Anterior Ocular Diseases Research Articles

Oxidative Stress in the Anterior Ocular Diseases: Diagnostic and Treatment

The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.

Design and optimization of gatifloxacin loaded polyvinyl alcohol nanofiber for the treatment of dry eye infection: In vitro and in vivo evaluation

According to a clinical report, nearly 50% of dry eye patients have an elevated risk of ocular infections and inflammations. Nanofiber could serve as a potential vehicle for treating anterior ocular disease because of its sterile nature, known solubility enhancing ability, capacity to carry multiple drugs, and controlled drug release capability, which can minimize overall dose and dosing frequency. As a result, the goal of this study was to assess the therapeutic potential of Gatifloxacin (GAF) loaded Polyvinyl alcohol (PVA) nanofiber for the treatment of dry eye syndrome with infection. Towards in vitro assessment, optimized nanofiber was characterized through surface imaging, swelling, release behavior, sterility, residual solvent, and degradation studies. Goat cornea was used to determine trans corneal penetrability. Therapeutic performance of the optimized nanofibers was assessed in a dry eye animal model. Results showed that applied potential of 12 kV, the flow rate of 3 μl/min, and plate to collector distance of 20 cm were the optimized electrospinning parameters for bead-free uniform fiber of around 200 nm. Longer precorneal contact time and biphasic release behavior, with an initial burst phase followed by a 7-h controlled release profile, are thought to reduce the need for frequent dosing to manage dry eye issues. Additionally, there was partial tear volume restitution and the tear ferns revival after 36h. Overall, the in-vitro and in-vivo results suggested that the developed product could be a viable alternative to manage dry eye infectious syndrome with less frequent dosing.

Cationic nanoemulsions with prolonged retention time as promising carriers for ophthalmic delivery of tacrolimus

Tacrolimus, also known as FK506, is a first-line drug for the topical treatment of immune-mediated inflammatory anterior ocular diseases (IIAODs). However, due to its limited water solubility, hydrophobic nature and relatively high molecular weight, topical application of FK506 features poor bioavailability. Numbers of formulations have been attempted to enhance the erratic bioavailability of FK506 through various techniques. But until now, none of them could satisfy the clinical needs completely. Here, a novel formulation of FK506, FK506-loaded cationic nanoemulsions (FK506 CNE), was developed to prolong the precorneal residence time of FK506, thereby enhancing the bioavailability of FK506 for IIAODs therapy. FK506 CNE was prepared by high-pressure homogenization, and its composition was screened and optimized by single-factor experiments. The FK506 CNE showed spherical morphology with a mean diameter of 178.8 ± 2.7 nm and a zeta potential of +25.6 ± 0.6 mV. Results from in vivo gamma scintigraphy studies proved that the precorneal residence time of FK506 CNE was significantly increased, compared with FK506-loaded neutral nanoemulsions (FK506 NE) and saline. The data of aqueous humor pharmacokinetic study in rabbits showed that the relative bioavailability of FK506 CNE was 1.68-fold and 1.77-fold of FK506 NE and the marketed FK506 eye drops (Talymus®), respectively. Finally, hematoxylin and eosin staining images and in vitro cytotoxicity data confirmed the safety of the FK506 CNE. Taking all these into consideration, we propose that FK506 CNE is a promising topical ophthalmic nanoformulation for the management of IIAODs.

ICON: Diagnosis and management of allergic conjunctivitis

Ocular allergy (OA), interchangeably known as allergic conjunctivitis, is a common immunological hypersensitivity disorder affecting up to 40% of the population. Ocular allergy has been increasing in frequency, with symptoms of itching, redness, and swelling that significantly impacts an individual's quality of life (QOL). Ocular allergy is an often underdiagnosed and undertreated health problem, because only 10% of patients with OA symptoms seek medical attention, whereas most patients manage with over-the-counter medications and complementary nonpharmacological remedies. The clinical course, duration, severity, and co-morbidities are varied and depend, in part, on the specific ocular tissues that are affected and on immunologic mechanism(s) involved, both local and systemic. It is frequently associated with allergic rhinitis (commonly recognized as allergic rhino conjunctivitis), and with other allergic comorbidities. The predominance of self-management increases the risk of suboptimal therapy that leads to recurrent exacerbations and the potential for development of more chronic conditions that can lead to corneal complications and interference with the visual axis. Multiple, often co-existing causes are seen, and a broad differential diagnosis for OA, increasing the difficulty of arriving at the correct diagnosis(es). Ocular allergy commonly overlaps with other anterior ocular disease disorders, including infectious disorders and dry eye syndromes. Therefore, successful management includes overcoming the challenges of underdiagnosis and even misdiagnosis by a better understanding of the subtleties of an in-depth patient history, ophthalmologic examination techniques, and diagnostic procedures, which are of paramount importance in making an accurate diagnosis of OA. Appropriate cross-referral between specialists (allergists and eyecare specialists) would maximize patient care and outcomes. This would significantly improve OA management and overcome the unmet needs in global health.

Ophthalmic Drug Delivery Systems for Antibiotherapy-A Review.

The last fifty years, ophthalmic drug delivery research has made much progress, challenging scientists about the advantages and limitations of this drug delivery approach. Topical eye drops are the most commonly used formulation in ocular drug delivery. Despite the good tolerance for patients, this topical administration is only focus on the anterior ocular diseases and had a high precorneal loss of drugs due to the tears production and ocular barriers. Antibiotics are popularly used in solution or in ointment for the ophthalmic route. However, their local bioavailability needs to be improved in order to decrease the frequency of administrations and the side effects and to increase their therapeutic efficiency. For this purpose, sustained release forms for ophthalmic delivery of antibiotics were developed. This review briefly describes the ocular administration with the ocular barriers and the currently topical forms. It focuses on experimental results to bypass the limitations of ocular antibiotic delivery with new ocular technology as colloidal and in situ gelling systems or with the improvement of existing forms as implants and contact lenses. Nanotechnology is presently a promising drug delivery way to provide protection of antibiotics and improve pathway through ocular barriers and deliver drugs to specific target sites.

Transcorneal Oxygenation of the Preretinal Vitreous

Transcorneal oxygenation is a promising approach to the treatment of various anterior ocular diseases, but its effect on the vitreous and retina is uncertain. The purpose of this study was to evaluate the ocular conditions necessary to permit transcorneal oxygenation of the preretinal vitreous in the rabbit eye. Oxygen at atmospheric pressure was supplied via a goggle to the eye while preretinal oxygen tensions were measured with a minimally invasive technique: fluorine-19 (19F) nuclear magnetic resonance spectroscopy of a small preretinal droplet of perfluorotributylamine. Experiments were performed on lensectomized eyes with intact posterior lens capsules (group 1) or in eyes that had also undergone posterior capsular discission (group 2) and mechanical vitrectomy (group 3). To better understand the results of the oxygenation studies, a water-soluble, freely diffusible contrast agent was applied topically to the cornea, and its penetration into the aqueous and vitreous was studied using T1-weighted magnetic resonance imaging. Preretinal PO2 was significantly increased after 30 minutes of transcorneal oxygenation in group 3 eyes (P = .002). In contrast, no change was observed in the other groups despite 30 minutes (group 1) or 3 hours (group 2) of oxygen exposure. The imaging studies demonstrated that contrast penetration of the vitreous was uniform and rapid in eyes in group 3, consistent with a fluid flow-dominated process. A much slower process of anterior and midvitreous enhancement was observed in groups 1 and 2 that was consistent with contrast diffusion. Because of bulk fluid movement, transcorneal oxygenation of the retina is feasible in single-compartment (vitrectomized, lensectomized) eyes within a reasonable period (30 minutes). This finding could prove useful in the treatment of retinal diseases in which hypoxia may play a role.

Tear plasmin activity with contact lens wear

Plasmin, a proteolytic enzyme, has been detected in the tears of patients experiencing anterior ocular disease, and during contact lens wear. Using a radial caseinolysis procedure, we examined tear plasmin levels in 66 patients who were wearing soft and rigid lenses for daily and extended wear. Compared to non-contact lens wearers, patients wearing soft and rigid lenses for extended wear were significantly more likely to exhibit tear plasmin activity. Eight hours of open-eye thick HEMA lens wear did not induce tear plasmin activity in a group of 10 subjects. However, significant increases in tear plasmin activity were recorded after short-term (1 hour) eye closure with and without lens wear, and following overnight (8 hours) eye closure without lens wear. Overnight eye closure also resulted in significantly increased numbers of epithelial cells and leucocytes in the tear fluid. Our results suggest that increased tear plasmin activity during extended contact lens wear may be attributable to the effects of eye closure rather than hypoxia or the presence of the contact lens per se.

TECHNIQUE OF OVERLAY SCLERAL HOMOGRAFT.

Human homograft techniques in ophthalmology are common today in the treatment of anterior ocular diseases, but relatively little has been written regarding the use of human sclera as a homograft material. Sclera is readily available from donor eyes, easily preserved for months, and almost universally accepted by the recipient. Human sclera, like cornea, is relatively avascular; thus hypersensitivity reactions have not been sufficient to cause rejection of the graft. As the principal ocular supporting structure, sclera is strong, yet flexible due to the triple coat of interwoven fibers. These factors make it applicable to use in any shape from a patch to an elongated strand. Sclera has been used previously as a graft in the treatment of chronic scleromalacia perforans with impending rupture, as in our case description. It has served as a supporting sling in the posterior ectasia of high myopia (Borley^1,2) and as a temporary or permanent