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Background To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. Methods 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post-treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. Results In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. Conclusions In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. Trial registration number CTRI/2013/07/003802.

To study intravitreal dexamethasone and vancomycin concentrations, when used together in patients with suspected postoperative bacterial endophthalmitis. Animal studies had suggested that dexamethasone might decrease the concentration of vancomycin. Prospective randomized clinical trial in a tertiary referral center. Twenty-nine consecutive patients with suspected postoperative bacterial endophthalmitis underwent a vitreous biopsy followed by intravitreal injection of antibiotics (0.2 mg vancomycin, 0.05 mg gentamicin) and 400 mug dexamethasone or placebo. After 3-4 days, the intravitreal injection of antibiotics and dexamethasone or placebo was repeated. In 18 patients, a second biopsy was taken for repeat culture and measurement of vancomycin and dexamethasone concentrations. In 20/29 patients (69%) the first vitreous cultures were positive; the second culture was negative in all cases. Thirteen out of 29 patients received dexamethasone. Dexamethasone concentrations showed an average of 25 ng/ml 3 days after injection, with an estimated half-life of 5.5 h. Vancomycin concentrations in patients given dexamethasone tended to be higher compared with those in the placebo group (P=0.061). Intravitreal dexamethasone does not lead to decreased vancomycin concentrations, when given simultaneously in the treatment of patients with suspected bacterial endophthalmitis.

Background/aims: To compare the penetration of levofloxacin, ofloxacin and ciprofloxacin in the aqueous humour of eyes with functioning filtering blebs.Methods: In this investigator-masked study, 48 patients with functioning filtering blebs requiring cataract surgery were randomised into six groups of eight patients. Groups 1, 2 and 3 received topical ofloxacin 0.3% (Ocuflox®), ciprofloxacin 0.3% (Ciloxan®) and levofloxacin (Quixin®) respectively; Groups 4, 5 and 6 received the same treatment with the corresponding oral dose of ofloxacin 400 mg (Floxin), ciprofloxacin 400 mg (Cipro) and levofloxacin 250 mg (Levaquin). Aqueous antibiotic levels were determined by mass spectrometry of aqueous samples from each patient.Results: The mean aqueous level for topical levofloxacin was significantly higher than those achieved by topical ofloxacin or ciprofloxacin (p value = 0.02 and 0.01, respectively). The combination of topical and oral levofloxacin was significantly higher than topical levofloxacin alone (p = 0.05) and the ciprofloxacin combination (p = 0.003) but not significantly higher than the ofloxacin combination therapy.Conclusions: Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).

Bacterial keratitis (BK) is an ocular disorder associated with poor visual prognosis. Quantification of the associated inflammatory response may provide insight into the pathogenesis of BK and guide treatment options. In this exploratory study, we evaluated 45 BK patients and 20 healthy controls by optical coherence tomography and pro-inflammatory tear cytokine analysis. The aim was to quantify the differential morphological and cytokine inflammatory response between Gram-negative and Gram-positive BK and to determine the diagnostic value of corneal thickness (CT) and infiltrate thickness (IT) in distinguishing Gram−ve BK in a clinical cohort. Greater CT and IT, at clinical presentation, were indicative of Gram−ve infection with values detected of ≥ 950 μm and ≥ 450 μm, respectively. Combination of these CT and IT values had a 100% sensitivity and 83.3% specificity as a diagnostic indicator of Gram−ve infection. Similarly, there were higher levels of IL-1β, IL-6 and IL-8 cytokines were quantified in keratitis caused by Gram-negative bacteria. Among the different tear cytokines analysed, a significant reduction after three days of treatment was detected for pro-inflammatory cytokines IL-1β, IL-2, IL-6, IL-8 and TNF-α, prior to starting with the administration of steroid drops. Overall, this study shows the potential value of serial OCT and tear cytokine measurements in the management of BK.

Background To investigate Quorum-Sensing inhibition by furanone compounds in Pseudomonas aeruginosa keratitis rabbit model. Methods Thirty adult New Zealand White rabbits were used. Anesthetized rabbits were intrastromally injected with Pseudomonas aeruginosa (P. aeruginosa). The rabbits were divided into six groups: the control group (infected only with P. aeruginosa), group A (50 mg/mL ceftazidime), group B (0.1 mg/mL furanone), group C (0.2 mg/mL furanone), group D (0.3 mg/mL furanone), and group E (20% dimethyl sulfoxide). One drop of the treatment was applied every hour for 3 days, starting 1-h post-inoculation. Rabbits were then sacrificed, and corneas were analysed clinically, microbiologically, histologically, and biochemically. One-way analysis of variance was used for the mean comparison of independent groups. The Least Significant Difference method was used as a post-hoc test for pairwise comparisons. Results In all evaluations, the antibiotic group (group A) showed the best therapeutic response. The slit-lamp examination score of group C was significantly lowered than those compared of to the control ( p  = 0.009) and E groups ( p  = 0.014). Histological evaluation showed that inflammation is decreased in groups B, C, and D. Levels of cyclooxygenase-2 (COX-2), superoxide dismutase-1, and reactive oxygen species (ROS) were lowest in the antibiotic-treated group, whereas the highest levels were detected in the control group. Notably, the COX-2 levels in group B and ROS levels in groups B and C were significantly lower than in control group. ( p  = 0.045, p  = 0.039 and p  = 0.045, respectively). Conclusion Furanone compounds may have minimal therapeutic effects against Pseudomonas keratitis. Its therapeutic effect has not been observed to be sufficient compared with that of antibiotics. Further studies are needed to investigate their protective effects and mechanisms.

B. cereus possesses flagella which allow the organism to migrate within the eye during a blinding form of intraocular infection called endophthalmitis. Because flagella is a ligand for Toll-like receptor 5 (TLR5), we hypothesized that TLR5 contributed to endophthalmitis pathogenesis. Endophthalmitis was induced in C57BL/6J and TLR5-/- mice by injecting 100 CFU of B. cereus into the mid-vitreous. Eyes were analyzed for intraocular bacterial growth, retinal function, and inflammation by published methods. Purified B. cereus flagellin was also injected into the mid-vitreous of wild type C57BL/6J mice and inflammation was analyzed. TLR5 activation by B. cereus flagellin was also analyzed in vitro. B. cereus grew rapidly and at similar rates in infected eyes of C57BL/6J and TLR5-/- mice. A significant loss in retinal function in both groups of mice was observed at 8 and 12 hours postinfection. Retinal architecture disruption and acute inflammation (neutrophil infiltration and proinflammatory cytokine concentrations) increased and were significant at 8 and 12 hours postinfection. Acute inflammation was comparable in TLR5-/- and C57BL/6J mice. Physiological concentrations of purified B. cereus flagellin caused significant inflammation in C57BL/6J mouse eyes, but not to the extent of that observed during active infection. Purified B. cereus flagellin was a weak agonist for TLR5 in vitro. These results demonstrated that the absence of TLR5 did not have a significant effect on the evolution of B. cereus endophthalmitis. This disparity may be due to sequence differences in important TLR5 binding domains in B. cereus flagellin or the lack of flagellin monomers in the eye to activate TLR5 during infection. Taken together, these results suggest a limited role for flagellin/TLR5 interactions in B. cereus endophthalmitis. Based on this and previous data, the importance of flagella in this disease lies in its contribution to the motility of the organism within the eye during infection.

Bacillus cereus causes a uniquely rapid and blinding intraocular infection, endophthalmitis. B. cereus replicates in the eye, synthesizes numerous toxins, and incites explosive intraocular inflammation. The mechanisms involved in the rapid and explosive intraocular immune response have not been addressed. Because Toll-like receptors (TLRs) are integral to the initial recognition of organisms during infection, we hypothesized that the uniquely explosive immune response observed during B. cereus endophthalmitis is directly influenced by the presence of TLR2, a known gram-positive pathogen recognition receptor. To address this hypothesis, we compared the courses of experimental B. cereus endophthalmitis in wild type C57BL/6J mice to that of age-matched homozygous TLR2(-/-) mice. Output parameters included analysis of bacterial growth, inflammatory cell (PMN) infiltration, cytokine/chemokine kinetics, retinal function testing, and histology, with N≥4 eyes/assay/time point/mouse strain. B. cereus grew at similar rates to10(8) CFU/eye by 12 h, regardless of the mouse strain. Retinal function was preserved to a greater degree in infected TLR2(-/-) eyes compared to that of infected wild type eyes, but infected eyes of both mouse strains lost significant function. Retinal architecture was preserved in infected TLR2(-/-) eyes, with limited retinal and vitreal cellular infiltration compared to that of infected wild type eyes. Ocular myeloperoxidase activities corroborated these results. In general, TNFα, IFNγ, IL6, and KC were detected in greater concentrations in infected wild type eyes than in infected TLR2(-/-) eyes. The absence of TLR2 resulted in decreased intraocular proinflammatory cytokine/chemokine levels and altered recruitment of inflammatory cells into the eye, resulting in less intraocular inflammation and preservation of retinal architecture, and a slightly greater degree of retinal function. These results demonstrate TLR2 is an important component of the initial ocular response to B. cereus endophthalmitis.

Microbial keratitis is a significant cause of global visual impairment and blindness. Corneal infection can be caused by a wide variety of pathogens, each of which exhibits a range of mechanisms by which the immune system is activated. The complexity of the immune response to corneal infection is only now beginning to be elucidated. Crucial to the cornea’s defences are the pattern-recognition receptors: Toll-like and Nod-like receptors and the subsequent activation of inflammatory pathways. These inflammatory pathways include the inflammasome and can lead to significant tissue destruction and corneal damage, with the potential for resultant blindness. Understanding the immune mechanisms behind this tissue destruction may enable improved identification of therapeutic targets to aid development of more specific therapies for reducing corneal damage in infectious keratitis. This review summarises current knowledge of pattern-recognition receptors and their downstream pathways in response to the major keratitis-causing organisms and alludes to potential therapeutic approaches that could alleviate corneal blindness.

Dr. Gnanasekaran et al. reported the bactericidal activity of various concentrations of povidone iodine (PI) solution in an agar plate experiment of respiratory flora. The study design and the pharmacokinetic properties of PI solution ensured that dilute PI would not be effective in this study. These results may not replicate the typical clinical situation and are significantly different than a previously reported agar plate experiment, again owing to subtle but very significant differences in methodology.