Adjunctive Thymosin Beta-4 Treatment Influences MΦ Effector Cell Function to Improve Disease Outcome in Pseudomonas aeruginosa-Induced Keratitis.

Our previous work has shown that topical thymosin beta 4 (Tß4) as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages/MΦ) while enhancing bacterial killing and wound healing pathway activation in an experimental model of P. aeruginosa-induced keratitis. This study aimed to mechanistically examine how Tß4 influences MΦ function in particular, leading to reduced inflammation and enhanced host defense following P. aeruginosa-induced infection of the cornea. Flow cytometry was conducted to profile the phenotype of infiltrating MΦ after infection, while generation of reactive nitrogen species and markers of efferocytosis were detected to assess functional activity. In vitro studies were performed utilizing RAW 264.7 cells to verify and extend the in vivo findings. Tß4 treatment decreases MΦ infiltration and regulates the activation state in response to infected corneas. MΦ functional data demonstrated that the adjunctive Tß4 treatment group significantly downregulated reactive nitrogen species (RNS) production and efferocytotic activity. In addition, the in vitro studies showed that both Tß4 alone and adjunctive Tß4 treatment influenced MΦ cellular function following LPS stimulation. Collectively, these data provide further evidence that adjunctive Tß4 + ciprofloxacin treatment offers a more efficacious option for treating bacterial keratitis. Not only does the adjunctive therapy address both the infectious pathogen and corneal wound healing response, but it also influences MΦ infiltration, activation, and function, as revealed by the current study.

A randomised controlled trial of azithromycin following surgery for trachomatous trichiasis in the Gambia.

BACKGROUND/AIM: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. METHODS: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. RESULTS: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. CONCLUSION: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.

Syphilitic uveitis in patients infected with human immunodeficiency virus.

BACKGROUND: This work investigates the incidence and clinical features of syphilitic uveitis in patients infected with human immunodeficiency virus (HIV). MATERIAL AND METHODS: We retrospectively reviewed syphilitic uveitis in patients coinfected with HIV that presented at a referral center between July 2001 and November 2003. RESULTS: Twelve patients (20 eyes) were included. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in three patients. All patients were male and homosexual. One patient has been previously treated for syphilis with benzathine penicillin G. One patient presented with anterior uveitis and 11 patients had panuveitis or posterior uveitis. Necrotizing retinitis was noted in seven eyes (35%), posterior placoid chorioretinitis in six eyes (30%) and optic nerve involvement in five eyes (25%). Of nine patients with available cerebrospinal fluid (CSF) studies, seven (77.8%) had CSF abnormalities. Eleven patients were treated with intravenous penicillin G and one with intravenous ceftriaxone sodium. One patient required a second course of antibiotics to control uveitis. Ocular inflammation decreased and visual acuity improved in all nine patients for whom follow-up was available after treatment. CONCLUSION: Manifestations of syphilitic uveitis in HIV-infected patients are multiple, with high frequencies of posterior uveitis, posterior placoid chorioretinitis, necrotizing retinitis and optic nerve involvement. Syphilitic uveitis in HIV-infected patients seems to have a more severe course and may relapse despite high-dose intravenous penicillin therapy.