Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BACKGROUND: Drug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines. DISCUSSION: We review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials. SUMMARY: As we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease

Osmolarité du film lacrymal (intérêt chez le porteur de lentilles de contact)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Pachymétrie cornéenne centrale et épaisseur de la couche des fibres optiques chez les sujets normotones et hypertones

National audienceTo evaluate the retinal nerve fiber layer thickness and the central corneal thickness in ocular hypertensive patients and healthy subjects. We prospectively included 55 ocular hypertensive patients (126 eyes) and 63 healthy subjects (110 eyes). In each individual we measured standard automatic perimetry, frequency doubling technique visual field, and central corneal thickness with an ultrasonic pachymeter and optical coherence tomography (OCT). Retinal nerve fiber layer thickness was evaluated with GDx-VCC and OCT. Central corneal thickness was significantly thicker in ocular hypertensive patients (p<0.009 and p<0.033 respectively). We found a significant correlation between ultrasonic pachymeter and OCT central corneal thickness in both groups (p<0.0001). Retinal nerve fiber layer thickness was not statistically different between healthy and ocular hypertensive subjects, but was significantly thinner in ocular hypertensive patients with thin central corneal thickness only with GDx-VCC. In the control group, no statistically significant linear correlation was noted between central corneal thickness and retinal nerve fiber layer thickness. In the ocular hypertensive group, we found a linear correlation between ultrasonic pachymeter and OCT central corneal thickness and the average retinal nerve fiber layer thickness with the GDx-VCC. Retinal nerve fiber layer thickness was globally similar in both healthy and ocular hypertensive subjects. Although some statistically significant differences in the retinal nerve fiber layer thickness were observed between these two groups, they were not clinically relevant.Introduction : Le but de cette étude était d’évaluer la pachymétrie cornéenne centrale et l’épaisseur de la couche des fibres optiques chez des patients normotones et hypertones. Patients et méthodes : Cent vingt-six yeux de 63 patients normotones et 110 yeux de 55 patients avec une hypertonie intraoculaire ont été inclus dans cette étude prospective comparative. Tous les patients ont eu un examen ophtalmologique complet, une périmétrie automatisée standard, une périmétrie par technologie en doublement de fréquence, une mesure par ultrasons et en tomographie à cohérence optique (OCT) de l’épaisseur cornéenne centrale et une mesure de l’épaisseur des fibres en polarimétrie laser (GDx-VCC) et en OCT. Tous les patients hypertones inclus avaient une périmétrie automatisée standard et une périmétrie par technologie en doublement de fréquence normale. Résultats : La pachymétrie ultrasonique et par OCT était statistiquement plus élevée chez les patients hypertones (p<0,009 et p<0,033 respectivement). Une corrélation a été retrouvée entre les pachymétries ultrasonique et par OCT dans les deux groupes (p<0,0001). Aucune différence statistiquement significative en terme d’épaisseur moyenne des fibres en GDx-VCC et en OCT n’était constatée entre les deux groupes (p=0,09 et p=0,56, respectivement). L’épaisseur moyenne des fibres en GDx-VCC était statistiquement plus faible chez les patients hypertones avec une cornée amincie. Dans le groupe des patients normotones, il n’existait pas de corrélation entre la pachymétrie par OCT ou ultrasonique et l’épaisseur des fibres en GDx-VCC et en OCT. Dans le groupe des patients hypertones, une corrélation marginale entre la pachymétrie ultrasonique et par OCT et l’épaisseur moyenne des fibres en GDx-VCC a été retrouvée. Discussion : Les patients hypertones avec une périmétrie par technologie en doublement de fréquence normale ne diffèrent pas des sujets normotones en terme d’épaisseur de la couche des fibres optiques. Conclusion : Cette étude a montré quelques différences statistiquement significatives au niveau de l’épaisseur des fibres optiques entre des patients normotones et des patients hypertones. Néanmoins, ces différences ne sont pas cliniquement signifiantes dans la population sélectionnée

Long-term outcome after topical ciclosporin in severe dry eye disease with a 10-year follow-up

Aim To report a 10-year follow-up of patients suffering from severe dry eye syndrome (DES) initially treated with topical ciclosporin A (tCSA) for 6months. Methods The charts of 26 patients with severe DES related to keratoconjunctivitis sicca (KCS) and followed for a minimum 10-year follow-up were retrospectively reviewed. All of them were treated initially with tCSA for 6months. The Schirmer I test, fluorescein and lissamine green staining scores and tear film break-up time (TBUT) were recorded to assess clinical symptoms before, during and after treatment. The subjective signs were evaluated with the ocular surface disease index (OSDI) questionnaire. Prolongation and reintroduction of tCSA after the initial treatment and combined treatments were also noted. Results Overall the median (IQR) duration of tCSA treatment was 23 (7-51) months after a prolonged induction treatment lasting 20 (8-41) months during the 10-year follow-up. For symptoms, a statistically significant difference in the OSDI between baseline and the end of the 10-year follow-up was not found (p=0.67). We noted a statistically significant improvement in all clinical signs after the initial treatment period, still present at the end of follow-up. Only 6.5% of the patients needed reintroduction of tCSA after their prolonged induction treatment. Conclusions The improvement observed after an initial tCSA treatment was sustained after a long-term follow-up with few cases requiring additional tCSA treatment. A prolonged induction treatment to decrease initial inflammatory local signs is a promising option in KCS

[An iris metastasis revealed a bronchopulmonary cancer]

We report the case of a 53-year-old patient referred by his ophthalmologist for a red, painful eye. On exam, he demonstrated findings of granulomatous uveitis with ocular hypertension (38 mm Hg) and a whitish, vascularized iris tumor with invasion of the irido-corneal angle. As our first hypothesis was an iris metastasis, a systemic work-up was carried out, which revealed moderately differentiated broncho-pulmonary carcinoma with multiple metastases (brain, cerebellum and adrenal). Emergency radio-chemotherapy was initiated, and the outcome was good, with rapid regression of the iris metastasis and good efficacy against the primary cancer. After one year of follow-up, the patient developed a metastasis at a new site, and his general condition deteriorated

Long-term outcome after topical ciclosporin in severe dry eye disease with a 10-year follow-up

International audienceAim: To report a 10-year follow-up of patients suffering from severe dry eye syndrome (DES) initially treated with topical ciclosporin A (tCSA) for 6months.Methods: The charts of 26 patients with severe DES related to keratoconjunctivitis sicca (KCS) and followed for a minimum 10-year follow-up were retrospectively reviewed. All of them were treated initially with tCSA for 6months. The Schirmer I test, fluorescein and lissamine green staining scores and tear film break-up time (TBUT) were recorded to assess clinical symptoms before, during and after treatment. The subjective signs were evaluated with the ocular surface disease index (OSDI) questionnaire. Prolongation and reintroduction of tCSA after the initial treatment and combined treatments were also noted.Results: Overall the median (IQR) duration of tCSA treatment was 23 (7-51) months after a prolonged induction treatment lasting 20 (8-41) months during the 10-year follow-up. For symptoms, a statistically significant difference in the OSDI between baseline and the end of the 10-year follow-up was not found (p=0.67). We noted a statistically significant improvement in all clinical signs after the initial treatment period, still present at the end of follow-up. Only 6.5% of the patients needed reintroduction of tCSA after their prolonged induction treatment.Conclusions: The improvement observed after an initial tCSA treatment was sustained after a long-term follow-up with few cases requiring additional tCSA treatment. A prolonged induction treatment to decrease initial inflammatory local signs is a promising option in KCS

Amélioration de l'information médicale des patients: intérêt pour un service d'ophtalmologie de disposer d'un site Internet

Doi : JFO-11-2008-31-9-0181-5512-101019-200807930National audienceIn order to improve medical information for the patients consulting at the Department of Ophthalmology, an Internet website was set up. We wanted to estimate the rate of patients connecting to this website. Then we evaluated how the patients could draw a benefit from visiting this Internet site. Prospective study of the patients seen in the department of ophthalmology over 4 consecutive days in May 2007. The first questionnaire was distributed to all patients and completed in the department. The second one was given only to the patients equipped with a broadband Internet connection and was to be completed at home after having visited the website. Six hundred twenty-one patients were admitted to the department during the period; 510 (82%) were included in the study. Among them, 382 (74.9%) responded to the first questionnaire. The broadband connection rate was 42.5%, 74.5% of these patients took an interest in our site, and 64.6% thought of visiting it. Forty-two (29%) responded to the second questionnaire. After having visited the site, 61.2% of the patients felt that their medical information was improved, 71.8% rated the quality of the site as good, and 87.9% would recommend this site to their relatives. This type of website is liable to efficiently supplement the information provided by the Ophthalmology Department doctors. It justifies the time and staff investment necessary for its operation

Retentissement de la version 11 de la T2A sur le financement de la chirurgie des glaucomes

National audienceIn this study, the potential impact of 11(th) version of the National Health System's Activity-Based Financing on the income of a University Hospital department was evaluated for glaucoma surgeries. The number of glaucoma surgeries in 2008 was analyzed based on the Medicalization Program of Information Systems. Using the 11(th) version of the Activity-Based Financing for Diagnosis-Related Groups (DRG), we compared the income of these surgical procedures on both an inpatient and an outpatient setting. One hundred and forty-nine patients undergoing glaucoma surgery between January and December 2008 were included, 94% of whom were treated on an outpatient basis. The lower reimbursement for outpatient surgery resulted in a loss of euro 100,000 or 64% of revenues compared to an inpatient procedure. Ambulatory glaucoma surgery is feasible but requires rigorous organization. Nonetheless, while department incomes are related to activity, ambulatory care seems financially disadvantageous. Many departments are trying to develop an ambulatory structure, but the apparent contradiction between the objectives of public health insurance and the hospital's need to balance its budget requires further clarification