Development and Characterization of a Photocrosslinkable, Chitosan-Based, Nerve Growth Factor-Eluting Hydrogel for the Ocular Surface.

Purpose: Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface. Methods: Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels. Results: Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24 hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12 hours; however, both were significantly better than control (P < 0.01). Conclusions: rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications. Translational Relevance: Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.

Contact lenses as novel tear fluid sampling vehicles for total RNA isolation, precipitation, and amplification.

The tear fluid is a readily accessible, potential source for biomarkers of disease and could be used to monitor the ocular response to contact lens (CL) wear or ophthalmic pathologies treated by therapeutic CLs. However, the tear fluid remains largely unexplored as a biomarker source for RNA-based molecular analyses. Using a rabbit model, this study sought to determine whether RNA could be collected from commercial CLs and whether the duration of CL wear would impact RNA recovery. The results were referenced to standardized strips of filtered paper (e.g., Shirmer Strips) placed in the inferior fornix. By performing total RNA isolation, precipitation, and amplification with commercial kits and RT-PCR methods, CLs were found to have no significant differences in RNA concentration and purity compared to Schirmer Strips. The study also identified genes that could be used to normalize RNA levels between tear samples. Of the potential control genes or housekeeping genes, GAPDH was the most stable. This study, which to our knowledge has never been done before, provides a methodology for the detection of RNA and gene expression changes from tear fluid that could be used to monitor or study eye diseases.

2021 Survey of Keratoplasty Postoperative Steroid Management.

PURPOSE: The aim of the study is to investigate US-based ophthalmologists' preferred corneal transplant techniques and postoperative steroid regimen. METHODS: Ophthalmologists attending the 2021 Cornea and Eye Banking Forum and/or Cornea Subspecialty Day were surveyed in person. RESULTS: Ninety-two ophthalmologists with a median of 13 years (range of 1-35; mean of 14.5; ±9.05 mean ± SD) of experience as attending clinicians were surveyed. One hundred percent of the surgeons performed penetrating keratoplasty, which was followed by 96.7% for Descemet stripping endothelial keratoplasty, 90.2% for Descemet membrane endothelial keratoplasty, and 72.8% for deep anterior lamellar keratoplasty. Prednisolone 1% for postoperative care was the preferred choice across all surveyed keratoplasty techniques and postsurgery time intervals. All surgeons reported steroid administration frequency of 4 times a day in the first month and once a day after 12 months postkeratoplasty. To manage ocular hypertension after corneal transplantation, the leading approach was adding a glaucoma medication (44.6%), and beta-adrenergic antagonists were ranked as the most preferred choice by 59 (66.3%) of the respondents. For graft rejection after corneal transplantation, topical steroids (79.8%) were the initial treatment of choice with hourly administration being the most common frequency prescribed (87.4%). Most surgeons either agreed or strongly agreed (78.4%) that a randomized clinical trial evaluating the safety and efficacy of different steroid regimens after corneal transplantation would influence their clinical decision making. CONCLUSIONS: Prednisolone remains the predominantly used steroid across different keratoplasties. Steroid regimens are similar for non-high-risk penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, and deep anterior lamellar keratoplasty. To treat graft rejection, surgeons tend to initially add a glaucoma medication than to reduce the potency or frequency of the steroid.

Topical Sustained Delivery of Miltefosine Via Drug-Eluting Contact Lenses to Treat Acanthamoeba Keratitis.

This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL's physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis.

Advances in biomaterials for the treatment of retinoblastoma.

Retinoblastoma is the most common primary intraocular malignancy in children. Although traditional chemotherapy has shown some success in retinoblastoma management, there are several shortcomings to this approach, including inadequate pharmacokinetic parameters, multidrug resistance, low therapeutic efficiency, nonspecific targeting, and the need for adjuvant therapy, among others. The revolutionary developments in biomaterials for drug delivery have enabled breakthroughs in cancer management. Today, biomaterials are playing a crucial role in developing more efficacious retinoblastoma treatments. The key goal in the evolution of drug delivery biomaterials for retinoblastoma therapy is to resolve delivery-associated obstacles and lower nonlocal exposure while ameliorating certain adverse effects. In this review, we will first delve into the historical perspective of retinoblastoma with a focus on the classical treatments currently used in clinics to enhance patients' quality of life and survival rate. As we move along, we will discuss biomaterials for drug delivery applications. Various aspects of biomaterials for drug delivery will be dissected, including their features and recent advances. In accordance with the current advances in biomaterials, we will deliver a synopsis on the novel chemotherapeutic drug delivery strategies and evaluate these approaches to gain new insights into retinoblastoma treatment.

Extracellular Vesicles in Corneal Fibrosis/Scarring.

Communication between cells and the microenvironment is a complex, yet crucial, element in the development and progression of varied physiological and pathological processes. Accumulating evidence in different disease models highlights roles of extracellular vesicles (EVs), either in modulating cell signaling paracrine mechanism(s) or harnessing their therapeutic moiety. Of interest, the human cornea functions as a refractive and transparent barrier that protects the intraocular elements from the external environment. Corneal trauma at the ocular surface may lead to diminished corneal clarity and detrimental effects on visual acuity. The aberrant activation of corneal stromal cells, which leads to myofibroblast differentiation and a disorganized extracellular matrix is a central biological process that may result in corneal fibrosis/scarring. In recent years, understanding the pathological and therapeutic EV mechanism(s) of action in the context of corneal biology has been a topic of increasing interest. In this review, we describe the clinical relevance of corneal fibrosis/scarring and how corneal stromal cells contribute to wound repair and their generation of the stromal haze. Furthermore, we will delve into EV characterization, their subtypes, and the pathological and therapeutic roles they play in corneal scarring/fibrosis.

Effect of Scleral Lens Oxygen Permeability on Corneal Physiology.

SIGNIFICANCE: This randomized, masked, crossover clinical study identifies that ≥125 Dk materials should be used for scleral lens daily wear if disruption to corneal oxygen is to be minimized. PURPOSE: Modern scleral lens use has increased and has proven to be successful where other types and materials have previously failed. Although the required oxygen permeability has been modeled, this has not been established clinically. METHODS: Fifteen masked participants aged 20.7 ± 2.3 years (10 female) were bilaterally fitted with five different scleral lenses (65, 100, 125, 163, and 180+ Dk) of the same shape profile and one soft silicone hydrogel lens compared with no lens wear on separate occasions in a randomized order. A masked researcher measured corneal thickness and fluid reservoir depth, corneal curvature, objective bulbar and limbal redness, corneal biomechanics, and ocular surface oxygen consumption before and after 8 hours of wear. In addition, comfort scores were obtained using a visual analog scale. RESULTS: Scleral lenses with oxygen permeability of 65 Dk resulted in greater corneal thickness (1.37 ± 1.25%) after 8 hours of wear versus ≥100 Dk materials (0.58 ± 0.99%; F = 17.215, P < .001) because of stromal thickening; edema with ≥100 Dk materials was associated with fluid reservoir depth (r = 0.231, P = .05). Fluid reservoir depth decreased similarly with all oxygen-permeable lenses from 325.6 ± 99.1 µm to 174.2 ± 100.8 µm after 8 hours of wear (F = 0.961, P = .44). Oxygen consumption reduced with ≤125 Dk lenses (χ = 604.196, P < .001). Soft and scleral lens wear had no effect on corneal curvature, corneal biomechanics, or ocular hyperemia (P > .05). Soft lenses were more comfortable than all the scleral lenses (P < .05), and the 180+ Dk lenses had the best comfort among the sclerals (P < .05). CONCLUSIONS: A ≥125 Dk is advised for safe scleral lens daily wear. Scleral lens wear leads to an increase in corneal thickness, regardless of lens-material oxygen permeability because of the fluid reservoir depth.

Global trends in myopia management attitudes and strategies in clinical practice - 2019 Update.

PURPOSE: A survey in 2015 identified a high level of eye care practitioner concern about myopia with a reported moderately high level of activity, but the vast majority still prescribed single vision interventions to young myopes. This research aimed to update these findings 4 years later. METHODS: A self-administrated, internet-based questionnaire was distributed in eight languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy of available strategies and adoption levels of such strategies, and reasons for not adopting specific strategies. RESULTS: Of the 1336 respondents, concern was highest (9.0 ±â€¯1.6; p < 0.001) in Asia and lowest (7.6 ±â€¯2.2; p < 0.001) in Australasia. Practitioners from Asia also considered their clinical practice of myopia control to be the most active (7.7 ±â€¯2.3; p < 0.001), the North American practitioners being the least active (6.3 ±â€¯2.9; p < 0.001). Orthokeratology was perceived to be the most effective method of myopia control, followed by pharmaceutical approaches and approved myopia control soft contact lenses (p < 0.001). Although significant intra-regional differences existed, overall, most practitioners did not consider single-vision distance under-correction to be an effective strategy for attenuating myopia progression (79.6 %), but prescribed single vision spectacles or contact lenses as the primary mode of correction for myopic patients (63.6 ±â€¯21.8 %). The main justifications for their reluctance to prescribe alternatives to single vision refractive corrections were increased cost (20.6 %) and inadequate information (17.6 %). CONCLUSIONS: While practitioner concern about myopia and the reported level of activity have increased over the last 4 years, the vast majority of eye care clinicians still prescribe single vision interventions to young myopes. With recent global consensus evidence-based guidelines having been published, it is hoped that this will inform the practice of myopia management in future.

How should initial fit inform soft contact lens prescribing.

PURPOSE: To investigate how initial HEMA and silicone-hydrogel (SiHy) contact lens fit on insertion, which informs prescribing decisions, reflect end of day fit. METHODS: Thirty participants (aged 22.9±4.9 years) were fitted contralaterally with HEMA and SiHy contact lenses. Corneal topography and tear break-up time were assessed pre-lens wear. Centration, lag, post-blink movement during up-gaze and push-up recovery speed were recorded after 5,10,20min and 8h of contact lens wear by a digital slit-lamp biomicroscope camera, along with reported comfort. Lens fit metrics were analysed using bespoke software. RESULTS: Comfort and centration were similar with the HEMA and SiHy lenses (p>0.05), but comfort decreased with time (p<0.01) whereas centration remained stable (F=0.036, p=0.991). Movement-on-blink and lag were greater with the HEMA than the SiHy lens (p<0.01), but movement-on-blink decreased with time after insertion (F=22.423, p<0.001) whereas lag remained stable (F=1.967, p=0.129). Push-up recovery speed was similar with the HEMA and the SiHy lens 5-20min after insertion (p>0.05), but was slower with SiHy after 8h wear (p=0.016). Lens movement on blink and push-up recovery speed was predictive of the movement after 8h of wear after 10-20min SiHy wear, but after 5 to 20min of HEMA lens wear. CONCLUSIONS: A HEMA or SiHy contact lens with poor movement on blink/push-up after at least 10min after insertion should be rejected.