Ophthalmic Emergencies: Endophthalmitis

Endophthalmitis is an infectious form of panuveitis and a devastating vision-threatening medical emergency; unfortunately, endophthalmitis is associated with a significant proportion of poor visual outcomes. Endophthalmitis most commonly occurs through the exogenous introduction of bacteria into the eye from surgery, trauma, or corneal infection. The eye can also be seeded endogenously from bloodstream infections, including fungal endophthalmitis after sepsis. Prompt diagnosis and initiation of treatment is essential for best visual outcomes.^1–4

Epidemiology, presentation, and management

The most common sources of endophthalmitis are related to surgery (e.g., cataract, intravitreal injection) and trauma.¹ Other causes include cases of delayed endophthalmitis, such as bleb-related endophthalmitis. Endophthalmitis is a clinical diagnosis, and providers should be familiar with the clinical manifestations to recognize and treat promptly. Timing and quality of symptoms depend upon the etiology, but typically include red eye, eye pain, and decreased vision. Signs of endophthalmitis include hypopyon, anterior chamber reaction, vitritis, and retinochoroidal thickening.^1,2

Be sure to consider endophthalmitis on your differential in patients with these clinical manifestations in the setting of recent ophthalmic surgery, intravitreal injection, penetrating trauma, or sepsis. On presentation, approximately 25% of patients with endophthalmitis may have light perception (LP) vision only.⁵

A complete ocular history and examination is essential in the diagnosis of endophthalmitis. Patients should be queried about recent eye surgery, a history of glaucoma procedures, recent intravitreal injections, recent trauma to the eye, a history of bacteremia or fungemia, presence of indwelling catheter, underlying medical conditions, immunocompromised status, and intravenous drug use. Patients with possible candida endophthalmitis should have a skin examination for signs of intravenous drug injection. Postoperative patients should be examined for wound or bleb leaks, exposed sutures, and blepharitis. B-scan ultrasonography should be performed to check for vitritis, retinochoroidal thickening and retinal detachment.

The presentation and management of endophthalmitis depends on the mechanism of the infection. Thus, it is useful to approach the understanding of endophthalmitis categorically based on the main causes.

Acute postoperative endophthalmitis

Acute postoperative endophthalmitis is a feared complication of cataract surgery.⁶ It is sometimes termed ‘acute postcataract endophthalmitis’ and is defined as endophthalmitis that occurs within six weeks postoperatively of intraocular surgery. Due to the large volume of cataract surgeries, it is a common cause of endophthalmitis carrying a risk of 0.04-0.1% per surgery.^1,6

To prevent endophthalmitis, intracameral antibiotics (e.g., vancomycin, moxifloxacin) may be given during cataract surgery as prophylaxis.6 Coagulase-negative staphylococci are the causative organism in 65-70% of cases (eg, Staphylococcus epidermidis). Other Gram-positive cocci account for 25% of cases.^1,2 Risk factors for acute postcataract endophthalmitis include breakage of the posterior capsule, clear corneal incisions, and use of a silicone intraocular lens (IOL).^1,6 In around 75% of cases, symptoms typically arise within one week and include decreased vision, red eye, and eye pain.¹ Eye exam may show marked cellular reaction, hypopyon, and vitritis; systemic symptoms are rare.^1,2,4,6

Endophthalmitis is a clinical diagnosis and initial treatment is empirical. Vitreous cultures are ideal for targeted therapeutic management; however, cultures are often falsely negative, and a negative culture does not rule out endophthalmitis.¹ Polymerase chain reaction (PCR) tests may be more sensitive than cultures, but its use is not yet widely adopted.² Intravitreal antibiotics are the mainstay of treatment, with vitrectomy reserved for severe cases.

After vitreous samples are taken for culture and Gram stain, the patient should receive empirical therapy of intravitreal vancomycin (1 mg) and ceftazidime (2.25 mg).^1,2,4,6 Vitrectomy should be performed in patients with LP vision or worse, as it leads to better visual outcomes in cases of severe endophthalmitis.⁵ Amikacin 0.4 mg may be used as an alternative to ceftazidime but is generally avoided due to the risk of retinal toxicity.² Vitrectomy should also be considered in patients with severe, progressive cases of endophthalmitis with vision better than LP or in patients treated with intravitreal antibiotics who do not improve after 24-48 hours.²

The benefit of adjunctive systemic antibiotics is unknown and rarely given but, if used, moxifloxacin (400mg daily) is recommended, as it has good intravitreal penetration. If the eye is not showing signs of improvement 48 hours after intravitreal antibiotics, then patients should receive repeat cultures, repeat antibiotics, and possible vitrectomy.²

The final visual outcome is highly correlated with the causative organism. Streptococci induce a severe endophthalmitis associated with poor visual outcomes. Coagulase-negative staphylococci endophthalmitis generally results in better visual outcomes. About half of the eyes with postcataract endophthalmitis will regain 20/40 or better vision, and around one-in-ten will have 20/800 or worse.¹

Chronic postoperative endophthalmitis

Chronic postoperative endophthalmitis, also called chronic postcataract endophthalmitis and chronic pseudophakic endophthalmitis, is rare and occurs at least six weeks after surgery. Isolated organisms are less virulent and cause chronic, low-grade inflammation with Cutibacterium acnes (formerly propionibacterium acnes) being the main offender. Symptoms include decreased vision and possible eye pain. Examination usually reveals cells in the anterior chamber with a distinctive white plaque on the posterior capsule. Hypopyon is often absent, and inflammation generally responds to steroids. Diagnosis can be difficult to make, and cultures are often negative. That said, culture of the white capsular plaque is frequently positive.^1–4,7,8

If chronic postoperative endophthalmitis is suspected, patients should have aqueous and vitreous humor cultures. Treatment is difficult, and patients should receive intravitreal vancomycin and a vitrectomy. However, cases often recur, and culture results are important to guide therapy. In recalcitrant cases, patients may need removal of the capsule and intraocular lens.^1,3,4,7,8

Post-intravitreal injection endophthalmitis

Intravitreal anti-VEGF injections are used in the treatment of neovascular age-related macular degeneration, macular edema after retinal vein occlusion, diabetic macular edema, and diabetic retinopathy. Due to their effectiveness, they have increased greatly in use over the recent years. Each injection carries with it a 0.025-0.2% chance of endophthalmitis, and they may be required to be repeated monthly.¹ In some centers, post-intravitreal injection endophthalmitis has become more common than acute postcataract endophthalmitis.¹ Coagulase-negative bacteria cause 60% of infections, similar to postoperative endophthalmitis.¹

However, intravitreal injections are associated with a higher proportion of cases due to oral flora, including viridans streptococci, which account for approximately 25-30% of infections.¹ Thus, patients are regularly asked to not speak during the intravitreal injection procedure. Intravitreal steroid injections may have a higher incidence of associated endophthalmitis than anti-VEGF injections.²

Presentation and management of post-intravitreal injection endophthalmitis is similar to acute postoperative endophthalmitis. Symptoms include eye pain and decreased vision and generally present within 5-10 days of the intravitreal injection. Ophthalmic exam reveals inflammation of the vitreous and cultures are often negative.¹

Diagnosis and management principles are similar to acute postsurgical exogenous endophthalmitis. Patients should have cultures and receive intravitreal vancomycin plus ceftazidime. Vitrectomy and repeat injections may be required. In severe cases, systemic moxifloxacin may be considered.^1,2

Post-traumatic endophthalmitis

The likelihood of developing endophthalmitis after an open globe injury is 7%⁴ and trauma is associated with 25% of all endophthalmitis cases.⁹ Retained intraocular foreign bodies have higher probability of causing endophthalmitis; other risk factors include lens disruption or traumatic cataract, exposed wound, and delayed presentation greater than 24 hours after injury. Bacillus and Staphylococcus species are the most common causative bacterial organisms. In particular, Bacillus cereus causes a fulminant infection with a poor visual prognosis.^1,4,9 Symptoms include rapid-onset red eye, eye pain, and decreased vision. Ocular exam usually shows considerable intraocular inflammation.⁹

Primary repair of an open globe with removal of intraocular foreign bodies should occur as soon as possible to reduce the risk of endophthalmitis. After penetrating eye injury, patients may receive two days of systemic antibiotics for endophthalmitis prophylaxis with IV vancomycin plus either systemic ceftazidime or oral ciprofloxacin.^1,2,9 For patients who develop endophthalmitis, vitreous cultures, vitrectomy, and intravitreal vancomycin plus ceftazidime are mainstays. Patients may also receive adjunctive systemic antibiotics for severe cases.

Bleb-related endophthalmitis

A filtering bleb is a surgical elevation in the conjunctiva and is most often associated with surgical treatments for glaucoma. Occasionally, pathogenic bacteria can enter through the filtering bleb and cause endophthalmitis, with a risk of 1.3% per patient-year.¹ Streptococci cause around 50% of cases. The diagnosis of bleb-related endophthalmitis is confirmed by vitreous cultures, but can possess false negatives. Bleb cultures should also be obtained. Symptoms include rapid onset eye pain and decreased vision. On examination, the eye is frequently red with purulence on the bleb (blebitis).^2,4

Current management recommendations include cultures, pars plana vitrectomy, and intravitreal vancomycin plus ceftazidime. Systemic antibiotics may be added in severe cases. Visual outcomes vary depending on the pathogen, with 40% improving to 20/40 or better and 30% losing vision in the infected eye.¹

Endogenous bacterial endophthalmitis

Endogenous bacterial endophthalmitis is caused by bacteria seeding the eye in the setting of bacteremia. The incidence of endogenous endophthalmitis from bacteremia is estimated to be around 0.04%.² The most common foci of infection are liver abscesses, pneumonia, endocarditis, and soft tissue infections. Patients often have predisposing risk factors, including diabetes, intravenous drug use, and malignancy.¹⁰ Diagnosis may be difficult as up to half of patients may report no systemic symptoms or may only complain of ophthalmic symptoms.²

Thus, endogenous bacterial endophthalmitis should be suspected in patients complaining of eye pain or decreased vision with possible bacteremia or intravenous drug use. Symptoms of endogenous endophthalmitis include eye pain and blurred vision.¹⁰

Patients with suspected endogenous bacterial endophthalmitis should have both blood and vitreous cultures taken, each of which have a relatively high positivity rate of (up to 75% in bacteremia cases).^2,10 Treatment involves systemic antibiotics to treat the underlying infection and possible intravitreal antibiotics for the eye. Guidance and co-management with an infectious disease specialist may prove helpful here. The duration of antibiotic treatment may be based on the source of the infection and culture results should guide antibiotic choice.^1,2,10

Fungal endophthalmitis

Fungal endophthalmitis can be divided into yeast (e.g., candida) or mold (e.g., aspergillus) sources and occur via endogenous or exogenous mechanisms. The most common cause of yeast endophthalmitis is endogenous seeding of candida in the bloodstream of candidemic patients, who are usually hospitalized. Major risk factors for candidemia include an indwelling venous catheter, intravenous drug use, and immunosuppression. The highly vascular choroid is regularly seeded first, causing choroiditis or chorioretinitis. These infections are often painless, and patients may not have ophthalmic symptoms, unless the macula is affected. Later progression of the infection into the vitreous causes decreased vision and pain.

Note the distinction between candida chorioretinitis from candida endophthalmitis; the latter involves the vitreous while the former does not. Exogenous candida endophthalmitis is rare and usually related to intravenous drug use.^1,4,11

In contrast to yeast endophthalmitis, mold endophthalmitis generally occurs exogenously, from eye surgery, ocular trauma, or extensions of fungal keratitis. Most patients with mold endophthalmitis lose vision, but newer antifungals may improve visual outcomes.¹ Mold endophthalmitis through exogenous sources is more common in tropical climates.¹

The role of screening patients with candidemia for endophthalmitis is unclear; nonetheless, if there are ocular symptoms suggestive of infection, vitreous samples should be obtained for stains and cultures. Ocular examination often reveals lesions in the choroid and/or retina. When the vitreous is involved, the infection may appear as fluffy white “snowballs” or a “string of pearls.”^1,4 Systemic antifungal therapy should be administered for four-six weeks, usually with the azole antifungal therapeutic class.

Patients with vitritis should receive intravitreal amphotericin B or voriconazole. Some recommend vitrectomy for fungal endophthalmitis with vitreous involvement, however,k there is no current consensus on the role of vitrectomy in the treatment of fungal endophthalmitis. The patient should be co-managed with an infectious disease specialist.^1,11

Differential diagnosis

Differential diagnosis for endophthalmitis includes the following list―however as noted in the discussion above―endophthalmitis, whether endogenous or exogenous, typically follows a clinical pattern that can help rule out other conditions. Suspicion should be high for infectious causes of inflammation and infectious etiologies must be ruled out first!

Toxic Anterior Segment Syndrome (TASS): TASS is a rare complication of anterior segment surgery, especially cataract surgery, characterized by sterile inflammation of the anterior chamber. It usually appears 12-48 hours after surgery and is responsive to topical steroids.
Noninfectious inflammatory endophthalmitis (NIE): NIE, also known as sterile endophthalmitis or simply intraocular inflammation (IOI), can occur after intravitreal injections. NIE is thought to result from an inflammatory reaction to one of the components of the pharmaceutical agent.
Lens-induced uveitis: Lens-induced uveitis is caused by an inflammatory reaction to retained lens material in the anterior chamber or vitreous following cataract surgery.
Iritis and uveitis: Patients may have flare-ups of iritis and uveitis following cataract surgery. Endophthalmitis must first be ruled out in postoperative patients with uveitis.

Conclusion

Endophthalmitis is a serious vision-threatening ophthalmic emergency and clinical diagnosis. Prompt diagnosis and treatment is essential in attaining the best possible visual outcomes. The presenting symptoms of endophthalmitis are similar, regardless of etiology, and include red eye, eye pain, and vision loss. Contextual understanding of patients at risk for endophthalmitis is critical, and clinicians should suspect endophthalmitis in patients with ocular complaints after intraocular surgery, intravitreal injection, or ocular trauma. Management involves empirical therapy with intravitreal antibiotics and possible vitrectomy.

Further recommended reading:

The Endophthalmitis Vitrectomy Study (EVS) from 1995 is a major source of knowledge on the management of endophthalmitis and ophthalmology residents are recommended to read this study (see in reference list).

References

Durand ML. Endophthalmitis. Clin Microbiol Infect. 2013;19(3):227-234. doi:10.1111/1469-0691.12118
Durand ML. Bacterial endophthalmitis. UpToDate. doi:10.1007/s11908-009-0042-2
Schwartz S, Flynn H, Das T, Mieler W. Ocular Infection: Endophthalmitis. Dev Ophthalmol. 2016;55:176-188. doi:10.1159/000431195.
Kresloff M, Castellarin A, Zarbin M. Endophthalmitis. Surv Ophthalmol. 1998;43(3):193-224. doi:10.1016/s0039-6257(98)00036-8
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 Endophthalmitis Vitrectomy Study Group Madison) was responsible for eval. Arch Ophthalmo. 1995;113(12):1479-1496. www.archophthalmol.com
Chen YH, Chen JT, Tai MC, Chou YC, Chen CL. Acute postcataract endophthalmitis at a referral center in northern Taiwan: Causative organisms, clinical features, and visual acuity outcomes after treatment: A retrospective cohort study. Med (United States). 2017;96(49). doi:10.1097/MD.0000000000008941
Clark WL, Kaiser PK, Flynn HW, Belfort A, Miller D, Meisler DM. Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis. Ophthalmology. 1999;106(9):1665-1670. doi:10.1016/S0161-6420(99)90348-2
Maalouf F, Abdulaal M, Hamam RN. Chronic postoperative endophthalmitis: A review of clinical characteristics, microbiology, treatment strategies, and outcomes. Int J Inflam. 2012;2012:6-11. doi:10.1155/2012/313248
Bhagat N, Nagori S, Zarbin M. Post-traumatic Infectious Endophthalmitis. Surv Ophthalmol. 2011;56(3):214-251. doi:10.1016/j.survophthal.2010.09.002
Jackson TL, Paraskevopoulos T, Georgalas I. Systematic review of 342 cases of endogenous bacterial endophthalmitis. Surv Ophthalmol. 2014;59(6):627-635. doi:10.1016/j.survophthal.2014.06.002
Durand ML, Kauffman CA. Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis. UpToDate. Published 2020. https://www.uptodate.com/contents/epidemiology-clinical-manifestations-and-diagnosis-of-fungal-endophthalmitis?search=endophthalmitis&source=search_result&selectedTitle=2~116&usage_type=default&display_rank=2