Trends in Endophthalmitis Associated With Intravitreal Injection of Anti-VEGF Agentsat a Tertiary Referral Center.

BACKGROUND AND OBJECTIVE: To report the incidence and clinical features of infectious endophthalmitis after intravitreal (IV) injection of anti-vascular endothelial growth factor inhibitors (VEGF) between 2018 and 2020 and to compare to prior rates. PATIENTS AND METHODS: Retrospective analysis of patients with endophthalmitis after anti-VEGF IV injections treated at Bascom Palmer Eye Institute between January 1, 2018, and December 31, 2020. RESULTS: Between 2018 and 2020, the rate of clinically diagnosed endophthalmitis was 0.014% (10/71,858) and of culture-positive was 0.008% (6/71,858). Clinically diagnosed endophthalmitis rates per injection were: aflibercept (0.022%); ranibizumab (0.019%); bevacizumab (0%); and brolucizumab (0%). Clinically diagnosed endophthalmitis rates were similar in the present study compared to those from 2005 to 2017 (P = .84). Fifteen eyes were diagnosed with endophthalmitis (10 in-house, five external referrals). Of culture-positive eyes, the organisms were coagulase-negative Staphylococcus (8/11), Streptococcus species (2/11), and Abiotrophia defectiva (1/11). A universal face-masking policy in 2020 did not lower infection rates (P = .73). CONCLUSION: Endophthalmitis rates after IV anti-VEGF remain low and are similar to prior reports. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:319-326.].

Counterfeit Avastin in India: Punish the Criminals, Not the Patients.

PURPOSE: To report the recent controversy surrounding the intraocular use of bevacizumab in India and its relationship to the broader problems of off-label drug use, medication compounding, and drug counterfeiting. DESIGN: Perspective. METHODS: Data for this perspective were obtained from several sources. Literature reviews for compounding-related endophthalmitis and drug counterfeiting were performed. Supplemental information was obtained through targeted Google searches for related published manuscripts. First-hand accounts of negotiations between representatives of the Vitreoretinal Society of India (VRSI) and India's Central Drugs Standards Control Organization (CDSCO) were provided by 2 of the authors (R.N., V.G.). RESULTS: In December, 2015, 15 cases of intraocular inflammation following injections of counterfeit bevacizumab occurred in Gujarat, India. CDSCO reacted by prohibiting the use of intraocular bevacizumab throughout the country. Intense negotiations between the VRSI and CDSCO resulted in the permission to use bevacizumab in accordance with new safety guidelines. These include an enhanced informed consent process, the stamping of the Kezzler code on all bevacizumab vials, a real-time digital verification process between the end user and Roche Pharmaceuticals, and mandatory destruction of empty drug vials. CONCLUSION: Counterfeit bevacizumab has caused outbreaks of sterile and infectious postinjection endophthalmitis in at least 3 countries during the past 5 years and has entered the supply chain in other countries. Physicians and compounding pharmacists need to be aware that international counterfeiters have targeted bevacizumab.

Bilateral acute pyogenic conjunctivitis with iritis induced by unilateral topical application of bacterial peptidoglycan muramyl dipeptide in adult rabbits.

The factors responsible for the conjunctivitis and iritis associated with acute ocular infection and post enteric inflammatory disease are not fully known. The pro-inflammatory activity of unilateral topical application of muramyl dipeptide (MDP; the smallest bio-active Gram-positive and Gram-negative bacterial cell wall component) was investigated in adult rabbits. The resultant bilateral conjunctivitis/iritis and pyogenic responses were characterized. Bilateral symptoms were graded by slit lamp examinations; tear fluid, Schirmer tests (tear production), blood and aqueous humor (AH) samples were obtained from MDP-treated and untreated rabbits. MDP concentration, gamma-glutamyltranspeptidase activity (GGT; key enzyme in glutathione recapture, xenobiotic detoxification, eicosanoid synthesis and neutrophil function), protein concentration, and tear cell density, cytology, and immunofluorescent antibody reactivity to GGT and calreticulin (CRT; MDP-binding protein) were determined. MDP was cleared from ipsilateral tears and serum by 6 h, but was undetected in mock-treated contralateral tears. Bilateral signs of acute transient pyogenic conjunctivitis, characterized by tearing, lid edema, conjunctival hyperemia, chemosis and leukocytic infiltrate with iritis (erythema and aqueous flare) were detected. Milder symptoms occurred in the mock-treated contralateral eyes. Bilateral symptoms, tear production, tear protein, GGT activity, and mucopurulent discharge (containing up to 2.5-5.0 × 10(6) cells/mL) were elevated 4-8 h post MDP and resolved to near pre-treatment levels by 24 h. Tear GGT activity and protein levels were higher in MDP-treated and mock-treated contralateral eyes than in eyes of untreated adult rabbits (p's < 0.001). Elevated tear GGT activity was associated with histopathology and increased vascular and epithelial permeability to serum protein, GGT-positive epithelia cells, macrophages and heterophils. Repeat MDP applications induced recurrent induction and resolution patterns of bilateral conjunctivitis/iritis and tear GGT activity, but ipsilateral GGT responses were lower. The results suggest unilateral topical MDP application to adult rabbit eyes induces a bilateral acute pyogenic conjunctivitis/iritis (PCI) characterized by increased vascular and epithelial permeability similar to acute bacterial conjunctivitis in man. The detection of CRT/GGT positive heterophils in tears suggests efferocytosis (phagocytosis of dead/dying cells). Tear GGT activity may be a useful means to quantify MDP-induced toxicity and extraocular inflammation.

[The estimation of systemic chemotherapy treatment administered in breast cancer on lysozyme activity in tears--preliminary report]. / Ocena wplywu systemowej chemioterapii stosowanej w leczeniu raka sutka na aktywnosc lizozymu zawartego we lzach--doniesienie wstepne.

PURPOSE: Estimation of cytostatics influence used in breast cancer treatment on lysozyme activity in human tears depend on time of treatment. MATERIAL AND METHODS: 8 women were treated at the base of chemotherapy schema: docetaxel with doxorubicin and 4 women treated with schema CMF: cyclophosphamide, methotrexate, 5-fluorouracil. Lysozyme activity in tears was assessed by measurement of diameter zone of Micrococcus lysodeicticus growth inhibition. RESULTS: It was revealed that both chemotherapy schema caused statistically significant reduction of diameter zone of M. lysodeicticus growth inhibition, after first and second course of chemotherapy treatment. After second chemotherapy course CMF schema induced loss of lysozyme activity in patient's tears (zero mm of M. lysodeicticus diameter zone growth inhibition). CONCLUSIONS: Systemic chemotherapy administered in breast cancer induce reduction of lysozyme activity in tears, that may cause higher morbidity of ocular surface infections caused by Gram-positive bacteria.

The use of topical honey in the treatment of corneal abrasions and endotoxin-induced keratitis in an animal model.

PURPOSE: To investigate the effect of topically applied honey on intact corneas, surgically induced corneal abrasions and endotoxin induced keratitis. MATERIALS AND METHODS: The effect of honey on the cornea was investigated by application of honey on intact corneas, wounded corneas and endotoxin-induced keratitis in Lewis rats. The corneas were wounded by creating an epithelial defect using a surgical blade, and the keratitis was induced by topically applying Pseudomonas aeruginosa endotoxin to scarified corneas. After treatment rats were sacrificed and cornea harvested in each case. Corneas were processed for paraffin embedding for histological and immuno-fluorescence staining. Corneas were also harvested and processed for total ribonucleic acid (RNA) isolation for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for various growth factors and inflammatory chemokines/cytokines). RESULTS: Histological analysis revealed that no inflammation or morphological changes occurred after honey treatment in naive intact corneas. Vascular endothelial growth factor (VEGF) levels were also not altered after honey treatment. Topical application of honey to injured corneas resulted in faster epithelial healing and decreased expression of VEGF, transforming growth factor beta (TGF-ß), interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in injured corneas. Our results also established that honey treatment reduced the inflammation in endotoxin-induced keratitis by reducing the levels of angiogenic factors (VEGF and TGF-ß), inflammatory cytokines (IL-12) and chemokines (CC chemokine receptor 5(CCR-5)). CONCLUSION: Short term use of honey on intact corneas can be safe. Honey has anti-angiogenic and anti-inflammatory properties that can be explored in several corneal inflammatory and infectious conditions.

Microbiological evaluation of chronic blepharitis among Iranian veterans exposed to mustard gas: a case-controlled study.

PURPOSE: To evaluate the microbiological characteristics of eyelid margin flora in chronic blepharitis in mustard gas-exposed individuals and compare the results with those in age- and sex-matched unexposed people. METHODS: In this comparative case series, 289 patients with ocular manifestations of mustard gas exposure (case) were evaluated for signs of chronic blepharitis. Additionally, microbiological evaluation of eyelid margins was conducted in these patients and compared with results of 100 unexposed patients with chronic blepharitis (control). RESULTS: One-hundred fifty (52.0%) of 289 mustard gas casualties had signs of chronic blepharitis. Microbiological evaluation revealed higher isolation rates of Staphylococcus epidermidis (78%) and Staphylococcus aureus (57%) in the case in comparison to control group (P < 0.01). Moreover, S. aureus isolated from the cases exhibited greater resistance to common antibiotics compared with control group. Fungi were isolated more frequent in the case compared with controls (30% vs. 4%, P < 0.01), with Cladosporium and Candida species being most common in the case group. CONCLUSIONS: Exposure to mustard gas seems to alter the microbiological flora of the eyelid margin. Staphylococcus spp., including antibiotic-resistant strains, and fungi were more frequently isolated in these patients. The relationship between microbial culture results and the severity of ocular surface manifestations in mustard gas-injured cases warrant further investigation.

Infectious and noninfectious endophthalmitis after intravitreal bevacizumab.

AIMS: The aim of this study was to evaluate the rate of infectious and noninfectious endophthalmitis after an intravitreal injection of bevacizumab. METHODS: This clinical interventional case-series study included 1218 intravitreal injections of 1.5 mg of bevacizumab consecutively performed for 684 eyes with exudative age-related macular degeneration. Among the injections were 534 reinjections. Follow-up after each injection was at least 4 weeks. RESULTS: One (1) eye developed an infectious endophthalmitis 3 days after a second injection. In none of the other eyes, were signs of an infectious or noninfectious endophthalmitis observed with the cellular infiltration or amorphous opacification of the vitreous as marked by the Tyndall phenomenon in the anterior chamber, retinal infiltration, or pain. CONCLUSIONS: The rate of infectious endophthalmitis after an intravitreal injection of 1.5 mg bevacizumab may be approximately 1:1000, similar to injections of other drugs available thus far.

Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker.

The development of anti-tumor necrosis factor (TNF) therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection.

PURPOSE: To report potentially distinguishing characteristics between bacterial endophthalmitis and presumed noninfectious endophthalmitis associated with intravitreal triamcinolone acetonide injection. METHODS: Records of two patients with culture-proven bacterial endophthalmitis and six patients with presumed noninfectious endophthalmitis from intravitreal triamcinolone acetonide injections were analyzed retrospectively. RESULTS: Two eyes in two patients with culture-proven bacterial endophthalmitis had decreased vision and hypopyon or vitritis, but no pain or conjunctival injection 2 weeks after intravitreal triamcinolone acetonide injection. Seven eyes in six patients with presumed noninfectious endophthalmitis had blurred vision, hypopyon, and variable pain all within 2 days of intravitreal triamcinolone injection. All seven eyes were followed up closely and had rapid resolution of hypopyon and symptoms. CONCLUSION: Bacterial endophthalmitis after intravitreal triamcinolone acetonide injection may present in an atypical, relatively delayed manner with decreased vision but no pain or redness. Presumed noninfectious endophthalmitis presents within 2 days after the injection, may be accompanied by discomfort, and has a hypopyon that may be the triamcinolone material itself or a sterile inflammatory reaction. In these eyes, the hypopyon and symptoms quickly resolve without treatment.