Epithelial Downgrowth
Epithelial Downgrowth
Historically, epithelial downgrowth was encountered more commonly than it is today; in fact, 20 percent
of enucleations after cataract extraction in the early part of the 20th century were related to epithelial
downgrowth. Recent estimates suggest that epithelial downgrowth occurs in less than 0.1 percent of
cataract surgeries, including intra- and extracapsular surgeries. The incidence has further decreased from
there thanks to current emphasis on phacoemulsification and better corneal wound construction. During
the past quarter century, the incidence has significantly decreased mainly due to technological advances
in ophthalmic surgery.
Although rare, epithelial downgrowth is an important entity to recognize, as its sequelae can lead to
significant ocular morbity and blindness. The treatment of epithelial downgrowth has been associated
with limited success, but recently there have been some advances.
Pathogenesis/Mechanism
Epithelial downgrowth is typically detected six to 11 months after the initial surgery or trauma, but it
can be seen as early as two weeks and as late as 10 years following the inciting event. Epithelium must
gain entry into the eye, as it does not develop de novo within the eye by metaplasia.
Several hypotheses exist about its etiology. The three main theories include 1) implantation of epithelial
cells within the eye by trauma or surgical manipulation, 2) incorporation of a conjunctival flap of tissue
through a traumatic or surgical wound and 3) delayed closure of a corneal or scleral wound.
Experimentally, simple implantation of epithelial tissue within the eye has failed to produce the typical
downgrowth pattern. The third mechanism is generally accepted to be the most likely, with migrating
epithelial cells gaining entry through a persistent open wound.
Dr. Seth is an ophthalmology resident. Dr. Huang is an assistant professor of ophthalmology. Both are
at Yale University. Dr. Foster is a professor of ophthalmology at the Massachusetts Eye Research and
Surgery Institute in Cambridge, Mass. The authors report no related financial interest
Complications
Laser photocoagulation is one technique that has helped to identify the borders of the
intraocular epithelial membrane on the iris surface. In areas of the iris covered by the
epithelial cells, the laser photocoagulation causes a fluffy whitening of the epithelial
membrane, not seen on normal iris tissue. Specular microscopy also has been used for the
detection of the advancing edge of epithelium on the corneal endothelium. Slit-lamp
examination may show evidence of other presenting signs, including iris incarceration,
vitreous wick or a positive Seidel test.
Treatment
Irradiation was first used to treat epithelial downgrowth in the early part of the 20th
century. It had a poor success rate and a variety of postoperative radiation-related
complications. More recent treatment modalities involve surgical scraping, peeling,
alcohol treatment, cryotherapy and wide excision of epithelial proliferation with ablative
therapy to adjacent structures in order to eliminate residual cells.More conservative
therapies are commonly associated with treatment of epithelial cysts with well-defined
boundaries. Treatment of these cysts include aspiration of the cystic fluid with or without
cauterization, aspiration and diathermy, aspiration and iridectomy, aspiration and
injection of sclerosing agents or alcohol, direct electrocautery and photocoagulation.
Unfortunately, all these modalities for epithelial downgrowth are associated with a high
failure rate. Failures associated with treatment are related to difficulty identifying the
borders of the lesion and the destructive nature of the surgical procedures.
In one study, more than 50 percent of epithelial downgrowth cases treated surgically with
most of the techniques described above eventually resulted in enucleation, and eyes that
did not have surgical therapy had an even higher enucleation rate.1 Despite the poor
surgical outcomes, aggressive management offered a better prognosis than the natural
progression of the disease. Another study showed that after surgical treatment of
epithelial downgrowth, the eye often continues to have problems with corneal edema,
glaucoma, hypotony, vitreous haze and possible retinal detachment. Some of these
postoperative complications ultimately lead to phthisis and enucleation. Only 27.5
percent of eyes in that study were considered to have a good result based on visual acuity
and the lack of complications.2
After a pars plana core vitrectomy and air-fluid exchange, the pupil is pharmacologically
constricted with acetylcholine (Miochol). Then, 500 µg of undiluted 5-fluorouracil in a
total of 0.2 cc volume is injected with a 30-gauge blunt-tip cannula into the anterior
chamber. Postoperatively, the patient maintains face-down positioning such that the drug
is localized and concentrated in the area of epithelial downgrowth while the posterior
segment remains filled with filtered air. Repeat injections of 5-fluorouracil may be
performed postoperatively to re-treat the residual area of epithelial downgrowth.
This nonexcisional approach eliminates the need for extensive surgical dissection using
viscoelastic or viscoelastic and 5-fluorouracil mixture, which is often associated with
difficulty in identifying the true border and the extent of the epithelial incursion.3 It also
helps to avoid damage related to the surgery, such as iatrogenic trauma to the
endothelium or bleeding from the iris or the ciliary body.
Summary