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Dr. Revathi Rajaraman Aravind Eye Hospital Coimbatore

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1 An analysis of the clinical behavior of mycotic keratitis caused by non sporing molds
Dr. Revathi Rajaraman Aravind Eye Hospital Coimbatore The authors have no financial interest in the subject matter of this poster

2 Purpose A significant percentage of fungal isolates recovered from keratitis patients fail to sporulate by standard laboratory methods. This group may consists of established ocular pathogens which behave differently due to unknown reasons and very rare or newer species. This study analyzes whether keratitis caused by non sporulating filamentous fungi whose species could not be identified, differ in clinical features and response to standard antifungal treatment from that caused by species identified dematiaceous and hyaline fungi.

3 Methods A retrospective analysis of data collected from case records of culture proven mycotic keratitis between January 2007 December 2008 to assess - The incidence of NSM keratitis - The casual relationship between trauma, injuring agents and previous treatment - Presenting clinical features and response to standard treatment in comparison to those of species identified fungal isolates Multiple logistic regression analysis was used to find the casual relationship to non-sporulation and associated clinical features and response to therapy was analyzed by Pearson Chi – Square

4 Species Identified & Unidentified by spores
Colony morphology on the solid medium Spore morphology A.Flavus Fusarium semitectum Aspergillus Flavus Fusarium semitectum Dematiaceous Freq NSDM (non sporing) Curvularia Bipolaris Alternaria Cladosporium Collectotrichium Exerohilum Lasidiplodia Nigrosporen 2 Aureobasidum 1 Exophila 1 Total 84 Slide culture LPCB Hyaline Freq. NSHM ( non-sporing) 87 Fusarium Aspergillus 81 Neocosmospora 1 Pencilium 4 Scedosporium 2 Trichothesium 2 Total 414

5 Results - Incidence Isolates NSHM SHM Total Freq Percent 102 20.86 387
FRQU PERCENT NSDM 23 22.55 SDM 79 77.45 Total 102 100 FUNGUS FREQ PERCENT NSM 125 21.04 SM 469 78.96 Total 594 100 Isolates Freq Percent NSHM 102 20.86 SHM 387 79.14 Total 489 100 NSM-nonsporing mold,SM-sporing mold, NSDM-non-sporing dematiaceus, NSHM-Nonsporing Hyaline

6 Causative clinical factors for non-sporulation
Variable Uni variate Multivariate OR (95% CI) P-value Injury with veg-mater 0.69 (0.45 – 1.08) 0.105 0.47 (0.14 – 1.57) 0.220 Injury with nonveg-mater 1.19 (0.74 – 1.92) 0.474 0.71 (0.22 – 2.24) 0.554 No injury 1.10 (0.73 – 1.66) 0.654 0.64 (0.20 – 2.02) 0.441 Injury with unknown object 1.11 (0.50 – 2.48) 0.791 0.78 (0.26 – 2.34) 0.662 Superficial plaques 0.94 (0.56 – 1.59) 0.816 0.70 (0.34 – 1.42) 0.320 Feathery edged infiltrates 1.02 (0.64 – 1.60) 0.945 0.72 (0.35 – 1.47) 0.361 Full thockness abscess 0.80 (0.48 – 1.33) 0.389 0.77 (0.37 – 1.58) 0.471 Endothelial plaque 0.87 (0.52 – 1.45) 0.592 1.23 (0.68 – 2.22) 0.493 Hypopyon 0.66 (0.44 – 0.99) 0.047 0.68 (0.42 – 1.07) 0.098 Perforated ulcer 0.94 (0.30 – 2.90) 0.909 0.75 (0.21 – 2.61) 0.646 Antifungal 0.79 (0.53 – 1.21) 0.287 0.88 (0.54 – 1.42) 0.594 Antibiotic 1.08 (0.70 – 1.67) 0.724 1.22 (0.75 – 2.00) 0.422 Time lag before treatment 0.69 (0.46 – 1.05) 0.08 0.74 (0.48 – 1.16) 0.188 There is no casual relationship between trauma, injuring agents and previous treatment Multiple logistic regression analysis of these features, time lag before consultation and clinical features also failed to show any significance

7 Multiple Logistic Regression - Presenting Clinical Features
Non-Sporing & Sporing Dematiaceous Molds Non-Sporing & Sporing Hyaline molds In non-sporulating dematiaceous group hypopyon was significantly a rare presentation (P-0.003, OR CI ). Among hyaline fungi there was no difference in clinical features

8 Response to Antifungal treatment
UID - Dematiaceous Fungus HEALED ( P value – ) * UIH - Hyaline Fungus HEALED ( P value – ) *Unidentified demateaceous (NSDM) * Unidentified Hyaline (NSHM) Nonsporing Dematiaceous responded relatively better to therapy Nonsporing Hyaline molds responded similar to other hyaline fungi

9 Discussion Non-sporulating filamentous fungi constitute significant percentage among keratitis pathogens No clinically significant causative factor for non-sporulation was found Non-sporulating dematiaceous group presented rarely with hypopyon and healed better But hyaline fungi did not showed any difference in presentation and outcome

10 Conclusion Non-sporing ocular fungal pathogens constitute an interesting area of research Polymerase Chain Reaction based DNA sequencing of the ocular fungal isolates identified some newer emerging pathogens in addition to established ones The reason for their non-sporing nature is not clear Their sensitivity to the existing antifungal agents is yet to be studied Clinically they behave almost similar to the established filamentous fungi

11 References R. Bagyalakshmi, K. L. Therese, S. Prasanna, and H. N. Madhavan. Newer Emerging Pathogens of Ocular Non-Sporulating Molds (NSM)Identified by Polymerase Chain Reaction (PCR)-Based DNA Sequencing Technique Targeting Internal Transcribed Spacer (ITS) Region Current Eye Research 2008; 33:139–147 La´szlo´ Kredics, Ja´nos Varga, Sa´ndor Kocsube´, Revathi Rajaraman et al, Infectious Keratitis Caused by Aspergillus tubingensis. Cornea Sep;28(8):951-4 Srinivasan M, Gonzales CA, George C, et al. Epidemiology and aetiological diagnosis of corneal ulceration in Madurai, south India. Br J Ophthalmol. 1997;81:965–971. Srinivasan M, Fungal keratitis. Curr Opin Ophthalmol 2004 Aug;15:321-7


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