Epidemiology and risk factors

Endogenous endophthalmitis remains an uncommon but serious cause of intraocular inflammation.¹ The incidence may be increasing, due to several factors. An increasing number of immunocompromised patients are receiving antineoplastic agents, immunomodulating agents, and newer broad-spectrum antimicrobial agents, all of which may reduce normal flora.^2,3 Low-birthweight premature infants and patients with a history of intravenous substance abuse are at increased risk for endogenous endophthalmitis.⁴ Other reported risk factors include long-term intravenous line placement, peripheral hyperalimentation, systemic corticosteroids, abdominal surgery, hemodialysis, HIV infection, systemic malignancy, diabetes mellitus, pregnancy or postpartum state,⁵ massive systemic trauma, alcoholism, hepatic insufficiency, and genitourinary manipulation.⁶

One recent series of 64 cases over 10 years reported a culture positivity rate of 64%. Of culture-positive cases, fungi (predominantly Candida spp.) were isolated in 66%, Gram-negative bacteria in 19%, and Gram-positive bacteria in 15%. Fungal cases were associated with better visual outcomes.⁷

Clinical assessment of the patient

Infectious endophthalmitis may be categorized by the cause of the infection and by the characteristic timing of clinical signs and symptoms. One proposed categorization scheme is presented in Box 87.1.⁸ In general, endogenous endophthalmitis is suspected in a patient without risk factors for exogenous endophthalmitis, such as prior surgery, trauma, or keratitis. Patients with endogenous endophthalmitis may present with varying degrees of pain, inflammation, and visual loss. In the anterior chamber, cell and flare, fibrin, posterior synechiae, and hypopyon may occur. In the posterior segment, findings may include vitreous opacification and chorioretinitis, including hemorrhage, cotton-wool spots, retinal opacification, and vasculitis. An insidious onset, focal vitreous opacities, and chorioretinal infiltrates suggest fungal etiology. Relatively more rapid progression and more severe intraocular inflammation suggest bacterial etiology.

Endogenous endophthalmitis may present as a relatively mild and nonspecific anterior uveitis.⁹ Early in the clinical course, the clinical features may be subtle, making the diagnosis difficult. The rate of initial misdiagnosis has been reported as high as 63% in one large series.¹⁰ A differential diagnosis of endogenous endophthalmitis is presented in Box 87.2.

Cases may be classified according to several criteria. One published classification scheme for endogenous bacterial endophthalmitis used zones of anatomic involvement (Box 87.3).¹¹ Another scheme, designed for endogenous fungal endophthalmitis, also used anatomic criteria (Box 87.4); in this series, the stage at initial diagnosis was statistically correlated to the final visual acuity.¹²

Medical evaluation of the patient

In contrast to patients with postoperative or post-traumatic endophthalmitis, nearly all patients with endogenous endophthalmitis have an identifiable systemic infection and require at least some degree of systemic evaluation. Generally, the medical evaluation is performed in consultation with an infectious disease specialist or other medical specialist. A high index of suspicion should be maintained, because both the ophthalmic and systemic symptoms are quite variable. In one series, 43% of patients with endogenous endophthalmitis had no nonocular symptoms.¹³ Endogenous endophthalmitis may present prior to the onset of systemic symptoms,¹⁴ or may occur in patients later found to have no other systemic infection.¹⁵ In one series, the rate of negative systemic workup was over 40%.¹⁶ In a patient not known to have systemic infection, intraocular cultures (aqueous, vitreous, or both) may be necessary to confirm the diagnosis. Intraocular cultures are also important in patients who progress despite treatment with empiric antimicrobial therapy.

Obtaining cultures from multiple sites may be necessary to make a specific diagnosis. In one series of patients with endogenous bacterial endophthalmitis, the rate of diagnostic cultures was 74% for vitreous, 72% for blood, and 96% overall.¹⁷ The rates of positive cultures are lower in patients with endogenous fungal endophthalmitis. Rates of positive cultures have been reported in the range of 44–70%,¹⁸ and as low as 18% in one prior series.¹⁹

Endogenous bacterial endophthalmitis

Endogenous bacterial endophthalmitis is reported to comprise between 2% and 8% of all cases of infectious endophthalmitis (Fig. 87.1).²⁰ Many bacteria have been reported to cause endogenous endophthalmitis. Gram-positive agents associated with bacterial endogenous endophthalmitis include Staphylococcus areus,²¹ group B Streptococcus,²² Streptococcus pneumoniae,²³ Streptococcus bovis,²⁴ Propionibacterium acnes,²⁵ Listeria monocytogenes,²⁶ Bacillus spp.,²⁷ Nocardia spp.,²⁸ and others. Gram-negative agents associated with bacterial endogenous endophthalmitis include Klebsiella pneumoniae,²⁹ Pseudomonas aeruginosa,³⁰ Escherichia coli,³¹ Enterococcus faecalis,³² Neisseria meningitidis,³³ Proteus spp.,³⁴ and others.

Fig. 87.1 Endogenous Klebsiella pneumonia endophthalmitis. (A) Note anterior chamber cell and flare. (B) Note hypopyon. (C) Note vitreous opacification overlying macular chorioretinitis and associated hemorrhage.

(Case courtesy of Lisa C. Olmos, MD, MBA.)

Endogenous fungal endophthalmitis

Over 50 000 species of fungi have been reported, yet fewer than 200 of these are associated with clinical disease in humans and even fewer have been reported to cause endogenous endophthalmitis (Box 87.5). Fungi may be differentiated using several criteria, but are commonly divided between unicellular yeasts and multicellular molds. Molds contain tubular structures (hyphae). Some fungi may grow with both yeast-like and mold-like morphology in tissues or culture. Fungi may also be classified by pigmentation (moniliaceous versus dermatiaceous), virulence (pathogenic versus opportunistic), or clinical presentation (cutaneous, subcutaneous, or systemic).

Candida albicans is the most common yeast isolate and the most common overall fungal isolate in patients with endogenous fungal endophthalmitis.^35,36 C. albicans may be found as a commensal organism in the gastrointestinal tract and mucous membranes of healthy individuals.³⁷Although the organism is of low virulence to healthy individuals, candidemia is associated with relatively high rates of morbidity and mortality.³⁸ In one series, the mortality rate among patients with candidemia and endogenous Candida endophthalmitis was reported as 77%.³⁹ Candida endophthalmitis is strongly associated with intravenous drug abuse.⁴⁰ Other Candida species reported to cause endophthalmitis include C. tropicalis, C. parapsilosis, C. glabrata, C. guilliermondii, and C. krusei. Among patients with diagnosed candidemia, reported rates of endogenous endophthalmitis range from less than 3%⁴¹ to 44%.⁴² The prevalence of Candida endophthalmitis may be decreasing, as systemic antifungals are now more commonly prescribed for patients with positive blood cultures.⁴³ The most characteristic clinical sign of Candida endophthlamitis is one or more creamy white, well-circumscribed chorioretinal lesion, less than 1 mm in diameter, most commonly in the posterior pole, with an overlying haze of vitreous inflammatory cells (Figs 87.2, 87.3). Yellow or fluffy-white vitreous opacities, sometimes connected by strands of inflammatory material (“string of pearls” configuration), may be noted. Recently, a subretinal abscess was reported in a patient with endogenous C. albicans endopthalmitis.⁴⁴ The initial misdiagnosis rate may be high; one series reported this rate to approach 50%.⁴⁵

Fig. 87.2 Endogenous Candida endophthalmitis. Note creamy white chorioretinal lesion, with associated retinal hemorrhage and evidence of vasculitis.

Fig. 87.3 Macular chorioretinitis, clinically suspected endogenous Candida endophthalmitis. This patient was an intravenous drug abuser and improved with empiric oral fluconazole.

(Case courtesy of Jeffrey K. Moore, MD.)

Aspergillus is the most common mold isolate and the second most common overall fungal isolate in patients with endogenous fungal endophthalmitis.⁴⁶ Reported risk factors include chronic pulmonary disease, liver transplantation,⁴⁷ and treatment with systemic corticosteroids, but rare cases are reported in apparently immunocompetent individuals.⁴⁸ Endogenous Aspergillus endophthalmitis is associated with a characteristic central macular chorioretinal inflammatory lesion.⁴⁹ A gravitational layering (pseudohypopyon) of inflammatory exudates in either the preretinal (subhyaloid) or subretinal space may be noted with the macular lesion. Additionally, Aspergillus endophthalmitis may be associated with retinal vascular occlusion, choroidal vascular occlusion, and exudative retinal detachment.⁵⁰ For these reasons, Aspergillus endophthalmitis generally has a poorer prognosis than Candida endophthalmitis. A case report documented a poor visual outcome, and eventual mortality, in a patient with acute myelogenous leukemia and bilateral endogenous Aspergillus fumigatus endophthalmitis despite prophylaxis with oral fluconazole. The intial ophthalmologic presentation was notable for diffuse hemorrhagic retinal necrosis, and the initial diagnosis was cytomegalovirus retinitis.⁵¹

Cryptococcus neoformans