Is tear proteome profile a predictor of developing uveitis in ANA-positive patients with oligoarticular juvenile idiopathic arthritis?

PURPOSE: Although less than one-third of anti-nuclear antibody (ANA) positive patients with oJIA develop uveitis, ANA positivity is still the most well-known marker for assessing the risk of uveitis in oligoarticular JIA (oJIA). Therefore, novel biomarkers are needed to better assess the risk of developing uveitis. For this purpose, we performed a comparative tear proteome analysis of uveitis patients to reveal the identity of differentially regulated proteins. DESIGN: Tear samples were collected using the Schirmer strips in 7 oJIA and 7 oJIA patients with uveitis (oJIA-U). All oJIA-U patients had developed bilateral anterior uveitis and were inactive and topical treatment-free. METHODS: The nHPLC LC-MS/MS system was used for protein identification and label-free proteome comparisons. The PANTHER and STRING analyses were carried out using UniProt accession numbers of the identified proteins. RESULTS: Patient characteristics, e.g., age, gender, disease duration, and treatments were similar. For protein identification, three different databases were searched. Twenty-two, 147, and 258 database searches, respectively. Of these, 15 were common to all three proteome databases. Of these 15 proteins, 10 proteins were upregulated, and 2 were downregulated, based on the twofold regulation criteria. The upregulated proteins were, namely, cystatin-S, secretoglobin family 1D member, opiorphin prepropeptide, mammaglobin-B, lysozyme C, mesothelin, immunoglobulin kappa constant, extracellular glycoprotein lacritin, beta-2-microglobulin, and immunoglobulin J chain. The downregulated proteins were dermcidin and prolactin-inducible protein. Among the differentially regulated proteins, cystatin-S was the most regulated protein with an 18-fold upregulation ratio in tear samples from uveitis patients. CONCLUSION: Here, the identities and regulation ratios of several proteins were revealed when tear samples from uveitis patients were compared to patients without uveitis. These proteins are putative biomarkers for assessing uveitis risk and require further attention.

The effect of transepithelial corneal collagen cross-linking treatment on optical quality of the cornea in keratoconus: 12-month clinical results.

PURPOSE: To evaluate the effect of transepithelial corneal collagen crosslinking (CXL) treatment on the optical performance of the cornea at 12-month follow-up after CXL in patients with progressive keratoconus. METHODS: One hundred and ten eyes of 67 patients were included. The following corneal optical aberrations over the 4-mm-diameter pupil were recorded via Sirius dual-scanning corneal tomography: total, anterior and posterior amount of corneal higher order aberrations [HOAs], vertical coma, horizontal coma, vertical trefoil, oblique trefoil, and spherical aberration, and Strehl ratio of point spread function (PSF). RESULTS: There were significant improvements in mean root mean square error values for corneal total HOA, total coma, anterior HOA, anterior coma, and vertical coma following CXL (P > 0.05, for all). No significant changes were found in the posterior aberometric parameters. PSF value did not change after CXL (P > 0.05). The corneal topographic measurements not revealed a change in the mean simulated keratometry-1, simulated keratometry-2, and maximum keratometry compared with the baseline measurements (P > 0.05, for all). At 12 months, there was a significant improvement in the uncorrected (UCVA) and best corrected (BCVA) visual acuity (P < 0.001, both). Most corneal aberrations correlated significantly with postoperative BCVA, but changes in HOAs were not statistically associated with improvements in visual acuity. CONCLUSIONS: Transepithelial CXL was effective in stabilizing the keratometric indices and improving the most corneal aberrations in keratoconic eyes 1 year after the procedure. While the healing effect on aberrations after CXL was in total and anterior parameters, no significant changes were observed in the posterior surface. In addition, it was observed that transepithelial CXL treatment did not cause a significant change in PSF distribution data.

The anti-scar effect of tyrosine-kinase inhibitor nintedanib in experimental glaucoma filtration surgery in rabbits.

PURPOSE: To investigate the efficacy of nintedanib on preventing postoperative scar in formation following glaucoma filtering surgery (GFC) in rabbits in comparison with Mitomycin-C (MMC). DESIGN: Experimental Animal Study. METHODS: 24 New Zealand rabbits were divided randomly into 3 groups as Sham, Nindetanib and MMC(n = 8). Limbal-based trabeculectomy was performed on the right eyes of the rabbits. Left eyes that did'nt undergo surgery were included in the control group (n = 8). Following surgery, Intraocular pressures (IOP), postoperative complications and morphological changes in the bleb were evaluated. On the 28th day, eight eyes from each group were enucleated and histologically and immunohistochemically analyzed. Matrix metalloproteinase-2 (MMP-2), Transforming Growth Factor-1 (TGF-B1) and alpha-smooth muscle actin (a-SMA) were evaluated. RESULTS: It was observed that nintedanib has no side effects and reduces subconjunctival fibrosis. Postoperative IOP values in the Nindetanib group were lower than the other groups (p < 0.05). The longest bleb survival was observed in the Nintedanib group and the shortest in the Sham group (p < 0.001). Conjunctival vascularity and inflammation was reduced in the Nintedanib group compared to the Sham group (p < 0.05). The highest subconjunctival fibrosis was observed in the Sham group and the least in the Nintedanib group (p < 0.05). Although the fibrosis score was found lower in the Nintedanib group compared to the MMC(p > 0.05). α-SMA TGF-ß1, MMP-2 expressions were similar in Nintedanib and MMC groups (p > 0.05), however, it was observed that significantly decreased in both groups compared to Sham group (p < 0.05). CONCLUSION: It has been observed that Nindetanib suppress fibroblast proliferation Thus, It may be a drug that can prevent subconjunctival fibrosis in GFC.

Is Corneal Subbasal Nerve Loss Associated With Meibomian Gland Loss in Inactive Mild and Moderate-to-Severe Graves' Ophthalmopathy?

PURPOSE: To evaluate meibomian gland and subbasal nerve plexus parameters in Graves' Ophthalmopathy (GO) and association of meibomian gland loss with corneal subbasal nerve plexus loss. METHODS: Fifty-two eyes of 52 mild and moderate-to-severe GO patients and 32 eyes of 32 healthy controls were enrolled. The meibomian gland dropout area (MGDA) and meibography scores were evaluated using noncontact meibography. In vivo confocal microscopy of corneal subbasal nerve plexus were conducted. ACCMetrics was used to obtain corneal parameters. RESULTS: Compared with healthy subjects, GO patients had worse upper and lower eyelid MGDA ( p < 0.001, for all) and upper, lower and total meibography scores ( p < 0.001, p = 0.001, and p < 0.001, respectively). Eyelid margin scores were worse in the GO group ( p < 0.001) and showed correlation with all noncontact meibography parameters ( p < 0.001 for all). All corneal subbasal nerve parameters were significantly lower in the GO group compared with the controls ( p < 0.05 for all). Subbasal nerve parameters of GO patients did not reveal a correlation with MGDA and meibography scores but showed correlations with ocular surface disease index score and Schirmer I test (r = -0.304; p = 0.042 and r = 0.336; p = 0.021, respectively). CONCLUSION: Meibomian gland and corneal nerve loss could be observed even in the inactive phase and mild GO. The lack of a correlation between meibomian gland loss and subbasal nerve loss suggests that meibomian gland loss is not a significant additional component in the pathogenesis of subbasal nerve damage in GO. Furthermore, our study revealed new evidence regarding the use of eyelid margin score to represent meibomian gland loss in GO.

In vivo confocal microscopy of corneal nerve fiber damage in early course of multiple sclerosis.

PURPOSE: To evaluate the corneal nerve fiber morphology in patients with multiple sclerosis (MS) by in vivo corneal confocal microscopy (CCM). METHODS: Retinal nerve fiber layer thickness (RNFLT), central macular thickness (CMT), corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber tortuosity (CNFT) were measured. Correlation of corneal nerve findings with duration and clinical severity of MS was calculated. RESULTS: CNFL (9.50 ± 0.60 vs. 11.20 ± 0.57 mm/mm2, P = 0.046) and CNBD (57.46 ± 5.04 vs. 77.65 ± 3.41 no/mm2, P = 0.001) were significantly lower with no significant difference in CNFD (21.24 ± 1.20 vs. 23.62 ± 0.95 no/mm2, P = 0.125), CNFT (2.00 ± 0.15 vs. 1.73 ± 0.12, P = 0.180), CMT (269.57 ± 12.53 vs. 271.10 ± 18.84 µm, P = 0.716) or RNFLT (102.82 ± 6.98 vs. 105.33 ± 12.70 µm, P = 0.351) between patients with RRMS compared to controls. There was no significant correlation between CCM parameters with EDSS and duration of disease in MS patients. CONCLUSION: The current study demonstrated that a decrease in CNFL, CNFD and CNBD in CCM analysis in the early course of MS.

Preclinical ocular microvascular changes in juvenile dermatomyositis: A pilot optical coherence tomography angiography study.

OBJECTIVES: To evaluate the macular and optic nerve head (ONH) vascular density, foveal avascular zone area, and outer retina and choriocapillaris flow in juvenile dermatomyositis (JDM) using optical coherence tomography angiography (OCTA). METHODS: Ten eyes of 10 patients with JDM and 15 age and sex-matched healthy controls were investigated in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, foveal avascular zone (FAZ) parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. RESULTS: Vessel density (VD) of the parafovea (p = 0.036) and parafoveal subregions (p = 0.041 for superior hemifield, p = 0.031 for inferior hemifield, p = 0.012 for superior, p = 0.019 for nasal, p = 0.026 for inferior, and p = 0.048 for temporal) in DCP were significantly lower in the JDM group compared to healthy controls. A high inverse correlation between disease duration and these parameters was found except parafoveal superior VD in DCP. There was no significant difference between the groups in VD parameters of SCP and ONH, FAZ parameters, outer retina, and choriocapillaris flow area as well as thickness parameters. (p > 0.05 for all). Furthermore, ROC analysis revealed that all parafoveal DCP parameters showed good ability to differentiate JDM from healthy controls. CONCLUSIONS: We demonstrated a decreased vessel density in the deep parafoveal region in JDM. As a result, we hypothesized that OCTA could detect retinal microvascular changes in JDM patients who did not have clinical evidence of ocular involvement.

Comparison of long-term results of trabeculectomy and phacotrabeculectomy in patients with pseudoexfoliation glaucoma and primary open-angle glaucoma: a single-center study.

PURPOSE: To evaluate long-term surgical success and complications in pseudoexfoliation glaucoma (PEXG) and primary open-angle glaucoma (POAG) after trabeculectomy or phacotrabeculectomy. METHODS: 96 PEXG eyes and 114 POAG eyes who underwent primary trabeculectomy and phacotrabeculectomy were retrospectively evaluated considering intraocular pressure (IOP), the number of glaucoma medications, surgical success, and rate of complications. Two success criteria were used: Complete success comprised IOP of 5-18 mmHg and 20% reduction of baseline IOP without medication. Qualified success comprised IOP of 5-18 mmHg and 20% reduction of baseline IOP irrespective of medication. Success rates in PEXG and POAG groups, trabeculectomy and phacotrabeculectomy groups, and four groups divided according to surgery and etiology were analyzed via Kaplan-Meier survival analysis. RESULTS: The complete and qualified success were not different between PEXG and POAG groups. The qualified success curves show a similar pattern among the four groups throughout the follow-up of 1,2,3,5,7 and 9 years. Baseline IOP and the number of medications were similar in all four groups (p = 0.275 and p = 0.209, respectively). IOP levels and the number of medications were not statistically different between the four groups during the follow-up of 2,5 and 7 years. The total number of complications and interventions were similar between PEXG and POAG groups (p = 0.258). CONCLUSIONS: Phacotrabeculectomy is an effective procedure as trabeculectomy with similar surgical success rates and few surgical complications when it comes to treating PAOG and PEXG patients. Both approaches resulted in similar postoperative IOP levels and medication numbers in both groups.

Ahmed glaucoma valve implantation for secondary glaucoma post-vitrectomy.

BACKGROUND AND OBJECTIVE: Ahmed glaucoma valv (AGV) implantation is one of the successful surgical methods in secondary glaucoma that develops after pars plana vitrectomy (PPV). In our study, we aimed to evaluate the 1-year results of AGV implantation in patients with a history of PPV. STUDY DESIGN: A total of 26 patients who underwent AGV implantation after PPV were included in our retrospective study. Fourteen of 26 patients had AGV implantation due to neovascular glaucoma (NVG) and 12 of them had secondary refractory galucoma. Data of these two groups of patients were evaluated in terms of IOP reduction, number of medication use, surgical complete and qualified success, surgical failure, and complications. RESULTS: The mean IOP was 29.54 ± 4.87 mmHg at the preoperative of AGV implantation and 12.88 ± 4.17 at the twelfth month visit in overal group. There was no statistically significant difference between two groups in terms of IOP in preoperative and all postoperative visits (p > 0.05). The mean intervals between PPV and AGV implantation were 67 ± 34 days in NVG and 391 ± 500 days in non-NVG group (p = 0.017). In overall group, 91.7% of patients had improvement in BCVA at the twelfth month visit. Complete and qualified surgical success rates were 75%, 83.3% in NVG group and 50%, 91.7% in non-NVG group, respectively. There was no devastating complication in both groups. CONCLUSION: AGV implantation is a safe and effective surgical method in uncontrolled IOP elevations after PPV. While surgical success and failure rates were similar between etiologies, the time required for AGV implantation after PPV was shorter in NVG etiology.

Protective effects of citicoline-containing eye drops against UVB-Induced corneal oxidative damage in a rat model.

It has been reported that citicoline increases antioxidant activity in some tissues. However, the effect of citicoline on corneal wound-healing has not yet been demonstrated. The aim was to investigate the protective effects of citicoline on ultraviolet B (UVB) radiation-induced corneal oxidative damage in a rat model. Four groups (eight animals each) were investigated: controls; UVB only; UVB/citicoline; and citicoline only. Corneal oxidative damage was induced by exposure to UVB radiation at 560 µW/cm2 for five days in the UVB-exposed groups and 1% citicoline eye drops were applied (3xday) for eight days in the two citicoline groups. Corneal surface damage was evaluated by opacity and fluorescein staining. Corneal injury was assessed biochemically by measuring the concentrations of glutathione (GSH) and malondialdehyde (MDA) and the activity of corneal superoxide dismutase (SOD) and catalase. Matrix metalloproteinase (MMP) -2 and -9 and caspase-3 were evaluated by immunofluorescent staining and microscopic examination and by Western blot analysis. Corneal gene expression analysis was performed for vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1ß) and transforming growth factor-beta (TGF-ß). UVB radiation caused significant epithelial damage and evident opacity in the cornea, together with a local decrease in SOD, catalase and GSH activity. Corneal MDA concentrations increased with UVB exposure. The UVB/Citicoline group had significantly less corneal damage, greater SOD, catalase and GSH activity, and decreased MDA concentrations compared to the UVB only group (p < 0.05). Expression of TGF-ß, IL-1ß and VEGF was significantly lower in the citicoline/UVB group compared to the UVB group (p < 0.05). Interestingly, TGF-ß expression was lower in the citicoline only group compared with controls. Immunfluorescent staining and Western blot analysis showed increased MMP-2, -9 and caspase-3 in the UVB only group compared with the UVB/citicoline group. It was shown that citicoline treatment may be effective in suppressing oxidative stress and controlling inflammation in UVB corneal injury.

Optical coherence tomography measurements in patients with systemic hypertension.

AIM: To evaluate the effect of systemic arterial hypertension (SAH) on retinal optical coherence tomography (OCT) parameters and investigate whether a correlation exists between ambulatory blood pressure monitoring (ABPM) and OCT measurements.Material-methods: 115 SAH patients (225 eyes) and 123 healthy control cases (234 eyes) were included. ABPM was performed on 89 of 115 SAH patients. All patients underwent detailed ophthalmologic examination including imaging with OCT. SAH patients were divided into two groups (dippers, non-dippers) according to their nocturnal blood pressure (BP) reduction, and OCT measurements were compared. RESULTS: Average and superior retinal nerve fiber layer (RNFL) quadrants were significantly thin in hypertensive cases (p:0.002, p < 0.001, respectively). Cup area, cup/disk (c/d) area, and c/d horizontal ratios were wider; the rim area was smaller in hypertensive cases (respectively: p:0.024, p:0.017, p:0.003, p < 0.001). Total macular volume (TMV), the thicknesses in 1-3 and 1-6 mm of the macula were less in hypertensives (p < 0.001). There was no significant difference between dippers and non-dippers in RNFL thickness, macula and optic nerve head (ONH) parameters. CONCLUSION: There were statistically significant differences between healthy cases and patients with SAH in terms of RNFL, macula thicknesses and ONH parameters.

Comparison of vessel density in macular and peripapillary regions between primary open-angle glaucoma and pseudoexfoliation glaucoma using OCTA.

PURPOSE: The aim of our study was to compare macular and peripapillary vessel density using optical coherence tomography angiography (OCTA) between eyes with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). METHODS: Thirty-six POAG and 34 PXG eyes with similar visual field defect (no statistically significant difference between average mean deviation and pattern standard deviation scores) were included. Macular superficial vessel density (msVD) in the superficial macular layer and foveal avascular zone (FAZ) parameters were assessed with (6 × 6 mm) and peripapillary vessel density (ppVD) in the radial peripapillary capillary (RPC) with (4.5 × 4.5 mm) OCTA scans. Area under the receiver operating curve was used for assessing diagnostic capability. RESULTS: In PXG group, all msVD parameters had lesser values, and especially in parafoveal region, statistically significant decrease was shown (p = 0.008) in all subdivisions except nasal (p = 0.053). FAZ area was more larger in PXG [0.32(0.25-0.36)] than POAG [0.28(0.22-0.39)],(p = 0.944). FAZ density - 300 µm had statistically significant decrease in PXG (47.22 ± 6.92) according to POAG groups (50.63 ± 7.25) (p = 0.048). Most of RPC VD parameters had decreasing values in PXG group (p > 0.05). VDs and corresponding thicknesses had significant remarkable positive correlation in both macular and peripapillary regions. Significant remarkable negative correlations were observed between fovea VD and FAZ area, FAZ perimeter and between fovea thickness and FAZ area, FAZ perimeter. CONCLUSION: PXG eyes were found to have lesser values in terms of VD in the macular area, especially in the parafoveal and FD-300 regions, compared to POAG eyes which had similar functional and structural glaucomatous damage. Patients whose etiology was PXG and who seemed to have the same functional damage as those with POAG were actually found to have greater macular vascular damage. In addition, it was observed that macular vascular parameters correlated with peripapillary vascular parameters.

Evaluation of serum and aqueous humor klotho levels in pseudoexfoliation syndrome, pseudoexfoliation and primary open-angle glaucoma.

PURPOSE: The aim of our study was to compare klotho in the serum and aqueous humor of patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEXG) and pseudoexfoliation syndrome (PEX). MATERIALS AND METHODS: 18 POAG, 20 PEXG, 19 PEX and 20 control patients were included in our study. Aqueous humor and serum samples were collected at the time of cataract surgery. Samples were collected using enzyme-linked immunosorbent assay to evaluate the levels of Klotho protein. RESULTS: Klotho levels in the serum and aqueous humor of PEXG patients (34.45 ± 3.59, 0.20 ± 0.15 ng/ml), PEX (35.85 ± 4.26, 0.23 ± 0.20 ng/ml) patients and POAG patients (35.99 ± 3.73, 0.25 ± 0.20 ng/ml) were significantly lower than control group (40.14 ± 3.85, 0.53 ± 0.39 ng/ml) (PEXG, P < 0.001, P < 0.001; PEX, P = 0.002, P = 0.003; POAG, P = 0.006, P = 0.003, respectively). Both serum and aqueous levels of klotho in the PEXG and PEX patients were lower than POAG patients, but the difference did not reach statistical significance (PEXG & POAG P = 0.149, P = 0.696), (PEX & POAG P = 0.845, P = 0.775). CONCLUSION: Klotho levels in the serum and aqueous humor decreased in PEX, PEXG and POAG groups compared to control group, but the reduction was most significant in PEXG group.

Effect of bone marrow and adipose tissue-derived mesenchymal stem cells on the natural course of corneal scarring after penetrating injury.

In the present study, we investigate and compare the efficacy of bone marrow- and adipose tissue-derived mesenchymal stem cell (MSCs) in corneal wound healing. A penetrating injury was created in the right corneas of Wistar rats (n = 40). Ten microliters of phosphate-buffered solution (PBS) containing 2 × 10(5) green fluorescent protein (GFP) labeled bone-marrow-derived MSCs to group 1 (n = 15), 10 µl of PBS containing 2 × 10(5) GFP-labeled adipose-tissue-derived MSCs to group 2 (n = 15), 10 µl PBS was injected into anterior chamber in group 3 (n = 10, control). Corneal opacity scoring, in vivo confocal microscopy, and histopathological evaluation were done at the end of 8 weeks. Immunofluorescence sections were evaluated to detect transplanted cells. Immune staining was performed to measure the expression levels of keratocan, aldehyde dehydrogenase (ALDH) and CD34. The gene expression levels of tumor necrosis factor (TNF-α), the interleukin 6 receptor (IL-6R), interleukin 12b (IL-12b), and transforming growth factor beta (TGF-ß1) was measured on corneas. The establishment of stem cells in the corneas of the transplanted groups was confirmed by immunofluorescence staining. The expression of keratocan, ALDH, and CD34 increased in the transplanted groups (p < 0.05). The density of keratocytes increased significantly in both transplanted groups according to the in vivo confocal microscopy data (p < 0.05). The expression of TNF-α, IL-6R, and IL-12b decreased significantly in the transplanted groups (p < 0.05). Based on our findings, we consider that allogeneic stem cells facilitate the regeneration of corneal stroma and can be a cell source for stromal repopulation in diseased cornea.

Evaluation of Effect of Topical Tacrolimus Treatment on Herpetic Stromal Keratitis in a Rat Model.

OBJECTIVES: To investigate the effectiveness of topical tacrolimus treatment on herpetic stromal keratitis (HSK) in a rat model. METHODS: The development of HSK was monitored for 14 days after the inoculation of rats with herpes simplex type 1 virus. Rats that developed HSK were divided into four groups as follows: (1) topical antiviral treatment (control), (2) topical antiviral and 1% prednisolone acetate, (3) topical antiviral and 0.03% tacrolimus ointment, and (4) topical antiviral plus 0.1% tacrolimus ointment. After 14 days of treatment, the severity levels of HSK were scored and compared with the levels before the treatment. The expression of CD3, CD4, and CD8 was evaluated by flow cytometry. The development of the disease was evaluated clinically and histologically. RESULTS: Significant improvement in vascularization was observed in the groups with the drug treatment in addition to the antiviral agent (P<0.05), but there was no obvious difference within groups 2, 3, and 4 in the vascularization severity. The regression of corneal edema was 8.05%±6% in group 1, 25.17%±14.55% in group 2 (P=0.01), 36.40%±21.69% in group 3 (P=0.03), and 46.39%±14.96% in group 4 (P=0.00). A significant decrease in the number of inflammatory cells in the groups with the drug treatment was evaluated by immunohistochemical staining and confirmed by flow cytometry analysis. CONCLUSIONS: Topical tacrolimus treatment caused a significant decrease in corneal vascularization accompanied by a lower number of inflammatory cells in the experimental HSK corneal edema model. Therefore, topical tacrolimus has the potential to be used in the treatment of HSK.

Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model.

BACKGROUND AIMS: The purpose of this study was to investigate the neuroprotective effects of bone marrow bone marrow-derived and adipose tissue-derived mesenchymal stromal cells (MSCs) that were intravitreally transplanted in an experimental ocular hypertension (OHT) model. METHODS: An OHT rat model was generated by means of intracameral injection of hyaluronic acid into the anterior chamber. MSCs labeled with green fluorescence protein were transplanted intravitreally 1 week after OHT induction. At the end of the second and fourth weeks, retinal ganglion cells were visualized with the use of a flat-mount retina method and were evaluated by means of immunofluorescence staining against green fluorescence protein, vimentin, CD105, and cytokines (interleukin [IL]-1Ra, prostaglandin E2 receptor, IL-6, transforming growth factor-ß1, interferon-γ and tumor necrosis factor-α). RESULTS: The retinal ganglion cell numbers per area were significantly improved in stem cell-treated OHT groups compared with that in the non-treated OHT group (P < 0.05). The results of immunohistochemical analyses indicated that a limited number of stem cells had integrated into the ganglion cell layer and the inner nuclear layer. The number of cells expressing proinflammatory cytokines (interferon-γ and tumor necrosis factor-α) decreased in the MSC-transferred group compared with that in the OHT group after 4 weeks (P < 0.01). On the other hand, IL-1Ra and prostaglandin E2 receptor expressions were increased in the rat bone marrow-derived MSC group but were more significant in the rat adipose tissue-derived MSC group (P < 0.01). CONCLUSIONS: After intravitreal transplantation, MSCs showed a neuroprotective effect in the rat OHT model. Therefore, MSCs promise an alternative therapy approach for functional recovery in the treatment of glaucoma.

Quantitative Assessment of Optic Nerve With Diffusion Tensor Imaging in Patients With Thyroid Orbitopathy.

PURPOSE: To detect abnormalities of the optic nerve in patients with thyroid orbitopathy using diffusion tensor MRI. METHODS: Twenty-eight patients with Graves orbitopathy prospectively underwent diffusion tensor imaging scanning. A full ophthalmic examination including visual acuity, intraocular pressure, fundoscopy, and visual field analysis was performed. Clinical activity scores were also calculated. Fractional anisotropy (FA) and mean diffusivity values of the patients were compared with age and sex-matched healthy control subjects. RESULTS: The mean FA values were decreased and mean diffusivity values were increased significantly in patients with Graves orbitopathy compared with the control subjects (p < 0.001). There was a strong reverse correlation between the FA levels and the visual fields in 4 quadrants of the optic nerve. In addition, there was a strong correlation between the degree of proptosis and the FA values in both eyes. The mean diffusivity levels were also correlated with changes in the visual field and the degree of proptosis. CONCLUSION: FA and mean diffusivity levels measured with the diffusion tensor imaging of the thyroid orbitopathy patients were affected. The changes in diffusion tensor imaging were also correlated with the ophthalmologic tests of the patients.

Retinal vessel density and choroidal flow changes in oligoarticular juvenile idiopathic arthritis with and without uveitis.

PURPOSE: This cross-sectional optical coherence tomography angiography (OCTA) study aimed to assess the macular and optic nerve head (ONH) vascular density, foveal avascular zone, and outer retina and choriocapillaris flow in oligoarticular juvenile idiopathic arthritis (oJIA). STUDY DESIGN: Prospective. METHODS: Twenty-two eyes of 22 oJIA patients with uveitis (oJIA-U), 20 eyes of 20 oJIA patients without uveitis (isolated oJIA), and 26 healthy volunteers of similar ages and sexes were investigated. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, foveal avascular zone (FAZ) parameters, the flow area of the outer retina, and choriocapillaris were evaluated. RESULTS: Compared with the control group, both the oJIA-U group and isolated oJIA group showed significantly decreased vessel density of parafovea (p = 0.031 and p = 0.047, respectively) in DCP. Choriocapillaris flow area at 1 mm radius was significantly lower in the oJIA-U group compared to the control group (p = 0.001). Choriocapillaris flow area at 2- and 3-mm radius were significantly lower in the oJIA-U group compared to the control group (p < 0.001, for both) and isolated oJIA-U group compared to the control group (p = 0.008 and p = 0.001, respectively). The VD and thickness parameters of SCP and ONH, FAZ, and outer retina flow area were similar between the groups. CONCLUSIONS: oJIA patients with and without uveitis revealed a decreased vessel density in the deep parafoveal region and choriocapillaris flow. Our findings suggest that retinal choroidal microvascular changes could be evident in oJIA-U patients without posterior segment involvement as well as oJIA patients without uveitis.

Retinal and Choroidal Vascularity Evaluation in Pediatric Radiologically Isolated Syndrome and Multiple Sclerosis.

BACKGROUND: To assess vessel density (VD) and flow of retinal plexuses and peripapillary region related with the pediatric radiologically isolated syndrome (RIS) and multiple sclerosis (MS). METHODS: We analyzed 24 eyes of 12 participants with the diagnosis of RIS, 24 eyes of 12 participants with the diagnosis of MS, and 26 eyes of 13 age- and sex-matched healthy controls in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus, foveal avascular zone, and the flow of choriocapillaris were investigated using optical coherence tomography angiography. RESULTS: Parafoveal VD and all subregion parameters in SCP were significantly decreased in the MS group compared with the controls, whereas only nasal and inferior VD were significantly decreased in the pediatric RIS group compared with the controls. Ganglion cell layer (GCL) thickness of all subregions of the inner ring was significantly decreased in the pediatric MS group compared with the control group. No significant difference was observed between the pediatric RIS group and the control group regarding thickness. CONCLUSIONS: We showed lower parafoveal VD in all subregions of SCP in pediatric MS, whereas only parafoveal nasal and inferior VD were decreased in pediatric RIS. GCL thickness of inner ring was significantly decreased in the pediatric MS, whereas GCL thickness did not change in pediatric RIS. Therefore, a decrease of parafoveal nasal and inferior VD without a decrease in thickness implies an early impairment of microvasculature in the RIS before impairment of thickness and that microvascular alterations begin from highly vascular superficial parafovea.

Pseudoexfoliation Glaucoma: Clinical Presentation and Therapeutic Options.

Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.

Subclinical Retinal Capillary Abnormalities in Juvenile Systemic Lupus Erythematosus without Ocular Involvement.

PURPOSE: This study aimed to evaluate subclinical retinal microvascular changes with OCTA in juvenile systemic lupus erythematosus (JSLE) patients without ocular involvement. METHODS: Ten eyes of 10 JSLE and 13 eyes of 13 age and sex-matched healthy controls (HCs) were enrolled. The superficial (SCP) and deep capillary plexus (DCP), FAZ parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. RESULTS: All vessel density (VD) parameters in DCP were significantly lower in JSLE group compared to HCs. There was no significant difference between the groups in VD parameters of both SCP and ONH, FAZ, outer retina and choriocapillaris flow area. All DCP VD parameters showed a good ability to differentiate JSLE from HCs. CONCLUSION: OCTA could detect retinal vascular impairment in the deep macular region in JSLE patients with normal ocular examination. Furthermore, all DCP VD parameters have a good ability to discriminate JSLE from HCs.