Perspectives of Molecularly Imprinted Polymer-Based Drug Delivery Systems in Ocular Therapy

Although the human eye is an easily accessible sensory organ, it remains a challenge for drug administration due to the presence of several anatomical and physiological barriers which limit the access of drugs to its internal structures. Molecular imprinting technology may be considered the avant-garde approach in advanced drug delivery applications and, in particular, in ocular therapy. In fact, molecularly imprinted polymers hold the promise to compensate for the current shortcomings of the available arsenal of drug delivery systems intended for ocular therapy. The present manuscript aims to review the recent advances, the current challenges and most importantly to raise awareness on the underexplored potential and future perspectives of molecularly imprinted polymer-based drug delivery systems intended for the treatment of eye diseases.

Treatment of Ocular Tumors Through a Novel Applicator on a Conventional Proton Pencil Beam Scanning Beamline

Treatment of ocular tumors on dedicated scattering-based proton therapy systems is standard afforded due to sharp lateral and distal penumbras. However, most newer proton therapy centers provide pencil beam scanning treatments. In this paper, we present a pencil beam scanning (PBS)-based ocular treatment solution. The design, commissioning, and validation of an applicator mount for a conventional PBS snout to allow for ocular treatments are given. In contrast to scattering techniques, PBS-based ocular therapy allows for inverse planning, providing planners with additional flexibility to shape the radiation field, potentially sparing healthy tissues. PBS enables the use of commercial Monte Carlo algorithms resulting in accurate dose calculations in the presence of heterogeneities and fiducials. The validation consisted of small field dosimetry measurements of point doses, depth doses, and lateral profiles relevant to ocular therapy. A comparison of beam properties achieved through the applicator against published literature is presented. We successfully showed the feasibility of PBS-based ocular treatments.

Rapid, Spontaneous Resolution of Prominent Subretinal Infiltrate in Vitreoretinal Lymphoma

Purpose: This case report describes a patient with vitreoretinal lymphoma who subacutely developed a large, peripapillary subretinal infiltrate that rapidly and spontaneously resolved. Methods: A case report is presented. Results: A 65-year-old Asian-American woman was referred for evaluation of a dense, peripapillary subretinal infiltrate in the left eye. A diagnostic vitrectomy revealed large, atypical lymphocytes with irregularly shaped nuclei, and mutational testing was positive for myeloid differentiation primary response 88 ( MYD88). Prior to surgery, the patient’s subretinal infiltrate had begun to resolve spontaneously, a process that continued after surgery without initiation of systemic or local ocular therapy. Conclusions: Patients with vitreoretinal lymphoma may present with transient, subretinal infiltrates that can resolve without treatment.

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

Ocular Delivery of Polyphenols: Meeting the Unmet Needs

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.

Sympathetic ophthalmia: Report of a case series and comprehensive review of the literature

Purpose: To evaluate the factors related to sympathetic ophthalmia (SO) in a series of patients in our ophthalmology center and previously published cases. Methods: A retrospective and noncomparative review was performed on 16 patients with SO attending our ophthalmology center from 2013 to 2019. A total of 87 previously published cases of SO were identified by searching the Medline database from 2009 to 2019. Results: Sixteen patients were included in the analysis, and six cases were induced by transscleral cyclophotocoagulation (TCP). All patients had achieved controlled inflammation at their last follow-up visit. Thirteen patients (81.3%) had improved best-corrected visual acuity (BCVA). A review of the literature revealed 87 previously reported cases of SO. Shared clinical features and treatment outcomes were summarized. Conclusion: Ocular therapies, including both penetrating ocular therapy and non-penetrating ocular intervention, have become increasingly prevalent risk factors for SO, and the latent period has increased compared to past reports. Visual prognosis with appropriate medical management is relatively good.

OCULAR DRUG DELIVERY SYSTEM: CHALLENGES AND APPROACHES

The ocular drug delivery deviates through a number of anatomical and physiological barriers, which have been a bottleneck for the ophthalmologists. The ocular barriers, static and dynamic, decrease the absorption of the therapeutic agents and the entry of the xenobiotics. Thus, a conventional ocular dosage form has various disadvantages of its use in ocular diseases. Hence, an ideal ocular delivery system has always been aimed, where the bioavailability of a drug is maintained for a longer period of time. The present review aims to focus on the drawbacks of the conventional ocular therapy and the advantages of designing novel delivery systems, with their certain specific advantages in ocular pharmacokinetics and the enhancement of bioavailability. These novel approaches emphasize on the benefits of various ocular drug delivery systems, like eye ointments, gels and use of viscosity enhancers, prodrugs, penetration enhancers, microparticles, liposomes, niosomes, ocular inserts, implants, intravitreal injections, nanoparticles, nanosuspension, microemulsion, dendrimers, in situ gels, iontophoresis and periocular injections. The compiled data presented in this review will act as a good information resource and reference point for further researches in the field of ocular drug delivery aiming non-invasive sustained release of drugs in the anterior and posterior segments of the eye.

Bortezomib-Induced Blepharitis: a Case Report

Introduction: Bortezomib is a proteasome inhibitor approved for the treatment of multiple myeloma, and has known manageable toxicities. Blepharitis is an inflammatory condition of the eyelid that leads to formation of chalazia both causing visual field disturbance. Bortezomib induced blepharitis has not been well reported in the literature. Case: we present a case of 76 year old lady with multiple myeloma who developed bortezomib-induced blepharitis and chalazia. Patient was successfully treated after topical ocular therapy, systemic antibiotherapy and omission of bortezomib.