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3.
Ophthalmology ; 108(4): 738-49, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11297491

ABSTRACT

PURPOSE: To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause. DESIGN: Observational case series and genetic study. PARTICIPANTS: Two unrelated probands presenting with absent central retinal vessels and 11 available family members. TESTING: Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed. MAIN OUTCOME MEASURES: Better defined characteristics of the papillorenal syndrome. RESULTS: Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected. CONCLUSIONS: In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.


Subject(s)
Coloboma/diagnosis , Kidney Diseases/diagnosis , Kidney/abnormalities , Optic Disk/abnormalities , Retinal Diseases/diagnosis , Retinal Vessels/abnormalities , Adult , Coloboma/complications , Coloboma/genetics , DNA-Binding Proteins/genetics , Evoked Potentials, Visual , Female , Fluorescein Angiography , Humans , Indocyanine Green , Infant , Kidney/diagnostic imaging , Kidney/pathology , Kidney Diseases/etiology , Kidney Diseases/genetics , Magnetic Resonance Imaging , Male , Middle Aged , Mutation , Optic Disk/diagnostic imaging , Optic Disk/pathology , Optic Nerve/diagnostic imaging , PAX2 Transcription Factor , Retinal Diseases/etiology , Retinal Diseases/genetics , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Syndrome , Transcription Factors/genetics , Ultrasonography, Doppler, Color , Visual Field Tests , Visual Fields
4.
J Glaucoma ; 9(2): 134-42, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10782622

ABSTRACT

PURPOSE: To study the risk associated with diurnal intraocular pressure (IOP) variations in patients with open-angle glaucoma. PATIENTS AND METHODS: Sixty-four patients (105 eyes) from the practices of two glaucoma specialists successfully performed home tonometry with a self-tonometer five times a day for 5 days. All patients had open-angle glaucoma and documented IOP below 25 mm Hg over a mean follow-up period of 5 years. Baseline status and time to progression of visual field loss were identified from the clinical charts. The level and variability of diurnal IOP obtained using home tonometry were characterized. Risk of progression was analyzed using a nonparametric time-to-event model, incorporating methods for correlated outcomes. RESULTS: Although mean home IOP and baseline office IOP were similar (16.4 +/- 3.6 mm Hg and 17.6 +/- 3.2 mm Hg, respectively), the average IOP range over the 5 days of home tonometry was 10.0 +/- 2.9 mm Hg. Baseline office IOP had no predictive value (relative hazard, 0.98). The diurnal IOP range and the IOP range over multiple days were significant risk factors for progression, even after adjusting for office IOP, age, race, gender, and visual field damage at baseline (relative hazards [95% confidence intervals], 5.69 [1.86, 17.35] and 5.76 [2.21, 14.98]). Eighty-eight percent of patients in the upper twenty-fifth percentile of IOP and 57% of patients in the lower twenty-fifth percentile progressed within 8 years. CONCLUSIONS: In patients with glaucoma with office IOP in the normal range, large fluctuations in diurnal IOP are a significant risk factor, independent of parameters obtained in the office. Fluctuations in IOP may be important in managing patients with glaucoma. Development of methods to control fluctuations in IOP may be warranted.


Subject(s)
Circadian Rhythm , Glaucoma, Open-Angle/physiopathology , Intraocular Pressure/physiology , Circadian Rhythm/physiology , Disease Progression , Female , Humans , Male , Odds Ratio , Prognosis , Prospective Studies , Risk Factors , Tonometry, Ocular , Visual Fields
5.
Ophthalmology ; 106(2): 269-73, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9951475

ABSTRACT

OBJECTIVE: Objective and sensitive measurements of the retinal thickness at the posterior pole are useful to detect and delineate macular edema or retinal atrophy. The authors therefore developed an instrument, the Retinal Thickness Analyzer (RTA), to map the retinal thickness rapidly. The RTA was used to study the normal thickness at the posterior pole and to provide a pilot baseline. DESIGN: Cross-sectional study. METHODS: A green (540-nm) laser slit was focused on the retina via a scanning mirror placed at the conjugate plane of the pupil. The intersection between the laser slit and the retina was viewed at an angle and recorded by a video camera. Nine scans, each acquired in 200 to 400 msec, covered the central 20 degrees of the fundus. PARTICIPANTS: The posterior pole was mapped in 29 normal subjects 19 to 76 years of age (mean, 48 years). RESULTS: The thickness maps matched the posterior pole anatomy. Points with maximum thickness were located in the perifovea in a C-shaped manner extending from the disc to above and below the fovea. The local variation (standard deviation) in retinal thickness among the subjects was, on average, 15 microns. Age, gender, and race did not have a large effect (< 35 microns) on the values. CONCLUSIONS: Rapid scanning thickness analysis with the RTA provides a detailed map of the retinal thickness. The relatively narrow range of thickness values in normal subjects indicates that the method may provide a sensitive detection of pathologic thickening or thinning of the retina.


Subject(s)
Anthropometry/methods , Retina/anatomy & histology , Adult , Aged , Cross-Sectional Studies , Diagnostic Techniques, Ophthalmological/instrumentation , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged
6.
Invest Ophthalmol Vis Sci ; 39(13): 2733-43, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9856784

ABSTRACT

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.


Subject(s)
Choroid/blood supply , Image Processing, Computer-Assisted/methods , Retinal Vessels/anatomy & histology , Animals , Choroid/surgery , Fluorescein , Fluorescein Angiography , Indocyanine Green , Laser Coagulation , Papio , Retina/surgery , Retinal Vessels/pathology
7.
Arch Ophthalmol ; 116(8): 1036-41, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9715684

ABSTRACT

OBJECTIVE: To assess the morphologic characteristics of the foveal abnormality in juvenile X-linked retinoschisis using the scanning retinal thickness analyzer (RTA). This characteristic foveal abnormality is present in 83% to 100% of patients with X-linked retinoschisis and has not been demonstrated histopathologically. METHODS: The RTA is a noncontact imaging device. The RTA scans an obliquely oriented slit laser beam across the macula to obtain a series of optical cross sections, which are digitized. PARTICIPANTS: The RTA was used to examine 7 eyes of 5 patients with X-linked retinoschisis. RESULTS: The RTA demonstrated foveal schisis in all eyes examined. In 2 eyes of 2 patients, a single schisis cavity, with an inner leaf in a dome-shaped configuration, was present. In 4 eyes of 3 patients, a single schisis cavity containing fine strands was present. Some of these strands partially, and others completely, bridged the cavity. In 1 eye of 1 patient, 2 separate schisis cavities with bridging strands were present in the fovea. CONCLUSIONS: Scanning RTA is a noninvasive imaging modality capable of producing optical cross sections that demonstrate the extent and structural details of the foveal schisis in X-linked retinoschisis. Scanning RTA seems to be effective in the detection, characterization, and quantification of foveal schisis.


Subject(s)
Diagnostic Techniques, Ophthalmological , Eye Diseases, Hereditary/pathology , Genetic Linkage , Image Processing, Computer-Assisted/instrumentation , Macula Lutea/pathology , Retinal Degeneration/pathology , X Chromosome , Child, Preschool , Eye Diseases, Hereditary/genetics , Fovea Centralis/pathology , Humans , Retina/pathology , Retinal Degeneration/genetics
8.
Ophthalmology ; 105(2): 224-31, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9479279

ABSTRACT

OBJECTIVE: The posterior pole ganglion cell bodies form a substantial fraction of the retinal thickness, prompting the authors to study the feasibility of detecting, by scanning retinal thickness analysis, retinal changes at the posterior pole due to glaucomatous damage. STUDY DESIGN: Nonconsecutive case series. PARTICIPANTS: One or both eyes of patients with chronic open-angle glaucoma who presented with either a superoinferior asymmetry in visual fields or a localized field loss or a nerve fiber layer defect visible on photography were recruited. Twenty-nine eyes of 18 patients were studied. INTERVENTIONS: A laser slit was projected on the retina and scanned, in 400 msec, across a 2- x 2-mm area of the fundus, yielding optical cross-sections that were digitally recorded. Nine such scans covered the central 20 degrees of the fundus. The optical cross-sections were analyzed by an operator-free algorithm to yield a three-or two-dimensional color map. The asymmetry (difference) between the visual sensitivity of the upper and lower hemifields was compared with the asymmetry in retinal thickness deviation from normal. RESULTS: Large losses (up to 34%) in retinal thickness were detected at the posterior pole of patients with glaucoma due to the loss of ganglion cells and nerve fibers. A statistically significant correlation was found between the asymmetry in visual sensitivity loss and the asymmetry in deviation from normal thickness (r = 0.72; P < 0.0005). CONCLUSIONS: Mapping of the retinal thickness may provide a sensitive method for the detection and monitoring of early glaucomatous tissue loss in the posterior pole, which is unique due to the combination of (1) the direct measurement of neuroretinal loss in the central field of vision; (2) the mapping capability; and (3) the rapid image acquisition.


Subject(s)
Glaucoma, Open-Angle/diagnosis , Retina/pathology , Adult , Aged , Female , Humans , Image Processing, Computer-Assisted , Intraocular Pressure , Lasers , Male , Middle Aged , Nerve Fibers/pathology , Pilot Projects , Retinal Ganglion Cells/pathology , Vision Disorders/diagnosis , Visual Acuity , Visual Field Tests , Visual Fields
9.
Ophthalmology ; 105(1): 66-77, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9442780

ABSTRACT

OBJECTIVE: This study aimed to examine the characteristics of intraretinal changes associated with macular holes and epiretinal membranes by scanning retinal thickness analysis. STUDY DESIGN: The study design was a nonconsecutive case series. PATIENTS: Fifty-six eyes of patients who had either a suspected or clinically diagnosed macular hole or epiretinal membrane were recruited. INTERVENTIONS: A commercial prototype of the scanning retinal thickness analyzer (RTA) was used. It projected a laser slit beam onto the retina and scanned it, in 200 or 400 msec, across a 2- x 2-mm area, yielding multiple optical cross sections that were recorded digitally. RESULTS: Epiretinal membranes were detected, and sites of attachment could be identified. Full-thickness holes corresponded to intraretinal cavities in which the inner retinal surface was broken, usually at the center. The majority of eyes with full-thickness macular holes showed increased retinal thickness surrounding the hole. The so-called "cuff of subretinal fluid," however, often was not present by retinal thickness analysis, despite clinical diagnosis to the contrary, even though retinal thickness analysis is capable of detecting such fluid. In 20 (42%) of 47 eyes diagnosed or suspected of having macular holes, scanning retinal thickness analysis showed findings different from those reported by retinal specialists. CONCLUSIONS: Examination of macular holes with the scanning RTA provides useful information in the diagnosis of macular holes in addition to that obtained through conventional techniques. The findings support the idea that many macular holes develop in association with intraretinal cystic changes. The precise chronology of the events remains to be determined.


Subject(s)
Epiretinal Membrane/pathology , Lasers , Retina/pathology , Retinal Perforations/pathology , Adult , Aged , Aged, 80 and over , Female , Fluorescein Angiography , Fundus Oculi , Humans , Male , Microscopy/instrumentation , Middle Aged , Retinal Perforations/physiopathology , Visual Acuity
10.
Ophthalmology ; 104(7): 1145-51, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9224468

ABSTRACT

PURPOSE: The authors have further developed their method of retinal thickness analysis to rapidly generate multiple optical cross sections of the retina and provide thickness maps at the posterior pole. The potential use of this method was evaluated in a number of macular disorders. METHODS: A commercial prototype of the scanning retinal thickness analyzer was used to examine patients with a variety of macular diseases. A laser slit beam was projected on the retina and scanned across a 2- X 2-mm retinal area in 200 to 400 msec. The images of the intersection of the laser slit beam with the retina were recorded digitally and used for visualization of disease. Nine scans were combined, and an operator-free algorithm generated a three-dimensional thickness map at the posterior pole. RESULTS: Cysts could be visualized in macular edema associated with diabetes mellitus and with retinal vein occlusion. The retinal thickness map quantitated the location, extent, and height of the edema. In serous detachment, the extent and the height of the retinal pigment epithelial elevation could be documented. In cases of suspected macular holes and pseudoholes, the diagnosis was considered more reliable than with conventional biomicroscopy. The extent of epiretinal membranes, the sites of adherence, and associated intraretinal cystic changes were identified. In glaucoma, the anatomic course of localized loss of neuronal retinal tissue could be traced. CONCLUSIONS: Scanning retinal thickness analysis provided multiple optical cross sections of the retina and yielded information useful in the diagnosis and monitoring of macular diseases. The three-dimensional thickness map provided quantitative information that may be useful for clinical management.


Subject(s)
Anatomy, Cross-Sectional/methods , Lasers , Retina/pathology , Retinal Diseases/diagnosis , Diabetic Retinopathy/diagnosis , Female , Fovea Centralis/pathology , Glaucoma/diagnosis , Humans , Macular Edema/diagnosis , Male , Reference Values , Retinal Perforations/diagnosis
11.
Invest Ophthalmol Vis Sci ; 38(13): 2702-10, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9418722

ABSTRACT

PURPOSE: A new method, laser-targeted photoocclusion, was developed to occlude choroidal neovascularization while minimizing damage to the overlying retina. The ability to occlude normal choriocapillary layer in rats was evaluated as a first test of the feasibility of treating choroidal neovascularization with this method. METHOD: A photosensitive agent, aluminum phthalocyanine tetrasulfonate, encapsulated in heat-sensitive liposomes, was administered intravenously along with carboxyfluorescein liposomes. A low-power argon laser (retinal power density of 5.7 W/cm2) locally released a photosensitizer bolus, monitored by the simultaneous release of carboxyfluorescein. A diode laser (operating at 675 nm with a retinal power density of 0.27 W/cm2) activated the photosensitizer with its release. RESULTS: Vessels in the choriocapillary layer were occluded at day 3 after laser treatment and remained unchanged during the 30-day follow-up. Larger choroidal vessels and retinal capillaries remained perfused. Control experiments excluded possible effects of heat or activation of free photosensitizer. Pilot histologic studies showed no damage to the retinal pigment epithelium. CONCLUSIONS: Laser-targeted photoocclusion caused selective occlusion of normal choriocapillaries while sparing overlying retinal pigment epithelium and retinal vessels. The method has potential as a treatment of choroidal neovascularization that may minimize iatrogenic loss of vision.


Subject(s)
Capillaries/drug effects , Choroid/blood supply , Indoles/therapeutic use , Lasers , Organometallic Compounds/therapeutic use , Photochemotherapy , Photosensitizing Agents/therapeutic use , Animals , Capillaries/pathology , Choroid/drug effects , Choroid/pathology , Drug Carriers , Feasibility Studies , Fluorescein Angiography , Fluoresceins , Fluorescent Dyes , Liposomes , Male , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Rats , Thrombosis/etiology , Thrombosis/pathology
12.
Invest Ophthalmol Vis Sci ; 37(10): 1994-2001, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8814139

ABSTRACT

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.


Subject(s)
Ophthalmology/methods , Retina/anatomy & histology , Adult , Anthropometry/methods , Female , Fovea Centralis/anatomy & histology , Humans , Male , Middle Aged , Ophthalmology/instrumentation , Reproducibility of Results
13.
Invest Ophthalmol Vis Sci ; 37(8): 1642-50, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8675408

ABSTRACT

PURPOSE: Laser-targeted angiography has unique advantages over conventional angiography of the fundus. Its efficacy in visualizing choroidal neovascular membranes was tested in a rat model and compared to that of fluorescein angiography. METHOD: Laser-targeted angiography was performed in rats with choroidal neovascularization (CNV) by injecting heat-sensitive carboxyfluorescein liposomes intravenously, locally releasing a bolus of dye in the choroid with a weak laser pulse, and recording advancement of the bolus on a video camera. Conventional fluorescein angiography also was performed. RESULTS: Laser-targeted angiography revealed CNV as an abnormal pattern of brightly fluorescent vessels. The flow pattern of the bolus and histology, performed in some cases, confirmed the choroidal nature of the vessels. The angiographic visualization was not dependent on dye leakage through the vessels or staining of their walls. Laser-targeted angiography also provided visualization of new vessels that could not be diagnosed by fluorescein angiography. It demonstrated that blood flow was typically more sluggish in CNV than in normal choriocapillaris. Fluorescein angiography failed to demonstrate flow dynamics in all cases of CNV. CONCLUSIONS: This study, in an animal model of CNV, shows that laser-targeted angiography demonstrates CNV and its flow dynamics in a manner not provided by conventional fluorescein angiography. It holds clinical promise as a method to delineate CNV considered difficult or impossible to detect by fluorescein angiography. The method also may permit selective photocoagulation of feeding vessels in the choroid, thereby limiting damage to the overlying retina.


Subject(s)
Choroid/blood supply , Neovascularization, Pathologic/diagnosis , Animals , Choroid/pathology , Disease Models, Animal , Drug Carriers , Fluorescein Angiography/methods , Fluoresceins , Fluorescent Dyes , Lasers , Liposomes , Membranes/pathology , Rats
14.
Invest Ophthalmol Vis Sci ; 37(2): 312-7, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8603835

ABSTRACT

PURPOSE: The rat has been used to generate models of various eye diseases. However, methods to study the choriocapillaris noninvasively have been inadequate in this species. Laser-targeted angiography was applied to generate local, repetitive angiograms of the choriocapillaris in the rat and to assess the similarity between the choriocapillaris of the rat and that of the subhuman primate. METHODS: Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously in rats. The liposome contents were then released locally in the choroid by the application of a short, noncoagulating heat pulse provided by an argon laser. Videoangiograms of the downstream spread of the bolus of dye were generated with excitation illumination provided by another output from the argon laser. RESULTS: Laser-targeted angiography demonstrated that the bolus of dye perfused the choriocapillaris. Clusters of choriocapillaris lobules were observed and appeared similar to those described in the primate. Dynamic filling and emptying patterns also were similar to those of the primate. Lobules were filled by a central arteriole and drained by a venous annulus. CONCLUSIONS: This study demonstrates the feasibility of noninvasively studying the choriocapillaris of the living rat using the technique of laser-targeted angiography. It demonstrates as well the similarity between the rat and the primate choriocapillaris, thus indicating that the rat is an acceptable and convenient model for the study of physiological and pathologic changes in the choroidal vasculature.


Subject(s)
Choroid/blood supply , Animals , Blood Flow Velocity/physiology , Capillaries/physiology , Fluorescein Angiography/methods , Fluoresceins/administration & dosage , Fluorescent Dyes/administration & dosage , Fundus Oculi , Lasers , Liposomes , Macaca , Rats
15.
Arch Ophthalmol ; 113(9): 1156-60, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7661749

ABSTRACT

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.


Subject(s)
Lasers , Macula Lutea/pathology , Microscopy/instrumentation , Retinal Perforations/classification , Retinal Perforations/diagnosis , Aged , Female , Fundus Oculi , Humans , Male , Middle Aged , Visual Acuity
16.
Br J Ophthalmol ; 79(8): 766-70, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7547790

ABSTRACT

AIMS/BACKGROUND: Neovascularisation occurs in many major ocular diseases such as diabetes, age-related macular degeneration, and sickle cell disease. Laser photocoagulation is typically used to obliterate the vessels but it also causes severe damage to adjacent normal tissues. This is a very significant limitation especially in the treatment of choroidal neovascularisation which often covers large areas of the posterior pole and the fovea. A method, laser targeted delivery, has been developed capable of releasing drugs locally and non-invasively in the choroidal or retinal vasculature. This method could be used to target a photo-sensitiser to neovascular membranes and cause their selective occlusion by irradiating them. The targeting properties of the method promise to yield a treatment for neovascularisation that does not damage adjacent tissues and thus preserves vision. The purpose of the present study was to test the feasibility of occluding ocular vessels with this method. METHOD: The iris vessels of the albino rat were chosen because the treatment could be assessed unequivocally and followed with time. Aluminium phthalocyanine tetrasulphonate was encapsulated in heat sensitive liposomes and administered systemically. The iris vessels were irradiated with a yellow laser to raise their temperature to 41 degrees C, cause a phase transition in the liposomes and thereby locally release the photosensitiser. The laser was also used to excite the released photosensitiser and cause occlusion. The effect was monitored immediately and for 8 months thereafter. Controls for the effect of the laser and the unencapsulated drug were conducted. RESULTS: The results demonstrated that occlusion can be achieved and sustained for the period of follow up. The controls showed that the effect was not due to heat or to the activation of the low dose of free drug. CONCLUSION: These preliminary findings indicate that laser targeted photo-occlusion is a promising new method for the treatment of neovascularisation.


Subject(s)
Iris/blood supply , Neovascularization, Pathologic/drug therapy , Photochemotherapy/methods , Animals , Feasibility Studies , Fluorescent Dyes/administration & dosage , Indoles/administration & dosage , Lasers , Liposomes , Male , Organometallic Compounds/administration & dosage , Radiation-Sensitizing Agents/administration & dosage , Rats , Rats, Sprague-Dawley , Treatment Outcome
17.
Invest Ophthalmol Vis Sci ; 36(7): 1240-6, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7775101

ABSTRACT

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.


Subject(s)
Light , Retina/metabolism , Retinal Vessels/physiology , Animals , Arterioles/physiology , Blood Flow Velocity/physiology , Fluorescein Angiography , Fundus Oculi , Hemodynamics/physiology , Image Processing, Computer-Assisted , Macula Lutea/blood supply , Microcirculation , Papio , Retina/radiation effects , Retinal Vessels/radiation effects
18.
J Ocul Pharmacol Ther ; 11(4): 575-84, 1995.
Article in English | MEDLINE | ID: mdl-8574821

ABSTRACT

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.


Subject(s)
Fluorescein Angiography/methods , Fluoresceins/administration & dosage , Fluoresceins/toxicity , Lasers , Animals , Blood-Retinal Barrier/drug effects , Capillaries/anatomy & histology , Capillaries/injuries , Choroid/blood supply , Choroid/injuries , Drug Carriers , Fluorescent Dyes/administration & dosage , Fluorescent Dyes/toxicity , Hot Temperature , Lasers/adverse effects , Liposomes , Male , Papio , Rats , Rats, Sprague-Dawley , Retinal Vessels/anatomy & histology , Retinal Vessels/injuries
19.
Br J Ophthalmol ; 78(11): 827-30, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7848977

ABSTRACT

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.


Subject(s)
Diabetic Retinopathy/surgery , Laser Coagulation , Retina/pathology , Aged , Diabetic Retinopathy/pathology , Edema , Follow-Up Studies , Humans , Macula Lutea/pathology , Macula Lutea/surgery , Middle Aged , Visual Acuity
20.
Invest Ophthalmol Vis Sci ; 35(10): 3724-31, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8088959

ABSTRACT

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.


Subject(s)
Capillaries/anatomy & histology , Choroid/blood supply , Fluorescein Angiography/methods , Fluoresceins , Animals , Blood Flow Velocity/physiology , Capillaries/physiology , Drug Carriers , Fluoresceins/administration & dosage , Fluoresceins/toxicity , Fundus Oculi , Lasers , Liposomes , Papio , Regional Blood Flow/physiology
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