The incidence of postoperative laser in situ keratomileusis (LASIK) infections are uncommon, with estimates ranging from 0% to 1.5%.1–4 Infections occurring within 10 days of surgery tend to be caused by gram-positive bacteria, whereas those occurring after 10 days tend to be caused by atypical mycobacteria and fungi.2 Here we report a rare case of mixed Acanthamoeba and staphylococcal keratitis, after femtosecond laser–assisted LASIK.
Patient Consent Statement
Written consent was obtained from the patient to publish the details of the case.
A 25-year-old woman underwent uneventful bilateral femtosecond LASIK for myopia (−7.50DS/ −0.50DC x 180 in the right eye and −7.75DS/ −2.00DC x 170 in the left eye; with an optical zone of 6.5 mm, flap diameter of 8.5 mm, and flap thickness of 110 μm in both eyes; and with residual stromal thickness of 327 μm in the right eye and 314 μm in the left eye). She presented with a painless decrease in vision in the right eye, at 30 months after LASIK.
At presentation, in the right eye, the uncorrected distance visual acuity was 20/32, and slitlamp examination revealed (Figure 1) stromal opacification (size 3.43 × 1.69 mm, with the RTVue optical coherence tomography [OptoVue Inc., v. 2018.0.0.18]) just inside the LASIK flap edge (Figure 2). The flap anterior to the opacification appeared relatively normal. Optical coherence tomography imaging (Figure 3) confirmed that the area of opacification was isolated and beneath the epithelium and Bowman layer, with the opacification discontinuous with the flap edge. The posterior stroma was transparent and appeared relatively normal. Confocal microscopy (Figure 4) demonstrated enlarged corneal epithelial cells, a decreased number of corneal nerves in the subepithelial layer, increased reflection within the basal epithelial layer, and an abnormal morphology in the stromal layer at the region of opacification. Distal to the area of opacification, the morphology of stromal and endothelial cells was normal. No Acanthamoeba cysts were observed.
Initially, the flap was lifted and the opacified area scraped, followed by the instillation of povidone–iodine 5% eyedrops (Shanghai Likang Disinfectant Hi-Tech Co, Ltd.). The sample was sent to the microbiology department for microscopic, culture, and sensitivity. After the flap lift and scraping, a bandage contact lens was placed (AcuVue Oasys, Johnson & Johnson, Inc.). The patient was reviewed the following day and the bandage contact lens exchanged. At day 2, the bandage contact lens was removed.
Giemsa staining demonstrated 2 Acanthamoeba cysts; no encysted amoebas were found (Figure 5). Microscopic examination demonstrated gram-positive cocci and pyogenic cells (Figure 6). Culture on nonnutrient agar with a lawn of Escherichia coli identified gram-positive Staphylococcus aureus that was sensitive to levofloxacin, rifampicin, chloramphenicol, cefoxitin, fusidic acid, and moxifloxacin. Culture on the nonnutrient agar with a lawn of E coli was negative for Acanthamoeba.
After the flap lift and scraping, topical therapy was commenced with fluconazole 0.3% (Shenyang Xingqi Pharmaceutical Co., Ltd.) eyedrops 6 times daily, levofloxacin 0.5% (Alcon Laboratories, Inc.) eyedrops twice daily, and fusidic acid 1% (Fucithalmic Eye Drops, LEO Laboratories Ltd.) eyedrops twice daily in the right eye. After 2 days, the patient complained of severe pain and redness in the right eye. Corneal stromal edema, conjunctival vessel congestion, and chemosis were observed (Figure 7). A course of topical prednisolone acetate eyedrops 1% (Allergan, Inc.) was commenced in the right eye (4 times daily for 1 week, 3 times daily for 1 week, twice daily for 1 week, and once daily for 1 week).
After observing the signs of resolving corneal edema (Figure 8) at 1 month, the topical 1% prednisolone acetate eyedrops were stopped; however, eyedrops of 0.1% fluorometholone (Alcon Laboratories, Inc.) were commenced twice daily for 2 months, then once daily for 1 month to the right eye. In addition, fluconazole was reduced to twice daily and continued for 3 months, and fusidic acid was reduced to once daily for a further 3 months. The levofloxacin was stopped at this 1-month point.
At 1.5 months, the active keratitis settled, leading to a scar with the corneal thickness measuring 524 μm over the scarred area and an uncorrected visual acuity of 20/25 (Figure 9). Mild refractive regression (−0.75DS/−0.5DC x 90) was also observed at this point (1.5 months after flap lift and scraping), which remained stable for further 6 months. Confocal microscopy examination at 1 month and 4 months showed no cysts (Figure 10). At 4 months (after flap lift and scraping), the patient developed mild epithelial ingrowth, as shown in Figures 11 and 12. This was observed closely for 3 further months during which time the uncorrected distance visual acuity (20/25) was unaffected and the epithelial ingrowth remained stable.
This case emphasized the importance of a precise microbiological diagnosis and the need for long-term treatment. Similarly, timely tapering of medications to avoid toxicity and judicious use of topical steroids, especially in confirmed cases involving Acanthamoeba, are also of utmost importance.
The reason for lifting the flap in this patient was to remove thick white mass for subsequent microbiological investigation and to permit the application of povidone–iodine solution. Reassuringly, the visual acuity improved albeit with a mild refractive regression after this procedure. The absence of pain may be attributable to nerve damage after femtosecond laser–assisted LASIK and/or infection localized to the interface layer without involvement of the corneal epithelium. Our case is significantly different from previously reported cases of Acanthamoeba keratitis post-LASIK.5,6 Acanthamoeba cysts were found in the interface layer, with this interface infection presenting a much milder disease process than that typically encountered with Acanthamoeba. This may be due to the lower toxicity of cysts and oxygen deficiency in the interface layer, which was also close to the flap edge. In our case, the active lesions settled at 1 month with a total treatment duration of 4 months. The epithelial ingrowth that was observed at 4 months after the flap lift was mild and has remained stable for a further 3 months.
The treatment used in our case was also very different than that typically used for Acanthamoeba keratitis, namely biguanides and diamidines.7 This was partly due to the low suspicion for Acanthamoeba keratitis and rapid response observed with the treatment initiation. Biguanides and diamidines are toxic agents and are associated with cataract, iris atrophy, and peripheral ulcerative keratitis.7
Although visual acuity improved in this case, the atypical symptoms were most challenging to make a diagnosis and treatment plan. A high index of suspicion of an infectious etiology should be considered in any patient presenting with a similar clinical picture to this case. Both medical and surgical management were key to allow direct sampling of the subflap opacification to permit the microbiological diagnosis.
WHAT WAS KNOWN
- Acanthamoeba species infection after femtosecond laser–assisted LASIK is rare. When it occurs, it often diffusely involves the epithelium and stroma layer and is usually associated with pain.
WHAT THIS PAPER ADDS
- Microbiology samples with flap lift can be invaluable when facing an atypical presentation of infectious keratitis, particularly in the absence of pain.
- The combination of confocal microscopy and optical coherence tomography may be helpful in cases of suspected infectious keratitis post-LASIK.
Professor Changning Zhang for sharing his clinical case and for his guidance through each stage of the process.
1. Chang MA, Jain S, Azar DT. Infections following laser in situ keratomileusis: an integration of the published literature.
Surv Ophthalmol 2004;49:269–280
2. Solomon R, Donnenfeld ED, Azar DT, Holland EJ, Palmon FR, Rubenstein JB Infectious keratitis after laser in situ keratomileusis: results of an ASCRS survey.
J Cataract Refract Surg 2003;29:2001–2006
3. Donnenfeld ED, Kim T, Holland EJ, Azar DT, Palmon FR, Rubenstein JB, Daya S, Yoo SH. ASCRS White Paper: management of infectious keratitis following laser in situ keratomileusis.
J Cataract Refract Surg 2005.31:2008–2011
4. Moshirfar M, Welling JD, Feiz V, Holz H, Clinch TH. Infectious and noninfectious keratitis after laser in situ keratomileusis occurrence, management, and visual outcomes.
J Cataract Refract Surg 2007;33:474–483
5. Annapurna NV, Bagga B, Garg P, Joseph J, Sharma S, Kalra P, Mittal R. Management of severe Acanthamoeba keratitis and complicated cataract following laser in situ keratomileusis.
Indian J Ophthalmol 2020;68:515–516
6. Chhadva P, Cabot F, Galor A, Karp CL, Yoo SH. Long-term outcomes of flap amputation after LASIK.
J Refract Surg 2016;32:136–137
7. Dart JK, Saw VP, Kilvington S. Acanthamoeba keratitis: diagnosis and treatment. Update 2009. Am J Ophthalmol 2009;148:487–499.e2