Safety of an Intracameral Fixed Combination for Mydriasis and Intraocular Anaesthesia During Cataract Surgery

Rudy MMA Nuijts,1 Béatrice Cochener-Lamard,2 Jacek P Szaflik,3 Rita Mencucci,4 Frédéric Chiambaretta,5 Anders Behndig6 1University Eye Clinic, Maastricht University Medical Center, Maastricht, the Netherlands; 2Ophthalmology Department, CHU Morvan, University Hospital of Brest, and University of Bretagne Occidentale (UBO), Brest, France; 3Department of Ophthalmology, Medical University of Warsaw, Warszawa, Poland; 4Eye Clinic, Department of Neurosciences, Psychology, Pharmacology, and Child Health, University of Florence, Florence, Italy; 5Ophthalmology Department, CHU Gabriel Montpied, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France; 6Department of Clinical Sciences/Ophthalmology, Umea University, Umea, SwedenCorrespondence: Anders Behndig, Department of Clinical Sciences/Ophthalmology, Umea University, SE-901 85 Umea, Sweden, Tel + 46 70  782 75 36, Fax + 46 90  13 34 99, Email [email protected]: To compare the safety of a standardized, commercially available intracameral combination of mydriatics and anesthetic (ICMA) with a reference topical mydriatic regimen for cataract surgery.Patients and Methods: The safety results from two international, randomized, controlled clinical studies were combined to compare ICMA at the beginning of cataract surgery (ICMA group) to the reference topical mydriatic regimen (reference group). Data were collected on ocular and systemic adverse events, corneal and anterior chamber examination, endothelial cell density, retinal thickness and visual acuity. Analysis was performed on a pooled safety set from both studies, preoperatively and up to 1 month postoperatively.Results: 342 patients received ICMA and 318 the reference topical regimen. Ocular adverse events were reported in 17.0% of patients in the ICMA group and 18.6% in the reference group. No difference was shown between groups in endothelial cell density (2208 ± 498 cells/mm2 for ICMA group versus 2241 ± 513 cells/mm2 for the reference group; p=0.547) and retinal thickness (change from baseline less than 50 μm in 94.7% versus 95.0% of patients, respectively) at 1 month postoperatively. At 1-day post-surgery, less patients in the ICMA group had moderate or severe (Grades 2 and 3) superficial punctate corneal staining (3.9% versus 7.0% for the reference group; p=0.064). Postoperatively, some ocular symptoms were also less frequently reported in the ICMA group. Best-corrected visual acuity increased in 96.0% of patients in the ICMA group and 95.8% in the reference group at 1 month.Conclusion: ICMA injection at the beginning of cataract surgery was demonstrated to be safe and may also provide perioperative and postoperative advantages over the standard topical mydriatic regimen.Keywords: cataract surgery, intracameral mydriasis, topical mydriasis, safety, tolerabilit

Krüppel-Like Factor 6 Expression Changes during Trophoblast Syncytialization and Transactivates ßhCG and PSG Placental Genes

BACKGROUND: Krüppel-like factor-6 (KLF6) is a widely expressed member of the Sp1/KLF family of transcriptional regulators involved in differentiation, cell cycle control and proliferation in several cell systems. Even though the highest expression level of KLF6 has been detected in human and mice placenta, its function in trophoblast physiology is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we explored KLF6 expression and sub-cellular distribution in human trophoblast cells differentiating into the syncytial pathway, and its role in the regulation of genes associated with placental development and pregnancy maintenance. Confocal immunofluorescence microscopy demonstrated that KLF6 is expressed throughout human cytotrophoblast differentiation showing no evident modifications in its nuclear and cytoplasmic localization pattern. KLF6 transcript and protein peaked early during the syncytialization process as determined by qRT-PCR and western blot assays. Overexpression of KLF6 in trophoblast-derived JEG-3 cells showed a preferential nuclear signal correlating with enhanced expression of human β-chorionic gonadotropin (βhCG) and pregnancy-specific glycoprotein (PSG) genes. Moreover, KLF6 transactivated βhCG5, PSG5 and PSG3 gene promoters. Deletion of KLF6 Zn-finger DNA binding domain or mutation of the consensus KLF6 binding site abolished transactivation of the PSG5 promoter. CONCLUSIONS/SIGNIFICANCE: Results are consistent with KLF6 playing a role as transcriptional regulator of relevant genes for placental differentiation and physiology such as βhCG and PSG, in agreement with an early and transient increase of KLF6 expression during trophoblast syncytialization

Krüppel-like Factor 4 Regulates Intestinal Epithelial Cell Morphology and Polarity

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which it regulates homeostasis and represses tumorigenesis in the intestine is not well understood. In our study, KLF4 was partially depleted in the differentiated intestinal epithelial cells by a tamoxifen-inducible Cre recombinase. We found a significant increase in the number of goblet cells in the KLF4-deleted small intestine, suggesting that KLF4 is not only required for goblet cell differentiation, but also required for maintaining goblet cell numbers through its function in inhibiting cell proliferation. The number and position of Paneth cells also changed. This is consistent with the KLF4 knockout study using villin-Cre [1]. Through immunohistochemistry (IHC) staining and statistical analysis, we found that a stem cell and/or tuft cell marker, DCAMKL1, and a proliferation marker, Ki67, are affected by KLF4 depletion, while an enteroendocrine cell marker, neurotensin (NT), was not affected. In addition, we found KLF4 depletion altered the morphology and polarity of the intestinal epithelial cells. Using a three-dimensional (3D) intestinal epithelial cyst formation assay, we found that KLF4 is essential for cell polarity and crypt-cyst formation in human colon cancer cells. These findings suggest that, as a tumor suppressor in colorectal cancer, KLF4 affects intestinal epithelial cell morphology by regulating proliferation, differentiation and polarity of the cells

A Scoping Review of Quality of Life Questionnaires in Glaucoma Patients

PRECIS: Multiple questionnaires exist to measure glaucoma's impact on quality of life (QoL). Selecting the right questionnaire for the research question is essential, as is patients' acceptability of the questionnaire to enable collection of relevant patient-reported outcomes. PURPOSE: QoL relating to a disease and its treatment is an important dimension to capture. This scoping review sought to identify the questionnaires most appropriate for capturing the impact of glaucoma on QoL. METHODS: A literature search of QoL questionnaires used in glaucoma, including patient-reported outcomes measures, was conducted and the identified questionnaires were analyzed using a developed quality criteria assessment. RESULTS: Forty-one QoL questionnaires were found which were analyzed with the detailed quality criteria assessment leading to a summary score. This identified the top 10 scoring QoL questionnaires rated by a synthesis of the quality criteria grid, considering aspects such as reliability and reproducibility, and the authors' expert clinical opinion. The results were ratified in consultation with an international panel of ophthalmologists (N=49) from the Educational Club of Ocular Surface and Glaucoma representing 23 countries. CONCLUSIONS: Wide variability among questionnaires used to determine vision related QoL in glaucoma and in the responses elicited was identified. In conclusion, no single existing QoL questionnaire design is suitable for all purposes in glaucoma research, rather we have identified the top 10 from which the questionnaire most appropriate to the study objective may be selected. Development of a new questionnaire that could better distinguish between treatments in terms of vision and treatment-related QoL would be useful that includes the patient perspective of treatment effects as well as meeting requirements of regulatory and health authorities. Future work could involve development of a formal weighting system with which to comprehensively assess the quality of QoL questionnaires used in glaucoma

Efficacy and safety of glycyrrhizin 2.5% eye drops in the treatment of moderate dry eye disease: results from a prospective, open-label pilot study

Carole Burillon,1 Frederic Chiambaretta,2 Pierre-Jean Pisella3 1Ophthalmology Department, University Hospital HCL, GH Edouard Herriot, Lyon, France; 2Ophthalmology Department, Clermont-Ferrand University Hospital, Hôpital Gabriel Montpied, Clermont Ferrand, France; 3Ophthalmology Department, Paris Nord Val-de-Seine University Hospitals, Hôpital Bretonneau, Tours, France Background: Dry eye disease (DED) is characterized by a loss of homeostasis of the tear film. It goes along with ocular symptoms, in which ocular surface inflammation and damage play etiological roles. High-mobility group box 1 protein (HMGB1) is a pro-inflammatory protein found in the tear fluid during conjunctivitis, blepharitis and DED. Glycyrrhizin binds to HMGB1, inhibiting cytokine activities, thus potentially improving DED.Aim: To assess the efficacy and tolerance of glycyrrhizin in moderate DED.Methods: Multicenter, open-label, prospective, nonrandomized clinical pilot study of glycyrrhizin 2.5% eye drops twice daily over 28 days in adult patients with moderate DED using standard evaluation parameters.Results: The overall mean age of the 37 patients included was 59.6±19.0 years, 70.3% of the patients were female and 77.0% of the patients had an Oxford score of II. After 28 days, 60.8% of the patients had an Oxford score of 0 or I; a significant mean improvement in the score of 0.97±0.86 (P<0.001) from 2.20±0.44 at day 1 to 1.23±0.88 at day 28 was observed. Tear break-up time and Schirmer scores had significantly improved while the number of patient-reported symptoms had significantly decreased (all P≤0.010). A large majority of patients still had a few spots on their naso-bulbar conjunctiva (86.1%), temporal-bulbar conjunctiva (81.4%) and cornea (84.7%). The investigators considered that DED had improved in 71.6% of the patients. Patients appreciated the eye drops for their efficacy and good tolerance profile, leading to a decreased use of artificial tears. No changes in intraocular pressure and visual acuity were observed; glycyrrhizin 2.5% eye drops were safe, with only one patient reporting a moderate, transient treatment-related contact allergy leading to the withdrawal of the patient. Overall, two patients reported three adverse events, two (moderate contact allergy in both eyes) were related to the eye drops and experienced by the same patient; treatment was stopped; the third event was not treatment-related.Conclusion: In this pilot study, glycyrrhizin 2.5% eye drops were well tolerated and provide a good clinical benefit to patients with moderate DED after 28 days of continued daily use. Keywords: dry eye disease, hyaluronic sodium, glycyrrhizin, inflammation, ocular lesion

A European Perspective on Topical Ophthalmic Antibiotics: Current and Evolving Options

Background Eye infections can be vision-threatening and must be treated effectively by appropriate and safe use of topical ophthalmic anti-infectives. This review will essentially consider the current and evolving treatment options for the various types of bacterial eye infections. Ocular surface bacterial infections affect subjects of all ages with a high frequency in newborns and children. Methods This article presents a review of the peer-reviewed published scientific literature in order to define the well-established uses of anti-infective eye drops in the field of ocular infections. A comprehensive search of the recent published literature including topical ophthalmic anti-infectives effective in bacterial ocular infections was performed. Clinical studies provide relevant data concerning the characteristics and clinical efficacy of antibacterial eye drops in ocular anterior segment infections or for perioperative prophylaxis. Publications were included to cover the current options of antibacterial eye drops available in Europe. Results Several recent publications identified effective topical ocular antibacterials requiring a reduced dose regimen and a short treatment course. Additional literature reviewed included data on novel perioperative prophylaxis, indications for topical fortified antibiotics and innovative research including the risk of resistance. Conclusions Safe and effective topical antibiotic eye drops for the treatment and prevention of ocular infections must be adapted to the type of bacteria suspected. Usual topical antimicrobials should be replaced by more recent and more effective treatments. The use of highly effective fluoroquinolones should be reserved for the most severe cases to avoid resistance. Short treatment courses, such as azithromycin, can be easily used in children, thereby improving quality of life

Intérêt de la substitution d'un traitement journalier de 2 instillations de timolol par 1 instillation quotidienne de bêtabloquant non conservé chez des patients présentant un glaucome chronique ou une hypertonie oculaire

National audienceDuring this study in daily practice, the switch from a twice-daily regimen of timolol to a once-daily application maintained stable intraocular pressure with a notable improvement in tolerance