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Copyright 1998 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.1998
We describe 4 patients who developed an acute bilateral microcystic corneal epitheliopathy with a marked reduction in visual acuity after using daily wear soft contact lenses. The cysts cleared over a period of 4 weeks with complete visual recovery, although 1 patient developed central corneal flattening. Examination of an epithelial biopsy specimen from 1 patient was negative for Acanthamoeba . However, apoptosis was demonstrated by staining with TUNEL (TdT-mediated dUTP nick-end labeling) assay . We believe that this phenomenon is the result of acute corneal hypoxia.
Epithelial microcysts are small (15- to 50-µm) inclusions previously described as a delayed response to extended contact lens wear.1 They have been noted less frequently after daily wear soft or rigid contact lens wear. Patients using extended wear soft lenses typically develop microcysts after 4 to 8 weeks. The number of cysts that develop is related to the oxygen permeability of the lens and the duration of wear, and they take several months to disappear after discontinuatiuon of lens wear. They typically occur in small numbers in the center or the midperiphery of the cornea and rarely produce symptoms. In contrast, we describe 4 patients who wore daily wear soft contact lenses who developed an acute reduction in vision associated with a gross microcystic epitheliopathy. The clinical features and the possible origin of this condition are discussed.
Four patients who had worn daily wear soft contact lenses and who presented with an acute bilateral corneal microcystic epitheliopathy were identified (Table 1). When first examined, all were advised not to wear their contact lenses; they were then given a topical antibiotic (0.5% chloramphenicol 4 times a day for 1 week) and reviewed until resolution of the microcysts was complete. The first patient had an epithelial biopsy performed to exclude Acanthamoeba keratitis as the cause; part of the biopsy specimen was incubated on nonnutrient agar seeded with killed Escherichia coli, while the remainder was examined using a rabbit anti–Acanthamoeba monoclonal antibody. A TUNEL (TdT-mediated dUTP nick-end labeling) assay (Gibco BRL, Paisley, United Kingdom), which identifies dying (apoptotic) cells by labeling fragmented DNA, was also performed.
Two patients wore lenses on a regular basis and 2 only wore lenses for social occasions. All patients denied previous lens problems, overnight wear, or contact lens abuse. All had worn their lenses on the day before the onset of symptoms and, on waking, had noted a marked reduction in vision with only a mild foreign body discomfort.
First examinations were between 1 and 3 days of the onset of symptoms. Vision was reduced in all eyes and deteriorated further in 2 patients despite the discontinuation of contact lens wear (Table 1). All had mild conjunctival hyperemia, slight chemosis, but no anterior uveitis. In 2 patients the microcysts extended to the limbus, but in the 2 who were seen later, there was a peripheral ring of normal epithelium approximately 2 mm in diameter (Figure 1). There was only scattered punctate uptake of fluorescein by the epithelium. Central corneal thickness was normal, there were no stromal striae, and, after resolution, all patients had a normal endothelial cell structure with no signs of epithelial basement membrane disease. Peripheral corneal neovascularization was not present.
Left, Clinical photograph of case 1 taken on the morning of the onset of symptoms. Note the large number of cysts that are almost confluent in the epithelium. Right, Clinical photograph of case 2 taken 3 days after the onset of symptoms. The peripheral cornea (inferior of photograph) is clear of cysts.
Resolution of the microcysts progressed centrally and all eyes were free of cysts within 4 weeks. Patient 3 developed a 2-mm-diameter epithelial erosion in one eye that healed without further symptoms. Patient 1 developed a bilateral faint subepithelial haze that had cleared by 4 weeks. This patient had keratometry readings in 1988 of (7.55 mm at 180/7.60 at 090 OD; 7.60 mm at 180/7.75 at 090 OS) when she was first fitted with Permaflex (Wesley Jesson, PBH Ltd, Southampton, United Kingdom) lenses (8.70:14.40:−9.50 OD, 8.70:14.40:−8.50 OS) that she wore uneventfully for 5 years. Four weeks after we saw her, her myopia had reduced from −9.50/−0.75 at 015 OD; −8.75/−1.25 at 180 OS to −5.25/−1.00 at 050 OD; −3.75/−1.00 at 145 OS, and this refraction has been stable for 24 months. Her keratometry readings have not changed, but videokeratoscopy demonstrated approximately 4 diopters of apical corneal flattening.
All patients have subsequently returned to contact lens wear. Patient 1 changed to daily wear rigid gas permeable contact lenses after 9 months without lenses, while the remainder have returned to daily wear soft contact lenses with a recommendation that the daily wearing time does not exceed 8 hours. There has been no recurrence of symptoms after a minimum follow-up of 20 months.
Findings from examination of the corneal epithelial biopsy specimen were negative for Acanthamoeba. Histologic investigation showed superficial cysts containing shrunken epithelial cells with small condensed nuclei or fragments of nuclear material, often with dark homogeneous eosinophilic cytoplasm (Figure 2). The TUNEL assay revealed that a few of these cells had nuclei with cleaved DNA (Figure 2, insert).
Photomicrograph of biopsy specimen taken from the corneal epithelium from case 1 that has folded such that the superficial surface is concave. Note the microcysts containing shrunken epithelial cells with condensed nuclear material (hematoxylin-eosin, original magnification × 60). Insert, A single TUNEL (TdT-mediated dUTP nick-end labeling) assay–positive cell (original magnification × 75).
The formation of corneal epithelial microcysts following extended contact lens wear is thought to result from chronic hypoxia that leads to cell death and an accumulation of debris in intercellular pockets.1 Increased metabolic activity after discontinuation of lens wear may then result in an increase in the number of microcysts that are then cleared by anterior migration from the epithelium.1 Associated abnormalities, such as faint axial stromal infiltrates, are uncommon.2
We propose that acute corneal microcystic epitheliopathy is also a response to hypoxia. The reason for the sudden onset after a period of trouble-free lens wear is unclear and the mechanism of the apical corneal flattening in one patient is unexplained. A recent study of corneal epithelial cell shedding has shown that a few surface cells normally have fragmented DNA and that cell death, as defined by a calcein-ethidium viability assay, is a normal feature of corneal epithelial cell turnover.3 Hypoxia is a recognized cause of apoptosis,4 and it is possible that premature cell death beneath the epithelial surface contributed to the formation of microcysts in our patients.
Other causes of epithelial microcystic keratopathy were considered.5 However, none of our patients had features of an associated corneal dystrophy or endothelial failure, history of infection, surgery, or abrasion, and associated external eye disease. No chemical component of the contact lens care systems was common to all cases, although a nonspecific toxic side effect cannot be excluded as a possible mechanism. Findings from the culturing and immunohistochemistry for Acanthamoeba, a further cause of epitheliopathy in contact lens wearers, were also negative. We therefore consider that hypoxia is the most likely cause and that the phenomenon may be a step on the way to contact lens–induced epithelial necrosis.
The rabbit anti–Acanthamoeba monoclonal antibody was a gift from Simon Kilvington, PhD, Public Health Laboratory, Bath, England.
Corresponding author: Stephen J. Tuft, MD, FRCOphth, Moorfields Eye Hospital, London EC1V 2PD, England (e-mail: email@example.com).
Tuft SJ, Luthert P. Acute Microcystic Corneal Epitheliopathy After Daily Soft Contact Lens Wear. Arch Ophthalmol. 1998;116(6):810–812. doi:
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