Microbiological efficacy of 3-day treatment with azithromycin 1.5% eye-drops for purulent bacterial conjunctivitis.

PURPOSE: Antibacterial efficacy of topically applied azithromycin 1.5% was compared with tobramycin 0.3% in a multicenter, randomized, investigator-masked study for the treatment of purulent bacterial conjunctivitis. METHODS: A total of 1043 adults and children received either azithromycin twice daily for 3 days (n=524) or tobramycin every 2 hours while awake for 2 days, then four times daily for 5 days (n=519). Conjunctival swabbing was taken at days 0, 3, and 9, using alginate swabs resuspended in a dissolution-transport medium, providing rapid and reproducible results. Cagle's criteria were used to define the pathogenicity level for each isolated bacterium. RESULTS: In the per-protocol set, the rate of bacteriologic resolution was 85.2% for azithromycin versus 83.8% for tobramycin on day 3, and 92.8% for azithromycin versus 94.6% for tobramycin on day 9. Azithromycin was demonstrated to be noninferior to tobramycin according to the 10% noninferiority margin. Although some bacteria were categorized as resistant to tested antibiotics, eradication was observed (for azithromycin: Acinetobacter, Enterobacteriaceae, Pseudomonas), highlighting the specific pharmacokinetics/pharmacodynamics of the ocular route. CONCLUSIONS: In total, topical therapy with azithromycin 1.5% administered only twice daily for 3 days effectively eradicates most pathogenic bacteria associated with bacterial conjunctivitis. These microbiologic results are in accordance with the observed clinical outcome. This new anti-infective product has the advantage of a short treatment course which could lead to an improvement in patient compliance.

Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers.

PURPOSE: To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS: In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS: T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS: Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).

Comparison of a non-preserved 0.1% T-Gel eye gel (single dose unit) with a preserved 0.1% T-Gel eye gel (multidose) in ocular hypertension and glaucomatous patients.

AIM: This comparative, open design, phase III study was to assess the non-inferiority of the non-preserved T-Gel 0.1% single dose unit (SDU) versus its preserved multidose (MD) reference. METHODS: 175 patients with bilateral POAG or OHT were randomised: 87 patients were to receive one drop daily of T-Gel 0.1% MD and 88 patients were to receive one drop daily of T-Gel 0.1% SDU, for a treatment period of 12 weeks. The primary efficacy variable was the change in intraocular pressure (IOP) in the worse eye between the baseline and the last assessment. Subjective and objective ocular signs as well as adverse events were recorded for safety. Global tolerance was assessed by the investigator and by the patient. RESULTS: The mean percentage reduction from baseline IOP was 24% for both treatments groups, which was consistent with previous studies. The safety results were comparable in both treatment groups. Because of gel formulation, mild short lasting episodes of blurred vision occurred for about 20% of patients. The global tolerance assessment reported that both treatments were well tolerated. CONCLUSION: The overall study results demonstrated that T-Gel 0.1% SDU is not inferior to T-Gel 0.1% MD.

[Acute portal thrombosis revealing hereditary hemochromatosis: report of a case]. / Thrombose portale aiguë révélant une hémochromatose héréditaire: à propos d'un cas.

The authors report the case of a 49-year old man in whom an inaugural portal vein thrombosis led to the diagnosis of hereditary hemochromatosis. In this case, the increase in ferritinemia and the T2-weighted MRI hepatic segmental hyposignal were considered as consequences of tissular necrosis while they did probe a real iron overload. Genetic testing, revealing C282Y/H63D compound heterozygoty, provided evidence for a diagnosis of hereditary hemochromatosis. Weekly venesections induced a calculated iron depletion of 3.5 g without occurrence of anemia, further supporting the diagnosis. We suggest that hemochromatosis should be considered in the differential diagnosis of idiopathic portal vein thrombosis when signs of abnormal iron accumulation exist.

Safety and efficacy of unpreserved timolol 0.1% gel in patients controlled by preserved latanoprost with signs of ocular intolerance.

PURPOSE: To assess the safety and efficacy of unpreserved timolol 0.1% gel in ocular hypertensive (OHT) or glaucomatous patients controlled by preserved latanoprost 0.005% but with signs of ocular intolerance. METHODS: Patients initially treated with preserved latanoprost were randomized to receive once daily either one drop of unpreserved timolol gel in the morning or one drop of preserved latanoprost in the evening for 84 days. All patients attended three visits (D0, D28 and D84). A patient was considered as responder to primary criteria at Day 84 if the sum of the scores of the eight ocular symptoms and the six objective signs had decreased by at least 20% and if the effect on intra-ocular pressure (IOP) was assessed as either satisfactory or acceptable. RESULTS: At D84, 91.5% of patients were responders to the primary combined efficacy/safety criteria under unpreserved timolol gel treatment versus 48.6% under preserved latanoprost treatment (P<0.001). As early as D28, 85.3% of patients were responders in the unpreserved timolol gel group compared to 40.3% of patients in the preserved latanoprost group (P<0.001). IOP change from baseline was not significant between treatments (P>0.05) at D28 or D84. Both signs and symptoms were significantly improved (P<0.001) with unpreserved timolol gel compared to preserved latanoprost. CONCLUSION: Unpreserved timolol 0.1% gel maintained the efficacy of preserved latanoprost and reduced signs and symptoms of intolerance in almost all glaucomatous/OHT patients on preserved latanoprost.

[Evaluation of NAAGA efficacy in dry eye syndrome]. / Evaluation de l'efficacité du NAAGA dans la sécheresse oculaire.

OBJECTIVES: The aim of this study was to assess the efficacy of Naabak((R)) eyedrops in reducing inflammation in dry eye syndrome. PATIENTS AND METHODS: This pilot, multicenter, randomized, double-blind, parallel study was carried out in adult patients suffering from moderate dry eye syndrome. Patients were treated for three months with preservative-free NAAGA (Naabak((R))) or with sodium chloride 0.9% without preservative (Larmabak(R)). They received the treatment four to six times a day during the 1(st) month and three to four times a day during the 2(nd) and 3(rd) months. At each visit (D28 and D84), clinical tests were performed as well as a biological evaluation of HLA-DR and MUC5AC expression on conjunctival imprints using flow cytometry. RESULTS: After three months of treatment, the ocular surface symptoms and overall discomfort were improved in patients treated with Naabak(R) and in those treated with Larmabak(R) with no significant difference between the groups. Cytological impression showed a significant decrease in the expression of inflammatory markers, notably antigen HLA-DR, in the Naabak(R) group. CONCLUSION: This study confirms the anti-inflammatory property of preservative-free NAAGA (Naabak(R)) in the context of dry eye syndrome with a similar clinical efficacy compared to sodium chloride solution (Larmabak(R)). Naabak(R) could present an additional advantage compared to artificial tears and could be indicated in the treatment of moderate inflammatory dry eye syndrome.

Clinical and biological efficacy of preservative-free NAAGA eye-drops versus levocabastine eye-drops in vernal keratoconjunctivitis patients.

AIMS: This comparative and randomised pilot study assessed the clinical and biological efficacy of Naaxia Sine(R) eye-drops versus levocabastine eye-drops in the treatment of vernal keratoconjunctivitis (VKC). METHODS: Twenty-three VKC patients were randomised and treated bilaterally for 28 days with N-acetyl-aspartyl-glutamate (NAAGA) or levocabastine (LEVO) eye-drops. The primary efficacy variable, overall evolution of eosinophil cationic protein (ECP) tear concentrations, was assessed in a masked fashion on D0, D7 and D28. Clinical symptoms and signs were reported at the same time points. Biological parameters were analysed with a non-parametric rank-based approach. Global tolerance was assessed by the investigator and patient. RESULTS: At all time points, ECP tear levels were significantly reduced in the NAAGA compared with the LEVO group (p = 0.023). Reduction of eosinophil leucocytes and tear lymphocytes was higher not significant in the NAAGA group. The same trend was observed for the evolution of total ocular symptom score. There were no significant differences between treatment groups in the occurrence of adverse effects, except for burning which was more frequent in the LEVO group (p = 0.002). CONCLUSION: The anti-eosinophilic actions of NAAGA were shown by a significant reduction of ECP tear concentrations. A decreased lymphocyte count and an overall improvement of the symptomatology were also noted. Moreover, the tolerability of NAAGA appeared to be better.

Optic neuropathy in cancer patients. Report of a case possibly related to 5 fluorouracil toxicity and review of the literature.

We report the case of a 72-year-old woman suffering from bone metastatic breast cancer and treated with continuous intravenous 5 fluorouracil (5FU) chemotherapy, who presented with a bilateral asymmetric anterior optic neuropathy (ON). A deficiency of dihydropyrimidine dehydrogenase (DPD) was documented. Patients with DPD deficiency are at increased risk for developing unusual and/or severe toxicity to 5FU. We discuss the differential diagnosis of anterior ON and we suggest that 5FU can be responsible for optic nerve toxicity in patients with DPD deficiency.

Frequent discordance of the light-chain isotypes expressed by serum monoclonal components and leukaemic B-cells.

In B-cell malignancies, it is generally held that the monoclonal components (MC) are produced by the malignant clones. Genetic relatedness implies the concordant expression of light-chain (LC) isotypes in the MC and at the surface of the malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias, immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought in 75 of these patients, and had been found in 23 (31%). Biclonal serum components were detected in three cases. LC concordance could not be assessed in three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients, light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias. The origin of LC discordance remains speculative. It could be due to the emergence of subclones with the same primal VDJ gene rearrangement or, alternatively, to the development of new B-cell clones escaping immune surveillance from deregulated T-cells.