Ocular Patches Research Articles

Microneedle-based ocular drug delivery systems - recent advances and challenges.

Eye diseases and injuries constitute a significant clinical problem worldwide. Safe and effective delivery of drugs to the eye is challenging mostly due to the presence of ocular barriers and clearance mechanisms. In everyday practice, the traditional eye drops, gels and ointments are most often used. Unfortunately, they are usually not well tolerated by patients due to the need for frequent use as well as the discomfort during application. Therefore, novel drug delivery systems with improved biopharmaceutical properties are a subject of ongoing scientific investigations. Due to the developments in microtechnology, in recent years, there has been a remarkable advance in the development of microneedle-based systems as an alternative, non-invasive form for administering drugs to the eye. This review summarizes the latest achievements in the field of obtaining microneedle ocular patches. In the manuscript, the most important manufacturing technologies, microneedle classification, and the research studies related to ophthalmic application of microneedles are presented. Finally, the most important advantages and drawbacks, as well as potential challenges related to the unique anatomy and physiology of the eye are summarized and discussed.

Next-generation contact lenses: Towards bioresponsive drug delivery and smart technologies in ocular therapeutics

In contrast to the conventional ocular formulations, contact lenses are well known for their diverse applications ranging from bio-sensing, prevention of myopia, cosmetics, and drug delivery. With a tremendous change in the lifestyle, contact lenses for therapeutic purposes have increased several fold. Contact lenses as medicated lenses suffer from several disadvantages, and to overcome the same numerous approaches have been explored. Researches worldwide have come a long way from cyclodextrin-based and vitamin E-based modified contact lenses to bioinspired approaches to enhance the effectiveness of the drug-eluting contact lenses. The bioinspired approach exploits bioinspired polymeric systems to enhance biocompatibility, specific molecule recognition technique by molecular imprinting, or stimuli-responsive system to improve the biocompatibility, drug loading, and drug delivery efficacy of the drug-eluting contact lenses. Moreover, recent innovations in ocular therapeutics such as nanowafers and microneedle contact lenses, and ocular patches have gained tremendous attention in ocular therapeutics. Another potential application of the contact lenses are smart lenses applied in the biosensing and diagnosis of various ocular disorders. The review summarizes and discusses the widespread therapeutic applications of next-generation contact lenses and various fabrication approaches, including its clinical implications, efforts taken by researchers in exploring the novel materials and diverse forms of the lenses, mechanisms of drug release, clinical trials, and their toxicity and safety concerns.

This issue ofActa, printed and electronic

The cover image is a schematic drawing of a retinal implant system for the blind. This is a described in an article by Velikay-Parel from Austria and Germany in the electronic part of this Issue of ACTA. Andrew and associates in Australia review inflammatory diseases in the orbit and their pathophysiology. Bjerrum et al. in Copenhagen found significantly higher risk of postoperative endophthalmitis after cataract surgery at a few private hospitals and clinics in Denmark compared with public hospitals. Hietala et al. in Helsinki and Australia found that individuals with higher age of onset of type 1 diabetes are more likely to develop macular oedema. Bertelsen et al. in Norway and UK found that microalbuminuria may be a useful risk predictor for diabetic retinopathy. van Dijk et al. in the Netherlands and USA found considerable variability in photocoagulation treatment plans influenced among other things by the assessment with slit lamp biomicroscopy versus OCT. Kofoed et al. in Copenhagen found abnormal cone function to correlate with carotid artery stenosis and reduced perfusion pressure. Vandewalle et al. Belgium and Iceland found that topical phenylephrine and tropicamide did not influence retinal oxygen saturation measurements or retinal vessel diameter. Ernest et al. in the Netherlands found a considerable prevalence of visual impairment in patients with glaucoma at the end of their life but the visual impairment was in many cases caused by other eye diseases. Ilmarinen et al. in Finland cultivated oral mucosal epithelium and treated severe ocular surface injuries with limbal stem cell deficiency. Konradsen and Zetterström in Stockholm found that flat cornea in Marfan syndrome reduces the myopic consequence of long axial length. Hirayama et al. in Japan describe symptomatic relief of ocular dryness and improved tear stability with moist cool air devices in offices. Pathak et al. in Oslo contribute a case series of patients who receive transplantation of ex vivo-expanded limbal epithelial cells with good results. González-López et al. in Spain found that only one temporal artery biopsy in four is positive in patients suspected of giant cell arteritis and suggest ways of improving this ratio. Næser et al. in Denmark present a case series of patients with Wegener's granulomatosis who underwent dacryocystorhinostomy. Peter Kristian Rasmussen presents his thesis on diffuse large B-cell and mantle cell lymphoma of the ocular adnexal region and lymphoma of the lachrymal gland. The following articles are published electronically only and are accessible on www.actaophthalmologica.com Lamoureux et al. in Australia and Singapore found good reliability and reproducibility with retinal oxygen saturation measurements. Velikay-Parel et al. in Austria and Germany tested an investigational epiretinal implant in a patient with retinitis pigmentosa. The device was found to be safe and stable. Koinzer et al. in Germany describe differences between OCT images and histology of photocoagulation lesions in retina. Hoffmann et al. in Germany, Italy and Portugal use Heidelberg retina tomography to study optic disc changes in people with ocular hypertension. They found strong associations between various structural optic nerve parameters. Saenz-Frances et al. in Spain find that peripheral corneal thickness may be important in intraocular pressure measurements and glaucoma in addition to central corneal thickness. Garcia-Martin et al. in Spain documented retinal nerve fibre layer loss in patients with multiple sclerosis, using OCT technology. Januschowski et al. in Germany used a microsensor to measure the wearing time of glasses and ocular patches in patients with amblyopia. Lara et al. in Italy examined gene mutations and immunoreactivity in conjunctiva melanomas. Montero et al. in Spain examined intravitreal drug dispersion with different size needles. Maschi-Cayla et al. in France used proton beam to treat conjunctival melanomas. Lesiewska-Junk et al. in Poland looked for oxidative stress markers on erythrocytes in patients with pseudoexfoliation. Tassignon et al. in Belgium used Scheimpflug camera to examine location of phakic intraocular lenses. Jakob and Van Calster in Belgium associate skin tattoos with uveitis. Brunner and Binder in Austria surgically excised retinal embolae. Purtskhvanidze et al. in Germany report open globe injuries from rotating wire brushes. Zhou et al. in China and Germany describe a series of bilateral retinal detachments. I wish you Merry Christmas and a Happy New Year and hope that you enjoy reading ACTA during the holidays.

Measuring wearing times of glasses and ocular patches using a thermosensor device from orthodontics

Amblyopia is one of the most common visual disorders in children. The risk of severe visual impairment on the healthy eye is doubled in patients with amblyopia. If detected early enough, the chances of visual rehabilitation are good. Treatment consists of refractive correction and occlusion of the dominant eye. Patient compliance is an important factor and can be monitored using thermosensors. It was the goal of our study to give proof of the principle that the wearing times of glasses and patches can be measured using a comparatively small and commercially available microsensor. Agreement between wearing times protocols of ocular patching/refractive correction and temperature measurements of thermosensors attached to the patches or glasses of three individuals were analysed using the Bland-Altman method. It was also analysed whether blinded persons could distinguish between temperature curves of patches and glasses, or temperature curves of an incubator or while worn in a pocket. The temperatures picked up by the microsensors indicate the beginning and the end wearing times of either glasses or ocular patches through steep temperature difference and a distinct temperature curve during measurements. Although blinded test persons were able to cleary distinguish between temperature profiles from incubator/pocket measurements compared to glasses/patching, glasses and patching curves could be discriminated correctly in only 50%. Differences between wearing time protocols and temperature measurements were within the limits of agreement as stated by the Bland-Altman plots. The TheraMon(®) microsensor can reliably measure wearing times of glasses and ocular patches without making the wearer uncomfortable, although the data are not unquestionable, especially in higher surrounding temperatures. Further studies on a larger number of individuals with different wearing profiles are needed.

Method optimization of ocular patches

The intraocular patches were prepared using gelatin as the polymer. Ocular patch were prepared by solvent casting method. The patches were prepared for six formulations GP1, GP2, GP3, GP4, GP5 and GP6. Petri dishes were used for formulation of ocular patch. Gelatin was used as a polymer of choice. Glutaraldehyde used as cross linking agent and (DMSO) dimethylsulfoxide used as solubility enhancer. The elasticity depends upon the concentration of gelatin. 400 mg amount of polymer i.e gelatin gave the required elasticity for the formulation.

Genetic alterations in thyroid carcinoma associated with familial adenomatous polyposis: clinical implications and suggestions for early detection.

Germ-line mutations of the adenomatous polyposis (APC) gene, responsible for familial adenomatous polyposis (FAP) were analyzed in 15 patients with FAP-associated papillary thyroid carcinomas: 13 had the mutation between codons 778 and 1309 (exon 15), 1 at codon 593 (exon 14), and 1 at codon 140 (exon 3). Therefore APC gene mutations clustered in the genomic area associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE) (codons 463-1387). Ocular patches were documented in 12 patients. In particular, 4 of the 15 patients, all women with a mean age of 23.5 (range 20-32), were found during the study of 15 consecutive kindreds who had undergone systematic screening for extra-colonic manifestations. Three of them belonged to the same kindred and were asymptomatic. These four patients were also screened for loss of heterozygosity of APC in the thyroid tumoral tissue. No biallelic inactivation of the APC gene was found. In contrast, three of these four patients had activation of the ret-PTC oncogene. In particular, there was activation of the ret-PTC1 isoform, a chimeric gene resulting from fusion of a gene named H4 with the RET gene. On histologic examination, three of the four patients showed Hashimoto-like lymphocytic infiltration. Present data suggest that: (1) the incidence of FAP-associated thyroid cancer probably has been underestimated in the past; (2) intensive screening could detect a larger than expected number of thyroid carcinomas; (3) systematic screening is recommended in patients with ocular patches and genetic mutation in exon 15; (4) Hashimoto-like findings do not exclude carcinoma but are a frequent accompanying finding; (5) despite frequent multicentricity and early lymph node involvement, FAP-associated thyroid tumors seem to have an excellent prognosis, in particular those showing ret-PTC activation.