Epithelial Sloughing During Laser In-Situ Keratomileusis
Laser in situ keratomileusis (LASIK) is an extremely safe procedure with a relatively rare incidence of complications, yet the procedure is not without risk. Among the potential complications of LASIK, epithelial sloughing is the most common, with an aggregate overall incidence of 9.5 – 14%, although in recent years the incidence has dropped significantly.
There appear to be a number of factors that increase the risk of developing this complication. Most notable is the strong, well-established link between epithelial basement membrane dystrophy (EBMD). There is also evidence to indicate that age, corneal thickness and ethnicity play a role. To mitigate these risks, several perioperative measures that can be implemented, including altering the preoperative eye-drop regimen and limiting the amount of suction used during surgery.
The sequelae of epithelial sloughing include diffuse lamellar keratitis (DLK), epithelial ingrowth and rarely, flap melting. Patients who experience epithelial sloughing/defects during LASIK are more likely to experience undercorrection and lost lines of vision as a result. To prevent these outcomes, patients should be thoroughly examined to rule out EBMD, and care should be taken to assess and mitigate other risk factors.
Epithelial sloughing or epithelial defects are defined as a break or loose area of corneal epithelium larger than 2.0 mm x 2.0 mm.
Epithelial defects are the most common intraoperative complication of LASIK. Overall incidence of epithelial sloughing or defects during LASIK is thought to be between 2.6-14% .
Natural Risk Factors
There are a number of characteristics that increase the risk of a patient experiencing epithelial sloughing or defects during LASIK.
Epithelial Basement Membrane Dystrophy
Epithelial basement membrane dystrophy (EBMD), also known as recurrent erosion syndrome or map-dot-fingerprint dystrophy, is a well-recognized risk factor for intraoperative epithelial sloughing. In a study of nine patients (16 eyes) with confirmed EBMD, 81% developed epithelial sloughing during LASIK or in the immediate postoperative period. In a second, retrospective study of six patients who experienced significant epithelial sloughing during LASIK, all were found to have microscopic evidence of EBMS.
Epithelial basement membrane dystrophy is a disease that affects the anterior cornea. It is defined as a weakened corneal basement membrane resulting in recurrent breakdown of the corneal epithelium.
Epithelial basement membrane dystrophy is the most common form of corneal dystrophy, with an estimated overall prevalence of 5%.
The disease may frequently be asymptomatic, but in symptomatic patients, it presents as pain and foreign-body sensation, usually first thing in the morning. Patients may also experience the sensation of their lid “sticking” to the cornea, and can occasionally complain of blurred vision. Regardless of whether a patient is symptomatic, or symptomatic only in one eye, the disease process is almost always bilateral.
The characteristic microscopic findings of EBMD are map-like subepithelial geographic opacities (maps), intraepithelial microcysts (dots), and subepithelial ridges that resemble fingerprints.
The underlying pathology is underdeveloped hemidesmosomes and an absence of anchoring fibrils8,9. The result is poor adherence of the corneal epithelium to the Bowman’s layer, such that even minor trauma can cause the epithelial layer to detach.
The risk of epithelial sloughing increases with age. One study reported epithelial defects and sloughing occurred in 4.1% of patients younger than 40, while the incidence increased to 13.2% in patients older than 40. Another noted the risk of epithelial complications increased 2.4% for every decade of life after 40.
Increased corneal thickness prior to surgery is also associated with an increased risk of epithelial sloughing. The risk of epithelial defects increased by 2.3% for each 50 μm increase in corneal thickness.
Patients undergoing hyperopic repairs are at an increased risk. The incidence of epithelial defects is roughly 17% in eyes undergoing hyperopic repairs, versus 8.0% for myopic repairs.
Skin Type & Ethnicity
It has been suggested that patients with light hair or light eye color are at an increased risk for intraoperative epithelial defects when compared to patients with dark hair and dark eye color. The lone study on this risk factor found that patients with a Franklin Skin Type (FST) of I or II were 10 times more likely to experience intraoperative epithelial sloughing than those with FST scores between III – VI. In the same study, patients with a score of 1 or 2 on the Lancer Ethnicity Scale (LES) were similarly 10 times more likely to experience epithelial sloughing during LASIK versus patients with scores below 3.
These are some reports that patients with diabetes mellitus are at an increased risk for epithelial sloughing during LASIK.Gender does not appear to be a significant factor, one study reported overall incidence of 9.5% in men compared with a 9.0% in women.
Surgical Risk Reduction
Eye Drop Regimen
Perioperative eye-drop regimen has proven to be one of the best ways to decrease the incidence of epithelial sloughing during LASIK. There is significant evidence to suggest that avoidance of preoperative anesthetic drops and preserved eye-drops decreases the incidence of epithelial defects.
Tekwani & Huang propose an eye-drop regimen that excludes preoperative topical anesthetic and preserved eye-drops, and additionally suggest the following: administration of lubricating drops (such as Refresh Plus) every five minutes, starting 30 minutes before surgery, avoidance of intraoperative Barraquer Tonometry, and application of a double layer of lubricant (BSS on top of Celluvisc) just prior to the microkeratome pass. This regimen was associated with a statistically significant decreased in the risk of epithelial sloughing when compared to an eye-drop regimen that excluded frequent preoperative lubricant and did not use the suggested double layer of lubricant.
Turning the suction ring off during the reverse pass of the microkeratome was associated with a reduced incidence of epithelial defects by an odds ratio of 1.76.
Use of the femtosecond laser is associated with significantly less epithelial defects when compared to the microkeratome. In a retrospective analysis comparing flap outcomes between a microkeratome and femtosecond laser; the rate of epithelial sloughing in patients who received the microkeratome treatment was 2.6% (23 eyes) compared to 0.6% (5 eyes) in the femtosecond laser group. The belief is that femtosecond laser-assisted flap creation eliminates the shear stress and compressive force that a microkeratome imposes on the epithelium.
Pathophysiology of Epithelial Sloughing
It is thought that patients who experience epithelial sloughing have inherent defects in corneal structure or integrity that predispose them to experiencing intraoperative epithelial sloughing3. The theory is that the operative shearing force exceeds the defective adhesive strength keeping the epithelium attached to the basement membrane. This theory may explain why there is a higher incidence of epithelial sloughing during LASIK using the microkeratome as opposed to LASIK with the femtosecond laser. Less stress on a compromised epithelial surface would result in a lower incidence of sloughing.
This would likewise explain why patients with EBMD are at a significantly increased risk for developing complications during LASIK. The proposed mechanism is the mechanical trauma inflicted on the cornea by the sliding motion of the microkeratome causes the already weak corneal epithelium to detach and slough off.
The proposed mechanism also accounts for the correglation between advanced age and increased risk of sloughing. Older patients tend to have thicker corneas and drier eyes. Thickened corneas weaken the integrity of the anchoring fibrils and result in a compromised corneal epithelium.Additionally, some hypothesize thicker corneas are more rigid, and increased rigidity leads to increased appositional force during surgery. Dry eye is thought to compound the frictional force during the procedure.
Epithelial sloughing during LASIK is associated with a number of significant postoperative complications.
Diffuse Lamellar Keratitis
Diffuse lamellar keratitis (DLK), defined as inflammatory cells invading the LASIK interface, has been reported as a significant sequalae of intraoperative epithelial defects. Incidence of DLK in patients who experienced epithelial sloughing is reportedly between 54.5%11 to 91%.
Epithelial ingrowth is a common postoperative complication of epithelial sloughing. Epithelial ingrowth is reported in a 46% to 71% of the eyes that experienced epithelial sloughing during LASIK.
Flap melting is a rare complication LASIK, with an incidence between 0% to 5.7%, but is significantly more frequent in patients who experience epithelial sloughing or defects during LASIK. The incidence of postoperative corneal melting in patients who experienced epithelial sloughing is roughly 30%.
The use of bandage contact lenses for a postoperative interval between five days and two weeks has been shown to reduce adverse outcomes in patients who experience intraoperative epithelial defects, and is considered the appropriate management for epithelial sloughing. There is some evidence to suggest patients with small (< 3mm) or peripheral defects can be managed with a standard postoperative care regimen of topical tobramycin five times daily, Lacrisifi six to eight times daily and watchful waiting. In a small study, patients with minor defects (<3 mm) were all found to have complete re-epithelialization on postoperative day one. In this same study, patients with larger defects (4-5 mm) who were not given bandage contact lenses did not achieve re-epithelialization until postoperative day 4-7; patients who were treated with bandage lenses achieved re-epithelialization of the affected area on postoperative day 1-3.
The use of topical steroid drops has been recommended to reduce the risk of, or limit the intensity of DLK.
In cases of epithelial defects complicated by epithelial ingrowth, conservative management is appropriate if the ingrowth is limited to isolated nests, as these often resolve on their own without sequelae. Ingrowth should be aggressively treated if it is continuous with the surface epithelium, if the sheet is unrelenting, or is causing visual symptoms. To prevent recurrence of ingrowth, the flap can be sutured after the ingrowth has been removed.
Evidence indicates that patients who experience epithelial sloughing during LASIK are more likely to experience undercorrection and lost lines of vision at 3 months when compared to control. However, there is some evidence to suggest that patients who experience very minor (<2 mm) defects or sloughing do not suffer from any long-term visual compromise.
The overall risk of epithelial sloughing in the general population is quite low, however epithelial defects/sloughing remains the most frequently seen complication of LASIK. There are certain patients who are at a significantly increased risk of developing this complication. There are also a number of measures refractive surgeons can take to minimize risk.
Epithelial Basement Membrane Dystrophy
All patients seeking LASIK should be meticulously screened for signs of EBMS. Patients with symptomatic EBMD are not candidates for LASIK. Those who are asymptomatic, but with findings consistent with EBMD can receive LASIK, but surgeons should have a heightened awareness of the potential for complications.
A preoperative eye-drop regimen that avoids the use of topical anesthetic and preserved eye-drops is recommended14. Additionally, the liberal use of preoperative lubricating eye drops (such as Refresh Plus) and the application of a double layer of lubricant just prior to the initiation of the microkeratome pass may further reduce risk.
The femtosecond laser is associated with significantly less incidence of epithelial sloughing versus the microkeratome1. There are other complications associated with the femtosecond laser than should be considered before deciding whether its use is appropriate to minimize the risk of sloughing.
Epithelial sloughing is a relatively rare complication of LASIK, however there are a number of factors that increase the risk of developing this complication. There is a strong and well-established link between EBMD and an increased risk for epithelial sloughing. There is also evidence to indicate age, corneal thickness and ethnicity play a role. There are also a number of surgical interventions that can affect the risk of developing this complication. The sequelae of epithelial sloughing include DLK, epithelial ingrowth and rarely, flap melting. Patients who experience epithelial sloughing/defects during LASIK are more likely to experience undercorrection and lost lines of vision. To prevent these outcomes, patients should be thoroughly examined to rule out EBMD, and care should be taken to assess other risk factors.
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