Integrated high-throughput drug screening microfluidic system for comprehensive ocular toxicity assessment.

Traditional experimental methodologies suffer from a few limitations in the toxicological evaluation of the preservatives added to eye drops. In this study, we overcame these limitations by using a microfluidic device. We developed a microfluidic system featuring a gradient concentration generator for preservative dosage control with microvalves and micropumps, automatically regulated by a programmable Arduino board. This system facilitated the simultaneous toxicological evaluation of human corneal epithelial cells against eight different concentrations of preservatives, allowing for quadruplicate experiments in a single run. In our study, the IC50 values for healthy eyes and those affected with dry eyes syndrome showed an approximately twofold difference. This variation is likely attributable to the duration for which the preservative remained in contact with corneal cells before being washed off by the medium, suggesting the significance of exposure time in the cytotoxic effect of preservatives. Our microfluidic system, automated by Arduino, simulated healthy and dry eye environments to study benzalkonium chloride toxicity and revealed significant differences in cell viability, with IC50 values of 0.0033% for healthy eyes and 0.0017% for dry eyes. In summary, we implemented the pinch-to-zoom feature of an electronic tablet in our microfluidic system, offering innovative alternatives for eye research.

Outcomes and Early Complications Using an Endothelium-in Pull-Through Descemet Membrane Endothelial Keratoplasty Technique With Preloaded Versus Surgeon-Loaded Donor Tissue in Fuchs Patients.

PURPOSE: This study aimed to compare outcomes and early complications using an endothelium-in pull-through Descemet membrane endothelial keratoplasty (DMEK) technique with preloaded versus surgeon-loaded donor tissue. METHODS: Data from 163 eyes of 125 patients at the Wilmer Eye Institute diagnosed with Fuchs endothelial corneal dystrophy who underwent DMEK with or without cataract extraction using surgeon-loaded tissue (n = 83) or preloaded tissue (n = 80) were reviewed. Best-corrected visual acuity and early postoperative complications including small graft detachment (less than one third of the graft area), large graft detachment (more than one third), graft failure, and rebubbling were compared. RESULTS: Baseline characteristics including age, sex, and visual acuity were not statistically different between the groups. Small graft detachment was observed in 18.1% of the surgeon-loaded and 22.5% of the preloaded group ( P = 0.48), whereas large detachment occurred in 12.0% and 5.0%, respectively ( P = 0.11). Among these, rebubbling was performed in 18 (21.7%) in the surgeon-loaded compared with 12 (15.0%) in the preloaded group ( P = 0.27). The rebubbling rate of the combined procedure (cataract surgery and DMEK) was 21.8% and of DMEK alone was 7.7% ( P = 0.048). Primary graft failure occurred in 2 surgeon-loaded cases (2.4%) and 1 preloaded case (1.3%) ( P = 0.58). There was no difference in postoperative best-corrected visual acuity at 1 year (logarithm of the minimum angle of resolution 0.21 ± 0.25 for the surgeon-loaded vs. 0.16 ± 0.16 for the preloaded group, P = 0.23). CONCLUSIONS: DMEK surgery using preloaded endothelium-in tissue has comparable outcomes with surgeon-loaded endothelium-in tissue. However, there was a trend toward the lower rebubbling rate in DMEK alone compared with combined procedures.

Topical ophthalmic anesthetics for corneal abrasions.

BACKGROUND: Despite potential analgesic benefits from topical ophthalmic amides and esters, their outpatient use has become of concern because of the potential for abuse and ophthalmic complications. OBJECTIVES: To assess the effectiveness and safety of topical ophthalmic anesthetics compared with placebo or other treatments in persons with corneal abrasions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase.com; Latin American and Caribbean Health Sciences (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The search was performed on 10 February 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of topical ophthalmic anesthetics alone or in combination with another treatment (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs)) versus a non-anesthetic control group (e.g. placebo, non-treatment, or alternative treatment). We included trials that enrolled participants of all ages who had corneal abrasions within 48 hours of presentation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included nine parallel-group RCTs with a total of 556 participants (median number of participants per study: 45, interquartile range (IQR) 44 to 74), conducted in eight countries: Australia, Canada, France, South Korea, Turkey, New Zealand, UK, and USA. Study characteristics and risk of bias Four RCTs (314 participants) investigated post-traumatic corneal abrasions diagnosed in the emergency department setting. Five trials described 242 participants from ophthalmology surgery centers with post-surgical corneal defects: four from photorefractive keratectomy (PRK) and one from pterygium surgery. Study duration ranged from two days to six months, the most common being one week (four RCTs). Treatment duration ranged from three hours to one week (nine RCTs); the majority were between 24 and 48 hours (five RCTs). The age of participants was reported in eight studies, ranging from 17 to 74 years of age. Only one participant in one trial was under 18 years of age. Of four studies that reported funding sources, none was industry-sponsored. We judged a high risk of bias in one trial with respect to the outcome pain control by 48 hours, and in five of seven trials with respect to the outcome complications at the furthest time point. The domain for which we assessed studies to be at the highest risk of bias was missing or selective reporting of outcome data. Findings The treatments investigated included topical anesthetics compared with placebo, topical anesthetic compared with NSAID (post-surgical cases), and topical anesthetics plus NSAID compared with placebo (post-surgical cases). Pain control by 24 hours In all studies, self-reported pain outcomes were on a 10-point scale, where lower numbers represent less pain. In post-surgical trials, topical anesthetics provided a moderate reduction in self-reported pain at 24 hours compared with placebo of 1.28 points on a 10-point scale (mean difference (MD) -1.28, 95% confidence interval (CI) -1.76 to -0.80; 3 RCTs, 119 participants). In the post-trauma participants, there may be little or no difference in effect (MD -0.04, 95% CI -0.10 to 0.02; 1 RCT, 76 participants). Compared with NSAID in post-surgical participants, topical anesthetics resulted in a slight increase in pain at 24 hours (MD 0.82, 95% CI 0.01 to 1.63; 1 RCT, 74 participants). One RCT compared topical anesthetics plus NSAID to placebo. There may be a large reduction in pain at 24 hours with topical anesthetics plus NSAID in post-surgical participants, but the evidence to support this large effect is very uncertain (MD -5.72, 95% CI -7.35 to -4.09; 1 RCT, 30 participants; very low-certainty evidence). Pain control by 48 hours Compared with placebo, topical anesthetics reduced post-trauma pain substantially by 48 hours (MD -5.68, 95% CI -6.38 to -4.98; 1 RCT, 111 participants) but had little to no effect on post-surgical pain (MD 0.41, 95% CI -0.45 to 1.27; 1 RCT, 44 participants), although the evidence is very uncertain. Pain control by 72 hours One post-surgical RCT showed little or no effect of topical anesthetics compared with placebo by 72 hours (MD 0.49, 95% CI -0.06 to 1.04; 44 participants; very low-certainty evidence). Proportion of participants with unresolved epithelial defects When compared with placebo or NSAID, topical anesthetics increased the number of participants without complete resolution of defects in trials of post-trauma participants (risk ratio (RR) 1.37, 95% CI 0.78 to 2.42; 3 RCTs, 221 participants; very low-certainty evidence). The proportion of placebo-treated post-surgical participants with unresolved epithelial defects at 24 to 72 hours was lower when compared with those assigned to topical anesthetics (RR 0.14, 95% CI 0.01 to 2.55; 1 RCT, 30 participants; very low-certainty evidence) or topical anesthetics plus NSAID (RR 0.33, 95% CI 0.04 to 2.85; 1 RCT, 30 participants; very low-certainty evidence). Proportion of participants with complications at the longest follow-up When compared with placebo or NSAID, topical anesthetics resulted in a higher proportion of post-trauma participants with complications at up to two weeks (RR 1.13, 95% CI 0.23 to 5.46; 3 RCTs, 242 participants) and post-surgical participants with complications at up to one week (RR 7.00, 95% CI 0.38 to 128.02; 1 RCT, 44 participants). When topical anesthetic plus NSAID was compared with placebo, no complications were reported in either treatment arm up to one week post-surgery (risk difference (RD) 0.00, 95% CI -0.12 to 0.12; 1 RCT, 30 participants). The evidence is very uncertain for safety outcomes. Quality of life None of the included trials assessed quality of life outcomes. AUTHORS' CONCLUSIONS: Despite topical anesthetics providing excellent pain control in the intraoperative setting, the currently available evidence provides little or no certainty about their efficacy for reducing ocular pain in the initial 24 to 72 hours after a corneal abrasion, whether from unintentional trauma or surgery. We have very low confidence in this evidence as a basis to recommend topical anesthetics as an efficacious treatment modality to relieve pain from corneal abrasions. We also found no evidence of a substantial effect on epithelial healing up to 72 hours or a reduction in ocular complications when we compared anesthetics alone or with NSAIDs versus placebo.

Fuchs Dystrophy and Cataract: Diagnosis, Evaluation and Treatment.

Corneal endothelium plays an important role in maintaining hydration homeostasis and clarity of the cornea. Fuchs endothelial corneal dystrophy (FECD) affects the corneal endothelium resulting in edema and characteristic excrescences on the Descemet's membrane known as corneal guttae. Descemet membrane endothelial keratoplasty (DMEK) has evolved to become the standard of care for patients with FECD with excellent visual acuity outcomes. Patients with FECD may have coexisting cataracts and therefore may require a cataract surgery, which increases the risk of corneal decompensation. The presence of FECD may not only influence the choice of intraocular lens but vision outcomes can also be affected by the corneal condition. The ability to combine the surgeries further raises important considerations regarding the timing and sequence of DMEK and cataract extraction for patients with FECD. This review provides a guide for corneal surgeons in choosing between endothelial keratoplasty and cataract surgery-alone, in combination or sequential-in their management of patients with FECD.

Intraocular lens prediction accuracy after corneal refractive surgery using K values from 3 devices.

PURPOSE: To compare results of intraocular lens (IOL) power calculation methods using different keratometry (K) values after myopic refractive surgery. SETTING: Seoul St. Mary's Hospital, Seoul, South Korea. DESIGN: Evaluation of diagnostic test or technology. METHODS: The IOL power of patients who had cataract surgery after refractive surgery was calculated using the SRK/T formula with true net power (TNP) and the equivalent K using the Pentacam Scheimpflug system. The simulated K, 2.0 mm zone of total mean power (TMP 2.0 mm) maps, and 4.0 mm zone of total optical power (TOP 4.0 mm) maps were calculated using the Orbscan II scanning-slit topographer and keratometer of the IOLMaster partial coherence interferometer (PCI). The IOL power was also calculated with the Haigis-L method with the corneal radius using the PCI system. The PCI axial length was used with all methods. RESULTS: The prediction error and absolute prediction error measured with the Haigis-L, TNP, TMP 2.0 mm, and TOP 4.0 mm were significantly lower than the equivalent K, simulated K, and PCI K (P<.05). The percentages of correct refraction predictions within ± 0.50 diopter (D), ± 1.00 D, and ± 2.00 D in the Haigis-L method were the highest (64.5%, 80.6%, and 100%, respectively) of all methods. CONCLUSIONS: The Haigis-L using corneal radius with the PCI measurement was the most predictable method for IOL calculation after corneal refractive laser surgery in patients without a clinical history. The TMP 2.0 mm in the scanning-slit topographer and the TNP in the Scheimpflug system may also be relatively predictable keratometric values for IOL calculation.