Diffuse lamellar keratitis
The presentation of diffuse lamellar keratitis (DLK) (Fig 6-12) can range from asymptomatic interface haze near the edge of the flap to marked diffuse haze under the center of the flap with decreased BCVA. The condition represents a nonspecific sterile inflammatory response to a variety of mechanical and toxic insults. The interface under the flap is a potential space; any cause of anterior stromal inflammation may trigger the accumulation of white blood cells therein. DLK has been reported in association with epithelial defects that occur during primary LASIK or during enhancement, or even months after the LASIK procedure from corneal abrasions or infectious keratitis. Other reported inciting factors include foreign material on the surface of the microkeratome blade or motor, trapped meibomian gland secretions, povidone-iodine solution (from the preoperative skin preparation), marking ink, substances produced by laser ablation, contamination of the sterilizer with gram-negative endotoxin, and red blood cells in the interface. The inflammation generally resolves with topical corticosteroid treatment alone without sequelae, but severe cases can lead to scarring or flap melting; therefore, early detection and management is important.
Figure 6-12 Diffuse lamellar keratitis (DLK). A, High magnification image of stage 2 DLK. Note accumulation of inflammatory cells in the fine ridges created by the oscillating microkeratome blade. B, Stage 3 DLK showing dense accumulation of inflammatory cells centrally. C, Stage 4 DLK with central scar and folds.
(Parts A and B courtesy of Roger F. Steinert, MD; part C courtesy of Jayne S. Weiss, MD.)
Table 6-2 Staging of Diffuse Lamellar Keratitis
DLK is typically classified by the stages described in Table 6-2. Although stages 1 and 2 usually respond to frequent topical corticosteroid application, stages 3 and 4 usually require lifting the flap and irrigating, followed by intensive topical corticosteroid treatment. Oral corticosteroids may be used adjunctively in severe cases. Some surgeons use topical and systemic corticosteroids in stage 3 DLK instead of, or in addition to, lifting the flap. Recovery of vision in DLK is usually excellent if the condition is detected and treated promptly.
A surgeon should have a low threshold for lifting or irrigating underneath the flap in suspected cases of severe DLK. Lifting the flap allows removal of inflammatory mediators from the interface and direct placement of corticosteroids and NSAIDs to suppress inflammation and necrosis. If there is any suspicion that the inflammation is due to infection, lifting the flap and obtaining samples for corneal cultures of the interface should be considered. Topical antibiotics can also be placed in the flap interface at the same time. In cases of suspected DLK not responsive to corticosteroids within 7–10 days of initiation, the diagnosis should be reconsidered, as infectious keratitis or pressure-induced stromal keratopathy (PISK, discussed later) can mimic DLK and require corticosteroid cessation.
Haft P, Yoo SH, Kymionis GD, Ide T, O’Brien TP, Culbertson WW. Complications of LASIK flaps made by the IntraLase 15- and 30-kHz femtosecond lasers. J Refract Surg. 2009; 25(11):979–984.
Holland SP, Mathias RG, Morck DW, Chiu J, Slade SG. Diffuse lamellar keratitis related to endotoxins released from sterilizer reservoir biofilms. Ophthalmology. 2000;107(7): 1227–1233.
Randleman JB, Shah RD. LASIK interface complications: etiology, management, and outcomes. J Refract Surg. 2012;28(8):575–586.
LASIK infectious keratitis
It is important to differentiate sterile interface inflammation from potentially devastating infectious inflammation. Increased pain and decreased vision are the primary indicators of infection. However, postoperative discomfort is common, so it is difficult for patients to distinguish between normal and abnormal eye pain. Moreover, because corneal nerves are severed during flap creation, corneal sensation may be reduced, along with the subjective symptom of pain that usually accompanies infection. Infection after LASIK is usually associated with redness, photophobia, and decreased vision. Several distinct features can help distinguish between DLK and infectious keratitis (Table 6-3). DLK is usually visible with slit lamp biomicroscopy within 24 hours of surgery and typically begins at the periphery of the flap. There is usually a gradient of inflammation, with the inflammation being most intense at the periphery and diminishing toward the center of the cornea. In general, the inflammatory reaction in DLK is diffusely distributed but localized and confined to the area of the flap interface; it does not extend far beyond the edge of the flap (Fig 6-13). In contrast, post-LASIK infectious keratitis usually begins 2 or 3 days after surgery and involves a more focal inflammatory reaction that is not confined to the lamellar interface. An anterior chamber reaction may further help differentiate between an infectious and a sterile process. The inflammatory reaction can extend up into the flap, deeper into the stromal bed, and even beyond the confines of the flap.
Infection within the interface can lead to flap melting, severe irregular astigmatism, and corneal scarring that may require corneal transplantation. If infection is suspected, the flap should be lifted and the interface cultured and irrigated with antibiotics. The most common infections are from gram-positive organisms, followed in frequency by those caused by atypical mycobacteria. Mycobacterial infection can be diagnosed more rapidly by using acid-fast and fluorochrome stains rather than by waiting for culture results (see Fig 6-5).
Table 6-3 Diffuse Lamellar Keratitis vs Infectious Keratitis After LASIK
Figure 6-13 DLK is differentiated from infectious keratitis by the confinement of the infiltrate to the interface alone in DLK.
(Reproduced with permission from Culbertson WW. Surface ablation and LASIK patients share similar infection potential. Refractive Eyecare. September 2006:12.)
In general, the timing of the onset of symptoms provides a clue as to the etiology of the infection. Infections occurring within 10 days of surgery are typically bacterial, with the preponderance being from gram-positive organisms (see BCSC Section 8, External Disease and Cornea). If the infection does not respond to treatment, amputation of the flap may be necessary to improve antimicrobial penetration. The fourth-generation fluoroquinolones gatifloxacin and moxifloxacin have excellent efficacy against the more common bacteria that cause post-LASIK infections, including some atypical mycobacteria; however, monotherapy with these drugs may not be sufficient. A LASIK flap infection may occur after a recurrent erosion (see Fig 6-6).
Freitas D, Alvarenga L, Sampaio J, et al. An outbreak of Mycobacterium chelonae infection after LASIK. Ophthalmology. 2003;110(2):276–285.
Llovet F, de Rojas V, Interlandi E, Martín C, Cobo-Soriano R, Ortega-Usobiaga J, Baviera J. Infectious keratitis in 204,586 LASIK procedures. Ophthalmology. 2010;117(2):232–238.
Moshirfar M, Welling JD, Feiz V, Holz H, Clinch TE. Infectious and noninfectious keratitis after laser in situ keratomileusis: occurrence, management, and visual outcomes. J Cataract Refract Surg. 2007;33(3):474–483.
Pressure-induced stromal keratopathy
A diffuse stromal and interface opacity termed pressure-induced stromal keratopathy (PISK) has been reported as a result of elevated IOP; it can be mistaken for DLK and is sometimes associated with a visible fluid cleft in the interface (Fig 6-14). The surgeon must be aware of this rare condition in order to properly diagnose and treat it. The pressure-induced haze from PISK is associated with prolonged corticosteroid treatment and usually presents after 10 days to 2 weeks. Key differentiators between DLK and PISK are that with DLK, the onset is earlier and the IOP is not elevated. IOP should be measured both centrally and peripherally in suspected cases, possibly with a pneumotonometer or Tono-Pen (Reichert Technologies, Depew, NY), because applanation pressure may be falsely lowered centrally in PISK by fluid accumulation in the lamellar interface. Several alternative techniques of measuring IOP have been suggested, but dynamic contour tonometry is the only technique shown to have sufficient reproducible accuracy in eyes that have undergone refractive ablation. Treatment of PISK involves rapid cessation of corticosteroid drops and the use of glaucoma medications to lower IOP. Severe glaucomatous vision loss has been reported in cases with delayed diagnosis.
Belin MW, Hannush SB, Yau CW, Schultze RL. Elevated intraocular pressure–induced interlamellar stromal keratitis. Ophthalmology. 2002;109(10):1929–1933.
Dawson DG, Schmack I, Holley GP, Waring GO III, Grossniklaus HE, Edelhauser HF. Interface fluid syndrome in human eye bank corneas after LASIK: causes and pathogenesis. Ophthalmology. 2007;114(10):1848–1859.
Hamilton DR, Manche EE, Rich LF, Maloney RK. Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid. Ophthalmology. 2002;109(4):659–665.
Moya Calleja T, Iribarne Ferrer Y, Sanz Jorge A, Sedó Fernandez S. Steroid-induced interface fluid syndrome after LASIK. J Refract Surg. 2009;25(2):235–239.
Figure 6-14 Pressure-induced stromal keratopathy (PISK) after LASIK. A, An optically clear, fluid-filled space between the flap and stromal bed. This condition is hypothesized to be caused by transudation of fluid across the endothelium as a result of corticosteroid-induced elevation of intraocular pressure (IOP). B, PISK without interface gap. A diffuse stromal and interface opacity without an interface fluid cleft can also result from elevated IOP with prolonged corticosteroid use (left panel). Close-up (right panel, arrows) further demonstrates the opacification of the stroma and interface.
(Part A reproduced with permission from Hamilton DR, Manche EE, Rich LF, Maloney RK. Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid. Ophthalmology. 2002;109(4):659–665; part B reprinted with permission from Randleman JB, Shah RD. Lasik interface complications: etiology, management, and outcomes. J Refract Surg. 2012;28(8):575–586.)
Epithelial ingrowth occurs in less than 3% of eyes (Fig 6-15). There is no need to treat isolated nests of epithelial cells in the peripheral lamellar interface that are not advancing and are not affecting vision. However, if the epithelium is advancing toward the visual axis, is associated with decreased vision from irregular astigmatism (Fig 6-16), or triggers overlying flap melting, it should be removed by lifting the flap, scraping the epithelium from both the underside of the flap and the stromal bed, and then repositioning the flap. After scraping the under-flap surface and stromal bed, some surgeons also remove epithelium from both the periphery of the flap and the bed to allow for flap adherence before the epithelial edge advances to the flap edge. Recurrent epithelial ingrowth can be treated with repeated lifting and scraping, with or without flap suturing or using fibrin glue at the flap edge. Some surgeons treat the undersurface of the flap with absolute alcohol to identify and treat any residual epithelium. Nd:YAG laser has also been described to treat early epithelial ingrowth.
Figure 6-15 Epithelial ingrowth in the interface under a LASIK flap. A, Peripheral ingrowth of 1–2 mm (arrows) is common and inconsequential and does not require intervention unless it induces melting of the overlying flap. B, Central nests of epithelial cells (arrow) disrupt the patient’s vision by elevating and distorting the flap. The flap must be lifted and the epithelium debrided. C, Inspection of the midperiphery shows the track followed by the invading epithelium from the periphery toward the center (arrows).
(Courtesy of Roger F. Steinert, MD.)
A, Epithelial ingrowth in visual axis. B, Corresponding topographic steepening and irregularity.
(Courtesy of J. Bradley Randleman, MD.)
The incidence of epithelial ingrowth is greater in eyes that develop an epithelial defect at the time of the procedure, undergo a re-treatment with lifting of a preexisting flap, or have traumatic flap dehiscence. In such cases, special care should be taken to ensure that no epithelium is caught under the edge of the flap when it is repositioned. Placement of a bandage contact lens at the conclusion of the procedure may also decrease the incidence of epithelial ingrowth for patients at higher risk of developing this complication.
Ayala MJ, Alió JL, Mulet ME, De La Hoz F. Treatment of laser in situ keratomileusis interface epithelial ingrowth with neodymium:yytrium-aluminum-garnet laser. Am J Ophthalmol. 2008;145(4):630–634.
Caster AI, Friess DW, Schwendeman FJ. Incidence of epithelial ingrowth in primary and retreatment laser in situ keratomileusis. J Cataract Refract Surg. 2010;36(1):97–101.
Henry CR, Canto AP, Galor A, Vaddavalli PK, Culbertson WW, Yoo SH. Epithelial ingrowth after LASIK: clinical characteristics, risk factors, and visual outcomes in patients requiring flap lift. J Refract Surg. 2012;28(7):488–492.
Rapuano CJ. Management of epithelial ingrowth after laser in situ keratomileusis in a tertiary care cornea service. Cornea. 2010;29(3):307–313.
Debris in the interface is occasionally observed postoperatively. The principal indication for intervention by flap lifting, irrigation, and manual removal of debris is an inflammatory reaction elicited by the foreign material. Small amounts of lint, nondescript particles, or tiny metal particles from stainless steel surgical instruments are usually well tolerated. A small amount of blood that may have oozed into the interface from transected peripheral vessels may also be tolerated and typically resolves spontaneously with time; however, a significant amount of blood usually elicits an inflammatory cell response and should be irrigated from the interface at the time of the LASIK procedure (Fig 6-17). Use of a topical vasoconstrictor such as epinephrine applied with a fiber-free sponge to facilitate constriction when the flap is being replaced helps minimize this problem. The surgeon should be aware that applying epinephrine prior to laser ablation can result in pupillary dilation, difficulty for the patient to fixate on a fixation light, and thus treatment decentration.
Excerpted from BCSC 2020-2021 series: Section 13 - Refractive Surgery. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.