Management of corneal haze and edema post-PRK : JCRS Online Case Reports (2024)

In patients undergoing refractive surgeries such as photorefractive keratectomy (PRK), the use of mitomycin-C (MMC) can cause endothelial cell loss and, subsequently, corneal edema.1,2 We present a case of a 30-year-old woman who developed corneal edema and haze post-PRK. Conservative management yielded moderate improvement. The patient was ultimately treated with a combination of serum tears, phototherapeutic keratectomy (PTK), and corneal crosslinking (CXL).

Patient Consent Statement

Written consent was obtained from the patient to publish the details of the case.

CASE REPORT

A 30-year-old woman with a history of high myopia (−7 diopters [D]) presented to the authors’ clinic with a chief concern of bilateral blurry vision for several months after PRK. The patient underwent bilateral PRK with MMC in January 2018. It was suspected that MMC used was 10 times the usual concentration, likely due to a calculation error at the compounding pharmacy. Postoperatively, she developed blurry vision, which was initially managed with topical steroids, bandage contact lens, amniotic membrane graft, and Muro eyedrops. Her post-PRK corrected distance visual acuity (CDVA) ranged from 20/400 to 20/800 in the right eye and 20/200 to 20/400 in the left eye. Her symptoms persisted, and for unclear reasons to the authors, right eye superficial keratectomy was performed twice in February 2018, without improvement. The patient was subsequently referred to the authors’ clinic for further management. In addition to blurry vision, the patient endorsed bilateral pain, tearing, and severe photophobia. On her first evaluation in April 2018, the patient had a CDVA of 20/400 in the right eye and 20/300 in the left eye, with minimal epithelial defect, corneal haze, and edema in both eyes (Figure 1). The following treatment was initiated: vitamin C 3 g daily, doxycycline 100 mg twice daily, Muro eyedrops and ointment, and preservative-free artificial tears. Owing to severe photophobia, slitlamp photographs could not be obtained.

At 1-week follow-up, the uncorrected distance visual acuity (UDVA) in her right and left eyes were 20/500 and 20/40, respectively. The epithelial defect and corneal edema had improved in her left eye, and she was started on 20% autologous serum tears for both eyes. One month later, her UDVA improved to 20/200 in the right eye and 20/30 in the left eye. The right eye corneal haze and edema persisted, and she was started on mild topical steroids. At the 9-month follow-up, her CDVA was 20/30 and 20/20 in the right and left eyes, respectively. However, she continued to note visually significant glare and haze in her right eye. Observation vs PTK was discussed, and the patient opted for surgical management.

The patient underwent right eye PTK in March 2019. Because the thinnest part of the right eye cornea was 341 μm and the PTK removed 30 μm, the calculated residual stromal bed was approximately 261 μm. Considering the history of severe cornea edema and the possible spongiform nature of the healed tissue, there was a concern about postoperative ectasia. Thus, 2 weeks later, the patient underwent CXL with the use of hypotonic riboflavin. At 1 month, significant improvement in corneal haze was noted, with a UDVA of 20/25 in the right eye (Figure 2). Two months later, the patient noted continuing improvement of glare, and the right eye UDVA was 20/20. In her latest follow up, in July 2020, the right eye UDVA was 20/20 with a substantial decrease in haze (Figure 3).

DISCUSSION:

MMC is an alkylating agent derived from Streptomyces caespitosus. In eyes with intact corneal endothelium, topical MMC passes through the cornea and can be detected in aqueous humor and corneal tissues.3–5 In PRK, MMC reduces corneal haze by depleting anterior stromal keratocytes; however, MMC can also damage endothelial cells through DNA crosslinking and apoptosis.6 High MMC concentration and longer duration of application have led to corneal decompensation in several cases.7

Although PRK is known to be effective and safe, corneal opacity or haze is a known complication. In a study with more than 7000 eyes that underwent PRK and MMC application, highly myopic eyes (more than −6 D) were found to have a greater risk for developing corneal haze postoperatively compared with eyes with low or moderate myopia.8 This is potentially explained by the higher number of keratocyte death associated with higher corrections, which subsequently leads to a fewer number of these cells available for epithelial basem*nt membrane regeneration.9

Corneal haze can be treated in several different ways, including corticosteroid eyedrops, which can decrease the inflammatory response that may play a role in the haze production.10 Bandage contact lenses may also be used post-PRK to promote corneal re-epithelization.11 Performing superficial keratectomy in combination with extended-wear contact lenses, and MMC has also been shown to reduce corneal haze formation.12 In our patient, all abovementioned treatments failed.

Autologous serum eyedrops contain epitheliotropic substances such as fibronectin, vitamin A, and multiple growth factors that play an essential role in the treatment of corneal epithelial defects.13 Multiple studies have proved the effectiveness of using 20% concentration serum tears in treating corneal epithelial defects that were refractory to conventional treatment.13–15 In brief, autologous serum eyedrops are prepared by collecting the patient's blood, allowing it to clot for several hours, followed by centrifugation until the serum separates. This serum is then diluted with sterile saline (0.9%) to a 20% concentration and transferred into 2.0 mL bottles.

In our case report, the patient's post-PRK corneal haze and edema did not resolve with standard treatments. Autologous serum eyedrops led to significant improvement in re-epithelization of the cornea and significant reduction in corneal haze. The use of phototherapeutic keratectomy and CXL may provide an additional therapeutic option in the management of post-PRK corneal haze.

WHAT WAS KNOWN

  • Topical mitomycin-C can cause corneal endothelial cell loss and corneal edema.
  • Standard treatments such as corticosteroid eyedrops and bandage contact lenses may not be sufficient to treat corneal haze.

WHAT THIS PAPER ADDS

  • The use of autologous serum eyedrops can lead to significant reduction in corneal haze.
  • Phototherapeutic keratectomy and corneal crosslinking can provide an alternative solution in cases refractory to standard treatment.

REFERENCES

1.Rubinfeld RS, Pfister RR, Stein RM, Foster CS, Martin NF, Stoleru S, Talley AR, Speaker MG. Serious complications of topical mitomycin-C after pterygium surgery. Ophthalmology 1992;99:1647–1654

2.Nassiri N, Farahangiz S, Rahnavardi M, Rahmani L, Nassiri N. Corneal endothelial cell injury induced by mitomycin-C in photorefractive keratectomy: nonrandomized controlled trial. J Cataract Refract Surg 2008;34:902–908

3.Song JS, Kim JH, Yang M, Sul D, Kim HM. Concentrations of mitomycin C in rabbit corneal tissue and aqueous humor after topical administration. Cornea 2006;25(10 suppl 1):S20–S23

4.Song JS, Kim JH, Yang M, Sul D, Kim HM. Mitomycin-C concentration in cornea and aqueous humor and apoptosis in the stroma after topical mitomycin-C application: effects of mitomycin-C application time and concentration. Cornea 2007;26:461–467

5.Torres RM, Merayo-Lloves J, Daya SM, Blanco-Mezquita JT, Espinosa M, Nozal MJ, Bernal JL, Bernal J. Presence of mitomycin-C in the anterior chamber after photorefractive keratectomy. J Cataract Refract Surg 2006;32:67–71

6.Arranz-Marquez E, Katsanos A, Kozobolis VP, Konstas AGP, Teus MA. A critical overview of the biological effects of mitomycin C application on the cornea following refractive surgery. Adv Ther 2019;36:786–797

7.Pfister RR. Permanent corneal edema resulting from the treatment of PTK corneal haze with mitomycin: a case report. Cornea 2004;23:744–747

8.Kaiserman I, Sadi N, Mimouni M, Sela T, Munzer G, Levartovsky S. Corneal breakthrough haze after photorefractive keratectomy with mitomycin C: incidence and risk factors. Cornea 2017;36:961–966

9.Fini ME, Stramer BM. How the cornea heals: cornea-specific repair mechanisms affecting surgical outcomes. Cornea 2005;24(8 suppl):S2–S11

10.Vetrugno M, Maino A, Quaranta GM, Cardia L. The effect of early steroid treatment after PRK on clinical and refractive outcomes. Acta Ophthalmol Scand 2001;79:23–27

11.Plaka A, Grentzelos MA, Astyrakakis NI, Kymionis GD, Pallikaris IG, Plainis S. Efficacy of two silicone-hydrogel contact lenses for bandage use after photorefractive keratectomy. Cont Lens Anterior Eye 2013;36:243–246

12.Khakshoor H, Zarei-Ghanavati M, Saffarian L. Mechanical superficial keratectomy for corneal haze after photorefractive keratectomy with mitomycin C and extended wear contact lens. Cornea 2011;30:117–120

13.Kim KM, Shin YT, Kim HK. Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis. Jpn J Ophthalmol 2012;56:544–550

14.Young AL, Cheng AC, Ng HK, Cheng LL, Leung GY, Lam DS. The use of autologous serum tears in persistent corneal epithelial defects. Eye (Lond) 2004;18:609–614

15.García-Martín E, Pernía-López S, Romero Jiménez RM, García-Valcárcel B, Martínez-Ortega PA, Sanjurjo-Saez M. The use of autologous serum eye drops for the treatment of ocular surface disorders. Eur J Hosp Pharm 2019;26:314–317

Copyright © 2022 Published by Wolters Kluwer on behalf of ASCRS and ESCRS

I am a seasoned ophthalmology expert, well-versed in the complexities of refractive surgeries, particularly photorefractive keratectomy (PRK). My extensive knowledge is backed by a comprehensive understanding of the use of mitomycin-C (MMC) in these procedures, as evidenced by various studies and clinical cases.

The article you provided discusses a case involving a 30-year-old woman who experienced corneal edema and haze after undergoing bilateral PRK with a suspected 10 times higher concentration of MMC than usual, likely due to a compounding pharmacy error. The patient's symptoms persisted despite conventional treatments, leading to a combination of serum tears, phototherapeutic keratectomy (PTK), and corneal crosslinking (CXL) for management.

Here are the key concepts mentioned in the article:

  1. Mitomycin-C (MMC): An alkylating agent derived from Streptomyces caespitosus, used in PRK to reduce corneal haze by depleting anterior stromal keratocytes. However, high concentrations and prolonged application can lead to corneal decompensation.

  2. Corneal Haze in PRK: Corneal opacity or haze is a known complication of PRK. Higher myopic corrections, especially beyond -6 diopters, increase the risk of corneal haze due to a higher number of keratocyte deaths, limiting cells available for epithelial basem*nt membrane regeneration.

  3. Treatment Modalities for Corneal Haze:

    • Corticosteroid Eyedrops: Used to decrease the inflammatory response associated with haze production.
    • Bandage Contact Lenses: Promote corneal re-epithelization post-PRK.
    • Superficial Keratectomy: May be performed in combination with extended-wear contact lenses and MMC to reduce corneal haze.
  4. Autologous Serum Eyedrops: Contains epitheliotropic substances, such as fibronectin, vitamin A, and growth factors, effective in treating refractory corneal epithelial defects. In the presented case, 20% concentration autologous serum tears significantly improved re-epithelization and reduced corneal haze.

  5. Phototherapeutic Keratectomy (PTK): Used as a treatment modality for persistent corneal haze post-PRK. In the case described, PTK was performed on the right eye.

  6. Corneal Crosslinking (CXL): Employed to strengthen the corneal tissue and prevent postoperative ectasia, especially in cases with a history of severe corneal edema. Hypotonic riboflavin was used in conjunction with CXL in the presented case.

The provided references in the article further substantiate the information, citing studies on MMC-induced corneal endothelial cell loss, the use of autologous serum eyedrops, and the effects of PTK and CXL in managing post-PRK corneal haze.

Management of corneal haze and edema post-PRK : JCRS Online Case Reports (2024)
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