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Figure 1.
Clinical slitlamp photographs of Actinomyces infectious crystalline keratopathy at the initial visit (A), immediately following the first repeat penetrating keratoplasty (B), and at low (C) and high (D) magnification of recurrent corneal opacities 6 months later. Arrows indicate temporal opacity within the host cornea.

Clinical slitlamp photographs of Actinomyces infectious crystalline keratopathy at the initial visit (A), immediately following the first repeat penetrating keratoplasty (B), and at low (C) and high (D) magnification of recurrent corneal opacities 6 months later. Arrows indicate temporal opacity within the host cornea.

Figure 2.
Histopathologic photomicrographs of intrastromal colonies of filamentous, branching, gram-positive bacteria consistent with Actinomyces species with minimal associated inflammation, showing staining with periodic acid–Schiff stain (original magnification ×100) (A), hematoxylin-eosin stain (original magnification ×1000) (B), and Brown-Hopps stain (original magnification ×1000) (C).

Histopathologic photomicrographs of intrastromal colonies of filamentous, branching, gram-positive bacteria consistent with Actinomyces species with minimal associated inflammation, showing staining with periodic acid–Schiff stain (original magnification ×100) (A), hematoxylin-eosin stain (original magnification ×1000) (B), and Brown-Hopps stain (original magnification ×1000) (C).

1.
Gorovoy  MSStern  GAHood  CIAllen  C Intrastromal noninflammatory bacterial colonization of a corneal graft. Arch Ophthalmol 1983;101 (11) 1749- 1752
PubMed
2.
Meisler  DMLangston  RHNaab  TJAaby  AA McMahon  JTTubbs  RR Infectious crystalline keratopathy. Am J Ophthalmol 1984;97 (3) 337- 343
PubMed
3.
Singh  MKaur  B Actinomycetic corneal ulcer. Eye (Lond) 1989;3 (pt 4) 460- 462
PubMed
4.
Karimian  FFeizi  SNazari  RZarin-Bakhsh  P Delayed-onset Actinomyces keratitis after laser in situ keratomileusis. Cornea 2008;27 (7) 843- 846
PubMed
5.
Roussel  TJOlson  ERRice  TMeisler  DHall  GMiller  D Chronic postoperative endophthalmitis associated with Actinomyces species. Arch Ophthalmol 1991;109 (1) 60- 62
PubMed
6.
Lin  SCKao  SCTsai  CC  et al.  Clinical characteristics and factors associated with the outcome of lacrimal canaliculitis [published online January 8, 2010]. Acta Ophthalmol
PubMed10.1111/j.1755-3768.2009.01827.x
Research Letters
April 11, 2011

Actinomyces Infectious Crystalline Keratopathy

Author Affiliations

Author Affiliations: Departments of Ophthalmology and Visual Sciences (Drs Shtein and Elner) and Pathology (Drs Newton and Elner), University of Michigan, Ann Arbor.

Arch Ophthalmol. 2011;129(4):512-526. doi:10.1001/archophthalmol.2011.55

We report a difficult-to-treat, indolent infection following penetrating keratoplasty (PKP) with the clinical appearance of infectious crystalline keratopathy. The causative agent was not recovered from multiple corneal scrapings but morphologically resembles Actinomyces species histopathologically in the deep stroma of corneal tissue removed at repeat PKP.

Report of a Case

A 75-year-old woman underwent uncomplicated combined right PKP and lenticular phacoemulsification for Fuchs corneal dystrophy and cataract. Three months postoperatively, she developed peripheral stromal opacities associated with 2 loose sutures. These opacities grew despite topical treatment with tobramycin, and marked conjunctival injection and a moderate anterior chamber inflammatory reaction developed. She was referred to our service for treatment of corneal ulceration in the nasal and temporal portions of the graft (Figure 1A). Corneal scrapings revealed no organisms on Gram or Giemsa staining, and no organisms grew on aerobic, anaerobic, fungal, or viral cultures. She was treated with fortified cefazolin and gentamicin sulfate eyedrops but developed 2 new stromal infiltrates and required repeat PKP (Figure 1B). Histopathologic analysis of the removed tissue revealed full-thickness corneal edema and stromal scarring, consistent with healed keratitis. Gram staining at multiple levels failed to reveal the presence of organisms.

Four months postoperatively, the patient noted a foreign body sensation and was found to have an area of corneal thinning at the graft-host junction near the temporal site of previous ulceration. A loose suture in that area was sent for culture and the patient was treated for presumed herpetic keratitis. No organisms grew from the suture, and the patient developed stromal opacities similar to her preoperative appearance. Repeat corneal ulceration (Figure 1C and D) prompted another PKP with removal of a 1-mm-larger disc to encompass the previous graft and additional host cornea affected by ulceration and thinning. Histopathologic analysis of the removed cornea revealed acute and chronic keratitis associated with centrifugal intrastromal colonies of strongly and uniformly gram-positive bacteria with short, stubby branches typical of Actinomyces species (Figure 2). Ziehl-Neelson acid-fast staining was negative, suggesting Actinomyces rather than Nocardia species. Cultures of stromal tissue again were negative.

Postoperatively, graft and host corneal clarity were maintained. After corneal suture removal, visual acuity of 20/20 was achieved with a rigid gas-permeable contact lens.

Comment

Actinomyces can be a rare cause of infectious crystalline keratopathy, especially in an immune-suppressed condition such as a corneal graft. Infectious crystalline keratopathy is a unique corneal infection characterized by the slowly progressive development of needlelike opacities in the corneal stroma, most commonly caused by streptococcal species.1,2 To our knowledge, this is the first case of infectious crystalline keratopathy due to an organism with morphologic characteristics consistent with Actinomyces. There have been other rare reports of Actinomyces corneal infections. Severe corneal ulceration from Actinomyces has been reported,3 as has delayed-onset keratitis after laser in situ keratomileusis.4 In both of these cases, cure was achieved with debridement of the infected cornea and intensive treatment with topical antibiotics, as well as oral penicillin in the case of the corneal ulcer. Actinomyces has also been associated with chronic postoperative endophthalmitis that required surgical treatment.5Actinomyces species are more commonly encountered in ophthalmology as a cause of canaliculitis.6 In these cases, Actinomyces is difficult to eradicate medically and usually requires surgical treatment.

Actinomyces can be a difficult organism to grow in culture and is difficult to treat even with aggressive medical treatment. The histopathologic appearance in this case is reminiscent of a biofilm with minimal associated inflammation. Similar to Actinomyces in canaliculitis, our case responded only to surgical excision with wide boundaries for complete removal of the causative agent.

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Article Information

Correspondence: Dr Shtein, Department of Ophthalmology and Visual Sciences, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105 (ronim@umich.edu).

Author Contributions: Dr Shtein had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This study was supported by grant EY017885 from the National Eye Institute, National Institutes of Health (Dr Shtein).

Role of the Sponsor: The funding agency had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

References
1.
Gorovoy  MSStern  GAHood  CIAllen  C Intrastromal noninflammatory bacterial colonization of a corneal graft. Arch Ophthalmol 1983;101 (11) 1749- 1752
PubMed
2.
Meisler  DMLangston  RHNaab  TJAaby  AA McMahon  JTTubbs  RR Infectious crystalline keratopathy. Am J Ophthalmol 1984;97 (3) 337- 343
PubMed
3.
Singh  MKaur  B Actinomycetic corneal ulcer. Eye (Lond) 1989;3 (pt 4) 460- 462
PubMed
4.
Karimian  FFeizi  SNazari  RZarin-Bakhsh  P Delayed-onset Actinomyces keratitis after laser in situ keratomileusis. Cornea 2008;27 (7) 843- 846
PubMed
5.
Roussel  TJOlson  ERRice  TMeisler  DHall  GMiller  D Chronic postoperative endophthalmitis associated with Actinomyces species. Arch Ophthalmol 1991;109 (1) 60- 62
PubMed
6.
Lin  SCKao  SCTsai  CC  et al.  Clinical characteristics and factors associated with the outcome of lacrimal canaliculitis [published online January 8, 2010]. Acta Ophthalmol
PubMed10.1111/j.1755-3768.2009.01827.x
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