Lasers in surgery and medicine reviewers. November 1, 1992 through October 31, 1993

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angio-graphically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5–30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels. © 1994 Wiley-Liss, Inc.     

Photocoagulation of chorioretinal anastomoses in far-advanced age-related macular degeneration

In age-related macular degeneration, communication between the retinal and choroidal circulations occurs spontaneously or following unsuccessful laser photocoagulation of subretinal new vessels. The resulting chorioretinal anastomotic complex, which includes the subretinal new vessels and their feeder retinal vessels, usually shows marked exudation and produces an extensive serous detachment of the neurosensory retina in the posterior pole, often associated with hard exudates. Eleven eyes with chorioretinal anastomotic complexes were treated using the monochromatic green argon laser. Adequate closure of the chorioretinal anastomotic complexes by photocoagulation resulted in retinal flattening in the posterior pole with resolution of the hard exudates and improvement of vision in eight of the 11 treated eyes.     

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.     

Argon green laser treatment of peripapillary choroidal neovascular membranes

Of 27 eyes with peripapillary choroidal neovascular membranes (PPCNM), 17 (63%) had age-related macular degeneration and ten (37%) were idiopathic. PPCNM were treated in 25 eyes using the monochromatic green argon laser. Two eyes were untreatable. After an average follow-up of 37.7 months, successful closure of the choroidal new vessels was obtained in 23 eyes (92%), and visual acuity was stabilized or improved in 20 (80%). Seven eyes (28%) had recurrences; in four, the new vessels extended into the macula. Post-treatment, three eyes ultimately had dry macular scars, and one had an exudative macular scar. Of these four eyes, only the one with a dry macular scar showed visual improvement. No treated cases showed arcuate scotoma.     

Comparison of intravenous and intravesical administration of chloro-aluminum sulfonated phthalocyanine for photodynamic treatment in a rat bladder cancer model.

Photodynamic therapy is an experimental treatment of superficial bladder tumors. Photofrin, a mixture of porphyrins, is the only photosensitizer in clinical use in the U.S.A. and its major side effect is prolonged cutaneous phototoxicity. In order to circumvent this problem of phototoxicity, new photosensitizers are being examined. Cutaneous phototoxicity may also be minimized by local administration of photosensitizer. Therefore, in this study, we investigated the photosensitizer chloro-aluminum sulfonated phthalocyanine (CASPc) in vivo in a rat bladder carcinoma model, and compared two different routes of CASPc administration. AY-27 rat bladder carcinoma cells were transplanted into rat bladders. Eight days after tumor transplantation the biodistribution of CASPc in bladder, skin, muscle and bladder tumor was determined by fluorescence measurements after dye extraction. Photosensitizer administered by intravenous injection and intravesical instillation, were compared. The concentration of CASPc in bladder and bladder tumor after intravenous injection and intravesical instillation was similar. The ratio of dye uptake between tumor and normal bladder after either administration was approximately two. Although no systemic absorption of the photosensitizer was observed after intravesical instillation, there was no reduction in tumor uptake or in the ratio between tumor to normal surrounding tissue. Therefore, no systemic side effects of skin phototoxicity are expected upon intravesical instillation. The microscopic biodistribution of CASPc after intravenous injection and intravesical instillation was also compared. After intravenous injection, the photosensitizer was distributed within the whole tumor with increased fluorescence around the microvasculature. In the normal bladder wall, weak fluorescence was seen in the area of the vasculature in the submucosa and the muscularis. After intravesical instillation, strong fluorescence was detected only at the tumor surface and in normal urothelium; no fluorescence was found in other areas of the tumor or in submucosa or muscularis. A comparison of the photodynamic treatment of model bladder tumors showed that tumor destruction after either method was similar but that there were less side effects to normal bladder wall after intravesical instillation of the CASPc. Intravesical administration of photosensitizers may, therefore, be a viable alternative to intravenous injection with potential for reduced systemic and normal tissue toxicity.     

Choroidal neovascularization in degenerative myopia: role of laser photocoagulation

Laser photocoagulation of extrafoveal choroidal new vessels was performed in 19 eyes with degenerative myopia. Sixteen eyes required only one treatment. Three eyes required more than one because of incomplete closure of the new vessels after the first treatment. Choroidal new vessel formation did not recur during the post-treatment follow-up period (average 29.2 months), and a dry, atrophic photocoagulation scar was achieved in all eyes. Visual acuity improved in only two eyes (11%), stabilized in four eyes (21%), and deteriorated in 13 eyes (68%). All except two eyes showed spontaneous progressive enlargement of the atrophic photocoagulation scar, which worsened visual acuity in 13 eyes (68%).     

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.     

Comparison of two routes of photosensitizer administration for photodynamic therapy of bladder cancer

Photodynamic therapy (PDT) consists in administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely the photosensitizer is given intravenously (i.v.). The goal of our study was to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible. Therefore, the uptake of chlor-aluminum-sulfonated phthalocyanine (CASPc) in bladder, bladder tumor, skin, and muscle in a rat bladder cancer model after i.v. injection and i.b instillation was compared. The efficacy of PDT after either method of administration was also evaluated. The CASPc concentration in bladder tumor after i.v. injection was approximately 1.5-fold that after i.b. instillation. The ratio of CASPc concentration between bladder tumor and normal bladder was approximately 2:1 after administration by either route. There was no systemic absorption of CASPc after i.b. instillation; hence no systemic side effects are expected. PDT showed similar effects on bladder tumor after either method of administration, but less side effects on normal bladder wall after i.b instillation. Our results demonstrate that i.b. instillation of CASP for PDT of superficial bladder cancer seems to have advantages over i.v. injection.     

Photodynamic laser cyclodestruction with chloroaluminum sulfonated Phthalocyanine (CASPc) or photofrin®(PII) Vs. Nd:YAG laser cyclodestruction in a pigmented rabbit model

Background and Objective: To investigate Photofrin® (PII) and CASPc for photodynamic therapy (PDT) of the ciliary body in rabbits. Study Design/Materials and Methods: PII (10 mg/kg) or CASPc (1 mg/kg) was given by ear vein. Pharmacokinetics were studied in frozen sections by fluorescence microscopy (CCD camera based low light detection system with digital image processing) at 1 and 24 h (8 rabbits;16 eyes). Laser light was delivered (argon pumped dye laser;630 and 675 nm;8 rabbits;16 eyes) by contact fiberoptic. To compensate for iris attenuation, irradiance was 125 mW/cm² (20, 40, 80, or 160 J/cm²). Controls (4 rabbits;8 eyes) received laser light without photochemicals (OD) and for comparison, continuous wave Nd:YAG laser by fiberoptic (0.8–1.2J;OS). Results: Localization studies showed intravascular distribution with some selective ciliary body distribution at 24 h (PII > CASPc). Rabbits treated with PII or CASPc exhibited variable amounts of gross ciliary body edema, infarction, and necrosis by 24–48 h. This response was not seen in PDT control tissues;damage was seen in the iris and ciliary body, with partial vacuolization of the pigment epithelium. Conclusion: PDT may offer a more selective approach to ciliary body destruction. A small but significant thermal effect was seen during PDT from melanin photon uptake with damage to iris and ciliary body. Thermal damage and potential interaction with ocular visual pigments may limit use of these photochemicals and wavelengths for PDT of the ciliary body © 1995 Wiley-Liss, Inc.     

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.     

Intraocular gas injection in the treatment of cornea-lens touch and choroidal effusion following fistulizing surgery

Five eyes with large choroidal detachments and flat anterior chambers following fistulizing surgery were treated with injection of perfluoropropane into the anterior chamber. In all cases the choroidal detachments resolved within 4 days, without the need for drainage. Three phakic eyes developed anterior capsular opacification in the area of contact between the gas bubble and the anterior capsule. Injection of perfluoropropane is recommended as a simple and effective approach to the management of choroidal detachments with flat anterior chamber in pseudophakic eyes and in cataractous phakic eyes.     

Long-term follow-up of photocoagulated choroidal neovascular membranes in age-related macular degeneration

Eighty-nine consecutive eyes with age-related macular degeneration and choroidal neovascularization treated with green argon laser were followed for an average of 54 months after photocoagulation. Good anatomical and functional results were obtained in 36 of 52 eyes (69%) with foveal new vessels, in 12 of 20 eyes (60%) with juxtafoveal new vessels, and in 13 of 17 eyes (76%) with perifoveal new vessels. Thirty-four of the 89 eyes (38%) had at least one recurrence of new vessels, which most often affected the edge of the previously treated area (30 eyes, 34%). In 18 eyes (20%), these recurrences involved the edge of the scar closer to the fovea.     

Retinal toxicity and in vitro efficacy study of cilofungin (LY121019)

We assessed the retinal toxicity of a new antifungal agent, cilofungin, by injecting it into the vitreous body of albino rabbit eyes in dosages of 2.5 micrograms to 320 micrograms. The maximum intravitreal drug concentration (320 micrograms) produced no histological evidence of retinal toxicity. Electroretinography data showed some variations, but no toxicity at the highest dose (320 micrograms). When efficacy was evaluated in vitro against Candida albicans, the minimal inhibitory concentration was 2.50 micrograms/mL, using Sabouraud's broth or M3 medium. The minimal fungicidal concentration was 5 micrograms/mL with Sabouraud's broth, and 10 micrograms/mL with M3 medium. Cilofungin is a potentially safe antifungal for the treatment of candida endophthalmitis.     

Enhancing integration of articular cartilage grafts via photochemical bonding

The integration of osteochondral grafts to native articular cartilage is critical as the lack of graft integration may lead to continued tissue degradation, poor load transfer and inadequate nutrient transport. Photochemical bonding promotes graft integration by activating a photosensitizer at the interface via a light source and avoids negative effects associated with other bonding techniques. We hypothesized that the bond strength depends on photosensitizer type and concentration in addition to light exposure. Photochemical bonding was evaluated using methylene blue (MB), a cationic phenothiazine photosensitizer, and two phthalocyanine photosensitizers, Al(III) phthalocyanine chloride tetrasulfonic acid (CASPc) and aluminum phthalocyanine chloride (AlPc). Exposure was altered by varying irradiation time for a fixed irradiance or by varying irradiance with a fixed irradiation time. MB was ineffective at producing bonding at the range of concentrations tested while CASPc produced a peak twofold bond strength increase over controls. AlPc produced substantial bonding at all concentrations with a peak 3.9‐fold bond strength increase over controls. Parametric tests revealed that bond strength depended primarily on the total energy delivered to the bonding site rather than the rate of light delivery or light irradiance. Bond strength persisted for 1 week of in‐vitro culture, which warrants further exploration for clinical applications. These studies indicate that photochemical bonding is a viable strategy for enhancing articular cartilage graft integration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2406–2415, 2018.

     

眼底血管荧光造影在评估视网膜挫伤预后方面临床研究

目的：评价眼底血管荧光造影（FFA）在视网膜挫伤预后评价中的应用。方法选取视网膜挫伤患者51例为研究对象,分别采用视觉诱发电位（VEP）、FFA进行检查,并全部随访51例患者的视力变化。结果挫伤的眼睛其VEP P100波振幅明显降低,潜伏期明显延迟;治疗后VEP P100波振幅、潜伏期均明显改善（P＜0.05）;FFA检查混合性损伤32眼,单纯性损伤19眼,其中38眼表现为视网膜震荡,14眼表现为视网膜出血,5眼表现为脉络膜裂伤,4眼表现为黄斑裂孔,8眼表现为视神经挫伤。治疗后1个月复查眼底血管荧光造影显示,51眼中,视盘渗漏1眼,周边视网膜血管仍有渗漏者3眼,视网膜新生血管未退行1眼。结论VEP、F-ERG及FFA检查均可对眼挫伤患者进行有效的诊断及预后评估,临床应用中可根据患者情况联合或单独应用。     

Accidental Nd:YAG laser-induced choroidal neovascularization

BACKGROUND: There are few reports in the literature to describe the natural history of an occupational Nd:YAG laser-induced retinal injury. METHODS: The chronological response to a Nd:YAG laser-induced injury was studied in a 48-year-old male using the techniques of color fundus photography, fluorescein angiography and optical coherence tomography. When he developed choroidal neovascularization his response to photodynamic therapy with verteporfin was recorded. RESULTS: The patient initially developed a macular hole, which spontaneously closed. Three months after the injury a choroidal neovascular membrane developed. This stabilized after the use of photodynamic therapy. CONCLUSIONS: Surgical closure of Nd:YAG induced macular holes should be delayed to allow spontaneous closure. Photodynamic therapy was successful in treating choroidal neovascularization in this case.     

A neodymium-YAG endolaser

We used a CW-YAG endolaser to photocoagulate the fundus of the rabbit and monkey. We varied the power settings, exposure durations, and probe-retina distances to establish the parameters for threshold and bursting (choroidal hemorrhage) lesions. We found that the amount of energy needed to create a retinal lesion increased proportionally with the distance between the probe and the retina. To produce a choroidal hemorrhage at a given distance required at least four times the power required for a threshold coagulative lesion at the same distance. We also found that we could achieve a strong choroidal reaction without hemorrhage by using the coagulative threshold parameters of power and distance with an increased exposure time. Photocoagulation of the retina using the CW-YAG depended on the presence of melanin.     

The rationale of photocoagulation therapy for proliferative diabetic retinopathy: a review and a model

A model is proposed for initiation and inhibition of growth in retinal vessels including the control of proliferative diabetic retinopathy by photocoagulation. The model assumes that chronic dilatation (constriction) of a retinal blood vessel causes (inhibits) growth. Destruction of rods and cones by photocoagulation allows more choroidal oxygen to reach the inner retina and constrict retinal vessels. The attenuated vessels in late stage retinitis pigmentosa are an analogous and exaggerated effect to that from photocoagulation. The control of proliferative diabetic retinopathy is compared to the cause of retrolental fibroplasma. Following vitrectomy the retina utilizes oxygen from the aqueous which results in dilatation of iris vessels followed by rubeosis iridis. From this model, neovascularization from the disc or angle vessels follows the dilatation resulting from increased flow in their distal vascular beds.     

Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema

The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme (APE) in the management of diabetic retinopathy and diabetic macular edema (DME). Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included. All cases were treated with an initial intravitreal injection of APE and reevaluated one month later, measuring changes in best-corrected visual acuity (BCVA), macular thickness and the status of the posterior hyaloid. A second APE injection was performed in cases with no evident posterior vitreous detachment (PVD) after the initial treatment. Sixty-three eyes were included in the present review. A complete PVD appeared in 38% of cases (24 eyes) after one injection of plasmin and the total increased to 51% (32 eyes) after the second injection, separated at least by one month. The central macular thickness improved in all cases (100%) and BCVA in 89%. Finally, in 50% of eyes with proliferative diabetic retinopathy, a high reduction of new vessels regression was observed. Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema.     

Comparative study of three fluorescent dyes for angiography: sodium fluorescein, carboxyfluorescein, and calcein

To compare the characteristics of carboxyfluorescein (CF) and calcein (Calc) with those of sodium fluorescein (Naf), the only fluorescent dye currently in clinical use, we performed angiography in rabbits and primates using these three dyes. The circulation decay time of all dyes was longer in primates than in rabbits. In primates, CF and Calc had longer decay times than Naf. Calc produced the greatest contrast between the choroidal and retinal vasculature. Tissue staining and dye leakage into the vitreous immediately after retinal photocoagulation were minimal with Calc, moderate with CF, and marked with Naf. The limited leakage and longer circulation time of Calc may permit simultaneous angiography and photocoagulation therapy without obscuring the fundus view with leaking dye from the photocoagulated structure.