Endogenous Endophthalmitis and Other Ocular Manifestations of Injection Drug Use

Preston M. Luong; Edmund Tsui; Nikhil N. Batra; Michael E. Zegans


Curr Opin Ophthalmol. 2019;30(6):506-512. 

In This Article

Endogenous Endophthalmitis

One of the most serious consequences of injection drug use is the hematogenous spread of microorganisms to the eye leading to intraocular infection and potential permanent vision loss. Endophthalmitis in general refers to inflammation of the aqueous or vitreous humor secondary to intraocular infection, with two different classifications according to source of infection. The vast majority of endophthalmitis is exogenous, in which infectious agents are directly introduced from the external environment into the eye as in cases that occur after cataract surgery or trauma. Endogenous endophthalmitis, which makes up 2–8% of all endophthalmitis cases, results from a hematogenous infection that enters the choroid and infiltrates the vitreous humor.[8] Injection drug use is a major risk factor for the development of endogenous endophthalmitis.[8] The source of microbes causing infection has been postulated to arise from the drug itself, injection paraphernalia, or local skin flora at the site of injection.[9] However, microbes isolated from heroin and injection paraphernalia appear distinct from those found to be causing clinically significant infection in IDUs, suggesting that local skin flora are the main sources of infection.[10] Drugs may also be dissolved with mixing agents such as lemon juice to enhance breakdown of tissues at the injection site. These mild acids can further serve as a culture medium.[11] Injection drug use may occur via intramuscular, intravenous, intra-arterial, or subcutaneous routes of administration.

Like other forms of endogenous endophthalmitis, prompt recognition is essential to preserve vision. Importantly, a thorough history and review of systems is necessary to elicit a history of illicit drug use. Often, patients with a history of injection drug use may not offer this history on initial interview. Common symptoms of injection drug use endogenous endophthalmitis include reduced vision, floaters, eye pain, eye redness, and sensitivity to light.[4–6,12] Bilateral disease occurs in a minority of cases. The average age of these patients in several recent studies have ranged from 30s to 40s.[4–7,12] The most common comorbidity among these patients is hepatitis C infection, with rates of coinfection ranging from 44 to 50%. Other less common comorbidities include HIV infection with or without AIDS, endocarditis, septic arthritis, meningitis, and presumed syphilis infection.[4,12] Commonly abused drugs included heroin (most common, irrespective of geographic region), cocaine, buprenorphine/naloxone, hydromorphone, and methadone. In addition, patients with a history of injection drug use delay their presentation to medical care despite earlier onset of symptoms, indicating that they may tend to normalize injection-related harms and lack readily available access to healthcare providers.[4,6] This pattern has been reported with other injection drug use-associated infections.[13] This delay may lead to an unknown number of undiagnosed cases, as some patients may be diagnosed with a nonspecific uveitis. For example, the natural history of endogenous endophthalmitis from Candida albicans may mimic a nonspecific intermediate or posterior uveitis.[14] Furthermore, up to one-fifth of patients with Candida spp. ocular infection may have a negative baseline examination but develop new lesions at follow-up owing to possibility of an indolent disease course.[15]

Dilated fundoscopic examination is essential and if necessary, B-scan ultrasonography should be obtained if there is an obscured view to the fundus. Features found in the funduscopic exam include vitritis, retinal and vitreous hemorrhage, cotton wool spots, and presence of retinal or choroidal abscesses.[16] The infection and signs of inflammation may extend anteriorly to cause an anterior chamber reaction, hypopyon, and infiltrates on the cornea. As with other forms of endogenous endophthalmitis, blood cultures should be obtained to rule out bacteremia and/or fungemia, and to determine antimicrobial sensitivities. However, blood cultures generally have a low 15% sensitivity of detection of endogenous endophthalmitis.[5,6] This is likely due to the transient nature of the bacteremia and fungemia, which is difficult to detect due to the delay in seeking care and the possibility that a bloodstream infection may resolve by the time of presentation. The IDU population, who are often younger, healthier, immunocompetent patients may quickly clear the fungemia or bacteremia. Many patients are also placed on systemic antimicrobials prior to presenting with ocular symptoms. Examination of the vitreous fluid is also important for diagnosis. Vitreous sampling should be obtained at presentation and sent for bacterial and fungal cultures. Positive rates of detection are generally higher than that of blood cultures, but still generally detect less than half of cases.[4–6] The most sensitive method of determining the infectious organism is direct vitreous biopsy obtained at the time of pars plana vitrectomy.[5] Although each individual culture source may not have high enough sensitivity to capture the infectious organism, the combined results of multiple culture sources yield the best chance of detecting the pathogen. As many cases of endogenous endophthalmitis may be culture negative due to commonly delayed presentations in IDUs, targeted PCR for suspected bacteria or fungi may be helpful.[6,17,18]

The most common offending organism overall in injection drug use-associated endogenous endophthalmitis is C. albicans.[4,5,7,12,14] Less common fungal pathogens include Candida dubliniesis, Candida tropicalis, and Aspergillus niger.[4,5,12] Bacterial involvement most commonly involves staphylococcal species, including methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal species including methicillin-sensitive Staphylococcus aureus. Infection with Bacillus cereus, Streptococcus mitis, Corynebacterium spp., Nocardia spp, Neisseria meningitidis, and Streptococcus pneumoniae have also been observed.[5,7,8,12,19] Mixed bacterial/fungal infections have been reported. Of note, emerging and novel pathogens that are not typically found in endogenous endophthalmitis, such as Scopulariopsis fungal species or Rhodotorula fungus have been recently reported.[20,21]

Since injection drug use-related endogenous endophthalmitis cases have only recently increased due to the opoid epidemic, there are no established guidelines for treatment. At initial presentation for both diagnostic and therapeutic purposes, patients with suspected endogenous endophthalmitis generally undergo immediate vitreous sampling with an intravitreal 'tap' and injection of intravitreal antibiotics. As many cases involve both fungal and bacterial pathogens, we advocate for appropriate coverage with intravitreal antifungals and antibiotics. Accepted intravitreal antifungals include amphotericin B (5 μg/ml, 0.1 ml) and voriconazole (100 μg/ml, 0.1 ml). Although intravitreal amphotericin B and voriconazole appear similar in efficacy of treatment of fungal endophthalmitis, voriconazole may be preferable as amphotericin B has been associated with retinal toxicity in animal models.[22] For bacterial endogenous endophthalmitis, intravitreal vancomycin (1 mg/ml, 0.1 ml) and ceftazidime (2.25 mg/ml, 0.1 ml) have been demonstrated to have adequate coverage of Gram-positive and negative organisms and are accepted as standard of practice.[23] Patients with suspected endogenous endophthalmitis from injection drug use may also benefit from intravenous vancomycin, ceftazidime, and voriconazole if there is suspicion of or confirmed active bloodstream infection.

The role of initial treatment with office-based vitreous sampling and intravitreal antibiotics compared with pars plana vitrectomy is undecided. In recent studies that investigated injection drug use-associated endogenous endophthalmitis relatively few eyes underwent vitrectomy initially, although most patients eventually required vitrectomy.[4,5,7] Operating on an acutely inflamed eye may increase the risk of a poor outcome; however, Modjtahedi et al. suggested that early vitrectomy may be beneficial. The patients in their study who underwent initial vitrectomy had similar best-corrected visual acuity at follow-up compared with those who had initial office-based intravitreal injection, despite the former having worse vision and presumably worse burden of disease at presentation.[5] Vitrectomy may remove residual bacterial debris and exotoxins that result in continued inflammation and retinal damage. If office-based management with intravitreal injections is performed, then ongoing evaluation should be performed to reassess the need for vitrectomy in cases of worsening vitritis or absence of improvement. Some patients should be admitted for administration of intravenous antimicrobials. There may be some degree of blood–ocular barrier breakdown, allowing improved penetration of systemic antibiotics.[23] Systemic antibiotics and antifungals may be transitioned from intravenous to oral administration once organism sensitivities have been determined.

The prognosis of injection drug use-associated endogenous endophthalmitis even with treatment is typically poor; however, there is great variation in outcomes, which may be attributed to low sample sizes, diversity of patient characteristics, delays in diagnosis, and differences in threshold for surgical treatment.[4,5,7,12,14,24,25] In endogenous endophthalmitis, regardless of cause, bacterial infection appears to portend a worse prognosis compared with fungal infection with exception of Aspergillus in injection drug use cases.[19] Ocular sequelae contributing to diminished vision include cataract formation, vitreous hemorrhage, cystoid macular edema, epiretinal membrane, retinal tear, retinal detachment with or without proliferative vitreoretinopathy, and macular scarring.