曲伏前列腺素滴眼液对原发性开角型青光眼患者眼压、血流动力学及ET-1、TIMP-2的影响

目的:探讨曲伏前列腺素滴眼液对原发性开角型青光眼(POAG)患者眼压、血流动力学及内皮素-1(ET-1)、基质金属蛋白酶-2抑制因子(TIMP-2)的影响。方法:选取2015年2月至2017年2月我院眼科收治的70例患者,按照随机数字表法分为对照组和观察组,每组各35例,对照组和观察组患者分别给予马来酸噻吗洛尔滴眼液和曲伏前列腺素滴眼液治疗,治疗周期为3个月。对比分析治疗前、治疗4周、8周及12周后两组患者的平均眼压(IOP)、昼夜IOP差,并对比治疗前、治疗12周后的睫状后动脉(PCA)、视网膜中央动脉(CRA)、收缩期峰值血流速度(PSV)、舒张末期血流速度(EDV)、血管阻力指数(RI)、血浆ET-1及房水TIMP-2的改善情况。结果:治疗前两组患者平均IOP、昼夜IOP差、PCA和CRA血流动力学、血浆ET-1及房水TIMP-2差异无统计学意义(P0.05);治疗4周、8周、12周后,两组平均IOP、昼夜IOP差明显低于治疗前,且治疗12周后观察组平均IOP、昼夜IOP差低于对照组,差异均有统计学意义(P0.05);治疗12周后,观察组PCA和CRA的PSV、EDV高于治疗前,RI低于治疗前,差异均有统计学意义(P0.05),且观察组PCA和CRA的PSV、EDV高于对照组,RI低于对照组,差异均有统计学意义(P0.05);治疗12周后,两组患者血浆ET-1和房水TIMP-2较治疗前显著下降,且观察组血浆ET-1和房水TIMP-2含量低于对照组,差异均有统计学意义(P0.05)。结论:曲伏前列腺素滴眼液治疗POAG患者,能够有效降低患者的眼压、血浆ET-1、房水TIMP-2水平,并改善患者PCA、CRA的血流动力学。     

复明片联合曲伏前列素滴眼液对原发性开角型青光眼患者眼部血流动力学和房水EPO、sCD44的影响

摘要 目的：探讨复明片联合曲伏前列素滴眼液对原发性开角型青光眼（POAG）患者眼部血流动力学和房水促红细胞生成素（EPO）、可溶性CD44（sCD44）的影响。方法：选择2017年4月~2020年11月在本院接受治疗的112例193眼的POAG患者,根据随机数字表法分为对照组（n=56,96眼）和研究组（n=56,97眼）,对照组患者接受曲伏前列素滴眼液治疗,研究组接受复明片联合曲伏前列素滴眼液治疗,对比两组疗效、眼部血流动力学和房水EPO、sCD44,视力、视野、眼压,观察治疗期间不良反应发生状况。结果：研究组的临床总有效率高于对照组（P<0.05）。治疗12周后,研究组平均光敏感度（MS）、视力高于对照组,24 h眼压平均值小于对照组（P<0.05）。治疗12周后,研究组舒张末期流速（EDV）、收缩期峰值流速（PSV）高于对照组,血流阻力系数（RI）小于对照组（P<0.05）。治疗12周后,研究组房水EPO、sCD44水平低于对照组（P<0.05）。两组不良反应发生率组间对比无统计学差异（P>0.05）。结论：复明片联合曲伏前列素滴眼液治疗POAG患者,可促进患者视力、视野、眼压改善,可能与调节眼部血流动力学和房水EPO、sCD44水平有关。     

Hydrogen peroxide in the aqueous humor and cataract formation in human diabetes

Hydrogen peroxide in the aqueous humor was measured in cataractous eyes from normal subjects and in cataractous eyes from diabetic subjects. The level of H2O2 in the aqueous humor was significantly higher in diabetes than in the idiopathic forms. It is likely that in the eye, impaired enzymic defenses lead to the accumulation of reactive species of O2, such as H2O2, which induces lipid peroxidation. This mechanism may be involved, as a direct consequence of retinal damage, in the pathogenesis of cataract in diabetes.     

Carbonic anhydrase inhibitors with strong topical antiglaucoma properties incorporating a 4-(2-aminopyrimidin-4-yl-amino)-benzenesulfonamide scaffold

Reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit several CA isozymes involved in aqueous humor secretion within the eye (such as CA II and CA IV), and (ii) to possess a pharmacological profile that allows easy penetration through the cornea, when administered as eye drops in solution or suspension, constituting thus a valuable therapeutic approach for glaucoma. Several of the obtained inhibitors showed low nanomolar affinities for the two isozymes involved in aqueous humor secretion, CA II and CA IV. Furthermore, in normotensive and hypertensive rabbits, some of them showed an effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% suspensions/solutions.     

Carbonic Anhydrase Inhibitors With Strong Topical Antiglaucoma Properties Incorporating a 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide Scaffold

Reaction of 4-(2-amino-pyrimidin-4-yl-amino)-benzenesulfonamide with alkyl/aryl-sulfonyl halides, acyl halides or arysulfonyl isocyanates afforded a series of derivatives which were tested for inhibition of three carbonic anhydrase (CA) isozymes. These compounds were designed in such a way as to (i) strongly inhibit several CA isozymes involved in aqueous humor secretion within the eye (such as CA II and CA IV), and (ii) to possess a pharmacological profile that allows easy penetration through the cornea, when administered as eye drops in solution or suspension, constituting thus a valuable therapeutic approach for glaucoma. Several of the obtained inhibitors showed low nanomolar affinities for the two isozymes involved in aqueous humor secretion, CA II and CA IV. Furthermore, in normotensive and hypertensive rabbits, some of them showed an effective and prolonged intraocular pressure (IOP) lowering when administered topically, as 2% suspensions/solutions.     

Parasite-specific antibody profile in the aqueous humor of rabbits with ocular toxocariasis

Human ocular toxocariasis is diagnosed using ophthalmologic and immunologic examinations. Many researchers have suggested that intraocular parasite-specific antibody levels are indicative of ocular toxocariasis, but little is known about the time course of the changes in these levels. We therefore investigated the anti-Toxocara canis antibody profile in the aqueous humor in an animal model of ocular toxocariasis. We intravitreally injected T. canis larvae into the right eye of 4 rabbits; 2 rabbits were orally administered T. canis eggs. We collected serum, aqueous humor, and tear samples weekly and determined the serum and aqueous humor levels of anti-T. canis immunoglobulin (Ig)G, IgA, IgM, and IgE antibodies and the tear IgG antibody level by enzyme-linked immunosorbent assay (ELISA). The severity of vitreous opacity and the aqueous humor IgG levels (measured using optical density [OD]) changed concordantly in the larvae-injected eyes; the OD exceeded 0.1 from 2–4 weeks after infection and remained elevated during active intraocular inflammation. However, the aqueous humor IgG levels were also elevated in 6 out of 8 eyes without intraocular larvae in both groups, and were low in 1 eye with live intravitreal larvae. In contrast, the serum IgG and IgM levels and the tear IgG levels increased in all rabbits, regardless of the presence of intraocular inflammation. Vitreous opacity occurred in all intravitreally infected eyes, but significant histopathological evidence of retinal damage was not detected. Thus, besides the presence of intraocular larvae, some other factors in the host may be required for the development of retinal lesions.     

Determination of voriconazole in aqueous humor by liquid chromatography-electrospray ionization-mass spectrometry

A novel method based on liquid chromatography-mass spectrometry with electrospray ionization (LC-MS) has been developed for analysis of voriconazole in aqueous humor. The separation was achieved on a reversed-phase C(18) column eluted by 70% acetonitrile-30% water-0.01% TFA. The correlation between the concentration of voriconazole to peak area was linear (r(2)=0.9990) between 0.04 and 60 ng, with a coefficient of variance of less than 3%. Limit of quantitation (LOQ) was estimated to be 5 ng/ml voriconazole with an injection volume of 2 microl of aqueous humor. Both intra-day and inter-day imprecision were less than 3% over the whole analytical range. Parallel analyses of voriconazole samples by LC-MS and by high-performance liquid chromatography (HPLC)-UV showed that the two methods were highly correlated (r(2)=0.9985). LC-MS was used to the determine voriconazole levels achieved in the aqueous humor of the rabbit eye, following topical application of 5 or 10 microg voriconazole in the form of eyedrops for 11 days b.i.d. The lower dosage produced an aqueous humor concentration of 7.29+/-5.84 microg/ml, while the higher dosage produced a concentration of 14.56+/-12.90 microg/ml.     

Guanylate cyclase activators, cell volume changes and IOP reduction

Glaucoma afflicts millions of people worldwide and is a major cause of blindness. The risk to develop glaucoma is enhanced by increases in IOP, which result from deranged flow of aqueous humor. Aqueous humor is a fluid located in the front of the eye that gives the eye its buoyancy and supplies nutrients to other eye tissues. Aqueous humor is secreted by a tissue called ciliary processes and exits the eye via two tissues; the trabecular meshwork (TM) and Schlemm's canal. Because the spaces through which the fluid flows get smaller as the TM joins the area of the Schlemm's canal, there is resistance to aqueous humor outflow and this resistance creates IOP. There is a correlation between changes in TM and Schlemm's canal cell volume and rates of aqueous humor outflow; agents that decrease TM and Schlemm's canal cell volume, increase the rate of aqueous humor outflow, thus decreasing IOP. IOP is regulated by guanylate cyclase activators as shown in humans, rabbits and monkeys. There are two distinct groups of guanylate cyclases, membrane guanylate cyclase and soluble guanylate cyclase (sGC); activation of both have been shown to decrease IOP. Members of the membrane guanylate cyclase family of receptors bind to peptide ligands, while the sGC responds to gases (such as NO and CO(2)) and compounds (such as YC1, [3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole), a benzyl indazole derivative, and BAY-58-2667); activation of either results in formation of cyclic GMP (cGMP) and activation of protein kinase G (PKG) and subsequent phosphorylation of target proteins, including the high conductance calcium activated potassium channel (BKca channel). While activators of both membrane guanylate cyclase and sGC have the ability to lower IOP, the IOP lowering effects of sGC are noteworthy because sGC activators can be topically applied to the eye to achieve an effect. We have demonstrated that activators of sGC increase the rate at which aqueous humor exits the eye in a time course that correlates with the time course for sGC-induced decreases in TM and Schlemm's canal cell volume. Additionally, sGC-induced decrease in cell volume is accompanied by both K(+) and Cl(-) efflux induced by activation of K(+) and Cl(-) channels, including the BKca channel and/or K(+)Cl(-) symport. This suggests that parallel K(+)Cl(-) efflux, and resultant H(2)O efflux result in decreases in cell volume. These observations suggest a functional role for sGC activators, and suggest that the sGC/cGMP/PKG systems are potential therapeutic targets in the treatment of glaucoma.     

Modulation of regulatory T cell immunity by the neuropeptide alpha-melanocyte stimulating hormone.

Although many immunosuppressive factors have been identified in the eye, one of these factors, alpha-melanocyte stimulating hormone (alpha-MSH), both suppresses the activation of inflammatory activity by primed T cells and induces the activation of regulatory T cells (Treg cells). This neuropeptide alone at its ocular physiological concentration can account for most of the immunosuppressive activity of aqueous humor (the fluid filing the anterior chamber of the eye). Aqueous humor made devoid of alpha-MSH no longer suppresses IFN-gamma production by Th1 cells. It is alpha-MSH that mediates aqueous humor induction of regulatory T cells. What we have found is that alpha-MSH mediates the induction of C4+ CD25+ Treg cells, and that if the alpha-MSH Treg cells are specific to an autoantigen they can be used to suppress autoimmune disease. It is the objective of this review to demonstrate how we came to discover that alpha-MSH could have such an important role in the extreme regional immunity of the immune privileged eye and how this discovery could be applied to create or reestablish tolerance to prevent autoimmune disease.     

Substance P and secretoneurin in vitreous aspirates of patients with various vitreoretinal diseases

By means of highly sensitive radioimmunoassays, the levels of substance P (SP) and secretoneurin (SN) were detected in vitreous aspirates of patients with macular holes which served as controls, in patients with nonproliferative diabetic retinopathy (DR), active proliferative diabetic retinopathy (active PDR), inactive PDR, rhegmatogenous retinal detachment and proliferative vitreoretinopathy (PVR). Furthermore, SN-like immunoreactivities were characterized by reversed phase-HPLC. The concentration of SN was more than 20-fold higher in macular holes when compared with SP and reversed phase HPLC revealed evidence that the vitreous levels of SN represent authentic SN. SN was significantly decreased in patients with nonproliferative DR, active PDR and inactive PDR by more than 70% which seems to result from a reduced expression and/or secretion from the cilary epithelium and a reduced release from the retina both due to diabetes mellitus. By contrast SP was increased in rhegmatogenous retinal detachment most obviously due to an enhanced outflow of the peptide through retinal breaks. Despite their proangiogenic activities, SP and SN are unlikely to be involved in the pathogenesis of neovascularizations in DR because of their unchanged and reduced levels, respectively, but the low levels of both peptides may facilitate the regression of vasoproliferations following laser photocoagulation.     

Intraocular penetration of pyruvate following its topical administration in mice

Previous studies from our laboratory have demonstrated that pyruvate, an endogenous α-keto acid metabolite, has a protective effect against oxidative stress induced damage to the ocular tissues including the lens, in which in addition to exerting its protective effect against tissue damage caused by oxyradicals generated under organ culture, it is also found effective in preventing actual cataract formation in vivo in animal models undergoing direct oxidative stress as well as in diabetes. In the latter studies, pyruvate was administered mixed with diet and drinking water. However, with the view of the desirability of treating eye diseases by topical administration of the pharmacological agents, the present studies were conducted to determine the penetrability of pyruvate through the cornea to the aqueous humor and the lens following its topical administration as its ester, ethyl pyruvate (EP). These experiments were done in CD-1 mice. After instillation of the drops in the conjunctival cul-de-sac, aqueous humor samples were aspirated at the desired times and analyzed for pyruvate. In a separate group of animals, analyses were done also in the lens. Analyses were done spectrophotometrically by monitoring the decrease in absorption of NADH due to the reduction of pyruvate to lactate by lactate dehydrogenase. The levels of pyruvate were found to be significantly elevated in both the aqueous humor as well as the lens, the peak concentrations being 4.7 and 3.6 mM, respectively. Such levels have been previously shown to be effective in exerting its antioxidant effects. The results are therefore considered pharmacological significant from the point of view of its potential use for topical treatment of cataracts induced by oxidative stress and diabetes.     

Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study.

Retinopathy is the most common microvascular diabetes complication and represents a major threat to the eyesight. The aim of this study was to address the role of pro- and anti-angiogenic molecules in diabetic retinopathy in the aqueous humor of the eye. Aqueous humor was collected at cataract surgery from 19 diabetic patients and from 13 age- and sex-matched normoglycemic controls. Levels of pro-angiogenic vascular endothelial growth factor (VEGF) and angiogenic inhibitor pigment epithelium-derived factor (PEDF) were determined. Angiogenic activity of the aqueous humor was quantified by measuring its effect on the migration of capillary endothelial cells. In the aqueous fluid, VEGF levels were increased in diabetics (mean values: 501 vs. 367 pg/ml; p = 0.05), compared to controls. PEDF was found to be decreased in diabetics (mean values: 2080 vs. 5780 ng/ml; p = 0.04) compared to controls. In seven diabetic patients with proliferative retinopathy, the most profound finding was a significant decrease of the PEDF level (mean value: 237 ng/ml), whereas VEGF levels were comparable to diabetic patients without proliferation (mean value: 3153; p = 0.003). Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF. Likewise, in diabetics without proliferation, angiogenic activity was also blocked by antibodies to PEDF. We will demonstrate here that the level of the natural ocular anti-angiogenic agent PEDF is inversely associated with proliferative retinopathy. PEDF is an important negative regulator of angiogenic activity of aqueous humor. Our data may have implications for the development of novel regimens for diabetic retinopathy.     

Biomechanics of Schlemm's canal endothelial cells: influence on F-actin architecture

Aqueous humor drains from the eye through Schlemm's canal, a small endothelial-lined collecting duct. Schlemm's canal endothelial cells may be important in controlling the pressure within the eye (and hence are of interest in glaucoma), and are subject to an unusual combination of shear stress and a basal-to-apical pressure gradient. We sought to characterize this biomechanical environment and determine its effects on F-actin architecture in situ. A theoretical model of flow in Schlemm's canal was used to estimate shear stresses applied to endothelial cells by flowing aqueous humor. Alignment of Schlemm's canal endothelial cells in human eyes was quantified by scanning electron microscopy. F-actin architecture was visualized by fluorescent labeling and compared for closely adjacent cells exposed to different biomechanical environments. We found that, despite the relatively low flow rate of aqueous humor, shear stresses experienced by Schlemm's canal endothelial cells could reach those in the arterial system. Schlemm's canal endothelial cells showed a statistically significant preferential alignment, consistent with a shear-mediated effect. Schlemm's canal endothelial cells subjected to a basal-to-apical pressure gradient due to transendothelial flow showed a prominent marginal band of F-actin with relatively few cytoplasmic filaments. Adjacent cells not subject to this gradient showed little marginal F-actin, with a denser cytoplasmic random network. We conclude that Schlemm's canal endothelial cells experience physiologically significant levels of shear stress, promoting cell alignment. We speculate that this may help control the calibre of Schlemm's canal. F-actin distribution depends critically on the presence or absence of transendothelial flow and its associated pressure gradient. In the case of this pressure gradient, mechanical reinforcement around the cell periphery by F-actin seems to be critical.     

Application of Anodic Stripping Voltammetry for Zinc, Copper, and Cadmium Quantification in the Aqueous Humor: Implications of Pseudoexfoliation Syndrome

Anodic stripping voltammetric (ASV) procedure, using mercury film electrode, was optimized and applied to determine the concentrations of zinc, cadmium, and copper in the aqueous humor. Concentration levels as low as 1 ppb of the test metals was possible to be detected using short electrolysis times (120 s) and microquantities of aqueous humor (up to 35 μL). As a first application of the voltammetric analysis of trace metals in the aqueous humor, the role of the three selected trace elements in the pseudoexfoliation (PEX) syndrome was examined. Samples from aqueous humor were collected during cataract extraction from patients with and without PEX. The zinc and copper concentration levels in the aqueous humor did not show statistically significant difference in the study and control group. Cadmium was detected in a small number of samples, without however statistical differences between the two groups. ASV proved to be a highly precise and sensitive tool for the quantification of heavy metal ions in aqueous humor. Further studies may lead to useful conclusions for the role of zinc, copper, or cadmium in PEX syndrome.     

曲伏前列素滴眼液联合复方丹参片对老年青光眼患者房水屏障功能 及MMP2 水平的影响

目的:研究曲伏前列素滴眼液联合复方丹参片对老年青光眼患者房水屏障功能、MMP2及临床疗效的影响。方法:选择2012年5月-2015年10月期间在我院就诊的90例青光眼患者作为研究对象,随机分为实验组和对照组,实验组患者接受曲伏前列素滴眼液联合复方丹参片治疗,对照组患者接受曲伏前列素滴眼液治疗,比较两组患者治疗前后的平均眼压水平、房水屏障功能以及血清MMP2含量、MMP2/TIMP1比值。结果:治疗后1个月、2个月、3个月时,实验组患者的平均眼压水平(17.2±2.2 vs 19.7±3.1 mm Hg)、(17.0±2.8 vs 20.2±3.2 mm Hg)、(16.7±2.5 vs 18.2±3.5 mm Hg)均显著低于对照组(P0.05);治疗后3个月时,实验组患者的房水闪辉值(18.3±2.8 vs 33.1±5.6 pc/ms)、房水细胞数以及血清MMP2含量(2.77±0.46 vs 4.02±0.72μg/L)及MMP2/TIMP1比例(0.48±0.07 vs 0.76±0.09)均显著低于对照组(P0.05)。结论:曲伏前列素滴眼液联合复方丹参片治疗能够更为有效地降低眼压水平、改善房水屏障功能,可能与其降低MMP2含量有关。     

Horseradish peroxidase: a reliable or a misleading tool for the investigations on the origin of the proteins of the aqueous humor?

The concept of the blood-aqueous barrier is largely based on the use of horseradish peroxidase (HRP). The present investigation was designed to check its reliability as a macromolecular tracer, especially with regard to the transport of plasma proteins. Rabbits were killed 5 min to 24 h after being intravenously injected with HRP. The tracer diffused rapidly, reaching the aqueous humor of the eye in 3 min or less and was detected at high concentration in the narrow space between the outer epithelial layer of the ciliary epithelium and the wall of the pervious capillaries in the stroma of the processes. HRP appeared to migrate from the blood to the posterior chamber, permeating the tight junctions, viz., the anatomical basis of the blood-aqueous barrier. It was detected at higher concentration at the anterior surface of the iris, at short time intervals; this was interpreted as penetration of the tracer from the aqueous humor of the anterior chamber. The choroid was also labeled in continuation with the reaction in the stroma of the pars plana of the ciliary body which, in turn, sometimes reached the iris root. Therefore, the pervious blood vessels of the choroid could be a source of macromolecules for the iris root. HRP also induced the formation of lysosomes in the ciliary epithelium. This can hardly be accepted as the way in which plasma proteins are physiologically transported to the aqueous humor. However, the pathway of HRP migration over short time intervals seems to be in agreement with previous research indicating that the entrance of serum albumin into the posterior chamber is the first step of its incorporation into the aqueous humor. Received: 7 June 1996 / Accepted: 15 January 1997     

Capillary high-performance liquid chromatographic determination of lutein and zeaxanthin in aqueous humor from a single mouse eye

To protect the eye from ultraviolet phototoxicity caused by free radicals, ocular components such as the aqueous humor accumulate antioxidants, such as the carotenoids. Lutein and zeaxanthin are the only carotenoids known to be present in the aqueous humor. Due to the small sample volume, pooling of samples from an undesirable large number of animals is often required for sufficient sensitivity and statistically significant differences to be achieved. In this paper we present a rapid, sensitive and robust packed capillary high-performance liquid chromatographic visible detection method for the quantification of lutein and zeaxanthin in the aqueous humor of single mouse eyes.     

Experimental data on the penetration of gentamicin into the media of the eye]

Penetration of Soviet gentamicin into the humor of the anterior chamber and vitreous body of the eye with aseptic inflammation was studied after the antibiotic administration by various routed, i.e. instillations of 8 per cent antibiotic solution and 8 per cent antibiotic solution methylcellulose into the conjunctival sac, injections of 20 mg of gentamicin subconjunctivally and retrobulbarly, injections of gentamicin intramuscularly in doses of 0.6 mg/kg. The studies showed that gentamicin penetrated into the humor of the anterior chamber and vitreous body of the eye after all the administration routes mentioned above in concentrations sufficient for the antibiotic antimicrobial effect and persisted in the eye media for prolong periods of time (24--48 hours). The highest concentrations of the antibiotic in the tumor of the anterior chamber were achieved after its administration subconjunctivally or after instillation of its 8 per cent on methylcellulose, while in the vitreous body its highest concentrations were achieved after injections subconjunctively, retrobulbarly or intramuscularly. Instillations of gentamicin solution on methylcellulose provided higher and more persistant concentrations of the antibiotic in the humor as compared to instillations of its aqueous solutions. Retrobulbar injections of gentamicin had no advantages as compared to subconjunctival administration with respect to providing higher concentrations of the antibiotic in the eye media.     

Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.     

Pharmacotherapies for glaucoma

Glaucoma is a group of progressive optic neuropathies in which the axons in the optic nerve are injured, retinal ganglion cell numbers are reduced and vision is gradually and permanently lost. The only approved and effective way to treat glaucoma is to reduce the intraocular pressure (IOP). This is usually accomplished by surgical and/or pharmacological means. Drugs designed to reduce IOP target one or more of the parameters that maintain it. These parameters (collectively known as aqueous humor dynamics) are the production rate of aqueous humor, the pressure in the episcleral veins and the drainage of aqueous humor through the trabecular or uveoscleral outflow pathways. Intraocular pressure lowering drugs can be classified as inflow or outflow depending on whether they reduce aqueous humor inflow into the anterior chamber or improve aqueous humor outflow from the anterior chamber. Inflow drugs, like β adrenergic antagonists and carbonic anhydrase inhibitors, reduce the rate of aqueous humor production. Outflow drugs, like prostaglandin analogs, cholinergic agonists and sympathomimetics, increase the rate of drainage through the uveoscleral outflow pathway and/or increase the facility of outflow through the trabecular meshwork. Some drugs have mixed inflow/outflow effects. This review summarizes the pharmacological treatments for glaucoma in use today and some new drugs showing potential for use in the future.