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1.
Artículo en Inglés | MEDLINE | ID: mdl-26736187

RESUMEN

Manual micro-surgical tasks are fundamentally divided into grasping, cutting and injecting maneuvers performed on biological tissues. Efficient dissection of fibrous tissue from the surface of the retina often requires grasping and cutting maneuvers carried out simultaneously. True bimanual surgery requires that the surgeon contend with the innate hand tremor of two hands at once as well as unpredicted patient's movement. In this study, we develop and test a dual SMART micro-surgical system to suppress bimanual hand tremor during micro-surgical dissection.


Asunto(s)
Microcirugia/métodos , Cirugía Asistida por Computador/métodos , Tomografía de Coherencia Óptica/métodos , Humanos , Retina/cirugía
2.
Hum Gene Ther ; 12(16): 2029-32, 2001 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-11727737

RESUMEN

Age-Related Macular Degeneration (AMD) is, together with Diabetic Retinopathy, the most common cause of vision loss among adults in the U.S. and other developed countries. In the U.S., at least 1.7 million people have impaired vision due to AMD. Every year, more than 165,000 people contract AMD and 16,000 go blind from it, predominantly from a rapidly progressing form of the disease called "wet" AMD. Wet AMD is characterized by serious or hemorrhagic detachment of the retinal pigment epithelium and choroidal neovascularization. The macula has the highest concentration of photoreceptors facilitating central vision and permitting high-resolution visual acuity. The damage caused by the leakage and fibrovascular scarring in wet AMD leads to profound loss of central vision and severe loss of visual acuity (usually 20/200 or worse). People with wet AMD have several limitations, including inability to read, inability to recognize faces or drive, and the disease often leads to blindness. The onset of severe visual changes in wet AMD can occur suddenly. More than 400,000 Americans are currently affected by this form of the disease, and the incidence is rising rapidly with the aging of the population. Therefore, the serious consequences of this disease along with the limited treatment options and their effectiveness make this a very good candidate for a gene transfer treatment approach. The investigational agent, Ad(GV)PEDF.11D, is an E1-, partial E3-, E4- deleted replication-deficient, adenovirus serotype 5, gene transfer vector. The transgene in this vector is the cDNA for human pigment epithelium-derived factor (PEDF). PEDF is one of the most potent known antiangiogenic proteins found in humans. While Ad(GV)PEDF.11D is able to transduce many somatic cell types, the natural barrier to other tissues created by the retina limits the ability of Ad(GV)PEDF.11D to affect tissues other than in the eye. Intravitreal administration of Ad(GV)PEDF.11D provides a convenient means of delivering PEDF to the relevant cells within the eye likely to result in a more prolonged duration of effect versus administration of the PEDF protein alone. In three murine disease models (the laser-induced choroidal neovascularization model, the VEGF transgenic model, and the retinopathy of prematurity model) significant inhibition of neovascularization (up to 85%) was demonstrated with doses of Ad(GV)PEDF vectors ranging from 1 x 10(8) to 1 x 10(9) pu. In toxicology studies performed in Cynomolgus monkeys, a dose-related inflammatory response was observed. A dose of 1 x 10(8) pu caused no adverse effects, while the inflammatory response observed at 1 x 10(9) pu was minimal and fully reversible. The observed inflammatory response at doses of 1 x 10(10) and 5 x 10(10) pu were increasingly severe. The proposed clinical trial is an open-label, dose-escalation, phase I study to investigate the safety, tolerability and potential activity of intravitreal injection of Ad(GV)PEDF.11D in patients with wet AMD. Ad(GV)PEDF.11D will be injected once via intravitreal injection into the eye with the most advanced AMD based on visual acuity. Subjects will be age 50 or over and have severe wet AMD in at least one eye defined by a best-corrected vision of 20/200 or worse. The primary objectives of this investigation are: (1) to assess the safety, tolerability and feasibility of intravitreal injection of Ad(GV)PEDF.11D in patients with severe, neovascular AMD, (2) to identify the maximum tolerated dose (MTD) of Ad(GV)PEDF.11D, and (3) to get some indication of potential activity of Ad(GV)PEDF.11D.


Asunto(s)
Proteínas del Ojo , Terapia Genética , Degeneración Macular/terapia , Factores de Crecimiento Nervioso , Proteínas/genética , Serpinas/genética , Adenoviridae/genética , Envejecimiento/patología , Vectores Genéticos , Humanos
3.
J Pediatr Ophthalmol Strabismus ; 38(5): 279-83, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11587176

RESUMEN

PURPOSE: To report a series of infants who progressed from mild retinopathy of prematurity (ROP) to severe ROP with retinal detachment without demonstrating detectable threshold disease. METHODS: Between January 1993 and August 1998, seven infants at Oregon Health Sciences University, followed in accordance with the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP) protocol, progressed to retinal detachment despite documentation that threshold had not been reached. This outlying subset of patients was analyzed and compared to the cohort in the CRYO-ROP study. RESULTS: Six of 7 patients were male, 6 (86%) patients had symmetric disease, and all patients were born outside the study hospital. Mean birth-weight was 877 g and mean gestational age was 26 weeks. Mean postconceptual age at the time of retinal detachment was 41 weeks. Because of bilateral detachment in 3 patients, the total number of study eyes is 10. Failure to achieve threshold resulted from insufficient clock hours or insufficient stage in 2 eyes and lack of plus in 8 eyes. Zone I disease was present in 1 eye. CONCLUSION: Rarely, despite adhering to ROP examination protocol, the retina may detach without demonstrating antecedent threshold disease. Very low birthweight is a factor that may lead to a less predictable course. This study found a lack of plus disease results in failure to reach threshold more often than the occurrence of insufficient clock hours of stage 3 disease. Further study is needed to determine if selected cases of subthreshold ROP may benefit from ablative therapy.


Asunto(s)
Desprendimiento de Retina/etiología , Retinopatía de la Prematuridad/complicaciones , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recién Nacido de muy Bajo Peso , Masculino , Desprendimiento de Retina/fisiopatología , Retinopatía de la Prematuridad/fisiopatología , Factores de Riesgo
4.
Curr Eye Res ; 13(8): 597-602, 1994 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7956312

RESUMEN

Increased intraocular pressure and vascular ligation models are often used in studies of global ocular ischemia. The purpose of this study is to perform a paired comparison of retinal recovery in these paradigms. Our data indicate that ERG b-wave recovery profiles, following identical periods of ischemia, differ significantly between models. We propose that increased intraocular pressure models induce greater retinal injury than vascular ligation models. We suggest that pressure or another aspect of the increased intraocular pressure model induces injury beyond that caused by ischemia alone and caution against direct comparison of results obtained using these two models.


Asunto(s)
Modelos Animales de Enfermedad , Isquemia/fisiopatología , Retina/fisiología , Vasos Retinianos/fisiopatología , Animales , Gatos , Constricción Patológica , Electrorretinografía , Angiografía con Fluoresceína , Presión Intraocular , Perfusión , Daño por Reperfusión/fisiopatología
5.
Invest Ophthalmol Vis Sci ; 34(10): 2871-7, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7689545

RESUMEN

PURPOSE: The iron chelating agent deferoxamine mesylate USP (Desferal, Ciba, Summit, NJ) is commonly used in the treatment of acute iron intoxication and chronic iron overload (associated with the transfusion-dependent anemias). When used for prolonged periods of time or in high doses deferoxamine is attended by a range of ocular toxicities. The visual symptoms associated with deferoxamine administration often limit effective iron chelation therapy and can result in permanent vision loss. Deferoxamine has recently been conjugated to certain high molecular weight biocompatible polymers without altering its iron-binding properties. Here the effect of conjugation of deferoxamine to hydroxyethyl starch on retinal toxicity is examined. METHODS: An albino rat model of electroretinographically determined, deferoxamine-induced retinal toxicity has been previously described. We use this model to evaluate and compare both native deferoxamine and hydroxyethyl starch conjugated deferoxamine. RESULTS: Our data show that retinal function, as assessed by the electroretinogram b-wave, is significantly depressed 1 day after a single dose of native deferoxamine, while the b-waves of rats receiving a single dose of hydroxyethyl starch-deferoxamine, are not significantly depressed at any time during the study. In addition, the administered dose of hydroxyethyl starch-deferoxamine resulted in plasma deferoxamine concentrations up to five times greater than those achieved with native deferoxamine. CONCLUSION: These results suggest that hydroxyethyl starch conjugated deferoxamine is associated with less retinal toxicity than native deferoxamine and that it may be a safer alternative for iron chelation therapy.


Asunto(s)
Deferoxamina/toxicidad , Derivados de Hidroxietil Almidón/toxicidad , Retina/efectos de los fármacos , Animales , Adaptación a la Oscuridad , Electrorretinografía/efectos de los fármacos , Masculino , Estimulación Luminosa , Ratas , Ratas Wistar , Enfermedades de la Retina/inducido químicamente
6.
Invest Ophthalmol Vis Sci ; 34(8): 2596-9, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8325761

RESUMEN

PURPOSE: To examine a photoelectric artifact associated with the ERG-jet corneal contact lens electrode (Universe SA, La Chaux-de-Fons, Switzerland). METHODS: An artifact associated with the ERG-jet, gold foil corneal contact lens electrode was reproduced in vitro and in vivo using 50 msec light flashes. In vitro responses were examined using light flashes that varied in intensity, duration, and wavelength. Ionic strength of the bathing solution and temperature dependence were also examined. In vivo responses were compared to similarly recorded signals using the Burian-Allen bipolar electrode. RESULTS: The artifact is not apparent with microsecond light flashes, as with the Grass PS22 Photo-stimulator connected to a Ganzfeld. Longer light flashes and increasing light intensities, however, elicit graded responses that may resemble the late PIII component of the ERG in profile and in magnitude. The artifact varies with temperature, ionic concentration of the bathing medium, and wavelength of stimulating light. The artifact also varies in magnitude and polarity from one disposable electrode to the next. Light flashes of shorter wavelengths elicit greater responses than light flashes of equal radiant energy but of longer wavelengths. CONCLUSIONS: The artifact derives from electrode polarization occurring at the interface between the gold foil and its ionic medium. Caution is required when using light stimuli longer than 2-3 msec with this and similar types of intrinsically polarizable metal electrodes.


Asunto(s)
Artefactos , Electrorretinografía , Microelectrodos , Lentes de Contacto , Córnea/fisiología , Oro , Humanos , Luz
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