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

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

BACKGROUNDPhotodynamic therapy (PDT) has been recommended as a main treatment for idiopathic choroidal neovascularization (I-CNV). But the visual results of PDT were inconsistent and variable, and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries. In recent years, intravitreal ranibizumab therapy, showing favorable visual outcomes, has developed as an advanced treatment for choroidal neovascularization (CNV). Although both methods have been reported to be effective in treating I-CNV, there is no detailed comparative report between the two methods. This study aimed to compare visual outcomes, retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV, and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.

METHODSThirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT. The best corrected visual acuity (BCVA) was recorded before and at each follow-up visit after treatments (logMAR). Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to evaluate the retinal structural changes, and to measure central retinal thickness (CRT) and central choroidal thickness (CCT).

RESULTSMean BCVA was 0.64 ± 0.27 in PDT group and 0.69 ± 0.22 in ranibizumab group at baseline (P = 0.55). When compared with the baseline, mean BCVA in PDT group was improved significantly at 3-month after PDT (0.41 ± 0.16, P = 0.002), then changed little (0.42±0.25 at 12-month, P = 0.88). Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit. It improved much more obviously in the first month and then remained stable. The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT (P < 0.05). When compared with the baseline, mean CRT in PDT group decreased significantly since 3-month visit, whereas mean CRT in ranibizumab group decreased significantly from 1-month visit. Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than that in PDT group, almost in the same period as BCVA improving. When compared with the baseline, mean CCT did not change significantly at each follow-up visit in each group (P > 0.05). The CCT difference was not statistically significant between the two groups at each same time visit (P > 0.05). Mean BCVA was correlated with CRT, but was not correlated with CCT.

CONCLUSIONSBoth intravitreal ranibizumab therapy and PDT are effective for the treatment of I-CNV. It is obvious that ranibizumab therapy is significantly superior to PDT in improving BCVA and decreasing CRT. CRT decreases much more rapidly in ranibizumab group than in PDT group, simultaneously with visual improvement. CRT reduction has significant correlation with the visual outcomes in the recovery of I-CNV, whereas BCVA prognosis may have no correlation with CCT. CCT is not changed significantly after each of the treatments. Both PDT and ranibizumab therapy may have no significant effect on choroid.

Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Choroidal Neovascularization ; drug therapy ; therapy ; Female ; Humans ; Intravitreal Injections ; Male ; Photochemotherapy ; methods ; Ranibizumab ; Retina ; drug effects ; pathology ; Visual Acuity ; drug effects

OBJECTIVETo study the retinal ultrastructure of streptozocin (STZ)-induced diabetic rats and the intervention effect of Lycium Barbarum Polysaccharides (LBP).

METHODSThe STZ-induced diabetic SD rat model was established. LBP was given to those in the treatment group by gastrogavage. Changes of body weight, blood glucose, and retinal ultrastructure at 24-week were observed.

RESULTSEarly retinal changes covered mitochondrion changes, cell degeneration and apoptosis of retinal neurons and neuroglia cells in the diabetic rats. No change of body weight or blood glucose was observed between the LBP group and the diabetic model group (P > 0.05). The ultrastructural changes were obviously relieved by LBP, and limited to the inner nuclear layer.

CONCLUSIONSLBP could obviously relieve pathological changes of mitochondrion, hinder neural cell apoptosis. Its effect might not be achieved by lowering blood glucose. It was expected to be used in preventing and treating early diabetic retinal neuropathy.

Animals ; Diabetes Mellitus, Experimental ; pathology ; Diabetic Retinopathy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects ; ultrastructure

To evaluate the effect of chlorogenic acid (CGA), a polyphenol abundant in coffee, on retinal vascular leakage in the rat model of diabetic retinopathy, Sprague-Dawley rats were divided into four groups: controls, streptozotocin-induced diabetic rats, and diabetic rats treated with 10 and 20 mg/kg chlorogenic acid intraperitoneally daily for 14 days, respectively. Blood-retinal barrier (BRB) breakdown was evaluated using FITC-dextran. Vascular endothelial growth factor (VEGF) distribution and expression level was evaluated with immunohistochemistry and Western blot analysis. Expression of tight junction proteins, occludin and claudin-5, and zonula occludens protein, ZO-1 was also evaluated with immunohistochemistry and Western blot analysis. BRB breakdown and increased vascular leakage was found in diabetic rats, with increased VEGF expression and down-regulation of occludin, claudin-5, and ZO-1. CGA treatment effectively preserved the expression of occludin, and decreased VEGF levels, leading to less BRB breakdown and less vascular leakage. CGA may have a preventive role in BRB breakdown in diabetic retinopathy by preserving tight junction protein levels and low VEGF levels.
Animals ; Blood-Retinal Barrier/*drug effects ; Chlorogenic Acid/metabolism/*pharmacology ; Claudin-5/metabolism ; Dextrans/chemistry ; Diabetes Mellitus, Experimental/complications/metabolism/*pathology ; Diabetic Retinopathy/etiology/prevention & control ; Down-Regulation ; Fluorescein-5-isothiocyanate/chemistry ; Male ; Occludin/metabolism ; Rats ; Rats, Sprague-Dawley ; Retina/*metabolism ; Tight Junction Proteins/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Zonula Occludens-1 Protein/metabolism

OBJECTIVETo study the effect of Vaccinium uliginosum L., (VU) on the electroretinogram (ERG) and retinal pathological changes in rabbits after light-induced damage.

METHODSTwenty-eight Chinchilla rabbits were randomly divided into four groups: administration beforehand (A), administration after injury (B), light injury without administration (C), and blank (D) groups. After a 4-week administration of VU homogenate at 4.8 g/(kg·d) once a day in group A, ERG in groups A, B and C were recorded according to the standards set by the International Society for Clinical Electrophysiology of Vision (ISCEV). Except for group D, the groups were then exposed to strong light. Just after that, group A stopped receiving VU treatment and group B started to receive it. Then ERGs in all groups were recorded after 1 day, 1 week, and 2 weeks. Throughout the whole process groups which were not fed with VU were fed with normal saline. Finally, the tissues and structures of all the groups were observed and the thickness of the outer nuclear layers (ONL) was measured.

RESULTS(1) After 4-week feeding with VU, the latency time of ERG in group A became shorter than those in the other groups and the amplitude increased. After being exposed to strong light, the latency time lengthened and amplitude decreased in all the injury groups, but comparing at each time point, the measured values in group A were better than those in group C. With the accumulation of VU, the ERG in group B improved, and finally, all of the detected values became better than those in group C. (2) Retinae in group D were normal in histology and the layers were in order but those in group C became disarranged. The injuries in groups A and B were minor compared with those in group C. The thickness of the ONL in group C was significantly thinner than in the other groups (P=0.000), and that in groups A and B was thicker than that in group C, although thinner than in group D. That in group A was thicker than in group B.

CONCLUSIONSVU can relieve the injury to rabbit retinae exposed to normal day and night rhythm, alleviate the harm caused by light when used beforehand, and repair the light damage to the retina.

Animals ; Electroretinography ; Light ; Plant Extracts ; pharmacology ; Rabbits ; Retina ; drug effects ; pathology ; physiopathology ; radiation effects ; Retinal Cone Photoreceptor Cells ; drug effects ; pathology ; radiation effects ; Retinal Rod Photoreceptor Cells ; drug effects ; pathology ; radiation effects ; Time Factors ; Vaccinium ; chemistry

OBJECTIVETo study toxic effects of 2,5-hexanedione (2,5-HD) on pathology and lipid peroxidation in mouse retina.

METHODSForty-eight mice were randomly divided into blank control group (12 mice), negative control group exposed to normal solution (12 mice) and group exposed to 2,5-HD for 2. 4 and 8 weeks, respectively (24 mice) by intraperitoneal injection (2.5% 2,5-HD) at the dose of 400 mg/kg. The pathological changes of mouse retina were examined under light microscope. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in mouse retina were detected.

RESULTSThe retinal structure in the blank and negative control groups was normal. In mice exposed to 2,5-HD for 8 weeks, the swelling of outer and inner segments and disorder arrangement of the segments without clear boundary were found. The staining of outer plexiform layers was uneven and the irregular loose structure appeared. The hyperchromatic pyknotic and necrosis nuclei were presented in ganglion cells layer. Compared with the control and blank groups, the activities of SOD gradually and significantly reduced and the concentrations of MDA increased in group exposed to 2,5-HD (P < 0.05).

CONCLUSION2,5-HD can induce the injury of retina tissues of mice, which may be associated with the lipid peroxidation.

Animals ; Hexanones ; toxicity ; Lipid Peroxidation ; drug effects ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred Strains ; Retina ; drug effects ; metabolism ; pathology ; Superoxide Dismutase ; metabolism

After two decades of ups and downs, gene therapy has recently achieved a milestone in treating patients with Leber's congenital amaurosis (LCA). LCA is a group of inherited blinding diseases with retinal degeneration and severe vision loss in early infancy. Mutations in several genes, including RPE65, cause the disease. Using adeno-associated virus as a vector, three independent teams of investigators have recently shown that RPE65 can be delivered to retinal pigment epithelial cells of LCA patients by subretinal injections resulting in clinical benefits without side effects. However, considering the whole field of gene therapy, there are still major obstacles to clinical applications for other diseases. These obstacles include innate and immune barriers to vector delivery, toxicity of vectors and the lack of sustained therapeutic gene expression. Therefore, new strategies are needed to overcome these hurdles for achieving safe and effective gene therapy. In this article, we shall review the major advancements over the past two decades and, using lung gene therapy as an example, discuss the current obstacles and possible solutions to provide a roadmap for future gene therapy research.
Adaptive Immunity ; Carrier Proteins ; genetics ; Cystic Fibrosis ; genetics ; therapy ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; Dependovirus ; genetics ; Eye Proteins ; genetics ; Gene Targeting ; Genetic Therapy ; methods ; Genetic Vectors ; Humans ; Immunity, Innate ; Leber Congenital Amaurosis ; genetics ; therapy ; Liposomes ; Lung ; drug effects ; metabolism ; pathology ; Mutation ; Retina ; drug effects ; metabolism ; pathology ; Retroviridae ; genetics ; cis-trans-Isomerases

PURPOSE: Retinopathy of prematurity (ROP) is one of the leading causes of blindness, with retinal detachment occurring due to oxygen toxicity in preterm infants. Recently, advances in neonatal care have led to improved survival rates for preterm infants, and ROP has increased in incidence. In the present study, we aimed to determine whether or not resveratrol exhibits protective effects in an animal model of ROP and in primary retinal cell cultures of neonatal rat via nitric oxide (NO)-modulating actions using western blotting and real-time PCR with inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) antibodies and mRNAs. METHODS: In an in vivo oxygen-induced retinopathy (OIR) model, cyclic hyperoxia was induced with 80% O2 for one day and 21% O2 for one day from P1 to P14 in newborn Sprague-Dawley (SD) rats. Resveratrol was injected intravitreally for seven days and rats were sacrificed at P21. In vitro OIR primary retinal cell culture was performed using P0-2 SD rats. Hyperoxia injuries were induced through 100% O2 exposure for six hours. Western blotting and real-time PCR using iNOS, eNOS, nNOS antibodies and primers were performed in the rat model of ROP and the dispersed retinal cell culture. RESULTS: In both in vivo and in vitro OIR, the expression of iNOS antibody and mRNA was increased and of eNOS and nNOS were reduced in the resveratrol-treated group. CONCLUSIONS: In conclusion, resveratrol appeared to exert retinal protective effects via modulation of NO-mediated mechanism in in vivo and in vitro OIR models.
Analysis of Variance ; Animals ; Animals, Newborn ; Blotting, Western ; Disease Models, Animal ; Electrophoresis, Polyacrylamide Gel ; Humans ; Infant, Newborn ; Nitric Oxide Synthase/*metabolism ; Oxygen/toxicity ; RNA/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Retina/drug effects/pathology ; Retinopathy of Prematurity/*metabolism/pathology/*prevention & control ; Reverse Transcriptase Polymerase Chain Reaction ; Stilbenes/*pharmacology

OBJECTIVETo investigate the injury in the retina of rats exposed to n-hexane.

METHODSThirty-two SD male rats were randomly divided into control group and four n-hexane groups. The rats in the four n-hexane groups inhaled 35.2 g/m3 n-hexane statically for 1, 3, 7 and 14 days respectively (6 rats in every group) while 8 rats in the control group inhaled air. Histopathology and ultrastructure changes of the retina of rats were analyzed.

RESULTSRats in control group had clear layers of retinal structure, stained evenly and with regular cell shape. Retinal degeneration was observed in the rats exposed to n-hexane for 7 d and 14 d, and aggravated by degrees with time exposed to n-hexane. In the rats exposed to n-hexane for 14 d, the outer segments of photoreceptor were arranged in a confusing order, and topically there appeared dissolution; in the inner segments, mitochondria were swollen or disappeared. Pyknotic chromatin and cytoplasmic edema were observed in the outer nuclear layer. There were degeneration of horizontal cells, bipolar cells and amacrine cells in the inner nuclear layer. Cytoplasmic edema and organelle dissolution were observed in ganglionic cells. In the neurofibromas layer, outer and inner plexiform layers, there was neuron cell tuber edema, and the microfilament and vacuole of synapse decreased.

CONCLUSIONThe histopathology and ultrastructure of retina are damaged in the rats exposed to n-hexane, thus leading to ocular fundus disease.

Animals ; Hexanes ; toxicity ; Male ; Rats ; Rats, Sprague-Dawley ; Retina ; drug effects ; pathology ; ultrastructure