Epithelial Downgrowth and Glaucoma
Epithelial downgrowth (also termed epithelial ingrowth) is an aggressive, vision-threatening complication of penetrating ocular injury or anterior segment surgery. In this disease, epithelial cells invade the intraocular structures through an incompetent wound and proliferate wildly causing pain and vision loss through a variety of mechanisms. This article will detail the relationship between epithelial downgrowth and glaucoma, focusing on the epidemiology, pathophysiology, diagnosis and management of this potentially devastating disease.
Epithelial downgrowth occurs when non-keratinized stratified squamous epithelial cells from the conjunctiva or cornea migrate through a wound and proliferate onto a variety of intraocular structures. Typically, the epithelium grows as a sheet, proliferating over the cornea, iris, trabecular meshwork, ciliary body, crystalline/artificial lens, vitreous body, and/or retina ,,. The ingrowth of the epithelium incites profound inflammation and tissue-damage. While most cases present within one year of the inciting event, this time interval is highly variable, ranging from three months to ten years post-trauma or post-operatively ,. This diffuse-sheet form of downgrowth is aggressive, difficult to remove, and often recurs after treatment .
Glaucoma is common with the diffuse sheet form of epithelial downgrowth. The sequence of events leading to glaucoma is multifactorial. The proliferating epithelium grows over the trabecular meshwork, blocking aqueous drainage. The trabecular meshwork can also be clogged by mucin secreted from aberrant conjunctival goblet cells . The epithelial proliferation and inflammation stimulates PAS formation, trabeculitis and trabecular necrosis--further impairing aqueous drainage. Pupillary block may occur as vitreous-pupillary adhesions form ,. And finally, many patients suffering from epithelial downgrowth are placed on topical steroids and this can further lead to increased eye pressures in susceptible individuals.
Epithelial downgrowth may also form in a cystic pattern with the proliferating cells from an inclusion cyst which is connected to the wound. The cystic variant is typically more benign and slow growing, although in some cases the cyst may grow rapidly and occlude the visual axis, causing inflammation or pupillary block glaucoma. If possible, surgical intervention is avoided, since recurrences may develop as the more aggressive diffuse sheet form of downgrowth.
Epithelial downgrowth may occur after essentially any type of penetrating trauma or intraocular surgery. The incidence of downgrowth after cataract surgery was historically found to be 0.08% - 0.12%  and up to 0.25% after penetrating keratoplasty . However, as advances in cataract surgical techniques have allowed for smaller and more precise wound healing, the incidence of epithelial downgrowth has greatly diminished . Despite this, it remains important to recognize this clinical entity because of its aggressive, vision-threatening disease course and potential to develop from any traumatic or surgical ocular penetrating wound.
Risk factors for development of epithelial downgrowth include the following: multiple intraocular surgeries, incomplete/delayed wound healing, wound fistulas, iris incarceration into the surgical wound, vitreous to the wound, implantation of epithelial cells with instruments, and suture track leaks . Newer surgical techniques have greatly diminished the risk; however, cases of epithelial downgrowth have been reported with more modern procedures including clear cornea phacoemulification , glaucoma drainage device implantation , DSAEK , and LASIK .
Epithelial downgrowth is classically described as either a translucent cystic or membranous growth with a scalloped border involving the posterior corneal surface or anterior iris in the area of the surgical incision. The membrane extends from the wound and rarely extends more than halfway across the cornea. Other potential findings that suggest epithelial downgrowth include distortion of the pupil and corneal microcystic edema overlying the affected area of the cornea. Hypotony may develop if there is a fistula, or glaucoma may develop as discussed above.
If the diagnosis is in question, a spot of argon laser photocoagulation is applied to the area overlying the iris. If a membrane is present, the laser spot will cause the tissue to blanch and whiten, while laser applied to normal iris will result in a sharp, darkened burn. Aqueous aspiration and cytologic examination can also be performed to assess for the presence of free epithelial cells.
Gonioscopy may reveal an epithelial sheet in the angle, however, this is not a very sensitive finding and the majority of cases of glaucoma caused by epithelial downgrowth have normal gonioscopic findings .
After the diagnosis of epithelial downgrowth is made, it is important to first grossly remove the invading epithelium. In general, this is typically done via a large en-bloc excision of any involved tissue along with a full-thickness corneoscleral graft . However, if only the posterior corneal surface, drainage angle, or ciliary body is involved, the invading epithelium can be devitalized using cryotherapy. Endothelial loss typically accompanies cryotherapy, and a corneal transplant may be needed at a later time.
In managing the glaucoma associated with epithelial downgrowth, glaucoma drainage devices have been the mainstay of treatment. Because outflow is profoundly reduced, medical treatment alone typically does not sufficiently lower eye pressure. Even with the use of anti-metabolite agents, trabeculectomy usually fails due to the invasion of sheets of epithelial cells . However, glaucoma drainage devices have better success in maintaining IOP control and some advocate leaving the intraocular portion longer or inserting the tube through the pars plana to minimize the invasion of the epithelial cells. Cycloablative procedures can also be used to lower the IOP. When managing patients with epithelial downgrowth and glaucoma, it appears that a combined approach using topical IOP lowering medications, judicious use of topical steroids, and a glaucoma drainage device and/or cycloablative procedure are essential in halting this devastating disease.
Epithelial downgrowth is an aggressive eye condition which can occur after penetrating trauma or any intraocular eye surgery. The incidence of this disease is decreasing due to improved surgical techniques. Glaucoma results from multiple mechanisms, including occlusion of the angle, inflammatory synechiae development, and steroid-induced glaucoma. Early treatment with a glaucoma drainage device is important to consider in patients with glaucoma and epithelial downgrowth. However, given the aggressive nature of this disease, the prognosis remains poor even with aggressive management. Prevention continues to be key in epithelial downgrowth and with continued improvements in surgical techniques, we hope that the incidence of this devastating disease continues to decrease.
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