Clinical features, management, and outcomes of patients with sterile endophthalmitis associated with intravitreal bevacizumab injection: retrospective case series.

PURPOSE: To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. METHODS: In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. RESULTS: Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. CONCLUSION: Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.

Sterile endophthalmitis after intravitreal injection of triamcinolone acetonide: case report and literature review.

Objectives: The first purpose is to present the diagnosis and therapeutic approach in a patient with sterile endophthalmitis associated with triamcinolone acetonide injection. The secondary objective is to assess the incidence of this complication and to summarize the risk factors described in the literature. Case presentation: A 76-year-old male patient presented for painless, unilateral, decreased visual acuity, four days after cataract surgery and simultaneously intravitreal triamcinolone acetonide injection for diabetic macular edema in the right eye. The diagnosis of sterile endophthalmitis was made. Eight days after the presentation, the symptoms subsided, the maximum corrected visual acuity reaching that before the procedures. Discussions: The incidence of sterile endophthalmitis varies in the literature between 0% and 23.8%. Visual prognosis is good, although the pathogenesis is not fully understood. Preservatives in injectable solutions have been suggested, however, there are studies in which inflammation was also present with preservative-free products. The particle size of triamcinolone was analyzed, demonstrating an association between smaller particles and an increased frequency of adverse reactions of this type. History of uveitis, posterior capsule rupture following cataract surgery, and Irvine-Gass syndrome are other associations described. Conclusion: The physiopathological mechanism of sterile endophthalmitis is not fully understood. However, the visual prognosis is good, the final vision being dependent on the underlying pathology.

Acute Sterile Endophthalmitis Following Intravitreal Rituximab Injection in Primary Vitreoretinal Lymphoma: Case Series.

OBJECTIVE OR PURPOSE: To describe sterile endophthalmitis following intravitreal rituximab (Rituxan, Genentech) injection for treatment of vitreoretinal lymphoma (VRL). DESIGN: Retrospective case series. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Medical records of biopsy-proven VRL patients who received intravitreal rituximab (RTX) between January 2011 and December 2021 in Kellogg Eye Center, University of Michigan were reviewed. 3 patients presented with sterile endophthalmitis after the second dose of intravitreal RTX were included.Methods, Intervention, or Testing: Intravitreal methotrexate (400µg/0.1ml) and rituximab (1mg/0.1ml) injections given a week apart, monthly.Main Outcome Measures: Clinical presentation and response to treatment including visual acuity, degree of inflammation and intraocular pressure . RESULTS: All cases had bilateral disease and received the first dose of intravitreal RTX without any side effects. All cases developed bilateral corneal edema with Descemet's folds, mutton-fat keratic precipitates, anterior chamber and vitreous cells with hazy fundus view approximately within 1 week after the second RTX injection. Intraocular pressures were increased in Cases 2 and 3. Clinical findings improved to baseline with topical corticosteroid therapy within 1 month in all cases, and additional topical antiglaucomatous medication in Cases 2 and 3. Additionally, Case 1 received the third dose of RTX injection to the right eye 1 month after the second injection and repeating dense anterior chamber and vitreous cells developed in 1 day. Her vision decreased to counting fingers from 20/40, and intraocular pressure increased. After topical steroids and antiglaucomatous medications, her intraocular inflammation subsided. Her vision improved to 20/30, and intraocular pressure became normal in the right eye. CONCLUSIONS: To our knowledge, this is the first case series documenting sterile endophthalmitis following intravitreal rituximab in vitreoretinal lymphoma. Recognition of sterile endophthalmitis is important in differentiating from vitreoretinal lymphoma recurrence and infectious endophthalmitis. Close observation and topical steroid drops seem to be effective.

Exogenous Endophthalmitis.

PURPOSE: Exogenous endophthalmitis (ExE) results from microbial infection as a complication of ocular surgery, penetrating ocular trauma, and intraocular foreign bodies. We herein review the classification of ExE, etiological agents, differential diagnosis and therapeutic challenges. METHODS: Narrative Literature Review. RESULTS: Identification of the causative agent through ocular fluid analysis is central in the diagnostic work-up of ExE. Prompt intravitreal antimicrobial therapy is key to successful management of ExE and vitrectomy is essential in severe cases. In culture-negative cases, and in the presence of specific features, a diagnosis of sterile intraocular inflammation or toxic syndrome should be suspected. CONCLUSION: Strict adherence to treatment guidelines may improve outcomes of ExE, however the ultimate prognosis, especially in severe cases, may depend more on the virulence of the causative organism and associated ocular complications. Accurate differential diagnosis and effective treatment are crucial elements in the management and prognosis of non-infectious masquerades of ExE.

Sterile endophthalmitis after intravitreal triamcinolone acetonide injection: A case report series.

Corticosteroids have proven their effectiveness in the treatment of cystoid macular edema. Especially after an intravitreal injection. Triamcinolone acetonide is the most commonly used in the treatment of macular edema. Noninfectious endophthalmitis is a form of endophthalmitis that can occur in the absence of a defined germ after an intravitreal injection of triamcinolone acetonide. We report here the case of three diabetic patients, who presented with visual blur, three days after an intra vitreal triamcinolone acetonide injection performed in the right eye. The vitreous inflammation resolved spontaneously in the first two cases after three weeks, and after four weeks for the third. The diagnosis of sterile endophthalmitis was made in view of the spontaneous resolution of the inflammation without the use of intravitreal injection of antibiotics and/or vitreoretinal surgery.

Differences in the incidence of aflibercept-related sterile endophthalmitis according to types of disposable syringes used.

PURPOSE: To evaluate the difference between the incidences of sterile endophthalmitis after administration of intravitreal aflibercept injection using two different types of syringes. METHODS: We administered a total of 498 intravitreal aflibercept injections between September 2017 and August 2021. The disposable syringe used was changed from a 1-mL disposable syringe (Profi syringe, Shinchang Medical., Ltd. Korea) to a 1-mL Becton Dickenson Luer-Lok syringe (BD, Franklin, NJ, USA) in September 2019. Thus, the patients who received injections before and after September 1, 2019, were classified into group 1 and group 2, respectively. The incidence of aflibercept-related sterile endophthalmitis between the two groups was compared. RESULTS: In group 1, six (2.791%) out of 215 cases were diagnosed with sterile endophthalmitis and prescribed topical or oral steroids. In group 2, one (0.353%) out of 283 cases was diagnosed with sterile endophthalmitis and prescribed a steroid eye drop. The incidence of sterile endophthalmitis was significantly different between the two groups (P = 0.046). CONCLUSION: The BD Luer-Lok syringe is associated with a lower incidence of aflibercept-related sterile endophthalmitis than the conventional polypropylene syringe. Differences in immunogenicity associated with silicone oil lubricants within the syringes might be one of the potential reasons behind the difference in the incidence of the sterile endophthalmitis.

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review.

BACKGROUND: Intraocular inflammation is an uncommon but potentially vision-threatening adverse event related to anti-VEGF therapy. This is of increasing importance given both the volume of injections performed, as well as the increased prevalence of inflammation seen with newer anti-VEGF agents. Brolucizumab, the newest anti-VEGF agent, has been associated with an inflammatory retinal vasculitis and the underlying mechanism is unclear. Reviewing potential mechanisms and clinical differences of intraocular inflammation may assist clinicians and scientists in reducing the risk of these events in the future. OBSERVATIONS: Two types of inflammation are seen with intravitreal injections, acute onset sterile inflammation and delayed onset inflammatory vasculitis. Acute onset inflammation can be subcategorized into subclinical anterior chamber inflammation and sterile uveitis/endophthalmitis. Subclinical anterior chamber inflammation can occur at rates as high as 19% after intravitreal anti-VEGF injection. Rates of sterile uveitis/endophthalmitis range from 0.05% to 4.4% depending on the anti-VEGF agent. Inflammatory vasculitis is only associated with brolucizumab and occurred in 3.3% of injections according to the post hoc review of the HAWK/HARRIER data. In addition, silicone oil from syringes can induce immunogenic protein aggregates. Agitation of the syringe, freeze thawing, shipping and improper storage prior to injection may increase the amount of silicone oil released from the syringe. CONCLUSION: The main factors which play a role in intraocular inflammation after anti-VEGF injection can be divided into three causes: patient-specific, medication-specific and delivery-specific. The majority of clinically significant inflammation seen after intravitreal injection is an acute onset inflammatory response with most patients recovering baseline VA in 3-5 weeks. The presence of pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss may help distinguish infectious from non-infectious etiologies of post injection inflammation. Avoiding temperature fluctuation, mechanical shock, agitation during transport and handling of syringes/drugs, and the use of SO-free syringes may help minimize intraocular inflammation. While a definitive mechanism has not yet been established, current knowledge of the clinical presentation and vitreous histopathology of brolucizumab-retinal vasculitis favors an auto-immune type IV hypersensitivity reaction.

Triamcinolone acetonide induces sterile endophthalmitis in patients with intermediate uveitis: A case report series.

Due to their anti-inflammatory, antiangiogenic and antiedematous properties, corticosteroids have been commonly used in the treatment of retinal diseases. Intravitreal administration of steroids offers the maximal drug efficacy and the lowest risk of systemic side effects. The authors report three cases of presumed sterile endophthalmitis induced by triamcinolone acetonide (TA) in three eyes with intermediate non-infectious uveitis. Each patient received a single intravitreal injection of TA of 4 mg. Because of the intense vitreous inflammatory reaction, retina examination and the optical coherence tomography could not be performed, although vitreous opacities were observed on the ocular ultrasound. The dense vitreous opacity is a defining factor, the anterior segment inflammation is mild to moderate and a hypopyon is present, which may be a sterile inflammatory reaction or the triamcinolone material itself. In cases of sterile endophthalmitis, the visual acuity increases progressively as the intraocular inflammation diminishes. Local treatment with topical antibiotics, prednisolone acetate and cycloplegic eyedrops is recommended to control the inflammatory reaction.

Clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal injection of antivascular endothelial growth factor. / Características clínicas, manejo y resultados de los pacientes con endoftalmitis estéril asociados con la inyección intravítrea de factores de crecimiento endotelial antivascular.

PURPOSE: Analyze clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal antivascular endothelial growth factor. METHODS: Observational retrospective case series of patients with sterile endophthalmitis following anti-VEGF intravitreal injections. Clinical data of patients treated with intravitreal anti-VEGFs during one year have been revised. Those who have presented an episode of sterile endophthalmitis are analyzed and their causality and management are studied. RESULTS: Seven patients have had a sterile endophthalmitis onset within 4days after intravitreal injection (aflibercept n=5 and ranibizumab n=2). These patients have some active neovascular condition: age related macular degeneration (n=4), myopic choroidal neovascularization (n=1) or macular edema: diabetic macular edema (n=1), branch retinal vein occlusion (n=1). Shared signs and symptoms included painless vision loss, anterior chamber and vitreous cell and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. CONCLUSION: Differentiating cases of sterile from infectious endophthalmitis may be challenging. It is crucial to differentiate both entities as a good diagnosis determines the visual prognosis. We should be aware of minimal inflammation after repeated intravitreal injections in order to establish the adequate treatment.

Sterile endophthalmitis rates and particle size analyses of different formulations of triamcinolone acetonide.

PURPOSE: To evaluate the rate of sterile endophthalmitis (SE) following intravitreal injection of three different formulations of triamcinolone acetonide (TA) in a single physician practice and also to assess the mean diameter and concentration of particles of the two TA formulations currently available commercially in the USA. It was hypothesized that TA formulations with smaller particles and/or greater concentrations would have a higher incidence of SE. METHODS: Single-site, interventional case series in which the medical records of 392 consecutive eyes receiving intravitreal TA as Triesence(®), Kenalog(®)-40, or preservative-free TA between September 2008 and October 2013 were retrospectively reviewed for the incidence of SE. Particle sizing of TA formulations was conducted by an independent commercial laboratory. RESULTS: Five cases of SE were identified. The four cases of SE following Triesence(®) (4.6%) represented a rate significantly higher than the one case of SE following preservative-free TA (0.6%; P=0.049) and the 0% incidence rate of SE following Kenalog(®)-40 (P=0.0210). Triesence(®) had significantly smaller particles than Kenalog(®)-40 (P<0.0001). CONCLUSION: The rate of SE was the highest with the formulation of TA that had the smallest particle size and highest particle load (number of particles injected). The lowest rate of SE was seen with Kenalog(®)-40, the only TA formulation that contained a benzyl alcohol preservative. The data do not support a principal causative role of benzyl alcohol in the development of TA-induced SE. Instead, the data support the particle theory of TA-induced SE; however, larger-scale, multicenter studies are needed to confirm and expand on these findings.