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Age-related eye disorders are chronic diseases that affect millions of people worldwide. They cause visual impairment and, in some cases, irreversible blindness. Drug targeting to the retina is still a challenge due to the difficulties with drug distribution, crossing eye barriers, and reaching intraocular tissues in an effective therapeutic concentration. Although intravitreal injections can directly deliver drugs to the posterior segment of the eye, it remains an invasive technique and leads to several side effects. Conventional formulations such as emulsions, suspensions, or ointments have been related to frequent instillation and inability to reach intraocular tissues. New drug delivery systems and medical devices have also been designed. Nevertheless, these treatments are not always effective and sometimes require the presence of a specialist for the administration of the dose. Therefore, treatments for age-related ocular diseases remain as one of the major unmet clinical needs to manage these widespread eye conditions. Nanotechnology may become the adequate tool for developing effective and non-invasive therapies suitable for self-administration. In this review, we discuss emerging therapeutic options based on nanoengineering of cyclodextrin nanocarriers for the treatment of age-related eye disorders, including their pathophysiology, pharmacological options, and feasibility of clinical translation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chrysin belongs to the group of natural polyphenols. It can be found, among others, in honey, propolis and fruits and has a wide range of biological activities, including the prevention of oxidative stress, inflammation, neurodegeneration and carcinogenesis. Being a part of the human diet, chrysin is considered to be a promising compound to be used in the prevention of many diseases, including cancers, diabetes and neurodegenerative diseases such as Alzheimer's or Parkinson's. Nevertheless, due to the low solubility of chrysin in water and under physiological conditions, its bioavailability is low. For this reason, attempts at its functionalization have been undertaken, aiming to increase its absorption and thus augment its in vivo therapeutic efficacy. The aim of this review is to summarize the most recent research on chrysin, including its sources, metabolism, pro-health effects and the effects of its functionalization on biological activity and pharmacological efficacy, evaluated both in vitro and in vivo.

Background: Onchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity., Methods: We developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios., Results: ONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity., Conclusion: We present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA., Competing Interests: The authors have declared that no competing interests exist.

In the homeostasis of the ocular surface, vitamins play a critical role in regulating inflammatory responses and promoting cell differentiation, development and correct function. Systemic vitamin supplementation has been available for many decades; in recent years, thanks to pharmacological advancements, topical vitamin delivery has also become available in an attempt to better treat ocular surface disease (OSD) and dry eye disease (DED). In this paper, we reviewed the current evidence on the role of vitamin supplementation in OSD and DED. We originally searched the PubMed archive, inspected the references and restricted the search to pertinent papers. The body of evidence was evaluated using the amelioration of both signs and symptoms as the outcome, when available. We found that in patients with vitamin deficiency, systemic supplementation of Vitamin A is effective in treating OSD, reducing both DED signs and symptoms. Additionally, systemic supplementation of vitamin D is useful in reducing DED symptoms and increasing tear volume. Vitamin A is also effective in reducing DED signs and symptoms when administered locally. The efficacy of supplementation with other vitamins is still not fully proven. In conclusion, the inclusion of vitamins into the treatment strategies for OSD and DED allows for better treatment customization and better outcomes in these patients.

Introduction: to evaluate the effect of dexamethasone biodegradable implant (DEX-I), on intraocular pressure (IOP), to determine the incidence of secondary ocular hypertension (OHT) and to analyze the IOP changes as per the treatment indication in Zambian cohort., Methods: retrospective consecutive case series of patients receiving one DEX-I between January 2016 and September 2018 with a minimum follow-up of four months in a tertiary care centre in Zambia. The IOP was recorded before the injection and at 1 st week, 1 st , 2 nd , 3 rd and 4 th month after the injection. Ocular hypertension was defined as IOP ≥ 21 mmHg or an increase of ≥ 10 mmHg from baseline., Results: the effects of 122 injections given to ninety - nine patients (65 male: 65%; mean age 57.3) were included. The main indications for treatment were diabetic macular edema (DME, 52%), retinal vein occlusion (18%), post-surgical macular edema (18%) and non-infectious posterior uveitis (10%). Mean IOP before the injection was was 14.7mmHg and at 1 st week, 1 st , 2 nd , 3 rd and 4 th months after the injection it was 14.4 (p=0.08), 16.1 (p=0.01), 17.5 (p<0.001), 15.7 (p=0.006) and 14.9 (p=0.06) mmHg, respectively. The incidence of secondary OHT was 30.32% in this cohort. Peak incidence of OHT was between 1 - 2 months, with majority of cases in DME group (75%) and 43% diabetic eyes followed by 23% non-infectious posterior uveitis cases developing OHT post injection. OHT was well managed with anti-glaucoma medications only., Conclusion: DEX-I showed a good pressure tolerance in this cohort. Secondary ocular hypertension developed in one-third of patients receiving injection which was transient and successfully managed with topical anti-glaucoma medications only. Diabetic eyes are more prone to develop ocular hypertension and therefore needs close monitoring following injection., Competing Interests: The authors declare no competing interests., (Copyright: Pallavi Raj et al.)

Corticosteroids remain the mainstay of the treatment for various ocular conditions affecting the ocular surface, anterior and posterior segments of the eye due to their anti-inflammatory, anti-oedematous, and anti-neovascularization properties. Prednisolone, prednisolone acetate, dexamethasone, triamcinolone acetonide, fluocinolone acetonide, and loteprednol etabonate are amongst the most widely used ophthalmic corticosteroids. Corticosteroids differ in their activity and potency in the eye due to their inherent pharmacological and pharmaceutical differences. Different routes and regimens are available for ocular administration of corticosteroids. Conventional topical application to the eye is the route of choice when targeting diseases affecting the ocular surface and anterior segment, while periocular, intravitreal, and suprachoroidal injections can be potentially effective for posterior segment diseases. Corticosteroid-induced intraocular pressure elevation and cataract formation remain the most significant local risks following topical as well as systemic corticosteroid administration. Invasive drug administration via intracameral, subconjunctival, and intravitreal injection can enhance ocular bioavailability and minimize dose and dosing frequency of administration, yet may exacerbate ocular side effects of corticosteroids. This review provides a critical appraisal of the ophthalmic uses of corticosteroid, routes of administration, drug delivery fundamentals and novel ocular implantable steroid delivery systems, factors influencing side effects, and future perspectives for ocular corticosteroid therapy.

The investigations discussed in this review indicate that iron may exacerbate different eye diseases. Therefore, it is plausible that reducing cellular or body iron stores could influence disease pathogenesis, so it is logical to consider the iron chelators' potential protective role in the various ophthalmic diseases in the form of topical eye drops or slow releasing injectable compounds as an adjuvant treatment.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia-reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

Ophthalmic disorders are amid the most common pathologies worldwide. In this regard, hyaluronan (HA) has gained widespread use in eye surgeries and treatment of eye diseases. HA-based materials are well tolerated and show excellent biocompatibility. Therefore, HA is a sought-after component of ophthalmic formulations. However, several parameters have to be adjusted to reach an optimal performance and effectiveness. The complexity of HA properties represents a major challenge for biological and structural characterization. This review covers fundamental aspects and recent developments in HA ophthalmic research. Biological mechanisms underlying the health benefits of HA and their potential therapeutic applications are elaborated. Furthermore, current pharmacokinetic and safety studies are discussed. Noticeably, the benefits of chemical modification and processed HA forms are described to broaden the applications of this unique polysaccharide. The current research challenges and prospects are also outlined and discussed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Quercetin is a natural flavonol antioxidant found in various plant sources and food samples. It is well known for its notable curative effects on the treatment of ophthalmic diseases due to various biological activities, such as antioxidant, anti-inflammatory, and anti-fibrosis activities. This review will discuss the latest developments in therapeutic quercetin for the treatment of keratoconus, Graves' orbitopathy, ocular surface, cataracts, glaucoma, retinoblastoma, and other retinal diseases., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

When prescribing medications, it is important to consider the ocular side effects of common systemic therapy as well as potential systemic side effects of ocular medications. Although not an exhaustive list of medications/classes of medications, this article does include many commonly used drugs and also provides information on some topical therapies commonly used by ophthalmologists. These ocular medications may result in systemic effects and/or alter patients' management of systemic conditions., Competing Interests: Disclosure None of the authors has any financial or commercial conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Anti-inflammatory effect of soluble secreted compounds of probiotic bacteria was widely demonstrated as therapy for different inflammatory diseases, but was not investigated in inflammatory eye disorders. The aim of this study was to determine whether Lactiplantibacillus plantarum CRL759 cell-free supernatant reduced inflammatory parameters and clinical signs in ocular inflammations. First, we evaluated the effect of L. plantarum CRL759 supernatant in vitro on human retinal cell line, ARPE-19 cells, stimulated with lipopolysaccharide (LPS). Then, we investigated in vivo its capacity to decrease inflammation by local administration on the eyes of mice with endotoxin induced inflammation. In vitro assays demonstrated that L. plantarum CRL759 supernatant reduced the production of interleukin (IL)-6, IL-8, nitric oxide and thiobarbituric acid reactive substances in LPS-stimulated ARPE-19 cells. Our in vivo data proved that L. plantarum supernatant significantly reduced the clinical score of endotoxin treated mice and diminished levels of tumour necrosis factor alpha, interferon gamma and protein concentration in aqueous humour. Histological examination showed reduction of infiltrating inflammatory cells in the posterior segment of the eyes. As far as we know, this is the first report showing that Lactobacillus spp. supernatant administered as drops reduces some parameters of ocular inflammation. This promising strategy is safe and could alleviate symptoms and signs of ocular inflammation in people that are refractories to the conventional therapies.

New, brand-name, ophthalmology drug products are developed, investigated, and submitted for marketing approval through premarket interactions with the Food and Drug Administration (FDA). These drug applications for novel drugs are reviewed by FDA for safety and effectiveness before being allowed on the market. Many brand-name drugs are allowed a period of marketing exclusivity and/or have patent protections that can delay generic competition. When these exclusivity periods or patents expire or are challenged (in the case of patents), generic competitors may then market equivalent products, as allowed by U.S. law (eg, Drug Price Competition and Patent Term Restoration Act, often referred to as "the Hatch-Waxman Act"). To be approved as a therapeutic equivalent, a generic product must demonstrate that it is both pharmaceutically equivalent and bioequivalent to the brand-name drug product, which can involve innovative analytical methods and study designs. To facilitate generic drug assessment and approval, the FDA has negotiated the Generic Drug User Fee Amendments (GDUFA) program that funds a rigorous generic drug development program that includes pre-Abbreviated New Drug Application (pre-ANDA) correspondence and meetings, targeted bioequivalence research, and publication of product-specific guidances (PSGs) to support generic drug research and development for manufacturers interested in developing generic drugs for the U.S. market. FDA's regulatory practices include the monitoring of quality and postapproval adverse events of all marketed products, including those for use in and around the eyes.

Optometrists in Australia employ ophthalmic medicines in their paediatric practice to assist clinical diagnosis and to treat ocular conditions. Prior to employing ocular medicines or initiating treatment, it is important to consider the risks versus benefits of ophthalmic medicines and determine the minimum dose required to safely achieve a diagnostic or therapeutic benefit. Instilling drops in infants and young children may require techniques that do not depend on full cooperation, particularly to maintain appropriate dosing and limit the rate of elimination from the eye. Diagnostic cycloplegic agents are highly recommended for the accurate determination of refractive error in infants and young children. Topical atropine is commonly prescribed in paediatric optometry practice in highly variable concentrations. 1% atropine eye drops are used for pharmacological penalisation in management of amblyopia, and, increasingly, low concentration (< 0.1%) atropine is used to manage the progression of childhood myopia. Doses of topical ocular medicines to treat inflammation, infection or glaucoma are generally identical to those use in adults; however, there is potential for increased ocular and systemic side effects with certain medications. It is, therefore, timely to present, summarise and comment on the use of ophthalmic diagnostic and therapeutic agents in children and reference where practitioners can look for more detailed information. The perspective is set in the Australian context of a collaborative approach between paediatric optometry and ophthalmology eye care practitioners for delivery of best practice care in infants and young children. Inclusion of the more complex spectrum of paediatric eye disease in a tertiary ophthalmological setting is provided to build practitioner knowledge of treatment regimens their patients may be using, even though management of these conditions lies outside their scope of practice.

Diabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Rosacea is a chronic inflammatory condition that affects the skin and the eyes. The pathogenesis of rosacea is complex and includes the interaction between genetic and environmental factors, dysregulation of the innate immune system, neurovascular modifications and the interaction with skin commensals. Clinical manifestations in children include the telangiectatic form, papulopustular rosacea, ocular rosacea, periorificial dermatitis, granulomatous rosacea and idiopathic facial aseptic granuloma. Management is aimed at identifying and avoiding triggers. Topical therapy is used for mild cases with topical antibiotics and anti-inflammatory agents. Oral agents are indicated, in combination with topical therapy, for moderate to severe cases. Prolonged therapy may be required., (© 2020 British Association of Dermatologists.)

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues. We carried out a PubMed query, using the keywords "SOD", "SOD mimetics", "SOD supplementation", which included papers published in the English language, between 2012 and 2020, on the potential therapeutic applications of SODs, including detoxification strategies. As highlighted in this paper, it can be argued that the generic antioxidant effects of SODs are beneficial under all tested conditions, from ocular and cardiovascular diseases to neurodegenerative disorders and metabolic diseases, including diabetes and its complications and obesity. However, it must be underlined that clinical evidence for its efficacy is limited and consequently, this efficacy is currently far from being demonstrated.

Ophthalmic diseases represent a significant problem as over 2 billion people worldwide suffer from vison impairment and blindness. Eye drops account for around 90% of ophthalmic medications but are limited in success due to poor patient compliance and low bioavailability. Low bioavailability can be attributed to short retention times in the eye caused by rapid tear turnover and the difficulty of drug diffusion through the multi-layered structure of the eye that includes lipid-rich endothelial and epithelial layers as well as the stroma which is high in water content. In addition, there are barriers such as tight junctional complexes in the corneal epithelium, lacrimal turnover, nasolacrimal drainage, blinking reflexes, efflux transporters, drug metabolism by ocular enzymes, and drug binding to or repulsion from conjunctival mucins, tear proteins, and melanin. In order to maximize transport through the cornea while minimizing drug loss through other pathways, researchers have developed numerous methods to improve eye drop formulations including the addition of viscosity enhancers, permeability enhancers, mucoadhesives, and vasoconstrictors, or using formulations that include puncta occlusion, nanocarriers, or prodrugs. This review explains the mechanism behind each of these methods, examines their history, analyzes previous and current research, evaluates future applications, and discusses the pros and cons of each technique.

Toxoplasmosis is one of the most important protozoa zoonotic diseases worldwide. The present study describes the clinical, seroprevalence findings with ocular toxoplasmosis and the outcome of medicinal treatment of these cats. This study was carried out on 105 cats with various ocular signs, no historical evidence of ocular trauma or drug/vaccine exposure for at least 3 months prior to admission, and without clinical or laboratory evidence of other systemic diseases. Complete case history, physical and ophthalmic examinations were carried out. The seroprevalence of Toxoplasma gondii antibodies was determined using the Toxoplasma Ab Rapid Test and Enzyme Linked Immunosorbent Assay. Out of 105 examined cats with ocular lesions, 60 cats representing 57.14% were seropositive to T. gondii. Out of these 60 cats, 15 cats (25%) had bilateral ocular abnormalities, 25 cats (41.67%) had right-sided ocular disease, and 20 cats (33.33%) had left-sided ocular disease. There were 38 cats (63.33%) with anterior uveitis, 12 cats (20%) with posterior segment involvement, 5 cats (8.33%) with anterior uveitis and anterior chamber abnormalities, 3 cats (5%) with corneal abnormalities and 2 cats (3.34%) with anterior uveitis with concurrent corneal involvement. There was a significant difference in the index values of IgM and IgG between seropositive and seronegative cats with T. gondii antibodies (p⟨0.05). There was no significant difference between the different ages, genders and breeds of cats with seroprevalence of T. gondii antibodies as well as between the age and total number of cats with seropositive and seronegative T. gondii. Out of 60 treated cats, 28 cats (46.7%), 25 cats (41.7%) and 7 cats (11.6%) showed complete, partial and poor response to treatment, respectively. In conclusion, cats showing ocular signs without obvious etiology should be examined serologically for toxoplasmosis and the seropositive cats should be treated with both specific topical and systemic treatments., (Copyright© by the Polish Academy of Sciences.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity-including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others-must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.

The ocular surface is facing various unspecific stress factors resulting in irritation and inflammation of the epithelia, causing discomfort to the patients. Ectoine is a bacteria-derived extremolyte with the ability to protect proteins and biological membranes from damage caused by extreme environmental conditions like heat, UV-light, high osmolarity, or dryness. Evidence from preclinical and clinical studies attest its effectiveness in treating several epithelium-associated inflammatory diseases, including the eye surface. In this review, we analysed 16 recent clinical trials investigating ectoine eye drops in patients with allergic conjunctivitis or with other unspecific ocular inflammations caused by e.g. ophthalmic surgery. Findings from these studies were reviewed in context with other published work on ectoine. In summary, patients with irritations and unspecific inflammations of the ocular surface have been treated successfully with ectoine-containing eye drops. In these patients, significant improvement was observed in ocular symptoms of allergic rhinoconjunctivitis, postoperative secondary dry eye syndrome, or ocular reepithelisation after surgery. Using ectoine as an add-on therapy to antihistamines, in allergy patients accelerated symptom relief by days, and its use as an add-on to antibiotics resulted in faster wound closure. Ectoine is a natural substance with an excellent tolerability and safety profile thus representing a helpful alternative for patients with inflammatory irritation of the ocular surface, who wish to avoid local reactions and side effects associated with pharmacological therapies or wish to increase the efficacy of standard treatment regimen., Competing Interests: AB reports personal fees from bitop AG. AH is employee of bitop AG. RM reports personal fees from ALK; grants from ASIT biotech; personal fees from Allergopharma; personal fees from Allergy Therapeutics; grants and personal fees from Bencard; grants from Leti, grants, personal fees, and nonfinancial support from Lofarma; nonfinancial support from Roxall; grants and personal fees from Stallergenes; grants from Optima; personal fees from Friulchem; personal fees from Hexal; personal fees from Servier; personal fees from Klosterfrau; nonfinancial support from Atmos; personal fees from Bayer; nonfinancial support from Bionorica; personal fees from FAES; personal fees from GSK; personal fees from MSD; personal fees from Johnson & Johnson; personal fees from Meda; personal fees and nonfinancial support from Novartis; nonfinancial support from Otonomy; personal fees from Stada; personal fees from UCB; nonfinancial support from Ferrero; grants from bitop AG; grants from Hulka; personal fees from Nuvo; and grants from Ursapharm, outside the submitted work., (Copyright © 2021 Andreas Bilstein et al.)

Nanomedicines offer nanoscale drug delivery system. They offer ways of promising drug transportation, and address the issues of lack of targeting and permeability of traditional drugs. The physical and chemical properties in the domain of nanomedicine applications in vivo have not been sufficiently delivered. What's more, the metabolic of nanomedicines is not clear enough. Those factors which mentioned above determine that many nanomedicines have not yet realized clinical application due to their safety problems and in vivo efficacy. For example, they may cause immune response and cytotoxicity, as well as the ability to clear organs in vivo, the penetration ability of them and the lack of targeting ability may also cause poor efficacy of drugs in vivo. In this review, the new progresses of different kinds of nanomedicines (including gold nanoparticles, nanorobots, black phosphorus nanoparticles, brain diseases, gene editing and immunotherapy etc.) in anti-tumor, antibacterial, ocular diseases and arteriosclerosis in recent years were summarized. Their shortcomings were pointed out, and the new methods to improve the biosafety and efficacy were summarized., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Importance: Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease., Objective: To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug., Design, Setting, and Participants: This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020., Interventions: Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism)., Main Outcomes and Measures: Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study., Results: A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy., Conclusions and Relevance: These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.

Eye diseases are currently a major public health concern due to the growing number of cases resulting from both an aging of populations and exogenous factors linked to our lifestyles. Thus, many treatments including surgical pharmacological approaches have emerged, and special attention has been paid to prevention, where diet plays a preponderant role. Recently, potential antioxidants such as resveratrol have received much attention as potential tools against various ocular diseases. In this review, we focus on the mechanisms of resveratrol against ocular diseases, in particular age-related macular degeneration, glaucoma, cataract, diabetic retinopathy, and vitreoretinopathy. We analyze, in relation to the different steps of each disease, the resveratrol properties at multiple levels, such as cellular and molecular signaling as well as physiological effects. We show and discuss the relationship to reactive oxygen species, the regulation of inflammatory process, and how resveratrol can prevent ocular diseases through a potential epigenetic action by the activation of sirtuin-1. Lastly, various new forms of resveratrol delivery are emerging at the same time as some clinical trials are raising more questions about the future of resveratrol as a potential tool for prevention or in therapeutic strategies against ocular diseases. More preclinical studies are required to provide further insights into RSV's potential adjuvant activity.

Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

Fungal keratitis (FK) is a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1 H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18 nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis.

Purpose : To report the clinical characteristics, treatment modalities and long term follow-up of 16 pediatric ocular acne rosacea patients. Methods : The medical records of pediatric ocular acne rosacea patients were reviewed. Results : There were 16 patients with a mean age of 7.7 ± 5 (1-16) years. The mean follow-up period was 52.8 ± 52 (3-150) months. Eight patients had skin involvement. The mean duration of delay for diagnosis was 16.2 ± 5.1 (4-48) months. Nine patients had a delayed diagnosis. Meibomitis, blepharitis, lid telangiectasia, and conjunctival hyperemia were present in all cases. Systemic antibiotics were prescribed in 12 patients. The mean delay in diagnosis was longer in patients with conjunctival/corneal involvement ( p = .001) and these patients required longer systemic treatment ( p = .001). Complete remission was achieved in 87.5% of cases. Conclusion : Children presenting with a long history of ocular irritation, meibomian gland disease, recurrent chalazia and peripheral corneal infiltrates should alert ophthalmologists to consider the diagnosis of ocular acne rosacea even in the absence of skin changes.

Introduction: Some medicinal plants have shown promising therapeutic potential for the management of the diseases. We aimed to systematically review the literature wherein the therapeutic effects of saffron have been studied on eye disorders., Methods: A systematic literature search was performed in PubMed, Scopus, Web of Science, Google scholar and other databases using eye disorders and saffron as key terms. No strict inclusion criteria were defined, and almost all clinical studies, as well as in vivo and in vitro studies were included. The reported data in each study were extracted and then qualitatively described., Results: Finally, 78 articles were found but only 29 relevant articles were included. Nine articles were clinical trials and 20 articles were studies conducted on cellular and molecular aspects of saffron on eye disorders. According to the included studies, crocin prevented the pro-inflammatory response in retinal cells and decreased glucose levels in diabetic mice. Also, crocetin prevented retinal degeneration and saffron protected photoreceptors from light-induced damage in retinal cells. Saffron also improved visual function in age-related macular edema and decreased intraocular pressure in patients with glaucoma. In addition, it was shown that crocin can improve best corrected visual acuity and decrease central macular thickness in patients with diabetic maculopathy., Conclusion: The results of this review indicated that saffron and its main ingredients such as crocin could be a potential candidate for the treatment of ocular disease especially eye inflammation; however, further clinical studies are needed to confirm such efficiency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Betaxolol is a relatively cardioselective β-adrenoceptor blocking drug, with no partial agonist (intrinsic sympathomimetic) activity and weak membrane-stabilizing (local anesthetic) activity. Betaxolol selectively and competitively binds to and blocks beta-1 (β1) adrenergic receptors in the heart, thereby decreasing cardiac contractility and rate. This leads to a reduction in cardiac output and lowers blood pressure. When applied topically in the eye, this agent reduces aqueous humor secretion and lowers the intraocular pressure (IOP). In addition, betaxolol prevents the release of renin, a hormone secreted by the kidneys that causes constriction of blood vessels. Betaxolol (S)-(-)-enantiomer shows higher pharmacological activity. This chapter provides a complete review of nomenclature, physiochemical properties, methods of preparation, identification techniques and various qualitative and quantitative analytical techniques as well as pharmacology of betaxolol. In addition, the chapter also includes review of several methods for enantiomeric separation betaxolol using chromatographic techniques., (© 2021 Elsevier Inc. All rights reserved.)

ANCA+ associated vasculitis (AAV) is a group of rare diseases with potentially vision-threatening complications. Ocular and orbital complications of these diseases are caused by vasculitis of the small vessels of the eye or by granulomatous mass formation. ANCA (anti-neutrophil cytoplasmic antibodies) represent a key component of pathophysiological pathways as well as a diagnostic marker. Various manifestations are reported in literature, scleritis and episcleritis being the most common, followed by pseudotumor orbitae. In vision-threatening orbital or ocular disease, aggressive systemic treatment with a combination of high-dose glucocorticoids and either cyclophosphamide or rituximab is needed. Certain cases require locoregional surgical management to preserve ocular integrity or vision. Ocular involvement of AAV remains a challenge in clinical practice, requiring multi-specialty cooperation in order to ensure the best possible visual outcome. Abbreviations: AAV = ANCA+ associated vasculitis, ANCA = anti-neutrophil cytoplasmic antibodies, GPA = granulomatosis with polyangiitis, EGPA = eosinophilic granulomatosis with polyangiitis, MPA = microscopic polyangiitis., (©Romanian Society of Ophthalmology.)

We describe the case of a HIV-infected patient, in whom a secondary syphilis with skin lesions and ocular involvement developed. On admission papular skin rash and partial visual loss with left eye were observed. Serological tests for syphilis were positive in very high titers. Ophthalmological examination revealed ocular abnormalities indicating ocular syphilis. Cerebrospinal fluid (CSF) tests showed elevated concentration of immunoglobulin G (IgG) with normal white blood count and albumin concentration, serological treponemal tests for syphilis were positive. Intravenous therapy with Penicillinum Crystallisatum (Benzylpenicillinum kalicum) was administered, according to the neurosyphilis treatment schedule, achieving resolution of the skin lesions and partial vision improvement, a month after the end of the treatment a complete recovery of the vision was noted. Serological tests` for syphilis titers decreased fourfold. Described case confirms reasonability of examination for syphilis in patients with sudden vision disturbances, especially those HIV-infected. It also indicates that early appropriate treatment of the ocular syphilis prevents permanent loss of vision., (© National Institute of Public Health NIH – National Research Institute.)

Tissue cells of the eye are sensitive to oxidative stress, leading to oxidative damage and inflammation, which have crucial roles in the pathogenesis of most of the eye diseases. Moreover, factors such as age, angiogenesis, ischemia, genetic predisposition, diabetes, obesity, and smoking affect the onset and progression of ocular anomalies. Major eye diseases are either age-related such as age-related macular degeneration, cataracts, diabetic retinopathy, glaucoma, dry eye, or inflammatory eye diseases such as blepharitis, conjunctivitis, uveitis and other retinal pathologies, which can cause ocular damage and visual problems through oxidative stress, inflammation pathways. Although there are conventional chemical or surgical treatments, due to their mainly antiapoptotic, anti- inflammatory and antioxidant properties, phytotherapeutic preparations and their natural compounds can be applied to prevent or treat eye disease as follows: oral, topical or both. Thus, this study aims to comprehensively evaluate the pre-clinical and clinical studies of the phytotherapeutics and natural compounds used in the prevention and treatment of common serious and painful eye diseases. Moreover, for the first time, nature-derived preparations/supplements commonly used for eye problems also included in this review to present applications of the extracts/compounds in the pharmaceutical field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present review paper focuses on the chemistry of oxidative stress mitigation by antioxidants. Oxidative stress is understood as a lack of balance between the pro-oxidant and the antioxidant species. Reactive oxygen species in limited amounts are necessary for cell homeostasis and redox signaling. Excessive reactive oxygenated/nitrogenated species production, which counteracts the organism's defense systems, is known as oxidative stress. Sustained attack of endogenous and exogenous ROS results in conformational and oxidative alterations in key biomolecules. Chronic oxidative stress is associated with oxidative modifications occurring in key biomolecules: lipid peroxidation, protein carbonylation, carbonyl (aldehyde/ketone) adduct formation, nitration, sulfoxidation, DNA impairment such strand breaks or nucleobase oxidation. Oxidative stress is tightly linked to the development of cancer, diabetes, neurodegeneration, cardiovascular diseases, rheumatoid arthritis, kidney disease, eye disease. The deleterious action of reactive oxygenated species and their role in the onset and progression of pathologies are discussed. The results of oxidative attack become themselves sources of oxidative stress, becoming part of a vicious cycle that amplifies oxidative impairment. The term antioxidant refers to a compound that is able to impede or retard oxidation, acting at a lower concentration compared to that of the protected substrate. Antioxidant intervention against the radicalic lipid peroxidation can involve different mechanisms. Chain breaking antioxidants are called primary antioxidants, acting by scavenging radical species, converting them into more stable radicals or non-radical species. Secondary antioxidants quench singlet oxygen, decompose peroxides, chelate prooxidative metal ions, inhibit oxidative enzymes. Moreover, four reactivity-based lines of defense have been identified: preventative antioxidants, radical scavengers, repair antioxidants, and those relying on adaptation mechanisms. The specific mechanism of a series of endogenous and exogenous antioxidants in particular aspects of oxidative stress, is detailed. The final section resumes critical conclusions regarding antioxidant supplementation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: Rosacea is one of the most common conditions affecting the ocular surface. The purpose of this review is to provide an update on the pathogenesis and treatment of rosacea based on the dermatology and ophthalmology literatures., Methods: Literature searches were conducted for rosacea and ocular rosacea. Preference was given to systematic reviews, meta-analysis, case-controlled studies, and documented case reports while excluding poorly documented case studies and commentaries. The data were examined and independently analyzed by more than two of the authors., Results: Rosacea is a complex inflammatory condition involving the pilosebaceous unit. Its underlying mechanism involves an interplay of the microbiome, innate immunity, adaptive immunity, environmental triggers, and neurovascular sensitivity. The latest classification of rosacea includes three dermatologic subgroups and a fourth subgroup, ocular rosacea. Ocular rosacea clinically displays many features that are analogous to the cutaneous disease, such as lid margin telangiectasia and phlyctenulosis. The role of environmental triggers in the exacerbation of ocular rosacea appears to be understudied. While lid hygiene and systemic treatment with tetracycline drugs remain the mainstay of treatment for ocular rosacea, newer dermatologic targets and therapies may have potential application for the eye disease., Conclusions: Ocular rosacea appears to embody many of the manifestation of the dermatologic disease. Hence, the basic pathophysiologic mechanisms of the ocular and cutaneous disease are likely to be shared. Better understanding of the ocular surface microbiome and the immunologic mechanisms, may lead to novel approaches in the management of ocular rosacea.

Several ocular drug delivery (ODD) systems, like hydrogels, microparticles, nano-emulsions, micro-emulsions, and liposomes have been researched, which can govern the drug release and sustain therapeutic levels for a delayed period in the eye. While new drugs targeting methods to the eye are possible by various nanoparticles. Presently in the market, there are fewer choices and need for novel nano-ocular delivery systems as well as therapies for prolonged delivery to the anterior and posterior eye segments. The primary objective of this article is to summarize current discoveries and proven activities of different nano- and microsystems in ODD. This article also depicts some regulatory updates along with the patents granted to the inventor for their work on ODD. Overall, a thought of how the different forthcoming of nanotechnologies like nanoparticles and nanomedicine can be used to investigate the frontiers of ODD and treatment can be withdrawn by this article.

Curcumin is one of the most valuable natural products due to its pharmacological activities. However, the low bioavailability of curcumin has long been a problem for its medicinal use. Large studies have been conducted to improve the use of curcumin; among these studies, curcumin metabolites have become a relatively new research focus over the past few years. Additionally, accumulating evidence suggests that curcumin or curcuminoid metabolites have similar or better biological activity than the precursor of curcumin. Recent studies focus on the protective role of plasma tetrahydrocurcumin (THC), a main metabolite of curcumin, against tumors and chronic inflammatory diseases. Nevertheless, studies of THC in eye diseases have not yet been conducted. Since ophthalmic conditions play a crucial role in worldwide public health, the prevention and treatment of ophthalmic diseases are of great concern. Therefore, the present study investigated the antioxidative, anti-inflammatory, antiangiogenic, and neuroprotective effects of THC on four major ocular diseases: age-related cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). While this study aimed to show curcumin as a promising potential solution for eye conditions and discusses the involved mechanistic pathways, further work is required for the clinical application of curcumin.

Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to "protect, seal, and heal". Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.

Background: To report a pilot experience of telemedicine in ophthalmology in open-care modality (i.e. direct video call), in a confinement period due to the COVID-19 pandemic., Methods: Descriptive study of the demographic and clinical characteristics of patients attended in a 10-week confinement period. Reported satisfaction of the participating patients and doctors was evaluated through an online survey., Results: In the 10-week period, 291 ophthalmologic telemedicine consultations were performed. The main reasons for consultation were inflammatory conditions of the ocular surface and eyelids (79.4%), followed by administrative requirements (6.5%), non-inflammatory conditions of the ocular surface (5.2%), strabismus suspicion (3.4%) and vitreo-retinal symptoms (3.1%). According to previously defined criteria, 22 patients (7.5%) were referred to immediate face-to-face consultation. The level of satisfaction was high, both in doctors (100%) and in patients (93.4%)., Conclusions: Open-care modality of telemedicine in ophthalmology during the pandemic period is a useful instrument to filter potential face-to-face consultations, either elective or emergency, and potentially reduce the risk of COVID-19 infection., (Copyright © 2020 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)- block -poly(ε-caprolactone) (PEG- b -PCL) and poly(ethylene glycol)- block -poly(lactic acid) (PEG- b -PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG- b -PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG- b -PLA micelles, respectively. The drug loading capacity was in the range of 6-12% and 15-25% for PEG- b -PCL and PEG- b -PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG- b -PCL and PEG- b -PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG- b -PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG- b -PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG- b -PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur frequently and contribute to morbidity and reduced quality of life. The musculoskeletal, ocular and cutaneous organ systems are frequently involved in IBD-related EIMs. By focusing on manifestations involving the joints, skin and eyes, this review will discuss the most common clinically relevant and burdensome EIMs that affect IBD patients, and strives for early recognition, adequate treatment and timely referral. For this purpose, we aimed to create a comprehensive overview on this topic, with the main focus on the treatment of reactive and associated EIMs, including spondyloarthropathies, pyoderma gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently developed biologicals enable simultaneous treatment of inflammatory disorders. This review can be used as a helpful guide in daily clinical practice for physicians who are involved in the treatment of IBD patients.

The ability of the adrenocorticotropic hormone (ACTH) to induce steroidogenesis and upregulate anti-inflammatory processes has long been known. More recently, however, extrasteroidal mechanisms, through which ACTH exerts anti-inflammatory processes, have been described. This has renewed hope that ACTH can combat inflammatory conditions even when resistant to steroids. This review article summarizes the literature on the use of ACTH in ocular disease. Unfortunately, much of the data regarding the clinical utility of ACTH are outdated, with many studies published in the 1950s and 1960s. Many of these older studies are inconsistent or incomplete with their reporting, making it difficult to ascertain the meaning of the outcomes. Despite the limitations, 2 important trends are evident. First, when used to treat an inflammatory disease, ACTH can be effective at decreasing or eliminating ocular inflammation, even in a refractory disease resistant to multiple treatment modalities. Second, adverse effects of ACTH are rare and are most likely to be reported with relatively high doses of ACTH therapy. Taken as a whole, these studies offer initial promising data that ACTH may be a safe and effective alternative in refractory ocular inflammatory disease. However, they highlight an important lack of prospective data to more rigorously understand the true safety and efficacy of this therapy.

Purpose of Review: Ocular manifestations of leprosy do occur despite advances in the areas of leprosy research. Understanding the nuances in the domain shall guide the clinician for effective patient-centered care., Recent Findings: Despite the existence of microbiologic cure for leprosy, ocular manifestations of this disease do occur. Advances in genetic and genomic studies have better characterized the interaction that the bacteria has with the host. The ocular features vary with the spectrum of the disease. Its careful correlation can help to predict the bacillary load of the patient. Investigations are particularly relevant in multibacillary cases. The WHO suggests a treatment duration longer than the 2 years in ocular involvement., Summary: The isolation of lepra bacilli from the iris biopsy in negative skin smear patients and multidrug therapy completion highlights the potential role of bactericidal agents in the planned intraocular treatment. Lepra reactions need careful titration of oral steroids and appropriate antibacterial agents. Advances in phacoemulsification with in the bag implantation of intraocular lenses is a game changer in the management of the most common cause of blindness of leprosy. Advances in vaccine research in leprosy are promising.