Hepatocyte Growth Factor Modulates Corneal Endothelial Wound Healing In Vitro.

In this study, we assessed the impact of hepatocyte growth factor (HGF) on corneal endothelial cells (CECs), finding that HGF concentrations of 100-250 ng/mL significantly increased CEC proliferation by 30%, migration by 32% and improved survival under oxidative stress by 28% compared to untreated controls (p < 0.05). The primary objective was to identify non-fibrotic pharmacological strategies to enhance corneal endothelial regeneration, addressing a critical need in conditions like Fuchs' endothelial dystrophy (FED), where donor tissue is scarce. To confirm the endothelial nature of the cultured CECs, Na+/K+-ATPase immunohistochemistry was performed. Proliferation rates were determined through BrdU incorporation assays, while cell migration was assessed via scratch assays. Cell viability was evaluated under normal and oxidative stress conditions using WST-1 assays. To ensure that HGF treatment did not trigger epithelial-mesenchymal transition, which could lead to undesirable fibrotic changes, α-SMA staining was conducted. These comprehensive methodologies provided robust data on the effects of HGF, confirming its potential as a therapeutic agent for corneal endothelial repair without inducing harmful EMT, as indicated by the absence of α-SMA expression. These findings suggest that HGF holds therapeutic promise for enhancing corneal endothelial repair, warranting further investigation in in vivo models to confirm its clinical applicability.

EVA NEXUS-Phaco performance study.

AIM: To investigate a novel phacoemulsification system "EVA NEXUS" (D.O.R.C., Dutch Opthalmic Research Center) in comparison to the existing system "EVA" in clinical use. And to compare both phacoemulsification systems in terms of efficiency, safety and postoperative inflammatory activity. METHODS: In this study standardized cataract surgery was performed on both eyes of the study participant, using the "EVA system" (control group, n=20) on one eye and the "EVA NEXUS system" (intervention group, n=20) on the other eye. Only patients with cataract LOCS Grading 1-3 and no accompanying eye diseases were included in this study. A total of 20 patients were included in this study, with each treatment arm including 20 eyes. During surgery a 0.1 mL aqueous humor sample was collected 1min after phacoemulsification to measure the total prostaglanin E2 concentrations using an enzyme-linked immunosorbent assay. The endothelial cell count, visual and refractive outcomes, and anterior chamber flare were evaluated preoperatively, and 1d, 1wk, and 3mo postoperatively. RESULTS: There were no statistically significant differences between both groups regarding intraoperative safety parameters including effective phacoemulsification time (P=0.904), balanced saline solution flow (P=0.701) and total surgery time (P=0.565). Postoperative prostaglandin E2 levels, anterior chamber flare as well as endothelial cell loss tended to be lower in the NEXUS-Group, however not being statistically significant (P=0.718; 0.164; 0.486). Both systems provided similar clinical outcomes, regarding best corrected visual acuity and refractive parameters, showing no statistically significant differences between both groups. CONCLUSION: Both systems show a high level of safety and efficency with similar results in terms of safety parameters including postoperative inflammatory activity and endothelial cell loss as well as visual and refractive outcomes. Although statistically not significant, the EVA NEXUS system tends to cause less postoperative inflammation with lower prostaglandin E2 levels and lower anterior chamber flare values.

Epithelial Remodeling and Epithelial Wavefront Aberrometry after Spherical vs. Cylindrical Myopic Small Incision Lenticule Extraction (SMILE).

Background/Objectives: To compare the epithelial thickness changes and the changes in epithelial wavefront aberrometry following spherical versus astigmatic myopic small incision lenticule extraction (SMILE). Methods: Eighty-six eyes of 86 patients who underwent SMILE were included in this retrospective study. A total of 43 eyes underwent myopic spherical correction (spherical group) and 43 eyes underwent myopic cylindrical correction (cylindrical group). The groups were matched according to the spherical equivalent of surgically corrected refraction. Subjective manifest refraction as well as high-resolution anterior segment optical coherence tomography (MS-39; CSO; Florence, Italy) were obtained preoperatively as well as 3 months postoperatively. The latter was utilized for computing epithelial wavefront aberrometry in addition to epithelial thickness mapping. Results: Epithelial thickness increased significantly in both groups after SMILE (p < 0.01). In the cylindrical group, epithelial thickening was more pronounced on the flat meridian compared to the steep meridian (p = 0.04). In both groups, epithelial wavefront aberrometry showed a significant postoperative increase in the epithelium's spherical refractive power, causing a myopization of -0.24 ± 0.42 diopters (D) in the spherical group (p < 0.01) and -0.41 ± 0.52 D in the cylindrical group (p < 0.0001). While no significant changes in epithelial cylindrical refractive power were observed in the spherical group, a significant increase was noted in the cylindrical group from -0.21 ± 0.24 D to -0.37 ± 0.31 D (p = 0.01). In both groups, epithelial higher-order aberrations increased significantly (p < 0.001). Conclusions: Postoperative epithelial remodeling after SMILE alters lower-order (sphere and cylinder) and higher-order aberrations of the corneal epithelial wavefront and might contribute to refractive undercorrection, especially in astigmatic corrections. Epithelial wavefront aberrometry can be used to quantify the refractive effect of epithelial remodeling processes after keratorefractive surgery.

Enhancing ectasia screening using advanced AS-OCT: a case series of challenging refractive candidates.

Purpose: Ectasia screening in candidates for laser refractive surgery is mandatory during preoperative evaluation. Despite the availability of modern imaging techniques, refractive surgeons often face borderline decisions when patients present with suspicious tomographic findings. This case series presents refractive candidates with suspicious tomographic findings and demonstrates how to interpret them using Scheimpflug imaging and additional anterior segment optical coherence tomography (AS-OCT). Setting: Department of Ophthalmology, University Hospital, LMU Munich. Case series: This case series examines six potential candidates for refractive surgery with a mean age of 29.2 ± 3.9 years, whose corneal assessments using Scheimpflug imaging raised suspicion for ectasia. Each candidate was additionally examined with AS-OCT and reevaluated. The mean manifest subjective spherical equivalent was -3.67 ± 1.8 diopters. The total corneal thickness measured 537 µm ± 30 µm at its thinnest point. None of the candidates had any reported underlying corneal or ophthalmic diseases, and slit lamp examinations revealed no abnormal morphological findings. Conclusions: Both Scheimpflug imaging and AS-OCT are appropriate tools for screening refractive candidates for ectasia. While topographic and elevation analyses yielded comparable results regarding corneal structure, the epithelial mapping provided by AS-OCT played a critical role in decision-making for cases with borderline tomographic findings. Establishing a global consensus on the use of epithelial mapping in ectasia screening is necessary.

Conditions for modifying intraocular lenses as drug carriers for methotrexate using poly (lactic-co-glycolic acid).

INTRODUCTION: The intraocular lens (IOL) can be used as a slow-release drug carrier in cataract surgery to alleviate posterior capsular opacification (PCO). The following is a systematic development of an IOL using methotrexate and the solvent casting process with poly (lactic-co-glycolic acid) (PLGA) as a carrier polymer. METHODS: Different solvents for PLGA and methotrexate were tested for dissolution properties and possible damage to the IOL. The required biological concentration of methotrexate was determined in human capsular bags implanted with an IOL. To detect fibrosis, α-SMA, f-actin, and fibronectin were labelled by immunofluorescence staining. Cell proliferation and extracellular matrix contraction were observed in a lens epithelial cell line (FHL-124). Finally, the IOL was designed, and an ocular pharmacokinetic model was used to measure drug release. RESULTS: Solvent mixtures were found to allow coating of the IOL with drug and PLGA without damaging it. PCO in the capsular bag model was inhibited above 1 µM methotrexate (p = 0.02). Proliferation in FHL-124 was significantly reduced above a concentration of 10 nM (p = 0.04) and matrix contraction at 100 nM (p = 0.02). The release profile showed a steady state within therapeutic range. CONCLUSION: After determination of the required physicochemical manufacturing conditions, a drug releasing IOL was designed. A favourable release profile in an ocular pharmacokinetics model could be shown.

[Current aspects of vernal and atopic keratoconjunctivitis]. / Aktuelles zur Keratoconjunctivitis vernalis und atopica.

BACKGROUND: Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often a challenge. OBJECTIVE: Discussion on the epidemiology, new pathogenetic concepts, interesting clinical findings, diagnostic possibilities and new treatment options and their side effects in severe ocular allergies. Analysis of the presentation of VKC in the internet. MATERIAL AND METHODS: Evaluation of recent review articles, original publications, and case reports on the topics of VKC and AKC over the past 5 years. RESULTS: Ocular allergies have significantly increased over the last decades. Recent concepts discussed in the pathogenesis of VKC and AKC are the role of the local and gut microbiome as well as the influence of neuroinflammation. Keratoconus is significantly more common in patients with VKC and AKC compared to the normal population. It is associated with faster progression and a more severe course of disease. A conjunctival provocation test is only rarely necessary in the diagnosis of allergic conjunctivitis. Treatment of atopic dermatitis with dupilumab, an interleukin 4 receptor alpha (IL-4Ra) antagonist, can cause ocular side effects. Unfortunately, information available on the internet for patients and parents on the topic of VKC is sometimes dangerously incorrect. CONCLUSION: From the abovementioned new pathogenetic concepts, preventive and personalized treatment options could be developed in the future. Keratoconus in AKC/VKC must be recognized and treated early. Official guidelines are now available for a standardized conjunctival provocation test in the diagnosis of allergic conjunctivitis. The unwanted ocular side effects of dupilumab are often difficult to discriminate from the actual underlying AKC and respond well to anti-inflammatory treatment. Patients with VKC must be informed about the incorrect information on the internet regarding their disease.

[New and future treatment approaches for allergic conjunctivitis]. / Neue und zukünftige Therapieansätze in der Behandlung der allergischen Konjunktivitis.

BACKGROUND: In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief. OBJECTIVE: Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given. MATERIAL AND METHODS: Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented. RESULTS: In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T­helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC). CONCLUSION: A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.

Long-term Outcomes of PreserFlo MicroShunt versus XEN45 Gel Stent in Open-Angle Glaucoma.

PURPOSE: To compare two glaucoma drainage devices with subconjunctival filtration (MicroShunt and XEN) for open-angle glaucoma (OAG), with respect to effectiveness and safety. PATIENTS AND METHODS: This is a single center, retrospective, interventional study. In total, 106 eyes of 95 patients with OAG underwent surgery. Of these patients, 51 eyes of 45 patients received a MicroShunt implantation and 55 eyes of 50 patients received an XEN implantation. Failure was defined as an intraocular pressure (IOP) lower than 5 or higher than 17 mmHg at the end of follow-up after 2 years, the need for surgical revision, secondary glaucoma surgery, or loss of light perception. Outcome was rated as complete success or qualified success, depending on whether it was achieved with or without anti-glaucomatous medications. Postoperative complications and interventions were also documented for both groups. RESULTS: In the MicroShunt group, mean IOP decreased from 20.6 ± 7.5 mmHg at baseline to 13.0 ± 3.9 mmHg (p < 0.0001) after 2 years. In the XEN group, mean IOP was lowered from 22.5 ± 7.9 mmHg to 13.5 ± 4.2 mmHg (p < 0.0001). In both groups, the mean number of medications was significantly reduced (MicroShunt 2.7 ± 1.2 to 0.9 ± 2.5; p < 0.0001 vs. XEN 3.2 ± 0.9 to 1.1 ± 1.5; p < 0.0001). In regard to success rates, 37% of MicroShunt patients achieved complete success and 57% qualified success at the end of follow-up. In the XEN group, rates were 25 and 45%, respectively. Patient demographics differed between the two groups with respect to age (MicroShunt 72.8 ± 8.7 vs. XEN 67.7 ± 9.0 years; p = 0.002). Postoperative complications were comparable between the two groups. CONCLUSION: Both MicroShunt and XEN are effective in significantly reducing IOP and glaucoma medications in OAG, and with a good safety profile.

Rotational stability of plate haptic toric intraocular lenses after combined 25-gauge vitrectomy and cataract surgery.

AIM: To evaluate the postoperative intraocular lens (IOL) rotational stability and residual refractive astigmatism following combined 25-gauge vitrectomy and cataract surgery with implantation of a plate haptic toric IOL. METHODS: In this retrospective case series, 32 eyes of 32 patients underwent a combined 25-gauge vitrectomy and phacoemulsification for vitreoretinal diseases and cataract with regular corneal astigmatism of at least 1 diopter (D). A plate haptic toric IOL (AT Torbi 709M, Carl Zeiss Meditec AG) was implanted in all eyes. The outcome measures were rotational stability and refractive astigmatism up to 6mo postoperatively as well as the best corrected visual acuity (BCVA). RESULTS: Preoperative refractive astigmatism was 2.14±1.17 D, which was significantly reduced to 0.77±0.37 D six to eight weeks postoperatively and remained stable throughout the observation period (0.67±0.44 D at three months and 0.75±0.25 D at six months; for all groups: P<0.0001 compared to baseline). BCVA improved significantly from 0.36±0.33 logMAR preoperatively to 0.10±0.15 logMAR following surgery (P=0.02). Mean IOL axis deviation from the target axis was 3.4°±2.9° after six to eight weeks and significantly decreased over time (2.4°±2.6° six months after surgery; P=0.04). In one patient IOL, re-alignment was performed. CONCLUSION: Corneal astigmatism is significantly reduced following combined 25-gauge vitrectomy and cataract surgery. The plate haptic toric IOL position and axis remain stable during the observation period of six months.

[Corneal disease in childhood-Hereditary, degenerative or infectious?] / Hornhauterkrankungen im Kindesalter ­ Hereditär, degenerativ oder infektiös?

BACKGROUND: Adequate visual acuity significantly contributes to the age-appropriate development of children's neurobehavior. Infantile corneal opacities are rare but implicate a high potential for amblyopia. OBJECTIVE: This review aims to provide an overview of the most common causes of infantile corneal opacities and highlights ophthalmopathological correlations. METHODS: The following review is based on an extensive literature search. RESULTS: If metabolic diseases, traumatic or infectious events can be excluded as a cause for an infantile corneal opacity, it is important to focus on the 3Ds, corneal dysgenesis, corneal dystrophy or corneal degeneration. DISCUSSION: If corneal opacities occur in childhood, early recognition, diagnosis, and initiation of treatment, including prophylaxis of amblyopia, are of utmost importance. In unexplained corneal opacities the histopathological work-up of the explanted cornea can contribute to the final diagnosis.

One-Year Outcomes of PreserfloTM MicroShunt Implantation versus Trabeculectomy for Pseudoexfoliation Glaucoma.

This retrospective, single-center study evaluates the safety and efficacy of PreserfloTM MicroShunt (MicroShunt) implantations compared to trabeculectomies (TETs) in patients diagnosed with pseudoexfoliation glaucoma (PEXG). A total of 31 eyes from 28 patients received a MicroShunt implantation, and 29 eyes from 26 patients received a TET. Surgical success was defined as an intraocular pressure (IOP) between 5 mmHg and 17 mmHg at the end of the follow-up period, no need for surgical revisions or secondary glaucoma surgery, and no loss of light perception. In the MicroShunt group, the mean IOP dropped from 20.8 ± 5.9 mmHg at baseline to 12.4 ± 2.8 mmHg (p < 0.0001) after one year. In the TET group, the mean IOP dropped from 22.3 ± 6.5 mmHg to 11.1 ± 3.7 mmHg (p < 0.0001) after 12 months. In both of the groups, the mean number of medications was reduced significantly (MicroShunt from 2.7 ± 1.2 to 0.2 ± 0.7; p < 0.0001 vs. TET from 2.9 ± 1.2 to 0.3 ± 0.9; p < 0.0001). Considering the success rates, 83.9% of the MicroShunt eyes achieved complete success, and 90.3% qualified for success at the end of the follow-up period. In the TET group, the rates were 82.8% and 93.1%, respectively. The postoperative complications were comparable between both groups. In conclusion, the MicroShunt implantation demonstrated non-inferiority regarding its efficacy and safety profile compared to TET in PEXG at a follow-up of one year.

Pharmacological Therapy of Proliferative Vitreoretinopathy: Systematic In Vitro Comparison of 36 Pharmacological Agents.

Purpose: Proliferative vitreoretinopathy (PVR) is currently treated surgically. Reliable pharmaceutical options would be desirable, and numerous drugs have been proposed. This in vitro study is intended to systematically compare and determine the most promising candidates for the treatment of PVR. Methods: A structured literature review was conducted in the "PubMed" database to identify previously published agents proposed for medical treatment of PVR -36 substances that met the inclusion criteria. Toxicity and antiproliferative effects were evaluated on primary human retinal pigment epithelial (hRPE) using colorimetric viability assays. The seven substances with the widest therapeutic range between toxicity and no longer detectable antiproliferative effect were then validated with a bromodeoxyuridine assay and a scratch wound healing assay using primary cells derived from surgically excised human PVR membranes (hPVR). Results: Among 36 substances, 12 showed no effect on hRPE at all. Seventeen substances had a significant (P < 0.05) toxic effect of which nine did not have an antiproliferative effect. Fifteen substances significantly reduced hRPE proliferation (P < 0.05). The seven most promising drugs with the highest difference between toxicity and antiproliferative effects on hRPE were dasatinib, methotrexate, resveratrol, retinoic acid, simvastatin, tacrolimus, and tranilast. Whereof resveratrol, simvastatin, and tranilast additionally showed antiproliferative and dasatinib, resveratrol, and tranilast antimigratory effects on hPVR (P < 0.05). Conclusion: This study presents a systematic comparison of drugs that have been proposed for PVR treatment in a human disease model. Dasatinib, resveratrol, simvastatin, and tranilast seem to be promising and are well-characterized in human use.

Comparison of Visual and Refractive Outcome between Two Methods of Corneal Marking for Toric Implantable Collamer Lenses (TICL) in Phakic Eyes.

PURPOSE: To compare the efficacy of digital-assisted reference marking for toric implantable collamer lenses (Callisto Eye System) with manual marking technique using a slit lamp markeur. METHODS: This study included patients that underwent implantation of a toric implantable collamer lens (EVO Visian toric ICL, Staar Surgical). Patients were included if they had a myopia above -3 diopters (D) and regular corneal astigmatism of 0.75 diopters or higher. Between both groups a 1:2 matching regarding similar preoperative level of myopia and astigmatism was performed. Visual and refractive outcomes were evaluated. Vector analysis was performed to evaluate total astigmatic changes. RESULTS: This study comprised 57 eyes of 57 patients with 19 eyes in the digital group and 38 eyes in the manual marking group. Postoperatively there were no statistically significant differences between both groups in UDVA (p = 0.467), spherical equivalent (SE) (p = 0.864), sphere (p = 0.761) and cylinder (p = 0.878). Vector analysis showed a slightly more accurate postoperative refractive astigmatism in the manual group (0.26 D at 107° ± 0.50 D) compared to the digital marking group (0.31 D at 107° ± 0.45 D), nevertheless with no statistically significant differences between both groups. CONCLUSIONS: A digital tracking approach for toric ICL alignment was an efficient and safe method for toric marking with similar results regarding visual and refractive outcomes compared to a conventional corneal marking method. Nevertheless, image-guided surgery helped to streamline the workflow in refractive ICL surgery.

Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, MAPK, mTOR or PI3K.

AIM: To screen five potential pharmacological substances specifically targeting EGF-R, MAPK, mTOR, or PI3K for their antiproliferative effects, possible impact on cell viability, as well as cell death rates on three different uveal melanoma metastasis cell lines in vitro. METHODS: Three different uveal melanoma metastasis cell lines (OMM2.5, OMM2.3, and OMM1), that originated from human hepatic and subcutaneous metastasis, were exposed to inhibitors of different targets: erlotinib (EGF-R), everolimus (mTOR), selumetinib (MAPK), trametinib (MAPK) or the alkylphosphocholine erufosine (PI3K). Cell viability was assessed with a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) dye reduction assay after 24h of treatment. Antiproliferative effects were evaluated separately after a 72-hour incubation of the cells with the pharmacological substance. Subsequently, the IC50 was calculated. Tumor cell death was investigated using a double stain apoptosis detection assay. RESULTS: Selumetinib, trametinib, and erufosine significantly decreased cell viability of all OMM cell lines (P<0.04). In addition, selumetinib and trametinib showed a significant inhibition of cell proliferation (P<0.05). Everolimus and erlotinib solely inhibited cell proliferation at the used concentrations (P<0.05). Besides an increase of necrotic cells after erufosine treatment (P<0.001), no changes in the number of dead cells for the other substances were observed. CONCLUSION: The preliminary drug screening demonstrates five new candidates, successfully targeting the canonical MAPK/ERK and PI3K/AKT/mTOR pathways in uveal melanoma metastasis cells in vitro. Hence, these findings provide an experimental basis to explore future single or combined therapy strategies for metastatic uveal melanoma.