Very late onset corneal haze in a photorefractive keratectomy patient associated with presumed viral keratoconjuctivitis.

We report a rare case of very late-onset haze triggered by viral conjunctivitis, > 20 years after treatment of moderate myopia with photorefractive keratectomy (PRK), and its successful management.

Photoreftactive keratectomy (PRK) is a safe and effective surgical procedure in correcting refractive errors. Corneal haze is a serious complication in PRK, clinically observed as subepithelial reticular opacities, consisting of a bright layer of subepithelial deposits that gradually develop at the epithelial-stromal junction. The most common type of haze occurring after PRK starts 1 week postoperatively, increases to a peak level between 1 and 3 months, and declines slowly thereafter, resolving within 1 year at maximum without causing clinical symptoms.[1] It has been usually correlated with the depth of ablation and the smoothness of the stromal surface after the ablation.[2] However, late onset haze, often noted between 2 and 5 months postoperatively, has been reported to occur in 1%–4% of eyes that have surface ablation procedures such as PRK without mitomycin-C prophylaxis and has been associated with moderate to high myopic ablations (more than −6.00 D).[3] It can severely compromise vision, lead to refractive regression and can last up to 3 years.[4]

Case Report

A 43-year-old man with free medical history underwent an uneventful PRK without MMC in 1996. His preoperative refraction was −5.25 −0.50 × 180 in the right eye (OD) and −5.00 D in the left eye (OS). His 6-month postoperative vision was 20/20 in both eyes (BE) uncorrected.

During a routine eye check in 2016, his BCVA was recorded 20/20 in BE with −1.50 OD and −1.75 −0.50 × 150 OS. Patient had still free medical history, including history of diseases that may possible impair his cornea such as rosacea or allergic/atopic diseases.

In April 2017, he suffered from an episode of adenorival keratoconjuctivitis in BE. Diagnosis was based on clinical presentation that apart from follicular conjunctivitis included pharyngoconjunctival fever and periauricular lymphadenopathy and had highly contagious character involving also other members of his family and work colleagues.[5] Herpetic involvement was also excluded with a negative PCR result. Following a 2-week course of treatment with lubricants and topical dexamethasone 0.1% qid, there was remission of symptoms and signs and BCVA was recorded 20/20 in BE without any change in his previous prescription.

He then presented in February 2018 complaining of blurred vision and decreased acuity in his left eye. He mentioned gradual deterioration of visual acuity over the past six months and symptoms of diplopia which interfered significantly with his job as a surgeon due to bad binocular and hence stereoscopic vision. The BCVA was 20/20 with −1.50 OD, and 20/32 with −6.00 −1.75 × 180 OS. Slit lamp examination revealed grade 3–4 stromal corneal haze over the papillary axis using the grading scale proposed by Hanna et al.[6] and corneal epithelial hyperplasia overlying left eye [Fig. 1a and b]. No corneal infiltrate or injection of the conjuctival vessels was noted. Topical dexamethasone 0.1% qid was initiated, with haze being unresponsive after 1-month treatment. Dexamethasone was replaced by prednisolone sodium phosphate 1% on a tapering dosage scheme for another month. At the end of the 2-month treatment, no improvement was observed. There was no change of initial VA and refraction. Corneal topography (Oculus Pentacam Scheimpflug imager) was fairly normal, whereas wavefront analysis revealed considerable distortion, corresponding to the clinical appearance of the cornea [Fig. 1c and d].

Figure 1

(a and b) Left eye stromal corneal haze and corneal epithelial hyperplasia overlying the papillary axis. (c) Fairly normal left eye corneal topography (Oculus Pentacam, Scheimpflug imager). (d) Left eye corneal wavefront analysis

At 3 months after the onset of haze, the patient underwent a manual superficial keratectomy, as he was reluctant to undergo an additional laser treatment. Following appropriate consent, epithelium was removed manually avoiding the use of ethanol solution to spare its proinflammatory properties and apoptotic effect on fibroblasts. Mechanical debridement was performed to the underlined stromal haziness until complete smoothness and clearness of the underlying stroma were achieved, followed by topical application of 0.02% mitomycin-C (MMC) for 1 min. At the end of the procedure, a bandage soft contact lens was placed, and apart from topical moxifloxacin, prednisone acetate 1% was applied on a tapering basis.

One month later, BCVA was 20/20 with −1.50 OD, and 20/25 with −1.25 −0.50 ×160 OS and visual disturbances disappeared. Slit-lamp examination showed only a minimal peripheral haze remaining [Fig. 2a and b]. An excellent outcome was remained 6 months postoperatively with an improvement in corneal wavefront values [Fig. 2c–e].

Figure 2

(a and b) One month following manual superficial keratectomy only a minimal peripheral haze remaining. (c) Excellent outcome 6 months postoperatively. (d) No significant changes in corneal topography. (e) Improvement in corneal wavefront analysis

Discussion

A number of factors unrelated to surgery such as oral contraceptives, mechanical trauma, ultraviolet exposure, atopy, autoimmune conditions, and allergic conjuctivitis have been described as risk factors for haze after PRK.[1] Viral conjunctivitis as a trigger for haze has been reported as a late onset complication, however one year post surgery.[7] The appearance of haze a year after the infection represents a delayed hypersensitivity immune response to viral antigens deposited in the corneal stroma during infection,[8] which causes activation of keratocytes in the anterior corneal stroma, upregulation of mediators such as chemokines, and as a result activation of fibroblasts.[910]

To the best of our knowledge very late onset haze is an extremely rare complication and has never been reported as a result of viral keratoconjuctivitis. Our case indicates that myofibroblasts can be generated years after the original PRK surgery. Hyperactive keratocytes or loss of Bowman's layer may explain the unusual response to the inflammatory molecules released from tear film, leading to epithelial hyperplasia, myofibroblast generation, and abnormal stromal repair.

Conclusion

The case described here illustrates the potential risk for severe corneal haze even decades postoperatively triggered by a common eye infection. However, with prompt medical treatment, a successful visual outcome and restoring of vision can be achieved.

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

Nil.

Conflicts of interest

There are no conflicts of interest.