In the ocular pharmacology market, there is a noteworthy unmet demand for more efficacious delivery of ocular therapeutics. Contact lenses are emerging as an alternative ophthalmic drug delivery system to resolve the drawbacks of the conventional topical application methods. Thus, contact lenses drug delivery systems have been developed to provide an increased residence time of the drug at the surface of the eye leading to enhanced bioavailability and more convenient and efficacious therapy. Several research groups have already explored the feasibility and potential of contact lenses loading conventional drugs used to treat anterior eye disorders. Drug incorporation to the lens body is achieved with techniques, like simple soaking, inclusion of drug-loaded colloidal nanoparticles, or molecular imprinting. Regardless of the technique used, key properties of the contact lens, such as transparency and oxygen permeability, should be preserved. In this article, we reviewed the different techniques used for drug delivery through contact lenses, analyzing their advantages and disadvantages, and focused on articles describing contact lens-based ophthalmic drug delivery systems with significant potential to use in ocular therapeutics.

Dementia, including Alzheimer's disease (AD), is a major disorder, leading to several ocular manifestations amongst the elderly population. These visual disorders may be due to retinal nerve degenerative changes, including nerve fibre layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. There is no cure for Alzheimer's, but medicines can slow down the development of many of the classic symptoms, such as loss of memory and communication skills, mood swings, and depression. The disease diagnosis is difficult, and it is only possible through PET scans of the brain, detecting evidence of the accumulation of amyloid and tau. PET is expensive and invasive, requiring the injection of radioactive tracers, which bind with these proteins and glow during scanning. Recently, scientists developed promising eye-scan techniques that may detect Alzheimer's disease at its earliest stage, before major symptoms appear, leading to improved management of the disease symptoms. In this review, we are discussing the visual abnormalities of Alzheimer's and other neurodegenerative diseases, focused on ocular functional-visual-structural biomarkers, retinal pathology, and potential novel diagnostic tools.

The eye is continuously exposed to solar UV radiation and pollutants, making it prone to oxidative attacks. In fact, oxidative damage is a major cause of age-related ocular diseases including cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. As the nature of lens cells, trabecular meshwork cells, retinal ganglion cells, retinal pigment epithelial cells, and photoreceptors is postmitotic, autophagy plays a critical role in their cellular homeostasis. In age-related ocular diseases, this process is impaired, and thus, oxidative damage becomes irreversible. Other conditions such as low-grade chronic inflammation and angiogenesis also contribute to the development of retinal diseases (glaucoma, age-related macular degeneration and diabetic retinopathy). As melatonin is known to have remarkable qualities such as antioxidant/antinitridergic, mitochondrial protector, autophagy modulator, anti-inflammatory, and anti-angiogenic, it can represent a powerful tool to counteract all these diseases. The present review analyzes the role and therapeutic potential of melatonin in age-related ocular diseases, focusing on nitro-oxidative stress, autophagy, inflammation, and angiogenesis mechanisms.

Glaucoma is a chronic progressive optic neuropathy, which can result in visual impairment and blindness. Elevated intraocular pressure (IOP) is currently the only modifiable risk factor. Several recent studies have shown the benefits of IOP reduction in open-angle glaucoma. Therefore, current glaucoma drugs are IOP-lowering substances such as α(2)-adrenergic agonists, β(2)-adrenergic antagonists, carbonic anhydrase inhibitors and hypotensive lipids, which are used separately or in combination. In spite of the wide variety of antiglaucoma medicines, all therapies have several undesirable side effects. As a consequence, there are constant research attempts on the discovery of novel ocular hypotensive drugs. In the current paper, we review the latest available patents and literature for the pharmacological treatment of glaucoma, focusing on their molecular targets and/or their chemical characteristics and especially directed to melatoninergic drugs. Melatonin is a hormone secreted into the blood mainly from the pineal gland allowing the entrainment of the circadian rhythms of several biological functions. Melatonin and its analogues potently reduce IOP in rabbits, monkeys and humans. In addition, there are indications of long-term hypotensive effects and a proven neuroprotective role of melatoninergic substances. Furthermore, antidepressant and normalizing circadian rhythm actions of melatonin analogues might be beneficial for glaucoma patients. All the above mentioned facts suggest these agents as proper candidates for the glaucoma treatment. Consequently, the scientific research has given new and significant progress on the development of new, potent and selective melatonin ligands.

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.

From the clinical trial results, the advancement in tear substitutes and secretagogues in addressing specific deficiencies of tear components even though not resolving the underlying conditions of the disease is evident. The vast majority of new compounds under development are anti-inflammatories, steroids, non-steroids and antibiotics; however, there are also some novel lubricating drops and mucin-tear secretagogues. A future aggressive therapy for dry eye, depending on the severity of the symptoms, would include combinations of soft steroids, anti-inflammatories, such as cyclosporine A, with the addition of the new polyvalent mucin and tear secretagogues.

Rho kinase inhibitors are widely considered as a new treatment for glaucoma. Rho kinase inhibition has been shown in vitro and in vivo to lower intraocular pressure. Furthermore in the first clinical reports involving healthy human subjects, the results were quite promising. The potential of this new class of medicines is enormous in a field where there were not many developments lately. The inhibition of Rho kinase lowers the intraocular pressure by increasing the outflow through the trabecular meshwork. Increased blood flow to the optic nerve and a possible delay of optic nerve cell death has also been reported. As a consequence, the exploration of pharmacological inhibitors of Rho kinase signaling is actively being pursued by a number of pharmaceutical companies such as Senju Pharmaceuticals, Novartis, Kowa, Santen, Aerie, Inspire and others. In this article, we review the latest patents in this field, with their corresponding literature, regarding Rho kinase inhibitors for the treatment of intraocular pressure and summarize the many roles of Rho kinase signaling in the eye.

The use of animals for the study of ocular diseases and the potentiality of melatonin and its analogs, as future therapeutic drugs, should be performed on the basis of a rationale study. It is important to note that melatonin receptors seem to be widespread all over the eye. This strongly suggests that, in order to modify the physiology and biochemistry of malfunctioning ocular tissue, the melatonin receptors which are present in that tissue must be first identified. Second there is the need to confirm that those receptors targeted perform the desirable responses, and as a third measure, to use selective agonists (or antagonists) instead of melatonin. However, although some animals mimic ocular pathologies relatively well, and these can be used in melatonin studies, there is still a long way to go till some of the results obtained in animal models could be used for human therapy.