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PubMed1976

Reevaluation of the optic disk vasculature.

The optic disk vessels of owl monkeys and humans were studied in whole mounts injected with silicone rubber and by serial sections of paraffin-embedded tissue. The capillary bed of the optic nerve head in continuous on one side with the retinal vessels and on the other side with the optic nerve behind the globe. The choriocapillaris is a separate capillary bed, even though it and the disk capillaries are both supplied by branches of the posterior ciliary artery. At the junction between choroid and optic disk is a cuff of vessels that seems equivalent to an anterior extension of the pial vessels. This cuff includes capillaries of the central nervous system, was well as arterial branches of the posterior ciliary artery that pass retrograde from the peripapillary choroid and sclera into the pial plexus. While not contradicting previous descriptions of the vascular anatomy in this region, we emphasized that the microvascular bed of the disk is anatomically an integral part of the retina-optic nerve vascular system and deemphasized its relationship to the choroidal vasculature.

Animals↗
PubMed1979

Sudden occlusion of the retinal and posterior choroidal circulations in a youth.

A 14-year-old boy was stabbed above the left eye and had subsequent loss of both retinal and choroidal perfusion to the posterior segment. Ophthalmoscopic examination ten days after the injury disclosed intense nerve fiber layer edema, most prominent in the posterior pole, and absence of a cherry-red spot. Intravenous fluorescein angiography showed no filling of retinal vessels and only patchy, segmental, peripapillary choroidal filling, probably secondary to collateral circulation developing from the episcleral arterial plexus. Leakage of dye from the peripapillary choroid into the overlying retina was caused by ischemic necrosis of the retinal pigment epithelium. Follow-up examination 11 days later revealed marked sclerosis of the smaller arterioles, optic pallor, atrophic retinal pigment epithelial changes, and loss of retinal substance, most marked in the posterior pole.

Adolescent↗
PubMed2001

Retreatment effect of NPe6 photodynamic therapy on the normal primate macula.

PURPOSE: To evaluate the safety and efficacy of repeated photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6) on normal primate fovea and choroid. METHODS: Macaca fuscata monkeys were used as experimental subjects. Mono-L-aspartyl chlorin e6 at a dose of 2 mg/kg was administered by intravenous infusion. Laser irradiation was applied within 5 minutes using a 664-nm diode laser at a power output of 5.9 mW (750 mW/cm2), spot size of 1,000 microm, and time of 10 seconds. This resulted in a fluence of 7.5 J/cm2. Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea and posterior fundus near the arcade vessels of each eye. The animals were killed and the eyes were enucleated for histologic study 2 weeks after the last treatment. RESULTS: Limited changes could be observed in the sensory retina under light microscopy. Photoreceptor cells and outer segments were not damaged, even after repeated PDT. Proliferation and duplication of the retinal pigment epithelial cells were common findings. A plaque of fibrous tissue was present, interwoven with retinal pigment epithelial cells in eyes that received repeated PDT. The retinal vessels remained patent even after three sessions of PDT. However, occlusion of the choriocapillaris and the large choroidal vessels was observed after repeated PDT treatment. CONCLUSION: Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture with damage confined to the retinal pigment epithelium and choriocapillaris.

Animals↗
PubMed1999

Nystagmus mimicking spasmus nutans as the presenting sign of Bardet-Biedl syndrome.

PURPOSE: To investigate the nystagmus of twin brothers presenting with spasmus nutans later diagnosed as Bardet-Biedl syndrome. METHODS: The twins presented at the age of 14 months with a presumed diagnosis of spasmus nutans. They were followed clinically and with quantitative electro-oculographic eye movement recordings until the age of 6 years. RESULTS: Polydactyly, truncal obesity, mild delay in cognitive development, visual acuity of 20/100, attenuated retinal vessels and pale disks, and bilaterally almost extinguished scotopic and photopic electroretinograms were found in both brothers. They had fine, fast, pendular, disconjugate, intermittent, oblique nystagmus. No head nodding was observed. CONCLUSION: As described in patients with other retinal diseases such as achromatopsia and congenital stationary night blindness, nystagmus of patients with Bardet-Biedl syndrome can mimic spasmus nutans.

Bardet-Biedl Syndrome↗
PubMed2005

Ophthalmological manifestations of Fabry disease: a survey of patients at the Royal Melbourne Fabry Disease Treatment Centre.

BACKGROUND: Fabry disease is a rare X-linked inborn error of glycosphingolipid metabolism. The aim of this study was to document the ophthalmological manifestations of patients attending the Royal Melbourne Hospital Fabry disease treatment centre. METHODS: Patients at the treatment centre had full ophthalmological examination performed. This included best corrected visual acuity, ocular motility examination and examination of the adnexae. Patients also underwent slit-lamp examination looking for the presence of features of Fabry disease, particularly examining the bulbar conjunctiva, cornea, lens and fundus. RESULTS: Thirty-four hemizygous male and 32 heterozygous female patients were recruited. The mean age of the hemizygous male patients was 37.7 years (range 18-57 years). The mean age of the heterozygous female patients was 34.6 years (range 1-78 years). Visual acuity was not affected. 97.1% of the hemizygotes and 78.1% of the heterozygotes had vascular abnormalities of the bulbar conjunctiva. Cornea verticillata was noted in 94.1% of the hemizygotes and 71.9% of the heterozygotes. 41.2% of the hemizygotes and 9.4% of the heterozygotes had anterior cataract formation. Posterior lens opacities were observed in 11.8% of the hemizygotes and none of the heterozygotes. Retinal vascular tortuosity was observed in 76.5% of the hemizygotes and 18.8% of the heterozygotes. CONCLUSION: Conjunctival vascular tortuosity was the most common manifestation in this series. Conjunctival and retinal vessel tortuosity, and corneal verticillata are frequently observed in Fabry disease. The incidence of lenticular changes is not consistently reported, but in this series and many others, it is much less common than that of corneal, conjunctival and retinal changes.

Adolescent↗
PubMed2001

Three-dimensional topographic angiography in chorioretinal vascular disease.

PURPOSE: To evaluate a new angiographic technique that offers three-dimensional imaging of chorioretinal vascular diseases. METHODS: Fluorescein (FA) and indocyanine green angiography (ICGA) were performed using a confocal scanning laser ophthalmoscope. Tomographic series with 32 images per set were taken over a depth of 4 mm at an image frequency of 20 Hz. An axial analysis was performed for each x/y position to determine the fluorescence distribution along the z-axis. The location of the onset of fluorescence at a defined threshold intensity was identified and a depth profile was generated. The overall results of fluorescence topography were displayed in a gray scale-coded image and three-dimensional relief. RESULTS: Topographic angiography delineated the choriocapillary surface covering the posterior pole with exposed larger retinal vessels. Superficial masking of fluorescence by hemorrhage or absorbing fluid did not preclude detection of underlying diseases. Choroidal neovascularization (CNV) appeared as a vascular formation with distinct configuration and prominence. Chorioretinal infiltrates exhibited perfusion defects with dye pooling. Retinal pigment epithelium detachments (PEDs) demonstrated dynamic filling mechanisms. Intraretinal extravasation in retinal vascular disease was detected within a well-demarcated area with prominent retinal thickening. CONCLUSIONS: Confocal topographic angiography allows high-resolution three-dimensional imaging of chorioretinal vascular and exudative diseases. Structural vascular changes (e.g., proliferation) are detected in respect to location and size. Dynamic processes (e.g., perfusion defects, extravasation, and barrier dysfunction) are clearly identified and may be quantified. Topographic angiography is a promising technique in the diagnosis, therapeutic evaluation, and pathophysiological evaluation of macular disease.

Choroid↗
PubMed2001

Retinal vasculitis associated with chickenpox.

PURPOSE: To report retinal vasculitis in a young, immunocompetent Asian female adult with chickenpox. METHODS: Interventional case report. A 32-year-old woman had chickenpox 2 weeks before blurred vision in the left eye. The visual acuity was 20/20 for the right eye and 30/50 for the left eye. The left eye presented keratic precipitates, moderate (2+) cells in the anterior chamber and numerous cells (3+) in the vitreous. The disk was normal. Perivenous exudation was noted mainly in the inferior retina. The sheathed retinal vessels showed late staining but no remarkable leakage on fluorescein angiography. The right eye was normal. RESULTS: After treatment with acyclovir for 10 days, the visual acuity in the left eye improved to 20/20, and the vasculitis resolved. CONCLUSION: Retinal vasculitis may present as a complication of primary varicella infection in an immunocompetent adult.

Acyclovir↗
PubMed1997

Insulin-like growth factor-1 retinal microangiopathy in the pig eye.

OBJECTIVE: Human recombinant insulin-like growth factor-1 (hrIGF-1), a ubiquitous angiogenic growth factor, was injected into the vitreous cavity of pigs to investigate the clinical and histopathologic consequences of supraphysiologic levels of this angiogenic growth factor on the retinal vasculature. DESIGN: Young male pigs were injected with 600 microg hrIGF-1 into the vitreous cavity and were observed with serial examinations by ophthalmoscopy, fundus photography, and fluorescein angiography for varying periods up to 6 months. In a separate set of experiments, a dose-response relation was explored in animals injected with varying doses of IGF-1. MAIN OUTCOME MEASURES: Histopathologic analysis included light and transmission electron microscopy and modified elastase digestion. Quantitative morphometric measurements were made of capillary basement membrane thickness and endothelial cell and pericyte densities of the retinal capillaries. RESULTS: Early clinical features of IGF-1-injected eyes included marked arteriolar tortuosity, vitreitis, and retinal vessel and optic nerve head vascular fluorescein leakage. By 4 weeks, hyperfluorescent dots consistent with microaneurysms appeared and increased in number until 8 weeks postinjection. Clinical findings did not change appreciably after 8 weeks. Elastase digestion showed microaneurysms of the retinal capillaries and no ischemia or pericyte ghosts. Quantitative analysis of the digested specimens showed increased endothelial density by 1 month after injection (P < 0.05). Transmission electron microscopic cross-sections of capillaries showed significant basement membrane thickening by 3 months (P < 0.05). Lower doses of IGF-1 showed fewer clinical and histopathologic changes, and no significant changes were noted with a single 6 microg injection. Suspending hrIGF-1 in acidic buffer produced less intraocular inflammation than use of bovine serum albumin at neutral pH. CONCLUSIONS: A single intravitreous injection of a large dose of hrIGF-1 produces a retinal microangiopathy that has a prolonged time of onset and remains stable from 2 to 6 months after injection. Some aspects of this angiopathy resemble diabetic retinopathy, suggesting growth factor effects in the morphologic vascular changes of diabetes.

Animals↗
PubMed1998

Increases in retinovascular prostaglandin receptor functions by cyclooxygenase-1 and -2 inhibition.

PURPOSE: To determine the relative contribution of cyclooxygenase (COX)-1 and COX-2 in regulating prostaglandin (PG) E2 and PGF2alpha receptors (EP and FP, respectively) densities and their functions in retinal vasculature of neonatal pigs. METHODS: Newborn pigs were treated intravenously every 8 hours for 48 hours with saline, 40 mg/kg nonselective COX inhibitor ibuprofen, 80 mg/kg COX-1 inhibitor valeryl salicylate, or 5 mg/kg DuP697 and 5 mg/kg NS398, COX-2 inhibitors. Retinal microvessel EP and FP receptor densities were measured by radioligand binding and receptor-coupled effects by determining second-messenger inositol 1,4,5-trisphosphate (IP3) and vasomotor responses. Retinal blood flow (RBF) response to incremental increases in blood pressure (BP) was measured by a microsphere technique. RESULTS: Valeryl salicylate, DuP697, and NS398 reduced retinal PGE2 and PGF2alpha concentrations in the newborn by approximately half, whereas ibuprofen caused further reduction to levels observed in adults. Retinal vessel EP1, EP3, and FP receptor densities increased approximately threefold after treatments with COX-1 or COX-2 inhibitors, and five- to sixfold after ibuprofen treatment. EP and FP receptor upregulation was associated with corresponding increases in IP3 production and retinal vasoconstriction in response to PGF2alpha, fenprostalene (an FP agonist), PGE2, 17-phenyl trinor PGE2 (an EP1 agonist), and M&B28,767 (an EP3 agonist) and with enhanced RBF autoregulation of high BP (> or =125 mm Hg). Conversely, EP2 receptor density and coupled functions were minimally affected by COX inhibition. CONCLUSIONS: Data suggest that increased COX-1- and COX-2-catalyzed prostaglandin synthesis contribute equivalently to the downregulation of retinovascular EP1, EP3, and FP receptors and their vasoconstrictor functions in newborn pigs; the EP2 receptor was not significantly influenced by ontogenic alterations in prostaglandin levels.

Animals↗
PubMed2006

Congenital macular macrovessels.

BACKGROUND: Congenital aberrant macular vessels are rare and may cause visual impairment when crossing the fovea, when causing the formation of foveolar cysts, or when haemorrhage occurs. METHODS: From the records of patients with vascular anomalies seen at the Retina Department of the University Federico II in Naples from 1980 to 2005, we reviewed all cases presenting an abnormal, large, retinal vessel crossing the macular region. RESULTS: An anomalous macular macrovessel was present in 13 cases. Follow-up ranged from 3 months to 21 years (mean 14 years). In all cases the abnormal vessel was a vein, presenting a fluoroangiographic early filling and delayed emptying. In some cases there were microvascular bed anomalies, such as enlargement of the foveal avascular zone, focal capillary dilation, or microaneurysmal abnormalities. In one case late, mild, intraretinal staining along the anomalous vessel indicated retinal oedema. Visual impairment occurred in five eyes, being caused by a preretinal haemorrhage in one case and by the mere presence of the macrovessel in the foveal area in four cases, and had not improved at following controls. CONCLUSION: In the presence of an aberrant vessel crossing the macular region, visual acuity and ophthalmoscopic and fluoroangiographic findings tend to have remained stable at long-term follow-up.

Adolescent↗
PubMed1991

Factors determining the migration of astrocytes into the developing retina: migration does not depend on intact axons or patent vessels.

Astrocytes migrate into the cat retina from the optic nerve, beginning from embryonic day (E) 52. Once they have entered the retina they concentrate along major axon bundles and fail to enter regions of the retina with high densities of neurones, in particular the area centralis region of the ganglion cell layer. These nonuniformities appear as the astrocytes spread over the retina during development, and in this study we have examined factors that might control their spread. First we examined astrocytes in a retina in which the axon bundles had degenerated following an optic nerve lesion at birth. The area over which astrocytes had spread was normal, suggesting that their spread does not depend on the presence of intact axons. Second, we noted that, despite the degeneration of all ganglion cells following the nerve lesion, astrocytes still did not spread over the area centralis. Their spread is apparently not inhibited by concentrations of neurones. Third, we examined astrocytes in retinas of animals raised in an atmosphere containing 70-80% oxygen, which prevents the formation of retinal vessels. Again, the area over which the astrocytes had spread was normal, suggesting that their spread does not depend on the presence of patent blood vessels. These negative findings led us to compare the distribution of spindle cells (precursors of retinal vasculature) and astrocytes in the cat during development. The close correspondence in their topographical distribution and the earlier spread of the spindle cells lead us to suggest that spindle cells provide a basal lamina component that may guide the migration of astrocytes.

Animals↗
PubMed1995

Retinal and choroidal blood flow response to hyperoxemia after severe hypoxemia in the newborn piglet.

To investigate the effect of hyperoxemia on the ocular circulation after a severe hypoxemic insult (8% O2 until base excess reached -20 mmol/l), we randomly reoxygenated newborn piglets with 100% (study group, n = 8) or 21% O2 (control group, n = 10). Retinal (RBF) and choroidal blood flow (ChBF) were measured with radioactive microspheres. The hypoxemic insult did not change RBF, while ChBF significantly decreased. However, a marked reduction in both retinal (RDO2) and choroidal oxygen delivery (ChDO2) was observed, probably resulting in hypoxia both in the inner and outer retina. At 5 and 20 min of reoxygenation a similar hyperemic response in the retina was seen in both groups. RDO2 also increased significantly and no significant differences between the 2 groups could be demonstrated. We found no indication of retinal vasoconstriction during hyperoxemia. We speculate that the vasodilating effect of the preceding hypoxemia overrules the vasoconstrictive effect of the retinal vessels normally found during hyperoxemia.

Animals↗
PubMed1988

Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography.

To observe microembolic events in the central nervous system during cardiopulmonary bypass, we subjected 21 patients undergoing elective coronary operations to retinal fluorescein angiograms 5 minutes before cardiopulmonary bypass was discontinued. Patients with diabetes or clinically evident cerebrovascular disease were excluded. Bubble oxygenation and nonpulsatile perfusion were used for bypass. After 31 to 167 minutes of cardiopulmonary bypass, all 21 (100%) patients had retinal microvascular occlusions indicative of microembolism. Control fluorescein angiograms obtained preoperatively and in five patients immediately before bypass but after aortic cannulation showed retinal perfusion. During bypass there was a mean of 3.5 (range 1 to 7) blocked arterioles of less than 50 micron caliber and a mean of 6.3 (range 1 to 10) focal areas of capillary nonperfusion per 30-degree field of retina centered on the macula per patient. Repeat studies 30 minutes after discontinuation of bypass showed partial reperfusion with occlusions in four of the five (80%) patients and a decrease in the mean total microembolic count from 12.6 to 4.8 (38%). In later studies at a median of 8 days postoperatively, only two of 16 (12.5%) patients had persistently occluded retinal vessels. The total microembolic count did not correlate with bypass time (r = 0.14) and was not reduced by arterial line filtration with a Pall 40 micron filter (Ultipore) in a subgroup of 11 patients. Twenty patients completed four standardized psychometric tests. Retinal microvascular occlusions were more numerous in those patients with a psychometric deficit (n = 7) than in those with no deficit (n = 13; p = 0.075). In a dog model of cardiopulmonary bypass, eight of nine (88.9%) had retinal microvascular occlusions after 10 to 90 minutes of bypass. Retinal histologic studies revealed intravascular platelet-fibrin microaggregates 20 to 70 micron in diameter and focal ischemic changes in seven of the nine (77.8%) dogs. Six dogs undergoing sham bypass had normal retinal perfusion and histologic findings. This study demonstrates a very high incidence of microvascular occlusions in the territory of the internal carotid artery during bypass consistent with a microembolic origin. The clinical significance of these findings is uncertain.

Animals↗
PubMed2000

Optical and visual impact of tear break-up in human eyes.

PURPOSE: The purpose of this study was to examine the optical and visual impact of tear break-up. METHODS: Optical quality of the eye was assessed during periods of nonblinking by quantifying vessel contrast in the fundus image and by monitoring the psychophysical contrast sensitivity and the spatial distribution of tear thickness changes by retroillumination. All measures were obtained from three eyes either with or without a soft contact lens. RESULTS: A noticeable decrease in retinal vessel contrast and contrast sensitivity were observed soon after a blink. Both of these measures of optical quality of the eye showed a similar pattern of image degradation both with and without a soft contact lens. Although trial-to-trial variability was considerable, sample means show that image contrast in the low spatial frequency range can drop to between 20% and 40% of initial values after 60 seconds of nonblinking. Retroillumination of the tear film showed local intensity fluctuations that progressively spread across the pupil with increasing time after the blink. CONCLUSIONS: Optical aberrations created by tear break-up contribute to the decline in image quality observed objectively and psychophysically. The decline in image quality that accompanies tear break-up may be a direct cause of the blurry vision complaints commonly encountered in dry-eye patients.

Adult↗
PubMed1980

[Unusual ophthalmic findings in a case of Niemann-Pick disease (author's transl)].

Case report on a woman patient who, although not Jewish, is suffering from Niemann-Pick disease. At the time of publication she is 55 years old, although this disease usually proves lethal in early childhood. Related atypical ocular changes were diagnosed, such as tortuosity of the retinal vessels and a conjunctival affection, which was demonstrated histologically.

Age Factors↗
PubMed2002

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.

Animals↗
PubMed1985

Multiple cotton wool spots following bone marrow transplantation for treatment of acute lymphatic leukaemia.

Three patients with acute lymphatic leukaemia developed visual impairment due to occlusion of small retinal vessels with multiple cotton wool spots after treatment which included whole body and skull irradiation followed by bone marrow transplantation and cyclosporin A. Withdrawal of cyclosporin A and treatment with corticosteroids was followed by recovery of visual acuity. This retinopathy and the retinal changes seen in the immunodeficiency syndrome are thought to be closely related. The possible role of cyclosporin A is discussed, though cotton wool spots and retinal haemorrhages have never been described in renal transplant patients during treatment with this drug. Withdrawal of cyclosporin A, which is highly effective in preventing graft-versus-host disease, can be fatal. Irradiation of the skull prior to bone marrow transplantation and intrathecal administration of methotrexate may be the most important factors causing the retinal ischaemic signs described here. The inclusion of an ophthalmologist in the team monitoring transplant patients would lead to increased documentation and a better understanding of this disease.

Adult↗