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Biomedical subjects

M Shahidi

Publications and source records attributed to M Shahidi.

18 recordsLinked to original sources

A new method for noninvasive optical sectioning of the chorioretinal vasculature.

PURPOSE: To report a new method for optical sectioning of the chorioretinal vasculature to improve the visualization of vascular abnormalities due to chorioretinal eye diseases. METHODS: An imaging system was developed for optical sectioning of the vasculature called chorioretinal optical sectioning (CROS). CROS consists of projecting a laser beam at an angle on the retina after injection of a fluorescent dye and viewing the fluorescence. On the fluorescence optical section (FOS) image, the vasculature of the retina and choroid appear laterally displaced according to their depth location. The laser beam is scanned over a 2 X 2-mm area to generate 40 FOS images, each spatially separated by 50 microm on the retina. Optical section images of the vascular layers are constructed from the series of FOS images. RESULTS: CROS permitted optical separation of vascular layers in living eyes. Optical section images of normal and laser-photocoagulated retinas had higher contrast than conventional angiography because of the separation of the fluorescence from the overlapping layers and allowed enhanced visualization of vascular abnormalities. CONCLUSIONS: CROS enhances the visualization of the retinal and subretinal vasculature and promises to be a beneficial tool for evaluation of chorioretinal diseases.

Animals

Clinical assessment of the macula by retinal topography and thickness mapping.

PURPOSE: To report a quantitative and objective method for assessing pathologic alterations in retinal structures to improve the evaluation of macular diseases. METHODS: We used a system based on the scanning retinal thickness analyzer to generate serial optical section images of the retina and provide mapping of the retinal topography and thickness in a normal subject and in patients with representative maculopathies including traumatic macular hole, central serous chorioretinopathy, branch retinal vein occlusion, diabetic macular edema, and retinal pigment epithelial detachment. RESULTS: The effectiveness of the system in imaging both the vitreoretinal and chorioretinal interfaces was confirmed in the normal subject and in patients with various maculopathies. Mapping of retinal topography and thickness in a normal eye correlated well with normal anatomy, delineating the foveal depression clearly. The retinal thickness map in a patient with diabetic macular edema showed thickening of the retina and absence of a foveal depression. The patients with central serous chorioretinopathy and branch retinal vein occlusion had an elevated vitreoretinal surface. Conversely, the patient with retinal pigment epithelial detachments had a relatively flat vitreoretinal interface but an irregularly elevated chorioretinal surface. CONCLUSION: Quantitative mapping of retinal topography and thickness is a promising tool that may improve evaluation of macular diseases.

Adult

A new method for rapid mapping of the retinal thickness at the posterior pole.

PURPOSE: An objective, quantitative, and sensitive method to map retinal thickness is needed to diagnose more effectively the conditions causing alterations in thickness, such as macular edema and neuroretinal atrophy. METHODS: An instrument, the retinal thickness analyzer, was developed into a rapid scanning instrument, capable of covering macular areas of 2 x 2 mm in 200 or 400 msec and generating a detailed map of the retinal thickness. The performance was assessed in vitro and in five normal subjects who were scanned on three separate visits. RESULTS: Optimal depth precision was 5 to 10 microns, and the optimal depth resolution was 50 microns. Reproducibility was +/- 12 microns on the same day, +/- 13 microns for single maps obtained in multiple visits, and +/- 10 microns for three averaged maps per visit obtained in multiple visits. CONCLUSIONS: This new method to analyze retinal thickness provides four unique features: multiple optical cross-sectioning of the retina, mapping of retinal thickness, high reproducibility, and short acquisition time. These capabilities promise to improve the diagnosis and management of common diseases such as macular edema and glaucoma.

Adult

Illustration of the stages of idiopathic macular holes by laser biomicroscopy.

BACKGROUND: The determination of the developmental stage of macular holes is difficult to assess clinically. This may be the reason for the conflicting reports on the risk of vision loss in patients with macular holes and on the value of prophylactic surgery. We have developed a new method, laser biomicroscopy, which provides visualization and photographic record of vitreoretinal structures at the macula. OBJECTIVE: To test the applicability of this method to the identification of macular holes stages. METHODS: Laser biomicroscopy and slit-lamp biomicroscopy were used to examine 18 patients with macular holes, identify the lesions, and classify them according to the various stages of development of idiopathic macular holes as proposed by Gass. RESULTS: Reflections considered to originate from the hyaloid membrane were observed more frequently by laser biomicroscopy than by conventional slit-lamp biomicroscopy. Two fellow eyes were diagnosed by laser biomicroscopy as having stage 1 lesions while slit-lamp biomicroscopy failed to yield a clear diagnosis. In four eyes with stage 3 holes the vitreoretinal separation was apparent only on laser biomicroscopy. Four cases were selected to illustrate the laser biomicroscopic findings in the different stages of macular hole development. CONCLUSIONS: The ease of visualization of the macular lesions with laser biomicroscopy may facilitate the evaluation of the early stages of macular holes and reduce the incidence of misdiagnosis. Furthermore, photographs obtained by laser biomicroscopy may be a useful tool in studies of early stages of macular holes.

Aged

Local response of the primate retinal microcirculation to increased metabolic demand induced by flicker.

PURPOSE: To study the response of the macular circulation to a local increase in metabolic demand created by a flickering source of illumination. METHODS: Laser-targeted angiography (release of a fluorescent dye from heat-sensitive liposomes using a laser pulse) was used to study, in subhuman primates, changes in hemodynamic parameters of the retinal circulation that were induced by a flickering source of illumination. Changes in the macular macrocirculation were compared with those in the macular microcirculation and were evaluated at various distances from the foveola. RESULTS: In response to monochromatic light flicker, the blood flow in retinal arteries increased by 30%. The response of the microcirculation was not homogeneous. It showed a maximum increase in the mid-perifoveal region where there is an increase in ganglion cells and nerve fibers. Interestingly, the maximum change in the index representing capillary blood flow exceeded the blood flow change in the artery (P < 0.08). CONCLUSIONS: A stimulus expected to cause increased metabolic demand results in a regulatory response by the retinal microcirculation. This response shows spatial variations that correspond with known variations in retinal anatomy. The authors propose that a redistribution of blood can occur between the capillary layers to fulfill high metabolic demands by neuronal tissue remote from the choroid.

Animals

Foveal thickening in retinitis pigmentosa patients with cystoid macular edema.

PURPOSE: Clinical evaluation of cystoid macular edema (CME), known to occur in patients with retinitis pigmentosa (RP), is based on the presence of vascular leakage on fluorescein angiography. Due to an inability to quantitatively assess retinal thickening, the degree of thickening from fluid accumulation and its relation to fluorescein dye leakage into the extravascular retinal space has not been established. The relationship between fluorescein dye leakage and foveal thickening and the effect of methazolamide treatment was studied. METHODS: The retinal thickness analyzer was used to measure the degree of thickening in six patients with RP and CME. A laser beam was projected at an oblique angle to the retina, and images of the intersection of the laser slit with the anterior and posterior retinal surfaces were recorded. The digitized images were analyzed using a dedicated software program to provide quantitative measurements of retinal thickness. Routine fluorescein angiography was performed. RESULTS: The amount of fluorescein dye leakage was not indicative of the degree of retinal thickening due to fluid accumulation. Foveal thickening and fluorescein dye leakage were reduced in five of six eyes after methazolamide treatment. Eyes with moderate thickening reversed to normal, whereas eyes with severe thickening showed only a minimal reduction in thickness. CONCLUSION: Retinal thickness measurement is a useful method of evaluating both the extent of and changes in retinal thickness after carbonic anhydrase treatment.

Adult

Retinal thickness change after focal laser treatment of diabetic macular oedema.

Laser photocoagulation has been used successfully for the treatment of clinically significant macular oedema to reduce the risk of loss of vision in diabetic patients. A quantitative method for measuring retinal thickness was applied to 20 patients with diabetic macular oedema before and 4 months after focal laser treatment to assess the reduction in retinal thickening and its relation to visual acuity. The degree of thickening at each location, defined by thickness index, was determined relative to the corresponding average value in normal subjects. Comparison of quantitative retinal thickness measurements before and after treatment demonstrated that treatment at thickness indices of approximately 1.6 (60% thickening) has nearly 50% probability for reversal of thickening to within the normal range (< or = 1.3), whereas at thickness indices greater than 2.8 (180% thickening) there is less than 2.5% probability that reversal will occur. The level of foveal thickening before treatment strongly correlated with the degree of thickening after treatment. Most of the eyes with an improvement in visual acuity had a foveal thickness within the normal range at 4 months' follow up. These findings suggest that quantitative retinal thickness measurement provides an objective assessment of the degree of macular oedema and can be useful for monitoring the efficacy of focal laser treatment in reducing the thickening and relating the latter to visual outcome.

Aged

Noninvasive visualization of the choriocapillaris and its dynamic filling.

PURPOSE: The choroidal microvasculature and its circulation are inadequately assessed by presently available techniques. Laser-targeted delivery was applied to generate local, repetitive angiograms of the choriocapillaris in primates. METHODS: Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously in monkeys. The liposome contents were then released locally in the choroid by application of a short heat pulse provided by an infrared laser. The bolus of dye spread rapidly downstream from the underlying arterioles into clusters of lobules. Video angiograms were generated with excitation illumination provided by an argon laser. RESULTS: Laser-targeted delivery choroidal angiography performed on three monkeys indicated that the fluorescence was emitted mainly from the choriocapillaris. Clusters of irregular shape with well-defined margins were observed. Adjacent arteries typically supplied separate clusters that fit together like a jigsaw puzzle. The dynamic filling and emptying patterns, recorded at video rate, revealed that macular lobules were filled by a central arteriole and drained by a venous annulus. The average dye transit time through a lobule (n = 10) was 118 +/- 26 msec (mean +/- SD), and the dye transit velocity was 2.53 +/- 0.55 mm/sec. CONCLUSIONS: This study clearly documents the segmental nature of the primate choroidal microvasculature. It also illustrates that choroidal angiography by laser-targeted dye delivery provides information useful for studying the response of the choriocapillaris to physiological and pathologic changes.

Animals

Enhanced visualization of vitreoretinal interface by laser biomicroscopy.

BACKGROUND: The use of slit-lamp biomicroscopy provides valuable information for the diagnosis and management of vitreoretinal disorders. However, intense backscatter from the fundus often precludes the visualization of fine structures in the vitreoretinal interface. METHODS: Laser biomicroscopy is a new method designed to improve the visualization of fine vitreoretinal structures at the macula. This method was applied to eyes suspected of traction maculopathies. With this method, the contrast and the lateral separation between the vitreal and retinal images are optimized while preserving information on the location of the slit on the fundus. RESULTS: The results indicated that fine structures in the vitreoretinal interface, which were difficult to observe with conventional slit-lamp biomicroscopy, could be clearly visualized. CONCLUSION: Laser biomicroscopy may be a useful tool in the diagnosis and management of diseases with vitreoretinal abnormalities.

Aged

Improved visualization of macular hole lesions with laser biomicroscopy.

We have developed instrumentation to improve the visualization of fine vitreoretinal structures at the macula during slit-lamp biomicroscopy. The instrument, mounted on a slit-lamp microscope, used a green helium-neon laser to deliver a narrow beam, 15 micron(s) in width and 2 mm in length. The intersection of the laser slit with the ocular structures was viewed at an angle, as in conventional slit-lamp biomicroscopy. The instrument was used to examine patients with idiopathic macular holes or cysts. The results indicated that the new illumination was superior due to the narrow width of the beam, the enhanced brightness, and the monochromacy in green, which reduced background scatter. These advantages allowed for visualization of fine retinal structures that are difficult to detect with conventional slit-lamp biomicroscopy. The findings in patients with idiopathic macular hole demonstrated that the operculum was located approximately 500 micron(s) anterior to the surrounding retina and moved minimally. This suggested that the operculum may be supported by partially detached posterior vitreous cortex, and that a macular hole is the result of tangential traction followed by axial traction caused by a contracted and detached cortical vitreous gel.

Aged

Retinal thickness analysis for quantitative assessment of diabetic macular edema.

Diabetic macular edema is a major cause of vision loss and is evaluated with qualitative or semiquantitative techniques. A new quantitative method for assessment of macular edema using retinal thickness analysis was applied to 19 patients with diabetic macular edema. Foveal thickening was frequently coupled with poor visual acuity. Slit-lamp biomicroscopy and stereophotography detected 80% and 78% of local areas of thickening, respectively, but failed to detect locations with average thicknesses of 1.5 and 1.6 times normal, respectively. Fluorescein leakage on angiography was generally associated with retinal thickening, but locations with similar degrees of leakage had widely varying retinal thickening. Fluorescein leakage in the posterior vitreous correlated poorly with the degree of foveal thickening. These results indicate that quantitative measurement of retinal thickness may become useful in the management of diabetic patients with macular edema.

Aged

Feasibility of targeted drug delivery to selective areas of the retina.

A new method was developed to deliver locally a bolus dose of a drug to the retinal vasculature. The targeted delivery system was based on encapsulating the drug in heat-sensitive liposomes, which are injected intravenously and lysed in the retinal vessels by a heat pulse generated by a laser. To test if substances delivered in the vessels could also penetrate into the surrounding tissue, 6-carboxyfluorescein was encapsulated in liposomes and used as a marker for drug penetration. Moderate argon laser pulses were applied to the retinal vessels of Dutch pigmented rabbits to induce breakdown of the blood-retinal barrier (BRB). A suspension of liposomes at a dose of 2 ml/kg body weight, corresponding to a carboxyfluorescein dose of 12 mg/kg, was injected into the ear vein. The dye was released from the liposomes proximal to the damaged portion of the vessel. Fundus fluorescein angiograms were recorded with a video camera and digitized for subsequent image analysis. The penetration of carboxyfluorescein into the retinal tissue was evaluated by comparing the fluorescence intensity of the area around the damaged vessel with that of an adjacent control area. The dye penetration increased with the numbers of laser applications (P less than 0.001). The leakage was localized distally to the released site and was restricted to areas with a disrupted BRB. The mass of carboxyfluorescein that penetrated gradually spread with time. Both veins and arteries could be used for the targeted delivery. These results indicated that this delivery system, which is fully controllable by laser through the pupil, can deliver drugs inside the vasculature and into the retinal tissue wherever the BRB is disrupted.

Animals

Topography of the retinal thickness in normal subjects.

A noninvasive method has been developed that is capable of providing quantitative thickness profiles of the retina. The method was used to map the retinal thickness in five normal human volunteers and determine the reproducibility of the measurements. The reproducibility or equivalent sensitivity of the measurements to detect changes was found to be 5% or 19 microns on the same day and 8% or 31 microns on different days. By averaging the values obtained in five normal subjects, ranging in age from 21 to 43 years (mean, 34 years), a preliminary normal baseline was derived for the thickness profile at the fovea and the thickness cross-section from the optic disc to the fovea. The results of the study indicated that this noninvasive method promises to be of clinical use in diagnosing ocular diseases that produce changes in the thickness of the retinal as well as in monitoring the effectiveness of therapy.

Adult

Quantitative analysis of retinal hemodynamics using targeted dye delivery.

A new method designed to allow repeated mapping of retinal hemodynamics on a macro- and microcirculatory level was evaluated in the primate eye. The method, called "targeted dye delivery," consists of encapsulating a fluorescent dye in temperature-sensitive liposomes, injecting the liposomes systemically, and using a light pulse from an argon laser to release a bolus of dye in a targeted retinal vessel. The follow-up of the well-defined dye front thus generated allows calculation of the blood flow and capillary transit time. Evaluation of targeted dye delivery in a monkey indicated that centerline blood velocity and the vessel diameter can be measured with a reproducibility of 10% and 4%, respectively, in vessels that are 40 microns and larger. These measurements yielded flow values that had a reproducibility of 10% on the same day and 13% on different days. The normalization of flow rate by the vessel diameter was consistent with theoretic estimates and promises to be a circulation indicator independent of variations between individual and species. The transit time across capillary beds at different locations was found to be similar, thus indicating that the method could be used to evaluate the local viability of the microcirculation.

Animals

Visualization of the retinal microvasculature by targeted dye delivery.

Although fluorescein angiography has proven to be an important tool in the diagnosis and management of retinal vascular diseases, it is subject to certain limitations, namely the presence of the choroidal background, which usually precludes a detailed examination of the retinal microvasculature. Moreover, the inability to repeat the bolus reduces the chance of obtaining high-quality photographs of early phases, and does not allow for a complete binocular examination or for testing the response to induced physiologic changes. We have developed a method of targeted dye delivery that consists of encapsulating the dye in lipid vesicles, injecting them intravenously, and causing them to release their contents locally when a short heat pulse is induced in a retinal artery by a laser. This method was applied in the rhesus monkey in order to visualize the retinal microvasculature. A well-defined bolus and absence of background fluorescence permitted both following of the dye front through the vasculature and clear imaging of the capillary network over the whole posterior pole. The bolus delivery could be repeated as many as 100 times in 45 min without significant loss of contrast. The comparison of these results with conventional fluorescein angiography illustrated the advantage of the new method. The examination of the safety of the delivery system indicates that there is no major obstacle to the eventual application to humans.

Animals

In vivo evaluation of a noninvasive method to measure the retinal thickness in primates.

To diagnose certain macular diseases earlier and monitor their therapy more sensitively, we are developing a noninvasive method to measure the retinal thickness. The new instrument, which is an extension of slit-lamp biomicroscopy, was used to obtain the data, which were analyzed with an algorithm to yield thickness measurements. The measurements performed in monkeys indicated that the retinal thickness can be visualized in a region extending from the optic disc to the fovea and that quantitative results can be obtained. The retinal thickness reproducibility was 6% for the same location on the same day, 15% for the same location on different days, and 12% for the same location in different eyes. The average retinal thickness in these areas was 335 microns, indicating that the reproducibility was between 20 and 50 microns. Measurements across the foveola illustrated that retinal thicknesses as low as 80 microns could be obtained.

Animals