Older man presents with spontaneous corneal perforation

He reported burning, irritation and foreign body sensation but no acute pain.

Issue: June 10, 2016

ByKamden Kopani, MD

ByJames Constans, MD

A 76-year-old man presented urgently to the New England Eye Center with decreased vision in the left eye after experiencing a “gush of fluid from the eye.” The symptoms were spontaneous in onset, without history of ocular trauma or mechanical insult. He reported no acute pain but did report continuing burning, irritation and mild foreign body sensation related to chronic dry eye syndrome. He had a history of myelodysplastic syndrome and previously had a bone marrow transplantation.

Examination

At time of presentation, the patient’s best corrected visual acuity was 20/200 in the left eye. There was no afferent pupillary defect. Extraocular motility was normal. IOP measurement was deferred due to corneal findings. Conjunctival superficial punctate keratopathy was noted, alongside diffuse injection and subepithelial fibrosis on lid eversion. The cornea was hazy in appearance and contained a 4.5 mm × 0.5 mm horizontal linear epithelial defect noted in the inferior portion of the central visual axis, originating nasally. The defect extended to variable depth throughout its length, full thickness in depth at the temporal most edge. There was a region of stromal thinning to the level of Descemet’s membrane temporally. The anterior chamber was shallow and contained fibrin strands. There was no cell, flare, hypopyon or hyphema.

Additional history

The patient’s bone marrow transplantation was performed roughly 5 years before the current presentation. His post-transplant course was complicated by graft-versus-host-disease (GVHD), diagnosed by his oncologist. He had presented to the New England Eye Center 1 month prior with similar symptoms in the contralateral eye, whereupon he was found to have sustained a spontaneous corneal perforation. This was repaired with dot application of cyanoacrylate adhesive, placement of a bandage contact lens and completion of a temporary lateral tarsorrhaphy. On follow-up, his primary ophthalmologist started him on high-dose systemic prednisone.

What is your diagnosis?

Spontaneous corneal perforation

Graft-versus-host-disease, a common complication of allogeneic bone marrow transplantation, occurs with an incidence of 25% to 70%. The condition has historically been classified as acute or chronic, based on the organ systems involved, the type of pathology seen and the temporal relation of symptom onset with the transplantation itself, utilizing 100 days as an accepted benchmark. Acute GVHD can affect any organ system but most commonly involves the skin, gastrointestinal tract and liver. Chronic GVHD resembles an autoimmune presentation, regularly affecting a more varied assortment of organs, including the skin, nails, mouth and, notably, the eyes.

Discussion

Ocular GVHD occurs with an incidence of 60% to 90% among patients with either acute or chronic GVHD, although as mentioned above, it is most commonly associated with chronic GVHD (40% to 60% of cases). While any portion of the globe and surrounding tissues may be affected, the most frequent presentations include keratoconjunctivitis sicca (most common), cataract formation and ocular hypertension. Additional findings of uveal and vitreoretinal involvement have also been described, including uveitis and retinal microvasculopathy, demonstrated by optic disc edema, cotton-wool spots, hemorrhage or lipid deposition. These changes create a hostile surface environment, whereupon patients commonly endorse symptoms of dry eye including burning, itching, photophobia, red eye, dull sensation, heaviness and foreign body sensation. The natural history of untreated keratoconjunctivitis sicca and its associated surface inflammation is wrought with sequelae including meibomian gland dysfunction, scarring, symblepharon and blepharitis with the potential to facilitate further corneal complications including ulceration, melt and perforation.

Ocular GVHD can be diagnosed clinically, with large emphasis placed on the coupling of the patient’s own history and the clinician’s findings on exam. Confirmation may then be obtained with conjunctival biopsy. Techniques aimed at objectively quantifying the condition’s severity include those commonly employed when assessing for routine dry eye syndrome, including tear breakup time, Schirmer test, meibomian gland expression and examination for corneal/conjunctival irregularity with surface staining.

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A wide variety of medical therapies are available for the treatment of dry eye syndrome related to ocular GVHD, the majority of which are aimed at improving surface lubrication and mitigating surface inflammation. Lin and colleagues describe success with a progressive spectrum of therapy involving initial use of artificial tears and topical anti-inflammatory agents such as prednisolone and cyclosporine, extending to the second-line use of undiluted autologous serum tears, rich in platelet-derived growth factor. For refractory dry eye syndrome related to GVHD or for cases involving multiple organ systems, patients may also benefit from the administration of systemic immunosuppression in addition to any ongoing systemic prophylaxis. Surgical management also lies along a therapeutic spectrum, with punctal occlusion providing a minimally invasive initial approach. Temporary tarsorrhaphy and the use of bandage contact lenses are typically reserved for refractory cases, particularly those with recurrent epithelial compromise. Tissue adhesive, such as cyanoacrylate glue, may be used for focal full-thickness corneal erosion, saving keratoplasty as a final option for recurrence or large-diameter erosions.

Other management considerations for the additional sequelae of ocular GVHD include regular monitoring of IOP, particularly with concomitant use of topical steroids, and early initiation of topical IOP-lowering medications when indicated. In those patients requiring surgical extraction of GVHD-induced cataracts, practitioners should remain vigilant for exacerbation of dry eye symptoms during the immediate postoperative course, as this is a likely time period for symptom flare.

Follow-up

Our patient’s perforation in the left eye was initially managed conservatively in the office with the application of cyanoacrylate glue and a bandage contact lens. Tarsorrhaphy was recommended although ultimately deferred per patient preference. He was followed closely over the next 4 weeks, during which time he demonstrated gradually worsening surface disease and exhibited additional perforations adjacent to the initial breach, despite escalating medical therapy and placement of punctal plugs. Of note, the corneal erosion in the right eye remained stable during this same period, providing supportive evidence for the significant protective effect of tarsorrhaphy in the setting of GVHD. The decision was then made to perform a more definitive repair, and the patient underwent penetrating keratoplasty in the left eye with creation of temporary lateral tarsorrhaphy. Initial consideration was given to performing a deep anterior lamellar keratoplasty in place of PK given the procedure’s comparatively lower risk of complication, notably rejection. It was unclear how the history of multiple perforations had affected the integrity of the underlying endothelium, however, and PK was viewed as a more appropriate option.

Given the increased risk of corneal melt in the setting of GVHD, the patient was admitted to the hospital and observed during the initial postoperative period. By postoperative day 5, his graft remained clear with visibly healing epithelium and without evidence of infiltrate or melt. He was then deemed safe for discharge home on continued oral prednisone therapy as well as a regimen of autologous serum tears to assist in lubrication and postoperative wound healing. Close multidisciplinary follow-up was arranged, including rheumatology referral for titration and eventual conversion to a steroid-sparing maintenance therapy for GVHD.

References:
Dean RM, et al. Curr Hematol Rep. 2003;2(4):287-294.
Ferrara JL, et al. Lancet. 2009;doi:10.1016/S0140-6736(09)60237-3.
Filipovich AH, et al. Biol Blood Marrow Transplant. 2005;doi:10.1016/j.bbmt.2005.09.004.
Lin X, et al. Clin Ophthalmol. 2015;doi:10.2147/OPTH.S84704.
Nassiri N, et al. J Ophthalmic Vis Res. 2013;8(4):351-358.
Ogawa Y, et al. Br J Ophthalmol. 1999;doi:10.1136/bjo.83.10.1125.

For more information:
James Constans, MD, and Kamden Kopani, MD, can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Kristen E. Dunbar, MD, and Kendra Klein, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.