exogenous endophthalmitis generally arises from a direct breech of external - ocular barrier as a complication of ocular trauma or intraocular surgery .
endogenous endophthalmitis is a rare form of endophthalmitis as it accounts for only 28% of all endophthalmitis cases [ 1 , 2 ] .
endogenous endophthalmitis is caused by breeching of the blood - ocular barrier by pathogens and is spread by blood - borne route originating from infective foci , for example , endocarditis , liver abscess , urinary tract infection ( uti ) , and meningitis .
although the infective foci can often be identified , isolated occurrence from iatrogenic source such as dental surgery and contaminated intravenous fluids are also possible [ 3 , 4 ]
. a number of systemic conditions might predispose patients in developing endogenous endophthalmitis , including diabetes mellitus , cardiac diseases , underlying malignancy , immunosuppression , and intravenous drug abuse .
the causative organisms of endogenous endophthalmitis have been found to vary largely between different geographical locations [ 57 ] . in most published series , which contained both fungal and bacterial endogenous endophthalmitis , fungal infections were the most common causes [ 810 ] . for bacterial endogenous endophthalmitis
, gram - positive organisms were more prevalent in north america and europe , while gram - negative organisms were more commonly found in asia .
prompt diagnosis and treatment of endogenous endophthalmitis are important as the final visual outcome of endogenous endophthalmitis is potentially devastating .
studies have suggested that endogenous endophthalmitis due to fungal infection , in particular candida species , were more likely to result in better visual outcome [ 810 ] .
the aim of this study is to evaluate the clinical features , causative organisms , infective sources , and outcomes of endogenous endophthalmitis in three tertiary eye centers in hong kong over an 8-year period .
we also aimed to assess whether the type of infection would influence the visual outcome by comparing eyes with bacterial endogenous endophthalmitis versus those with fungal endogenous endophthalmitis .
this was a retrospective study of consecutive cases of infective endogenous endophthalmitis in three hospitals including hong kong eye hospital , queen elizabeth hospital , and prince of wales hospital in hong kong .
inclusion criteria included diagnosis of infective endogenous endophthalmitis proven by blood culture from 2000 to 2007 .
exclusion criteria included patients with ocular surgery within one year of presentation , those with history of ocular trauma , and delayed onset of exogenous endophthalmitis .
the clinical information studied included age and gender , preexisting ocular and medical conditions , presenting ocular features , infective foci and microbiological results , treatment , final visual outcome , and survival .
the study was performed in accordance with the declaration of helsinki and was approved by an institutional review board .  
all data were entered into a spreadsheet program ( microsoft excel for mac 2011 , microsoft inc . ,
redmond , wa , usa ) and analyzed using a statistical software ( statplus : mac 2009 , analystsoft inc . ,
the main outcome measure of the study was the visual outcome at the latest follow - up visit , in particular , the proportion of eyes with vision of finger counting ( fc ) or better
. eyes which had been enucleated or eviscerated were assigned to have vision of no light perception ( nlp ) .
categorical variables were compared using the chi - square test , and odds ratios were calculated . based on the study by connell et al . , we hypothesized that eyes with fungal endogenous endophthalmitis will have a better visual prognosis , with 90% of eyes having vision of fc or better , compared with 50% of eyes for bacterial endogenous endophthalmitis . with an alpha of 5%
, our sample size of 16 eyes with bacterial endogenous endophthalmitis and 6 eyes with fungal infection will have a 54% power to detect a significant difference between the two groups
a total of 22 eyes of 21 patients ( one patient with bilateral involvement ) was identified to have endogenous endophthalmitis during the study period ( table 1 ) .
the mean  standard deviation ( sd ) age of the patients at presentation was 61.8  13.9 years ( range : 22 to 89 years ) .
the mean follow - up duration of the patients was 2.7  2.2 years ( range : 1 month to 6.3 years ) .
twenty ( 95.2% ) of the 21 patients presented within 30 days of the onset of ocular symptoms such as blurring of vision , eye redness , or eye pain , with only one patient presenting 90 days after the onset of ocular symptoms .
the median and mean duration from the onset of ocular symptoms to presentation was 2 and 12 days , respectively ( range : 1 to 90 days ) .
preexisting medical conditions that predisposed the development of endogenous endophthalmitis included diabetes mellitus ( 11 eyes , 50% ) , urinary tract infection ( 8 eyes , 36.4% ) , septicemia ( 7 eyes , 31.8% ) , recent general surgery ( 5 eyes , 22.7% ) , liver abscess ( 4 eyes , 18.2% ) , and malignancy ( 4 eyes , 18.2% ) .
two subjects ( 9% ) had undergone renal transplant and were on systemic immunosuppressive therapy .
other medical conditions included indwelling catheter , intravenous drug use , pneumonia , and soft tissue abscess in one case each .
all eyes at presentation were found to have inflammation involving the anterior chamber with cells of 1 + or more .
other common ocular clinical findings included vitritis ( 19 eyes , 86.4% ) , hypopyon ( 13 eyes , 54.5% ) , conjunctival chemosis ( 10 eyes , 45.5% ) , posterior synechiae ( 6 eyes , 27.7% ) , and keratic precipitates ( 6 eyes , 27.7% ) . at presentation , eight ( 36.4% ) eyes had vision of fc or better and the remaining had visual acuity of hand motion ( hm ) or worse .
eyes that had endogenous endophthalmitis due to fungal infection were more likely to have vision of fc or better compared with eyes that had endogenous endophthalmitis due to bacterial infection ( 83.3% versus 25% resp .
, odds ratio = 15.0 , chi - square test , p = 0.013 ) . following the onset of endogenous endophthalmitis , all patients had diagnostic tapping for ocular specimen for microbiological investigations , including vitreous tap in 15 ( 68.2% ) eyes and aqueous tap in 10 ( 45.5% ) eyes .
all diagnostic taps were performed at the time of initial presentation with ocular symptoms and prior to commencement of intravitreal antimicrobial therapy .
four samples from the vitreous tap and two samples from the aqueous tap were found to be culture positive .
blood cultures were also performed in the patients and were positive in all ( 100% ) cases .
gram - negative organisms were found to be the causative microorganism in 11 eyes ( 50% ) , gram - positive organisms in 5 eyes ( 22.7% ) , and fungus in 6 eyes ( 27.3% ) ( table 2 ) .
the most common microorganisms were klebsiella pneumoniae ( 8 cases ) followed by candida sp .
the most common primary focus was urinary tract ( 7 eyes , 31.8% ) , followed by liver ( 4 eyes , 18.2% ) ( table 1 ) . topical antibiotics ( 17 eyes ) , intravitreal antibiotics ( 16 eyes ) , and systemic antibiotics ( 17 eyes ) were used in the treatment of bacterial endogenous endophthalmitis .
antifungal drugs , given as intravitreal injection ( 5 eyes ) and/or systemically ( 6 eyes ) , were used in cases with fungal endogenous endophthalmitis .
topical corticosteroid treatments were also used in 9 selected cases to reduce the extent of ocular inflammation .
systemic corticosteroid was also used in one patient to control the severe intraocular inflammation associated with neovascularization of the iris .
pars plana vitrectomy ( ppv ) was performed in 4 ( 18.2% ) eyes following the development of endogenous endophthalmitis , and 6 ( 27.3% ) eyes were enucleated or eviscerated due to uncontrollable infection with nlp vision .
there was a suggestive trend of having more enucleation or evisceration in eyes that had bacterial endogenous endophthalmitis ( 6 eyes , 37.5% ) compared with fungal endogenous endophthalmitis ( 0 eye , 0% ) but the difference failed to reach the level of statistical significance ( chi - square test , p = 0.07 ) .
ten ( 45.5% ) eyes had va of nlp , with five eyes having final va between 20/400 and 20/200 .
there was no significant difference in the proportion of eyes having vision of fc or better at the latest follow - up between bacterial and fungal cases ( 25% versus 16.7% , p = 0.68 ) .
eyes with more acute presentation ( within 48 hours of the onset of symptoms ) were less likely to have a final vision of fc or better compared with those who presented later ( 7.7% versus 44.4% , odds ratio = 0.10 , p = 0.041 ) .
the final visual acuity of one patient was not available as the patient died 1 month after presentation of endogenous endophthalmitis .
there were 3 ( 14.3% ) deaths during the follow - up period , two of which were related to systemic sepsis and the third death was due to disseminated nasopharyngeal carcinoma with multiple metastases .
endogenous endophthalmitis is a rare form of endophthalmitis which occurs when pathogen crosses the blood - ocular barrier and causes intraocular infection .
diagnosis of endogenous endophthalmitis is mainly based on clinical findings , and empirical treatment is usually administered while waiting for the microbiological investigations results from blood or intraocular specimens .
endogenous endophthalmitis is commonly associated with systemic conditions that can cause a relative immunocompromised state . in a major review of 267 cases of bacterial endogenous endophthalmitis by jackson et al .
, 56% of patients had an underlying condition that increased the risk of infections . in our current study ,
90.9% of patients had one or more identifiable preexisting predisposing condition and the commonest systemic condition found was diabetes mellitus ( 50% ) .
other coexisting potential risk factors included uti ( 36.4% ) , septicemia ( 31.8% ) , liver abscess ( 18.2% ) , malignancy ( 18.2% ) and renal transplant ( 9.1% ) with use of immunosuppressive therapy .
similar results can also be found in the literature as studies have demonstrated that up to 42% of endogenous endophthalmitis patients had underlying diabetes mellitus [ 6 , 11 ] .
connell et al .   also reported that 14.2% with bacterial infection had coexisting malignancy . in our series
the most common source was urinary tract in 36.4% , followed by liver abscess in 18.2% and soft tissue abscess and pneumonia in 4.5% each .
chung et al .   reported in their series of korean patients that 22.2% had pneumonia and 16.7% had liver abscess , while wong et al . reported in a singapore cohort that 48% of bacteremia arose from the hepatobiliary tract .
intravenous drug use ( ivdu ) was reported to be another risk factor more commonly in the west .
connell et al .   reported a figure of 48.1% of fungal infection cases that had ivdu , while leibovitch et al
.   showed that that 23.1% were ivdu and all of them suffered from fungal infection . in our series ,
only 1 case ( 4.5% ) of ivdu was identified but the patient had staph .
this relatively low positive rate revealed the difficulty of making a microbiological diagnosis in endogenous endophthalmitis . in order to improve the sensitivity and the speed of diagnosis
, the use of polymerase chain reaction ( pcr ) technique for diagnosing endogenous endophthalmitis has been advocated .
however , the technique is not without disadvantages as there is a false - positive rate of 5% due to sample contamination and antibiotics sensitivity can not be determined with pcr .
most of the published series that have included both fungal and bacterial endogenous endophthalmitis showed that fungal endogenous endophthalmitis was more common compared with bacterial cause [ 811 ] . in our current series
the commonest species found was klebsiella pneumoniae , which was present in 8 eyes ( 36.3% ) .
these results were different compared with those reported in north america and europe , where the majority of organisms found were fungal or gram - positive bacteria .
there has been a rising trend of gram - negative organisms causing endogenous endophthalmitis recently , especially in the south east asia [ 7 , 10 , 12 , 1416 ] .
the exact cause for the higher proportion of cases with gram - negative endogenous endophthalmitis is unknown but might be due to the higher prevalence of hepatobiliary infections in asian countries [ 12 , 17 , 18 ] .
endogenous endophthalmitis associated with klebsiella sp . is well documented to be associated with a poorer prognosis [ 19 , 20 ] . in our series
, 50% eyes requiring enucleation or evisceration were infected with klebsiella sp . 62.5% klebsiella infection coexisted with diabetes mellitus and 50% of them had liver abscess . in a 20-year review , ang et al
.   concluded that , in endogenous klebsiella endophthalmitis , presence of hypopyon and unilateral involvement are associated with poorer prognosis .
similar association of worse prognosis in eyes with hypopyon was also observed in our patients with klebsiella endogenous endophthalmitis .
six ( 75% ) of eight eyes with klebsiella endogenous endophthalmitis had hypopyon at presentation and all ended having nlp vision with 50% requiring evisceration .
for the two ( 75% ) eyes without hypopyon , the va at presentation was hm and fc , respectively , but the final va of these two cases both improved to 20/100 after prompt treatment .
treatment modality for bacterial endogenous endophthalmitis employed in our series included intravitreal and systemic antibiotics and antifungal as well as surgical treatments like ppv .
intravitreal antibiotics are generally essential in treating bacterial endogenous endophthalmitis as most topical or systemic antibiotics do not reach sufficient therapeutic level in the vitreous .
the use of intravitreal antibiotics has been reported to reduce the chance of evisceration or enucleation but it did not significantly improve the visual prognosis .
ppv is another important treatment option as previous study has demonstrated that ppv can result in an 85% anatomical success rate with 80% retained a vision of fc or better after surgery .
in addition , the chance of requiring enucleation or evisceration was also reduced after ppv . despite treatment ,
although previous studies suggested that fungal endogenous endophthalmitis was associated with better vision compared with bacterial endogenous endophthalmitis [ 810 ] , our findings showed no significant difference in the proportion of eyes with fc or better vision at the latest follow - up .
this highlights the need to have better therapeutic agents for intraocular fungal infections .   in conclusion ,
in contrast with previous studies , our series showed that bacterial causes in particular gram - negative bacteria were more common than fungal causes of endogenous endophthalmitis . despite recent advances in the medical and surgical treatment of postoperative exogenous endophthalmitis
, there appeared to be little improvement in the clinical outcome of endogenous endophthalmitis in the recent years .
a higher index of suspicion with early diagnosis with new molecular techniques and aggressive treatment might hopefully improve the prognosis in the future .
 
 purpose . to evaluate the clinical features , microbiological spectrum , and treatment outcomes of endogenous endophthalmitis 
 . methods . 
 retrospective review of consecutive cases with infective endogenous endophthalmitis presenting from 2000 to 2007 . 
 the main outcome measure was the visual outcome at the latest follow - up visit . 
 other outcome measures included microbiological investigations , anatomical and clinical outcomes . results . 
 22 eyes of 21 patients were included , and the mean follow - up duration was 2.7 years . 
 eyes with fungal endogenous endophthalmitis were more likely to have visual acuity of finger counting or better at presentation compared with those with bacterial endogenous endophthalmitis ( odds ratio = 15.0 , p = 0.013 ) . 
 gram - negative microorganisms accounted for 50% of infections , while fungal and gram - positive organisms accounted for 27.3% and 22.7% , respectively . despite treatment , 
 the visual outcome was poor in general as 10 ( 45.5% ) eyes had no light perception at the latest follow - up visit and 6 ( 27.3% ) eyes required enucleation or evisceration . 
 contrary to previous studies , fungal endogenous endophthalmitis did not appear to have better visual outcome compared with bacterial endogenous endophthalmitis . conclusion . 
 gram - negative microorganisms were the main causative pathogens of endogenous endophthalmitis in hong kong . 
 the visual prognosis of endogenous endophthalmitis is generally poor as almost 50% of eyes were blind despite treatment . 
1. Introduction
2. Methods
3. Results
4. Discussion