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.
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 4 Additional Resources
- 5 References
Epithelial cells invade the space between the corneal flap and stromal bed.
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
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
Stratified squamous epithelial cells with a basement membrane invade the intrastromal interface made during the LASIK procedure.
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.
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 is generally made during routine slit lamp examination. See below.
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.
- Visual acuity
- Slit lamp biomicroscopy
- Fluorescein staining
- Corneal topography
- 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
Decreased vision, dryness or foreign body sensation, light sensitivity, glare, haloes.
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)
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.
- Meibomian gland secretions
- Basement membrane dystrophy
- Diffuse lamellar keratitis
- Infectious keratitis
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.
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 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.1,7,8,16 The recurrence rate of lifting and scraping the cells alone has been reported to be as high as 44%.1 Adjuvant treatments such as ethanol, mitomycin, phototherapeutinc keratectomy (PTK) have been described for recurrent epithelial ingrowth, however, these may cause adverse effects.1,8-10 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.1,11 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.12-14 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.15
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.17
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.
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.
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.
- American Academy of Ophthalmology. Refractive Management/Intervention: Epithelial ingrowth after laser in situ keratomileusis Practicing Ophthalmologists Learning System, 2017 - 2019 San Francisco: American Academy of Ophthalmology, 2017.
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.
7. Walker MB, Wilson SE. Incidence and prevention of epithelial growth within the interface after laser in situ keratomileusis. Cornea. 2000 Mar;19(2):170-3.
8. Helena MC, Meisler D, Wilson SE. Epithelial growth within the lamellar interface after laser in situ keratomileusis (LASIK) Cornea. 1997 May;16(3):300-5.
9. Haw WW, Manche EE. Treatment of progressive or recurrent epithelial ingrowth with ethanol following laser in situ keratomileusis. J Refract Surg. 2001 Jan-Feb;17(1):63-8.
10. Vroman DT, Karp CL. Complication from use of alcohol to treat epithelial ingrowth after laser-assisted in situ keratomileusis. Arch Ophthalmol. 2001 Sep;119(9):1378-9.
11. Waring GO 3rd. Epithelial ingrowth after laser in situ keratomileusis. Am J Ophthalmol. 2001 Mar;131(3):402-3.
12. Anderson NJ, Hardten DR. Fibrin glue for the prevention of epithelial ingrowth after laser in situ keratomileusis. J Cataract Refract Surg. 2003 Jul;29(7):1425-9.
13. Rapuano CJ. Management of epithelial ingrowth after laser in situ keratomileusis on a tertiary care cornea service. Cornea. 2010 Mar;29(3):307-13.
14. Narváez J, Chakrabarty A, Chang K. Treatment of epithelial ingrowth after LASIK enhancement with a combined technique of mechanical debridement, flap suturing, and fibrin glue application. Cornea. 2006 Oct;25(9):1115-7.
15. Lindfield MD, D., G. Ansari MD, and T. Poole MD. "Nd:YAG Laser Treatment for Epithelial Ingrowth After Laser Refractive Surgery." Ophthalmic Lasers Surgery Imaging 1.43 (2012): 247-49.
16. Lahners MD, W. J., D. R. Hardten MD, and R. L. Lindstrom MD. "Alcohol and Mechanical Scraping for Epithelial In-Growth Following Laser in Situ Keratomileusis." Journal of Cataract and Refractive Surgery 21 (2005): 148-51.
17. Lee MD, E. S., H. K. Lee MD, S. C. Kim MD, Mi I. Lee MD, K. Y. Seo MD, and E. K. Kim MD. "Amniotic Membrane as a Biologic Pressure Patch for Treating Epithelial Ingrowth Under a Damaged Laser in Situ Keratomileusis Flap." Journal of Cataract and Refractive Surgery 32 (2006): 162-65.