Outcome of endophthalmitis treatment in a tertiary referral center in southern iran.

PURPOSE: The purpose of this study was to investigate the causative organisms, the clinical characteristics, visual outcomes, and the incidence of acute endophthalmitis after cataract surgery.
MATERIALS AND METHODS: In this retrospective study, a chart review was performed for patients treated in a tertiary referral center for acute endophthalmitis after cataract surgery from January 2005 to December 2009. During the study period, 62 additional patients with acute postoperative endophthalmitis were referred to and treated in this center. Therefore the cohort comprised 70 patients (8 of whom underwent cataract surgery at our center, and 62 who were referred). Demographic, clinical, and laboratory data were analyzed. The primary outcome measure was final visual acuity. P<0.05 indicated statistical significance
RESULTS: During the study period, 7737 cataract surgeries were performed in this center. Eight (0.10%) of 7737 eyes developed acute postoperative endophthalmitis. Subgroup analysis indicated that extracapsular cataract extraction was associated with a fourfold higher risk of endophthalmitis compared with phacoemulsification. We found better initial visual acuity (VA) (≥ hand motion) (P<0.001) and negative cultures (P=0.021) were independently associated with a more favorable visual outcome. Patients with relative afferent papillary defect (RAPD) were associated with lower initial VA (P<0.001) and worse visual outcome (P=0.001). Positive microbial cultures were found for 33 (42.9%) cases. Staphylococcus aureus was the most common organism isolated. Positive cultures were more frequently found in patients with RAPD. The "gram-positive coagulase-negative" and "no growth" groups had the best visual outcome. Associated keratitis and avoiding intraocular steroids were associated with the risk of evisceration.
CONCLUSION: The visual outcome after endophthalmitis was generally poor and only one eighth of the eyes achieved a final corrected visual acuity of ≥20/200. Therefore, better treatment strategies are warranted. Immediate treatment is essential and the role of primary vitrectomy requires further investigation. In addition, RAPD, as an objective test, may complement VA for predicting the prognosis and planning the course of treatment.

INTRODUCTION

Cataract surgery is one of the most effective and most commonly performed surgical procedures worldwide.1 Postoperative endophthalmitis is a rare but devastating complication of cataract surgery.2–4 During the past century, innovations in surgical techniques, instruments, and intraocular lens (IOL) design led to substantial decline in the incidence of postoperative endophthalmitis from 0. 58% in the mid-1900s56 to 0.04% in the 1990s.7 Over the last decade, other advances in cataract surgery include small incision, sutureless, phacoemulsification surgery with foldable IOLs implantation under local anesthesia.8 Ongoing advances in the surgical technique and instrumentation may raise new issues regarding the rate and characteristics of postoperative endophthalmitis; while shorter duration of surgery and smaller incisions may decrease the chance of endophthalmitis, sutureless techniques may increase the early postoperative intraocular penetration of offending bacteria.

Although several large series on the epidemiology and incidence of endophthalmitis have been conducted, data from Middle Eastern countries such as Iran are inadequate. It is unclear whether the results of studies from northern America and Europe are applicable to other populations and settings. As cataract surgery is one of the most commonly performed surgical procedures in Iran, a study on the incidence of cataract surgery related complications is warranted. Therefore, we have conducted this study to report the rate and characteristics of endophthalmitis after cataract surgery in southern Iran.

MATERIALS AND METHODS

A retrospective chart review was performed of 70 patients (70 eyes) who were admitted in Khalili eye and ear infirmary (affiliated to Shiraz University of Medical Sciences) with a diagnosis of acute endophthalmitis after cataract surgery from January 2005 to December 2009. Khalili hospital is located in Shiraz and is a tertiary referral center for several southern provinces of Iran. This study was performed in accordance with the tenets of Helsinki. In addition, the study protocol was approved by the Ethics Committee of the Shiraz University of Medical Sciences.

The diagnosis of acute endophthalmitis was based on clinical examination and defined as intraocular inflammation involving both the vitreous and the anterior chamber attributable to bacterial or fungal infection occurring within 6 weeks after surgery.9 Patients with previous or concomitant surgeries such as trabeculectomy, pars plana vitrectomy or penetrating keratoplasty on the same eye were excluded from the study.

Data were collected on patient demographic, systemic conditions and medications, type of cataract surgery (intracapsular, extracapsular, or phacoemulsification), interval between cataract surgery and onset of symptoms, interval between onset of symptoms and admission, causative organisms, the hospital in which cataract surgery was performed, and treatment modalities. Findings of the ophthalmic examination with specific focus on initial and final corrected visual acuity visual acuity (VA), relative afferent pupillary defect (RAPD), associated keratitis, and vitreoretinal findings were recorded as well.

In general, the treatment approach adhered to the Endophthalmitis Vitrectomy Study (EVS) guidelines.2 For eyes with an initial VA of light perception (LP), primary vitrectomy was performed, while intravitreal injections of wide spectrum antibiotics were delivered for eyes with better initial VA. Intravitreal injection was also performed for patients with LP vision with a hazy cornea that precluded vitrectomy. The vitrectomy procedure included obtaining 0.5-1 ml of undiluted vitreous sample from the mid-vitreous at the start of the procedure followed by a pars plana vitrectomy with 20 μg/ml vancomycin and 40 μg/ml ceftazidime in an infusion bottle of balanced salt solution. For cases with VA of hand motion (HM) or better, intraocular samples were taken by anterior chamber and vitreous tap (0.1 ml) obtained with a 27-gauge needle connected to an insulin syringe. Then vancomycin (1 mg in 0.1 ml) and ceftazidime (2.25 mg in 0.1 ml) were injected intravitreally. In patients with associated retinal findings primary vitrectomy was performed despite VA of HM or better. All patients were also treated with frequent topical fortified, subconjunctival and systemic vancomycin, and ceftazidime as a standard protocol which was then tailored according to the results of culture and antibiogram study. Intravitreal, topical, and systemic steroid were prescribed depending on the type of offending organism, degree of inflammation, and judgment of the treating ophthalmologist.

Samples were immediately sent to the microbiology laboratory for bacterial and fungal smear and culture. Gram stain and potassium hydroxide solution (KOH) preparation were analyzed by expert microbiologists. The samples were directly inoculated on blood agar, chocolate agar, Sabouraud's agar, and brain heart infusion broth. A positive culture was defined as a growth of the same organisms on 2 or more media or confluent growth on one solid medium. Polymicrobial infection was defined as growth of more than one bacteria or a positive bacterial culture along with a positive fungal culture from the same eye. Sterile endophthalmitis was defined as a case suspected of being infectious but with negative cultures.10

Statistical analysis

Statistical analysis was performed using Statistical Package for Social Sciences software version 17 (SPSS Inc., Chicago, Illinois). Nominal and continuous variables were analyzed using the Chi-square test and Mann-Whitney U test, respectively. Regression analysis was used to determine any possible predictive association between different factors. A P value ≤ 0.05 was considered statistically significant.

RESULTS

During the 5-year study period, 70 patients (70 eyes) with acute endophthalmitis after cataract surgery were treated at Khalili hospital. The mean age was 65.04±13.70 years (range, 22-85 years). Males comprised 52.9% (n = 37) of the cohort. The right eye was involved in 50% of the cases. Patients were referred by 38 ophthalmic surgeons from 25 hospitals (0.37 cases/surgeon/year). Eight (11.4%) of 70 cases had undergone cataract surgery at Khalili hospital and the remaining cases were referred from other hospitals in Shiraz and the southern provinces of Iran.

From January 2005 to December 2009, a total of 7737 cataract surgeries (6710 phacoemulsification, 927 extracapsular cataract extraction (ECCE), 100 intracapsular cataract extraction (ICCE)) were performed at Khalili hospital of which 8 eyes developed endophthalmitis. Thus, the total rate of acute endophthalmitis at Khalili hospital was 0.1%. The rate was calculated as 0.074%, 0.22%, and 1%, for phacoemulsification, ECCE, and ICCE, respectively (P<0.001).

Of a total of 70 cases that were treated at Khalili hospital for endophthalmitis, the primary operation was phacoemulsification, ECCE, and ICCE in 50 cases, 19 cases, and 1 case respectively. All eyes were pseudophakic except for one that was aphakic. The median interval from primary operation to onset of symptoms was 4 (range, 1-42) days. The interval of 4 or less days occurred in 52.9% (n = 37) of patients. The median interval since onset of symptoms to admission was 2 days (range, 1-45 days). The interval of 4 or less days occurred in 80% (n = 56) of patients. Mean duration of hospitalization was 8.17 ± 2.96 (range, 3-19) days; 35 patients (50%) were admitted for 7 days or less. Vitrectomy was the initial approach in 15 (21.4%) patients. Due to coexisting conditions, only 36.6% of cases that presented with LP visual acuity were treated with primary vitrectomy. Of those who primarily underwent intravitreal injection (n = 55), 14.5% (n = 8) received more than 1 injection, and 49.1% (n = 27) required a secondary vitrectomy. Time of first intervention was on the day of admission in 84.3%, and on the day after admission in the remainder. On admission, 57 patients (81.4%) had hypopyon and 9 eyes (12.9%) had associated keratitis.

Microbial and fungal cultures were negative in 37 (52.9%) patients. Among those with positive culture, Staphylococcus aureus was the most organism isolated. The cases with “no growth” cultures and “gram-positive coagulase-negative” isolates showed better visual outcomes compared with “gram-positive coagulase-positive” or “gram-negative” isolates (P<0.001, Table 1). Pseudomonas aeruginosa (n = 2) and Staphylococcus aureus (n = 2) were isolated from sample of eyes that were eviscerated. Older age (>65 years), presence of hypopyon, and RAPD were predictive factors for positive cultures. In multiple regression analysis, however, RAPD was the only factor that showed an independent association.

Table 1

Different types of micro-organisms isolated from cultures of intraocular fluids of patients with acute postoperative endophthalmitis categorized by presenting visual acuity

Ninety percent of eyes presented with VA of ≥HM were treated with intravitreal injections. Additionally, 60% of eyes with initial VA of LP were treated with intravitreal injections. Intravitreal injections were performed because the seven (77.8%) corneas with associated keratitis were not clear enough for vitrectomy. In 13.3% of eyes treated with primary vitrectomy, a second vitrectomy procedure was performed, and one patient (7.6%) received secondary intravitreal antibiotic injection. Intravitreal steroids (dexamethasone or betamethasone) were used in 77.7% and 60% of eyes treated with intravitreal injections or primary vitrectomy, respectively. Overall, the treatment was associated with significant increase in VA (P<0.001, Figure 1). VA improved in 72.8% of eyes, remained stable in 24.3% of eyes and deteriorated in 2.8% of eyes. For eyes with an initial VA of LP, primary vitrectomy was associated with better final VA, while in eyes with primary VA of ≥HM, intravitreal injections resulted in better outcomes. The difference, however, did not reach statistical significance [Figure 2]. Several factors showed an association to final VA [Table 2]. Initial VA of LP and positive cultures were independently associated with final visual acuity of ≤HM.

Figure 1

Effect of standard treatments on visual acuity of patients with acute postcataract surgery endophthalmitis. CF: Counting fingers, HM: Hand motion, LP: Light perception, NLP: No light perception, VA: Visual acuity

Figure 2

Effect of primary vitrectomy versus tap/injection on final visual acuity, based on the presenting visual acuity. CF: Counting fingers, HM: Hand motion, LP: Light perception, VA: Visual acuity

Table 2

Association between characteristics of the patients and selected dependent outcomes

RAPD was not evaluated in 12 eyes (17.1%) due to bilaterally sluggish or fixed pupils. RAPD was present in 19 eyes (27.1%). Of those with RAPD, 84.2 % (n = 16) were older than 65 years (P=0.015). The majority of eyes (73.7% (n =14) of eyes) with RAPD presented with VA of LP, whereas 77% (n = 30) of patients without RAPD had initial VA of ≥HM (P<0.001). In those without RAPD, 66.7% of eyes had a final VA of >HM, while only 21.1% of eyes with RAPD had the same VA (P = 0.001). Primary vitrectomy was performed in 73.7% of eyes with RAPD and 46.2% of eyes without RAPD (P=0.087). Primary vitrectomy did not lead to better visual outcomes in eyes with RAPD compared to eyes without RAPD (P=0.60).

Signs in the anterior segment included corneal edema in 51 (72.8%) eyes. Eight (88.9%) eyes with associated keratitis had initial VA of LP (P=0.003). The associated posterior segment signs included retinal detachment in 5 (7.1%) eyes, choroidal detachment in 3 (4.3%) eyes and vitreous hemorrhage in 1 (1.4%) eye.

Diabetes mellitus was not associated with worse final VA or a longer duration of hospitalization (P=0.23, and P=0.91, respectively). Eyes with initial VA of LP had a higher risk of longer hospitalization. Patients who received the intervention on the day after admission had 4.41-fold greater chance of longer hospitalization (greater than 7 days) compared with eyes treated on the day of admission. Multiple injections in the subgroup of patients who were initially treated with intravitreal injections were also associated with longer duration of hospitalization.

Four patients ended up in eviscearation. One of them underwent primary evisceration, two eyes underwent evisceration despite intravitreal injections, and one eye was eviscerated after unsuccessful vitrectomy. Initial VA in all patients whose eyes underwent evisceration was LP (P = 0.03, Fisher's exact test). All four eyes that underwent evisceration were associated with keratitis and had not received intravitreal steroids [Table 2].

DISCUSSION

Several approaches have been advocated to decrease the rate of postoperative endophthalmitis. Applying povidone iodine 5% solution in the conjunctival sac a few minutes prior to surgery is the most widely accepted intervention. Other modalities such as proper wound construction, injectable intraocular lenses, prophylactic intracameral or subconjunctival antibiotics, postoperative patching for at least 4 hours, and initiating topical antibiotics beginning the day of surgery have also been advocated to lower the rate of postoperative endophthalmitis.11–13 In Khalili hospital, we have used several modalities to prevent endophthalmitis. In nearly all cases, a cotton-tipped applicator soaked in povidone iodine 10% solution was applied to the lid margins and into inferior cul-de-sac before starting the procedure. We have also used subconjunctival gentamicin or cefazolin at the end of surgery. In addition, cases with active conjunctivitis or nasolacrimal duct obstruction underwent cataract surgery only after adequate antibiotic therapy and resolution of the infectious process.

In Khalili hospital the rate of acute endophthalmitis after cataract surgery was 0.1%, a little higher than that reported from Saudi Arabia (10-year incidence = 0.068%).14 As the present study was retrospective in nature, the rate of endophthalmitis in our center may be confounded by the possibility of patient referral to other centers. The incidence of endophthalmitis varies in different studies; some studies report higher rates1516 and others found lower incidence compared with ours.1791718 Two studies reported a nearly similar rate as the current study.1920 Geographic variations, and different settings, surgical techniques, prophylaxis, and methodologies may be responsible for this variability in the reported incidence of endopthalmitis.

The present study showed that endophthalmitis is fourfold more common after ECCE than that after phacoemulsification. To the contrary, Al-Mezaine et al.14 reported that the incidence of acute-onset endophthalmitis was 0.049% and 0.085% for ECCE and clear corneal phacoemulsification, respectively. Similarly, Wong and Chee21 found the risk of endophthalmitis after phacocmulsification was 1.8 times higher than that after ECCE. Other studies did not find a significant difference between ECCE and phacoemulsification.2223 In this study, there was no significant difference in visual outcomes between post-ECCE and postphacoemulsification cases. On the other hand, Al-Mezaine et al.14 showed that the outcome was much worse in post-ECCE endophthalmitis cases. It has been proposed that the larger incision in ECCE (compared with phacoemulsification) may facilitate a retrograde flow of fluid from the ocular surface into the eye. However, sutureless clear corneal incision during phacoemulsification may be more permeable compared with a well-apposed ECCE wound.

Pars plana vitrectomy or tap/injection represent standard treatments for acute postoperative endophthalmitis.24 The endophthalmitis vitrectomy study (EVS) advocates primary vitrectomy only in patients with initial VA of LP, while other studies suggest early vitrectomy in more patients.225 Accordingly, Kuhn et al. reported that 91% of 47 eyes treated with vitrectomy achieved a final VA of ≥20/40.25 In our hospital, the decision to perform primary vitrectomy is primarily based on the EVS findings. However, several coexisting conditions such as media opacity, and nonavailability of a vitreoretinal surgeon or an emergency operating room on the day of admission precluded primary vitrectomy in all patients with LP vision. There was no significant difference in visual outcome of patients treated with primary vitrectomy compared to tap/injection. Nevertheless, because the rate of early reintervention was lower with initial vitrectomy, it may be a better approach compared to tap/injection in selected cases with postoperative endophthalmitis. Finally, our study showed that early intervention (either vitrectomy or tap/injection) was significantly associated with a shorter hospital course which in turn may decrease the overall burden of the disorder.

The visual outcome after endophthalmitis is generally poor. Prompt and appropriate treatment can improve the visual outcome.26 Although our results showed that standard interventions led to significant improvement in VA, only a minority of patients achieved final VA of ≥20/200. In the studies by Kamalarajah et al. and Al-Mezaine et al.,14 66% and 35% of patients attained VA of ≥20/200, respectively. Better visual outcome in these series compared with ours seems to be rooted in the lower presenting VA of our patients. Wong and Chee21 found a direct relationship between presenting and final VA. EVS showed that VA at presentation, bacterial culture results, and the type of treatment influenced visual outcome.2 Our results confirmed the association between lower initial VA and culture positivity with poor visual outcome. As would be expected, our study showed that patients with lower initial VA were more likely to have longer hospital course.

To the best of our knowledge (via MEDLINE browsing), this is the first study that found a relationship between RAPD and poor visual outcome in postcataract surgery endophthalmitis. In multiple regression analysis, however, RAPD did not show independent association with final VA. This may be because of the high correlation between RAPD and lower initial VA. Anyway, RAPD seems to be a good objective test for planning the treatment and predicting the final visual potential. It can be used as a complementary and/or alternative test to presenting VA in whom VA testing is inconclusive due to poor cooperation (i.e., children, elderly, and mental retards).

The time from surgery to signs of endophthalmitis in our study was comparable to previous studies.2728 In our study there was no difference on visual outcome between patients with signs of endophthalmitis within 4 days and those presented after 4 days. However, other studies suggested that a short time from surgery to signs of endophthalmitis is a measure of virulence of the causative bacteria, with an expected worse treatment outcome.429

The rate of culture positivity was 47.1% in the present study, which is less than that of reported in the EVS (67%),2 and other studies in Canada (60%),7 Australia (67%),30 Sweden (75%),31 and Saudi Arabia (90%).14 The low rates of culture positivity in our study may have been resulted from suboptimal culture media or laboratory settings as well as poor techniques in taking or transferring the samples. We found that culture positivity was associated with poor final visual acuity, while others claimed that patients with culture-negative ocular samples had a worse outcome.4

Causative organism is considered a major determinant in the outcome of postcataract surgery endophthalmitis.13212732 It seems that there may be some geographic variations in infectious agents causing endophthalmitis. In this study, of those with positive cultures, 55.7% were gram positive and 39.3% were gram negative. In contrast, a referral center in northern Taiwan found that 44.1% of the culture-positive isolates were gram positive and 55.9% were gram negative.33 Our data showed that the most isolated organisms were staphylococcus species (22.9%) [Table 1]. The study conducted in Saudi Arabia found staphylococcus species in 35% of eyes, streptococcus species in 35%, polymicrobial or mixed infections in 15%, and propionibacterium acnes in 5%.14 In our series, fungus was isolated from only one eye. EVS2 reported no fungi isolate from 420 eyes with endophthalmitis. On the other hand, two studies from India reported that pseudomonas aroginosa and fungi were the most common isolated organisms.3435 Rehak et al. reported that endophthalmitis associated with microbial keratitis was mainly caused by filamentous fungi (37.2%) and gram-negative bacilli (37.2%);36 however, according to our data the most common bacterial isolates were staphylococcus aureus and pseudomonas aroginosa.

In our study, the eyes with gram-negative or staphylococcus aureus bacterial growth had worst visual outcome. Three (23%) of our 13 cases with a bacterial culture of staphylococcus aureus achieved a final VA of ≥20/200, compared to 20.0%, 36.7%, and 0.0% in other reports.32728 Differences may have been resulted from various types of antibiotics used as well as variations in virulence and resistance of bacteria.

Our results showed that RAPD, age >65 years, and presence of hypopyon were associated with positive cultures, of which RAPD was the only independent risk factor. Elderly and associated lid changes are probably linked to decreased ocular surface immunity. Therefore, organisms isolated from these eyes may have greater chance of colonizing in culture media. This may also be true for eyes with RAPD who probably infected with more virulent organisms. In the EVS, it was suggested that diabetics may have a higher culture positivity compared to nondiabetics.29 However, we did not find any significant difference between these subgroups.

Although the use of intravitreal steroide was not studied in the EVS, this adjunctive treatment has gained popularity as a means to potentially decrease intraocular inflammation and thereby improve visual outcomes. It was reported that early intravitreal administration of 400 μg dexamethasone seems to be beneficial in treating postoperative staphylococcus epidermidis-related endophthalmitis.37 However, adding steroid to the intravitreal antibiotics did not show a significant effect on final VA in our study. Overall, results from previous studies are inconclusive and further investigation is warranted.38–40

The rate of evisceration in our study was 5.7% compared with 25% in the series by Wejde et al.20 In the present study bacterial isolates in eyes who underwent evisceration were pseudomonas aeroginosa (n = 2, 50%) and staphylococcus aureus (n = 2, 50%). The rate of evisceration was 50% and 16.7% in eyes with Pseudomonas aeruginosa and Staphylococcus aureus endophthalmitis, respectively. Our findings concur with those of Pinna et al.41 who found that 50% of cases with endophthalmitis after cataract surgery due to Pseudomonas aeruginosa, underwent evisceration or had phthisis of the affected eye. Aifrig et al.42 showed that endophthalmitis caused by Pseudomonas aeruginosa is associated with evisceration or enucleation despite prompt treatment.

Tsai et al.43 showed that older age, no light perception at presentation, endogenous endophthalmitis, and endophthalmitis associated with corneal ulcer were statistically significant factors associated with the need for evisceration or enucleation. Our data confirmed that accompanying keratitis was associated with the risk of evisceration, while intravitreal steroids decreased the chance. Keratitis may intensify the media opacity and consequently interfere with evaluation of posterior segment and is also a source of persistent infection, both of which may explain why eyes with associated keratitis had poor outcomes. Primary vitrectomy did not influence the rate of evisceration in our study.

In summary, our study confirmed results of previous studies that document the reduced visual potential after acute postcataract surgery endophthalmitis. We also found that RAPD can accurately predict the visual outcome and may be used as an adjunct to presenting VA for planning the treatment, especially in uncooperative patients in whom VA testing is inconclusive. This study is limited by its retrospective nature. In addition, patients were referred from diverse centers in southern Iran. Therefore, the results represent the characteristics of postoperative endophthalmitis in southern Iran and outcome of treatment in a tertiary referral center in Shiraz. With continued innovations in cataract surgery and treatment of endophthalmitis, and the increasing resistance of microbes, continued evaluation of incidence, characteristics, and treatment outcomes of endophthalmitis is required.