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.

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.].

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 Crystalline Keratopathy After Corneal Cross-linking.

To report a rare case of infectious keratitis after collagen cross-linking (CXL) for keratoconus. A 20-year-old male patient underwent CXL for keratoconus in his right eye. Four weeks after the procedure, he reported blurred vision and redness with increasing pain in the treated eye. Ophthalmic examination revealed a corneal epithelial defect with corneal infiltrates that exhibited branching needle-like opacities. The patient was diagnosed with infectious crystalline keratopathy (ICK). Corneal scrapings and culture indicated the presence of Streptococcus sanguinis. The patient was successfully treated with fortified vancomycin and ceftazidime over several weeks. ICK is a potential post-operative complication of CXL that can lead to corneal scarring with a permanent reduction in visual acuity.

[Intravitreal triamcinolone acetonide Complication of infectious and sterile endophthalmitis]. / Intravitreales Triamcinolonacetonid Komplikation von infektiöser und steriler Endophthalmitis.

PURPOSE: Intravitreal triamcinolone acetonide (TA), applied as treatment for various edematous and neovascular ocular diseases, was analyzed for infectious or sterile endophthalmitis and pseudoendophthalmitis. METHODS: In a prospective interventional study, 645 eyes were treated with approximately 20 mg intravitreal TA. The removal of the vehicle and the intravitreal injection were performed under sterile conditions. A total of 97 eyes received a second TA injection, 13 a third, 1 a fourth, 2 a fifth, and 1 a sixth injection. The mean follow-up was 7.5 months (median: 5.7 months). RESULTS: In the 1st week after 759 TA injections, 758 resulted in no hypopyon or Tyndall phenomenon >2(+), but in one eye a pseudoendophthalmitis with hypopyon was present. Anterior chamber lavage demonstrated TA crystals, and the culture was negative. In the 2nd week, one patient developed infectious endophthalmitis after a fall had caused ocular perforation. CONCLUSIONS: Intravitreal TA injections (approximately 20 mg) harbor a low risk of infectious or sterile endophthalmitis and pseudoendophthalmitis, if the injection and vehicle removal are performed under sterile conditions.

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.

Epidemiological and microbiological diagnosis of suppurative keratitis in Gangetic West Bengal, eastern India.

PURPOSE: To determine the epidemiological pattern and risk factors involved in suppurative corneal ulceration in Gangetic West Bengal, eastern India, and to identify the specific microbial agents responsible for corneal infections. METHODS: All patients with suspected microbial keratitis presenting to the corneal clinic at Disha Eye Hospital, Barrackpore, West Bengal, India, from January 2001 to December 2003 were evaluated. Sociodemographic data and information pertaining to the risk factors were recorded. After diagnosing infective corneal ulcer clinically, corneal scraping and cultures were performed. RESULTS: Over a three-year period, 1198 patients with suppurative keratitis were evaluated. Ocular trauma was the most common predisposing factor in 994 (82.9%) patients (P< 0.0001), followed by use of topical corticosteroids in 231 (19.28%) patients. Cultures were positive in 811 (67.7%) patients. Among these culture positive cases, 509 (62.7%) patients had pure fungal infections (P< 0.001), 184 (22.7%) patients had pure bacterial infections and 114 (14.1%) had mixed fungal with bacterial infections. Acanthamoeba was detected in 4 (0.49%) patients. The most common fungal pathogen was Aspergillus spp representing 373 (59.8%) of all positive fungal cultures (P< 0.0001), followed by Fusarium spp in 132 (21.2%) instances. Most common bacterial isolate was Staphylococcus aureus, representing 127 (42.6%) of all the bacterial culture (P< 0.0001) followed by Pseudomonas spp 63 (21.1%). CONCLUSION: Suppurative keratitis in Gangetic West Bengal, most often occurs after a superficial corneal trauma with vegetative or organic materials. Fungal ulcers are more common than bacterial ulcers. Aspergillus spp and Staphylococcus aureus were the most common fungus and bacteria respectively. These "regional" findings have important public health implications for the treatment and prevention of suppurative corneal ulceration in this region of India.

Pseudomonas aeruginosa protease IV produces corneal damage and contributes to bacterial virulence.

PURPOSE: A Pseudomonas mutant deficient in protease IV has significantly reduced virulence in experimental keratitis. In the present study, the corneal toxicity of purified protease IV and its ability to augment the virulence of protease-IV-deficient bacteria were analyzed. METHODS: The toxicity of purified protease IV was determined by intrastromally injecting the exoenzyme (20-200 ng) into the cornea. The effects of protease IV on the corneal virulence of the protease-IV-deficient strain, PA103-29::Tn9, were determined by injecting eyes with 1000 CFU of log phase bacteria plus either 200 ng active purified protease IV or 200 ng heat-inactivated protease IV. Changes in ocular disease, determined by slit-lamp examination, were measured at 3, 16, 22, and 27 hours after infection. Colony-forming units per cornea were quantified at 27 hours after infection. RESULTS: Purified protease IV at doses from 50 to 200 ng induced epithelial defects within 3 hours of injection. Injection of 20 ng active protease IV or heat-inactivated protease IV (200 ng) had no effect on ocular tissue. Corneal virulence of the protease-IV-deficient strain was augmented by intrastromal injection with purified protease IV but not with heat-inactivated protease IV (P < or = 0.0001). Neither active nor heat-inactivated protease IV altered the growth of bacteria in the cornea (6 log units; P = 0.81). CONCLUSIONS: The important role of protease IV in corneal virulence was demonstrated by direct toxicity and by its ability to significantly augment the virulence of protease-IV-deficient Pseudomonas.

Corticosteroid-induced modulation of acute syphilitic posterior placoid chorioretinitis.

PURPOSE: To report a case of corticosteroid-induced modulation of acute syphilitic posterior placoid chorioretinitis. DESIGN: Interventional case report. METHOD: A 38-year-old homosexual male who presented with a unilateral uveitis secondary to syphilis developed large placoid macular lesions after treatment with oral prednisone that resolved when the corticosteroids were discontinued. RESULTS: A cause-and-effect relationship was demonstrated between oral prednisone and the appearance of acute syphilitic posterior placoid chorioretinitis. CONCLUSIONS: The clinical appearance of posterior placoid chorioretinitis in syphilis may be modulated by the immune status of the patient.

Lacrimal function and ocular complications in patients treated with systemic isotretinoin.

PURPOSE: To evaluate the effect on lacrimal function and ocular complications in patients with severe acne vulgaris during systemic treatment with 13-cis-retinoic acid (isotretinoin). METHODS: Forty patients with acne vulgaris were treated with systemic isotretinoin at dosages of 0.5-1 mg/kg per day for two months. Full ophthalmologic examination, Schirmer I test, fluorescein break-up (BUT) and microbiological investigations of the conjunctival flora were done before, during the second month and at least one month after the end of the treatment. RESULTS: The average Schirmer values before and after the treatment were 21.6 mm/5 minutes (SD +/- 7.01) and 18.48 mm/5 minutes (SD +/- 7.87) respectively. After the treatment BUT was less than 10 seconds in 50% of the patients and 55% had blepharitis. Subjective symptoms like dryness, itching and contact lens intolerance occurred in 42.5% and colonization of the conjunctiva by Staphylococcus aureus increased significantly during treatment (p= 0.031). All abnormal findings disappeared one month after the cessation of treatment. DISCUSSION: Isotretinoin causes signs and symptoms of dry eye, probably by reducing meibomian gland function, but ocular complications are generally not serious when low doses are used for a limited time, and are reversible after discontinuation.

[A 16-year-old female patient with massive bilateral blepharedema]. / Sechzehnjährige Patientin mit massivem beidseitigem Lidödem.

CASE REPORT: A 16-year-old female patient initially presented with bilateral swelling and redness of the eyelids already existing for the duration of two days. The symptoms had started after the patient dyed her eyelashes and eyebrows with henna. THERAPY: Systemic antihistamine and glucocorticoid therapy led to no visible improvement. An intravenous antibiotic treatment was started which resolved the symptoms entirely. CONCLUSION: The diagnosis of an allergic contact dermatitis with a secondary bacterial infection was made.

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.

Chlamydial heat shock proteins and trachoma.

Two chlamydial proteins (HSP-60 and HSP-70) have marked homology with bacterial and mammalian heat shock proteins. Previous studies have indicated that when inoculated into the eyes of immune animals, a Triton X-100 extract of chlamydia containing HSP-60 induces an ocular delayed-type hypersensitivity reaction. The potential for HSP-70 to induce a similar reaction was tested in six cynomolgus monkeys that had been sensitized to both antigens by previous ocular chlamydial infection. Whereas the chlamydial extract containing HSP-60 induced a marked clinical response within 24 h of inoculation, no response followed inoculation of HSP-70 in the contralateral eye. The lack of a response to HSP-70 suggests that further assessment of its potential as a trachoma vaccine is warranted.