[Interval between two smear tests for cervical cancer screening and characteristics of women with a short interval: Study in the department of Isère]. / Délai entre deux frottis de dépistage du cancer du col utérin et caractéristiques des femmes présentant un délai court : étude dans le département de l'Isère.

AIMS: In France, guidelines for cervical cancer screening recommend that women between the ages of 25-65 have a smear test performed once every three years. However, some women are screened significantly more frequently. In this study, we used a data-driven approach as opposed to a traditional hypothesis-driven approach to characterise the population of women who are screened more frequently than advised. METHODS: Data came from an organised cervical cancer screening programme of a French department in the Alps (Isère). We retrospectively selected women aged between 25 to 65 years old who had at least two smear tests during the follow up period (2011-2015). We used a data-driven clustering approach to compare the population of over-screened women with other populations. We then performed a descriptive analysis of the over-screened population using univariate (Chi2 test) and multivariate (logistic regression) methods. RESULTS: A total of 10,000 patients were randomly chosen from a population of 54,073. In our univariate analysis, women in the over-screened population were significantly younger, participated less in organised screening, were more likely to be followed by a gynaecologist and had more smear test results showing inflammation than the other populations. Patient location (urban v.s. rural area) was not significant for this population. The multivariate analysis confirmed these results. CONCLUSION: This data-driven approach based on an unsupervised learning method enables us to more accurately characterise the over-screened population. These data invite to improve communication with the youngest women and the gynecologists to recall the benefit of an interval between two normal smears complying with the recommendations. This approach could help to improve the prevention and have a real impact on this Public Health issue.

Using high-throughput sequencing for investigating intra-host hepatitis C evolution over long retrospective periods.

Collections of biological samples held by hospitals represent invaluable resources for conducting retrospective evolutionary studies of chronic infections. Using high-throughput sequencing, those collections permit analysis of within-host genetic diversity over long follow-up periods, and allow a better understanding of resistance to treatment regimes during disease evolution. Here, we studied the evolution of hepatitis C virus (HCV) populations in two patients with an absence of response to dual therapies. We implemented amplicon sequencing to survey genomic variation at the Core and NS5B regions of HCV over a period of 13 years from blood samples obtained at multiple time points. We observed mixed infection by multiple HCV genotypes in both patients. Genetic heterogeneity and sample composition analysis provided information about the changes in viral population over the course of clinical treatment, with NS5B experiencing an increase in diversity after treatment initiation. Secondary infections were estimated to predate treatment year, and our results pointed towards diversifying selection occurring post-treatment, acting on standing genomic variation and maintaining high genetic heterogeneity during infection. For these two patients infected with multiple HCV genotypes, the maintenance of viral diversity was explained with the hypothesis of soft selective sweep started at the same time as antiviral treatment was initiated.

Influence of aqueous humor convection current on IOL opacification.

BACKGROUND AND PURPOSE: The opacification of Akreos Adapt (Bausch & Lomb, Rochester; NY) intraocular lens (IOL) has been previously reported in Literature. A metabolic change in aqueous humour was considered as the main trigger factor to IOL opacification. We report our case and discuss the association with Ex-PRESS, highlighting the particular pattern of IOL opacification and its possible relation with the intraocular convective motions of the aqueous. MATERIAL AND METHODS: We analyzed our case using both digital slit lamp acquisition and OCT Visante (Zeiss, Germany) images. A literature review was conducted to evaluate our results with that previously reported. CONCLUSION: The role of a relative stationary flow was reported as suggested concurrent mechanism in IOL opacification phenomenon.

First next-generation sequencing full-genome characterization of a hepatitis C virus genotype 7 divergent subtype.

We report the near-full-length genome sequence of a hepatitis C virus (HCV) isolate from a man originating from Democratic Republic of Congo, the genotype of which could not be determined by the routinely used sequencing technique. The near-complete genome sequence of this variant BAK1 was obtained by the association of two next-generation sequencing technologies. Evolutionary analysis indicates that this isolate, BAK1, could be the first reported strain belonging to a new HCV-7b subtype. This new subtype has been incorrectly identified as genotype 2 by the Versant HCV Genotype 2.0 assay (LiPA). The requirement of three independent isolates has been filled, and a new subtype can be assigned. More examples of HCV-7 are required to better understand its origin, its pathogenicity and its relationship with genotype 2.

Amplification and pyrosequencing of near-full-length hepatitis C virus for typing and monitoring antiviral resistant strains.

Directly acting antiviral drugs have contributed considerable progress to hepatitis C virus (HCV) treatment, but they show variable activity depending on virus genotypes and subtypes. Therefore, accurate genotyping including recombinant form detection is still of major importance, as is the detection of resistance-associated mutations in case of therapeutic failure. To meet these goals, an approach to amplify the HCV near-complete genome with a single long-range PCR and sequence it with Roche GS Junior was developed. After optimization, the overall amplification success rate was 73% for usual genotypes (i.e. HCV 1a, 1b, 3a and 4a, 16/22) and 45% for recombinant forms RF_2k/1b (5/11). After pyrosequencing and subsequent de novo assembly, a near-full-length genomic consensus sequence was obtained for 19 of 21 samples. The genotype and subtype were confirmed by phylogenetic analysis for every sample, including the suspected recombinant forms. Resistance-associated mutations were detected in seven of 13 samples at baseline, in the NS3 (n = 3) or NS5A (n = 4) region. Of these samples, the treatment of one patient included daclatasvir, and that patient experienced a relapse. Virus sequences from pre- and posttreatment samples of four patients who experienced relapse after sofosbuvir-based therapy were compared: the selected variants seem too far from the NS5B catalytic site to be held responsible. Although tested on a limited set of samples and with technical improvements still necessary, this assay has proven to be successful for both genotyping and resistance-associated variant detection on several HCV types.

Trastuzumab-induced corneal ulceration: successful no-drug treatment of a "blind" side effect in a case report.

BACKGROUND: We report the first successful treatment of limbal lesions and corneal erosion experienced by a breast cancer patient undergoing trastuzumab treatment. CASE PRESENTATION: A 49-year-old Caucasian woman with early stage breast cancer was treated with adjuvant trastuzumab and subsequently showed persistent bilateral corneal marginal infiltrates resistant to topical steroid and antibiotic treatment. Autologous serum was applied in the conjunctival sac as an experimental treatment to antagonize the inhibitory effect of the HER2 receptor antibody on the corneal epithelial cells. Topical application of autologous serum led to rapid improvement of the ulcerative keratitis, with complete healing of the corneal defect after 7 days. Continued administration of the serum allowed the resumption of trastuzumab therapy without any further side effects. CONCLUSIONS: Persistent bilateral corneal marginal infiltrates may occasionally arise as a side effect of trastuzumab treatment. Topical medication with autologous serum may be an effective therapeutic option for the ocular side effects of trastuzumab therapy.

Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment.

Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment.

A randomized prospective study comparing trabeculectomy with and without the use of a new removable suture.

INTRODUCTION: The aim of this prospective study is to verify, in terms of both early postoperative complications and intraocular pressure (IOP) outcomes, the performance of a scleral flap removable suture. MATERIALS AND METHODS: Sixty-six patients that underwent trabeculectomy were randomly divided into two groups: in the first group (group A, 33 eyes) a standard fornix-based trabeculectomy was performed by using a conjunctival chain suture. In the second group (group B, 33 eyes) the same technique was performed with the additional employment of a new removable suture to the scleral flap. The patients were followed-up for 12 months. RESULTS: After 1 year the mean IOP was 16.58 mmHg (+/-3.73 mmHg) in group A, and 16.12 mmHg (+/-4.21 mmHg) in group B; statistical analysis did not show significant differences between the two groups (P = 0.19). Early postoperative hypotony and shallowing of the anterior chamber were significantly more frequent after standard trabeculectomy than after trabeculectomy using the removable suture (P < 0.02). CONCLUSIONS: The employment of a fornix-based conjunctival chain suture for the flap allows the use of the removable scleral flap suture, which has proved very effective in preventing insufficient flap resistance with aqueous overdrainage and hypotony, and which is also easy to apply and to remove. Compared with standard trabeculectomy, this device has proved to have similar IOP-lowering efficacy, together with a lower rate of early postoperative complications.

Air-guided manual deep anterior lamellar keratoplasty: long-term results and confocal microscopic findings.

PURPOSE: To evaluate the long-term results of air-guided manual deep anterior lamellar keratoplasty (DALK) and to perform confocal microscopy on postoperative DALK corneas. METHODS: Seven postoperative consecutive DALK corneas were evaluated 1 year after suture removal. All patients underwent a complete ophthalmologic examination evaluating visual acuity, astigmatism, corneal thickness, and endothelial cell count. Confocal microscopy was performed to examine the corneas of the seven eyes and to obtain the measured interface depth. RESULTS: Eighteen months after surgery, the mean postoperative uncorrected visual acuity was 20/38 and the mean best-corrected visual acuity was 20/23. Postoperative mean value of residual recipient stroma thickness was 65.57 microm +/- 28.74. CONCLUSIONS: Maximum depth DALK can lead to significant advantages for quality of vision when compared to other types of anterior lamellar keratoplasty. Still, it remains a challenging procedure. These results show that a deep dissection without baring Descemet membrane makes good visual results possible, preventing corneal perforation and conversion to penetrating graft.

Control of inflammation and prophylaxis of endophthalmitis after cataract surgery: a multicenter study.

PURPOSE: To compare two different postcataract surgery antibiotic/steroid therapeutic combinations, for clinical results as well as patient satisfaction. METHODS: Prospective randomized clinical trial of patients with bilateral operative cataract. Postoperatively, for 15 days one eye was randomly assigned to therapy with the combination chloramphenicol 0.25%-betamethasone 0.13% gel three times a day (Group 1) and the other to the combination tobramycin 0.3%-dexamethasone 0.1% eyedrops four times a day (Group 2). RESULTS: A total of 142 patients (284 eyes) completed the study. The authors could not detect any significant difference between Group 1 and Group 2 concerning preoperative evaluation, surgical procedure, and complications. Pertaining to the two therapeutic regimens, efficacy, side effects, and clinical findings such as uncorrected visual acuity, intraocular pressure, edema or hyperemia of eyelids and/or conjunctiva, conjunctival and/or ciliary vessels congestion, decreased corneal transparency, corneal edema, Descemet folds, anterior chamber Tyndall and depth, and posterior synechiae were also comparable. Postoperative subjective pain and dry eye sensation were comparable between the two groups, while the gel preparation elicited a significantly more pleasant sensation in the patients (p=0.04). CONCLUSIONS: The motivation for use of a gel is to prolong the permanence of associated drugs on the ocular surface, increasing potency and decreasing concentration of the drug and rate of administration. This in order to improve compliance and decrease potential side effects. Chloramphenicol 0.25%-betamethasone 0.13% gel combination proved to have comparable efficacy, tolerance, and better acceptance by the patients than an aqueous tobramycin 0.3%-dexamethasone 0.1% preparation.

Keratoconus associated with corneal macular dystrophy: in vivo confocal microscopic evaluation.

PURPOSE: The authors present a case, studied through in vivo confocal microscopy, of concomitant keratoconus and macular corneal dystrophy (MCD). METHODS: A 29-year-old man underwent a penetrating keratoplasty in the right eye in May 2005. Confocal microscopy was performed to examine the cornea of the right eye. RESULTS: A diagnosis of concomitant keratoconus and MCD was suspected, due to the simultaneous findings of corneal ectasia and stromal opacities. CONCLUSIONS: In this case, using in vivo confocal microscopy, morphologic changes were detected in many corneal layers and compared with the histopathologic findings. The morphologic alterations were found mainly in the area of the cornea apex.

Conservative treatment of keratoconus by riboflavin-uva-induced cross-linking of corneal collagen: qualitative investigation.

PURPOSE: To assess corneal tissue modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus as well as regeneration of epithelium and subepithelial nerve plexus by in vivo HRT II system confocal microscopy in humans. METHODS: Ten patients with progressive keratoconus were treated by riboflavin-UVA-induced cross-linking of corneal collagen, involving assessment of ultrastructural modifications of the corneal epithelium and subepithelial nerve plexus by HRT II system confocal microscopy. Treatment included instillation of 0.1% riboflavin-20% dextrane solution 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. Radiant energy was 3 mW/cm 2 or 5.4 Joule/cm 2 and the source was dual UVA (370 nm) light-emitting LED. The protocol included the operation followed by antibiotic medication and eye dressing with a soft therapeutic contact lens. Changes in epithelium and subepithelial and stromal nerve plexus were assessed by HRT II system confocal microscopy in vivo. RESULTS: After 5 days of soft contact lens wearing, corneal epithelium has a regular morphology and density. Disappearance of subepithelial stromal nerve fibers was observed in the central irradiated area where, 1 month after the operation, initial reinnervation was microscopically observed. No changes in nerve fibers were observed in the peripheral untreated with a clear lateral transition between the two areas. Six months after the operation, the anterior subepithelial stroma was recolonized by nerve fibers with restoration of corneal sensitivity. CONCLUSIONS: HRT II system confocal microscopy confirms corneal epithelium restore and re-innervation after riboflavin-UVA-induced collagen cross-linking directly in vivo in humans.

Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: effect of sodium naproxen.

PURPOSE: To investigate whether topical nonsteroidal antiinflammatory drugs (NSAIDs) are useful, in the absence of concomitant corticosteroid therapy, in limiting postoperative inflammation after uncomplicated cataract surgery. METHODS: A total of 328 patients were enrolled in a prospective, randomized, double-masked, parallel-group, active-controlled study. Anterior chamber inflammation (ACI) was evaluated as the primary efficacy parameter. Only patients with moderate inflammation (ACI score of < or =4) the day after surgery were randomized and treated with NSAIDs. A novel topical formulation containing 0.2% sodium naproxen was compared with 0.1% diclofenac. Both were administered three times a day for 14 consecutive days. Ocular inflammation was measured after 7 and 14 days by using slit-lamp biomicroscopy. Safety parameters were also evaluated at the same time. RESULTS: Both treatments were equally effective in controlling postsurgical inflammation. No statistically significant differences between treatment groups were observed for the safety variables. No serious adverse events (AEs) occurred during the course of the study. The most frequent AE reported with naproxen was eye redness. CONCLUSIONS: NSAIDs can effectively be used without concurrent administration of corticosteroids to control postoperative inflammation after uncomplicated cataract surgery. In addition, naproxen ophthalmic solution may be considered a suitable alternative to the currently available NSAIDs.

Manual deep lamellar keratoplasty: alternative methods and air-guided technique.

PURPOSE: To describe the techniques proposed for performing deep lamellar keratoplasty (DLK) and to evaluate the efficacy of a new, modified technique. METHODS: Fourteen eyes in 11 patients with keratoconus of moderate degree were included. All patients underwent a DLK with manual dissection from a limbal side port after an air bubble injection in the anterior chamber. All patients had complete ophthalmologic examination 6 months after the suture removal, evaluating best corrected visual acuity, corneal thickness, endothelial cell count, and topographic astigmatism. RESULTS: One case (7.1%) was converted to penetrating keratoplasty because of microperforation. In the 13 successful cases, 10 eyes (71.4%) achieved 20/30 or better 6 months after suture removal. Mean postoperative pachymetry was 628.39 micro (SD 57.34). Specular microscopy 6 months after suture removal revealed average endothelial cell count of 2261 (SD 287/mm(2)). CONCLUSIONS: Comparing this modified DLK technique with other methods proposed by several authors, air-guided DLK seems to be safe and effective and, after a short learning curve, can be performed with a low risk of conversion to penetrating keratoplasty.

Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery.

PURPOSE: To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma. DESIGN: Interventional study. METHODS: A total of 83 consecutive patients (83 eyes) awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for listing were inadequate intraocular pressure (IOP) control despite medical therapy and documented progression of visual field loss. All patients discontinued the previous treatment and were switched to bimatoprost 0.03% QD (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90 of treatment; less than 20% IOP reduction was considered as a failure. RESULTS: An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained IOP readings 20% lower than baseline after 60 and 90 days. In these patients, visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). CONCLUSIONS: This preliminary study shows that bimatoprost 0.03% could represent a useful therapeutic tool that might defer filtration surgery.

Topical nonsteroidal anti-inflammatory drugs in uncomplicated cataract surgery: Effect of sodium naproxen.

PURPOSE: To investigate whether topical nonsteroidal antiinflammatory drugs (NSAIDs) are useful, in the absence of concomitant corticosteroid therapy, in limiting postoperative inflammation after uncomplicated cataract surgery. METHODS: A total of 328 patients were enrolled in a prospective, randomized, double-masked, parallel-group, active-controlled study. Anterior chamber inflammation (ACI) was evaluated as the primary efficacy parameter. Only patients with moderate inflammation (ACI score of <=4) the day after surgery were randomized and treated with NSAIDs. A novel topical formulation containing 0.2% sodium naproxen was compared with 0.1% diclofenac. Both were administered three times a day for 14 consecutive days. Ocular inflammation was measured after 7 and 14 days by using slit-lamp biomicroscopy. Safety parameters were also evaluated at the same time. RESULTS: Both treatments were equally effective in controlling postsurgical inflammation. No statistically significant differences between treatment groups were observed for the safety variables. No serious adverse events (AEs) occurred during the course of the study. The most frequent AE reported with naproxen was eye redness. CONCLUSIONS: NSAIDs can effectively be used without concurrent administration of corticosteroids to control postoperative inflammation after uncomplicated cataract surgery. In addition, naproxen ophthalmic solution may be considered a suitable alternative to the currently available NSAIDs. (Eur J Ophthalmol 2005; 15: 598-606).

Clinical evaluation of corneal epithelialization after photorefractive keratectomy in patients treated with polydeoxyribonucleotide (PDRN) eye drops: a randomized, double-blind, placebo-controlled trial.

PURPOSE: The effect of polydeoxyribonucleotide (PDRN) eye drops vs placebo on corneal epithelial healing after photorefractive keratectomy (PRK) for correction of myopic and myopic-astigmatic defects was evaluated in a randomized, double-blind clinical trial. Primary endpoint for efficacy was the evolution of corneal re-epithelialization. Secondary endpoint was the evaluation of PDRN eye drops tolerability. METHODS: Sixty eyes were enrolled in the study, randomly allocated into standard therapy plus placebo eye drops (30 eyes), or standard therapy plus PDRN eye drops (30 eyes). Checks were carried out preoperatively and at days 1, 2, 3, and 7 of the follow-up. Six eyes dropped out (four in PDRN group, two in placebo group) for reasons unrelated to the study. RESULTS: On day 2, the disepithelialized area was 8.4 mm2+/-9.2 (mean+/-SD) in controls and 6.0 mm2+/-6.8 in PDRN group. On day 3 a complete corneal re-epithelialization was found in 20 out of 26 (77%) eyes of PDRN group and in 17 out of 28 (61%) eyes of placebo group (p<0.05 in percentage terms). On day 7 of follow-up, all eyes appeared to be completely re-epithelialized. The mean score of corneal evaluation on day 3 was 2.9 in PDRN group and 3.75 in control group (p<0.05 between groups). No adverse events occurred during the study. CONCLUSIONS: The data of the study have shown that after PRK, PDRN stimulates corneal epithelium regeneration. PDRN eye drops administration four times a day is well tolerated by patients during the re-epithelialization stage. A much larger clinical study should be performed in order to prove the results obtained in this pilot study.

Air-guided manual deep lamellar keratoplasty.

PURPOSE: To evaluate the efficacy of a new modified technique of deep lamellar keratoplasty (DLK). METHODS: Nine eyes of eight patients with keratoconus of moderate degree were included. All patients underwent DLK with manual dissection from a limbal side port after an air bubble injection in the anterior chamber. The patients underwent a complete ophthalmologic examination 6 months after the suture removal, evaluating best-corrected visual acuity, corneal thickness, endothelial cell count, and topographic astigmatism. RESULTS: One case (11.1%) was converted to penetrating keratoplasty because of microperforation. In the eight successful cases, 7 eyes (77.8%) achieved 20/30 or better visual acuity 6 months after suture removal. Mean postoperative pachymetry was 604.76 microm (SD 46.76). Specular microscopy 6 months after suture removal revealed average endothelial cell count of 2273/mm2 (SD 229). CONCLUSIONS: This modified DLK technique is a safe and effective procedure and could facilitate, after a short learning curve, this kind of surgery with a low risk of conversion to penetrating keratoplasty.

Clinical evaluation of corneal epithelialization after photorefractive keratectomy in a patient treated with Polydeoxyribonucleotide (PDRN) eye drops: a randomized, double-blind, placebo-controlled trial.

PURPOSE: The effect of polydeoxyribonucleotide (PDRN) eye drops vs placebo on corneal epithelial healing after photorefractive keratectomy (PRK) for correction of myopic and myopic-astigmatic defects was evaluated in a randomized, double-blind clinical trial. Primary endpoint for efficacy was the evolution of corneal re-epithelialization. Secondary endpoint was the evaluation of PDRN eye drops tolerability. METHODS: Sixty eyes were enrolled in the study, randomly allocated into standard therapy plus placebo eye drops (30 eyes), or standard therapy plus PDRN eye drops (30 eyes). Checks were carried out preoperatively and at days 1, 2, 3, and 7 of the follow-up. Six eyes dropped out (four in PDRN group, two in placebo group) for reasons unrelated to the study. RESULTS: On day 2, the disepithelialized area was 8.4 mm2 9.2 (mean SD) in controls and 6.0 mm2 6.8 in PDRN group. On day 3 a complete corneal re-epithelialization was found in 20 out of 26 (77%) eyes of PDRN group and in 17 out of 28 (61%) eyes of placebo group (p<0.05 in percentage terms). On day 7 of follow-up, all eyes appeared to be completely re-epithelialized. The mean score of corneal evaluation on day 3 was 2.9 in PDRN group and 3.75 in control group (p<0.05 between groups). No adverse events occurred during the study. CONCLUSIONS: The data of the study have shown that after PRK, PDRN stimulates corneal epithelium regeneration. PDRN eye drops administration four times a day is well tolerated by patients during the re-epithelialization stage. A much larger clinical study should be performed in order to prove the results obtained in this pilot study.(Eur J Ophthalmol 2004; 14: 284-9).

Closed-system and open-sky capsulorhexis for combined cataract extraction and corneal transplantation.

We describe a triple procedure combining corneal transplantation, cataract extraction, and intraocular lens implantation in which the continuous curvilinear capsulorhexis (CCC) is performed in a closed system when corneal transparency is sufficient or using an open-sky method when corneal transparency is poor. With the closed system, the CCC is performed first followed by trephination and hydroexpulsion of the nucleus. A Caporossi coaxial forceps is used to reduce the corneal incision to 1.2 mm, preventing the need for sutures. Tunnel formation, which could limit the size of trephination, is avoided. In addition, endothelial cell loss at the periphery of the recipient cornea is reduced. This technique was performed in 10 eyes without intraoperative complications. With the open-sky method, the CCC is created while counterpressure is applied to the center of the lens with a large spatula, reducing posterior pressure and thus the risk of capsule tear. This technique was performed in 9 eyes without intraoperative complications.