RESUMEN
The surface structure of crystalline particles affects the functionality of the particles in drug delivery. Prediction of the final structure of particles that crystallize easily within the spray drying process is of interests for many applications. A theoretical framework was developed for the prediction of crystal structure precipitating on the surface of the particle. This model was based on the dimensionless Damkohler number (Da), to be an indicator of final particle morphology. Timescales of evaporation and reaction were required for calculation of the Damkohler number. The modified evaporation time scale was estimated based on the time that is available for the crystal to precipitate after supersaturation. The reaction time scale was estimated based on the time scale for induction time. Mannitol was produced under different processing conditions in order to validate the theoretical model. Results showed for the high Damkohler numbers, the surface structure of the particle was rough, while smaller Damkohler numbers led to relatively smooth particle surfaces. Additionally, although the beta polymorph was dominant in all of the experiments, alpha polymorph was precipitated in the experiments with a large Damkohler number. The theoretical framework developed will be a useful predictive tool to guide the manipulation of particle crystallization in spray dryers.
Asunto(s)
Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos , Excipientes/química , Manitol/química , Cristalización , Desecación , Modelos Teóricos , Propiedades de Superficie , Factores de TiempoRESUMEN
PURPOSE: To investigate the relationship between optic disk topography and intraocular pressure before and after trabeculectomy with confocal scanning laser ophthalmoscopy. METHODS: The eyes of 49 consecutive patients undergoing trabeculectomy at a university-based glaucoma practice underwent preoperative and postoperative imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph). Three images of one eye of each patient were obtained with a 15-degree field of view. Preoperative images were obtained approximately 2 months before surgery (mean +/- SD, 2.4 +/- 1.6 months). Postoperative images were obtained at least 3 months after surgery (mean, 4.5 +/- 2.6 months). RESULTS: Mean preoperative intraocular pressure, postoperative intraocular pressure, and percent change in intraocular pressure respectively were 23.1 +/- 6.8 mm Hg, 12.7 +/- 7.1 mm Hg, and 43.8% +/- 29.9%. A significant association (P < .01) was found between percent decrease in intraocular pressure and decreases in cup area, cup volume, and cup/disk area ratio as well as between percent decrease in intraocular pressure and increases in rim area, rim volume, mean height contour, retinal cross-section area, and height in contour. Between 11.7% and 31.2% of the variability (R2) in these parameters was explained by the percent change in intraocular pressure. Topography changes were more strongly associated with percent change than with mean change in intraocular pressure. We found no association between percent decrease in intraocular pressure and reference plane height or maximum cup depth. CONCLUSIONS: Changes in optic nerve topography were associated with reduction in intraocular pressure after trabeculectomy.
Asunto(s)
Glaucoma/cirugía , Disco Óptico/patología , Trabeculectomía , Centros Médicos Académicos , Anciano , Humanos , Presión Intraocular , Rayos Láser , Oftalmoscopios , Nervio Óptico/patología , Retina/patologíaRESUMEN
PURPOSE: To evaluate the association between quantitative nerve fiber layer measurements and visual field loss in patients with primary open-angle glaucoma. METHODS: Quantitative retinal nerve fiber layer measurements were obtained in 53 patients with primary open-angle glaucoma by using confocal scanning laser ophthalmoscopy (cross-section area) and confocal scanning laser polarimetry (retardation ratio). For each eye, three images were obtained with each instrument. An image that was the mean of those three was created and used in all analyses. We investigated the association between global, regional, and hemifield differences in retinal nerve fiber layer measurements and visual field loss with linear regression techniques. RESULTS: The retardation ratio decreased with increasing mean visual field loss, measured both globally and regionally; R2 (the amount of variation explained by the model) ranged from 8% to 21%. Retinal nerve fiber layer cross-section area was not significantly associated with global measures of visual field loss. The inferior visual field mean deviation increased with decreasing superior retinal nerve fiber layer cross-section area (R2 = 8.2%, P = .04); superior visual field mean deviation was not associated with inferior retinal nerve fiber layer cross-section area (R2 = 2.6%, P = .25). Hemifield differences in visual field mean deviation increased with increasing hemifield differences in retinal nerve fiber layer cross-section area (R2 = 20.0%, P < .001), but not with retardation ratio (R2 = 0.9%, P = .48). CONCLUSIONS: Quantitative measures of the retinal nerve fiber layer using both confocal scanning laser ophthalmoscopy and confocal scanning laser polarimetry were correlated with visual field loss in glaucoma patients.
Asunto(s)
Glaucoma/patología , Glaucoma/fisiopatología , Retina/patología , Campos Visuales , Anciano , Femenino , Humanos , Masculino , Microscopía Confocal , Persona de Mediana Edad , Fibras Nerviosas/patologíaRESUMEN
Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.
Asunto(s)
Aciclovir/análogos & derivados , Antivirales/farmacología , Fosfatidilgliceroles/farmacología , Profármacos/farmacología , Cuerpo Vítreo/metabolismo , Aciclovir/farmacocinética , Aciclovir/farmacología , Aciclovir/toxicidad , Animales , Antivirales/farmacocinética , Antivirales/toxicidad , Células Cultivadas , Citomegalovirus/efectos de los fármacos , Portadores de Fármacos , Ganciclovir/farmacocinética , Humanos , Liposomas , Fosfatidilgliceroles/farmacocinética , Fosfatidilgliceroles/toxicidad , Profármacos/farmacocinética , Profármacos/toxicidad , Conejos , Replicación Viral/efectos de los fármacosRESUMEN
PURPOSE: To determine whether retardation (change in polarization) measurements of healthy subjects and glaucoma patients obtained by using a confocal scanning laser polarimeter correspond to known properties of the nerve fiber layer. METHODS: A polarimeter, an optical device used to measure the change in linear polarization of light (retardation), was interfaced with a scanning laser ophthalmoscope to obtain retardation data at 65,536 locations (256 x 256 pixels) in a study of normal subjects and patients with primary open-angle glaucoma. To validate the instrument, we compared our measurements with known properties of the human retinal nerve fiber layer in 105 normal subjects. Additionally, we compared retardation measurements in eyes of 64 normal subjects and 64 age-matched glaucoma patients treated in a referral practice. RESULTS: In normal eyes, mean (+/- S.D.) peripapillary retardation was highest in the superior and inferior arcuate regions and lowest in the temporal and nasal regions, 12.0 +/- 1.9, 13.1 +/- 2.0, 7.0 +/- 1.8, and 7.0 +/- 1.6 degrees, respectively. Retardation decreased toward the periphery and was lower over blood vessels. In normal eyes, retardation decreased with increasing age in the superior and inferior regions. Mean retardation was statistically significantly higher among normal eyes than glaucoma eyes in the inferior and superior regions but not in the temporal or nasal areas. CONCLUSIONS: Scanning laser polarimetry provides quantitative measurements that correspond to known properties of the retinal nerve fiber layer in normal and glaucomatous eyes.
Asunto(s)
Glaucoma de Ángulo Abierto/patología , Fibras Nerviosas/patología , Oftalmoscopios , Nervio Óptico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fondo de Ojo , Humanos , Rayos Láser , Masculino , Persona de Mediana Edad , Disco Óptico/patología , Dispositivos Ópticos , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: We assessed agreement between cup/disk ratio measurements obtained by glaucoma expert evaluation of stereoscopic photographs of the optic disk and those obtained with a confocal scanning laser ophthalmoscope. METHODS: Three glaucoma experts estimated vertical and horizontal cup/disk ratios from stereoscopic photographs of 15 normal subjects and 15 patients with glaucoma. These estimates were compared to vertical, horizontal, and area cup/disk ratios measured with a confocal scanning laser ophthalmoscope. Intraobserver and interobserver agreements were also estimated. RESULTS: Agreement between clinicians and the confocal scanning laser ophthalmoscope varied by clinician. Agreement was moderate to substantial for vertical cup/disk ratio and fair to moderate for horizontal cup/disk ratio; kappas ranged from 0.57 to 0.72 and from 0.21 to 0.55, respectively. The mean confocal scanning laser ophthalmoscope area cup/disk ratio measurements were smaller than each clinician's mean vertical and horizontal cup/disk ratio estimates; differences ranged from 0.10 to 0.24 and from 0.06 to 0.16, respectively. Differences were smaller between clinician estimates and instrument measurements of horizontal and vertical cup/disk ratios of patients with glaucoma than normal subjects. CONCLUSIONS: These results demonstrate good agreement between confocal scanning laser ophthalmoscope measurements and clinician estimates of the vertical cup/disk ratios from stereoscopic photographs, particularly of patients with glaucoma. However, as differences between clinician and instrument estimates of cup/disk ratios were found, new quantitative criteria must be established for characterizing a disk as glaucomatous using confocal scanning laser ophthalmoscopy.
Asunto(s)
Glaucoma de Ángulo Abierto/patología , Microscopía Confocal , Oftalmoscopía/métodos , Disco Óptico/patología , Nervio Óptico/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Fotograbar , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To determine the intraocular tolerance of perfluorooctylbromide (perflubron) in vitrectomized rabbit and pig eyes and evaluated its use as a vitreous substitute in virteoretinal surgery. METHODS: Pars plana vitrectomy was performed on 33 Dutch pigmented rabbits and 11 micro mini pigs. After vitrectomy the eyes were filled with perflubron for 2 hours, 1 week, 2 weeks, 1 month, and up to 6 months. RESULTS: No clinical, electroretinographic, or light and electron microscopic evidence of adverse effects on the retina and lens were observed. Perflubron emulsified and dispersed into small bubbles after 2-3 weeks. The lens showed mild posterior subcapsular cataracts in pig eyes after long-term retention of perflubron. CONCLUSION: These findings indicate that perflubron is safe for intraoperative and for long-term use intravitreally. However, emulsification and the breakdown into small bubbles limits the view of the retina when perflubron is used as a long-term tamponade.
Asunto(s)
Fluorocarburos/toxicidad , Retina/efectos de los fármacos , Vitrectomía , Animales , Catarata/inducido químicamente , Catarata/patología , Tolerancia a Medicamentos , Electrorretinografía , Emulsiones , Hidrocarburos Bromados , Cristalino/efectos de los fármacos , Cristalino/patología , Estudios Longitudinales , Conejos , Retina/fisiología , Retina/ultraestructura , Porcinos , Porcinos Enanos , Cuerpo Vítreo/efectos de los fármacosRESUMEN
PURPOSE: Human cytomegalovirus (HCMV) is an important pathogen in the immunocompromised patient. CMV retinitis is a leading cause of blindness in patients with AIDS. Ganciclovir and foscarnet are currently the treatments being used for this retinitis, but they both have major toxicities when used systemically. Intravitreal therapy with ganciclovir has been used in some patients who cannot tolerate systemic treatment. The major problem with this modality is the necessity for administration of between 1 and 3 intravitreal injections per eye per week. 2'-nor-cyclic GMP is a nucleotide analog, a cyclic phosphate derivative of ganciclovir. Neutral salts of the compound are extremely water soluble, and the charged phosphate group at neutral pH make it an ideal candidate for encapsulation into a multivesicular liposome system. METHODS: The authors evaluated the retinal toxicity of the diethanolammonium salt 2'-nor-cyclic GMP by using electroretinographic, morphologic, and ophthalmoscopic techniques after intravitreal injections in rabbit eye. RESULTS: The intraocular therapeutic index for 2'-nor-cyclic GMP is 20. At the 10 micrograms dose, electroretinogram, ophthalmoscopic examination, and both light and electron microscopy revealed no abnormalities. Toxicity was evident at 50 micrograms and higher doses with ERG changes (loss of amplitude) and retinal pathology that varied from vacuolization of the retinal pigment epithelium and loss of height of the outer photoreceptor segment to loss of the entire outer retina. In addition, an in vitro drug release half-life of 1,000 hours (more than 75 times that of ganciclovir) was found for 2'-nor-cyclic GMP in liposome, which may be able to be exploited in the therapy of patients with CMV retinitis unable to tolerate toxic systemic therapy. CONCLUSION: The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.