A novel neuroprotectant against retinal ganglion cell damage in a glaucoma model and an optic nerve crush model in the rat

PURPOSE: To investigate the effects of repeated treatments with a neuroprotective compound, R(-)-1-(benzo [b] thiophen-5-yl)-2-[2-(N, N-diethylamino) ethoxy] ethanol hydrochloride (T-588), on retinal ganglion cell (RGC) survival in rat eyes with elevated intraocular pressure (IOP) or after optic nerve crush. METHODS: An increase in IOP was induced by a single laser treatment to the trabecular meshwork in one eye of adult Wistar rats. Crush injury was unilaterally produced by clipping the optic nerve 2 mm behind the globe. RGC density was estimated by counting fluorescent dye-labeled cells in the flatmount of the retina. The optic nerve damage in the crush model was also evaluated histologically. RESULTS: In the elevated IOP model, RGC survival decreased to 72.9% +/- 3.8% (mean +/- SEM) of that of the contralateral control eye on the eighth day after laser irradiation. Repeated treatments with T-588 at 30 mg/kg twice daily significantly enhanced RGC survival (86.0% +/- 2.2%, P = 0.0242) without the reduction of IOP. In the optic nerve crush model, RGC survival diminished to 37.2% +/- 8.4% of that of the contralateral control eye after 4 weeks. Repeated applications with T-588 at 10 mg/kg twice daily significantly enhanced RGC survival (77.8% +/- 2.1%, P = 0.0038). Histologically, the rat optic nerve in the group treated with T-588 at 10 mg/kg retained a near-normal morphology. CONCLUSIONS: T-588 has a neuroprotective effect against RGC death caused by elevated IOP and optic nerve crush in the rat.     

Induction of heat shock protein 72 protects retinal ganglion cells in a rat glaucoma model

PURPOSE: To investigate whether heat shock protein (Hsp) 72 is induced in retinal ganglion cells (RGCs) in experimental rat glaucoma and whether the induction of Hsp72 by heat stress or zinc (Zn(2+)) administration can increase survival of RGCs in the model. METHODS: Intraocular pressure (IOP) was elevated unilaterally in Wistar rats with argon laser irradiation of the trabecular meshwork 5 days after intracameral injection of india ink. Immunohistochemical staining for Hsp72 was performed. The rats with elevated IOP were treated with heat stress once a week (six rats) or intraperitoneal injection of zinc (10 mg/kg) every two weeks (six rats). Untreated rats with elevated IOP served as a control group (six rats). Quercetin, an inhibitor of Hsp expression was injected in the rats with heat stress (six rats) and zinc injection (seven rats). Subsequent to 4 weeks of IOP elevation, RGCs were counted. RESULTS: The IOP increase compared with the contralateral eyes was 48% +/- 4% throughout the study period. Hsp72 was detected only in the eyes with elevated IOP at 1 and 2 days and was weakly detected at 1 week of IOP elevation. A single administration of zinc strongly induced Hsp72 in RGCs of rats with elevated IOP for 2 weeks. Treatment with heat stress or zinc in rats with elevated IOP increased RGC survival after 4 weeks of IOP elevation, compared with the untreated control group (P = 0.004, n = 6). Quercetin reversed the positive effect of heat stress or zinc injection on RGC survival. CONCLUSIONS: These results demonstrate the possibility of a novel therapeutic approach to glaucoma through an enhanced induction of the endogenous heat shock response.     

Trabecular bypass stents decrease intraocular pressure in cultured human anterior segments

PURPOSE: To determine the effect on intraocular pressure (IOP) of bypassing the trabecular meshwork in cultured human anterior segments. DESIGN: Prospective laboratory investigation using normal human eyes obtained at autopsy. METHODS: Anterior segments from 21 eyes were placed in perfusion culture, and trabecular bypass stents were inserted through the trabecular meshwork, with the lumen of the tube opening into Schlemm's canal. Eyes received from one to four stents, placed equidistant apart. In eyes receiving one or two stents, additional stents were later added to a maximum of four per eye. RESULTS: Intraocular pressure was lowered after placement of a single stent, from 21.4 +/- 3.8 mm Hg to 12.4 +/- 4.2 (P < .001). This corresponded to an 84% increase in facility of outflow. Eyes receiving more than one stent had final IOP of 11.9 +/- 3.7 mm Hg. Nine eyes had sequential addition of stents, and seven of these had a further decrease of IOP (13.6 +/- 4.1 to 10.0 +/- 4.3; P = .02). Excision of the entire meshwork, between stents, dropped IOP to 6.3 +/- 3.2 mm Hg, indicating some residual meshwork or canal resistance remained even after placement of three stents. CONCLUSIONS: Bypass of the trabecular meshwork lowers IOP in cultured human anterior segments. One stent produced the greatest change in pressure. The sequential addition of more stents further lowered pressure in seven of nine eyes. This technique holds promise as a new clinical surgery for glaucoma.     

Effects of travoprost on aqueous humor dynamics in monkeys

PURPOSE: To determine the mechanism by which travoprost, a prodrug of a prostaglandin F2alpha analog, reduces intraocular pressure (IOP) in cynomolgus monkey eyes. METHODS: One eye each of 12 monkeys was treated with laser burns to the trabecular meshwork to elevate IOP. At least 4 months later (Baseline Day), IOP was measured by pneumatonometry (9:00 AM and 11:45 AM), and aqueous flow and outflow facility were determined by a fluorophotometric method. Uveoscleral outflow was calculated. Both eyes were treated with travoprost 0.004% at 9:00 AM and 5:00 PM for two days and at 9:30 AM on the third day (Treatment Day), when measurements were repeated as on Baseline Day. Statistical analyses were performed using two-tailed, paired t tests. RESULTS: On Treatment Day compared with Baseline Day, IOP in hypertensive eyes was reduced at 2.25 hours (25.8 +/- 11.2 vs 33.7 +/- 13.2 mm Hg; mean +/- standard error of the mean [SEM]; P = 0.02) and 16 hours (26.3 +/- 10.2 vs 35.1 +/- 13.6 mm Hg; P = 0.02) after treatment. The increase in uveoscleral outflow was not significant. In normotensive eyes, IOP was reduced at 2.25 hours (19.0 +/- 3.7 vs 23.0 +/- 4.0 mm Hg; P = 0.03) and 16 hours (20.7 +/- 5.4 vs 23.4 +/- 5.3 mm Hg; P = 0.01) after treatment, and uveoscleral outflow was significantly (P = 0.02) increased (1.02 +/- 0.43 vs 0.35 +/- 0.72 microL/min). CONCLUSION: Travoprost reduces IOP in normotensive monkey eyes by increasing uveoscleral outflow. The IOP reduction in hypertensive eyes is probably via the same mechanism, although the increased uveoscleral drainage did not reach statistical significance. Travoprost had no effect on aqueous flow or outflow facility.     

经房角镜光凝小梁网法建立慢性高眼压大鼠模型及其与经角膜缘光凝法的比较

背景 慢性高眼压动物模型的建立是青光眼发病机制研究的基础,以往激光光凝建立慢性高眼压动物模型的方法存在模型眼压波动大,需要重复光凝和并发症多的问题,造模方法的改良对于顺利开展相关的实验研究具有重要意义. 目的 用经房角镜光凝小梁网法建立大鼠慢性高眼模型,并与以往的经角膜缘光凝法进行比较. 方法 选取8 ～12周龄清洁级Fischer344大鼠36只,将动物分为正常对照组、经角膜缘光凝组和经房角镜光凝组,每组12只,经角膜缘光凝组采用532 nm YAG激光经角膜缘光凝大鼠右眼小梁网建立慢性高眼压模型,激光能量为440 ～ 500 mW,激射光斑40 ～ 60个;经房角镜光凝组激光能量为800 ～850 mW,激射光斑100～120个.光凝后用Tonolab眼压计测量并观察各组大鼠眼压变化;于光凝后第3周每组处死5只大鼠,分离视网膜,采用免疫荧光技术检测并比较各组大鼠视网膜中Tuj-1阳性的视网膜神经节细胞(RGCs)数目.实验动物的使用及喂养遵循ARVO声明.结果 造模后3周各组大鼠一般情况可,眼表无明显损伤.经角膜缘光凝组和房角镜光凝组慢性高眼压模型的成模率分别为75％和100％.正常对照组、经角膜缘光凝组和经房角镜光凝组大鼠模型眼造模后3周的平均眼压分别为(11.0±1.3)、(23.4±12.6)和(25.3±4.9)mmHg(1 mmHg=0.133 kPa),峰眼压分别为(12.3±1.0)、(50.5±7.3)和(44.3±12.3)mmHg,组间总体比较差异均有统计学意义(F=25.496、80.762,均P＜0.001),其中经角膜缘光凝组和经房角镜光凝组大鼠模型眼平均眼压均明显高于正常对照组,差异均有统计学意义(均P＜0.001),而2个组间平均眼压和峰眼压差异均无统计学意义(P=1.000、0.195).正常对照组、经角膜缘光凝组和经房角镜光凝组大鼠视网膜中Tuj-1阳性RGCs数目分别为(2 048.2±148.5)、(645.2±177.1)及(1 223.7±148.6)/mm2,总体比较差异有统计学意义(F=98.767,P＜0.001),其中经角膜缘光凝组和经房角镜光凝组大鼠视网膜中Tuj-1阳性RGCs数目均明显少于正常对照组,且经角膜缘光凝组大鼠视网膜中Tuj-1阳性RGCs数目明显少于经房角镜光凝组,差异均有统计学意义(均P＜0.01). 结论 经房角镜光凝小梁网能够诱导大鼠慢性高眼压并导致RGCs损害,但眼压升高模式及RGCs损害程度与经角膜缘光凝法有所不同,经房角镜光凝法建立慢性高眼压模型成模率更高.     

激光光凝法诱导大鼠高眼压模型的有效性评估

目的　评估激光光凝法诱导大鼠高眼压模型的有效性。方法　５３２ｎｍ激光光凝小梁网法诱导大鼠左眼高眼压（ｎ＝４５,右眼为对照眼）,评估激光后大鼠眼压、视网膜神经节细胞及视网膜电图的变化;采用Ｔｏｎｏ-Ｌａｂ眼压计测量清醒状态下的双眼眼压,每天１次;激光后３周,采用双盲法计数双眼视网膜铺片上免疫组织化学法标记的阳性节细胞数;记录大鼠双眼基线及处死前的视网膜电图。结果　激光后９０．７０％（３９／４３眼）的大鼠眼压升高,其中需要第２次激光者占７４．４２％（３２／４３眼）。激光后右眼的眼压为（１６．１３±１．１１）ｍｍＨｇ（ｎ＝３９;１ｋＰａ＝７．５ｍｍＨｇ）;左眼中有２８．２１％眼（ｎ＝１１）眼压升高（１８．２７±２．５３）ｄ,其余眼（ｎ＝２８）眼压升高（７．９３±２．４０）ｄ,两者的眼压分别为（３５．５９±４．５７）ｍｍＨｇ、（２１．５６±３．０６）ｍｍＨｇ,两者的峰值眼压分别为（６３．３６±４．２３）ｍｍＨｇ、（４９．４３±７．２２）ｍｍＨｇ;实验眼与对照眼之间的峰值眼压差为（３１．１３±８．６４）ｍｍＨｇ,累积眼压差为（１８２．３１±１４０．３５）ｍｍＨｇ,左右眼的眼压相比差异有显著统计学意义（Ｐ＝０．０００）。激光后３周,两个高眼压组的节细胞数相比,差异无统计学意义（Ｐ＝０．６９３）,左眼的节细胞丢失率为６７．４％ ±１４．８％,与右眼相比差异有显著统计学意义（Ｐ＝０．０００）。左眼视网膜电图明适应ｂ波、ＰｈＮＲ波及暗适应ｂ波的潜伏期与激光前相比,差异均有统计学意义（Ｐ＝０．０００、０．０４６、０．０００）,其振幅与激光前相比,差异也均有显著统计学意义（Ｐ＝０．００１、０．０００、０．０００）,而明适应ａ波的潜伏期、振幅及暗适应ａ波的潜伏期与激光前相比,差异均无统计学意义（Ｐ＝０．１３８、０．１９８、０．０９２）。结论　激光光凝法诱导大鼠眼压升高成功率较高,但持续时间有限,峰值眼压过高,且需重复激光,高眼压引起的节细胞丢失率高,视网膜电图提示视网膜损伤主要累及双极细胞及节细胞。     

Use of YAG-Selecta laser and argon laser in the treatment of open angle glaucoma

INTRODUCTION: The falling success rate of ALT (Argon Laser Trabeculoplasty) has raised the interest in some new laser techniques, such as q-switched Nd:YAG laser trabeculoplasty (Coherent Selecta 7000). The "selective" laser trabeculoplasty destroys melanosomes of pigmented trabecular meshwork cells, sparing adjacent non-pigmented cells and tissues. AIM: Our goal was to establish the IOP lowering effect of selective laser trabeculoplasty (SLT--Selecta Laser Trabeculoplasty) in comparison with ALT. MATERIAL AND METHODS: We have examined 27 patients (10 men, 17 women) aged 35-82, with open angle glaucoma and visual field deterioration despite maximal tolerated topical therapy (21 patients--POAG, 3--NPG, 1--pigmentary glaucoma, 1--pseudoexfoliative glaucoma, 1--juvenile glaucoma). One eye of each patient was randomly chosen for SLT, the other eye underwent ALT. In each method 50 burns were applied in 180 degrees angle with power settings of 600-1000 mW for ALT and energy settings of 0.5-1.4 mJ for SLT. The IOP was measured 1 hour before laser treatment and 1, 2, 24 hours and 3 months after treatment. RESULTS: The mean initial IOP in eyes selected for SLT was significantly higher (21.26 +/- 4.82 mm Hg) than in eyes selected for ALT (20.26 +/- 4.01 mm Hg), t-test: p = 0.037. However, there was no statistically significant difference in the IOP lowering effect between eyes treated with SLT and eyes treated with ALT. The mean IOP drop from the pre-treatment values was -2.85 +/- 4.62 mm Hg after SLT and -2.63 +/- 3.60 mm Hg after ALT (t-test, p = 0.84). All values: 2, 24-hours and 3 months after treatment were significantly lower than pre-treatment values in both groups (t-test, p < 0.03). Only in the 1st hour after SLT the IOP drop was not significant. There was a significant correlation between the amount of pigment on the trabecular meshwork and the IOP fall (U Mann-Whitney test). In SLT group 6 patients (21%) developed mild iritis during 1st day after laser treatment, which disappeared after fluorometholon drop therapy. CONCLUSION: Both methods--SLT and ALT--have equivalent IOP lowering effect in short time observation (3 months). Due to entirely novel mode of Selecta laser action, long term results may show significant differences.     

非穿透性小梁手术联合双层羊膜植入物治疗青少年型青光眼

目的　探讨非穿透性小梁手术 (NPTS)联合羊膜植入物治疗青少年型青光眼的临床效果。方法　对 2 6例 (32只眼 ) 12～ 2 8岁青少年型青光眼患者进行非穿透性小梁手术联合羊膜植入物治疗。术后观察患者眼压、眼内反应及滤过泡情况 ,并做前房角镜检查。患者术后平均随访时间 (8 3± 4 2 )个月。结果　患者术后视力较术前无明显变化。患者术前平均眼压 (2 8 6± 7 3)mmHg(1mmHg =0 133kPa) ,术后 (15 7± 3 7)mmHg ,差异有显著意义 (t=4 82 ,P <0 0 1)。术前用药2～5种 ,平均 3 2种 ;术后用药 0～ 2种 ,平均 0 8种 ,差异有显著意义 (秩和检验 ,t=12 8,P <0 0 1)。随访期间眼压≤ 2 1mmHg者 30只眼 (93 8% ) ,无需药物治疗而眼压正常者 18只眼 (5 6 3% ) ,用药后眼压保持正常者 12只眼 (37 5 % )。术后 6只眼有轻微前房出血 ;无前房变浅、眼部炎性反应、脉络膜脱离等并发症发生。术后患者经前房角镜检查 ,可见术区后弹力膜及残存小梁网变薄 ,5只眼可见小梁处有微穿孔。结论　NPTS联合羊膜植入术能有效降低眼压 ,减少抗青光眼药物的应用 ,术后并发症少 ,是治疗青少年型青光眼的有效方法之一。     

Selective ganglion cell functional loss in rats with experimental glaucoma

PURPOSE: To characterize retinal functional consequences of elevated intraocular pressure (IOP) in a rat model of experimental glaucoma. METHODS: Unilateral elevation of IOP was produced by hypertonic saline injection into an episcleral vein in 20 adult male Brown-Norway rats. IOP was measured in both eyes of awake animals four to five times per week. After 5 weeks, animals were dark adapted overnight (>12 hours) and full-field electroretinograms (ERGs) were obtained simultaneously from both eyes. Scotopic ERG stimuli were brief white flashes (-6.64-2.72 log cd-s/m(2)). Photopic responses were also obtained (0.97-2.72 log cd-s/m(2)) after 15 minutes of light adaptation (150 cd/m(2)). Eyes were processed the following day for histologic evaluation by light microscopy, including masked determination of optic nerve injury grade (ONIG; 1, normal; 5, severe, diffuse damage). RESULTS: Among experimental eyes, the group average IOP (+/-SD) was 34.5 +/- 4.1 mm Hg, whereas the average for control eyes was 28.1 +/- 0.5 mm Hg (t = 7.1, P < 0.0001). The average ONIG for experimental and control eye groups, respectively, was 3.4 +/- 1.7 and 1.0 +/- 0.02 (t = 6.3, P < 0.0001). The ONIG increased with mean IOP in experimental eyes (r(2) = 0.78, P < 0.0001) and was unrelated to mean IOP in control eyes (r(2) = 0.09, P = 0.18). In experimental eyes with relatively mild IOP elevation (mean IOP < 31 mm Hg) and no structural (histologic) damage to the optic nerve evident by light microscopy (ONIG = 1.1 +/- 0.2, n = 5), there was a selective reduction of the positive scotopic threshold response (pSTR; P < 0.001), whereas other ERG components remained unaltered. In four of the five eyes, pSTR amplitude was reduced by more than 50%, whereas all five had normal scotopic a-wave, b-wave, and OP amplitudes. Eyes with mean IOP of more than 35 mm Hg had reduced a-wave, b-wave, and oscillatory potential (OP) amplitudes. CONCLUSIONS: As demonstrated by prior studies, selective loss of the pSTR is indicative of selective retinal ganglion cell (RGC) injury. In this rat model of experimental glaucoma, selective RGC functional injury occurred before the onset of structural damage, as assessed by light microscopy of optic nerve tissue. The highest IOP levels resulted in nonselective functional loss. Thus, in rodent models of experimental glaucoma, lower levels of chronically elevated IOP may be more relevant to human primary chronic glaucoma.     

Circumferential viscodilation and tensioning of Schlemm canal (canaloplasty) with temporal clear corneal phacoemulsification cataract surgery for open-angle glaucoma and visually significant cataract: one-year results

PURPOSE: To evaluate the safety and efficacy of circumferential viscodilation and tensioning of the inner wall of Schlemm canal, a new nonpenetrating surgical procedure (canaloplasty) to treat open-angle glaucoma (OAG), combined with clear corneal phacoemulsification and posterior chamber intraocular lens (IOL) implantation. SETTING: Multicenter surgical sites. METHODS: This international multicenter prospective study comprised adult patients with OAG having combined glaucoma and cataract surgery. Patients with qualifying treated preoperative intraocular pressure (IOP) of at least 21 mm Hg or higher and open angles were eligible. Evaluation was performed at baseline and 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. Intraoperative and postoperative high-resolution ultrasound imaging was used to assess Schlemm canal and anterior segment angle morphology, including distension of the trabecular meshwork due to the tensioning suture. RESULTS: Data from 54 eyes that had combined glaucoma and cataract surgery performed by 11 surgeons at 9 study sites were analyzed for this interim analysis. The mean baseline IOP was 24.4 mm Hg+/-6.1 (SD) with a mean of 1.5+/-1.0 medications per eye. In all eyes, the mean postoperative IOP was 13.6+/-3.8 mm Hg at 1 month, 14.2+/-3.6 mm Hg at 3 months, 13.0+/-2.9 mm Hg at 6 months, and 13.7+/-4.4 mm Hg at 12 months. Medication use dropped to a mean of 0.2+/-0.4 per patient at 12 months. Surgical complications were reported in 5 eyes (9.3%) and included hyphema (n=3, 5.6%), Descemet tear (n=1, 1.9%), and iris prolapse (n=1, 1.9%). Transient IOP elevation of more than 30 mm Hg was observed in 4 eyes (7.3%) 1 day postoperatively. CONCLUSION: Circumferential viscodilation and tensioning of Schlemm canal combined with clear corneal phacoemulsification and posterior chamber IOL implantation was a safe and effective procedure to reduce IOP in adult patients with OAG.     

非穿透性小梁手术联合透明质酸钠生物胶植入术的临床疗效观察

目的观察非穿透性小梁手术(nonperforating trabecular surgery,NPTS)联合透明质酸钠生物胶植入术的临床疗效.方法对20例(28只眼)中、晚期开角型青光眼患者行NPTS联合透明质酸钠生物胶植入术.术后观察眼压、眼内反应和滤过泡,并做前房角镜及超声生物显微镜检查.结果术后随访4.5～18.0个月,平均(9.2±3.4)个月.术前平均眼压(28.1±10.2) mm Hg(1 mm Hg=0.133 kPa),术后(17.5±4.1) mm Hg;差异有非常显著性(t=5.776,P<0.001).术前平均用药(2.04±0.74)种,术后(0.71±0.71)种,差异有非常显著性(t=8.103,P<0.001).随访期间眼压≤21 mm Hg者27只眼(96.4%),其中12只眼(42.8%)不用抗青光眼药物,15只眼(53.6%)加用抗青光眼药物.眼压下降≥10 mm Hg者13只眼(46.4%),其中不加药者6只眼.术后14只眼无任何眼内反应;10只眼有轻微房水闪光,2～6 d消失;4只眼有少量前房积血,3～7 d消失.术后28只眼均形成显著弥散滤过泡;随访期间,19只眼有功能性滤过泡;9只眼于术后1.5～3.0个月功能性滤过泡消失.5只眼于术中发现小梁网处有小穿孔,但无虹膜膨出,术后经前房角镜检查可见3只眼有小穿孔;另4只眼术中未见小穿孔,但前房角镜下观察有小裂隙,1～8个月时,用超声生物显微镜检查可见生物胶未降解.结论 NPTS联合透明质酸钠生物胶植入术可有效降低眼压,并减少抗青光眼药物的应用,术后并发症少,为一种具有良好应用前景的抗青光眼新手术.     

Combined cataract-glaucoma surgery using the intracanalicular Eyepass glaucoma implant: first clinical results of a prospective pilot study

PURPOSE: To study prospectively the safety and pressure-reducing efficacy of the Y-shaped Eyepass glaucoma implant (GMP Vision Solutions, Inc.). SETTING: Departments of Ophthalmology, University of Cologne, Cologne, and University of Erlangen, Erlangen, Germany. METHODS: This study comprised 12 patients with primary open-angle or exfoliative glaucoma and cataract who had phacoemulsification with endocapsular implantation of a foldable intraocular lens and intracanalicular implantation of an Eyepass glaucoma implant. The implant is a silicone microtube shunt that bypasses the trabecular meshwork and connects the lumina of Schlemm canal with the anterior chamber in combined cataract-glaucoma surgery. Perioperative complications, intraocular pressure (IOP), and pressure-reducing topical medications were monitored over a preliminary follow-up. RESULTS: Perforation of the trabecular meshwork during Eyepass implantation occurred in 2 eyes; the antiglaucoma procedure was converted to trabeculotomy after the shunt was explanted, and both eyes were excluded from further follow-up. In the remaining 10 eyes, the mean maximum IOP was 30.4 mm Hg +/- 7.5 (SD) (range 21 to 46 mm Hg) preoperatively, 12.0 +/- 6.1 mm Hg (range 2 to 20 mm Hg) 1 day postoperatively, 17.2 +/- 4.1 mm Hg (range 12 to 27 mm Hg) at 4 weeks, and 18.3 +/- 4.5 mm Hg (range 12 to 25 mm Hg) at the end of the preliminary follow-up. The mean number of topical medications was 3.2 +/- 0.8 preoperatively and 0.9 +/- 0.7 at the end of follow-up (mean 7.1 months). Although there were no major complications requiring surgical revision, 4 eyes had an IOP of 18 or higher at the end of follow-up. CONCLUSION: Combined cataract surgery with Eyepass shunt implantation was safe and appeared to be beneficial in glaucomatous eyes with cataract not requiring a low target IOP.     

非穿透小梁手术中应用丝裂霉素C的疗效

目的　评价非穿透小梁手术中应用丝裂霉素C治疗原发性开角型青光眼的临床疗效。方法　对 18例 (2 5只眼 )原发性开角型青光眼患者行非穿透小梁手术 ,术中联合应用丝裂霉素C。术后随访 6～ 2 8个月 ,平均 16个月。结果　患者术前平均眼压 (2 7 93± 7 6 2 )mmHg(1mmHg =0 133kPa) ;术后 3个月 ,平均眼压降至 (14 6 2± 3 5 3)mmHg ;差异有显著意义 (t=11 82 ,P <0 0 0 1)。术后2 5只眼均形成明显的弥散滤过泡。术后 3个月 ,2 1只眼有功能性滤过泡 ,4只眼功能性滤过泡消失。术后前房反应轻 ,1只眼发生前房出血 ;4只眼术中发现小梁网处有小穿孔 ,但无虹膜膨出 ,术后前房角镜检查均可见小穿孔 ;2只眼术中未发现小穿孔 ,而前房角镜下观察有小裂隙。结论　非穿透小梁手术中应用丝裂霉素C ,能有效降低开角型青光眼的眼压。术后患者视力恢复快 ,并发症少而轻。     

Retinal glutamate transporter changes in experimental glaucoma and after optic nerve transection in the rat

PURPOSE: High levels of glutamate can be toxic to retinal ganglion cells. Effective buffering of extracellular glutamate by retinal glutamate transporters is therefore important. This study was conducted to investigate whether glutamate transporter changes occur with two models of optic nerve injury in the rat. METHODS: Glaucoma was induced in one eye of 35 adult Wistar rats by translimbal diode laser treatment to the trabecular meshwork. Twenty-five more rats underwent unilateral optic nerve transection. Two glutamate transporters, GLAST (EAAT-1) and GLT-1 (EAAT-2), were studied by immunohistochemistry and quantitative Western blot analysis. Treated and control eyes were compared 3 days and 1, 4, and 6 weeks after injury. Optic nerve damage was assessed semiquantitatively in epoxy-embedded optic nerve cross sections. RESULTS: Trabecular laser treatment resulted in moderate intraocular pressure (IOP) elevation in all animals. After 1 to 6 weeks of experimental glaucoma, all treated eyes had significant optic nerve damage. Glutamate transporter changes were not detected by immunohistochemistry. Western blot analysis demonstrated significantly reduced GLT-1 in glaucomatous eyes compared with control eyes at 3 days (29.3% +/- 6.7%, P = 0.01), 1 week (55.5% +/- 13.6%, P = 0.02), 4 weeks (27.2% +/- 10.1%, P = 0.05), and 6 weeks (38.1% +/- 7.9%, P = 0.01; mean reduction +/- SEM, paired t-tests, n = 5 animals per group, four duplicate Western blot analyses per eye). The magnitude of the reduction in GLT-1 correlated significantly with mean IOP in the glaucomatous eye (r(2) = 0.31, P = 0.01, linear regression). GLAST was significantly reduced (33.8% +/- 8.1%, mean +/- SEM) after 4 weeks of elevated IOP (P = 0.01, paired t-test, n = 5 animals per group). In contrast to glaucoma, optic nerve transection resulted in an increase in GLT-1 compared with the control eye (P = 0.01, paired t-test, n = 15 animals). There was no significant change in GLAST after transection. CONCLUSIONS: GLT-1 and GLAST were significantly reduced in an experimental rat glaucoma model, a response that was not found after optic nerve transection. Reductions in GLT-1 and GLAST may increase the potential for glutamate-induced injury to RGC in glaucoma.     

The effect of MK-927, a topical carbonic anhydrase inhibitor, on IOP in glaucomatous monkeys

MK-927 is a water soluble, potent inhibitor of human carbonic anhydrase (CA) II in vitro. Topical administration of MK-927 reduces intraocular pressure (IOP) in rabbits. Elevated IOP was produced in cynomolgus monkey eyes by argon laser photocoagulation of the trabecular meshwork. IOP was measured at 0 hr, 0.5 hr and hourly for 8 hrs in 8 eyes for two baseline days, one day on vehicle and five days of therapy with 2% MK-927 b.i.d., after initial single-dose trials of various concentrations. IOP was not significantly different comparing baseline and vehicle treated days. Significant (p less than 0.05) reductions of IOP occurred for five days lasting at least 8 hrs after each dosing. At 3 hrs after treatment with vehicle the IOP was 31.6 +/- 3.4 (SE) mm Hg. Maximum reduction of IOP occurred at 3 hrs after application of MK-927, the IOP decreasing from day 1 (19.9 +/- 1.0 mm Hg) to day 5 (16.5 +/- 1.6 mm Hg). MK-927 appears to have great clinical potential.     

眼内窥镜下睫状体光凝对角膜植片存活的影响

目的探讨对穿透性角膜移植术（PKP）后眼压升高且药物不能控制的患者,采用眼内窥镜直视下睫状体光凝术（ECP）进行治疗的疗效和对角膜植片存活的影响。方法选择2000年3月至2004年4月期间,于中山大学中山眼科中心就诊的34例（34只眼）PKP术后眼压升高且药物不能控制患者,在眼内窥镜直视下,行半导体激光睫状体光凝术（12例）或联合玻璃体切除术（22例）（ECP组）。选择26例（26只眼）患者作为对照,采用经巩膜面半导体激光睫状体光凝术（TCP）（TCP组）。术前、术后随访观察视力、眼压、植片透明度、内皮细胞密度及前房反应,超声活体显微镜（UBM）检查睫状突和房角情况,注意术后并发症等。结果ECP组术后3个月和6个月时,分别有13例（38．2％）和23例（67．7％）眼压低于21mmHg。TCP组术后3个月和6个月时,分别有10例（38．5％）和8例（30．8％）眼压低于21mmHg。两组之间术后眼压控制率比较,在3个月时差异无统计学意义（X^2=0．0003,P=0．986）,但6个月时差异有统计学意义（X^2=8．024,P=0．005）。ECP组和TCP组术后植片内皮细胞密度分别为（1013±170）个／mm^2和（847±136）个/mm^2,差异有统计学意义（t=-0．009,P=0．033）。ECP组和TCP组术后分别有9例（26．5％）和21例（80．8％）出现反应性虹膜炎,两组之间比较差异有统计学意义（x^2=17．376,P=0．001）。结论ECP对降低PKP术后青光眼患者眼压的远期疗效优于TCP。ECP对角膜植片内皮细胞的损伤和引起术后葡萄膜炎的程度均较TCP轻,相对提高了PKP术后角膜植片的生存质量。     

Diode laser transscleral cyclophotocoagulation for refractory glaucoma

PURPOSE: To evaluate the efficacy of contact diode laser transscleral cyclophotocoagulation using different treatment parameters. METHODS: All eyes undergoing contact diode laser transscleral cyclophotocoagulation between April 1991 and September 1997 at our two institutions were enrolled. Success was defined as an intraocular pressure less than or equal to 22 mm Hg or absence of pain for poorly sighted and blind eyes. RESULTS: Two hundred six eyes of 204 patients (Salzburg, 117 eyes; New York, 89 eyes) were enrolled. Mean patient age was 65.8 +/- 18.7 years (range, 4-96 years). Mean follow-up was 9.2 +/- 11.2 months (range, 3-56 months). Mean preoperative and postoperative IOPs were 42.1 +/- 11.0 mm Hg (range, 24-76 mm Hg) and 17.3 +/- 10.9 mm Hg (P < 0.001) and 20.3 +/- 13.2 mm Hg (P < 0.001) at 12 and 24 months, respectively. The number of laser applications (mean, 18.6 +/- 4.2; range, 10-40) and maximal laser power (mean, 2,352 +/- 408.5 mW; range, 1,500-3,000) were not associated with a lower postoperative IOP. An IOP less than or equal to 22 mm Hg was achieved in 72.7% of eyes at the mean follow-up of 9 months. Thirty-three (16.0%) eyes required at least one retreatment. Phthisis occurred in four (1.9%) eyes. CONCLUSION: Contact diode laser transscleral cyclophotocoagulation is useful in eyes with refractory glaucoma in which the risks of outflow surgery are deemed unacceptable.     

Induction of significant intraocular pressure diurnal fluctuation in rats using a modified technique of microbead occlusion

AIM: To investigate the effect of microbead iridocorneal angle occlusion on intraocular pressure (IOP) diurnal fluctuation in rat eyes. METHODS: Male Dark Agouti (DA) rats, 8-10 week old, were each given a single intracameral injection of microbeads, followed by injection of dispersive viscoelastic solution. The right eye served as the experimental eye, while the left eye served as the control. IOP was measured twice daily postoperatively for 3wk and compared between groups. At the end of 3wk, the rats were sacrificed and the eyes were harvested for histological analysis and retinal ganglion cell (RGC) counting. RESULTS: After microbead injection, experimental eyes had significantly higher dark time IOP than controls from the second week to the third week [2nd week: 22.92±1.631 mm Hg (n=5) vs 17.35±0.751 mm Hg (n=5); 3rd week: 23.59±1.494 mm Hg vs 17.73±0.592 mm Hg (n=5)], while light time IOP was comparable between groups. The fluctuation levels of IOP in the experimental eyes were 7.21±0.398 mm Hg (n=5), 9.50±1.017 mm Hg (n=5) and 10.66±0.894 mm Hg (n=5) from the first week to the third week after injection. Comparatively, they were significantly lower in the control eyes, which were 4.69±0.323 mm Hg (n=5), 2.84±1.122 mm Hg (n=5) and 4.98±0.603 mm Hg (n=5) respectively. However, at the end of 3wk, the larger fluctuations in IOP in the experimental eyes was not associated with a significant loss of RGCs. CONCLUSION: Microbead occlusion exacerbates diurnal IOP fluctuation in rats. This reported model may serve as a method of investigating the pathological effects of IOP fluctuation. A longer observation period, or repeated injections, may be needed to observe a significant change in RGC density.