The Multi—channel VEP Topographies in Patients with Late—stage Glaucoma

Purpose: To study the clinical application of multi-channel VEP topographies in patients with late-stage glaucoma.Methods: The multi- channel checkerboard reversal VEP waves of 25 normal persons and 15 patients with late-stage gloucoma were recorded and analyzed, All patients were examined using Humphrey Field Analyzer. The VEP topographies of multi-channel VEP waves were shown by computer processing system.Results: In normal subjects , the topographies showed symmetric distribution to full-field pattern stimulation . In all patients with late-stage glaucoma, even whose visual field was severely damaged, multi-channel VEP could be recorded, All channels showed simple 'NPN' wave form, N1,N2 waves were not conspicuous, even both were lost, all channels showed the reduced amplitudes of PI waves, and longer latency. The multi-channel VEP topographies showed irregular distribution, Some showed amplitude asymmetry, other limited or widespread, lateralized.Conclusions : Despite the severely damaged visual fiel     

Characterization of Glucocorticoid Receptor on Lymphocytes in Chinese Patients with Glucocorticoid-induced Glaucoma

Purpose : We studied the pathogenesis of glucocorticoid-induced glucoma (GIG) through characterization of glucocorticoid receptor (GR) on lymphocytes in Chinese patients with GIG.Methods:By radioligand receptor binding followed by Scatchard analysis, the specific binding sites were characterized and quantitated for glucocorticoid receptors on peripheral blood lymphocytes obtained from patients with GIG and the control group.Results:The binding sites we detected were as follows; 12.7 ± 1.47 × 103 receptors per cell with a KD of 3.02 ± 0.62nmol/L in patients with GIG, 7.26 ± 0.45 × 103 receptors per cell with a KD of 3.03 ± 0.56nmol/L in the control group. The statistical difference of receptors per cell is significant between two groups (p < 0.05), patients with GIG having more GR binding sites, while the difference of Kd is not significant ( p > 0.05 ) . Conclusion: The preliminary findings suggest that patients with GIG are more sensitive to glucocorticoid and the increase of binding sites of GR     

The Comparison Study of Renin and Angiotensin AⅡ Levels on Normal Tension Glaucoma Patients and Normal Individuals

Purpose: To investigate the levels of renin-angiotension system (RAS) components in normal tension glaucoma patients and normal controls. Methods: Blood samples were obtained from 11 normal tension glaucoma(NTG)patients and 11 age and sex matched controls. The levels of renin and angiotensin AⅡof 11 NTG patients and normal controls were examined by radio-immunity test. Statistical analyses were performed by paired t test. Results:The levels of renin of NTG patients and normal controls are (769.085±183.217) pg/ml/n and (822.035 ±124.140) pg/ml/n, while the levels of angiotensin A Ⅱof NTG patients and normal controls are (37.347±10.669)pg/ml and (24.836±10.665)pg/ml respectively. No statistically significant differences were observed between the levels of renin and angiotensin among NTG patients and normal controls. Conclusion: There were not many abnormalities of the levels of circulating rennin and angiotensin AⅡof NTG patients in our study. Eye Science 2005 ;21 :192-195.     

Relationship of MMP-2 and TGF-β2 levels in human vitreous with axial length

AIM: To investigate the relationship of matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 2 (TGF-β2) levels in human vitreous with axial length (AL) of patients with high myopia. METHODS: The concentrations of MMP-2 and TGF-β2 levels were tested by enzyme-linked immunosorbnent assay (ELISA). Fifty-five human vitreous samples of 55 patients were collected during vitrectomy surgery, and were divided into two groups according to their spherical equivalent (SE) and AL. High myopia group (25 cases): AL≥26.00 mm, and control group or non-high myopia group (30 cases): AL<26.00 mm. RESULTS: The MMP-2 levels in vitreous of high myopia group (96.87±55.95 ng/mL) was significantly higher than that of control group (77.24±41.81 ng/mL, P<0.05), but not correlated with AL (r=0.088, P=0.544). While the vitreous TGF-β2 concentration was negatively correlated with AL (r=-0.344, P=0.014), and there was significant difference of TGF-β2 vitreous levels between high myopia group (3729.08±1890.88 pg/mL) and control group (3926.00± 1333.88 pg/mL, P<0.05). CONCLUSION: MMP-2 and TGF-β2 in human vitreous may play a critical role in human high myopia development, and the TGF-β2 appears to be associated with AL.     

Relationship of MMP-2 or TGF-β2 levels in human vitreous with axial length

目的:探究高度近视患者眼轴与玻璃体中MMP-2和TGF-β2水平的相关性.方法:研究患者玻璃体切除术中获取玻璃体样本55份.依据角膜表面曲率大小及眼轴长度,将研究对象分为两组:即高度近视组(25例):SE>-6.00D,AL≥26.00mm和对照组或非高度近视组(30例):SE<-6.00D,AL<26.00mm.利用ELISA的方法测量研究对象玻璃体MMP-2和TGF-β2浓度.结果:高度近视组玻璃体MMP-2浓度(96.87±55.95ng/mL)显著高于对照组(77.24±41.81ng/mL,P<0.05),但与眼轴没有相关性(r=0.088,P=0.544).高度近视组(3729.08±1890.88pg/mL)与对照组(3926.00±1333.88pg/mL,P<0.05)TGF-β2浓度具有显著差异性,且TGF-β2浓度与眼轴长度呈负相关(r=-0.344,P=0.014).结论:人玻璃体中MMP-2和TGF-β2两种分子浓度在高度近视进展中具有重要作用,TGF-β2浓度与眼轴长度具有相关性.     

Epidemiology of Glaucoma in Asia-Pacific

Primary open angle glaucoma is the second most important cause of permanent blindness in the Asia Pacific region. Thus it is very important to identify epidemiological and other risk factore which are associated with open angle glaucoma. The risk for glaucoma optic nerve damage increases with the age and with the level of the intraocular pressure. In this paper, I will highlight our study of several risk factors for development of the open angle glaucoma like (1) elevated intraocular pressure, (2) myopia, (3) suspicious large optic disc cup, (4) cupping with disc haemorrhages and (5) nerve fibre defect. The general and systemic conditions which are implicated as risk factore are (1)family history of glaucoma, (2)increase in age, (3)diabetes mellitus, (4) cardio vascular conditions like central retinal vein occlusion etc. (5) the endocrine disorders with increased thyroid and increased cortico steroids responsiveness in patients with glaucoma will be discussed.     

The role of mechanical stretch and TGF-β2 in epithelial-mesenchymal transition of retinal pigment epithelial cells

AIM: To explore the effects and mechanisms of mechanical stress and transforming growth factor-beta2 (TGF-β2) on epithelial-mesenchymal transition (EMT) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Human RPE cells were inoculated on BioFex 6-well plates and RPE cells received 0, 1, 2, 3, or 4 mild stretch injuries delivered 3h apart after 24h of culture. The device of mechanical stress parameters were set to sine wave, frequency 1 Hz, stretch strength 20%. For treatment with TGF-β2, when the inoculated RPE cells in 6-well plates were around 60% con?uent, serum was reduced to 0 for 12h and recombinant human TGF-β2 (0, 1, 5, 10 ng/mL) was added for 48h. α-SMA, Vimentin and N-Cadherin, fibronectin proteins expressions were detected by Western blotting, confocal cell immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). Then we detected the change of miRNA-29b and ascertained the changes of phosphatidylinositol 3-kinase-serine threonine protein kinase (PI3K/Akt) pathway after RPE cells were stretched by the device of mechanical stress and induced by TGF-β2 by Western blotting, confocal cell immunofluorescence and qRT-PCR. RESULTS: Mechanical stress induce EMT and activate the PI3K/Akt pathway in ways that lead to the EMT process. TGF-β2 induce RPE cells EMT and in a certain range and TGF-β2 decrease the miRNA-29b expression in RPE cells, and the inhibitory effect is more obvious with the increase of TGF-β2 concentration. CONCLUSION: Our findings are crucial steps in determining the critical roles of the PI3K/Akt signaling pathway and miRNA-29b in pathogenesis of proliferative vitreoretinopathy (PVR) which may be a potential target for preventing or treating PVR.     

Hemodynamics of Ophthalmic Artery and Central Retinal Artery and Correlation with Other Factors in Patients with Primary Open Angle Glaucoma

Objective : To investigate the hemodynamics of ophthalmic artery (OA) and central retinal artery (CRA) in patients with primary open angle glaucoma(POAG) and analyse the correlation between hemodynamics of OA and CRA and other factors.Methods:The hemodynamics of OA and CRA in normal persons (102 eyes) and glaucoma-tous patients (102 eyes) were measured by Colour Doppler Image (GDI). The linear correlation analysis was made between OA and CRA about each of the following parameters: the peak systolic flow velocity (Vmax), the end diastolic velocity (Vmin). The multiple step-wise regression analysis was taken to investigate the correlation between each of the following hemodynamics of OA and CRA; Vmax and Vmin in 74 eyes with POAG and each of the following related factors in hemorrheology; whole blood apparent viscosity at low, medium and high shear rate, plasma viscosity and hematocrit. The multiple linear regression was applied to investigate the correlation between each of the following hemodynamics of     

Long-term treatment with Pilogel/β-blocker in glaucoma patients

In a multicentre clinical trial thirteen patients with primary open angle glaucoma or ocular hypertension were followed during at least six months while selfinstilling Pilogel (once daily) and topical -blocker (twice daily). After six months of combination therapy there was an average decrease in intra-ocular pressure (IOP) of 33.6% 9.5 hours after Pilogel administration and an IOP decrease of 23.4% 22.5 hours after Pilogel administration. With topical -blocker alone, an average IOP decrease of 15% was measured. Throughout the study we observed in six patients (46.1%) a superficial punctate keratitis which mostly spontaneously cleared. We did not see any serious side-effects after six months of combination therapy.     

Effects of β-agonists on b- and c-waves implicit for adrenergic mechanisms in cat retina

Nylidrin (buphenine) is a -adrenergic agonist known to dilate peripheral vessels and used therapeutically in retinal degeneration and glaucoma. We studied retinal function under -agonists in arterially perfused cat eyes and observed a dose-dependent, reversible increase in b-wave amplitude and a decrease in c-wave amplitude in concentrations from 4.5 to 120M. A half maximal response was obtained at 40 to 50M. The optic nerve response to light showed dose-dependent reversible changes under nylidrin. Standing potential, light peak, intraocular pressure, vascular resistance, and diameter of or retinal vessels showed no consistent changes under nylidrin.The effects were inhibited by each of the -blocking agents propranolol, ICI 118, and oxprenolol (in sequence of decreasing potency).Another potent ₂-agonist, clenbuterol, was used to determine the extent to which the responses to nylidrin were due to -receptor-mediated action. Clenbuterol had similar effects on the b-wave and optic nerve response at slightly higher concentrations (30–200 M) but more variable effects on the c-wave.The data are interpreted as functional evidence that -adrenergic mechanisms are involved in retinal signal processing. This concept is corroborated by identification of -adrenergic binding sites in cat retina (Bruinink et al., 1986).     

Influence of topical and systemic β-blockers on tear production

Summary The influence of varous -blockers on tear production in rabbits was studied by means of direct cannulation of the lacrimal gland excretory duct. Tear production was significantly decreased (p<0,001) after systemic (I.M.) administration of either selective ¹-blockers (metoprolol, betaxolol), B₂-selective (butoxamine) or non-selective ones (timolol, propranolol) or finally those with I.S.A. (oxprenolol), although differences in the size of tear production decreasing response of each -blocker were recorded.Bilateral topical application of timolol (50 l of 0,5% b.i.d. for three days), decreased also tear production significantly, while the response of betaxolol administered under the same regime was rather negligible.It is concluded that although ²-blockers adrenergic receptors are mainly involved in tear production, the administration of selective ¹-blockers in high doses disappears their selectivity, decreasing tear production too.     

The distribution of (-)-propranolol in the isolated rabbit iris

It has been postulated that propranolol lowers the intraocular pressure by adrenergic neurone block. However, in the isolated iris of albino rabbits, there was only a small degree of cocaine-sensitive (i.e., neuronal) accumulation of ³H-(-)-propranolol, and none at all after pretreatment of the animals with reserpine. Moreover, after preloading of the iris with ³H-(-)-propranolol, veratridine failed to release any labelled material. Hence, any adrenergic neurone blocking action of propranolol is highly unlikely.Albino and pigmented irides were first exposed to ³H-(-)-propranolol and then washed out. The results and their compartmental analysis indicated an extensive binding of ³H-(-)-propranolol in or at pigment cells; the binding is characterized by a low dissociation constant. It is very likely that the initial binding and the subsequent slow dissociation from pigment cells explains the long duration of action of beta-adrenoceptor antagonists in human therapy.     

Intraokulare Injektion von Bevacizumab – Eine mögliche Therapie der sekundären CNV bei „angioid streaks“

Zusammenfassung Angioid streaks sind die ophthalmologische Manifestation bei Pseudoxanthoma elasticum, einer erblichen Systemerkrankung. Sternförmig von der Papille ausgehende gefäßähnliche streifige Läsionen auf der Ebene des retinalen Pigmentepithels und der Bruch-Membran kennzeichnen das typische klinische Bild. Für oft erhebliche Sehminderungen sind sekundäre chorioidale Neovaskularisationen verantwortlich. Eine erfolgreiche Behandlung dieser Neovaskularisationen ist bisher nicht bekannt. Die Argonlasertherapie extrafoveolärer Membranen zeigte eine hohe Rezidivrate mit zentropedaler Ausrichtung. Auch die PDT mit Verteporfin brachte allein und in Kombination mit intravitrealer Applikation von Triamcinolon nicht die erhoffte Wirksamkeit wie sie bei der altersabhängigen Makuladegeneration (AMD) erwartet werden kann. Nach dem Einzug der Angiogenesehemmer (Bevacizumab, Ranibizumab, Pegaptanib) in die Therapie von chorioidalen Neovaskularisationen bei der AMD stellte sich für uns die Frage, ob diese Substanzen ähnliche Wirkungen bei sekundären chorioidalen Neovaskularisationen erzielen könnten. In dem hier vorgestellten Fall konnte nach erfolgloser Behandlung mit Verteporfin mit fortschreitender Visusminderung und persistierender Leckage der CNV durch die intravitreale Applikation von Bevacizumab ein morphologisch und funktionell gutes Ergebnis erzielt werden. Zu Evaluierung dieser Therapie sind weitere Ergebnisse dringend notwendig.     

Switch to Latanoprost Monotherapy from Combined Treatment with β-Antagonist and Other Antiglaucoma Agents in Patients with Glaucoma or Ocular Hypertension

Purpose To investigate the effects on intraocular pressure (IOP) and the occurrence of adverse events upon switching directly to latanoprost monotherapy from multiple drug therapy, including a -antagonist, for glaucomatous eyes.Methods Patients with primary open-angle glaucoma or ocular hypertension and receiving long-term therapy with two or three topical ocular hypotensive drugs (including one topical -antagonist) were switched to latanoprost monotherapy for 12 weeks without any intervening washout period. Observations were performed before switching (baseline) and at weeks 4, 8, and 12 after switching to latanoprost monotherapy.Results Of the 29 enrolled patients, 26 (90%) completed this protocol. Three patients had excessive IOP elevation, and these patients were withdrawn. The switch to latanoprost monotherapy was followed by a significant (P < 0.0001) mean reduction of 3.9mmHg at week 12 in per-protocol cases (n = 26) and a significant (P = 0.0016) mean reduction of 2.8mmHg at last postswitch visit in patients in the intent-to-treat analysis group (n = 29). Adverse ocular events other than IOP elevation were mild.Conclusions The switch to latanoprost monotherapy in glaucoma patients receiving multiple drug therapy resulted in an additional, significant IOP reduction. Jpn J Ophthalmol 2004;48:276–280 © Japanese Ophthalmological Society 2004     

Vitreous Fluid Levels of β-Amyloid(1–42) and Tau in Patients with Retinal Diseases

Purpose A decrease in -amyloid_1–42 (A42) and an increase in tau in the cerebrospinal fluid are reported to be characteristic phenomena in Alzheimers disease patients. To test the idea that A42 and tau contribute to the development of retinal diseases, we measured A42 and tau concentrations in the vitreous fluid from patients with macular hole (n = 13), diabetic retinopathy (n = 15), or glaucoma concurrent with other ocular diseases (n = 8).Methods Vitreous samples were collected from patients who underwent vitrectomy, and sensitive and specific enzyme-linked immunosorbent assays were used to determine the concentrations of A42 and tau.Results By comparison with the levels in the control macular-hole patients (33.9 ± 7.1pg/ml for A42; 3.3 ± 3.2pg/ml for tau), there was a significant decrease in the A42 level and a significant increase in the tau level in patients with diabetic retinopathy (1.8 ± 1.9pg/ml for A42, P = 0.002; 153.7 ± 71.6pg/ml for tau, P = 0.041) or glaucoma concurrent with other ocular diseases (2.8 ± 1.8pg/ml for A42, P = 0.006; 113.6 ± 43.1pg/ml for tau, P = 0.023).Conclusions Our findings indicate the possibility of a role for A42 and tau in the pathogenesis of some retinal diseases. Jpn J Ophthalmol 2005;49:106–108 © Japanese Ophthalmological Society 2005     

Efficacy and safety of the combination therapy Pilogel®/β-blocker: Interim results

The interim results of a multicentered clinical trial with the combination therapy Pilogel^®/topical -blocker (twice daily) in patients with primary open angle glaucoma or ocular hypertension are discussed. Six patients were treated with Pilogel^® and a topical -blocker for one month. Four out of six patients responded well to the combination therapy. Most patients experienced some difficulty in applying the gel and their eyelids stuck together on awakening. In two patients a superficial punctate keratitis was observed. We found an average decrease in intra-ocular pressure (IOP) of 22.5% 22.5 hours after Pilogel^® administration, but there was some tendency towards higher evening values compared to morning values. In view of the appearance of a corneal haze as described by Johnson et al. during long-term treatment, longer follow-up is necessary.     

The effect of β-blocker on ERG c-wave of the rabbit

The toxicity of -blocker, Befunolol HCl (BFE), to the retinal pigment epithelium was investigated electrophysiologically. Rabbit in vivo ERG b- and c-waves were recorded after intravitreal injections of 0.1 ml of 0.25, 1, 2, 4, 6 and 10% BFE solutions with osmolalities of 304, 340, 383, 432, 493 and 618 mOsm repsectively. Phosphate solutions with osmotic pressure corresponding to the BFE solutions were injected as control.In eyes injected with 0.25% BFE, amplitude of either b- and c-waves were unchanged for 60 min, while in eyes injected with BFE with a higher concentration than 1%, the b-waves attenuated but the c-waves enhanced in proportion to the BFE concentrations.In the control group, the b-waves attenuated and the c-waves enhanced by the injection of the high osmotic phosphate solutions up to 500 mOsm, which corresponded to the osmotic pressure of 6% BFE, but attenuated by the phosphate solutions higher than 600 mOsm.Based on the above result, no acute toxicity of BFE to the retina was suggested in dose of its therapeutic use. The attenuation of b-waves by BFE was likely due to the influence of osmotic pressure since no significant difference in the b-waves amplitudes was found between BFE and equimolar phosphate solutions. However, high concentration of BFE itself was suggested to exhibit an effect to enhance the c-wave because a manifest difference was observed in the c-wave amplitudes between the group at higher BFE concentrations and the correspond control group.