Humans ; Diabetic Retinopathy/pathology* ; Retina ; Diabetes Mellitus

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.
Alzheimer Disease ; etiology ; metabolism ; pathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Animals ; Dietary Supplements ; Disease Models, Animal ; Folic Acid ; therapeutic use ; Homocysteine ; Hyperhomocysteinemia ; complications ; metabolism ; pathology ; therapy ; Male ; Rats, Sprague-Dawley ; Retina ; metabolism ; pathology ; Retinal Vessels ; metabolism ; pathology ; Vitamin B 12 ; therapeutic use ; tau Proteins ; metabolism

PURPOSE: To assess whether the asymmetry in the peripapillary retinal nerve fiber layer (pRNFL) thickness between superior and inferior hemispheres on optical coherence tomography (OCT) is useful for early detection of glaucoma. MATERIALS AND METHODS: The patient population consisted of Training set (a total of 60 subjects with early glaucoma and 59 normal subjects) and Validation set (30 subjects with early glaucoma and 30 normal subjects). Two kinds of ratios were employed to measure the asymmetry between the superior and inferior pRNFL thickness using OCT. One was the ratio of the superior to inferior peak thicknesses (peak pRNFL thickness ratio; PTR), and the other was the ratio of the superior to inferior average thickness (average pRNFL thickness ratio; ATR). The diagnostic abilities of the PTR and ATR were compared to the color code classification in OCT. Using the optimal cut-off values of the PTR and ATR obtained from the Training set, the two ratios were independently validated for diagnostic capability. RESULTS: For the Training set, the sensitivities/specificities of the PTR, ATR, quadrants color code classification, and clock-hour color code classification were 81.7%/93.2%, 71.7%/74.6%, 75.0%/93.2%, and 75.0%/79.7%, respectively. The PTR showed a better diagnostic performance for early glaucoma detection than the ATR and the clock-hour color code classification in terms of areas under the receiver operating characteristic curves (AUCs) (0.898, 0.765, and 0.773, respectively). For the Validation set, the PTR also showed the best sensitivity and AUC. CONCLUSION: The PTR is a simple method with considerable diagnostic ability for early glaucoma detection. It can, therefore, be widely used as a new screening method for early glaucoma.
Area Under Curve ; Color ; Early Diagnosis ; Female ; Glaucoma/diagnosis ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; Nerve Fibers/pathology ; ROC Curve ; Reproducibility of Results ; Retina/pathology ; Retinal Ganglion Cells ; Sensitivity and Specificity

BACKGROUNDObstructive sleep apnea syndrome (OSAS) has been shown to generate hypertension and endothelial dysfunction. Retinal vessel is the only vessel that can be observed directly and noninvasively; retinal vascular abnormalities can serve as a predictive marker for the occurrence, clinical course, and prognosis of cardiovascular and cerebrovascular diseases. The objective of this study was to identify the effect of OSAS severity on the morphological changes of retinal vessels.

METHODSAdult patients complained of snoring were included in this study. The patients' general information, polysomnography, and fundus photography parameters including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were collected. Patients were divided into four groups according to their apnea-hypopnea index (AHI) results: Group I, AHI ≤5/h; Group II, 5/h < AHI ≤30/h; Group III, 30/h < AHI ≤60/h; and Group IV, AHI> 60/h.

RESULTSA total of 133 patients were included in this study with 111 males (83.5%) and 22 females (16.5%). Mean age was 41.6 ± 9.9 years, and the mean body mass index was 28.1 ± 4.0 kg/m2. AHI ranged between 0 and 130.8/h with a mean of 39.1 ± 30.7/h. There were 24, 34, 35, and 40 patients in Group I, Group II, Group III, and Group IV, respectively. Significant differences were found for AHI (F = 388.368, P< 0.001), minimal pulse oxygen saturation (F = 91.902, P< 0.001), and arousal index (F = 31.014, P< 0.001) among four groups; no significant differences were found for CRAE (F = 0.460, P = 0.599) and CRVE (F = 0.404, P = 0.586) among groups; there were significant differences for AVR between Group I and Group IV (63.6 ± 5.1% vs. 67.2 ± 5.5%, P = 0.010) Group II and Group IV (64.5 ± 6.0% vs. 67.2 ± 5.5%, P = 0.030), and Group III and Group IV (64.7 ± 4.1% vs. 67.2 ± 5.5%, P = 0.043). A main group-by-AHI effect was found on the AVR: patients with higher AHI showed higher AVR results (r = 0.225, P = 0.009). Multivariate logistic regression analysis was used for multi-variable factors. A group-by-age effect was found on the AVR: younger patients showed higher AVR results (β = -0.001, P = 0.020).

CONCLUSIONSThis study indicated that increased AVR of retinal vessel can be observed in extremely severe OSAS patients. For patients with OSAS, retinal vascular abnormalities may become an early indication for further cardiovascular abnormalities.

Adult ; Female ; Humans ; Male ; Middle Aged ; Polysomnography ; Retina ; pathology ; physiopathology ; Retinal Artery ; pathology ; physiopathology ; Retinal Vein ; pathology ; physiopathology ; Sleep Apnea, Obstructive ; pathology ; physiopathology ; Young Adult

BACKGROUNDMorphological changes of the vasculature system in patients with myopia have been observed by Doppler ultrasound and fundus fluorescein angiography (FFA); however, these studies have limitations. Doppler ultrasound provides low-resolution images which are mainly obtained from visualized large vessels, and FFA is an invasive examination. Optic coherence tomography (OCT) angiography is a noninvasive, high-resolution measurement for vascular density. The purpose of this study was to investigate the change of vascular density in myopic eyes using OCT angiography.

METHODSThis cross-sectional study includes a total of 91 eyes from 47 participants including control, moderate, and high myopia that were evaluated by OCT angiography. Patients with myopia were recruited from the Refractive Department, Shenzhen Aier Eye Hospital, from August 5, 2015 to April 1, 2016. Emmetropic eyes were from healthy volunteers. The vascular density at macula and optic disc regions, ganglion cell complex (GCC) thickness, and retinal nerve fiber layer (RNFL) thickness were measured. Their relationships with axial length (AL) and refractive error were analyzed. One-way analysis of variance (ANOVA), Pearson's correlation, and generalized estimating equation were used for statistical analysis.

RESULTSBoth superficial and deep macular vascular density were highest in control (25.64% ± 3.76% and 37.12% ± 3.66%, respectively), then in moderate myopia (21.15% ± 5.33% and 35.35% ± 5.50%, respectively), and lowest in high myopia group (19.64% ± 3.87% and 32.81% ± 6.29%, respectively) (F = 13.74 and 4.57, respectively; both P < 0.001). Both superficial (β = -0.850 and 0.460, respectively) and deep (β = -0.766 and 0.396, respectively) macular vascular density were associated with AL and spherical equivalent (all P < 0.001). Superficial macular vascular density was associated with GCC thickness (β = 0.244, P = 0.040), independent of spherical equivalent. The vascular density in optic disc region had no difference among the three groups, and it was not associated with AL, spherical equivalent, or RNFL thickness.

CONCLUSIONOur results suggested that with the increase of myopia, the vascular density decreased in macular region, but not in optic disc region.

Adult ; Cross-Sectional Studies ; Eye ; blood supply ; Female ; Fluorescein Angiography ; Humans ; Macula Lutea ; pathology ; physiopathology ; Male ; Middle Aged ; Myopia ; pathology ; physiopathology ; Optic Disk ; pathology ; physiopathology ; Prospective Studies ; Retina ; pathology ; physiopathology ; Retinal Ganglion Cells ; pathology ; Tomography, Optical Coherence ; Young Adult

Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.
Animals ; Apoptosis ; Diabetic Retinopathy* ; Excitatory Amino Acids ; Ganglion Cysts ; Glial Fibrillary Acidic Protein ; Glutamate-Ammonia Ligase ; Glutamic Acid ; Humans ; In Vitro Techniques ; Interleukin-17* ; Interleukins ; Intravitreal Injections ; Leukostasis ; Mice ; Neurons ; Pathology ; Plasma ; Retina ; Retinaldehyde ; Vascular Endothelial Growth Factor A

BACKGROUNDPediatric infectious endophthalmitis is a serious sight-threatening disease for children. The purpose of this study was to investigate the etiology, microbiological spectrum, and visual outcomes of infectious endophthalmitis in children at a single institution in China.

METHODSIt is a retrospective study of the medical records of all patients under 14 years of age with histories of infectious endophthalmitis, treated at a single institution from January 1, 2009 to January 1, 2015. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. The Kappa test and Chi-square test were used in the statistical evaluation.

RESULTSA total of 271 children were identified, with a mean age of 5.61 ± 2.93 years (range 5 months to 14 years). Ocular trauma (94.8%) and previous ocular surgery (3.0%) were the most common etiologies. Overall, 147 (54.2%) cases had positive cultures, and 176 organisms were isolated from these patients. A single species was isolated in 120 (81.6%) cases, with multiple organisms in 27 (18.4%) cases, and the most commonly identified organisms were coagulase-negative Staphylococcus and Streptococcus species, comprising 29.5% and 26.8% of the isolates, respectively. Moreover, of 176 isolates, 142 (80.8%) were Gram-positive organisms, 23 (13.0%) were Gram-negative organisms, and 11 (6.2%) were fungi. The final visual outcomes were 20/200 or better in 66 (24.4%) eyes, counting fingers to 20/200 in 34 (12.5%), hand motions in 30 (11.1%), light perception in 33 (12.2%), no light perception in 32 (11.8%), and 9 (3.3%) eyes were enucleated or eviscerated. The visual outcomes were not available in 67 (24.7%) patients.

CONCLUSIONSPenetrating ocular trauma is the most frequent cause of pediatric endophthalmitis in China. Streptococcus and Staphylococcus species are the most commonly identified organisms in exogenous pediatric endophthalmitis whereas Fusarium species are commonly seen in endogenous endophthalmitis. In this research, in spite of aggressive management with antibiotics and vitrectomy, the visual prognosis was found to be generally poor.

Adolescent ; Anti-Bacterial Agents ; therapeutic use ; Child ; Child, Preschool ; China ; Endophthalmitis ; drug therapy ; microbiology ; pathology ; Eye Infections, Fungal ; drug therapy ; microbiology ; pathology ; Eye Injuries, Penetrating ; microbiology ; Female ; Fusarium ; pathogenicity ; Humans ; Infant ; Male ; Retina ; microbiology ; Retrospective Studies ; Staphylococcus ; pathogenicity ; Streptococcus ; pathogenicity ; Vitrectomy

No abstract available.
Angiogenesis Inhibitors/administration & dosage/adverse effects ; Bevacizumab/administration & dosage/*adverse effects ; Follow-Up Studies ; Hemangioma, Capillary/diagnosis/*drug therapy ; Humans ; Intravitreal Injections ; Male ; Photochemotherapy/*adverse effects ; Retina/*pathology ; Retinal Detachment/*chemically induced/diagnosis ; Retinal Neoplasms/diagnosis/*drug therapy ; Time Factors ; Young Adult

PURPOSE: To investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD). METHODS: A retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection. RESULTS: One month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 microm and 121.68 microm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up. CONCLUSIONS: VA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*therapeutic use ; Female ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Male ; Middle Aged ; Ranibizumab/*therapeutic use ; Retina/pathology ; Retinal Diseases/*physiopathology ; Retrospective Studies ; Tissue Adhesions ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/drug effects ; Vitreous Body/*pathology ; Wet Macular Degeneration/*drug therapy/physiopathology

PURPOSE: To compare the clinical characteristics of unilaterally progressing glaucoma (UPG) and simultaneously bilaterally progressing glaucoma (BPG) in medically treated cases. METHODS: Primary open angle glaucoma patients were classified as having UPG or BPG according to an assessment of optic disc and retinal nerve fiber layer photographs and visual field analysis. Risk factors including the presence of systemic diseases (hypertension, diabetes, cerebrovascular accident, migraine, and dyslipidema) were compared between the UPG and BPG groups. Baseline characteristics and pre- and post-treatment intraocular pressure (IOP) were compared between the progressing eye (PE) and the non-progressing eye (NPE) within the same patient in the UPG group and between the faster progressing eye and the slower progressing eye in the BPG group. RESULTS: Among 343 patients (average follow-up period of 4.2 years), 43 were categorized into the UPG group and 31 into the BPG group. The prevalence of all analyzed systemic diseases did not differ between the two groups. PEs in the UPG group had more severe pathology in terms of baseline visual field parameters than NPEs (mean deviation -6.9 ± 5.7 vs. -2.9 ± 3.9 dB, respectively; p < 0.001). However, baseline IOP, mean follow-up IOP, and other clinical characteristics were not significantly different between the PE and the NPE in the UPG group. The progression rate was significantly higher in the faster progressing eye in patients with BPG than in the PE for patients with UPG (-3.43 ± 3.27 vs. -0.70 ± 1.26 dB/yr, respectively; p = 0.014). CONCLUSIONS: There were no significant differences in the prevalence of systemic diseases between the UPG and BPG groups. Simultaneously bilaterally progressing patients showed much faster progression rates than those with a unilaterally progressing eye.
Disease Progression ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/*diagnosis/physiopathology ; Humans ; Intraocular Pressure/*physiology ; Male ; Middle Aged ; Optic Disk/*pathology ; Retina/*pathology ; Retrospective Studies ; Time Factors ; Visual Fields/*physiology