Current Eye Research最新文献

Purpose: To validate the quantification of the prominent middle limiting membrane (PMLM) sign, a marker of mild-to-moderate acute ischemic damage on optical coherence tomography (OCT), by measuring middle limiting membrane (MLM) reflectivity in patients with central retinal vein occlusion (CRVO) and to investigate the prognostic impact of this measure.

Methods: Spectral Domain (SD)-OCT B-scans of 30 patients with CRVO, either sole CRVO or combined central retinal artery and vein occlusion (CCRAVO), were analyzed retrospectively and graded as PMLM present or absent. Normalized MLM reflectivity was calculated as a ratio of the maximum reflectivity within a MLM target layer and the average reflectivity of the retinal pigment epithelium (RPE).

Results: Discrimination between OCT B-scans graded as PMLM present or absent based on ROC analysis was far superior with normalized MLM reflectivity (AUC >0.90) than using MLM reflectivity without normalization (AUC = 0.70). Normalized MLM reflectivity was significantly higher in study eyes than healthy fellow eyes as well as in patients with CCRAVO versus sole CRVO. Although normalized MLM reflectivity correlated significantly with baseline and outcome BCVA, we found no significant difference comparing patients with ischemic CRVO versus non-ischemic CRVO.

Conclusions: Quantifying MLM reflectivity requires normalization due to shadowing, which is usually caused by retinal haemorrhages in CRVO. RPE reflectivity proved to be a suitable reference layer. Greater normalized MLM reflectivity as a measure of mild-to-moderate acute ischemic damage indicated a worse prognosis regarding visual function in CRVO, however, it allows no risk assessment regarding the development of capillary non-perfusion or anterior segment neovascularization.

Purpose: To explore the contribution and impact of fibrous scleral remodeling in the early recovery from lens induced myopia of chicks.

Method: Refractive error, axial length and histopathological studies were performed on chicks subject to myopic influence with -10 D goggles unilaterally on the day of hatching for a period of 14 days, after which the eyes were enucleated and immediately fixed for histopathological assessment. Three groups, myopia (measurements taken directly after 14 days), early recovery from induced myopia (chicks allowed a three-hour recovery period by removing goggles before analysis) and control (no goggles) were evaluated. The histological slides were assessed with bright field microscopy using Leica image analysis software.

Results: Early recovery from induced myopia resulted in a significant increase in the thickness of fibrous sclera to levels twice as high as the ones observed in the control or myopia groups. Histochemical staining revealed three times increase in fibroblast cell count of the early recovery from induced myopia group along with a statistically significant increase in levels of elastin contents relative to the control. However, fibroblast morphometry revealed no difference in maximum cell diameter, perimeter, and area between all experimental groups.

Conclusion: Recovery from induced experimental myopia results in fibrous scleral remodeling. Significant increase in the scleral thickness is related to heightened cell proliferation and elastic fiber contents. These results indicate that the fibrous sclera is not a passive component in the emmetropization process, but rather plays a significant and active role in the adaptation changes of the eye during early recovery from induced myopia.

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.6 µg/mL, 3 µg/mL, 6 µg/mL, 300 µg/mL, and 3000 µ/mL or its solvent or PBS. The surface expression of platelet activation markers GPIIb/IIIa and P-selectin was determined by multispectral imaging flow cytometry, which combines flow cytometry and fluorescence microscopy. Two different methods were used to examine the interaction of brolucizumab with platelets: 1) A cross-pretreatment experiment was performed with FITC-labeled brolucizumab and bevacizumab; 2) Resting and activated platelets were pretreated with brolucizumab or its solvent or PBS, followed by anti-brolucizumab antibody generated by rabbit immunization.

Results: Brolucizumab did not significantly affect platelet activation compared to solvent or PBS, across a range of concentrations. No significant upregulation of CD62P and no activation of the fibrinogen receptor (GPIIb/IIa) were observed in resting and TRAP-activated platelets. After pretreatment with PBS, the level of brolucizumab-FITC was significantly lower in comparison to bevacizumab-FITC (normalized MFI = 3.32, CI = 3.16-3.48 vs. normalized MFI = 7.19, CI = 7.04-7.35; p < 0.001). Both brolucizumab- and bevacizumab-FITC were downregulated after pretreatment with brolucizumab or bevacizumab compared to pretreatment with PBS. Antibodies against brolucizumab did not show any significant difference between pretreatment with brolucizumab and its solvent in resting and TRAP-activated platelets.

Conclusion: Brolucizumab does not appear to directly affect platelet activation or reactivity to thrombin receptor agonists. No platelet interaction was observed after increasing brolucizumab concentrations or anti-brolucizumab antibodies in resting and activated platelets. However, brolucizumab might be taken up in platelets.

Purpose: To assess the efficacy of a low-cost optical magnifier created from the repurposed femtosecond laser interface used in cataract surgery to reduce healthcare waste and financial burden for low-vision patients.

Methods: This prospective study included 16 Brazilian patients from the Low Vision Department of the Irmandade da Santa Casa de Misericórdia de São Paulo. Participants had visual acuity between +0.5 and +1.3 logMAR and visual field constrictions under 20°. The Catalys^® femtosecond laser interface lens, usually discarded after surgery, was sterilized and attached to a recyclable support to create a magnifying device. Patients were trained to use it for 30 days. Visual function was assessed with the NEI VFQ-25, and reading performance was measured using the MNREAD-P test.

Results: Thirteen patients (81.25%) completed the study. The use of the optical device led to significant improvements in all MNREAD-P parameters. Reading acuity improved from 0.74 ± 0.19 logMAR (20/110 Snellen) to 0.41 ± 0.22 logMAR (20/50 Snellen) (p < 0.001). Critical print size decreased from 0.85 ± 0.19 logMAR (20/140 Snellen) to 0.56 ± 0.24 logMAR (20/70 Snellen) (p < 0.001). Maximum reading speed increased from 41.4 ± 18.0 words per minute (wpm) to 56.2 ± 25.2 wpm (p < 0.001). NEI VFQ-25 scores improved from 32.7 ± 13.8 to 46.9 ± 15.0 (p < 0.001), with increases observed in all subcategories, particularly in "Reactions to Vision Problems."

Conclusion: Repurposing the femtosecond laser interface lens as a low-cost magnifier showed promising improvements in reading and visual function for low-vision patients while addressing healthcare waste. Further studies with larger samples are recommended to validate and expand this sustainable approach in visual rehabilitation.

Purpose: This study aims to describe an innovative suprachoroidal space injection technique using a combination of 30 G and 22 G needles attached to a 1 ml injector. The efficacy and applicability of this technique in suprachoroidal injections are evaluated.

Methods: In this study, we conducted both in vitro and in vivo injection experiments using isolated porcine eyes and live SD rats, respectively. The injector needle was inserted into the sclera with the bevelled tip facing the sclera and parallel to the corneal limbus, and the methylene blue solution was injected into the suprachoroidal space. The accuracy of the injection was confirmed by OCT imaging and frozen section microscopy, demonstrating that the dye was successfully delivered to the suprachoroidal space.

Results: The suprachoroidal injector successfully injected the solution into the suprachoroidal space of isolated porcine eyes and live rats without entering the vitreous cavity.

Conclusion: The 22 G needle demonstrated sufficient rigidity and stability to ensure proper scleral compression, supporting the consistency of the injection depth. The 30 G needle exhibited exceptional sharpness and precision, allowing for more accurate control of the drug dosage. The appropriate force applied to the sclera facilitated the precise depth of injection. The angle of the needle, parallel to the corneal limbus, helped avoid penetration into the vitreous or subretinal space, reducing the risk of complications. This device offers new tools and methods for ophthalmic research and clinical practice, with significant clinical application prospects.

Purpose: This minireview discusses desmosome and hemidesmosome disassembly and/or internalization and subsequent release via exosomes in retinal pigmented epithelium (RPE) under oxidative stress conditions, and whether it may be a precursor to epithelial-mesenchymal transition in early Age-related Macular Degeneration (AMD).

Methods: Literature review and discussion of novel findings relevant to the focus of the review.

Results: The RPE forms the outer blood-retinal barrier, and like other epithelia it has several different types of cell-cell junctions, such as desmosomes. The RPE provides key metabolic and nutrient support to photoreceptors and the function of normal vision. The RPE is a principal location of disease-associated changes in AMD, due to its essential role in visual homeostasis. Exosomes are lipid bilayer membrane vesicles of nanometer sizes that are released via a dedicated machinery by all cells and carry out a multitude of functions related to cellular signaling and waste management. In the RPE they are released from both the apical and basal sides, and the cargo composition reflects this polarization. We have recently showed that exosomes released from the basolateral side of RPE cells under chronic oxidative stress conditions, contain desmosome and hemidesmosome proteins. Here we discuss the composition of desmosomes and hemidesmosomes in the RPE, the role of exosomes and ubiquitination pathways in their disassembly, and whether this dismantling is a precursor to epithelial-mesenchymal transition. Further considerations include how the exosome-mediated shedding of desmosome and hemidesmosome components is related to lysosomal and/or proteasomal overload, and how these pathways can be modulated to intervene in early stages of AMD.

Conclusions: This review provides an overview of the current knowledge about desmosome and hemidesmosome disassembly in RPE, its intersection with the exosome pathway, and potential role in epithelial-mesenchymal transition. We discuss several potential targets for therapeutic intervention in pre-symptomatic or early-stage AMD in these pathways.

Purpose: To assess the association of HLA-DR on ocular surface conjunctival cells with the severity of signs and symptoms of dry eye disease (DED) in patients enrolled in the NORTHERN LIGHTS phase 2 trial.

Methods: Patients with moderate to severe DED were recruited from 10 different countries in Europe. Symptoms of DED were assessed using the visual analog scale (VAS) global discomfort score, and signs via corneal fluorescein staining (CFS), lissamine green staining, Schirmer's test, and tear osmolarity. HLA-DR expression was evaluated via flow cytometry from impression cytology of conjunctival cells using the EyePrim™ device sampled from 205 DED patients.

Results: HLA-DR expression was detected in a mean of 3.4% of cells at baseline. HLA-DR expression was significantly associated with corneal staining severity at baseline (p < 0.01). HLA-DR expression was not significantly associated with DED symptoms (VAS global discomfort score), nor lissamine green staining, Schirmer's test, tear osmolarity, or Sjogren's syndrome.

Conclusion: HLA-DR was present in a wide range of percentages among DED patients indicating the heterogeneous nature of DED. HLA-DR was significantly associated with corneal fluorescein staining suggesting a correlation of the biomarker with ocular surface damage.

Purpose: The nomograms for the laser procedure "Laser Blended Vision" (Presbyond^®) for myopia were developed based on a 6 mm zone. The aim of these studies is to demonstrate that customized nomograms are necessary when changing the optical zone. The three-month results after the Presbyond^® correction using a 6.4 mm to 6.5 mm optical zone were analyzed in myopic patients. All patients were treated at the University Hospital Gießen and Marburg and for analyses purposes they were divided into two groups. Group 1 was treated from 2017-2019 without a nomogram for this larger optical zone, and group 2 from 2019-2022 with a customized nomogram.

Methods: In the retrospective monocentric study, 86 eyes from 43 patients in group 1 and 120 eyes from 60 patients in group 2 were analyzed. All eyes were treated with the 500 kHz VisuMax^® Laser and the Mel90^® Excimer Laser using a 6.4 mm to 6.5 mm optical zone. The results are collected using Datagraph^® software.

Results: The three-month results show overcorrection in both groups concerning the targeted refractive goal. In group 2, the analysis of distance and near vision shows that eyes treated for near vision deviate more than predicted. This is also confirmed in the refractive outcome. However, patient satisfaction is comparable in both groups, and retreatment rate is lower than published, although higher in group 1 than in group 2.

Conclusion: Since PRESBYOND^® targets both, good distance vision does not fully reflect the goal of this procedure. The importance of personalized nomograms for distance and near vision is supported by our results, also the retreatment rate improved, and patient satisfaction influences the decision for retreatment. A separate nomogram for the distance and reading eye to further improve correction predictability is necessary, as predictability in both eyes is differing.

Purpose: The primary aim of this article was to investigate differences in the metabolomic profile of tear fluid obtained from pre-operative cataract patients, with or without dry eye disease. The objective was to look for metabolomic signatures that might discriminate between the two groups.

Methods: A total of 222 patients were enrolled in the study. Eighty-one were randomly selected for metabolomic analysis from both dry eye positive and dry eye negative groups, categorized prior to cataract surgery. Tear film was collected using Schirmer-1 strips and analyzed using an optimized method developed for low-volume Schirmer samples and allowing for repeated analyses, including other -omics approaches at a later stage. Metabolomic data were collected using a global liquid chromatography-mass spectrometry method. Samples were compared using principal component analysis and volcano plots to look for overall global differences as well as group-specific metabolic signatures.

Results: All samples were analyzed with a high number of features identified. No group-specific clustering was observed in principal component analysis for the dry eye positive or dry eye negative groups. However, volcano plots revealed that a majority of the metabolomic features had lower concentration in the dry eye positive group compared to the dry eye negative group. Four of these features had a Log₂-fold change ≤ -1 and p value ≤.05. These warrant further study.

Conclusion: Although no overall global difference was observed on the principal component analysis plots, a general trend of lower metabolite concentrations in the dry eye disease group was shown. Moreover, several metabolites of interest were discovered with significantly different signal intensities between the groups. These metabolites may aid future diagnostics and serve as possible biomarkers and therapeutic targets for dry eye disease in pre-operative cataract patients.

Purpose: This study aimed to compare the intraocular pressure (IOP)-lowering effects of timolol (a β-blocker), brinzolamide (a carbonic anhydrase inhibitor), brimonidine (an α2-agonist) and netarsudil (a rho kinase inhibitor) in rabbits.

Methods: The experiments were performed on 52 female New Zealand white rabbits. The IOP was measured in normotensive rabbits and in water loading-induced ocular hypertension model rabbits. Thirty microliters of timolol, brinzolamide, brimonidine, netarsudil or saline was administered topically to the randomly chosen eye. Ocular hypertension was induced by the oral administration of 60 mL/kg of tap water.

Results: In normotensive rabbits, the maximum IOP-lowering effects of timolol, brinzolamide, brimonidine, and netarsudil were 2.9 mmHg (2 h), 5.2 mmHg (1 h), 5.7 mmHg (2 h), and 3.3 mmHg (4 h), respectively. In water loading-induced ocular hypertension model rabbits, the maximum IOP-lowering effects of timolol, brinzolamide, brimonidine, and netarsudil were 3.6, 5.0, 12.2, and 5.0 mmHg, respectively. The IOP-lowering effects of brimonidine and netarsudil were sustained until 90 min after water loading.

Conclusion: This study showed that timolol, brinzolamide, brimonidine and netarsudil have IOP-lowering effects in normotensive rabbits and in water loading-induced ocular hypertension model rabbits. In an ocular hypertension rabbit model, brimonidine and netarsudil, which promote aqueous humor outflow, exhibited stronger IOP-lowering effects than timolol and brinzolamide, which suppress aqueous humor production. These results could provide data for characterizing each medication. These data may aid in the development of new glaucoma medications through the combination of existing medications.