Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

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

PURPOSE: This study aimed to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber hereditary optic neuropathy (LHON). DESIGN: This phase II, prospective, randomized, vehicle-controlled, single-center clinical trial involved administration of elamipretide 1% topical ophthalmic solution to patients with LHON over a 52-week double-masked treatment period, followed by an open-label extension (OLE) for up to 108 additional weeks of treatment. PARTICIPANTS: Twelve patients with LHON were included in this study. Patients aged 18 to 50 years with decreased vision for at least ≥ 1 year and ≤ 10 years, and a genetically confirmed diagnosis of m.11778G>A LHON were eligible for this trial. METHODS: For the first 52 weeks of the study, patients were randomized to 1 of 3 groups: elamipretide in both eyes or elamipretide in 1 eye (left eye and right eye were considered separate groups) and vehicle in the other eye, followed by an OLE in which both eyes were treated with elamipretide. MAIN OUTCOME MEASURES: The primary outcome measure was assessment of adverse events (AEs) from the administration of topical elamipretide, and the primary efficacy end point was change in best-corrected visual acuity (BCVA). Secondary outcome measures included changes in color vision, visual field mean deviation, and electrophysiological outcomes. RESULTS: Elamipretide was well tolerated with the majority of AEs 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 with baseline, both treatment groups showed improvement in color discrimination and contrast sensitivity in the OLE. CONCLUSIONS: Elamipretide treatment was generally well tolerated, with no serious AEs reported. Although this study did not meet its primary BCVA efficacy end point, improvements across assessments on visual function during the OLE and the post hoc findings of the Humphrey automated visual field central region were encouraging and require further exploration. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Co-delivery of Brinzolamide and Timolol from Micelles-laden Contact Lenses: In vitro and In Vivo Evaluation.

PURPOSE: Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide. METHODS: Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 µL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses. RESULTS: In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards. IN CONCLUSION: The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.

Allergic Conjunctivitis Management: Update on Ophthalmic Solutions.

PURPOSE OF REVIEW: The aim of this review, is to present an updated revision of topical management of SAC and PAC, based on the available scientific evidence and focused on the impact of ophthalmic solution formulations on eye surface. RECENT FINDINGS: Physicians treating ocular allergy should be aware of tear film and tear film disruption in SAC and PAC, and how eye drop composition and additives affect the physiology of the allergic eye. Seasonal and perennial allergic conjunctivitis (SAC and PAC) are the most frequent causes of ocular allergy (OA), and both conditions are underdiagnosed and undertreated. SAC and PAC are immunoglobulin E (IgE)-mediated hypersensitivity reactions. The additional tear film disruption caused by the release of inflammatory mediators increases and exacerbates the impact of signs and symptoms and may trigger damage of the ocular surface. Comorbidities are frequent, and dry eye disease in particular must be considered. Clinical guidelines for the management of SAC and PAC recommend topical therapy with antihistamines, mast cells stabilizers or dualaction agents as first-line treatment, but care should be taken, as many medications contain other compounds that may contribute to ocular surface damage.

Allogeneic serum-based eye drops may give better results than autologous drops in Sjögren's syndrome dry eye.

PURPOSE: Sjögren's syndrome (SS) may cause severe dry eye symptoms. One of the therapeutic option known for almost 40 years are autologous serum eye drops (ASEDs). Due to the presence of many pro-inflammatory factors in the autologous serum of SS patients, the use of allogeneic serum is often considered a better option. In our facility almost one-fifth of the patients using allogeneic serum-based eye drops (alloSEDs) suffered from autoimmune diseases, including SS. The study aim was to compare the effectiveness of both ASEDs and alloSEDs in SS patients. METHODS: From the group of SS patients using alloSEDs, five female SS patients aged 39-73 years were selected. They had the longest history of the use of the product. The analysis was based on OSDI forms and internal questionnaires which compared the effects of ASEDs and alloSEDs application. The patients used alloSEDs for a period of 5-28 months. All had previously used ASEDs for at least 2 years. RESULTS: For all five patients the mean OSDI after application of ASEDs and before introducing alloSEDs was 68.71, while the mean OSDI after the use of alloSEDs was 30.49. CONCLUSION: In SS the treatment results are better with alloSEDs than with ASEDs. Almost all SS patients who applied both autologous and allogeneic drops reported better effects with the latter as also confirmed by the study cases.

Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.

A Comparative Pharmacokinetic Study for Cysteamine-Containing Eye Drops as an Orphan Topical Therapy in Cystinosis.

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of "gold dust" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.

[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

Timolol maleate, a ß blocker eye drop, improved edema in a retinal vein occlusion model.

Purpose: To investigate the therapeutic effects of eye drops, namely, timolol maleate, a ß-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model. Methods: An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema. Results: Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO. Conclusions: These results indicate that timolol eye drops may be a potential option for RVO treatment.

Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial: Six-Year Results of Primary Selective Laser Trabeculoplasty versus Eye Drops for the Treatment of Glaucoma and Ocular Hypertension.

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This article reports health-related quality of life (HRQoL) and clinical effectiveness of initial treatment with SLT compared with intraocular pressure (IOP)-lowering eye drops after 6 years of treatment. DESIGN: Prospective, multicenter randomized controlled trial. PARTICIPANTS: Treatment-naive eyes with OAG or OHT initially treated with SLT or IOP-lowering drops. METHODS: Patients were allocated randomly to initial SLT or eye drops. After the initial 3 years of the trial, patients in the SLT arm were permitted a third SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. This study is registered at controlled-trials.com (identifier, ISRCTN32038223). MAIN OUTCOME MEASURES: The primary outcome was HRQoL at 6 years; secondary outcomes were clinical effectiveness and adverse events. RESULTS: Of the 692 patients completing 3 years in the LiGHT Trial, 633 patients (91.5%) entered the extension, and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase). At 6 years, no significant differences were found for the EuroQol EQ-5D 5 Levels, Glaucoma Utility Index, and Glaucoma Quality of Life-15 (P > 0.05 for all). The SLT arm showed better Glaucoma Symptom Scale scores than the drops arm (83.6 ± 18.1 vs. 81.3 ± 17.3, respectively). Of eyes in the SLT arm, 69.8% remained at or less than the target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs. 19.6%, respectively; P = 0.006). Trabeculectomy was required in 32 eyes in the drops arm compared with 13 eyes in the SLT arm (P < 0.001); more cataract surgeries occurred in the drops arm (95 compared with 57 eyes; P = 0.03). No serious laser-related adverse events occurred. CONCLUSIONS: Selective laser trabeculoplasty is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years.

Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: In Vivo Study in a Fungal Keratitis Model.

Fungal keratitis (FK) is a fungal infection of the cornea, which is part of the eye and causes corneal ulcers and an increased risk of permanent blindness, which is often found in Candida albicans species. Amphotericin B (AMB), which is a group of polyenes as the first-line treatment of FK, is effective in annihilating C. albicans. However, AMB preparations such as eye drops and ointments have major drawbacks, for instance, requiring more frequent administrations, loss of the drug by the drainage process, and rapid elimination in the precornea, which result in low bioavailability of the drug. An ocular dissolving microneedle containing the solid dispersion amphotericin B (DMN-SD-AMB) had been developed using a mixture of poly(vinyl alcohol) (PVA) and poly(vinylpyrrolidone) (PVP) polymers, while the solid dispersion AMB (SD-AMB) was contained in the needle as a drug. This study aims to determine the most optimal and safest DMN-SD-AMB formula for the treatment of FK in the eye as well as a solution to overcome the low bioavailability of AMB eye drops and ointment preparations. SD-AMB had been successfully developed, which was characterized by increased antifungal activity and drug release in vitro compared to other treatments. Furthermore, DMN-SD-AMB studies had also been successfully performed with the best formulation, which exhibited the best ex vivo corneal permeation profile and antifungal activity as well as being safe from eye irritation. In addition, an in vivo antifungal activity using a rabbit infection model shows that the number of fungal colonies was 0.98 ± 0.11 log10 CFU/mL (F3), 5.76 ± 0.32 log10 CFU/mL (AMB eye drops), 4.01 ± 0.28 log10 CFU/mL (AMB ointments), and 9.09 ± 0.65 log10 CFU/mL (control), which differed significantly (p < 0.05). All of these results evidence that DMN-SD-AMB is a new approach to developing intraocular preparations for the treatment of FK.

Efficacy of apraclonidine eye drops in treating ptosis secondary to myasthenia gravis: A pilot clinical trial.

INTRODUCTION/AIMS: Most patients with myasthenia gravis (MG) develop ocular manifestations during their illness and up to 22% may have isolated ocular myasthenia gravis (OMG). Apraclonidine elevates the eyelid by activating alpha-2 receptors on Muller's muscle, an accessory eyelid elevator muscle. In this study we evaluate the effect of apraclonidine in alleviating ptosis secondary to MG. METHODS: This clinical trial (NCT05045248) was done at the American University of Beirut Medical Center. Patients with ptosis secondary to MG were administered two drops of apraclonidine 0.5% solution to the most affected eye. We measured palpebral fissure height (PF), marginal reflex distance-1 (MRD1), marginal reflex distance-2 (MRD2), and levator function (LF) before drug administration and at 1, 5, 30, and 60 minutes after administration. RESULTS: Ten participants were enrolled in the study. Improvement in all eyelid measurements was noted in all participants as early as 1 minute after apraclonidine administration. From baseline to 60 minutes after administration, average PF increased from 8.8 ± 1.9 mm to 14.2 ± 2.6 mm, MRD-1 from 1.7 ± 1.4 mm to 5.4 ± 2.9 mm, MRD-2 from 7.1 ± 1.3 mm to 8.8 ± 1.7 mm, and LF from 13.4 ± 2.9 mm to 17.5 ± 2.4 mm. All increases were statistically significant. DISCUSSION: Apraclonidine may alleviate ptosis secondary to MG and may be an effective alternative treatment for this group of patients.

Eye drops of human origin-Current status and future needs: Report on the workshop organized by the ISBT Working Party for Cellular Therapies.

BACKGROUND AND OBJECTIVES: Serum eye drops (SEDs) are used to treat ocular surface disease (OSD) and to promote ocular surface renewal. However, their use and production are not standardized, and several new forms of human eye drops have been developed. MATERIALS AND METHODS: The International Society for Blood Transfusion Working Party (ISBT WP) for Cellular Therapies held a workshop to review the current types of eye drops of human origin (EDHO) status and provide guidance. RESULTS: The ISBT WP for Cellular Therapies introduced the new terminology 'EDHO' to emphasize that these products are analogous to 'medical products of human origin'. This concept encompasses their source (serum, platelet lysate, and cord blood) and the increasingly diverse spectrum of clinical usage in ophthalmology and the need for traceability. The workshop identified the wide variability in EDHO manufacturing, lack of harmonized quality and production standards, distribution issues, reimbursement schemes and regulations. EDHO use and efficacy is established for the treatment of OSD, especially for those refractory to conventional treatments. CONCLUSION: Production and distribution of single-donor donations are cumbersome and complex. The workshop participants agreed that allogeneic EDHO have advantages over autologous EDHO although more data on clinical efficacy and safety are needed. Allogeneic EDHOs enable more efficient production and, when pooled, can provide enhanced standardization for clinical consistency, provided optimal margin of virus safety is ensured. Newer products, including platelet-lysate- and cord-blood-derived EDHO, show promise and benefits over SED, but their safety and efficacy are yet to be fully established. This workshop highlighted the need for harmonization of EDHO standards and guidelines.

Prevention of myopia shift and myopia onset using 0.01% atropine in premyopic children - a prospective, randomized, double-masked, and crossover trial.

This study aims to evaluate the efficacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, and crossover trial was conducted over 13 months. Sixty premyopic children aged 6-12 years with cycloplegic spherical equivalent refraction (SER) > - 0.75 D and ≤ + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤ - 0.75D) and fast myopic shift (change in SER ≤ - 0.25D) in the two periods. Generalized estimating equation (GEE) model performed a statistically significant treatment effect of 0.01% atropine compared with placebo (pSER = 0.02, pAL < 0.001), with a mean SER and AL difference of 0.20D (- 0.15 ± 0.26D vs. - 0.34 ± 0.34D) and 0.11 mm (0.17 ± 0.11 mm vs. 0.28 ± 0.14 mm) in period 1, and 0.17D (- 0.18 ± 0.24D vs. - 0.34 ± 0.31D) and 0.10 mm (0.15 ± 0.15 mm vs. 0.24 ± 0.11 mm) in period 2. The GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) was significantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically significant (all p > 0.05). A total of 0.01% atropine significantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China. CONCLUSION: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020. WHAT IS KNOWN: • Minimal studies on interventions for pre-myopia, despite the International Myopia Institute stating that preventing myopia is an "even more valuable target" for science and practice than reducing progression after onset. WHAT IS NEW: • A total of 0.01% atropine eye drops may safely and effectively reduce the proportion of myopia onset and fast myopic shift in premyopic schoolchildren.

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

Effect of Atropine 0.01% Eye Drops on the Difference in Refraction and Axial Length between Right and Left Eyes.

INTRODUCTION: This study sought to determine whether the application of 0.01% atropine eye drops could impact the disparity in refraction and axial length (AL) between the right and left eyes in Chinese children. METHODS: The study was designed as a double-blind, placebo-controlled randomized trial. A total of 220 children aged 6-12 years were recruited from the Beijing Tongren Hospital in Beijing, China. Participants were randomized in a 1:1 ratio and were prescribed 0.01% atropine or placebo eye drops to be administered once a night to both eyes for the duration of 1 year. The cycloplegic refraction and AL were recorded including baseline, 6 months, and again at the 12 months. RESULTS: After 1-year follow-up period, 76 (69%) and 83 (75%) subjects of the initial 220 participants were identified as the 0.01% atropine and placebo groups, respectively. The inter-ocular difference in spherical equivalent refraction (SER) and AL demonstrated stable values in the 0.01% atropine treatment group (SER: p = 0.590; AL: p = 0.322) analyzed after 1 year, but found a significant increase (SER: p < 0.001; AL: p = 0.001) in the placebo group. Furthermore, over 1 year, eyes with greater myopia in the atropine group exhibited slower myopia progression (0.45 ± 0.44 D) than the lesser myopic eye (0.56 ± 0.44 D) (p = 0.003). CONCLUSION: This study demonstrated that 0.01% atropine could maintain the inter-ocular SER and AL difference. And 0.01% atropine appeared to be more effective in delaying the progression of myopia in eyes with more myopia than in the less myopic eyes.

A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.

Evaluation of antiglaucoma drug treatment awareness and patient-reported medication adherence: Determinants of glaucoma management.

Introduction: Primary open angle glaucoma (POAG) treatment is characterized by long-duration therapy, prescription variability, and non-adherence. Patient awareness toward drug treatment is crucial to ensure adherence. The present study was planned to evaluate drug treatment awareness, patient-perceived drug adherence, and prescription patterns in POAG patients. Methodology: This was a cross-sectional, single-center, questionnaire-based study conducted in the ophthalmology out patient department of a tertiary care hospital from April 2020 to November 2021. Patients of either gender, aged 40-70 years, with a confirmed diagnosis of POAG, who had records of POAG medications for at least last 3 months and who provided written informed consent, were included. Prescription details were recorded, and subsequently, patients were administered a pre-validated drug treatment awareness (14 items) questionnaire, a self-reported medication adherence (9-item) questionnaire, and then they performed eye drop instillation in a simulated setting. Results: The total number of patients enrolled was 180, which yielded 200 prescriptions. The mean drug treatment awareness score was 8.18 ± 3.30, and 135 (75%) patients scored more than 50% (≥7/14). Similarly, 159 patients (83.33%) had scored >50% (i.e. >5/9), with a mean score of 6.30 ± 1.70 in the medication treatment adherence questionnaire. The mean eye drop instillation performance score was 7.18 ± 1.20. The 200 POAG prescriptions containing 306 drugs were analyzed, with beta blockers (184/200, 92%) and timolol (168/200, 84% encounters) being the highest prescribed classes/drugs. Conclusion: POAG patients did have adequate treatment awareness with good self-reported medication adherence and performance of eye drop instillation technique. Around 25% patients lacked awareness; hence, reinforcement education programs on medication regimens need to be implemented.

Effectiveness of rb-bFGF Eye Drops for Post-Cataract Surgery Dry Eye and Observation of Changes in Tear Secretion and Corneal Damage in Patients.

Objective: Dry eye syndrome after cataract surgery is a common complication that may affect the patient's visual comfort and quality of life. Because the surgery may affect the secretion and quality of tears in the eye, resulting in dry and uncomfortable eyes.This study aimed to investigate the therapeutic effects of recombinant bovine basic fibroblast growth factor (rb-bFGF) eye drops on dry eye syndrome after cataract surgery and to analyze its impact on tear secretion and corneal injury. Methods: This is a retrospective study. A total of 126 patients (126 eyes) with dry eye syndrome after cataract surgery were treated between January 2021 and October 2022. patients were randomly divided into a study group (64 patients, 64 eyes) and a control group (62 patients, 62 eyes). Both groups were treated with sodium hyaluronate eye drops, while the study group received rb-bFGF eye drops for four weeks in addition to the sodium hyaluronate eye drops. The clinical efficacy, results of tear secretion test (SIT), tear film break-up time (BUT), corneal fluorescein staining, corneal topography examination, oxidative stress indicators, ocular surface disease index (OSDI) score, and drug adverse reactions were compared between the two groups. Results: The study group exhibited a significantly higher total effective treatment rate (96.88%) compared to the control group (85.48%), suggesting the enhanced efficacy of rb-bFGF eye drops. Moreover, the study group demonstrated extended tear secretion length and tear film break-up time, indicating improved tear film stability and ocular surface health. Additionally, the study group showed reduced corneal fluorescein staining score and improved corneal surface regularity index, indicative of enhanced corneal integrity and smoothness. Notably, tear superoxide dismutase levels were elevated, while lipid peroxide levels were lowered in the study group, underscoring the potential antioxidative effects of rb-bFGF. The study group also exhibited a lower OSDI score, suggesting reduced ocular discomfort and improved quality of life. Although the study group had a slightly higher incidence of adverse reactions (9.38%) compared to the control group (8.06%), the difference was not statistically significant. Particularly significant is the statistical significance highlighting the heightened total effective treatment rate in the study group, indicating the potential of rb-bFGF eye drops in promoting favorable therapeutic outcomes. Conclusion: rb-bFGF eye drops are safe and effective in treating dry eye syndrome after cataract surgery. They can help regulate tear secretion, repair corneal damage, and improve dry eye symptoms. Despite the retrospective design and relatively small sample size of this study, further randomized controlled trials and larger sample size may be needed to verify the robustness of the results, but this study is important for guiding the treatment strategy and optimizing patient care for dry eye after cataract surgery.

Multifocal Contact Lenses and 0.01% Atropine Eye Drops for Myopia Control Study: Research Protocol for a 1-Year, Randomized, Four-Arm, Clinical Trial in Schoolchildren.

OBJECTIVES: Previous studies have shown that combined use of orthokeratology and 0.01% atropine (AT) eye drops can strongly prevent axial elongation in myopic children. However, the efficacy of combined use with multifocal contact lens (MFCL) and 0.01% AT remains unclear. The aim of this trial is to clarify the efficacy of MFCL+0.01% AT combination therapy for myopia control and safety. METHODS: This prospective study is a randomized, double-masked, placebo-controlled trial with four arms. A total of 240 children aged 6 to 12 years with myopia is recruited and randomly assigned to one of the four groups in a ratio of 1:1:1:1 as follows: group 1: MFCL+AT combination therapy, group 2: MFCL monotherapy, group 3: AT monotherapy, and group 4: placebo. The participants will continue the assigned treatment for 1 year. The primary and secondary outcomes are the comparisons of axial elongation and myopia progression in the four groups during the 1-year study period. DISCUSSION: The present trial would determine whether the MFCL+AT combination therapy is more effective in slowing axial elongation and myopia progression in schoolchildren as compared with each monotherapy or placebo, and it also confirm acceptable safety of the combination therapy.