Ginseng Extract Modified by Pectin Lyase Inhibits Retinal Vascular Injury and Blood-Retinal Barrier Breakage in a Rat Model of Diabetes.

GS-E3D is an enzymatically modified ginseng extract by pectin lyase. In this study, we evaluated the preventive effects of GS-E3D on blood-retinal barrier (BRB) leakage in a rat model of diabetes. To produce diabetes, rats were injected with streptozotocin. GS-E3D was orally gavaged at 25, 50, and 100 mg/kg body weight for 6 weeks. We then compared the effect of GS-E3D with that of an unmodified ginseng extract (UGE) on retinal vascular leakage. The administration of GS-E3D significantly blocked diabetes-induced BRB breakdown. Immunofluorescence staining showed that GS-E3D reduced the loss of occludin in diabetic rats. In TUNEL staining, the number of apoptotic retinal microvascular cells was dose dependently decreased by GS-E3D treatment. GS-E3D decreased the accumulations of advanced glycation end products in the retinal vessels. In addition, the inhibition potential of GS-E3D on BRB breakage was stronger compared with UGE. These results indicate that GS-E3D could be a beneficial treatment option for preventing diabetes-induced retinal vascular injury.

Frosted branch angiitis with penetrating ocular trauma and retained intraocular foreign body.

A 54-year-old male sustained ocular trauma with a projectile. Examination of the right eye revealed an intraocular foreign body (IOFB) adjacent to the optic nerve head, vitritis, vitreous hemorrhage, and translucent perivascular sheathing of the retinal vessels in all quadrants suggesting frosted branch angiitis (FBA). The patient underwent vitrectomy with removal of the IOFB and silicone oil tamponade under steroid cover. With continued use of systemic and topical steroids after surgery, complete resolution of FBA and improvement in vision were noted in a week. Prompt resolution of FBA after IOFB removal points toward a strong association between the presence of IOFB and FBA.

Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways.

Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.

Atrofia macular en el síndrome de Terson / Macular atrophy in Terson‘s syndrome

CASO CLÍNICO: Se presenta el caso clínico de un varón de 63 años con una atrofia macular en el curso de un síndrome de Terson. El paciente mostraba una disminución de la agudeza visual con adelgazamiento macular observado en la tomografía óptica de coherencia. DISCUSIÓN: El paciente presentó una atrofia macular probablemente secundaria a una hemorragia en polo posterior, tras síndrome de Terson causado por la rotura de un aneurisma cerebral

CASE REPORT: The case is presented on a 63-year-old patient with Terson's syndrome who complained of loss of visual acuity. The optical coherence tomography showed macular atrophy. DISCUSSION: The patient developed macular atrophy probably secondary to macular hemorrhage caused by the rupture of a cerebral aneurysm

Macrovaso congénito retiniano: presentación atípica con baja visión y engrosamiento macular / Congenital retinal macrovessel: An atypical presentation with low vision and macular thickening

CASO CLÍNICO: Se presenta el caso de un varón de 35 años sin antecedentes de interés que consulta por mala visión del ojo izquierdo objetivada de forma fortuita, en el cual tras un completo estudio se llega al diagnóstico de macrovaso congénito retiniano con engrosamiento macular. DISCUSIÓN: Los macrovasos congénitos retinianos son una rara anomalía vascular cuyo diagnóstico suele ser casual ya que la repercusión visual es mínima. En los pocos casos en que se produce afectación visual importante, esta se debe a hemorragias maculares, quistes foveales, desprendimiento seroso macular o al propio transcurso del vaso por la zona avascular foveal

CASE REPORT: We report a case of a 35 year old male patient with no medical history, who experienced decreased vision in his left eye that he noticed by chance. After a complete ophthalmic examination, he was diagnosed with congenital retinal macrovessel with macular thickening. DISCUSSION: Congenital retinal macrovessels are rare vascular anomalies, in which the diagnosis is usually incidental as their visual impact is minimal. In the rare cases where there is a significant visual impairment, this is due to macular hemorrhages, foveal cysts, serous macular detachment, or the course of the vessel itself through the foveal avascular zone

Retinal hemorrhage in abusive head trauma.

Retinal hemorrhage is a cardinal manifestation of abusive head trauma. Over the 30 years since the recognition of this association, multiple streams of research, including clinical, postmortem, animal, mechanical, and finite element studies, have created a robust understanding of the clinical features, diagnostic importance, differential diagnosis, and pathophysiology of this finding. The importance of describing the hemorrhages adequately is paramount in ensuring accurate and complete differential diagnosis. Challenges remain in developing models that adequately replicate the forces required to cause retinal hemorrhage in children. Although questions, such as the effect of increased intracranial pressure, hypoxia, and impact, are still raised (particularly in court), clinicians can confidently rely on a large and solid evidence base when assessing the implications of retinal hemorrhage in children with concern of possible child abuse.

Temperature distribution during ICG-dye-enhanced laser photocoagulation of feeder vessels in treatment of AMD-related choroidal neovascularization.

Laser photocoagulation of the feeder vessels of age-related macula degeneration-related choroidal neovascularization (CNV) membranes is a compelling treatment modality, one important reason being that the treatment site is removed from the fovea in cases of sub- or juxtafoveal CNV. To enhance the energy absorption in a target feeder vessel, an indocyanine green dye bolus is injected intravenously, and the 805 nm wavelength diode laser beam is applied when the dye bolus transits the feeder vessel; this tends to reduce concomitant damage to adjacent tissue. A 3D theoretical simulation, using the Pennes bioheat equation, was performed to study the temperature distribution in the choroidal feeder vessel and its vicinity during laser photocoagulation. The results indicate that temperature elevation in the target feeder vessel increases by 20% in dye-enhanced photocoagulation, compared to just photocoagulation alone. The dye bolus not only increases the laser energy absorption in the feeder vessel but also shifts the epicenter of maximum temperature away from the sensitive sensory retina and retinal pigment epithelial layers and toward the feeder vessel. Two dominant factors in temperature elevation of the feeder vessel are location of the feeder vessel and blood flow velocity through it. Feeder vessel temperature elevation becomes smaller as distance between it and the choriocapillaris layer increases. The cooling effect of blood flow through the feeder vessel can reduce the temperature elevation by up to 21% of the maximum that could be produced. Calculations were also performed to examine the effect of the size of the laser spot. To achieve the same temperature elevation in the feeder vessel when the laser spot diameter is doubled, the laser power level has to be increased by only 60%. In addition, our results have suggested that more studies are needed to measure the constants in the Arrhenius integral for assessing thermal damage in various tissues.

A picture worth remembering: posttraumatic Purtscher's retinopathy in a child.

Purtscher's retinopathy is frequently described and reviewed in the ophthalmology literature but is rarely described in the neurology literature, although neurologists are routinely involved in the care of head and chest trauma patients with abnormal neurologic and funduscopic findings. The case of a 6-year-old girl with Purtscher's retinopathy is described, and the relevant literature is reviewed.

Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells.

Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34(+) cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34(+) cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34(+) cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.

Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic retinopathy (DR) is a highly specific vascular complication of type 1 and type 2 diabetes mellitus. Calcium dobesilate (DOBE) has been tested in the treatment of diabetic retinopathy showing a slowdown of the progression of the disease after long-term oral treatment. The aim of this study was to determine the effects of DOBE on vascular and diabetic retinopathy in streptozotocin (STZ) diabetic rats. METHODS: Diabetes was induced in wistar rats by the administration of STZ (60 mg/kg, i.p.). Rats were divided into three groups (n = 30). Group 0 (GO): nondiabetic rats. Group 1 (G1): 14 months of insulin treatment after diabetes development. Group 2 (G2): 14 months of insulin treatment after diabetes development plus DOBE (500 mg/kg/day). At the end of the treatment, vascular reactivity was tested. The study of the vascularization of the retina was performed on wholemounts of trypsin retinal digest preparations and retinal sections. RESULTS: Relaxation induced by acetylcholine decreased in the aorta arteries from diabetic rats but it was restored to control values in the DOBE-treated group (71.8 +/- 4.5%, 53.3 +/- 0.5%, 67.4 +/- 4.6% in group 0, 1 and 2 respectively). DOBE treatment also restored noradrenaline (1.08 +/- 0.05 g, 1.70 +/- 0.08 g, 1.13 +/- 0.05 g in group 0, 1 and 2 respectively) and caffeine-induced contractions. Diabetic state did not cause any alteration in mesenteric arteries. The analysis of the retinal digests showed vascular tortuosity, acellular capillaries, focal accumulations of capillaries and reduction of the number of pericytes in G1. The vascular changes observed in G2 seem to be intermediate between the control and the diabetic rats. CONCLUSIONS: We showed that long-term treatment with DOBE attenuated the progression of diabetic retinopathy and the alterations in vascular reactivity in streptozotocin-induced diabetic rats.

[Prognosis and differential diagnosis of Purtscher's retinopathy]. / Prognose und Differenzialdiagnose des Morbus Purtscher.

BACKGROUND: Purtscher's retinopathy is accompanied by a distinct loss of vision as a result of severe trauma to the chest or skull. Reports on visual prognosis in the literature are not uniform. PATIENTS: The data of 10 patients with Purtscher's retinopathy from the department of Ophthalmology in Freiburg, published data from 55 patients with Purtscher's retinopathy and 20 patients with traumatic retinal hemorrhages taken from the literature were evaluated. RESULTS: The average visual acuity of the 10 patients from Freiburg was 0.3 within a short period after the accident and the final average visual acuity was 0.46. The average visual acuity of the 55 patients with Purtscher's retinopathy was 0.21 within a short period after the accident with an average final visual acuity of 0.61. The average visual acuity of the 20 patients with traumatic retinal hemorrhages from the literature was 0.45 within a short period after the accident with an average final visual acuity of 0.74. Therefore the initial and the final visual acuity were better in patients with traumatic retinal hemorrhages compared to patients with Purtscher's retinopathy. CONCLUSION: In spite of severe initial retinal findings, the visual prognosis is usually not disappointing. Prognosis of visual acuity was better in patients with traumatic retinal hemorrhages compared to patients with Purtscher's retinopathy.

Echographic evaluation of a patient with diabetes and dense vitreous hemorrhage: an avulsed retinal vessel may mimic a tractional retinal detachment.

PURPOSE: To report that an avulsed retinal vessel may appear as a tractional retinal detachment on echographic evaluation. METHODS: Case report. RESULTS: A 57-year-old diabetic woman presented with a nonclearing vitreous hemorrhage of 2 months duration in the left eye. Echography was consistent with a localized tractional retinal detachment on longitudinal sections; transverse sections demonstrated a pinpoint opacity in the vitreous cavity. Intraoperatively, an avulsed retinal vessel was noted in the area of echographic abnormality. CONCLUSION: An avulsed retinal vessel may mimic tractional retinal detachment on echography. Although trained ophthalmic echographers routinely perform both longitudinal and transverse sections during an echographic evaluation, less skilled observers must be aware of the importance of performing both longitudinal and transverse sections for accurate echographic diagnosis.

Müller cells in the preconditioned retinal ischemic injury rat.

The role of Müller cells in the preconditioned retinal ischemic injury rat was investigated. In anesthetized Sprague Dawley rats, retinal ischemia for 5 minutes constituted the preconditioning stimulus for the left eye. After 24 hours, both eyes were clamped for 60 minutes. In 30, 60, 90, and 120, minutes and 1 day, 3 days, and 7 days after ischemia, electroretinograms were recorded, and the eyeballs were enucleated. After fixation with 4% paraformaldehyde, the avidin-biotin-peroxidase technique was applied to show glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). Furthermore, for the solubilized retinas, Western blot analysis and enzyme-linked immunosorbent assay were performed to detect GS and GFAP in the extracts. Preconditioning performed 24 hours before ischemia significantly improved the recovery of the a-, and b-waves 1 day after 60 minute ischemia. In the 30, 60, 90, and 120 minutes after ischemia, the recovery of the a-wave only was observed. There was a nonsignificant trend toward greater recovery in the first 120 minutes after 60 minute ischemia, especially in the b-wave. GS immunoreactivity had no significant difference between non-preconditioned and preconditioned groups 30, 60, 90, and 120 minutes after ischemia. In 1 day after ischemia, GS immunoreactivity decreased in both groups. In 3 and 7 days after ischemia, GS immunoreactivity recovered only in the preconditioned group. The retinas at 3 and 7 days after 1 hour of ischemia showed increased GFAP immunoreactivity in the non-preconditioned group. In the preconditioned group, only slight GFAP immunoreactivity was observed. These results suggested that the mechanism of preconditioned retinal ischemia may be related to Müller cells in the retina.

A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits.

PURPOSE: Intravitreal injections of tissue plasminogen activator have been used to lyse fibrin from blood in the subretinal space, despite the lack of proof that tissue plasminogen activator can diffuse across the retina. We tested whether tissue plasminogen activator injected into the vitreous could penetrate the neural retina and enter the subretinal space. METHODS: We injected a mixture of 50 microg of tissue plasminogen activator (70 kD) labeled with fluorescein isothiocyanate and rhodamine B isothiocyanate-labeled dextran, which has a lower molecular weight (20 kD), into the midvitreous cavity of one eye in each of 18 rabbits. The eyes were enucleated after 3, 6, and 24 hours, and cryosections were examined with epifluorescent microscopy to determine the distribution of the labeled molecules. We also evaluated tissue plasminogen activator pharmacokinetics in one eye each of 18 rabbits in which a subretinal clot was induced by injecting autologous blood (50 microL) into the subretinal space through the sclera. Fluorescein isothiocyanate-labeled tissue plasminogen activator was injected into the vitreous 2 days after induction of the subretinal clot. RESULTS: Fluorescein isothiocyanate-labeled tissue plasminogen activator was present at the vitreal surface of the retina in a linear array in all 36 eyes studied, whereas the rhodamine B isothiocyanate-labeled dextran had diffused throughout the neural retina in the same sections. No fluorescein isothiocyanate signal was observed in the neural retina or in the subretinal clot. Vitreous hemorrhage caused by retinal perforation was observed in all eyes with intraretinal hemorrhage in which fluorescein isothiocyanate fluorescence was seen in the neural retina and inside the clot. CONCLUSION: Intravitreal tissue plasminogen activator did not diffuse through the intact neural retina to reach a subretinal clot. This study demonstrates no scientific rationale for the intravitreal tissue plasminogen activator treatment of submacular hemorrhage without vitreous hemorrhage presumably caused by an overlying retinal break.

[Color Doppler echography study of ocular blood flow velocity in patients with proliferative diabetic retinopathy after performance of retinal pan-photocoagulation: 2 years' follow-up]. / Estudio mediante ecografía Doppler color de las velocidades de flujo sanguíneo ocular en pacientes afectos de retinopatía diabética proliferante tras la realización de panfotocoagulación retiniana: dos años de seguimiento.

PURPOSE: Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the authors compared 25 eyes with proliferative diabetic retinopathy before, 6 months, 1 year, and 2 years after panretinal photocoagulation with a matched control group of 30 healthy volunteers. METHODS: The ophthalmic artery, short posterior ciliary artery, central retinal vessels and vortex veins of all patients were examined, and the systolic, diastolic and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1s, 500 micron argon laser. RESULTS: Student's t test revealed that the perfusion velocity was significantly lower in diabetic patients than in normals (Vsystolic in the ophthalmic artery: 31.7 (6.7) cm/s vs 36.6 (7.0) cm/s, respectively, P = 0.03). After treatment, blood flow velocities were significantly lower than before photocoagulation (Vsystolic in the ophthalmic artery: 6 months after treatment 26.9 (7.2) cm/s, P = 0.018 and 1 year after photocoagulation 25.5 (7.0) cm/s, P = 0.009; and 2 years after photocoagulation, 25.7 (6.8) cm/s, P = 0.01). No statistically significant differences were found between 6 months, 1 year, and 2 years after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. CONCLUSIONS: Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals. Photocoagulation resulted in a reduction in ocular blood flow velocities; these values did not change during 2 years of follow-up.

Systemic toxicology and laser safety of laser targeted angiography with heat sensitive liposomes.

Angiography is currently limited by its lack of local and tissue specificity. The dye rapidly fills both the retinal and choroidal vessels and leaks out of the vessels thus hampering visualization of small vascular beds such as occult choroidal neovascularization. We have developed a method of laser targeted delivery based on encapsulating the dye in heat sensitive liposomes, administering the liposomes intravenously and causing them to release their content by noninvasively warming the target tissue with a laser pulse delivered through the pupil. The local release yields a bright fluorescent bolus which selectively highlights retinal or choroidal vessels. A preliminary investigation of the potential side effects of the method is presented. In rats the systemic toxicity of carboxyfluorescein-entrapped liposomes was compared with that of the free dye. No significant difference was found between the two. Non-human primates exposed to repeated laser targeted angiography were monitored over time and no significant side effects were observed. The safety of the laser exposures was assessed by conventional fluorescein angiography and histopathology. Choroidal laser targeted angiography was achieved without damage. Retinal laser targeted angiography was accompanied by mild and local damage in an area remote from the fovea. The study indicates that laser targeted choroidal angiography can be performed safely and holds promise for diseases such as age related macular degeneration with occult choroidal neovascularization. Further improvements are needed to ensure that no side effects accompany retinal laser targeted angiography.