exam was normal in each eye. Slit lamp exam was notable for upper eyelid madarosis bilaterally that prevented upper eyelid eversion, as well as bilateral inferior fornix foreshortening with conjunctival subepithelial fibrosis. There were symblephara centrally and temporally in the right lower fornix (Figure 1), and in the left lower fornix, there were symblephara nasally and temporally (Figure 2). Examination of the cornea was notable for decreased tear breakup time and diffuse superficial punctate keratitis bilaterally. The anterior chambers were deep and quiet bilaterally. There were well-centered posterior capsule IOLs bilaterally, with a dense posterior capsular opacification in the right eye and an open posterior capsule in the left eye.

Posterior segment exam showed mild optic disc pallor with peripapillary atrophy as well as myopic macular degeneration bilaterally. There was also scarring in the peripheral retina of the right eye.

What is your diagnosis?

See answer on next page.

PAGE BREAK

Bilateral symblephara

The differential diagnosis for bilateral symblephara includes several inflammatory and infectious etiologies. Ocular cicatricial pemphigoid typically presents in elderly patients with conjunctival subepithelial fibrosis, forniceal foreshortening and symblepharon, all of which our patient had. The inferior fornix is usually the initial site of involvement. Stevens-Johnson syndrome with ocular involvement can present with mucopurulent conjunctivitis and can lead to symblepharon formation. This condition was thought to be less likely in our patient, as she did not have mucopurulent discharge and had no known triggers for a systemic inflammatory reaction, such as recent viral illnesses or changes in medications. Conjunctival chemical and thermal burns can result in scarring and lead to symblepharon formation, but our patient did not have a history of such burns. Adenoviral, herpes and other viral infections can also lead to symblepharon. Repeat episodes of active trachoma can lead to conjunctival scarring and symblepharon formation as well, but this was less likely in our patient who did not have documented past episodes of follicular conjunctivitis. Of note, trachoma usually involves the superior conjunctiva before the inferior.

Additional workup

The patient underwent conjunctival biopsy with removal of tissue adjacent to the superior limbus of the right eye. Direct immunofluorescence of the conjunctival specimen showed linear IgM and fibrinogen deposits in the basement membrane of the conjunctival epithelium (Figure 3), consistent with a diagnosis of ocular cicatricial pemphigoid.

Direct immunofluorescence of the conjunctival specimen
Figure 3. Direct immunofluorescence of the conjunctival specimen showed linear IgM and fibrinogen deposits in the basement membrane of the conjunctival epithelium.

Discussion

Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune conjunctivitis that leads to scarring (cicatrization) of the conjunctiva. OCP is estimated to represent about 60% of cicatricial conjunctivitis. Its incidence is between one in 12,000 to one in 60,000. Women are generally affected more frequently than men. The average age of onset is usually between 60 and 80 years, with individuals younger than 30 years of age rarely affected. The exact pathogenesis of the condition is not well known at this time.

OCP typically presents as persistent conjunctivitis that has limited response to topical treatment. In early stages, subepithelial fibrosis of the conjunctiva and shortening of the fornices can be seen. Symblepharon formation can subsequently occur, as well as cicatricial entropion and trichiasis. In severe cases, keratinization of the cornea and ankyloblepharon formation can occur. Vision loss is common if the disease progresses to involve the cornea. Severe dry eye can result from conjunctival damage.

It is important to remember that OCP is the ocular manifestation of mucous membrane pemphigoid, which can cause oral, nasopharyngeal, anal, genital and, less commonly, tracheal and esophageal ulceration. Eye involvement can be isolated or occur along with inflammation of the other mucosal sites.

Diagnosis of OCP requires a conjunctival biopsy that should be submitted unfixed for direct immunofluorescence. Samples are then stained for IgG, IgA, IgM and C3 complement. Positive staining shows a linear pattern of deposition at the level of the basement membrane of the conjunctival epithelium.

Treatment typically requires systemic therapy, with topical therapy as an adjunct for surface disease. Corticosteroids and other systemic immunosuppressive medications are used.

PAGE BREAK

Clinical course continued

Our patient’s condition appeared to be in remission after the biopsy, and her symptoms and surface exam were much improved with treatment of the ocular surface, with more frequent topical treatment with loteprednol etabonate ophthalmic gel and artificial tear ointment bilaterally. Her exam has been stable for more than 5 months, and she has not required initiation of systemic immunosuppressive therapy.