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Table of Contents
Year : 2022  |  Volume : 4  |  Issue : 1  |  Page : 20

Case report and literature review of epithelial downgrowth post-penetrating keratoplasty

1 Department of Ophthalmology, University of Pittsburgh Medical Eye Center, Pittsburgh, Pennsylvania, USA
2 Department of Ophthalmology, University of California, Davis Eye Center, Sacramento, California, USA

Date of Submission14-Feb-2022
Date of Decision19-Mar-2022
Date of Acceptance23-Mar-2022
Date of Web Publication19-May-2022

Correspondence Address:
Mark J Mannis
Department of Ophthalmology, University of California, Davis Eye Center, Sacramento, California
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_9_22

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Epithelial downgrowth (ED) after penetrating keratoplasty (PK) is a rare but troublesome complication, often leading to vision loss. We present a case of refractory ED and review of the literature on ED after keratoplasty. Case presentation and literature review was the study design. Intracameral 5-fluorouracil at the time of wound revision and placement of a tube implant for glaucoma control were successful in securing the closure of a fistulous wound after multiple transplant surgeries. In this case, the successful management of ED after PK was achieved with meticulous wound closure, adequate pressure control, and the mitigation of ED with chemoablation of the proliferating epithelial cells. More advanced cases may require repeated injections of antiproliferative medication, cryotherapy, or surgical excision of involved tissues.

Keywords: Epithelial downgrowth, glaucoma, graft failure, keratoplasty

How to cite this article:
Melachuri S, Seipel S, Li J, Brandt JD, Mannis MJ. Case report and literature review of epithelial downgrowth post-penetrating keratoplasty. Pan Am J Ophthalmol 2022;4:20

How to cite this URL:
Melachuri S, Seipel S, Li J, Brandt JD, Mannis MJ. Case report and literature review of epithelial downgrowth post-penetrating keratoplasty. Pan Am J Ophthalmol [serial online] 2022 [cited 2023 Jun 3];4:20. Available from: https://www.thepajo.org/text.asp?2022/4/1/20/345498

  Introduction Top

Epithelial downgrowth (ED), the infiltration of surface epithelial cells into the anterior segment, is a rare but significant complication of intraocular surgery or trauma.[1] It is classified as sheets, cysts, or pearls of the epithelium that grows over the cornea, iris, trabecular meshwork, lens, and ciliary body.[2] Clinically, ED appears as a translucent or gray membrane with a smooth border and rolled edges, which can occlude the trabecular meshwork or cause peripheral anterior synechia formation, leading to secondary glaucoma.[1] ED can lead to corneal decompensation, refractory glaucoma, visual deficits, and permanent vision loss.[3] Risk factors for ED include multiple intraocular surgeries, inadequate wound closure, trauma, prolonged inflammation, corneal vascularization, damage to Descemet's layer/corneal endothelium, wound fistulas, and hypotony.[1],[4],[5]

The source of the epithelial cells may be unclear, but the cells may be corneal or conjunctival in origin. Studies have demonstrated continuity between the surface epithelium and the ED into the anterior chamber through fistulous tracts and previous surgical scars.[2] This ingrowth can result in profound inflammation and tissue damage, leading to the destruction of blood–aqueous barrier. The inflammation may stimulate the growth factors necessary for epithelium to proliferate.[2] Itty et al. demonstrated donor tissue corneal cells at the graft–host interface as the source of epithelium in penetrating keratoplasty (PK).[6] Damaged endothelial cells in corneal transplant may lose their ability for contact inhibition, permitting epithelial growth.[7]

Studies have shown the incidence of ED following PK to be 0.27%.[2] We describe a case of ED after multiple PKs and discuss the medical and surgical management along with a review of the literature.

  Case Report Top

A 71 year-old male with a history of keratoconus status postmultiple bilateral PK procedures presented with subacute, progressive, worsening visual acuity in the right eye over the previous month. His ocular history was significant for two prior PKs in the right eye and three prior PKs in the left eye; the most recent PK was performed in 2016 in the right eye. In addition, he was functionally monocular in the right eye due to advanced secondary glaucoma and hand motion vision with loss of fixation in the left eye.

His visual acuity measured 20/150 OD, down from 20/25 OD 1 month prior, and hand motion OS. Intraocular pressure (IOP) were 10 mmHg OU. At the slit lamp, the corneal graft showed diffuse microcystic edema with patches of bullae, indicating graft failure. At that time, prednisolone acetate was increased from 4 to 6 times per day and sodium chloride drops were started 6 times per day. There were minimal change and no improvement in visual acuity. The decision was made to repeat the PK in the right eye. On postoperative day 1, after uneventful surgery, the eye was Seidel positive at the 1:00–2:00 o'clock position at the graft–host interface. After 6 weeks of bandage contact lens (BCL) wear, aqueous suppression, and selective replacement of sutures at the site of the leak, the eye remained Seidel positive. [Table 1] details the ocular management.
Table 1: Treatment timeline

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PK was repeated in the right eye, and the surgical pathology was notable for ED. On postoperative day 1 of the re-graft, there was Seidel positivity now at 10:00. After 2 months of BCL wear, aqueous suppression, and selective suture placement, the eye remained Seidel positive [Table 1]. A repeat PK was performed with a larger recipient bed to excise the fistulous graft–host interface. An 8.25 mm donor in 8.0 mm bed compared to the previous 7.75 mm donor in 7.5 mm bed was employed. The surgical pathology was positive for ED. Postoperative day 1 showed a Seidel positive leak at 5:30 on the graft–host interface. After 5 weeks of treatment with a BCL, aqueous suppression, and selective suture replacement, the IOP rose to 21 mmHg despite the persistent Seidel-positive wound leak. Given increasing IOP despite full aqueous suppression and a brisk persistent leak, it was determined that the patient's own aqueous outflow system was now irreversibly compromised by ED. Therefore, we chose to place a nonvalved glaucoma drainage device (Baerveldt Glaucoma Implant, Johnson & Johnson Vision, Santa Ana, CA USA) at the same time as interventions to close the leak.

The patient was brought to the operating room and underwent placement of a Baerveldt Glaucoma Implant, followed by replacement of suture at the site of leak. At the conclusion of the surgery, 0.5 mg/0.1 mL intracameral 5-fluorouracil (5FU) was instilled into the anterior chamber, at the location of the previously noted wound leak, and a BCL was placed over the graft. Two weeks postoperatively, the BCL was removed, and the graft was noted to be Seidel negative. The patient's IOP is well controlled, and his visual acuity has improved to 20/40. The patient is currently being fit with a custom scleral contact lens.

  Discussion Top

The incidence of ED after PK is, fortunately, very low (0.27%).[2] We present a patient with persistent ED despite multiple attempts to close the site of downgrowth, including suture replacement, gluing, and replacement of the graft with a larger donor. Ultimately, intracameral 5FU in combination with debridement of the graft/host interface at the fistula site as well as a larger donor graft was used to close the leak created by ED.

There are a wide variety of medical and surgical treatment options for ED, depending on its extent and progression. Foremost, it is important to remove the invading epithelium.[1],[6],[8] If only the posterior corneal surface, drainage angle, or ciliary body is involved, the invading epithelium can sometimes be devitalized via medical therapies such as irradiation, cryotherapy, cautery, and laser photocoagulation.[1],[5],[8],[9],[10],[11],[12] Endothelial loss typically accompanies surgery, radiation, and cryotherapy; therefore, a repeat corneal transplant may be required once ED is resolved. Studies have shown partial or complete regression of ED after intracameral injections of 5FU.[4],[6],[13] A less destructive alternative, 5FU only affects cells that are actively proliferating and, as such, may be a less destructive alternative than cryoablation or surgical excision. Multiple doses may be required to retarget cells temporarily in a rest phase which may later activate and grow after drug clearance.[13] Given methotrexate's (MTX) antiproliferative properties, MTX has been used to treat ocular conditions such as intraocular lymphoma and proliferative vitreoretinopathy.[13],[14],[15] Recent studies have shown complete resolution of ED after a series of intravitreal MTX injections following unsuccessful surgical and medical treatments.[13],[14],[15] Observation of ED can also be an option if there is no sign of progression. If glaucoma results as a complication of ED, drainage devices, cycloablative procedures, and photocoagulation have been effective in lowering IOP.[2] [Table 2] displays an extensive literature search of previous studies on ED after keratoplasty and attempted treatment options.[3],[6],[8],[9],[10],[11],[12],[13],[14],[15]
Table 2: Literature review

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  Conclusions Top

ED is a rare but problematic complication of PK and can be managed either surgically or medically. In our case, the patient was successfully treated with intracameral 5FU.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Theophanous CN, Avdagic E, Farooq AV, Skondra D, Qiu M. Management of severe epithelial versus fibrous downgrowth following trabeculectomy: Case report and literature review. Am J Ophthalmol Case Rep 2021;23:101183.  Back to cited text no. 1
Mihail Z, Alina-Cristina S, Speranta S. Retrocorneal membranes after penetrating keratoplasty. Rom J Ophthalmol 2015;59:230-4.  Back to cited text no. 2
Venkateswaran N, Yeaney GA, Hindman HB. Epithelial downgrowth: An atypical clinicopathological case report. Arch Ophthalmol 2012;130:1613-5.  Back to cited text no. 3
Wong RK, Greene DP, Shield DR, Eberhart CG, Huang JJ, Shayegani A. 5-Fluorouracil for epithelial downgrowth after Descemet stripping automated endothelial keratoplasty. Cornea 2013;32:1610-2.  Back to cited text no. 4
Le VN, Wabnig F, Bachmann B, Cursiefen C. Epithelial downgrowth after Descemet membrane endothelial keratoplasty. Eur J Ophthalmol 2021;31:P27-32.  Back to cited text no. 5
Itty S, Proia AD, DelMonte DW, Santaella RM, Carlson A, Allingham RR. Clinical course and origin of epithelium in cases of epithelial downgrowth after Descemet stripping automated endothelial keratoplasty. Cornea 2014;33:1140-4.  Back to cited text no. 6
Sidrys LA, Demong T. Epithelial downgrowth after penetrating keratoplasty. Can J Ophthalmol 1982;17:29-31.  Back to cited text no. 7
Walker BM, Hindman HB, Ebrahimi KB, Green WR, Eberhart CG, Garcia I, et al. Epithelial downgrowth following Descemet's-stripping automated endothelial keratoplasty. Arch Ophthalmol 2008;126:278-80.  Back to cited text no. 8
Karabatsas CH, Hoh HB, Easty DL. Epithelial downgrowth following penetrating keratoplasty with a running adjustable suture. J Cataract Refract Surg 1996;22:1242-4.  Back to cited text no. 9
Groh MJ, Naumann GO. Cystic epithelial growth after penetrating keratoplasty: Successful curative treatment by block excision. Br J Ophthalmol 2001;85:240.  Back to cited text no. 10
Diel RJ, Morrow NC, Jiang L, Huffman JM, Greiner MA. Transcorneal cryotherapy and descemet membrane endothelial keratoplasty to treat epithelial downgrowth and corneal decompensation after cataract surgery. Cornea 2020;39:1171-3.  Back to cited text no. 11
Gorovoy MS, Ratanasit A. Epithelial downgrowth after Descemet stripping automated endothelial keratoplasty. Cornea 2010;29:1192-4.  Back to cited text no. 12
Ni N, Goldberg MA, Eagle RC Jr., Rapuano CJ, Haller JA. Epithelial downgrowth after intraocular surgery treated with intracameral 5-fluorouracil. Case Rep Ophthalmol Med 2015;2015:325485.  Back to cited text no. 13
Lambert NG, Wilson DJ, Albert DM, Chamberlain WD. Intravitreal methotrexate for recurrent epithelial downgrowth. JAMA Ophthalmol 2019;137:1082-3.  Back to cited text no. 14
Lee MD, Wu F, Schallhorn JM. Successful treatment of epithelial ingrowth with intravitreal methotrexate. Ophthalmology 2019;126:48.  Back to cited text no. 15


  [Table 1], [Table 2]


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