Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Assessment of area and structural irregularity of retinal layers in diabetic retinopathy using machine learning and image processing techniques.

Diabetes retinopathy prevention necessitates early detection, monitoring, and treatment. Non-invasive optical coherence tomography (OCT) shows structural changes in the retinal layer. OCT image evaluation necessitates retinal layer segmentation. The ability of our automated retinal layer segmentation to distinguish between normal, non-proliferative (NPDR), and proliferative diabetic retinopathy (PDR) was investigated in this study using quantifiable biomarkers such as retina layer smoothness index (SI) and area (S) in horizontal and vertical OCT images for each zone (fovea, superior, inferior, nasal, and temporal). This research includes 84 eyes from 57 individuals. The study shows a significant difference in the Area (S) of inner nuclear layer (INL) and outer nuclear layer (ONL) in the horizontal foveal zone across the three groups (p < 0.001). In the horizontal scan, there is a significant difference in the smoothness index (SI) of the inner plexiform layer (IPL) and the upper border of the outer plexiform layer (OPL) among three groups (p < 0.05). There is also a significant difference in the area (S) of the OPL in the foveal zone among the three groups (p = 0.003). The area (S) of the INL in the foveal region of horizontal slabs performed best for distinguishing diabetic patients (NPDR and PDR) from normal individuals, with an accuracy of 87.6%. The smoothness index (SI) of IPL in the nasal zone of horizontal foveal slabs was the most accurate at 97.2% in distinguishing PDR from NPDR. The smoothness index of the top border of the OPL in the nasal zone of horizontal slabs was 84.1% accurate in distinguishing NPDR from PDR. Smoothness index of IPL in the temporal zone of horizontal slabs was 89.8% accurate in identifying NPDR from PDR patients. In conclusion, optical coherence tomography can assess the smoothness index and irregularity of the inner and outer plexiform layers, particularly in the nasal and temporal regions of horizontal foveal slabs, to distinguish non-proliferative from proliferative diabetic retinopathy. The evolution of diabetic retinopathy throughout severity levels and its effects on retinal layer irregularity need more study.

The Potential of Mesenchymal Stem/Stromal Cell Therapy in Mustard Keratopathy: Discovering New Roads to Combat Cellular Senescence.

Mesenchymal stem/stromal cells (MSCs) are considered a valuable option to treat ocular surface disorders such as mustard keratopathy (MK). MK often leads to vision impairment due to corneal opacification and neovascularization and cellular senescence seems to have a role in its pathophysiology. Herein, we utilized intrastromal MSC injections to treat MK. Thirty-two mice were divided into four groups based on the exposure to 20 mM or 40 mM concentrations of mustard and receiving the treatment or not. Mice were clinically and histopathologically examined. Histopathological evaluations were completed after the euthanasia of mice after four months and included hematoxylin and eosin (H&E), CK12, and beta-galactosidase (ß-gal) staining. The treatment group demonstrated reduced opacity compared to the control group. While corneal neovascularization did not display significant variations between the groups, the control group did register higher numerical values. Histopathologically, reduced CK12 staining was detected in the control group. Additionally, ß-gal staining areas were notably lower in the treatment group. Although the treated groups showed lower severity of fibrosis compared to the control groups, statistical difference was not significant. In conclusion, it seems that delivery of MSCs in MK has exhibited promising therapeutic results, notably in reducing corneal opacity. Furthermore, the significant reduction in the ß-galactosidase staining area may point towards the promising anti-senescence potential of MSCs.

The effect of povidone-iodine 2% eye drops in the treatment of adenoviral keratoconjunctivitis.

BACKGROUND: Keratoconjunctivitis is one of the most common pathologies worldwide, caused by several infectious and noninfectious factors. This study aimed to determine the effect of povidone-iodine 2% eye drops in treating adenoviral keratoconjunctivitis. METHODS: This analytic cross-sectional study was conducted on patients referred to Farabi Eye Hospital Records of patients with adenoviral keratoconjunctivitis, more than 12 years of age, and no allergy to iodine who were treated by povidone-iodine 2% eye drops four times a day were assessed. Data included demographic characteristics, family history of adenoviral keratoconjunctivitis, follicular conjunctivitis, petechial conjunctival hemorrhages, periauricular lymphadenopathy, and the presence of conjunctival pseudomembrane were collected from the records. Discharge decrease, injection decrease, swelling decrease, pseudomembrane formation, periauricular lymphadenopathy, and subepithelial infiltration on the 7thday of assessment by physical examination were reported. RESULTS: Patients with a mean (±standard deviation) age of 33.77 (11.01) years were assessed. At the baseline, 95 (99.0%) follicular conjunctivitis, 94 (97.9%) petechial conjunctival hemorrhages, 29 (30.2%) periauricular lymphadenopathy, and 5 (5.2%) conjunctival pseudomembrane were recorded. On the 7thday of treatment, the discharge decreased in 92.7% of patients, and the injection decreased in 90.6%. The swelling decrease was also detected in 79.2% of patients. Subepithelial infiltration was only seen in 21.9% of the study population. Results showed that 2.1% of patients had periauricular lymphadenopathy, and only 13 out of 96 patients (13.5%) had pseudomembrane formation after 7 days. CONCLUSIONS: Based on the safety, availability, and tolerability of povidone-iodine and its promising effects on patients with adenoviral keratoconjunctivitis, further clinical trials assessing the impact of this drug in a longer duration of follow-up can be recommended.

Comparison of the fluorescein angiography-guided and indocyanine green angiography-guided photodynamic therapy in the treatment of non-resolving central serous chorioretinopathy.

To compare the functional and anatomical outcome of fluorescein angiography (FA) versus indocyanine green angiography (ICGA) guided photodynamic therapy (PDT) in the treatment of non-resolving central serous chorioretinopathy (CSCR). In this prospective interventional case series, all patients with non-resolving CSCR, defined as persistent SRF involving subfoveal area for at least three months, were nonrandomly assigned to receive either FA or ICGA-guided half dose PDT. Baseline and 4 months post-treatment data including best corrected visual acuity (BCVA), the status of foveal subretinal fluid, subfoveal choroidal thickness, choroidal vascularity index, pigment epithelial detachment area, treatment and PDT spot numbers were collected. Thirty-six eyes were included; 24 received ICGA-guided and 12 received FA-guided PDT. Overall, improvement in BCVA and choroidal parameters were observed in all patients. There was no significant difference in baseline parameters as well as follow-up measurements between groups. However, the mean total energy dose and spot number in the IGCA-guided PDT were significantly higher than the FA-guided PDT group (P = 0.001). Both FA-guided and ICGA-guided half-dose PDT were effective in the treatment of non-resolving CSCR, with favorable functional and anatomical outcome. In FA group, PDT with smaller spot sizes and fewer numbers of spots were applied.

Retinal misregistration and effect of surgery on its improvement in patients with epiretinal membrane.

PURPOSE: To evaluate the prevalence of retinal misregistration, that is, misalignment of retinal elements that affect central and peripheral fusion, and the effect of surgery in patients with epiretinal membrane (ERM). METHODS: This prospective interventional case-series was performed on 32 patients with symptomatic ERM with the complaint of binocular diplopia or decreased visual acuity. After the diagnosis of ERM, optotype frame, synoptophore, and lights on-off tests were used to evaluate retinal misregistration. Patients with severe symptoms underwent surgery and were followed for 3 months. RESULTS: Of the 32 patients, 6 (19%) had preoperative diplopia. Optotype frame, synoptophore, and lights on-off tests had positive results in 20 (63%), 19 (63%), and 11 (34%) cases, respectively. Of the 6 diplopia cases, 5 showed positive results in all 3 tests and 1 was positive on optotype frame and synoptophore testing. Of the 26 cases without diplopia, 15 (58%) showed positive results in at least one test, including 6 (23%) in all three tests, 6 (23%) in two tests, and 3 (12%) in only one test. Ten patients underwent surgery. Postoperatively, all patients had negative lights on-off test, but optotype frame and synoptophore tests were negative in eight patients (80%). Two cases (20%) had postoperative diplopia, including 1 case with postoperative new-onset diplopia. CONCLUSIONS: The prevalence of retinal misregistration was higher than the rate of diplopia. Surgery improved diplopia and results of tests of retinal misregistration.

Keratin pearl cyst formation after traumatic implantation of an eyelash into the anterior chamber: A case report.

Purpose: We introduce a case with creamy white pearl-like keratin cysts in the anterior chamber after a penetrating injury associated with eyelash implantation. Observations: A 5-year-old girl presented with a history of penetrating corneal injury with a knife ten months ago. An eyelash was removed from the anterior chamber during her previous primary repair. Her parents complained about the presence of a white mass in her repaired eye, which had appeared about nine months after surgery. After the visco-expression of these solid masses, the histopathological evaluation revealed keratinous material surrounded by multinucleated giant cells. Conclusions and importance: In a case of post-traumatic implantation of eyelash into the anterior chamber, despite removing the cilia, cysts may develop, which suggests proliferating epithelial cells embedded within the anterior chamber.

The Role of Early Vitrectomy in the Healing of Retinal Lesions in Progressive Outer Retinal Necrosis.

Purpose: To report on the efficacy of early pars plana vitrectomy (PPV), silicone oil (SO) tamponade, and intravitreal ganciclovir injection in the treatment of a case with progressive outer retinal necrosis (PORN). Case Presentation. A 33-year-old man with a history of shingles on the chest skin 2.5 months ago presented with progressive vision loss in both eyes over the past 20 days. Fundus examination revealed retinal necrosis with perivascular clearance. Human immunodeficiency virus (HIV) infection was confirmed by western blot analysis. Treatment with intravenous acyclovir and intravitreal ganciclovir injections was unable to stop the progression of retinitis. Along with highly active antiretroviral therapy, the patient underwent PPV with SO tamponade and intravitreal ganciclovir injection in both eyes. A few days after surgery, retinal lesions started to improve. Conclusion: Early PPV, SO tamponade, and intravitreal ganciclovir injection may be considered an effective intervention in PORN patients with an unfavorable response to medical treatment.

Structural and functional outcomes of pars plana vitrectomy in patients with lamellar macular hole.

PURPOSE: To investigate the short-term functional and microstructural outcomes of pars plana vitrectomy (PPV) without gas tamponade in lamellar macular holes (LH). MATERIALS AND METHODS: In this prospective case series, LH cases diagnosed by optical coherence tomography (OCT) underwent PPV with epiretinal membrane (ERM) removal and internal limiting membrane peeling without gas tamponade. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA) and OCT imaging preoperatively and 3 months after the surgery. RESULTS: Among 22 eyes, 10 degenerative (Deg) LH, 8 tractional (Trac) LH, and 4 mixed-type LH were assessed. After the surgery, anatomical closure occurred in 20 eyes (91%) without any significant difference between LH subgroups. Comparing preoperative and postoperative values, no significant changes was detected regarding BCVA neither totally (P = 0.5) nor in subgroups (P for Deg = 1.0, Trac = 0.71, Mix = 0.18). The overall central foveal thickness was increased significantly after surgery (P < 0.01), but in subgroup analysis, the increase was significant only for Trac LH (P = 0.02). The tractional LH eyes had less ellipsoid zone (EZ) disruptions compared to Deg or mixed subgroups before surgery. There were no changes in EZ integrity before and after the surgery. In regression analysis, no correlation was found between demographic or clinical characteristics and anatomical closure or BCVA improvement postoperatively. CONCLUSION: PPV resulted in 91% anatomical closure of all cases of LH but without functional improvement in short-term. Further prospective clinical trials with larger sample size and longer follow-up would be required to confirm the clinical significance of these findings.

A ten-year report of microbial keratitis in pediatric population under five years in a tertiary eye center.

PURPOSE: To report characteristics of microbial keratitis in pediatric patients under five years. METHODS: Patients with infectious keratitis under the age of 5 years were included in this retrospective cross-sectional study for ten years. All patients were admitted and corneal scraping was performed in 81 children. Fortified empiric antibiotic eye drops including cefazolin (50 mg/cc) and amikacin (20 mg/cc) were started and the antibiotic regimen was continued or changed according to culture results. In the case of fungal keratitis, topical voriconazole (10 mg/cc) or natamycin (50 mg/cc) and topical chloramphenicol (5 mg/cc) were started. A tectonic procedure was done when corneal thinning or perforation was present. RESULTS: Ninety-Three Patients between 1 to 60 months with a mean age of 33 ± 18 months old with corneal ulcer were included in the study. The most common risk factor was trauma (40.9%) followed by contact lens use (8.6%). Cultures were negative for microbial growth in 28 (30.1%) patients. The most common pathogens were S. epidermidis (10.8%) and P. aeruginosa (10.8%). Fluoroquinolone antibiotics (ciprofloxacin; 93.8% sensitivity) were the most potent antibiotic against bacterial pathogens. Forty-one patients underwent tectonic procedures, which the most common ones were cyanoacrylate glue 18.3% followed by keratoplasty 16.1%. CONCLUSION: This study emphasizes the role of trauma as the primary cause and S. epidermidis as the most frequent microorganism in pediatric keratitis; according to antibiogram results and poor cooperation of patients under five years, monotherapy with fluoroquinolones could be a good regimen in small non-central lesions without thinning.