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

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

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

[Activity-based financing: is ambulatory care profitable for the institution].

International audienceINTRODUCTION: The aim of this study was to evaluate the impact of the 11th version of the National Health System's Activity-Based Financing on the income of a University Hospital department for palpebral, lacrimal, and orbital surgeries. PATIENTS AND METHODS: The number of such surgeries in 2008 was based on the Medicalization Program of the Information System. Using the 11th version of the Activity-Based Financing for Diagnosis-Related Groups, we compared the income in both inpatient and outpatient settings. RESULTS: Two hundred and forty-eight patients undergoing palpebral, lacrimal, or orbital surgery between January and December 2008 were included, with 87% treated on an outpatient basis. The lower reimbursement for outpatient surgery resulted in a loss of 184,500 euros (79%) for our department compared to the inpatient procedure. DISCUSSION: With rigorous organization, ambulatory surgery is feasible for palpebral, lacrimal, and orbital surgery. Nonetheless, with department incomes related to activity, ambulatory care seems financially disadvantageous. Many departments are trying to develop an ambulatory structure, but the need to balance their budget requires improved coherence

Œil et maladie des griffes du chat : à propos de 7 cas

International audienceIntroduction. - Cat scratch disease is a pleiomorphic condition, sometimes with isolated ophthalmic involvement. We report the clinical observations of seven cases with ophthalmologic manifestations of cat scratch disease. Observations. - There were seven patients, with a median age of 52 years, of whom five were women and three had unilateral involvement. Six exhibited Leber's stellate neuroretinitis, an incomplete syndrome in two cases, and one associated with chorioretinal foci. One patient had isolated retinal infiltrates. The diagnosis of cat scratch disease was confirmed by Bartonella henselae serology, positive in all cases. All patients received treatment with doxycycline. Ocular complications (with optic atrophy and macular retinal pigment epithelial changes) were noted in five cases. Discussion. - Ocular bartonellosis is an atypical clinical form. It requires a directed ancillary work-up with serology or PCR, which has the peculiarity of being highly specific if not very sensitive. Treatment is above all preventive. Antibiotics may be initiated. Conclusion. - Cat scratch disease must be excluded in the work-up of posterior uveitis. (C) 2016 Elsevier Masson SAS. All rights reserved

Ocul Surf

PURPOSE: To estimate the prevalence of dry eye disease (DED) in the elderly and to describe systemic and ocular factors associated with DED in a population-based study, the Montrachet (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) study. METHODS: Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. A self-reported history of dry eye symptoms and artificial tear use were also recorded. Every participant underwent an ophthalmic evaluation, which included the Schirmer test without anesthesia (Schirmer I), tear film breakup time (TFBUT) measurement, and fluorescein corneal staining evaluation. RESULTS: A total of 1045 subjects were included in the study. The mean age was 82.2 +/- 3.8 years. The prevalence of DED according to symptoms, signs, or both was 34.4% [95% confidence interval ({CI)} 31.5-37.2], 34.5% [95% CI 31.6-37.3] and 13.0% [95% CI 10.9-15.0], respectively. Compared with men, women were more likely to self-report DED and artificial tear use, more often displayed an OSDI >22, and more often suffered from subjective and definite DED. In multivariate analysis, associated factors with definite DED were an educational level of short secondary school (to age 15 years), best-corrected visual acuity <20/60, dark iris color, systemic hypertension, and anxiolytic agent and antihistamine eye drop use. CONCLUSION: Dry eye disease is a major ophthalmologic condition with a high prevalence among the elderly. We report well-documented factors associated with DED and new associations deserving further investigation