Inclusion criteria
Exclusion criteria
Visual acuity—light perception (LP) or better and worse than 36 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) acuity chart placed at 4 m (equivalent to approximately 20/50 or worse)
Known eye disease limiting visual acuity to 20/100 before development of cataract
Sufficient clarity of the cornea and anterior chamber of the involved eye to allow visualization of at least some part of the iris
Prior intraocular surgery other than cataract or IOL surgery
Sufficient clarity of the cornea to perform pars plana vitrectomy
Prior penetrating ocular trauma
A hypopyon or sufficient clouding of the anterior chamber or vitreous to obscure a view of second-order retinal arterioles
Previous injection of intravitreal antibiotics
Prior pars plana vitrectomy, retinal detachment, or moderately high choroidal detachment, as judged by indirect ophthalmoscopy or ultrasound
Probable intolerance to any study drugs (with exception of penicillin allergy, in which case alternatives to beta-lactam drugs were used)
Strong suspicion of fungal endophthalmitis
Treatment Assignment
The eligible patients were assigned at random to a 2 × 2 factorial design to one of the four treatment groups (Table 32.2).
Table 32.2
Two-by-two factorial design in the EVS
Group VIT-IV | Group VIT-NOIV |
Initial vitrectomy (VIT) Intravenous antibiotics (IV) | Initial vitrectomy (VIT) No intravenous antibiotic (NO IV) |
Group TAP-IV Initial tap or biopsy (TAP) Intravenous antibiotics (IV) | Group TAP-NOIV Initial tap or biopsy (TAP) No intravenous antibiotics (NO IV) |
Treatment Strategy
Treatment was initiated within 6 h of initial examination. In all four groups, undiluted vitreous specimen was collected before performing the assigned procedure, usually with a vitreous cutter in the VIT group and using a needle in the TAP group. Patients assigned to VIT received a three-port pars plana vitrectomy, and no additional attempt was done to separate the posterior vitreous, if not separated already. A vitreous volume of 0.1–0.3 ml was collected in patients assigned to TAP. Two intravitreal antibiotics were injected in all four groups, vancomycin 1.0 mg in 0.1 ml and amikacin 0.4 mg in 0.1 ml. Patients assigned to intravenous (IV) antibiotics received ceftazidime and amikacin.
Culture
Undiluted vitreous and vitrectomy effluent, when vitrectomy was done, were cultured. Three media were used—chocolate agar (37 °C in CO2), thioglycolate broth, and Sabouraud dextrose agar. The vitrectomy effluent was filtered through a sterile 0.45 μm membrane filter; the filter was divided into three pieces under sterile conditions. The three pieces of filter papers were cultured in chocolate agar, in Sabouraud dextrose agar, and thioglycolate broth. Gram stain was used for microscopy. The microbiological results were categorized into “confirmed positive,” “equivocal,” and “negative.” The microbiology and infection category is shown in Table 32.3 [2].
Table 32.3
Microbiology and infection category in EVS
Confirmed positive | Equivocal | Negative | |
---|---|---|---|
Microbiology category | At least semi-confluent (≥11 cfu growth on at least one solid medium) Growth in two or more media Growth in two media, one from the vitreous/AC fluid sample and the other from vitrectomy cassette | Any growth <11 cfu | No growth in any medium |
Infection category | Confirmed positive culture Equivocal culture + positive Gram stain of corresponding tinctorial properties | Equivocal culture + gram stain equivocal or negative Gram stain positive, culture negative | No growth in any medium |
In the EVS there was 69.3% (n = 291) confirmed growth, 12.9% (n = 54) was equivocal growth, and 17.9% (n = 75) was no growth. Gram-positive cocci were more common (94.2%) than gram-negative bacilli (5.9%), and gram-positive coagulase-negative micrococci were the most common isolation (n = 226; 70%).
All gram-positive coagulase-negative micrococci were sensitive in descending order to vancomycin (100%), amikacin (86.1%), and ciprofloxacin (77.9%); gram-negative bacilli were sensitive in descending order to ciprofloxacin (94.7%) and both ceftazidime and amikacin (89.5% each). In nearly all instances, the study drug combination was sensitive to the isolates in the EVS (Table 32.4).
Table 32.4
Susceptibility of organisms to trial drug combinations in EVS
Drug combination | Possible routes in EVS | Total no. of isolates | No isolates susceptible to at least one drug | |
---|---|---|---|---|
Vancomycin | Amikacin | Intravit/subconj | 321 | 319 (99.4%) |
Vancomycin | Ceftazidime | Subconj | 321 | 319 (99.4%) |
Amikacin | Ciprofloxacin | Systemic | 320 | 287 (89.7%) |
Amikacin | Ceftazidime | Systemic | 318 | 281 (88.4%) |
Study Medications
The EVS used medicines through all routes—topical, subconjunctival, intravitreal, and systemic (intravenous or oral). These consisted of antibiotics, vancomycin, ceftazidime, amikacin, and ciprofloxacin, and corticosteroids, dexamethasone and prednisolone. The details and route of delivery are shown in Table 32.5.
Table 32.5
EVS medicines and routes of delivery
Drug | Route | |||
---|---|---|---|---|
Intravitreal | Subconj | Systemic | Topical | |
Vancomycin | 1.0 mg/0.1 ml | 25 mg/0.5 ml | x | 50 mg/ml |
Amikacin | 0.4 mg/0.1 ml | 25 mg/0.1 ml | 7.5 mg/kg IV 1, then 6 mg/kg IV q 12 h for 5–10 days | 20 mg/ml |
Ceftazidime | x | x | 2 g IV q8h for 5–10 days | x |
Dexamethasone | x | 6 mg/0.25 ml | x | x |
Ciprofloxacin | x | x | 750 mg PO twice daily (if allergic to penicillin) for 5–10 days | x |
Prednisone | x | x | 30 mg PO twice daily for 5–10 days | |
Delivery schedule | During of VIT/TAP | At end of VIT/TAP | Post VIT/TAP | Post VIT/TAP |
Summary of Major Results
In the EVS 420 patients were recruited in 24 study centers. The major results are tabulated in Table 32.6 [3].
Table 32.6
EVS major results
Category | Results | ||
---|---|---|---|
Symptoms | Reduced vision. 26% had LP only; 12% had afferent pupillary defect; 5% had corneal ring ulcer Pain was absent in 25% patients | ||
Signs | Hypopyon. 86% patients had hypopyon | ||
Culture | Culture positivity rate: 69.3% (n = 291) 68% gram-positive coagulase-negative organisms 22% other gram-positive organisms 6% gram-negative organisms 4% poly-bacterial infection | ||
Higher rate of confirmed growth gram-positive coagulase-negative micrococci | Diabetes mellitus was the only factor associated with significantly higher incidence of gram-positive coagulase-negative micrococci (58.6%) | ||
Baseline features of higher confirmed growth | Five factors correlated with higher rates (84.5%) of gram negative and gram positive (other than coagulase-negative micrococci) include: • Corneal infiltrate • Cataract wound abnormalities • Afferent pupillary defect • Loss of red reflex • Light presentation vision at presentation • Symptoms onset with 2 days of cataract surgery | ||
Additional procedures | 44 (10.5%) patients needed additional surgery within 7 days; 38 (9%) due to worsening intraocular inflammation/infection 31 (7.6%) needed reinjection of intravitreal antibiotics; all these patients were pooled from 44 patients (70.5%) Additional procedures were more often required in cases of gram-negative or gram-positive infection other than gram-positive coagulase-negative microorganism | ||
Media clarity and visual acuity outcome | Media cleared more quickly after vitrectomy than tap-biopsy | ||
Final vision | % eyes | ||
20/40 or better | 53% | ||
20/100 or better | 74% | ||
5/200 or better | 11% | ||
No LP | 5% | ||
VIT vs. TAP visual acuity outcome | No statistical difference in the visual acuity outcome in VIT and TAP groups
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