The document discusses fungal infections of the eye. It begins by providing an overview of various fungal infections that may affect the eye, including periocular fungal infections, mycoses of the anterior segment, and fungal endophthalmitis. It then focuses on specific types of fungal keratitis caused by organisms like Aspergillus, Fusarium, and Candida. The document discusses the epidemiology, pathogenesis, clinical features, and management of various ocular fungal infections. It also provides data on fungal keratitis prevalence from studies conducted in different parts of India.

1. I See Trees of Green

2. Red Roses Too

3. I See Them Bloom For Me & For You

4. And I Think To Myself , Such A Wonderful World

5. I See Skies Of Blue
And Clouds Of White

6. The Bright Sunny Days

7. The Dark Sacred Nights

8. And I Think To Myself
What A Wonderful World

9. Prevent trauma
Tears :
Lysozyme,
Lactoferrin,
ceruloplasmin,B
lysin, Complement
& Ig`s
Conjunctival
follicles &
leukocyte
defense

10. ANATOMY

11. ANATOMY
Rich vascular
supply

12. FUNGAL INFECTIONS OF THE EYE
Presenter: Dr. Vinaykumar Hallur
Moderator: Dr. M.R. Shivaprakash

13. 
Periocular Fungal Infections

Mycoses of the Anterior Segment of the Eye

Fungal Endophthalmitis

Laboratory diagnosis

Management

Experimental models

14. KERATOMYCOSIS





First described by Leber (Aspergillus species) in 1879
Major cause of blindness in Asia
Incidence low in Britain & North USA
6-53% of all cases of ulcerative keratitis in Asia
Can occur alone or coexist with a bacterial
infection(14.1%)
[Basak et al Indian J Ophthalmol. 2005 Jun;53(2):143]

Earlier phaeoid fungi (Dematiaceous) not considered to
be significant but now are important cause of
keratomycosis .

15. Rare

16. EPIDEMIOLOGY
PREVALENCE
North India
South India
Eastern India
Western India
North India : Aspergillus40% ,Fusarium
16%, Curvularia 8%, 1994- Chander et al.,
Aspergillus 35 %, Fusarium 23%, Acremonium
12%, 1993-Chander et al.
82.3%
46.1%
32.0%
38.9%
South India : 34.4% fungal keratitis,
Fusarium 2007 Bharathi et al, Fusarium
43%, Aspergillus 26%, 30.00% Fungi
keratitis in India isDematitiousof
25% 2003 – Bharathi et al
Total prevalence of fungal
total cases
Total prevalence of fungal keratitis in western 8.00%
countries
IJO Sep 2001

17. 
AGE
21 -50 YEARS

SEX
M>F

RESIDENCE

SOCIOECONOMIC STATUS

OCCUPATION
 SEASONS
(3:1)
RURAL >URBAN
LOW > HIGH
FARMERS, LABOURER.
AUTUMN, RAINY.
Cornea 2000; August:555-59

18. PREDISPOSING FACTORS
• Trauma
vegetable matter
metallic foreign body
sand/stone
• Chronic topical medication
• Diabetes Mellitus
• Topical or systemic corticosteroids
• Extended wear/bandage contact lens
• Penetrating keratoplasty
• Anterior uveitis
• Herpes simplex keratitis

19. ETIOPATHOGENESIS
Over 70 genera can cause mycotic keratitis
 Fungi of importance in microbial keratitis
 Moniliaceae
-- Aspergillus (90%) Most common cause in World
-- Fusarium(1%)Second most common cause
--Paecilomyces.
--Penicillium.
--Pseudallescheria.

Data in brackets from Dept of ophtahlmology, PGIMER

20. CONTD..
• Dematiaceae.
--Curvalaria. (2%)
--Alternaria.
--Phialophora.
--Bipolaris.
--Exserohilum.
--Cladosporium.
-- Colletotrichum
• Yeast.
--Candida. (2.5%)
--Cryptococcus
• Dimorphic fungi.
--Blastomyces.
--Coccidioides.
--Histoplasma.
--Sporothrix.

22. • PATHOGENESIS
-Breach in epithelium
-Compromised cornea
-Immunocompromised
Contact of fungal hyphae with cornea
Filamentous
Yeast

23. FUNGAL ADHERENCE

Filamentous Fibrinogen receptors on mature
conidia of aspergillus and fusarium

Yeast Integrin analogue, Fibronectin
receptor, Adhesive mannoprotn, Aspartyl
proteinase, Factor 6 , Endo. adhesions.

24. PENETRATION

Filamentous fungi: Parallel growth of hyphae to stroma, f/b
release of mycotoxins, proteolytic enzymes, soluble fungal
antigen

Yeast: Proliferate parallel & perpendicular to corneal stroma
f/b release of protease and lipase

25. HOST RESPONSE FILAMENTOUS
inablity of PMN,leucocyte cell for phagocytosis
destruction of corneal stroma
penetrate descement membrane
enterAC
accumulate around lens
seclusion of pupil
fungal glaucoma

26. HOST RESPONSE YEAST
inability of PMN cell to ingest pseudohyphae and hyphae
furstated phagocytosis by PMN
destruction of stroma
melting of cornea

27. CLINICAL FEATURES
•
•
•
•
•
Signs >> symptoms
Manifest within 24 – 48 hours
Patient present within 1st week
EARLY BI-MICROSCOPIC FINDING
Fine or coarse granular infiltrate within the epithelium
and anterior stroma
• Minimal stromal infiltrate
• Epithelial surface is dry rough textured, dirty gray in color

28. CONT………
• Epithelium may be intact or ulcerated.
• Pigmented and delicate ,feathery branching hyphae with
surrounding infiltrate
• Multifocal suppurative microabsscess or satellite lesion

29. CONTD….
• Advanced lesions
o Dense fibrinous material adhering to endothelium and iris
o Total stromal infiltrate and necrosis

30. CONTD…………..
•
•
•
•
•
•
•
Other signs
White ring (Wessely`s ring)
Conjunctival hyperemia
AC reaction
Hypopyon
endothelial plaque
Mild iritis

31. YEAST KERATITIS
• Risk Fatcors
• Previously compromised cornea
• SYSTEMIC DISEASE
Sjogren’s syndrome
Erythema multiforme
IgA deficiency
HIV
Endocrinopathy

32. CLINICAL FEATURE OF CANDIDA INFECTION
• Ulcer is small oval with expanding discrete sharply
demarcated ,dense yellow –white stromal suppuration
• Feathery margins are not seen

33. FUNGAL ENDOPHTHALMITIS

a suppurative inflammation of inner ocular coats
and their adjacent structure

with involvement of anterior chamber and
vitreous fluid,

caused by various fungal agents

34. FUNGAL ENDOPHTHALMITIS

Clinically two types

Endogenous due to hematogenous spread

Exogenous due to trauma or post operative

35. EPIDEMIOLOGY

The first description of endogenous fungal
endophthalmitis was by Dimmer in 1913

Candida endopthalmitis clinical entity in 1958

In U.S.A. compared to previous decades Endophthalmitis
Increase from last few decades.

Incidence is increasing because of modern medical
practices

USA 30 % candidemia(Last 3 decdes) develop
endopthalmitis, now there is a lower incidence because
of prophylacyic antifungals
CMR, October 2000, p. 662–685

36. PATHOGENESIS ENDOGENOUS

Multifactorial.

It is likely that sustained fungemia with even
saprophytic fungi can lead to endopthalmitis
Gupte et al -contaminant IV fluids,11 / 72 IV fluid samples culture
positive for fungi

At the time of initial infection with some
dimorphic, fungi, such as H. capsulatum & C.
immitis, unrecognized fungemia occurs and often
leads to endophthalmitis.

37. ENDOGENOUS
ENDOPHTHALMITIS
 Predisposing
factors

Systemic debilitating disease

Malignancy

IVDU

Chemotherapy

Systemic antibiotics

Alcoholism &

Diabetes

38. PATHOGENESIS ENDOGENOUS

More common in immunocompromised ie pts on
chemo or IV drug abuse

Marked trophism for eye because peculiar blood
supply of the eye.

39. PATHOGENESIS: EXOGENOUS

Occurs in immunocompetent people

Direct introduction of the organisms following

Surgery(Catarct removal with placement of IOL mainly
Candida spp)

Trauma(Mainly Fusarium spp. )

I/O spread from Fungal keratitis

40. EPIDEMIOLOGY

RACE – no racial preponderance

SEX – Male preponderance (3:1)

AGE – Young and middle age.

41. MORBIDITY
 Prognosis




depends upon
virulence of organism
extent of involvement
timing
mode of intervention
 Prompt
therapy following early diagnosis helps to
reduce visual loss
 Visual
outcome of aspergillus endo. is poor d/t
macular involvement.

42. AGENTS
Endogenous Endotphthalmitis

Candia albicans

Fusarium species

Aspergillus species

Histoplasma capsulatum

Coccidioides immitis

Blastomyces dermatitidis

Cryptococcus neoformnas

43. C. ALBICANS

M.C.C of endogenous endopthalmitis

Infection usually starts from Choroid and then spreads to
retina

Non candida albicans fungemia & endopthalmitis is increasing
and is concern because of antimicrobial resistance

44. CANDIDIAL ENDOPTHALMITIS
Current Eye Research, 1–11, Early Online, 2010

45. ASPERGILLUS ENDOPTHALMITIS

A. flavus second MCC

Spreads from lungs to eye

This is f/b A. fumigatus, A. niger, A. terreus, A.
glaucus , & A. nidulans .

46. CRYPTOCOCCAL ENDOPH.

Cryptococci spores survive in pigeons dropping

From lung, fungus – disseminated
haematogenesouly and can affect CNS causing
fungal meningitis & endophthalmitis in eye

Choroids is the probably first site of ocular
infections

47. AGENTS
Exogenous
Endophthalmitis
Aspergillus spp.
 C. albicans,C. glabrata, C. tropicalis, C. parapsilosis
 Paecilomyces spp.
 Fusarium spp.
 Acremonium spp.
 Curvularia spp.


48. PRESUMED OCULAR
HISTOPLASMOSIS

Occurs in immunocompetent individuals

Recognized by presence of multiple atrophic chorioretinal
scars w/o vitreous or aqueous humor inflmn.

Affect 2,000 new individuals a year in areas of endemicity and
in some cases may lead to visual loss and blindness

Arises from hematogenous spread

Not detectable in the scars of POH

Strong epidemiological evidence, principally deriving from skin
test surveys, linking the scars to histoplasmosis

49. CLINICAL FEATURES
Symptoms
Visual loss
 Pt. may be asymptomatic if the lesion is in the
peripheral retina
 Red eye.
 Photophobia.
 Pain.
 Floaters.
 Scotoma


50. 
Many have a classical appearance with
progressive granulomatous uveitis
 diffuse retinitis
 deep vitreous abscess.


Time to make diag. from onset of symptoms, 3 d to
4 months.

51. DEPARTMENTAL DATA

53. PERIOCULAR INFECTIONS
Agent
 Palpebral
Aspergillosis
Blastomycosis
involvement
No of cases in literature
2
12
As a part of generalized or local disease
3
C. albicans
 First reported case  1922 case of sporotrichosis
6
Coccidioidomycosis

3
Cryptococcus spp.
 Tinea faciale
11
Dermatophyte
 Aspergilloma, sporotrichosis  Chalazion
5
Paracoccidioidomycosis
7
Rhinosporidiosis
 Blastomycosis, Coccidioidomycosis  Basal cell carcinoma
5
Sporothrix spp.

54. INFECTIONS OF THE LACRIMAL GLAND

Fungi found to account for only 5% of infections .

14% of cases of congenital dacryocystitis

Principally Aspergillus spp. and C. albicans implicated

Epiphora is only clinical finding

Lid edema, conjunctival injection, and swelling in the
medial canthus; pressure over the area usually results in
a purulent discharge through the lower punctum
Thomas, CMR, Oct 2003,

55. FUNGAL INFECTIONS OF ORBIT
Proximity of sinuses to orbit, susceptible host & pathogen
 Zygomycosis

Rhinoorbitocerebral : one-third to one-half of all cases,
Incidence increasing
 Major risk factor : uncontrolled diabetes mellitus(70% DKA)
 Other predisposing factors







Chronic alcoholism
Renal transplantation
Hematological malignancies
Steroid therapy
Breach of skin
Starts with symptoms consistent with sinusitis Bloody nasal
discharge  Diplopia and loss of vision
Chakrabarti et al., 2006

56. INFECTIONS OF ORBIT

Invasive aspergillosis
 Increased frequency infection :widespread prophylaxis with
fluconazole
[VanBurikJH et al. The effect of prophylactic fluconazole on the clinical Spectrum of fungal diseases
in bone marrow transplant recipients with special attention to hepatic
candidiasis.Medicine(Baltimore) 1998;77:246−54.]

Exact prevalence of invasive aspergillosis in India is not known
[Chakrabarti et al , Japanese Journal of Medical Microbiology vol 49, 165-72, 2008]

57. INVASIVE ASPERGILLOSIS

Other fungi mimicking aspergillosis
Bipolaris spp.
 Alternaria spp.
 Curvularia spp.
 C. immitis
 B. dermatitidis
 Histoplasma spp.
 Penicillium spp.


C/F
orbital inflammation & a red proptotic eye with or without
associated pain
 ophthalmoplegia may develop
 Embolization of vessels of the optic nerve, or direct
involvement of the nerve may occur


58. FUNGAL CONJUNCTIVITIS




Can occur indepently or with keratomycosis
Clinically rare entity
Fungi may be present without causing inflammation in~
25% pts
Topical application tetracycline X 4 wks increased
prevalence 28.7%
[Nema, H.V., O.P. Ahuja, A. Bal and L.N. Mohapatra, Effects of topical corticosteroids
and antibiotics on mycotic flora of conjunctiva. Am. J. Ophthal., 1968. 65: p. 747–750].

Topical applications of corticosteroids X 3 wks increase
prevalence of fungi 18.8-67%
[Mitsui, Y. and J. Hanabusa, Corneal infections after cortisone therapy.
Br. J.Ophthal., 1955. 39: p. 244–250.]


C. albicans follows steroid LA  Pseudomembrane
Other organisms Aspergillus, Blastomycosis, Sporothrix,
Coccidiodomycosis

59. EXPERIMENTAL MODELS FK

Albino, wild rabbit , Dutch belted rabbit

Previously immunocompromised


Fractionated cobalt whole-body radiation

administration of antilymphocyte serum


corticosteroids locally or systemically
alloxan-induced diabetes
Intra lamellar injection or Superficial inoculation of
spore suspension

60. CONTD..

IL inoculation :

C. albicans, C. krusei, C. tropicalis, C. pseudotropicalis,
Aspergillus spp., Cephalosporium spp., F. solani, Lasiodiplodia sp.

Superficial inoculation:

C. albicans, C. tropicalis, C. pseudotropicalis, Aspergillus spp.,
Allescheria boydii, Cephalosporium spp., Geotrichum sp.

Antibacterial prophylaxis & use of characterized strain
ensures reproducibilty.

IO penetration of ketokonazole in rabbit has been tried
as a therapeutic modaliities

61. OTHERS

Mice
BALB/c mice
 ip cyclophosphamide 180 mg/kg 1,3, & 5d
 Scarified corneas /keratoplasty rat cornea in b/w space
 topically inoculated
 Easy handling


Rat
Wistar rats or Lewis rats
 Suitable size & immune response
 Size of eyes better surgical manipulation


Pigs


Large size, ease of fitting contact lens
Owl monkeys

Not better than Rabbit keratomycosis model

62. ENDOPHTHALMITIS MODELS

Rabbits
Both immunocompetent and immunocompromised rabbits are used
 Used mainly for endogenous endophthalmitis
 0.5 ml of 2 X 107 org/ ml into auricular vein
 intravitreal inoculation of 1,000 CFU of susceptible C. albicans

Junko et al Jpn. J. infect. Dis., 60, 33-39, 2007

Mice
Fusarium solani in immunocompetent mice
 Inocula of 5 x 10(6) conidia
 injected into the lateral tail vein

Mayayo et al Med Mycol. 1998 Oct;36(5):249-53

64. DIAGNOSIS

History

Physical examination

Detailed examination of the affected

High risk of suspicion

65. LABORATORY DIAGNOSIS

Sample collection and transport






Biopsy
Corneal scraping, corneal button
AC tap
Vitreous tap
Fluids
Lens

Swabs not encouraged

Sterile leak proof container ASAP

Delay 4°C with exception of blood and vitreous (30-37°C ) &
swab (15%)

66. SAMPLES

Detailed examination of affected eye using slit lamp

Tissues diagnostic material harvested by
experienced ophthalmologist after LA or SA
Biopsy
 Scraping :15 Bard – parker surgical blade from the base &
margin(thoroughly) of ulcer aseptically or Kimura’s platinum
spatula
 Impression smear(Jain et al 2006 – PGIMER, Chandigarh –
equally sensitive and specific as Scrappings)
 Vitreous tap 300 microL using 23 G needle
 Aqeous tap 200 microL using 23 G needle


67. CONVENTIONAL TECHNIQUES

Direct microscopy
Rapid and cost effective
 10% KOH preparation
 Gram & Geimsa stain
 Calcoflour Stain – Easy and fast
 H&E, GMS, PAS, cytologic preparation


Culture
SDA, Blood agar,
 CHROM agar


Susceptibility testing

According to CLSI guidelines

68. CONVENTIONAL

Nonspecific fluorescent stain – {calcoflour
white, blankophor, uvitex 2B} –

used in tissue sections and

cytopathologic preparation of rapid diagnosis of mycotic infections.

Chander et al. Sensitivity of Calcofluor white – 95.2% compared to
71.4 % for KOH and culture.

fluorescent microscope

wavelength of 365 nm.

Acridine orange staining – useful in early diagnosis of
keratomycosis

PAS (Periodic acid schiff) stain can also use.

69. CULTURE

Corneal scraping inoculated on agar plate as a ‘C’ or ‘S’
shaped streak incubated at 25 & 37°C X 4wks

Fungal growth in the form of the streak ensure that the
growth is from the inoculum / specimen rather than a
laboratory contaminant.

Two sets of SDA with antibiotic, inoculated and incubated
at 250 C & 370C separately x 4 wks.
Keeping a possibility of dimorphic fungi

70. CULTURE

Vitreous fluid inoculated on routine fungal culture
media .

Vitreous sample should be concentrate either by


centrifugation
Millipore filtration

71. CULTURE

All the culture checked
everyday during first week and
 twice a week during next 3 week weeks.


Positive culture are more convincing

when growth is obtained on more than one occasion.

72. CONVENTIONAL TECHNIQUES

Serological techniques

Diagnosis of Histoplasmosis, Blastomycosis

73. MOLECULAR TECHNIQUES

PCR based detection methods

PCR
Rapid molecular identification of fungal pathogens in corneal samples from suspected
keratomycosis cases. J Med Microbiol. 2006 Nov;55(Pt 11):1505-9.

PCR - SSCP
Sensitive and rapid polymerase chain reaction based diagnosis of mycotic keratitis
through single stranded conformation polymorphism. Am J Ophthalmol. 2005
Nov;140(5):851-857.

Nested PCR
Comparative study of Gram stain, potassium hydroxide smear, culture and nested PCR in the
diagnosis of fungal keratitis. Ophthalmic Res. 2010;44(4):251-6.

74. MOLECULAR TECHNIQUES

PCR-RFLP
Diagnosis of Aspergillus fumigatus endophthalmitis from formalin fixed paraffinembedded tissue by polymerase chain reaction-based restriction fragment
length polymorphism Indian J Ophthalmol. 2008 Jan-Feb;56(1):65-6.

Real time quantitative PCR
Detection and quantification of pathogenic bacteria and fungi using
real-time polymerase chain reaction by cycling probe in patients with
corneal ulcer. Arch Ophthalmol. 2010 May;128(5):535-40.

75. PRINCIPLES OF TREATMENT

As with any other fungal infection , look & treat for
any predisposing illness

Confirm lab diagnosis

Look for and treat any superadded infection

Remember

Poor penetration of antifungal drugs

Corticosteroids are contraindicated

Use both surgical and medical approach whenever needed

Close follow up is required

76. FUNGAL KERATITIS

Superficial (early keratitis):
Topical natamycin (5%) (hyphae)
 Topical 0.15% amphotericin B or topical fluconazole (yeasts)
 Debridment of the epithelium


Deeper and larger lesions:
Subconjunctival or intravenous miconazole
 Ketoconazole, itraconazole, fluconazole or voriconazole (p.o.)
 Intracameral amphotericin B


Surgical treatment:
Cyanoacrylate tissue adhesive
 Amniotic membrane transplantation
 Penetrating keratoplasty


77. ENDOGENOUS
ENDOPHTHALMITIS

Systemic antifungal agents: Fluconazole,
voriconazole (azole compounds)

Systemic antifungal agents: Amphotericin B:
Parenteral ± intravitreal

Pars plana vitrectomy

78. EXOGENOUS ENDOPHTHALMITIS



Intraocular (intracameral ± intravitreal) amphotericin B
Intravitreal voriconazole or miconazole
Subconjunctival antifungal agents: when associated with
keratitis

Systemic antifungal agents:
fluconazole, ketoconazole, voriconazole, itraconazole, m
iconazole, and amphotericin B: important in
immunocompromised patients

Pars plana vitrectomy

79. MUCORMYCOSIS

Radical surgery+ antifungal therapy + correcting
underlying conditions

Amphotericin B Ist DOC(Amphotericin B given IV at
a daily dose of 1.0-1.5 mg/kg infused during 2-4 hr
for a total of 1-4 g)

Lipid formulations of amphotericin B alternative
Ferri: Practical Guide to the Care of the Medical Patient, 8th ed

80. INVASIVE ASPERGILLOSIS

Voriconazole 6 mg/kg IV q12h for 2 doses, then
4 mg/kg q12h PO Rx for adults is 200 mg bid or
4 mg/kg bid.

Caspofungin in pts who fail to respond to or are
unable to tolerate other antifungal drugs. The
recommended dosage is 70 mg on the first day and
50 mg qd thereafter given as a single dose IV over
1 hr.
Ferri: Practical Guide to the Care of the Medical Patient, 8th ed

81. Even though we cannot live forever, let our eyes live and give
sight for the needy! I have pledged my eyes, you can do that too..