Sublingual administration of atropine eye drops for treating sialorrhea after stroke: A randomized controlled trial.

BACKGROUND: Sialorrhea is a common concern in patients with swallowing disorders after stroke. Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production. OBJECTIVE: The present study aimed to assess the safety, efficacy, and tolerability of sublingual administration of atropine eye drops for treating sialorrhea after stroke. DESIGN: This was a prospective cohort study. SETTING: This study was conducted at Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei Province, China. POPULATION: Stroke patients with sialorrhea were analyzed. METHODS: One hundred stroke patients with sialorrhea were randomly assigned to the control group and the test group (n = 50 per group). The control group received routine swallowing rehabilitation training and neuromuscular electrical stimulation. The test group received therapy with 1% atropine eye drops, wherein one drop was administered sublingually 3 times per day. The Sialorrhea Scoring Scale and the incidence of adverse events were used to compare the severity of sialorrhea in the two groups. RESULTS: The mean (standard deviation) sialorrhea score improved from 5.12 for the control group with routine rehabilitation training to 3.94 for the test group with atropine eye drop administration (P < 0.01). No significant differences in the incidence of adverse events were observed between the two groups. CONCLUSIONS: The sublingual administration of 1% atropine eye drops three times per day can reduce the degree of sialorrhea to an extent more than that achieved with routine rehabilitation training; thus, this approach is effective, safe, and minimally invasive for treating sialorrhea after stroke.

Comparative fluorophotometric evaluation of the ocular surface retention time of cross-linked and linear hyaluronic acid ocular eye drops on healthy dogs.

PURPOSE: Evaluate and compare the retention time on the canine ocular surface of crosslinked hyaluronic acid (X-HA), linear hyaluronic acid (L-HA) and saline solution using fluorescent compounds (fluorescein sodium salt, Alexa Fluor 488 cadaverine and Alexa Fluor 488 maleimide). METHODS: 0.9% saline solution (SAL) was combined with fluorescein sodium salt. X-HA and L-HA were covalently modified using Alexa Fluor 488 reactive moieties. Eye drops were applied to 70 eyes of 35 dogs that were previously assessed and determined to have a normal ocular surface. Employing a blue light filter (450-490 nm), digital images were captured from instillation to 180 min. Images were analyzed to assess the percent of the total ocular area covered with green fluorescence at various time points. RESULTS: X-HA exhibited a dual phase behavior: A broad microgel coverage first, followed by accumulation in tear film meniscus and medial canthus in the second phase, remaining in contact with the ocular surface up to 180 min. Coverage with L-HA and SAL eye drops quickly migrated to the tear meniscus. No traces of the fluorescent compounds were observed by 45 min in eyes treated with SAL solution compound and, by 120 min, eyes treated with L-HA. CONCLUSIONS: X-HA exhibited a significantly increased ocular surface contact time with the ocular surface compared with L-HA and SAL. Not only could this indicate extended lubrication time but also supports the potential use of this compound as a method for topical sustained-release drug application.

Enhancement of sensitivity for moxifloxacin spectrofluorimetric analysis through photoinduced electron transfer inhibition. Green assessment with application to pharmaceutical eye drops.

A green, simple, rapid, selective, and highly sensitive fluorimetric protocol has been established for quantitative analysis of the antibacterial drug moxifloxacin in its pure form and pharmaceutical dosage form. Owing to photoinduced electron transfer, moxifloxacin exhibits low native fluorescence in neutral media. Based on that, the developed fluorimetric protocol depends on inhibiting the photoinduced electron transfer effect of the nitrogen atom presented on the pyrrolidine ring in moxifloxacin by suitable adjusting of pH of the medium surrounding it, leading to its protonation. It is simply achieved by using 0.5 M acetic acid. This protonation enhances the native fluorescence of moxifloxacin, turning it into a stronger one. This fluorescence was measured at 498 nm after excitation at 295 nm with a linearity range from 10 to 60 ng mL-1 and a high correlation coefficient value of 0.9998. The fluorimetric approach could be applied for moxifloxacin detection with a limit of 0.89 ng mL-1 and a quantification limit of 2.69 ng mL-1. The developed method has been validated according to ICH guidelines, indicating high accuracy and excellent precision. Furthermore, the developed fluorimetric protocol was applied successfully for moxifloxacin analysis in pharmaceutical eye drops. As a result, the proposed protocol could be easily applied for quality control of moxifloxacin in different laboratories all over the world.

Autologous serum eye drops for patients with dry eye disease: a systematic review and meta-analysis of randomized controlled trials.

Background: Dry eye disease (DED) is highly prevalent worldwide, leading to increased medical costs, economic burdens on families and society, and a diminished quality of life for patients. The utilization of autologous serum eye drops (ASEDs) for the treatment of DED is progressively rising. Objective: To further evaluate the efficacy and safety of ASEDs in the treatment of DED. Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. This search encompassed the inception of each database up to April 1, 2024, with a specific focus on identifying RCTs evaluating the efficacy and safety of ASEDs for the treatment of DED. Data analysis was conducted utilizing Stata 15.0 software and the Cochrane Risk of Bias Assessment Tool was utilized to appraise the literature's quality. Results: The study encompassed 12 RCTs. In comparison to the use of artificial tears (AT), patients diagnosed with DED who utilized ASEDs displayed elevated the Schirmer test (ST) scores [WMD = 2.35, 95% CI (1.45, 3.24), p < 0.001] and tear-film breakup time (TBUT) scores [WMD = 2.83, 95% CI (2.27, 3.39), p < 0.001], decreased Corneal fluorescence staining (CFS) scores [SMD = -2.11, 95% CI (-3.07, -1.15), p < 0.001] and the Ocular Surface Disease Index (OSDI) scores [WMD = -10.54, 95% CI (-13.31, -7.77), p < 0.001], and experienced a reduced frequency of adverse events [RR = 0.36, 95% CI (0.13, 0.99), p = 0.048]. Conclusion: In this study, ASEDs had been shown to enhance tear secretion, extend tear film break-up time, mitigate corneal epithelial damage, ameliorate OSDI scores, and exhibit greater safety compared to AT.

Clinical Effectiveness, Safety, and Compliance of Two Compounded Formulations of Tacrolimus Eye Drops: An Open-Label, Sequential Prospective Study.

Ophthalmic tacrolimus compounded formulations are usually made from the commercial intravenous presentation, which contains ethanol as a solubilizer due to the low solubility of tacrolimus. The use of cyclodextrins is presented as an alternative to ethanol, an ocular irritant excipient, to avoid its long-term irritant effects. Open-label, sequential, prospective study to compare effectiveness, safety, and adherence of a new formulation of 0.015% tacrolimus with cyclodextrins (TCD) versus 0.03% tacrolimus with ethanol (TE). The ocular evaluation was assessed by ocular signs, corneal staining, subjective questionnaires as Visual Function Questionnaire (VFQ-25) and Visual Analogue Scale (VAS) of symptoms, lacrimal stability, ocular redness, and intraocular pressure. Compliance was assessed by VAS of adherence and empirically (difference between theoretical and actual consumption). Clinical ocular signs and corneal staining score remained stable for most patients 3 months after switching formulations. The TCD formulation did not modify the tear stability and intraocular pressure of the treated patients compared to the TE formulation. TCD eye drops significantly decreased the subjective pain values on VFQ-25 scale and burning sensation on the VAS symptom scale in comparison to TE formulation after 3 months after the change to TCD formulation. The novel tacrolimus in cyclodextrins formulation is a promising alternative for treating inflammatory ocular pathologies refractory to first-line treatments.

Nanomedicine in glaucoma treatment; Current challenges and future perspectives.

Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment.

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1ß, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1ß and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1ß and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Localized Angiokeratomas in healthy adolescence responded to topical Timolol.

Angiokeratoma (AK) is an uncommon vascular cutaneous illness that is characterized by benign vascular ectasias of the papillary dermis combined with papillomatosis, acanthosis, and hyperkeratosis of the epidermis. It often presents as mainly asymptomatic. Here, we present a case of a 14-year-old Saudi male who presented to the dermatology clinic with red-to-black nodules of varying sizes on the palmar and dorsal surfaces of his left hand. Upon examination, the nodules were painless with no other constitutional symptoms. Laboratory investigations were unremarkable. A 4-mm skin punch biopsy showed dilated vascular channels at the papillary dermis and corneal layer with acanthotic epidermis with granulation tissue; these findings were suggestive of AKs of Mibelli. Timolol drops were prescribed twice daily for 1 month, and the patient was seen after a month with a 90% resolution of lesions. This case study describes an intriguing instance of eruptive AK of Mibelli that was treated with Timolol 0.5% drops and was localized unilaterally over the left hand in a youngster who had previously been in good health. To the best of our knowledge, no previously reported AK of Mibelli cases that responded to Timolol 0.5% drops.

Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.

Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.

Timing and Efficacy Evaluation of 755-nm Long Pulse Alexandrite Laser and 2% Carteolol Hydrochloride Eye Drops Co-Treatment for Thicker Superficial Infantile Hemangioma.

Purpose: Superficial Infantile hemangioma (SIH) is the most common type of IH. Some studies have shown the efficacy of 755-nm long pulse alexandrite laser (LPAL) and topical 2% carteolol hydrochloride (C-HCL) eye drops for the treatment of SIH. This article retrospectively analyzes the safety and efficacy of 755-nm LPAL combined with 2% C-HCL eye drops for treating thicker SIH, and explores the optimal treatment time for SIH. Materials and Methods: This study included 2-5 mm thick SIH patients who received co-treatment of 755-nm LPAL and 2% C-HCL eye drops. The SIH patients were divided into 3 groups based on their age and IH growth curve: ≤ 1 month (≤ 1M), 1-3 months (excluding 1 month; 1-3M), and 3-12 months (excluding 3 months; 3-12M). Results: There was no difference in efficacy between the ≤ 1M and the 1-3M group, and were both better than the 3-12M group. Furthermore, there was no difference in the average number of treatments between the ≤ 1M and 1-3M groups and were both less than the 3-12M group. There was no significant difference in the incidence of adverse reactions between the groups. Compared with the ≤ 1M and 1-3M groups, the 3-12M group indicated more permanent skin lesions after the treatment. Conclusion: It was revealed that co-treatment with 755-nm LPAL and 2% C-HCL eye drops is safe and effective against thicker SIH. Compared with the 3-12M group, ≤ 3 months can achieve better efficacy, requires a shorter treatment time, less likely to leave permanent skin lesions such as scars. Moreover, patients with no proliferation can be observed to 1 month.

Corneal vascularisation and haemorrhage associated with netarsudil drops.

We report an interesting case of superficial corneal vascularization along with haemorrhages and microcystic edema confined to the inferior cornea in a female patient that are clearly attributed to netarsudil eye drops which she had been instilling for the last 8 weeks . Complete regression of all these corneal changes was noted after 3 months of discontinuation of this Rho kinase inhibitor. This is a unique finding and to our knowledge ; has not been reported so far.

Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.

Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German-Austrian-Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects.

Long-Term Observation of Prognostic Factors and Clinical Outcome of Vernal Keratoconjunctivitis in Childhood.

Purpose: Vernal keratoconjunctivitis (VKC) is a refractory ocular allergic disorder that mainly affects boys. Long-term follow-up has been rarely reported for VKC. We investigated the long-term clinical outcome of VKC to identify relevant clinical features of prognostic value based on follow-up for a median of 70 months. Methods: In total, 45 consecutive patients clinically diagnosed with VKC aged 4 to 12 years at onset at the Department of Ophthalmology of Fukuoka University Hospital were included. Patients were treated with immunosuppressive eye drops without simultaneous corticosteroid eye drops, except for the occurrence of exacerbations. Collated variables were gender, age at onset, clinical score of ocular lesions (conjunctival giant papillae, limbal edema and corneal epithelial lesions) at the first visit, and clinical score of atopic dermatitis (AD) at baseline. Cumulative cure rate was estimated using Kaplan-Meier method. A binomial logistic predictive model was used to determine the most reliable clinical predictors of VKC outcome. Results: The observation period ranged from 24 to 188 months, with median of 70 months. Among the 45 cases enrolled, all non-cured cases (14 cases) observed clinically were complicated by AD. Cumulative cure rate was 74.5% and 84.9% at eight- and ten-year follow-up, respectively. Ten-year cumulative cure rates of cases with and without AD were 50.5% and 100%, respectively, and a significant difference was found between these cumulative cure curves. Binomial regression analysis revealed that AD and gender were significantly related to worse outcome, and this binomial regression model had high sensitivity and specificity. Conclusion: This study demonstrated that th eclinical outcomeof VKC might be predicted by several factors that can beobtained in the early clinical phase. Information on the long-term prognosis of VKC patients might play an important role for precision medicine for VKC in childhood.

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.

Phase I Study of Tivozanib Eye Drops in Healthy Volunteers and Patients with Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the safety, pharmacokinetics, and exploratory efficacy of tivozanib eye drops in healthy volunteers and patients with neovascular age-related macular degeneration (nAMD). Design: This multicenter group-sequential dose escalation phase I study consisted of a placebo-controlled double-masked study of healthy volunteers (cohorts 1 and 2) and an open-label study of patients with nAMD (cohort 3). Participants: Healthy volunteers: Japanese or White men aged 20 to <50 years. Patients with nAMD with central subfield thickness (CST) ≥300 µm and best-corrected visual acuity score ≥23 letters in the study eye. Methods: In the single-dose cohort of healthy men (cohort 1: steps 1-5), 1 or 2 tivozanib eye drops (30 µL/drop, 5-minute interval; 0.5, 1.0, and 2.0 w/v%) or placebo were administered in 1 eye once. In the multiple-dose cohort of healthy men (cohort 2: steps 1-6), 1 or 2 tivozanib eye drops (0.5, 1.0, and 2.0 w/v%) or placebo were administered 3 times daily in 1 eye for 21 days. In the multiple-dose cohort of patients with nAMD (cohort 3, steps 1-3), 1 or 2 tivozanib eye drops (0.5 and 1.0 w/v%) were administered 3 times daily in 1 affected eye for 21 days. Main Outcome Measures: The safety outcome measures included adverse events (AEs). The pharmacokinetic outcome was serum tivozanib concentration. Among the exploratory efficacy outcomes, CST was evaluated. Results: In total, 40, 48, and 28 participants were enrolled in cohorts 1, 2, and 3, respectively. Serious AEs did not occur in cohorts 1 to 3. The most frequent AE in multiple-dose cohorts was reversible punctate keratitis: placebo arm, 8.3% (healthy men, 1/12); tivozanib arm, 47.2% (healthy men, 17/36) and 14.3% (nAMD, 4/28). Serum tivozanib exposure increased dose-dependently and was similar in healthy men and patients with nAMD. In patients with nAMD, mean CST changes from baseline to day 22 were -27.6 ± 54.88 (0.5 w/v%; 1 drop, 3 times daily), -35.6 ± 49.64 (1.0 w/v%; 1 drop, 3 times daily), and -43.7 ± 55.19 µm (1.0 w/v%; 2 drops, 3 times daily). Conclusions: Tivozanib eye drops showed a favorable safety profile in healthy Japanese and White men and Japanese patients with nAMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Autologous Serum Eye Drops Diluted with Cyclosporine A 0.05% and Sodium Hyaluronate 0.1%: An Experimental Comparative Study.

PURPOSE: The purpose of this study was to assess in-vitro efficacy of a suffusion of autologous serum withcyclosporine 0.05% (CsA) and sodium hyaluronate 0.1% (SH). METHODS: The expression of proinflammatory markers interleukin 6 (IL-6) and TNF-Alpha (TNF-α) in limbal epithelial cells was evaluated. Also, assessment of the stability of epithelial growth factor and transforming growth factor-beta (EGF, TGF-ß) in the 50% combinations with autologous serum (AS) was done. The characteristics (pH, density, osmolality) of the two combinations were also evaluated. Additionally, cytotoxicity effect of given test compounds was evaluated on human limbal epithelial cells (LEpiC). RESULTS: The percentage of cells expressing IL-6 subjected to AS + SH and AS + CsA were 6.23% and 5.69% respectively. There was no significant difference in percentage of cells expressing TNF-α between the formulations (5.87%, 5.83% respectively). The growth factors; EGF and TGF-ß remained stable forone month duration (on 2 and 4 weeks) at 4 °C without significant difference between the time intervals tested. The results of MTT assay suggested that limbal epithelial cells treated with AS + CsA and AS + SH combinations showed minimal toxicity however it was not significant statistically (p ≤ 0.05). CONCLUSION: Two test combinations (AS + CsA, AS + SH) showed stable growth factors (EGF, TGF-ß) and good anti-inflammatory property against pro-inflammatory markers. Also, the 2 combinations were found safe on cultured limbal epithelial cells. The novel combination of autologous serum in CsA may provide added benefit in dry eye disease (DED) through their combined anti-inflammatory and epitheliotropic effects.

Comparative study on corneal epithelium healing: effects of crosslinked hyaluronic acid and amniotic membrane extract eye drops in rats.

Introduction: Corneal ulcers are common lesions in both human and veterinary medicine. However, only a few studies have evaluated the efficacy of cross-linked hyaluronic acid (X-HA) eye drops on corneal wound healing. To our knowledge, this is the first study to demonstrate and compare the efficacy of amniotic membrane extract eye drops (AMEED) and X-HA for corneal wound healing in rats. Material and methods: A total of 15 male Wistar rats (30 eyes) were used in this study. Then, 10 eyes were treated with X-HA, AMEED, or 0.9% saline. After general and topical anesthesia, a superficial corneal ulcer was created using a corneal trephine. The defect was further polished with a diamond burr. Three groups of 10 eyes each were treated with either one drop of 0.75% X-HA or AMEED or 0.9% saline (control), administered every 12 h for a duration of 72 h. The median epithelial defect area (MEDA), expressed as a percentage of the total corneal surface, was measured at 0, 12, 24, 36, 48, and 72 h. Re-epithelization time scores were also evaluated. The Kruskal-Wallis test was used to compare median times for re-epithelization and histopathologic scores between groups, while the Friedman test (for paired data) was employed to compare results from the serial analysis of MEDA and vascularization scores between groups. Results: MEDA was not significantly different between X-HA and AMEED. However, MEDA was significantly smaller in the X-HA group compared to the control group at 36 h (2.73 interquartile range (IQR) 5.52% x 9.95 IQR 9.10%, P=0.024) and 48 h (0.00 IQR 0.26% x 6.30 IQR 8.54%, P=0.030). The overall time for re-epithelization was significantly lower in the X-HA group (3.00 IQR 3.00) compared to the AMEED (6.5 IQR 3.00) and control (7.00 IQR 1.00) groups (P=0.035). Vascularization, hydropic degeneration, and epithelial-stromal separation were significantly less observed in samples in the X-HA-treated compared to samples in the AMEED- and saline-treated groups. Significantly more corneal epithelium cells were labeled for caspase3 in samples from the AMEED- and saline-treated groups compared to those from the X-HA-treated group. Discussion: Topical X-HA has been shown to accelerate corneal epithelial healing. AMEED did not decrease corneal re-epithelialization time. X-HA may also potentially be used as an adjunct therapy for treating corneal ulcers in clinical situations.

An Investigation Into the Orthoptist Experience of Instilling Eye Drops in Children Attending the Eye Clinic.

Purpose: Eye drops instillation in children is a fundamental part of accurately examining a child's eyes. Unfortunately eye drops can be a distressing experience for children, parents/guardians and orthoptists. The purpose of this research is to focus on the experiences of orthoptists and delve deeper into their views and explore if improvements can be made. Methods: This was a Qualitative study involving semi-structured interviews with 8 registered and currently practicing orthoptists in the UK. The interviews were undertaken online via Microsoft TEAMS. Thematic analysis was carried out for the purposes of data analysis. Results: 3 major themes were identified (1) how orthoptist frame instilling eye drops, (2) techniques to address challenges, and (3) improvements to eye drops instillation process. Orthoptists were aware that instilling eye drops in children brought specific challenges such as distress and resistance; however they saw it as an essential part of their job. Orthoptists understood their role within a wider team which delivered eye care to children effectively and that there was a division of they believed that. Orthoptists were aware that the eye drops may cause some distress, however this did not affect compliance with treatment such as wearing glasses and/or a patch. Orthoptists believed verbal and non-verbal communication with the child was essential. Help was sought from parents or colleagues for physical restraint if required. Orthoptists suggested adapting to children with additional needs and giving out eye drops to parents/carers to instill at home if dilation in the eye clinic became difficult. They suggested improvements such as assistance from play specialists, developing a pre-procedural information video, practise as a student, the study of the medical exemptions module and the potential of using eye sprays instead of eye drops. Conclusion: The study reiterates the importance of verbal and non-verbal communication. The results may facilitate recommendations for change such as encouraging the study of medical exemptions and help support a case for play specialist support regularly, and the encouragement to develop a pre-procedural information video to improve quality of care. This is currently inconsistent across different Trusts in the UK. The study could result in improvements to current practise and influence other fields of medicine such as blood tests and MRI scans in children. The study also recommends further studies to investigate the parental perspective of instillation of eye drops in their child's eyes when they attend the eye clinic.

Safety and efficacy of ripasudil eye drops in preterm infants with retinopathy of prematurity: phase 1/2, open label, single-arm trial.

PURPOSE: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). STUDY DESIGN: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. METHODS: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. RESULTS: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. CONCLUSION: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

Malignant Transformation of Reese's Melanosis: A Case of Conjunctival Melanoma and Related Therapeutic Modalities.

Conjunctival melanoma is a rare but aggressive condition that can arise from healthy conjunctiva, pre-existing nevi, or precancerous conditions like Reese's melanosis. This acquired primary conjunctival melanosis can significantly impact an individual's quality of life due to its potential for recurrence and metastasis. Effective treatment typically requires a multidisciplinary approach to optimize outcomes. We present the case of a 56-year-old patient with recurrent Reese melanoma who underwent multiple surgeries. During the last intervention, a malignant transformation into melanoma was discovered. Due to the absence of brachytherapy facilities, the patient received local treatment with mitomycin C eye drops. Despite this limitation, the patient showed no signs of recurrence one year post-treatment. Given the high risk of local recurrence after surgery alone, additional radiotherapy is recommended and should be systematically discussed. Regular monitoring and timely intervention are essential to prevent disease progression. Notably, the frequent BRAF (B-Raf proto-oncogene, serine/threonine kinase) mutation in conjunctival melanoma opens possibilities for targeted therapies, such as BRAF inhibitors, offering promising options for management alongside traditional surgical approaches.