微脉冲半导体激光与氩激光对兔视网膜损伤及修复的组织学研究

目的观察微脉冲半导体激光与氩激光对兔视网膜损伤和修复的组织学反应。方法在黄斑水肿治疗参数下分别对兔眼行微脉冲阈下光凝和氩激光光凝,观察视网膜组织学改变。结果微脉冲阈下光斑不可见而氩激光可见;激光后两者光镜下视网膜感光细胞损伤不明显但脉络膜小静脉轻度充血,4周后消退;电镜下氩激光光斑处外节排列稀疏,色素上皮细胞（RPE）和节细胞肿胀,外核层细胞异染色质增多,4周后RPE和胶原增生明显,脉络膜内色素颗粒增生;而微脉冲光斑变化不明显。结论微脉冲激光光凝视网膜较氩激光损伤更轻微。     

微脉冲半导体激光对兔视网膜损伤的实验研究

目的初步研究微脉冲半导体激光对兔眼视网膜损伤的生物学效应。方法8只有色兔(16眼)中每只眼的上、下方视网膜随机分别行810nm半导体激光连续波阈值光凝及微脉冲阈下光凝,于光凝后即刻观察光斑反应和眼底荧光造影后荧光素渗漏情况,并在光镜和电镜下观察其对视网膜和脉络膜造成的组织学改变。结果微脉冲激光阈下光凝后光斑不可见,亦无荧光素渗漏,视网膜损伤不明显;阈值光凝后可见光斑反应并有荧光素渗漏,视网膜损伤明显,外核层细胞数量减少,内、外核层均出现少量核固缩和胞浆空泡化,视网膜色素上皮细胞增生,Bruch膜完整无损。结论微脉冲激光光凝视网膜不会损伤视网膜,但确定阈能量时要从低能量起,且选择周边视网膜。     

微脉冲半导体激光对兔眼视网膜损伤的形态学观察

目的:研究微脉冲半导体激光对兔眼视网膜损伤的生物学效应.方法:有色兔8只16眼,每眼上、下方视网膜随机分别行810nm半导体激光连续波阈值光凝及微脉冲阈下光凝,于光凝后即刻观察光斑反应和眼底荧光造影后荧光素渗漏情况,并在光镜和电镜下观察其对视网膜和脉络膜造成的组织学改变.结果:微脉冲激光阈下光凝后光斑不可见,亦无荧光素渗漏,视网膜损伤不明显;阈值光凝后可见光斑反应并有荧光素渗漏,视网膜损伤明显,外核层细胞数量减少,内、外核层均出现少量核固缩和胞质空泡化,视网膜色素上皮细胞增生,Bruch膜完整无损.结论:微脉冲激光光凝视网膜不会损伤视网膜,但确定阈能量时要从低能量起,且选择周边视网膜.     

微脉冲半导体激光与氩激光对兔视网膜损伤的形态学比较

目的:研究微脉冲半导体激光和氩激光对兔眼视网膜损伤的形态学改变。方法:有色兔8只16眼,每只兔的两眼随机分别行810nm微脉冲阈下光凝和514nm氩绿激光光凝,在黄斑水肿治疗参数下,光凝后即刻观察光斑反应并在光镜和电镜下观察其对视网膜和脉络膜造成的组织学改变。结果:微脉冲激光阈下光凝后光斑不可见,氩激光光凝后可见光斑反应;激光后即刻两者光镜下视网膜感光细胞损伤不明显但脉络膜毛细血管、小静脉轻度充血,电镜下氩激光光凝处外节排列稀疏,色素上皮细胞和节细胞肿胀,外颗粒层细胞异染色质增多。微脉冲光凝处外节排列较整齐,外颗粒层变化不明显。结论:微脉冲激光光凝视网膜较氩激光损伤更轻微。     

微脉冲阈值下半导体激光在视网膜疾病中的应用研究进展

激光光凝治疗已经在多种视网膜疾病治疗中取得了满意的效果,已成为眼底疾病治疗的重要手段之一。微脉冲阈值下半导体激光（subthreshold diode micropulse laser,SDM）是近年来激光治疗中研究较热门的一种,目前SDM在多种视网膜疾病引起的黄斑水肿的治疗中取得了较满意的疗效,且有效降低了并发症的发生。本文就SDM的概念、治疗原理以及其对视网膜组织产生的影响进行总结,并就其在多种视网膜疾病治疗中的应用进展进行综述。     

眼科微脉冲半导体激光技术的研究现状

微脉冲半导体激光作为一种新的激光治疗手段,在获得与传统激光相同疗效的同时,可以最大程度地减少治疗区域周边组织的损伤,最大限度地保护接受激光治疗的患者视力。然而,目前临床上尚缺乏明确的激光参数标准,使得该技术未能得以广泛应用。本文就微脉冲半导体激光技术的研究现状作一综述。     

阈下微脉冲激光在黄斑疾病中的应用

微脉冲激光是一种短促高频的重复脉冲激光,已成为多种视网膜疾病的有效治疗方式。与传统激光相比,阈下微脉冲激光不伴有视网膜的热损伤,可用于黄斑区疾病的治疗。目前已广泛用于治疗糖尿病性黄斑水肿(diabetic macular edema,DME)、视网膜静脉阻塞(retinal vein occlusion,RVO)伴发的黄斑水肿以及中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)并取得了一定效果,但其能量参数的设置标准、安全性及成功率等问题还需要进一步研究。     

577nm阈下微脉冲激光与577nm激光光凝对兔视网膜组织影响的比较

背景 近年来研究表明,577 nm阈下微脉冲激光治疗视网膜疾病可达到传统577 nm激光光凝的治疗作用且对视网膜组织损伤小,但其具体作用机制和敏感的靶细胞尚未完全阐明. 目的 探讨和比较577 nm阈下微脉冲激光与577 nm激光光凝视网膜后成年中华黑兔视网膜组织形态学变化,为577 nm阈下微脉冲激光光凝在临床上的应用提供依据.方法 采用抽签法按照视网膜光凝条件不同将26只中华黑兔分为正常对照组(2只)、577 nm激光组(6只)和阈下微脉冲激光组(18只),其中阈下微脉冲激光组按照激光工作负载率的不同亚分为9％、12％和15％阈下微脉冲激光组,每组各6只,正常对照组不做任何处理.光凝后行彩色眼底照相及OCT检查,摘取兔眼球壁行苏木精-伊红染色,光学显微镜下观察兔脉络膜和视网膜组织结构的变化.结果 彩色眼底照相和OCT显示正常对照组兔眼视网膜组织结构清晰.9％阈下微脉冲激光组OCT扫描可见视网膜神经上皮层稍模糊;12％阈下微脉冲激光组光凝斑处视网膜神经上皮层轻度水肿,视网膜色素上皮(RPE)层稍模糊;15％阈下微脉冲激光组可见光凝斑处视网膜神经上皮层明显水肿,RPE层局限性隆起;各阈下微脉冲激光组彩色眼底照相均未见光凝斑.577 nm激光组兔眼彩色眼底照相可见灰白色光凝斑,OCT扫描层面可见视网膜呈多灶性隆起,视网膜各层组织结构模糊,伴浆液性神经上皮层脱离.视网膜组织病理学检查可见,与正常对照组兔眼相比,9％和12％阈下微脉冲激光组兔眼脉络膜血管变形或出血,但视细胞形态结构、双极细胞层和视网膜神经节细胞(RGC)层未见明显改变;15％阈下微脉冲激光组视细胞扁平状膜盘肿胀,双极细胞层和RGC层未见明显改变;577 nm激光组兔眼视细胞层、双极细胞层和RGC层结构紊乱,RPE层变薄.结论 577 nm阈下微脉冲激光对脉络膜层和RPE层具有高度选择性,视网膜光凝后对视网膜神经上皮层的损伤程度轻微,既可发挥治疗作用,又不损伤视网膜神经上皮;577 nm激光视网膜光凝可对视网膜全层造成损伤.     

微脉冲半导体激光治疗CSC的初步观察

目的:探讨微脉冲半导体激光治疗中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的疗效。方法:自身对照病例研究。将经荧光素眼底血管造影(fundus fluorescein angiography,FFA)和光学相干断层扫描(optic coherence tomography,OCT)检查确诊的典型性CSC患者12例12眼行微脉冲半导体激光治疗前及治疗后随访观察1,2wk;1,3mo的临床资料进行分析,主要以治疗前后的视力、自觉症状、眼底情况、FFA及OCT检查的改变为观察指标,以评价微脉冲半导体激光对CSC的治疗效果。结果:所有患者自觉症状减轻或消退,视力及视觉质量均有不同程度改善。激光光凝2wk和1mo后,分别有9眼(75.0%)和11眼(91.7%)的黄斑区水肿完全消退,3mo后全部患者黄斑区水肿消退。光凝2wk后,FFA检查发现有9眼荧光素渗漏完全消失,3眼渗漏减轻;OCT检查有9眼黄斑区视网膜下积液消失,中心凹视网膜厚度恢复正常,3眼黄斑区视网膜下积液大部分吸收。光凝1mo后,FFA检查有11眼荧光素渗漏完全消失;OCT检查有11眼黄斑区视网膜下积液消失,中心凹视网膜厚度恢复正常。光凝3mo后,FFA显示所有患眼的荧光素渗漏完全消失,未见明显"窗样缺损"样荧光;OCT检查发现所有患眼黄斑区视网膜下积液完全吸收。结论:微脉冲半导体激光治疗CSC是一种安全、有效的治疗方法,能有效缩短病程,提高患者视力,避免并发症的发生。     

微脉冲半导体激光照射对正常大鼠视网膜损伤的观察

目的观察810 nm微脉冲半导体激光照射对正常棕色挪威大鼠（BN 大鼠）视网膜的损伤。方法使用不同能量及负载系数（duty cycle, D C）的810 nm微脉冲半导体激光对130只BN大鼠眼进行照射。分别于激光照射后第1、3、7、1 4、28 d进行彩色眼底照相、荧光素眼底血管造影及组织病理学观察，并检测热休克蛋白(HSP-70)在视网膜的表达情况，用TdT介导dUTP缺口末端标记法(TUNEL)检查细胞凋亡 。结果阈值及阈上能量条件下，低DC时激光照射部位无光学显微镜下的组织病理学改变，高DC时出现可累及视网膜内核层组织的严重损伤；微脉冲半导体激光照 射后1 d大鼠视网膜内核层细胞HSP-70阳性表达细胞即较正常视网膜明显增加，3 d时达到高峰，以后逐渐下降，14 d时恢复近正常水平。HSP-70阳性细胞数量 随激光能量提高而增加。TUNEL染色可见激光照射部位凋亡细胞主要存在于视网膜色素上皮（RPE）层、外核层、内核层，甚至脉络膜层，其数量随激光能量增高而增多。在激光照射后第3 d，凋亡细胞数量最多。结论810 nm微脉冲半导体激光照射后，视网膜损伤程度与激光能量及DC呈正相关。低能量高负载系数（50 mW，50％）或高能量低负载系数（100 mW，5％～15％）时，损伤限于RPE层，避免了神经上皮层的损伤。激光照射后HSP-70高表达及细胞凋亡可能在组织损伤修复过程发挥重要作用。 （中华眼底病杂志，2008，24：122-126）     

Micropulsed Diode Laser Therapy: Evolution and Clinical Applications

Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications.     

Diode laser-induced mitosis in the rabbit retinal pigment epithelium.

BACKGROUND AND OBJECTIVE: The induction of retinal pigment epithelium (RPE) proliferation without damaging the inner layers of the retina might be helpful in patients with RPE atrophic changes and degeneration. This study aimed to induce mitosis in the RPE of the rabbit after subthreshold photocoagulation with the diode laser. MATERIALS AND METHODS: Twenty-five male Dutch rabbits received retinal photocoagulation using an 810-nm diode laser with different power settings and exposure times. The eyes were processed for light microscopy, electron transmission microscopy, and immunohistochemistry. RESULTS: Neither morphological alterations nor mitotic activity was found after 5-mJ energies. Retinal layers were not affected and RPE hyperplasia appeared in the treated areas associated with mitotic activity when 10 mJ was used. Mitosis induction and retinal damage appeared with 20, 50, and 100 mJ and were associated with ophthalmoscopic damage. CONCLUSIONS: The use of subthreshold 810-nm diode laser treatment may induce mitosis in the RPE without causing damage to the neighboring layers.     

Argon laser vs. subthreshold infrared (810-nm) diode laser macular grid photocoagulation in nonexudative age-related macular degeneration

BACKGROUND: A diode laser can be used to create a subthreshold (invisible end point) lesion in patients with age-related macular degeneration (AMD). This has the potential benefit of localizing the treatment effect to the retinal pigment epithelium and sparing more of the overlying sensory retina. We performed a study to compare the safety and efficacy of argon laser and subthreshold infrared (810-nm) diode laser macular grid photocoagulation in reducing the number of drusen in patients with AMD. METHODS: We reviewed the charts of 144 patients with bilateral early-stage nonexudative AMD, characterized by soft drusen. One eye of each patient was treated, and the other eye served as a control. Seventy-eight eyes of 78 patients with a mean age of 67.5 (standard deviation [SD] 8.3) years underwent argon laser macular grid photocoagulation at a university-affiliated hospital in Bologna, Italy, and 66 eyes of 66 patients with a mean age of 66.4 (SD 6.3) years underwent subthreshold infrared (810-nm) diode laser macular grid photocoagulation at a private clinic in Bologna. Each group was classified into three subgroups based on the number of drusen (more than 20, 10 to 20, or less than 10). The patients underwent fluorescein angiography, fundus examination, measurement of far (Snellen chart) and near (Jaeger chart) best corrected visual acuity, and visual field and contrast sensitivity testing. The mean length of follow-up was 18 (SD 0.5) months. RESULTS: At 18 months, far and near best corrected visual acuity were statistically significantly improved in the treatment groups compared with the untreated group (p < 0.001, Mann-Whitney U test). There was no significant difference in visual acuity between the treatment groups. Compared with baseline, the number of drusen was significantly reduced in both treatment groups (p < 0.001). Evolution of the disease was observed in the untreated group. The visual field was slightly but significantly reduced after argon laser treatment (p < 0.001) but not diode laser treatment; the difference in visual field between the two groups was not significant. There was a slight reduction in contrast sensitivity, particularly with night vision, after argon laser treatment but not diode laser treatment. The difference between the two treatment groups was significant (p < 0.01). INTERPRETATION: Subthreshold infrared diode macular grid photocoagulation may be a safe and viable method for preventing progression of nonexudative AMD.     

Subthreshold micropulse diode laser photocoagulation for clinically significant diabetic macular oedema: a three-year follow up

PURPOSE: To report the long-term visual outcome of subthreshold micropulse diode laser photocoagulation for clinically significant diffuse diabetic macular oedema (CSME). DESIGN: Non-comparative case-series. METHODS: The main outcome measures of this 3-year follow-up study of infrared (810 nm) subthreshold diode micropulse laser photocoagulation for CSME were visual outcome and the angiographic CSME status of 19 patients (25 eyes). RESULTS: Visual acuity stabilized or improved in 84% of treated eyes by the end of the first year. The result was maintained in the second year and by the third year, 92% maintained vision. However, more patients needed supplementary grid laser in the third year than in the second year. CSME decreased in 92% of the eyes and resolved in 88% in the first year. By the second year, 92% showed complete resolution. However, in the third year, recurrent CSME was noted in 28% of patients. CONCLUSION: This study has the longest follow up reported so far and demonstrating that subthreshold micropulse diode laser photocoagulation has a beneficial long-term effect on visual acuity and resolution of CSME with minimal chorio-retinal damage.     

Serial optical coherence tomography of subthreshold diode laser micropulse photocoagulation for diabetic macular edema.

BACKGROUND AND OBJECTIVE: To use serial optical coherence tomography (OCT) to evaluate low-intensity, high-density subthreshold diode laser micropulse photocoagulation treatment of clinically significant diabetic macular edema. PATIENTS AND METHODS: Eighteen consecutive eyes of 14 patients with clinically significant diabetic macular edema and a minimum foveal thickness of 223 microm or greater were prospectively evaluated by OCT preoperatively and 1, 4, and 12 weeks following treatment. RESULTS: Overall, estimated macular edema 3 months postoperatively (minimum foveal thickness--223 microm) was reduced a mean of 24% (P = .02). Eleven eyes treated for recurrent or persistent clinically significant diabetic macular edema following prior treatment more than 3 months before study entry were most improved, with a mean reduction in estimated macular edema 3 months postoperatively of 59%. No treatment complications were observed. No patient demonstrated laser lesions following treatment. CONCLUSIONS: Low-intensity, high-density subthreshold diode laser micropulse photocoagulation can reduce or eliminate clinically significant diabetic macular edema measured by OCT. Further study is warranted.     

Subthreshold micropulse diode laser treatment in diabetic macular oedema

BACKGROUND/AIM: Enlargement of laser scars after retinal argon laser photocoagulation can give rise to deterioration in visual acuity. Subthreshold micropulse diode laser may decrease this risk. The aim of this study was to compare the effectiveness of subthreshold micropulse diode laser (810 nm) and conventional argon laser (514 nm) photocoagulation for the treatment of clinically significant macular oedema in diabetic patients. METHODS: 23 eyes of 16 patients were randomised to either treatment. Follow up was conducted for a minimum of 5 months. Changes in visual acuity and macular oedema measured by optical coherence tomography were examined. RESULTS: Visual acuity remained stable in all treatment groups throughout the observation period. Changes in retinal thickness were small both foveally and perifoveally. In patients with focal macular oedema a significant reduction in retinal thickness (9% approximately -26 microm, p = 0.02) was seen foveally 3 months after diode laser photocoagulation. CONCLUSION: Subthreshold micropulse diode laser and conventional argon laser treatment showed an equally good effect on visual acuity. Subthreshold micropulse diode laser showed a stabilising or even improving effect on macular oedema. The combination of primary diode laser and supplementary argon laser might be particularly favourable in reducing diabetic macular oedema.     

Indocyanine green dye-enhanced micropulsed diode laser: a novel approach to subthreshold RPE treatment in a case of central serous chorioretinopathy

PURPOSE: To present a case of central serous chorioretinopathy (CSC) treated with indocyanine green (ICG) dye-enhanced subthreshold micropulsed diode laser photocoagulation. METHODS CASE REPORT: A 35-year-old man presenting with recurrent CSC with persistent serous detachment of the sensory retina in his left eye who declined treatment with a 532 nm laser. Subthreshold treatment, with no visible endpoint, was performed with an 810 nm diode laser 15 minutes after the injection of 25 mg ICG in 2 cc of 5% glucose solution. The laser energy was delivered over the active leakage sites with a sequence of repeated 500 ms "envelopes" each containing a train of 250 micropulses with 500 mW peak power at 10% duty cycle (200 micros ON and 1,800 micros OFF) and each separated by 500 ms intra-envelopes relaxation time. Due to the absence of visible laser-induced lesions, post treatment ICG digital angiographic images were taken without further dye injection to verify that the hypofluorescent spots resulting from the subthreshold laser applications coincided with the points of leakage. RESULTS: After 7 days, the patient presented with a less hyperopic refraction, improved visual acuity, and reduction of serous neuroepithelial detachment. No signs of laser treatment were visible at fluorescein angiography. After 8 weeks, the serous neuroepithelial detachment was almost completely resolved. CONCLUSIONS: ICG dye-enhanced subthreshold micropulsed diode laser photocoagulation appears to be a safe and effective treatment and represents a possible approach for the management of chronic CSC with persistent central serous neuroepithelial detachment. Immediate post treatment ICG angiography, without ICG reinjection, allows documenting the actual number and location of the delivered subthreshold laser applications.     

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment.DESIGN: Randomized controlled clinical trial.METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes.RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes.CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.     

Recent developments in retinal lasers and delivery systems

Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has offered us newer lasing mediums, wavelengths and delivery systems. Pattern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical effect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more effective for vascular structures and offers a more uniform effect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.