Determination of retinal blood velocity with respect to the cardiac cycle using laser-triggered release of liposome-encapsulated dye

A system of selective angiography has been developed for measuring blood velocity in retinal arteries and veins. It uses a liposome-encapsulated fluorescent dye that is released by application of laser energy in a specific retinal vessel. The method is shown to be able to distinguish between peak systolic velocity and minimum diastolic velocity. In the cynomolgus monkey, the two values were found to differ by approximately a factor of three. It is known that many ocular and systemic diseases affect retinal circulation, and therefore a method of blood velocity measurement with such sensitivity may prove highly valuable in the practice of ophthalmology. As an example, the velocity in a retinal vein was measured before and after partial occlusion by photocoagulation. The two values obtained were significantly different, and the blood velocity was found to return to the value prior to occlusion when measured at 18 days.     

Inflammation induced by photocoagulation laser is minimized by copper chelators

The effect of trientine hydrochloride (TRIEN), a copper-selective chelating agent, on retinal inflammation induced by photocoagulation laser treatment was studied. Nine Long-Evans rats were treated with TRIEN (0.5 mmol/kg per day, intraperitoneal injection) for 9 days. On day 8, each animal underwent unilateral photocoagulation laser treatment with an argon dye laser. On day 9, animals were killed and the eyes processed for immunohistochemistry and light microscopy. In the TRIEN-treated group, retinal thickness and number of macrophages (ED-1) were both significantly lower than in the saline-treated, control group exposed to laser photocoagulation. The results support the hypothesis that selective copper chelation prior to laser treatment may inhibit ocular inflammation. The results suggest that pretreatment with a selective copper-chelating compound can minimize retinal inflammation secondary to laser photocoagulation treatment, which may improve overall outcome of photocoagulation treatment for diabetic retinopathy.     

Dye laser photocoagulation through experimentally induced retinal hemorrhage

The histological effects of photocoagulation obtained by using each of 4 wavelengths of the dye laser (577, 590, 610, and 630 nm) on experimentally induced retinal hemorrhage in cat eyes were examined. Energy from 577, 590, and 610 nm laser was directly absorbed by red blood cells in the retinal hemorrhage and destroyed the inner layers of the retina. Red blood cells were not directly coagulated with the use of 630 nm laser, and the retinal pigment epithelial cells (RPE cells) and choroidal melanocytes were coagulated. These results suggest that the use of yellow or orange dye lasers for photocoagulative therapy in a retinal hemorrhage is dangerous, because of the risk for destruction of the inner layers of the retina. A 630 nm dye laser is useful for photocoagulation of a retinal hemorrhage, while the laser energy is unable to reach the RPE cells and the choroid with the use of other wavelengths.     

Laser-induced experimental vascular occlusion using liposome-encapsulated ADP.

The therapeutic occlusion of retinal vessels is often helpful in treating various pathological conditions. We compared the combined effects of argon laser photocoagulation and adenosine diphosphate (ADP) released from temperature-sensitive liposomes with argon laser photocoagulation alone on occlusion of retinal vessels in pigmented rats. In Group A, 8 eyes were treated with liposome-encapsulated ADP and laser photocoagulation. In Group B, 8 eyes were treated with laser photocoagulation alone. The laser parameters (power, spot size, exposure time) were maintained at the same levels for both groups. The laser was focused on the retinal vessels at the optic nerve head. The treated retinal vessels were observed at time zero, day 1, day 4, and weekly for a period of 3 months. At time zero, 6 of 8 eyes were totally occluded in Group A, with best results obtained at 80 mW. Only 1 of 8 eyes in Group B achieved total occlusion. After 3 months, 4 of 8 eyes in Group A remained totally occluded; no eyes in Group B were occluded. Complete and permanent occlusion of retinal vessels can be achieved by using ADP and laser photocoagulation of lower power density than traditional laser photocoagulation alone.     

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10

BACKGROUND AND OBJECTIVE: To determine the optimal treatment parameters for selective occlusion of choroidal neovascularization (CNV) by photodynamic therapy (PDT) by using the photosensitizer ATX-S10 and a diode laser (wavelength = 670 nm). MATERIALS AND METHODS: Experimental CNV was induced in rat fundi by argon laser photocoagulation. The distribution of ATX-S10 in the chorioretina was analyzed by fluorescence microscopy, and the optimal treatment parameters for selective occlusion of CNV were investigated by changing the dosage and timing of laser irradiation. CNV closure and resulting damage of the surrounding tissue were documented by fluorescein angiography and light and electron microscopies. RESULTS: Fluorescence of ATX-S10 was observed to be localized in the vascular lumen of the retina and choroid within 5 min after dye injection and increased in intensity in CNV up to 2-6 h and decreased rapidly in normal tissue. Laser irradiation with radiant exposures of 7.4 J/cm2 applied immediately after dye injection or with 22.0 J/cm2 at 2-4 h later effectively occluded the induced CNV without causing significant damage to normal retinal capillaries and large choroidal vessels. CONCLUSIONS: PDT using ATX-S10 can selectively occlude CNV. ATX-S10 is a potentially useful photosensitizer for the treatment of CNV.     

Fundus Fluorescein Angiographic Findings in Patients Who Underwent Ventricular Assist Device Implantation

Disruption of microcirculation in various tissues as a result of deformed blood rheology due to ventricular assist device (VAD) implantation causes novel arteriovenous malformations. Capillary disturbances and related vascular leakage in the retina and choroidea may also be seen in patients supported by VADs. We aimed to evaluate retinal vasculature deteriorations after VAD implantation. The charts of 17 patients who underwent VAD implantation surgery for the treatment of end‐stage heart failure were retrospectively reviewed. Eight cases (47.1%) underwent pulsatile pump implantation (Berlin Heart EXCOR, Berlin Heart Mediprodukt GmbH, Berlin, Germany); however, nine cases (52.9%) had continuous‐flow pump using centrifugal design (HeartWare, HeartWare Inc., Miramar, FL, USA). Study participants were selected among the patients who had survived with a VAD for at least 6 months, and results of detailed ophthalmologic examinations including optic coherence tomography (OCT) and fundus fluorescein angiography (FA) were documented. All of the 17 patients were male, with a mean age of 48.5 ± 14.8 years (15–67 years). Detailed ophthalmologic examinations including the evaluation of retinal vascular deteriorations via FA were performed at a mean of 11.8 ± 3.7 months of follow‐up (6–18 months). Mean best‐corrected visual acuity and intraocular pressure were found as logMAR 0.02 ± 0.08 and 14.6 ± 1.9 mm Hg, respectively in the study population. Dilated fundoscopy revealed severe focal arteriolar narrowing in two patients (11.8%), and arteriovenous crossing changes in four patients (23.5%); however, no pathological alteration was present in macular OCT scans. In patients with continuous‐flow blood pumps, mean arm‐retina circulation time (ARCT) and arteriovenous transit time (AVTT) were found to be 16.8 ± 3.0 and 12.4 ± 6.2 s, respectively; whereas those with pulsatile‐flow blood pumps were found to be 17.4 ± 3.6 and 14.0 ± 2.1 s in patients (P = 0.526 and P = 0.356, respectively). FA also revealed a tendency for increased frequency of dye leakage from the optic disc in our study population. Except for remarkable delays in both ARCT and AVTT as well as a tendency for increased frequency of dye leakage from the optic disc, ophthalmologic evaluations revealed no other significant pathology or vascular deterioration in the retina that could be attributed to artificial heart systems.     

Transscleral contact retinal photocoagulation with an 810-nm semiconductor diode laser

Since the 810-nm wavelength has marked transmissibility through the sclera and absorption by melanin, it would be ideal for transscleral photocoagulation. We performed experiments to determine if consistent transscleral chorioretinal lesions could be produced in Dutch belted pigmented rabbits using the 810-nm laser, and if this modality caused less blood-retinal barrier disruption than retinal cryopexy of clinically equivalent treatment areas. The laser applications produced whitish to grayish-white retinal lesions when the surgeon, under direct visualization, used low powers and long durations (5 to 10 seconds), and controlled the treatment duration. Histopathologic evaluation of a lesion demonstrated an intact sclera overlying the chorioretinal lesion. Vitreous protein concentration, which was measured to assess blood-retinal barrier disruption, was significantly less in eyes treated with transscleral photocoagulation than in eyes treated with cryopexy of clinically equivalent treatment areas. We conclude that transscleral 810-nm laser treatment may be a viable clinical alternative to retinal cryopexy.     

Photoelectric dye-coupled polyethylene film as a prototype of retinal prostheses

Photoelectric dyes, which absorb light and convert photon energy to electric potentials, have been previously shown to stimulate retinal neurons in culture. In this study, a photoelectric dye was coupled to a polyethylene film surface and tested in vitro using retinal tissues from chick embryos at the 12-day embryonic stage, at which time outer segments of retinal photoreceptor cells have not yet developed. Carboxyl moieties were introduced to a polyethylene film surface by fuming nitric acid, and then a photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the film through amide linkage. Intracellular calcium elevation was observed with Fluo-4 in retinal tissues placed on the dye-coupled polyethylene film, in contrast to retinal tissues which had no contact with the film. The response was inhibited by calcicludine, a voltage-gated calcium channel blocker, and also by extracellular calcium depletion. The photoelectric dye, coupled to the polyethylene film surface, absorbed light under a dissecting microscope and stimulated neurons in retinal tissues, showing that the dye-coupled film could be used as a prototype of retinal prostheses.     

Dynamic reflectometer for control of laser photocoagulation on the retina

In retinal laser photocoagulation, constant exposure parameters do not result in identical lesions. This lack of reproducibility increases the rate of complications from over-or undertreatment and inhibits determination of the optimal treatment endpoints for different retinal disorders. To this end, a feedback-controlled photocoagulator could make retinal photocoagulation a safer, more reproducible, and faster procedure. A dynamic confocal reflectometer was integrated into a slit lamp laser delivery system. Real-time reflectance changes on the retinas of pigmented rabbits were obtained by monitoring the increasing back-scattered light of the coagulating beam during argon laser photocoagulation. Reproducible temporal reflectance patterns were measured that correlated with ophthalmoscopically assessed lesion intensity independent of the exposure parameters, the transparency of the optical media, and the focusing conditions. As a step toward the development of a feedback-controlled photocoagulator, the confocal reflectometer has been proven in animal trials closely resembling clinical practice. © 1994 Wiley-Liss, Inc.     

Cerebral hemodynamics in patients with moyamoya disease. A study of the epicerebral microcirculation by fluorescein angiography

Fluorescein angiography was performed in 12 hemispheres of eight young patients with moyamoya disease to study the epicerebral microcirculation. Regional circulation time and the time interval between carotid injection of the dye and first filling of the cortical arteries were various and prolonged in the most parts. There were nonfilling areas by carotid injection of the dye in six hemispheres. By venous injection, the dye appeared in all vessels of the exposed areas. Extravasation of the dye was seen in four hemispheres. The degree of these abnormalities of the epicerebral microcirculation was well correlated with the findings in conventional cerebral angiography.     

Macular edema in branch retinal vein occlusion: types and treatment

In this study of branch retinal vein occlusion, we distinguished between cystoid macular edema caused by increased capillary pressure and noncystoid edema due to hard exudates in the macula caused by chronic leakage from vascular abnormalities in the posterior pole or midperiphery. We performed laser photocoagulation in 51 eyes with cystoid macular edema to achieve focal narrowing of the retinal arterioles perfusing the macular area affected by the cystoid edema; good anatomic and functional results were achieved in 40 of these eyes (78%). In 25 of the five eyes, the treated segment of the retinal arteriole was outside the area of macular edema; results were successful in 19 of these eyes (76%). In 14 eyes with noncystoid exudative macular edema, we performed laser photocoagulation to the vascular abnormalities; good anatomic and functional results were obtained in 12 of these (86%).     

Possibility of choriocapillary occlusion under experimental subretinal hemorrhage by photocoagulation with lasers of different wavelengths

To clarify the possibility of occluding choroidal neovascularization in subretinal hemorrhage with various laser wavelengths, lesions of experimental subretinal hemorrhage were photocoagulated with argon, dye, and krypton lasers and were examined by light and electron microscopy. Our experimental results revealed that laser photocoagulation with wavelengths longer than 590 nm was effective in occluding the choriocapillaries under a thin subretinal hemorrhage. Complete occlusion of choriocapillaries was accomplished by red dye laser (630 nm) or krypton red laser. The choroidal lesion coagulated by 590 nm dye laser showed more extensive reaction than the other lesions at a posttreatment interval of 7 days. The red dye laser (630 nm) or krypton red laser is recommended for the treatment of neovascular maculopathy under thin subretinal hemorrhage because of less reaction and complete occlusion of the choroidal neovascularization.     

Juxtapapillary exophytic retinal capillary hemangioma treated by yellow krypton (568 nm) laser photocoagulation

A 30-year-old man was found to have juxtapapillary exophytic capillary hemangioma complicated by circinate maculopathy and peripapillary exudative retinal detachment. The diagnosis was made from the appearance of the tumor and confirmed by fluorescein angiography. The presence of intermittent hematuria associated with a cystic kidney supported the diagnosis of von- Hippel-Lindau disease. subsequently, and attempt to treat the vascular lesion by yellow krypton (586 nm) laser photocoagulation failed to arrest the progression of the exudative retinal detachment, which finally became total.     

Oxygenation and vasodilatation in relation to diabetic and other proliferative retinopathies

The features of proliferative retinopathies are reviewed with reference to the vasodilatation that is a common stage in their pathogenesis. Vasodilatation in the retina is discussed in terms of a model in which vessel wall stretch in the retinal venules leads to leakage and proliferation. The beneficial effects of treatments such as panretinal photocoagulation and vitrectomy on the retinal hemodynamics are shown to agree with the hypothetical model.     

Long-term effectiveness of photodynamic therapy by using a hydrophilic photosensitizer ATX-S10(Na) against experimental choroidal neovascularization in rats

BACKGROUND AND OBJECTIVE: We previously demonstrated that a hydrophilic photosensitizer ATX-S10 had a potent photodynamic effect. This study was designed to reveal the long-term effectiveness of photodynamic therapy (PDT) with this agent in occluding choroidal neovascularization (CNV) and its selectivity in the neovascular tissue. STUDY DESIGN/MATERIALS AND METHODS: Experimental CNV was induced by intense photocoagulation in rat eyes. Immediately or 2 hours after intravenous injection of 8 mg/kg body weight of ATX-S10(Na), a cis isomer of ATX-S10, eyes were irradiated by a diode laser at the radiance of 3.25-65.3 J/cm(2) Vascular occlusion was identified by fundus photography, fluorescein angiography, and histology at 1, 3, 7, 14, and 28 days after PDT. As controls, non-neovascular eyes were subjected to PDT and similarly analyzed. RESULTS: By using the following treatment parameters, PDT with ATX-S10(Na) successfully occluded CNV without causing occlusion of retinal capillaries for 28 days; 7.4 and 19.6 J/cm(2) immediately after dye injection and 36.7 and 65.3 J/cm(2) 2 hours after injection. Although these conditions also caused occlusion of normal choriocapillaries and mild injuries of retinal vessels, retinal pigment epithelium, and photoreceptors at 1 day, retinal vessels and pigment epithelial cells recovered from damages by 28 days. No injuries were found in the inner retina. CONCLUSION: In optimal treatment conditions, PDT with ATX-S10(Na) can induce long-term, selective occlusion of CNV without causing irreversible damages in the inner retina.     

Peripheral multifield scanning fluorescein angiography for the evaluation of proliferative sickle cell retinopathy

Evaluation of proliferative sickle cell retinopathy requires detailed studies of the retina periphery, including pre-treatment documentation of active neovascular (sea fan) lesions. Multifield angiography of the periphery (MAP) is recommended for the analysis of these lesions. This method is also valuable for the pre- and post-treatment quantitative angiographic evaluation of peripheral circumferential retinal scatter photocoagulation (PCRP).     

Experimental study on changes of the spinal-evoked potential and circulatory dynamics following spinal cord compression and decompression

In an attempt to elucidate the pathogenesis of spinal cord injury, the authors investigated the changes in spinal-evoked potential (SEP) and serial fluorescein angiography during compression and after decompression of the thoracolumbar cord in dogs. The degree of compression was correlated well with the changes in SEP during compression and after decompression. The findings of serial fluorescein angiography immediately after decompression indicated hyperemia and extravasation of the fluorescein dye, especially in the group weighted with 36 and 60 g. Poor filling of the arteries and veins with fluorescein dye, and prolongation of the regional circulation time were observed at between 30 and 120 minutes after decompression in the group weighted with 36 and 60 g. These findings suggest that secondary circulatory disturbance plays an important role in the pathogenesis of spinal cord injury. The relation between changes of SEP and the circulation are also discussed.     

Experimental study on the circulatory dynamics of the spinal cord by serial fluorescein angiography

The circulatory dynamics on the dorsal surface of the spinal cord were observed by serial fluorescein angiography . Fluorescein dye appeared in the posterior spinal artery and pial arterial plexus, although the direction of blood flow might be opposite and the time taken for fluorescein dye to enter the arteries was different for each. Fluorescein dye appeared in the veins after various periods, and the directions of flow of the dye were also variable and complicated. Laminar flow often was observed in veins of less than 200 microns in diameter. The regional circulation time was calculated to be 2.1 +/- 0.4 seconds. There was no extravasation.     

Delay of retinal fluorescence as a death criterion

Retinal fluoroscopy with measurement of the arm to retina circulation time can be used to evaluate the blood supply to the brain. When the brain tissue suffers from ischaemia as a result of circulatory failure, the arm to retina circulation time will be prolonged. Sixteen patients in deep coma resulting from serious cerebral disease were examined to verify cerebral ischaemia. The results of retinal fluoroscopy and cerebral angiography agreed. We find that retinal fluoroscopy is a simple and reliable method that can be used to detect brain death in comatose patients treated by automatic ventilation. We conclude that the main cerebral circulation can be regarded as occluded if the retinal fluorescence does not appear within 25 seconds after antecubital intravenous injection of fluoresceine. We suggest that the arm to retina circulation time exceeding 25 seconds may be used as a criterion of death.     

糖尿病视网膜病变激光光凝术的疗效观察

目的观察糖尿病性视网膜病变(diabetic retinopathy,DR)激光光凝疗效,探讨DR激光光凝术的治疗时机和治疗方式。方法对79例(114眼)DR患者,根据分期、病情,选择不同方式的光凝治疗,记录患者激光前及激光后1⁶个月的最佳视力及眼底血管荧光造影(FFA)情况,评定疗效。结果 79例(114眼)DR患者接受光凝治疗前后视力及FFA结果表明,非增生性DR(nonproliferative diabetic retinopathy,NPDR)患者激光光凝疗效优于增生期DR(proliferative diabetic retinopathy,PDR)患者。结论眼底激光是治疗DR有效、安全的方法。严格规范的治疗方式,合理的治疗时机,可保存中心视力,提高疗效,有效治疗糖尿病视网膜病变。