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Clinicopathologic Reports, Case Reports, and Small Case Series
October 2002

Bilateral Epithelial Downgrowth Managed in One Eye With Intraocular 5-Fluorouracil

Arch Ophthalmol. 2002;120(10):1396-1398. doi:

Epithelial downgrowth into the anterior chamber is an extremely rare complication of intraocular surgery. Epithelial cells gain access via incisional defects or by direct implantation at the time of surgery. The tissue can grow in the form of cysts or as layered sheets. If these sheets are left untreated, devastating complications such as intractable glaucoma and retinal detachment result in destruction of the eye.

Historically, the preferred treatment methods are surgical.1 Weiner et al1 suggested that combining antimetabolites with surgical treatments might be superior to surgery alone in controlling the disease. There are reported cases of the use of multiple subconjunctival injections of substantial amounts of 5-fluorouracil to control the disease.2,3 However, these failed once the injections were stopped.2,3

Report of a Case

A 70-year-old, aphakic white woman underwent penetrating keratoplasty (PKP) for interstitial keratitis in 1994 in the right eye and 2 years later in the left eye. In 1997, slitlamp examination of the left eye showed a retrocorneal membrane without a clear site of origin. Argon laser photocoagulation confirmed the presence of epithelial downgrowth, and ultrasound biomicroscopy showed anterior synechiae. Repeat PKP was performed in combination with anterior vitrectomy, release of anterior synechiae, and cryopexy. Histopathological examination of the host corneal button showed stratified epithelial tissue extending along the posterior surface of the cornea. Epithelial downgrowth recurred in 1998, and a repeat PKP combined with anterior vitrectomy and cryopexy were done but failed to prevent recurrence. In 1999, cyclocryotherapy and repeat PKP were performed. Histopathological examination of each of the corneal buttons showed the typical extensive stratified squamous epithelium along the posterior corneal surface. The left eye was ultimately lost to epithelial downgrowth and secondary retinal detachment.

In 1999, the patient experienced graft rejection in the right eye and a repeat PKP was done. Postoperatively, vitreous incarceration in the superior aspect of the graft was managed with pars plana vitrectomy. Thereafter, the intraocular pressure remained elevated despite maximum medical therapy and was successfully controlled with implantation of an Ahmed valve in October 2000. The patient returned 1 month later with complaints of blurry vision. Slitlamp examination showed a retrocorneal membrane. The membrane originated temporally and was thought to be from the site of the paracentesis done at the time of the seton surgery. Internal cryopexy was performed but failed to halt extension of the membrane (Figure 1). In December 2000, one anterior chamber injection of a low dose (0.2 mg) of 5-fluorouracil,4 with a sodium hyaluronate (Healon-GV; Pharmacia Canada Inc, Mississauga, Ontario) pupillary plug, was performed in an attempt to retain the 5-fluorouracil in the anterior chamber and minimize its diffusion into the vitreous. This failed to halt the extension of the membrane. The injection was repeated with a higher dose of 5-fluorouracil (1 mg) mixed with chondroitin sulfate–sodium hyaluronate (Viscoat; Alcon Laboratories, Fort Worth, Tex) after a temporal paracentesis. The mixture was applied directly to the epithelial membrane, which was viscodissected from the posterior corneal surface (Figure 2). Viscodissection was achieved by lifting the edge of the membrane with the cannula and using the viscoelastic–5-fluorouracil mixture to separate the epithelial membrane free of the posterior corner. The chondroitin sulfate–sodium hyaluronate was left in the eye, and there were no problems with elevated intraocular pressure after this treatment. Five months after this treatment, there was no recurrence of the membrane, but a repeat PKP was done in May 2001 for graft failure. Histopathological examination of the host corneal button did not show epithelial downgrowth but showed remnants of a fibrous network. There was no recurrence after this second treatment with 5-fluorouracil during 14 months of follow-up.

Figure 1. 
Slitlamp photograph of the right
eye showing the retrocorneal membrane (arrow) extending from the temporal
aspect of the graft before treatment with intraocular 5-fluorouracil.

Slitlamp photograph of the right eye showing the retrocorneal membrane (arrow) extending from the temporal aspect of the graft before treatment with intraocular 5-fluorouracil.

Figure 2. 
Slitlamp photograph of the right
eye, 1 week after treatment with 5-fluorouracil, showing regression of the
retrocorneal membrane seen in Figure 1.

Slitlamp photograph of the right eye, 1 week after treatment with 5-fluorouracil, showing regression of the retrocorneal membrane seen in Figure 1.


To our knowledge, there are no previous reports of noncongenital bilateral epithelial downgrowth and no reports of treatment using anterior chamber injections of 5-fluorouracil. In the present case, surgical treatment of epithelial downgrowth in the left eye failed to control the disease, resulting in loss of that eye. However, in the right eye, 2 anterior chamber injections of a total of 1.2 mg of 5-fluorouracil, the latter mixed with a visoelastic and combined with viscodissection of the membrane itself, were successful in halting the disease process and preventing recurrence 14 months after the treatment. The advantages of intraocular injections include direct delivery of 5-fluorouracil to the actively proliferating membrane. This allowed use of a substantially smaller effective dose of 5-fluorouracil, compared with subconjunctival injections, and potentially decreased the risk of toxic side effects to the cornea.2,3 Finally, the small number of injections was easily performed and well tolerated. Intraocular injections of 5- fluorouracil may be a viable treat ment option for epithelial downgrowth in selected patients.

Corresponding author: Peter J. Kertes, MD, FRCSC, The University of Ottawa Eye Institute, 501 Smyth Rd, Ottawa, Ontario, Canada K1H 8L6 (e-mail: pkertes@ottawahospital.on.ca).

Weiner  MJTrentacoste  JPon  DMAlbert  DM Epithelial downgrowth: a 30-year clinicopathological review.  Br J Ophthalmol. 1989;736- 11Google ScholarCrossref
Loane  MEWeinreb  RN Glaucoma secondary to epithelial downgrowth and 5-fluorouracil.  Ophthalmic Surg. 1990;21704- 706Google Scholar
Weinreb  RN Adjusting the dose of 5-fluorouracil after filtration surgery to minimize side effects.  Ophthalmology. 1987;94564- 570Google ScholarCrossref
Blumenkranz  MHernandez  EOphir  ANorton  EW 5-Fluorouracil: new applications in complicated retinal detachment for an established antimetabolite.  Ophthalmology. 1984;91122- 130Google ScholarCrossref