The following review focuses on the manufacturing and parameterizing of ocular drug delivery systems (DDS) using polymeric materials to create soft contact lenses. It discusses the types of drugs embedded into contact lenses, the various polymeric materials used in their production, methods for assessing the mechanical properties of polymers, and techniques for studying drug release kinetics. The article also explores strategies for investigating the stability of active substances released from contact lenses. It specifically emphasizes the production of soft contact lenses modified with Cyclosporine A (CyA) for the topical treatment of specific ocular conditions. The review pays attention to methods for monitoring the stability of Cyclosporine A within the discussed DDS, as well as investigating the influence of polymer matrix type on the stability and release of CyA.

The eye is one of the most important organs in the human body providing critical information on the environment. Many corneal diseases can lead to vision loss affecting the lives of people around the world. Ophthalmic drug delivery has always been a major challenge in the medical sciences. Since traditional methods are less efficient (∼5%) at delivering drugs to ocular tissues, contact lenses have generated growing interest in ocular drug delivery due to their potential to enhance drug bioavailability in ocular tissues. The main techniques used to achieve sustained release are discussed in this review, including soaking in drug solutions, incorporating drug into multilayered contact lenses, use of vitamin E barriers, molecular imprinting, nanoparticles, micelles and liposomes. The most clinically relevant results on different eye pathologies are presented. In addition, this review summarizes the benefits of contact lenses over eye drops, strategies for incorporating drugs into lenses to achieve sustained release, results of in vitro and in vivo studies, and recent advances in the commercialization of therapeutic contact lenses for allergic conjunctivitis.

An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.

The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.

Excessive reactive oxygen species (ROS) play a significant role in the pathogenesis of many eye diseases. Controlling oxidative stress by reducing the amount of ROS is a potential therapeutic strategy for the prevention and treatment of eye diseases, particularly ocular surface diseases. Ceria nanoparticles (CeNPs) have been investigated owing to their efficient ROS-scavenging properties. To overcome the disadvantages of eyedrop administration due to rapid elimination on the surface of the eye and to retain the intrinsic properties of contact lenses, we developed an ROS-scavenging water-soluble CeNP-embedded contact lens (CeNP-CL) for the prevention of ocular surface diseases. The intrinsic ROS-scavenging property of the CeNPs, which mimicked the activities of superoxide dismutase and catalase, was incorporated into polyhydroxyethyl methacrylate-based contact lenses. The CeNP-CL exhibited high transparency and physical properties comparable to those of a commercial contact lens, along with excellent extracellular ROS-scavenging properties. The viabilities of human conjunctival epithelial cells and human meibomian gland epithelial cells were significantly enhanced in the presence of CeNP-CLs, even in media with high H2O2 contents (100 and 500 μM). Additionally, the wearing of CeNP-CLs on the eyes had a protective effect in a mouse model when 3% H2O2 eyedrops were administered. These results indicate the salvaging effect of the CeNP-CL in a high-ROS environment on the ocular surface, which may be helpful for the treatment of ocular surface diseases.

Therapeutic contact lenses were developed from bacterial cellulose (BC) by the Institute of Chemistry at Brazil\'s São Paulo State University (UNESP). In a previous study, cyclodextrins (CD) and medications such as ciprofloxacin (CP) and diclofenac sodium (DS) were incorporated into the lenses to provide therapeutic properties and control drug release. However, significant opacity was seen in the material inherent to cellulose. In order to achieve full material transparency, the lenses were coated with an organic-inorganic hybrid compound containing aluminum alkoxide and glycidoxypropyltrimethoxysilane (GPTS)(H), or chitosan (Q) nanoparticles. This study evaluated the toxicity of these contact lenses to ensure the safety of these materials for future availability to the medical device industry. Lenses composed of BC and coated with either GPTS (H) or chitosan (Q), incorporating ciclodextrin (CD) to release diclofenac sodium (DS) or ciprofloxacin (CP), were submitted to cytotoxicity assays (XTT and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus assay) directly in cell culture. Statistical analyses were performed using the Tukey and Dunnett or Kruskal-Wallis and Dunn tests. All of the nanoparticles used in the lense coatings did not show cytotoxic effects by the XTT test (p > 0.05; Dunnett). Only materials associated with diclofenac sodium (BC-H-CD-DS and BC-Q-CD-DS) presented significantly different survival fractions compared to negative control (p < 0.001; Dunnett). Genotoxicity evaluation revealed a genotoxic effect in BC-H-CD-DS (p < 0.05; Dunn). All tested lenses did not present any mutagenic effect. These results indicate that improvements in DS incorporation are needed to eliminate toxicity. We demonstrated promising results in the safety of employing BC lenses functionalized with a drug delivery system permitting the bioavailability of ophthalmic drugs. Further studies utilizing other specific tests, such as corneal lineage are required before safe and efficient ophthalmologic use.

OBJECTIVE: The immediate postoperative management of patients undergoing pterygium excision usually includes eye patching in order to alleviate pain and prevent accidental tissue damage. Commonly applied tight patching with gauze bandages results in decreased field of monocular vision and discomfort. The aim of this study was to evaluate the patient-centered outcome of pterygium surgery when therapeutic contact lenses (TCL) are used instead of tight bandage patching in the first 24 postoperative hours.
METHODS: Prospective randomized controlled study. Sixty patients with primary pterygium who underwent pterygium surgery consisting of conjunctival autografting with 10-0 Vicryl sutures were randomized into two groups, bandaged with TCLs and tight bandage patching.
METHODS: Degree of pain on an 0-10 scale, use of pain killers, level of patient discomfort, sleep quality, and visual acuity (VA).
RESULTS: Sixty patients were studied. The pain level and pain duration during the first postoperative day was significantly lower in the tight bandage patching group compared with the TCL group (P = 0.034, P = 0.04 respectively). Sleep quality was significantly poorer in the TCL group (P = 0.004). The VA on the first postoperative day was similar for the two groups.
CONCLUSIONS: The application of TCL in the first 24 h after pterygium surgery resulted in more discomfort and pain and decreased quality of sleep compared with tight bandage patching. Despite the limitation in monocular vision and the inconvenience of gauze bandages, they are preferred over TCL for alleviating pain following pterygium surgery.

An extended wear therapeutic contact lens (TCL) for the sustained delivery of timolol maleate (TML) was fabricated based on molecular imprinting technique. The designed TCL comprised of a TML imprinted copolymer of carboxymethyl chitosan-g-hydroxy ethyl methacrylate-g-polyacrylamide (CmCS-g-HEMA-g-pAAm) embedded onto a poly HEMA matrix (pHEMA). Successful reloading of TML onto the lens was monitored using a simple and novel UV-Visible spectrophotometric method which showed an excellent reloading capacity of 6.53μgTML/TCL. The in vitro drug release profile in lacrimal fluid after each cycle was fitted onto Higuchi model of drug release suggesting diffusion release mechanism with no polymer degradation. Also, the TML release kinetics indicated a sustained drug delivery which can effectively achieve the therapeutic index of TML leading to a onetime medication for glaucoma. Biological activity of eluted drug after each cycle and cell viability of the TCL were verified using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,3-bis(2-methoxynitro-5-sulfophenyl)-5-(phenylaminocarbonyl)-2H-tetrazolium hydroxide (XTT) assay, respectively.

Contact lenses for ophthalmic drug delivery have become very popular, due to their unique advantages like extended wear and more than 50% bioavailability. To achieve controlled and sustained drug delivery from contact lenses, researchers are working on various systems like polymeric nanoparticles, microemulsion, micelle, liposomes, use of vitamin E, etc. Numerous scientists are working on different areas of therapeutic contact lenses to treat ocular diseases by implementing techniques like soaking method, molecular imprinting, entrapment of drug-laden colloidal nanoparticles, drug plate/film, ion ligand polymeric systems, supercritical fluid technology, etc. Though sustained drug delivery was achieved using contact lens, the critical properties such as water content, tensile strength (mechanical properties), ion permeability, transparency and oxygen permeability were altered, which limit the commercialization of therapeutic contact lenses. Also issues like drug stability during processing/fabrication (drug integrity test), zero order release kinetics (prevent burst release), drug release during monomer extraction step after fabrication (to remove un-reacted monomers), protein adherence, drug release during storage in packaging solution, shelf life study, cost-benefit analysis, etc. are still to be addressed. This review provides an expert opinion on different methodology to develop therapeutic contact lenses with special remark of their advantages and limitations.

OBJECTIVE: To provide a consensus clinical guideline for management of dry eye disease associated with Sjögren disease by evaluating published treatments and recommending management options.
METHODS: Consensus panel evaluation of reported treatments for dry eye disease.
METHODS: Using the 2007 Report of the International Workshop on Dry Eye (DEWS) as a starting point, a panel of eye care providers and consultants evaluated peer-reviewed publications and developed recommendations for evaluation and management of dry eye disease associated with Sjögren disease. Publications were graded according to the American Academy of Ophthalmology Preferred Practice Pattern guidelines for level of evidence. Strength of recommendation was according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.
RESULTS: The recommendations of the panel are briefly summarized herein. Evaluation should include symptoms of both discomfort and visual disturbance as well as determination of the relative contribution of aqueous production deficiency and evaporative loss of tear volume. Objective parameters of tear film stability, tear osmolarity, degree of lid margin disease, and ocular surface damage should be used to stage severity of dry eye disease to assist in selecting appropriate treatment options. Patient education with regard to the nature of the problem, aggravating factors, and goals of treatment is critical to successful management. Tear supplementation and stabilization, control of inflammation of the lacrimal glands and ocular surface, and possible stimulation of tear production are treatment options that are used according to the character and severity of dry eye disease.
CONCLUSIONS: Management guidelines for dry eye associated with Sjögren\'s disease are presented.