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Year : 2023  |  Volume : 3  |  Issue : 2  |  Page : 295-297

Questionable effect of collagen cross-linking for keratoconus in a pregnant female: A case report

Department of Cornea and Refractive Services, The Eye Foundation Hospital, Coimbatore, Tamil Nadu, India

Date of Submission01-Oct-2022
Date of Acceptance21-Nov-2022
Date of Web Publication28-Apr-2023

Correspondence Address:
Shreesha Kumar Kodavoor
582-A, Diwan Bahadur Rd., R S Puram West, Coimbatore, Tamil Nadu - 641 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJO.IJO_2518_22

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We report a rare case of keratoconus (KC) progressing to advanced stage in a pregnant female with previously stable KC managed with collagen cross-linking 7 years back. A 26-year-old female first visited during the second month of her pregnancy with stable KC managed with collagen cross-linking 7 years back. She was found to have corneal melt with haze and was advised to undergo keratoplasty surgery. However, the patient was not willing for that, and the surgery was deferred. After 4 months, the patient came with similar complaints. On examination, the corneal melt was advanced and the patient was suggested surgery again. However, she again deferred the surgery. At the eighth month of pregnancy, the patient came with advanced melt with well-epithelized descemetocele, which was then successfully operated on an emergency basis with full-thickness penetrating keratoplasty.

Keywords: Corneal melt, Collagen cross linking, Penetrating Keratoplasty

How to cite this article:
Kodavoor SK, Rathi N, Dandapani R. Questionable effect of collagen cross-linking for keratoconus in a pregnant female: A case report. Indian J Ophthalmol Case Rep 2023;3:295-7

How to cite this URL:
Kodavoor SK, Rathi N, Dandapani R. Questionable effect of collagen cross-linking for keratoconus in a pregnant female: A case report. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 10];3:295-7. Available from: https://www.ijoreports.in/text.asp?2023/3/2/295/374947

Keratoconus (KC) is a bilateral, noninflammatory, degenerative, and ectatic disorder of the cornea. It is characterized by corneal steepening, visual distortion, apical corneal thinning, and central corneal scarring.[1],[2] The appearance of KC is usually in the second decade of life, which shows progression during puberty and stabilizes by the fourth decade of life. There are several case reports revealing its progression during pregnancy.[3] One of the proven management strategies in restricting its progression is collagen cross-linking (CXL), which is also suggested in pregnant patients with KC. Multiple postoperative complications are noted, such as corneal haze, scarring, infectious and noninfectious corneal melt, and others. However, progressive corneal thinning post CXL, which is sight threatening, is observed in multiple occasions, which will be discussed in this article.

Here, we report a case of KC progression leading to severe melt during pregnancy in a previously stable disease which was treated with CXL.

  Case Report Top

A 26-year-old female came to our outpatient department in her second month of pregnancy with progressive blurring of vision and watering in right eye. Past history revealed that CXL procedure was performed in both the eyes 7 years back after being diagnosed with KC at our hospital. On examination, her best corrected visual acuity was 6/60 in right eye and 6/6 in left eye with −4.00 diopters of cylinder (DC) at 70° and −9.00 diopters of sphere (DS) and −4.50 diopters of cylinder (DC) at 160°, respectively. Slit-lamp examination of right eye revealed central inactive mild corneal thinning and increased corneal haze, left eye showed minimal central deep stromal scar post CXL. Anterior segment optical coherence tomography also revealed a corresponding thinning of cornea secondary to corneal melt [Figure 1]. Patient was managed conservatively with topical antibiotics, lubricants, and steroids. Patient was suggested to undergo deep anterior lamellar keratoplasty; however, she did not turn up.
Figure 1: (a) Slit-lamp photo at 2 months of pregnancy showing mild corneal thinning due to corneal melt. (b) Corresponding AS-OCT picture showing the same. AS-OCT = anterior segment optical coherence tomography

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After 4 months, she again came with mild pain and redness and further drop in vision in right eye, which revealed corneal erosion with increased haze and thinning [Figure 2]; she was given lubricating eye drops for this. She was again suggested for corneal transplant surgery; however, she did not want to undergo any procedure until delivery. In her eighth month of pregnancy, the patient came with severe drop in vision and severe photophobia with watering. Her visual acuity in right eye was finger counting 1 m, which showed no improvement with glasses. On examination, severe corneal melt with thinning leading to large descemetocele in the central cornea was discovered [Figure 3], and she was again suggested to undergo corneal transplant surgery. Finally, the same was done on an emergency basis under peribulbar anesthesia with informed consent obtained from the patient.Deep anterior lamellar keratoplasty (DALK) was attempted in the beginning, but ended up with penetrating keratoplasty due to perforation of central descemetocele. Postoperatively, she was doing well [Figure 4]. On the patient's final follow-up, at 6 months postsurgery, her best corrected visual acuity was 6/9 with −3.25 DS and −3.50 DC at 60°.
Figure 2: (a) Slit-lamp photo at 6 months of pregnancy showing increased corneal melt. (b) Corresponding AS-OCT picture showing the same. AS-OCT = anterior segment optical coherence tomography

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Figure 3: (a) Slit-lamp photo at 8 months of pregnancy showing advanced melt with well epithelized descemetocele. (b) Corresponding AS-OCT picture showing the same. AS-OCT = anterior segment optical coherence tomography

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Figure 4: Postoperative day 1 photo after penetrating keratoplasty

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  Discussion Top

In our case, corneal melt could be due to two major reasons: first, disease progression during pregnancy and second, possible stromal degeneration post CXL, which has been reported at multiple occasions in the past.

Spontaneous corneal perforation in a known case of KC during pregnancy has been well reported in the past and numerous factors are responsible for its progression. Park et al.[4] demonstrated increase in corneal steepening during second and third trimesters of pregnancy. Also, Spoerl et al.[5] revealed fluid retention and increase in corneal estrogen levels as the causes for corneal steepening.

Estrogen receptors are found over the cornea, due to which during their increase in pregnancy causes reduction in corneal biomechanical stability. Spoerl et al.[5] also reported increased susceptibility of ectasia in keratoconic or post-refractive laser surgery corneas.

Increase in the synthesis of matrix metalloproteinases (MMPs), especially MMP-9, by trophoblastic cells during the first trimester of pregnancy, caused by the release of human chorionic gonadotropin hormone is the possible reason for KC progression in pregnancy.[6]

Performing CXL in pregnant females have been considered effective and safe since long time. However, progressive stromal degeneration and corneal thinning have been reported as the deleterious effects of CXL due to ultraviolet (UV) radiation. Zare et al.[7] conducted a study which reported failure of complete stromal keratocyte repopulation after 6 months of the procedure, which could result in progressive corneal thinning. They also revealed UV rays causing deeper damage to nerves and failure of complete regeneration of nerve plexus before 6 months, leading to corneal thinning.

Lim et al.[8] also conducted a study which described UVA exposure as the cause for keratocyte death leading to sublethal effect in the deeper stroma, which receives lower dose of radiation, resulting in fibroblastic transformation of the keratocytes with subsequent scar formation, which may further decrease the supply of nutrition from the aqueous to superficial stroma.

Case series reports describing the deleterious effects of CXL have been published describing stro mal degeneration and progressive corneal thinning as a rare, but sight-threatening complication of CXL.[9]

Contrary to this, one of the case reports also described spontaneous resolution of acute corneal hydrops in a pregnant female already treated with CXL for KC, indicating the strength of collagen fibers in the anterior stroma post CXL, which proved to be beneficial.[10]

Also, multiple case studies are published describing the dynamics of progression in pregnant females after a previous successful accelerated CXL treatment during and after pregnancy.[11]

These could be the possible reasons for the progression observed in the first trimester of pregnancy in our patient.

Nonetheless, in this case report, we would like to highlight the advanced progression of KC in a pregnant female leading to impending perforation, irrespective of previous successful management with CXL 7 years back. The patient was then successfully managed with full-thickness penetrating keratoplasty.

  Conclusion Top

Corneal melt post CXL in a pregnant female with stable KC is a rare occurrence. Hormonal changes during pregnancy with multiple associated factors are responsible for progression of KC and are well documented in the past. Early diagnosis and prompt treatment in such patients prove to be beneficial with predictable outcomes. However, the efficacy of CXL requires further probing and evaluation.

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

Cozma I, Atherley C, James NJ. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asian and white patients. Eye (Lond) 2005;19:924-5.  Back to cited text no. 1
Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998;42:297-319.  Back to cited text no. 2
Hafezi F, Iseli HP. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg 2008;34:1219-21.  Back to cited text no. 3
Park SB, Lindahl KJ, Temnycky GO, Aquavella JV. The effect of pregnancy on corneal curvature. CLAO J 1992;18:256-9.  Back to cited text no. 4
Spoerl E, Zubaty V, Raiskup-Wolf F, Pillunat LE. Oestrogen-induced changes in biomechanics in the cornea as a possible reason for keratectasia. Br J Ophthalmol 2007;91:1547-50.  Back to cited text no. 5
Curry TE Jr, Smith MF. Impact of extracellular matrix remodeling on ovulation and the folliculo-luteal transition. Semin Reprod Med 2006;24:228-41.  Back to cited text no. 6
Zare MA, Mazloumi M, Farajipour H, Hoseini B, Fallah MR, Mahrjerdi HZ, et al. Effects of corneal collagen crosslinking on confocal microscopic findings and tear indices in patients with progressive keratoconus. Int J Prev Med 2016;7:132.  Back to cited text no. 7
  [Full text]  
Lim LS, Beuerman R, Lim L, Tan DT. Late-onset deep stromal scarring after riboflavin-UV-A corneal collagen cross-linking for mild keratoconus. Arch Ophthalmol 2011;129:360-2.  Back to cited text no. 8
Prabhakar GV, Panickar N, Reddy JK, Sivasubramaniam SK, Singh A. Severe focal stromal degeneration up to Descemet membrane after corneal collagen cross-linking. Indian J Ophthalmol 2020;68:224-6.  Back to cited text no. 9
[PUBMED]  [Full text]  
Stock RA, Thumé T, Bonamigo EL. Acute corneal hydrops during pregnancy with spontaneous resolution after corneal cross-linking for keratoconus: A case report. J Med Case Rep 2017;11:53.  Back to cited text no. 10
Sarac O, Yesilirmak N, Caglayan M, Yaman D, Ozdas D, Toklu Y, et al. Dynamics of keratoconus progression after a previous successful accelerated crosslinking treatment during and after pregnancy. J Cataract Refract Surg 2022;48:599-603.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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