Hypoxic viscosity and diabetic retinopathy.

Diabetic and sickle retinopathy have features in common--for example, venous dilatation, microaneurysms, and capillary closure preceding neovascularisation. Bearing in mind that haemoglobin in poorly controlled diabetes is abnormal and that extremely low oxygen tensions (known to cause sickling) exist in the healthy cat retina, we wished to explore the possibility that diabetic blood, like that of sickle cell disease, may become more viscous when deoxygenated. To do this we measured whole blood viscosity, under oxygenated and deoxygenated conditions, of 23 normal persons, 23 diabetic patients without retinopathy, and 34 diabetic patients with retinopathy. The shear rate used was 230 s-1, which is similar to that thought to prevail in the major retinal veins. The viscosity of blood from normal persons, corrected for packed cell volume, did not change significantly on deoxygenation: mean 4.54 (SD 0.38) cps, versus, 4.57 (0.39) paired t test, p = 0.66. Similarly the blood from diabetics without retinopathy showed no change: 4.42 (0.45) versus 4.42 (0.30), p = 0.98; whereas the blood from patients with retinopathy changed from 4.82 (0.48) to 4.95 (0.63), p = 0.027. The hypoxic viscosity ratio (deoxygenated divided by oxygenated viscosity) correlated with total serum cholesterol (r = 0.44, p = 0.018) but not with HbA1, serum glucose, triglycerides, or age. A disproportionate increase in venous viscosity relative to arterial viscosity would lead to increased intraluminal and transmural pressure and therefore exacerbate leakage across capillary walls.     

高海拔地区非颞动脉炎性前部缺血性视神经病变的病因与临床研究

目的:探讨高海拔地区非颞动脉炎性前部缺血性视神经病变(non-arteritic anterior ischemic optic neuropathy,NAION)的发病因素与临床的相关研究。方法:将2011-03/2012-09来我科门诊就诊,并确诊为NAION的住院患者纳为病例组。并将同一时期来我院参加门诊体检并与病例组年龄、性别相匹配的人群作为对照组。将纳入对象的个人资料进行详细登记和详尽的眼科检查,并进行血压监测及血常规、血脂、血糖、血液流变等化验检查,并将观察指标详细记录。结果:病例组与对照组之间总胆固醇、HDL-脂蛋白、血常规无统计学差异(P>0.05),而甘油三脂、血糖、血压有统计学差异(P<0.05),NAION组较高。全血黏度高切、血浆黏度、全血还原黏度中切、红细胞变形指数、血沉、血沉方程K值二组之间无统计学差异(P>0.05),而全血黏度中低切、红细胞压积、全血还原黏度高低切、红细胞聚集指数有统计学差异(P<0.05),NAION组较高。结论:高海拔地区NAION的发病因素不是单一的,是多因素相互作用的结果。高海拔低压低氧等环境条件下,NAION的发病与人体微循环发生的一系列病理生理变化相关。甘油三脂、血压、血糖对高海拔地区NAION的发生具有统计学差异(P<0.05)。高血黏度是高海拔地区NAION发生的危险因素。应加强高海拔地区人群对NAION的健康教育,提高其对NAION防治的认识。     

Hemodynamic processes in eye models with different levels of intraocular pressure

Intraocular pressure effects on blood flow volumic rate in an eye model were examined in various arterial pressure levels and perfused liquid viscosity values. The findings evidence an exponential relationship between intraocular pressure elevation and blood flow volumic rate reduction. Hypotensive drugs should be prescribed with care to glaucoma patients, with the blood viscosity values monitored.     

原发性开角型青光眼眼底荧光血管造影与血液粘度及其它因素的关系

探讨原发性开角型青光眼眼底荧光血管造影与血液粘度及其它因素的关系。方法将１２２只原发性开角型青光眼的眼底荧光血管造影（ｆｕｎｄｕｓｆｌｕｏｒｅｓｃｅｉｎａｎｇｉｏｇｒａｐｈｙ，ＦＦＡ）的臂－脉络膜充盈时间〔ａｒｍ－ｃｈｏｒｏｉｄｆｉｌｌｉｎｇｔｉｍｅ，Ａ－ＣＴ）、臂－视网膜动脉充盈时间（ａｒｍ－ｒｅｔｉｎａｌａｒｔｅｒｙｆｉｌｌｉｎｇｔｉｍｅ，Ａ－ＡＴ）和视网膜动－静脉充盈时间（ｒｅｔｉｎａｌａｒｔｅｒｙ－ｖｅｎｏｕｓｆｉｌｌｉｎｇｔｉｍｅ，Ａ－ＶＴ）与高、中和低切变率下全血表观粘度、血浆粘度及红细胞压积进行逐步回归分析，将７０只眼ＦＦＡ的Ａ－ＡＴ、Ａ－ＶＴ与收缩压、舒张压、年龄和低切变率下全血表现粘度进行逐步回归分析。结果低切变率下全血表观粘度可明显影响Ａ－ＣＴ和Ａ－ＡＴ，而红细胞压积可明显影响Ａ－ＶＴ。低切变率下全血表现粘度和年龄均可影响Ａ－ＡＴ和Ａ－ＶＴ，尤以低切变率下全血表观粘度影响为大。结论血液粘度可明显影响原发性开角型青光眼ＦＦＡ各循环时间。     

Physiology of vitreous surgery

Vitreous surgery has various physiological and clinical consequences, both beneficial and harmful. Vitrectomy reduces the risk of retinal neovascularization, while increasing the risk of iris neovascularization, reduces macular edema and stimulates cataract formation. These clinical consequences may be understood with the help of classical laws of physics and physiology. The laws of Fick, Stokes-Einstein and Hagen-Poiseuille state that molecular transport by diffusion or convection is inversely related to the viscosity of the medium. When the vitreous gel is replaced with less viscous saline, the transport of all molecules, including oxygen and cytokines, is facilitated. Oxygen transport to ischemic retinal areas is improved, as is clearance of VEGF and other cytokines from these areas, thus reducing edema and neovascularization. At the same time, oxygen is transported faster down a concentration gradient from the anterior to the posterior segment, while VEGF moves in the opposite direction, making the anterior segment less oxygenated and with more VEGF, stimulating iris neovascularization. Silicone oil is the exception that proves the rule: it is more viscous than vitreous humour, re-establishes the transport barrier to oxygen and VEGF, and reduces the risk for iris neovascularization in the vitrectomized-lentectomized eye. Modern vitreous surgery involves a variety of treatment options in addition to vitrectomy itself, such as photocoagulation, anti-VEGF drugs, intravitreal steroids and release of vitreoretinal traction. A full understanding of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and improves retinal hemodynamics. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and the permeability effect of VEGF reduced with corticosteroids. Starling’s law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains the effect of VEGF-induced vascular permeability changes on plasma protein leakage and the osmotic gradient between vessel and tissue. At the same time, it takes into account hemodynamic changes that affect the hydrostatic gradient. This includes the influence of arterial blood pressure, and the effect oxygen (laser treatment) has in constricting retinal arterioles, increasing their resistance, and thus reducing the hydrostatic pressure in the microcirculation. Reduced capillary hydrostatic pressure and increased osmotic gradient reduce water fluxes from vessel to tissue and reduce edema. Finally, Newton’s third law explains that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient between vessel and tissue, and stimulates water fluxes from vessel into tissue, leading to edema.     

Blood viscosity in ocular hypertension

Blood viscosity and its determinants were measured in 27 patients with primary open-angle glaucoma, 15 patients with ocular hypertension and 18 healthy control subjects matched for sex, blood pressure and smoking habits. The mean blood viscosity value was significantly higher in the glaucoma group than in the two other groups at all three shear rates studied; there was no difference in viscosity between the hypertension group and the control group. The mean hematocrit value was significantly lower in the hypertension group than in the two other groups. The results suggest that blood viscosity may contribute to nerve damage in patients with primary open-angle glaucoma. The low hematocrit observed in the patients with ocular hypertension may, by contributing to low viscosity, in some measure protect this group from optic nerve damage.     

Optic nerve oxygenation

The oxygen tension of the optic nerve is regulated by the intraocular pressure and systemic blood pressure, the resistance in the blood vessels and oxygen consumption of the tissue. The oxygen tension is autoregulated and moderate changes in intraocular pressure or blood pressure do not affect the optic nerve oxygen tension. If the intraocular pressure is increased above 40 mmHg or the ocular perfusion pressure decreased below 50 mmHg the autoregulation is overwhelmed and the optic nerve becomes hypoxic. A disturbance in oxidative metabolism in the cytochromes of the optic nerve can be seen at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen tension. Lowering the intraocular pressure tends to increase the optic nerve oxygen tension, even though this effect may be masked by the autoregulation when the optic nerve oxygen tension and perfusion pressure is in the normal range. Carbonic anhydrase inhibitors increase the optic nerve oxygen tension through a mechanism of vasodilatation and lowering of the intraocular pressure. Carbonic anhydrase inhibition reduces the removal of CO2 from the tissue and the CO2 accumulation induces vasodilatation resulting in increased blood flow and improved oxygen supply. This effect is inhibited by the cyclo-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical trials and needed to test this hypotheses.     

Measurement and manipulation of the partial pressure of oxygen in the rat anterior chamber

PURPOSE: To measure the partial pressure of oxygen in the anterior chamber of the rat eye under a variety of physiological conditions. METHODS: Polarographic oxygen electrode measurements were made in methoxyflurane-anesthetized Wistar or Sprague-Dawley rats. After ketamine-xylazine or pentobarbital induction, animals were artificially ventilated with a variety of gas mixtures; gases were directed over the corneal surface during measurement of the partial pressure of oxygen in the middle of the pupil at the surface of the lens. RESULTS: The partial pressure of oxygen in the anterior chamber of the rat eye was measured as 63 +/- 9 mm Hg (mean +/- S.D. ). Breathing 100% oxygen and delivery of 100% oxygen to the cornea additively increased aqueous humor oxygen partial pressure to levels above 279 +/- 45 mm Hg with the greatest increase coming from inhaled 100% oxygen. Conversely, inhalation and subsequent transcorneal delivery of 10% oxygen reduced levels to 22 +/- 11 mm Hg. CONCLUSIONS: These results suggest that the partial pressure of oxygen in the anterior chamber is sensitive to the environment in contact with the cornea. In the rat eye, the delivery of oxygen to the anterior chamber via transcorneal diffusion may be more significant than for larger animals.     

Blood viscosity in primary open-angle glaucoma

To determine whether hemorrheologic factors play a part in optic nerve cupping and visual field loss in glaucoma, blood viscosity was measured at three shear rates in 27 patients with primary open-angle glaucoma and 18 healthy control subjects matched for sex, mean arterial blood pressure and smoking habits. The study was conducted between 1984 and 1986. The mean viscosity was significantly higher in the glaucoma group than in the control group at all three shear rates. The possible relevance of raised blood viscosity as a causal factor in optic nerve cupping in patients with glaucoma is discussed.     

Lenticular oxygen toxicity

PURPOSE: To investigate the possible toxic effect of oxygen on lenses in an organ culture. METHODS: Bovine lenses were exposed to four different combinations of ambient pressure and oxygen concentration in an organ culture throughout a 7-day period. Lens transparency, histology, enzymatic activities, and photomicrographs were compared in study and control groups. RESULTS: No differences were observed between study and control lenses in all measured parameters in a group subjected to a single exposure of 100% oxygen under increased (i.e., hyperbaric) ambient conditions and a group exposed repeatedly to high ambient pressure and normal oxygen partial pressure. Decreased lenticular transparency and enzymatic activities along with structural changes were observed in lenses exposed repeatedly to 100% oxygen concentration under both normal and increased ambient pressures. The observed changes were oxygen-load-dependent: the higher the oxygen partial pressure and the longer the time of exposure, the more severe the changes observed. Optical and structural changes in the lens occurred in a centripetal orientation: the greater the oxygen load, the more central the damage. CONCLUSIONS: High oxygen load has a toxic effect on bovine lenses in organ culture. These effects appear to be cumulative: the higher the oxygen partial pressure and the greater the number of exposures, the more severe the changes observed in the lenses. Changes marking toxicity follow the route of oxygen diffusion into the lens, from the periphery to the center. Cautious interpretation of the results may indicate a role of oxygen (and/or its derivatives) in human cataract formation.