Central retinal vein occlusion: natural history, associated medical conditions and treatment.
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Biomedical subjects
Publications and source records attributed to E M Kohner.
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The effects of treatment by argon laser and xenon arc photocoagulation in 165 diabetic patients with optic disc new vessel formation have been studied retrospectively. Visual acuity and degree of new vessel formation have been assessed over a period of between six months and seven years of follow-up (mean 23 months). Visual acuity improved in 36% of treated eyes and remained unchanged in 34%. Improvement was most marked in those with initially poor acuity (less than 6/36). There was no association between improvement in visual acuity and regression of disc vessels, the latter occurring in 79% of treated eyes. Only 6% of eyes became blind during the period of follow-up, principally as a result of vitreous haemorrhage and retinal detachment. There was no difference between the results produced by the use of separate or combined argon laser and xenon arc photocoagulation on the regression of disc new vessels. However, our results suggest that argon laser treatment was more effective than xenon arc photocoagulation in improving visual acuity. These findings suggest that either form of treatment or a combination offers considerable benefit in the management of proliferative diabetic retinopathy, even when very severe at presentation.
Two aspects of endothelial cell function were examined in two matched groups of male insulin-dependent diabetics, six with background retinopathy and seven without retinopathy. Leakage of fluorescein from the retinal capillaries was estimated by vitreous fluorophotometry. In addition, factors VIII/von Willebrand (vWF) and VIII-related antigen (VIII-RAG), which are synthesized by the endothelial cells, were measured, together with VIII-antihaemophilic factor (VIII-AHF). The patients without retinopathy had normal leakage of fluorescein in the macula (mean +/- SEM: 1.10 +/- 0.10 g X 10(-8)/ml) and the posterior vitreous (0.45 +/- 0.11 g X 10(-8)/ml), and normal circulating levels of vWF (123% of a normal reference plasma +/- 18%), VIII-RAG (137 +/- 14%) and VIII-AHF (112 +/- 18%). In contrast, the patients with background retinopathy showed higher leakage of fluorescein in the macula (6.34 +/- 1.74 g X 10(-8)/ml; p less than 0.01), and the posterior vitreous (3.09 +/- 0.94 g X 10(-8)/ml; p less than 0.02), as well as increased levels of vWF (177 +/- 16%; p less than 0.05). There was a trend towards increased VIII-RAG (195 +/- 24%; p less than 0.1), but not VIII-AHF (126 +/- 13%). Alterations of endothelial cell function thus accompany the development of retinopathy. It cannot be said from the present study whether these alterations also precede the appearance of retinopathy.
Factor VIII/von Willebrand factor (vWF) could play a role in the pathogenesis of diabetic microangiopathy. It has been suggested that its biologic activity is controlled by hormonal and metabolic mechanisms. To verify this hypothesis, vWF was monitored over a 24 hr period in 9 insulin treated patients with diabetic retinopathy, together with factor VIII-related antigen (VIII-RAG), plasma glucose, growth hormone (GH) and prolactin. vWF levels oscillated during the 24 hr, the mean values being higher during the day than at night-time, p less than 0.01. Compared to a group of normal controls in whom blood samples were taken randomly between 9.00 and 13.00, the levels of vWF were significantly increased at 11.00, p less than 0.02, and at 13.00, p less than 0.02, but at no other time. VIII-RAG values were also higher during the day than at night-time, p less than 0.01. The mean 24 hr levels of vWF correlated with those of VIII-RAG, p less than 0.01, with the age of the patients, p less than 0.01, and with the duration of disease, p less than 0.01. The levels of plasma glucose were higher during the day, while GH and prolactin rose at night-time. No correlations were found between vWF or VIII-RAG and plasma glucose, GH or prolactin, nor between the mean 24 hr levels of all these parameters and ponderal index, daily insulin dose, degree of metabolic control, severity of retinopathy. Insulin treated diabetics with microangiopathy show circadian variations in their plasma concentrations of vWF and VIII-RAG which should be taken into account when measuring these factors for clinical or research purposes.
Plasma levels of 6-oxo-PGF1 alpha, the hydrolysis product of prostacyclin, were significantly reduced in men with proliferative diabetic retinopathy, compared with normal controls. Male diabetics with background or no retinopathy formed an intermediate group with plasma levels of 6-oxo-PGF1 alpha lower than controls and higher than patients with proliferative retinopathy. Forearm ischaemia increased plasma levels of 6-oxo-PGF1 alpha by 30% in normal subjects. The increase occurred during arterial occlusion and was diminished by pretreatment with aspirin. The increase after ischaemia may reflect increased prostacyclin production. In diabetic patients forearm ischaemia produced an increase in plasma 6-oxo-PGF1 alpha similar to that seen in control subjects.
We report the case history of a 20-year-old diabetic girl with long-standing poorly controlled disease who presented with severe retinopathic features and who was treated with continuous subcutaneous insulin infusion (CSII). When first seen she had macular oedema and a visual acuity of 6/18 in her only eye, together with multiple blot haemorrhages and intraretinal microvascular abnormalities. Marked reversal of the retinal lesions occurred within 65 days of initiating SCII and after only 36 days of constant normoglycaemia. Subsequent good blood glucose control on conventional subcutaneous insulin injections has been achieved, and the retinopathy remains quiescent with a visual acuity of 6/5. We suggest that CSII may be a potentially useful method of arresting and reversing early diabetic retinopathy.
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Serum prolactin and growth hormone levels were measured hourly over 24 h in 8 insulin-treated diabetic males, 4 of whom were impotent. All patients showed normal sleep-related peaks of both hormones during the night. The mean 24-hour concentrations of prolactin and growth hormone were similar in patients with impotence (9.4 +/- 1.0 ng/ml and 3.8 +/- 0.4 microIU/ml, respectively) and without it (10.5 +/- 1.0 ng/ml and 4.7 +/- 1.1 microIU/ml, respectively). The mean prolactin and growth hormone concentration during the day time (7.00 a.m. to 7.00 p.m.) and the night time (7.00 p.m. to 7.00 a.m.) were also similar in patients with and without impotence. These results suggest that impotence in diabetic patients is not mediated by abnormalities of prolactin and growth hormone secretion.
In a group of long-standing diabetics low shear blood viscosity was increased compared with matched non-diabetic controls, being highest in patients with vascular and microvascular complications. Plasma viscosity was also elevated in the diabetics. Conclusions about erythrocyte deformability depended critically on the methodology used. With filtration, red cell deformability was impaired in the diabetic, with centrifugation, diabetic cells were more deformable whilst there was no differences between diabetic and normal red cells by the method of viscometry of packed red cells. The effect of poor metabolic control on blood rheology was investigated in patients recovering from diabetic ketoacidosis and in newly diagnosed maturity onset diabetics being treated at the clinic with diet alone. In both groups, the initially high levels of blood viscosity fell toward normal with improved metabolic control. It is concluded that multiple rheological abnormalities are present in diabetics and appear to be influenced by the metabolic state of the patient. The relationships between these complex changes and the development of microangiopathy remain to be elucidated.
Abnormalities of platelet function may be related to the pathogenesis of diabetic retinopathy. A method for the in vitro assessment of platelet shape change (PSC), as induced by ADP in calcium-deprived platelet-rich plasma, is presented. The outcome of this test is dependent on the concentrations of ADP and of the chelating agent used. Studies in electron microscopy shoed that the parameter measured is not related to the disappearance of spiny-spherical forms. The values measured for PSC were significantly increased in a group of diabetic subjects, when compared to normal controls. In particular, patients with proliferative retinopathy showed more profound alterations of the PSC. No relations were found between the PSC values and ADP induced platelet aggregation, the plasma levels of von Willebrand factor and of factor VIII-related antigen.
Vitreous fluorophotometry is as yet in its early phase of development, where probably many of the readings obtained represent artefacts. It is, however, a potentially exciting and useful clinical research tool which may indicate early changes in blood-retinal barrier function and which enables studies of fluid dynamics in the eye. Before it can be used extensively, more work on the development of reliable, uniformly acceptable equipment is necessary.
The relationship between the development of microangiopathy and the degree of diabetic control was investigated in 61 noninsulin-dependent diabetics after 5-10 years of known duration of diabetes. The degree of diabetic control was assessed by fasting blood glucose (FBG) at the last assessment, haemoglobin A1 (HbA1) and by the mean of all the fasting blood glucose values throughout the follow up (MWFBG). The 29 patients who developed microangiopathy had higher FBG at last assessment (10.1 +/- 0.6 vs 8.2 +/- 0.5 mmol/l, p less than 0.02), HbA1 (13.4 +/- 0.8 vs 11.0 +/- 0.6%, p less than 0.02) and MWFBG (8.0 +/- 0.4 vs 7.5 +/- 0.4 mmol/l, p less than 0.05) than those without microangiopathy. The FBG values at each year of the follow-up were higher in the microangiopathy group. HbA1 determined in 1979 correlated with the mean FBG values of each one of the years 1975-1978 (r = 0.575, r = 0.646, r = 0.657, r = 0.631, p less than 0.001, respectively). These data support the hypothesis that in noninsulin-dependent diabetics the development of microangiopathy is related to the degree of diabetic control.
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In vitro platelet aggregation has been studied in 29 normal subjects and 35 diabetic patients with retinopathy by conventional aggregating agents and by a new technique which evaluates the platelet shape change. --Plate shape change, expressed as % light transmission variation induced by the addition of ADP (10 mumol/l) in calcium-deprived platelet rich plasma, was determined. Significant differences were found between the controls (12.6 +/- 0.7%) and the 35 diabetics (15.6 +/- 1.0%, p less than 0.02) and between controls and the subgroup of patients with proliferative retinopathy (17.3 +/- 1.1%, n = 15, p less than 0.001). Platelet aggregation induced by ADP, collagen and ristocetin did not show significant differences between normal and diabetic subjects. --The shape change is the physiological early phase of platelet aggregation and is related to energy requiring mechanisms. As yet unexplored metabolic abnormalities at this stage could account for previously described platelet abnormalities in diabetes.
Pathological changes in the optic disc and anterior part of the optic nerve of monkeys were studied 5 hours and several days after occlusion of the temporal short posterior ciliary arteries. Ischaemic vacuolation of neural tissue was observed in some of the animals studied and was restricted to the lamina cribrosa and the immediately retrolaminar portion of the optic nerve. Axonal swelling and organelle aggregation were demonstrated in the prelaminar region, and autoradiography after intravitreal injection of tritiated leucine revealed an associated obstruction of rapid and slow orthograde axoplasmic transport. The experimental findings correlate with those seen clinically in acute ischaemic optic neuropathy. The pale swelling of the optic disc in this condition represents an accumulation of axoplasmic debris in retinal ganglion-cell axons owing to obstruction of axoplasmic transport at the lamina cribrosa; it is thus equivalent to a 'cotton-wool spot' of the disc.
The capillary abnormalities of diabetes include both dilatation and occlusion. Occlusion is the more important, as vision-threatening lesions are secondary to capillary occlusion. Capillary occlusion could result from abnormalities of blood coagulation and from endothelial cell disease. Evidence is presented of the predominant role of endothelial disease--abnormal coagulation is probably secondary. While there is no known treatment which can reliably prevent or reverse capillary changes, approaches by antiplatelet agents and normalization of blood sugar are possible methods.
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