Développement d’une lentille cornéenne médicamentée

L’utilisation de lentilles cornéennes peut servir à améliorer le profil d’administration d’un principe actif dans les yeux. Avec une efficacité d’administration de 5% par l’utilisation de gouttes, on comprend rapidement que l’administration oculaire doit être améliorée. Cette faible administration a donné naissance à plusieurs tentatives visant à fabriquer des lentilles cornéennes médicamentées. Cependant, à cause de multiples raisons, aucune de ces tentatives n’a actuellement été mise sur le marché. Nous proposons dans cette étude, une possible amélioration des systèmes établis par le développement d’une lentille cornéenne à base de 2-(hydroxyéthyle)méthacrylate (HEMA), dans laquelle des microgels, à base de poly N-isopropylacrylamide (pNIPAM) thermosensible encapsulant un principe actif, seront incorporé. Nous avons donc débuté par développer une méthode analytique sensible par HPCL-MS/MS capable de quantifier plusieurs molécules à la fois. La méthode résultante a été validée selon les différents critères de la FDA et l’ICH en démontrant des limites de quantifications et de détections suffisamment basses, autant dans des fluides simulés que dans les tissus d’yeux de lapins. La méthode a été validée pour sept médicaments ophtalmiques : Pilocarpine, lidocaïne, proparacaïne, atropine, acétonide de triamcinolone, timolol et prednisolone. Nous avons ensuite fait la synthèse des microgels chargés négativement à base de NIPAM et d’acide méthacrylique (MAA). Nous avons encapsulé une molécule modèle dans des particules ayant une taille entre 200 et 600 nm dépendant de la composition ainsi qu’un potentiel zêta variant en fonction de la température. L’encapsulation de la rhodamine 6G (R6G) dans les microgels a été possible jusqu’à un chargement (DL%) de 38%. L’utilisation des isothermes de Langmuir a permis de montrer que l’encapsulation était principalement le résultat d’interactions électrostatiques entre les MAA et la R6G. Des cinétiques de libérations ont été effectuées à partir d’hydrogels d’acrylamide chargés en microgels encapsulant la R6G. Il a été trouvé que la libération des hydrogels chargés en microgels s’effectuait majoritairement selon l’affinité au microgel et sur une période d’environ 4-24 heures. La libération à partir de ces systèmes a été comparée à des formules d’hydrogels contenant des liposomes ou des nanogels de chitosan. Ces trois derniers (liposomes, microgels et nanogels) ont présenté des résultats prometteurs pour différentes applications avec différents profils de libérations. Enfin, nous avons transposé le modèle développé avec les gels d’acrylamide pour fabriquer des lentilles de contact de 260 à 340 µm d’épaisseur à base de pHEMA contenant les microgels avec une molécule encapsulée devant être administrée dans les yeux. Nous avons modifié la composition de l’hydrogel en incorporant un polymère linéaire, la polyvinylpyrrolidone (PVP). L’obtention d’hydrogels partiellement interpénétrés améliore la rétention d’eau dans les lentilles cornéennes. L’encapsulation dans les microgels chargés négativement a donné de meilleurs rendements avec la lidocaïne et cette dernière a été libérée de la lentille de pHEMA en totalité en approximativement 2 heures qu’elle soit ou non encapsulée dans des microgels. Ainsi dans cette étude pilote, l’impact des microgels n’a pas pu être déterminé et, de ce fait, nécessitera des études approfondies sur la structure et les propriétés de la lentille qui a été développée. En utilisant des modèles de libération plus représentatifs de la physiologie de l’œil, nous pourrions conclure avec plus de certitude concernant l’efficacité d’un tel système d’administration et s’il est possible de l’optimiser.

Some account of the manor of Apuldrefield in the parish of Cudham, Kent,

"From the 'Topographer and genealogist', vol. III."

History of the county of Lincoln; from the earliest period to the present time,

First portion published in 1830 bearing Allen's name; present copy contains additional illustrations.

Westmoreland, Cumberland, Durham, and Northumberland : illustrated from original drawings by Thomas Allom &c. : with historical & topographical descriptions /

Running title: Picturesque illustrations of Westmorland, Cumberland, Durham and Northumberland.

University of Michigan Men's Basketball Team, 1909

Back Row: coach George D. Corneal, Frank West, mngr. Ralph Sayles, J. Griffith Hays, trainer George E. "Doc" May

Middle Row: Gregory Peck, captain Joseph P. Wilson, Henry Farquhar

Front Row: Carl Raiss, Charles Lathrop?

Unidentified: Charles Lather. Not pictured: Glenn M. Ely

Topical interferon alfa-2b for the treatment of recalcitrant ocular surface squamous neoplasia

center dot PURPOSE: To evaluate topical interferon alfa-2b (IFN-alpha 2b) for the treatment of recalcitrant ocular surface squamous neoplasia (OSSN). center dot DESIGN: Prospective, noncomparative, interventional consecutive case series. center dot METHODS: Ten patients with recalcitrant OSSN were treated with topical IFN-alpha 2b (1 million IU/ml) four times a day until clinical resolution of the lesion or until the lesion appeared nonresponsive-that is, treatment failure. Progress was assessed by clinical examination and photographic records, with a minimum follow,up of six months. center dot RESULTS: Eight of 10 patients achieved clinical resolution from topical IFN-alpha 2b treatment. One patient developed invasive squamous cell carcinoma and underwent exenteration. The other patient required further mitomycin C therapy to achieve clinical resolution. The mean duration to clinical resolution for the eight patients treated with IFN-alpha 2b was 21.9 weeks (range six to 59 weeks). There have been no recurrences for any of the nine patients during follow-up (mean 55.0 weeks; range 26 to 84 weeks). center dot CONCLUSIONS: Topical IFN-alpha 2b is an important treatment modality for recalcitrant OSSN; it avoids the risks of further limbal stem cell destruction from other agents and surgical excision. If invasive disease is diagnosed at any stage, topical therapy is contraindicated, necessitating surgical excision. (Am J Ophthalmol 2006; 142:568-571. (c) 2006 by Elsevier Inc. All rights reserved.)

Objective grading of the anterior eye

Purpose. To convert objective image analysis of anterior ocular surfaces into recognisable clinical grades, in order to provide a more sensitive and reliable equivalent to current subjective grading methods; a prospective, randomized study correlating clinical grading with digital image assessment. Methods. The possible range of clinical presentations Of bulbar and palpebral hyperaemia, palpebral roughness and corneal staining were represented by 4 sets of 10 images. The images were displayed in random order and graded by 50 clinicians using both subjective CCLRU and Efron grading scales. Previously validated objective image analysis was performed 3 times oil each of the 40 images. Digital measures included edge-detection and relative-coloration components. Step-wise regression analysis determined correlations between the average subjective grade and the objective image analysis measures. Results. Average subjective grades Could be predicted by a combination of the objective image analysis components. These digital ``grades'' accounted for between 69%, (for Efron scale-graded palpebral redness) and 98% (for Efron scale-graded bulbar hyperaemia) of the subjective variance. Conclusions. The results indicate that clinicians may use a combination of vessel areas and overall hue in their judgment of clinical severity for certain conditions. Objective grading call take these aspects into account, and be used to predict an average ``objective grade'' to be used by a clinician in describing the anterior eye. These measures are more sensitive and reliable than subjective grading while still utilizing familiar terminology, and can be applied in research or practice to improve the detection, and monitoring of ocular surface changes.

Visual signs and symptoms of Creutzfeldt-Jakob disease

A number of neurodegenerative diseases caused by prions have been described recently. These include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and BSE in cows. Patients with CJD may suffer a range of visual problems including eye movement deficits and visual hallucinations. In addition, it is possible that CJD may be acquired via corneal transplant and that prions may be transmitted by reusable contact lenses.

Clinical evaluation of the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100K autorefractor

Purpose. A clinical evaluation of the Shin-Nippon NVision-K 5001 (also branded as the Grand Seiko WR-5100K) autorefractor (Japan) was performed to examine validity and repeatability compared with subjective refraction and Javal-Schiotz keratometry. Methods. Measurements of refractive error were performed on 198 eyes of 99 subjects (aged 23.2 ± 7.4 years) subjectively (noncycloplegic) by one masked optometrist and objectively with the NVision-K autorefractor by a second optometrist. Keratometry measurements using the NVision-K were compared with the Javal-Schiotz keratometer. Intrasession repeatability of the NVision-K was also assessed on all 99 subjects together with intersession repeatability on a separate occasion separated by 7 to 14 days. Results. Refractive error as measured by the NVision-K was found to be similar (p = 0.67) to subjective refraction (difference, 0.14 ± 0.35 D). It was both accurate and repeatable over a wide prescription range (-8.25 to +7.25 D). Keratometry as measured by the NVision-K was found to be similar (p > 0.50) to the Javal-Schiotz technique in both the horizontal and vertical meridians (horizontal: difference, 0.02 ± 0.09 mm; vertical: difference, 0.01 ± 0.14 mm). There was minimal bias, and the results were repeatable (horizontal: intersession difference, 0.00 ± 0.09 mm; vertical: intersession difference, -0.01 ± 0.12 mm). Conclusion. The open-view arrangement of the Shin-Nippon NVision-K 5001 facilitates the measurement of static refractive error and the accommodative response to real-world stimuli. Coupled with its accuracy, repeatability, and capability to measure corneal curvature, it is a valuable addition to objective instrumentation currently available to the optometrist and researcher.

Simplified recording of soft contact lens fit

Purpose: To determine the critical fitting characteristics of modern soft contact lens fits and from this to devise a simplified recording scheme. Methods: Ten subjects (aged 28.1 ± 7.4 years) wore eight different modern soft contact lenses. Video was captured and analysed of blink (central and up-gaze), excursion lag (up, down, right and left gaze) and push-up movement, centration and coverage. Results: Lens centration was on average close to the corneal centre. Movement on blink was significantly smaller in up-gaze than in primary-gaze (p<0.001). Lag was greatest in down-gaze and least in up-gaze (p<0.001). Push-up test recovery speed was 1.32±0.73mm/s. Overall lens movement was determined best by assessing horizontal lag, movement on blink in up-gaze and push-up recovery speed. Steeper lens base-curves did not have a significant effect on lens fit characteristics. Contact lens material did influence lens fit characteristics, particularly silicone-hydrogels which generally had lower centration and a faster push-up speed of recovery than HEMA lenses (p<0.05). Conclusion: Lag on vertical gaze, and movement on blink in primary gaze generally provide little extra information on overall lens movement compared to horizontal lag, movement on blink in up gaze and push-up recovery speed. They can therefore be excluded from a simplified recording scheme. A simplified and comprehensive soft contact lens fit recording system could consist of a cross-hairs indicating the centre of the cornea; a circle to indicate the lens centration; a mark on the relevant position of the circle to indicate any limbal incursion; a grade (‘B’) below for movement with blink in up-gaze, a grade (‘L’) to the side for horizontal lag and a grade above (‘P’) for the assessed push-up recovery speed.

Childhood ethnic differences in ametropia and ocular biometry:the Aston Eye Study

Purpose: To describe the methodology, sampling strategy and preliminary results for the Aston Eye Study (AES), a cross-sectional study to determine the prevalence of refractive error and its associated ocular biometry in a large multi-racial sample of school children from the metropolitan area of Birmingham, England. Methods: A target sample of 1700 children aged 6–7 years and 1200 aged 12–13 years is being selected from Birmingham schools selected randomly with stratification by area deprivation index (a measure of socio-economic status). Schools with pupils predominantly (>70%) from a single race are excluded. Sample size calculations account for the likely participation rate and the clustering of individuals within schools. Procedures involve standardised protocols to allow for comparison with international population-based data. Visual acuity, non-contact ocular biometry (axial length, corneal radius of curvature and anterior chamber depth) and cycloplegic autorefraction are measured in both eyes. Distance and near oculomotor balance, height and weight are also assessed. Questionnaires for parents and older children will allow the influence of environmental factors on refractive error to be examined. Results: Recruitment and data collection are ongoing (currently N = 655). Preliminary cross-sectional data on 213 South Asian, 44 black African Caribbean and 70 white European children aged 6–7 years and 114 South Asian, 40 black African Caribbean and 115 white European children aged 12–13 years found myopia prevalence of 9.4% and 29.4% for the two age groups respectively. A more negative mean spherical equivalent refraction (SER) was observed in older children (-0.21 D vs +0.87 D). Ethnic differences in myopia prevalence are emerging with South Asian children having higher levels than white European children 36.8% vs 18.6% (for the older children). Axial length, corneal radius of curvature and anterior chamber depth were normally distributed, while SER was leptokurtic (p < 0.001) with a slight negative skew. Conclusions: The AES will allow ethnic differences in the ocular characteristics of children from a large metropolitan area of the UK to be examined. The findings to date indicate the emergence of higher levels of myopia by early adolescence in second and third generation British South Asians, compared to white European children. The continuation of the AES will allow the early determinants of these ethnic differences to be studied.

The influence of corneoscleral topography on soft contact lens fit

To evaluate the influence of peripheral ocular topography, as evaluated by optical coherence tomography (OCT), compared with traditional measures of corneal profile using keratometry and videokeratoscopy, on soft contact lens fit.

Creutzfeldt-Jakob disease and vision

This review describes a group of diseases known as the transmissible spongiform encephalopathies (TSEs), which affect animals and humans. Examination of affected brain tissue suggests that these diseases are caused by the acquisition and deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most important form of TSE in humans with at least four different varieties of the disease. Variant CJD (vCJD), a new form of the disease found in the UK, has several features that differ from the classical forms including early age of onset, longer duration of disease, psychiatric presentation (for example, depression) and extensive florid plaque development in the brain. About 10 per cent of patients with CJD exhibit visual symptoms at disease presentation and approximately 50 per cent during the course of the disease. The most commonly reported visual symptoms include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations and cortical blindness. Saccadic and smooth pursuit movements appear to be more rarely affected. The agent causing vCJD accumulates in lymphoid tissue such as the spleen and tonsils. The cornea has lymphoid tissue in the form of corneal dendritic cells that are important in the regulation of the immune response in the anterior segment of the eye. The presence of these cells in the cornea has raised the possibility of transmission between patients via optical devices that contact the eye. Although such transmission is theoretically possible it remains highly improbable.

A novel, dynamic, in vivo, non-contact method of measuring oxygen depletion rate of the anterior eye

Despite the importance of oxygen measurements, techniques have been limited by their invasive nature and small corneal area of assessment. The aim of this study was to assess a non-contact way of measuring oxygen uptake of the whole anterior eye.

A review of the surgical options for the correction of presbyopia

Presbyopia is an age-related eye condition where one of the signs is the reduction in the amplitude of accommodation, resulting in the loss of ability to change the eye's focus from far to near. It is the most common age-related ailments affecting everyone around their mid-40s. Methods for the correction of presbyopia include contact lens and spectacle options but the surgical correction of presbyopia still remains a significant challenge for refractive surgeons. Surgical strategies for dealing with presbyopia may be extraocular (corneal or scleral) or intraocular (removal and replacement of the crystalline lens or some type of treatment on the crystalline lens itself). There are however a number of limitations and considerations that have limited the widespread acceptance of surgical correction of presbyopia. Each surgical strategy presents its own unique set of advantages and disadvantages. For example, lens removal and replacement with an intraocular lens may not be preferable in a young patient with presbyopia without a refractive error. Similarly treatment on the crystalline lens may not be a suitable choice for a patient with early signs of cataract. This article is a review of the options available and those that are in development stages and are likely to be available in the near future for the surgical correction of presbyopia.