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 Table of Contents  
Year : 2021  |  Volume : 59  |  Issue : 1  |  Page : 70-73

Nonhealing epithelial defect after collagen cross-linking for keratoconus with vernal keratoconjunctivitis

1 Department of Cornea and Refractive Services, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Puducherry, India
2 Department of Pediatric and Squint Services, Peadiatric and Squint Ophthalmology Services, Aravind Eye Hospital and Post Graduate Institute of Ophthalmology, Puducherry, India

Date of Submission08-Jun-2020
Date of Decision21-Sep-2020
Date of Acceptance14-Oct-2020
Date of Web Publication27-Mar-2021

Correspondence Address:
Dr. Josephine S Christy
Aravind Eye Hospital, Cuddalore Main Road, Thavalakuppam, Puducherry - 605 007
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/tjosr.tjosr_107_20

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Here we report a case of nonhealing epithelial defect after corneal collagen cross-linking (C3R) in a 24-year-old young adult with progressive keratoconus and concomitant vernal keratoconjunctivitis (VKC). Epithelium off C3R with hypoosmolar riboflavin and ultraviolet -A irradiation was done in the right eye for progressive keratoconus. The preoperative minimum corneal thickness was 388 microns. Chronic VKC was stabilized with mast cell stabilizer and lubricants before C3R. The patient presented with nonhealing epithelial defect until 1-month post cross-linking due to possible limbal stem cell deficiency (LSCD) and underlying VKC with giant papillae. Amniotic membrane grafting was done twice for ocular surface stabilization which occurred at the end of 7 weeks. Final best-corrected visual acuity at 1 year was 6/12 with nebular corneal scarring. Preemptive management of giant papillae and proper stabilization of the ocular surface is essential before C3R. In cases of keratoconus with VKC, LSCD should be strongly suspected and reactivation of VKC with a prolonged course of epithelial healing can be a possible complication after C3R.

Keywords: Collagen cross-linking, keratoconus with keratoconjunctivitis, nonhealing epithelial defect

How to cite this article:
Christy JS, Mouttapa F, Narayana S. Nonhealing epithelial defect after collagen cross-linking for keratoconus with vernal keratoconjunctivitis. TNOA J Ophthalmic Sci Res 2021;59:70-3

How to cite this URL:
Christy JS, Mouttapa F, Narayana S. Nonhealing epithelial defect after collagen cross-linking for keratoconus with vernal keratoconjunctivitis. TNOA J Ophthalmic Sci Res [serial online] 2021 [cited 2021 May 6];59:70-3. Available from: https://www.tnoajosr.com/text.asp?2021/59/1/70/312270

  Introduction Top

Keratoconus is a progressive, noninflammatory corneal thinning disorder characterized by changes in the structure and organization of corneal collagen, resulting in ectasia. Definite association of keratoconus and ocular allergy has been well documented in the literature.[1] It has been hypothesized that the increase in protease activity in keratoconjunctivitis (VKC) may be further exacerbated during forceful eye rubbing, contributing to the development and progression of KC.[1]

Corneal collagen cross-linking (C3R) is an established treatment modality for halting the progression of keratoconus.[2] Many studies have validated an excellent safety profile. One of the acceptable complications includes mild stromal haze[3] which usually resolves over time with the use of steroid drops. Peripheral sterile corneal infiltrates due to enhanced cell-mediated immunity have also been noted. Bare cornea devoid of the epithelium in the postoperative period, can be an important risk factor for the development of microbial infections.[4],[5],[6] However, the constant ocular surface inflammation along with limbal stem cell deficiency (LSCD) which is usually seen in the chronic mixed type of VKC can pose a significant challenge during the management of keratoconus with collagen cross-linking. This report details on a rare complication, a nonhealing epithelial defect which required amniotic membrane transplantation post C3R.

  Case Report Top

A 24-year-old young adult presented with defective vision in both eyes, left eye worse than right since childhood. He gave a history of chronic VKC for the past 9 years and also an episode of shield ulcer in the right eye 3 years back. His best-corrected visual acuity (BCVA) was 6/9 in the right eye and 6/60 in the left eye. Slit-lamp examination showed Vogt's striae, Fleischer's ring, and corneal thinning in both eyes. The right eye had a subepithelial scar in the superior cornea. Upper tarsal conjunctiva showed quiescent papillae in both eyes.

Corneal topography (ORBSCAN–Technolas Perfect Vision GmbH, Munchen, Germany) showed a superior cone in the right eye. Topographic keratometry was 52.7/43.2 D in the right eye and 57.9/45.9 D in the left eye. Maximum corneal power was 53.7 D in the right eye and 58.1 in the left eye. The minimum topographic corneal thickness was 388 μm in the right eye and 448 μm in the left eye.

He was prophylactically given olopatadine eye drops two times per day in both eyes for 1 month and advised hypoosmolar collagen cross-linking for the right eye.

The patient underwent the same after 2 weeks under retrobulbar anesthesia. 9.5 mm of the cornea was marked and 20% isopropyl alcohol was used for 20 s followed by thorough wash with 10 ml saline for loosening of the epithelium. Once the epithelium was scraped, hypotonic riboflavin drops (NanoSigma Biotech. Co. Ltd, Taiwan) was applied once every 2 s for 30 min. Anterior chamber flare was confirmed for penetration of riboflavin and ultraviolet (UV)-A irradiation (UV-X, 365 ± 10 nm IROC AG, Zurich, Switzerland) was done for the next 30 min with simultaneous application of riboflavin every 2 s. A bandage contact lens (BCL) was applied at the end of the procedure. The patient was given moxifloxacin eye drops 6 times/day and carboxy methylcellulose 0.5% eye drops 6 times/day.

At the first postoperative day, the patient complained of spontaneous fall of BCL. Examination revealed a poor fit of BCL and hence changed to a steeper fit. Even after 3 days, the epithelial defect did not show any signs of healing and the patient was intolerant to BCL. On day 5, epithelial defect of 8 mm × 8 mm with diffuse cellular stromal infiltration was noted. The patient was started on moxifloxacin and tobramycin eye drops for every 2 h along with carboxymethylcellulose eye drops 6 times/day and D-panthenol eye ointment thrice per day. On the 6th postoperative day, 1 mm discrete stromal infiltrates developed at the edge of the superior margin of epithelial defect which was now 7 mm × 5 mm along with intense vascularization. Upper tarsal conjunctiva (UTC) revealed active giant papillae. Scraping off the corneal infiltrate was unproductive. Dexamethasone with chloramphenicol eye drops was added in low dose (twice daily) in view of severe inflammation associated and bare cornea. Three weeks post-C3R patient still had 3 * 3 mm epithelial defect with superior conjunctivisation and active giant papillae in UTC [Figure 1]. Autologous serum prepared under aseptic precautions was started at 4 times/day. Four weeks' post-C3R due to nonhealing epithelial defect, amniotic membrane grafting (AMG) was done on the cornea with fibrin glue along with stepped-up topical 1% prednisolone acetate eye drops (6 times a day). Due to the mechanical rubbing of giant papillae, AMG got eroded and hence was replaced again 3 days later along with BCL. Topical steroids were then tapered with clinical response. Three weeks later, BCL was removed and epithelial defect had healed well [Figure 2].
Figure 1: The right eye showing giant papillae in the upper tarsal conjunctiva with nonhealing epithelial defect 3 weeks post-C3R

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Figure 2: The right eye showing healed epithelium 3 weeks' postamniotic membrane grafting

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The patient was advised olopatadine OD eye drops once a day, carboxymethyl cellulose eye drops 4 times/day, and tacrolimus eye ointment 0.03% 2 times/day for control of VKC. Six months post-C3R slit-lamp examination revealed nebular scar with BCVA of 6/12.

  Discussion Top

India being a tropical country with a hot and arid climate has a high incidence of VKC.[7] It usually affects young boys and tends to subside in puberty. However, in a small subset of patients, it persists beyond puberty, mostly with associated keratoconus. Since the inflammatory process is perennial in most of these patients, there is also a risk of rapid progression that may not halt on its own. Collagen cross-linking is by far, the definite, and safe treatment modality for halting the progression of keratoconus.

In the pathogenesis of VKC, the corneal epithelium plays an important barrier function, by secluding the corneal stroma and corneal keratocytes from the inflammatory environment of the conjunctiva.[8] The removal of corneal epithelium in a rat model augmented the late phase clinical signs of conjunctival eosinophilia, which in turn delayed corneal epithelial wound healing.[8] Similarly, in the present case, though the conjunctiva was quiescent and the patient was asymptomatic at presentation, following epithelium off C3R, symptoms worsened, and there were signs of active VKC such as enlarged papillae, shield ulcer, and delayed epithelial healing. Whereas the contralateral eye with a similar picture of papillae had a stable ocular surface with a clear cornea [Figure 3]. The presence of a bare epithelium prevented us in using a high dose of steroids for control of inflammation in VKC. Although the grade 2 shield ulcers usually respond to medical treatment and minimal surgical debridement,[6] considering the prolonged course and suspected mechanical rubbing from enlarged papillae, AMT was opted in our case.
Figure 3: The left eye showing quiescent papillae and normal conjunctiva

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Since the conventional epithelium off C3R poses a presumed risk of reactivation of VKC and further corneal complications, a transepithelial C3R would be helpful although it may not be as effective as the conventional one. There have been reports of suboptimal outcomes after trans-epithelial pediatric cross-linking, in which K readings and higher order aberrations (HOAs) showed statistically significant worsening and a demarcation line depth of only 105 um.[9] This necessitates the need for early detection as well as intervention for KC in patients with associated VKC. Videokeratographic methods can be useful in the early identification of keratoconus. Yuksel et al.[10] has reported 26.8% incidence of keratoconus in VKC by videokeratography. According to Ruth et al., superior steepening was found to be more common in VKC patients, although superior keratoconus is considered to be rare.

In the retrospective study by Sangwan et al.,[11] partial or total LSCD has been reported in 1.2% of patients with chronic VKC. In our patient, though there was a mild superior vascularization and presentation with delayed epithelial healing, LSCD was not confirmed by conjunctival impression cytology. Since he had a history of chronic VKC for 9 years, the possibility of LSCD cannot be ruled out.

There is a single case report on recurrent shield ulcer following penetrating keratoplasty for keratoconus with associated VKC.[12] Activation of VKC with punctate erosions and enlarged tarsal papillae was reported at 1 month postoperative period, even though when the patient was on constant topical steroids. Hence, in addition to medical management with anti-inflammatory drugs before surgery, management of giant papillae with mucous membrane grafting[13] would offer a good choice to prevent corneal complications in patients with chronic VKC and those awaiting surgical treatment such as C3R or penetrating keratoplasty.

  Conclusion Top

To summarize, a holistic management of VKC with anti-inflammatory agents and topical immunosuppressants along with proper addressal of giant papillae is very essential before planning any surgical intervention.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sharma N, Rao K, Maharana PK, Vajpayee RB. Ocular allergy and keratoconus. Indian J Ophthalmol 2013;61:407-9.  Back to cited text no. 1
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Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long-term results. J Cataract Refract Surg 2008;34:796-801.  Back to cited text no. 2
Herrmann CI, Hammer T, Duncker GI. Hazeformation (corneal scarring) after cross-linking therapy in keratoconus. Ophthalmologe 2008;105:485-7.  Back to cited text no. 3
Pollhammer M, Cursiefen C. Bacterial keratitis early after corneal crosslinking with riboflavin and ultraviolet-A. J Cataract Refract Surg 2009;35:588-9.  Back to cited text no. 4
Sharma N, Maharana P, Singh G, Titiyal JS. Pseudomonas keratitis after collagen crosslinking for keratoconus: Case report and review of literature. J Cataract Refract Surg 2010;36:517-20.  Back to cited text no. 5
Zamora KV, Males JJ. Polymicrobial keratitis after a collagen cross-linking procedure with postoperative use of a contact lens: a case report. Cornea 2009;28:474-6.  Back to cited text no. 6
Saboo US, Jain M, Reddy JC, Sangwan VS. Demographic and clinical profile of vernal keratoconjunctivitis at a tertiary eye care center in India. Indian J Ophthalmol 2013;61:486-9.  Back to cited text no. 7
[PUBMED]  [Full text]  
Solomon A. Corneal complications of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol 2015;15:489-94.  Back to cited text no. 8
Kankariya VP, Kymionis GD, Diakonis VF, Yoo SH. Management of pediatric keratoconus– Evolving role of corneal collagen cross-linking: An update. Indian J Ophthalmol 2013;61:435-40.  Back to cited text no. 9
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Totan Y, Hepşen IF, Çekiç O, Gündüz A, Aydın E. Incidence of keratoconus in subjects with vernal keratoconjunctivitis: A videokeratographic study 11 the authors have no proprietary or financial interest in the instruments used in this study. Ophthalmology 2001;108:824-7.  Back to cited text no. 10
Sangwan VS, Jain V, Vemuganti GK, Murthy SI. Vernal keratoconjunctivitis with limbal stem cell deficiency. Cornea 2011;30:491-6.  Back to cited text no. 11
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Iyer G, Agarwal S, Srinivasan B. Outcomes and rationale of excision and mucous membrane grafting in palpebral vernal keratoconjunctivitis. Cornea 2018;37:172-6.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3]


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