The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes

Purpose.: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface. Methods.: Formulations were prepared with propylene glycol (0.275%), carboxymethyl cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 μM) was assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human corneal-limbal epithelial cells and normal human conjunctival cells. In vivo tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes. The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit eyes. Results.: All the formulations demonstrated good in vitro and in vivo tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately 7 hours. Conclusions.: The hypotensive effect of 5-MCA-NAT was increased by using bioadhesive polymers in formulations that are suitable for the ocular surface and also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined with bioadhesive polymers is a good strategy in the treatment of ocular hypertension and glaucoma.

A decade of silicone hydrogel development:surface properties, mechanical properties, and ocular compatibility

Since the initial launch of silicone hydrogel lenses, there has been a considerable broadening in the range of available commercial material properties. The very mobile silicon–oxygen bonds convey distinctive surface and mechanical properties on silicone hydrogels, in which advantages of enhanced oxygen permeability, reduced protein deposition, and modest frictional interaction are balanced by increased lipid and elastic response. There are now some 15 silicone hydrogel material variants available to practitioners; arguably, the changes that have taken place have been strongly influenced by feedback based on clinical experience. Water content is one of the most influential properties, and the decade has seen a progressive rise from lotrafilcon-A (24%) to efrofilcon-A (74%). Moduli have decreased over the same period from 1.4 to 0.3 MPa, but not solely as a result of changes in water content. Surface properties do not correlate directly with water content, and ingenious approaches have been used to achieve desirable improvements (e.g., greater lubricity and lower contact angle hysteresis). This is demonstrated by comparing the hysteresis value of the earliest (lotrafilcon-A, >40°) and most recent (delefilcon-A, <10°) coated silicone hydrogels. Although wettability is important, it is not of itself a good predictor of ocular response because this involves a much wider range of physicochemical and biochemical factors. The interference of the lens with ocular dynamics is complex leading separately to tissue–material interactions involving anterior and posterior lens surfaces. The biochemical consequences of these interactions may hold the key to a greater understanding of ocular incompatibility and end of day discomfort.

Ocular biotribology and the contact lens:Surface interactions and ocular response

Biotribology is essentially the study of friction, lubrication and wear in biological systems. The area has been widely studied in relation to the behaviour of synovial joints and the design and behaviour of hip joint prostheses, but only in the last decade have serious studies been extended to the eye. In the ocular environment - as distinct from articular joints - wear is not a major factor. Both lubrication and friction are extremely important, however; this is particularly the case in the presence of the contact lens, which is a medical device important not only in vision correction but also as a therapeutic bandage for the compromised cornea. This chapter describes the difficulty in replicating experimental conditions that accurately reflect the complex nature of the ocular environment together with the factors such as load and rate of travel of the eyelid, which is the principal moving surface in the eye. Results obtained across a range of laboratories are compared.

A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery

The aim of the present work was to obtain an ophthalmic delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the treatment of ocular diseases. For this, an in situ forming gel comprised of the combination of a thermosetting polymer, poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) (PEO-PPO-PEO, poloxamer), with a mucoadhesive agent (chitosan) was developed. Different polymer ratios were evaluated by oscillatory rheology, texture and mucoadhesive profiles. Scintigraphy studies in humans were conduced to verify the retention time of the formulations developed. The results showed that chitosan improves the mechanical strength and texture properties of poloxamer formulations and also confers mucoadhesive properties in a concentration-dependent manner. After a 10-min instillation of the poloxamer/chitosan 16:1 formulation in human eyes, 50-60% of the gel was still in contact with the cornea surface, which represents a fourfold increased retention in comparison with a conventional solution. Therefore, the developed formulation presented adequate mechanical and sensorial properties and remained in contact with the eye surface for a prolonged time. In conclusion, the in situ forming gel comprised of poloxamer/chitosan is a promising tool for the topical treatment of ocular diseases. (C) 2010 Elsevier B.V. All rights reserved.

Vascular leakage stimulates phenotype alteration in ocular cells, contributing to the pathology of proliferative vitreoretinopathy

Plasma leaking from damaged retinal blood vessels can have a significant impact on the pathologies of the posterior segment of the eye. Inflammation in the eye and metabolic change resulting from diabetes mellitus causes vascular leakage with alteration of the phenotype of retinal pigment epithelial (RPE) cells and fibrocytes, resulting in changes in cell function. Phenotypically altered cells then significantly contribute to the pathogenesis of retinopathies by being incorporated into tractional membranes in the vitreous, where they secrete matrix molecules, such as fibronectin, and express altered cell surface antigens. We hypothesize that there is a direct relationship between the leaking of plasma and the proliferation and phenotypic change of RPE cells and fibroblasts, thus exacerbating the pathology of retinal disease. If the hypothesis is correct, control of vascular leakage becomes an important target of therapy in proliferative vitreoretinopathy.

The ocular morphology of the southern hemisphere lamprey Geotria australis gray with special reference to optical specialisations and the characterisation and phylogeny of photoreceptor types

This paper describes the ocular morphology of young adults of the southern hemisphere lamprey Geotria australis, the sole representative of the Geotriidae, and makes comparisons with those of holarctic lampreys (Petromyzontidae). As previously reported for the holarctic lamprey Ichthyomyzon unicuspis [Collin and Fritzsch, 1993], the lens of G. australis is non-spherical and possesses a cone-shaped posterior that may be capable of mediating variable focus. The avascular retina of G. australis is well differentiated, containing three retinal ganglion cell populations, three layers of horizontal cells and three photoreceptor types, in contrast to petromyzontids that contain only two photoreceptor types (short and long), G. australis possesses one rod-like (R1) and two cone-like (C1 and C2) photoreceptors. Although the rodlike receptor in G. australis may be homologous with the short receptors of holarctic lampreys, the two cone-like receptors have morphological characteristics that differ markedly from those of the long receptors of their holarctic counterparts. The features which distinguish the two cone-like receptors from those of the long receptor type in holarctic lampreys are the characteristics of the mitochondria and the presence of large amounts of two different types of stored secretory material in the endoplasmic reticulum of the myoid (refractile bodies). The endoplasmic reticulum of each receptor type has a different shape and staining profile and is polymorphic, each showing a continuum of distension. It is proposed that the presence of two cone-like photoreceptors with different characteristics would increase the spectral range of G. australis and thus be of value during the parasitic phase, when this lamprey lives in the surface marine waters. The irideal flap, present in G. australis but not petromyzontids, would assist in reducing intraocular flare during life in surface waters. The results of this study, which are discussed in the context of the proposed evolution of lampreys, emphasise that it is important to take into account the characteristics of the eyes of southern hemisphere lampreys when making generalizations about the eyes of lampreys as a whole.

A comparison of dissected follicle numbers and follicle counts on the ovarian surface for the evaluation of ovarian follicular populations in Bos indicus cows

Ovaries (n = 140) from 70 mixed-age multiparous, lactating Brahman cross (3/4-7/8 Bos indicus) cows were used to examine the hypothesis that counts of follicles visible on the surface of the ovaries of Bos indicus cows and their classification into diameter size classes, are closely correlated with numbers of follicles in those size classes found by complete dissection of the ovary. immediately after ovariectomy, mean diameters (long and short axes averaged) of all follicles greater than or equal to 2 mm visible on the surface of each ovary were measured. All follicles greater than or equal to 2 mm were dissected from the ovaries, excess stroma removed and follicle diameters measured under a stereomicroscope using an ocular graticule. For each ovary, follicles were classified in either small (8 mm) categories based on either diameters of surface or dissected follicles. Data for numbers of surface and dissected follicles (mean +/- SE) in small, medium, large categories and total follicle numbers, respectively, were 24.4 +/- 1.6 vs. 28.0 +/- 1.9, 1.6 +/- + 0.2 vs. 11.6 +/- 1.0, 0.5 +/- 0.1 vs. 0.7 +/- 0.1 and 26.4 +/- 1.6 vs. 40.4 +/- 2.5. Correlation coefficients (r) for counts of surface and dissected follicles in small, medium, large and total follicle numbers were 0.76, 0.40, 0.69 and 0.79, respectively. Medium size follicles presented only a small translucent area on the surface of the ovary, leading to an underestimate of numbers when categorised by surface evaluation. Counts of follicles visible on the surface of the ovaries of Bos indicus cows and their classification into size classes based on estimated diameter, are closely correlated with numbers of follicles in those size classes found at dissection of the ovary for small (8 mm) and total follicles but not for medium sized (4-8 mm) follicles. (C) 1997 Elsevier Science B.V.

Ocular biocompatibility of novel Cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers.

Topical ocular drug delivery has always been a challenge for pharmaceutical technology scientists. In the last two decades, many nano-systems have been studied to find ways to overcome the typical problems of topical ocular therapy, such as difficult corneal penetration and poor drug availability. In this study, methoxy poly(ethylene glycol)-hexylsubstituted poly(lactides) (MPEG-hexPLA) micelle formulations, which are promising nanocarriers for poorly water soluble drugs, were investigated for the delivery of Cyclosporin A (CsA) to the eye. As a new possible pharmaceutical excipient, the ocular compatibility of MPEG-hexPLA micelle formulations was evaluated. An in vitro biocompatibility assessment on human corneal epithelial cells was carried out using different tests. Cytotoxicity was studied by using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), and clonogenic tests and revealed that the CsA formulations and copolymer solutions were not toxic. After incubation with MPEG-hexPLA micelle formulations, the activation of caspase-dependent and -independent apoptosis as well as autophagy was evaluated using immunohistochemistry by analyzing the localization of four antibodies: (1) anti-caspase 3; (2) anti-apoptotic inducing factor (AIF); (3) anti-IL-Dnase II and (4) anti-microtubule-associated protein 1 light chain 3 (LC3). No apoptosis was induced when the cells were treated with the micelle solutions that were either unloaded or loaded with CsA. The ocular tolerance was assessed in vivo on rabbit eyes by Confocal Laser Scanning Ophthalmoscopy (CLSO), and very good tolerability was seen. The observed corneal surface was comparable to a control surface that was treated with a 0.9% NaCl solution. In conclusion, these results demonstrate that MPEG-hexPLA micelles are promising drug carriers for ocular diseases involving the activation of cytokines, such as dry eye syndrome and autoimmune uveitis, or for the prevention of corneal graft rejection.

Long-term close follow-up of chorioretinal lesions in presumed ocular tuberculosis

Purpose: To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines. Methods: Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOTTB test was performed when it became available. Results: Visual acuity (VA) significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8±20.9 (arbitrary units) and decreased to 32.5±16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5±13.3 and decreased to 10.8±5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5±1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively. Conclusions: A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.

Long-term close follow-up of chorioretinal lesions in presumed ocular tuberculosis.

PURPOSE: To evaluate the long-term outcome (up to 7 years) of presumed ocular tuberculosis (TB) when the therapeutic decision was based on WHO guidelines. METHODS: Twelve out of 654 new uveitic patients (1998-2004) presented with choroiditis and positive tuberculosis skin test (TST) (skin lesion diameter >15 mm). Therapy was administered according to WHO recommendations after ophthalmic and systemic investigation. The area size of ocular lesions at presentation and after therapy, measured on fluorescein and indocyanine green angiographies, was considered the primary outcome. Relapse of choroiditis was considered a secondary outcome. The T-SPOT TB test was performed when it became available. RESULTS: Visual acuity significantly improved after therapy (p=0.0357). The mean total surface of fluorescein lesions at entry was 44.8 ± 20.9 (arbitrary units) and decreased to 32.5 ± 16.9 after therapy (p=0.0165). The mean total surface of indocyanine green lesions at entry was 24.5 ± 13.3 and decreased to 10.8 ± 5.4 after therapy (p=0.0631). The T-SPOT TB revealed 2 false TST-positive results. The mean follow-up was 4.5 ± 1.5 years. Two relapses out of 10 confirmed ocular TB was observed after complete lesion healing, 2.5 years and 4.5 years after therapy, respectively. CONCLUSIONS: A decrease of ocular lesion mean size and a mean improvement of VA were observed after antituberculous therapy. Our long-term follow-up of chorioretinal lesions demonstrated relapse of ocular tuberculosis in 10% of patients with confirmed ocular TB, despite complete initial retinal scarring.

Orbital Implants Insertion to Improve Ocular Prostheses Motility

The objectives of this study were, through a literature review, to point the differences between orbital implants and their advantages and disadvantages, to evaluate prosthesis motility after orbital implants are inserted, and to point the implant wrapping current risks. Sixty-seven articles were reviewed. Enucleation implants can be autoplastics or alloplastics and porous (including natural and synthetic hydroxyapatite [HA]) or nonporous (silicone). Hydroxyapatite is the most related in the literature, but it has disadvantages, too, that is, all orbital implants must be wrapped. Exposure of the porous orbital implant can be repaired using different materials, which include homologous tissue, as well as autogenous graft, xenograft, and synthetic material mesh. The most used materials are HA and porous polyethylene orbital implant. The HA implant is expensive and possibly subject corals to damage, different from porous polyethylene orbital implants. Porous implants show the best prosthesis motility and a minimum rate of implants extrusion. Implant wraps can facilitate smoother entry of the implant into the orbit and allow reattachment of extraocular muscles. They also serve as a barrier between the overlying soft tissue and the rough surface of the implant, protecting implants from exposure or erosion.

Influence of Investment, Disinfection, and Storage on the Microhardness of Ocular Resins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of weathering and thickness on the superficial microhardness of acrylic resin and ocular button

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Alteration of blue pigment in artificial iris in ocular prosthesis: Effect of paint, drying method and artificial aging

The artificial iris is the structure responsible for the dissimulation and aesthetics of ocular prosthesis. The objective of the present study was to evaluate the color stability of artificial iris of microwaveable polymerized ocular prosthesis, as a function of paint type, drying method and accelerated aging. A total of 40 discs of microwaveable polymerized acrylic resin were fabricated, and divided according to the blue paint type ( n = 5): hydrosoluble acrylic, nitrocellulose automotive, hydrosoluble gouache and oil paints. Paints where dried either at natural or at infrared light bulb method. Each specimen was constituted of one disc in colorless acrylic resin and another colored with a basic sclera pigment. Painting was performed in one surface of one of the discs. The specimens were submitted to an artificial aging chamber under ultraviolet light, during 1008 h. A reflective spectrophotometer was used to evaluate color changes. Data were evaluated by 3-way repeated-measures ANOVA and the Tukey HSD test (alpha = 0.05). All paints suffered color alteration. The oil paint presented the highest color resistance to artificial aging regardless of drying method. (C) 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Effect of weathering and thickness on roughness of acrylic resin and ocular button

Purpose: The aim of this study was to evaluate the roughness of colorless ocular button and four brands of colorless acrylic resins designed to fabricate ocular prosthesis as a function of weathering (1008 h) and different thickness (1 and 3.5 mm). Materials and methods: One-hundred-and-twenty specimens were fabricated and distributed in 12 groups. The analysis was carried out by means of digital roughness meter. Results: Data were analyzed statistically by ANOVA and Tukey test at 1% significance. The results showed that there was no statistically significant difference after the weathering period. Both the Vipi Cril acrylic resin with 3.5 mm in thickness and ocular button with 1 mm in thickness presented the lowest roughness values (0.12. Ra). Conclusion: The roughness of the acrylic resins and the ocular button was not affect by the weathering of 1008 h. However, the thickness of the specimens proved to have a major influence on roughness property. © 2010.