Serum and Macular Carotenoids in Relation to Retinal Vessel Caliber Fifteen Years Later, in the Second Carotenoids in Age-Related Eye Disease Study.

Purpose: We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative. Methods: Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016-2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994-1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001-2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5° from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling. Results: In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 µm vs. 140.8 ± 1.4 µm; P = 0.05) and venule caliber (214.6 ± 2.2 µm vs. 207.5 ± 2.2 µm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 µm vs. 141.1 ± 1.4 µm [P = 0.12] and 213.3 ± 2.1 µm vs. 206.0 ± 2.1 µm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 µm vs.135.8 ± 3.0 µm; P = 0.001). Conclusions: Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.

Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy.

Previous studies demonstrated that brief (3 to 4 min) daily application of light at 670 nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR) and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods. Vitamin D receptor and Cyp24a1 transcripts were quantified by quantitative real-time PCR, and the abundance of c-Kit+ stem cells in blood and retina were assessed. Long-term daily administration of PBM significantly inhibited the diabetes-induced leakage and degeneration of retinal capillaries and also significantly inhibited the diabetes-induced reduction in visual function. PBM also inhibited diabetes-induced reductions in retinal Cyp24a1 mRNA levels and numbers of circulating stem cells (CD45-/c-Kit+), but these effects may not account for the beneficial effects of PBM on the retinopathy. PBM significantly inhibits the functional and histopathologic features of early DR, and these effects likely are mediated via multiple mechanisms.

Movement of retinal vessels toward the optic nerve head after increasing intraocular pressure in monkey eyes with experimental glaucoma.

A shift or displacement of the retinal blood vessels (RBVs) with neuroretinal rim thinning indicates the progression of glaucomatous optic neuropathy. In chronic open angle glaucoma, individuals with RBV positional shifts exhibit more rapid visual field loss than those without RBV shifts. The retinal vessels reportedly move onto the optic nerve head (ONH) in response to glaucoma damage, suggesting that RBVs are pulled toward the ONH in response to increased cupping. Whether this phenomenon only applies to RVBs located in the vicinity or inside the ONH or, more generally, to RBVs also located far from the ONH, however, is unclear. The aim of this study was to evaluate the movement of RBVs located relatively far from the ONH edge after increasing intraocular pressure (IOP) in an experimental monkey model of glaucoma. Fundus photographs were obtained in 17 monkeys. High IOP was induced in the monkeys by laser photocoagulation burns applied uniformly with 360° irradiation around the trabecular meshwork of the left eye. The right eye was left intact and used as a non-treated control. Considering the circadian rhythm of IOP, it was measured in both eyes of each animal at around the same time-points. Then, fundus photographs were obtained. Using Image J image analysis software, an examiner (N.E.) measured the fundus photographs at two time-points, i.e. before laser treatment (time 1) and the last fundus photography after IOP elevation (time 2). The following parameters were measured (in pixels): 1) vertical diameter of the ONH (DD), 2) distance from the ONH edge to the first bifurcation point of the superior branch of the central retinal vein (UV), 3) distance from the ONH edge to the first bifurcation point of the inferior branch of the central retinal vein (LV), 4) ONH area, and 5) surface area of the cup of the ONH. We calculated the ratios of UV to DD (UV/DD), LV to DD (LV/DD), and the cup area to disc area ratio (C/D). The mean UV/DD at time 1 (0.656 ± 0.233) was decreased at time 2 (0.542 ± 0.192) (p < 0.01), and the mean LV/DD at time 1 (0.642 ± 0.151) was decreased at time 2 (0.534 ± 0.171) (p < 0.01). The mean C/D at time 1 (0.303 ± 0.035) was increased at time 2 (0.556 ± 0.110) (p < 0.01). The mean IOP at time 1 was 19.8 ± 2.5 and that at time 2 was 54.2 ± 15.8. The amount and rate of the change in LV/DD and C/D between time 1 and time 2 were significantly correlated (r = -0.654 and -0.536, p = 0.004 and 0.026, respectively). Therefore, in an experimental monkey model of glaucoma, RBVs located relatively far from the ONH were pulled toward the ONH as cupping increased.

Effects of carotid baroreceptor stimulation on retinal arteriole remodeling evaluated with adaptive optics camera in resistant hypertensive patients.

BACKGROUND AND AIM: Baroreceptor activation therapy (BAT) leads to a decrease in blood pressure (BP) in patients affected by resistant hypertension (RH) by reducing sympathetic outflow. This study aimed at evaluating the effects of BAT on RH patients' retinal arteriolar microvasculature, a territory devoid of adrenergic innervation. PATIENTS AND METHODS: Five patients defined as affected by RH after excluding secondary causes of hypertension and based on number of antihypertensive treatments, underwent the implantation of Barostim™ neo™. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed by office and 24-hours ambulatory BP monitoring (ABPM). Adaptive Optics Camera RTX1® (ImagineEye, Orsay, France) was used to measure wall thickness (WT), internal diameter (ID), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR). A cohort of 21 not-controlled hypertensive patients matched for age, gender and follow-up time, undergoing standard-antihypertensive therapy changes, was selected as a control group. SBP and DBP were assessed by office and home BP monitoring (HBPM). Evaluations were performed at baseline and after 6 months mean follow-up. RESULTS: Office SBP decreased by 9.7±12.3% and 29.7±12.4% in standard-therapy and BAT group respectively, while office DBP decreased by 7.6±17.4% and 14.8±15.7%. Concerning ABPM/HBPM, a mean reduction of both SBP and DBP of 7.9±11% was observed for the standard-therapy while a reduction of 15.8±10.5% and 15.8%±5.3% was observed for SBP and DBP respectively in BAT group. While in the standard-therapy group a significant reduction in WLR (-5.9%) due to both ID increase (+2.3%) and WT reduction (-5.7%) was observed, without changes in WCSA (-0.3%), RH patients had a significant reduction in WCSA (-12.1%), due to a trend in both WT and ID reduction (-6.5% and -1.7% respectively), without significant changes in WLR (-2%). CONCLUSION: While a reverse eutrophic remodeling was observed in patients undergoing a standard-antihypertensive treatment, hypotrophic changes were found in RH patients undergoing BAT. Despite the lack of adrenergic receptors on retinal vessels, chronic baroreflex stimulation may exert an effect on retinal microvasculature in RH patients by more systemic than local mechanisms.

Lycium barbarum polysaccharide extracts preserve retinal function and attenuate inner retinal neuronal damage in a mouse model of transient retinal ischaemia.

BACKGROUND: Retinal ischaemia is a common feature shared by numerous eye diseases. Ischaemic insult leads to retinal dysfunction and neuronal death. Lycium barbarum polysaccharides are well known for eyesight preservation. We have previously reported the effect of Lycium barbarum polysaccharides on cell death, blood ocular barrier and oxidative stress within 24 h retinal ischaemia. This study focuses on retinal function and looks for ultrastructural and cellular correlates after a relatively long period of reperfusion for 7 days. METHODS: Two-hour ischaemia was induced by intraluminal occlusion of the internal carotid artery. Either Lycium barbarum polysaccharides or phosphate-buffered saline was orally pre-administered daily for 7 days before ischaemia and continued for 1, 3 and 7 days after reperfusion. Electroretinogram was performed to evaluate visual function. Paraffin-embedded retinal sections were prepared 7 days after reperfusion and utilized for histological and immunohistochemical analyses. RESULTS: Ischaemia led to sustained inhibition of b-wave amplitude and oscillatory potentials. Lycium barbarum polysaccharide-treated mice exhibited greater b-wave and oscillatory potential responses from days 1 to 7 after reperfusion. In addition, increased number of viable cells and calretinin-positive cells, as well as enhanced immunoreactivity of protein kinase C alpha and attenuated glial fibrillary acidic protein expression, was noted in Lycium barbarum polysaccharide-treated retina. CONCLUSIONS: Daily consumption of Lycium barbarum polysaccharides effectively alleviated ischaemia-induced retinal dysfunction as well as reduced correlated neuronal death and glial activation. This prolonged effect could last at least 7 days. It suggested that Lycium barbarum polysaccharides might serve as a neuroprotective agent in ischaemic retinopathies.

Lonicerae Japonicae Flos attenuates diabetic retinopathy by inhibiting retinal angiogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (Jin-Yin-Hua) is a well-known traditional Chinese medicine used for clearing away heat and toxic material. AIM OF THE STUDY: This study aims to observe the attenuation of aqueous extract of Lonicerae Japonicae Flos (FL) against streptozotocin (STZ)-induced diabetic retinopathy (DR) and its engaged mechanism. MATERIALS AND METHODS: STZ-induced proliferative DR (PDR) for 5 month in C57BL/6 mice was used in this study. Retinal vessels were observed by immunofluorescence staining with cluster of differentiation 31 (CD31) and histopathological evaluation. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum vascular endothelial growth factor (VEGF) content. Cell proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay in choroid-retinal endothelial RF/6A cells. VEGF-induced tube formation in RF/6A cells was observed. The contents of chlorogenic acid (CGA), caffeic acid (CA), and luteolin in FL were detected by high-performance liquid chromatography (HPLC). RESULTS: Histopathological evaluation demonstrated that retinal vessels were increased in STZ-induced PDR mice, whereas FL decreased such increase. The results of CD31 staining also showed that FL decreased the increased number of retinal vessels in STZ-induced PDR mice. In addition, FL reduced the increased serum VEGF content in STZ-induced PDR mice. FL reduced VEGF-induced RF/6A cell proliferation in the concentration-dependent manner, but had no obvious effect on RF/6A cell viability without VEGF stimulation. VEGF-induced tube formation in RF/6A cells was inhibited by different concentrations of FL. CGA, CA and luteolin all inhibited VEGF-induced tube formation in RF/6A cells, and the lowest effective concentration of CGA and CA was both 0.625µM, but of luteolin was 5µM. Furthermore, the results of HPLC demonstrated that the amount of CGA was the highest in FL. CONCLUSIONS: FL ameliorates STZ-induced PDR by inhibiting retinal angiogenesis. Phenolic acid CGA is the main compound contributing to the inhibition of FL on retinal angiogenesis.

Andrographolide ameliorates diabetic retinopathy by inhibiting retinal angiogenesis and inflammation.

BACKGROUND: Andrographolide (Andro) is the main compound distributed in medicinal herb Andrographis paniculata. This study aims to observe the amelioration of Andro on streptozotocin (STZ)-induced diabetic retinopathy (DR) in mice. METHODS: STZ-induced non-proliferative DR (NPDR) for 2 months and proliferative DR (PDR) for 5 month in C57BL/6 mice were used in this study, respectively. Retinal vessels were observed by immunofluorescence staining for cluster of differentiation 31 (CD31). Evans blue permeation assay was used to detect the breakdown of blood-retinal barrier (BRB). Real-time PCR and immune-blot were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß. RESULTS: Retinal immunofluorescence staining with CD31 showed that Andro reduced the increased retinal vessels in STZ-induced PDR mice. Evans blue permeation results demonstrated that Andro attenuated the breakdown of BRB in STZ-induced NPDR mice. In STZ-induced PDR mice, Andro decreased the increased vascular endothelial growth factor (VEGF) in serum and vitreous cavity, and reduced the increased retinal mRNA expression of VEGF and its receptors. In STZ-induced NPDR mice, Andro abrogated the nuclear translocation of nuclear factor κB (NF-κB) p65 and early growth response-1 (Egr-1), and reduced the increased phospho-NF-κBp65, -inhibitor of kappa B (IκB), and -IκB kinase (IKK). Andro also decreased the increased serum and retinal mRNA expression of TNF-α, IL-6, IL-1ß, serpine1, and tissue factor (TF). CONCLUSIONS: Andro ameliorates DR via attenuating retinal angiogenesis and inflammation, and VEGF, NF-κB, and Egr1 signaling pathways all play important roles in this process.

Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model.

PURPOSE: Beneficial effects of dietary supplements in age-related macular degeneration (AMD) are related to antioxidative properties. In the Age-Related Eye Disease Study 1 (AREDS 1), a reduced progression to late stage AMD was found using vitamin C, E, zinc, and ß-carotene. We showed previously that the AREDS 1 formulation restores the O2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (lipopolysaccharide [LPS]) model. METHODS: We hypothesized that the abnormal O2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (vitamin C, E, and zinc, lutein/zeaxanthin, selenium, taurine, Aronia extract, and omega-3 free fatty acids). A total of 43 healthy subjects was included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity, and flow to 100% O2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14-day period of daily dietary supplement intake. RESULTS: The decrease in retinal arterial diameter, RBC velocity, and flow during 100% O2 breathing was diminished significantly after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O2 after LPS administration. This effect was significant for retinal arterial diameter (P = 0.03 between groups), and RBC velocity and flow (each P < 0.01 between groups). CONCLUSIONS: The present data indicate restoring of the RBC flow response to 100% O2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology. (ClinicalTrials.gov number, NCT00914576.).

Study of clinical applications and safety for Pascal® laser photocoagulation in retinal vascular disorders.

PURPOSE: To establish safe laser parameter standards for 10-30 ms Pascal(®) laser in clinical practice and to evaluate clinical and visual outcomes using this 532-nm multi-spot photocoagulation system. METHODS: Retrospective observational case series of 313 patients treated between 2006 and 2008. Evaluation of eight groups: A - panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR); B - focal laser treatment for clinically significant diabetic macular oedema; C - grid laser for diffuse diabetic macular oedema; D - sector PRP for ischaemic branch retinal vein occlusions (I-BRVO); E - full PRP for ischaemic central retinal vein occlusions (I-CRVO); F - macular laser treatment for macular oedema secondary to non-ischaemic BRVO; G - full PRP for rubeosis iridis and/or neovascular glaucoma (NVG) secondary to I-BRVO, I - CRVO or PDR; H - laser retinopexy for retinal breaks/degenerations. RESULTS: Mean LogMAR visual acuity for all procedures improved postlaser (p = 0.065), and laser prevented visual loss in 85% eyes. Topical anaesthesia was only required. At mean follow-up of 5 months, 72% procedures had a successful clinical outcome. Significantly higher powers were required for PRP using Pascal(®) compared to conventional laser (p = 0.001) in PDR, I-BRVO, I-CRVO and NVG. Sixty-seven per cent of patients (15/20) were successfully treated with single-session 20-ms PRP using a mean 1952 burns. There were no laser-associated adverse effects or ocular complications associated with multi-spot PRP or macular Pascal(®) arrays. CONCLUSIONS: The clinical efficacy using 10- to 30-ms pulse duration Pascal(®) laser is comparable to conventional standard protocols used for the treatment of vascular retinal disorders. Higher power, 10- to 30-ms pulse duration laser may be safely and effectively used in clinical practice.

Effect of qiming granule on retinal blood circulation of diabetic retinopathy: a multicenter clinical trial.

OBJECTIVE: To objectively assess the effect of Qiming Granule in the treatment of diabetic retinopathy (DR) by fluorescence fundus angiography (FFA). METHODS: In a multi-center, randomized, parallel controlled clinical trial, patients with DR were randomly assigned to the control group (calcium dobesilate capsule) and the test group (Qiming Granule). Changes in the retinal blood circulation time were recorded by FFA after 3 months of medication. RESULTS: Significant reduction was observed in the retinal arterio-venous circulation time (AVCT) in both groups (P<0.01), the value was 7.635+/-3.149 s before treatment and 5.165 +/-3.382 s after treatment in the treated group, and 7.737+/-3.413 s and 5.313+/-3.472 s in the control group respectively. Qiming Granule also reduced the arm-to-retinal circulation time (ARCT, P<0.05). The value was 17.867+/-3.872 s before treatment and 15.643+/-4.648 s after treatment in the treated group, and 17.217+/-3.833 s and 16.312+/-3.613 s in the control group (P>0.05) respectively. The ARCT in the tested group was reduced, with a statistically significant difference post-medication (P<0.01). CONCLUSION: As a Chinese medicine complex prescription, Qiming Granule may alleviate retinal hypoxia and ischemia by increasing retinal blood flow and improving the blood circulation.

Low power laser treatment of the retina ameliorates neovascularisation in a transgenic mouse model of retinal neovascularisation.

This study was designed to determine if low power laser therapy can achieve amelioration of vasoproliferation yet preserve useful vision in the treated area in a transgenic mouse model of retinal neovascularisation. The mice were anaesthetised and the pupils dilated for ERG and fundus fluorescein angiography on postnatal day 32. The left eyes were treated with approximately 85 laser spots (532 nm, 50 ms, 300 microm diameter) at a power level of 20 mW at the cornea. The eyes were examined using ERG and fluorescein angiography, one, four and six weeks later. Flat mounts of FITC-dextran infused retinas, retinal histology and PEDF immunohistochemistry was studied one or six weeks after laser treatment. In untreated eyes the expected course of retinal neovascularisation in this model was observed. However, retinal neovascularisation in the laser treated eye was significantly reduced. The laser parameters chosen produced only mild lesions which took 10-20 s to become visible. ERG responses were comparable between the treated and untreated eyes, and histology showed only partial loss of photoreceptors in the treated eyes. PEDF intensity corresponded inversely with the extent of neovascularisation. Low power panretinal photocoagulation can inhibit retinal neovascularisation and yet preserve partial visual function in this transgenic mouse model of retinal neovascularisation.

Hyperbaric oxygen therapy ameliorates the blood-retinal barrier breakdown in diabetic retinopathy.

BACKGROUND: To study the effect of hyperbaric oxygen (HBO) therapy on diabetic retinopathy in a streptozotocin-induced diabetic rat model. METHODS: Sprague-Dawley albino male rats were divided into three groups. The three groups were as follow: (i) non-diabetic control group (non-DM control); (ii) diabetic control group (DM control); and (iii) diabetic rats receiving hyperbaric oxygen therapy (DM HBO). Rats in DM HBO group were incubated in an oxygen monoplace chamber. The HBO condition was set at 2.5 atmospheres and 100% oxygen. The duration of a single HBO treatment was 90 min. Rats in DM HBO groups received HBO three times per week for 3 months. Retinal vascular permeability was assessed by measuring fluorescein isothiocyanate-labelled bovine albumin and retinal Evans blue leakage into the retina. RESULTS: We found that the retinal parenchyma showed prominent thickening but not statistically significant in rats with DM, corresponding to the retinal oedema, compared with the control and DM HBO groups. fluorescein isothiocyanate relative fluorescence intensity (Mean+/-SE) in normal control animals, diabetic animals, and HBO-treated diabetic animals was 356+/-47, 865+/-78, and 518+/-49, respectively, demonstrating significant difference between the means of diabetic and HBO-treated diabetic animals, and between means of control and diabetic animals (n=8, P<0.05). Retinal Evans blue leakage in control animals, diabetic animals, and HBO-treated diabetic animals was 7.6+/-2.9, 18.5+/-4.2 and 10.2+/-3.1 microL plasma/g retinal dry weight/h, respectively, demonstrating significant difference between the means of diabetic and HBO-treated diabetic animals, and between means of control and diabetic animals (n=8, P<0.05). CONCLUSION: HBO therapy may diminish the extent of the increased blood-retinal barrier breakdown in diabetic animals.

Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats.

Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. alpha-Lipoic acid, a thiol antioxidant, has been shown to have beneficial effects on polyneuropathy and on the parameters of oxidative stress in various tissues, including nerve, kidney, and retina. The purpose of this study was to examine the effect of alpha-lipoic acid on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without alpha-lipoic acid (400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of alpha-lipoic acid administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. alpha-Lipoic acid administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the two diabetic groups (with and without alpha-lipoic acid). Retinal 8-OHdG and nitrotyrosine levels were increased by over twofold and 70%, respectively, in diabetes, and alpha-lipoic acid administration inhibited these increases. Our results demonstrate that the long-term administration of alpha-lipoic acid has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. alpha-Lipoic acid supplementation represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.

[Feeder vessel treatment of choroidal neovascularization in age-related macular degeneration]. / Traitement des vaisseaux nourriciers de la néovascularisation choroïdienne rétrofovéale dans la DMLA.

INTRODUCTION: To report on the results of feeder vessel treatment for choroidal neovascularization in age-related macular degeneration (AMD). MATERIAL AND METHODS: Retrospective study of 40 patients presenting subfoveal classic choroidal neovascularization (CCNV) and/or occult choroidal neovascularization (OCNV) with or without fibrovascular pigment epithelium detachment (PED), based on fluorescein angiography (FA) and indocyanine green angiography (ICG). Visual acuity was measured using Snellen lines and/or ETDRS. The feeder vessels were visualized with high-speed ICG angiography (confocal scanning laser ophthalmoscope, Heidelberg HRA, Heidelberg, Germany). Feeder vessels were identified as very thin vessels with early filling and rapid emptying. Feeder vessel closure was achieved by laser photocoagulation treatment with either minipulse infrared laser therapy (810 nm), microburst, or yellow laser (568 nm). Post-treatment high-speed ICG angiography follow-up was recommended to the patient immediately or the day after the treatment. The number of treatments and location of the feeder vessels in relation to the macula as well as FA, ICG, and visual acuity results were assessed. If necessary, other treatment techniques such as photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) were offered to the patient when leakage was still present. RESULTS: The patients were followed for an average of 6.2 months (2-9 months). Twenty-six women and 14 men (mean age, 72 years; range, 51-95) were included. Eight patients demonstrated classic neovascularization, 32 presented occult neovascularization, including 17 cases of vascularized PED and 15 retrofoveal plaques. The average number of treatments was 1.8 (range, 1-4 treatments). Location of feeder vessels were as follows: nine superior-macular, 18 inferior-macular, six nasal-macular and 11 temporal-macular. Visual acuity improved two lines or more in nine patients (22.5%), decreased 2 lines or less in five patients (12.5%) and was stable in 26 patients (65%). After feeder vessel treatment, seven patients showed improvement of the anatomical aspect of the AMD lesions, with a reduction in leakage. Except for one subretinal hemorrhage, no complications after feeder vessel treatment were observed. CONCLUSION: Feeder vessel treatment is a technique requiring high-speed ICG angiography to detect the feeder vessels located at a distance from the subfoveal OCNV, CCNV, and PED. Although the final visual acuity result was for the most part stabilization, the technique appeared to be safe and reproducible. In patients who were not eligible for other therapies such as PED, feeder vessel treatment seemed to be a reasonable alternative.

Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity.

A newborn rat model of retinopathy of prematurity was used to test the hypothesis that a lack of superoxide dismutase contributes to the retinal vaso-attenuation seen during exposure of the animals to hyperoxic conditions. To determine the endogenous superoxide dismutase activity of the retina under hyperoxic conditions, litters of albino rats were placed in either constant 80% ambient oxygen (constant hyperoxia), or placed in 21% oxygen (room air) immediately after birth. Every other day, for 14 days, several rat pups were sacrificed and their retinas removed for the determination of total superoxide dismutase (SOD) activity and manganese-associated SOD activity. An attempt was made to increase retinal SOD activity by intraperitoneal administration of exogenous SOD encapsulated in polyethylene glycol-modified liposomes. Additional litters were exposed to the same oxygen treatments and supplemented twice daily with either liposome-encapsulated superoxide dismutase in saline or liposomes containing saline without SOD. Animals were sacrificed at various time points for the determination of total superoxide dismutase activity and computer-assisted analysis of vessel density and avascular area. Animals raised in an atmosphere of constant 80% oxygen had significantly reduced levels of retinal superoxide dismutase activity through 6 days of life when compared to their room air-raised littermates. At 6 days of age, daily supplementation with liposome-encapsulated SOD had significantly increased retinal superoxide dismutase activity and reduced oxygen-induced vaso-attenuation as evidenced by increased vessel density and decreased avascular area, when compared to littermates exposed to constant hyperoxia that received control liposomes. Superoxide dismutase had no adverse effects on any of the animals regardless of treatment. Tracing experiments demonstrated that liposomes entered the retina and were found in cells morphologically resembling microglia. Delivery of SOD to the retina via long-circulating liposomes proved beneficial, suggesting that restoration and/or supplementation of endogenous antioxidants in oxygen-damaged retinal tissue is a potentially valuable therapeutic strategy.

Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids.

Omega-3 fatty acids exert several important biological effects on factors that may predispose to diabetic retinopathy. Potential pathogenetic mechanisms include platelet dysfunction, altered eicosanoid production, increased blood viscosity in association with impaired cell deformability and pathologic leucocyte/endothelium interaction. Therefore, we tested whether a 6-month administration of fish oil (750 mg Maxepa, 5 times per week), containing 14% eicosapentaenoic acid (EPA) and 10% docosahexaenic acid, could inhibit the development of experimental retinopathy of the streptozotocin-diabetic rat. The efficiency of fish oil supplementation was evaluated by measuring EPA concentrations in total, plasma and membrane fatty acids and by measuring the generation of lipid mediators (leukotrienes and thromboxanes). Retinal digest preparations were quantitatively analysed for pericyte loss, and the formation of acellular capillaries. Omega-3 fatty acid administration to diabetic rats resulted in a twofold increase of EPA 20:5 in total fatty acids, and a reduction of the thromboxane ratio from 600 (untreated diabetic rats) to 50 (treated diabetic rats). Despite these biochemical changes, diabetes-associated pericyte loss remained unaffected and the formation of acellular, occluded capillaries was increased by 75% in the fish oil treated diabetic group (115.1 +/- 26.8; untreated diabetic 65.2 +/- 15.0 acellular capillary segments/mm2 of retinal area). We conclude from this study that dietary fish oil supplementation may be harmful for the diabetic microvasculature in the retina.

Effects of Chinese herbal products on mammalian retinal functions.

Ocular ischemia and inflammation are two major factors which induce retinal degeneration. Treatment of these diseases has been difficult, though numerous agents have been tried. Natural products could be a good field to venture into because various medicinal plants have been used for centuries to treat circulation stasis, inflammation, visual disturbances, and eyesight failure. Tetramethyl-pyrazine, coumarin, methyl tyramine, rescinnamine, apocynin, and hesperetin are some natural products isolated from Chinese herbs for improving ocular blood flow, particularly in the choroid and retina. For ocular inflammation, at least a dozen natural products are reviewed in this article. Among those, matrine, tetrandrine and osthole draw particular attention, because they are effective mainly as interleukin-1 blockers, but not as arachidonate blockers. As a result, these agents are potent anti-inflammatory agents and are even more potent than the prototype corticosteroid, prednisolone. It is hoped that all aforementioned agents can be used to treat retinopathies resulting from ocular ischemia and/or ocular inflammation. Scoparone, corylifolinin, epigallocatechin-3-0-gallate, esculetin, and lespedezaflavanone A are some natural products which can improve retinal functions measured with electroretinogram's b-wave recovery. Further research should be carried out to relate natural products which can improve ocular blood flow and inflammation to retinal function and vice versa.

Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate.

BACKGROUND: Lesions resembling those of human retinopathy of prematurity can be provoked in newborn Wistar rats by exposure to an FiO2 of 80% for the first 5 days of life followed by 5 days recovery under room-air conditions. METHODS: We evaluated the effects of moderate hyperbarism (+60.75 kPa, i.e. 455 mmHg or 0.6 atm) and topical administration of 0.25% timolol maleate on oxygen-induced retinopathy (OIR) in this experimental model. RESULTS: OIR (including neovascularization in most cases) was observed in 100% of the retinas of normobaric oxygen-reared ratlings that did not receive timolol. OIR was less frequent in oxygen-reared ratlings treated with hyperbarism (60%) or timolol (65%). Hyperbaric oxygen supplementation combined with timolol treatment during both the hyperoxic and room-air phases reduced the incidence of OIR to 30%. There was no sign of vasoproliferation in any of the retinas from the latter three groups. CONCLUSIONS: The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery.

[The modality of Huoxue-Huayu in treatment of retinal vein occlusion].

80 patients with retinal vein occlusion were randomly divided into 2 groups A and B to be treated with Fundus-III (a composite herbal recipe for Huoxue-Huayu or invigoration of blood circulation and reduction of blood stasis) and urokinase respectively for 1 month. The visual acuity in group A was remarkably improved while that in group B did not change. The extravasated retinal blood was evidently absorbed in 92.7% of the cases in group A and in 66.7% of those in group B, the difference being significant. Fundus-III also improved the retinal circulation, decreased the whole blood viscosity and fibrinogen content, and reduced leakage of the retinal capillaries. The total effective rates were 83.7% in group A and 58.7% in group B, with significant statistical difference between the 2 groups (P < 0.01).