The word "endophthalmitis" can be broken down in greek to "interior-eye-inflammation" and is used to describe an infection of the vitreous and/or the aqueous humor within the eye. An intraocular infection has devastating consequences, leading to decreased vision and possibly irreversible blindness. The interior of the eye is a sterile environment, but this sterility can suffer compromise by exogenous sources such as penetrating trauma and surgery, or endogenous sources via bacteria in the patient's circulatory system. Endophthalmitis results from either bacteria or fungi invading and multiplying within the vitreous or aqueous humor. If bacterial endophthalmitis is diagnosed in a timely fashion and is treated accordingly with the proper antibiotic, patients can preserve their vision and make a full recovery. Given the time-sensitive nature of bacterial endophthalmitis, it is of the utmost importance for healthcare providers to be able to recognize this ocular malady and put the patient on the quickest path to recovery.
Bacteria are not present in the vitreous or aqueous humor of a healthy eye but seeding into the eye can occur either from an exogenous or endogenous source. Exogenous seeding is the most common cause of bacterial endophthalmitis and comes from the exterior ocular surface during penetrating ocular trauma, surgery, or from intra-ocular injections. Although rare, bacterial endophthalmitis can also be the result of hematogenous spread from infections elsewhere in the body or IV drug use. Approximately anywhere from 40 to 80% of all endophthalmitis is caused by cataract surgery, of these cases, 70% are the result of coagulase-negative staphylococci, 10% result from Staphylococcus aureus, and 9% are from streptococci. The second most common cause of endophthalmitis occurs after intravitreal injection, with coagulase-negative staphylococci and streptococci being the primary pathogens. Penetrating eye trauma is the third most common cause and constitutes anywhere from 2 to 15% of all cases of endophthalmitis.
Coagulase-negative staphylococci predominate this category, but other bacteria such as Bacillus, gram-negative bacilli, and fungi can cause infection. Bleb-related endophthalmitis is the fourth most common cause with the bacterial etiology in descending order of Streptococcus pneumonia, enterococci, or Haemophilus Influenzae. Keratitis resulting in organisms penetrating the cornea is the fifth most common cause, but 50% of keratitis related cases are due to fungi with S. aureus, streptococci and pseudomonas causing a minority of these infections. Endogenous blood-borne endophthalmitis is the rarest cause with Klebsiella pneumonia being the most common aggressor followed by Candida, streptococci, S. aureus, and E. coli.
Cataract surgery and intravitreal injections are the leading causes of endophthalmitis presently. However, endophthalmitis is a rare condition that has been controlled by the advent of antibiotics. In the pre-antibiotic era from 1920 to 1940, the incidence of post-cataract surgery, bacterial endophthalmitis was 2% and decreased to 0.3% by 1950. Today, of all patients undergoing cataracts surgery, approximately only 0.1% will suffer from endophthalmitis. Traumatic penetrating eye injury, however, can cause bacterial endophthalmitis 1 to 18% of the time. Hematogenous bacterial endophthalmitis is the rarest form with an incidence rate of between 0.04% to 0.4% and is associated with IV drug use, diabetes mellitus, immunosuppression, malignancy, prolonged hospital stay or IV antibiotic administration.
Cataract surgery is the single most significant cause of bacterial endophthalmitis and has risk factors associated with preoperative, intraoperative, postoperative stages:
Preoperative risk factors:
Blepharitis or lid abnormalities
Application of 2% xylocaine gel before povidone-iodine
Intraoperative risk factors:
Poor sterile technique
Posterior capsular rupture
Vitreous loss and wound leak
Use of intracameral miotics/staining dyes and epinephrine
Contamination during mixing of compounded medications
Postoperative risk factors:
Postoperative wound leak
Nonsilicon Intraocular lens type
Endogenous endophthalmitis is associated with infectious diseases involving the liver, lungs, heart, brain, the urinary tract, as well as patients suffering from diabetes mellitus and immunosuppression or people with a history of recent hospitalization or surgery. Hematogenous bacterial endophthalmitis is the rarest form with an incidence rate of between 0.04% to 0.4%.
Exogenous seeding is the most common cause of bacterial endophthalmitis and depends on host factors, pathogen factors, as well as inoculum size. Bacteria such as coagulase-negative staphylococci typically colonize the conjunctiva and can be introduced to the inner ocular cavity during surgery, injections, or trauma. After cataract surgeries, research reveals that one-third of patients aqueous humor cultured coagulase-negative staphylococci. However, only 1-in-500 to 1-in-1000 of cataract surgeries result in bacterial endophthalmitis. These numbers highlight how host factors such as the immune response can clear small inoculum of bacteria. Another host factor that is preventative of infection is the constant turnover of aqueous fluid. The vitreous humor has no such turnover rate, and the stagnancy of this fluid shows by the fact that bacterial seeding of the vitreous during cataract surgery increases the likelihood of postoperative endophthalmitis 6-fold. Inoculum size has also been shown to overload the immune system and leads to infection.
Pathogen factors can also play a role in the pathogenesis of bacterial endophthalmitis. Bacteremia is a rare cause of bacterial endophthalmitis, but when it does occur, the culprit is usually Klebsiella pneumoniae. The magA gene endows the Serotype K1 or K2 of Klebsiella pneumoniae with a mucopolysaccharide-web capsule that allows hypermucoviscous virulence and is a common cause of pyogenic liver abscess in southeastern Asia. As many as 7% of patients with K1 or K2 Klebsiella pneumonia liver abscess will experience hematogenous spread to their retina. Experimental models with mice confirm that eyes injected with Klebsiella with the hypermucoviscosity (HMV) phenotype have increased retinal function loss and inflammation than eyes injected with HMV-negative strains.
Bacillus cereus can cause posttraumatic endophthalmitis and can also present in IV drug users. Bacillus cereus is a major pathogen that can cause fulminant endophthalmitis. Quorum-sensing by Bacillus initiates toxin release and migration that contributes to the rapid deterioration of the retina and is unique for the destructive course of Bacillus endophthalmitis. The virulence factors of Bacillus species that accommodate this destruction include membrane-damaging toxins such as hemolysins, sphingomyelinases, and phospholipases. The quorum sensing-dependent transcriptional regulator PlcR regulates virulence factor production. Neutrophils themselves lead to damage to the retina, and chemokine CXCL1 and other factors contribute to neutrophil recruitment and the damaging inflammation seen during Bacillus endophthalmitis.
In bleb-related endophthalmitis, Streptococcus pneumoniae is the most common pathogen and can cause severe endophthalmitis. Virulence factors such as the pneumococcal capsule, pneumolysin, and autolysin all appear to contribute to pathogenesis. Studies have shown that intraocular infection with pneumolysin-deficient S. pneumoniae results in less severe tissue damage in the first 24 hours of disease compared with infection with pneumolysin-producing strains of S. pneumoniae.
Streptococcus pneumoniae central virulence includes its use of exotoxins and enzymes as well as a polysaccharide capsule that prevents phagocytosis. Streptococcus pneumoniae virulence also uses pneumolysin, which has been shown to inhibits host responses involved with antibody synthesis and lymphocyte proliferation. Inflammation results from the cell wall components Streptococcus pneumoniae, which cause the symptoms that patients usually end up noticing and for which they seek care.
Pseudomonas Aeruginosa endophthalmitis causes rapid tissue necrosis caused by Pseudomonas toxins such as pyocyanin, pyoverdin, exotoxin A, and elastase. These toxins are used to disrupt membranes and epithelial barriers, leading to cytotoxicity.
A complete history and physical are critical in diagnosing and treating bacterial endophthalmitis in a timely and effective manner. Prompt and effective diagnosis can be the difference between a lifetime of vision or a lifetime of blindness. The most common symptom of endophthalmitis that patients will complain of is decreased vision. Eye pain, discharge, or red-eye are also common but may be present or absent in different cases of bacterial endophthalmitis. The timeline of symptoms can also be a clue to healthcare providers whether the patient is suffering from a bacterial etiology versus a fungal etiology.
Bacterial endophthalmitis presents in a much more acute timeframe, often within days of a penetrating event; versus fungal endophthalmitis which has a much more subacute presentation, worsening over days to weeks. Healthcare providers should inquire about a history of ocular surgery, ocular injections, or any penetrating ocular injury that are often present in exogenous endophthalmitis. If healthcare providers should also inquire about systemic symptoms such as fevers, chills, recent infections, recent surgery, recent hospitalization for sepsis, recent antibiotic use, intravenous drug use, that are often present in endogenous endophthalmitis cases.
Patient presentation is most commonly unilateral and can vary, ranging from asymptomatic to symptoms of a painful eye, conjunctival injection, photophobia, corneal edema, iritis, vitritis, anterior chamber cells, floaters, or reduced vision. On examination, a hypopyon, which represents a layer of white blood cells in the anterior chamber can occur in most cases of bacterial endophthalmitis and up to 80% of postcataract cases. Funduscopic examination reveals intraocular inflammation, which often obscures the view of the retina with white blood cells that create a "hazy" look. The type of intraocular inflammation can also be a clue, with bacterial endophthalmitis having diffuse intraocular inflammation whereas fungal endophthalmitis will present with "clumps" of inflammation in the aqueous or vitreous. Using ultrasound B-scan can help identify vitritis, or chorioretinal infiltrates. Vitreous fluid obtained via vitrectomy has a higher diagnostic yield than vitreous fluid from needle biopsies. If a patient contracts endophthalmitis from anti-VEGF intravitreal injections, vitreous culture is helpful in the prognosis of visual outcomes, but not necessarily influential in the clinical course. Aqueous humor tap is the lowest yielding fluid to culture, most likely due to the increased distance from the nidus of infection. Blood cultures yield true-positive results in approximately a third of cases. whereas polymerase chain reaction can identify both bacterial and fungal culture-negative cases.
Endogenous endophthalmitis is most often unilateral, but up to a third of cases have bilateral involvement. Diagnosing endogenous endophthalmitis requires a high degree of suspicion with the presence of systemic risk factors. However, a clinical diagnosis of endogenous endophthalmitis is always difficult as it has a high false-negative rate, and multiple clinic visits may be required to confirm the diagnosis. Some patients may present asymptomatically while symptomatic patients might present with symptoms such as hypopyon, vitritis, conjunctival injection, corneal edema, iritis, anterior chamber cells, or reduced visual acuity. White infiltrate originating in the choroid and protruding into the vitreous cavity is a key diagnostic finding of endogenous endophthalmitis. The presence of endogenous endophthalmitis is generally not a major concern in patients with life-threatening sepsis secondary to a bacterial etiology, and hence the diagnosis of endogenous endophthalmitis may be delayed with other morbidities under acute management. A 2015 study helped stratify the likelihood of endogenous endophthalmitis as a diagnosis:
Bacterial endophthalmitis necessitates prompt and early management with intraocular antibiotics often combined with a pars plana vitrectomy. Patients should be hospitalized, and have broad-spectrum intravenous, topical, and potentially intravitreal antibiotics initiated after collecting the appropriate cultures. The antibiotic of choice should be determined once the etiology of the infection is verified, and once cultures come back, the clinician can make appropriate changes to antibiotic therapy. Patients should receive topical cycloplegic such as atropine 1% twice daily, and topical prednisolone acetate 1% every 1 to 6 hours. Intravitreal antibiotics offer higher intraocular concentrations of antibiotics and can be a consideration if they cover the correct etiology. Intravitreal antibiotics include ceftazidime 2.2 mg, vancomycin 1 mg, and amikacin 0.4 mg. The susceptibility of gram-positive bacteria was highest to vancomycin. Pars plana vitrectomy is beneficial because it reduces the infective and inflammatory load as well as providing material for diagnostic studies.
Periocular injections or subtenon injections can also be options if necessary. A current study showed the most common isolate in cases of endophthalmitis following evisceration was Streptococcus pneumoniae, followed in order by Aspergillus and Pseudomonas aeruginosa, respectively. Endophthalmitis can convert to panophthalmitis if the infection spreads to the sclera and the Tenon’s capsule. Regarding panophthalmitis, the affected eye usually needs to undergo evisceration or enucleation, with studies suggesting the evisceration rate of panophthalmitis ranges from 14.3% to 23.2%. All isolates showed susceptibility to ceftazidime and levofloxacin, and all MIC 90s for isolates in the current period compared with isolates from 1987 to 2001 remained identical. Despite early and appropriate treatment, outcomes were generally poor with a high rate of enucleation. IV drug users are given aminoglycosides and clindamycin to cover for the most likely causative organism, bacillus cereus.
Studies on endophthalmitis resulting from Streptococcus pneumoniae suggest a poor visual outcome. Miller et al., in their study on pneumococcal endophthalmitis, reported 3/27 (11.11%) eyes required evisceration. Pseudomonas endophthalmitis has a high enucleation rate with one study suggesting that 64% endophthalmitis caused by Pseudomonas will end up with evisceration and enucleation. Similarly, high evisceration rates post Pseudomonas endophthalmitis were also seen in other studies. One study found risk factors that are strongly associated with evisceration or enucleation include endogenous endophthalmitis, corneal ulcer, older age, poor initial visual acuity, female gender, and delayed treatment. However, patients with traumatic or postoperative endophthalmitis were less likely to be eviscerated or enucleated. Multivariate analysis indicates that patients suffering from a corneal ulcer, endogenous endophthalmitis, and poor initial visual acuity were much more likely to require evisceration or enucleation.
The use of intracameral cefuroxime following cataract surgery reduced the incidence of postoperative endophthalmitis. Additional risk factors associated with endophthalmitis after cataract surgery included clear corneal incisions (CCI) and the use of silicone intraocular lenses (IOL). A study reviewing 45954 cataract procedures performed by the same surgeon discovered that the incidence of postoperative endophthalmitis could be reduced by 72% if the patient had pretreatment with periocular penicillin injections and topical chloramphenicol-sulphadimidine. The efficacy of this method had confirmation by a concurrent masked, randomized study of 6618 cataract operations that demonstrates that topical regimen alone was as ineffective as penicillin prophylaxis alone. Prevention of postcataract endophthalmitis remains a difficult topic to study given the low incidence. In addition to appropriate wound construction, a combination of povidone-iodine and antibiotics provide a reasonable approach in reducing the risk of this rare but severe infection.
Bacterial endophthalmitis frequently poses a diagnostic dilemma. These patients may exhibit non-specific signs and symptoms such as blurry vision, eye pain, or leukocytosis. The cause of bacterial endophthalmitis may be due to either endogenous or more commonly exogenous causes such as traumatic or surgical. While the slit-lamp exam may reveal that the patient has endophthalmitis, the etiology is difficult to ascertain without proper diagnostic studies. While the ophthalmologist is almost always involved in the care of patients with bacterial endophthalmitis, it is essential to consult with an interprofessional team of specialists that include infectious disease, pharmacology, and the patient's primary care provider.
Nurses are also vital members of the interprofessional group, as they will monitor the patient's status. The pharmacist will ensure that the patient receives the right antibiotics as well as cycloplegic and steroid eye drops, and perform dose checking and medication reconciliation, reporting any issues to the interprofessional team. Without providing a proper history, the ophthalmologist may not be sure what to look for or what additional diagnostic exams may be needed. This problem gets even more complicated when immunocompromised patients present with bacterial endophthalmitis. The outcomes of bacterial endophthalmitis depend on the cause. However, to improve outcomes, prompt consultation with an interprofessional group of specialists is recommended. [Level V]
|||Durand ML, Bacterial and Fungal Endophthalmitis. Clinical microbiology reviews. 2017 Jul; [PubMed PMID: 28356323]|
|||Relhan N,Forster RK,Flynn HW Jr, Endophthalmitis: Then and Now. American journal of ophthalmology. 2018 Mar; [PubMed PMID: 29217351]|
|||Lu X,Ng DS,Zheng K,Peng K,Jin C,Xia H,Chen W,Chen H, Risk factors for endophthalmitis requiring evisceration or enucleation. Scientific reports. 2016 Jun 15; [PubMed PMID: 27302573]|
|||Valdez-García JE,Climent A,Chávez-Mondragón E,Lozano-Ramírez JF, Anterior chamber bacterial contamination in cataract surgery. BMC ophthalmology. 2014 Apr 30; [PubMed PMID: 24885986]|
|||Srinivasan R,Tiroumal S,Kanungo R,Natarajan MK, Microbial contamination of the anterior chamber during phacoemulsification. Journal of cataract and refractive surgery. 2002 Dec; [PubMed PMID: 12498855]|
|||Lundström M,Wejde G,Stenevi U,Thorburn W,Montan P, Endophthalmitis after cataract surgery: a nationwide prospective study evaluating incidence in relation to incision type and location. Ophthalmology. 2007 May; [PubMed PMID: 17324467]|
|||Wiskur BJ,Hunt JJ,Callegan MC, Hypermucoviscosity as a virulence factor in experimental Klebsiella pneumoniae endophthalmitis. Investigative ophthalmology [PubMed PMID: 18586871]|
|||Callegan MC,Kane ST,Cochran DC,Novosad B,Gilmore MS,Gominet M,Lereclus D, Bacillus endophthalmitis: roles of bacterial toxins and motility during infection. Investigative ophthalmology [PubMed PMID: 16123424]|
|||Ng EW,Costa JR,Samiy N,Ruoff KL,Connolly E,Cousins FV,D'Amico DJ, Contribution of pneumolysin and autolysin to the pathogenesis of experimental pneumococcal endophthalmitis. Retina (Philadelphia, Pa.). 2002 Oct; [PubMed PMID: 12441729]|
|||Sanders ME,Norcross EW,Robertson ZM,Moore QC 3rd,Fratkin J,Marquart ME, The Streptococcus pneumoniae capsule is required for full virulence in pneumococcal endophthalmitis. Investigative ophthalmology [PubMed PMID: 21051708]|
|||Dave TV,Dave VP,Sharma S,Karolia R,Joseph J,Pathengay A,Pappuru RR,Das T, Infectious endophthalmitis leading to evisceration: spectrum of bacterial and fungal pathogens and antibacterial susceptibility profile. Journal of ophthalmic inflammation and infection. 2019 May 16; [PubMed PMID: 31098742]|
|||Patel SN,Storey PP,Pancholy M,Obeid A,Wibbelsman TD,Levin H,Hsu J,Garg SJ,Dunn JP,Vander JF, Changes in management based on vitreous culture in endophthalmitis after intravitreal anti-vascular endothelial growth factor injection. American journal of ophthalmology. 2019 Jun 12; [PubMed PMID: 31201794]|
|||Christy NE,Sommer A, Antibiotic prophylaxis of postoperative endophthalmitis. Annals of ophthalmology. 1979 Aug; [PubMed PMID: 318049]|
|||Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. Journal of cataract and refractive surgery. 2007 Jun; [PubMed PMID: 17531690]|
|||Sadiq MA,Hassan M,Agarwal A,Sarwar S,Toufeeq S,Soliman MK,Hanout M,Sepah YJ,Do DV,Nguyen QD, Endogenous endophthalmitis: diagnosis, management, and prognosis. Journal of ophthalmic inflammation and infection. 2015 Dec; [PubMed PMID: 26525563]|
|||Sridhar J,Kuriyan AE,Flynn HW Jr,Miller D, ENDOPHTHALMITIS CAUSED BY PSEUDOMONAS AERUGINOSA: Clinical Features, Antibiotic Susceptibilities, and Treatment Outcomes. Retina (Philadelphia, Pa.). 2015 Jun; [PubMed PMID: 25658178]|
|||Miller JJ,Scott IU,Flynn HW Jr,Smiddy WE,Corey RP,Miller D, Endophthalmitis caused by Streptococcus pneumoniae. American journal of ophthalmology. 2004 Aug; [PubMed PMID: 15289132]|
|||Yu CQ,Ta CN, Prevention of postcataract endophthalmitis: evidence-based medicine. Current opinion in ophthalmology. 2012 Jan; [PubMed PMID: 22081026]|