Demographic features
Included were 74 eyes of 70 patients (39 males (56%)) diagnosed with endophthalmitis based on the clinical presentation. Mean±SD age at presentation was 60±19.5 years (median 59, range 3-90). Endophthalmitis was of an exogenous etiology in the majority of eyes (58 eyes, 78%). Mean follow-up time was 24 months (median 24 months, range 1 month- 8 years).
Exogenous Endophthalmitis (ExE)
Of the 58 eyes with ExE, 36 eyes (62%) presented following an eye operation, 12 eyes (21%) presented after intravitreal anti-vascular endothelial growth factor (VEGF) injection, six eyes (10%) presented secondary to infectious keratitis and four eyes (7%) presented after a penetrating trauma of the globe (Table 1).
Of the 36 postoperative cases: Seventeen eyes (47%) were infected following cataract extraction and intraocular lens (IOL) implantation, 10 eyes (28%) after glaucoma procedures, four eyes (11%) after vitrectomy, four eyes (11%) after combined phacoemulsification and vitrectomy and one eye (3%) after penetrating keratoplasty (Table 1).
Positive vitreous cultures were obtained in 35 (60%) out of the 58 eyes (57 patients), all of which indicated bacterial infection. Eleven patients (19%) had diabetes mellitus type 2 (DM2) and two were on immunosuppressive medications because of lupus in one patient and after bone marrow transplantation in another patient.
Endogenous Endophthalmitis (EnE)
EnE was observed in 16 (22%) eyes of 13 patients. Ten of them (77%) were occultly or overtly immunocompromised (Table 2) (5 patients (38%) had DM2).
Positive vitreous cultures were obtained in nine eyes (56%), of them; fungal infection was detected in five eyes (56%) and bacterial infection in four eyes (44%). Fungal isolates included Candida in four samples and Pseudallescheria boydii in one sample (Table 2, 3). Bacterial infections included Streptococcus anginosus, Streptococcus salivarius, Staphylococcus aureus and Staphylococcus epidermidis.
Three patients had bilateral EnE (Table 2): in patient #4, Candida albicans was isolated from the vitreous sample of one eye, in patient #9 it was presumed to be fungal because of the compatible clinical findings on funduscopy and in patient #10 it was secondary to Methicillin-resistant staphylococcus aureus (MRSA) isolated from blood sample.
Microbial Spectrum
Table 3 presents the microbial isolates from the 44 (59%) culture-positive samples. Gram-positive bacteria were the most commonly isolated microorganisms, detected in 33 samples (75%). Gram-negative bacteria were isolated in six (14%) and fungi were present in five samples (11%).
Among all the 44 isolates, Staphylococcus epidermidis was the most commonly isolated microbe present in 14 samples (32%). Enterococcus faecalis was the second most commonly detected microbe observed in four samples (9%).
Clinical Presentation
All patients were symptomatic. The majority of patients (41 patients, 59%) presented with a combination of symptoms. The most common presenting symptom was deterioration of vision reported by 50 patients (71%). Thirty-four patients (49%) presented with pain, 30 patients (43%) presented with eye redness and 14 patients (20%) presented with eye discharge.
Mean presenting LogMAR±SD VA was 2.38±1.21 and even though it remained poor throughout the entire study, it improved at one month of follow-up to 1.68±1.29 (p=0.002, paired t-test) and at the last visit to 1.7±1.37 (p=0.004, paired t-test, baseline VA compared to VA of last visit). At presentation, 56 eyes (76%) had severe visual loss and this significantly decreased to 42 eyes (57%) by the last follow-up (p= 0.004) (Table 4). On the other hand, only 7 eyes (9%) had good VA at presentation and this significantly increased to 17 eyes (23%) at the last follow-up (p= 0.02). Subgroup analysis by the microorganism type (Figure 1) demonstrated improvement in VA at one month and at the last visit in comparison to baseline VA in eyes with gram-positive endophthalmitis (2.17±1.24 at presentation vs. 1.35±1.18 and 1.34±1.34, respectively, p=0.06, p=0.09, paired t-test). VA in eyes with gram-negative endophthalmitis did not improve (2.75±1.19 at presentation vs. 2.41±1.16 and 2.55±1.21, respectively, p= 0.45, p=0.62, paired t-test). On first presentation, hypopyon was observed in 41 eyes (55%), dense vitritis obscuring the view of the fundus in 55 eyes (74%) and retinal infiltrates in 10 eyes (14%).
Univariate and multivariate analysis were used to assess the correlation between last VA and microbe type, positivity of blood and vitreous cultures, presenting signs and symptoms, source and etiology of the infection, immune system status and treatment modality. In those models, cases secondary to gram-positive microbes were associated with improved VA during the follow-up while cases secondary to gram-negative microbes were correlated with poor final VA (p=0.046, r2=0.4). Figure 1 shows the changes in VA throughout the study period per microorganism type.
Ocular Complications
The most common complication was rhegmatogenous retinal detachment, documented in 12 eyes (16%). Phthisis bulbi developed in 12 eyes (16%), five of which were eviscerated/enucleated (Table 5). The mean age± SD of patients who developed phthisis bulbi was 68± 20 years (median 72 years, females 58%). The preceding events were cataract operation in four eyes, infectious keratitis in three eyes, glaucoma filtering valve in two eyes, intravitreal injection in two eyes and endogenous fungal endophthalmitis after near-drowning in one eye. In six eyes (50%), no pathogen was isolated. The most commonly isolated microorganism was Enterococcus faecalis in two eyes. Mycobacterium chelonae, Streptococcus mitis, Streptococcus agalactiae, and Pseudallescheria boydii were each isolated in one eye. Of the five eyes that were enucleated/eviscerated, no growth was documented in three eyes whereas Mycobacterium chelonae and Pseudallescheria boydii were detected in the remaining two eyes.
Treatment
Seventy-one eyes (96%) were treated empirically with a combination of intravitreal ceftazidime (2 mg/ 0.1 mL) and vancomycin (1 mg/0.1 mL). Of those 71 eyes, seven received voriconazole (100 mcg/0.05 mL) and two received amphotericin (5 mcg/0.1 mL) concomitantly.
Amikacin monotherapy (0. 4 mg/0.1 ml) was injected to one eye (1.3%) based on a positive vitreous culture result of amikacin-sensitive Pseudomonas aeruginosa from another hospital. Voriconazole monotherapy was injected to one eye (1.3%) of a patient with candidemia. One eye (1.3%) did not receive intravitreal therapy given the late presentation and the lack of potential vision that necessitated evisceration (Table 2, pt #13). Intravitreal dexamethasone (0.4 mg/0.1 mL) was administered to 22 eyes (31%) in combination with intravitreal antimicrobial therapy. The median number of intravitreal antimicrobial injections was two (mean 1.77, range 1-5).
Systemic intravenous antibiotics were part of the treatment regimen in 44 patients (63%) (All patients with EnE received systemic antibiotics). Vancomycin was the most commonly used systemic antibiotic treatment, administered to 25 patients; Ceftazidime was used in 16 and ceftriaxone in 11 patients. Oral prednisone was administered in 13 patients (19%). Pars plana vitrectomy was performed in 57 eyes (77%) at a median of 1 day after presentation.
Antibiograms did not reveal resistance to the used antimicrobial agents (Table 6).