Post LASIK Epithelial Ingrowth Management

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.^1,2 The incidence may be less with femtosecond-assisted flap creation.^3,4 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 a flap melt.

Disease Entity

Disease

Epithelial cells invade the space between the corneal flap and 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 has also been associated with epithelial ingrowth.^1,2

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.^1-2,5-6

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.^3,4

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.  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
Fourescein staining

Corneal topography

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
Flourecein 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:^5,6
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

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

Reported techniques for removing epithelial ingrowth  include ligting the flap and scraping the epithelial cells from the stromal bed and nudersurface of the flap, with or without adjuvant treatments suchas ethanol, mitomycin, phototherapeutinc keratectomy (PTK).  The recurrence rate of lifting and scraping the cells alone has been reported to be as high as 44%.  Adjunctive use of ethanol, mitomycin, and PTK have been reported ot reduce this rate of recurrence, however 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 other ajunctive treatments.  Adjunctive glueing of the flap to improve flap adhesion to the stromal bed has been reported to have favorable outcomes as well.   

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.⁵ 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.

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.

Additional Resources

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References

1. Wang MY, Maloney RK. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol. 2000 Jun;129(6):746-51.
2. Asano-Kato N, Toda I, Hori-Komai Y, et al. Epithelial ingrowth after laser in situ keratomileusis: clinical features and possible mechanisms. Am J Ophthalmol. 2002 Dec;134(6):801-7.
3. . Kamburoglu G, Ertan A. Epithelial ingrowth after femtosecond laser-assisted in situ keratomileusis. Cornea. 2008 Dec;27(10):1122-5.
4. Letko E, Price MO, Price FW Jr. Influence of original flap creation method on incidence of epithelial ingrowth after LASIK retreatment. J Refract Surg. 2009 Nov;25(11):1039-41. doi: 10.3928/1081597X-20090617-13. Epub 2009 Nov 13.
5. Machat JJ, Slate S, Probst SE. The Art of LASIK, 2nd ed. Thorofare, NJ SLACK;1999. 427-33.
6. Krachmer JH, Mannis MJ, Holland EJ. Cornea Surgery of the Cornea and Conjunctiva, 2nd ed. St. Louis, MO: Mosby; 2005.1992-95.

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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

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