Endophthalmitis
Stephen G. Schwartz
Harry W. Flynn Jr.
Roy D. Brod
POSTOPERATIVE ENDOPHTHALMITIS
ACUTE-ONSET POSTOPERATIVE ENDOPHTHALMITIS
Introduction
Endophthalmitis is characterized by marked inflammation of intraocular tissues and fluids. In a patient with endophthalmitis, the etiology and most likely infecting organisms may be predicted by the clinical setting. The largest category is acute-onset postoperative endophthalmitis, generally defined as presenting within 6 weeks of intraocular surgery.
Etiology and Epidemiology
• Incidence rates are variable, but are usually reported as being between about 0.03% and 0.2%.
• In a recent large single-center series, reported rates were 0.025% overall, 0.028% following cataract surgery, 0.108% following penetrating keratoplasty, and 0.011% following pars plana vitrectomy (PPV; in this series, all endophthalmitis cases followed 20-gauge PPV). In a prior series from the same institution, the reported rate following secondary intraocular lens (IOL) implantation was 0.2%.
• The Endophthalmitis Vitrectomy Study (EVS) recruited patients with acute-onset postoperative endophthalmitis following cataract surgery or secondary IOL implantation; in the EVS, 69% of patients had positive vitreous cultures, and of these, the most common etiologic organisms were coagulase-negative staphylococci.
• Preoperative risk factors include immune compromise (including diabetes mellitus), active systemic infection, active blepharitis or conjunctivitis, and disease of the lacrimal drainage system.
• Intraoperative risk factors include prolonged or complicated surgery, secondary IOL implantation, posterior capsular rupture, vitreous loss, iris prolapse, contaminated irrigating solutions or IOLs, and inferotemporal placement of clear corneal incisions.
• Postoperative risk factors include wound leak, vitreous incarceration in the incision, and contaminated eye drops.
Symptoms
• Rapid onset of visual loss, redness, and pain
Signs
• Marked intraocular (anterior chamber and vitreous) inflammation with anterior chamber fibrin and hypopyon (Fig. 10-1)
• Eyelid edema, conjunctival congestion, corneal edema, and retinal periphlebitis may occur to a variable degree.
• Marked vitreous opacities by echography
Differential Diagnosis
• Toxic anterior segment syndrome, which generally occurs earlier (within 1 or 2 days), usually has “wall-to-wall” corneal edema, and may be associated with little or no pain, as well as little or no posterior segment inflammation.
• Retained lens material
• Flare-up of preexisting uveitis
• Triamcinolone acetonide particles
• Long-standing (dehemoglobinized) vitreous hemorrhage
Testing
• Acute-onset postoperative endophthalmitis is a clinical diagnosis,
followed by laboratory confirmation.
• If the posterior segment cannot be visualized, B-scan echography may be helpful to rule out retinal detachment, suprachoroidal hemorrhage, or retained lens fragments.
• Aqueous and vitreous cultures: Vitreous samples are more likely to yield a positive culture than aqueous samples.
• Vitreous cultures may be obtained either with a needle (tap) or with PPV instrumentation.
• Commonly used culture media include 5% blood agar (most common organisms), chocolate agar (fastidious organisms, such as Neisseria gonorrhoeae and Haemophilus influenza), sabouraud agar (fungi), thioglycollate broth (anaerobes), and anaerobic blood agar (anaerobes).
• Blood culture bottles may also be used and are helpful in after-hours cases.
• Polymerase chain reaction (PCR) may provide more rapid identification of organisms but, at this time, is available only in some major centers.
Treatment
• The EVS reported that for patients with acute-onset postoperative endophthalmitis following cataract surgery or secondary IOL implantation and presenting visual acuity of light perception (LP), PPV was associated with improved visual outcomes when compared to vitreous tap.
• In the EVS, in diabetic patients with presenting visual acuity of hand motions or better, there was a trend toward better visual outcomes in patients treated with PPV, but this was not statistically significant.
• The EVS required all treatments to be performed within 6 hours of presentation, but this may not be practicable in some settings; if a patient with acute-onset endophthalmitis and visual acuity of LP cannot be treated with PPV within 6 hours, then prompt tap and inject, followed by close observation, is a reasonable option.
• The EVS treated all patients with intravitreal vancomycin (1 mg in 0.1 mL) and amikacin (0.4 mg in 0.1 mL); however, to reduce the risk of aminoglycoside toxicity, either ceftazidime (2.25 mg in 0.1 mL) or ceftriaxone (2 mg in 0.1 mL) may be considered.
• The EVS reported no additional visual benefit associated with the adjunctive use of systemic amikacin and ceftazidime.
• Fourth-generation systemic fluoroquinolones such as moxifloxacin achieve intraocular penetration and may be considered for
adjunctive use, but supporting evidence of efficacy is lacking, and fluoroquinolones are associated with serious risks (“black box” Food and Drug Administration warning).
adjunctive use, but supporting evidence of efficacy is lacking, and fluoroquinolones are associated with serious risks (“black box” Food and Drug Administration warning).
• In patients with acute-onset postoperative endophthalmitis with suspected bacterial etiology, intravitreal dexamethasone (0.4 mg in 0.1 mL) may be considered.
• The EVS treated all patients with subconjunctival vancomycin (25 mg in 0.5 mL), ceftazidime (100 mg in 0.5 mL), and dexamethasone (6 mg in 0.25 mL); however, subsequent clinical trials have demonstrated that there may be no additional benefit associated with subconjunctival antibiotics.
• The EVS treated all patients with systemic prednisone (30 mg twice daily for 5 to 10 days); however, systemic corticosteroids should be used with caution in certain at-risk patients, including diabetic patients and the elderly.
• The EVS treated all patients with fortified topical vancomycin (50 mg/mL) and fortified topical amikacin (20 mg/mL), up to every hour, but fortified topical antibiotics may require access to a compounding pharmacy, which may not be available in all locations; as a substitute, commercially available topical antibiotics (such as fourth-generation fluoroquinolones) may be considered.
• The EVS treated all patients with topical corticosteroids and cycloplegics.
• If the clinical status appears to be worsening at 48 to 72 hours, consideration should be given to reculturing and reinjection of antibiotics on the basis of initial culture results; if the initial culture was a needle tap, PPV can be considered for the subsequent procedure.
Prevention
• It is probably not feasible to prevent all cases of acute-onset postoperative endophthalmitis, but the rates may be reduced with certain practices.
• Because the ocular adnexa and ocular surface are the main sources of bacteria causing acute-postoperative endophthalmitis, the most important preventive measure is aimed at reducing the periocular and ocular bacteria load.
• Patient education, including the role of proper preoperative and postoperative hygiene as well as discouraging the use of old and potentially contaminated eye drops, is suggested.
• Application of a topical 5% povidone-iodine solution onto the eyelids and conjunctival surface as part of the operative “prep” is the only preventive measure that has documented category II evidence.
• Isolating the eyelids and eyelashes from the surgical field by covering with a sterile plastic drape also is recommended.
• Meticulous surgical technique is important, paying particular attention to incision construction and closure and avoiding excessive pooling of fluid around the incision during surgery.
• Preoperative topical antibiotics have been reported to reduce the ocular surface bacterial colony counts at the time of surgery but have not been reported to reduce the rate of endophthalmitis.
• Intracameral antibiotics have been proposed and used as a preventive measure, especially in Europe, but their role is controversial in the United States; the proposed benefit may not outweigh the cost and potential complications associated with their use.
• Postoperative topical antibiotics are commonly used but have not been reported to reduce endophthalmitis rates.
Prognosis
• The strongest predictor of final visual outcome in the EVS was presenting visual acuity; therefore, prompt initiation of treatment is
more important than any other factor, including vitreous tap versus PPV.
more important than any other factor, including vitreous tap versus PPV.
• Other predictors of less favorable outcomes in the EVS included older age, diabetes mellitus, corneal infiltrate, abnormal intraocular pressure, anterior segment neovascularization, absent red reflex, and open posterior capsule.
REFERENCES
Ciulla TA, Starr MB, Masket S. Bacterial endophthalmitis prophylaxis for cataract surgery: an evidence-based update. Ophthalmology. 2002;109:13-24.
Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol. 1995;113:1479-1496.
Garg SJ, Dollin M, Storey P, et al. Microbial spectrum and outcomes of endophthalmitis after intravitreal injection versus pars plana vitrectomy. Retina. 2016;36(2):351-359.
Grzybowski A, Schwartz SG, Matsuura K, et al. Endophthalmitis prophylaxis in cataract surgery: overview of current practice patterns around the world. Curr Pharm Des. 2017;23(4):565-573.
Javey G, Schwartz SG, Moshfeghi AA, Asrani S, Flynn HW Jr. Methicillin-resistant Staphylococcus epidermidis isolation from the vitrectomy specimen four hours after initial treatment with vancomycin and ceftazidime. Clin Ophthalmol. 2010;4:101-104.
Kuklo P, Grzybowski A, Schwartz SG, Flynn HW Jr, Pathengay A. Hot topics in perioperative antibiotics for cataract surgery. Curr Pharm Des. 2017;23(4):551-557.
Rachistskaya AV, Flynn HW Jr, Fisher YL, Ayres B. Correlation between baseline echographic features of endophthalmitis, microbiological isolates, and visual outcomes. Clin Ophthalmol. 2013;7:779-785.
Rachitskaya AV, Flynn HW Jr, Wong J, Kuriyan AE, Miller D. A 10-year study of membrane filter system versus blood culture bottles in culturing vitrectomy cassette vitreous in infectious endophthalmitis. Am J Ophthalmol. 2013;156:349-354.
Schwartz SG, Flynn HW Jr, Grzybowski A, Relhan N, Ferris FL 3rd. Intracameral antibiotics and cataract surgery: endophthalmitis rates, costs, and stewardship. Ophthalmology. 2016:123;1411-1413.
Schwartz SG, Flynn HW Jr, Scott IU. Endophthalmitis: classification and current management. Expert Review Ophthalmol. 2007;2:385-396.
Smiddy WE, Smiddy RJ, Ba-Arth B, et al. Subconjunctival antibiotics in the treatment of endophthalmitis managed without vitrectomy. Retina. 2005;25:751-758.
Sridhar J, Yonekawa Y, Kuriyan AE, et al. Microbiologic spectrum and visual outcomes of acute-onset endophthalmitis undergoing therapeutic pars plana vitrectomy. Retina. 2017;37(7):1246-1251.
Vaziri K, Schwartz SG, Kishor K, Flynn HW Jr. Endophthalmitis: state of the art. Clin Ophthalmol. 2015;9:95-108.
Wykoff CC, Parrott MB, Flynn HW Jr, et al. Nosocomial acute-onset postoperative endophthalmitis at a university teaching hospital (2002-2009). Am J Ophthalmol. 2010;150:392-398.
Yannuzzi NA, Si N, Relhan N, et al. Endophthalmitis after clear corneal cataract surgery: outcomes over two decades. Am J Ophthalmol. 2017;174:155-159.
 FIGURE 10-1. Acute endophthalmitis. Acute-onset postoperative endophthalmitis. |
DELAYED-ONSET (CHRONIC) POSTOPERATIVE ENDOPHTHALMITIS
Introduction
Delayed-onset (chronic) postoperative endophthalmitis is defined as presenting more than 6 weeks after intraocular surgery, but may present months or years later.
Etiology and Epidemiology
• In one single-center series, the reported rate of delayed-onset (chronic) postoperative endophthalmitis following cataract surgery was 0.017%.
• Common causative organisms in cases of delayed-onset (chronic) postoperative endophthalmitis include Propionibacterium acnes, fungi, and various less virulent gram-positive and gram-negative organisms.
Symptoms
• Insidious onset of visual loss, redness, and pain
• Symptoms are typically less severe than in patients with acute-onset postoperative endophthalmitis.
Signs
• Signs are typically less severe, and presenting visual acuity is usually better, than in patients with acute-onset postoperative endophthalmitis.
• Slowly progressive intraocular inflammation and variable occurrence of hypopyon and keratic precipitates
• A white intracapsular plaque may be present and may be indicative of P. acnes infection (Fig. 10-2).
• Eyelid edema, conjunctival congestion, corneal edema, and aqueous and vitreous inflammation may occur, but generally to a lesser degree than in acute-onset postoperative endophthalmitis.
Differential Diagnosis
• Noninfectious uveitis
• Retained lens material
• Triamcinolone acetonide particles
• Long-standing (dehemoglobinized) vitreous hemorrhage
Testing
• Delayed-onset (chronic) postoperative endophthalmitis is a clinical diagnosis, followed by laboratory confirmation.
• If the posterior segment cannot be visualized, B-scan echography may be helpful to rule out retinal detachment, suprachoroidal hemorrhage, and retained lens fragments.
• Ultrasound biomicroscopy of the anterior segment may provide additional information.
• Aqueous and vitreous cultures: Vitreous samples are more likely to yield a positive culture than aqueous samples.
• Vitreous cultures may be obtained either with a needle (tap) or with PPV instrumentation.
• Commonly used culture media include 5% blood agar (most common organisms), chocolate agar (fastidious organisms, such as N. gonorrhoeae and H. influenza), sabouraud agar (fungi), thioglycollate broth (anaerobes), and anaerobic blood agar (anaerobes).
• If delayed-onset (chronic) postoperative endophthalmitis is suspected, the laboratory should be instructed to hold the cultures for at least 2 weeks to allow isolation of fastidious organisms.
• Blood culture bottles may also be used.
Treatment
• The EVS did not enroll patients with delayed-onset (chronic) postoperative endophthalmitis, so its findings regarding vitreous tap versus PPV are not necessarily applicable to these patients.
• Many authors recommend initial PPV with capsulectomy in cases of delayed-onset (chronic) postoperative endophthalmitis.
• Alternatively, one may consider initial tap and inject, followed by more invasive surgery if the clinical examination does not improve.
• Similar to acute-onset postoperative endophthalmitis, a reasonable initial treatment would include intravitreal vancomycin (1 mg in 0.1 mL) and amikacin (0.4 mg in 0.1 mL); however, to reduce the risk of aminoglycoside toxicity, either ceftazidime (2.25 mg in 0.1 mL) or ceftriaxone (2 mg in 0.1 mL) may be considered (ceftriaxone does not cover Pseudomonas but does cover most other gram-negative organisms).
• If fungal endophthalmitis is suspected, either intravitreal amphotericin B (0.005 mg in 0.1 mL) or intravitreal voriconazole (0.1 mg in 0.1 mL) may be used; adjunctive systemic antifungals may be used, typically in consultation with an internist or infectious disease specialist.
• In patients with suspected bacterial etiology, intravitreal dexamethasone (0.4 mg in 0.1 mL) may be considered; however, fungal infections are relatively more common in patients with delayed-onset (chronic) postoperative endophthalmitis, so intravitreal dexamethasone should be used with caution in these patients.
• Similar to acute-onset postoperative endophthalmitis, it is reasonable to use subconjunctival vancomycin (25 mg in 0.5 mL), ceftazidime (100 mg in 0.5 mL), and dexamethasone (6 mg in 0.25 mL); however, there is no proven benefit associated with subconjunctival medications.
• Similar to acute-onset postoperative endophthalmitis, systemic corticosteroids should be used with caution in certain at-risk patients, including diabetics and the elderly; in addition, fungal infections are relatively more common in patients with delayed-onset (chronic) postoperative endophthalmitis, and systemic corticosteroids should be used with caution if fungal infection is suspected.
• Fortified topical vancomycin (50 mg/mL) and fortified topical amikacin (20 mg/mL) may be beneficial, but fortified topical antibiotics may require access to a compounding pharmacy, which may not be available in all locations; as a substitute, commercially available topical antibiotics (such as fourth-generation fluoroquinolones) may be considered.
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