Delhi Journal of Ophthalmology
Major Review
Endophthalmitis
Shivani Pahuja1, Ritesh Narula2
1 Guru Nanak Eye Centre, 2 Shroff Charity Eye Hospital.
Endophthalmitis is an inflammation of the internal layers of
the eye resulting from intraocular colonization of infectious
agents and manifesting with an exudation into vitreous cavity.
Though the word endophthalmitis means any inflammation of
the internal ocular spaces but in clinical practice it is usually
taken to mean inflammation secondary to intraocular infection.
Endophthalmitis can be divided into two main types based
on the mode of infection as: Exogenous and Endogenous
(ie, metastatic). Exogenous endophthalmitis results from
direct inoculation as a complication of ocular surgery, foreign
bodies, blunt or penetrating ocular trauma. Endogenous
endophthalmitis [1] results from the hematogenous spread of
organisms from a distant source of infection (eg, endocarditis).
Endogenous endophthalmitis is quite rare. Various studies have
reported incidence varying from 2% to 15%. In endogenous
endophthalmitis, blood-borne organisms permeate the bloodocular barrier either by direct invasion (septic emboli) or by
changes in vascular endothelium caused by substrates released
during infection. Destruction of intraocular tissues may be due
to direct invasion by the organism and/or from inflammatory
mediators of the immune response. Due to increase in the
spread of AIDS, more frequent use of immunosuppressive
agents, and the use of more invasive procedures, the patients
at risk of endogenous endophthalmitis are increasing .
Most cases of exogenous endophthalmitis (49% to 76% as
reported by various studies) occur after intraocular surgery.
When surgery is implicated in the cause, endophthalmitis
usually begins within 1 week after surgery.
Post
cataract endophthalmitis [2] is the most common form,
with approximately 0.1-0.3% of operations having this
complication. This is largely due to large number of cataract
surgeries being done. But the exact incidence varies in
different set ups and may be very low at certain places. The
overall incidence of endophthalmitis has decreased over
the past several decades largely due to improved surgical
technique and patient preparation. Modern estimates indicate
that the incidence of infectious endophthalmitis ranges from
0.13% to 0.7%.
Endophthalmitis following penetrating keratoplasty [3] may
occur early or late, the incidence of which is reported upto
2%. The infection could be due to contamination of donor
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material, infectious keratitis or as a complication of suture
removal. These patients are also at risk of infections due to
prolonged corticosteroid use following surgery.
Endophthalmitis as a complication of vitreoretinal surgery is
relatively uncommon. Scleral buckle infection usually appears
between the second and seventh day of surgery, and, presents as
severe lid oedema with conjunctival chemosis associated with
severe ocular pain and headache. Intraocular inflammation
may develop associated with media haziness, subretinal
exudation and localised exudative retinal detachment. In
delayed subacute cases fistula and granuloma form, resulting
in exposure of the buckle. Diabetes and prolonged duration
of surgery have been identified as specific risk factors in this
setting. Incidence of endophthalmitis following pars plana
vitrectomy has been reported as low as 0.051%.
The risk factors are different for isolated and cluster
endophthalmitis. Patient factors play a predominant role in
isolated postoperative endophthalmitis. Patients own bacterial
flora may gain entry at the time of surgery and thus increasing
the development of postoperative endophthalmitis. It is
very important to rule out diseases like chronic blepharitis,
conjunctivitis, canaliculitis and keratoconjuntivitis sicca,
chronic dacryocystitis before planning ocular surgery for the
patient. The other important intraoperative risk factors for
isolated postoperative endophthalmitis are inadequate eyelid
or conjunctival disinfection, prolonged surgery, vitreous
loss, prolene haptics of IOLs. The above factors can be taken
care of by the use of pre-operative topical antibiotics for 24
hours, facial scrub, povidone iodine into the conjunctival sac,
adhesive plastic drapes to separate eyelashes, surgeon gloves,
subconjunctival antibiotics at the end of the surgery. The role
of antibiotics in the irrigating solutions is still questionable.
One drop of 5% povidone iodine [4] has proved to be beneficial
in protecting against endophthalmitis.
External factors are the major risk factors in the causation
of cluster postoperative endophthalmitis. There have been
various reports from all over the world describing bacterial as
well as fungal postoperative cluster endophthalmitis. Defects
in sterlisation of instruments, contamination of tap water,
multiple dose fluids and drugs have been held responsible
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Endophthalmitis
for bacterial cluster postoperative endophthalmitis. Fungal
cluster postoperative endophthalmitis has been reported
after contaminated irrigating solutions, IOLs, viscoelastics,
improper ventilation system, poor OT hygiene and even after
hospital construction activity. To prevent the occurrence of
these cluster infections, we have to remain on guard for any
breach in infection control measures and use standardized
irrigating solutions and drugs.
Infectious postoperative endophthalmitis needs to be carefully
differentiated from non infectious vitreous inflammation
following surgery. This form of sterile endophthalmitis is also
known as the toxic anterior segment syndrome (TASS).There
are multiple potential causes of TASS including toxic effects
from intraocular fluids, medications, lenses, instruments,
endotoxins, and sterilization techniques. The differentiation
from infectious endophthalmitis is vital , as the treatments and
positive outcomes are different. Often, the presenting signs and
symptoms of infectious endophthalmitis occur within the first
48 to 72 hours after surgery. If endophthalmitis is caused by
fungal or less virulent organisms, the onset of symptoms can
occur as late as weeks to months after surgery. TASS usually
presents sooner than infectious endophthalmitis (12 to 24 hours
after surgery) and differs from infectious endophthalmitis
in presentation. Patients often have decreased visual acuity,
corneal edema, a nonreactive, dilated pupil, and a moderate to
severe anterior chamber reaction with cells, flare, hypopyon,
and especially fibrin. Pain is mild to moderate if present.
Patients with TASS can have marked corneal edema and even
permanent, irreversible corneal decompensation. The corneal
edema is characteristically limbus to limbus. Inflammation
secondary to TASS will respond readily to topical steroid
treatment as apposed to patients of endophthalmitis who will
show worsening.
Clinical Features of Endophthalmitis
The typical clinical characteristics are increasing pain and
redness associated with decreasing visual acuity or sometimes
profound loss of vision. Hypopyon is usually present but may
be absent. lid oedema and raised intraocular pressure may be
present. Occasionally the signs and symptoms may be subtle
and misleading in the early stages until the course becomes
more fulminant and Intraocular inflammation greater than
expected in the postsurgical period should always be viewed
with suspicion. Blurring of vision is the most common
symptom and was reported by 94% of patients in the EVS
study. Pain was characteristically absent in 25% cases in the
EVS study group. Other clinical signs which may be present are
lid edema, conjunctival hyperemia, chemosis, circumcorneal
congestion, ring abscess, suture abscess, wound dehiscence,
fibrinous AC reaction, posterior synchiae, vitreous cells,
vitreous exudates, retinal exudates and periphelbitis.
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Delhi Journal of Ophthalmology
Post surgical endophthalmitis can be again divided into 2
categories Early onset post operative endophthalmitis and
late onset post operative endophthalmitis depending on the
time after the surgery at which the patient presents.
Majority of patients of post cataract endophthalmitis usually
present in the first post op week. Severe acute postoperative
endophthalmitis usually presents within 1-4 days after surgery.
Patients usually present with decreased visual acuity and pain.
Ciliary injection is usually present. corneal oedema ,anterior
chamber reaction and vitreous inflammation are important
clinical features indicating acute endophthalmitis. Afferent
pupillary defect may be present. The organisms implicated
are Staphylococcus aureus, Streptococcus and gramnegative organisms such as Serratia marcescens, Proteus and
Pseudomonas.
Chronic or late endophthalmitis usually presents after about
6 weeks of cataract surgery. It usually presents with minimal
pain, hypopyon, granular keratic precipitates and mild vitritis.
Staph. Epidermidis[5], candida and Propionobacterium acnes
are usually responsible for chronic endophthalmitis.
The most important clinical feature of P acnes endophthalmitis
[6] is the presence of a white intracapsular plaque composed
of sequestered micro-organisms in the capsular bag. It is a low
grade chronic smouldering type of endophthalmitis. Because
of its atypical presentation it is often difficult to diagnose and
may be confused with posterior capular opacification.
Other important type of endophthalmitis which deserve
special mention include Post traumatic endophthalmitis [7]. It
occurs in 4-13% of all penetrating ocular injuries. Incidence
of endophthalmitis with perforating injuries in rural settings
is higher when compared with non rural settings. Delay in
the repair of a penetrating globe injury is correlated with
increased risk of developing endophthalmitis. Incidence of
endophthalmitis with retained intraocular foreign bodies
is 7-31%. Common agents are Staph epidermidis, Bacillus
species, streptococcus species, Staph. aureus, various fungi
and P. acnes[8].
Endophthalmitis associated with filtering blebs is also
sometimes seen in patients. Bacteria enter the eye through
intact or leaking conjunctival filtering blebs. Streptococcus,
Pneumococcus and Haemophilus influenzae are some of the
organisms.
HOW TO EXAMINE A CASE OF ENDOPHTHALMITIS ?
The examination of the suspected patient should include a
detailed history, visual acuity assessment, examination of
ocular adnexa (any sign of lid swelling), anterior chamber
evaluation (using a slit lamp) and examination of the vitreous.
Associated signs like leaking filtering blebs, wound leak etc.
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Delhi Journal of Ophthalmology
should be noted if any. Fundus view may be obscured because
of anterior chamber reaction or due to vitreous exudates.
The clarity of ocular media could be assessed by indirect
ophthalmoscopy.
Management
The prognosis in postoperative endophthalmitis depends on
the virulence of the microorganisms and early intervention.
For early recognition of postoperative infection, frequent
postoperative follow up at 24 hours, 72 hour and 7 days
is necessary. Every follow up examination comprises of
recording visual acuity, slit lamp biomicroscopic examination
and looking for media clarity. After the clinical diagnosis of
endophthalmitis is made, the further management depends on
the presenting visual acuity and the microbiological spectrum..
Data from the Endophthalmitis Vitrectomy Study indicate
that initial management for patients who meet EVS entry
criteria should include 3 port pars plana vitrectomy if patients
present with vision worse than hand motions, but that an
initial vitreous tap/biopsy with intravitreal antibiotics should
generally be sufficient if presenting vision is hand motions or
better. Systemic antibiotics were not found of benefit in this
study.
Limitations of Endophthalmitis Vitrectomy Study
It only includes cases of post operative endophthalmitis
70% of which were due to Staph. Epidermidis. The results
cannot be extrapolated to other forms of endophthalmitis
such as bleb related, traumatic and endogenous which
are more likely to be caused by organisms of greater
virulence.
Amikacin and Ceftazidime were the only systemic
antibiotics evaluated in the EVS. Although patients in
the EVS derived no demonstrable benefit from these
systemic antibiotics, the study made no recommendations
regarding treatment with additional antimicrobial agents
(eg, systemic fluoroquinolones) or systemic antimicrobial
agents for other types of endophthalmitis (eg, chronic,
bleb-associated, traumatic, fungal, and endogenous
forms)
Potential study subjects with significant opacification of
the anterior chamber or without light perception were
excluded from the EVS. Because these eyes with more
severe infection or involving more virulent organisms
were excluded from the EVS, the effect might have
shifted the EVS outcomes to more favorable results.
Endophthalmitis
an immediate vitreal tap and instillation of intravitreal
antibiotics. Vitreous sample is immediately subjected to gram
stain[11], KOH and calcoflour smear. The sample is also
innoculated on blood agar, chocolate agar, liquid agar and
Sabaurauds dextrose agar. A eubacterial PCR and fungal PCR
should be done if the facilities are available.
A combination of Intravitreal antibiotics[12] which is
commonly used include Vancomycin (1 mg/0.1ml) and
Ceftazidime (2.25mg/0.1ml) because 94% of the culture
positive cases are caused by gram positive organisms which
are 100% sensitive to Vancomycin and 6% of culture positive
cases are by gram negative group of organisms which are 90%
sensitive to Ceftazidime.
EVS did not recommend systemic antibiotics for cases of
acute bacterial postoperative endophthalmitis. However,
the drug used in EVS were the once with poorer intravitreal
penetration. The current generation of fluoroquinolones which
have a high intravitreal penetration and achieve required MICs
for most organisms should be used as an adjunct.
The indications for pars plana vitrectomy are
Poor visual acuity at presentation
deterioration or no improvement despite intravitreal
antibiotics
delayed onset endophthalmitis
fungal endophthalmitis.
The precautions while performing pars plana vitrectomy in
endophthalmitis are
use of 6mm infusion cannula
clearing AC hypopyon and exudative membrane
collection of undiluted vitreous sample from midvitreous
cavity
aim to clear only core vitreous
IOL explantation in cases of gross infection
Treatment approaches for P acnes endophthalmitis [14]
include
Intra-vitreal vancomycin 1mg / 0.1 ml which has to be
given into the capsular bag
May have to be combined with vitrectomy, total
capsulectomy and IOL explantation.
Fungal Endophthalmitis
Though EVS did provide general guidelines for treatment of
endophthalmitis, clinicians should individualise treatrment for
each patient based on the clinical course, signs and symptoms.
Once a clinical diagnosis of acute bacterial endophthalmitis
made, it is to be considered as a medical emergency requiring
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Endogenous fungal endophthalmitis is frequently an
ocular manifestation of a systemic disease.
Endogenous infections usually occur in patients risk
factors like immunosuppression, intravenous drug abuse,
bacterial sepsis, prolonged hyperalimentation, systemic
antibiotics, corticosteroid therapy, recent abdominal
surgery, malignancy, alcoholism, diabetes mellitus,
trauma, and hemodialysis.
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Delhi Journal of Ophthalmology
Endophthalmitis
Candida albicans is by far the most common pathogen
isolated in endogenous fungal endophthalmitis.
Other pathogens include Aspergillus, Coccidioides,
Cryptococcus, Blastomyces, and Sporothrix species.
The diagnosis of endogenous fungal endophthalmitis
should be considered in patients who present with vitritis
accompanied by a chorioretinal focus in the clinical
setting of a recent or current debilitating illness. Clinical
suspicion plays an important role in identifying patients
who may have fungal endophthalmitis
Exogenous infections usually are secondary to trauma
or surgery. A variety of fungi, including Paecilomyces,
Acremonium, and Sporothrix species, have been
associated with endophthalmitis following intraocular
surgery or trauma
The prognosis of fungal endophthalmitis depends on
the virulence of the organism, the extent of intraocular
involvement, and the timing and mode of interventions.
Blood cultures, urine cultures, sputum cultures, and
cerebrospinal fluid (CSF) cultures should be obtained
in patients suspected of endogenous endophthalmitis.
In addition, direct examination of fungi with Giemsa,
Gomori-methenamine-silver (GMS), and periodic-acid
Schiff (PAS) stains should be obtained.
Culture of the fungus confirms the diagnosis. Fungal
cultures can be positive in 44-70% of patients diagnosed
clinically. Vitrectomy samples are more sensitive for
fungal cultures than vitreous needle biopsies. The culture
must be kept at the laboratory for at least 4-6 weeks to
ensure that slow-growing or fastidious fungal organisms
are not missed.
A useful, recently introduced diagnostic tool for fungal
endophthalmitis is the polymerase chain reaction (PCR)
[15]. The main advantages of PCR over conventional
fungal cultures are the higher sensitivity and the rapid
results obtained with PCR. It helps to make an early
differentiation between bacterial endophthalmitis and
fungal endophthalmitis
Systemic amphotericin has been the treatment of choice
because of its broad-spectrum coverage; however, the
penetration of the vitreous cavity is poor. Doses of 5- to
10-mg intravitreal amphotericin [16] have been used.
A new systemic treatment is voriconazole [17], when
administered orally or intravenously, it has good
intravitreal concentrations. Intravitreal administration of
voriconazole [18] seems safe without evidence of retinal
toxicity with concentrations up to 25 mg/mL.
The advent of pars plana vitrectomy has improved the
treatment results of fungal endophthalmitis.
The advantages of pars plana vitrectomy are that it
provides material for culture, removes viable organisms
and inflammatory end products from the infected vitreous,
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and provides intravitreal access to antifungal agents (eg,
amphotericin B).
Vitrectomy and intravitreal amphotericin B[19] should
be considered in those cases of endogenous fungal
endophthalmitis where the disease is progressing despite
initial therapy with an appropriate systemic antifungal
agent.
Voriconazole may be a particularly attractive agent
to consider for infections with fluconazole-resistant,
voriconazole-susceptible strains.
Choroidal neovascularization at the site of chorioretinal
scars, epiretinal membranes, tractional retinal detachment
are some of the complications of fungal endophthalmitis.
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