Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.

PURPOSE: The purpose of this study was to characterize local distribution and systemic absorption of the tumor necrosis factor (TNF)-alpha inhibitory single-chain antibody fragment (scFv) ESBA105 following topical administration to the eye in vivo. METHODS: Rabbits received ESBA105 as topical eye drops in two dosing regimens. First, pharmacokinetics after the topical route of administration was compared to the intravenous (i.v.) route by means of applying the identical cumulative daily dose of ESBA105. In a second study rabbits received five eye drops daily for six consecutive days in a lower frequency topical dosing regimen. Kinetics and biodistribution of ESBA105 in ocular tissues and fluids as well as in sera were determined in all animals. RESULTS: After topical administration to the eye, ESBA105 quickly reaches therapeutic concentrations in all ocular compartments. Systemic exposure after topical administration is 25,000-fold lower than exposure after i.v. injection of the identical cumulative daily dose. ESBA105 levels in vitreous humor and neuroretina are significantly higher on topical administration than after i.v. injection. Absolute and relative intraocular biodistribution of ESBA105 is different with topical and systemic delivery routes. Compared to its terminal half-life in circulation (7 hours), the vitreal half-life of ESBA105 is significantly enhanced (16-24 hours). CONCLUSIONS: On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders.

Ophtalmologie. Thérapie génique des rétinopathies héréditaires: premiers résultats [Gene therapy for hereditary eye diseases: where are we?]

Les résultats préliminaires de trois essais cliniques de thérapie génique d'une forme agressive de rétinite pigmentaire (l'amaurose congénitale de Leber) ont prouvé que le traitement des maladies dégénératives de la rétine par transfert de gène peut être sûr et efficace pour rétablir une fonction visuelle. Il faudra encore attendre les résultats à long terme de ces études pour que soit définitivement validée cette approche thérapeutique. Dans l'intervalle, il importe de se préparer à son introduction en ophtalmologie de façon à la rendre accessible à nos malades. Pratiquement cela revient à promouvoir: 1) le recrutement; 2) la caractérisation du phénotype et du génotype des sujets atteints et 3) la constitution d'un registre des rétinopathies héréditaires. Recently, preliminary results of three clinical gene therapy trials for early onset retinitis pigmentosa--Leber congenital amaurosis--suggested that treating this degenerative retinal disease by gene transfection can be safe and efficient to restore a visual function. The definitive validation of this therapeutic approach depends on the long-term results. The forthcoming availability of gene therapy in ophthalmology prompts the implementation: of 1) recruitment, 2) phenotyping and genotyping of affected patients, 3) and creation of a hereditary retinopathy registry.

Extremity and eye lens doses in interventional radiology and cardiology procedures: first results of the ORAMED project.

The main objective of WP1 of the ORAMED (Optimization of RAdiation protection for MEDical staff) project is to obtain a set of standardised data on extremity and eye lens doses for staff in interventional radiology (IR) and cardiology (IC) and to optimise staff protection. A coordinated measurement program in different hospitals in Europe will help towards this direction. This study aims at analysing the first results of the measurement campaign performed in IR and IC procedures in 34 European hospitals. The highest doses were found for pacemakers, renal angioplasties and embolisations. Left finger and wrist seem to receive the highest extremity doses, while the highest eye lens doses are measured during embolisations. Finally, it was concluded that it is difficult to find a general correlation between kerma area product and extremity or eye lens doses.

Eye colour as a genetic marker for fertility and fecundity of Triatoma infestans (Klug, 1834) Hemiptera, Reduviidae, Triatominae

Eye colour of Triatoma infestans is controlled at a single autosomal locus, with black-eye as the dominant gene and red-eye as the recessive. Inheritance of these characters follows a classical Mendelian system, enabling eye colour to be used as a marker for studies of mating frequency. We found no significant differences in oviposition rates and egg hatching rates irrespective of parental phenotypes. Different mating schedules between red-eye and black-eye parents showed that eye colour did not affect mating competence. Females mated with a single male or with different males together or in succession produced similar numbers of fertile eggs, with the eye colour of the offspring reflecting exposure to the different males. We conclude that although a single mating can provide sufficient sperm for the whole reproductive life of the female, multiple matings can result in balanced assortative sperm usage from the spermatheca.

A bird's eye survey of central american planorbid molluscs

In the course of two trips to Central America (June 1967 and JulyAugust 1976) I had the opportunity of collecting topotypic specimens of Planorbis nicaraguanus Morelet, 1849, anatomically defined in this paper, and of P. yzabalensis Crosse & Fischer, 1879, the identity of the latter with Drepanotrema anatinum (Orbigny, 1835) is confirmed. The following planorbid species were also found: Helisoma trivolvis (Say, 1817) in Nicaragua, Guatemala, Costa Rica and Belize; H. duryi (Wetherby, 1879) in Costa Rica; Biomphalaria helophila (Orbigny, 1835) in Guatemala, Belize, Nicaragua, Costa Rica and El Salvador; B. kuhniana (Clessin, 1883) in Panama; B. obstructa (Morelet,1849) in Guatemala, Belize and El Salvador; B. straminea (Dunker, 1848) in Costa Rica; B. subprona (Martens, 1899) in Guatemala; D. anatinum (Orbigny,1835) in Belize, Guatemala, Nicaragua and Costa Rica; D. depressissimum (Moricand,1839) in Nicaragua, Costa Rica and Panama; D. lucidum (Pfeiffer, 1839) in Guatemala, Belize and Nicaragua; D. surinamense (Clessin, 1884) in Costa Rica and Panama; and Gyraulus percarinatus sp. n. in Panama. The occurrence of B. kuhniana and D. surinamense is first recorded in Central America, and Gyraulus percarinatus is the first representative of the genus provenly occurring in the American continent south of the United States. The following synonymy is proposed: Planorbis declivis Tate, 1870 = Biomphalaria helophila (Orbigny, 1835); Planorbis isthmicus Pilsbry, 1920 = Biomphalaria kuhniana (Clessin, 1883); Planorbis cannarum Morelet, 1849 and Segmentina donbilli Tristram, 1861 = Biomphalaria obstructa (Morelet, 1849); and Planorbis yzabalensis Crosse & Fischer, 1879 = Drepanotrema anatinum (Orbigny, 1835), confirming Aguayo (1933).

Towards standardization of UV eye protection: what can be learned from photodermatology?

While knowledge about standardization of skin protection against ultraviolet radiation (UVR) has progressed over the past few decades, there is no uniform and generally accepted standardized measurement for UV eye protection. The literature provides solid evidence that UV can induce considerable damage to structures of the eye. As well as damaging the eyelids and periorbital skin, chronic UV exposure may also affect the conjunctiva and lens. Clinically, this damage can manifest as skin cancer and premature skin ageing as well as the development of pterygia and premature cortical cataracts. Modern eye protection, used daily, offers the opportunity to prevent these adverse sequelae of lifelong UV exposure. A standardized, reliable and comprehensive label for consumers and professionals is currently lacking. In this review we (i) summarize the existing literature about UV radiation-induced damage to the eye and surrounding skin; (ii) review the recent technological advances in UV protection by means of lenses; (iii) review the definition of the Eye-Sun Protection Factor (E-SPF®), which describes the intrinsic UV protection properties of lenses and lens coating materials based on their capacity to absorb or reflect UV radiation; and (iv) propose a strategy for establishing the biological relevance of the E-SPF.

Staff eye lens and extremity exposure in interventional cardiology: Results of the ORAMED project

Within the ORAMED project a coordinated measurement program for occupationally exposed medical staff was performed in different hospitals in Europe. The main objectives of ORAMED were to obtain a set of standardized data on doses for staff in interventional cardiology and radiology and to optimize staff protection. Doses were measured with thermoluminescent dosemeters on the ring finger and wrist of both hands, on legs and at the level of the eyes of the main operator performing interventional procedures. In this paper an overview of the doses per procedure measured during 646 interventional cardiology procedures is given for cardiac angiographies and angioplasties (CA/PTCA), radiofrequency ablations (RFA) and pacemaker and defibrillator implantations (PM/ICD). 31% of the monitored procedures were associated with no collective protective equipment, whereas 44% involved a ceiling screen and a table curtain. Although associated with the smallest air kerma - area product (KAP), PM/ICD procedures led to the highest doses. As expected, KAP and doses values exhibited a very large variability. The left side of the operator, most frequently the closest to the X-ray scattering region, was more exposed than his right side. An analysis of the effect of parameters influencing the doses, namely collective protective equipment, X-ray tube configuration and catheter access route, was performed on the doses normalized to KAP. Ceiling screen and table curtain were observed to reduce normalized doses by atmost a factor 4, much smaller than theoretical attenuation factors typical for such protections, i.e. from 10 to 100. This observation was understood as their inappropriate use by the operators and their non-optimized design. Configurations with tube above the patient led to higher normalized doses to the operator than tube below, but the effect of using a biplane X-ray suite was more complex to analyze. For CA/PTCA procedures, the upper part of the operator's body received higher normalized doses for radial than for femoral catheter access, by atmost a factor 5. This could be seen for cases with no collective protection. The eyes were observed to receive the maximum fraction of the annual dose limit almost as frequently as legs and hands, and clearly the most frequently, if the former 150 mSv and new 20 mSv recommended limits for the lens of the eye are considered, respectively.

Eye screening for diabetics - prevents blindness

Diabetes is a common condition affecting around 69,000 people in Northern Ireland. One of the possible complications of diabetes is a condition called diabetic retinopathy, which can cause sight loss and blindness. Retinopathy causes damage to the tiny blood vessels (capillaries) that nourish the retina, the tissues in the back of the eye that deal with light. This can seriously affect vision.Research shows that if retinopathy is identified early, for example through retinal screening, and treated appropriately, blindness can be prevented in the majority of people with diabetes, both type 1 and type 2.Screening programmeIn Northern Ireland, a diabetic retinopathy screening programme (DRSP), run by the Public Health Agency, has been put in place to screen all eligible people with diabetes aged 12 years and over. Dr Bernadette Cullen, Consultant in Public Health Medicine, PHA, said: "Screening detects problems early and allows appropriate treatment to be offered. It is vital that everyone with diabetes attends diabetic retinopathy screening when it is offered. Early detection of potential problems offers a very real opportunity to intervene and, with appropriate treatment, can prevent blindness in the majority of those at risk."The screening testThe screening test involves photographs being taken of the back of each eye, using a special camera. The test is painless and takes about 15 minutes. If the person is over 50 years of age, they will need to have drops put in their eyes about 15 minutes before the test to dilate their pupils.The photographs are sent to the regional screening centre for analysis by trained graders. Results will show whether patients require further referral for assessment or treatment by hospital eye services (HES). If this is not required, screening will be offered again the following year.GPs are informed of all results and if the patient is under the care of a diabetologist, they too will be informed. Patients are informed of results by their GP and if they need an urgent referral, protocols are in place to ensure this happens.Many people with diabetes attend their optometrist (optician) on a regular basis to have a sight test for glasses. It is important they continue to do this - this test is free to people with diabetes. It is also vital that people with diabetes attend for diabetic retinopathy screening when invited, regardless of how or where their diabetes is treated, or whether they visit a hospital consultant/GP for their diabetic care.Patients are invited to screening via their GP practice. An information leaflet to help patients make an informed decision to attend for screening is also sent. This can be accessed via the PHA website: www.publichealth.hscni.net.

Aganirsen Antisense Oligonucleotide Eye Drops Inhibit Keratitis-Induced Corneal Neovascularization and Reduce Need for Transplantation: The I-CAN Study.

OBJECTIVE: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. DESIGN: Multicenter, double-masked, randomized, placebo-controlled phase III study. PARTICIPANTS: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. MAIN OUTCOME MEASURES: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. RESULTS: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. CONCLUSIONS: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

The development of professional guidelines for the eye examination of people with dementia

Recently published guidelines��in the UK��relating to sight tests among people with dementia go some of the way to addressing the specific needs of this group. However, there is still a long way to go in terms of improving the provision of eye care services and optimising the visual health of this group.A��study, published by the Thomas Pocklington Trust,��which examines this subject - The development of professional guidelines for the eye examination of people with dementia - was presented at the first ever national “Dementia and Sight Loss conference” in London (1st December) - a forum where 100 dementia and sight loss professionals met to discuss ways to tackle the challenge of concurrent dementia and sight loss. The study, by researchers at the University of Bradford Schools of Optometry and Health Studies, reviewed procedures for sight tests and eye examinations among those with dementia. It found that policy and practice were hampered by a serious lack of basic research into concurrent dementia and sight loss and prompted recommendations which could lead to improved procedures, tools and techniques.Recommendations prompted by the study outline seven steps towards improving policy and practice:Conduct a systematic study of the availability and uptake of sight tests among people with dementia. Set up a website for people with dementia and their carers with information on how dementia affects eye health, and the importance of eye examinations. Develop education and training for optometrists and care home staff. Compile a list of optometrists experienced in providing eye care for people with dementia. Develop a template for recording the results of eye examinations in people with dementia – something which can be endorsed by professional bodies and made available to care homes. Measure the effectiveness of eye care, such as sight tests and cataract removals, on the quality of life of people with dementia. Research clinical testing methods so that guidelines can be strengthened. Measuring contrast sensitivity, for example, in someone with dementia could be vital as an inability to judge contrasts can make daily tasks impossible.To access the discussion paper please follow this link: The development of professional guidelines for the eye examination of people with dementia ��

Pathology and first report of natural infections of the eye trematode Philophthalmus lachrymosus Braun, 1902 (Digenea, Philophthalmidae) in a non-human mammalian host

The avian eye trematode Philophthalmus lachrymosus Braun, 1902 is for the first time referred naturally occurring in a non-human mammalian host. Previously, natural infections with P. lachrymosus and other species of Philophthalmus have been occasionally reported from man, with few data on experimental infections of non-human mammals. Results presented here are related to the report of two cases of philophthalmosis due to natural infections of wild Brazilian capybaras, Hydrochaeris hydrochaeris L., 1766 with P. lachrymosus and associated pathology. Clinical signs, gross and microscopic lesions as well as new morphometric data on the parasite are presented.

West Belfast Eye Health Equity Profile

The West Belfast Eye Health Equity Profile is a working report designed to inform the development of the Community Engagement Project (CEP) for the RNIB and provide information for a wider Eye Health Strategy for the Public Health Agency (PHA) and the Health�and Social Care Board (HSCB) with the aim of improving the equity, outcomes and quality of life for people with or at risk of poor eye health.

Notch signaling in the pigmented epithelium of the anterior eye segment promotes ciliary body development at the expense of iris formation.

The ciliary body and iris are pigmented epithelial structures in the anterior eye segment that function to maintain correct intra-ocular pressure and regulate exposure of the internal eye structures to light, respectively. The cellular and molecular factors that mediate the development of the ciliary body and iris from the ocular pigmented epithelium remain to be fully elucidated. Here, we have investigated the role of Notch signaling during the development of the anterior pigmented epithelium by using genetic loss- and gain-of-function approaches. Loss of canonical Notch signaling results in normal iris development but absence of the ciliary body. This causes progressive hypotony and over time leads to phthisis bulbi, a condition characterized by shrinkage of the eye and loss of structure/function. Conversely, Notch gain-of-function results in aniridia and profound ciliary body hyperplasia, which causes ocular hypertension and glaucoma-like disease. Collectively, these data indicate that Notch signaling promotes ciliary body development at the expense of iris formation and reveals novel animal models of human ocular pathologies.