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

BACKGROUNDCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings.

METHODSOf 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigate the correlation between retinal vessel changes and MRI lesions.

RESULTSIn CADASIL patients, mean SFCT (268.37 ± 46.50 μm) and mean arterial inner diameter (93.46 ± 9.70 μm) were significantly lower than that in controls (P < 0.001,P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 μm), venous inner (128.99 ± 13.62 μm) and outer diameter (164.82 ± 14.77 μm), and mean arterial (19.13 ± 1.85 μm) and venous (17.91 ± 2.76 μm) wall thickness were significantly higher than that in controls (P = 0.023,P = 0.004,P < 0.001,P < 0.001, respectively). Arterial inner diameter (rs= -0.39, P= 0.044), AVRin (rs= -0.65,P < 0.001), and AVRout (rs= -0.56, P= 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P= 0.002), outer diameter (rs = 0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs= -0.52, P= 0.007) and AVRout (rs= -0.40, P= 0.048) showed a negative correlation with the number of CMBs.

CONCLUSIONSMeasurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.

Adult ; Brain ; metabolism ; CADASIL ; Cerebral Infarction ; pathology ; Female ; Humans ; Leukoencephalopathies ; pathology ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Mutation ; Receptor, Notch3 ; genetics ; Retinal Vessels ; metabolism ; Tomography, Optical Coherence ; methods

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

PURPOSE: To report the clinical features, clinical course, and treatment outcomes after laser photocoagulation in infants with aggressive posterior retinopathy of prematurity (APROP) and capillary-free zones in vascularized retina. METHODS: Six patients (12 eyes) with APROP and capillary-free zones in vascularized retina were retrospectively reviewed. Twelve eyes of six infants were included and were treated with laser photocoagulation for avascular retina and for capillary-free zones in vascularized retina, except for the posterior pole, and fundus findings were photographically-documented in sequence. In addition, anatomic and visual outcomes were evaluated with complications of APROP. RESULTS: Among all of the consecutive infants with APROP, capillary-free zones in vascularized retina were demonstrated in 24% of the infants. All of the infants were >27 weeks of gestation age and had birth weights >1,000 g. After laser treatment, 7 eyes (58.3%) had favorable outcomes, and late capillary filling in capillary-free zones of vascularized retina were noted, however 4 eyes (33.3%) progressed to retinal detachment and 1 eye (8.3%) was complicated by a retinal fold-distorting posterior pole. The visual outcomes were associated with anatomic outcomes. CONCLUSIONS: The anatomic outcomes in infants with APROP who had capillary-free zones were comparable to previously reported infants with APROP. The late capillary filling of capillary-free zones in vascularized retina was noted, and angiogenesis was considered to be involved. This process toward normal capillary formation or neovascularization in APROP, might determine its outcome.
Capillaries/*pathology ; Female ; Humans ; Infant ; Laser Coagulation/*methods ; Male ; Retina/*pathology/surgery ; Retinal Vessels/*pathology/surgery ; Retinopathy of Prematurity/*pathology/*surgery ; Retrospective Studies ; Treatment Outcome

INTRODUCTIONThis study describes the pathologic changes in the retina of a group of young Asian subjects with myopia worse than -10 diopters spherical equivalent (SE) refraction.

MATERIALS AND METHODSThe study population consists of 20 male subjects undergoing preemployment screening for public service for a 1-year period from 2009 to 2010. A detailed series of visual tests of function, fundus examination and grading, ocular biometry and posterior segment optical coherence tomography were performed for all eyes.

RESULTSA total of 21 eyes with mean SE of -10.88 diopters, [standard deviation (SD) , 1.28 diopters], and mean age of 21.8 years (SD, 1.3 years) were included. Out of 21 eyes, 17 (81.0%) had beta peripapillary atrophy, 10 (47.6%) had clinically detectable optic disc tilt, 1 (4.8%) had positive T-sign and 18 (85.7%) had retinal tessellation, 4 (19.0%) had posterior vitreous detachment and 14 (66.7%) had peripheral retina degeneration. The mean retinal nerve fibre layer (RNFL) thickness was 92.48 mm (SD, 9.99 mm).

CONCLUSIONNone of the 21 highly myopic eyes had features of myopic retinopathy but most of these young males had clinically visible myopia-associated abnormalities of the optic disc, vitreous and peripheral retina. Generally, these eyes had thinner RNFL. Further longitudinal studies are required to investigate if these eyes will eventually develop complications of pathological myopia.

Adolescent ; Adult ; Age of Onset ; Choroid Diseases ; diagnosis ; Fluorescein Angiography ; Humans ; Male ; Myopia ; classification ; pathology ; Nerve Fibers ; pathology ; Ophthalmoscopy ; Optic Atrophy ; diagnosis ; Optic Disk ; pathology ; Optic Nerve Diseases ; diagnosis ; Posterior Eye Segment ; pathology ; Retina ; pathology ; Retinal Degeneration ; diagnosis ; Retinal Diseases ; diagnosis ; Retinal Vessels ; pathology ; Singapore ; Tomography, Optical Coherence ; methods ; Vision Tests ; Visual Acuity ; Vitreous Detachment ; diagnosis ; Young Adult

This paper is aimed to fulfill a prototype system used to classify and retrieve retinal image automatically. With the content-based image retrieval (CBIR) technology, a method to represent the retinal characteristics mixing the fundus image color (gray) histogram with bright, dark region features and other local comprehensive information was proposed. The method uses kernel principal component analysis (KPCA) to further extract nonlinear features and dimensionality reduced. It also puts forward a measurement method using support vector machine (SVM) on KPCA weighted distance in similarity measure aspect. Testing 300 samples with this prototype system randomly, we obtained the total image number of wrong retrieved 32, and the retrieval rate 89.33%. It showed that the identification rate of the system for retinal image was high.
Algorithms ; Fundus Oculi ; Humans ; Image Processing, Computer-Assisted ; methods ; Information Storage and Retrieval ; methods ; Numerical Analysis, Computer-Assisted ; Ophthalmoscopy ; standards ; Pattern Recognition, Automated ; methods ; Retina ; pathology ; Retinal Vessels ; pathology

PURPOSE: To evaluate and compare the clinical and angiographic characteristics of retinal vein occlusion (RVO) in glaucomatous and non-glaucomatous eyes with unilateral RVO in the fellow eye. METHODS: Twenty-one glaucomatous eyes (GL group) and 25 age-matched non-glaucomatous eyes (non-GL group) with unilateral RVO in the fellow eye were included in this study. Fluorescein angiographic images were assessed in both groups by 3 retina specialists in order to determine the RVO occlusion site. The occlusion site was divided into 2 types: arteriovenous (AV)-crossing and non-AV-crossing (optic cup or optic nerve sited). The clinical characteristics and prevalence of AV-crossing and non-AV-crossing RVO were compared between the 2 groups. RESULTS: The mean baseline intraocular pressures of the RVO eye and the fellow eye did not differ between the 2 groups (RVO eye: 14.3 +/- 2.5 mmHg [non-GL group], 15.5 +/- 3.9 mmHg [GL group], p = 0.217; fellow eye: 14.4 +/- 2.5 mmHg [non-GL group], 15.7 +/- 3.7 mmHg [GL group], p = 0.148). The prevalence of systemic disease did not differ between the 2 groups (e.g., diabetes mellitus and hypertension, p = 0.802 and 0.873, respectively). AV-crossing RVO was significantly more frequent in the non-GL group (19 eyes; 76%) than in the GL group (4 eyes, 19%, p < 0.001). CONCLUSIONS: Non-AV-crossing RVO, i.e., optic cup- or optic nerve-sited RVO, is more frequently associated with glaucomatous changes in the fellow eye. Therefore, this type of RVO should be monitored more carefully for indications of glaucoma in the fellow eye.
Female ; Fluorescein Angiography/*methods ; Follow-Up Studies ; Fundus Oculi ; Glaucoma, Open-Angle/*diagnosis ; Humans ; Male ; Middle Aged ; Retinal Vein Occlusion/*diagnosis ; Retinal Vessels/*pathology ; Retrospective Studies ; Severity of Illness Index

OBJECTIVETo investigate the association of retinal vascular calibers with hyperuricemia in a middle-aged and elderly population.

METHODSA cross-sectional design was applied in this study and 869 participants aged =40 years from a high-risk group for diabetes were recruited. All participants received the anthropometrical measurements and laboratory tests. Retinal arteriolar and venular caliber of the participants were measured with a semi-automated system. Hyperuricemia was defined as a serum uric acid level >420 μmol/L in men and >360 μmol/L in women. Linear regression models were used to assess the association of hyperuricemia with retinal vascular calibers. These models were additionally adjusted for age, central obesity, hypertension, dyslipidemia, weekly activity, smoking status, and education.

RESULTSAmong the 869 participants, 133 (15.3%) suffered from hyperuricemia. The crude mean serum uric acid level was 312.3 μmol/L (Standard Deviation 79.5); mean concentration was 355.0 μmol/L (SD 75.5) in male participants, and 288.0 μmol/L (SD 71.1) in female participants (age-adjusted difference 58.1 μmol/L, 95% Confidence Internal 48.5, 67.6). After adjusting for additional covariates, male participants with hyperuricemia had 3.77 μm (95% CI -0.46, 8.00) smaller arteriolar caliber and 6.20 μm (95% CI 0.36, 12.04) larger venule than those without hyperuricemia; the corresponding numbers among female participants were 1.57 μm (95% CI -1.07, 4.21) for retinal arteriolar caliber and 2.28 μm (95% CI -1.72, 6.27) for retinal venular caliber.

CONCLUSIONHyperuricemia was associated with smaller retinal arteriolar caliber and larger venular caliber mainly in male participants in this study.

Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus ; epidemiology ; Female ; Humans ; Hyperuricemia ; complications ; Male ; Middle Aged ; Retinal Vessels ; pathology ; Risk Factors ; Sex Characteristics

PURPOSE: To describe the clinical characteristics of idiopathic juxtafoveal telangiectasis (IJT) in Koreans. METHODS: Medical records of 16 patients with IJT were analyzed during the period from 1997 to 2009. Diagnosis was based on biomicrosopic and fluorescein angiographic findings and the group was determined according to the Gass and Blodi classification. RESULTS: We analyzed eight patients in group 1A (50%), two in group 1B (12.5%), and six in group 2A (37.5%). Diverse treatment modalities, such as macular laser photocoagulation, photodynamic therapy, intravitreal antiangiogenic agent, and steroid injection, were applied for macular edema in nine eyes; however, only two eyes showed visual improvement. CONCLUSIONS: In this case series, group 1A was the most common. For macular edema related to IJT, current treatment strategies had no consistent effect.
Adolescent ; Adult ; Aged ; Angiogenesis Inhibitors/administration & dosage ; Child ; Female ; Fluorescein Angiography ; Follow-Up Studies ; Fovea Centralis/*blood supply ; Fundus Oculi ; Glucocorticoids/administration & dosage ; Humans ; Incidence ; Intravitreal Injections ; Male ; Microscopy, Acoustic ; Middle Aged ; Photochemotherapy/methods ; Prognosis ; Republic of Korea/epidemiology ; Retinal Diseases/*diagnosis/drug therapy/epidemiology ; Retinal Vessels/*pathology/ultrasonography ; Retrospective Studies ; Risk Factors ; Telangiectasis/*diagnosis/drug therapy/epidemiology ; Visual Acuity ; Young Adult

OBJECTIVETo explore VEGF siRNA's effect on the immature fetal retinal microvascular endothelial cells in vitro.

METHODThe fresh retinal micrangium was primarily cultured to obtain microvascular endothelial cells. CoCl2 was used to simulate oxygen-deficient conditions. siRNA directed against human VEGF was designed and chemically synthesized. There were 3 groups in our experiment: VEGF siRNA group, hypoxia control group, and negative siRNA control group. The fetal retinal micrangium vascular endothelial cells were transfected by using liposome. The expression levels of VEGF mRNA and protein were evaluated by RT-PCR and Western blotting 24, 48, 72 h after transfection, cell proliferation was evaluated by MTT method.

RESULTThe expression levels of VEGF mRNA decreased by 21.05%, 79.67%, and 90.48% 24 h, 48 h, and 72 h after transfection as compared to those in hypoxia control group, the expression level of VEGF protein had decreased by 14.58%, 66.97%, and 81.61% as compared to those in hypoxia control group. The siRNA could decrease cell proliferation under hypoxia too, the multiplication rate after 12, 24, 48, and 72 h decreased by 15.0%, 42.9%, 78.3% and 65.9%.

CONCLUSIONVEGF siRNA could down-regulate the expression of VEGF in immature fetal retinal microvascular endothelial cells and suppressed cell proliferation. Application of siRNA to inhibit expression of VEGF may be a hopeful way to prevent and cure ROP.

Cell Hypoxia ; Cell Line ; Endothelial Cells ; metabolism ; Humans ; Infant, Newborn ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Retina ; metabolism ; pathology ; Retinal Vessels ; cytology ; metabolism ; Retinopathy of Prematurity ; metabolism ; Transfection ; Vascular Endothelial Growth Factor A ; genetics ; metabolism