Post LASIK Epithelial Ingrowth Management

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Article initiated by:

Ricardo M. Santaella, M.D.

All contributors:

Brad H. Feldman, M.D., Ricardo M. Santaella, M.D., Vandana Reddy, MD, Severin Pouly, M.D., Nishi Prasad

Assigned editor:

Severin Pouly, M.D.

Review:

Assigned status Update Pending

 by Severin Pouly, M.D. on February 26, 2024.

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Contributing Editors:	add

Ingrowth of epithelium into the corneal flap interface is a relatively uncommon complication of LASIK. The incidence of visually significant epithelial ingrowth is about 1% in primary cases and 2% on enhancement cases in microkeratome-assisted flap creation. The incidence may be less with femtosecond-assisted flap creation. Ingrowth of these cells into the corneal stromal interface is usually asymptomatic, however, these cells may lead to decreased vision due to irregular corneal astigmatism, direct intrusion of cells into the visual axis, or lead to melting of the overlying flap. Treatment is generally needed in instances where there is decreased vision or threat for flap melting.

Disease Entity

Disease

Epithelial cells invade the space between the corneal flap and underlying stromal bed.

Etiology

Etiology remains unclear, however, poor flap adhesion or apposition may allow surface epithelium to migrate into this space. Disturbance of the corneal epithelium intraoperatively or post-operatively has also been associated with epithelial ingrowth. Epithelial ingrowth can also be associated with flap melt, which is the keratolysis of flap tissue secondary to collagenase released by hypoxic intra-flap epithelial cells.

Risk Factors

Several preoperative and intraoperative risk factors have been identified. Preoperative risk factors include any factor that contributes to an epithelial defect; such as epithelial basement membrane dystrophy, history of recurrent erosions, increased patient age, diabetes mellitus, and epithelial ingrowth in the contralateral eye. Operative risk factors include intraoperative epithelial defect, postoperative inflammation (lamellar keratitis), flap relift, enhancement procedure, flap edema from any cause, flap misalignment or shift, ablation extending past the flap diameter, irregular flaps, buttonholes, free cap, LASIK in prior corneal transplantation or radial keratotomy.

General Pathology

Stratified squamous epithelial cells with a basement membrane invade the intrastromal interface made during the LASIK procedure.

Pathophysiology

Poor flap adhesion may allow epithelial cells to grow into the flap interface. Epithelial defect may contribute to poor flap adhesion due to focal flap hydration and edema. The invading cells may become ischemic or necrotic, which can lead to scarring, fibrosis, and keratolysis of surrounding stromal elements.

Primary Prevention

LASIK patients should be evaluated for risk factors which may lead to an intraoperative epithelial defect. These include recurrent corneal erosions, epithelial basement membrane dystrophy, or chronic eye rubbing. The surgeon should practice excellent surgical technique with minimal epithelial manipulation and accurate flap apposition. Excessive topical anesthetic use, interface irrigation, or surface drying may contribute to epithelial defect formation. A bandage contact lens should be strongly considered in the event of an intraoperative epithelial defect. The incidence of epithelial ingrowth is lower when the flap is created using a femtosecond laser as compared to microkeratome. This may be attributed to reduced trauma during flap creation. Femtosecond LASIK also appears to have an advantage in flap lift enhancements.

When performing an enhancement procedure, attention should be given to removing the peripheral epithelium from the flap interface and obtaining excellent flap apposition when replacing the flap.

Diagnosis

Diagnosis is generally made during routine slit lamp examination. See below.

History

Epithelial ingrowth is usually asymptomatic and is diagnosed during slit lamp examination. It is seen most frequently in the first 3 months after surgery but may occur or be recognized later. Decreased vision may occur secondary to astigmatic changes from irregular flap contour due to the underlying cells causing focal areas of topographic elevation and less commonly from cell migration into the visual axis. Occasionally patients will complain of dryness or foreign body sensation and light sensitivity.

Physical Examination

• Visual acuity
• Refraction
• Slit lamp biomicroscopy
• Fluorescein staining
• Corneal topography
• Anterior segment optical coherence tomography

Signs

• Nests of cells at flap interface, usually close to the edge of the flap
• Fibrosis in area of longstanding epithelial ingrowth
• White plaque of cells in flap interface
• Irregular astigmatism
• Fluorecein staining at border of flap where cellular invasion may originate

Symptoms

Decreased vision, dryness or foreign body sensation, light sensitivity, glare, haloes.

Clinical Diagnosis

Epithelial ingrowth may be categorized using the Probst/Machat epithelial ingrowth classification:

Grade 1: thin ingrowth, 1-2 cells thick, limited to within 2 mm of flap edge, transparent, difficult to detect, well-delineated white line along advancing edge, no associated flap changes, nonprogressive. (No treatment required)

Grade 2: thicker ingrowth, discrete cells evident within nest, at least 2 mm from flap edge, individual cells translucent, easily seen on slit lamp, no demarcation line along nest, corneal flap edge rolled or grey, no flap edge melting or erosion, usually progressive. (Requires non-urgent treatment within 2-3 weeks)

Grade 3: pronounced ingrowth, several cells thick, greater than 2 mm from flap edge, ingrowth areas appear opaque, obvious on slit lamp, white geographic areas of necrotic epithelial cells without a demarcation line, corneal flap margins rolled with thickened white-greyish appearance. Progression results in large areas of flap melting from collagenase release from necrotic epithelium. Confluent haze develops peripheral to the flap edge as flap pulls away, leaving exposed stromal bed in contact with surface epithelium. (Urgent treatment required with close follow-up due to frequent recurrences)

Diagnostic procedures

Fluorescein staining may assist in highlighting area of epithelial fistula that needs to be treated.

Fluorescein will stain the area of epithelial fistula formation or may pool in the area next to a retracted or elevated flap edge highlighting the area that will likely need to be addressed in order to prevent a postoperative recurrence.

Corneal topography may show irregular astigmatism due to the epithelial cells affecting the corneal contour of the overlying corneal flap.

Laboratory test

None.

Differential diagnosis

• Meibomian gland secretions
• Basement membrane dystrophy
• Diffuse lamellar keratitis
• Infectious keratitis

Management

See below.

General treatment

Grade 1 ingrowth may be observed. Grades 2 and 3 require treatment. Treatment involves removing the invading epithelial cells from the interface and achieving closure of the flap edge to prevent recurrent invasion of epithelium into the flap stromal interface space.

Medical therapy

Topical antibiotics and steroids are given postoperatively as per routine after LASIK surgery. A bandage contact lens may be placed to improve comfort. Glasses and contact lenses may be used to improve vision at least until the patient is treated surgically.  

Medical follow up

Patients diagnosed with grade 1 epithelial ingrowth should be seen weekly for one month with accurate documentation and measurements to determine stability or progression. If stable, resume routine follow up care. If progression is noted, treatment should be considered as per the Probst/Machat grading criteria.

Surgery

Surgery should be considered as per the Probst/Machat grading criteria.  The general treatment for removing epithelial ingrowth is lifting the flap and scraping the epithelial cells from the stromal bed and undersurface of the flap, typically followed by placed of a bandage contact lens.

The recurrence rate of lifting and scraping the cells alone has been reported to be as high as 44%. Adjuvant treatments such as ethanol, mitomycin, phototherapeutinc keratectomy (PTK) have been described for recurrent epithelial ingrowth, however, these may cause adverse effects. Suturing the flap after removal of the epithelial cells to create a tight apposition between the flap and the stromal bed has been shown to reduce the recurrence rate without the adverse effects of the listed adjunctive treatments. Adjunctive gluing of the flap after epithelial debribement in recurrent ingrowth cases to improve flap adhesion to the stromal bed has also been reported to have favorable outcomes. Additionally, Nd:YAG laser is another method used to destroy epithelial cells. This option may be especially useful when cells are encroaching the visual axis.

There are also reports of using amniotic membrane as an adjuvant therapy for the prevention of epithelial in-growth in patients who require placement of sutures in the visual axis. The membrane has intrinsic elasticity and if sutured tightly to the episclera, it can serve as a gentle pressure patch over the flap.

Surgical follow up

Patients undergoing a debridement procedure to remove the invading epithelium should be monitored for recurrence. These patients are generally seen the day following the procedure, one week, one month, and 3 months after the procedure if the exam findings show no evidence for recurrence. The contact lens is generally removed at the one-week visit.

Complications

Epithelial ingrowth that has been persistent in the flap interface for weeks to months may lead to flap melting within 2 weeks. Flap melt usually begins at the flap edge overlying the area of epithelial invading cells. Flap melting has been described as secondary to collagenase release from hypoxic epithelial cells underneath the flap. The patient may be asymptomatic, however, flap melts can lead to a distortion of the corneal surface with possible astigmatic changes and secondary tear film disruption leading to dry eye problems.

Once flap melt has occurred, treatment may not be necessary as the trapped epithelial cells have reached the surface. However, enhancements by relifting the flap after a flap melt may be quite difficult as the flap will be very adherent at the site of the melt.

Haze and scarring from inactive or treated epithelial ingrowth may be associated with glare, haloes, ghosting, and decreased vision. Diffuse lamellar keratitis similar to the occurrence with primary LASIK and flap lift.

Prognosis

Most epithelial ingrowth can be categorized as grade 1 and is visually insignificant. The visual results and overall outcome of treatment of visually significant ingrowth is generally excellent when the ingrowth is diagnosed early and treated adequately with preservation of flap integrity.