February 2019


Presentation spotlight
Long-term management of epithelial downgrowth after phakic IOL implantation

by Stefanie Petrou Binder, MD, EyeWorld Contributing Writer

Case presentation of sheet-like epithelial downgrowth from 12 o’clock nasally and temporally

Cystic epithelial downgrowth treated by intracyst injection of mitomycin C with trypan blue under visco protection
Source (all): Rudy Nuijts, MD


Handling epithelial downgrowth can involve numerous surgeries that span many years

Epithelial downgrowth is the aggressive migration and proliferation of epithelial cells within the eye, associated with penetrating eye injuries or anterior segment surgery. The wild growth of these cells can greatly impair vision, cause pain, and induce high intraocular pressures leading to bouts of acute glaucoma. The growth of cells over the intraocular structures is often sheet-like, causing inflammation and tissue damage. Epithelial ingrowth is difficult to remove and frequently recurs. Rudy Nuijts, MD, professor of corneal transplantation and refractive surgery, Maastricht UMC+, University Eye Clinic, Maastricht, the Netherlands, described a case of epithelial downgrowth in a patient who required treatments for well over 12 years. He presented the case at the 22nd ESCRS Winter Meeting.
“We performed nine surgeries over a 12-year time period in this patient,” he said. “If you are going to handle epithelial downgrowth, be prepared for multiple, difficult surgeries in cases of sheet-like, cystic epithelial downgrowth.”

Case study

Dr. Nuijts presented the case of a 40-year-old female patient who received an Artisan phakic IOL (Ophtec, Groningen, the Netherlands) in 2006. The simple surgery would turn into a 12-year, ongoing case. Two years later, the patient underwent excision of an iris cyst in her left eye together with part of the corneal stroma of the eye. After another 2 years, recurrent iris prolapsing led to surgery with amnion membrane transplantation treatment. At this point (2010), due to persistent leakage, the patient was referred to Dr. Nuijts.
Dr. Nuijts observed corneal pigmentation, synechiae, and an elevated phakic lens. His examination further revealed right-sided uncorrected distance visual acuity (UDVA) of 1.5 logMAR, left-sided UDVA of 1.0 logMAR, right-sided corrected distance visual acuity (CDVA) of +1.25, and left-sided CDVA of –1.75 x 67°:1.2. The patient’s endothelial cell density (ECD) was 2217 cells/mm2 (right eye) and 1438 cells/ mm2 (left eye).
Lamellar keratoplasty was undertaken to reconstruct the cornea (October 2010), involving trephination 3.0 mm behind the thinned cornea at 12 o’clock and the implantation of a mushroom-shaped graft. He dissected the anterior synechiae in preparation of the lamellar keratoplasty using a Moria (Antony, France) microkeratome with its 200 µm head and diameter of 3.0 mm. The postoperative visual outcomes were UDVA 0.6 logMAR and CDVA +0.5 logMAR. The left-sided ECD was 1309 cells/mm2.

Managing a new development

Sheet-like epithelial downgrowth from 12 o’clock toward both the nasal and temporal sides was noted about 1.5 years later (April 2012). At this time, the patient’s CDVA was –0.25: –0.75 x 40°: 1.0– and ECD was 1175 cells/ mm2. To manage this new development, Dr. Nuijts decided on a combined procedure of 5 fluorouracil (FU) and a full thickness perforating graft, at this site, based on a study that he was previously involved in that corroborated the lack of endothelial cell toxicity with the use of the antimetabolite 5 FU at concentrations of 50 mg/ml.1 He injected 0.1 cc 5 FU 10 mg/ml intracamerally for 5 min and performed penetrating keratoplasty at the site of the earlier lamellar keratoplasty.
“Epithelial downgrowth may initially retract after intracameral injection of 5 FU or mitomycin C,” Dr. Nuijts said. “It is not toxic to the endothelium when given up to 5 minutes, for even as much as 50 mg/ml concentrations. It may show a delayed effect of up to 3–4 months.”
Nine months after the combined procedure, the patient’s vision was decreased to CDVA 0.6 logMAR. Dr. Nuijts observed a membrane that had proliferated on the anterior surface of the tilted Artisan lens and crept along its edge that began lifting the IOL. There was minimal enclavation temporally due to traction of the membrane. Dr. Nuijts excised the membrane and repositioned the Artisan lens (March 2013). A follow-up 3 months later revealed an increasing membrane formation on the IOL, UDVA of 0.6 logMAR, and ECD of 712 cells/mm2. Dr. Nuijts opted for a second intracameral injection of 0.1 ml 10 mg/ml 5 FU for 5 minutes under visco protection. He explained, “Epithelial downgrowth recurred in this case, and the patient preferred not to perform an extensive block excision but to use medical antimetabolite treatment.”
Approximately 6 months later, the patient experienced an acute bout of glaucoma with decreased vision and pain that required an emergency visit. The patient’s CDVA was 0.05 logMAR and her IOP was 64 mm Hg. She presented with a shallow anterior chamber with the pIOL touching the endothelium and synechia formation. The pIOL was explanted the next day. Eight months following the pIOL explantation (June 2014), the patient’s CDVA (with contact lens) was 0.9 logMAR and the ECD was 438 cells/mm2. The endothelial membrane appeared to retract, and there was increasing ovalization of the pupil and evidence of a subcapsular posterior cataract. Dr. Nuijts removed the mature cataract via phaco, dissected the synechiae, and implanted an AcrySof IQ SN60WF (Alcon, Fort Worth, Texas).

After cataract surgery

In July 2015, 7 months after the cataract surgery, CDVA for plano was –1.75 x 155°, giving the patient a vision of 20/16. The ECD was 696 cells/mm2 and the cornea was clear, with some ectropion uveae. A few months later, the patient developed cyst formation with cystic epithelial downgrowth. Dr. Nuijts injected 5 FU into the cyst (1ml 25 mg/ml) in the patient’s left eye, mixed with trypan blue under simultaneous drainage and visco protection of the anterior chamber. He used two syringes that he injected into the cyst, one for the drainage and the other for the injection of the 5 FU. The cyst persisted between 10 and 3 o’clock. The left sided CDVA was 20/25 with plano –1.5 x 150°. It was treated by an intracyst injection of 0.002 mg/ml mitomycin C with trypan blue under visco protection 1 year later (March 2016). “Mitomycin C attacks cells that are in their rest phase as well, so it was seen to be effective in studies. We used the same double injection technique as above,” Dr. Nuijts explained.
Within 2 months of the mitomycin C injection, he noted the cyst starting to close and continuing to do so over a time period of roughly 6 months. One year after the mitomycin C treatment, there was recurrence of the cyst. CDVA decreased to 0.16 logMAR, and the patient’s IOP was 15 mm Hg. The corneal pachymetry was 663 µm and corneal edema was evident. At this point, Dr. Nuijts excised the cyst in combination with a DSAEK procedure. He noted extensive posterior capsular opacification (PCO) roughly 6 months later that he treated with YAG capsulotomy. At 9 months post-DSAEK, the patient’s CDVA was 20/40, the left-sided IOP was slightly elevated at 22 mm Hg, the DSAEK graft was clear, and pachymetry was 664 micrometers. The patient received fluorometholone 2 dd for the graft and dorzolamide/timolol 2 dd.
Despite the repeated efforts involved to keep the epithelial downgrowth in check, Dr. Nuijts thinks that medical treatment with 5 FU is preferable to surgery. “Do not rush too quickly into block excision,” Dr. Nuijts said. “Our patient had worries about a block excision and that is why we decided to follow this strategy. 5 FU and MMC are not cytotoxic at the right concentrations and can be effective in stopping epithelial downgrowth.”


1. Nuyts RM, et al. The effects of 5-fluorouracil and mitomycin C on the corneal endothelium. Curr Eye Res. 1992;11:565–70.

Editors’ note: Dr. Nuijts has financial interests with Johnson & Johnson Vision (Santa Ana, California), Alcon, Asico (Westmont, Illinois), Bausch + Lomb (Bridgewater, New Jersey), Carl Zeiss Meditec (Jena, Germany), Chiesi (Cary, North Carolina), HumanOptics (Erlangen, Germany), Ophtec, Oculentis (Berlin, Germany), and Thea (Clermont-Ferrand, France).

Contact information

: rudy.nuijts@mumc.nl

Long-term management of epithelial downgrowth after phakic IOL implantation Long-term management of epithelial downgrowth after phakic IOL implantation
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