The Relationship between Visual-Evoked Potential and Optic Coherence Tomography and Clinical Findings in Parkinson Patients.

Background: In Parkinson's disease (PD), dopamine deficiency is present not only in the nigrostriatal pathway but also in the retinal and visual pathways. Optic coherence tomography (OCT) can be used as morphological evidence of visual influence from early nonmotor symptoms. The aim of this study was to investigate the relationship of OCT and visual evoked potentials (VEPs) of eyes with the severity of clinical findings and ocular findings in PD. Methods: A group of 42 patients diagnosed with idiopathic PD and a control group of 29 people between the ages of 45-85 were included in our study. VEP was recorded in the patient and control groups. OCT measurement was made with the Optovue spectral-domain device. Foveal thickness and macular volume were measured in the foveal region and in the parafoveal and perifoveal regions in the temporal, superior, nasal, and inferior quadrants. RNFL (retinal nerve fiber layer) was measured in temporal, superior, nasal, and inferior quadrants. Ganglion cell complex (GCC) was evaluated in the superior and inferior quadrants. Using the UPDRS clinical scale, the relationship between measurements and the differences between the control group and the patient group were evaluated. Results: Among the OCT values in our study, foveal, parafoveal, perifoveal thickness, macular volume, RNFL, and GCC measurements were performed for the right and left eyes, and no difference was found between the patient group and the control group. There was no difference in VEP amplitude and latency values between the patient and control groups. The relationships between UPDRS and modified Hoehn Yahr staging and OCT and VEP measurements in the patient revealed no correlation. Conclusions: Studies on whether OCT measurements can functionally be a marker or which segments are more valuable for disease progression in patients with PD are needed. Visual dysfunction in PD cannot be attributed only to retinal pathology; however, the retina may provide monitoring of the status of dopaminergic neurodegeneration and axonal loss in PD.

Evaluation of the cytotoxic and genotoxic/antigenotoxic effects of resveratrol in human limbal explant cultures.

PURPOSE: Resveratrol (RSV) is a natural polyphenol phytoalexin compound and has long been considered to possess antioxidant and anti-inflammatory effects. In order to exploit the protective potential of RSV in anterior segment diseases, we investigated the possible cytotoxic, genotoxic/antigenotoxic effects of human limbal explant cultures to RSV and MMC or H2O2 alone and in combination. METHODS: A total of 18 limbal explant tissues obtained from three corneal donors were placed on the 12 well tissue culture polystyrene plates and cultured for 14 days. Cell growth from limbal explants was observed by inverted phase contrast microscopy. The cytotoxic effects of RSV was studied by neutral red uptake assay. For the assessment of the genotoxic and antigenotoxic effects, basic alkaline technique of comet assay was performed. RESULTS: It was found that the concentrations of RSV up to 100 µM did not significantly affect the viability of outgrowth cells of limbal explant during 24 h exposure. When compared to negative control, all concentrations of RSV alone caused an increase in DNA strand breakage. Interestingly, 10 µg/mL MMC alone caused similar tail intensity and tail moment values with RSV alone. On the other hand, RSV treatment in all doses seemed to decrease the DNA damage induced by either H2O2 or MMC. CONCLUSION: RSV is an attractive natural compound for the purpose of oxidative stress reduction in ocular surface and can be utilized as a supplement to promote ocular surface regeneration in vivo.

High body weight-related retinal vasculopathy in children with obesity.

PURPOSE: To investigate the foveal avascular zone (FAZ) and the microvascular alterations in both macula and peripapillary region in obese children. METHODS: We included a total of 222 eyes of 111 children (54 obese children and 57 healthy subjects). Capillary vessel density (VD) of superficial (SCP) and deep (DCP) retinal capillary plexuses were measured in macular slabs. Peripapillary region was also evaluated. The FAZ parameters were measured based on the whole retinal slab. A commercial optical coherence tomography-angiography system was used. RESULTS: The mean ages were 13.33 ± 2.55 years (range, 8-17) and 13.41 ± 2.90 years (range, 7-18) in patients with obesity and healthy controls, respectively (p = 0.84). The mean area of the FAZ were 0.278 ± 0.10 mm2 and 0.272 ± 0.11 mm2 in children with obesity and in control participants, respectively (p = 0.68). There were significant increases in the superior region of the parafoveal VD of SCP (p = 0.008 for superior hemisphere and p = 0.003 for superior quadrant). There was no significant difference in any measure of the macular DCP and peripapillary region (p > 0.05, for all). CONCLUSION: Increased vascular density measurements were found in the superior part of the parafoveal region of SCP in children with obesity. The results of the study should be taken into consideration during the course of the disease to define whole systemic response to obesity in childhood and will be of interest for pediatrician's clinical practice.

Topographic and specular microscopic evaluation of cornea and meibomian gland morphology in children with isolated growth hormone deficiency.

PURPOSE: To evaluate whether the anterior segment topographic measurements, meibomian gland (MG), and non-invasive tear film break-up time (NITFBUT) differ between healthy children and children with isolated growth hormone deficiency (GHD). METHODS: A total of 74 eyes of 37 children with GHD and 84 eyes of 42 age- and sex-matched healthy children were included in the study. The spherical equivalence (SE), mean keratometry (Km), corneal thickness, corneal volume (CV), anterior chamber depth (ACD), topographic NITFBUT, qualitative and quantitative MG measurements, corneal endothelial cell density (CD), and proportion of hexagonal cells (HG) were analysed. RESULTS: The mean SE level of GHD group was similar between groups (p = 0.017). Back Km values were insignificantly steep in children with GHD (p = 0.004, with Bonferroni correction). Specular microscopy analysis was not different between groups. MG loss of GHD group were higher than control group (p < 0.001). The MG morphology analysis and distortion grade were not different between groups (p > 0.05). CONCLUSIONS: Our results showed that the growth hormone (GH) may have an important role on the anterior segment parameters; however, it is not clear that this misregulation leads to a clinical scenario in childhood. Future studies investigating GHD and/or GH therapy on the ocular surface system are required to clearly demonstrate basic mechanism of GH action.

Evaluation of retinal microvasculature and foveal avascular zone by the optical coherence tomography angiography in pediatric migraine patients.

To compare the foveal avascular zone (FAZ), macular and peripapillary vessel density and retinal nerve fiber layer (RNFL) thickness between pediatric migraine patients and healthy subjects. A total of 108 eyes of 54 children with migraine without aura and 94 eyes of 47 age- and gender-matched healthy subjects were included. Capillary vessel density (CVD) in superficial (SCP) and deep (DCP) retinal capillary plexus, peripapillary region, FAZ, and RNFL thickness were analyzed by optical coherence tomography-angiography. The mean ages were 12.4 ± 3.3 years (range 6-18) in patients with migraine and 12.6 ± 2.9 years (range 5-18) in healthy controls (p = 0.742). The mean FAZ area measured 0.27 ± 0.09 mm2 in the pediatric migraineurs and 0.26 ± 0.09 mm2 in healthy controls (p = 0.53). There was no significant difference in any measurement of SCP, DCP, peripapillary CVD, and RNFL thickness between study groups (p > 0.05 for all). The pediatric migraine disability assessment test (PedMIDAS) negatively correlated with some of the CVD and RNFL measurements in pediatric migraine patients (p < 0.05). The macular and peripapillary microvasculature were not significantly different during an attack-free period in pediatric migraine patients than in healthy subjects.

Subclinical retinal microvascular alterations assessed by optical coherence tomography angiography in children with systemic hypertension.

PURPOSE: To compare the foveal avascular zone (FAZ) macular and peripapillary vessel density between children with high blood pressure and healthy subjects. METHODS: A total of 40 eyes of 20 children with hypertension and 40 eyes of 20 age- and sex-matched healthy controls were included. Capillary vessel density (CVD) in superficial (SCP) and deep (DCP) retinal capillary plexus, peripapillary region, and FAZ were analyzed by optical coherence tomography angiography. RESULTS: The mean ages were 15.2 ± 1.5 years (range, 10-18) in patients with hypertension and 14.4 ± 2.8 years (range, 10-18) in healthy controls (P = 0.742). The mean FAZ area measured 0.25 ± 0.10 mm2 in children with hypertension and 0.25 ± 0.09 mm2 in healthy controls (P = 0.765). There was no significant difference between study groups in any measure of the macular SCP (P > 0.05 for all); however, the mean whole image, inferior hemisphere, and para- and perifoveal measurements of the macular DCP were significantly lower in children with hypertension than in controls (P < 0.05 for all). CONCLUSIONS: Although there was no evidence of hypertensive retinopathy, subthreshold microvascular alterations were found in the DCP of the retinal circulation in pediatric hypertensives. These alterations should be considered as prognostic cues when defining whole systemic response to high blood pressure in childhood.

Surgical and Immunohistochemical Outcomes of Scleral Reconstruction with Autogenic, Allogenic and Xenogenic Grafts: An Experimental Rabbit Model.

Purpose: Choukroun's platelet-rich fibrin (PRF), a second-generation platelet concentrate, has unique morphological and chemical features and may be considered as a scaffold for scleral reinforcement and regeneration. The purpose of this study was to compare the use of xenogenic human-derived amniotic membrane (HAM), allogenic sclera, and autogenic PRF in rabbit lamellar scleral defect model with respect to both anatomical and immunohistochemical improvement. Methods: A total of 45 adult New Zealand rabbits were randomized into five groups: normal control; without surgical procedure, negative control; scleral defect model (SDM), xenogenic HAM; SDM+HAM graft, allogenic sclera; SDM+allogenic sclera graft, autogenic PRF; SDM+autogenic PRF graft. Clinical findings, Hematoxylin&Eozin (HE), Masson Trichrome, Verhoeff Acid Fuchsin, Transforming Growth Factor ß Receptor 1, Fibroblast Growth Factor, Bone Morphogenetic Protein 2, collagen type 1, aggrecan, and Matrix Metalloproteinase 2 were evaluated. Results: Ocular surface inflammation was significantly lower in normal control and autogenic PRF groups (p < .001). Graft was avascular and not integrated to scleral wound area in 25% rabbits of allogenic sclera group (p = .02), was out of the scleral wound in 33.3% rabbits of xenogenic HAM group (p > .05), all the grafts were at the normal location and viable in autogenic PRF group. The inflammation and vascularization in autogenic PRF group was significantly lower than negative control and xenogenic HAM groups in HE (p < .001). The collagen score of negative control and xenogenic HAM groups were significantly lower than normal control (p < .001) and autogenic PRF (p < .001) groups. There were insignificant differences between allogenic sclera and autogenic PRF groups (p > .05). For immunohistochemistry, the closest values to normal control group were detected in autogenic PRF group for all immunomarkers. Conclusion: Autogenic PRF showed superior features via its excellent anatomical and chemical composition for scleral regeneration when compared to single-layered xenogenic HAM and allogenic sclera grafts.

Quantitative analysis of macular and peripapillary microvasculature in adults with anisometropic amblyopia.

INTRODUCTION: The aim of this study was to compare the macular and peripapillary capillary vessel density (CVD) and foveal avascular zone (FAZ) in amblyopic eyes of adults with their fellow eyes and with eyes of healthy controls using optical coherence tomography-angiography (OCT-A). METHODS: A total of 34 eyes of 17 patients with anisometropic amblyopia and 80 eyes of 40 age- and gender-matched healthy controls were included. CVD in superficial (SCP) and deep retinal capillary plexuses (DCP), peripapillary region, and FAZ were analyzed by OCT-A. RESULTS: The median ages were 31 years (range 20-64) in patients with amblyopia and 34.5 years (range 24-65) in healthy controls (p = 0.242). The mean FAZ area measured was 0.329 ± 0.024 mm2 in amblyopic eyes, 0.332 ± 0.025 mm2 in fellow eyes, and 0.269 ± 0.015 mm2 in control eyes (p < 0.05). The amblyopic eye of participants showed a decrease in CVD of SCP and DCP (p < 0.001, for all). The inside optic disk CVD measurements were lower in the amblyopic eyes than in the fellow eyes (p = 0.001) and healthy subjects (p = 0.015). CONCLUSION: Significant differences in macular and peripapillary microvasculature were found in anisometropic amblyopic patients. The clinical significance of the results requires further investigation.

Noninvasive evaluation of anterior segment and tear film parameters and morphology of meibomian glands in a pediatric population with hypogonadism.

PURPOSE: To compare the meibomian gland (MG), non-invasive tear film break-up time (NITFBUT), anterior segment measurements between healthy children and children with hypogonadism. METHODS: A total of 80 eyes of 40 children with hypogonadism and 86 eyes of 43 age- and sex-matched healthy subjects were included in the study. The mean keratometry (Km), maximum keratometry (Kmax), central (CCT), thinnest (TCT) and apical (ACT) corneal thicknesses, corneal volume (CV), anterior chamber depth (ACD), irido-corneal angle (ICA), first and average non-invasive NITFBUT, MG loss, morphology of MGs, and MG distortion grade, specular endothelial cell density (CD), coefficient of variation (CoV), and percentage of hexagonal cells (HG) were analysed. RESULTS: The mean CCT and TCT values were approximately 20 µm lower on average in patients with hypogonadism (p < 0.05). MG loss was present 56.1% of the healthy children, the ratio increased to 81.3% in children with hypogonadism (p < 0.001). The morphology and distortion grade did not show any significant differences between groups (p > 0.05). The mean NITFBUT value were similar between groups (p > 0.05). The mean CD value did not show any significant difference between groups, however it decreased in the hormone replacement therapy (HRT) group (p = 0.005). CONCLUSIONS: MG loss is a physiological process that is prominent in the condition of sex steroid deficiency, but does not cause tear film alterations in children. Future studies investigating sex and gender effect on the ocular surface system in an age-based fashion are required to clearly communicate influences in the arenas of ocular surface research.

A simple and efficient method for cultivation of limbal explant stem cells with clinically safe potential.

BACKGROUND: Several methods to cultivate limbal epithelial stem cells (LESCs) in vitro with the support of feeder layers and different growth medium formulations have been established for several years. The initial green medium consists of various ingredients that exhibit a non-optimal level of biosafety, therefore, different modifications have been made to suit it to safe clinical applications. However, the question of which formulation is the most appropriate remains to be answered. AIMS: This study evaluated the outgrowth kinetics and stemness of cells cultured from human limbal explants with the aim of preserving LESC characteristics in the human-derived platelet-rich fibrin (HPRF)-conditioned medium with no feeder cell layer or carrier for the first time. The final composition of the cell culture system included only human-derived products without any xenobiotic or chemical substances to minimize the potential risk for human health, which will be useful for clinical purposes. METHODS: To test our hypothesis, limbal explants were incubated with either Dulbecco's Modified Eagle's Medium (DMEM)/F12-10% human serum (HS), human-derived amniotic membrane (HAM)-conditioned DMEM/F12-10% HS or HPRF-conditioned DMEM/F12-10% HS to determine whether outgrowth kinetics and stemness of cells show any differences among groups. RESULTS: The results showed that the HPRF-conditioned medium showed higher concentration levels of growth factors, which may be involved in the promotion of LESC expansion while preserving the stem cell characteristics. HPRF-conditioned medium had significantly superior capacity to enhance the cell growth rate, the stem/progenitor cell phenotype and the expressions of putative stem cell markers. CONCLUSION: This novel xeno-feeder-chemical-free, completely human-derived and biologically safe culture system including HPRF and HS would be of interest to replace conventional cell culture strategies to meet safety requirements mandatory for clinical use in humans.

An assessment of ocular elasticity using real time ultrasound and ocular response analyzer in active or remission rheumatoid arthritis.

PURPOSE: To investigate the elasticity of ocular structures in patients with rheumatoid arthritis (RA) without ocular involvement. METHODS: The study included 56 RA patients (study group) and 24 healthy volunteers as the control group. The rheumatoid arthritis patients were divided into two subgroups as those in active phase (Group 1, n = 25) or in remission phase (Group 2, n = 31) according to the disease activity index (DAS 28) score. The elastography values of the ratio of orbital fat-sclera (ROF/S) were measured with real-time US elastography, and corneal mechanical values were measured with the Reichert Ocular Response Analyzer in each eye. RESULTS: The mean ROF/S value was 5.2 ± 1.8 in Group 1, 0.7 ± 0.4 Group 2, and 0.6 ± 0.1 in the control group. There was a significant difference between the Group 1 and control group with regard to ROF/S (p < 0.001), but no significant difference was determined between Group 2 and control group (p > 0.05). The mean ROF/S value was a significant difference between the Group 1 and 2 (p < 0.001). ROF/S was significantly correlated with DAS-28 and C-reactive protein (CRP) (r = 0.816, p < 0.001 and r = 0.259, p = 0.006). CONCLUSIONS: ROF/S was significantly increased in patients in the active phase of RA. Findings revealed that ocular tissue structural changes may occur in the active phase and these could be related to ocular complications as a prognostic factor.

A completely human-derived biomaterial mimicking limbal niche: Platelet-rich fibrin gel.

Platelet-rich fibrin (PRF) is a natural biomaterial and has excellent biochemical and physical properties with a history of proven biocompatibility in the field of tissue engineering and regenerative medicine. Recent reports of fibrin-based matrices have offered new opportunities to apply PRF as a supplement for in vitro cell culture. Here, custom-modified human-derived PRF (HPRF) was produced via different centrifugation protocols, then, characterized by morphologically and chemically and utilized as a substrate and as a conditioned medium for limbal explant culture for the first time. It was found that the HPRF released significantly higher levels of growth factors which are essential for epithelial cell growth. The enhanced physicochemical properties of the HPRF were also proven in the limbal explant cultures in terms of cell growth, migration, viability, and stemness in comparison with the conventional limbal explant culture on human-derived amniotic membrane. Consequently, HPRF hydrogels are appealing natural biomaterials for the purpose of mimicking limbal niche and the discovery elucidates this new, xeno-chemical-free, completely human-derived biomaterial can be utilized as a supplement to promote epithelial cell behaviour in vitro.

A Novel Technique for Conjunctivoplasty in a Rabbit Model: Platelet-Rich Fibrin Membrane Grafting.

Purpose. To investigate the effect of platelet-rich fibrin (PRF) membrane on wound healing. Methods. Twenty-four right eyes of 24 New Zealand rabbits equally divided into 2 groups for the study design. After the creation of 5 × 5 mm conjunctival damage, it was secured with PRF membrane, which was generated from the rabbit's whole blood samples in PRF membrane group, whereas damage was left unsutured in the control group. Three animals were sacrificed in each group on the 1st, 3rd, 7th, and 28th postoperative days. Immunohistochemical (IHC) stainings and biomicroscopic evaluation were performed and compared between groups. Results. PRF membrane generated significant expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-ß), and platelet-derived growth factor (PDGF) in the early postoperative period. However, the IHC evaluation allowed showing the excessive staining at day 28, in control group. Biomicroscopic evaluation revealed complete epithelialization in PRF membrane group, but none of the cases showed complete healing in the control group. Conclusions. This experimental study showed us the beneficial effects of the PRF membrane on conjunctival healing. Besides its chemical effects, it provides mechanical support as a scaffold for the migrating cells that are important for ocular surface regeneration. These overall results encourage us to apply autologous PRF membrane as a growth factor-enriched endogenous scaffold for ocular surface reconstruction.

Urgent Therapeutic Grafting of Platelet-Rich Fibrin Membrane in Descemetocele.

PURPOSE: To report the clinical and histopathological results of a novel autologous scaffold grafting, platelet-rich fibrin (PRF) membrane, in cases with descemetocele. METHODS: Three patients with severe corneal stromal melting and central descemetocele caused by neurotrophic keratopathy and infective keratitis underwent PRF membrane grafting on the central cornea for the prevention of imminent corneal perforation. After a quiescent 3-month period, penetrating keratoplasty and cataract extraction were performed for visual rehabilitation in 1 patient and host corneal tissue was examined histopathologically. RESULTS: Pain was significantly relieved, conjunctival inflammation was markedly resolved, and the central descemetocele area became thicker with scar formation in all patients. Histopathological examination revealed fibrosis formation over the descemetocele area without any tissue gap. Newly formed tissue containing irregular corneal lamellae covered the fibrosis formation and accounted for the prevention of perforation. CONCLUSIONS: Temporary PRF membrane grafting may be an alternative intervention to avoid impending corneal perforation in cases with severe descemetocele.

[Fungal keratitis caused by Scedosporium apiospermum: first report from Turkey]. / Scedosporium apiospermum'a Bagli Fungal Keratit: Ülkemizden Ilk Olgu.

Fungal keratitis, an eye infection with poor prognosis, is difficult to treat and can lead to loss of vision. Among filamentous fungi Scedosporium spp. rarely lead to fungal keratitis. Here we present a case of keratitis caused by Scedosporium apiospermum. A 61-year-old female patient was admitted to our hospital with the complaints of right eye pain and decreased vision after a foreign body trauma to the right eye. The patient was diagnosed as keratitis by biomicroscopic examination. Conjunctival swabs collected from both eyes were inoculated onto sheep blood agar, chocolate agar, eosin methylene blue agar and Sabouraud dextrose agar. Corneal scrapings from the right eye were inoculated onto the same solid media by "C-streak" method, and in brain-heart-infusion broth by immersion. While gram-stained smears of conjunctival swabs showed no significant finding, smears of corneal scrapings revealed abundant neutrophils and profuse septate hyphae. Fungal keratitis was diagnosed and topical enhanced amphotericin B (0.5 mg/ml) therapy was initiated with netilmicin sulfate and oxytetracycline HCl plus polymyxin B sulfate. At the 10th day of therapy a mold growth was detected in corneal scraping cultures and was identified microscopically as S.apiospermum. Based on the relevant literature, therapy was changed to enhanced topical voriconazole (2 mg/ml) applied hourly, plus systemic voriconazole administration. At the third day of treatment, reduction of epithelial defect and decline in the focus of keratitis were observed. In the following days, however, a progression occurred in the focus of keratitis and 5% natamycin ophthalmic suspension was added to the therapy. Since the patient did not respond to any of the medical treatments, therapeutic penetrating keratoplasty was planned; yet, the patient refused the operation and was discharged with her own request. As far as the local literature was concerned, this is the first report of keratitis caused by S.apiospermum in Turkey. Though a very rare causative agent of keratitis, S.apiospermum is generally resistant to antifungal therapy and often require surgical treatment. Especially in patients with predisposing factors, this organism should be kept in mind as a potential causative agent and relevant microbiological examinations should be performed.