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[Experimental branch vein occlusion: the effect of carbogen breathing on preretinal PO2].

PURPOSE: To evaluate the variations in preretinal PO2 in normal and in ischemic postexperimental branch vein occlusion (BRVO) retinal areas during normoxia, hyperoxia (100% O2) and carbogen (95% O2, 5% CO2) breathing. METHODS: Preretinal PO2 measurements were obtained in intervascular retinal areas far from the retinal vessels of 13 anesthetized miniature pigs with oxygen-sensitive microelectrodes (10 microm tip diameter) introduced through the vitreous cavity by a micromanipulator. The microelectrode tip was placed at 50 microm from the vitreoretinal interface in the preretinal vitreous. PO2 was measured continuously for 10 minutes in systemic normoxia, hyperoxia (100% O2 breathing) and carbogen (95% O2, 5% CO2) breathing. A BRVO was induced with an argon green laser, and oxygen measurements were repeated in normoxia, hyperoxia and carbogen breathing. RESULTS: In hyperoxia, preretinal PO2 remained almost constant in both normal retinas (DeltaPO2=1.33 mmHg +/- 3.39; n=13) and ischemic retinas (DeltaPO2=3.73 mmHg +/- 2.84; n=8), although systemic PaO2 significantly increased. Carbogen breathing induced a significant increase in systemic PaO2 and PaCO2. Furthermore, it significantly increased preretinal PO2: DeltaPO2=23.05 mmHg +/- 17.06 (n=12) in normal retinas, and DeltaPO2=22.54 mmHg +/- 5.96 (n=6) in ischemic retinal areas. CONCLUSIONS: Systemic hyperoxia does not increase preretinal PO2 significantly in normal and ischemic post-BRVO retinal areas of miniature pigs, as hyperoxia induces a decrease in the retinal blood flow. Carbogen breathing significantly increases preretinal PO2 in normal and in ischemic post-BRVO retinal areas. This effect is probably due to the vasodilatation of the retinal arterioles induced by the intravascular PaCO2 increase.

Animals↗

Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats.

Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance.

Animals↗

Systemic non-Hodgkin's lymphoma with optic nerve infiltration in a patient with AIDS.

PURPOSE: To report the clinicopathologic features of a patient with AIDS and clinically regressed systemic non-Hodgkin's lymphoma who subsequently developed lymphomatous infiltration of the optic nerve and occlusion of the central retinal vein in both eyes. METHODS: The eyes of this patient were examined ophthalmologically and by fluorescein angiography. The eyes, brain, and body were obtained after death and studied by light microscopy. RESULTS: Ophthalmic examination and fluorescein angiography revealed optic nerve swelling and central retinal vein occlusion first in the left eye and shortly thereafter in the right eye. Postmortem histopathologic examination showed dense infiltration of both optic nerves by lymphoma as well as necrotizing vasculitis involving the retinal vessels near the left optic nerve head. Examination of the brain revealed lymphomatous involvement in the paraventricular region with associated necrosis and inflammation. No bone marrow recurrence or other residual systemic lymphoma was present. CONCLUSION: This case demonstrates that infiltrative optic neuropathy may occur as the sole ocular manifestation of disease recurrence in a patient with systemic non-Hodgkin's lymphoma otherwise thought to be in clinical remission.

Biomarkers, Tumor↗

Vascular changes and their mechanisms in the feline model of retinopathy of prematurity.

This study documents changes to retinal vasculature during the feline form of retinopathy of prematurity (ROP). The authors describe the closure and obliteration of retinal vessels during exposure to high oxygen, the pattern and tempo of growth of proliferative vasculature, which, after the return of the animal to room air, extends from the optic disc in a spectacular "rosette" pattern, the formation of preretinal vascular growths, and an initial lack of barrier properties in the new vessels. Finally, the response of the vasculature to the relief of hypoxia is reported, including the gradual establishment of barrier properties in the intraretinal vessels, the partial normalization of the proliferative vessels, and the abnormalities that persist. It is suggested that the vascular changes occur in successive stages: closure and obliteration during hyperoxia, vasoproliferation induced by hypoxia, and normalization after the relief of hypoxia with distinct cellular mechanisms and stimuli. It is argued that the same stages can be seen in the human form of ROP; two possible stimuli for the fibroplasia that damages the retina in human ROP are discussed.

Animals↗

Preretinal neovascularization induced by experimental retinal vein occlusion in albino rats.

Retinal ischemia and neovascularization have been demonstrated in several animal models. To determine 1) whether the retinal or preretinal neovascularization can be induced in albino rats by retinal vein occlusion and 2) the type and rate of occurrence on neovascularization, we occluded retinal veins in albino rats by photodynamic thrombosis. After anesthesia, each of 36 rats received an injection of rose bengal photosensitive dye, and their veins underwent argon green laser treatment. Half or all the major retinal veins were occluded in 12 eyes and in 24 eyes, respectively. Ten control rats underwent the same procedures but the laser beam was directed between major retinal vessels. In 46 control eyes, rose bengal dye was seen to have perfused without laser treatment. Retinal detachment developed in most vein occluded eyes within one day of venous occlusion, which was confirmed by fluorescein angiography. On follow-up at two weeks, only four of 24 eyes (16.7%) had undergone occlusion of all retinal veins showed new preretinal vessels on the optic disc. In these four eyes, severe disturbance of both retinal arterial and venous blood flow was observed, but no other eyes showed such severe combined disturbance. These data suggest that preretinal neovascularization in albino rats can be induced by this minimally traumatic method and that venous occlusion is severe enough to compromise arterial blood flow for a certain threshold period, thus inducing the development of preretinal neovascularization.

Animals↗

Low gestational age associated with abnormal retinal vascularization and increased blood pressure in adult women.

The objective was to investigate any possible relationship between functional and structural vascular changes in women with low gestational age and/or low birth weight by analyzing the retinal vascular pattern in women with thoroughly documented blood pressure. Retinal vessel morphology was evaluated by digital image analysis of ocular fundus photographs in 47 subjects, aged 23-30 y. The women were allocated into three groups: 1) those born preterm and appropriate for gestational age (AGA), with a median gestational age at birth of 30 wk and a median birth weight of 1250 g (n = 14); 2) those born small for gestational age (SGA) but full term (median 40 wk), with a median birth weight of 2130 g (n = 17), and 3) those born full term, AGA, and with a median birth weight of 3640 g (n = 16). Women born preterm had significantly higher length index for arterioles compared with the other two groups (median 1.11 and 1.08, respectively, p = 0.005). In addition, the preterm-born women had significantly fewer number of vascular branching points compared with the controls (median 27 and 30, respectively, p = 0.03). The abnormal retinal vascularization observed in ex-preterm women together with an increased casual blood pressure observed in these subjects suggests that being born preterm does have effects on the vascular system that persist into adult life. In addition, it demonstrates that preterm birth seems to affect the vascular system both functionally and structurally, which, in adulthood, could result in a lower threshold for the development of vascular disease.

Adult↗

Microglia and macrophages are increased in response to ischemia-induced retinopathy in the mouse retina.

PURPOSE: The ability of microglial cells (MG) and macrophages (MAC) to release cytokines, induce apoptosis, as well as perform phagocytic functions suggests a possible role in wound healing following oxygen-induced injury. This study was performed to determine the temporal and spatial expression of F4/80 (F4/80+) positive microglia/macrophages (MG/MAC) in areas of retinal damage in the mouse model of oxygen-induced retinopathy. METHODS: C57BL/6 postnatal day 7 (P7) mice were exposed to 75% O2 for 5 days (P12) then allowed to recover in room air. Hyperoxia-exposed (O2) mice (O2 refers to hyperoxia exposure from P7 to P12 only) were sacrificed on P12, P14, P17, and P21 and their eyes were examined. Localization of F4/80+ cells in FITC-dextran-perfused retinas allowed coordinate visualization of retinal vessels and MG/MAC via fluorescence microscopy. BrdU, a cellular proliferation marker, was injected intraperitoneally 1 h prior to sacrifice. Immunostaining was performed for a microglia and macrophage-specific antigen (F4/80) and BrdU. CCL2 (monocyte chemoattractant protein-1; MCP-1) expression was examined by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: There was a marked increase (>500%) in MG/MAC in hyperoxia-exposed retinas on P17O2 and P21O2 compared to control retinas. At P17O2, MG/MAC were localized in areas of neovascularization (NV), revealing an intimate relationship between MG/MAC and neovascular tufts. However, P21O2 retinas demonstrated MG/MAC associated with avascular regions in the outer layers of the retina. Immunostaining for F4/80 and BrdU revealed rare co-localization in hyperoxia-exposed retinas. Real time RT-PCR results demonstrated increased expression of CCL2 in P14O2- and P17O2- exposed retinas. CONCLUSIONS: Our results suggest that resident retinal microglia proliferation occurs at a low frequency in response to injury in this model. The substantial increase in total F4/80+ cells in hyperoxia-exposed retinas in conjunction with the upregulation of CCL2 is consistent with recruitment of hematogenous macrophages into the retina. The temporal and spatial localization of MG/MAC adjacent to neovascular tufts suggests these cells are modulating the retinal response to ischemia-induced retinopathy.

Animals↗

Increased retinal vascular tortuosity in gestational diabetes mellitus.

The authors report the first study which demonstrates that women with gestational diabetes mellitus (GDM) have increased tortuosity of their retinal vessels. Women with GDM underwent fundus photography and were compared with a normal control group (NC) and a pregnant nondiabetic control group (PC). Five ophthalmologists evaluated the unlabeled photographs, resulting in a combined mean prevalence of tortuosity of 21.6% NC, 24.7% PC, and 60.3% GDM. Statistical analysis showed that the GDM group was significantly different from both the NC and PC groups. Tortuosity was unrelated to acute elevation in blood glucose and was still present at 5 months postpartum.

Adult↗

[Routine funduscopic examination in hypertensive patients not useful].

Funduscopic examination according to the classification of Keith, Wagener and Barker has been used since 1939 to assess retinal damage in patients with hypertension. Improved treatment possibilities and the screening of patients with hypertension seem to have led to a decrease in the incidence and severity of the retinal abnormalities found. The following findings have been published during the past ten years. The assessment of retinopathy is subject to a large interobserver-variability, especially with respect to venous-crossings and arteriolar narrowing of retinal vessels. The positive and negative predictive value of retinopathy for high blood pressure is low. The association of retinopathy with other predictive indicators for organ damage is inconsistent and its association with cardiovascular complications is weak. These findings indicate that the usefulness of funduscopic examination as an instrument for assessing organ damage in patients with hypertension is limited. Therefore it should not be used as a routine diagnostic tool unless a hypertensive crisis is indicated.

Female↗

Ultrasonographic screening of carotid artery in patients with vascular retinopathies.

BACKGROUND AND PURPOSE: Retinal vasculopathy is commonly found with complaint of burred vision by ophthalmologist and closely related to asymptomatic cerebrovascular disease. The purpose of this study was to evaluate patients with microvascular retinopathy by ultrasound sonography of neck carotid artery and to find high risk group for stroke at outpatient of ophthalmology with associated retinopathy. METHODS: Between 1999 and 2001, a total of 480 consecutive patients visited at outpatient of ophthalmology with a complaint of burred vision were evaluated by ultrasound sonography of neck carotid artery. The patients were divided to with retinopathy (n=253) and without retinopathy (n=227). The former was subgrouped as follows; central retinal vein occlusion (CRVO; n=11), branch of retinal vein occlusion (BRVO; n=71), retinal artery occlusion (RAO; n=8), hypertensive retinopathy group-I (according to Keith, Wagener and Barker's criteria) (HTN-R I; n=43) and group-II (HTN-R II; n=42), and diabetic retinopathy (DM-R; n=78). The latter group was with various ophthalmological diseases, mainly inflammation of cornea, with healthy retinal vessels and constituted as the control group. RESULTS: There was no statistically significant difference between patients with retinopathy and the control group with respect to sex distribution, nor among the retinopathy groups. Patients with retinopathy had a mean age of 68 years, while those with HTN-R I and II were older with a mean age of 71 years. By ultrasonography, RAO showed pathology in intima-media thickness (IMT; 1.13 +/- 0.55 vs. 0.81 +/- 0.26 mm in control), average number of plaques (1.88 +/- 0.99), degree of stenosis of internal carotid artery (42.4 +/- 28.5%) and common carotid artery (27.4 +/- 21.3%). Those with DM-R had the second thickest IMT (0.96 +/- 0.42 mm) and the second highest quantity of plaque (1.23 +/-1.23), and the second most stenotic common carotid artery (13.1 +/- 17.28%). CONCLUSION: Moderate sclerotic changes are found in ophthalmology patients with RAO and DM-R, although the degree pathology do not indicate medical nor surgical prophylactic treatment. Retinal vein occlusion, that has been discussed with diminished retinal blood circulation, does not show any differences in comparison with control group and ultra sonography has less value for screening of asymptomatic carotid atherosclerosis.

Aged↗

Evidence for upregulation and redistribution of vascular endothelial growth factor (VEGF) receptors flt-1 and flk-1 in the oxygen-injured rat retina.

There is considerable evidence that vascular endothelial growth factor (VEGF) is important in the pathogenesis of retinal neovascular diseases. The effects of this endothelial cell-specific mitogen are mediated by specific cell surface receptors. In this study we probed for the two VEGF receptors (VEGFRs) known to have highest affinity in the rat--flt-1 and flk-1. Using a well-characterized rat model of the neovascular disease retinopathy of prematurity (ROP), we performed immunohistochemical assays on methacrylate sections of eyes from normal and oxygen-injured animals at the time neovascularization is first observed (16 days of age) and at its peak (day 20). In day 16 room air retinas there was light, diffuse labeling of the inner nuclear layer and outer plexiform layer. In contrast, in 4 of 5 oxygen-injured eyes on day 16, there was specific labeling of small neovascular growths and normal retinal vessels, and the outermost (sclerad) limit of the label had shifted inward to the vitread border of the inner nuclear layer and the inner plexiform layer. Day 20 room air eyes showed a pattern similar to day 16, although with stronger labeling. However, in oxygen-injured eyes on day 20 the labeling pattern had shifted toward the vitreous, with extremely strong labeling of the preretinal neovascular growths. As on day 16 there was also labeling of the inner plexiform layer and the inner portion of the inner nuclear layer, but not the outer plexiform layer. Comparison of VEGF protein immunolabel with both of the VEGFR immunolabels revealed overlap and strong similarity on day 20 in the oxygen-injured eyes. This is the first report of VEGF receptor protein being concentrated in preretinal neovascular growths in a model of ROP. These results lend themselves to further investigation of the roles of VEGFRs in preretinal neovascularization in ROP and other retinal diseases and suggest avenues of research toward therapies using VEGFR antagonists.

Animals↗

[Entoptic detection of choriocapillaris].

Entopic perception of the central choriocapillaris is documented by personal experience. Seen in this manner, the choriocapillaris appears due to circulatory conditions as a wavy convolute of fresh capillaries whose paths are paralleled by numerous, irregularly distributed, round, black structures. The latter have been presumed to be corpuscles, i.e. erythrocytes, and can be seen entopically as single rows of radial capillaries. Histological studies have shown, however, that these rows of erythrocytes are not always isolated; they have also been found in the choriocapillaris in clusters of rows. Moreover, analogously to the lack of entopic perception of erythrocytes in the retinal vessels in Purkinje's images, the erythrocytes of the choriocapillaris may likewise not be perceived for physical and optical reasons. Therefore the round, black formations are not entoptically perceivable erythrocytes of the choriocapillaries but can only originate in the circular network of the central choriocapillaris. Light directed experimentally into the eye and focussed on the choriocapillaris through a narrow slit positioned nasally leads via reflection to stimulation of the retina from outside to inside and so to entoptic perception of the choriocapillary network. Closer analysis of entoptic perception of the choriocapillaris is significant in view of its heuristic value.

Adult↗

Horseradish peroxidase as a histological indicator of mechanisms of porcine retinal vascular damage and protection with perfluorocarbons after massive air embolism.

BACKGROUND AND PURPOSE: This laboratory has previously shown that a second-generation perfluorocarbon emulsion (PFE) reduces the severity of cerebral injury induced by air embolism during cardiopulmonary bypass (CPB). Horseradish peroxidase examines vascular permeability and was used in this study of the mechanisms of cellular protection afforded by the PFE. METHODS: Twenty domestic pigs underwent CPB with a prime of standard crystalloid or PFE (5 mg/kg) and crystalloid. After 10 minutes on CPB, a 5-mL/kg bolus of room air or saline (control) was delivered via the right carotid artery. The air insult was delivered as either a single bolus or double bolus. After 1 hour of CPB and 1 hour of spontaneous reperfusion, horseradish peroxidase was injected intravenously and circulated for 15 minutes. After euthanasia, both eyes were removed, and the retinas were isolated for histological analysis. RESULTS: Total length of retinal vessels exhibiting horseradish peroxidase extravasation was significantly less in PFE pigs (P < .05). Vascular spasm and red blood cell hemorrhages were unaffected by PFE. PFE pigs exhibited mild to moderate vascular nonperfusion and red blood cell sludging; crystalloid groups demonstrated severe nonperfusion and sludging. CONCLUSIONS: Histological staining with horseradish peroxidase indicated that mechanisms of cerebral air embolism include vascular endothelial leakage, vascular nonperfusion, and red blood cell sludging and hemorrhage. Pretreatment with PFE prevented some sequelae associated with massive air embolism and CPB.

Animals↗

[Ocular findings in Fabry's disease].

INTRODUCTION: Fabry's disease is a recessive X-linked disorder that results from a deficiency of the lysosomal hydrolase a-galactosidase A (alpha-Gal A). The absence of alpha-Gal A enzyme activity leads to accumulation of glycosphingolipid globotryaosyl ceramide (GL-3) in the lysosomes of a variety of cell types. Subsequently, angiokeratoma and ocular signs develop until, in most cases after the third decade of life, severe renal dysfunction or cardiomyopathy becomes obvious. Corneal opacities (cornea verticillata) occur in 90% conjunctival vascular changes in 60%, retinal vessel tortuosity in 55%, and cataracts in 50% of cases. Recently, enzyme replacement therapy has been shown to be an effective treatment modality that can eliminate glycolipid stores and reverse the disease pathology. CASE REPORT: A male patient born in 1971 was admitted for clinical examination due to proteinuria and erythrocyturia. During further evaluation nephrologist suspected Fabry's disease, because patient had skin changes early referred as petechiae, and acroparesthesias. He had also low heat tolerance and virtually no sweat. Physical status: angiokeratoma on gluteat regions and upper arms. Urine analysis in several occasions 10-15 E in sediment, alb. positive. On ECG, 2-mm depression of ST in precordial region. Heart ultrasound: low mitral regurgitation angio stage 1, left ventricle hypertrophy. Abdomen ultrasound: both kidneys around 12 cm large, parapyelic cysts in both kidneys of 2.5 cm in diameter. Biomicroscopy of both eyes: cornea verticillata. Fundus of both eyes: papillae n. optici with poorly defined edges, but without prominence, very tortuotic retinal blood vessels. In March 2002, very low alpha GAL enzyme activity in blood (alpha-Gal A = 0.5 +/- 0.2 nmol of substrate hydrolyzed hourly per serum mL--normal serum enzyme level 8.5-18.9 nmol/mL/h). In May 2002, enzyme replacement therapy was started with recombinant alpha-Gal A enzyme (Fabrazyme) 1 mg/kg every 14 days. Control evaluation and examination showed good cardiac and renal function. The patient felt better and stronger with improved heat tolerance. CONCLUSION: Fabry's disease occurs in all ethnic groups. It is estimated that one in 200 people is a carrier, and one in 40,000-100,000 has the disease. Today in Croatia, Fabry's disease has been diagnosed in only one patient, and according to the usual prevalence there are still 45-100 unrecognized patients. The ophthalmologists are in excellent position to diagnose Fabry's disease in early stages. Therefore it is very important that the ophthalmologists in Croatia become aware of the importance of ocular findings in Fabry's disease, so they can participate in the identification of unrecognized patients.

Adult↗

A small foveal avascular zone may be an historic mark of prematurity.

OBJECTIVE: To compare in children the area and diameter of the foveal avascular zone (FAZ) of former preterm infants, when no significant retinopathy of prematurity (ROP) developed, to the area and diameter of the FAZ of former term infants. DESIGN: Retrospective observational case series and literature review. PARTICIPANTS: Forty-nine children (39 former preterm infants and 10 former term infants) between the ages of 1 and 17 years had fluorescein angiograms. All of these children had been appropriate weight for gestational age at birth and had no genetic disorders. Neither eye of any of these children had any macular ectopia or vessel traction, had been treated for active ROP, had developed active ROP >stage 3 mild, or had any refractive error > +/- five diopters. Every child had a visual acuity of 20/40 or better in both eyes. METHODS: The area and greatest diameter of the FAZ were measured using digital image analysis of masked fundus fluorescein angiograms. Variables of gender, race, multiple birth, gestational age, birth weight, ROP stage, age, and refraction at the time of fluorescein angiography, and final visual acuity were recorded. RESULTS: Increasing FAZ area and greatest diameter correlated significantly with increasing gestational age and birth weight: FAZ area (microm2) versus gestational age (weeks) (R/F/P = 0.88/166.70/<0.0001); FAZ greatest diameter (microm) versus gestational age (weeks) (R/F/P = 0.87/151.10/<0.0001); FAZ area (micro/m2) versus birth weight (g) (R/F/P = 0.88/167.06/<0.0001); and FAZ greatest diameter (microm) versus birth weight (g) (R/F/P = 0.87/148.74/ <0.0001). A small or absent FAZ was found in all former preterm infants who had been < or = 30 weeks gestational age or had weighed < or = 1100 g at birth. A normal FAZ was present in all children who had been > or = 36 weeks gestational age or had weighed > or = 2650 g at birth. None of the other parameters studied correlated with FAZ area or greatest diameter. CONCLUSION: This study provides evidence that the FAZ in developing humans is initially densely vascularized with a fine meshwork of inner retinal vessels during vasculogenesis. This vascular meshwork undergoes regression by apoptosis in all infants > or = 36 weeks gestational age at birth to form a normal FAZ, but apoptosis almost never occurs in preterm infants < or = 30 weeks gestational age at birth. Although there is no effect on final visual acuity, a small or absent FAZ may be an historic mark of prematurity.

Adolescent↗

Free radicals in retinal and choroidal blood flow autoregulation in the piglet: interaction with prostaglandins.

PURPOSE: To study the role of free radicals in autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) and the contribution of the cyclooxygenase pathway in free radical formation during blood pressure changes in 1- to 3-day-old pigs. METHODS: Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and the aortic root to induce hypertension and hypotension, respectively. Blood flow was measured using the microsphere technique. Also, the effects of peroxides on retinal artery diameter were studied on eyecup preparations using time-frame photography processed by digital imaging. RESULTS: Blood gases and intraocular pressure (13 +/- 1 mm Hg) remained stable throughout the experiments. In control animals, RBF was constant only between 30 and 75 mm Hg of ocular perfusion pressure and ChBF increased as a function of ocular perfusion pressure (tau = 0.58, P < 0.01). Inhibition of peroxidation with the free radical scavenger 21-aminosteroid U74389F (2.5 mg/kg) widened the range of RBF and ChBF autoregulation (ocular perfusion pressure from 30 to 131 mm Hg). Hypertension caused an increase in the products of peroxidation, malondialdehyde, and hydroperoxides, as well as in prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in the retina and choroid of control animals; these changes were inhibited by the free radical scavengers U74389F (2.5 mg/kg) and high-dose allopurinol (140 mg/kg) as well as by the cyclooxygenase inhibitors ibuprofen (40 mg/kg) and indomethacin (5 mg/kg). In isolated eyecup preparations, H2O2 and cumene hydroperoxide dilated retinal vessels, and this effect was completely blocked by indomethacin. CONCLUSIONS: These findings indicate that free radicals play a major role in setting the upper limit of RBF and ChBF autoregulation of the newborn animal. In addition, there exists a positive feedback interaction between free radicals and cyclooxygenase activity in ocular tissues, such that during hypertension the cyclooxygenase pathway is an important producer of free radicals and in turn is also activated by them.

Animals↗

Laser Doppler velocimetry study of retinal circulation in diabetes mellitus.

Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal circulation in 26 normal subjects and in 51 insulin-treated diabetic patients with no retinopathy, background retinopathy (BDR), proliferative retinopathy (PDR), and patients with PDR who had been treated by panretinal photocoagulation (PDR-PRP). Measurements were obtained from main temporal retinal vessels in each eye. Venous diameter at the site of laser Doppler velocimetry measurements was significantly greater than normal in patients with BDR and PDR. The maximum velocity of red blood cells was significantly lower than normal in eyes with diabetic retinopathy. Calculated volumetric blood flow rate, however, was not significantly different from normal in eyes with no retinopathy, BDR, and PDR, and was significantly decreased from normal in patients with PDR who had been treated by panretinal photocoagulation. A comparison between this technique and the fluorescein dye dilution technique is provided.

Adult↗

Detection of optic nerve involvement in retinoblastoma with enhanced computed tomography.

PURPOSE: The study was designed to evaluate the value of enhanced computed tomography (CT) as a non-invasive test in the detection of optic nerve invasion in retinoblastoma. METHODS: Nineteen eyes in 17 consecutive retinoblastoma patients underwent CT studies performed with high spatial resolution (512 x 512) and 1.5 mm sections, both with enhancement and without enhancement. If the central retinal vessels (CRV) were subjectively visualised with intravenous enhancement, the optic nerve was considered to be free of retinoblastoma. Nineteen enucleated globes were processed for histopathology, and the optic disc and nerve examined with light microscopy for the presence or absence of tumour and the level of involvement. RESULTS: The correlation between the visualisation of CRV and the presence or absence of optic nerve involvement histopathologically was found to be highly significant (p = 0.0006, Fisher exact test). CONCLUSION: In high spatial resolution CT with enhancement and 1.5 mm or thinner sections, non-visualisation of the CRV appears to be a reliable indicator of optic nerve invasion with retinoblastoma.

Child↗