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Nocardiakeratitis after laser in situ keratomileusis: Clinicopathologic correlation

Patel, Nisha R. MD; Reidy, James J. MD; Gonzalez-Fernandez, Federico MD, PhD

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Journal of Cataract & Refractive Surgery: October 2005 - Volume 31 - Issue 10 - p 2012-2015
doi: 10.1016/j.jcrs.2005.02.049
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Three weeks after uneventful bilateral laser in situ keratomileusis (LASIK) was performed, Nocardial keratitis developed at the flap interface in 1 eye of the patient. The infection failed to respond to conventional therapy and eventually required therapeutic keratoplasty.


A 53-year-old white woman had uneventful bilateral LASIK. Three weeks postoperatively, the patient began experiencing redness, tearing, photophobia, foreign-body sensation, and decreased vision in the left eye. She was treated with steroids for presumed diffuse lamellar keratitis. The signs and symptoms failed to resolve so the flap was lifted, irrigated with topical ciprofloxacin 0.3% (Ciloxin), and refloated. Signs and symptoms of keratitis persisted, and corneal swabs were submitted for bacterial culture, which demonstrated no growth after 72 hours.

The patient was referred for corneal consultation 3 weeks after the initial symptoms began. The visual acuity in the affected eye was counting fingers at 1 foot. The patient had been placed on cefazolin 5%, ofloxacin (Ocuflox 0.3%), and natamycin (Natacyn 5%) every 2 hours starting 4 days before referral. Slitlamp biomicroscopy revealed diffuse conjunctival injection, a paracentral epithelial defect with underlying stromal melting, and multiple discrete areas of infiltrate with feathery borders (Figure 1). A hypopyon 5% was present as well as diffuse stromal edema.

Figure 1.
Figure 1.:
Left eye showing an intact LASIK flap with a paracentral epithelial defect. Underlying and inferior to the defect is a broader region of stromal melting. Additional scattered satellite lesions with characteristic “feathery borders” can be seen.

The cefazolin 5% and ofloxacin drops were continued every 2 hours. After several days, there was resolution of the hypopyon and reepithelialization of the ulcer. One week later, an epithelial defect recurred with a small hypopyon and discrete crystalline infiltrates. The base of the ulcer was scraped and smears prepared for Giemsa and acid-fast stains. Cultures were prepared including specific media for fungi and mycobacteria. Both Giemsa and acid-fast stains revealed filamentous bacteria. Cultures grew Nocardia asteroides beginning at 5 days. The patient was started on hourly topical amikacin 2.5% for 3 weeks. The ulcer progressed, and therefore the flap was excised. The specimen contained numerous acid-fast, positive filamentous branching rods consistent with Nocardia species.

Over the following 8 weeks, the patient was treated with sulfacetamide 30% drops every 2 hours. The clinical response to therapy was incomplete, and a therapeutic penetrating keratoplasty (PKP) was performed. No organisms were noted at the edge of the incision. Postoperatively, the patient was placed on a combination of topical moxifloxacin 0.3% (Vigamox) 4 times a day and prednisolone 1% acetate twice a day. Two months after the PKP, a recurrence of infection was noted at the graft–host interface. This resolved after 4 weeks of therapy with moxifloxacin administered twice hourly; however, within 2 months, another recurrence occurred (culture positive for Nocardia), eventually requiring the addition of imipenem 0.5% (Primaxin) every 2 hours. The recurrence resolved completely with no sign of reactivation after 7 months of follow-up.

Repeat keratoplasty was performed 18 months after the original therapeutic keratoplasty to treat irregular astigmatism induced by stromal scarring from the recurrent infection. No organisms could be identified in the excised corneal specimen.

Histopathology of the excised cornea is shown in Figure 2. The sections showed that the ulcer bed was free of organisms. The edge of the ulcer was associated with a small degree of epithelial growth into the stroma. From this point, a necrotic tract could be followed into the stroma along which Nocardia organisms were present (Figure 2, A). Higher magnification of the peripheral edge of the interface suggests that the organisms advanced peripherally between the stromal lamellae (Figure 2, B). The organisms were restricted to the necrotic stromal tract and its advancing peripheral edge (boxed region in Figure 2, B) with associated skip infiltrates (data not illustrated). The skip infiltrates are foci of organisms at the same horizontal plane but not visibly continuous with the necrotic tract.

Figure 2.
Figure 2.:
Midstromal extension of Nocardia organisms. A: Histopathologic cross-section showing a necrotic track (between arrows) extending from the central ulcer bed (not shown) into the deep stroma of the midperipheral cornea. The advancing edge of the infiltrate is demarcated by a square (Ziehl-Neelsen acid-fast stain; original magnification ×20). B: Higher magnification of the advancing stromal infiltrate (boxed region in panel A) reveals numerous organisms (arrows) (Ep = corneal epithelium; DM = Descemet's membrane) (original magnification ×60).


Nocardia asteroides is a weakly acid-fast, gram-positive aerobe found ubiquitously in the environment. Smears reveal thin filamentous gram-negative bacteria branching at right angles with intracellular gram-positive beads. Nocardia keratitis occurs in immunocompromised patients, after trauma, or after eye surgery.1–3 Infections follow an indolent course and appear as a well-defined ulceration. Stromal infiltrates have feathery margins with a “wreath-like” appearance and satellite lesions.4 Most reports mention an anterior chamber reaction with or without hypopyon. Identification of organisms is generally made by corneal scrapings stained with various agents such as the Kinyoun 1% acid-fast stain or Gram stain. Nocardia will grow on most culture media. It is important to note that N asteroides is a slow-growing organism, and it is therefore necessary to keep culture plates for a minimum of 5 to 7 days.

Medical management includes topical trimethoprim-sulfamethoxazole (1:5 ratio in intravenous preparation) for a better clinical response compared with sulfonamides.5,6 Sulfonamides, amikacin,7,8 fourth-generation fluoroquinolones, and imipenem may also be effective.

Various organisms can cause post-LASIK keratitis including atypical mycobacteria,9–11N asteroides,12,13 fungi (Scedosporium apiospermum, Curvularia, Acremonium atrogriseum, Fusarium solani, Aspergillus fumigatus, Scopulariopsis),14–16 gram-positive cocci such as Staphylococcus aureus, Pneumococcus, and Streptococcus viridans,17–20 and reactivation of presumed adenovirus.21 Diffuse lamellar keratitis must be included in the differential.22 To date, 3 cases of post-LASIK Nocardia keratitis have been reported (Table 1). Kim et al.12 report a case of Nocardia keratitis after LASIK in a traumatized eye, and Pérez-Santonja et al.13 and Nascimento et al.23 report cases in patients who had LASIK retreatment. The patient in this report had no history of trauma and an uneventful intraoperative course. Except for having routine postoperative treatment with topical steroids, she was not immunocompromised. No other patients treated that same day developed Nocardia infections.

Table 1
Table 1:
Reported cases of post-LASIK Nocardia asteroides keratitis.

The present case of post-LASIK Nocardia keratitis illustrates several important points. Although Nocardia is a rare causative agent for bacterial keratitis, one must maintain a high index of suspicion and include Nocardia on the differential diagnosis of post-LASIK keratitis. Cultures are crucial in the diagnosis of this entity, and once inoculated, plates must be kept for greater than 5 days to isolate the slower growing organisms such as Nocardia and Mycobacteria. Communication between the pathologist, the ophthalmologist, and the microbiologist is vital in diagnosing rare causes of post-LASIK keratitis as special staining and isolation techniques are used to identify these rare organisms.

The mechanism of post-LASIK Nocardia keratitis is not well understood. For example, it is not clear why antibiotic treatment was ineffective in clearing the initial infection and preventing recurrence in the transplant. One possibility is that the organism avoids topical antibiotics by deeply penetrating the stroma. The present case supports this concept by providing histopathology showing the organisms restricted to the necrotic tract, which lies deep in the corneal stroma. The organisms extend laterally from this tract along the interlamellar planes. We hypothesize that the interlamellar spread allows spread of the organisms beyond the initial ulcer site and may explain the known propensity for “satellite lesions,” which would correspond to the intrastromal “skip infiltrates” that we observe. These considerations may have an important bearing on the pathogenesis of post-LASIK nocardial keratitis.


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