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Topical ophthalmic drug product development is a niche research domain as the drug formulations need to be designed to perform in the unique ocular physiological conditions. The most common array of small molecule drug formulations intended for topical ophthalmic administration include solutions, suspensions, emulsions, gels, and ointments. The formulation components such as excipients and container closure are unique to serve the needs of topical ophthalmic delivery compared to other parenteral products. The selection of appropriate formulation platform, excipients, and container closure for delivery of drugs by topical ophthalmic route is influenced by a combination of factors like physicochemical properties of the drug molecule, intended dose, pharmacological indication as well as the market trends influenced by the patient population. In this review, data from literature and packaging inserts of 118 reference listed topical ophthalmic medications marketed in the US are collected and analyzed to identify trends that would serve as a guidance for topical ophthalmic formulation development for small molecule drugs. Specifically, the topics reviewed include current landscape of the available small molecule topical ophthalmic drug products in the US, physicochemical properties of the active pharmaceutical ingredients (APIs), formulation platforms, excipients, and container closure systems., Competing Interests: Declaration of Competing Interest Anand Ubhe, Heidi Oldenkamp, Ke Wu are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The forkhead box protein O3 (FOXO3a) belongs to the subgroup O of the forkhead transcription factor family and plays an important role in regulating the aging process by participating in the regulation of various life processes, including cell cycle arrest, apoptosis, autophagy, oxidative stress, and DNA repair. The eye is an organ that is affected by aging earlier. However, the functional role and potential clinical applications of FOXO3a in age-related eye diseases have not received widespread attention and lacked comprehensive and clear clarification. In this review, we demonstrated the relationship between FOXO3a and visual system health, summarized the functional roles of FOXO3a in various eye diseases, and potential ocular-related therapies and drugs targeting FOXO3a in visual system diseases through a review and summary of relevant literature. This review indicates that FOXO3a is an important factor in maintaining the normal function of various tissues in the eye, and is closely related to the occurrence and development of ophthalmic-related diseases. Based on its vital role in the normal function of the visual system, FOXO3a has potential clinical application value in related ophthalmic diseases. At present, multiple molecules and drugs targeting FOXO3a have been reported to have the potential for the treatment of related ophthalmic diseases, but further clinical trials are needed. In conclusion, this review can facilitate us to grasp the role of FOXO3a in the visual system and provide new views and bases for the treatment strategy research of age-related eye diseases., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ocular inflammation-associated diseases are leading causes of global visual impairment, with limited treatment options. Adiponectin, a hormone primarily secreted by adipose tissue, binds to its receptors, which are widely distributed throughout the body, exerting powerful physiological regulatory effects. The protective role of adiponectin in various inflammatory diseases has gained increasing attention in recent years. Previous studies have confirmed the presence of adiponectin and its receptors in the eyes. Furthermore, adiponectin and its analogs have shown potential as novel drugs for the treatment of inflammatory eye diseases. This article summarizes the evidence for the interplay between adiponectin and inflammatory eye diseases and provides new perspectives on the diagnostic and therapeutic possibilities of adiponectin., 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 © 2024 Elsevier Inc. All rights reserved.)

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melatonin, a versatile hormone produced by the pineal gland, has garnered considerable scientific interest due to its diverse functions. In the eye, melatonin regulates a variety of key processes like inhibiting angiogenesis by reducing vascular endothelial growth factor levels and protecting the blood-retinal barrier (BRB) integrity by enhancing tight junction proteins and pericyte coverage. Melatonin also maintains cell health by modulating autophagy via the Sirt1/mTOR pathways, reduces inflammation, promotes antioxidant enzyme activity, and regulates intraocular pressure fluctuations. Additionally, melatonin protects retinal ganglion cells by modulating aging and inflammatory pathways. Understanding melatonin's multifaceted functions in ocular health could expand the knowledge of ocular pathogenesis, and shed new light on therapeutic approaches in ocular diseases. In this review, we summarize the current evidence of ocular functions and therapeutic potential of melatonin and describe its roles in angiogenesis, BRB integrity maintenance, and modulation of various eye diseases, which leads to a conclusion that melatonin holds promising treatment potential for a wide range of ocular health conditions., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Injectable hydrogels based on biopolymers, fabricated utilizing diverse chemical and physical methodologies, exhibit exceptional physical, chemical, and biological properties. They have multifaceted applications encompassing wound healing, tissue regeneration, and across diverse scientific realms. This review critically evaluates their largely uncharted potential in ophthalmology, elucidating their diverse applications across an array of ocular diseases. These conditions include glaucoma, cataracts, corneal disorders (spanning from age-related degeneration to trauma, infections, and underlying chronic illnesses), retina-associated ailments (such as diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration (AMD)), eyelid abnormalities, and uveal melanoma (UM). This study provides a thorough analysis of applications of injectable hydrogels based on biopolymers across these ocular disorders. Injectable hydrogels based on biopolymers can be customized to have specific physical, chemical, and biological properties that make them suitable as drug delivery vehicles, tissue scaffolds, and sealants in the eye. For example, they can be engineered to have optimum viscosity to be injected intravitreally and sustain drug release to treat retinal diseases. Their porous structure and biocompatibility promote cellular infiltration to regenerate diseased corneal tissue. By accentuating their indispensable role in ocular disease treatment, this review strives to present innovative and targeted approaches in this domain, thereby advancing ocular therapeutics., 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 © 2024 Elsevier B.V. All rights reserved.)

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science)., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Eyes are directly exposed to the outer environment and susceptible to infections, leading to various ocular disorders. Local medication is preferred to treat eye diseases due to its convenience and compliance. However, the rapid clearance of the local formulations highly limits the therapeutic efficacy. In the past decades, several carbohydrate bioadhesive polymers (CBPs), such as chitosan and hyaluronic acid, have been used in ophthalmology for sustained ocular drug delivery. These CBP-based delivery systems have improved the treatment of ocular diseases to a large extent but also caused some undesired effects. Herein, we aim to summarize the applications of some typical CBPs (including chitosan, hyaluronic acid, cellulose, cyclodextrin, alginate and pectin) in treating ocular diseases from the general view of ocular physiology, pathophysiology and drug delivery, and to provide a comprehensive understanding of the design of the CBP-based formulations for ocular use. The patents and clinical trials of CBPs for ocular management are also discussed. In addition, a discussion on the concerns of CBPs in clinical use and the possible solutions is presented., 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 © 2023 Elsevier B.V. All rights reserved.)

Luliconazole (LCZ) is a novel antifungal imidazole with broad-spectrum and high susceptibility of Aspergillus and Fusarium are the dominant species of fungal keratitis, may potentially be a new medical treatment option for ocular fungal infection. To evaluate LCZ distribution in ocular tissues after topical application for the development of ophthalmic delivery system, it is important to have a bioanalytical method for measuring the drug concentrations in different ocular tissues and aqueous humor (AH). A selective and sensitive ultrahigh performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantification of LCZ in rabbit ocular tissues, including conjunctiva, cornea, AH, iris, lens, vitreous humor (VH), retinal choroid and sclera, using lanoconazole as internal standard (IS). Chromatographic separation was achieved on a Xterra MS, C18 column (2.1 × 50 mm, 3.5 μm) using mobile phase with formic acid solution (0.2%, v/v): acetonitrile (50:50, v/v) at a flow rate of 0.2 ml/min, and the run time was 2.5 min. Detection was performed using the transitions 354.1 → 150.3 m/z for LCZ and 320.1 → 150.3 m/z for IS by positive ion electrospray ionization in multiple reaction monitoring (MRM) mode. Method validation was conducted in accordance with U.S. Food and Drug Administration's regulatory guidelines for bioanalytical method validation. The calibration curves were linear over the concentration range from 2.80 ng/ml to 2038 ng/ml for conjunctiva, cornea and sclera, 2.09 ng/ml to 1019 ng/ml for AH, 2.09 ng/ml to 509.5 ng/ml for iris, 2.09 ng/ml to 203.8 ng/ml for retinal choroid and VH, 2.04 ng/ml to 101.9 ng/ml for lens, with all the squared correlation coefficients (r 2 ) more than 0.99. The accuracy of the method was within the acceptable limit of 89.34%∼112.78% at the lower limit of quantification and other concentrations, Inter-day and intra-day precision values, expressed in terms of RSD (%), in all tissues were within 15% at all concentrations. The mean recoveries of LCZ in rabbit ocular tissues was 84.85%∼100.52%. No interference was found due to matrix components. Luliconazole was stable during the stability studies, including autosampler stability, benchtop stability, freeze/thaw stability and long-term stability. The method was successfully applied to the ocular pharmacokinetic and tissues distribution studies of LCZ in rabbit after topical administration of LCZ ophthalmic drug delivery system., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Newer antiepileptic drugs such as levetiracetam, lacosamide, topiramate, gabapentin, oxcarbazepine, lamotrigine, and zonisamide are prescribed by physicians for the treatment of epilepsy. These drugs are also associated with a series of eye disorders. However, very few studies have systemically compared eye disorders associated with newer AEDs in a large sample of patients diagnosed with epilepsy., Objective: This study aimed to evaluate the association between eye disorders and several newer AEDs, and also to examine the differences in the frequency of adverse events across individual AEDs through data mining of the self-reporting US Food and Drug Administration Adverse Event Report System (FAERS) database., Methods: The definition relied upon system organ class and preferred terms according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was used to detect the risk signals from the FAERS database. The proportional reporting ratio, and χ2 (chi-square) values were calculated to assess the association between AEs and AED use., Results: FAERS reports for 158,095 cases from January 1 of 2015 to September 30 of 2020 were included. AEDs were associated with a series of eye-related AEs that were defined by 106 preferred terms and could be classified into 10 aspects., Conclusion: There is variation in the types and severity of eye-related AEs across individual AEDs. Typically, topiramate and lamotrigine are more likely to cause serious eye-related AEs. In contrast, lacosamide rarely results in any severe eye-related AEs, and only diplopia and metamorphopsia are significant. levetiracetam tends to produce ocular neuromuscular disorder-related AEs. Macula-related AEs are associated with gabapentin. zonisamide appears to be closely associated with choroidal effusion and angle-closure glaucoma. oxcarbazepine is primarily associated with several cornea-related AEs., (Copyright © 2022. Published by Elsevier Ltd.)

Dirofilariasis is an emerging zoonosis caused by nematodes of the genus Dirofilaria, most often D. repens and D. immitis. The main final hosts and reservoirs of pathogens are dogs. The intermediate hosts and vectors of infection are female mosquitoes (Culicidae). Human is an accidental host in which the parasite does not usually mature. Over the past 20 years, the range of Dirofilaria spp. in Europe has expanded. We present an unusual case of multifocal dirofilariasis of mixed subcutaneous-ocular course caused by D. repens in a 52-year-old Polish patient who was probably infected in Spain or Croatia, where she stayed one year before the onset of symptoms. Surgical removal of the nematodes followed by treatment with Ivermectin in a single dose of 1200 μg and Doxycycline 200 mg daily for 7 days resulted in complete recovery. We believe that all cases of human dirofilariasis, especially in countries where the disease is not frequent at present, should be registered for epidemiological purposes. Moreover, due to the widening of the range of D. repens and D. immitis occurrence and the possibility of atypical courses of infection with both nematodes, diagnostics should include the species identification of the parasite., (Copyright © 2021 Elsevier B.V. All rights reserved.)

An increasing number of people worldwide are affected by eye diseases, eventually leading to visual impairment or complete blindness. Conventional treatment involves the use of eye drops. However, these formulations often confer low ocular bioavailability and frequent dosing is required. Therefore, there is an urgent need to develop more effective drug delivery systems to tackle the current limitations. Hydrogels are multifunctional ophthalmic drug delivery systems capable of extending drug residence time and sustaining release of drugs. In this review, common ocular diseases and corresponding therapeutic drugs are briefly introduced. In addition, various types of hydrogels reported for ophthalmic drug delivery, including in-situ gelling hydrogels, contact lenses, low molecular weight supramolecular hydrogels, cyclodextrin/poly (ethylene glycol)-based supramolecular hydrogels and hydrogel-forming microneedles, are summarized. Besides, marketed hydrogel-based opthalmic formulations and clinical trials are also highlighted. Finally, critical considerations regarding clinical translation of biologics-loaded hydrogels are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to provide evidence on the therapeutic prescribing activity by community optometrists in Scotland and to determine its impact on workload in general practice and ophthalmology clinics., Study Design: Scottish administrative healthcare data for a 53-month period (November 2013-April 2018) were used to analyse non-medical prescribing practice by optometrists., Methods: Using interrupted time-series regression (Autoregressive Integrated Moving Average), we assessed the impact of optometrist prescribing on ophthalmology outpatient attendances and general practice prescribing for eye disorders., Results: A total of 54,246 items were prescribed by 205 optometrists over the study period. Since the commencement of data recording, optometrist prescribing activity increased steadily from a baseline of zero to 1.2% of all ophthalmic items prescribed. Neither the monthly number of items prescribed nor the size of optometric workforce were associated with a reduction in ophthalmology outpatient appointments over time., Conclusions: Optometrists increasingly contribute to community ophthalmic prescribing in Scotland, releasing capacity and lessening general practice, but not secondary care workload. There appears to be an underutilisation of optometrists related to the management of dry eye, which represents an opportunity to release further capacity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To estimate temporal trends in total and out-of-pocket (OOP) expenditures for ophthalmic prescription medications among adults in the United States., Design: Retrospective, longitudinal cohort study., Participants: Participants in the 2007 through 2016 Medical Expenditure Panel Survey (MEPS) 18 years of age or older. The MEPS is a nationally representative survey of the noninstitutionalized, civilian United States population., Methods: We estimated trends in national and per capita annual ophthalmic prescription expenditures by pooling data into 2-year cycles and using weighted linear regressions. We also identified characteristics associated with greater total or OOP expenditures with multivariate weighted linear regression. Costs were adjusted to 2016 United States dollars using the gross domestic product price index., Main Outcome Measures: Trends in total and OOP annual expenditures for ophthalmic medications from 2007 through 2016 as well as factors associated with greater expenditures., Results: From 2007 through 2016, 9989 MEPS participants (4.2%) reported ophthalmic medication prescription use. Annual ophthalmic medication use increased from 10.0 to 12.2 million individuals from 2007 and 2008 through 2015 and 2016. In this same period, national expenditures for ophthalmic medications increased from $3.39 billion to $6.08 billion and OOP expenditures decreased from $1.34 to $1.18 billion. Per capita expenditure increased from $338.72 to $499.42 (P < 0.001), and per capita OOP expenditure decreased from $133.48 to $96.67 (P < 0.001) from 2007 and 2008 through 2015 and 2016, respectively. From 2015 through 2016, dry eye (29.5%) and glaucoma (42.7%) medications accounted for 72.2% of all ophthalmic medication expenditures. Patients who were older than 65 years (P < 0.001), uninsured (P < 0.001), and visually impaired (P < 0.001) were significantly more likely to have greater OOP spending on ophthalmic medications., Conclusions: Total ophthalmic medication expenditure in the United States increased significantly over the last decade, whereas OOP expenses decreased. Increases in coverage, copayment assistance, and use of expensive brand drugs may be contributing to these trends. Policy makers and physicians should be aware that rising overall drug expenditures ultimately may increase indirect costs to the patient and offset a decline in OOP prescription drug spending., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Liposomes, lipid-based vesicular systems, have attracted major interest as a means to improve drug delivery to various organs and tissues in the human body. Recent literature highlights the benefits of liposomes for use as drug delivery systems, including encapsulating of both hydrophobic and hydrophilic cargos, passive and active targeting, enhanced drug bioavailability and therapeutic effects, reduced systemic side effects, improved cargo penetration into the target tissue and triggered contents release. Pioneering work of liposomes researchers led to introduction of long-circulating, ligand-targeted and triggered release liposomes, as well as, liposomes containing nucleic acids and vesicles containing combination of cargos. Altogether, these findings have led to widespread application of liposomes in a plethora of areas from cancer to conditions such as cardiovascular, neurologic, respiratory, skin, autoimmune and eye disorders. There are numerous review articles on the application of liposomes in treatment of cancer, which seems the primary focus, whereas other diseases also benefit from liposome-mediated treatments. Therefore, this article provides an illustrated detailed overview of liposomal formulations, in vitro characterization and their applications in different disorders other than cancer. Challenges and future directions, which must be considered to obtain the most benefit from applications of liposomes in these disorders, are discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Collapsin response-mediator protein 5 (CRMP5) immunoglobulin G (IgG) has been associated with paraneoplastic optic neuritis, vitritis, retinitis, or a combination thereof, but few reports of these findings exist in the literature. We reviewed the neuro-ophthalmic findings and visual outcomes in a large series of CRMP5 IgG-positive patients to characterize further its clinical phenotype and response to treatment., Design: Retrospective case series., Participants: Seventy-six patients with CRMP5 autoimmunity examined at the Mayo Clinic, Rochester, Minnesota., Methods: Single academic medical center chart review of all CRMP5 IgG-positive (serum titer, >1:240) patients seen between 2001 and 2017., Main Outcome Measures: Neuro-ophthalmic manifestations and outcomes of CRMP5 autoimmunity, coexisting neural autoantibody presence and paraneoplastic associations, and the impact of immunosuppressant therapy., Results: Twenty-nine of 76 patients (38%) demonstrated neuro-ophthalmic manifestations. Of the 29 patients with neuro-ophthalmic findings, the median age was 67 years (range, 33-88 years) and 20 (69%) were women. Cancer was diagnosed in 62% of the patients (small-cell carcinoma in 83%). Neuro-ophthalmic symptoms occurred before the diagnosis of cancer in 72%. Seventeen of 29 patients (59%) showed ocular (i.e., anterior visual pathway or intraocular) manifestations; presenting median visual acuity was 20/50 (range, 20/20-counting fingers) and the final median visual acuity was 20/40 (range, 20/20-hand movements). Fourteen of 17 patients (82%) demonstrated optic neuropathy, with 12 of these patients also showing retinitis or uveitis. Three of 17 patients (18%) showed retinitis or uveitis without optic neuropathy. All 12 patients with optic neuropathy and a documented fundus examination at visual symptom onset demonstrated optic disc edema. No patients showed optic nerve enhancement on magnetic resonance imaging. Twelve of 29 patients (41%) demonstrated ocular motility dysfunction consisting of central nystagmus and diplopia. Among those receiving immunosuppressive therapy, visual function improved in 50%., Conclusions: In our cohort of 29 CRMP5 IgG-positive patients with neuro-ophthalmic manifestations, optic neuropathy presented with optic disc edema, often associated with uveitis, retinitis, or both. The combination of retinitis, vitritis, and optic disc edema without optic nerve enhancement should prompt serologic testing for CRMP5 IgG to expedite vision-sparing immunosuppressant therapy and a targeted search for a systemic cancer., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Treatment of majority of eye diseases involve the use of eye drops or eye ointments, which have major drawbacks of needing frequent administration, lower bioavailability and inability to cross the various eye barriers. This necessitates the use of novel delivery systems. Microneedles (MNs) as an alternate novel delivery system facilitate drug delivery to various ocular diseases with promising approaches in healthcare. Advances in pharmaceutical technology have made MNs provide localized, effective, less invasive and targeted drug delivery in the eye. The purpose of this review is to provide an insight to efficacious therapeutic applications the MNs can bring in various ocular diseases. Out of which, glaucoma, age-related macular degeneration, uveitis, retinal vascular occlusion and retinitis pigmentosa are majorly discussed. Among the various types of MNs; solid coated, hollow and dissolving polymeric MNs are specifically focused for their applications in ocular diseases. In addition, MNs shows improvement in the visual acuity and decreases the progression of the different ocular diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To compare United States and international drug pricing for commonly prescribed intravitreal and topical ophthalmic medications., Design: Cross-sectional observational study., Methods: For 25 commonly used ophthalmic medications (3 intravitreal, 22 topical), we obtained 2017 third quarter United States average wholesale price (AWP), drug acquisition cost, or consumer pricing through United States government health insurance plans (Veterans Affairs [VA], Medicaid, Medicare Part B, and Medicare Part D) and commercial drug plans (CVS Caremark and Navitus Health Solutions), online pricing without insurance through a large United States warehouse retailer (Costco), and international drug pricing through government-sponsored health plans in Italy, Spain, Turkey, Canada, and Japan., Main Outcome Measures: Drug acquisition costs and consumer pricing of ophthalmic drugs through various payment systems. All prices were converted to United States dollars., Results: For intravitreal medications in the United States, aflibercept and ranibizumab were priced similarly to each other and were more expensive than dexamethasone implants. Pricing of aflibercept and ranibizumab through government health insurance plans in Italy, Spain, Turkey, Canada, and Japan were less expensive by as much as 84.3% compared with the United States. For topical medications in the United States, pricing varied significantly both across different classes of medications and also between nonbranded and branded medications. Drug acquisition costs through the VA and Medicaid were inexpensive on average, but pricing through a hospital-employee drug insurance plan offered the smallest range (between $2.35 and $60.00). In all 5 non-United States countries studied, each topical medication with the exceptions of cyclosporine emulsion and difluprednate was less than $100, and 94.4% of topical medications in these countries had a nonbranded or branded option that was less than $50., Conclusions: In the United States, for topical more than intravitreal medications, significant price variation exists across both different drug pricing systems and different medications. Price differentials between nonbranded and branded medications can be significant. Internationally, topical medications exhibited a more limited and lower price range compared with drug pricing in the United States., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This report describes a 10-month-old dog with a sudden loss of vision and severe dyspnoea. The ocular examination revealed bilateral panuveitis, lens subluxation, secondary glaucoma, and retinal detachment. In addition, the ocular ultrasound showed in the vitreous body of the right eye, a small doubled-lined foreign body compatible with an intraocular parasite. Radiographs of the thorax revealed an increased opacity with mixed lung pattern (alveolar and bronchial) and thoracic ultrasonography showed several subpleural nodules. The presence of Angiostrongylus vasorum first stage larvae was confirmed with 324 larvae per gram of feces and an antigen test for the parasite (AngioDetect, IDEXX) also yielded a positive result. The severe and irreversible ocular lesions described in this case enhanced the complexity of the clinical picture of canine angiostrongylosis. Infection with the parasite should be included in the list of differential diagnoses for ocular uveitis to avoid potentially serious complications related to a missed or delayed diagnosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There has been a trend in the past five years in Jordan for ophthalmic anticholinergic preparations to be misused or abused. This is done mainly to experience mental altering effects such as mood changes, euphoria or hallucinations. Such products are mostly obtained from community pharmacies without a prescription., Objectives: This study aimed to observe the requests of ophthalmic preparations in community pharmacies in Amman, Jordan, and evaluating the most popular and frequently requested ophthalmic drops suspected of abuse. Also, it aimed to describe the current methods that Jordanian community pharmacists use to manage such requests., Methods: A prospective cross-sectional observational study was conducted between November 2016 and January 2017 at sixteen different community pharmacies in Amman. All ophthalmic products requested were observed during this period., Results: A total of 140 ophthalmic product requests for 130 customers were observed. Dry eye was the most common complaint for which the customer requested the medication (n = 30, 23.1%) and direct self-medication (ie-requesting the product by name), was the most frequent method of purchase (n = 63, 48.5%). In 19 cases (14.6%), product requests were suspected to be for non-medical (ie-abuse) purposes. Most of the suspected cases were for Pentolate ® (n = 11, 57.9%), whereas 7 were for Prisoline ® (36.8%) and 1 for Naphcon-A ® (5.3%). The majority of observed cases were for products requested without a prescription (n = 16, 84.2%), and in 12 cases out of which, sale was refused (63.2%)., Conclusion: More effort and enforcement of pharmacy regulation for safe dispensing is needed to reduce the abuse of ophthalmic products. Educating pharmacists and ophthalmologists would help raise awareness and control the type of drug abuse., (Copyright © 2019 Elsevier Inc. All rights reserved.)

With the significant advances made in nanotechnology, research efforts focused on developing novel drug delivery platforms that can overcome the multitude of challenges encountered in ophthalmic drug delivery. Surface active agents (SAAs) have been extensively used for the formulation of many of the dosage forms targeting ocular tissues. Novel ophthalmic carriers utilizing SAAs were broadly classified into particulate, vesicular, and controlled release drug delivery systems. Depending on their physicochemical properties, SAAs can perform a variety of roles ranging from wetting agents, emulsifiers, stabilizers, charge inducers, solubilizers, antimicrobial agents, corneal permeation enhancers, and gelling agents. Nevertheless, their use is limited by their potential toxicity and possible interactions with other formulation ingredients. This review provides a comprehensive analysis of the different functional roles of SAAs in novel ophthalmic drug delivery platforms, their mechanism of action, and limitations that need to be considered during formulation to maximize their potential benefit. Understanding the mechanisms by which they perform their different roles and the possible interactions between SAAs and other formulation ingredients can help orientate the choice of formulators toward the SAA most suitable for the intended ocular application at a concentration that is both safe and effective., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Oxidative stress, due to insufficiency of antioxidants or over-production of oxidants, can lead to severe cell and tissue damage. Oxidative stress occurs constantly and has been shown to be involved in innumerable diseases, such as degenerative, cardiovascular, neurological, and metabolic disorders, cancer, and aging, thus highlighting the vital need of antioxidant defense mechanisms. Vascular endothelial growth factor B (VEGF-B) was discovered a long time ago, and is abundantly expressed in most types of cells and tissues. VEGF-B remained functionally mysterious for many years and later on has been shown to be minimally angiogenic. Recently, VEGF-B is reported to be a potent antioxidant by boosting the expression of key antioxidant enzymes. Thus, one major role of VEGF-B lies in safeguarding tissues and cells from oxidative stress-induced damage. VEGF-B may therefore have promising therapeutic utilities in treating oxidative stress-related diseases. In this review, we discuss the current knowledge on the newly discovered antioxidant function of VEGF-B and the related molecular mechanisms, particularly, in relationship to some oxidative stress-related diseases, such as retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease., (Copyright © 2019. Published by Elsevier Ltd.)

Contact lenses (CLs) designed to deliver medication gradually to the eye are being developed and investigated for the use in ocular drug delivery. The aim of the current research is to determine patients' acceptance of the use of lenses for ocular drug delivery. In addition, the study aimed to seek the views and perceptions of healthcare professionals (HCPs) on CLs as a method of ocular drug delivery and whether it will be prescribed to treat ocular conditions. This was a cross-sectional survey targeted at patients and HCPs. Two separate questionnaires were created with open-closed ended and multiple response questions, gauging the perceptions and acceptance of CLs as drug delivery tool. The patients' survey was distributed in John Radcliffe (JR), Oxford and Moorfields eye hospital (MEH), London, UK. The HCPs' questionnaire was manually distributed and was also devised on Survey Monkey and sent by email to ophthalmologists, optometrists, opticians, GPs and hospital and community pharmacists. The data were analysed using SPSS statistical software and Excel. Over 60% (92/151) of patients would accept the use of CLs for their ocular treatment with the highest acceptance being reported by patients in the age group of 30-49 years old. The most frequently used conventional treatment formulation was eye drops as indicated by 87% (131/151) of the responses. More than half of eye drop users (57%, 75/131) indicated that they would accept using CLs expecting them to reduce the frequency of application of the medicine and be less time consuming. Interestingly, half of HCPs were not aware of CLs as an ocular drug delivery method; nevertheless, a total of 65 HCPs out of the 112 surveyed stated that they would prescribe/dispense CLs to treat ocular disease., (Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Thermosensitive gels have been developed and optimized in such a way that they become gels at corneal temperature and with a viscosity that allows the adequate release of the Fluorometholone (FMT)-loaded PLGA nanoparticles (NPs) in order to improve ocular anti-inflammatory efficacy against a commercial formulation. It has been shown that gels avoid burst release of the drug in the first hours with a slow and increasing profile after administration. NPs have maintained their average size and spherical shape within the gels as confirmed by transmission electron microscopy (TEM). In turn, the in-situ gelling of the formulations allows the administration in eye drops dosage form due to its state of sol at temperatures below 25 °C. Ocular tolerance studies have shown that no formulation causes eye irritation. The administration of the developed formulations has improved the precorneal residence time reflected in the ocular bioavailability, where deep tissues as aqueous humour and crystalline were reached. In conclusion, the use of thermosensitive gels for the topical application of NPs has demonstrated their effectiveness in the acute and preventive treatment of ocular inflammatory conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Triblock poloxamer copolymer (PM) has been extensively utilized to deliver various ophthalmic pharmaceutical compounds. The aim of efficient ophthalmic drug delivery strategy is to attain the longer precorneal resident time and good bioavailability of drugs. In this pursuit, the influence of cellulose nanocrystals (CNC) on the in situ gelation behavior of PM and in vitro release of pilocarpine hydrochloride from the nanocomposites formulations was studied. The critical concentration of gelation of PM being 18% (wt/v) was dropped to 16.6% (wt/v) by the addition of a very low percentage of CNC. The reinforcing nature of CNC via H-bonding in the in situ nanocomposite gel also led to an increase in gel strength along with the sustained release of loaded drugs when compared with the pure PM gel. All formulations revealed that the drug release mechanism is controlled by the Fickian diffusion. Thus, the CNC has a significant effect on the gelation behavior, gel strength, and drug release kinetics of PM-CNC formulations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The psychoactive property of cannabinoids is well known and there has been a continuous controversy regarding the usage of these compounds for therapeutic purposes all over the world. Their use for medical and research purposes are restricted in various countries. However, their utility as medications should not be overshadowed by its negative physiological activities. This review article is focused on the therapeutic potential and applications of phytocannabinoids and endocannabinoids. We further highlights their mode of action, overall effects on physiology, various in vitro and in vivo studies that have been done so far and the extent to which these compounds can be useful in different disease conditions such as cancer, Alzheimer's disease, multiple sclerosis, pain, inflammation, glaucoma and many others. Thus, this work is an attempt to make the readers understand the positive implications of these compounds and indicates the significant developments of utilizing cannabinoids as therapeutic agents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herpes simplex virus (HSV)-1 and HSV-2 cause painful blisters and shallow ulcers in exposed skin and mucosae during primary or recurrent infection. In addition, recurrent and potentially blinding HSV-1 infections of the eye afflict nearly half a million persons in the U.S. Current clinical therapies rely on nucleoside analog drugs such as acyclovir (ACV) or ganciclovir to ameliorate primary infections and reduce the frequency and duration of reactivations. However, these treatments do not fully suppress viral shedding and drug-resistant mutants develop in the eye and in vulnerable, immunosuppressed patients. Herpesvirus DNA replication requires several enzymes in the nucleotidyl transferase superfamily (NTS) that have recombinase and nuclease activities. We previously found that compounds which block NTS enzymes efficiently inhibit replication of HSV-1 and HSV-2 by up to 1 million-fold in Vero and human foreskin fibroblasts. Among the compounds with potent suppressive effects in culture is the anti-fungal drug ciclopirox. Here we report that topical application of ciclopirox olamine to the eyes of mice infected with HSV-1 reduced virus shed from the corneal epithelium compared with saline control, and reduced development of blepharitis to the level of mice treated with ACV. Results were dose-dependent. In addition, treatment with ciclopirox olamine significantly reduced acute and latent HSV-1 infection of the peripheral nervous system. These results support further development of ciclopirox olamine as a repurposed topical agent for HSV infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To report the effectiveness of repeated intravitreal dexamethasone (DEX) inserts in noninfectious uveitis patients., Design: Prospective, single-center, interventional clinical trial between February 2010 and March 2015., Participants: Patients with noninfectious uveitis with cystoid macular edema and/or vitreitis., Methods: Patients were treated with a 700-μg intravitreal DEX insert (Ozurdex; Allergan, Inc., Irvine, CA). Follow-up visits were scheduled 1, 3, and 6 months after injection. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze (VH) score, intraocular pressure (IOP), and adverse events were recorded., Main Outcome Measures: Primary outcome was the reduction of CRT. Secondary outcome was the improvement in BCVA and reduction of VH., Results: In total, 109 eyes of 76 patients received 298 DEX inserts. Fifty-two patients were women (68%). The mean age of all participants was 57 years (range, 24-88 years). More than 3 DEX inserts were injected into 44% of eyes. Mean number of injections were 1.54±0.5 (standard deviation [SD]), 1.98±0.84, and 2.46±1.1 over 12, 18, and 24 months, respectively. Central retinal thickness decreased significantly (P < 0.001) from 465 μm at baseline to 318, 342, and 388 μm after 1, 3, and 6 months, respectively. Similar trends were seen in eyes receiving a second, third, and fourth DEX insert. Patients with idiopathic uveitis and sarcoidosis benefited well from DEX inserts. The greatest overall benefit was achieved in patients with no systemic treatment and patients receiving antimetabolites and cyclosporin A. A significant VH score reduction was documented in 44% of eyes after 1 month. A gain of more than 3 lines in BCVA was recorded in 31% to 37%, 26% to 39%, and 8% to 32% of eyes after 1, 3, and 6 months, respectively. A transient rise in mean IOP after 1 month (P < 0.001) and after 3 months (P = 0.001) was seen., Conclusions: The repeated longer-term administration of DEX inserts in noninfectious uveitis patients, either alone or in combination with other therapies, led to improved CRT, BCVA, and VH. Underlying diseases and concomitant systemic therapy seem to have an impact on overall treatment benefit. Ocular complications were reversible and were managed by local treatment, with exception of cataract formation., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze vitreoretinal (VR) complications and treatment outcomes in eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery., Design: Retrospective case series., Participants: All patients who underwent modified OOKP (mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013 were included., Methods: Medical records were reviewed for relevant medical history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound scan, oral examination findings, and VR complications., Main Outcome Measures: The BCVA at the last visit. Optimal anatomic outcome was attached retina with a normal intraocular pressure at the last visit., Results: A total of 92 eyes of 90 patients were included. Indications for OOKP included Stevens-Johnson syndrome (n = 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A total of 41 eyes of 39 patients developed VR complications, including vitritis (n = 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane (RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage (VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median, 41.9 months; range, 0.2-95.5 months). After treatment of VR complication, visual improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1-2.5 logMAR), visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4 logMAR; range, 0.3-1.8 logMAR), and no change in BCVA in 17 eyes (42%). However, BCVA ≥6/60 was retained in 19 eyes and ≥6/18 was retained in 9 eyes after final VR treatment., Conclusions: Vitreoretinal complications constitute a significant cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging situation to manage. However, appropriate and timely intervention can achieve encouraging results., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Development of newer drug carrier systems by the researchers has resulted in numerous breakthroughs in the development and manufacturing of ocular products. The ocular bioavailability of drugs at the posterior segment of the eye is a challenging task in the present scenario. Naturally derived macromolecular carriers are widely used to increase the efficacy of ocular drugs. They provide enhanced corneal permeability and retention effect at the surface of cornea for a prolonged period of time. In this regimen the present review focuses towards the major ocular diseases and their prevalence and development of efficient drug carrier systems utilizing various naturally derived macromolecules for improved delivery of drugs to treat ocular diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To quantify costs of eye care providers' Medicare Part D prescribing patterns for ophthalmic medications and to estimate the potential savings of generic or therapeutic drug substitutions and price negotiation., Design: Retrospective cross-sectional study., Participants: Eye care providers prescribing medications through Medicare Part D in 2013., Methods: Medicare Part D 2013 prescriber public use file and summary file were used to calculate medication costs by physician specialty and drug. Savings from generic or therapeutic drug substitutions were estimated for brand drugs. The potential savings from price negotiation was estimated using drug prices negotiated by the United States Veterans Administration (USVA)., Main Outcome Measures: Total cost of brand and generic medications prescribed by eye care providers., Results: Eye care providers accounted for $2.4 billion in total Medicare part D prescription drug costs and generated the highest percentage of brand name medication claims compared with all other providers. Brand medications accounted for a significantly higher proportion of monthly supplies by volume, and therefore, also by total cost for eye care providers compared with all other providers (38% vs. 23% by volume, P < 0.001; 79% vs. 56% by total cost, P < 0.001). The total cost attributable to eye care providers is driven by glaucoma medications, accounting for $1.2 billion (54% of total cost; 72% of total volume). The second costliest category, dry eye medications, was attributable mostly to a single medication, cyclosporine ophthalmic emulsion (Restasis, Allergan, Irvine, CA), which has no generic alternative, accounting for $371 million (17% of total cost; 4% of total volume). If generic medications were substituted for brand medications when available, $148 million would be saved (7% savings); if generic and therapeutic substitutions were made, $882 million would be saved (42% savings). If Medicare negotiated the prices for ophthalmic medications at USVA rates, $1.09 billion would be saved (53% savings)., Conclusions: Eye care providers prescribe more brand medications by volume than any other provider group. Efforts to reduce prescription expenditures by eye care providers should focus on increasing the use of generic medications, primarily through therapeutic substitutions. Policy changes enabling Medicare to negotiate prescription drug prices could decrease costs to Medicare., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The advent of nanotechnology promises to drastically accelerate progress toward nanomedicine. Nanoscale particles in the size range of cellular and molecular structures, which are usually referred to as nanoparticles (NPs), can be designed to improve penetration, sustained delivery, and controlled release of different drugs for ophthalmic therapeutic applications. After explaining different forms of routinely-used NPs such as nanomicelles, nanosuspensions, liposomes, and dendrimers, potential applications of NPs for the treatment of anterior and posterior eye diseases will be discussed by highlighting their ubiquitous properties. Furthermore, genotoxicity, cytotoxicity, and neuronal toxicity, as the major limiting factors in the wider application of NPs in medical sciences have been discussed, and novel diagnostic techniques and nanomedical tools being utilized in ophthalmology have been introduced. The development of an effective, nontoxic nanoscale biomaterials, in combination with identifying the best delivery systems, will shed more light on the future applications of nanotechnology in ophthalmology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Inflammation of the eye is a usual clinical condition that can implicate any part of the eye. The nomenclature of variety of such inflammations is based on the ocular part involved. These diseases may jeopardize normal functioning of the eye on progression. In general, corticosteroids, antihistamines, mast cell stabilizers and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory diseases/disorders of the eye. There have been several attempts via different approaches of drug delivery to overcome the low ocular bioavailability resulting from shorter ocular residence time. The features like safety, ease of elimination and ability to sustain drug release have led to application of biopolymers in ocular therapeutics. Numerous polymers of natural origin such as gelatin, collagen, chitosan, albumin, hyaluronic acid, alginates etc. have been successfully employed for preparation of different ocular dosage forms. Chitosan is the most explored biopolymer amongst natural biopolymers because of its inherent characteristics. The emergence of synthetic biopolymers (like PVP, PACA, PCL, POE, polyanhydrides, PLA, PGA and PLGA) has also added new dimensions to the drug delivery strategies meant for treatment of ophthalmic inflammations. The current review is an endeavor to describe the utility of a variety of biomaterials/polymers based drug delivery systems as carrier for anti-inflammatory drugs in ophthalmic therapeutics., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Thelazia callipaeda (Spirurida, Thelaziidae) has been documented as agent of ocular infection in domestic animals (dogs and cats), wildlife (e.g., foxes, hares, rabbits), and humans. In the last two decades, this parasitosis has been increasingly reported in several European countries. Both adult and larval stages of the eyeworm are responsible for symptoms ranging from mild (e.g., lacrimation, ocular discharge, epiphora) to severe (e.g., conjunctivitis, keratitis, and corneal opacity or ulcers). The present study evaluated the clinical efficacy and safety of imidacloprid 10% and moxidectin 2.5% spot on (Advocate(®), Bayer Animal Health) in comparison to milbemycin oxime/praziquantel tablets (Milbemax(®), Novartis-Animal Health), as positive control, in the treatment of canine thelaziosis in naturally infected dogs and, a third group was used as an untreated control. Forty-seven dogs (27 females and 20 males) harbouring at least one live adult worm of T. callipaeda in one eye were enrolled from an endemic area of southern Italy. Each dog was then weighed and assigned in accordance with a random treatment allocation plan to one of the treatment groups (G1: imidacloprid 10% and moxidectin 2.5% spot on, G2: Untreated control and G3: milbemycin oxime/praziquantel tablets). On Day (D) 7, 14, 28 and 35 dogs were physically examined and the infection level was assessed by examination of both eyes, including conjunctival pouch and third eyelid for live adult T. callipaeda count and clinical scores. Dogs in G1 were treated on D0 and D28, whereas those in G3 on D0 and D7. Efficacy in G1 was 100% at each day post treatment (p<0.01). For the G3 group efficacy was 57.39% on D7 (p<0.05), 92.79% on D14 and 100% on D28 and D35 (p<0.01). The application of the spot on formulation moxidectin 2.5% and imidacloprid 10% was highly effective in the treatment of canine thelaziosis caused by T. callipaeda. Advocate(®) spot on can be recommended for the control of T. callipaeda infection, considering that this formulation is currently licensed in Europe for the treatment of a wide range of parasites affecting dogs., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Although the number of dermatologic conditions with ocular manifestations is relatively limited, these entities have a high prevalence and represent a large proportion of clinic visits to both dermatologic and ophthalmic practices. This contribution will review oculocutaneous diseases that are not part of the allergic or autoantibody-mediated spectrum., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Corticosteroids are the drug of choice for the treatment of sarcoidosis. Because the natural course of sarcoidosis may be self-limiting and/or cause no long-term harm, treatment is not mandatory. Corticosteroids are usually effective for all forms of sarcoidosis, and they work quickly. However, because of the potential toxicities of corticosteroids, alternative medications often need to be considered. Efforts should be made to minimize the corticosteroid dose while keeping the risk of toxicity as low as possible. This article outlines the indications for corticosteroid therapy for sarcoidosis, discusses various dosing regimens, and suggests when alternative corticosteroid agents should be considered., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 2-compartment in vitro eye flow model has been developed to estimate ocular drug clearance by the anterior aqueous outflow pathway. The model is designed to accelerate the development of longer-acting ophthalmic therapeutics. Dye studies show aqueous flow is necessary for a molecule injected into the vitreous cavity to clear from the model. The clearance times of proteins can be estimated by collecting the aqueous outflow, which was first conducted with bevacizumab using phosphate-buffered saline in the vitreous cavity. A simulated vitreous solution was then used and ranibizumab (0.5 mg) displayed a clearance time of 8.1 ± 3.1 days, which is comparable to that observed in humans. The model can estimate drug release from implants or the dissolution of suspensions as a first step in their clearance mechanism, which will be the rate-limiting step for the overall resident time of a candidate dosage form in the vitreous. A suspension of triamcinolone acetonide (Kenalog®) (4.0 mg) displayed clearance times spanning 26-28 days. These results indicate that the model can be used to determine in vitro-in vivo correlations in preclinical studies to develop long-lasting therapeutics to treat blinding diseases at the back of the eye., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Oleanolic acid (OA) and ursolic acid (UA) are ubiquitous pentacyclic triterpenes compounds in plants with great interest as anti-inflammatory therapeutics. The aim of this study was the design and optimization of polymeric nanoparticles (NPs) loaded with natural and synthetic mixtures (NM, SM) of these drugs for ophthalmic administration. A 2(3) + star central rotatable composite design was employed to perform the experiments. Results showed optimal and stable formulations with suitable physicochemical properties (mean diameter<225 nm), homogeneous distribution (polydispersity index∼0.1), negatively charged surface (∼-27 mV) and high entrapment efficiency (∼77%). Release and corneal permeation studies showed that NM release was faster than SM. Amounts of drug retained in the corneal tissue were also higher for NM. In vitro and in vivo tests showed no signs of irritation or toxicity and successful in vivo anti-inflammatory efficacy for both formulations, being NM-OA/UA NPs the most effective. From the clinical editor: Oleanolic acid (OA) and ursolic acid (UA) are compounds found in plants with anti-inflammatory properties. The authors in this paper designed nanoparticles (NPs) using poly(dl-lactide-coglycolide) acid (PLGA) loaded with these compounds for ophthalmic administration. Both in vitro and in vivo experiments showed no toxicity and significant anti-inflammatory efficacy. This may provide new drugs for ocular anti-inflammatory treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of a single intravitreal injection of ocriplasmin 125 μg across relevant subpopulations of patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction (VMT), including when associated with macular hole., Design: Two multicenter, randomized, placebo-controlled, double-masked, 6-month studies., Participants: A total of 652 randomized patients (464 receiving ocriplasmin; 188 receiving placebo)., Methods: A single intravitreal injection of ocriplasmin 125 μg or placebo in the study eye., Main Outcome Measures: Prespecified subgroup analyses were conducted to evaluate the effects on the proportion of patients with nonsurgical resolution of focal VMA at day 28, nonsurgical full-thickness macular hole (FTMH) closure at month 6, and categoric improvement in best-corrected visual acuity (BCVA) at month 6., Results: Resolution of VMA at day 28 was achieved more often in younger patients (<65 years), eyes without epiretinal membrane, eyes with FTMH, phakic eyes, and eyes with a focal VMA ≤ 1500 μm. Eyes with FTMH width ≤ 250 μm were more likely to achieve nonsurgical FTMH closure. Categoric ≥ 2-line and ≥ 3-line improvement in BCVA occurred more often in younger patients (<65 years) and in patients with a lower baseline BCVA (<65 letters). Treatment differences in favor of ocriplasmin were generally observed across each subgroup of subpopulations studied., Conclusions: Subgroup analyses confirmed the positive effect of ocriplasmin across relevant subpopulations., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Glucocorticoids (GCs) are broadly used in the treatment of inflammation and in suppressing hyperactivity of the immune system expressed in allergies, asthma, autoimmune diseases and sepsis. They are pleiotropic in nature, showing a wide range of diverse effects, including those which are harmful for the organism. Dexamethasone (DEX) is one of the most frequently used GCs and is considered as one of the safest. Still serious side-effects have been observed for this drug, mostly due to its hydrophobicity and low bioavailability. The potentially promising polymeric carrier systems to deliver DEX effectively are revised., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Chronic inflammatory eye diseases are a common manifestation of pediatric rheumatologic diseases, potentially leading to lifelong vision impairment and disability. The mechanisms leading to the breach of the blood eye/brain barrier and the subsequent immune attack against a variety of intraocular mostly unidentified antigens remains poorly understood. Pediatric rheumatologists need to be familiar with the various inflammatory eye diseases because they are often responsible for selecting and supervising treatment in close collaboration with the ophthalmologist. This article provides an update of recent developments in the pathogenesis and treatment of the most relevant ocular diseases encountered in rheumatologic practice., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to highlight the increasing chance of Western physicians encountering patients (both immigrants and expatriates/travelers) seeking help for loiasis., Methods: We describe three cases of imported loiasis observed at two hospitals in Italy and France, and present a review of all previously published cases in the medical literature in the last 25 years (1986-2011). The search was performed using PubMed and Scopus databases using the terms "Loa loa" AND "loiasis"., Results: We reviewed 101 cases of imported loiasis of which 61 (60.4%) were reported from Europe and 31 (30.7%) from the USA. Seventy-five percent of infestations were acquired in three countries: Cameroon, Nigeria, and Gabon. Overall, peripheral blood microfilariae were detected in 61.4% of patients, eosinophilia in 82.1%, eye worm migration in 53.5%, and Calabar swellings in 41.6%. However, Calabar swellings and eosinophilia were more common among expatriates/travelers, whereas African immigrants were more likely to have microfilaremia. Eye worm migration was observed in a similar proportion in the two groups. Only 35 patients (including the three described here) underwent clinical follow-up for a median period of 10.5 months (range 1-84 months); clinical relapse occurred in three of these patients and persistence or reappearance of blood microfilaria in another two., Conclusions: Due to increasing travel and the migration of people from the endemic countries of West Africa to Europe and the USA, we speculate on the possible emergence of loiasis. Western physicians should be aware of the typical (eye worm migration and Calabar swellings) as well as unusual clinical presentations., (Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)