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CLINICAL COMMUNICATION

Recalcitrant Pseudomonas keratitis after epipolis laser-assistedin situ keratomileusis: case report and review of the literature

Clin Exp Optom 2012; 95: 460–463 DOI:10.1111/j.1444-0938.2012.00727.x

Namrata Sharma MDAnimesh Jindal MBBSShveta J Bali MDJeewan S Titiyal MDCornea and Refractive Surgery Services,Dr Rajendra Prasad Centre forOphthalmic Sciences, All India Instituteof Medical Sciences, New Delhi, IndiaE-mail: namrata.sharma@gmail.com,namrata103@hotmail.com

We report a case of recalcitrant microbial keratitis after epipolis laser-assisted in situkeratomileusis (epi-LASIK) surgery caused by Pseudomonas aeruginosa and review theliterature on resistant Pseudomonas keratitis after excimer laser surgery.

Microbial keratitis occurred two weeks after epi-LASIK surgery and was resistant tofluoroquinolones, aminoglycosides and macrolides but sensitive to meropenem. Thepatient had total corneal melting and required therapeutic penetrating keratoplasty.The globe could be salvaged and the distance visual acuity was 6/60 in the right eye.

Recalcitrant Pseudomonas keratitis might require a therapeutic graft and necessitatethe use of intravenous meropenem to prevent recurrence of infection.

Submitted: 11 May 2011Revised: 22 January 2012Accepted for publication: 28 January2012

Key words: cornea, epi-LASIK, fractive surgery, keratitis, LASEK, resistant Pseudomonas

Microbial keratitis is an uncommon butdreaded complication, which might occurafter laser-assisted in situ keratomileusis(LASIK). Infectious keratitis complica-tions cause ocular morbidity and have anegative psychological impact on patientsand their families. The incidence of infec-tion after LASIK has been reported to be0.035 per cent.1 The causative organismsmight range from diverse bacteria likeMycobacterium chelonae, Nocardia asteroids,Staphylococcus aureus, Streptococcus pneumo-nia and fungal pathogens.2 Althoughthere are few reports of isolation ofPseudomonas keratitis following ablative

refractive surgeries,3–6 this microorganismhas not been reported in cases of infec-tious keratitis after epipolis LASIK (epi-LASIK) surgery.

Epi-LASIK is a procedure for the cor-rection of low-to-moderate myopia andmyopic astigmatism.7 As opposed to con-ventional LASIK where a stromal flap israised, the epithelium alone is raised inthis surgery. In comparison to the photo-refractive keratectomy, it is associated withreduced post-operative pain and hazelevels.8 A bandage contact lens is requiredat the end of the procedure to enhanceepithelialisation.

Pseudomonas aeruginosa tends to adhereto the surface of the contact lens andmight be transferred through thebreached corneal epithelium into thedeeper layers of the cornea causing micro-bial keratitis. We report a rare case ofPseudomonas keratitis in a patient who hadundergone bilateral epi-LASIK surgery.

CASE REPORT

A 23-year-old woman presented to ourtertiary care clinic with complaints ofpain, redness, watering, photophobia anddecreased vision in the right eye for the

C L I N I C A L A N D E X P E R I M E N T A L

OPTOMETRY

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previous 40 days. Ocular history was sig-nificant for the weeks leading to her pre-sentation in our office. The patient hadundergone bilateral simultaneous epi-LASIK in a private clinic two months priorto presentation. There was no medicalhistory suggestive of immunocompro-mised status or use of oral steroids orimmunosuppressants for any systemicillness. Post-operative protocol hadincluded application of a bandage contactlens in both eyes and topical gatifloxacinhydrochloride 0.3% (Zymar, Allergan,Mumbai, India) and fluorometholone0.1% (FML, Alcon, Fort Worth, TX, USA)four times a day. There were no associatedocular or systemic complaints in the im-mediate post-operative period. Two weeksafter surgery, the patient developed red-ness, pain, watering and decreased visionin the right eye and a diagnosis of micro-bial keratitis was made at the private clinicwhere the procedure was performed.

A smear of the corneal scrapingrevealed the presence of gram-negativebacilli and the culture confirmed the pres-ence of Pseudomonas aeruginosa. A diagno-sis of post-epi-LASIK Pseudomonas keratitiswas made. Antibiotic sensitivity testsrevealed resistance to fluoroquinolones,aminoglycosides and macrolides includ-

ing chloramphenicol. The organism wasfound to be mildly sensitive to vancomycinand sensitive to meropenem.

The patient was on treatment with onedrop of moxifloxacin hydrochloride 0.5%(Vigamox, Alcon), vancomycin hydrochlo-ride 5% and amikacin sulphate 10% eyedrops every hour for the initial 48 hours(round the clock) followed by a two-hourly dosage while awake. The patientwas instructed to use these drops at five-minute intervals if the times of instillationoverlapped. Because there was no clinicalresponse to topical medications over atwo-week period, the patient was referredto our tertiary care centre.

Informed consent was obtained and theguidelines required by the InstitutionalReview Board were followed at our centre.The investigation was conducted in accor-dance with the Declaration of Helsinki.On detailed assessment, the distancevisual acuity was hand motion close to theface with inaccurate projection of rays inthree quadrants in the right eye. In the lefteye her visual acuity was 6/6. The righteyelids were oedematous and the conjunc-tiva was congested. The cornea showed anepithelial defect with stromal infiltrationmeasuring 10.5 mm ¥ 10.5 mm. Periph-eral corneal melting was noted from 3

o’clock to 8 o’clock positions. The ante-rior chamber was full of hypopyon andwhite coloured exudates obscuring visuali-sation of the underlying lens (Figure 1).Digital intraocular pressure was normaland the posterior segment was anechoicon B scan ultrasonography. Examin-ation of the left eye did not reveal anyabnormality.

The patient was hospitalised and startedtreatment with one-hourly fortified vanco-mycin hydrochloride 5% eye drops, ami-kacin sulphate eye drops and polymyxin50,000 IU/ml eye drops along with atro-pine sulphate 1% eye ointment threetimes a day. Intravenous meropenem tri-hydrate (Merocrit, Cipla, Mumbai, India)was started in the dose of one gram everyeight hours for 24 hours and an emer-gency therapeutic penetrating kerato-plasty was performed with a donor corneaof 12 mm, the host graft disparity being1.0 mm. Intraoperatively, the hypopyon/exudate was seen in the anterior chamberand a thick membrane was present at thepupillary plane. Following removal of thehypopyon and the membrane, the lens wasclear. Posterior synechiae were presentand were released. Intracameral wash wasgiven with 1% vancomycin hydrochloride.The donor graft was sutured to thehost bed with 16 10-0 monofilamentnylon interrupted sutures. Post-operativelytopical antibiotics were continued alongwith intravenous meropenem for onemore week. Prednisolone acetate 1%(Pred Forte, Alcon) was started once theepithelial defect healed after one week.Six weeks post-operatively, visual acuitywas 6/60 with accurate projection of raysin all quadrants (Figure 2). Six monthsafter therapeutic keratoplasty, the periph-ery of the graft showed vascularisation anda membrane was noted in the pupillaryarea. There was no recurrence ofinfection. At the time of presentation,the patient was awaiting an opticalkeratoplasty.

DISCUSSION

Microbial keratitis is an uncommoncomplication after excimer laser-basedsurgery. The possible sources of contami-

Figure 1. Pseudomonas keratitis after epipolos laser-assistedin situ keratomileusis with conjunctival hyperaemia, largecorneal infiltrates and inferior corneal melting

Infection after epi-LASIK surgery Sharma, Jindal, Bali and Titiyal

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nation include the surgeon, instruments,topical drugs and poor patient hygiene.Surgical trauma and temporary break-down of the epithelium increase the riskfor infection following surgery. Use ofbandage contact lenses is an added riskfactor for development of microbialkeratitis; however, it is uncommon to haveinfection after the use of bandage contactlenses, especially if the patients are coun-

selled about the meticulous post-operativeregime and sterile manoeuvres duringinstillation of the topical drops.

The common organisms that causeinfections after excimer-based lasersurgery include Mycobacterium chelonae,Nocardia asteroids, Staphylococcus aureus,Streptococcus pneumonia and fungal infec-tions.2 Four cases have been reported dueto Pseudomonas species following ablative

refractive procedures, three cases afterLASIK and one after photo-refractive kera-totomy (Table 1).3–6 To the best of ourknowledge, this is the first case of infec-tious keratitis due to Pseudomanas aerugi-nosa after epi-LASIK surgery. Pseudomonaskeratitis after excimer laser surgery usuallymanifests within two weeks, although inone such report symptoms appearedapproximately six years after the epi-LASIK surgery.6 In surface ablativesurgery, a bandage contact lens acts as anadditional risk factor for the developmentof microbial infectious keratitis because itmight cause hypoxia and forms a microen-vironment for growth of organisms.Ocular infection caused by Pseudomonasaeruginosa is usually severe. Two of thefour cases reviewed ultimately requiredpenetrating keratoplasty.3,4

In a study of changing trends in theantibiotic susceptibility of Pseudomonasspecies isolated from bacterial keratitisover a nine-year period by Smitha and col-leagues,9 the fluroquinolones, especiallyciprofloxacin and ofloxacin, were effec-tive; however, they emphasised that therewas a need to continuously monitor thebacterial resistance trends in view of thedeveloping resistance due to indiscrimi-nate use of these antibiotics.9Figure 2. Six-weeks post-penetrating keratoplasty. Slitlamp

evaluation shows peripheral vascularisation and pupillarymembrane formation.

Author Excimer laser surgery Onset ofsymptoms

Culture sensitivity Medical therapy Surgical therapy Outcome

Reinhard, Knorz andSundmacher3

LASIK for post-PKPastigmatism

1 week Sensitive to mezlocillin,piperacillin andtacobactam

Topical mezlocillin andsystemic piperacillin plustacobactam

PKP for recurrence NA

Moshirfar andcolleagues4

PRK 3 days Moderate sensitivity tociprofloxacin

Fortified vancomycin andtobramycin

PKP for descemetocele 6/6 at 4 months

Sharma andcolleagues5

LASIK 2 weeks Ciprofloxacin Topical and systemicciprofloxacin

6/12 at 6 weeks

Vieira andcolleagues6

LASIK 6 years NA Fortified topical amikacin NA

Present study Epi-LASIK 2 weeks Sensitive to meropenem Topical vancomycin,amikacin, polymyxin andsystemic meropenem

PKP for corneal melting 6/60 at 6 weeks

epi-LASIK: epipolos laser-assisted in situ keratomileusis, LASIK: laser-assisted in situ keratomileusis, NA: not available, PKP: penetrating keratoplasty, PRK: photorefractivekeratectomy

Table 1. Case reports of Pseudomonas keratitis after excimer laser refractive procedures

Infection after epi-LASIK surgery Sharma, Jindal, Bali and Titiyal

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462 Clinical and Experimental Optometry © 2012 Optometrists Association Australia

In the case presented, the organism wasfound to be resistant to all the antibioticstested including flouroquinolones andaminoglycosides, which ultimately led tothe failure of the initial medical therapy atthe private clinic. In the United Kingdomand Australia, chloramphenicol is a bacte-riostatic agent used to treat bacterialkeratitis; however, in the present case theorganism was resistant to chlorampheni-col and hence this drug was not used. Thepatient came at a later stage when uncon-trolled infection had led to melting of thecornea necessitating a therapeutic pen-etrating keratoplasty, which was donewithin 24 hours after presentation. Thedebulking of the corneal microbial loadafter excision of the infected buttoncoupled with the use of a large therapeuticgraft helped to combat the infection. Post-operative use of meropenem aided in pre-venting recurrence of infection in thegraft. Combined surgical and medicalmanagement of the eye helped to salvagethe globe so that the patient’s projectionwas accurate and visual acuity of 6/60 wasachieved.

Manipulation of the side chains of theinitial fluroquinolone molecule hasimproved efficacy and reduced resistanceof the latest fluroquinolones (moxifloxa-cin, gatifloxacin) for gram-positive bacte-ria.10 There is no additional benefit of thenewer fluroquinolones against gram-negative bacteria compared with the olderfluoroquinolones.11,12 Oliveira, D’Azevedoand Francisco12 reported that ciprofloxa-cin is the most potent fluoroquinolone forPseudomonas spp; however, reports ofciprofloxacin-resistant Pseudomonas aerugi-nosa (CRPA) infections are also availablein ophthalmic literature.13,14 Combina-tions such as b-lactam and amikacin andamikacin and carbapenem are effective inmulti-drug-resistant Pseudomonas aerugi-nosa systemic infections.15,16 We believethat a similar adaptation to ophthalmicCRPA infections might be useful.

Pseudomonas is a known virulentcorneal pathogen associated with rapidliquefactive necrosis of the cornea.17

There are many methods by which acornea can be compromised, includingrefractive procedures like LASIK and

epi-LASIK. When bacterial keratitisoccurs, appropriate management includ-ing prompt diagnosis and treatmentbased on the sensitivity patterns of theorganism must be initiated. As demon-strated in the present case, severe cornealulcer due to Pseudomonas infectionafter LASIK surgery might necessitate atherapeutic keratoplasty. Additionally,with the emergence of a greater numberof drug-resistant microorganisms, there isa need for ocular adaptation of medica-tions used in systemic multi-drug-resistantPseudomonas aeruginosa infections.

REFERENCES

1. Solomon R, Donnenfeld ED, Azar DT, Holland EJ,Palmon FR, Pflugfelder SC,Rubenstein JB. Infec-tious keratitis after laser in situ keratomileusis:results of an ASCRS.Survey. J Cataract Refract Surg2003; 29: 2001–2006.

2. Chang MA, Jain S, Azar DT. Infections followinglaser in situ keratomileusis: an integration of thepublished literature. Surv Ophthalmol 2004; 49:269–280.

3. Reinhard T, Knorz M, Sundmacher R. Recurrentinterface infiltration with hypopyon after astig-matic laser in situ keratomileusis on a penetratingcorneal graft. J Cataract Refract Surg 2004; 30: 257–258.

4. Moshirfar M, Mirzaian G, Feiz V, Kang PC. Fourth-generation fluoroquinolone-resistant bacterialkeratitis after refractive surgery. J Cataract RefractSurg 2006; 32: 515–518.

5. Sharma N, Sinha R, Singhvi A, Tandon R.Pseudomonas keratitis after laser in situ kera-tomileusis. J Cataract Refract Surg 2006; 32: 519–521.

6. Vieira AC, Pereira T, de Freitas D. Late-onsetinfections after LASIK. J Refract Surg 2008; 24: 411–413.

7. Pallikaris IG, Kalyvianaki MI, Katsanevaki VJ, GinisHS. Epi-LASIK: preliminary clinical results of analternative surface ablation procedure. J CataractRefract Surg 2005; 31: 879–885.

8. Gamaly TO, El Danasoury A, El Maghraby A. Aprospective, randomized, contralateral eye com-parison of epithelial laser in situ keratomileusisand photorefractive keratectomy in eyes prone tohaze. J Refract Surg 2007; 23: S1015-S1020.

9. Smitha S, Lalitha P, Prajna VN, Srinivasan M. Sus-ceptibility trends of pseudomonas species fromcorneal ulcers. Indian J Med Microbiol 2005l; 23:168–171.

10. Mather R, Karenchak LM, Romanowski EG, Kow-alski RP. Fourth generation fluoroquinolones:new weapons in the arsenal of ophthalmic antibi-otics. Am J Ophthalmol 2002; 133: 463–466.

11. Kowalski RP, Dhaliwal DK, Karenchak LM,Romanowski EG, Mah FS, Ritterband DC, GordonYJ. Gatifloxacin and moxifloxacin: an in vitro sus-ceptibility comparison to levofloxacin, ciprofloxa-cin and ofloxacin using bacterial keratitis isolates.Am J Ophthalmol 2003; 136: 500–505.

12. Oliveira AD, D’Azevedo PA, Francisco W. In vitroactivity of fluoroquinolones against ocular bacte-rial isolates in São Paulo, Brazil. Cornea 2007; 26:194–198.

13. Chaudhry NA, Tabandeh H, Rosenfeld PJ, MillerD, Davis J. Scleral buckle infection withciprofloxacin-resistant Pseudomonas aeruginosa.Arch Ophthalmol 1998; 116: 1251.

14. Garg P, Sharma S, Rao GN. Ciprofloxacin-resistantPseudomonas keratitis. Ophthalmology 1999; 106:1319–1323.

15. Giamarellos-Bourboulis EJ, Grecka P, GiamarellouH. Comparative in vitro interactions of ceftazi-dime, meropenem, and imipenem with amikacinon multi-resistant Pseudomonas aeruginosa. DiagnMicrobiol Infect Dis 1997; 29: 81–86.

16. Lang BJ, Aaron SD, Ferris W, Hebert PC, Mac-Donald NE. Multiple combination bactericidalantibiotic testing for patients with cystic fibrosisinfected with multi-resistant strains of Pseudomo-nas aeruginosa. Am J Respir Crit Care Med 2000; 162:2241–2245.

17. Brown SF, Bloomfield SE, Tam WI. The corneadestroying enzyme of Pseudomonas aeruginosa.Invest Ophthalmol 1974; 13: 174–180.

Corresponding author:Professor Namrata SharmaDr Rajendra Prasad Centre forOphthalmic SciencesAll India Institute of Medical SciencesNew DelhiINDIAE-mail: namrata.sharma@gmail.com,namrata103@hotmail.com

Infection after epi-LASIK surgery Sharma, Jindal, Bali and Titiyal

© 2012 The Authors Clinical and Experimental Optometry 95.4 July 2012

Clinical and Experimental Optometry © 2012 Optometrists Association Australia 463