Crosstalk among miR-29, α-SMA, and TGFß1/ß3 in melatonin-induced exosome (Mel-prExo) treated human limbal mesenchymal stem cells (hLMSCs): An insight into scarless healing of the cornea.

Inflammatory mediators that infiltrate the corneal stroma after corneal infections, trauma or refractive surgery can trigger the transformation of corneal keratocytes into myofibroblasts, resulting in highly irregular collagen deposition and subsequently corneal scarring. Mesenchymal stem cells (MSCs) can be used as therapeutic agents to regenerate corneal and conjunctival tissue damage, regulate inflammation, and reduce the development of limbal stem cell failure. The use of MSC-derived exosomes as a cell-free therapeutic vector is a novel therapeutic approach. This study aimed to assess the effect of exosomes obtained from melatonin (Mel)-treated human limbal mesenchymal stem cells (hLMSCs) on naïve hLMSCs and to determine their influence on the antifibrotic and pro-regenerative pathways involved in corneal scarring. hLMSCs were treated with varying concentrations of Mel, followed by isolation and characterization of the procured exosomes (Mel-prExos). These exosomes were added to the cell culture media of naïve hLMSCs to examine their antifibrotic and pro-regenerative effects. The expression of miR-155, miR-29, TGFß1, TGFß3, PPARγ, and α-SMA miRNAs and genes were compared between Mel-treated hLMSCs and Mel-prExo-treated hLMSCs by using real-time PCR. We found that at 1 µM Mel and in the presence of Mel-prExos, TGFß1 was expressed 0.001-fold, while TGFß3 was expressed 0.6-fold. miR-29 expression was increased 38-fold in the control-Exo group compared to that in the control group. Changes in TGFß1/ß3 and α-SMA expression are associated with miR-29 and miR-155. This approach could prove beneficial for ocular surface tissue engineering applications.

The Effect of Prolactinoma on Tear Film Function.

Objectives: To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia. Materials and Methods: Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients. Results: The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036). Conclusion: Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent.

Distal renal tubular acidosis, autoimmune thyroiditis, enamel hypomaturation, and tooth agenesis caused by homozygosity of a novel double-nucleotide substitution in SLC4A4.

BACKGROUND: Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta. In this study, the authors describe the clinical manifestations, and investigate the molecular etiology, in a patient with RTA. CASE DESCRIPTION: The authors report on a girl with distal RTA who carried a novel homozygous base substitution of 2 consecutive base pair variants (NM_001098484.3:c.808-2A>C and NM_001098484.3:c.808-1G>C) in the SLC4A4 gene. The patient had clinical manifestations of autoimmune thyroiditis and distal RTA, including hypercalciuria, nephrocalcinosis, and nephrolithiasis. In addition to the presence of hypoplastic-type amelogenesis imperfecta, generalized enamel hypomaturation, a feature seen in mice lacking Slc4a4, was also observed in the patient. The basic defect in this patient appeared to be impaired hydrogen ion secretion, leading to an inability to acidify the urine, resulting in alkaline urine (despite a normal serum anion gap), hypokalemic, and hyperchloremic metabolic acidosis. The pulp stones found in the patient may likely be the consequences of a disrupted acid-base homeostatic environment that precipitated mineral deposits. Even with proper treatments for distal RTA, the patient has had frequent recurrences of band keratopathy, pupillary membrane, and cataract. PRACTICAL IMPLICATIONS: This is the first report of distal RTA, autoimmune thyroiditis, tooth agenesis, enamel hypomaturation, and pulp stones associated with an SLC4A4 mutation. It is important for dentists to be aware that amelogenesis imperfecta in patients may be a sign of systemic diseases including RTA, nephrocalcinosis, or nephrolithiasis.

Evaluation of the reasons for the microvascular changes in patients with Fabry disease using optic coherence tomography angiography.

PURPOSE: To investigate the blood flow changes in the choriocapillaris and the superficial and deep capillary plexus of the retina using optic coherence tomography angiography (OCTA) in patients with Fabry disease (FD) and reveal any possible association of these changes with the systemic findings. METHODS: This cross-sectional study included 38 patients with FD and age- and gender-matched 40 healthy controls. OCTA images were obtained from all patients. Superficial (sCVD) and deep capillary vascular density (dCVD) in the foveal, parafoveal, and perifoveal zones and the whole image were recorded for each patient. Flow area in the choriocapillaris and central macular thickness (CMT) were also recorded. RESULTS: Patients with FD showed a lower whole image (54.45 ± 5.99% vs 57.32 ± 6.71%, p = 0.004), foveal (34.94 ± 7.60% vs 39.65 ± 7.03%, p = 0.003), parafoveal (57.41 ± 4.85% vs 59.19 ± 4.67%, p = 0.043), and perifoveal (55.87 ± 6.43% vs 58.87 ± 7.02%, p = 0.003) dCVD compared to the healthy controls without a significant difference in the sCVD and choriocapillaris blood flow (p > 0.05). A significantly lower whole image and foveal dCVD in the FD patients with renal involvement was observed compared to the healthy controls (p = 0.027 and p = 0.024, respectively) without any significant difference between the FD patients without renal involvement and healthy controls (p = 0.17 and p = 0.13, respectively). CMT was significantly higher in FD patients with renal involvement compared to the ones without renal involvement (252.1 ± 18.5 µm vs 235.5 ± 17.6 µm, p = 0.016). CONCLUSION: Patients with FD showed a lower dCVD without any change in sCVD and choriocapillaris compared to the healthy controls. This decrease was associated mostly with the renal involvement and duration of treatment.

Six-Month Results of Descemet Membrane Endothelial Keratoplasty in 100 Eyes: First Clinical Results from Turkey

Objectives: To evaluate the 6-month outcomes of Descemet membrane endothelial keratoplasty (DMEK) in patients with pseudophakic bullous keratopathy (PBK) and Fuchs' endothelial dystrophy (FED) in a single center in Turkey. Materials and Methods: The medical records of patients who underwent DMEK were reviewed retrospectively. Best corrected visual acuity (BCVA), donor corneal endothelial cell density (ECD), donor age, duration in solution after obtaining the donor tissue, and duration after exitus of the donor were evaluated preoperatively and BCVA, ECD, and ECD loss (%) at postoperative 6 months were evaluated postoperatively. Graft detachment, graft failure, and pupillary block were recorded as surgical complications. Patients with cataract and FED underwent combined or staged procedures. Two different graft preparation techniques were utilized: 8 and 9.5 mm. Results: One hundred eyes of 74 patients were included in the study. Fifty-two of the eyes had FED and the remaining 48 had PBK. Mean ECD loss in 6 months was 29.2±4.4% in the FED group and 29.7±5% in the PBK group (p=0.415). Mean BCVA at 6 months was 0.06±0.05 in the patients with FED and 0.07±0.05 in the patients with PBK (p=0.378). Mean ECD loss in 6 months was 28.3±5.3% in the 8 mm group vs. 29.7±4.5% in the 9.5 mm group (p=0.255), and 28.5±5.6% in the combined group vs. 29.8±2.9% in the staged group (p=0.279). Conclusion: Different graft preparation techniques can be utilized with similar efficiency for DMEK surgery. A staged or combined approach can be used efficiently in the management of patients with FED and cataract. Our results are promising both for PBK and FED patients.

Intraoperative relaxed muscle positioning technique results in a tertiary Center for Thyroid Orbitopathy Related Strabismus.

BACKGROUND: Previous techniques resulted with low rates of successful fusion after the surgeries and high necessity of additional surgeries in the treatment of thyroid orbitopathy related strabismus. In this study, reviewing the results of our patients who had surgical correction with relaxed muscle positioning technique due to thyroid orbitopathy related strabismus to evaluate the effectiveness of the surgery was aimed. METHODS: The medical records of 8 patients who had surgical correction with intraoperative relaxed muscle positioning (IRMP) technique were studied retrospectively. The extent of strabismus was determined with prism cover test both at near and distance. The extent of recession was determined by marking the natural place of the released tendon during the primary position. The muscle then sutured to the globe at this precise point. RESULTS: Seven eyes (87.5%) of 8 patients had orthophoria after the surgery and they reported no diplopia in primary and reading gaze. The mean age of the patients was 51 ± 8.8 years. The mean follow-up time was 32.7 ± 18.5 months. Three patients had inferior rectus recession (IRR), 3 had bilateral medial rectus recession (MRR), 1 had only right MRR and 1 had combined MRR with IRR during the surgical correction of the strabismus. The mean amount of recession for IR was 7.5 ± 1.34 mm and it was 6.75 ± 0.95 mm for the MR muscles. The mean prism diopter before the surgery was 37.8 ± 23.3 and it was 0 after surgery except only one of the patients who had > 60 prism diopter (PD) left esotropia (ET) before surgery and had 30 PD left ET after surgery (3.3 ± 9.4). CONCLUSION: IRMP technique is a unique option for the surgical correction of thyroid orbitopathy related strabismus. By showing a dramatic increase in the quality of life of the patients, our surgical results are promising despite limited number of patients.

Effect of Intracameral Ophthalmic Cefuroxime Solution (Aprokam®) in the Prophylaxis of Cataract Surgery in Patients with Keratoplasty.

BACKGROUND: Development of endophthalmitis during cataract surgery is one of the most severe complications and it may also result in blindness and globe loss. AIMS: To evaluate the effect of an ophthalmic cefuroxime solution (Aprokam®) that is prophylactically used in phacoemulsification surgery performed due to cataract that eventually occurs in patients with or without penetrating keratoplasty. STUDY DESIGN: Case-control study. METHODS: In this retrospective study, patients who had undergone penetrating keratoplasty and for whom phacoemulsification surgery was performed due to cataract and an intracameral ophthalmic cefuroxime solution (Aprokam®) was administered for prophylaxis were evaluated in comparison with patients with cataract without keratoplasty. The following parameters were evaluated: postoperative anterior chamber reaction, intraocular pressure, best corrected visual acuity, corneal endothelial cell density, and central corneal thickness alterations. RESULTS: A total of 42 patients (18 males, 24 females) with keratoplasty and 42 patients (17 males, 25 females) without keratoplasty were included in this study. An increase in visual acuity was observed in all the patients after cataract surgery (p<0.001). The mean corneal endothelial cell densitys were determined to be 2437.20±148.5 cells/mm2 preoperatively in the study group and 2807.1±152.4 cells/mm2 preoperatively in the control group. The mean corneal endothelial cell densitys were determined to be 2103.85±196.5 cells/mm2 after the first postoperative month (p<0.001) in the study group and 2755.92±182.7 cells/mm2 in the control group (p=0.17). The mean central corneal thickness in the study group were 565.78±11.5 µm preoperatively and 584.65±12.7 µm after the first postoperative month (p<0.001). No difference was observed in the control group in terms of preoperative and postoperative central corneal thickness and endothelial cell density. There was no significant difference between the groups in terms of the intraocular pressure, anterior chamber reaction. CONCLUSION: There was no significant effect of the prophylactic intracameral use of ophthalmic cefuroxime solution (Aprokam®) on the endothelial cells which was used in patients with keratoplasty for whom cataract surgery was performed.

Comparison of Two Intraocular Lens Implantation Techniques in Pediatric Cataract Surgery in Terms of Postoperative Complications.

BACKGROUND: Pediatric cataract surgery differs substantially from adult cataract surgery. Numerous studies have focused on reducing the development of postoperative complications. AIMS: To compare two intraocular lens implantation techniques used in pediatric cataract surgery in terms of postoperative complications. STUDY DESIGN: Case-control study. METHODS: Patients who underwent pediatric cataract surgery and intraocular lens implantation between 2008 and 2016 were evaluated in this retrospective study. Patients aged 3-15 years with unilateral or bilateral cataract and without corneal pathology were included in the study. The patients were categorized into the following two groups: those who underwent posterior capsulorhexis and anterior vitrectomy using in-the-bag intraocular lens implantation (group 1) and those who underwent posterior capsulorhexis and intraocular lens implantation with the optic fixed behind the posterior capsulorhexis (group 2). Rates of postoperative visual axis opacification and complications (glaucoma, posterior synechiae, uveitic reaction, and intraocular lens decentration) were evaluated in these groups. The implanted intraocular lenses were either monoblock (AcrySof SN60AT intraocular lens), triple-piece (AcrySof MA60BM intraocular lens) foldable hydrophobic acrylic lenses, or multifocal lenses (AcrySof IQ ReSTOR). RESULTS: This retrospective study included 52 eyes of 37 patients. Group 1 comprised 26 eyes of 20 patients and group 2 comprised 26 eyes of 17 patients. During the follow-up, visual axis opacification was observed in two patients in group 1 but no patients in group 2. Regarding postoperative complications, there was no uveitic reaction, posterior synechiae, or intraocular lens decentration in either group. There was no significant difference between the groups in terms of the postoperative complications (p>0.05). CONCLUSION: There was no significant difference between in-the-bag intraocular lens implantation after posterior capsulorhexis and intraocular lens optic capture through posterior capsulorhexis in terms of the complications.

Effect of the Rigid Gas-Permeable Contact Lens Use on the Endothelial Cells in Patients With Keratoconus.

OBJECTIVES: To compare the changes in the corneal endothelial cells of both the patients with keratoconus who use rigid gas-permeable (RGP) contact lens and who do not use any contact lens with healthy population. METHODS: Thirty-three patients with keratoconus who use RGP contact lenses (group 1), 20 patients with keratoconus who do not use any contact lens (group 2), and 40 healthy controls were included in the study. Changes in the corneal endothelial cells of all patients were evaluated using a noncontact specular microscope. Endothelial cell density (ECD), coefficient of variability (CV), hexagonal cell percentage (%HEX), and central corneal thickness (CCT) of the patients were evaluated in the study. RESULTS: In the groups 1, 2, and 3, the mean ECD was 2,420.8±247, 2,579.5±240, and 2,589.5±271 cells/mm, the mean CV was 357±9, 34±7, and 34±6, the mean %HEX was 54.3±13, 59.1±14, and 57.4±10, and the mean CCT was 508±33, 504±43, and 561±34 µm, respectively. There was no significant difference between the groups in terms of ECD, CV, and %HEX. Although significant differences between the groups 1 to 3 and groups 2 to 3 in terms of CCT were detected (P=0.001 and P=0.004, respectively), no significant difference was observed between the groups 1 and 2. CONCLUSIONS: Although significant difference was found between the groups 1 to 2 and normal population in terms of CCT, no difference was detected between all the groups in terms of the other parameters. In this study, we report that long-term use of RGP contact lens in patients with keratoconus had no effect on the corneal endothelial cells.