An analysis of the clinical behavior An analysis of the clinical behavior of mycotic keratitis caused by non of mycotic keratitis caused by non

sporing moldssporing molds

The authors have no financial interest The authors have no financial interest in the subject matter of this posterin the subject matter of this poster

Dr. Revathi RajaramanDr. Revathi RajaramanAravind Eye HospitalAravind Eye Hospital

CoimbatoreCoimbatore

PurposePurpose

A significant percentage of fungal isolates recovered from A significant percentage of fungal isolates recovered from keratitis patients fail to sporulate by standard laboratory keratitis patients fail to sporulate by standard laboratory methods.methods.

This group may consists of established ocular pathogens This group may consists of established ocular pathogens which behave differently due to unknown reasons and very which behave differently due to unknown reasons and very rare or newer species.rare or newer species.

This study analyzes whether keratitis caused by non This study analyzes whether keratitis caused by non sporulating filamentous fungi whose species could not be sporulating filamentous fungi whose species could not be identified, differ in clinical features and response to standard identified, differ in clinical features and response to standard antifungal treatment from that caused by species identified antifungal treatment from that caused by species identified dematiaceous and hyaline fungi. dematiaceous and hyaline fungi.

MethodsMethods

A retrospective analysis of data collected from case records of culture A retrospective analysis of data collected from case records of culture proven mycotic keratitis between January 2007 December 2008 to assess proven mycotic keratitis between January 2007 December 2008 to assess

- The incidence of NSM keratitis- The incidence of NSM keratitis

- The casual relationship between trauma, injuring agents and previous - The casual relationship between trauma, injuring agents and previous treatmenttreatment

- Presenting clinical features and response to standard treatment in - Presenting clinical features and response to standard treatment in comparison to those of species identified fungal isolatescomparison to those of species identified fungal isolates

Multiple logistic regression analysis was used to find the casual Multiple logistic regression analysis was used to find the casual relationship to non-sporulation and associated clinical features and relationship to non-sporulation and associated clinical features and response to therapy was analyzed by Pearson Chi – Squareresponse to therapy was analyzed by Pearson Chi – Square

Species Identified & Unidentified by Species Identified & Unidentified by sporesspores

Dematiaceous Dematiaceous FreqFreq--------------------------------------------------------------------NSDM (non sporing) NSDM (non sporing) 2020Curvularia Curvularia 14 14 Bipolaris Bipolaris 1919Alternaria Alternaria 7 7Cladosporium Cladosporium 4 4 Collectotrichium Collectotrichium 3 3Exerohilum Exerohilum 8 8Lasidiplodia Lasidiplodia 5 5 Nigrosporen Nigrosporen 2 2Aureobasidum Aureobasidum 1 1 Exophila Exophila 1 1-----------------+------------------- -----------------+------------------- TotalTotal 8484

Hyaline Hyaline Freq. Freq. --------------------------------------------------------------------------------NSHM ( non-sporing) NSHM ( non-sporing) 87 87 Fusarium Fusarium 237 237 Aspergillus Aspergillus 81 81 Neocosmospora Neocosmospora 1 1 Pencilium Pencilium 4 4 Scedosporium Scedosporium 2 2Trichothesium Trichothesium 2 2--------------+------------------------- --------------+------------------------- Total Total 414414

Colony morphology on the solid mediumColony morphology on the solid medium

Aspergillus Flavus Aspergillus Flavus Fusarium semitectumFusarium semitectum

Spore morphologySpore morphology

A.Flavus A.Flavus Fusarium semitectumFusarium semitectum

Slide culture LPCB Slide culture LPCB

Results - IncidenceResults - Incidence125, 21%

469, 79%

NSM

SM

FUNGUSFUNGUS FREQFREQ PERCENTPERCENT

NSMNSM 125125 21.0421.04

SMSM 469469 78.9678.96

TotalTotal 594594 100100

ISOLATESISOLATES FRQUFRQU PERCENTPERCENT

NSDMNSDM 2323 22.5522.55

SDMSDM 7979 77.4577.45

TotalTotal 102102 100100

23, 23%

79, 77%

NSDM

SDM

IsolatesIsolates FreqFreq PercentPercent

NSHMNSHM 102102 20.8620.86

SHMSHM 387387 79.1479.14

TotalTotal 489489 100100387, 79%

102, 21%

NSHM

SHM

NSM-nonsporing mold,SM-sporing mold, NSDM-non-sporing dematiaceus, NSHM-Nonsporing Hyaline

Causative clinical factors for non-sporulationCausative clinical factors for non-sporulation

Variable Uni variate Multivariate  

OR (95% CI) P-value 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 There is no casual relationship between relationship between trauma, injuring trauma, injuring agents and previous agents and previous treatmenttreatment

Multiple logistic Multiple logistic regression analysis of regression analysis of these features, time these features, time lag before lag before consultation and consultation and clinical features also clinical features also failed to show any failed to show any significancesignificance

Multiple Logistic Regression - Presenting Clinical Multiple Logistic Regression - Presenting Clinical FeaturesFeatures

Non-Sporing & Sporing Hyaline molds

Non-Sporing & SporingNon-Sporing & Sporing Dematiaceous Dematiaceous Molds Molds

In non-sporulating dematiaceous group hypopyon was significantly a rare presentation (P-In non-sporulating dematiaceous group hypopyon was significantly a rare presentation (P-0.003, OR 0.197 95 CI 0.067-0.579). Among hyaline fungi there was no difference in clinical 0.003, OR 0.197 95 CI 0.067-0.579). Among hyaline fungi there was no difference in clinical featuresfeatures

Response to Antifungal treatmentResponse to Antifungal treatmentHEALED

368 70.0

158 30.0

526 100.0

Healing

Non Healing

Total

Frequency Percent

Crosstab

Count

12 8 20

58 13 71

70 21 91

UID

Demataceous Fungi

UID - DemataceousFungus

Total

Healing Non Healing

HEALED

Total

UID - Dematiaceous Fungus HEALED ( P value – 0.042 )

*Unidentified demateaceous (NSDM)

* UIH - Hyaline Fungus HEALED ( P value – 0.294 )

Crosstab

Count

58 33 91

237 104 341

295 137 432

UIH

Hyaline Fungi

UIH - HyalineFungus

Total

Healing Non Healing

HEALED

Total

* Unidentified Hyaline (NSHM)

Nonsporing Dematiaceous responded relatively better to therapy Nonsporing Hyaline molds responded similar to other hyaline fungi

Discussion Discussion

Non-sporulating filamentous fungi constitute Non-sporulating filamentous fungi constitute significant percentage among keratitis pathogens significant percentage among keratitis pathogens

No clinically significant causative factor for non-No clinically significant causative factor for non-sporulation was found sporulation was found

Non-sporulating dematiaceous group presented rarely Non-sporulating dematiaceous group presented rarely with hypopyon and healed better with hypopyon and healed better

But hyaline fungi did not showed any difference in But hyaline fungi did not showed any difference in presentation and outcomepresentation and outcome

ConclusionConclusion

Non-sporing ocular fungal pathogens constitute an Non-sporing ocular fungal pathogens constitute an interesting area of researchinteresting area of research

Polymerase Chain Reaction based DNA sequencing Polymerase Chain Reaction based DNA sequencing of the ocular fungal isolates identified some newer of the ocular fungal isolates identified some newer emerging pathogens in addition to established onesemerging pathogens in addition to established ones

The reason for their non-sporing nature is not clearThe reason for their non-sporing nature is not clear Their sensitivity to the existing antifungal agents is Their sensitivity to the existing antifungal agents is

yet to be studiedyet to be studied Clinically they behave almost similar to the Clinically they behave almost similar to the

established filamentous fungiestablished filamentous fungi

ReferencesReferences

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La´szlo´ Kredics, Ja´nos Varga, Sa´ndor Kocsube´, Revathi Rajaraman et al, Infectious Keratitis Caused by Aspergillus tubingensis. Cornea. 2009 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