chief author: chintan malhotra co-authors: arun k jain, partha chakma advanced eye centre, post...

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Fungal Keratitis and Endophthalmitis After Artificial Cornea Implantation in a Patient With Coexisting Onychomycosis: A Photographic Documentation Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh, India The authors have no financial interest to disclose.

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Page 1: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Fungal Keratitis and Endophthalmitis After Artificial Cornea Implantation in a Patient With Coexisting Onychomycosis: A Photographic Documentation

Chief Author: Chintan MalhotraCo-Authors: Arun K Jain, Partha Chakma

Advanced Eye centre, Post Graduate Institute of Medical Education and ResearchChandigarh, India

The authors have no financial interest to disclose.

Page 2: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Introduction

Keratoprosthesis implantation is increasingly being performed world wide for patients with severe corneal blindness, who are at increased risk of graft failure after a conventional full thickness corneal transplant.1

The ‘Auro K Pro’ is a keratoprosthesis made in India , based on the Boston Type 1 keratoprosthesis design.

The most favourable indication for implantation of the Type 1 Boston K Pro remains previous multiple failed keratoplasties. 2 With an increased safety profile , it is now also being used as a primary procedure in high risk cases, without a history of antecedent unsuccessful corneal grafting.3

Fungal infections after K Pro implantation are being reported with increasing frequency in recent years.4-8 These have partly been attributed to the prolonged use of broad spectrum antibiotics and therapeutic contact lenses after K pro implantation.4

Though the overall rate of fungal infections in eyes implanted with the Boston K Pro was found to be 2.6% (8 of 300 eyes) in a multicentric trial,5 these were the cause of K pro failure in 42.8% (8 of 21 eyes) cases in this series. In contrast bacterial endophthalmitis was reported as a cause of failure in only 4.7% (1 of 21 failed cases) in the same series.5 Thus fungal infections are a significant emerging complication of K Pro use.

Page 3: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Purpose

To document the occurrence , subsequent management, course and outcome of fungal

keratitis and endophthalmitis in a patient implanted with the ‘Auro K Pro’ keratoprosthesis

having coexisting onychomycosis.

Methods

Serial Photographic demonstrating the salient clinical findings are shown in subsequent

slides for a patient who underwent implantation with an ‘Auro K Pro’

which is based on the Boston Keratoprosthesis tyoe 1 design :

Size of carrier graft taken was – 9mm

Size of PMMA backplate of the Auro K Pro- 8.5 mm with a 3 mm central hole

Page 4: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Clinical Profile

OD OS

70 year old male patient from a rural, lower income socioeconomic background living in a predominantly agricultural community , presented with bilateral corneal opacification and vascularization secondary to trachoma .

Visual acuity OD PL+, accurate projection of rays in all 4 quadrants, OS No perception of lightIntraocular pressure ( Goldmann Applanation tonometry) OD 16 mmHg OS 40 mm Hg B Scan of right eye: Retina on, No lens or IOL shadow seen, Axial length 23.5 mm

Co -existing fingernail onychomycosis for which patient had taken 6 months of systemic antifungal therapy (Itraconazole 100 mg BD) off andon .

Page 5: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Aphakic Auro K Pro (+61.5 D) + bandage contact lens (BCL) implanted OD

Surgery was uneventful except for presence of some bleed from the iris which was adherent to the cornea. As patient was aphakic from a cataract surgery performed 20 years ago, the blood trickled into the vitreous cavity.

Topical vancomycin 5% was started six times/day in addition to moxifloxacin 0.5% six times/day and prednisolone acetate 1% QID. Epithelial defect was present initially on the carrier graft but healed by the 10th post op day.

Visual acuity OD improved to 20/80 by the end of the third week. Patient was called for follow up after 3 weeks.

Page 6: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Follow up in the sixth post operative week

Patient came for follow up as scheduled, was asymptomatic, had no complaints of decreased visual acuity.BCL was missing. White thread like deposits were present on the back of the carrier graft superiorly ( Figure A) . No infiltrates were present on the anterior surface.

•Epithelial defect was present on carrier graft (Figure B)

Whitish fluffy ‘mulberry like deposits’ were also noted on the back of the stem of the keratoprosthesis (Fig C).

No vitritis was noted, media clarity remained grade 1with a good view of the fundus.

Clinical picture was suggestive of fungal keratitis. Topical steroids were stopped.Topical + systemic antifungals were started (G. Amphoterecin B 0.15 % 1 hourly +G Natamycin 5% 1 hourly) and Tablet Fluconazole 200 mg BD. Topical vancomycin was continued.

Patient was advised admission to monitor progress which he refused and came for follow up 3 days later.

A B C

Page 7: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

3 days after starting anti fungals

Visual acuity had decreased from 20/80 to 20/400.An increase was noted in the infiltrates at the back of the cornea and the stem of the optic. (Fig A). Significant vitritis was present. Media clarity had decreased to grade 3 with a faint view of the disc and fundus (Fig. B)In view of the clinical picture , a presumptive diagnosis of fungal keratitis progressing to fungal endophthalmitis was made.Intravitreal Amphotericin B (5µgms/0.1ml) + dexamethasone ( 400µgms/ 0.1 ml) + moxifloxacin (500 µgms/0.1ml))was given and the vitreous specimen subjected to microbiological examination and polymerase chain reaction (PCR) for pan bacterial and pan fungal genome.Gram stain, KOH wet mount and culture from the vitreous sample were negative.Panfungal PCR of the vitreous sample was strongly positive (Fig. C, sample No 537, lane 2)

A B C

Page 8: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Media clarity started improving 48 hrs after the first intravitreal injection. Fungal colonies at back of optic stem did not show significant resolution (Fig A) .Corneal infiltrates also became more confluent and extended from 7’o clock to 3’o clock around the front plate of the optic (Fig. B- black arrows)

Repeat intravitreal amphotericin B + dexamethasone was given 72 hours after the first injection as the eye was unicameral and the corneal infiltrates at the back of the optic stem were not showing sufficient resolution. Additionally Amphotericin B 5µgms/0.1ml was injected intrastromally into the carrier graft around the edge of the infiltrates ( Fig. B- dotted line)

Over the course of the next 2 weeks fungal colonies at the back of the optic stem and the infiltrates of the carrier graft corneal stroma started resolving ( Fig. A and B- insets). Visual acuity improved from 20/400 to 20/200.

A B

Page 9: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Though the keratitis and endophthalmitis resolved ,an epithelial defect persisted 3600 around the anterior plate of the K pro optic stem , with significant thinning of carrier graft in some areas.

To deal with this cryopreserved amniotic membrane grafting ( inlay + overlay) was done subsequently (Fig. A)

A B

The patient remained stable for the next month with a visual acuity of 20/200, healing of the epithelial defect, vascularization of the carrier graft, and resolution of the keratitis and endophthalmitis. Some inflammatory vitreous membranes persisted for which he was advised close follow up.The patient however missed a scheduled follow up and 3 months later reported with decreased visual acuity when he was detected to have developed an inoperable closed funnel retinal detachment (Fig. B- arrow).

Final Outcome / Result

Page 10: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

The rate of fungal colonization of the ocular surface in K Pro eyes has been reported to be approximately 10%. Candida has been implicated as being the most common organism to cause surface colonization (C.parapsilosis, C albicans). Surveillance cultures have however not reported to be useful in predicting subsequent development of infection in keratoprosthesis eyes.4

Barnes et al4 have reported that cases of fungal infection show signs of early colonization of the contact lens or infection of the cornea days before endophthalmitis onset hence giving time to prevent deeper infection. Consequently in western literature the visual outcome in cases of fungal infection in KPro eyes has been reported to be good in most cases in contrast with the very poor visual outcome of bacterial endophthalmitis cases.

Experience from the Indian subcontinent , though limited has however been different. Jain et al6 have reported 2 cases of fungal keratitis and endophthalmitis where one eye was eviscerated and the other lost potential for useful vision. Aspergillus fumigatus was cultured from one case while the other showed septate hyphae on KOH wet mount.

Our case also had a poor outcome inspite of aggressive management and initial resolution. A lack of adherence to scheduled follow ups possibly compromised the final outcome as the inflammatory vitreous membranes progressed to a total retinal detachment.

Discussion

Page 11: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

Though in our case we could not identify the causative fungus (as the infiltrates were initially limited to the back of the carrier graft and hence scrapings could not be taken ) the fluffy, mulberry like fungal colonies seen on the back of the stem of the Auro K pro, resemble the clinical description of candida deposits described by Barnes et al4 on the soft contact lens covering the keratoprosthesis in their case.

Multiple factors probably contributed to the development of fungal keratitis and endophthalmitis in our case: - environment- the patient lived in a predominantly agricultural area and belonged to the lower socioeconomic strata probably accounting for the poor compliance and delay in seeking medical care. - presence of onychomycosis may have been a predisposing factor. Candida and nondermatophytic molds are frequently the causative agents of fingernail infections in tropics and in areas with a hot and humid climate.9,10

Outcomes after fungal keratitis/endophthalmitis in K Pro eyes in the developing countries like India, may be much more devastating as compared to those in the western world. An interplay of environmental (e.g hot and humid climate)and socioeconomic factors ( predominant involvement in agricultural activities , lack of adequate financial resources, lack of easy access to medical care, delay in seeking medical care) may be responsible for this .

Measures like frequent changing of the contact lens, and use of topical povidone iodine wash when the patient follows up in the hospital may help in reducing the incidence of these devastating infections. Prophylactic long term use of topical antifungals is an area which should be explored further in the developing nations.

Conclusion

Page 12: Chief Author: Chintan Malhotra Co-Authors: Arun K Jain, Partha Chakma Advanced Eye centre, Post Graduate Institute of Medical Education and Research Chandigarh,

References

1. Ilhan-Sarac O, Akpek EK. Current concepts and techniques in keratoprosthesis. Curr Opin Ophthalmol. 2005;16:246–250.

2. Yaghouti F, Nouri M, Abad JC, et al. Keratoprosthesis: preoperative prognostic categories. Cornea. 2001;20:19-23.

3. Aldave AJ, Kamal KM, Vo RC et al. The Boston Type I Keratoprosthesis. Improving Outcomes and Expanding Indications. Ophthalmology 2009;116:640–651.

4. Barnes SD, Dohlman CH, Durand ML. Fungal colonization and infection in Boston keratoprosthesis. Cornea. 2007;26:9–15.

5. Ciolino JB, Belin MW, Todani A et al. Retention of the Boston Keratoprosthesis Type 1: Multicenter Study Results. Ophthalmology 2013;120:1195–1200

6. Jain V, Mhatre K, Shome D, Pineda R. Fungal Keratitis with Type 1 Boston keratoprosthesis: Early Indian experience. Cornea 2012: 31: 841-43

7. Chan CC, Holland EJ. Infectious Keratitis after Boston Type 1 Keratoprosthesis implantation. Cornea 2012; 31: 1128-1134

8. Behlau I, Martin KV, Martin JN et al. Infectious endophthalmitis in Boston Keratoprosthesis: incidence and prevention. Acta Ophthalmologica 2014;92: e546-555

9. Chi CC, Wang SH, Chou MC . The causative pathogens of onychomycosis in southern Taiwan". Mycoses 2005; 48 413–20

10. Kaur R, Kashyap B, Bhalla P. Onychomycosis - epidemiology, diagnosis and management. Indian J Med Microbiol 2008;26:108-16