Editor s Bio Gholam A. Peyman, MD, a vitreoretinal surgeon, is a pioneer in many areas of ophthalmology, including the intravitreal injection of antibiotics for the treatment of endophthalmitis, evaluation of drugs, surgical resection of ocular tumors, drug delivery systems, lasers, vitreous substitutes, vitrectomy, treatment of uveitis, and transplantation of retinal pigment epithelial cells in age-related macular degeneration,. Reviews "…This profusely illustrated book provides comprehensive coverage of this relatively specialized topic….
The Bookshelf application offers access: Offline Computer — Download Bookshelf software to your desktop so you can view your eBooks with or without Internet access. The country you have selected will result in the following: Product pricing will be adjusted to match the corresponding currency. The title will be removed from your cart because it is not available in this region. The most reliable way of diagnosing systemic infection is blood culture. Blood must be drawn on three consecutive days using sterile precautions. Previous large series have shown higher rates of positivity following blood culture as compared to vitreous aspirate possibly due to larger volume sampled.
It is also important to culture other extra ocular sites to identify the possible nidus of infection and guide systemic therapy accordingly, for example, urine cultures. Identification of these infectious foci is particularly important in cases where vitreous cultures are negative [ 15 ]. Imaging of ocular tissues is an important means to diagnose intraocular infection. Presence of exudates in the vitreous cavity can present as echoes in the ultrasound B-scan of the eye. Patients with EE can present with abscesses in the choroid Fig. These can be detected as dome-shaped lesions arising from the choroid on B-scan.
Complications of EE, including retinal detachment may be difficult to assess clinically. In such situations, ultrasound B-scan can help in identification of retinal detachment Fig. Optical coherence tomography OCT has also been used as an imaging modality in patients with EE where it helps in localizing the pathology within the retinal layers as well as sub-retinal space [ 58 , 59 ]. It can demonstrate sub-retinal exudates with elevation of retinal pigment epithelium, intra-retinal lesions with or without extrusion into the vitreous, choroidal thickening, and posterior vitreous cells [ 59 , 60 ].
Ultrasound B-scan of a patient diagnosed with endogenous bacterial endophthalmitis following septic arthritis. There is presence of dense, hyper-reflective echoes in the vitreous cavity suggestive of exudates yellow arrow. The membrane-like echo in the scan marked by yellow triangles suggests presence of a total retinal detachment. As an ophthalmological emergency, prompt management is required for any patient with suspected EE.
Approach to management of such a patient involves assessment of degree of ocular involvement, identification of the causative organism, and the underlying source of infection and then treatment of both the endophthalmitis and the underlying systemic infection. Summary of the steps in the diagnosis and management of EE are illustrated in Fig. A proposed management of patients with endogenous endophthalmitis.
In a neonate with white reflex, endophthalmitis along with other considerations such as malignancy must be kept as a possibility in the differential diagnosis. Sight-threatening lesions involving the fovea, optic nerve head, cornea, limbus, or sclera may require prompt surgical management.
What are the symptoms of endophthalmitis?
Treatment of the underlying source of bacteremia is necessary with systemic antibiotics. Systemic antibacterial therapy should be initiated after blood cultures have been obtained. However, treatment with systemic antibiotics tailored to systemic infection alone is not sufficient, and most patients with severe endogenous bacterial endophthalmitis may require intravitreal antibiotics. In addition, pars plana vitrectomy PPV may also be needed for the treatment of endogenous bacterial endophthalmitis. Cultures of vitreous obtained by needle aspiration or vitrectomy are indicated as soon as infectious endophthalmitis is suspected.
Timing of administration of the intravitreal antibiotics has not been officially established; however, Yonekawa et al. Treatment is first initiated with empirical intravitreal antibiotics that provide a cover for both gram-positive and gram-negative organisms, when the etiology is unknown. For gram-positive infections, vancomycin is the primary drug used because of emergence of many cases of methicillin-resistant organisms [ 28 ]. However, recently, there have been reports of gram-positive cases resistant to vancomycin [ 61 ]. There are multiple therapeutic agents that can be used for gram-negative infections.
The most commonly used drug to provide gram-negative coverage is ceftazidime 2. Fluoroquinolones also have good gram-positive and gram-negative coverages, especially the fourth generation fluoroquinolones [ 61 ]. However, recently, resistance against fluoroquinolones is on a rapid rise [ 64 — 66 ].
Antibiotics can be tailored further once the organism is identified and susceptibility pattern is known from vitreous and blood cultures. Commonly used intravitreal antibacterial drugs used for pharmacotherapy of bacterial endogenous endophthalmitis. Early diagnosis and treatment is essential for a better prognosis.
However, patients with endogenous bacterial endophthalmitis may have a delayed diagnosis which may lead to poor prognoses [ 3 , 11 , 67 ]. Two important groups that need special attention while administering antibiotics are pregnant and breastfeeding women. Penicillins, cephalosporins, and erythromycin are among the mainline agents in these groups due to good safety profiles [ 29 ].
Fluoroquinolones have been associated with abnormalities of developing cartilage in animal studies [ 68 ]. Even though there have been no reports of such cases during human pregnancies, it is recommended to use fluoroquinolones only when other safer alternatives are not available despite their good vitreous penetration [ 29 , 68 , 69 ]. For severe vitritis, the best approach appears to be vitrectomy accompanied by intravitreal injection of amphotericin or voriconazole and systemic antifungal therapy [ 70 , 71 ].
Voriconazole is a newer agent in the armory of drugs used to treat ocular fungal infections. It achieves an excellent intravitreal concentration after oral or intravenous administration [ 36 ]. Fluconazole is also a broad spectrum agent with a better side effect profile than AMB. Therefore, it has been used in place of AMB as the first-line agent against endogenous fungal endophthalmitis EFE as shown by Hamada et al.
Alternatively, fluconazole can be used as well. For severe cases of endophthalmitis or vitritis, the adjunctive use of vitrectomy is recommended [ 73 ]. With severe involvement, usually a longer duration of therapy may be required. Treatment in immunocompromised patients includes systemic antifungal therapy e. If the patient is able to tolerate surgery, vitrectomy and removal of intraocular lens should be performed followed by intravitreal antifungal therapy using amphotericin or voriconazole. However, if the patient cannot tolerate surgery, intravitreal injection with amphotericin or voriconazole should be administered initially and repeated as needed.
Voriconazole has been used to treat fungal infections resistant to fluconazole and amphotericin B [ 75 ]. Other reports also stated successful treatment of Fusarium and Aspergillus endophthalmitis using voriconazole [ 77 , 78 ]. IDSA guidelines for the treatment of Aspergillus endophthalmitis recommend the use of IV amphotericin B with addition of intravitreal amphotericin B and pars plana vitrectomy for sight-threatening cases [ 79 ].
The recommended alternate therapy is systemic or intravitreal voriconazole. Commonly used intravitreal antifungal drugs employed for pharmacotherapy of fungal endogenous endophthalmitis along with their sensitivity. PPV is a commonly used modality in the treatment of EE. It is recommended for severe and sight-threatening Candida , Aspergillus , or bacterial endophthalmitis [ 5 , 73 , 79 ]. It serves as a diagnostic as well as therapeutic purpose. It may remove a large number of organisms seeding the vitreous cavity thus lowering the disease burden [ 2 , 5 , 80 ].
An intravitreal injection of drugs may also be given while performing the surgery. However, almost all reported cases where a therapeutic vitrectomy was performed are of patients presenting with either sight-threatening disease or of those that were irresponsive to systemic therapy [ 15 , 17 , 49 , 52 , 67 , 80 ].
Decision of early vitrectomy has also been associated with a decrease in incidence of retinal detachment and evisceration or enucleation [ 15 , 81 ]. On the other hand, Sheu et al. However, they still suggested the use of surgical intervention, especially in patients with anterior chamber inflammation that did not respond well to intravitreal antibiotics. Currently, no clear guidelines exist regarding the use of corticosteroids in endophthalmitis.
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Inflammation, although essential in combating invading organisms, may end up damaging retinal structures [ 84 ]. Steroids have multiple anti-inflammatory effects which include but are not limited to decrease in leucocyte recruitment, attenuating production of various inflammatory cytokines and stabilizing membrane barriers including blood-retinal barrier [ 85 ].
Clinical studies have reported controversial results on the use of intravitreal as well as systemic steroids for endophthalmitis [ 2 ]. In two case series by Jackson et al. An interim safety analysis of a prospective multicenter randomized placebo-controlled trial of IVT dexamethasone as an adjuvant therapy for endophthalmitis did not report any safety risks associated with the use of steroids [ 85 ]. On the other hand, Shuwan lee et al. In summary, data on the use of steroids in endophthalmitis is limited, and the results of studies are conflicting.
Therefore, judicious use of steroids is recommended. In general, EE does not have a favorable prognosis and results in complete vision loss, especially if the diagnosis is missed early on and therefore treatment is delayed [ 21 ].
Endogenous endophthalmitis: diagnosis, management, and prognosis
The major risk following vitreous aspirate in patients with EE is high incidence of retinal detachment. Surgery for retinal detachment in these cases is difficult, and there is a need for long-term tamponade in such patients post vitrectomy [ 88 ]. A clinician has to maintain a very high level of suspicion when a patient with a possible risk factor presents in association with decreased vision and vitreoretinal changes on examination.
This is well above the percentage of patients reported with similar improvement before this study [ 11 ]. Virulence of the organism plays an important role in the visual outcome [ 15 ]. Aspergillus and other molds cause more aggressive disease compared to yeasts and therefore carries a worse prognosis [ 16 , 18 , 30 , 43 , 91 ].
Endogenous endophthalmitis: diagnosis, management, and prognosis
Similarly MRSA endophthalmitis has been reported to be associated with significant mortality [ 28 ]. The association of MRSA endophthalmitis with visual outcome has been variable, with some studies reporting no association while others associating it with worse visual outcome [ 28 , 92 , 93 ]. In a study conducted to determine factors resulting in poor visual outcome, worse initial visual acuity and centrally located lesions were found to be associated with poor visual outcomes [ 81 ].
The same study showed that early vitrectomy prevented the development of retinal detachment. The results of another study in patients with fungal EE showed that early stages were associated with better prognosis.
American Association for Pediatric Ophthalmology and Strabismus
This underscores the importance of detecting and promptly treating the disease at early stages to preserve visual acuity [ 80 ]. According to Ang et al. Other prognostic factors found in the same study include rapid onset of ocular symptoms, unilateral involvement, and panophthalmitis. Another study found no association between final visual acuity log MAR values and diabetes, causative organism, source of infection, and performance of vitrectomy [ 15 ].
However, the study did report better final visual outcomes in patients with initial visual acuity better than counting fingers. EE is an ophthalmological emergency that requires prompt diagnosis and management. The main challenges in the management of EE are early identification and delivering an adequate concentration of the drug in the vitreous cavity.
It may be possible to overcome this challenge with direct intravitreal administration of the antibiotic. Systemic therapy is used to treat the focus of infection causing the metastatic spread of the organism to the ocular cavity. In mild cases of EE, systemic therapy is the mainstay of treatment. However, in severe cases, systemic therapy is adjuvant to the more aggressive intravitreal administration of drugs.
PPV has a diagnostic as well as therapeutic role in the management of EE. Visual acuity, systemic debility, etiology of infection, and ocular examination must guide the decision to intervene in such cases. MAS participated in the design and coordination and helped to draft the manuscript. MdH participated in the design of the study and helped to draft the manuscript. AA participated in the analysis and revision of the manuscript.
SS helped analyze the data and revised the manuscript. ST drafted and revised the manuscript. MKS participated in drafting the manuscript.
Prognosis of endophthalmitis varies widely depending upon the cause of the infection, the severity, and the amount of damage done to the eye by inflammation and scarring. Mild cases of endophthalmitis can have excellent visual outcomes. Severe cases may result not only in loss of sight, but eventually in loss of the entire eye.
American Association for Pediatric Ophthalmology and Strabismus. The outside of eye is in constant contact with viruses, fungi and bacteria and infection of this part of the eye is conjunctivitis or keratitis How does endophthalmitis occur?
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