Target intraocular pressure in the management of glaucoma

Achievement of target intraocular pressure is the goal of every efficient antiglaucoma therapy. Target intraocular pressure is the level of intraocular pressure which is associated with minimal likelihood of visual field or optic nerve lesion, or an existing lesion progression due to elevated intraocular pressure. Results of large clinical studies which have offered some new concepts on target intraocular pressure in the management of glaucoma are reviewed. An association between the curve of intraocular pressure decrease and glaucoma progression was demonstrated in these studies. Generally, a lower value of target intraocular pressure implies better protection from the loss of vision and visual field impairment in glaucoma patients. In advanced glaucoma, the greatest possible reduction from the initial intraocular pressure should be attempted. A 20% reduction from the initial intraocular pressure or decrease to < 18 mmHg in advanced glaucoma has been recognized as a favorable strategy to reach target intraocular pressure. In normal tension glaucoma, a lower value of target intraocular pressure is associated with a slower disease progression. In patients with initial glaucoma, 25% reduction from the initial intraocular pressure will slow down the disease progression by 45%. The value of target intraocular pressure depends on the pretreatment level of intraocular pressure, optic nerve condition, glaucoma disease state, rate of glaucoma progression, patient's age, and other risk factors for the development of glaucoma.     

The relationship between IMPS-measured stress score and intraocular pressure among public school workers

The aim of this study was to examine the relationship between psychosocial stress and intraocular pressure among apparently healthy subjects. Psychosocial stress among 1,461 public school workers (883 men and 578 women) was measured using the inventory to measure psychosocial stress (IMPS) and intraocular pressure was measured using a non-contact tonometer (Topcon CT-90). After controlling for the effects of likely confounding variables such as age, body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, alcohol consumption, smoking status, and exercise, partial correlations and hierarchical multiple regression analysis were performed in order to test the hypothesis that IMPS-measured stress score was associated with intraocular pressure. IMPS-measured stress score was found to correlate positively with intraocular pressure in women after controlling for the effects of confounding variables, whereas this relationship was not found in men. Hierarchical multiple regression analysis indicated that IMPS-measured stress score was positively associated with intraocular pressure in women independent of confounding variables, but not in men. Perturbations of the hypothalamic-pituitary-adrenal (HPA) axis associated with stress are considered to be partly responsible for an increase in intraocular pressure among people suffering from psychosocial stress. Further research is needed to elucidate the relationship between this stress-associated increase in intraocular pressure and open-angle glaucoma.     

Intraocular pressure in cats is lowered by drops of hornet venom

1. Nine cats were given an intravenous injection of the Oriental hornet (Vespa orientalis, Vespinae; Hymenoptera) venom sac extract (VSE) and seven cats had the same VSE administered as eye drops. 2. When injected intravenously, the hornet VSE decreased the intraocular pressure in both eyes sharply during the first 20 min and with a slower rate later on until the end of the 3 hr experiment. The intraocular pressure dropped to zero in some cases. 3. VSE eye drops decreased the intraocular pressure only in the treated eye, while in the second eye (left as a control) the intraocular pressure remained the same throughout the experiment. 4. The decrease in the intraocular pressure was sharp during the first 20 min and slowed down afterwards until the end of the experiment. 5. The intraocular pressure did not reduce to zero. 6. This study shows that the active components of the hornet venom which caused a decrease in the intraocular pressure can cross the cornea and exert a hypotensive effect in the eye.     

Correcting effect of the locus coeruleus on ophthalmic hypertension of the hypothalamic genesis

We studied the intraocular pressure and the humor aquosus volume changes after a chronic emotional stress produced by a prolonged electrical stimulation of the multiple ventromedial (VMHN) hypothalamic nuclei and the locus coeruleus. The VMHN stimulation caused an increase in the intraocular pressure and production of the humor aquosus, as well as a decrease in the outflow ratio. Stimulation of the locus coeruleus increased the intraocular pressure to a lesser extent. A combined effect of both types of stimulation normalised the intraocular pressure due to a decrease in the humor aquosus production, the outflow ratio remaining unchanged.     

Could White Coat Ocular Hypertension Affect to the Accuracy of the Diagnosis of Glaucoma? Relationships Between Anxiety and Intraocular Pressure in a Simulated Clinical Setting

Sixty-one healthy subjects participated in a laboratory study carried out in a simulated clinical setting. Anticipatory anxiety-state was assessed at the arrival and immediately after, with no brief phase of adaptation, measurements of intraocular pressure, heart rate, systolic and diastolic blood pressure were collected. At the end of the procedure, anxiety-trait was also assessed. Results suggest that high levels of both anxiety-state and anxiety-trait significantly predicted a clinically relevant increase of intraocular pressure. Anxiety-state mediated the relationship between anxiety-trait and intraocular pressure, which also was found to be related with heart rate but not related to both systolic and diastolic blood pressure. These results suggest a common mechanism of regulation underlying anxiogenic variability found on both intraocular pressure and heart rate. A reduction in parasympathetic activity appears as a possible mechanism underlying to this phenomenon. This anxiety-enhanced intraocular pressure could be considered a phenomenon analogous to white coat hypertension found in the measurement of blood pressure; therefore, it probably should be taken into account in the clinical context to prevent errors in the diagnosis of glaucoma. Further research on cognitive and emotional regulation of intraocular pressure is needed to best characterize this hypothetical phenomenon.     

Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies.     

Intraocular and intraorbital compartment pressure changes following orbital bone grafting: a clinical and laboratory study

Visual loss is an uncommon but catastrophic complication after intraorbital bone grafting for the reconstruction of acute traumatic defects or long-standing enophthalmos. Increased intraocular or intraorbital compartment pressure may be pathogenic in this setting. A two-part study was designed to test the null hypothesis that intraocular and intraorbital compartment pressure values remain constant despite orbital volume reduction with graft material. Laboratory study: Intraocular and intraorbital compartment pressures were measured during sequential orbital volume reduction in New Zealand White rabbits that had been randomized to one of three groups: intact orbits (n = 10), acute orbital wall defects (n = 8), and chronic (3 months) orbital wall defects (n = 11). Intraocular pressure was significantly (p<0.05) elevated in all three groups of orbits undergoing orbital volume reduction compared with control, nonoperated orbits. Intraorbital compartment pressure values did not change significantly from control levels throughout the grafting sequence. Although no significant differences existed between groups in the maximum levels of intraocular pressure attained, the chronic group demonstrated a greater rate of rise and slower rate of decline. Clinical study: Using applanation tonometry, intraocular pressure was measured before and serially after orbital floor exploration and intraorbital placement of split calvarial bone grafts in 19 patients who presented with orbital-zygomatic complex fractures that required surgery. A separate group of 16 patients with orbital-zygomatic complex fractures that required exploration of the orbital floor but not bone grafting was used for comparison. A significant (p<0.05) elevation of intraocular pressure was observed immediately after bone grafting compared with nongrafted orbits, but values returned to normal within 30 minutes and remained stable through the third postoperative day. There were no cases of visual impairment in any patients in either group as the result of surgical treatment. These data indicate that orbital volume reduction with graft material results in significant, temporary elevation of intraocular pressure. No significant elevations of intraorbital compartment pressure were detected in the rabbit orbits. Data from this study may have direct relevance in defining guidelines for "tolerable" changes in orbital tissue and globe pressures after surgery.     

New prostaglandin derivative for glaucoma treatment

A hydrogen sulphide-releasing derivative of latanoprost acid (ACS 67) was synthesized and tested in vivo to evaluate its activity on reduction of intraocular pressure and tolerability. Glutathione (GSH) and cGMP content were also measured in the aqueous humour. The increased reduction of intraocular pressure, with a marked increase of GSH and cGMP and the related potential neuroprotective properties, make this compound interesting for the treatment of glaucoma. This is the first time that an application of a hydrogen sulphide-releasing molecule is reported for the treatment of ocular diseases.     

Effect of anterior chamber paracentesis on decreased retinal circulation due to retrobulbar hematoma in dogs

An experimental canine model for blindness following blepharoplasty was developed to demonstrate occlusion of retinal circulation resulting from simulated retrobulbar hematoma. Seven mongrel dogs were studied, monitoring retinal vascular patterns by funduscopic examination and intraocular pressure by pneumotonometry. Anterior chamber paracentesis was performed in five dogs 10 minutes after injecting blood retrobulbarly, with an immediate decrease in pressure and return of retinal blood flow. In two dogs without paracentesis, increased pressure and blindness persisted. Anterior chamber paracentesis has been shown to reduce intraocular pressure from hematoma of the retro-orbital area in dogs. Although controversial, anterior chamber paracentesis may represent a useful temporizing adjunct in the treatment of increased intraocular pressure and impaired vision from hematoma following blepharoplasty.     

The molecular dynamics of hyaluronates in solution.

The dynamic properties of hyaluronate solutions are discussed with relevance to some problems in sensory physiology (mechanoelectrical transduction), renal physiology, interstitial fluid regulation, and especially to the causes of open-angle glaucoma. With respect to the last problem: as recent biochemical evidence indicates that the hyaloid membrane does not exist, it now seems worthwhile to consider the increase in intraocular pressure present in the eye with glaucoma to be due--at least in the open-angle case--to a change in the specific gravity and hydrophilic nature of the hyaluronic acid in the vitreous body in particular, as well as in the trabecular meshwork. Densimetric experimental evidence indicates that the hyaluronate system could, indeed, produce the pressure changes seen in glaucoma, if intraocular pH changed but slightly. A hypothesis concerning the effect of acetazol amide on intraocular pressure is also presented.     

Effect of amitriptyline and nortriptyline on the intracular pressure and aqueous humor dynamics in rabbits (author's transl)]

Both amitriptyline and nortriptyline applied conjunctivally produced pupil size enlargement, intraocular pressure decrease and a fall in aqueous humor formation. Phenoxybenzamine and superior cervical sympathetic ganglionectomy prevented the amitriptyline or nortriptyline inducing intraocular pressure changes. Either systemic administered or conjunctivally applied amitriptyline or nortriptyline, potentiated the effects on the pupil and intraocular pressure of exogenously norepinephrine.     

布林佐胺与噻吗洛尔滴眼液对新生血管性青光眼患者眼压及血清和房水IL-6、PEDF和VEGF水平的影响

目的:探讨布林佐胺联合噻吗洛尔滴眼液对新生血管性青光眼(NVG)患者眼压及血清和房水中白细胞介素-6(IL-6)、色素上皮衍生因子(PEDF)、血管内皮生长因子(VEGF)水平的影响。方法:选取我院2014年6月～2016年12月择期行手术治疗的86例NVG患者,按照随机数字表法均分为两组。对照组术后采取噻吗洛尔滴眼液治疗,观察组在此基础上加用布林佐胺滴眼液治疗。记录比较两组临床疗效,治疗前后眼压及血清和房水中IL-6、PEDF和VEGF水平的变化及不良反应的发生情况。结果:术后6个月,观察组总有效率为95.3%,较对照组明显升高(79.1%,P0.05)。与术前对比,两组术后7天、6个月时24 h眼压峰值、平均眼压、眼压波动值、血清和房水中IL-6、VEGF水平均显著下降(P0.01),血清和房水中PEDF水平均显著上升(P0.01),且观察组以上眼压指标较对照组同期改善更为明显(P0.01)。对照组和观察组不良反应的发生率对比差异无统计学意义(7.0%vs 11.6%,P0.05)。结论:术后应用布林佐胺联合噻吗洛尔滴眼液治疗NVG患者更能有效降低眼压和控制其波动,调节机体血管生成促进/抑制因子平衡,提高治疗效果,且安全性高。     

Comparison of evening and morning dosing of travoprost 0.004%/timolol 0.5% fixed combination in 6 month period

An open label, multi-center, 6 months observational study of new fixed combination (travoprost 0.004%/timolol 0.5%), in order to evaluate both efficacy (intraocular pressure lowering) and tolerability (patient and investigator satisfaction) of two dosing regimens--evening (PM) and morning (AM). After screening for enrollment, to 40 patients (79 eyes with primary open angle glaucoma or ocular hypertension), new fixed combination travoprost 0.004%/timolol 0.5% was prescribed once a day in the evening (PM). Patients were enrolled according to each investigator decision on indication for travoprost 0.004%/timolol 0.5% fixed combination once a day, without washout period after previous medication. Intraocular pressure was measured at 9 AM at all time control points: at baseline, after 1 month, after 3 months and after 6 month. After 1 month, screening for nonresponders (criteria: 20% intraocular pressure lowering) and subjects with major side effects was performed. At second control visit, after 3 months PM dosing, intraocular pressure was measured and patients were instructed to continue once a day the same medication, but in the morning (AM) for consequent 3 months. After 1 month, reduction in mean intraocular pressure value was 21.66%. At the visit after 3 month, the mean intraocular pressure was 15.67 +/- 2.17 mm Hg (reduction 21.14%). 3 month after dosing regimen changed to AM (6 month after beginning of travoprost 0.004%/timolol 0.5% combination therapy), reduction in intraocular pressure value was 19.86%. The differences (mean +/- standard deviation) in intraocular pressure values after 1, 3 and 6 month were all highly statistically significant compared to baseline values. The tolerability was evaluated in five steps (Likert scale) ranging from unsatisfactory to excellent by both patient and investigator--taken at 3 and 6 month control visit. 95% of patients and 100% of investigators were satisfied with the possibility of choosing dosing regimen for travoprost 0.004%/timolol 0.5% fixed combination. Travoprost 0.004%/timolol 0.5% fixed combination proved sufficient intraocular pressure control dosed either PM or AM with no statistically significant difference between two dosing regimens. Possibility to choose between two dosing regimens gives each practitioner additional reassurance that glaucoma therapy will be individualised to needs of each patient.     

A mathematical model of transmural transport of oxygen to the retina

A mathematical model of transmural transport of oxygen to a metabolizing retina is presented based on the equations of fluid dynamics. The equations of oxygen transfer are derived and then solved subject to the condition that the capillaries begin to transport oxygen at an initial time. The resulting transient analysis gives us insight into how diffusive and filtrative processes lead to the oxygen distributions both inside and outside capillaries. On the other hand, the steady state solution allows us to predict the cutoff intraocular pressure above which no oxygen is transferred to retinal tissue. It also gives quantitative relationships which allow us to postulate how intracapillary hypertension counterbalances elevated intraocular pressures and how low pressure glaucoma may arise from ineffective diffusive and filtrative processes of oxygen transport.     

Determination of the true intraocular pressure and modulus of elasticity of the human cornea in vivo

The purpose of this study was to determine the true intraocular pressure and modulus of elasticity of the human cornea in vivo. The cornea was modeled as a shell, and the equations for the deformations of a shell due to applanating and intraocular pressures were combined to model the behavior of the cornea during applanation tonometry. At certain corneal dimensions called the calibration dimensions, the applanating and intraocular pressures are considered to be equal. This relationship was used to determine the modulus of elasticity of the cornea and the relationship between the applanating and intraocular pressures. The true intraocular pressure (IOPT) was found to be related to Goldmann’s applanating pressure (IOPG) as (IOPT = IOPG/K, where K is a correction factor. For the calibration corneal thickness of 0.52 mm, the modulus of elasticity E in MPa of the human cornea was found to be related to the true intraocular pressure IOPT in mmHg as E = 0.0229IOPT. The generalization of the Imbert—Fick law that takes into account the effect of corneal dimensions and stiffness was found to be given by IOPT = 73.5W/(K A), where W is the applanating weight in gf (gram force) and A is the applanated area in mm². The calculated true intraocular pressure and modulus of elasticity were found to agree with published experimental results. The mathematical model developed may therefore be used to improve results from applanation tonometry and to estimate the mechanical property of the cornea in vivo.     

Corneal thickness in congenital glaucoma

Central corneal thickness is very important measurement in glaucoma treatment because it influences the eye pressure measurements. A thinner cornea gives us artifactually lower intraocular pressure and a thicker cornea gives higher intraocular pressure reading, so it has to be corrected in both cases. The aim of this study is to compare central corneal thickness between congenital glaucoma patients and normal subjects. Prospective study included 27 patients with congenital glaucoma and 35 patients in control group. First group was subdivided in two subgroups: A--8 earlier operated patients, B--19 patients treated with topic therapy. Patients had no other corneal disorders, history of trauma, corneal surgery and they were not contact lens wearers. Measurements were performed by specular microscope Tomey EM 3000 on central corneas. This study showed that patients with congenital glaucoma have lower central corneal thickness than normal subjects. Also, the study showed that antiglaucomatous operation doesn't influence central corneal thickness. Central corneal thickness need to be a routine part of examination measurements because of need to correct intraocular pressure according to it, but also the thinner corneas values can suggest congenital glaucoma diagnosis beside the other parameters.     

Effects of the R(+)- and S(-)-isomers of beta-adrenoceptor blockers with intrinsic sympathomimetic activity, befunolol and carteolol, on rabbit intraocular pressure.

Effects of the R(+)- and S(-)-isomers of befunolol and carteolol, beta-adrenoceptors with intrinsic sympathomimetic activity, on the rabbit intraocular pressure were tested. The intraocular pressure was decreased by instillation of the R(+)- and S(-)-isomers of befunolol (0.1 and 0.3%) and of carteolol (1.0%) to the eye and attained the minimum level at 60 min. However, 0.3% of the R(+)- and S(-)-isomers of carteolol did not influence the pressure. The corresponding time courses for the intraocular pressure for the R(+)- and S(-)-isomers did not differ, suggesting that in the treatment of glaucoma, the therapeutic advantage of the R(+)-isomers of befunolol and carteolol may be similar to the S(-)-isomers.     

马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响

目的:探讨马来酸噻吗洛尔眼液联合拉坦前列素眼液对原发性开角型青光眼患者眼压的影响。方法:选取2015年1月-2016年5月在我院接受治疗的原发性开角型青光眼患者84例,其中给予马来酸噻吗洛尔眼液治疗的42例记为对照组,给予拉坦前列素眼液联合马来酸噻吗洛尔眼液治疗的42例记为观察组,两组均治疗6个月。对比两组患者治疗过程中的眼压变化情况,并对比两组患者的临床总有效率、药物依从性和并发症情况。结果:观察组治疗2、4、6个月后的眼压均显著低于对照组(P0.05),观察组患者治疗6个月后与治疗前的眼压差值大于对照组(P0.05)。两组患者治疗2、4、6个月后的眼压呈下降趋势,两两比较差异均有统计学意义(P0.05)。观察组的临床总有效率95.24%显著高于对照组的80.95%(P0.05)。两组患者在治疗过程中结膜充血、眼内异物感、眼睛疼痛、视力模糊、味觉异常以及总并发症发生率对比差异不显著(P0.05)。观察组患者的药物依从性比例显著低于对照组(P0.05)。结论:马来酸噻吗洛尔眼液联合拉坦前列素眼液治疗原发性开角型青光眼患者具有较好的临床疗效,可显著降低患者眼压,同时具有较好的安全性,但药物依从性较差。     

The Effect of Spatial Inhomogeneity of the Cornea on the Deformation Properties of the Eyeball and the Results of Maklakoff Applanation Tonometry

A two-component model of the eyeball that represents the cornea as a momentless, linearly elastic deformable surface and the scleral region, as an elastic element that responds to intraocular pressure changes by volume changes, has been used to analyze the effect of spatial inhomogeneity in the distribution of effective corneal stiffness on the mechanical properties of the eye. The effective stiffness of the cornea characterized both the elastic properties and the thickness of the cornea within the framework of the model. Various axisymmetric forms of the effective stiffness distribution characterized by monotonic increase along the arc between a point on the corneal surface and the apex of the cornea were studied. The considered distributions simulated both natural inhomogeneity and apical region weakening due to surgical interventions. Numerical simulation yielded the dependences of deformation parameters on intraocular pressure changes. These parameters characterized the deformation properties of both the cornea (apex displacement) and the eyeball as a whole (intraocular volume change). In the case of moderate inhomogeneity, the dependences were only slightly different from those for a homogeneous cornea with an effective stiffness equal to the mean value for the corresponding inhomogeneous distribution. A noticeable increase in the integral response of the cornea and the eyeball as a whole to changes in pressure was observed if the effective stiffness amplitude was very high (two or more times higher than the mean value). The effect of inhomogeneity on the results of tonometric measurements with a Maklakoff tonometer (flat stamp) was studied. The tonometric difference, that is, the difference between the tonometric pressure (in the loaded eye) and the true pressure (before loading), mainly depended on the average stiffness of the cornea in this case as well, with a substantial increase observed at very high stiffness amplitudes only. Apical weakening of the cornea led to an increase (although not very pronounced) of the tonometric difference.