Retinal Vessels In Patients Research Articles

Intact calibers of retinal vessels in patients with systemic sclerosis.

A primary endothelial cell dysfunction is thought to be involved in systemic sclerosis (SSc)-associated fibroproliferative vasculopathy of the microcirculation and small arterioles, even in sites not affected by fibrosis. Because the role of fibroblasts in pathologic modifications and vascular wall remodeling is relatively unclear, and because the retina provides a unique opportunity to assess microcirculation in the absence of resident fibroblasts, we systematically evaluated retinal vessels in patients with SSc. Digital retinal images were obtained from both eyes of 93 consecutive patients with fully characterized SSc and 29 healthy controls matched 1:1 for age and sex with selected patients without diabetes, hypertension history, or antihypertensive treatment. Internal microvascular calibers (erythrocyte column width in μm) by central retinal arteriolar and venular equivalents and arteriolar to venular ratio were measured using validated software. Arteriolar and venular calibers were similar in patients and their matched controls (mean ± SEM; 187 ± 2 vs 184 ± 3, p = 0.444, and 211 ± 2 vs 216 ± 3, p = 0.314, respectively). Both arteriolar and venular calibers and their ratio in patients with SSc were not associated with disease duration, extent of skin involvement, pulmonary fibrosis, digital ulcers or pitting scars, amputations, digital capillaroscopic findings, inflammatory indices, or autoantibodies. The evidence that retinal microcirculation is spared in SSc suggests that fibroproliferative vasculopathy may depend on specific cellular or soluble factors not present in the retinal environment.

Neuroimaging and clinical features of patients with optic nerve hypoplasia in Taiwan

PurposeTo investigate the clinical and neuroradiographic features of Chinese patients with optic nerve hypoplasia (ONH). MethodsThis was a retrospective case series study. The medical records and magnetic resonance imaging (MRI) studies of patients diagnosed with ONH from September 2001 to December 2013 in the neuro-ophthalmology clinic of Taipei Veterans General Hospital were reviewed. ResultsA total of eight eyes of five patients with ONH were enrolled in this study (1 male, 4 females). The mean age at diagnosis was 14.5 ± 12.0 years (range 0.25–30 years). Ocular examination revealed approximately half of the eyes had tortuous retinal vessels. In MRI studies, all patients had midline brain abnormalities including ectopic posterior pituitary gland (60%), agenesis of septum pellucidum (20%), and Rathke's cleft cyst (20%). Two patients had endocrinopathies—one suffered from hypopituitarism and the other had hyperprolactinemia. Both of them showed ocular findings of tortuous retinal vessels. ConclusionA high prevalence of midline brain abnormalities was noted in ONH patients of Chinese ethnicity. The presence of tortuous retinal vessels in patients with a midline brain anomaly may indicate the occurrence of endocrinopathy.

Morphology of retinal vessels in patients with optic nerve head drusen and optic disc edema.

We quantitatively investigated the peripapillary vascular morphology in patients with optic nerve head drusen (ONHD) and optic disc edema (ODE). Computer-based fundus analysis was used to investigate peripapillary vascular morphology, including length, branching, and diameter of arteries and veins calibrated by optical coherence tomography. Patients with ONHD showed significantly larger diameters of arteries without branching (P = 0.05), and arteries after primary/before secondary branching (P = 0.04) and secondary venous branching started closer to the optic disc (P = 0.03) compared to healthy controls. The ODE patients had significantly reduced number of small peripapillary veins and larger number of veins without branching compared to ONHD and controls (P = 0.02). Anomalous branching with arterial and venous trifurcation presented in the ODE and ONHD groups, with significant higher prevalence in ODE patients for venous trifurcations compared to ONHD and controls (P = 0.02). The diameter of vessels in ONHD patients were significantly larger in arteries without branching (P = 0.05), after primary branching (P = 0.04), and venous branching closer to the disc area (P = 0.03) compared to controls. The ODE patients demonstrated widening of the small peripapillary veins measured by a significantly larger number of veins without branching (P = 0.001 and P = 0.02, compared to controls and ONHD, respectively) and less small veins (P = 0.001 and P = 0.04, compared to controls and ONHD, respectively).

Retinal and choroidal intravascular spectral‐domain optical coherence tomography

To examine retinal and choroidal blood vessels using spectral-domain optical coherence tomography (SD-OCT). Retrospective case series. Scans through retinal blood vessels in healthy subjects demonstrated vessel wall reflexes and a tri-layer profile of the blood column on longitudinal scans and a figure-of-eight configuration on cross-sectional scans. Intravascular reflectivity decreased with increasingly oblique angles of observation and was absent when blood flow was parallel to the line of sight. The high blood flow in the choroidal vessels in healthy subjects and the low flow in the retinal vessels in patients with ocular ischaemic syndrome and central retinal artery occlusion were both associated with lower reflectivity of the blood and an unstructured intravascular SD-OCT profile. This qualitative in vivo study found a characteristically structured SD-OCT profile of the blood column in retinal vessels with normal blood flow. Both structure and total reflectivity faded when blood flow was lower or higher than normal or at oblique angles to the line of sight. In conclusion, SD-OCT scans of the vessels in the posterior pole of the eye may assist the clinical assessment of gross abnormalities of ocular blood flow, e.g. in carotid artery stenosis.

Oxygen metabolism in age related macular degeneration

AbstractPurpose To determine whether oxygen saturation in retinal vessels of patients with age‐related macular degeneration (AMD) is different from that of a healthy population.Methods The non‐invasive retinal oximeter is based on a fundus camera. It simultaneously captures images of the retina at 600 nm and 570 nm and estimates retinal vessel oxygen saturation. Mean oxygen saturation of hemoglobin was measured in retinal arterioles and venules of 28 individuals with AMD, 6 were males. Eight patients had early AMD in at least one eye, 8 patients had untreated exudative AMD in at least one eye, and 12 patients had early AMD in one eye and untreated exudative AMD in the other eye. The age of AMD patients was 78 ± 9 years (mean ± SD) compared to 66 ± 4 years for the healthy controls (n=26).Results Oxygen saturation of hemoglobin in arterioles, after adjusting for vessel width, was 94.3 ± 3.7% in the healthy population compared to 93.5 ± 3.1% in early AMD (n= ;p=0.42) and 93.7 ± 3.8% in exudative AMD (n= ;p=0.55). The corresponding values in venules were 60.9 ± 5.6% in healthy eyes compared to 64.9 ± 7.0% in exudative AMD (p=0.017). In eleven patients with early AMD in one eye and exudative AMD in the other eye, oxygen saturation in arterioles was 93.5 ± 3.0% and 92.4 ± 2.8% (p=0.52) and in venules 66.3 ± 4.9% and 64.4 ± 5.3% (p=0.080).Conclusion Oxygen saturation in venules in exudative AMD is higher than in healthy controls and there is a similar trend in early AMD. Arteriovenous difference is smaller in AMD subjects than normals. The study suggests that retinal oxygen metabolism is affected in AMD. Commercial interest

Retinal blood flow velocity measured by retinal function imaging in retinitis pigmentosa

To measure the retinal blood flow velocity in patients with retinitis pigmentosa using the retinal function imaging technique. The clinical observational investigation included a study group of five eyes of five patients (age: 55.7 ± 8.6years) with retinitis pigmentosa (RP) and a control group of five eyes of five healthy subjects. We used a randomly chosen eye of the RP patients, and compared its results to the normal subjects using a mixed linear model, correcting for heart rate, age, and gender. The mean blood velocity in the narrow retinal veins (1.7 ± 0.35cm/s versus 3.0 ± 0.35cm/s; P < 0.001) and wide retinal veins (1.5 ± 0.35cm/s versus 3.1 ± 0.30cm/s; P < 0.001) was significantly lower in the study group than in the control group not correcting for heart rate, age or gender. Correspondingly, the arterial blood flow velocity was significantly lower in the study group than in the control group for the narrow arterial vessels (2.3 ± 0.55 versus 4.2 ± 0.5; P = 0.006) and for the wide retinal arteries (2.5 ± 1.05cm/s versus 4.8 ± 1.0cm/s; P < 0.001). Using the retinal function imaging technology revealed significantly lower retinal blood flow velocities in the small and large retinal vessels in patients with retinitis pigmentosa than in healthy subjects. This corresponds with the known decrease in the retinal vessel diameters as observed upon ophthalmoscopy in patients with retinitis pigmentosa. Retinal function imaging technology may hold promise for measurements of retinal blood flow parameters.

Wall‐to‐lumen ratio of retinal vessels in patients with cerebrovascular damage

Abstract Purpose There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole‐to‐venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall‐to‐lumen ratio (WLR) and wall cross‐sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in patients with cerebrovascular damage. Methods In this cross‐sectional study, 23 patients (57.5 +/‐ 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age‐matched control groups: 83 subjects with essential hypertension (53.7 +/‐ 5.5 years) and 16 normotensive subjects (52.2 +/‐ 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima‐media thickness (IMT) of the carotid artery was measured. Results WLR (0.44 +/‐ 0.1 vs. 0.34 +/‐ 0.1 vs. 0.30 +/‐ 0.1, P &lt; 0.001) and carotid IMT (P &lt; 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups. Conclusion The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles

Retinal microvasculature in acute lacunar stroke

In their interesting and novel study in this issue of The Lancet Neurology, Lindley and colleagues1 report microvascular abnormalities in the retinal vessels of patients who have had ischaemic small vessel stroke (lacunar stroke). These retinal changes, which include a smaller arteriole:venule ratio, arteriovenous crossing abnormalities, enhanced arteriolar light reflex, and wider retinal venules in patients without diabetes, support an underlying mechanism of intracerebral vessel narrowing in lacunar infarction that has a non-atherothrombotic origin.

Reduced Retinal Vessel Response to Flicker Stimulation but Not to Exogenous Nitric Oxide in Type 1 Diabetes

Various studies have shown that retinal vessels in patients with diabetes mellitus have a reduced capacity to adapt to changes in perfusion pressure and to stimulation with flickering light. Structural and functional changes in retinal vessels in diabetes could lead to a general reduction of vasodilator and/or vasoconstrictor capacity. To gain more insight into this topic, we compared the response of retinal vessel diameters to systemic glyceryl trinitrate (GTN) and stimulation with diffuse luminance flicker in patients with diabetes and healthy control subjects. Twenty patients with type 1 diabetes mellitus featuring no or mild nonproliferative diabetic retinopathy and 20 healthy, age-matched subjects were included in this study. A vessel analyzer was used for measurement of diameters of retinal arteries and veins. The response of diameters was measured continuously during stimulation with flickering light, as well as immediately after sublingual application of 0.8 mg GTN. The response of retinal vessels to flickering light was significantly reduced in the patients with diabetes (arteries: 2.9% in diabetes versus 7.0% in control subjects, P < 0.002; veins: 4.6% in diabetes versus 6.8% in control subjects, P = 0.020). GTN-induced vasodilatation was not different between the patients with diabetes and the healthy control subjects (P >or= 0.70). The present study confirmed reduced response of retinal vessels to stimulation with flickering light in diabetes. The response of retinal vessels to a direct NO-donor, however, was maintained. This result indicates that abnormal flicker-induced vasodilatation in diabetes is not a consequence of generally reduced retinal vascular reactivity (ClinicalTrials.gov number, NCT00432029).

Retinal Vessels in Patients with Multiple Sclerosis: Baseline Diameter and Response to Flicker Light Stimulation

Transparency of ocular media enables the precise quantitative analysis of vessels of retina, a neuronal tissue which can be affected by multiple sclerosis (MS). Eyes with no history of optic neuritis (non-ON eyes) of 21 patients with MS were examined with Retinal Vessel Analyzer. Segments of vessels of 500 microm length were measured proximal and distal from the optic disc and compared to those of 21 age- and gender-matched controls. Baseline diameters and peak response to flicker light stimulation of retinal vessels were analyzed. MS eyes had thinner arterioles (p = 0.02) and thicker venules (p = 0.008) than controls: arterioles 111 +/- 14 microm (proximal), 99 +/- 11 microm (distal) in MS eyes and 121 +/- 15 and 107 +/- 9 in controls, respectively. Values for venules were 157 +/- 18 and 136 +/- 20 (MS); 147 +/- 15 and 119 +/- 20 (controls). Peak response was higher in MS eyes than in controls for arterioles (p = 0.007), but comparable for venules (p = 0.35). Narrower arterioles and wider venules might be a consequence of subclinical swelling of optic nerve axons in eyes with negative history of ON in MS patients.

Rigidity of Retinal Vessels in Patients with Multiple Sclerosis

The aim of this study was to analyze pulse wave propagation in the ocular circulation by assessing the phase delay between retinal arterioles and venules and calculating the pulse delay between the retinal and choroidal circulations in MS patients and in control subjects. Twenty patients with multiple sclerosis (38.3 +/- 6.2 years) and twenty healthy subjects (37.4 +/- 15.2 years) were examined with the Retinal Vessel Analyzer. In addition, an average peripapillary RNFL (retinal nerve fiber layer) thickness was measured by means of ocular coherence tomography in MS patients. The phase delay between the arteriole and venule pulsations was assessed at three sites: in the close retinal vicinity of the disc, 1 - 2 disc diameters and 3 - 4 disc diameters away from the disc. Assuming that venules are counterphased to the choroidal circulation, a choroid-to-retina pulse delay was calculated. The choroid-to-retina pulse delay was 0.26 +/- 0.11, 0.27 +/- 0.13 and 0.34 +/- 0.15 sec in eyes with history of optic neuritis (ON-eyes); in eyes of MS patients without such a history (non-ON eyes) the corresponding values were 0.27 +/- 0.14, 0.29 +/- 0.11 and 0.30 +/- 0.15 sec, and in control eyes 0.32 +/- 0.19, 0.38 +/- 0.16 and 0.45 +/- 0.20 sec, respectively, at three sites centrifugal from the disc. The choroid-to-retina pulse delay was significantly longer in healthy control eyes than both in ON eyes (p = 0.012) and non-ON eyes of MS patients (p = 0.004). The interocular difference of the choroid-to-retina pulse delay and OCT RNFL thickness showed a significant correlation in MS patients (Pearson r = 0.54, p = 0.015; Spearman R = 0.66, p = 0.0016). Patients with multiple sclerosis seem to demonstrate an increased rigidity of the retinal vessels. The interocular difference in retinal vessel rigidity was significantly correlated with the interocular difference in RNFL thickness in MS patients.

Wall-to-Lumen Ratio of Retinal Arterioles and Arteriole-to-Venule Ratio of Retinal Vessels in Patients with Cerebrovascular Damage

There is evidence that generalized retinal arteriolar narrowing, which can be measured by the arteriole-to-venule ratio (AVR) of retinal vessels, predicts cerebrovascular events. The wall-to-lumen ratio (WLR) and wall cross-sectional area (WCSA) of retinal arterioles reflect structural arteriolar parameters. The primary objective was to test the association between WLR and AVR in a distinct cohort of patients with cerebrovascular damage. In this cross-sectional study, 23 patients (57.5 +/- 9.4 years) with acute transitory ischemic attack or lacunar cerebral infarct were compared with two age-matched control groups: 83 subjects with essential hypertension (53.7 +/- 5.5 years) and 16 normotensive subjects (52.2 +/- 8.3 years). Retinal arteriolar parameters (WLR, WTH, and WCSA) were assessed in vivo with scanning laser Doppler flowmetry (SLDF). AVR and a qualitative evaluation of retinal vessels were obtained from digital retinal color photographs. The intima-media thickness (IMT) of the carotid artery was measured. WLR (0.44 +/- 0.1 vs. 0.34 +/- 0.1 vs. 0.30 +/- 0.1, P < 0.001) and carotid IMT (P < 0.05) were significantly greater in the cerebrovascular event group compared with normotensive subjects. WLR and WCSA were significantly higher in the cerebrovascular event group compared with subjects with mild arterial hypertension. AVR was similar in all three study groups (0.75 +/- 0.07 vs. 0.74 +/- 0.07 vs. 0.78 +/- 0.1, P = 0.18). The increase in WLR and WCSA of retinal arterioles, as well as in IMT in patients with cerebrovascular damage suggests vascular hypertrophy in the microvascular and macrovascular bed. The lack of association between AVR of retinal vessels and WLR of retinal arterioles may point to different stages of cerebrovascular disease and/or different pathophysiological changes in the arteriolar wall.

Retinal oximetry: clinical studies

Abstract Purpose Disturbances in blood flow and oxygenation are believed to be involved in diseases such as diabetic retinopathy, retinal vascular occlusion and possibly glaucoma. The purpose of the studies presented here is to measure haemoglobin oxygen saturation (SatO2) in retinal vessels in patients with these diseases. Methods Our retinal oximeter is based on a fundus camera, which is coupled with beam splitters and narrow band‐pass light filters. The oximeter yields fundus images with 4 wavelengths of light simultaneously. Two wavelengths, 605nm and 586nm, are used for estimation of SatO2. Measurements were made on (A) 7 patients with CRVO, (B) 19 patients before and after glaucoma surgery and (C) 21 patient with diabetic retinopathy, who were compared with 20 healthy volunteers. Results (A) Venous SatO2 was 53±9% in CRVO eyes and 65±4% in fellow eyes (mean±SD, p=0.015, n=7). (B) Glaucoma surgery has a minimal effect on SatO2 in both arterioles (2% rise, p=0.046, n=19) and venules (no change). IOP was lowered by 13mmHg. (C) SatO2 in retinal venules was 60±8% in healthy volunteers (n=20), 67±7% in patients with non‐proliferative DR (n=12, p&lt;0.05 compared to healthy) and 68±6% (n=9, p&lt;0.05) in patients with proliferative DR after PRP treatment. Conclusion Human retinal vessel oximetry can detect changes in various ocular diseases and this may help us understand the pathophysiology. The decreased venous SatO2 in CRVO is probably caused by decreased blood flow. A small change in SatO2 after glaucoma surgery may indicate a large change in oxygen delivery since blood flow may be increased with IOP lowering. Higher venous SatO2 in DR patients may for example be explained with arteriovenous shunting of blood. Commercial interest

No‐induced retinal vasodilatation is maintained in type 1 diabetes

Abstract Purpose Various studies have shown that retinal vessels in patients with diabetes mellitus have a reduced capacity to adapt to changes of perfusion pressure. The mechanisms lying behind this abnormal autoregulation have not been completely identified yet. Histomorphological changes of retinal vessels in diabetes could possibly reduce their capacity of vasodilation and vasoconstriction. To test this hypothesis we compared the response of retinal vessel diameters to systemic glyceryl trinitrate (GTN) in patients with diabetes and healthy controls. Methods 20 patients with insulin dependent diabetes mellitus featuring no or mild non‐proliferative diabetic retinopathy were included into this study. In addition, 20 healthy and age‐matched subjects were included as controls. Retinal vessel diameters were measured before and immediately after sublingual application of 0.8 mg of the NO‐donor GTN. The IMEDOS Retinal Vessel Analyzer was used for continuous measurement of diameters of retinal arteries and veins. Results Oral application of GTN induced vasodilatation of retinal arteries and veins. This effect was not different between patients with diabetes and healthy controls. Systemic arterial blood pressure was reduced in both groups after GTN application, but to a comparable degree. Conclusion The present study indicates that in patients with no or mild non‐proliferative diabetic retinopathy the vasodilatory response of retinal vessels to a direct NO‐donor is maintained. This indicates that abnormal retinal autoregulation in diabetes mellitus, as observed previously, is not a consequence of generally reduced retinal vascular reactivity.

Color Doppler Imaging of Ocular Hemodynamic Changes in Behçet Disease and Uveitis Patients with Different Etiologies

Purpose: To investigate blood flow velocity changes and resistivity index values of orbital vessels in Behçet disease with or without ocular involvement, in uveitis patients with different etiologies, and in healthy volunteers. Methods: Subjects were divided into four groups: those with ocular involvement in Behçet disease (group I), those without ocular involvement in Behçet disease (group II), uveitis patients with different etiologies (group III), and a control group (group IV). Twenty-seven eyes in group I, 14 eyes in group II, 25 eyes in group III, and 27 eyes in group IV were investigated. The blood flow in the central retinal artery (CRA), ophthalmic artery (OA), nasal posterior ciliary artery (NPCA), and the temporal posterior ciliary artery (TPCA) was measured using color Doppler ultrasonography (CDU) to determine the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI). Results: The PSV and EDV value of CRA in groups I, II, and III were found to be significantly lower than those in the control group (p < 0.05 for each). The PSV and EDV values of TPCA and NPCA in groups I, II, and III were significantly lower than those in the control group (p < 0.05 for each). Resistivity indexes of all arteries were higher in groups I, II, and III than the control group. The PSV and EDV in CRA, TPCA, and NPCA in Behçet disease patients with ocular involvement were significantly lower than all other groups (p < 0.05). Conclusions: There are significant reductions in the blood flow values of the orbital arteries in patients with Behçet disease and uveitis patients with different etiologies when compared with healthy volunteers. The decrease in blood flow values in Behçet disease is more evident in patients with ocular involvement than the patients without ocular involvement. This might be the result of occlusive vasculitis, which is frequently seen in the retinal vessels of patients with Behçet disease.

The effects of high ambient glucose on the radiosensitivity of retinal microvascular endothelial cells and pericytes

Purpose. The metabolic peturbations of diabetes cause functional and structural changes in the retinal microvasculature which are termed diabetic retinopathy. Exposure of the eye to ionising radiation results in retinal vascular damage with a clinical manifestation known as radiation retinopathy. Anecdotal studies have suggested that exposure to even low levels of ionising radiation may accelerate development of pathological changes in the retinal vessels of patients with diabetes. This in vitro study was designed to test the hypothesis that the combination of a high ambient glucose environment (mimicking hyperglycaemia and diabetes) along with exposure to ionising radiation would result in more accentuated damage to cultured retinal vascular cells. Methods. Retinal microvascular endothelial cells and pericytes were propagated for 5 days in either 5 mM (euglycaemia) or 15 mM (hyperglycaemia) glucose. Cells were irradiated with 250, 500 or 1000 cGy of ionising radiation using a 6 MV beam photon accelerator which was used for radiotherapy. Similarly treated but unirradiated cells were used as controls. DNA damage was assessed using the single-cell gel electrophoresis (comet) assay. Results. Unirradiated control cells pre-exposed to glucose at either 5 mM or 15 mM for 5 days showed no significant difference in mean percentage tail DNA representing damage. However, in both pericytes and endothelial cells exposed to ionising radiation, cells cultured in 15 mM glucose showed significantly higher levels of DNA damage compared with those cultured in 5 mM glucose, with maximal differences being seen at the higher radiation doses (500 and 1000 cGy). Conclusions. This study has demonstrated that retinal microvascular cells cultured in high glucose express more DNA damage when exposed ionising radiation. These findings have important implications for the management of patients with diabetes if they require radiotherapy for neoplastic disease.

Increased expression of endothelial antigen PAL-E in human diabetic retinopathy correlates with microvascular leakage

The Pathologische Anatomie Leiden-Endothelium (PAL-E) antigen is a marker for loss of the blood-brain barrier function in brain tumours. It is endothelium specific and is associated with the endothelial plasmalemmal vesicles (caveolae) involved in transcellular transport. To test whether blood-retinal barrier loss in diabetic retinopathy is associated with cellular changes in the endothelium, the expression of antigen PAL-E in relation to microvascular leakage in human diabetic retinopathy was investigated. Immunohistochemical staining of frozen tissue sections of postmortem eyes obtained from 30 persons without and 41 persons with diabetes mellitus was carried out with monoclonal antibodies against PAL-E and CD31 and with antibodies against endogenous fibrinogen, albumin and IgG as indicators of vascular leakage. Patchy or uniform microvascular PAL-E staining was observed in the retina of 17 of the 41 eyes of diabetic patients and in 2 of the 30 normal control eyes. In the diabetic eyes, PAL-E staining co-localized with microvascular staining for endogenous fibrinogen, albumin and IgG. Strong staining for PAL-E was observed in sites without blood-tissue barriers, like the choroid. In microvessels with an intact blood-retina barrier the endothelial antigen PAL-E is absent. Its expression is increased in retinal vessels of patients with diabetic retinopathy and correlates with microvascular leakage of plasma proteins. This phenotypic shift involving an antigen associated with caveolae suggests that dysfunction of the endothelium forms the cellular basis for microvascular leakage in diabetic retinopathy, rather than passive endothelial damage.

Capillary microaneurysms in the human diabetic heart.

RETINAL microaneurysms and thickening of the capillary basement membrane are the hallmarks of diabetic small-vessel disease.1 2 3 4 Microaneurysms of retinal vessels in patients with long-standing ...

Electron Microscopy of Ocular Muscle in Type Ii Glycogenosis (Pompe's Disease)

In 1928, von Gierke described a small group of young patients who showed mas­ sive deposition of glycogen in their liver and kidneys at autopsy. A few years later, Pompe reported the case of a child who died with glycogen deposits in many organs as well as in skeletal muscle. Subsequently, Cori, Hers, and others have identified the inherited enzyme deficiency responsible for these and other disorders of glycogen metabolism. Pompe's disease (type II glycogenosis) results from absence of the enzyme alpha 1-4 glucosidase (acid maltase). Abnormal depo­ sition of glycogen is found in cardiac and skeletal muscle, liver, kidney, thyroid, and spleen. Because of the wide distribution of abnormal glycogen deposits, Pompe's disease is also referred to as generalized glycogeno­ sis. The light and electron microscopic changes in Pompe's disease have been thor­ oughly studied in skeletal and cardiac muscle and in other organs. Cogan was the first to observe deposits of glycogen in the mural cells of the retinal vessels in patients with Pompe's disease. Toussaint described the light microscopic ocular changes in a fivemonth-old infant with type II glycogenosis. He found deposits of glycogen in retinal ganglion cells, in mural cells of the retinal vessels, and in the smooth and striated mus­ cle fibers of the eye. Their illustrations of the rectus muscle showed a complete disap-

Certain Appearances Observed in the Eyeground of the Tuberculous

The writer has observed a special fullness and tortuousity oE the retinal vessels in patients suffering from tuberculosis, and those whose family history included cases of this disease. No heart lesions were present in these patients. Attention is called to these changes in the hope that they will be looked for by other ophthalmologists.