Endophthalmitis Clinical Categories (Incidence Rates, Signs/Symptoms, Risk Factors, Microbiology, Treatment, and Follow-Up)

, Nidhi Relhan Batra¹, Stephen G. Schwartz² and Andrzej Grzybowski^{3, 4}

(1)

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA

(2)

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples, Florida, USA

(3)

Chair of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland

(4)

Institute for Research in Ophthalmology, Poznan, Poland

Postoperative Endophthalmitis: Acute-Onset Postoperative Endophthalmitis Following Cataract Surgery

Acute-onset postoperative endophthalmitis occurs within 6 weeks of cataract surgery or secondary intraocular lens (IOL) implantation.

Incidence

Reported rates vary between about 0.03 and 0.2%.

Signs/Symptoms

The patient presents with lid swelling, pain, redness, discharge, marked decrease in the vision, etc. Slit-lamp examination may show lid swelling, conjunctival congestion, chemosis, corneal edema, epithelial defect, hypopyon, infiltrates/fibrin membrane in the anterior chamber, loss of red reflex from the retina, and infiltrates in the vitreous cavity (Fig. 4.1).

Figure 4.1

Acute-onset endophthalmitis . A 78-year-old male patient with acute-onset postoperative endophthalmitis following cataract surgery. (a) The patient presented with conjunctival congestion, mild corneal edema, hypopyon, hazy view to the posterior segment, and counting fingers (CF) vision. Patient underwent vitreous tap and intraocular antibiotics (vancomycin and ceftazidime) and was culture positive for coagulase-negative Staphylococcus resistant to all fluoroquinolones. (b) At 6-month follow-up, the patient regained best corrected visual acuity of 20/80 with resolution of inflammation. At 2-year follow-up, the patient achieved visual acuity of 20/20

Risk Factors

Preoperative:
- Diabetes mellitus
- Older age
- Blepharitis
- Use of corticosteroids
- Prosthesis in fellow eye
- Active systemic infection
Intraoperative:
- Failure to use topical povidone–iodine preparation
- Prolonged surgery
- Intraoperative complications or Posterior capsular rupture (Fig. 4.2)
Postoperative:
- Inpatient status
- Wound leak (Fig. 4.3)
- Contaminated eye drops

Figure 4.2

Acute-onset endophthalmitis . A 69-year-old male patient with acute-onset postoperative endophthalmitis following cataract surgery and anterior chamber intraocular lens implantation following posterior capsular rent. (a) The patient presented with conjunctival congestion, corneal edema, hypopyon, fibrinous membrane in the anterior chamber, hazy view of the posterior segment, and hand motions (HM) vision. Patient underwent vitreous tap and intraocular antibiotics. (b) At 1-year follow-up, the patient regained best corrected visual acuity of 20/50

Figure 4.3

Wound leak -associated endophthalmitis . A 57-year-old male with acute-onset endophthalmitis after cataract surgery. (a) Slit-lamp examination revealed conjunctival congestion, corneal edema, anterior chamber inflammation, hypopyon, and single nylon suture placed temporally with a leaking clear corneal wound. Visual acuity was hand motions (HM). The patient underwent pars plana vitrectomy and additional suture placement onto the leaking wound. (b) 2 months after suture removal visual acuity improved to 20/25

Microbial Isolates

Following are the microorganisms most commonly associated with acute-onset postoperative endophthalmitis following cataract surgery (Endophthalmitis Vitrectomy Study data):

Coagulase-negative Staphylococci—70.0%
Staphylococcus aureus—9.9%
Streptococcus species—9.0%
Enterococcus species—2.2%
Gram-negative bacteria—5.9%
Other gram-positive bacteria—3.1%

Initial Management of Acute-Onset Postoperative Endophthalmitis

Vitreous TAP or pars plana vitrectomy
Injection if intravitreal antimicrobial agents

Vitreous tap: A small needle is inserted through pars plana into the vitreous, and a sample is withdrawn. The vitreous sample is then sent to the microbiology laboratory for culture and analysis to identify the microorganism and the antibiotic or antifungal medication that it is sensitive to. Following are important considerations while performing vitreous tap:

Location—Clinic lane/minor procedure room/operating room.
Anesthesia—Peribulbar/retrobulbar/topical may be considered.
Equipment—23 gauge, 1 inch needle (butterfly-style needle may be helpful) (Fig. 3.4).
Microbiology—Culture plates or blood culture bottles for specimen (Fig. 3.6).

Pars plana vitrectomy (PPV): Pars plana vitrectomy is a surgical procedure that involves removal of infectious infiltrates and vitreous gel from the eye. A vitreous sample is sent to the microbiology laboratory for culture and analysis (Fig. 4.4). Following are important considerations while performing PPV:

Location—Operating room
Anesthesia—Peribulbar/retrobulbar/topical
Equipment—Transconjunctival small gauge, standard 3 port PPV, or 2 port approach if view is limited

Figure 4.4

Pars plana vitrectomy (25 gauge assisted by wide field viewing)

Intravitreal antimicrobials (Fig. 4.5)

Figure 4.5

Intravitreal injections in syringes. Syringes (1 cc) filled with vancomycin (1 mg/0.1 mL), ceftazidime (2.25 mg/0.1 mL), and dexamethasone (0.4 mg/0.1 mL). The reconstituted syringes have a lot number, date of expiration, and storage guidelines (2–8 °C)

For presumed bacterial cases (in separate syringes):

Vancomycin 1 mg/0.1 mL (for coverage of gram-positive organisms)
Ceftazidime 2.25 mg/0.1 mL (for coverage of gram-negative organisms)
- Ceftriaxone 2 mg/0.1 mL may be substituted for ceftazidime if this is more readily available.
- Amikacin 0.4 mg/0.1 mL can be substituted for ceftazidime but has the risks of aminoglycoside macular toxicity.
- Dexamethasone 4 mg/0.1 mL may be considered for acute-onset bacterial cases but should be avoided in suspected fungal endophthalmitis and delayed-onset (chronic) endophthalmitis until the organism is identified.

For presumed fungal cases:

Amphotericin B 0.005 mg/0.1 mL
Voriconazole 0.1 mg/0.2 mL

Follow-Up Management of Acute-Onset Postoperative Endophthalmitis (Fig. 4.6)

First Morning After Initial Treatment

Topical antimicrobials
- Consider fortified topical antibiotics if available:
  
  Vancomycin 25 mg/mL hourly during the day
  
  Ceftazidime 50 mg/mL hourly during the day
- Alternatively, commercially available topical antibiotics are used.
- For fungal cases, topical amphotericin B has poor intraocular penetration and is not used.
Topical steroids four times daily (not for suspected/proven fungal infection)
Topical cycloplegics daily

Figure 4.6

Follow-up of endophthalmitis. Follow-up course of a patient with acute-onset postoperative endophthalmitis following cataract surgery. (a) Conjunctival congestion, mild corneal edema, hypopyon, and hand motions (HM) vision on the day of presentation (b) 1 day after vitreous tap and intraocular antibiotics hypopyon reduced, fibrinous membrane contracted in the pupillary zone, and vision improved to 3/200 (c) At 2-day follow-up, inflammation reduced further and vision improved to 20/400 (d) At 6-week follow-up, the patient regained best corrected visual acuity of 20/20 with resolution of inflammation

*Topical antibiotics hourly may result in corneal epithelial toxicity as a result of preservatives in commercial preparations. Topical medications are generally not used during night hours while sleeping. Subconjunctival antibiotics at the time of initial treatment provide adequate ocular surface medication for nighttime coverage.

Two to Three Days After Initial Treatment

If clinically improving—Continue to observe and taper topical steroids over several weeks.
If clinically worsening:
- Consider repeat intraocular cultures and/or reinjection of intraocular antibiotics (and possibly intraocular steroids in acute-onset bacterial cases).
- Consider PPV if not performed initially.

Change antibiotics if indicated by initial culture results.

References: Acute-Onset Postoperative Endophthalmitis Associated with Cataract Surgery

Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol. 1995;113(12):1479–96.
Lalwani GA, Flynn HW, Jr., Scott IU, Quinn CM, Berrocal AM, Davis JL, et al. Acute-onset endophthalmitis after clear corneal cataract surgery (1996–2005). Clinical features, causative organisms, and visual acuity outcomes. Ophthalmology. 2008;115(3):473–6.
Pathengay A, Khera M, Das T, Sharma S, Miller D, Flynn HW, Jr. Acute postoperative endophthalmitis following cataract surgery: a review. Asia—Pacific Journal of Ophthalmology (Philadelphia, Pa). 2012;1(1):35–42.
Shirodkar AR, Pathengay A, Flynn HW, Jr., Albini TA, Berrocal AM, Davis JL, et al. Delayed— versus Acute-onset endophthalmitis after cataract surgery. Am J Ophthalmol. 2012;153(3):391–8 e2.
Yannuzzi NA, Si N, Relhan N, Kuriyan AE, Albini TA, Berrocal AM, et al. Endophthalmitis after clear corneal cataract surgery: outcomes over two decades. Am J Ophthalmol. 2017;174:155–9.

Endophthalmitis Vitrectomy Study (EVS )

The Endophthalmitis Vitrectomy Study (EVS) was a randomized clinical trial (RCT) which provides guidelines for the management of postoperative endophthalmitis following cataract surgery or secondary intraocular lens (IOL) implantation (Tables 4.1 and 4.2).

Table 4.1

The Endophthalmitis Vitrectomy Study (EVS): enrollment criteria, exclusion criteria, treatment arms, and results

Endophthalmitis Vitrectomy Study (EVS)
EVS enrollment criteria • Acute-onset postoperative endophthalmitis • Within 6 weeks of cataract surgery or secondary intraocular lens (IOL) implantation • Visual acuity between 20/50 and light perception (LP)
EVS exclusion criteria • Other endophthalmitis etiologies • Presence of cloudy cornea preventing pars plana vitrectomy • Preexisting comorbidities (advanced glaucoma, age related macular degeneration) which could result in <20/200 visual acuity outcomes
Patients were randomized into four treatment arms: • PPV without intravenous antibiotics • PPV with intravenous ceftazidime and amikacin • Vitreous tap (TAP) without intravenous antibiotics • TAP with intravenous ceftazidime and amikacin
EVS results • For patients with presenting visual acuity of – Hand motions (HM) or better: No significant differences in visual outcomes Between PPV and TAP With or without intravenous ceftazidime and amikacin – Light perception (LP): PPV was associated with significantly better visual outcomes Threefold increase in frequency of achieving visual acuity 20/40 or better (33% PPV, 11% TAP) Approximately twofold increase in frequency of achieving visual acuity of 20/100 or better (56% PPV, 30% TAP) Twofold decrease in frequency of sustaining severe visual loss defined as visual acuity worse than 5/200 (20% PPV, 47% TAP) – No significant differences in visual outcomes with or without intravenous ceftazidime and amikacin

Table 4.2

The Endophthalmitis Vitrectomy Study (EVS): patient selection, guidelines, conclusions, and comments

EVS: patient selection, guidelines, conclusions and comments
• Patient selection – EVS selected only patients with acute-onset postoperative endophthalmitis within 6 weeks of cataract surgery of secondary IOL implantation – Other forms of endophthalmitis (post-traumatic/endogenous/bleb-associated endophthalmitis) were not studied in EVS
• Cataract surgery techniques at the time of the EVS – Cataract surgery was predominantly extracapsular cataract extraction or limbal tunnel phacoemulsification – Topical antibiotics gentamicin or polymixin B-trimethoprim were commonly used for cataract surgery – Subconjunctival antibiotics (generally gentamicin) were routinely administered during cataract surgery – 10 EVS patents received antibiotics in the irrigating fluid at the time of the cataract surgery and yet developed endophthalmitis.
• EVS criteria and guidelines for selection of initial treatment – Based on visual acuity at presentation HM or better: TAP without systemic antibiotics LP: PPV is preferable if this is achievable – Initial TAP, followed by close observation and PPV when practicable, may lead to excellent outcomes – The EVS results did not report that PPV was contraindicated in eyes with VA HM or better but initial management with TAP is more time and cost efficient
• EVS-Conclusions and comments – Intravenous ceftazidime and amikacin were not reported to be beneficial in the EVS – Oral gatifloxacin and moxifloxacin may achieve vitreous penetration but their value is uncertain – Oral gatifloxacin is no longer available due to systemic adverse events – Systemic antibiotics may be considered in selected patients with more severe signs and symptoms: Rapid-onset Presenting visual acuity of LP Large hypopyon No red reflex
• The role of systemic steroids – All patients in EVS were treated with prednisone 30 mg twice daily for 5–10 days – The value of this treatment is uncertain – There are significant risks especially in diabetic patients

The findings of EVS should be interpreted with caution, especially when applying its findings to categories of endophthalmitis other than acute-onset postoperative endophthalmitis

References: Endophthalmitis Vitrectomy Study

Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol. 1995;113(12):1479–96.
Microbiologic factors and visual outcome in the endophthalmitis vitrectomy study. Am J Ophthalmol. 1996;122(6):830–46.
Bannerman TL, Rhoden DL, McAllister SK, Miller JM, Wilson LA. The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis. Arch Ophthalmol. 1997;115(3):357–61.
Barza M, Pavan PR, Doft BH, Wisniewski SR, Wilson LA, Han DP, et al. Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the Endophthalmitis Vitrectomy Study. Arch Ophthalmol. 1997;115(9):1142–50.
Davis JL. Intravenous antibiotics for endophthalmitis. Am J Ophthalmol. 1996;122(5):724–6.
Doft BH. The endophthalmitis vitrectomy study. Arch Ophthalmol. 1991;109(4):487–9.
Doft BH, Kelsey SF, Wisniewski SR. Additional procedures after the initial vitrectomy or tap-biopsy in the Endophthalmitis Vitrectomy Study. Ophthalmology. 1998;105(4):707–16.
Doft BH, Wisniewski SR, Kelsey SF, Fitzgerald SG, Endophthalmitis Vitrectomy Study G. Diabetes and postoperative endophthalmitis in the endophthalmitis vitrectomy study. Arch Ophthalmol. 2001;119(5):650–6.
Doft BM, Kelsey SF, Wisniewski SR. Retinal detachment in the endophthalmitis vitrectomy study. Arch Ophthalmol. 2000;118(12):1661–5.
Durand M. Microbiologic factors and visual outcome in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol. 1997;124(1):127–30.
Flynn HW, Jr., Scott IU. Legacy of the endophthalmitis vitrectomy study. Arch Ophthalmol. 2008;126(4):559–61.
Flynn HW Jr., Meredith TA. Interpreting the results of the EVS (Letter to Editor). Arch Ophthalmol. 1996;114: 1027–8.
Han DP, Wisniewski SR, Wilson LA, Barza M, Vine AK, Doft BH, et al. Spectrum and susceptibilities of microbiologic isolates in the Endophthalmitis Vitrectomy Study. Am J Ophthalmol. 1996;122(1):1–17.
Johnson MW, Doft BH, Kelsey SF, Barza M, Wilson LA, Barr CC, et al. The Endophthalmitis Vitrectomy Study. Relationship between clinical presentation and microbiologic spectrum. Ophthalmology. 1997;104(2):261–72.
Peyman GA. EVS, a different point of view. (Editorial) Arch de la Sociedad Espanola de Oftalmologia 1996;3: 205–7.
Sternberg P, Jr., Martin DF. Management of endophthalmitis in the post-endophthalmitis vitrectomy study era. Arch Ophthalmol. 2001;119(5):754–5.
Wisniewski S. Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmology. 2000;107(7):1274–82.
Wisniewski SR, Hammer ME, Grizzard WS, Kelsey SF, Everett D, Packo KH, et al. An investigation of the hospital charges related to the treatment of endophthalmitis in the Endophthalmitis Vitrectomy Study. Ophthalmology. 1997;104(5):739–45.

Chronic/Delayed-Onset Postoperative Endophthalmitis Following Cataract Surgery

Chronic endophthalmitis may occur due to the introduction of low virulence infectious organism at the time of intraocular procedure. This slowly progressive chronic endophthalmitis may become clinically apparent months or years after the procedure.

By contrast, delayed-onset postoperative endophthalmitis results from a weakness in the ocular surface allowing entry of organisms. Examples of delayed-onset endophthalmitis include infection through glaucoma filtering blebs, corneal sutures, or fistulas from previous trauma.

However, these terms are used interchangeably in this chapter.