Evaluation of ostium size following endoscopic dacryocystorhinostomy as a predictive factor of outcome: A prospective study.

INTRODUCTION: Endonasal dacryocystorhinostomy (DCR) is a surgical procedure that aims to increase tear drainage to treat epiphora caused by nasolacrimal obstruction by creating a bypass through the bone between the lacrimal sac and the nasal cavity. A silicone stent is temporarily put in place for 2 months to avoid early obstruction of the rhinostomy. One of the causes of surgical failure is related to progressive stenosis of intranasal ostium, due to fibrosis and new bone growth, inducing a relapse of epiphora and/or dacryocystitis. Few studies have described changes in the size of the intranasal ostium on direct post-DCR measurement or kinetics of its shrinkage. The purpose of this study is to determine whether changes in the size of intranasal ostium might be a predictor of final functional efficacy. MATERIALS AND METHODS: A prospective cohort of eighteen consecutive patients undergoing endonasal DCR for chronic epiphora or chronic dacryocystitis between January 2017 and April 2018 was analyzed. Eight patients who underwent bilateral DCR, and twenty-six intranasal ostia were finally analyzed. Follow-up took place every two months for 1 year, with the silicone tube removed at 2 months. Functional success was defined as absence of recurrent epiphora or dacryocystitis. Ostium size was systematically measured on photos taken during intranasal endoscopy performed every 2 months for 1 year. RESULTS: At 2 months after endonasal DCR, 23 of the 26 ostia (88.5%) were functional, but only 19 (73.1%) of them were directly measurable. The mean horizontal diameter at 2 months was 1.44 (SD 0.61) mm, and the mean vertical diameter was 0.86 (SD 0.37) mm, which corresponded to a mean area of 10 (SD 0.84)mm2. We noted a statistically significant decrease in ostium size and area between 2 and 4 months after the procedure (P -0.001), followed by a stabilization period with no statistical correlation between the size of the ostium and its final functional efficacy. At 6 months after DCR, of the 7 ostia that were not initially measurable, 3 were immediately non-functional at 2 months, 3 had a relapse of epiphora at 4 months, and 1 had a relapse of dacryocystitis at 6 months, i.e., 100% clinical failures at 6 months. The other procedures all remained functional after 1 year of follow-up. CONCLUSION: The intranasal ostium of an endonasal DCR shrinks significantly within the 2 months after removal of the silicone tube and remains stable thereafter. There is no correlation between the size or area of intranasal ostium and its final functional efficacy. However, when the ostium is not measurable at the time of 2-month stent removal, all patients experienced a relapse of epiphora or dacryocystitis within 6 months.

Risk factors for keratoconus progression after treatment by accelerated cross-linking (A-CXL): A prospective 24-month study.

PURPOSE: Identification of potential predictive factors for keratoconus progression after treatment by accelerated Cross-linking (A-CXL) SECONDARY OBJECTIVES: Evaluation of clinical and topographic outcomes for two years following accelerated cross-linking treatment for progressive keratoconus including: best spectacle corrected visual acuity (BSCVA), thinnest pachymetry, maximum keratometry (Kmax), cylinder. STUDY: Prospective, interventional, monocentric study. SITE: Metz-Thionville Regional Medical Center, Lorraine University, Mercy Hospital, Metz, France. PATIENTS AND METHODS: We included 82 eyes of 60 patients between March 2014 and June 2016 who underwent accelerated corneal cross-linking (A-CXL) with epithelial debridement for progressive keratoconus, with a minimum follow-up of 2 years. A complete clinical evaluation and corneal topography were performed before cross-linking, and subsequently at 6, 12 and 24 months post-procedure. The following parameters were monitored during follow-up: best spectacle corrected visual acuity (BSCVA), minimal pachymetry, maximum keratometry (Kmax), mean anterior and posterior curvatures, maximum posterior curvature, presence of optical aberrations, subdivided into spherical aberration, coma, astigmatism, higher order optical aberrations and residual optical aberrations. After a 2-year follow-up, two groups, defined as "responders" and "non-responders" to treatment, were separated for analysis, and their initial characteristics were compared. RESULTS: Data for 82 eyes of 60 patients with progressive keratoconus with a mean age of 24±7 years were studied. Fourteen eyes (17.1%) showed signs of progression after treatment by A-CXL (non-responders), and 68 eyes (82.9%) showed stabilization of the disease (responders). Characteristics of non-responding eyes after A-CXL included a younger mean age (20±5 vs. 25±7 years) (P=0.04) and a lower initial mean BCVA for non-responders of 0.44±0.16 logMAR vs. 0.29±0.19 logMAR (P=0.03). Non-responders also had a higher mean maximal posterior curvature (AKB) of -10.84±1.72D vs. -9.46± 1.12D (P=0.03). They also showed more higher order optical aberrations (3.84±1.72D vs. 2.4±1.02D; P=0.01), including coma (3.85±1.81D vs. 2.1±1.01D; P=0.03) and more residual aberrations than responders (1.05±0.44D vs. 0.45±0.6D; P=0.005). No significant differences were found between responders and non-responders for the other parameters in our study. CONCLUSION: Eyes with progressive keratoconus who did not respond to A-CXL treatment were the most aggressive cases in the youngest patients, with highest maximum corneal curvatures and most pronounced optical aberrations. These patients should be informed in advance of the high risk of non-response to A-CXL treatment, and of the potential need for additional treatment in the future.

Supracapsular phacoemulsification: Description of the "Garde à vous" technique and comparative clinical results.

Phacoemulsification techniques can be divided into 2 categories: endocapsular and supracapsular techniques. Supracapsular techniques involve phacoemulsification of the nucleus outside and above the capsular plane. The "Garde-à-vous" technique described in this manuscript is a modified and improved version of the supracapsular procedure with up-to-date technology in micro-coaxial surgery. It maintains the known advantages of supracapsular techniques such as faster surgical times and lower rates of capsular tears and brings a standardized technique with well-defined surgical steps in order to achieve tilting of the nucleus in a vertical or oblique position in almost 100% of cases by performing a double-wave hydro-dissection. The authors also give the results of a non-randomized prospective study, comparing the "Garde-à-vous" technique and the standard "cracking" technique in 2856 cases. The results show that for the "Garde-à-vous group", the patients were significantly younger (P<0.001), the power of ultrasound used was greater (P<0.001) for lower UST (ultrasound time or average phacoemulsification time APT) and EPT (effective phacoemulsication time) (P<0.001), the duration of the procedure was shorter (P<0.001), patient discomfort was less (P<0.001), and the power of the implants used was lower (P<0.01). With regard to the gender of the patients, the percentage of topical anesthesia and the rate of intraoperative complications (posterior capsular rupture), there was no statistically significant difference.

Reconstruction of exenteration socket with Integra® dermal substitute and skin graft.

The authors report their experience with the use of Integra® dermal substitute, in combination with a thin skin graft, following an orbital exenteration. The clinical case described relates to a 42-year-old gentleman with an ulcerative retractile lesion of the right lower eyelid. Histopathological examination diagnosed a moderately differentiated epidermoid carcinoma infiltrating the orbit. Total exenteration was necessary as well as secondary radiation therapy and chemotherapy. Rehabilitation of the exenterated socket was performed by inserting an Integra® patch, followed by an additional thin skin graft one month later. The authors review the various available techniques for exenterations, their indications and the various possible secondary rehabilitations. Despite being less utilized, the dermal substitute technique, which is relatively new, seems to offer quicker and easier rehabilitation compared to traditional techniques. A comparative study would be necessary to define superiority among the different techniques of exenteration, with respect to the speed of rehabilitation and resistance to radiation therapy.

Tobacco smoking in crosslinked keratoconus patients.

PURPOSE: The aim of this study was to evaluate the possibly protective link of smoking in keratoconic patients treated with accelerated cross-linking. METHODS: A telephone survey was conducted among 80 KC patients treated by accelerated cross-linking (A-CXL). The questions focused on general history, possible atopy and smoking habits. Results were compared to those of the general population by indirect standardization by age and sex according to the French national INPES survey. RESULTS: Sixty-two patients with KC were analyzed. The mean age at diagnosis was 22 years (SD 5). The mean age at which A-CXL was performed was 23 years (SD 6). Daily smokers represented 19 %, occasional smokers 8 %, ex-smokers 21 % and non-smokers 52 %. The mean age at which the patients began smoking was 17 (SD 2) years. Ex-smokers quit at a mean age of 24 (SD 4) years. The observed rates and expected rates of daily smokers were 19 % and 39 % respectively at the time of the survey (P=0.01), 24 % and 35 % at the time of the A-CXL treatment (P=0.10) and 31 % and 35 % at the time of diagnosis (P=0.58). The decrease in the rate of observed daily smokers over time was significant (P=0.02). DISCUSSION: Our data does not appear to suggest a significant protective effect of smoking on the occurrence of KC. It shows a lesser proportion of smokers in KC patients after A-CXL, but this difference did not exist at the time of KC diagnosis.

Developmental regulation of neuronal K+ channels by target-derived TGF beta in vivo and in vitro.

The functional expression of Ca2+-activated K+ channels (KCa) in developing chick ciliary ganglion (CG) neurons requires interactions with target tissues and preganglionic innervation. Here, we show that the stimulatory effects of target tissues are mediated by an isoform of TGFbeta. Exposure of cultured CG neurons to TGFbeta1, but not TGFbeta2 or TGFbeta3, caused robust stimulation of KCa. The KCa stimulatory effects of target tissue extracts were blocked by a neutralizing pan-TGFbeta antiserum but not by specific TGFbeta2 or TGFbeta3 antisera. Intraocular injection of TGFbeta1 caused robust stimulation of KCa, whereas intraocular injection of pan-TGFbeta antiserum inhibited expression of KCa in CG neurons developing in vivo. The effects of TGFbeta1 were potentiated by beta-neuregulin-1, a differentiation factor expressed in preganglionic neurons.

Lateral tarsal strip versus lateral tarsal strip with three-snip punctoplasty for managing epiphora in involutional ectropion.

PURPOSE: To compare the efficacy of two surgical techniques-lateral tarsal strip (canthoplasty) alone, and lateral tarsal strip with three-snip punctoplasty-in reducing epiphora arising from involutional ectropion with partial punctal stenosis. METHODS: Fourty patients with involutional ectropion and partial stenosis of the lacrimal punctum were randomly allocated to two treatment groups. Group 1 patients received lateral tarsal strip alone with only non-invasive stenting of the punctum, and group 2 patients received tarsal strip plus three-snip punctoplasty. Subjective assessment of epiphora was achieved via completion of a quality of life (QoL) questionnaire preoperatively and at postoperative month 3. Eyelid position, adverse outcomes and corneal dryness (via Oxford grading scheme) were also assessed postoperatively. Only patients with unilateral problems were included in the study. RESULTS: Forty eyes of 40 patients were included: 20 in each group. The mean ages of group 1 and group 2 patients were 79±11 and 80±9 years, respectively. All patients reported significantly reduced eye watering after surgery, with no significant intergroup difference in subjective outcomes, except that computer usage and night driving (P<0.05), improved in a more significant way in group 2. Eyelid malposition was corrected in all cases, there were no cases of postoperative punctal eversion, and no significant adverse events or complications occurred. Finally, the mean improvements in the dryness/keratitis score (using the Oxford scheme) were comparable between the 2 groups (P=0.34). CONCLUSION: The study findings indicate that treatment of involutional ectropion with partial punctal stenosis by lateral tarsal strip with three snip punctoplasty does not provide greater reduction in discomfort secondary to epiphora than conventional lateral tarsal strip alone, except for specific situations such as night driving or computer use.

Central corneal thickness assessment after phacoemulsification: Subluxation versus Divide-and-Conquer.

PURPOSE: To compare the impact of two phacoemulsification techniques (subluxation versus divide-and-conquer) on postoperative corneal edema at postoperative hour 1 and day 4. DESIGN: Comparative study. METHOD: Ninety-six consecutive patients (110 eyes; 43 men and 53 women, mean age 70.9±9.8 years) with equivalent cataract grades underwent cataract surgery and were followed up for 6 months. The presence of corneal edema was determined using central corneal thickness (CCT). CCT was measured preoperatively, and at postoperative hour 1 and day 4. MAIN OUTCOME MEASURES: Ultrasound power (US %), duration of ultrasound (TPA), effective ultrasound time (TPE), surgical duration and final suture (%). RESULTS: Eyes of participants were divided into two phacoemulsification technique groups: subluxation (n=50 eyes) and divide-and-conquer (n=60 eyes). Non-inferiority analysis revealed similar CCT increases at postoperative hour 1 in both groups, with 69.9±44.9µm and 64.4±42.9µm, observed in the subluxation and divide-and-conquer groups, respectively (P=0.033). TPE was similar in both groups, taking 6.2±3.4 and 7.3±4.5seconds in the subluxation and divide-and-conquer groups, respectively (P=0.150). No correlation was seen between TPE and edema at postoperative hour 1, or between TPE and day 4 edema. Rate of final suture use was similar between the subluxation and divide and conquer groups, at 36% and 30%, respectively. CONCLUSION: The study findings suggest that cataract surgery performed using the subluxation technique does not result in greater CCT than the divide-and-conquer technique. CCT appears to normalize by postoperative day 4, regardless of the technique used.

Influence of muscle cells on the development of calcium currents in Xenopus spinal neurons.

The influence of muscle cells on the development of voltage-dependent Ca2+ currents was investigated in Xenopus spinal neurons grown in neuron muscle co-cultures or in muscle-free cultures. Whole-cell currents were separated into low- and high-voltage-activated currents. Developmental changes were assessed by comparing the results obtained at two different periods after plating: 5-10 h (young neurons) and 20-30 h (mature neurons). Our results show a drop in the incidence of low-voltage-activated Ca2+ current with time in both environments: the fraction of young versus mature neurons expressing this current was 67% and 36% in neuron-muscle co-cultures, and 69% and 23% in muscle-free cultures. In both neuron muscle and muscle-free cultures, the density of low-voltage-activated Ca2+ current (when expressed) did not change during the development. In contrast, the density of high-voltage-activated Ca2+ currents increased more than two-fold during the first 30 h in neuron muscle co-cultures, but remained unchanged in muscle-free cultures. This difference was not related to neuronal growth since the increase in neuronal membrane capacitance with time was similar in the two environments. In addition, direct cell-cell interaction through the establishment of functional neuron-muscle synaptic contacts did not further modify the overall expression of high-voltage-activated Ca2+ currents. In conclusion, these results suggest the presence of diffusible factors in neuron muscle co-cultures which up-regulate the expression of high-voltage-activated Ca2+ currents during neuronal development, but do not have any effect on low-voltage-activated Ca2+ currents.

Developmental regulation of neuronal KCa channels by TGFbeta 1: transcriptional and posttranscriptional effects mediated by Erk MAP kinase.

An avian ortholog of transforming growth factor beta1 (TGFbeta1) is the target-derived factor responsible for the developmental expression of large-conductance Ca(2+)-activated K(+) (K(Ca)) channels in chick ciliary ganglion (CG) neurons developing in vivo and in vitro. Application of TGFbeta1 evokes an acute stimulation of K(Ca) that can be observed immediately after cessation of a 12 hr exposure to this factor, that persists in the presence of protein synthesis inhibitors, and that is therefore mediated by posttranslational events. Here we show that a single 3 hr exposure to TGFbeta1 can also induce long-lasting stimulation of macroscopic K(Ca) that persists for at least 3.5 d after the end of the treatment. In contrast to the acute stimulation, this sustained effect is dependent on the transcription and synthesis of new proteins at approximately the time of TGFbeta1 treatment. However TGFbeta1 does not cause increases in the levels of slowpoke alpha subunit transcripts in CG neurons, suggesting that induction of some other protein or proteins is required for sustained enhancement of macroscopic K(Ca). In addition, application of TGFbeta1 evoked an almost immediate but transient phosphorylation of the mitogen-activated protein kinase Erk in CG neurons. TGFbeta1-evoked Erk activation was blocked by the specific MEK1 inhibitor 2- (2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059). Moreover, application of PD98059 blocked both acute and sustained K(Ca) stimulation evoked by TGFbeta1. These results indicate that TGFbeta1 elicits a biphasic stimulation of K(Ca) via activation of an MEK1-Erk pathway and raise the possibility that other neuronal effects of TGFbeta superfamily members entail Erk activation.

TGFbeta1 regulates the gating properties of intermediate-conductance KCa channels in developing parasympathetic neurons.

The developmental expression of Ca2+-activated K+ channels (KCa) in chick ciliary ganglion (CG) neurons is regulated by a target-derived avian isoform of TGFbeta1, which evokes a robust increase in the number of functional large-conductance (BK) KCa channels but which produces no change in their kinetics. However, CG neurons express multiple KCa channel subtypes. Here we show that TGFbeta1 regulates the gating properties of intermediate-conductance (IK) KCa channels in developing CG neurons. IK channels in inside-out patches excised from control E9 CG neurons became active on exposure to 1-5 microM free Ca2+ but then remained active on return to Ca2+-free salines. In contrast, IK channels in TGFbeta1-treated cells became active on exposure to 1-5 microM Ca2+, but became quiescent immediately on return to Ca2+-free salines. In contrast to its effects on BK channels, TGFbeta1 had no effect on the mean number of IK channels detected in excised patches. IK channels were not activated in cell-attached patches on E9 neurons depolarized by bath application of 145 mM KCl in the presence of 5 mM external Ca2+. However, BK channels were activated immediately by this procedure and were detected at a higher density in TGFbeta1-treated cells. In addition, analyses of macroscopic KCa fluctuations, and the voltage-dependence of KCa tail currents, suggest that IK channels do not contribute to voltage-evoked whole cell KCa. IK channels therefore may have some other function. These results indicate that the effects of TGFbeta1 on CG neurons entail distinct actions on multiple KCa channel subtypes.

Functional expression of the Ile693Thr Na+ channel mutation associated with paramyotonia congenita in a human cell line.

1. The Ile693Thr mutation of the skeletal muscle Na+ channel alpha-subunit is associated with an unusual phenotype of paramyotonia congenita characterized by cold-induced muscle weakness but no stiffness. This mutation occurs in the S4-S5 linker of domain II, a region that has not been previously implicated in paramyotonia congenita. 2. The Ile693Thr mutation was introduced into the human skeletal muscle Na+ gene for functional expression in human embryonic kidney (HEK) cells. The currents expressed were recorded with the whole-cell voltage-clamp technique. 3. In comparison with wild-type currents, Ile693Thr mutant currents showed a clear shift of about -9 mV in the voltage dependence of activation. 4. In contrast to other mutations of the Na+ channel known to cause paramyotonia congenita, the Ile693Thr mutation did not induce any significant change in the kinetics, nor in the voltage dependence, of fast inactivation. 5. In conclusion, this study provides further evidence of the involvement of the S4-S5 linker in the voltage dependence of Na+ channel activation. The negative shift in the voltage dependence found in this mutation must be associated to other defects, plausibly an impairment of the slow inactivation, to account for the long periods of muscle weakness experienced by the patients.