Epithelial downgrowth (also called epithelial ingrowth) is a complication in which non-keratinized stratified squamous epithelial cells from the conjunctiva or cornea enter the eye through an incompletely closed wound after penetrating ocular trauma or anterior segment surgery and proliferate on various intraocular tissues. The epithelium grows in sheets, spreading over the cornea, iris, trabecular meshwork, ciliary body, lens or intraocular lens, vitreous, and retina.
Glaucoma due to epithelial downgrowth is primarily caused by coverage and obstruction of the trabecular meshwork by proliferating epithelium, with inflammatory peripheral anterior synechiae and pupillary block also contributing. According to the EGS guidelines, treatment includes intraocular pressure-lowering medications, excision/destruction of invasive tissue, filtration surgery with antimetabolites (limited success), drainage devices, and cyclodestructive procedures1).
Most cases develop within one year of the causative event, but the range is from 3 months to 10 years postoperatively. Although the incidence has decreased significantly due to advances in surgical techniques, it is important to recognize this clinical entity because it is highly invasive and threatens visual function.
Typically, it is identified on slit-lamp examination as a translucent membrane with scalloped edges extending from the surgical wound. If the diagnosis is uncertain, a test using argon laser photocoagulation of the membrane on the iris is useful. If the membrane is present, the irradiated area becomes pale or white; in normal iris, dark coagulation spots appear. Alternatively, aqueous humor can be aspirated for cytology to check for free epithelial cells. Gonioscopy may reveal an epithelial sheet in the angle, but sensitivity is low, and many cases show normal findings.
| Risk Factor | Details |
|---|---|
| Multiple intraocular surgeries | Higher number of surgeries increases risk |
| Impaired wound healing | Incomplete or delayed wound healing |
| Wound fistula | Persistent epithelial ingrowth pathway |
Risk remains even with modern surgical techniques. Cases have been reported with clear corneal incision cataract surgery, glaucoma drainage device implantation, DSAEK, and LASIK.
In glaucoma associated with epithelial ingrowth, aqueous outflow is severely reduced, so medication alone is usually insufficient.
Treatment of Epithelial Ingrowth
En bloc excision + keratoplasty: Standard treatment aiming for complete removal of invasive tissue
Cryotherapy: Indicated for localized cases. Risk of corneal endothelial damage
Intracameral MTX injection: 400 μg/0.1 mL once a week. Minimally invasive alternative treatment2)
Glaucoma Management
Drainage device: Mainstay of treatment. Consider leaving a longer tube or pars plana insertion
Trabeculectomy: Usually fails due to epithelial invasion
Cyclodestructive procedures: Additional intraocular pressure-lowering measure1)
Glaucoma drainage devices (tube shunt surgery) are the mainstay of treatment. Because aqueous outflow is significantly reduced, medication alone is usually insufficient. Trabeculectomy is not recommended as it often fails due to sheet-like invasion of epithelial cells. Cyclodestructive procedures are also used as additional intraocular pressure-lowering measures. For epithelial ingrowth itself, in addition to en bloc excision and cryotherapy, intracameral methotrexate injection has been reported as a minimally invasive alternative treatment.
Diffuse sheet type
Morphology: Epithelium proliferates in a sheet-like manner, covering the cornea, iris, trabecular meshwork, and ciliary body.
Invasiveness: High. Difficult to remove and frequently recurs.
Glaucoma: Commonly associated.
Treatment: Requires wide en bloc excision and keratoplasty.
Cystic type
Morphology: Proliferating cells arise from an inclusion cyst connected to the wound.
Invasiveness: Usually more benign and slow-growing.
Glaucoma: Rapid enlargement may cause visual axis obstruction or pupillary block glaucoma.
Treatment: Surgical intervention is carefully considered due to possible transition to sheet type upon recurrence.
Glaucoma due to epithelial ingrowth is multifactorial.
According to the EGS guidelines, epithelial or fibrous ingrowth after anterior segment surgery or penetrating trauma can cause inflammatory membrane formation and lead to secondary glaucoma1).
Multiple mechanisms are involved. The most primary mechanism is that the proliferating epithelial sheet directly covers the trabecular meshwork and blocks aqueous humor outflow. In addition, clogging of the trabecular meshwork due to mucin secretion from ectopic conjunctival goblet cells, peripheral anterior synechiae formation and trabecular necrosis due to inflammation, and pupillary block due to vitreous-iris adhesions also contribute. Steroid eye drops used for treatment may also cause further intraocular pressure elevation. As severe aqueous outflow obstruction results from these multifactorial causes, intraocular pressure control is often difficult with medication alone, and drainage devices are required.
Salari et al. reported weekly intracameral injections of methotrexate (MTX) 400 μg/0.1 mL for epithelial ingrowth occurring after Ahmed valve implantation2). After an initial 7 injections and 4 additional injections due to regrowth one month later (total 11 injections), the epithelial ingrowth disappeared, and no recurrence was observed during the 11-month follow-up period2). The antiproliferative effect of MTX is thought to contribute to the suppression of epithelial ingrowth2).
Although MTX has demonstrated safety and efficacy for intraocular administration in vitreoretinal lymphoma, further evidence is needed regarding the safety of intracameral administration2). Potential neuroretinal toxicity has been noted, and establishment of a dose-response curve is required2). The greatest advantage is that it is less invasive compared to surgical excision.
Advances in cataract surgery techniques (smaller and more precise wound creation) have significantly reduced the incidence of epithelial ingrowth. However, sporadic cases have been reported even with modern procedures such as clear corneal incision, glaucoma drainage device implantation, DSAEK, and LASIK.
Prevention remains paramount, and continued improvement in surgical techniques is expected to further reduce the incidence.
- European Glaucoma Society. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2025.
- Salari F, Fakhraie G, Asadi Amoli F, ZareiGhanavati M. Intracameral Injection of Methotrexate for Treatment of Epithelial Ingrowth. J Curr Ophthalmol. 2022;34:115-7.
