Journal of Refractive Surgery

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Bilateral Non-tuberculous Mycobacterial Keratitis After Small Incision Lenticule Extraction

Hsin-Yu Liu, MD; Hsiao-Sang Chu, MD, MS; Wei-Li Chen, MD, PhD; Fung-Rong Hu, MD; I-Jong Wang, MD, PhD

Abstract

PURPOSE:

To report a case of bilateral non-tuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE) that was successfully treated with oral and topical fortified antibiotics.

METHODS:

Case report and literature review.

RESULTS:

An otherwise healthy 21-year-old woman presented with culture-proven bilateral Mycobacterium abscessus keratitis 8 days after undergoing SMILE, showing multiple white stromal infiltrates in the interface in both eyes. Progressive, diffuse flap edema followed by pocket abscess, exudation in the anterior chamber, granulation tissue formation in the pocket, intrastromal neovascularization, and eventually partial resolution of corneal opacity were noted after topical and oral antibiotic treatment for 6 months. Her corrected distance visual acuity was 20/32 and 20/50 in the right and left eyes, respectively, 12 months after initial presentation.

CONCLUSIONS:

This is the first report of successful medical management of bilateral non-tuberculous mycobacterial keratitis after SMILE. The manifestations are different from and even more difficult to treat than those of keratitis after LASIK.

[J Refract Surg. 2018;34(9):633–636.]

Abstract

PURPOSE:

To report a case of bilateral non-tuberculous mycobacterial keratitis after small incision lenticule extraction (SMILE) that was successfully treated with oral and topical fortified antibiotics.

METHODS:

Case report and literature review.

RESULTS:

An otherwise healthy 21-year-old woman presented with culture-proven bilateral Mycobacterium abscessus keratitis 8 days after undergoing SMILE, showing multiple white stromal infiltrates in the interface in both eyes. Progressive, diffuse flap edema followed by pocket abscess, exudation in the anterior chamber, granulation tissue formation in the pocket, intrastromal neovascularization, and eventually partial resolution of corneal opacity were noted after topical and oral antibiotic treatment for 6 months. Her corrected distance visual acuity was 20/32 and 20/50 in the right and left eyes, respectively, 12 months after initial presentation.

CONCLUSIONS:

This is the first report of successful medical management of bilateral non-tuberculous mycobacterial keratitis after SMILE. The manifestations are different from and even more difficult to treat than those of keratitis after LASIK.

[J Refract Surg. 2018;34(9):633–636.]

Although the incidence of infectious keratitis after refractive surgery is decreasing, it remains difficult to treat and the prognosis is still poor.1,2 Non-tuberculous mycobacteria remain resistant to treatment. Patients who respond poorly to topical antibiotics sometimes require surgical amputation of the flap or therapeutic keratoplasty.3–5 Small incision lenticule extraction (SMILE) has recently become popular because of its biomechanical advantage over LASIK.6,7 SMILE corrects refractive errors by removing an intrastromal lenticule through a small peripheral incision without creating a flap,8 leaving a pocket in the corneal stroma. Consequently, infection in the pocket, if it occurs, may cause suboptimal penetration of topical or systemic antibiotic treatment.

The only two reports describing infectious keratitis after SMILE with microorganisms identified were caused by Streptococcus pneumonia and Staphylococcus.9,10 Reports on non-tuberculous mycobacterial keratitis after SMILE and its management remain relatively scant compared with keratitis after LASIK. To our knowledge, we describe the first case of bilateral Mycobacterium abscessus keratitis after SMILE and its successful management with topical and systemic antibiotics.

Case Report

A 21-year-old woman who was otherwise healthy underwent bilateral SMILE at a private eye clinic for myopia of −6.25 and −7.00 diopters in the right and left eyes, respectively. She was given topical 0.5% levofloxacin (Cravit 0.5%; Santen Pharmaceutical Co., Ltd., Osaka, Japan) and 1% prednisolone acetate (Pred Forte; Allergan, Inc., Irvine, CA) every 6 hours. The corrected distance visual acuity (CDVA) was 20/20 in both eyes on postoperative day 1. She reported bilateral discomfort 8 days postoperatively and the frequency of topical antibiotic was increased to every 4 hours, along with interface irrigation of moxifloxacin 0.5% ophthalmic solution (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX) on two separate occasions in both eyes. She was referred to our hospital due to a lack of improvement at 2 weeks after SMILE.

On presentation in our clinic, her CDVA was 20/32 and 20/132 in the right and left eyes, respectively. Slit-lamp examination revealed multiple white infiltrates at the paracentral area and within the corneal incision in the right eye (Figure 1A). The left eye showed an infiltrate with a feathery border at the mid-periphery and an overlying epithelial defect (Figure 2A). Anterior segment optical coherence tomography (AS-OCT) (Visante OCT; Carl Zeiss Meditec, Dublin, CA) identified hyperreflectivity in the anterior stromal caps corresponding to the infiltrates in both eyes (Figures 1A and 2A).

Images of the right eye acquired at different time points during follow-up. (A) Initial presentation after interface irrigation (left) and anterior segment optical coherence tomography (AS-OCT) showing hyperreflectivity in the anterior stromal cap (right). (B) After 1 month of treatment, decreased infiltration with opacity (right) and the corresponding AS-OCT image. (C) After 6 weeks of treatment, worsening of previous interface infiltrates with overlying epithelial defects (left) and stronger anterior chamber reaction with endothelial plaques (right). (D) After 2 months of treatment, persistent infiltrations and corneal edema (left) with the corresponding AS-OCT image (right). (E) After 3 months of treatment, neovascularization ingrowth into the previous infiltration site with intrastromal bleeding (left) and corneal edema on AS-OCT (right). (F) After 6 months of treatment, corneal opacity with ghost vessels (left) and resolution of corneal edema on AS-OCT (left). (G) Regression of corneal opacity at 12 months after initial presentation.

Figure 1.

Images of the right eye acquired at different time points during follow-up. (A) Initial presentation after interface irrigation (left) and anterior segment optical coherence tomography (AS-OCT) showing hyperreflectivity in the anterior stromal cap (right). (B) After 1 month of treatment, decreased infiltration with opacity (right) and the corresponding AS-OCT image. (C) After 6 weeks of treatment, worsening of previous interface infiltrates with overlying epithelial defects (left) and stronger anterior chamber reaction with endothelial plaques (right). (D) After 2 months of treatment, persistent infiltrations and corneal edema (left) with the corresponding AS-OCT image (right). (E) After 3 months of treatment, neovascularization ingrowth into the previous infiltration site with intrastromal bleeding (left) and corneal edema on AS-OCT (right). (F) After 6 months of treatment, corneal opacity with ghost vessels (left) and resolution of corneal edema on AS-OCT (left). (G) Regression of corneal opacity at 12 months after initial presentation.

Images of the left eye acquired at different time points during follow-up. (A) Initial presentation after interface irrigation (left) and anterior segment optical coherence tomography (AS-OCT) showing hyperreflectivity in the anterior stromal cap (right). (B) After 1 month of treatment, increased pocket abscess with edema (left) and corresponding AS-OCT image (right). (C) After 6-week treatment, enlarging infiltrates (left) and stronger anterior chamber reaction with endothelial plaques (right). (D) After 2 months of treatment, persistent infiltrations and corneal edema (left) with the corresponding AS-OCT image (right). (E) After 3 months of treatment, neovascularization ingrowth into the previous infiltration site with intrastromal bleeding (left) and corneal edema on AS-OCT (right). (F) After 6 months of treatment, corneal opacity with ghost vessels (left) and resolution of corneal edema on AS-OCT (right). (G) Regression of corneal opacity at 12 months after initial presentation.

Figure 2.

Images of the left eye acquired at different time points during follow-up. (A) Initial presentation after interface irrigation (left) and anterior segment optical coherence tomography (AS-OCT) showing hyperreflectivity in the anterior stromal cap (right). (B) After 1 month of treatment, increased pocket abscess with edema (left) and corresponding AS-OCT image (right). (C) After 6-week treatment, enlarging infiltrates (left) and stronger anterior chamber reaction with endothelial plaques (right). (D) After 2 months of treatment, persistent infiltrations and corneal edema (left) with the corresponding AS-OCT image (right). (E) After 3 months of treatment, neovascularization ingrowth into the previous infiltration site with intrastromal bleeding (left) and corneal edema on AS-OCT (right). (F) After 6 months of treatment, corneal opacity with ghost vessels (left) and resolution of corneal edema on AS-OCT (right). (G) Regression of corneal opacity at 12 months after initial presentation.

The patient was administered fortified cefazolin 33 mg/mL and fortified gentamicin 15 mg/mL hourly. Acid-fast bacilli were identified in the right eye 5 days after referral; thus, the antibiotic regimen was changed to topical fortified imipenem 5 mg/mL, fortified amikacin 15 mg/mL, and moxifloxacin 0.5% every 2 hours, and oral clarithromycin 1,000 mg daily. After 4 weeks, scraping culture in the left eye revealed M. abscessus. Topical fortified clarithromycin 12.5 mg/mL every 2 hours was added for both eyes. The CDVA decreased to 20/125 in the right eye and counting fingers in the left eye.

The patient was reluctant to undergo stromal cap amputation or interface irrigation. Reduced infiltration in the right eye and persistent infiltration in the left eye were noted after 1 month of treatment (Figures 1B and 2B). However, the right eye developed increased infiltrates and endothelial plaques confirmed by ASOCT, suggesting the extension of a pocket abscess (Figure 1C). Increased infiltrates, flap edema, and localized anterior stromal melting developed in the left eye, whereas AS-OCT showed progression of the previous pocket abscess (Figure 2C). At 2 months, infiltrations and corneal edema increased in both eyes (Figures 1D and 2D). Notably, circumferential neovascularization was observed, being more prominent near the infiltrations in both eyes (Figures 1E and 2E). Episodes of neovascular ingrowth into previous infiltration, intrastromal bleeding, spontaneous resolution, and neovascular attenuation were documented during the following 4 months of the treatment course. The topical and oral antibiotics were gradually tapered according to the clinical presentation.

After 6 months of antibiotic treatment for both eyes, infiltrates gradually resolved with ghost vessels and stromal opacity remaining (Figures 1F and 2F). AS-OCT revealed hyperreflectivity corresponding to the stromal scar (Figures 1F and 2F). At 1 year after initial presentation, CDVA was 20/32 and 20/50 in the right and left eyes, respectively (Figures 1G and 2G).

Discussion

Two large-scale studies have described the incidence of infectious keratitis after SMILE thus far; one reported 5 cases in 1,800 eyes,6 whereas the other observed 1 case in 279 eyes.11 Neither study identified specific pathogens. Only 2 case reports have described infectious keratitis after SMILE with microorganisms identified, both caused by Gram-positive cocci.9,10 Therefore, we cannot compare the treatment of infectious keratitis after SMILE with that reported previously. In recent years, cases of postoperative infectious keratitis have shown a decline in the incidence of non-tuberculous mycobacterial keratitis because of prophylactic use of fourth-generation fluoroquinolone, whereas the incidence of Gram-positive cocci infection is increasing.12 Potential pathogens for infectious keratitis after SMILE and LASIK may be similar because both share similar procedures in preoperative preparations and sterilization of surgical instruments. Our patient demonstrated similar intervals of symptom onset with the two aforementioned case reports on keratitis after SMILE, but culture yielded M. abscessus, a late-onset pathogen. This can be partially explained by the flapless SMILE, limiting the penetration of prophylactic antibiotics and enabling faster growth of pathogens. In addition, the lenticular extraction of SMILE requires longer intrastromal manipulation time than femtosecond laser–assisted LASIK, resulting in an increased risk of intrastromal seeding of microbes. Moreover, no irrigation is applied after lenticular extraction in SMILE, which may further increase the risk of infectious keratitis.

Eyes suspected of having infectious keratitis are recommended to undergo flap lifting for culture and irrigation of the interface and the underlying stroma with antibiotics.13 Except in the case of treatment resistance or flap necrosis, topical antibiotics are the mainstay of treatment. Despite intensive treatment, non-tuberculous mycobacterial keratitis remains a clinical challenge due to resistance or slow response to antibiotics. Furthermore, surface toxicity and patient discomfort may interrupt the prolonged treatment with a combination of topical or oral antibiotics.14–16 The clinical courses of our patient's two eyes were different: the left eye had persistent infiltrates that improved after 5 months of intensive antibiotics and neovascular ingrowth, and the right eye appeared to respond well after 1 month of treatment but recurred at week 6 to show a clinical manifestation similar to that of the left eye. Unlike a lifted flap, dead space exists in the pocket, which may limit effective contact with antibiotics and impede draining of irrigation fluid. Moreover, one-time irrigation and short-term topical antibiotic therapy may be insufficient because mycobacteria are highly invasive and can penetrate the cornea, producing rough colonies resistant to antibiotics.17 Healing of epithelial defects may further hinder the penetration of topical antibiotics, potentially promoting recurrence.

Because our patient refused to receive further surgical intervention, it is not clear whether stromal cap amputation might have helped. Among cases of nontuberculous mycobacterial keratitis after LASIK, a substantial proportion treated with oral clarithromycin still requires flap lifting, removal, or even therapeutic lamellar keratolasty.18–20 The successful outcome in our case without stromal amputation or therapeutic keratoplasty may be attributed to the combination of a prolonged course of topical and oral antibiotics plus corneal neovascularization, which may facilitate the immune system to completely eradicate the infection. Despite the initial scarring, we observed gradual regression of neovascularization and scar remodeling coincided with visual improvement. Corneal cross-linking (CXL) was recently shown to be effective for early-stage bacterial keratitis and is considered an alternative to antibiotics (Table A, available in the online version of this article).21,22 Chan et al.10 reported a promising outcome of Staphylococcus keratitis after SMILE treated with CXL. However, the application of CXL in non-tuberculous mycobacterial infections requires further investigation.

Current and Previous Studies of Infectious Keratitis After SMILE

Table A:

Current and Previous Studies of Infectious Keratitis After SMILE

To our knowledge, this is the first reported case of non-tuberculous mycobacterial infection after SMILE that was treated successfully without lamellar keratoplasty. Non-tuberculous mycobacteria should be considered as a possible causative agent for infectious keratitis after SMILE with similar, but not identical, clinical onset compared with cases after LASIK. Our case emphasizes the importance of a proper combination and duration of oral and topical antibiotics in the management of non-tuberculous mycobacterial infection after SMILE.

References

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  2. Gritz DC. LASIK interface keratitis: epidemiology, diagnosis and care. Curr Opin Ophthalmol. 2011;22:251–255. doi:10.1097/ICU.0b013e3283477b52 [CrossRef]
  3. Hamam RN, Noureddin B, Salti HI, Haddad Khoury JM. Recalcitrant post-LASIK Mycobacterium chelonae keratitis eradicated after the use of fourth-generation fluoroquinolone. Ophthalmology. 2006;113:950–954. doi:10.1016/j.ophtha.2006.02.028 [CrossRef]
  4. de la Cruz J, Pineda R 2nd, . LASIK-associated atypical mycobacteria keratitis: a case report and review of the literature. Int Ophthalmol Clin. 2007;47:73–84. doi:10.1097/IIO.0b013e318037751b [CrossRef]
  5. Susiyanti M, Mehta JS, Tan DT. Bilateral deep anterior lamellar keratoplasty for the management of bilateral post-LASIK mycobacterial keratitis. J Cataract Refract Surg. 2007;33:1641–1643. doi:10.1016/j.jcrs.2007.04.036 [CrossRef]
  6. Ivarsen A, Asp S, Hjortdal J. Safety and complications of more than 1500 small-incision lenticule extraction procedures. Ophthalmology. 2014;121:822–828. doi:10.1016/j.ophtha.2013.11.006 [CrossRef]
  7. Yang E, Roberts CJ, Mehta JS. A review of corneal biomechanics after LASIK and SMILE and the current methods of corneal biomechanical analysis. J Clin Exp Ophthalmol. 2015;6:507–12. doi:10.4172/2155-9570.1000507 [CrossRef]
  8. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95:335–339. doi:10.1136/bjo.2009.174284 [CrossRef]
  9. Chehaibou I, Sandali O, Ameline B, Bouheraoua N, Borderie V, Laroche L. Bilateral infectious keratitis after small-incision lenticule extraction. J Cataract Refract Surg. 2016;42:626–630. doi:10.1016/j.jcrs.2016.03.024 [CrossRef]
  10. Chan TC, Chow VW, Jhanji V. Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for bacterial keratitis after small incision lenticule extraction (SMILE). J Refract Surg. 2017;33:278–280. doi:10.3928/1081597X-20170126-01 [CrossRef]
  11. Vestergaard A, Ivarsen AR, Asp S, Hjortdal JO. Small-incision lenticule extraction for moderate to high myopia: predictability, safety, and patient satisfaction. J Cataract Refract Surg. 2012;38:2003–2010. doi:10.1016/j.jcrs.2012.07.021 [CrossRef]
  12. Randleman JB, Shah RD. LASIK interface complications: etiology, management, and outcomes. J Refract Surg. 2012;28:575–586. doi:10.3928/1081597X-20120722-01 [CrossRef]
  13. Donnenfeld ED, Kim T, Holland EJ, et al. ASCRS white paper: management of infectious keratitis following laser in situ keratomileusis. J Cataract Refract Surg. 2005;31:2008–2011. doi:10.1016/j.jcrs.2005.10.030 [CrossRef]
  14. Daines BS, Vroman DT, Sandoval HP, Steed LL, Solomon KD. Rapid diagnosis and treatment of mycobacterial keratitis after laser in situ keratomileusis. J Cataract Refract Surg. 2003;29:1014–1018. doi:10.1016/S0886-3350(02)01613-9 [CrossRef]
  15. Pacheco PA, Tam PM. Oral moxifloxacin and topical amikacin for Mycobacterium abscessus keratitis after laser in situ keratomileusis. J Cataract Refract Surg. 2010;36:843–846. doi:10.1016/j.jcrs.2009.10.054 [CrossRef]
  16. Ford JG, Huang AJ, Pflugfelder SC, Alfonso EC, Forster RK, Miller D. Nontuberculous mycobacterial keratitis in south Florida. Ophthalmology. 1998;105:1652–1658. doi:10.1016/S0161-6420(98)99034-0 [CrossRef]
  17. Greendyke R, Byrd TF. Differential antibiotic susceptibility of Mycobacterium abscessus variants in biofilms and macrophages compared to that of planktonic bacteria. Antimicrob Agents Chemother. 2008;52:2019–2026. doi:10.1128/AAC.00986-07 [CrossRef]
  18. Kamiya K, Kasahara M, Shimizu K. A case of intractable infectious keratitis and subsequent flap necrosis after laser in situ keratomileusis. Clin Ophthalmol. 2009;3:523–525. doi:10.2147/OPTH.S6576 [CrossRef]
  19. Moshirfar M, Meyer JJ, Espandar L. Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis. J Cataract Refract Surg. 2007;33:1978–1981. doi:10.1016/j.jcrs.2007.07.019 [CrossRef]
  20. Chung SH, Roh MI, Park MS, Kong YT, Lee HK, Kim EK. Mycobacterium abscessus keratitis after LASIK with IntraLase femtosecond laser. Ophthalmologica. 2006;220:277–280. doi:10.1159/000093084 [CrossRef]
  21. Makdoumi K, Mortensen J, Sorkhabi O, Malmvall BE, Crafoord S. UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study. Graefes Arch Clin Exp Ophthalmol. 2012;250:95–102. doi:10.1007/s00417-011-1754-1 [CrossRef]
  22. Tabibian D, Richoz O, Hafezi F. PACK-CXL: corneal cross-linking for treatment of infectious keratitis. J Ophthalmic Vis Res. 2015;10:77–80. doi:10.4103/2008-322X.156122 [CrossRef]

Current and Previous Studies of Infectious Keratitis After SMILE

StudyNo. of CasesOnsetLocationOrganismManagementTime to ResolutionPresenting VAFinal VA
Current study2 eyes in 1 case8 daysOD: multiple in paracentral interface and within the corneal cap opening incision; OS: along the temporal edge of interfaceMycobacterium abscessusFortified topical antibiotics with imipenem, amikacin, moxifloxacin and clarithromycin; oral clarithromycin and interface irrigation with moxifloxacin4 monthsOD: 20/32; OS: 20/132OD: 20/32; OS: 20/50
Ivarsen et al., 201465 eyes in 1,800 eyesWithin 7 daysInterfaceNot identifiedTopical antibiotics with chloramphenicol and moxifloxacin in 5 eyes, interface irrigation with cefuroxime in 1 eyeWithin 3 monthsNANA
Vestergaard et al., 2012111 in 279 eyes7 daysNANot identifiedTopical antibiotics with chloramphenicol and moxifloxacin and interface irrigation with cefuroximeNANANA
Chehaibou et al., 201692 eyes in 1case2 daysOD: multiple in central and paracentral interface; OS: multiple along the temporal edge of interface and within the corneal cap opening incisionStreptococcus pneumoniaeFortified topical antibiotics with ticarcillin, gentamicin and vancomycin; interface irrigation with povidone–iodine and vancomycin3 monthsOD: CF 50 cm; OS HMOD: 20/32; OS 20/25
Chan et al., 2017101 eye in 1 case5 daysOD: paracentral interface and anterior capStaphylococcus haemolyticus and warneriFortified topical antibiotics with vancomycin and corneal cross-linking with photoactivated riboflavin2 weeks20/5020/20
Authors

From the Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China (H-YL, H-SC, W-LC, F-RH, I-JW); and Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung, Taiwan, Republic of China (I-JW).

The authors have no financial or proprietary interest in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (H-SC, W-LC, F-RH, I-JW); data collection (H-YL, I-JW); analysis and interpretation of data (H-YL, I-JW); writing the manuscript (H-YL, I-JW); critical revision of the manuscript (H-YL, H-SC, W-LC, F-RH, I-JW); administrative, technical, or material support (I-JW); supervision (I-JW)

The authors thank the Department of Medical Research at National Taiwan University Hospital for constructive criticism of the manuscript.

Correspondence: I-Jong Wang, MD, PhD, Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan, Republic of China. E-mail: ijong@ms8.hinet.net

Received: March 16, 2018
Accepted: July 23, 2018

10.3928/1081597X-20180827-01

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