[Evaluation of in vitro efficacy of combined riboflavin and ultraviolet-A (365 nm) for Acanthamoeba]. / Efficacité anti-amibienne in vitro de l'association riboflavine/UV-A.

INTRODUCTION: Acanthamoeba keratitis is a rare but serious disease and is particularly difficult to treat when the diagnosis is delayed, partly because of the limitations of current therapies. The purpose of our study is to evaluate the anti-amoebic effectiveness of riboflavin and UV-A on Acanthamoeba castellani. MATERIALS AND METHODS: We tested the effect of 0.02% chlorhexidine alone (C), the combination of riboflavin 1% and UV-A (UV-A+R), and the combination of the two treatments (R+C+UV-A) on cultures of vegetative and cystic forms of A. castellani. We conducted a parasite count under optical microscopy for each treated area at day 1, 4 and 8. RESULTS: There was a decrease in the number of cysts for all three treatments (C, UV-A+R, R+C+UV-A). This reduction was greater for the plates treated with R+UV-A (P <0.01 at D8) and those treated with C+R+UV-A (P<0.001 at D8) compared to those exposed to chlorhexidine alone (C). There was no decrease in the number of amoebic trophozoites for the three treatments (C, UV-A+R, R+C+UV-A), but encystment was observed. DISCUSSION: Given the in vitro efficacy of riboflavin combined with UV-A against cystic forms of A. castellani and excellent in vivo tolerance of the procedure, the treatment of acanthamoeba keratitis might be improved by this new therapeutic approach.

[Annular keratopigmentation (PresbyRing®) for treating presbyopia: postmortem animal feasibility study]. / La kératopigmentation annulaire (ou PresbyRing®) dans la prise en charge de la presbytie: étude expérimentale de faisabilité post-mortem chez l'animal.

INTRODUCTION: Annular keratopigmentation (PresbyRing(®)) is a new technique which creates an intrastromal ring centered on the visual axis, using a femtosecond laser, into which a black or a colored pigment is then injected. The internal diameter of the ring is dimensioned so as to create a pinhole and improve the near and intermediate vision of the non-dominant eye while only slightly altering the distance vision of that eye. MATERIAL AND METHODS: We used five pig eyes for our postmortem feasibility study; all five were treated with the Intra Corneal Ring program (ICR(®)) of the Visumax(®) laser. The dye used (Biochromaderm(®)) has EU approval. RESULTS: Spectral domain OCT examinations demonstrate complete opacity of the dye. Histological analysis with hematoxylin and eosin stain highlights a continuous pigmented layer located along the incision, which does not diffuse in the adjacent stroma. The possibility of rinsing the dye must be confirmed by future in-vivo animal studies. CONCLUSION: To our knowledge, this study represents the first experimental attempt to combine two ideas which did not appear to have anything in common: the creation of an intracorneal pinhole to treat presbyopia, and corneal tattooing. The first postmortem feasibility study in animals for annular keratopigmentation (PresbyRing(®)) gave encouraging results. It must be confirmed by in vivo animal studies, and ultimately in humans.

Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.

[Efficacy of early injection of intravitreal triamcinolone acetonide (IVTA) versus delayed injection for macular edema resulting from retinal vein occlusion]. / Efficacité des injections intravitréennes immédiates et retardées de triamcinolone dans l'œdème maculaire des occlusions veineuses rétiniennes.

PURPOSE: To assess the efficacy of early injection of intravitreal triamcinolone acetonide (IVTA) versus delayed injection for macular edema from retinal vein occlusion. METHODS: This was a retrospective monocentric study. Forty-four patients received an IVTA (4 mg) for macular edema resulting from central retinal vein or branch retinal vein occlusion. The patients were assigned to two groups: group 1 consisted of patients who received an IVTA less than 6 weeks after the diagnosis of macular edema, while group 2 consisted of patients who received the injection more than 6 weeks after. All patients underwent a comprehensive ophthalmological examination before the injection and 1, 3, and 6 months after. Each visit included best-corrected visual acuity measurement (BCVA), slit lamp examination, intraocular pressure measurement, fundus examination and central macular thickness (CMT) measurement by OCT. RESULTS: The two groups were comparable in terms of age, sex-ratio, and the percentage of branch retinal vein occlusion (54 and 61% in groups 1 and 2, respectively). In group 1, the BCVA (logMAR) was 0.87 before the IVTA and significantly improved at 1 and 3 months (0.46 and 0.48, respectively; P<0.05) before worsening at the 6-month visit (0.62; P>0.05). The mean CMT was also significantly improved (from 567 µm before the injection to 276, 307, and 386 µm at the 1-, 3-, and 6-month visits, respectively) (P<0.05 at 1 and 3 months). In group 2, there were no significant differences in visual acuity at any time point (0.86 before the IVTA, 0.76, 0.76, and 0.78 at the 1-, 3-, and 6-month visits; P>0.05). The CMT was reduced after the injection from 552 µm to 294, 446, and 456 µm at the 1-, 3-, and 6-month visits, respectively (P<0.05 at 1 month). CONCLUSION: Patients with macular edema due to retinal vein occlusions, who received a single intravitreal injection of triamcinolone acetate less than 6 months after the diagnosis, displayed both anatomical and functional improvement, whereas patients injected more than 6 weeks after the diagnosis of macular edema showed a CMT reduction but with less improvement in visual acuity. The difference observed at 1 month disappeared after 6 months.

Retinal dystrophy in Bardet-Biedl syndrome and related syndromic ciliopathies.

Primary cilia are almost ubiquitously expressed in eukaryotic cells where they function as sensors relaying information either from the extracellular environment or between two compartments of the same cell, such as in the photoreceptor cell. In ciliopathies, a continuously growing class of genetic disorders related to ciliary defects, the modified primary cilium of the photoreceptor, also known as the connecting cilium, is frequently defective. Ciliary dysfunction involves disturbances in the trafficking and docking of specific proteins involved in its biogenesis or maintenance. The main well-conserved ciliary process, intraflagellar transport (IFT), is a complex process carried out by multimeric ciliary particles and molecular motors of major importance in the photoreceptor cell. It is defective in a growing number of ciliopathies leading to retinal degeneration. Retinitis pigmentosa related to ciliary dysfunction can be an isolated feature or a part of a syndrome such as Bardet-Biedl syndrome (BBS). Research on ciliopathies and BBS has led to the discovery of several major cellular processes carried out by the primary cilium structure and has highlighted their genetic heterogeneity.

[New findings on the synthesis of the centrally acting muscle relaxant chlormezanone and its resolution of a gram scale using a Chiralcel OD column]. / Neue Befunde zur Synthese des chiralen Muskelrelaxans Chlormezanon und dessen Racematspaltung an einer präparativen Chiralcel OD-Säule.

2-(4-Chlorophenyl)-4-metathiazanone (2) is the intermediate product for the two step-synthesis of chlormezanone (1), a centrally acting muscle relaxant. The second step includes the oxidation of its sulfur atom. It has been found that the foregoing reaction of 4-chlorobenzaldehyde with methylamine forming the hemiaminale and the subsequent addition of beta-mercaptopropionic acid leads to a remarkable better yield (67% of th.) than the route via the hemimercaptale (42% of th.). 2 could be oxidized with sodium perborate superior to potassium permanganate. The racemic chlormezanone (1) is resolved quickly on a gram scale by preparative column chromatography on a Chiralcel OD column (tris(3,5-dimethyl-phenyl-carbamoyl)cellulose on silicagel). The resolution needed only 40 min, if flow rate, composition of the mobile phase and temperature as the most important factors are determined prior with an analytical column. Both dissociation constants could be determined for the first time with the aid of a log pKa-Titrator of the Sirius Co., which needs for the registration of the curves only 15-17 min in the pH range of 2-12. This speed outplayed the disturbing cleavage of the S-C bond of chlormezanone at strong acidic and alkaline pH values.