Ring Infiltrate in Staphylococcal Keratitis 1

1 Batriti S Wallang, DO 1 Sujata Das, MS, FRCS (Glasg.) 2 Savitri Sharma, MD 1 Srikant K Sahu, MS 3 Ruchi Mittal, MD

1 Cornea and Anterior Segment Service 2 Ocular Microbiology Service 3 Ocular Pathology Service

L. V. Prasad Eye Institute, Bhubaneswar, Odisha, India, 751024

Key Word : Ring infiltrate, Staphylococcous infection, Cornea, Keratitis

Financial Support : None.

Conflict of Interest : No conflicting relationship exists for any author.

Running Head : Corneal Ring Infiltrate

Address for Reprints

Sujata Das, MS, FRCS (Glasg.) Consultant, Cornea and Anterior Segment Service L. V. Prasad Eye Institute Bhubaneswar, Odisha India, 751024 T: +91 (674) 398-7999 F: +91 (674) 398-7130 sujatadas@lvpei.org

2

Copyright © 2012, American Society for Microbiology. All Rights Reserved.J. Clin. Microbiol. doi:10.1128/JCM.02191-12 JCM Accepts, published online ahead of print on 24 October 2012

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ABSTRACT 3

Smear and culture of the corneal scrapings from a patient with a ring infiltrate confirmed 4

significant growth of Staphylococcus species, resistant to fluoroquinolones. Due to non-5

response to medical management, patient underwent therapeutic penetrating keratoplasty. 6

Staphylococcous infection of the cornea may present as ring like infiltrate and recalcitrant to 7

medical management. 8

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CASE REPORT 10

A 66-year-old man presented with complaints of sudden diminution of vision in his left eye for 11

four days. He had undergone left eye punctoplasty for lower lid punctal stenosis in the past and 12

was receiving treatment for chronic meibomitis. He also had a history of recurrent uveitis and 13

secondary glaucoma in this eye. At the time of presentation, he was using loteprednol 14

etabonate (0.5%) and brimonidine tartrate (0.2%) eye-drops twice daily. 15

During presentation his visual acuity was hand movement close to face. Corneal 16

examination revealed a large epithelial defect measuring 8.0x7.5mm. Stromal ring infiltrate was 17

present corresponding to the dimensions of the epithelial defect (Figure-1a,b). It was 18

approximately 1.5mm wide and away from the limbus with associated surrounding stromal 19

edema. The anterior chamber showed a hypopyon measuring 2mm in height. While KOH+CFW 20

(10% potassium hydroxide with calcofluor white) stain did not show any organism, Gram stain 21

showed plenty of polymorphonuclear cells and gram-positive cocci in groups. 22

The patient was put on fortified cefazolin (5%) and gatifloxacin (0.3%) eye-drops one-23

hourly. Culture grew Staphylococcus species (non-S. aureus) which was significant (consistent 24

in direct microscopy result and confluent growth in two solid media), and sensitive to 25

vancomycin, cefazolin and methicillin. Hence, cefazolin 5% eye drops were continued. 26

On subsequent follow-up, persistent epithelial defect of size >8mm in all dimensions, deep 27

stromal ring infiltrate and hypopyon remained same. Loteprednol etabonate eye-drop four-times 28

daily was added on 5th day of presentation for control of inflammatory component along with 29

intensive lubrication. It was tapered over a period of four weeks. A repeat corneal scraping, 26 30

days after presentation, revealed no organisms in direct smear by Gram and KOH+CFW 31

staining as well as in culture. Finally, with the failure in resolution of clinical signs and 32

symptoms, the patient was given the option of left eye therapeutic penetrating keratoplasty. 33

Culture of the corneal tissue for bacteria, fungus and Acanthamoeba did not grow any 34

organism. The histopathology evaluation of the corneal tissue showed completely denuded 35

epithelium with continuous Bowman’s membrane. Stroma showed diffuse loss of 36

fibrokeratocytic nuclei in stroma (Figure-1c,d). Peripheral stroma showed presence of plump 37

myofibroblastic cells. Central and paracentral corneal stroma showed patchy stromal necrosis 38

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with eosinophilic granular debris between the stromal fibres. Descemets membrane was 39

continuous with occasional subendothelial polymorphonuclear cells. Special stains did not show 40

any organism. 41

Postoperatively, there was large epithelial defect in the graft, which was managed with 42

bandage contact lens. At his last follow-up, the visual acuity was 20/125 with a clear graft. 43

DISCUSSION 44

Corneal ring infiltrates have been described to occur in infections by a variety of organisms. 45

These include Acanthamoeba, gram-negative bacilli like Pseudomonas aeruginosa or 46

Moraxella, herpes simplex virus, fungi, varicella zoster virus, as well as immune-related 47

conditions like rheumatoid arthritis.1-3 Corneal ring infiltrates are most consistently associated 48

with Acanthamoeba keratitis. Ring infiltrate has been reported after corneal collagen 49

crosslinking procedure with postoperative use of contact lens due to polymicrobial infection 50

caused by Streptococcus salivarius, Streptococcus oralis, and coagulase-negative 51

Staphylococcus sp.4 We report an atypical case of corneal ring infiltrate associated with 52

Staphylococcus infection with an unusual clinical course. 53

Staphylococcus keratitis occurs more frequently in compromised cornea such as bullous 54

keratopathy, chronic herpetic keratitis, keratoconjunctivitis sicca, etc. While S. aureus tends to 55

produce a rapidly progressive corneal infiltration and moderate anterior chamber reaction with 56

hypopyon, Staphylococcus species other than S. aureus tend to progress slowly and present as 57

superficial localised infiltrate. Although Staphylococcus has been known to cause ring 58

infiltrates, it is uncommon and there are limited reports of such cases.5,6 More interesting was 59

the clinical course of the disease in this patient, where a persistence of the epithelial defect and 60

infiltrate despite medical therapy, presented a diagnostic and therapeutic dilemma. 61

Ring infiltration with Staphylococcus is thought to be immune-mediated in pathogenesis. It 62

is a type III hypersensitivity reaction to staphylococcal antigens or toxins, resulting in 63

complement activation and influx of polymorphonuclear leucocytes and mononuclear cells that 64

form the infiltrate.7 Clinically, differentiating an infective infiltrate from a sterile infiltrate is 65

difficult, although the management differs significantly in the two. While infective cases would 66

be associated with pain, suppuration, larger epithelial defects with anterior chamber reactions, 67

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sterile infiltrates would be milder in signs and symptoms, and not usually associated with 68

epithelial defects of greater than 2mm.8 69

In our patient, risk factor of chronic meibomitis was present, which is most commonly 70

associated with marginal infiltrate by Staphylococcus infection, and perhaps a localised 71

immunocompromised state from chronic topical steroid use. Despite in-vitro susceptibility-72

based treatment and steroid cover for any immunological component, the patient did not 73

respond to the treatment. Repeat microbiological evaluation and culture of the corneal tissue 74

failed to reveal any organism, while histopathology showed a non-specific stromal necrosis with 75

absence of any inflammatory infiltrate. This might be due to chronic steroid use causing 76

localized immune-suppression. 77

Significant growth of Staphylococcus in culture and non-response to steroid treatment in 78

our patient has proven that there is absence of immunologic component in the pathogenesis of 79

the ring infiltrate. The multidrug resistance may be an association or a coincidental finding of 80

ring infiltrate. 81

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REFERENCES 83

1. Meyers-Elliott RH, Pettit TH, Maxwell WA. Viral antigens in the immune ring of Herpes 84

simplex stromal keratitis. Arch Ophthalmol 1980; 98(5): 897-904. 85

2. Khan AO, Al-Assiri A, Wagoner MD. Ring corneal infiltrate and progressive ring thinning 86

following primary varicella infection. J Pediatr Ophthalmol Strabismus 2008; 45(2): 116-117. 87

3. Illingworth CD, Cook SD. Acanthamoeba keratitis. Surv Ophthalmol 1998; 42(6): 493-508. 88

4. Zamora KV, Males JJ. Polymicrobial keratitis after a collagen cross-linking procedure with 89

postoperative use of a contact lens: a case report. Cornea 2009; 28(4): 474-476. 90

5. Thygeson P. Marginal corneal infiltrates and ulcers. Trans Am Acad Ophthalmol 91

Otolaryngol 1947; 51:198-209. 92

6. Hogan MJ, Diaz-Bonnet V, Okumoto M, Kimura SJ. Experimental staphylococcic keratitis. 93

Invest Ophthalmol 1962; 1: 267-272. 94

7. Chignell AH, Easty DL, Chesterton JR, Thomsitt J. Marginal ulceration of the cornea. Br J 95

Ophthalmol 1970; 54(7): 433-440. 96

8. Stein RM, Clinch TE, Cohen EJ, Genvert GI, Arentsen JJ, Laibson PR. Infected vs sterile 97

corneal infiltrates in contact lens wearers. Am J Ophthalmol 1988; 105(6): 632-636. 98

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FIGURE LEGENDS 100

FIGURE-1 101

Slit-lamp photograph showing ring infiltrate in: (a) Diffuse illumination, and (b) Slit-view. (c) 102

Corneal stroma showing diffuse loss of fibrokeratocytic nuclei with complete absence of 103

inflammatory cells (Periodic Acid-Schiff stain, x100); (d) Eosinophilic granular debris between 104

the stromal fibres (Hematoxylin and Eosin stain, x400). 105

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