Fungal lesions of the eye

fungal eye lesions.

1. Fungal INFECTIONS of the eye Dr.Vaibhav.K

2. Fungi are ubiquitous organisms found in soil and decaying organic matters. They are generally saprophytes but becomes pathogens to cause opportunistic infection when there is a decline in the immunity local or systemic.

3. The fungi contain rigid cell wall made up of polysaccharide and chitin. They have cytoplasmic membrane that contain sterol. They are eukaryotes, i.e. contain true nuclei with nuclear membrane, paired chromosomes, mitochondria, ribosome and food reserve. They may be unicellular or multicellular . Pleomorphism is common. They propagate asexually, bisexually or by combined methods.

4. Morphological Classification of Fungi Four classes: 1. Yeast 2. Yeast-like fungi 3. Moulds 4. Dimorphic fungi The yeasts are unicellular, spherical organisms that multiply by budding. The only pathogenic yeast is cryptococcus neoformis . Rarely it causes endogenous endophthalmitis . Yeast-like fungi: Some of them develop partially as yeasts and others by pseudomycellia which are chains of elongated budding cells joined end-to-end. The example is Candida albicans

5. Moulds: These are mycelial or filamentous fungi. The moulds consist of cylindrical branches called hyphae . Entangled mass of hyphae are called mucelium . Dimorphic fungi: These fungi assume two different shapes at different temperature in soil and in culture. They are moulds but in host body they appear like yeast. Most fungi causing systemic infections are dimorphic.

6. fungi causing ocular infection [1]Hyaline filamentous fungi [2] Dematiaceous fungi [3] Yeasts and zygomycetes [4] Thermally dimorphic fungi [5] Fungi of uncertain classification.

7. Hyaline filamentous septate - Fusarium spp – F.solani , F.oxysporum , F.dimerum Aspergillus spp – A.fumigatus , A. flavus , A.niger , A.terreus Scedosporium spp - S.apiospermum [ Pseudallereschiaboydii ], S.prolificans Paecilomyces spp – P.lilanicus , P.variotti Acremonium spp –A. kiliense

8. Dematiaceous ( Phaeoid ) fungi Bipolaris Curvularia Exophiala Lecytophora Phialophora Lasiodiplodia Cladosporium

9. [3] Yeasts and Zygomycetes Yeasts Candida – C.albicans,C.parapsilosis , C.guilliermondii Cryptococcus – C.neoformans Zygomycetes Rhizopus – R.arrhizus Mucor Rhizomucor Absidia Apophysomyces

10. Thermally dimorphic fungi Causes lid and conjunctival lesions, granulomatous anterior uveitis,episcleritis , endophthalmitis , orbital infections, but rarely ever keratitis . Paracoccidioides - P.brasiliensis Coccidiodes - C.immitis Blastomyces – B.dermatitidis Sporothrix – S.schenckii Histoplasma – H.capsulatum , H.duboisii

11. Of uncertain classification Pythium.insidiosum -resembles zygomycetes ; causes severe keratitis & orbital cellulitis Rhinosporidium – R.seeberi - not associated with keratitis Pneumocystis – P.carinii -not associated with keratitis

12. BROAD GROUPS OF FUNGI PATHOGENIC TO EYE The fungi pathogenic to the eye include:16,17 • Filamentous fungi – Aspergillus – Fusarium – Curvularia – Paecilomyces – Phialophora • Other emerging fungi – Aureobasidium – Rhodotorula – Fonanscea – Penicillium sp • Yeast – Candida

13. Methods to demonstrate fungi Wet preparation Staining of slides Demonstration in histopathological slide

14. Wet mount preperation . Corneal scrapping, conjunctival swab or fluids from the lesions. A drop of 10% KOH is put on a clean dry glass slide A thin cover slip is put over the fluid. Press the cover slip over the fluid to make the specimen flat. Wait for 5 minutes and then examine under low power. High power may be needed to see fungal elements that look like hyaline structures. The hyphae and arthrospores standout well. Instead of KOH, 10% NaOH can also be used. The function of the alkali is to digest organic material other than fungi. Other less commonly used wet mount is to use glycerine along with KOH. To make a wet mount, 10 ml of glycerine and 20 gm of KOH are taken, to this 90 ml distilled water is added.

15. No stains are required while using alkaline wet preparation. The wet mounts where stains are used are: 1. Lactophenol cotton blue 2. Indian ink

16. Other Methods 1. Calcoflour white can be added to KOH mount and seen under fluorescent microscope. 2. Fluorescent antibody staining is used when few fungi are available in the specimen. It requires specific antisera . 3. Giemsa stain helps to identify both yeast and hyphae . 4. Periodic acid-Schiff (PAS) and methanamine sliver stains are used to see fungi in histopathological slide.

17. Culture Fungi require special culture media at room temperatures and long-time to grow. All the fungi are aerobes. 1. Sabouraud dextrose with or without antibiotics. 2. Sabouraud dextrose agar broth (SAB) 3. Blood agar with or without antibiotic. 4. Brain heart infusion 5. Corn-meal agar 6. Potato dextrose agar Out of these Sabouraud media are the most commonly used media.

18. Molecular techniques PCR based detection methods PCR PCR - SSCP single stranded conformation polymorphism Nested PCR

19. Molecular techniques PCR-RFLP Real time quantitative PCR .

20. Anti fungals :

21. Infections of eye lids and conjunctiva. The eyelids may be the site of inoculation of S. schenckii , resulting in a chronic suppurating ulcer . Eyelid lesions are common in patients with disseminated blastomycosis ; Blastomycosis ,however , may present solely as a conjunctival lesion apart from any external eyelid involvement . Paracoccidioides brasiliensis often causes disease of the eyelids and conjunctiva resulting in disfiguring lesions. This systemic mycosis, acquired by inhalation of conidia into the lungs, is endemic to Mexico and Central and South America and has a predilection for mucocutaneous surfaces, particularly the mouth and nares .

22. Blepharitis and lid skin involvement can occur with infection of Microsporum canis . Yeasts such as Candida species have been associated with cases of ulcerative blepharitis in patients with skin atopy . M. furfur has been implicated as a cause of blepharitis and seborrhic dermatitits . P. carinii has been documented to cause conjunctivitis

23. The high incidence of fungal isolation from the conjunctiva of humans is related to the frequency with which fungi can be isolated from cosmetics. Shared-use cosmetics, including eye products, yielded fungi in 10.4% of the products, representing 69 different species of fungi . Chronic use of topical ophthalmic antibiotics predisposes humans to fungal carriage in the conjunctiva likely by removing the normal microbes P. carinii has been documented to cause conjunctivitis

24. Rhinosporidiosis

25. Infections of orbit: Orbital fungal infection is by predominantly two classes of fungi- mucor and aspergillus .

26. Orbital Mucormycosis Orbital mucormycosis , by species of rhizopus , is commonly seen in debilitated, immunocompromised patients. Uncontrolled diabetics are a susceptible group of patients, as are patients on chemotherapy for hematological malignancies. Orbital disease is frequently associated with sinus or cerebral disease.

27. Clinical features ocular ,facial pain. Fever. Facial and periocular edema. Vision is diminished; Proptosis and ptosis . Orbital apex involvement will cause total ophthalmoparesis . Other cranial nerves involved are the fifth and seventh nerves. Conjunctival congestion and chemosis are present. Relative afferent pupillary defect. Blackened areas of necrosis and eschar are visible in the external nares or palate. The periocular and facial skin shows necrosis with advanced disease.

28. Orbital mucormycosis with lid necrosis.

29. Investigations : Suspected mucormycosis warrants orbital imaging, preferably with CT scan. CT scan shows homogenous, well circumscribed or diffuse irregular soft tissue density mass in the orbit, extending to para -nasal sinus or intra-cranially. Any bone erosion can be made out. MRI scan better visualizes intracranial extension into the frontal lobe or into the carotid artery siphon. Diagnosis is by biopsy from the affected tissue, the biopsy specimen showing fungal filaments on staining, or growing mucor species on inoculation into culture media. Biopsy material may be obtained by endoscopic sinus surgery or from the orbit, and stained by both hematoxylin -eosin and specific fungal stains. Investigations for DKA, hematological malignancies, chronic renal failure and other immunosuppressed states.

30. Treatment Mucormycosis is best treated by a multi-specialty team of infectious disease specialist, orbital surgeon, neuro -surgeon and ENT surgeon. Patients with rhino- orbito -cerebral mucormycosis require extensive and repeated debridation of the sinuses, orbit and other infected areas aim is to remove dead tissue. Orbital exenteration may be required in nearly half the patients with severe orbital disease. The mainstay of treatment is intravenous amphotericin B, at the dose of 1 to 1.5 mg/kg body weight per day.

31. Liposomal amphotericin B - more effective. Newer systemic antifungals such as posaconazole and voriconazole have been used in addition. Hyperbaric oxygen may aid in the treatment. Supportive therapy is required for the concurrent systemic conditions

32. Orbital Aspergillosis The saprophyte aspergillus can infect the orbit insidiously, and affects both immunocompetent and immunocompromised individuals. It may also be related to drug addiction, renal transplants, alcoholism and diabetes mellitus.

33. Signs and Symptoms Orbital aspergillosis presents with a slowly progressive mass extending into the orbit from the adjacent paranasal sinus. Progressive proptosis and globe displacement. Orbital apex syndrome, with visual loss, ptosis and ophthalmoparesis . Pain and headache.

34. The orbital inflammatory signs are less marked. The vision is relatively better preserved unless there is orbital apex involvement. Occasionally there may be abscess formation. Rarely, the condition may be rapidly progressive. In the disseminated form, endophthalmitis may occur

35. Investigations CT scan imaging of the orbit and paranasal sinuses will detect localized mass from a sinus with bony erosion and infiltrating into the orbit. Rarely there may be an isolated orbital mass. An MRI scan will help early detection of cranio -cerebral spread of the disease. Biopsy of the sinus or orbital mass will show septate fungal filaments by hematoxylin -eosin and special fungal stains. Confirmation is by culture of aspergillus from the biopsy material.

36. Differential Diagnosis Aspergillosis should be differentiated from other mass lesions arising from the sinus and extending into the orbit. A fulminant presentation of aspergillosis may mimic mucormycosis . Secondary orbital invasion by paranasal sinus malignancies can also have a similar presentation.

37. Treatment Disseminated aspergillosis responds poorly to treatment. Local disease can be managed by surgical debridement and irrigation with amphotericin B. Adjuvant systemic therapy with amphotericin B, ketoconazole or itraconazole . The patients may be followed up with endoscopy and CT scan to detect recurrences early.

38. 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

39. Fungal infections of lacrimal system. Rhinosporidiosis of the lacrimal sac: It is a fungal infection caused by Rhinosporidium seeberi . Common in India and Sri Lanka. Water born infection. Ocular rhinosporidiosis can also affect conjunctiva, canaliculi , lids and sclera in addition to the lacrimal sac. Dacryocystectomy is usually necessary

40. Candida or Rhodotorula spp. have been implicated in dacrocystitis and NLD obstruction. Fungi can be isolated from ;30% of eyes with congenital dacryocystitis , and C. albicans is most often cultured

41. Keratomycosis First described by Leber ( Aspergillus species ) in 1879 Major cause of blindness in Asia . 6-53% of all cases of ulcerative keratitis in Asia Can occur alone or coexist with a bacterial infection(14.1%) Earlier phaeoid fungi (Dematiaceous) not considered to be significant but now are important cause of keratomycosis .

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

43. 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

44. 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 .  

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

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

47. 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.

48. 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

49. 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

50. inability of PMN cell to ingest pseudohyphae and hyphae furstated phagocytosis by PMN destruction of stroma melting of cornea Host response Yeast

51. Hyphate ulcer: Fungal ulcer has a dry appearing epithelial surface with a rough texture and dirty gray-white color. The epithelium may be elevated and intact or occasionally it may ulcerate.Delicate feathery branching hyphae with surrounding stromal infiltrate. The extension of the hyphate margins beyond the ulcer edge present a distinctive feature and is a useful diagnostic finding. Severe ocular reaction Ciliary flush and flare in anterior chamber.

52. Hypopyon : Hypopyon is invariably present in fungal keratitis and usually result from sterile reaction to fungus and its toxins. Fungi may invade the anterior chamber through intact Descemet's membrane and result in a fixed hypopyon . Satellite lesions Pigmented Ulcers: The ulcer infiltration can be pigmented (e.g. brown) in infection due to dematiaceous fungi. Endothelial plaque: An endothelial plaque is composed of fibrin and leukocytes. Located under the stromal lesion and may be present in the absence of hypopyon . Micro abscesses, satellite lesion and ring infiltrates are non-specific and represent an immune response

53. In advanced cases, the entire cornea becomes homogeneously yellowish-white and can resemble any microbial keratitis . Stromal ulceration and necrosis may lead to perforation and endophthalmitis .

54. Satellite lesions.

55. Weasly white ring. Endothelial plaque

56. Specific fungal ulcers Yeast keratitis causes a small oval ulceration with an expanding, discrete, sharply demarcated, dense, yellowish-white stromal suppuration lacking delicate features of filamentous organisms. Aureobasidium pullulans -an emerging pathogen. The ulcers are usually central in location with multiple round ball like infiltrates around the ulcer with extension to periphery.

57. Severe candidal kerartitis Superficial mycotic ulcer Fusarium keratitis Deep mycotic keratitis with chronic smouldering infection

58. Fixed hypopyon in an eye with fungal corneal ulcer

59. Method of Sample Collection Corneal Scraping Anterior Chamber (AC) Paracentesis Done In very rare circumstances like suspected fungal infection with repeated negative culture reports but progressive infection It is also called for, when there is scanty material available from scraping and there is thick hypopyon . Sharp 22/20 gauge needle is inserted into the anterior chamber between 6 o'clock and 7 o'clock area directly into the hypopyon and the material is aspirated.

60. Corneal scraping being taken

61. Corneal Biopsy It is indicated in cases with deep stromal abscess or in case where repeated culture shows negative reports but there is strong suspicion of infection. The cornea is anesthetized and 0.2 to 0.3 mm trephine is used to outline the area to be biopsied. Usually a depth of about 0.1 to 0.2 mm is dissected out and sent for histopath .

62. Corneal biopsy with microtrephine .

63. Post LASIK cases: Scraping of the surface is not indicated in these eyes due to fear of button holing of the flap. It can be performed by lifting of the flap, as following infection the flap becomes edematous and thus provide little resistance. Careful handling of the flap is mandatory. The specimen collection should be done both from the bed and undersurface of the flap. If there is necrosis of the flap, either excision or amputation of the flap should be done to reduce the load of infection.

64. Emerging Investigations Molecular techniques: Polymerase chain reaction (PCR).rapid results and even in partially treated cases. Clinical aids like confocal microscopy is also being used for identifying fungal keratitis whereby actual fungal elements can be visualized in vivo. It provides epithelial, stromal , endothelial details and makes it possible to observe microorganisms in vivo without use of dyes, stains or tissue fixation. In cases of fungal keratitis with deep seated infiltrates and delayed growth in culture, confocal microscopy can detect fungal filaments accurately and thus preclude the need for more invasive procedures like corneal biopsy

65. PCR Confocal microscopy showing aspergillus .

66. aspergillus colonies

67. Management : General measures are as for bacterial keratitis . Removal of the epithelium over the lesion may enhance penetration of antifungal agents. Topical antifungals should initially be given hourly for 48 hours and then reduced as signs permit. Treatment should be continued for at least 12 weeks. Candida infection is treated with amphotericin B 0.15% or econazole 1%; alternatives include natamycin 5%, fluconazole 2%, clotrimazole 1% and voriconazole 1 or 2%.

68. Filamentous infection is treated with natamycin 5% or econazole 1%; alternatives are amphotericin B 0.15%, miconazole 1% and voriconazole 1 or 2%. Several others are available. A broad-spectrum antibiotic might also be considered to address or prevent bacterial co-infection. Cycloplegia . Subconjunctival fluconazole may be used in severe cases .

69. Systemic antifungals may be given in severe cases, when lesions are near the limbus , and for suspected endophthalmitis . Options include voriconazole 400 mg twice daily for one day then 200 mg twice daily, itraconazole 200 mg once daily, reduced to 100 mg once daily, or fluconazole 200 mg twice daily. Tetracycline (e.g. doxycycline 100 mg twice daily) may be given for its anticollagenase effect when there is significant thinning.

70. IOP should be monitored. Perforation –A small perforation in which infection is controlled may be manageable with a bandage contact lens; tissue glue is often adequate for slightly larger dehiscences . A penetrating keratoplasty or corneal patch graft may be necessary for larger perforations, or in those where infection is extensive or inadequately controlled. Superficial keratectomy can be effective to de-bulk a lesion. Therapeutic keratoplasty (penetrating or deep anterior lamellar) is considered when medical therapy is ineffective or following perforation. Anterior chamber washout with intracameral antifungal injection may be considered for unresponsive cases in which there is a stable corneal infiltrate but enlarging endothelial exudation.

71. Bandage contact lens in a case of ulcer

72. Scleritis Fungal infectious scleritis are devastating cause of infectious scleritis . They are most difficult to diagnose because of their varied clinical picture. The reported incidence of fungal scleritis varies; 11 to 38 % of total infectious scleritis cases. Case series from India on infectious scleritis showed relatively higher incidences of fungal involvement which can be attributed to the hot and humid climate and higher prevalence of fungal spores in the environment

73. Like other infectious scleritis , the treatment of fungal scleritis is frustrating and requires rapid and aggressive multidrug fungal therapy. The topical and oral voriconazole is often used with capsofungin as both the drugs have synergistic activity and may be useful in severe form of fungal scleral infections. However, poor penetration of antifungals into the tightly bound collagen fibers of the scleral layer, allows fungi to remain in the intrascleral lamellae for a long time even after extensive antifungal therapy. Most of the diagnosis is delayed and lead to poor visual outcome. Scleral biopsy is required to confirm the diagnosis in such cases

74. FUNGAL UVEITIS Presumed ocular histoplasmosis syndrome (POHS) Histoplasma capsulatum infection occurs following inhalation of the yeast form of this dimorphic fungus, and can lead to the systemic mycosis. Pulmonary involvement is the most common feature. It is common in AIDS. POHS is relatively common in areas of endemic histoplasmosis (e.g. the Mississippi river valley in the USA), This is reinforced by data from skin antigen testing, but has not been established with certainty and it is possible that other causative agents. Eye disease represents an immune-mediated response to microbial antigen, rather than immediate damage due to active infection.

75. Ocular features Sixty per cent have bilateral signs. Presentation. POHS is usually asymptomatic unless macular choroidal neovascularization supervenes. Classic triad: ( i ) multiple white atrophic chorioretinal ‘ histo ’ spots about 200 μ m in diameter (ii) peripapillary atrophy (iii) vitritis is absent. Linear midperipheral scars also occur (5%).

76. C.Linear streaks A. Peripheral histo spots B.Circumferential peripapillary atropy and histo spots

77. Choroidal neovascularization (CNV) is a late manifestation occurring in less than 5% of affected eyes. Usually associated with a pre-existing macular histo spot. Associated subretinal fluid and haemorrhage leading to DOV. Acute chorioretinitis is almost always asymptomatic and rarely identified, but discrete oval–round whitish lesions <400 μm in diameter that may develop into classic punched-out histo spots have been described.

78. Choroidal neovasc in POHS.

79. Investigation Skin antigen testing was of limited utility and may have worsened POHS in some cases; it is no longer routinely available. HLA testing. POHS is associated with HLA-B7 and DRw2. Serological testing is helpful if positive, but is usually negative in the absence of systemic mycosis. FA and OCT when CNV is suspected.

80. Treatment Spontaneous regression of CNV may occasionally occur, but without treatment 60% of eyes with CNV have a final visual acuity of less than 6/60. Intravitreal anti-vascular endothelial growth factor (VEGF) injection for CNV. Amsler grid testing of the fellow eye at least weekly, particularly if a macular histo spot is present (25% risk of CNV). antioxidant supplements

81. Pneumocystis choroiditis The fungus Pneumocystis jirovecii , a pulmonary commensal , is a major cause of mortality in uncontrolled AIDS. Systemic antimicrobial prophylaxis has replaced pulmonary-only preventative treatment with inhaled pentamidine , and along with immune reconstitution has dramatically reduced the incidence of Pneumocystis choroiditis . Multiple slowly progressing deep round yellow– orange lesions commonly bilateral, are characteristic. There is minimal vitritis , and visual loss is often negligible

82. Choroidal pneumocystis ; multifocal lesions Large coalescent lesion.

83. Cryptococcal choroiditis Cryptococcus neoformans , a dimorphic yeast, enters the body through inhalation, and can spread to the eye in the bloodstream or from the CNS via the optic nerve. Ocular involvement may occur directly as multifocal choroiditis with vasculitis and exudate or more commonly indirectly with papilloedema and ocular motility dysfunction.

84. Multifocal choroidal cryptococcosis .

85. Coccidioidomycosis Coccidioides immitis acquired by inhalation. Causes a mild pulmonary infection, Ocular features include severe granulomatous anterior uveitis and multifocal choroiditis .

86. 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

87. 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

88. Pathogenesis Endogenous Multifactorial. It is likely that sustained fungemia with even saprophytic fungi can lead to endopthalmitis At the time of initial infection with some dimorphic, fungi , such as H. capsulatum & C. immitis , unrecognized fungemia occurs and often leads to endophthalmitis .

89. Endogenous Endophthalmitis Predisposing factors Systemic debilitating disease Malignancy IVDU Chemotherapy Systemic antibiotics Alcoholism & Diabetes

90. 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.

91. 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

92. Epidemiology RACE – no racial preponderance SEX – Male preponderance (3:1) AGE – Young and middle age.

93. Agents Endogenous Endotphthalmitis Candia albicans Fusarium species Aspergillus species Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitidis Cryptococcus neoformnas

94. Agents Exogenous Endophthalmitis Aspergillus spp. C. a lbicans,C. glabrata , C. tropicalis , C. parapsilosis Paecilomyces spp. Fusarium spp. Acremonium spp. Curvularia spp.

95. candidal endophthalmitis : Candida ( commensal C. albicans ) Predisposing factors:trauma or surgery or can spread from fungal keratitis , endogenous infection is an important alternative route. Risk factors for metastatic spread include intravenous drug abuse, a septic focus associated with an indwelling catheter, chronic lung disease such as cystic fibrosis, general debilitation and diabetes. It is relatively uncommon in AIDS.

96. Ocular involvement may occur directly as multifocal choroiditis with vasculitis and exudate or more commonly indirectly with papilloedema and ocular motility dysfunction.

97. Clinical features Presentation. Systemic candidiasis may already have been diagnosed. One third of patients with untreated candidaemia will develop ocular involvement. Peripheral fundus lesions may cause little or no visual disturbance while central lesions or severe vitritis will manifest earlier. Progression is typically much slower than bacterial endophthalmitis . Bilateral involvement is common. Anterior uveitis is uncommon or mild in early disease but may become prominent later.

98. Vitritis . May be marked with fluffy ‘cotton ball’ or ‘string of pearls’ colonies, sometimes progressing to abscess formation. Chorioretinitis : one or more small creamy white lesions with overlying vitritis . Retinal necrosis may lead to retinal detachment, with severe proliferative vitreoretinopathy .

99. Severe vitritis . Cotton ball colonies Focal chorioretinitis Retinal necrosis. Candidal endophthalmitis

100. Investigation Vitreous biopsy (preferably using a vitreous cutter rather than a needle) to identify the organism (PCR and culture) and identify sensitivities. Systemic investigation, e.g. blood and urine cultures

101. Treatment Antifungal treatment. Intravenous amphotericin -B in combination with oral flucytosine , but resistance is a concern. Voriconazole orally or intravenously has a broad spectrum of antifungal action with low reported resistance and high ocular penetration Adjunctive intravitreal treatment may be given (100 μg in 0.1 ml), with serial injections. Pars plana vitrectomy should be considered at an early stage, especially for severe or unresponsive disease; as well as providing a substantial culture specimen, it reduces fungal and antigen load, facilitates therapeutic agent penetration and clears the ocular media.

102. Aspergillus endophthalmitis Aspergillus species are common environmental fungi, but cause disease in humans less commonly than Candida. Spores - airborne spread, and risk factors for infection include intravenous drug abuse, chronic lung disease, organ transplantation, and blood disorders; Neutropenia may be of particular importance. Iridocyclitis and vitritis are common. Yellowish retinal and subretinal infiltrates tend towards macular involvement. The disease progresses more rapidly, and the visual outcome is often worse. Occlusive retinal vasculitis is common. Systemic assessment is critical; Endocarditis presents a particular risk.

103. Macular disease in aspergillus endophthalmitis .

104. Thank you. Thank you