ophthalmology residency program

1. Viruses And Fungi
Dr.mohammed muneer

2. The characteristics of viruses are
• 1. They are very small
smaller than smallest bacteria.( The exception being mycoplasma ).
• 2. They are submicroscopic
not visible by light microscope. The exception being pox viruses which are visible
under light microscope with special stain.
• 3. The viruses do not possess a cellular organization.
• 4. They do not have a formed nuclei.
• 5. They possess only one type of nucleic acid either RNA or DNA.
• 6. The viruses are metabolically inert outside the living cells.
• 7. They lack enzymes needed to build protein or nucleic acid.
• 8. The viruses use the host cells metabolism.
• 9. They do not contain ribosomes.
• 10. They do not divide by binary fission.

3. • 11. They are insensitive to antibiotics and respond to anti- viral durgs.
• 12. The viruses can not be grown in usual media used to grow bacteria.
• 13. They grow on living cells only.
• 14. Some of the viruses grow in the bacterial cells and are called
bacteriophage.
• 15. The replication of the viruses is inhibited by interferon.
• 16. They are filterable.
• 17. The viruses have tendency to mutate, to change the virulence and
antigenicity.

4. Morphology
• The size varies between 20 to 400 nm.
• The viruses have various shapes, i.e. spherical, cubical, etc.
• The extracellular infectious virus particle is called virion.
The virion consists of a nucleic acid core that is surrounded by a layer of
protein called capsid.
The capsid and the nucleic acid core form the nucleocapsid.
The capsid protects the core from nuclease and other toxic matters.
The capsid is made up of polypeptides known as capsomers.
The other function of the capsid is to introduce viral genome in the host cell.
• Some of the viruses have envelopes round the nucleocapsid. The envelopes have
antigenic properties and are responsible for biological and chemical characters of the
virus.
The virus particle are of three types—the cubical (icosahedral), helical and complex.

5. • Most viruses are heat labile and destroyed with in few seconds at 100°C.
• The other methods to destroy the viruses are—ultraviolet radiation, gamma radiation,
chloroform, ether, oxidizing chemicals like halogens, i.e. chlorine and iodine.
• They are also destroyed by hydrogen peroxide, chlorhexidine, sodium hypochlorite and
many disinfectants.
• They remain stable in extreme low temperature and are stored between –40 to –70°C
in lyophilized or freeze dried state.

6. Classification of Viruses
1. Clinical presentation:
Clinical presentation of some of the virus infections are so
specific that the viruses are named after the disease, i.e. smallpox,
herpes zoster.
2. Based on tropism (affinity to particular system):
The viruses infecting skin are known as
dermotropic, i.e. smallpox, measles, chickenpox.
Poliomyelitis and rabies are put under neurotropic.
Similarly, there are pneumotropic and viscerotropic. However, they
failed to explain involvement of other systems.

7. • The best classification is based on their chemical structure , on the basis of presence of nucleic acid.
Thus the viruses are grouped as:
1. RNA viruses
2. DNA viruses
The RNA viruses of ophthalmic interest are:
1. Measles and mumps
2. Rubella
3. HIV and AIDS
The DNA viruses of ophthalmic interest are:
1. Smallpox, molluscum
2. Herpes simplex, herpes zoster, cytomegalovirus, Epstein- Barr virus
3. Adenovirus
4. Papovaviruses

8. • Mutation
is a characteristic of viruses of all types. It occurs in vivo as well as tissue culture. The
virus changes its behavior, virulence and antigenic property by mutation.
• Multiplication:
• The viruses do not multiply by binary fission. As the viruses do not contain biosynthetic
enzymes, they have to use enzyme system of the host cells to form specific molecule to
replicate.
• The nucleic acid of the virus carries the genetic information.
• The replication of virus is a complicated procedure. They can be broadly divided into
following phase:
1. Adsorption
2. Penetration
3. Uncoating
4. Biosynthesis
5. Maturation
6. Release

9. Cultivation of the Viruses
• The common methods used to cultivate viruses are:
1. Animal inoculation:
2. Embryonated eggs:
3. Cell culture:
Three types of tissue cultures are available.
i. Organ culture
ii. Explant culture
iii. Cell culture

10. Virus Infection
• The route of infection are varied, they enter the human body by any of
the following routes:
1) Skin: Through cuts, abrasion
2) Oral: GI tract, contaminated food and drink.
3) Respiratory: Droplet infection
4) Conjunctiva: Droplet or via fomites
5) Sexually transmitted: HIV, AIDS
6) Hematogenous: By contaminated needles, bite of vector.
7) Transplacental: Congenital rubella

11. Cellular Changes
• 1. They may enter the host body without causing any cellular damage
and may coexist with the host cell.
• 2. The cellular changes may be minimal and the diseases pass off
without any long standing effect.
• 3. There is an initial mild symptomatic phase followed by a period of
latency that is followed by a phase of reactivation (herpes simplex
and zoster).
• 4. Some viruses cause death of the cells or lysis of the cells, other
cause proliferation of the cells as in molluscum or other oncogenic
viruses, they may damage the chromosome of the host cell.

12. • The important histological changes of viral infection are formation of
inclusion bodies.
• The inclusion bodies are visible under light microscope after staining
with Giemsa stain or eosin methyl blue.
• They can be acidophilic or basophilic in nature.
• The inclusion bodies may be seen in cytoplasm, nucleus or both.
• Presence of some of the inclusion bodies are diagnostic.

13. Diagnosis of Viral Disease
1. Clinical presentation:
Some viral infections have so specific presentation that they do not require any
specific test. The examples are smallpox, herpes zoster, herpes simplex and molluscum.
2. Serological tests: Rise in titre of antibodies of a virus during period of disease confirms
the diagnosis.
3. IgM specific test
4. ELISA test
5. Microscopy:
i. Presence of elementary bodies in stained slide has given way to electron microscopy.
ii. Demonstration of viral inclusion bodies has no role in ocular virology, they are mostly
used in rabies.
6. Demonstration of viral antigen in tissue culture.

14. • 6. Organism-specific humoral responses can be detected in ocular
fluids:
Goldmann and Witmer reported a method to calculate whether
antimicrobial antibodies are being produced within tissues and hence
demonstrating local infection.

15. DNA VIRUSES OF OCULAR
IMPORTANCE

16. •Pox Viruses
Pox viruses are the largest human viruses. They belong to the family Pox
viridae. The viruses of ocular importance are variola (smallpox), vaccinia and
molluscum.
1. Variola
 It is large enough to be seen under light microscope.
 The virus is stable in dark. It can survive for years when frozen.
 The organism is destroyed by ultraviolet rays.
 They are killed by oxidizing disinfectants and formalin.
 The diagnosis is confirmed by demonstrating Guarnieri’s inclusion bodies.
 The infection gives a lifelong immunity. Prophylactic immunization can be given
by vaccine.
 There is no known antiviral drug against smallpox.

17. 2. Vaccinia
• Vaccinia is similar to variola virus morphologically but differs clinically
and biologically.
• Vaccine prepared from vaccinia virus is used to vaccinate against
smallpox.
• Although smallpox has been eradicated in 1980, the vaccine is still
used routinely in many countries.

18. 3. Molluscum Contagiosum
• Molluscum contagiosum is another pox virus .
• It is a double-stranded enveloped DNA virus.
• It is a large virus (Molluscum virion can be seen by light microscope)
• It causes contagious disease that can be transmitted through close body contact including sexual
contact.
• The cheesy material expressed from the lesion stains blue by Giemsa stain.
• Inclusion bodies are visible only on electron microscopy, they are called molluscum bodies.
• There is no known prophylaxis or effective antiviral drug against molluscum infection.
• Effects:
- Conjunctivitis
- Pearly white or flesh-coloured lesions on the face, extremities, and trunk.
- Epidermal hyperplasia is due to the production of a protein that is related to the conserved domain
of epidermal growth factor.

20. Human papilloma virus
• Double-stranded DNA virus .
• The DNA is arranged into a circular molecule with areas known as open reading frames.
• These are divided into early (E) and late (L) regions.
• E regions code for viral replication proteins.
• Effect of HPV:
1. HPV generally infects epithelial cells and some possess the ability to induce proliferation
(benign papilloma).
HPV 6 and HPV 11 are associated with benign conjunctival papillomata.
2. Malignant change due to insertion of a particular type of HPV DNA into the host genome.
The E2 gene is an important regulator of HPV and disruption of this gene is found in all tumors that
have HPV DNA integration.
• Disruption of E2 production of E6 and E7.
• E6 forms complexes with p53 (tumour-suppressor gene) and hence promotes oncogenesis.This is
seen in HPV 16 and HPV 18. They cause conjunctival dysplasia and carcinoma.
• E7 inactivates the gene product of the retinoblastoma tumour-suppressor gene.

21. Herpes Virus
• There are about 80 viruses in this family of Herpes viridae, out of which
only following are involved in systemic and ocular infection and are
collectively called human herpes viruses (HHV).
• They are divided into three subfamilies,
 alpha
 beta
 Gamma
• The herpes simplex type 1 and 2 along with varicella zoster are cytolytic.
• The cytomegalovirus is cytomegalic.
• Epstein- Barr, human B herpes virus type 6 and type 7 are
lymphoproliferative.

22. General Properties of Herpes Viruses
1. The genome of HHV is double-stranded DNA
2. The capsid is icosahedral with 162 capsomers.
3. The nucleocapsid is surrounded by an envelope which is derived from host
cell nuclear membrane and is lipid in nature.
4. The envelope has eight surface spikes.
5. The replication takes place in the host cell nucleus.
6. Inclusion bodies are intranuclear.
7. The HHV are susceptible to ether, chloroform and bile salt. They are heat
labile.
8. Most of the HHV have latency , after primary infection they remain dormant
and are reactivated periodically.
9. Each type has different antigen except the herpes simplex type 1 and 2.

23. Herpes Simplex Virus
• Human beings are the natural host of herpes simplex virus and the disease
is seen only in humans.
• The virus belongs to subfamily of alpha herpes virinae.
• There are two types of herpes simplex, type 1 and type 2.
• The type 1 generally involves the body above the waist.
• The type 2 generally involves the body below the waist and is called genital
herpes.
• Both types can infect the eyes.
• The disease caused by type1 spreads by saliva, respiratory droplets. one
remains latent in trigeminal ganglion
• The type2 is mostly spread sexually.remains latent in sacral ganglion.

24. • Effect of HSV on eye :
– Conjunctivitis.
– Keratitis.
– Uveitis.
– Uveoretinitis.
The viral envelope is highly immunogenic and stromal disease, e.g. disciform
keratitis, is due to a hypersensitivity reaction to viral antigen rather than the virus
itself.

25. Diagnosis
• The diagnosis is confirmed by microscopy, virus isolation and serology.
• Microscopy
1. The smear is stained by toluidine blue O for 15 seconds that shows multinucleotid giant cells.
2. Inclusion bodies: Intranuclear inclusion bodies are stained by Giemsa stain.
3. Virus particles are seen on electronic microscopy.
4. Fluorescent antibody method is used to demonstrate herpes virus antigen.
• Virus Isolation
Tissue culture is the best method to isolate the virus. The commonly used tissues are
human embryonic kidney, human amnion and rabbit kidney cells.
• Serology
is helpful only in primary infection. In recurrent herpes, there is hardly any change in
antibody titre.

26. Treatment
• Many antiviral drugs are available against herpes simplex viruses. All
do not give uniform result and fail to stop recurrence. Most
commonly used drug is acyclovir.

27. Varicella Zoster Virus
• The virus belongs to the family herpes viridae, subfamily alpha herpes virinae and
known as herpes virus type III.
• Varicella zoster virus can be distinguished from herpes simplex virus by using highly
specific antisera.
• The virus causes two clinically different manifestations,
 1ry infection chickenpox (vesicles on the trunk, face, and mouth).
 Reactivation shingles (If reactivated in the trigeminal ganglion HZO)
The chickenpox occurs in non-immune children and gives a lifelong immunity.
Herpes zoster is generally seen in adults (children are not absolutely immune)
Who had contracted chickenpox in childhood and the organism has remained dormant
in root ganglion and the infection is reactivated later.
 Contact with zoster may cause chickenpox but the reverse is not true

28. Diagnosis
• The fluid removed from the lesion of varicella zoster shows intranuclear
inclusion bodies similar to those of herpes simplex.
• Herpes simplex and zoster can be differentiated by electron microscopy of
typical viral particle. The presence of immunofluorescent antibodies may help.
• IgM amd IgG are found in varicella only.
• IgG is seen in zoster.
• Many antiviral drugs,
acyclovir, valaciclovir have been found effective against the virus.
• Active immunization against chickenpox is available.
• Its efficacy against herpes zoster has not been proved.

29. Cytomegalovirus
• This DNA virus belongs to family herpes viridae and subfamily beta herpes virinae
• labeled as herpes virus type V.
• It is called cytomegalic because it cause enlargement of host cells in contrast to
herpes simplex and varicella zoster that are cytolytic.
• It is differentiated from other herpes viruses by electron microscopy.
• Like other herpes viruses it shows latency in children and adults with normal
immunity, it does not cause any symptom unless reactivated.
• It causes disseminated disease in neonates and immunocompromised persons of
all ages.
• The cytomegalovirus (CMV) is largest among all herpes viruses.
• The CMV is not related to other herpes viruses.
• It causes severe congenital and less symptomatic acquired disease.

30. • If the 1ry infection occurs in pregnancy (especially in 1st trimester) it
will lead to congenital anomalies
• Strabismus.
• Chorioretinitis.
• Microphthalmia.
• Hepatitis.
• Post-transfusion mononucleosis.
 CMV infection in the immunosuppressed can lead to:
• CMV retinitis.
• Transplant rejection.
• CMV pneumonia.

32. • The infection causes prominent intranuclear inclusion body called
Owl’s eye appearance.

33. • The diagnosis is confirmed by:
1. Demonstration of cytomegalic cells in centrifuged urine.
2. Recovery of virus from human fibroblast culture after it has been inoculated
with urine or saliva.
3. Antibodies are found only in primary disease.
4. Serological tests employed include ELISA, complement fixation,
immunofluorescence and radioimmunoassay.
5. CMV genome can be detected by PCR.

34. Epstein-Barr virus
• This DNA virus belongs to family herpes viridae and subfamily gamma herpes viridae and known
as human herpes virus type IV.
• The virus too has latency and shows periodic reactivation that lasts for rest of life.
• It has affinity for lymphoid ( The virus is lymphoproliferative )
• The virus activates B. lymphocytes and cause secretion of immunoglobulin.
• The IgM predominate other immunoglobulins, IgG, IgA and IgD are also produced in smaller
quantity.
• The disease spreads by saliva and respiratory secretions.
• The virus produces
i. Infectious mononucleosis
ii. Burkitt’s lymphoma
iii. Lymphomas in immunodeficient
iv. Chronic fatigue syndrome
v. Ocular infection
vi. Nasopharyngeal carcinoma

35. • Laboratory tests used to confirm the disease are:
1. Paul-Bunnel test
2. Specific antibodies test for Epstein-Barr virus when Paul- Bunnel
test is negative.
3. IgG virus capsid antigen
No antiviral drugs effective against Epstein-Barr virus.

36. Adenoviruses
• contain linear double stranded DNA, with no envelop
• It infects conjunctiva very frequently with or without involving the respiratory
• There are 47 serotypes of human adenoviruses which are divided into six sub
genera labeled A to F.
• Serotypes 1, 2, 3, 5, 7, and 14 are associated with pharyngoconjunctival fever.
• Serotypes 8, 19 & 37 are associated with epidemic keratoconjunctivitis.
• The viruses can survive for about seven to ten days at room temperature. They
are killed at 50°C.
• Adenovirus has the ability to avoid immune defenses by:
suppressing transcription and presentation of MHC Class I molecules on the
infected cell surface.

37. • The diagnosis can be confirmed by:
1. Electron microscopy
2. Complement fixation test
3. ELISA test
4. PCR
5. Virus isolation in specimen collected from throat, conjunctiva, urine are grown
on human embryonic kidney and epithelial cells.
( Adenovirus is cultured on HeLa cell lin )
There are no antiviral drugs that are effective in adeno- viral diseases.

38. RNA Viruses of Ophthalmic Interest
• The RNA viruses comprise of following:
1. Picorna viruses
2. Paramyxoviruses
3. Retrovirus
4. Togavirus

39. Picorna Viruses
• The word picorna comprises of two parts, i.e. ‘pico’ meaning small and rna standing for RNA.
• The characteristics of picorna viruses are:
1. They are very small in size – 20 to 30 nm
2. The capsid is icosahedral, symmetrical.
3. There are 60 capsomeres in them
4. They lack envelope
5. They contain single strand RNA.
The picorna viruses are broadly divided into two groups.
1. Those which cause human infection:
i. Enterovirus
ii. Rhinovirus
2. Those that cause infection in animals and birds.

40. Paramyxovirus
• RNA virus containing single strand RNA.
• They belong to the family Paramyxo viridae.
• The family consists of three genera:
1. Paramyxo virus:
i. Mumps
ii. Parainfluenza
iii. New castle disease
2. Morbilli virus ( Measles virus )
3. Pneumovirus—respiratory syncytial virus.
Out of these only mumps and measles have ocular involvement.

41. Mumps Virus
• The virus gives a lifelong immunity hence second attack does not occur.
• The incubation period is 16-18 days.
• The virus causes hemagglutination followed by hemolysis.
• Diagnosis is simple on the basis of clinical presentation. Atypical cases may require
laboratory tests which consist of:
1. Demonstration of virus by immunofluorescent method.
2. Culture
3. Serology
i. Four-fold rise in antibody titre in paired serum sample.
ii. Complement fixation test
iii. Hemagglutination inhibition test
iv. ELISA

42. Clinical features :
fever and parotitis
Complications:
- Orchitis and reduced fertility.
- Pancreatitis.
- meningo-encephalitis.
- Ocular complications include dacryoadentitis and extraocular muscle palsies.

43. Measles ( Rubeola-Morbilli )
• RNA virus belonging to family Paramyxo viridae and genera moribilli virus.
• It is fully preventable by vaccination.
• A single attack of measles gives lifelong immunity.
• The virus is heat and ultraviolet labile.
• It is destroyed by formaldehyde.
• C/P prodroma of :
cough, coryza, and conjunctivitis THEN fever*
• Complications:
• 2ry bacterial respiratory infection
• Encephalitis(1:1000 case)*
• Subacute sclerosing panencephalitis (SSPE) (rare) , which can be associated with
chorioretinitis and maculopathy
• Measles can cause death by 2ry bacterial infection
• Measles can cause blindness by corneal scarring (which occur in patients with vitamin A
deficiency)

44. Laboratory Diagnosis
• Clinical diagnosis of measles in non-immunized child is easy.
• It is only the atypical form that require laboratory tests.
• They consists of:
1. Demonstration of multinucleated giant cells when nasal discharge is stained by
Giemsa stain.
2. Detection of measles antigen by immunofluorescent method.
3. Positive growth on human kidney and amnion cells.
4. Demonstration of measles specific IgM.
5. Hemagglutination inhibition, complement fixation tests.
 There is no known antiviral drug that is effective against measles. It is fully
preventable.

45. Rubella (German Measles)
• is an important RNA virus
• The virus can pass the placental barriers during the first trimester to cause widespread ocular and
systemic congenital anomalies
• It produces two distinct clinical pictures.
1. Acquired:
A mild self-limiting infection that is generally ignored as flu with fever and lymphadenopathy
without any complication in nonpregnant women.
In pregnant mother, the infection is passed to the fetus causing congenital rubella syndrome. The mother
passes the IgG to the fetus which gradually disappears over next six months. The IgM does not pass the
placental barrier. The disease gives a lifelong immunity.
2. Congenital:
The fetus gets the infection if the mother is infected during first trimester. Presence of rubella
IgM in infant is conclusive proof of congenital rubella.

46. Congenital defects include:
• Eye:
i. Cataract
ii. Microphthalmia
iii. ‘Salt and pepper’ retinitis
iv. Glaucoma
• Ear:
Neurosensory deafness
• Heart:
patent ductus arteriosus

47. Laboratory Diagnosis
1. Virus isolation—In throat swab taken within four days of infection.
2. Tissue culture
3. Immunofluorescent with specific antibody.
4. Serology—Hemagglutination inhibition test in avian blood.
5. ELISA for IgG and IgM
The disease is fully preventable by live attenuated MMR vaccine that
consist of viruses of mumps, measles and rubella.

48. Notes
• Measles & mumps do NOT cause congenital anomlaies
• Infection that cause congenital anomalies:
i. Toxoplasmosis
ii. Rubella
iii. CMV – Chicken pox
iv. Herpes - HIV
v. Syphilis
vi. Listeria monocytogenes
Rubella: maximal infectivity coincide with appearance of rash
Measles: maximal infectivity before appearance of rash
TORCH S.L

49. Retrovirus
• The retroviruses are RNA viruses.
• The viruses of ophthalmic interest are:
1. Lentivirinae
2. Oncovirinae
Lenti virinae: This subfamily belongs to human immunodeficiency virus (HIV)
that causes AIDS.
Human immunodeficiency virus becomes dormant for long-time to be activated.

50. • HIV is a retrovirus that infects CD4+ T cells , and macrophages
their destruction and a defective immune system.
• Sub-types: [There is a possibility of more HIV subtypes]
- HIV-1
- HIV-2

51. Diagnosis
• A person is said to have AIDS if the laboratory tests confirm to have
the following.
1. CD4+ cell count less than 200 cells/cm3
2. Confirmed infection by HIV
3. Infected by at least on opportunistic organism
4. Presence of AIDS related malignancy (Kaposi’s sarcoma) and
lymphoma

52. The laboratory tests
The following are useful in diagnosis of HIV infection :
• PCR
• ELISA
• P24 protein assay
• Immunoglobulin assay
• CD4:CD8 ratio

54. fungi
• They are generally saprophytes but becomes pathogens to cause
opportunistic infection when there is a decline in the immunity local or
systemic.
• The peculiarities of the fungi are:
1. They are said to be plants of lower order without leaves, branches and
roots.
2. They do not contain chlorophyll, depend upon decaying organic matter for
nutrition.
3. The fungi contain rigid cell wall made up of polysaccharide and chitin.
4. They have cytoplasmic membrane that contain sterol.
5. They are eukaryotes, ( contain true nuclei with nuclear membrane, paired
chromosomes, mitochondria, ribosome and food reserve ).

55. 6. They may be unicellular or multicellular.
7. Pleomorphism is common.
8. They propagate asexually, bisexually or by combined methods.
9. The organisms are gram-positive, some are acid-fast.
10. Some fungi show agglutination.
11. Some fungi cause complement fixation reaction.
12. Fungi can produce endotoxin.
13. Hypersensitization to fungi is well established.
14. Fungi are not known to cause epidemics. They cause chronic
diseases both local and systemic. Some of the systemic infections
can be fatal.

56. 16. The fungi are easy to visualize under light microscope. Some of
them are fluorescent under ultraviolet light.
17. They are difficult to culture, take long-time to grow.
18. Biochemical and serological tests are of less diagnostic value
than direct visualization and positive culture.
19. Antibiotic sensitivity to fungi is not available.

57. Various methods to demonstrate fungi are :
1. Wet preparation
2. Staining of slides
3. Demonstration in histopathological slide.

58. CLASSIFICATION OF FUNGI
• The fungi belong to Phyllum thallophyta.
• The phyllum contains two groups, ( algae and fungi ).
• The former contain chlorophyll and are not known to cause human
infection.
• The fungi are again divided into Pseudomycetes and Eumycete( the true
fungi ).
• The pseudomycetes are now considered to be higher bacteria.
• The eumycetes can either be with septate hyphae or without septate
hyphae.

59.  Morphological Classification of Fungi
• As per morphology the fungi are divided into four classes:
1. Yeast
- Candida albicans
- Cryptococcus neoformans
2. Moulds (Filamentous fungi )
-Aspergillus fumigates
-Mucoraceae
3. Dimorphic fungi
Histoplasma capsulatum

60. The yeasts
are unicellular, spherical organisms that multiply by budding.
The only pathogenic yeast is Cryptococcus neoformans that cause fungal
meningitis.
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.

61. • 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.

62. The spores are the reproductive parts in fungi
Reproduction
Sexual Asexual Combined

63. Factors predisposing to fungal disease in the eye:
1. Exogenous:
i. Local trauma: exogenous mycotic infection may follow a local corneal
abrasion with vegetable matter, e.g. if a foreign body is present
ii. Contact lens wear
iii. Topical antibiotic and steroids
2. Endogenous:
i. Immunocompromised : haematogenous
ii. Non-ketotic diabetic ketoacidosis from adjacent air sinuses
iii. Contamination of indwelling catheters or intravenous lines

64. FUNGI OF OCULAR IMPORTANCE
• contains about 900 species and sub- species, out of which 21 species
are human pathogens.
• The Aspergillus fumigatus is the commonest human pathogen.
• On lactophenol cotton blue stain, they show hyaline septate, hyphae
• The organism is better visualized in Gram’s, Giemsa and Gomori
methenamine silver stain than KOH mount.
• The organism is sensitive to local natamycin, amphotericin B, systemic
amphotericin B, itraconazole, fluconazole and ketaconazole.
Aspergillus

65. • Aspergillus fumigatus is an opportunistic pathogen. It can cause:
- Conjunctivitis.
- Keratitis.
- Endophthalmitis.
- Granulomatous orbital inflammation.
Endophthalmitis requires intravitreal antifungal injection.

66. Blastomyces
• Blastomyces is a dimorphic fungus.
• It is thermal dimorphic, i.e. its phases changes with temperature. At 25°C, it is mycelial and at 37°C, it is
yeast.
• In the eyes, it cause
i. orbital cellulitis
ii. granuloma of the lids
iii. Keratitis
iv. Choroiditis
v. endogenous endophthalmitis.
• Its incidence is reported to be high in AIDS.
• It is visualized on KOH 10% mount and hematoxylin- eosin stain, periodic acid schiff (PAS) and Gomori
methenamine silver stain are used to see it in tissue section.
• It is best cultured on Sabouraud’s media without antimicrobial.
• The organism causing human disease is Blastomyces dermatitidis which is a spherical double-walled
structure.
• The organism is sensitive to amphotericin B, itraconazole, ketaconazole and fluconazole.

67. Candida (Monilia)
• It is a commensal of all the mucous membranes of the human body and skin including
conjunctiva.
• The candidal infection is so common that Candida skin test is almost universally positive
hence is not diagnostic but an indicator of cell-mediated immunity
• The Candidiasis is the foremost fungal infection of the eyes. It reaches the eye in two
ways:
1. Exogenous following trauma.
2. Endogenous due to hematological spread from systemic site.

68. • Incidence of candial infection is high in immuno- compromised persons.
• Immunocompetent persons are liable to get the infection when the defense mechanism
breaks down.
• The predisposing factors are
− prematurity,
− prolonged use of antibiotic and steroids,
− radiation,
− diabetes,
− debility due to malnutrition,
− leukemia,
− lymphoma,
− person on cancer chemotherapy and radiation are at higher risk groups, so are the person
with in dwelling catheters and intravenous catheters.

69. • The Candida albicans is a gram-positive organism, it stains darker than cocci.
• The organism stains with Gram’s stain, Giemsa stain, Gomori’s methenamine
silver stain and periodic acid-Schiff.
• It is a common contaminant of bacterial culture. It grows on Sabouraud dextrose
agar with chloramphenicol without cyclohexamide. Other media used are blood
agar and corn- meal media.
• The organism produces two types of spores, the chlamydospores and
blastospores.
• Serologically, Candida albicans has two sero types—A and B. The other test used
is ELISA.
• The organism is sensitive to amphotrecin B, natamycin, miconazole, econazole,
ketaconazole and triazole.

70. Coccidioides
• The organism coccidioides belongs to the family of thermal dimorphic fungi.
• It has two phases:
1. The saprophyte phase
The organism in this phase has branching pattern with septate. They form barrel-shaped
arthro- spores (Arthroconidia).
2. The parasitic phase
is an endospore that develops in the lung. The endospores are contained in spherules that
are spherical and thick-walled. The spherules rupture to release the endospores in the tissue.
• The fungus is cultured on Sabouraud dextrose agar with or without antibiotic or cycloheximide.
• The fungus is visualized in 10% KOH mount or calcoflour white stain. The tissue is stained with
periodic acid-Schiff stain.
• The aspirated intraocular fluid may be stained by Papa- Nicolaou stain to see the organism.

71. • The second form of the disease is disseminated disease which is rare but may be
fatal.
• The other form of ocular inflammation is hypersensitization of the fungal antigen
causing phlycten, episcleritis and scleritis.
• The hematogenous spread leads to chronic and progressive pan uveitis.
• Incidence of coccidioidomycosis is so common with AIDS that it is considered to be
AIDS defining opportunistic infection in person with HIV.
• The organism is sensitive to amphotericin B, fluconazole and itraconazole.

72. Dermatophytes
• It consists of 40 species of filamentous fungi that infect nails, hair,
skin, rarely cornea and conjunctiva.
• They have been divided into three genera
i. Trichophyton
ii. Epidermophyton
iii. Microsporum.
• The organisms have different morphology in tissue and culture.
In tissue, they have hyphae and produce arthospores.
In culture, they have hyphae and asexual spore.

73. • The dermatophytes grow well in Sabouraud’s dextrose agar with chloramphenicol.
• The ocular involvement is mostly in the lids as :
− scaly rash,
− dermatitis,
− madarosis,
− blepharitis,
− allergic conjunctivitis.
Corneal ulcer is rarest of all ocular involvements.
• The fungi are sensitive to many antifungal agents both local as well as systemic.

74. Histoplasma
• There are two types of histoplasma according to their place of
occurrence:
1. The American histoplasma
2. African histoplasma.
• The former is more common and has extensive systemic involvement
and better known as Histoplasma capsulatum.
• The latter is known as Histoplasma duboisii. It only involves the
cutaneous and subcutaneous tissue.

75. • It is a dimorphic fungus.
The dimorphism is related to ambient temperature. It is mycelial at 25°C and yeast
at 37°C.
Though American histoplasm is called Histoplasma capsulatum, it does not have a formed
capsule.
• The spores are asexual and unicellular, the large spores are called macroconidia.
• The organism is seen with light microscope under oil immersion. The organism is stained
by Giemsa stain or Wright’s stain.
• Histoplasmin is the antigen found in filtrate of mycelial broth.
• Complement fixation test for antibodies to histoplasmin is found to be positive within
two to five weeks after infection.
• The other tests used are latex agglutination precipitation test, enzyme immunoassay.

76. • Skin test:
The histoplasmin skin test is similar to tuberculin test.
It becomes positive soon after infection and remains so for years.
It becomes negative in progressive disseminated disease.
• The disease in acute phase does not require any treatment.
• Intravenous amphotericin B is required for progressive disseminated disease.
• Ocular involvement is known as presumed ocular histoplasmosis.

77. Rhinosporidium
• The organism has been put in the class of Phycomycetes which consists of fungi of
lower class.
• The sporangia are visible on KOH wet mount or when the tissue is soaked in normal
saliva.
• The organism causes chronic granuloma in various mucus membrane including
conjunctiva. It may disseminated to bones and skin.
• There is no medical treatment. The best treatment is removal of the growth.