Selective laser trabeculoplasty in the treatment of pseudoexfoliation glaucoma in patients allergic to all anti-glaucoma drops

Secondary chronic open-angle glaucoma associated with pseudoexfoliation (PEX) syndrome accounts for approximately 25% of all glaucomas and represents the most common identifiable cause of glaucoma overall. Selective laser trabeculoplasty (SLT) is effective in reducing intraocular pressure (IOP) in glaucomatous patients and has the advantage of preserving surrounding structures. We report here SLT treatment of a 82 year old female with a secondary developed open-angle pseudoexfoliation glaucoma allergic to all anti glaucoma eye drops especially those which contain bensalconium chloridum as preservative. Since patient was allergic also to methyl-cellulose, we performed SLT with water as a mediator. Patient had PEX syndrome for 10 years, immature cataracts on both eyes, and best corrected visual acuity (BCVA) 0.7 on the right and 0.2 on the left eye. We have monitored intraocular pressure (IOP), the changes in the visual field and optic nerve. Preoperative IOP was 28 mmHg on the right and 30 mmHg on the left eye. The follow up period was 24 months with time points for measured parameters every 3 months. After 18 months IOP remained in the normal values (average 17 mmHg) on the right eye, but on the left eye it increased up to 28 mmHg. SLT re-treatment was carried out on the left eye and the IOP stabilized again on the values between 16-18mmHg. There were no significant change in the visual field and optic nerve configuration before and after SLT (C/D value for right eye: 0.3-0.4; C/D left eye: 0.5). Based on this case report, SLT seems to be very effective treatment for maintaining regular IOP in patient with PEX who is allergic to all types of medications.     

Hemodynamic effects of blood loss during a passive response to a stressor in the conscious rabbit

In the conscious rabbit, exposure to an air jet stressor increases arterial pressure, heart rate, and cardiac output. During hemorrhage, air jet exposure extends the blood loss necessary to produce hypotension. It is possible that this enhanced defense of arterial pressure is a general characteristic of stressors. However, some stressors such as oscillation (OSC), although they increase arterial pressure, do not change heart rate or cardiac output. The cardiovascular changes during OSC resemble those seen during freezing behavior. In the present study, our hypothesis was that, unlike air jet, OSC would not affect defense of arterial blood pressure during blood loss. Male New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood until mean arterial pressure decreased to 40 mmHg. We repeated the experiment in each rabbit on separate days in the presence and absence (SHAM) of OSC. Compared with SHAM, OSC increased arterial pressure 14 +/- 1 mmHg, central venous pressure 3.3 +/- 0.4 mmHg, and hindquarter blood flow 34 +/- 4% while decreasing mesenteric conductance 32 +/- 3% and not changing heart rate or cardiac output. During normotensive hemorrhage, OSC enhanced hindquarter and renal vasoconstriction. Contrary to our hypothesis, OSC (23.5 +/- 0.6 ml/kg) increased the blood loss necessary to produce hypotension compared with SHAM (16.8 +/- 0.6 ml/kg). In nine rabbits, OSC prevented hypotension even after a blood loss of 27 ml/kg. Thus a stressful stimulus that resulted in cardiovascular changes similar to those seen during freezing behavior enhanced defense of arterial pressure during hemorrhage.     

A study of replacement of timolol-pilocarpine with latanoprost in pseudoexfoliation glaucoma

The aim of the study was to evaluate the efficacy of replacing current dual local therapy (timolol and pilocarpine) with latanoprost 0.005% in 71 pseudoexfoliation glaucoma patients with controlled intraocular pressure (IOP). 39 patients switched to latanoprost 0.005%) and 32 patients continued timolol-pilocarpine therapy. Mean diurnal (IOP) was measured at baseline, after 0.5, 1, 3 and 6 months of treatment. After 6 months 38 patients with latanoprost and 30 patients with timolol-pilocarpine had completed the study. At baseline the mean diurnal IOP was 20.4 +/- 2.0 mmHg for patients in latanoprost treatment group and 21.4 +/- 2.1 mmHg for patients in timolol-pilocarpine group. At the end of the study, after 6 months of treatment, the mean diurnal IOP values were 16.6 +/- 2.4 and 17.9 +/- 2.0 mmHg respectively. IOP was statistically significantly reduced from baseline (p < 0.001). The mean diurnal IOP change from baseline was -3.3 +/- 0.5 mmHg (mean +/- SEM, ANCOVA) for the patients treated with latanoprost and -3.2 +/- 0.4 mmHg for the patients treated with timolol + pilocarpine. This difference in IOP reduction between groups was not statistically significant (z = 0.69; p = 0.49). This study showed that combination therapy (timolol plus pilocarpine) in pseudoexfoliation glaucoma can effectively be replaced by latanoprost monotherapy.     

Effects of a non-selective beta-blocker on adult rat anterograde axonal transport and retinal ganglion layer after increased intraocular pressure

The aim of this study was to examine the effects of timolol in an experimental model of elevated intraocular pressure (IOP). Three episcleral veins of rats with normal IOP were cauterized. Three months later we examined the effects on anterograde axonal transport from the retinal ganglion cells (RGCs) to the superior colliculus (SC) as well as on the number of neurons in the retinal ganglion layer (RGL). These parameters were also studied in a group of rats submitted to treatment with timolol after confirming that their IOP was still raised after two weeks. After the surgical procedure, the mean IOP of the experimental eyes increased to 33.5+/-1.06 mmHg (1.25 fold compared to the control group) and three months later the IOP remained significantly elevated; however, after a long period of treatment with timolol the IOP was 14.05+/-0.81 mmHg, similar to that of the control group. In the group with normal IOP, labelling with horseradish rabbit peroxidase (HRP) at 120 minutes and 24 hours postinjection showed continuous staining from the retina to the SC. In the experimental group the optic nerve head (ONH) was completely negative, although in the group treated with timolol there was partial block of axonal transport in the ONH, in which the staining was slightly more intense. The number of neurons in the RGL, counted by immunohistochemical labelling with Neu-N, showed that in eyes with normal and elevated IOP there were 423+/-11 neurons/mm(2) and 283+/-10 neurons/mm(2), respectively. After treatment with timolol the number of neurons (331+/-10 cells/mm(2) increased compared with elevated IOP eyes, although the number did not reach that of the control group. These results indicate that treatment with timolol, started two weeks after the surgical procedure, was partially neuroprotective because the loss of neurons in the RGL was lower than in untreated animals, though not sufficient to re-establish normal axonal transport.     

A promising drug candidate for the treatment of glaucoma based on a P2Y6-receptor agonist

Extracellular nucleotides can regulate the production/drainage of the aqueous humor via activation of P2 receptors, thus affecting the intraocular pressure (IOP). We evaluated 5-OMe-UDP(α-B), 1A, a potent P2Y6-receptor agonist, for reducing IOP and treating glaucoma. Cell viability in the presence of 1A was measured using [3-(4, 5-dimethyl-thiazol-2-yl) 2, 5-diphenyl-tetrazolium bromide] (MTT) assay in rabbit NPE ciliary non-pigmented and corneal epithelial cells, human retinoblastoma, and liver Huh7 cells. The effect of 1A on IOP was determined in acute glaucomatous rabbit hyaluronate model and phenol-induced chronic glaucomatous rabbit model. The origin of activity of 1A was investigated by generation of a homology model of hP2Y6-R and docking studies. 1A did not exert cytotoxic effects up to 100 mM vs. trusopt and timolol in MTT assay in ocular and liver cells. In normotensive rabbits, 100 μM 1A vs. xalatan, trusopt, and pilocarpine reduced IOP by 45 vs. 20–30%, respectively. In the phenol animal model, 1A (100 μM) showed reduction of IOP by 40 and 20%, following early and late administration, respectively. Docking results suggest that the high activity and selectivity of 1A is due to intramolecular interaction between Pα-BH³ and C5-OMe which positions 1A in a most favorable site inside the receptor. P2Y6-receptor agonist 1A effectively and safely reduces IOP in normotense, acute, and chronic glaucomatous rabbits, and hence may be suggested as a novel approach for the treatment of glaucoma.     

Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production

Aquaporin (AQP) water channels are expressed in the eye at sites of aqueous fluid production and outflow: AQP1 and AQP4 in nonpigmented ciliary epithelium, and AQP1 in trabecular meshwork endothelium. Novel methods were developed to compare aqueous fluid dynamics in wild-type mice versus mice lacking AQP1 and/or AQP4. Aqueous fluid production was measured by in vivo confocal microscopy after transcorneal iontophoretic introduction of fluorescein. Intraocular pressure (IOP), outflow, and anterior chamber compliance were determined from pressure measurements in response to fluid infusions using micropipettes. Aqueous fluid volume and [Cl(-)] were assayed in samples withdrawn by micropipettes. In wild-type mice (CD1 genetic background, age 4-6 wk), IOP was 16.0 +/- 0.4 mmHg (SE), aqueous fluid volume 7.2 +/- 0.3 microl, fluid production 3.6 +/- 0.2 microl/h, fluid outflow 0.36 +/- 0.06 microl/h/mmHg, and compliance 0.036 +/- 0.006 microl/mmHg. IOP was significantly decreased by up to 1.8 mmHg (P < 0.002) and fluid production by up to 0.9 microl/h in age/litter-matched mice lacking AQP1 and/or AQP4 (outbred CD1 and inbred C57/bl6 genetic backgrounds). However, AQP deletion did not significantly affect outflow, [Cl(-)], volume, or compliance. These results provide evidence for the involvement of AQPs in intraocular pressure regulation by facilitating aqueous fluid secretion across the ciliary epithelium. AQP inhibition may thus provide a novel approach for the treatment of elevated IOP.     

Effect of oestradiol 3-benzoate on the concentrations of retinal and lipids in cod plasma

1. Determinations of retinal, total lipid and lipid phosphorus were made on 10ml. samples of cod plasma. 2. Immature control fish, injected with 0.2ml. of carrier oil/kg. wt., had 0.73+/-0.12mug. of retinal/100ml. of plasma, and maturing male fish had similar concentrations. Maturing female fish had about 10mug. of retinal/100ml. of plasma. 3. Immature male or female cod given single intramuscular injections of 1mg. of oestradiol-17beta 3-benzoate in 0.2ml. of oil/kg. wt. had 8.54+/-0.59 mug. of retinal/100ml. of plasma after 5 days and about 25mug./100ml. of plasma after 10 days. 4. Oestradiol injections had little effect on the concentration of plasma phospholipids, and no effect on lipids other than phospholipids. 5. For all 116 fish examined, regardless of sex or treatment, the concentration of plasma phospholipid was significantly correlated with that of lipids other than phospholipids (r=0.727), and phospholipids formed 50.4% of the total lipids in cod plasma. 6. Alcohol dehydrogenase was purified from cod liver and shown to oxidize retinol to retinal. It was completely inhibited by 0.1mm-oestradiol. Alternative modes of action of oestradiol are discussed.     

封闭负压引流联合局部给氧治疗兔耳缺血性创面的实验研究

目的:观察封闭负压引流联合局部给氧促进兔耳缺血性创面愈合的效果。方法:28只大耳白兔,双耳背各造成直径2.5cm全层皮肤缺损,结扎中央血管神经束及后边缘动静脉,形成缺血创面。56个创面随机分为七组:A组(-50mmHg负压同时给氧,浓度为40%±5%,每日4小时)、B组(持续-50mmHg负压4小时继之局部给氧1小时)、C组(负压治疗4min,停止1min,每日4小时,之后给氧1小时),D组(-50mmHg负压治疗每日4小时)、E组(-125mmHg负压治疗每日4小时)、F组(单纯给40%±5%氧1小时)和G组(空白对照)。在创面形成第0、1、3、5、7、10、14、18天拍照,测量创面面积,计算创面愈合率及创面愈合时间;在各时相点切取创面标本,组织学观察创面肉芽、上皮生长、水肿和炎细胞,Ki67免疫组化标记增殖细胞并计算增殖指数,TUNEL法计算凋亡指数。结果:负压给氧组在相同时相点创面愈合率高于单纯负压、氧疗或空白组(P<0.05),创面肉芽生长快,水肿和炎症轻,细胞增殖指数高于对照组(P<0.05),而细胞凋亡指数显著低于对照组(P<0.05)。结论:负压联合局部给氧能显著促进兔耳缺血创面的愈合。     

Partial Contact Indentation Tonometry for Measurement of Corneal Properties-Independent Intraocular Pressure

Inter-individual differences in corneal properties are ignored in existing methods for measuring intraocular pressure IOP, a primary parameter used in screening and monitoring of glaucoma. The differences in the corneal stiffness between individuals can be more than double and this difference would lead to IOP measurement errors up to 10 mmHg. In this study, an instrumented partial-contact indentation measurement and analysis method that can account for inter-individual corneal difference in stiffness is developed. The method was tested on 12 porcine eyes ex vivo and 7 rabbit eyes in vivo, and the results were compared to the controlled IOPs to determine the method's validity. Analyses showed that without corneal stiffness correction, up to 10 mmHg of measurement error was found between the existing approach and the controlled IOP. With the instrumented indentation and analysis method, less than 2 mmHg of differences were founded between the measured IOP and the controlled IOP. These results showed that instrumented partial-contact indentation can effectively account for inter-individual corneal variations in IOP measurement.     

Prostaglandin E2 and gestational hypotension in rabbits

Arterial levels of 13,14-dihydro-15-keto-PGE2 (PGE2-M), a stable metabolite of prostaglandin E2 (PGE2) were compared between unanesthetized pregnant (n = 12) and nonpregnant (n = 8) rabbits with the aim of elucidating the role PGE2 in the development of physiological hypotension associated with pregnancy. On the 20th and 22nd days of the 30 day gestation period the mean arterial concentrations of PGE2-M were about 10-times higher (p less than 0.05) and largely variable as compared to that of nonpregnant rabbits. Mean arterial pressure was not lower on either the 20th (69 +/- 4 mmHg, mean +/- SD) or the 22nd (70 +/- 3 mmHg) days of gestation (dg) than in nonpregnant rabbits (69 +/- 4 and 73 +/- 6 mmHg, respectively). On the 23rd dg hypotension was invariably present (61 +/- 5 mmHg vs 72 +/- 4 in nonpregnants, p less than 0.001), but arterial levels of PGE2-M (31.0 +/- 31.6 ng/ml) did not overcome those measured on earlier, normotensive days of gestation. Hypotension was also evident in a subgroup of pregnant rabbits (n = 4) with low PGE2-M concentrations in the nonpregnant range (3.2 +/- 1.5 ng/ml vs 1.9 +/- 1.2 in nonpregnant rabbits, ns). Since the arterial level of PGE2-M proved to correlate (p less than 0.001) with both the uteroplacental venous and renal venous PGE2 concentrations, we suggest that a key role of uteroplacental and renal PGE2 played in the development of gestational hypotension is not probable in rabbits.     

Evaluation of the intraocular pressure-reducing effect of latanoprost as monotherapy in open-angle glaucoma

Objective of this study was to evaluate the intraocular pressure-reducing effect of latanoprost as monotherapy after replacing current dual therapy in glaucoma patients. The 6-months study comprised 189 patients with primary open angle glaucoma who were treated at least 6 months with two different kind of topical medications (beta-blockers, pilocarpine, dorzolamide and brimonidine). Due to local side effects, multiple dosing regime and inadequately controlled intraocular pressure (IOP), they where switched to latanoprost 0.005% monotherapy. After switched to latanoprost, mean (IOP) was measured at baseline, after 15 days, 2 and 6 months of treatment. After six-months 178 patients had completed the study. These analyses enrolled all patients (n = 189), thus, the Intention-To-Treat (ITT) results were shown instead of the results of the reduced population. IOP was clinically importantly reduced from baseline level. Five patients had uncontrolled IOP. The difference between IOP before (21.9 +/- 2.4) and after 15 days (17.4 +/- 1.7), 2 months (16.7 +/- 1.8) and 6 months (16.6 +/- 1.4) was statistically significant (p < 0.001). 90% patients has reached target IOP < or = 18 mm. A conjunctional hyperaemia in 18 (9%), stinging and itching in 7 (4%) patients was reported. Increased iris pigmentation was seen in 3 (2%) patients. The results of this study indicate that dual therapy in open-angle glaucoma can effectively be replaced by latanoprost monotherapy in many patients.     

Comparison of the effect of two viscoelastic agents on an early postoperative intraocular pressure

This prospective study compares the effect of two viscoelastic agents (Viscoat and Provisc) on an early postoperative intraocular pressure after phacoemulsification and intraocular lens implantation. The study compares 36 patients with senile cataract. Intraocular pressure (IOP) was measured by standard Goldmann aplanation tonometry preoperatively as well as on the first postoperative day, after 24 hours and 1 week postoperatively. The mean postoperative IOP at first postoperative day in the Viscoat group was 24.2 mmHg and in the Provisc group was 21.2 mmHg. The increase was significantly higher in the Viscoat group than in the Provisc group but after 24 hours and 1 week postoperatively the mean IOP was not statisticaly different. The two viscoelastic agents cause equivalent pressure elevation postoperatively.     

两种手术方式治疗原发性闭角型青光眼疗效比较

目的:探讨治疗原发性闭角型青光眼二种手术方式的适应症和初步临床疗效观察。方法:拟订手术适应症,对临床收治的42例48眼原发性闭角型青光眼进行手术处理:单纯抗青光眼手术--小梁切除术(Trabeculectomy,Trab)、青白联合手术--超声乳化白内障吸除联合小梁切除+人工晶体植入术(Phacotrabeculectomy+IOL,PhacoTrab+IOL)。比较不同适应症下二种手术方式初步的临床疗效。包括术前术后眼压情况、前房深度、眼轴长度的变化。随访时间平均1个月。结果均经统计学处理。结果:原发性闭角型青光眼患者术后眼压有显著改变,有统计学差异,Trab组手术后平均(10.92±1.74)mmHg,Phaco Trab+IOL组手术后平均(10.86±1.73)mmHg。术后眼压明显降低(t检验,P值<0.001),Trab组和Phaco Trab+IOL组两组间术后眼压无显著差异(t检验,P值>0.05)。Trab组手术前后前房深度无统计学差异(t检验,P值>0.05),Phaco Trab+IOL组手术前后前房深度有统计学差异(t检验,P值均<0.001)。术前分别为(1.74±0.16)mm、(1.72±0.16)mm,术后分别为(1.74±0.17)mm、(2.06±0.14)mm。Trab组及Phaco Trab+IOL组手术前后眼轴长度无统计学差异(t检验,P值>0.05)。结论:青-白联合手术可以改善前房深度,明显降低眼压,不同手术方式适合不同的病人情况,但要注意适应症的选择。利用A超检查可快速、有效、准确地观察眼前节结构,有助于早期进行手术。     

Effect of estrogen replacement therapy on distribution of myocardial blood flow in female anesthetized rabbits

Estrogen replacement therapy reduces risk of cardiovascular events by altering coronary vasoregulation and distribution of blood flow. Vessel reactivity and blood flow distribution were assessed in anesthetized female rabbits in the following groups: 1) sham, 2) ovariectomy, 3) ovariectomy + 17beta-estradiol, and 4) ovariectomy + dehydroepiandrosterone. After a 2-wk treatment, cardiac hemodynamics, vascular reserve, and blood flow were evaluated during the following infusions: 1) NaCl, or vehicle (0.5 ml/min), 2) acetylcholine (2 mg/kg), 3) isoproterenol (2 mg. kg(-1). min(-1)), and 4) chromonar (8 mg/kg). In hearts from ovariectomized rabbits, autoregulatory blood flow was preserved despite lower diastolic perfusion pressures (55 +/- 8 vs. 64 +/- 8 mmHg in sham) and rate-pressure product (14.4 +/- 0.8 vs. 19.3 +/- 0.8 beats/min. mmHg x 10(-3)). Estrogen replacement therapy restored coronary pressure and reserve, and all drugs increased vascular conductance. In conclusion, in hearts from ovariectomized rabbits, vascular reserve declined because coronary pressure was lower; however, blood flow was preserved at a higher level than expected for oxygen demand. Estrogen replacement therapy restores myocardial oxygen supply-demand indices and returns coronary pressure-flow data to levels observed in animals with intact ovaries.     

Glaucoma Surgery Calculator: Limited Additive Effect of Phacoemulsification on Intraocular Pressure in Ab Interno Trabeculectomy

PurposeTo compare intraocular pressure (IOP) reduction and to develop a predictive surgery calculator based on the results between trabectome-mediated ab interno trabeculectomy in pseudophakic patients versus phacoemulsification combined with trabectome-mediated ab interno trabeculectomy in phakic patients.MethodsThis observational surgical cohort study analyzed pseudophakic patients who received trabectome-mediated ab interno trabeculectomy (AIT) or phacoemulsification combined with AIT (phaco-AIT). Follow up for less than 12 months or neovascular glaucoma led to exclusion. Missing data was imputed by generating 5 similar but non-identical datasets. Groups were matched using Coarsened Exact Matching based on age, gender, type of glaucoma, race, preoperative number of glaucoma medications and baseline intraocular pressure (IOP). Linear regression was used to examine the outcome measures consisting of IOP and medications.ResultsOf 949 cases, 587 were included consisting of 235 AIT and 352 phaco-AIT. Baseline IOP between groups was statistically significant (p≤0.01) in linear regression models and was minimized after Coarsened Exact Matching. An increment of 1 mmHg in baseline IOP was associated with a 0.73±0.03 mmHg IOP reduction. Phaco-AIT had an IOP reduction that was only 0.73±0.32 mmHg greater than that of AIT. The resulting calculator to determine IOP reduction consisted of the formula -13.54+0.73 × (phacoemulsification yes:1, no:0) + 0.73 × (baseline IOP) + 0.59 × (secondary open angle glaucoma yes:1, no:0) + 0.03 × (age) + 0.09 × (medications).ConclusionsThis predictive calculator for minimally invasive glaucoma surgery can assist clinical decision making. Only a small additional IOP reduction was observed when phacoemulsification was added to AIT. Patients with a higher baseline IOP had a greater IOP reduction.     

心房钠泵因子对颈动脉窦压力感受器反射的易化作用

Effects of atriopeptin II (APII) on the carotid sinus baroreflex in anesthetized rats and on the sinus nerve afferent activity in the anesthetized rabbits were investigated. The results were as follows: (1) By perfusing the isolated left carotid sinus with APII (1 microgram/ml) in anesthetized rats (n = 10), the threshold pressure (TP) of the carotid baroreflex did not show any change, while the equilibrium pressure (EP), the saturation pressure (SP) and the operating range (OR) were decreased from 101 +/- 2.8 to 95 +/- 2.0 mmHg (P less than 0.05), 202 +/- 5.2 to 168 +/- 6.1 mmHg (P less than 0.001) and 128 +/- 5.5 to 93 +/- 6.3 mmHg (P less than 0.001), respectively. The function curve of the baroreflex was shifted to the left and downward with a peak slope (PS) increased during perfusing with APII. In contrast, by perfusing the carotid sinus with sodium nitroprusside (NP, 0.5 micrograms/ml), TP and EP remained unchanged, whereas SP and OR were increased from 188 +/- 6.4 to 218 +/- 6.0 mmHg (n = 6, P less than 0.01) and from 107 +/- 6.9 to 132 +/- 7.6 mmHg (P less than 0.05), respectively. The function curve of the baroreflex and its PS were not affected by NP. The sinus nerve afferent activity was quite stable with the perfusion of carotid sinus at constant intrasinus pressure (ISP) in the rabbits (n = 6) and increased during the elevation of ISP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autotaxin-lysophosphatidic Acid axis is a novel molecular target for lowering intraocular pressure

Primary open-angle glaucoma is the second leading cause of blindness in the United States and is commonly associated with elevated intraocular pressure (IOP) resulting from diminished aqueous humor (AH) drainage through the trabecular pathway. Developing effective therapies for increased IOP in glaucoma patients requires identification and characterization of molecular mechanisms that regulate IOP and AH outflow. This study describes the identification and role of autotaxin (ATX), a secretory protein and a major source for extracellular lysophosphatidic acid (LPA), in regulation of IOP in a rabbit model. Quantitative proteomics analysis identified ATX as an abundant protein in both human AH derived from non-glaucoma subjects and in AH from different animal species. The lysophospholipase D (LysoPLD) activity of ATX was found to be significantly elevated (by ∼1.8 fold; n = 20) in AH derived from human primary open angle glaucoma patients as compared to AH derived from age-matched cataract control patients. Immunoblotting analysis of conditioned media derived from primary cultures of human trabecular meshwork (HTM) cells has confirmed secretion of ATX and the ability of cyclic mechanical stretch of TM cells to increase the levels of secreted ATX. Topical application of a small molecular chemical inhibitor of ATX (S32826), which inhibited AH LysoPLD activity in vitro (by >90%), led to a dose-dependent and significant decrease of IOP in Dutch-Belted rabbits. Single intracameral injection of S32826 (∼2 µM) led to significant reduction of IOP in rabbits, with the ocular hypotensive response lasting for more than 48 hrs. Suppression of ATX expression in HTM cells using small-interfering RNA (siRNA) caused a decrease in actin stress fibers and myosin light chain phosphorylation. Collectively, these observations indicate that the ATX-LPA axis represents a potential therapeutic target for lowering IOP in glaucoma patients.     

不同术式治疗新生血管性青光眼的疗效比较

目的:比较不同手术方法治疗新生血管性青光眼(neovascular glaucoma,NVG)的疗效。方法:对接受不同术式治疗的57例57只眼NVG的临床资料进行回顾性分析,其中行单纯睫状体冷凝术20例(A组),改良小梁切除术15例(B组),引流阀植入术联合全视网膜光凝术22例(C组)。比较各组患者手术前后主观眼痛症状、眼压及视力变化情况,并随访3~6个月。结果:A组患者出院时的平均眼压为(28.13±4.83)mmHg,B组为(19.24±5.48)mmHg,C组为(21.22±4.76)mmHg。随访期间,术后A组9例眼压正常,手术成功率45%;B组11例眼压正常,手术成功率73.3%;C组13例眼压正常,手术成功率57.1%。B组手术成功率最高,A组最低。结论:三种手术方法均可不同程度降低新生血管性青光眼的眼压。单纯睫状体冷凝术后眼压控制效果欠佳,有视力眼不宜采用此种手术方式;改良小梁切除术是治疗新生血管性青光眼安全、有效、经济的手术方式;引流阀植入术联合全视网膜光凝术费用较高。     

兔先天性青光眼网络膜血管改变

目的　研究青光眼对视网膜脉络膜血液循环的影响。方法　选24月龄、体重3.5～4kg的先天性青光眼大耳白兔5只(7只眼),选10只同龄大耳白兔作为对照组。另选10只2月龄、体重2kg大耳白兔前房内灌注生理盐水制成急性高眼压模型。对三组兔进行眼底照像、闪光视诱发电位(FVEP)检查,观察视网膜脉络膜血管形态和FVEP的变化。对人工急性高眼压组还进行了闪光视网膜电流图(FERG)检查。结果　先天性青光眼组与同龄对照组相比视网膜脉络膜末梢血管网明显减少;人工急性高眼压组眼压升高后首先使视网膜脉络膜末梢血管网灌流不足,随着眼压的继续升高脉络膜大血管变细,末梢血管网灌流不足加重,眼压极度升高时脉络膜大血管血流中断。同龄正常对照组的FVEP的主波P100潜伏期是(83±9)ms,先天性青光眼组则为(112±14)ms,差异有非常显著意义(P＜0.01);人工急性高眼压组高眼压前为(69±5)ms,眼压60～80mm　Hg时延长为(81±7)ms,眼压在100～130mmHg时FVEP波形低平,近似直线;眼压恢复正常后2hFVEP的P100潜伏期为(82±8)ms。人工急性高眼压前后FERG变化显著。结论　青光眼可以影响视网膜脉络膜血液循环;可使FVEP、FERG发生变化。     

AL-12182, a novel 11-oxa prostaglandin analog with topical ocular hypotensive activity in the monkey

A series of 11-oxa prostaglandin analogs was evaluated for FP receptor binding and activation. Several compounds having aryloxy-terminated lower chains were found to be potent agonists. Topical ocular dosing of AL-12182, the isopropyl ester prodrug of the potent agonist 13, lowered intraocular pressure in the monkey by 40% accompanied by minimal conjunctival hyperemia in the rabbit. AL-12182 was synthesized on multigram scale starting with D-sorbitol.