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Background: Phase I/II clinical trials using fetal retinal pigment epithelium (fRPE), human embryonic stem cell (hESC)-derived RPE, or human induced pluripotent stem cell (hiPSC)-derived RPE as potential sources of materials for cell-based therapy to treat degenerative retinal diseases have been carried out during the past decade. Challenges for successful translational cell-based therapy include cell manufacture, cell quality, cell storage, and cell behavior in vivo. In this study, we investigated the culture-induced changes in passaged fetal RPE, hESC-RPE and hiPSC-RPE cells in vitro and explored the differentiation and maturation effect of all-trans retinoic acid (ATRA) on those RPE cells. Methods: A total of 9 fetal RPE cell lines, hESC-RPE and hiPSC-RPE cell lines were set up using previously described methods. The culture-induced changes in subsequent passages caused by manipulating plating density, dissociation method and repeated passaging were studied by microscope, real-time quantitative PCR, western blot and immunofluorescent assays. Gene and protein expression and functional characteristics of fRPE, hESC-RPE and hiPSC-RPE incubated with ATRA at different concentration were also evaluated.Results: Compared with fRPE, hESC-RPE and hiPSC-RPE showed decreased gene and protein expression of RPE markers. Passage 3 RPE of all three types seeded at a density of 6×105 and 9x105 cells/mL in basal medium maintained pigmented polygonal, cobblestone-like morphology. RPE cells underwent mesenchymal changes showing increased expression of mesenchymal markers including a-SMA, N-cadherin, fibronectin and decreased expression of RPE markers including RPE65, E-cadherin and ZO-1, as a subsequence of low plating density, inappropriate dissociated method, and repeated passaging. fRPE, hESC-RPE and iPSC-RPE treated by ATRA at different concentrations showed increased expression of RPE markers such as RPE65, bestrophin (BEST) and CRALBP, and increased expression of negative complement regulatory proteins (CRP) including complement factor H (CFH), CD46, CD55 and CD59, and increased transepithelial resistance (TER) as well.Conclusion: Although hESC and hiPSC-derived RPE are morphologically similar to fRPE, and also have the tendency to undergo epithelial-to-mesenchymal transition (EMT) changes during the culturing and passaging process in vitro, differences in protein and gene expression among three RPE types exist. Moreover, ATRA can increase RPE markers expression, as well as to increase the expression levels of CRPs gene and protein in fRPE and stem cell-derived RPE.

Purpose: To explore the relationship between single-nucleotide polymorphisms (SNPs) in complement factor I (CFI), interleukin-8 (IL-8), transferrin (TF), and transferrin receptor 2 (TFR2) and age-related macular degeneration (AMD) in a northeastern Chinese population. Methods: A total of 400 AMD patients (200 wet AMD and 200 dry AMD) and 200 controls were enrolled in this study, and genetic polymorphisms in the above genes were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The χ2 test was used to compare differences in allele frequencies in each group, and the associations of genotype frequencies with AMD were determined by multivariate logistic regression analysis. Results: Our research shows that CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 are associated with the incidence of AMD. In wet AMD, allele T of CFI rs141853578, IL-8 rs2227543 and TFR2 rs2075674 may be a risk factor. Allele A of TF rs8177178 may increase the risk of dry AMD. Conclusions: CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 genetic polymorphisms are associated with the occurrence of AMD in a northeastern Chinese population, especially wet AMD.

Purpose The purpose of this study was to examine the expression of glial derived neurotrophic factor (GDNF), the GDNF receptors GFRα1 and GFRα2, ciliary neurotrophic factor (CNTF), and the CNTF receptor CNTFRα in normal and glaucomatous human tissue. Methods Human retinas were collected from 8 donors that had been clinically diagnosed and treated for glaucoma, and also from 9 healthy control donors. Immunohistochemical analysis for each trophic factor and receptor was performed. The percent of each retinal section labeled with each antibody was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with measures of the subject's ocular histories. Results The percentage area immunopositive for GFRα2 was significantly decreased in the total retinal thickness containing all retinal layers and in the combined RGC complex + RNFL in glaucomatous eyes in both the peripapillary region and more peripheral retinal locations. We also observed a decrease in GFRα1 expression in the peripapillary RGC Complex + RNFL in glaucoma patients compared to healthy control patients. We also observed a relationship between GDNF and its receptors with several outcomes obtained from the medical record. No differences in CNTF or CNTFR labeling were observed. Conclusion Decreases in GDNF receptor expression in glaucomatous tissue may limit the potential for neuroprotective therapy by supplementation with GDNF.

In ophthalmology, data from both eyes of a person are frequently included in the statistical evaluation. This violates the requirement of data independence for classical statistical tests (e.g. t-Test or analysis of variance (ANOVA)) because it is correlated data. Linear mixed models (LMM) were used as a possibility to include the data of both eyes in the statistical evaluation. The LMM is available for a variety of statistical software such as SPSS or R. The application was applied to a retrospective longitudinal analysis of an accelerated corneal cross-linking (ACXL (9*10)) treatment in progressive keratoconus (KC) with a follow-up period of 36 months. Forty eyes of 20 patients were included, whereas sequential bilateral CXL treatment was performed within 12 months. LMM and ANOVA for repeated measurements were used for statistical evaluation of topographical and tomographical data measured by Pentacam (Oculus, Wetzlar, Germany). Both eyes were classified into a worse and better eye concerning corneal topography. Visual acuity, keratometric values and minimal corneal thickness were statistically significant between them at baseline (p < 0.05). A significant correlation between worse and better eye was shown (p < 0.05). Therefore, analyzing the data at each follow-up visit using ANOVA partially led to an overestimation of the statistical effect that could be avoided by using LMM. After 36 months, ACXL has significantly improved BCVA and flattened the cornea. The evaluation of data of both eyes without considering their correlation using classical statistical tests leads to an overestimation of the statistical effect, which can be avoided by using the LMM.

PURPOSE: The DBA/2J (D2) mouse is an established model of pigmentary glaucoma, a type of primary open angle glaucoma. Prior studies have documented defects in flash electroretinogram (ERG) responses in D2 mice, but the origin of those defects is not clear. The purpose of this study was to understand the origin of these A-wave and B-wave changes in D2 ERGs. MATERIALS & METHODS: To accomplish this, we analyzed the differences between 9-month-old DBA/2J-Gpnmb+ (D2-control) and D2 mouse eyes in relation to ERG responses, intraocular pressure (IOP), outer nuclear layer thickness, and pupil area. RESULTS: D2 scotopic ERGs showed lower A-wave amplitude and longer implicit time as well as a significant rightward shift in the intensity-response curve. D2 IOP increased at approximately seven months of age and had a weak correlation with the ERG A-wave sensitivity. Outer nuclear layer thickness was not significantly different in D2s compared to D2-control retinas. D2 mouse pupils also showed abnormal pupillary shape and no dilation following treatment with tropicamide eye drops. The pupil size moderately correlated with the A-wave sensitivity and this was pharmacologically replicated in C57Bl/6J mice following administration of pilocarpine to constrict the pupils. However, pilocarpine treatment did not affect ERG amplitudes. CONCLUSIONS: These data suggest that the smaller pupil sizes prevented light from reaching the photoreceptors and thus contributed to reduced ERG sensitivity in D2 mice. The reduced ERG A-wave amplitude in D2 mice likely results from dysfunctional photoreceptor responses.

Atropine has been proven to be effective in retarding myopia progression. However, the underlying mechanism remains unknown. Our purpose was to detect morphological and functional changes caused by atropine during myopic inhibition. Twenty 2-week-old guinea pigs were randomly assigned to either the saline group (n = 10) or the atropine group (n = 10). Form-deprived myopia (FDM) and intravitreal injections were applied on the right eyes. The injections were given every 3 days, lasting for 2 weeks. The left eyes served as control. Ocular refraction, axial length, retinal, and choroidal thickness were collected at the start and the end of the experiment. Retinal function was evaluated via full-field electroretinogram (ERG) at the end of treatment. The interocular differences (experimental eye minus control eye) of refraction error (RE), vitreous chamber depth (VCD), and axial length (AL) in the saline group were significantly greater than those in the atropine group (RE, VCD: P < .001, AL: P < .0001). The differences in choroidal thickness between the two groups did not reach statistical significance. However, a decreasing trend of choroidal thickness was observed in the saline group but not in the atropine group. Furthermore, the interocular differences of total retinal and outer retinal thickness in the atropine group were much thicker than in the saline group (P < .001 and P < .01, respectively). The treatment did not affect inner retinal thickness. In photopic ERG, the atropine-treated FDM eyes showed significantly greater a-wave amplitudes compared to the saline group. During the process of inhibiting FDM, atropine showed an effect on the outer retina, most likely on the cones, in guinea pigs.

Purpose: The purpose of this in vitro prospective nonrandomized study is to compare the toxicity and strength of cyanoacrylate and hydrogel adhesives on human retinal pigment epithelium (RPE) cells and porcine retina, respectively. Methods: The toxicity of cyanoacrylate (histoacryl, dermabond, superglue), ReSure PEG, and Tisseel fibrin glue on human RPE cells was determined by growing RPE cells in vitro, applying the different adhesives to the cells, and monitoring for disruption of growth over 3 days. The relative strength of these adhesives was tested by gluing a 3 mm piece of foam to a porcine retina and determining the amount of force needed to break the attachment. Results: 0.085 N of force was required to break the porcine retinal tissue (p=0.913). Histoacryl adhesive exhibited high strength (0.247 N) and high RPE toxicity (0.55 mm inhibition zone after 24 hrs). The strength of Tisseel fibrin glue was 0.078 N while that of ReSure was only 0.053 N. Both Tisseel and ReSure were nontoxic to the RPE cells. Conclusions: Tisseel VH fibrin sealant may provide the best option for sealing retinal breaks because of its high strength and low retinal toxicity.

Purpose To investigate amphiregulin (AREG) expression in the sclera during the development of form-deprivation myopia (FDM) and after the recovery of FDM in guinea pigs. Methods Sixty-four 2-week-old guinea pigs were randomly divided into the control and FDM groups. The right eyes of animals in FDM group were covered for 2 weeks (2 W) and 4 weeks (4 W), or were covered for 4 weeks and then uncovered for the subsequent 2 weeks (6 W). The diopters and axial lengths (AL) in the right eyes of guinea pigs were measured. Reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence, and western blotting assays were used to detect the relative mRNA and protein expressions of AREG in the sclera of guinea pigs. Results Before masking (0 W), the refraction and AL in the right eyes of guinea pigs in the control and FDM groups did not differ significantly (both p > .05). Myopic shift was induced in guinea pigs with the diopters gradually decreased and AL increased in the FDM group. While no significant difference was found in control group at different time points, the relative AREG mRNA and protein expression levels in the FDM group were significantly increased in 2 W and 4 W and then decreased after 4 weeks of covering followed by uncovering for 2 weeks (all p Conclusions AREG was expressed in the sclera of guinea pigs. Moreover, the expression levels of AREG increased during the development of FDM and downregulated after recovery of FDM. Therefore, AREG may be involved in the regulation of scleral remodeling in myopia.

OBJECTIVE To investigate CYP4V2 gene variants and ocular clinical characteristics of Bietti corneoretinal crystalline dystrophy in China so as to provide more references for genotype and phenotype of BCD. METHODS Sixteen Chinese probands were recruited in Beijing Tongren Hospital in a retrospective study. All patients underwent CYP4V2 gene detection and ophthalmic clinical examinations. RESULTS CYP4V2 gene variants were detected in all patients. Eight variants were identified, and the most common one was c.802-8_810del17bpinsGC. Onset age of BCD was from 12 to 44 years, and the first symptoms mostly were decreased visual acuity or night blindness. Corneal crystalline depositions were observed in all patients and were found not only in epithelium and superficial stroma near the limbus but also in corneal endothelium. OCT showed atrophy of RPE in all patients, outer retinal tubulation in ten patients, macular edema in four patients, macular hole in three patients with one accompanied with retinal detachment, and choroidal neovascularization in one patient. CONCLUSION CYP4V2 gene variants were detected in all patients consistent with the genetic locus homogeneity of BCD, and c.802-8_810del17bpinsGC was the most common mutation. Corneal crystalline depositions were observed in all patients, which may be features of BCD and helpful for the diagnosis of BCD patients, especially those in the advanced stage without typical fundus crystalline depositions or without gene detection. However, considerable phenotypic variability was detected. Corneal crystalline deposits were observed not only in epithelium and superficial stroma but also in endothelium, which has not been reported before. This may provide further evidence for the variable phenotypic expression between affected individuals.

PURPOSE This study aimed to investigate the clinical and histopathological effects of corneal cross-linking (CXL) and matrix-regenerating agent (RGTA) treatments after corneal alkali burn. MATERIALS AND METHODS Twenty-four alkali-burned corneas from 24 rabbits were divided into three groups: control, CXL, and RGTA. All animals were investigated for epithelial healing, opacification, ulceration, and neovascularization at days 1, 7, 14, and 21 after the alkali burn. Corneas were excised and sent for histological examination on day 21. RESULTS One animal each from the CXL and control groups exhibited moderate ulceration, while no ulceration was observed in the RGTA group. No significant difference was observed among the groups in corneal thickness or corneal opacity measurements at the final visit (p = .058 and p = .544, respectively). Both RGTA and CXL treatments were effective in terms of epithelial healing and neovascularization (p = .023 and p = .03, respectively). On histological examination, the CXL and RGTA groups were more effective in treating epithelial loss, stromal edema, corneal vascularization, and leukocytic infiltration than the control group (p .05). In contrast, the stromal staining scores of the CXL and RGTA groups were lower than those of the control group (p

To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation.One hundred and thirty-one eyes from 66 patients enrolled this cross-sectional study. An extensive ocular examination was carried out prior to tropicamide and phenylephrine instillation. Power and axis value from flat, steep, and mean keratometry were calculated using an Auto Kerato-Refractometer (AKR). Later, topography and tomography maps were evaluated with Pentacam HR® (Oculus, Wetzlar, Germany). Subsequently, a single drop of tropicamide 1% and phenylephrine hydrochloride 10% were instilled twice, with a five-minute gap between each instillation. After 30 minutes, the AKR and Pentacam HR® tests were repeated.Incyclotorsion was found in 59 eyes (45.1%) and mean absolute incyclotorsion change was 3.91 ± 3.62 degrees (0.10 to 14.20). Excyclotorsion was found in 72 eyes (54.9%) and mean excyclotorsion change was 4.99 ± 5.94 degrees (0.20 to 36.20). We observed that 74.6% and 68.1% of eyes experienced incyclotorsion and excyclotorsion within 0 to 5 degrees, respectively. Fewer patients experienced incyclotorsion and excyclotorsion changes within 5 to 10 degrees, precisely 11.8% and 19.4%, respectively. Eyes that experienced over 10 degrees of incyclotorsion and excyclotorsion were 13.6% and 12.5%, respectively.Astigmatism axis could change after combined tropicamide and phenylephrine instillation. Reference axis marking in astigmatism correction surgery should be performed under the same circumstances as the astigmatism axis has been measured.

Impaired tear production - a common sign of keratoconjunctivitis sicca (KCS) - is associated with qualitative or quantitative tear deficiency. OTX-101 0.09% is a novel, nanomicellar formulation of cyclosporine A approved in the US for increasing tear production in patients with KCS. We present a pooled analysis of the phase 2b/3 and phase 3 studies evaluating the effect of OTX-101 on tear production in a subgroup of patients with keratoconjunctivitis sicca with severely impaired tear production (Schirmer's score5 mm in either eye at baseline).In these randomized, double-masked studies, patients instilled 1 drop OTX-101 or vehicle per eye twice daily for 84 days. Pooled efficacy endpoints included percent (%) of patients with ≥10 mm change from baseline and mean change from baseline in Schirmer's score at day 84. Pooled safety endpoints included adverse event monitoring.Subgroup analyses included 133 and 113 patients receiving OTX-101 and vehicle, respectively. Mean baseline (BL) Schirmer's score ± standard deviation was 2.7 ± 1.2 for OTX-101 and 2.5 ± 1.1 mm for vehicle (OTX-101 administered twice daily for 84 days significantly improved tear production vs vehicle in patients with severely impaired tear production, as evidenced by significantly larger proportion of patients with ≥10 mm increases from baseline and higher mean change from baseline in Schirmer's scores.

Background: Parkinson's Disease (PD) is the second-most common neurodegenerative disease affecting the elderly population. The eye has been referred to as a window to the brain due to its inseparable relationship with the central nervous system. The development of Swept-Source Optical Coherence Tomography (SS-OCT) and Optical Coherence Tomography Angiography (OCTA) technologies has offered us a better imaging modality to study the impact of PD on the retina.Method: Seventy-five eyes of 42 early-stage PD patients and 150 eyes of 75 matched healthy controls were enrolled in the current study. We performed SS-OCT and SS-OCTA to assess retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) + inner plexiform layer (IPL), internal nuclear layer (INL) thickness, and retinal flow density and flow ratio.Results: Our study indicates decreasing superficial and deep flow density in most regions of the retina. Superficial and deep flow parameters were also associated with RNFL, GCL+IPL, and INL thickness. ROC analysis reveals superficial flow density demonstrated an Area Under Curve (AUC) of 0.688, which is greater than deep flow density and retinal thickness measurements.Conclusion: To the best of our knowledge, we are the first study using SS-OCT and SS-OCTA to study superficial and deep retinal flow changes in early-stage PD patients. Our study suggests decreasing retinal flow density provides greater diagnostic power than retinal thickness measurements in the early stage of PD. SS-OCTA parameters could potentially serve as imaging biomarkers in PD diagnosis and staging.

Purpose Pachychoroid spectrum disease encompasses a set of macular disorders secondary to an abnormally thick choroid. However, the pathological process underlying pachychoroid spectrum disease and its overlap with age-related macular degeneration (AMD) remain unclear. This review aimed to understand the underlying pathology, classification, and phenotypes of pachychoroid spectrum disease. Methods This comprehensive literature review was performed based on a search of peer-reviewed published papers relevant to the current knowledge of pachychoroid disease spectrum. Results Pachychoroid is primarily a bilateral phenomenon; the main pathological lesions include choriocapillaris attenuation and abnormally dilated pachyvessels. Chronic central serous chorioretinopathy (CSC) and pachychoroid neovasculopathy (PNV) show similar morphological changes and angiogenic cytokine levels. The subretinal fluid in PNV may not accurately indicate PNV activity. Besides, types 1 and 2 of choroidal neovascularization (CNV) may be involved in primary pachychoroidal disease. Both choroidal arteriosclerosis and higher hydrostatic pressure contribute to hyalinized choroidal arteries and aneurysmal dilatations, resulting in PNV progression to polypoidal choroidal vasculopathy (PCV). Thus, pachychoroid-related type 2 CNV and chronic CSC could be considered as PNV (IIIc) and as a precursor of PNV (IIIa), respectively. Tangled PCV on optical coherence tomography angiography that fails to develop aneurysms should be classified as a subtype of PNV or a forme fruste of PCV. Conclusions Multiple disorders of the pachychoroid spectrum are considered as a continuous disease process, ultimately stimulated by choroidal malfunction. PCV overlaps both AMD and pachychoroid disease, especially for thin-choroid and bilateral types. The terminology and classification of pachychoroid spectrum disease should be used cautiously.

This study aimed to investigate the effect of nimodipine on peripapillary and macular capillary vessel density (VD) in patients with normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA).Sixty mg nimodipine was administered to 20 enrolled NTG patients for 3 months. Patients were treated with glaucoma medication simultaneously. The macular and peripapillary VD were measured automatically by OCTA at baseline, 1.5 h after administering nimodipine, and after 3 months of administering the drug. The retinal nerve fibre layer (RNFL), ganglion cell complex thickness, visual field (VF) testing, intraocular pressure (IOP), blood pressure and pulse rate in each subject were assessed during each follow-up.Compared with the baseline, the parafovea VD was higher (50.89 ± 4.26 versus 46.80 ± 5.40,Nimodipine effectively increased superficial macular capillary VD, but did not affect peripapillary capillary VD in patients with NTG. This finding indicates that patients with NTG may benefit from the administration of nimodipine.

PURPOSE: Fibrillar collagen network and glycosaminoglycans (GAGs) are the primary components of extracellular matrix (ECM) of the sclera. The main goal of this study was to investigate the possible structural roles of GAGs in the scleral tensile properties as a function of preconditioning and displacement rate. METHODS: Four-step uniaxial stress-relaxation tests were used for characterizing the viscoelastic tensile response of the posterior porcine sclera with and without enzymatic GAG removal. The scleral strips were divided into different groups based on the displacement rate and the presence or absence of a preconditioning step in the loading protocol. The groups were 1) displacement rate of 0.2 mm/min without preconditioning, 2) displacement rate of 1 mm/min without preconditioning, 3) displacement rate of 0.2 mm/min with preconditioning, and 4) displacement rate of 1 mm/min with preconditioning. The peak stress, equilibrium stress, and the equilibrium elastic modulus were calculated for all specimens and compared against each other. RESULTS: Increasing the displacement rate from 0.2 mm/min to 1.0 mm/min was found to cause an insignificant change in the equilibrium stress and equilibrium elastic modulus of porcine scleral strips (P > 0.05). Removal of GAGs resulted in an overall stiffer tensile behavior independent of the displacement rate in samples that were not preconditioned (P < 0.05). The behavior of preconditioned samples with and without GAG removal was not significantly different from each other (P > 0.05). CONCLUSIONS: The experimental measurements of the present study showed that GAGs play an important role in the mechanical properties of the posterior porcine sclera. Furthermore, using a preconditioning step in the uniaxial testing protocol resulted in not being able to identify any significant difference in the tensile behavior of GAG depleted and normal scleral strips.

This study aimed to investigate the effect of Raf-1 kinase inhibitory protein (RKIP) on diabetic retinal neurodegeneration in streptozotocin-treated rat model and high glucose-treated rat Müller cells.Control and streptozotocin-treated rats were intravitreally injected with saline, RKIP gene overexpression lentivirus (oeRKIP) or negative control lentivirus (RKIP-vector). Normal or high glucose-treated Müller cells were transfected with saline, RKIP gene overexpression lentivirus or negative control lentivirus. Western blotting and immunofluorescence assay were utilized to evaluate the function of RKIP on the expression of RKIP, p38 mitogen-activated protein kinase (p38-MAPK), glutamate/aspartate transporter (GLAST), glutamine synthetase (GS), glial fibrillar acidic protein (GFAP) and cysteine-aspartic acid protease-3 (caspase-3). A glutamate assay kit was adopted to detect glutamate level in retina samples. Apoptosis of Müller cells was determined by Annexin-V/PI staining and flow cytometry.High glucose-treated Müller cells exhibited promoted apoptosis, while RKIP overexpression in high glucose-treated Müller cells down-regulated the enhanced apoptosis. Compared with rats injected with saline, streptozotocin-treated hyperglycemic rats displayed enhancement in the immunoreactivities of p38-MAPK and GFAP as well as in the protein expression of p38-MAPK and caspase-3. Strikingly, intravitreal injection of RKIP gene overexpression lentivirus in the hyperglycemic rats reversed the augmented immunoreactivities and protein expression mentioned above. Meanwhile, RKIP overexpression in the hyperglycemic rats improved the immunoreactivities and protein expression of RKIP, GS and GLAST. Besides, RKIP down-regulated the increased level of retinal glutamate in the hyperglycemic rats.Intravitreal injection of RKIP gene overexpression lentivirus functioned in preventing diabetic retinal neurodegeneration in a rat model of diabetes presumably by inhibiting p38-MAPK pathway.

Purpose: To assess the neuroprotective effects of methylene blue (MB) in a rat model of acute ocular hypertension (AOH) and explore its possible mechanisms.Methods: Our AOH rat model was obtained with anterior chamber perfusion for 60 min. After that, 100 μM MB was injected into the vitreous cavity immediately after injury. Electroretinogram, fundus photography, optical coherence tomography (OCT) and retina morphology examination were utilized to quantify retinal damage before surgery, as well as 7, 14 and 28 days after. The average number of surviving retinal ganglion cells (RGCs) was counted after fluorescent retrograde labelling with 4% DiI. And TUNEL assay was used to investigate retinal cell apoptosis at 24 hours after AOH. Nrf2 and BACE1 in the retina were determined by RT-qPCR analysis.Results: AOH did produce a severe degeneration effect on the whole retinal layer. Intravitreally injected MB maintained certain retinal thickness after AOH, reduced the destruction of electroretinograms, and enhanced RGCs survival. The average number of TUNEL-labelled cells statistically reduced in the MB-treated retina tissue compared with retina treated with normal saline. The relative mRNA level of Nrf2 was also much higher in the MB-treated retinas after AOH, and the expression of BACE1 had a decline in the AOH + MB group.Conclusions: MB can protect the retina from AOH injury and the possible mechanism might involve the inhibition of BACE1 expression and the activation of Nrf2 antioxidant pathway.

PURPOSE To quantitatively compare reflectivity and other morphological changes of the photoreceptors of normal eyes with amblyopic eyes using the longitudinal reflectance profile (LRP) on swept-source optical coherence tomography (SS-OCT) images in children and adolescents with unilateral high myopia. The relationships between OCT parameters and visual acuity were investigated. METHOD Twenty-six amblyopes with unilateral high myopia and 34 age-, axial length- and spherical equivalent-matched normal controls were recruited. All participants underwent SS-OCT and detailed ophthalmic investigations. The reflectivity of the outer retinal and photoreceptor outer segment layer thickness were quantified by LRP using ImageJ software. All parameters were measured at three selected regions: at the fovea, 1 mm nasal to the fovea and 1 mm temporal to the fovea. Differences between the groups were evaluated. RESULTS The mean choroidal thickness was thinner in amblyopic eyes compared with controls (165.19 ± 59.02 μm vs 214.97 ± 66.41 μm at the fovea; 128.77 ± 57.06 μm vs 161.54 ± 57.37 μm at 1 mm nasal to the fovea; 188.13 ± 59.51 μm vs 219.87 ± 61.78 μm at 1 mm temporal to the fovea, P

Purpose: To compare the expression levels of miR-15a between pterygium and normal conjunctiva, and further investigate the potential role of miR-15a in the progression of pterygium.Methods: 21 cases of primary pterygium were enrolled in our study. The length of the pterygium invaded into the cornea and the total thickness of the pterygium were measured with anterior segment optical coherence tomography (AS-OCT). The pterygial and adjacent normal conjunctival samples of the 21 patients were collected. Expressions of miR-15a, BCL-2, Bax in both pterygium and normal conjunctiva were measured, and correlations between miR-15a and BCL-2, miR-15a and Bax, miR-15a and clinical parameters were made. Pterygium epithelial cells (PECs) were isolated, cultured and transfected with miR-15a mimic or miR-15a inhibitor to interfere the miR-15a expression levels. The regulation of BCL-2 expression by miR-15a was examined with Real-Time PCR (RT-PCR), Western blot and immunofluorescence. The regulation of Bax expression by miR-15a was also examined with Real-Time PCR (RT-PCR) and Western blot. The cell viability of the transfected PECs was measured with the CCK-8 assay and the apoptosis in these cells was detected using the TUNEL assay.Results: The expression of miR-15a, Bax were significantly decreased while the BCL-2 was significantly increased in pterygium (p < .05). There was a negative correlation in expression between miR-15a and BCL-2 in pterygium tissues (r = -0.516, p < .05). We also found that relative miR-15a level was positively correlated with the length of pterygium invaded into the cornea (r = -0.570, p < .05). In cultured PECs, miR-15a could downregulate the expression of BCL-2 and upregulate the expression of Bax. Promotion of miR-15a could suppress cell proliferation and promote cell apoptosis in cultured PECs.Conclusions: Our study demonstrated that decreased expression of miR-15a in pterygium might be associated with the apoptosis and proliferation of abnormal cell via regulating BCL-2, which could subsequently contribute to the development of pterygium. Downregulation of miR-15a might also contribute to the pathogenesis of pterygium by other mechanisms including abnormal proliferation and neovascularization, which remain to be investigated.

To investigate the change in individual retinal layer thickness by spectral-domain optical coherence tomography (SD-OCT) in eyes underwent femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and photorefractive keratectomy (PRK).In patients who underwent PRK and FS-LASIK, changes in the thickness of all retinal layers in the foveal, parafoveal, and perifoveal regions were evaluated by SD-OCT automated segmentation analysis at pre-operatively and different time points post-operatively.Seventy-one eyes of 71 patients (38 patients in PRK, 33 patients in LASIK) were included. In the pre-operative period, mean spherical equivalent (SE), mean keratometry, axial length, and segmentation values of the retinal layers were similar (The findings of our study suggest that the increase of INL thickness may be due to temporary structural and circulatory changes of the retina that may occur in the suction phase in the FS-LASIK procedure.

Introduction: To compare the optic nerve head (ONH) structure and microvasculature in patients with optic atrophy due to non-arteritic anterior ischemic optic neuropathy (NAION), compressive optic neuropathy (CON), methanol-induced optic neuropathy (MION), and traumatic optic neuropathy (TON) using optical coherence tomography angiography.Methods: In this comparative, cross-sectional study, 32 eyes with NAION, 18 eyes with CON, 32 eyes with MION, 23 eyes with TON, and 55 normal eyes were enrolled. Radial peripapillary capillary (RPC) vessel density, peripapillary retinal nerve fiber layer (RNFL) thickness, disc area, cup volume, and cup/disc area ratio were obtained using the RTVue XR Avanti system (Optovue Inc., Fremont, CA, USA).Results: RPC vessel density and peripapillary RNFL thickness in all patients were significantly lower than normal subjects. A positive correlation was found between the RPC vessel density and peripapillary RNFL thickness in normal subjects and all study groups. The positive correlation between the inside and outside disc RPC vessel density was only found in the NAION (r = 0.36, P = .042) and MION (r = 0.42, P = .018) groups. No significant difference was found among the groups in terms of peripapillary and inside disc vascular densities (all P > .05). Disc area and cup volume in patients with MION was larger than the values in patients with NAION (P = .018) and TON (P = .044) and normal subjects (P = .015). The discriminating features among the study groups were the larger cup volume and cup/disc area ratio in patients with MION, and lower RNFL thickness in patients with TON.Conclusions: There was a positive correlation between the RNFL thickness and peripapillary RPC vessel density regardless of the cause of optic disc pallor. Structural evaluation of the ONH seems to be a better way to differentiate the cause of optic nerve head atrophy than the microangiographic changes.

The visual acuity is very important for glaucoma patients in their lives. The purpose of this study was to examine about the correlation of visual acuity and visual field (VF) parameters or optical coherence tomography (OCT) parameters in patients with glaucoma. We evaluated 210 eyes of 210 patients (110 men and 100 women; mean age, 69.6 ± 9.6 years) with open-angle glaucoma and 68 eyes of healthy controls. In glaucomatous eyes including healthy eyes, correlation between visual acuity and each of the VF parameters or each of the OCT parameters was estimated using regression analyses. The average visual acuity of control group was - 0.08, and that of glaucoma group was - 0.06 (early stage), - 0.03 (moderate stage), and 0.08 (severe stage), respectively. Regression analyses including healthy eyes and glaucomatous eyes revealed significant correlations between visual acuity and mean deviation (MD) of 30-2 Humphrey VF (

The development of a polyarginine cell-penetrating peptide (CPP) could enable the treatment of age-related macular degeneration, with drugs like bevacizumab, to be administered using eye drops instead of intravitreal injections. Topical formulations have a vast potential impact on healthcare by increasing patient compliance while reducing the financial burden. However, as the ocular preparations may contain several doses, it is essential to understand the stability of the bevacizumab+CPP conjugate produced.In this work, we examine the stability of a bevacizumab solution with and without cell-penetrating peptide using dynamic light scattering and circular dichroism to assess the physical stability. We use HPLC to assess the chemical stability and ELISA to assess its biological activity. We also examine the potential of the CPP to be used as an antimicrobial agent in place of preservatives in the eye drop.The structural stability of bevacizumab with and without the CPP was found not to be affected by temperature: samples stored at either 20°C or 4°C were identical in behavior. However, physical instability was observed after five weeks, leading to aggregation and precipitation. Further investigation revealed that the addition of the polypeptide led to increased aggregation, as revealed through dynamic light scattering and concentration analysis of the peptide through HPLC. Complexing the bevacizumab with CPP had no effect on biological stability or degradation.Our findings suggest that the shelf life of CPP+bevacizumab complexes is at least 38 days from its initial formulation. Currently, the mechanism for aggregation is not fully understood but does not appear to occur through chemical degradation.

Purpose: To assess the safety and long-term scleral biomechanical stability of rhesus eyes after blue light scleral CXL by investigating the biomechanical and microstructural changes.Methods: Seven rhesus monkeys (14 eyes) were observed in this study. All right eyes received blue light scleral CXL at the superior temporal equatorial sclera, and the left eyes served as controls. Biological ocular parameters were followed up to 1 year after scleral CXL. Stress-strain measurements of three rhesus sclera were measured, three rhesus retinas were examined histologically by H&E and TUNEL staining. And the microstructure of both the sclera and retina were observed by transmission electron microscopy at 1 year.Results: As for the retinal thickness, choroidal thickness, flow density of retinal superficial vascular networks and flash electroretinography (f-ERG) results, no significant differences were observed between the paired eyes at 1 year (P >.05). At the same time, the scleral collagen fibril distribution was much tighter, and the scleral biomechanical properties were significantly increased in the experimental eyes. However, apoptotic cells and retinal ultrastructural changes could still be found in the retina of the experimental eyes.Conclusion: This study demonstrates that blue light scleral CXL could effectively increase the scleral stiffness of the rhesus eye for at least 1 year, but ultrastructural change was still observed in the retina of scleral CXL eye. Therefore, the long-term intraocular safety of the blue light scleral CXL technique for preventing myopia progression should be investigated further.

Purpose: To establish normative data for macular thickness in Chinese aged 30 to 80 years using the swept-source optical coherence tomography (SS-OCT) device.Methods: The study included 290 normal eyes, 430 NDR eyes and 150 DR eyes of community residents aged 30 to 80 years in Guangzhou, China. Mean macular thicknesses in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, central point thicknesses (CPT), and macular volume was measured by SS-OCT (Triton DRI OCT, Topcon, Tokyo, Japan) and Spectral-Domain OCT (SD-OCT; Heidelberg Engineering, Heidelberg, Germany). We assessed agreement between SS-OCT and SD-OCT measurements by intraclass correlation coefficients (ICC) and Bland-Altman plots. We established a conversion equation relating central subfield (CSF), CPT and macular volume between the two OCT devices.Results: Macular thickness measurements in SS-OCT were significantly thinner than in SD-OCT. The mean CSF thickness in normal eyes measured by SS-OCT and SD-OCT were 227.8 ± 19.4 μm and 260.0 ± 19.7 μm (p 0.9). The conversion equations for CSF, CPT and macular volume from SS-OCT to SD-OCT were derived, with over 95% of the predicted values fell within 10% of the actual measurements in DR and NDR eyes.Conclusion: We propose SS-OCT CSF thicknesses of 275 μm for males and 260 μm for females as the minimum criteria for macular edema in Chinese aged 30 to 80 years based on 2 SDs above the mean CSF. SS-OCT measurements were significantly thinner than SD-OCT. We derived equations from converting SS-OCT measurements to SD-OCT equivalents.

Purpose/aim In the United States, high rates of vision impairment and eye disease disproportionately impact those who lack access to eye care, specifically vulnerable populations. The objective of our study was to test instruments, implement protocols, and collect preliminary data for a larger 5-year study, which aims to improve detection of eye diseases and follow-up eye care in vulnerable populations using community health workers (CHW) and patient navigators. In the study, trained CHWs conducted vision screening and patient navigators scheduled on-site eye exams and arranged appointments for those referred to ophthalmology to improve adherence to follow-up eye care. Materials and methods Eligible individuals age 40-and-older were recruited from the Riverstone Senior Center in upper Manhattan, New York City. Participants underwent on-site vision screening (visual acuity with correction, intraocular pressure measurements, and fundus photography). Individuals who failed the vision screening were scheduled with an on-site optometrist for an eye exam; those with ocular pathologies were referred to an ophthalmologist. Participants were also administered the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ-8) and Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test by community health workers. Results Participants (n=42) were predominantly older adults, with a mean age of 70.0 ± 9.8, female (61.9%), and Hispanic (78.6%). Most individuals (78.6%, n=33) failed vision screening. Of those who failed, 84.8% (n=28) attended the on-site eye exam with the optometrist. Ocular diagnoses: refractive error 13/28 (46.4%), glaucoma/glaucoma suspect 9/28 (32.1%), cataract 7/28 (25.0%), retina abnormalities 6/28 (21.4%); 13 people required eyeglasses. Conclusion This study demonstrates the feasibility of using CHWs and patient navigators for reducing barriers to vision screening and optometrist-based eye exams in vulnerable populations, ultimately improving early detection of eye disease and linking individuals to additional eye care appointments. The full five-year study aims to further examine these outcomes.

Purpose: To evaluate the effect of aqueous flare intensity as a measurement of inflammation and microvascular changes on retinal neurodegeneration in diabetic eyes.Materials and Methods: In cross-s...

Submitted by Maria da Luz Antunes (mluz.antunes@estesl.ipl.pt) on 2021-08-04T14:37:34Z No. of bitstreams: 1 Corneal subbasal nerve plexus evaluation by in vivo confocal microscopy in multiple sclerosis.pdf: 1317032 bytes, checksum: 86be831615d41642d36aa9409b5f2dd8 (MD5) Made available in DSpace on 2021-08-04T14:37:34Z (GMT). No. of bitstreams: 1 Corneal subbasal nerve plexus evaluation by in vivo confocal microscopy in multiple sclerosis.pdf: 1317032 bytes, checksum: 86be831615d41642d36aa9409b5f2dd8 (MD5) Previous issue date: 2021-04 info:eu-repo/semantics/publishedVersion

Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to...

Purpose/Aim: Glaucomatous optic neuropathy (GON) remains the world’s leading cause of irreversible blindness. Treatments including topical medications are directed at reducing intraocular pressure ...

Aim: To assess and compare the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) for detecting the extent of tumor invasion in eyes with advanced retinoblastoma prior to enucleation using histopathologic analysis as a reference.Methods: A total of 56 patients (68 eyes) enucleated for retinoblastoma were reviewed. Eyes with complete data (CT 28, MRI 16) were included for analysis. Imaging data were reviewed by a pediatric radiologist, blinded to histopathology results. Four high-risk factors which included scleral, choroidal, anterior eye segment invasion, and postlaminar optic nerve invasion were assessed.Results: For CT, the diagnostic odds ratio (DOR), sensitivity, and specificity for detecting postlaminar optic nerve invasion were 1.7%, 25%, and 83.3%. Choroidal invasion was correctly identified in only 2 of 10 eyes (DOR 0.5, sensitivity 20%, specificity 66.7%). For scleral invasion, CT showed a diagnostic ratio of 1.5%, sensitivity 40%, specificity 69.6% whereas for anterior segment invasion DOR was 9.2%, sensitivity 100%, and specificity 65.4%. MRI showed a higher DOR for detecting postlaminar optic nerve invasion of 39%, sensitivity 77.8%, and specificity 100%. Choroidal and scleral invasion on MRI had a DOR of 6.5% (sensitivity 25%, specificity 100%) and 6% (sensitivity 33.3%, specificity 92.3%) respectively while DOR for anterior segment invasion was 1.3% (sensitivity 50%, specificity 57.1%).Conclusion: CT showed a poor diagnostic accuracy for all four high-risk factors in advanced retinoblastoma and therefore may not be a useful tool for assessment of tumor extension. For MRI, detection of postlaminar optic nerve invasion was moderately accurate although less accurate for detection of other risk factors. Decision-making for each child should not be based on any single parameter but rather on consideration of clinical factors in combination with radiologic findings.

Purpose Vitrectomized eyes pose a technical challenge when performing endothelial keratoplasty (EK). The aim of the study was to compare outcomes of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in complex eyes undergoing pars plana vitrectomy (PPV) prior to or during surgery. Methods This retrospective study included consecutive eyes that underwent pars plana infusion-assisted DMEK or pull-through DSAEK which underwent PPV prior to or during the EK at a tertiary center. Included were eyes with at least 1-year follow-up. The main outcome measures were best-corrected visual acuity (BCVA) and serious adverse events. Results Fifty-two eyes (n = 52) with a mean follow-up time of 24.6 ± 7.4 months were included. Both groups were similar in terms of baseline characteristics although the DMEK group had a significantly larger proportion of Fuchs' patients (p = .009). There was no significant difference in postoperative logMAR BCVA between groups at each visit (p > .05 for all). There was a significantly higher proportion of overall serious adverse events (50.0% versus 15.4%, p = .02), retinal detachments (19.2% versus 0.0%, p = .05) and cystoid macular edema (23.1% versus 0.0%, p = .02) following DMEK. Graft detachment occurred more often following DMEK (53.9% versus 11.5%, p = .001) with no significant difference in rebubbling rates (23.1% versus 11.5%, p = .27). Conclusions A significant and similar improvement in BCVA was achieved following DMEK and DSAEK in complex vitrectomized eyes. Patients should be advised regarding the higher rates of potential serious complications associated with a pars plana infusion DMEK in this situation.

This study aims to assess the bony lacrimal fossa changes in chronic cases of primary acquired nasolacrimal duct obstruction versus acute dacryocystitis.A prospective study was performed on 25 bony lacrimal fossae of 25 eyes of 15 patients who underwent endoscopic dacryocystorhinostomy at a tertiary care Dacryology service over a period of 6 months. Ten patients with chronic PANDO (1 year) with bilateral involvement and five patients of unilateral acute dacryocystitis were recruited in the study. None of the patients had a history of trauma or previous surgeries or nasal disease in the past. The bone samples from the frontal process of the maxilla and the lacrimal bone were obtained during the osteotomy and subjected to routine histopathological examination. Special stains used were von Kossa, Masson trichrome, periodic acid Schiff, and Alcian blue. Immunohistochemistry was performed using CD68 antibodies. Patient demographics, clinical presentation, duration of the disease, and bony changes were analyzed in different patient subsets.The mean disease duration in the chronic PANDO subset was 3.1 years, whereas acute dacryocystitis was 6.8 days. There was no correlation between the bony changes and the laterality in the chronic subset. Periosteal thickness and fibrosis were universal in the chronic group but not in the acute dacryocystitis. There were also differences in the number of osteocytes per sq mm, osteoblast, osteoclast, bony remodeling, bony canals structure, and intrastromal fibrosis between the subsets. These changes within the chronic group increased with the duration of the disease. Interestingly, there was no evidence of any bony inflammation across the subsets in all the samples studied.Characteristic bony changes can be demonstrated in patients with chronic PANDO but not in acute dacryocystitis. The lack of bony inflammatory infiltrates may provide clues in understanding the peri-sac disease pathogenesis in acute dacryocystitis.

Previous studies have used subjective assessments to implicate darker skin color as a risk factor for glaucoma. This study used objective measurements to determine whether skin melanin is a risk fa...

Purpose/Aim: To investigate the risk of laser damage to the unprotected fellow eye of patients undergoing laser retinal photocoagulation with 532 nm diode pumped solid-state laser.Materials and Met...

This study aims to assess the performance of an analysis method to measure in vivo the movement speed of tear film particles post-blink as a measure of tear film spreading. Ocular surface parameter...

Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions.Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis.Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile.This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues.

Magnetic resonance imaging of the eye and orbit (MReye) is a cross-domain research field, combining (bio)physics, (bio)engineering, physiology, data sciences and ophthalmology. A growing number of reports document technical innovations of MReye and promote their application in preclinical research and clinical science. Realizing the progress and promises, this review outlines current trends in MReye. Examples of MReye strategies and their clinical relevance are demonstrated. Frontier applications in ocular oncology, refractive surgery, ocular muscle disorders and orbital inflammation are presented and their implications for explorations into ophthalmic diseases are provided. Substantial progress in anatomically detailed, high-spatial resolution MReye of the eye, orbit and optic nerve is demonstrated. Recent developments in MReye of ocular tumors are explored, and its value for personalized eye models derived from machine learning in the treatment planning of uveal melanoma and evaluation of retinoblastoma is highlighted. The potential of MReye for monitoring drug distribution and for improving treatment management and the assessment of individual responses is discussed. To open a window into the eye and into (patho)physiological processes that in the past have been largely inaccessible, advances in MReye at ultrahigh magnetic field strengths are discussed. A concluding section ventures a glance beyond the horizon and explores future directions of MReye across multiple scales, including in vivo electrolyte mapping of sodium and other nuclei. This review underscores the need for the (bio)medical imaging and ophthalmic communities to expand efforts to find solutions to the remaining unsolved problems and technical obstacles of MReye, with the objective to transfer methodological advancements driven by MR physics into genuine clinical value.

Purpose The optical coherence tomography (OCT) has been used to evaluate the changes of retinal degeneration in patients with diabetic peripheral neuropathy (DPN) in recent years, but the results of previous studies were controversial. Therefore, a systematic review and meta-analysis was performed to evaluate the degree of retinal neurodegeneration in DPN measured by OCT. Methods A comprehensive search of PubMed, Embase, Web of Science, Scopus, China Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases were performed to identify studies that evaluate retinal neurodegeneration in DPN by using OCT. The included studies were critically reviewed and meta-analyses were performed to evaluate differences of the OCT-derived parameters between the DPN and non-DPN patients. Results Twelve studies were included in the final meta-analysis, involving a total of 1,807 eyes (573 in the DPN group and 1,229 in the non-DPN group). The mean peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly lower in the DPN group than in the non-DPN group (weighted mean difference [WMD] = -8.37μm; 95% CI: -11.00, -5.74). The reduction of pRNFL thickness was the most pronounced in the inferior quadrant, and the differences in the nasal and temporal quadrants were also statistically significant, with WMD (95% CI) being -4.63μm (-7.51, -1.76) and -3.92μm (-6.86, -0.98), respectively. Similar results were observed for macular parameters, with WMD and 95% CI being -1.0μm (-1.5, -0.5) for macular retinal nerve fiber layer (mRNFL), -2.7μm (-10.7, -5.3) for macular ganglion cell-inner plexiform layer (mGCIPL), and -2.2μm (-4.4, -0.04) for macular ganglion cell complex (mGCC), respectively. Conclusions Patients with DPN present with significant retinal neurodegeneration, with reduced pRNFL, mRNFL, mGCIPL, and mGCC thickness. Measurements of OCT parameters may serve as a biomarker for diagnosing and monitoring DPN.

To assess the sensitivity and specificity of lateral midpupil lid distances for the detection of upper lid lateral flare.Lateral lid flare was determined by unanimous agreement among six experienced oculoplastic surgeons in the grading of photographs obtained for patients with Graves orbitopathy (GO). Bézier lines were employed to extract the upper eyelid contours of the patients and a control group of age and sex matched subjects. Custom software was employed to determine 5 lateral midpupil eyelid distances. The sensitivity and specificity of each measurement in detecting lateral flare were estimated from receiver operating characteristic curves. The non-parametric Kruskal-Wallis one-way analysis of variance (ANOVA) with Dunn's posthoc test was used to compare the median values of the contour parameters between groups.The degree of agreement between judges evaluated with the Fleiss' Kappa test was relatively high (K = 0.69, z = 16.6

Twenty-five eyes of 25 patients with bipolar disorder and 74 eyes of 74 healthy controls underwent retinal measurements of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness. Measurements were obtained using the Spectralis-OCT device with the new Posterior Pole protocol which assesses the macular area by analyzing retinal thickness in a grid of 64 (8*8) cells.Significant differences (Posterior Pole OCT protocol is a useful tool to assess changes in the inner retinal layers in bipolar disorder. These observed changes, especially those affecting the GCL, may be associated with disease evolution and may be predictive of the presence of the disease. OCT data could potentially be a useful tool for clinicians to diagnose and monitor BD patients.

To compare 2 mg intravitreal triamcinolone (IVT) versus 40 mg posterior sub-Tenon triamcinolone acetonide (STT) for the treatment of eyes with pseudophakic cystoid macular edema.A retrospective, single-center review of eyes receiving 2 mg IVT between 3/1/2012-3/1/2017 and 40 mg STT between 1/1/2015-3/1/2017. Visual acuity (VA) and central macular thickness (CMT) were recorded at baseline, 1-, 3-, and 6-month follow-up visits.Forty-five eyes were included in the IVT group and 50 eyes in the STT group. Change in VA from baseline to 1, 3, and 6 months was not significantly different between IVT and STT (6 months: 2.3 lines vs. 2.4 lines,2 mg IVT and 40 mg STT both achieved significant improvement in vision and CMT with no significant difference between interventions at 3- and 6-month follow-up.

To evaluate the agreement between the predicted and measured central corneal thickness (CCT) reduction after the small incision lenticule extraction (SMILE) surgery and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery.A total 165 patients were enrolled in this prospective study. Eighty patients with a mean spherical equivalent (SE) of -4.72 ± 1.80 Diopters (D) were treated with the FS-LASIK procedure and Eighty-five patients with a mean SE of -4.78 ± 1.63 D were treated with SMILE procedure. One eye for each patient was randomly selected and included for statistical analysis. Ultrasound pachymetry measurement and Scheimpflug camera corneal topography were performed preoperatively and 3 months postoperatively. The measured CCT reduction was calculated by comparing the preoperative examinations with postoperative examinations. Comparative statistics and linear regression analyses were performed.The mean predicted CCT reduction was 95.02 ± 21.39 μm in FS-LASIK group and 103.49 ± 22.87 μm in SMILE group (A systematic overestimation of measured CCT reduction in FS-LASIK group did not influence the refractive precision of FS-LASIK. Due to the different biomechanical distributions in post-SMILE cornea, the measured CCT reduction was influenced as the changes in refractive correction. Nomogram adjustment for high myopic correction needs further research.

Objectives: To present the clinical features of and diagnostic methods used for macular coloboma (MC), and to analyze the factors associated with best-corrected visual acuity (BCVA) in patients wit...

Objective: To determine whether the combination of meibomian gland expression (MGX) with intense-pulsed light (IPL) has a better efficacy to treat meibomian gland dysfunction (MGD) than IPL alone.Methods: One hundred patients with MGD were randomly divided into three groups: MGX, IPL, and IPL+ MGX. Clinical parameters included the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), noninvasive keratograph tear breakup time (NIBUT), redness, meibomian gland dropout, tear breakup time (TBUT), corneal fluorescent staining (CFS), eyelid margin score, meibomian gland secretion function, and Schirmer I tests were collected before treatment and at 1 and 3 months after treatment. Compare the indexes of each group before and after treatment and also compare the differences of each group on follow-up.Results: Compared to the baseline, OSDI, TBUT, and meibomian gland secretion function in IPL group improved throughout the follow-up period (all P < .05) and part of the meibomian gland secretion function increased continuously. OSDI, TBUT, lower eyelid margin scores, and meibomian gland secretion function in IPL + MGX group improved at the both follow-up visits (all P < .05), and continued improvement in meibomian gland secretion function can be observed. Lower meibomian gland dropout and CFS reduced at 1 month and 3 months respectively in IPL ± MGX group (P = .001,P = .001).Compared to IPL group, only CFS has reduction in IPL + MGX group at 1-month (P < .001), CFS, upper and lower MGYCS were improved at the 3 months (P = .037,P = .014, P = .049).Conclusions: MGX may have synergistic effect when combined with IPL therapy, and the effect can last at least 3 months.

Purpose: To investigate the association between meibomian gland (MG) loss and corneal subbasal nerve plexus density in patients with chronic graft-versus-host disease (GVHD) related dry eye disease...

To investigate the change and recovery of choroid thickness after short-term application of 1% atropine gel and its influencing factors in 6-7-year-old children.71 right eyes of 71 children were enrolled and divided into myopia and control group. 1% atropine gel was administered twice a day for one week and then stopped. Spherical equivalent (SE), accommodative amplitude (AA), keratometry (K), axial length (AL), and choroidal thickness (CT) were obtained at baseline and 1In both groups, all CTs increased following the change in SE, AA, and AL after administration of 1% atropine for one week. They gradually recovered to baseline levels seven weeks after withdrawal. The change (Δ) in CT at 3 mm superior from the fovea was significantly higher in the myopia group than in the control group. In both groups, ΔCT at subfovea had no significant correlation with SE, AA, and AL, both at baseline and one week. However, ΔCT at subfovea was negatively correlated with ΔAL in the control group.One-week application of 1% atropine gel may increase CT in 6-7-year-old Chinese children. Meanwhile, the recovery process after withdrawal lasts seven weeks. During the recovery process, the changes in structural parameters (AL, CT) and functional parameters (AA, SE) in both groups occurred synchronously. The SE, AA, and AL at baseline may not predict the extent of atropine's effect on CT.

Pentosan polysulfate sodium (PPS; Elmiron) is a FDA-approved heparanase inhibitor for the treatment of bladder pain and interstitial cystitis. The chronic use of PPS has been associated with a novel pigmentary maculopathy, associated with discrete vitelliform deposits that exhibit hyperfluorescence, macular hyper-pigmentary spots, and foci of nodular RPE enlargement. Therefore, this study aimed to investigate the retinal morphology of heparanase knockout mice. The retinal morphology of heparanase knock-out and age-matched control wild type mice of 3-, 9- and 15-weeks old was characterized by means of histological evaluation. Immuno-histological stains for RPE65, F4/80 and Ki67 were performed for investigating the RPE, inflammatory and proliferating cells, respectively. Histological analysis showed no changes in age-matched wild-type controls, whereas the eyes of heparanase null mice were characterized by alterations in RPE and neural retina, as manifest by RPE folds and choroidal thickening, detached RPE cells, thickening of the photoreceptor layer and retinal disorganization. The presence of discrete hyperfluorescent foci, however, was absent. The prevalence of the RPE/choroidal changes or protrusions seemed to progress over time and were correlated with more RPE65 signal rather than influx of F4/80- or Ki67-positive cells. These results indicate that the subretinal alterations were mostly RPE driven, without influx of inflammatory or proliferating cells. Our results indicate that heparanase deficiency in the mice leads to RPE folds, choroidal thickening, and retinal disorganization. The presence of discrete hyperfluorescent foci, a key characteristic of the human disease, was not observed. However, it can be concluded that some of the observations in mice are similar to those seen after chronic use of PPS in humans. These findings indicate that the toxicity observed in the presence of heparanase inhibitors is target-related and will preclude the clinical use of heparanase inhibition as a therapeutic intervention.