History
A 72-year-old woman with an indwelling bladder catheter developed a mixed bacterial urinary tract infection.
She was receiving a course of intravenous antibiotics when vision in her left eye markedly decreased.
Diagnosis
Acute bacterial endophthalmitis (panophthalmitis)
Histopathology
Gross examination reveals a normal sized eye with hypopyon. On sectioning, yellow and white material
suggestive of pus is prominent around anterior segment structures, as well as within vitreous cavity and in
the region of the optic nerve head. Partial retinal detachment is identified.
On microscopy, acute inflammation is visible throughout the globe - within corneal epithelium and anterior
and mid-stroma, in the anterior chamber, throughout the uveal tract but especially in the choroid,
surrounding the cataractous lens, within vitreous, within and partially destroying retina, subretinally, and
in sclera and episcleral tissues. Only the optic nerve beyond the lamina cribrosa is not affected. An
occasional cluster of Gram-positive cocci is observed in vitreous. No granulomatous inflammation is seen
but chronic non-granulomatous inflammation is apparent in choroid.
Discussion
Endophthalmitis is defined as inflammation of one or more coats of the eye and adjacent cavities. This
means involvement of several intraocular structures or all of the intraocular contents. Panophthalmitis
denotes inflammation of the entire globe including sclera. However, the term endophthalmitis often is used
loosely to cover both limited inflammations and panophthalmitis. Endophthalmitis may be infectious or
non-infectious. Infectious endophthalmitis is an uncommon but potentially sight-threatening condition which
is either exogenous or endogenous, the former outnumbering the latter 3 to 1.1 In exogenous
endophthalmitis microorganisms enter the globe from the external environment while in endogenous
endophthalmitis, infection is spread hematogenously from elsewhere in the body.
Exogenous endophthalmitis can occur following surgery, trauma and severe keratitis. Postoperative
endophthalmitis develops mainly after cataract surgery, the most common surgical procedure, with an
incidence of 0.07 to 0.13%.2 The organisms primarily responsible are from the patient's own local
microbiologic flora (Staphylococcus epidermidis and aureus and Streptococcus pneumoniae in acute
endophthalmitis, and Staphylococcus epidermidis and Propionibacterium sp. in chronic endophthalmitis).
Postraumatic endophthalmitis has an overall frequency of 7%. Prognosis is poorer than with other forms of
endophthalmitis due to mixed flora infections and trauma associated damage and inflammation obscuring signs
of infection. Staphylococcus epidermidis is the most common pathogen but Bacillus sp. infections are
increasing and are noteworthy for the rapid destruction they can cause2 Only 1.8% of patients with
ulcerative keratitis developed endophthalmitis with Pseudomonas and Streptococcus sp. predominating.3
Endogenous (metastatic) endophthalmitis, the least common form of infectious endophthalmitis, typically
occurs in the settings of immunosuppression, indwelling prostheses or catheters, bacteremia/fungemia, major
surgery or intravenous drug abuse. However, patients occasionally have no risk factors or source of
infection evident. Bilateral infections may occur. The onset may be rapid (bacterial) or insidious
(fungal), making diagnosis and institution of vision-saving treatment difficult. Particularly in
immunocompromised individuals, unusual fungi and bacteria may be the offending agents.
Most endogenous endophthalmitis is due to fungi, typically Candida sp. with Aspergillus sp. ranking second.4,5
Aspergillus generally produces extensive retinal necrosis and choroidal damage as a result of
vascular and/or direct tissue invasion whereas Candida causes small foci of retinal damage from invasion of
the organisms with multiple microabscesses surrounding organisms in the vitreous.6 Although only
approximately 10% of patients with systemic fungal infections develop endophthalmitis, it has been shown at
autopsy that those with ocular lesions generally have widespread fungal disease, even if not appreciated
clinically.5 Bacterial endogenous endophthalmitis is less common; pathogens include Streptococcus sp.,
Staphylococcus aureus, Bacillus cereus, and enteric Gram-negative organisms.2 Escherichia coli
endophthalmitis is very rare and almost exclusively occurs in diabetics, typically with urinary tract
infections as the primary site.7
Clinically, infectious endophthalmitis varies in presentation depending on the type of endophthalmitis and
the organism(s) involved. Patients complain of increasing pain, decreasing visual acuity, ocular discharge,
headache, red eye and photophobia; signs consist of lid swelling, corneal edema, fibrin and/or cells in the
anterior chamber which can amount to hypopyon (pus in the anterior chamber), retrolenticular cells,
increased intraocular pressure and hemorrhages within retina or iris.8 Diagnostic measures include
sampling of aqueous humor, vitreous and/or tissue for culture, light microscopic examination with or without
immunohistochemical or other special stains, electron microscopy, and molecular techniques such as PCR. The
latter is emerging as an important method for identifying small numbers of organisms present in symptomatic
but culture negative eyes.
On microscopy, inflammation may be acute suppurative chronic granulomatous, chronic non-granulomatous or
mixed.
Suppurative endophthalmitis ranges from focal abscesses in choroid and retina to abundant inflammation
throughout the eye with destruction of intraocular tissues. Prominent inflammation posteriorly particularly
within choroid suggests endogenous endophthalmitis, in which organisms gain access through choroidal
vessels. Exogenous infections tend to be centred more anteriorly with less choroidal inflammation.3
Bacteria may be seen with hematoxylin and eosin if numerous but usually Gram stain is required. One must
ensure the organisms are genuine since debris and dispersed melanin granules sometimes can mimic organisms.
Although suppurative inflammation alone typically indicates a bacterial pathogen, Candida sp. and
Aspergillus sp. may be present without granulomatous inflammation,6 also, in immunocompromised patients,
inflammation may be minimal and atypical with respect to the organism involved. Therefore, it is useful to
routinely perform Methenamine silver and PAS stains. Absence of organisms does not eliminate the
possibility of infectious endophthalmitis since bacteria particularly may be few and obscured by intense
inflammation. In post-traumatic endophthalmitis, a foreign body may be observed. If only necrotic debris
is evident, it is important to exclude completely necrotic tumor such as retinoblastoma which may mimic
clinically and histologically suppurative endophthalmitis.
Granulomatous endophthalmitis may involve the eye focally or diffusely. Frequently, granulomas with or
without necrosis are prominent within the uveal tract. Mycobacteria and fungi are important diagnostic
considerations in this setting, the latter particularly if acute inflammation is also present. In exogenous
endophthalmitis, fungi can penetrate intact tissues and fungal keratitis progressing to endophthalmitis does
not require rupture of Descemet's membrane for the organisms to gain access to the interior of the eye,
unlike the situation for bacteria. In mycobacterial infections granulomas need not show caseation.
Differential diagnoses for granulomatous endophthalmitis include sarcoidosis, sympathetic ophthalmia,
necrotizing scleritis, and phacoanaphylactic endophthalmitis. Sarcoidosis and sympathetic ophthalmia are
characterized by non-necrotizing granulomas without acute inflammation. Necrotizing scleritis consists of
necrotic tissue surrounded by palisading histiocytes and giant cells; it may involve intraocular contents
but is centred around sclera.
Sometimes endophthalmitis may appear histologically with fibrosis and chronic non-granulomatous
inflammation. This can occur if the organism is of low virulence, with retained foreign bodies, if the
inflammation is neglected or in non-infectious endophthalmitis. If occasional granulomas or microabscesses
are seen or eosinophils are prominent, particularly in a child, infection with Toxocara sp. should be
considered.
Sequelae of endophthalmitis include corneal edema with band keratopathy (calcium deposits in the region of
Bowman's layer) and stromal vascularization; blockage of anterior chamber either by inflammatory debris or
by formation of peripheral anterior synechiae may result in glaucoma; cataract; posterior synechiae
(adhesions between iris and lens) which also may cause glaucoma; vitreous fibrosis and vascularization;
retinal detachment secondary to subretinal inflammation or epiretinal membrane formation; retinal and/or
choroidal scarring; and cystoid macular edema. Ultimately, the eye may become shrunken with disorganization
of intraocular contents (phthisis bulbi); osseous metaplasia may be seen, sufficient to require
decalcification before processing for histology.
Ocular Infections In AIDS
Ocular complications of HIV infection can be seen in approximately 95% of patients.9 The spectrum
includes infectious, neoplastic, vascular and iatrogenic processes affecting adnexal, anterior segment,
posterior segment, neuroophthalmic and orbital structures.10 About 75% of AIDS patients will develop
ocular infections attributable to viruses, parasites, fungi and bacteria, the organisms responsible varying
with the population of affected individuals and country studied.9, 11 Multiple types of organisms may be
present in the eye of a given patient, and viruses, parasites and fungi are more common pathogens than
bacteria. Posterior segment infections are the most devastating, the most frequent being cytomegalovirus
retinopathy, found in up to 40% of AIDS patients until recently, when, with the use of highly active
antiretroviral therapy, the incidence dropped by at least half.9 Approximately 5% of patients have
Toxoplasma gondii retinitis and/or ocular cryptococcosis, the former producing differing patterns of injury
in individuals with AIDS versus immunocompetent patients. More than 80% of AIDS patients develop
pneumocystis pneumonia but despite this, ocular involvement (pneumocystis choroiditis) is rare. Other
intraocular pathogens include Herpes simplex and Varicella zoster viruses, BK virus, Histoplasma, Candida,
Aspergillus, Treponema pallidum and mycobacteria. Ocular surface infections such as Microsporidium and
Molluscum contagiosum also may be found .
Non-infectious Endophthalmitis
This includes a range of etiologies, including systemic autoimmune diseases, local ocular inflammations of
unknown cause, endophthalmitis related to lens material (phacoanaphylactic endophthalmitis and phacotoxic
endophthalmitis) and endophthalmitis attributable to intraocular foreign bodies.
Phacoanaphylactic endophthalmitis (lens-induced granulomatous inflammation) is a rare consequence of lens
injury and represents an autoimmune response to lens protein to which the body is normally tolerant.12
Histopathologically a mixed neutrophilic and granulomatous response is centred about the lens, typically in
a zonal pattern: neutrophils around degenerating lens material are surrounded by giant cells and
histiocytes which in turn are surrounded by chronic non-granulomatous inflammation. Clinically, the
condition is suspected in only 5% of histologically proven cases. Seventy percent of cases are associated
with patchy choroidal chronic non-granulomatous inflammation, 60% with retinal detachment, 50% with retinal
mononuclear cell perivasculitis, 30% with optic atrophy and 3-7% with sympathetic ophthalmia.12 The term
"phakotoxic" endophthalmitis covers a mixed group of conditions related to intraocular lens implant surgery
and possibly low-grade reactions to lens proteins.1,12
References
- Wilson FM II: Causes and prevention of endophthalmitis. Int Ophthalmol Clin 1987;27:67-73.
- Kresloff MS, Castellarin AA, Zarbin MA: Endophthalmitis. Surv Ophthalmol 1998;43:193-224.
- Margo CE: Eyes removed for primary ulcerative keratitis with endophthalmitis: microbial and histologic
findings. Ophthalmic Surg Lasers 1999;30:535-539.
- Klotz SA, et al: Fungal and parasitic infections of the eye. Clin Microbiol Rev
2000;13:662-685.
- McDonnell PJ, et al: Ocular involvement in patients with fungal infections. Ophthalmology
1985;92:706-709.
- Rao NA, Hidayat AA: Endogenous mycotic endophthalmitis: variations in clinical and histopathologic
changes in candidiasis compared with aspergillosis. Am J Ophthalmol 2001;132:244-251.
- Park SB, et al: Endogenous endophthalmitis caused by Escherichia coli. Ann Ophthalmol
1993;25:95-99.
- Rowsey JJ, Jensen H, Sexton DJ: Clinical diagnosis of endophthalmitis. Int Ophthalmol Clin
1987;27:82-88.
- Kuo I, Rao NA: Ocular disease in AIDS. Springer Semin Immunopathol 1999;21:161-177.
- Ryan-Graham MA, Durand M, Pavan-Langston D: AIDS and the anterior segment. Int Ophthalmol Clin
1998;38:241-263.
- Pecorella I, et al: Postmortem histological sussrvey of the ocular lesions in a British
population of AIDS patients. Br J Ophthalmol 2000;84:1275-1281.
- Marak GE Jr: Phacoanaphylactic endophthalmitis. Surv Ophthalmol 1992;36:325-339.
