Topical Ophthalmic Solution Research Articles

Design and Development of Ophthalmic Liposomes from the QbD Perspective.

Due to significant lachrymation, drug washing out, and poor adhesion to the lipophilic outer layer of the precorneal and cornea membrane, topical ophthalmic solution drops have poor ocular bioavailability. The rate of transcorneal absorption is impacted in the case of hydrophilic drug molecules as brimonidine tartrate, timolol maleate, cyclosporine, etc. Ophthalmic solution administered in many doses is less patient-compliant. The limitation of multiple-dose and its negative effects can be overcome by the development of delayed- release liposomes. Liposomes are regulatory-approved novel drug delivery systems. Its vesicular form aids in delaying medication release, and its lipidic makeup enables it to stick to the cornea's lipophilic layer. As a result, it will prevent precorneal clearing, extend corneal contact time, and provide sufficient transcorneal absorption. The aim of this review article is to portray the benefits of liposomes for ophthalmic drug delivery and its formulation development in the light of QbD. The review discusses the composition, preparatory methods and quality aspects of ophthalmic liposomes. It then accordingly reasonably proposes the quality target product profile, critical quality attributes, critical material attributes and critical process parameters, involved in liposome development for ophthalmic drug delivery. This review shall help formulation scientists to formulate ophthalmic liposomes of desirable quality.

Drug-eluting contact lenses: Progress, challenges, and prospects.

Topical ophthalmic solutions (eye drops) are becoming increasingly popular in treating and preventing ocular diseases for their safety, noninvasiveness, and ease of handling. However, the static and dynamic barriers of eyes cause the extremely low bioavailability (<5%) of eye drops, making ocular therapy challenging. Thus, drug-eluting corneal contact lenses (DECLs) have been intensively investigated as a drug delivery device for their attractive properties, such as sustained drug release and improved bioavailability. In order to promote the clinical application of DECLs, multiple aspects, i.e., drug release and penetration, safety, and biocompatibility, of these drug delivery systems were thoroughly examined. In this review, we systematically discussed advances in DECLs, including types of preparation materials, drug-loading strategies, drug release mechanisms, strategies for penetrating ocular barriers, in vitro and in vivo drug delivery and penetration detection, safety, and biocompatibility validation methods, as well as challenges and future perspectives.

Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial

PurposeThe purpose of this study was to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber’s Hereditary Optic Neuropathy (LHON). DesignThis Phase 2, prospective, randomized, vehicle controlled, single-center clinical trial involved administration of elamipretide (MTP-131) topical ophthalmic solution to LHON patients over a 52-week double-masked treatment period (DMTP), followed by an open extension label (OLE) for up to 108 additional weeks of treatment. SubjectsTwelve patients affected with LHON were included in this study. Patients between ages 18 and 50 with decreased vision, for at least one year and no more than ten years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this trial. MethodsFor the first 52 weeks of the study, patients were randomized to one of two arms, elamipretide in both eyes or elamipretide in one eye and vehicle in the other eye, followed by an OLE where both eyes were treated with elamipretide. Main outcome measuresThe primary outcome measure was the assessment of adverse events from the administration of topical elamipretide 1% and the primary efficacy endpoint was change in best corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes. ResultsElamipretide was well tolerated with the majority of treatment-emergent adverse events (TEAEs) being mild to moderate and resolving spontaneously. The change from baseline in BCVA in elamipretide-treated eyes was not significantly different from the vehicle eyes at any time point. Six of 12 subjects met the criteria for clinically relevant benefit (CRB). In the post-hoc analysis, change from baseline in mean deviation in the central visual field was significantly greater in elamipretide treated eyes versus the vehicle eyes. Compared to baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE. ConclusionsElamipretide treatment was generally well tolerated with no serious adverse events reported. Although this study did not meet its primary BCVA efficacy endpoint, improvements across assessments on visual function during the OLE, and the post-hoc findings of the HVF central region, were encouraging and require further exploration.

Atropine-eluting silicone contact lenses for myopia control.

Myopia, also known as nearsightedness, is one of the prime reasons for vision impairment worldwide. Atropine in topical ophthalmic solutions (e.g., 0.01% atropine sulfate eye drops) is the primary medical treatment for controlling myopia, especially for pseudomyopia or true myopia in rapid progress. However, aqueous atropine solution is unstable and easily breaks down to tropic acid, which will result in vision blur. Drug-eluting contact lenses (CLs) have been explored as a potentially superior alternative to effectively control the drug release and improve the drug efficacy. In this work, an atropine-eluting contact lens was developed by encapsulating an atropine implant in a silicon-based contact lens, towards functioning in vision correction and controlling myopia. The safety and effectiveness of this atropine-eluting contact lens were verified with rabbit and guinea pig models. The results showed that the lenses reduced the side effects like mydriasis and no other adverse events were observed in rabbit eyes. More importantly, atropine-loaded lenses could effectively delay the progress of form-deprivation myopia with guinea pig eyes as the model. Thus, we concluded that atropine-eluting CLs prepared by implantation technology may be an option for the treatment of myopia.

Scleral Lenses Improve Ptosis in Patients with Concurrent Ocular Surface Disease: A Case Series

Scleral lenses are a well-established contact lens option for patients with corneal irregularity and/or ocular surface disease. They provide a unique design by vaulting over the limbus of the cornea and rest on the conjunctiva with no blood vessel compression. Scleral lenses have an additional benefit of improving eyelid ptosis; however, this use has been minimally reported in the literature. This use has probably not been reported as frequently because the primary goals of fitting these lenses are most often improvement in vision, protection/support of the ocular surface, and/or improvement in comfort. It is hypothesized that the increased bulk of scleral lenses contribute to an increase in lid aperture size and the marginal reflex distance. Scleral lenses offer a non-surgical and non-pharmacological option for ptosis improvement, particularly in cases of mild ptosis and/or when the patient is not a good surgical candidate. They are a good option for improving ptosis in patients with concurrent ocular surface disease as they offer corneal protection as the eyelid retracts. They serve as an appropriate option for patients who are susceptible or experience adverse side effects of topical ophthalmic solutions for ptosis including dry eye, pain, and headache.1 The following case series highlights several cases in which scleral lenses improved ptosis measurements following scleral lens fitting. CE Notification: This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/scleral-lenses-improve-ptosis-in-patients-with-concurrent-ocular-surface-disease-a-case-series). Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

In vitro activity of cysteamine against SARS-CoV-2 variants.

Global COVID-19 pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Continuous emergence of new variants and their rapid spread are jeopardizing vaccine countermeasures to a significant extent. While currently available vaccines are effective at preventing illness associated with SARS-CoV-2 infection, these have been shown to be less effective at preventing breakthrough infection and transmission from a vaccinated individual to others. Here we demonstrate broad antiviral activity of cysteamine HCl in vitro against major emergent infectious variants of SARS-CoV-2 in a highly permissible Vero cell line. Cysteamine HCl inhibited infection of wild type, alpha, beta, gamma, delta, lambda, and omicron variants effectively. Cysteamine is a very well-tolerated US FDA-approved drug used chronically as a topical ophthalmic solution to treat ocular cystinosis in patients who receive it hourly or QID lifelong at concentrations 6 times higher than that required to inhibit SARS CoV-2 in tissue culture. Application of cysteamine as a topical nasal treatment can potentially1) mitigate existing infection 2) prevent infection in exposed individuals, and 3) limit the contagion in vulnerable populations.

Safety and efficacy of risuteganib ophthalmic solution in the treatment of dry eye disease: A prospective, randomized, double-masked, vehicle-controlled study

Objectives: The aim of the study was to compare the safety and efficacy of ALG-1007 (0.125% sodium hyaluronate [SH] + 0.6% risuteganib [RSG] ophthalmic solution) to 0.6% RSG alone, 0.125% SH alone, and vehicle alone in subjects with dry eye disease (DED). Material and Methods: Eligible participants aged ≥18 years old with symptoms of DED for ≥ 6 months were randomized into four treatment groups: ALG-1007, RSG, SH, and vehicle. The treatment for all groups was administered one drop twice a day and subjects were evaluated at weeks 2, 4, 8, and 12. Primary efficacy endpoints were change in nasal conjunctival staining and change in Dry Eye Management Scale (DEMS) score from baseline to week 12. Secondary efficacy endpoints were changes in tear breakup time (TBUT), total ocular staining (TOS), inferior corneal staining score, and individual and combined reported symptoms by Visual Analog Scale (VAS), from baseline to week 12. Results: All parameters tested and analyzed – nasal conjunctival staining, DEMS, TBUT, inferior corneal staining score, and VAS (combined, burning, discomfort, dryness, foreign body sensation, and photophobia) – improved in all study groups over the 12-week observation period. The greatest improvements in all parameters tested were seen in the ALG-1007 group followed by RSG only, SH only, and then vehicle. Comparison of 12-week change from baseline (CFB) values demonstrated statistically significant differences in all group comparisons for all the measurements done except for comparison of ALG-1007 versus RSG (P = 0.3154) for nasal conjunctival staining. No adverse events were reported. Conclusion: 0.60% RSG topical ophthalmic solution was effective in improving the signs and symptoms of DED and demonstrated therapeutic properties. ALG-1007, a combination of 0.60% RSG + 0.125% SH, was superior to RSG alone and will provide the most therapeutic benefit to patients with DED. ALG-1007 and RSG were well-tolerated with no drug-related AEs or SAEs reported over a 12-week observation period.

The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure

Cannabidiol (CBD) is a phytocannabinoid that has a great clinical therapeutic potential. Few studies have been published on its efficacy in ocular inflammations while its impact on intraocular pressure (IOP), a major risk factor for glaucoma, remains unclear. Moreover, due to its lability and high lipophilicity, its formulation within a prolonged stable topical ophthalmic solution or emulsion able to penetrate the highly selective corneal barrier is challenging. Therefore, various CBD nanoemulsions (NEs) were designed and evaluated for stability in accelerated conditions. Further, the optimal formulation was tested on a murine LPS-induced keratitis inflammation model. Lastly, increasing CBD concentrations were topically applied, for two weeks, on mice eyes, for IOP measurement. CBD NEs exhibited optimal physicochemical characteristics for ocular delivery. A specific antioxidant was required to obtain the stable, final, formulation. In vivo, 0.4 to 1.6% CBD w/v reduced the levels of key inflammatory cytokines, depending on the concentration applied. These concentrations decreased or did not affect the IOP. Our results showed that a well-designed CBD ocular dosage form can be stabilized for an extended shelf life. Furthermore, the significant decrease in inflammatory cytokines levels could be exploited, provided that an adequate therapeutic dosage regimen is identified in humans.

Once-Weekly Nocturnal Ocular Choroidal Vascular Decongestion by Topical Long-acting Timolol Ophthlamic Solution Applied to Headache-Ipsilateral eye to Prevent Weekend-Migraine Attacks: Smartphone-app

This clinical study evaluates over medium-to-long term the hypothesis that intermittent spontaneous ocular choroidal vasculature-related congestive and nociceptive corneoscleral envelope distention have a pathogenetic role in genesis of episodic lateralizing migraine headache attacks. No neuro-anatomic or -physiologic difference prevails between the three divisions of the trigeminal nerve, but migraine dominantly affect the ophthalmic division. Use of topical ophthalmic solution for managing acute headache attacks of migraine has given contradictory results in controlled trials. I report the distribution of weekend-migraine headache attacks on a single‐participant (N=1) level for 2 patients over a 3-year period (2017-2020) without misuse of any recreational drug other than caffeine on week-days. After a run-in basal period of 6-months recorded on their Smartphones app, with their informed consent, a trial was carried out with topical long-acting β-blocker timolol maleate 0.5% w/v ophthalmic solution once weekly on Saturday night just before sleeping with no other advice to promote nocturnal sleeping or early awakening the next morning; only alcohol binge was proscribed. No week-end attacks of lateralizing migraine headache were reported in the 2 patients over a period of 3- years, a long-term consistent response. The biologically-plausible and defensible mechanistic link between migraine, intraocular pressure, ocular choroidal vasculature, nociceptive corneoscleral envelope aberration, and the pharmacologic basis for therapeutic ocular hypotension for prophylaxis of migraine headache attacks is elucidated for the first time in migraine literature.

Role of topical ophthalmic solutions (0.1%) olopatadine hydrochloride and (0.05%) epinastine hydrochlloride in vernal keratoconjuntivitis

VKC is of great concern to all ophthalmologists in India because it is found to be quite common in our country and the tropical countries and if untreated it can lead to sight threatening complications.The present study was carried out in fourty patients who attended the outpatient department ophthalmology, Darbhanga Medical College and Hospital, Laheriasarai. The study was carried out from July 2007 Dec 2008. Forty patients with symptoms of VKC (ocular itching, ropy discharge discharge, papillary hypertrophy, gelatinous thickening and (horner-trantas spots) were selected and included in our study. Olopatadine treated group- Means score of itching at 0, 14, 28, 42 days in olopatadine treated eye were 3.2, 2.1, 1.2, and 0.4 respectively having value P&amp;#60;0.01, &amp;#60;0.01 and &amp;#60;0.001 respectively while means score at same stages in Placebo eye were 3.2, 3.1, 3 and 2.6 having p value &amp;#62;0.05. Olopatadine Treated Group-Mean scores of ropy discharge at 0, 14, 28, and 42 days in were 2.9, 2.1, 1.3 and 0.6 respectively having P value &amp;#60;0.01, &amp;#60;0.01, &amp;#60;0.001 and &amp;#60;0.001 in between them and mean scores at same stages in placebo eye were 2.9, 2.8, 2.7 and 2.4 respectively having P value &amp;#62;0.05. It was concluded thatthe present study shown that both olopatadine and epinastine is effective and reducing itching and ropy discharge of VKC as compared to placebo.

Steroid-eluting contact lenses for corneal and intraocular inflammation

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. Statement of SignificanceInflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.

Safety and efficacy of ALG-1007 topical ophthalmic solution – A synthetic peptide that regulates inflammation, in patients with dry eye disease: An exploratory Phase I, open-label, single-center clinical study

Objectives: The objective of the study was to evaluate the safety and efficacy of ALG-1007 topical ophthalmic solution in patients with dry eye disease (DED). Materials and Methods: This Phase I, prospective, open-label, 12-week study enrolled subjects ≥18 years old with symptoms of DED for at least 6 months and at least one of the following: Total ocular staining score ≥2 or tear film breakup time (TBUT) ≤7 s. Subjects were randomized to four treatment arms: 0.125%, 0.25%, 0.4%, and 0.6% ALG-1007. Subjects received the test drug, 1 drop twice daily, and were followed at multiple time points for 12 weeks. SICCA total ocular staining score, corneal and conjunctival staining score, TBUT, and subject-reported symptoms using the visual analog scale (VAS) symptom index were assessed at baseline and at every visit. The primary safety outcome was percentage and severity of adverse events (AEs). Results: Forty eyes (21 patients) were assigned randomly to four treatment groups (n = 10 per group). Improvement in TBUT, SICCA, and VAS was seen in all groups. The highest dose tested (0.6%) was compared to the lowest dose tested (0.125%) based on change from baseline for all assessments using analysis of variance. Improvement was significantly greater in 0.6% treatment group in terms of TBUT, conjunctiva staining, SICCA, burning, discomfort, photophobia, and the composite symptom score. No serious AEs were reported after 12 weeks of treatment. Conclusion: Outcome measures improved in all the treatment groups. At the highest dose, ALG-1007 demonstrated statistically significant improvement compared to the lowest dose in 7 out of 12 assessments, indicating a dose response. This suggests that the active pharmaceutical ingredient in ALG-1007 is effective in improving signs and symptoms of DED. ALG-1007 was well-tolerated with minimal instillation discomfort and no reported serious AEs.

Randomized, Double-Masked, Placebo-Controlled Dose Escalation Study of TAK-639 Topical Ophthalmic Solution in Subjects with Ocular Hypertension or Primary Open-Angle Glaucoma.

PurposeTAK-639 is a topical, nine-amino acid, synthetic, C-type natriuretic peptide analog in Phase 1 development for the treatment of ocular hypertension (OHT) and primary open-angle glaucoma (POAG). TAK-639 is postulated to lower intraocular pressure (IOP) through a novel mechanism of action (MOA) that increases trabecular meshwork outflow. We investigated the safety and tolerability of TAK-639 in subjects with OHT or POAG.MethodsThis was a phase 1, multicenter, randomized, double-masked, placebo-controlled, single- and multiple-dose escalation study. Subjects (aged 18–90 years) with OHT or POAG were randomized 5:2 to TAK-639 or placebo. Three dose levels were planned (0.1%, 0.3%, 0.6% TAK-639), each with four dosing regimens (QD, BID, TID, QID). Safety measures included treatment-emergent adverse events (TEAEs) and ophthalmologic examinations. Pharmacokinetics and pharmacodynamics (reduction of IOP) were also evaluated.ResultsIn total, 63 subjects were randomized and received 0.1%, 0.3% and 0.6% TAK-639, as single dose, QD, or BID, and 0.1% and 0.3% TID. The study was terminated before 0.6% TID or QID dosing cohorts were studied; instead, 0.6% BID was repeated in a new cohort. TEAEs were instillation related and of mild-to-moderate intensity. There were no TEAEs leading to premature discontinuation, and no serious TEAEs. The most common treatment-related TEAEs were instillation site pain and transient corneal staining with fluorescein. There were no clinically significant concerns across dose groups for all other safety measures, including drop comfort, best corrected visual acuity, slit-lamp biomicroscopy, and corneal epithelial integrity. Little or no systemic exposure was observed. There was a marginal reduction in IOP in one cohort at the highest dose (0.6%) and regimen (BID) tested, suggesting biological plausibility of targeting the trabecular meshwork through this mechanism.ConclusionTAK-639 was generally well tolerated up to 0.6% BID. Further non-clinical studies will improve understanding of the MOA and the penetration of TAK-639 to the anterior chamber.

Clinical Evaluation of a Novel Electromechanical Topical Ocular Drug Delivery System: Two Phase 1 Proof of Concept Studies.

PurposeSelf-administration of topical ophthalmic therapies remains challenging for many patients as errors due to improper technique are common. The aim of the current studies was to evaluate a novel electromechanical topical ocular drug delivery device designed to facilitate precise dosing and accurate delivery with substantially lower drug exposure than conventional eye drops.Patients and MethodsTwo randomized Phase 1 studies were performed to evaluate the efficacy and safety of a single dose of a topical ophthalmic solution administered as a ~9 μL microfluid stream via the test device compared with a ~30–40 μL drop delivered via conventional dropper in healthy subjects (Trial 1) and glaucoma patients (Trial 2). In Trial 1, a 1% tropicamide/2.5% phenylephrine solution was administered via the test device in one eye and by conventional dropper in the contralateral eye. Pupil dilation was measured at 30 min intervals post-instillation and subject comfort was assessed using a visual analogue scale (range, 0–100). In Trial 2, patients were randomized to receive latanoprost 0.005% via the test device or conventional dropper. Intraocular pressure was measured at baseline and 4–8 hrs post-instillation.ResultsIn Trial 1 (N=20), mean (SD) pupil diameter 30 mins post-instillation increased by 3.4 (0.9) and 3.5 (1.0) mm in the test and control eyes, respectively. The mean comfort score was 81.7 for the test device versus 57.3 for conventional dropper delivery. In Trial 2 (N=18), the mean change in intraocular pressure following administration of latanoprost was –5.0 (1.8) and –4.3 (3.3) mm Hg in the test and control groups, respectively. No serious adverse events were observed in either study.ConclusionAdministration of a single dose of topical ophthalmic therapy via an electromechanical drug delivery device resulted in comparable effects on pupil dilation and intraocular pressure with lower drug exposure and increased patient comfort compared with conventional dropper delivery.

İki Kedide Hiperlipidemi ile İlişkili Anterior Üveit ve Aköz Lipidozis

A 9 months old male and a 1-year old female crossbreed cats were presented with history of unilateral sudden onset cloudy eye has been reported in this study. Ophthalmological examination was revealed clear corneal surface, corneal edema did not occurred, homogeneous blurred with white color in the anterior chamber of the eyes in both cases and laboratory findings were revealed hypertriglyceridemia and hypercholesterolemia. According to the ocular and laboratory examination findings after the anamnesis, the patients were diagnosed with hyperlipidemia-related aqueous lipidemia. Topical ophthalmic solution of prednisolone sodium fosfat 1% was applied 2 drops, 5 times in a day and low-fat diet was recommended. Both patients were responded to medical treatment within one week, positively. No complications were encountered during the 2-year follow-up period of the patients.

Investigation of comet assays under conditions mimicking ocular instillation administration in a three-dimensional reconstructed human corneal epithelial model

Purpose: A comet assay is one of the genotoxicity methods for evaluating the potential of chemicals to induce DNA strand breaks. To investigate the usefulness of comet assays for evaluating the genotoxic potential of ophthalmic solutions, a three-dimensional (3D) reconstructed human corneal epithelial model (3D corneal model) was exposed to conditions mimicking topical ocular instillation administration.Methods: The 3D corneal model was exposed to acridine orange, ethidium bromide, hydrogen peroxide, 1,1′-dimethyl-4,4′-bipyridinium dichloride (paraquat), 4-nitroquinoline 1-oxide (4-NQO), acrylamide and methyl methanesulfonate (MMS). To mimic the ocular surface condition to which ophthalmic solutions are administered, the exposure time was set to 1 minute. Likewise, human corneal epithelial (HCE-T) cells, as monolayer cultured cells, were exposed to the same chemicals, for comparison.Results: In the 3D corneal model, the amount of DNA fragments was statistically significantly increased in cells treated with each of the test chemicals except acrylamide. In HCE-T cells, the amount of DNA fragments was statistically significantly increased in acridine orange-, ethidium bromide-, hydrogen peroxide-, 4-NQO- and MMS-treated cells but not in paraquat- or acrylamide-treated cells. In the 3D corneal model, the lowest concentrations at which we observed DNA damage were about 100 times higher than the concentrations in HCE-T cells. Since the 3D corneal model is morphologically similar to human corneal tissue, form a multilayer and having tight junctions, it may be that the test chemicals only permeated about 1% into the 3D corneal model.Conclusion: These results suggest that the comet assay using 3D cell culture models may reflect in vivo conditions better than do monolayer cultured cells, and that the comet assay may be useful for the evaluation of genotoxic potential of topical ophthalmic solution.

Ocular anti-inflammatory activity of prednisolone acetate loaded chitosan-deoxycholate self-assembled nanoparticles.

Background and purpose: Conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. The aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (PA), to increase dosing accuracy, bioavailability, and accordingly, efficiency of PA in treating inflammatory ocular diseases.Methods: A novel formulation of self-assembled nanoparticles was prepared by the complexation of chitosan (CS) and, the counter-ion, sodium deoxycholate (SD), loaded with the poorly-water-soluble PA. Particle size, zeta potential, encapsulation efficiency (EE) and drug loading content (LC) of prepared nanoparticles were assessed. Moreover, the nanoparticles were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Drug release and eye anti-inflammatory potential of the prepared novel formulation was investigated.Results: Mean particle size of the nanoparticles have dropped from 976 nm ±43 (PDI 1.285) to 480 nm ±28 (PDI 1.396) when the ratio of CS-SD was decreased. The incorporation of 0.1-0.3% of polyvinyl alcohol (PVA), in the preparation stages, resulted in smaller nanoparticles: 462 nm ±19 (PDI 0.942) and 321 nm ±22 (PDI 0.454) respectively. DSC and FTIR results demonstrated the interaction between CS and SD, however, no interactions were detected between PA and CS or SD. Drug release of PA as received, in simulated tears fluid (pH 7.4), showed a twofold increase (reaching an average of 98.6% in 24 hours) when incorporated into an optimized nanoparticle gel formulation (1:5 CS-SD).Conclusion: The anti-inflammatory effect of PA nanoparticles loaded gel on female guinea pig eyes was significantly superior to that of the micronized drug loaded gel (P < 0.05).

Efficacy and Tolerability of Ketotifen in the Treatment Of Seasonal Allergic Conjunctivitis: Comparison between Ketotifen 0.025% and 0.05% Eye Drops

ABSTRACTPurpose: To study the tolerability and efficacy of two formulations of topical ketotifen ophthalmic solutions for the treatment of seasonal allergic conjunctivitis (SAC).Methods: 81 active SAC patients were treated with either ketotifen 0.025% or 0.05% eye drops for 3 weeks. Allergic signs and symptoms were evaluated at baseline (V0), after 7 (V1) and 21 days (V2). Drugs tolerability and ratings of global efficacy were recorded.Results: Both concentrations of ketotifen were highly effective. The total signs and symptoms scores (TSSS) were significantly better reduced by ketotifen 0.025% compared to 0.05% at both V1 and V2 (p < 0.001). Ketotifen 0.025% was better tolerated than 0.05% at the first instillation and at days 2, 4, and 6 (p < 0.0001), and had a better responder rate (p < 0.001) according to the patient’s and investigator’s assessments.Conclusions: Ketotifen 0.025% was more effective and better tolerated than 0.05% in SAC.

Corneal Cross-Linking: Current USA Status: Report From the Cornea Society.

The initial published clinical report on riboflavin/ultraviolet A corneal cross-linking (CXL) for treatment of progressive keratoconus dates back to 2003. CXL has since then been widely used outside the United States for treatment of progressive keratoconus and post-laser in situ keratomileusis ectasia. The Food and Drug Administration (FDA) approved Avedro Inc.'s corneal cross-linking system (KXL) for treatment of patients with progressive keratoconus and post-laser in situ keratomileusis ectasia in April 2016. The procedure is not currently approved for stable keratoconus. There are 2 FDA-approved topical ophthalmic solutions for use in CXL. Riboflavin 5'-phosphate in 20% dextran ophthalmic solution 0.146% (Photrexa Viscous) and Riboflavin 5'-phosphate ophthalmic solution 0.146% (Photrexa) are intended for use with the KXL system. Photrexa Viscous is used in all CXL procedures, whereas Photrexa is indicated for use when the corneal stroma is thinner than 400 µm after completion of the Photrexa Viscous induction period. The FDA-approved procedure using the Dresden protocol (UV-A, 3 mW/cm for 30 min) induces cytologic and morphologic changes in the anterior 250 to 300 µm of the corneal stroma. It has been believed that a minimum thickness of 400 μm was necessary to protect the corneal endothelium from potential damage. The CXL procedure using the standard Dresden protocol is established as the gold standard for treatment of progressive keratoconus. CXL treatment is indicated for a list of conditions ranging from corneal ectasia to infectious keratitis. Newer protocols, treatment regimens, and expanded indications will require further refinements, investigations, and long-term studies.

Apraclonidine in the treatment of ptosis

Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20–30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis.