Graefes Arch Clin Exp Ophthalmol (2014) 252:1457–1462 DOI 10.1007/s00417-014-2732-1

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Risk factors, microbial profiles and prognosis of microbial keratitis-associated endophthalmitis in high-risk eyes Evelyn C. O’Neill & Jonathan Yeoh & David C. A Fabinyi & Dermot Cassidy & Rasik B. Vajpayee & Penelope Allen & Paul P. Connell

Received: 19 July 2013 / Revised: 6 May 2014 / Accepted: 1 July 2014 / Published online: 17 July 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Background Microbial keratitis (MK) is a sight-threatening emergency. Delayed diagnosis and treatment may exacerbate the condition and infection may spread to the posterior segment with resultant endophthalmitis. We describe the presentation, management, visual outcomes and microbial profiles of MK-associated endophthalmitis presenting to a tertiary referral centre. Methods Prospective collection of data on all patients presenting with presumed MK-associated endophthalmitis from 1997 to 2007, to the Royal Victorian Eye and Ear Hospital. Outcome measures included: visual acuity, microbial profiles, and management strategy. Results Thirty-seven cases of MK-associated endophthalmitis were identified over the study period, with a mean age of 73 years and 19 were male. Presenting acuities ranged from Snellen 2/60 to no perception of light (NPL). Thrity-four (91.9 %) patients had a prior history of ocular disease. Identifiable non-ocular risk factors were present in 31 (83.8 %), including steroid use, dementia, nursing home care or relative systemic immunosuppression. A culture positivity rate of E. C. O’Neill : J. Yeoh : R. B. Vajpayee : P. Allen : P. P. Connell Centre for Eye Research Australia, The Royal Victorian Eye and Ear Hospital, University of Melbourne, 32 Gisborne Street, East Melbourne, VIC 3002, Australia J. Yeoh : D. C. A. Fabinyi : P. Allen : P. P. Connell Vitreo-retinal Unit, The Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC 3002, Australia D. Cassidy : R. B. Vajpayee Corneal Unit, The Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC 3002, Australia E. C. O’Neill (*) : P. P. Connell Department of Ophthalmology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland e-mail: [email protected]

83.8 % was recorded. The most common organisms identified included: Streptococcal species in 12 (32.4 %), Pseudomonas aeruginosa in 11 (29.7 %), and Staphylococcus aureus in eight (21.6 %). Final acuities ranged from 6/36 to NPL. Sixteen (43.2 %) eyes were eviscerated/enucleated as primary treatment. Overall, 23 (62.2 %) patients required evisceration/ enucleation, of which nine (39.1 %) were due to Pseudomonas aeruginosa and seven (30.4 %) to Streptococcal species (Streptococcal pneumonia). Conclusions MK-associated endophthalmitis is a serious ocular condition occurring more frequently in elderly populations, and those with long standing severe pre-existing ocular disease. Visual outcomes are poor, often requiring evisceration/enucleation. Keywords Endophthalmitis . Microbial keratitis . Cornea . Microbiology . Visual acuity . Risk factors

Introduction Both microbial keratitis and infective endophthalmitis are sight-threatening ophthalmic emergencies. Infective endophthalmitis is defined as intraocular inflammation secondary to intraocular infection [1], and is classified as either exogenous or endogenous depending on the route of infection [2, 3]. Where several studies have investigated the risk factors, microbial profiles and outcomes following post-traumatic and postoperative endophthalmitis [2–13], there has been limited work to date examining microbial keratitis (MK)-associated endophthalmitis [14–16], and many studies detailing this entity consist of small case series or subsections from larger studies [17, 18]. Studies have found that MK-associated endophthalmitis may account for up to 6–10 % of exogenous endophthalmitis [18]. However, endophthalmitis is an uncommon complication of MK in otherwise healthy eyes [15, 16,

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19]. In their series, Scott et al. found that 14 of 1,699 (0.8 %) of all suspected MK cases (culture proven and culture negative) and 14 of 825 (1.7 %) culture positive cases of MK developed endophthalmitis [15]. They defined MKassociated endophthalmitis as having both corneal and intraocular specimen culture positivity. Therefore, they may have underestimated the true incidence by excluding cases with negative samples. Bourcier et al. reported that two of 300 (0.7 %) MK cases developed endophthalmitis, and Santa Cruz et al. found that 17 of 965 (1.8 %) of patients admitted for management of severe MK required evisceration or enucleation due to uncontrolled infection [19]. Uncomplicated MK, where the infection remains limited to the cornea, with no posterior extension confers a relatively good prognosis, generally occurs in otherwise healthy eyes and accounts for the majority of cases [20–22]. MK complicated by intraocular extension and endophthalmitis often occurs in a compromised eye, with multiple risk factors and often carries a poorer visual prognosis [14, 23]. This complication is uncommon, with a prevalence of 0.5–1.7 % [15, 20, 21, 23]. To date, clinical series describing microbial and ulcerative keratitis have focused on the former group, with few studies investigating MK-associated endophthalmitis in high risk eyes. While traditionally, visual outcome is poor, less is understood on the relative contribution of both ocular and systemic risk factor profiles to this outcome. The importance of isolate identification also remains poorly understood. The primary aims of this study were to investigate the incidence, presentation, management, visual outcomes and microbiological profile of all cases of MK-associated endophthalmitis presenting to a tertiary referral centre.

Materials and methods One of the authors (PA) maintains a prospective database of all cases of infective endophthalmitis presenting to The Royal Victorian Eye and Ear Hospital, Melbourne, Australia. All cases of presumed microbial keratitis with associated endophthalmitis presenting between 1997 and 2007 were included in the present study. Inclusion criteria were: evidence of MK and endophthalmitis in either eye, defined as the presence of anterior/posterior segment inflammation on ophthalmic examination, vitritis and evidence of associated concurrent MK. Collected data included: demographics, predisposing risk factors, clinical examination, investigations performed, microbiological profiles, treatment modalities and final corrected visual acuity (VA) at last follow-up. Institutional review board approval was obtained for this project and the research was conducted in accordance with the Declaration of Helsinki and local ethics committee guidelines.

Graefes Arch Clin Exp Ophthalmol (2014) 252:1457–1462

All microbiological analysis was carried out at the microbiology laboratory at St Vincent’s Hospital, Melbourne. Confirmed microbiological diagnosis was based on microscopy (Gram-staining) and culture positivity. For microbial analysis, corneal scrapes, anterior chamber (AC) aqueous samples and vitreous samples were taken unless primary evisceration/ enucleation was performed, whereby aqueous and vitreous taps were not performed. All samples were obtained in accordance with hospital protocols using aseptic technique. Aqueous samples were obtained with a 1 mL syringe through an AC paracentesis and vitreous samples were obtained through an aspirated tap via the pars plana, or during formal vitrectomy. All samples were processed without delay on appropriate culture media. A culture was deemed positive if there was growth of the same organism in more than one medium according to defined protocols. Management of all cases consisted of initial biopsy and intravitreal broad spectrum antibiotics or antifungals. Primary evisceration/enucleation was performed in cases out of clinical necessity. Intravitreal ceftazidime (2.25 mg/ml) and vancomycin (1.0 mg/ml) were given in all suspected bacterial cases. In suspected fungal cases, based on clinical presentation or associated history, intravitreal amphotericin B (5 μg/ml) was also administered. All patients were also treated with concomitant systemic intravenous therapy (ciprofloxacin or voriconazole) or oral therapy (ciprofloxacin). No case underwent vitrectomy. Due to the number of patients presenting with beyond Snellen acuities [i.e., count fingers (CF), hand movements (HM), perception of light (PL) or no perception of light (NPL)], visual results were obtained from the difference in VA pre-treatment and post-treatment and categorised into four groups: (1) improved, (2) no change, (3) deteriorated and (4) evisceration/enucleation. An improvement was defined as either a gain of≥two lines of Snellen VA, where subjects were within Snellen acuity rang,es or, for those presenting within the “beyond Snellen” category, an improvement of one measured step or more (e.g., from HM to CF, or CF to 6/60). A deterioration was defined as either a loss of≥two lines of Snellen VA where subjects were within Snellen acuity ranges, or, for those presenting with, or following treatment ending up in the “beyond Snellen” category, a loss of one measured step or more (e.g., from CF to HM, or HM to PL).

Results Demographics and clinical presentation Of 571 cases of infective endophthalmitis presenting over the 10-year study period, 37 (6.5 %) had MK and associated endophthalmitis. The mean age was 73 years (range 45–92) and 19 were male. In all cases, patients presented with reduced

Graefes Arch Clin Exp Ophthalmol (2014) 252:1457–1462

VA, marked corneal pathology (corneal ulcer/abscess +/ −perforation), conjunctival injection, anterior chamber hypopyon and vitritis. All patients had a limited fundal view at presentation. B-scan performed on presentation revealed the presence of vitreous opacities and debris suggestive of endophthalmitis by comparison to the fellow eye. Presenting Snellen VA ranged from 2/60 to NPL with a median Snellen VA of PL. The mean time to presentation was 11 days (range 1–60). Surprisingly, despite the relative lack of spread of presenting visual acuities, there was no association between VA and age or time to presentation (p>0.05). Eight (21.6 %) eyes had documented perforations at the time of presentation. Seventeen (45.9 %) were pseudophakic or aphakic (one secondary to trauma) at the time of presentation, of which eight (47.1 %) underwent evisceration/enucleation. Microbiology Of 37 patient samples taken for microbiological analysis, 31 (83.8 %) were culture positive. Microbiological samples included: corneal scrapes, anterior chamber (AC) aqueous samples and/or vitreous samples unless primary evisceration/ enucleation was performed. There was no growth documented in six (16.2 %), despite repeat biopsy in initial negative cases. Of the culture positive cases, 26 (83.9 %) isolated grampositive and 14 (45.2 %) gram-negative bacteria. The most frequently isolated bacteria included Streptococcal species in 12 (32.4 %) [Streptococcal pneumoniae (9), Stretococcal viridians (3)], Pseudomonas aeruginosa in 11 (29.7 %), and Staphylococcus aureus in eight (21.6 %) (Table 1). No fungal isolates were identified. Eight (21.6 %) cases had a polymicrobial profile. Corneal scrapes were performed in 28 (75.8 %) patients on presentation and isolated cultures matched the aspirated posterior segment pathogen in all cases. The remaining had either primary evisceration/enucleation and contents were sent for microbiological analysis or had aqueous and vitreous tap alone, as corneal scrapes were not possible. Pre-existing ocular conditions and ocular and general risk factors Thirty-four of 37 eyes (91.9 %) had significant pre-existing ocular pathology and poor VA prior to the present episode (Table 2). These included: prior or recurrent MK, corneal ulcer or abscess in nine (24.3 %), documented severe dry eye, ectropion or blepharitis in nine (24.3 %), rubeotic glaucoma with poor VA in eight (21.6 %), prior or recurrent severe herpes simplex keratitis (HSK) in seven (18.9 %) and previous trauma or documented corneal thinning in seven (18.9 %). Twenty-one (56.8 %) had had previous ocular surgery, with 16 (43.2 %) having cataract extractions, 12 (32.4 %) having previous penetrating keratoplasty (PK), three (8.1 %) having

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excision of pterygia, two (5.4 %) having trabeculectomies and one (2.7 %) having vitrectomy. Fourteen patients (37.8 %) were on current topical steroids. Significant other non-ocular risk factors were present in 83.8 % of the group (Table 2). These included: chronic intellectual impairment, dementia or nursing home care in 16 (43.2 %) and relative systemic immunosuppression (secondary to systemic steroid use, rheumatoid arthritis, diabetes mellitus or other systemic disease) in 13 (35.1 %). In culture positive isolates, 27 of 29 (93.1 %) patients had a significant ocular history, and 29 of 29 (100 %) had an identifiable risk factor. In culture negative patients, 5 of 6 (83.3 %) patients had an identifiable risk factor. Visual acuities Of all cases, 36 patients presented with beyond Snellen visual acuities. All patients who underwent primary or secondary evisceration/enucleation presented with PL vision or worse. Of the 14 remaining patients, the presenting VA ranged from 2/60 to NPL with the median presenting VA being HM. Eight (57.1 %) of these patients improved and six (42.9 %) had no change in VA. (Table 3) Eyes requiring removal Overall, a total of 23 (62.2 %) patients required evisceration/ enucleation, of which nine (39.1 %) were due to Pseudomonas aeruginosa and seven (30.4 %) to Streptococcal species (all but one, Streptococcal pneumonia) (Table 3). The mean time from onset of symptoms to presentation for those requiring evisceration/enucleation was 13.2 days (range 2–60). Sixteen (43.2 %) eyes were eviscerated/enucleated as primary treatment; all had a prior history of ocular disease and poor visual prognosis. Six (37.5 %) were in eyes with a prior history of CRVO and rubeotic glaucoma, four (25 %) in eyes with a prior history of recurrent HSK, poor VA and perforation on presentation, and four (25 %) had severe MK and panendophthalmitis on a background of prior ocular disease (neurotrophic cornea, severe age-related macular degeneration, advanced end-stage glaucoma and HSK). Nine (56.3 %) also had a documented history of dementia/ learning disability and 13 (56.5 %) a history of dementia and/or nursing home care (p

Risk factors, microbial profiles and prognosis of microbial keratitis-associated endophthalmitis in high-risk eyes.

Microbial keratitis (MK) is a sight-threatening emergency. Delayed diagnosis and treatment may exacerbate the condition and infection may spread to th...
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