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PubMed1993

[Effects of intravitreal injection of endothelin on the visual system].

Endothelin, a novel, potent, and long-acting vasoconstrictor peptide, is thought to regulate retinal circulation and its autoregulation. A disturbance in the regulation of endothelin production might contribute to the pathogenesis of retinochoroidal or optic nerve diseases. We examined the effects of endothelin on the retina and the optic nerve using the electroretinogram (ERG) and visual evoked potential (VEP). Six male albino rabbits underwent intravitreal injection of 0.1 ml (10(-5) mol/l) endothelin-1 in the right eye. Six other male albino rabbits, which were injected intravitreally with 0.1 ml of Opeguard-MA in the right eye, were used as controls. Endothelin-1 caused marked constriction of retinal vessels and pallor of the optic nerve head. These findings persisted for 10 days after endothelin-1 injection. The amplitude of the b-wave and the latency of the oscillatory potential in the ERG were not significantly different from those in controls. On the other hand, prolongation of the VEP-N1 latency was observed for 14 days after the injection. These results indicate that endothelin acts on the circulation of the optic nerve head rather than that of the retina, and that effects persist for a relatively long period.

Animals↗
PubMed1983

Retinal vascular endothelial cells and pericytes. Differential growth characteristics in vitro.

Long-term cultures of retinal capillary endothelial cells (RCEC) and of pericytes were grown from collagenase-treated calf retinal vessels. By the use of mechanical separation and differential growth response in various media, pure cell lines were derived from cloned capillary cells as well as from multiple vessel fragments. RCEC and pericytes appeared different under phase contrast microscopy. In addition, RCEC produced factor VIII antigen and angiotensin-converting enzyme, and pericytes did not. RCEC preferred to grow in tumor-conditioned medium, whereas pericytes preferred a standard tissue culture medium supplemented with calf serum. Extracellular matrix, together with tubular structures, developed in postconfluent RCEC but not in pericytes. This study demonstrates that it is possible to grow long-term, pure cultures of RCEC and of pericytes that possess distinctive morphology, growth, and synthetic capabilities in vitro.

Animals↗
PubMedDate not supplied

Type a syndrome of insulin resistance: anterior chamber anomalies of the eye and effects of insulin-like growth factor-I on the retina.

BACKGROUND: The purpose of this work was to describe the anterior chamber and iris anomalies as well as to evaluate the effects of recombinant human insulin-like growth factor-I (rhIGF-I) on the retinal vessels in 2 diabetic patients with type A syndrome of insulin resistance, a rare condition associated with acanthosis nigricans. METHODS: Ophthalmologic examinations, including photographs and fluorescein angiograms, were performed before, and 2 and 4 weeks after starting subcutaneous rhIGF-I treatment, and 3 months after withdrawal of rhIGF-I treatment. RESULTS: Both patients had goniodysgenesis with mild elevation of the intraocular pressure. Before and after 2 weeks of treatment with rhIGF-I, the fundus and the fluorescein angiograms were mainly normal. After 4 weeks of rhIGF-I treatment both patients' retinas revealed leakage of fluorescein. Three (case 1) and 4 months (case 2) after withdrawal of rhIGF-I, the fundus of all four eyes were again without leakage. CONCLUSIONS: The anterior chamber anomalies found in these patients may be part of the type A syndrome of insulin resistance and could alert clinicians that these patients might not have the usual type of diabetes. Moreover, the data show that exogenous rhIGF-I administration in patients with type A syndrome of insulin resistance alters the permeability of the superficial layer of retinal capillaries which is comparable to the earliest angiographic changes in childhood diabetic retinopathy. Whether this is a direct effect of rhIGF-I, as suggested by experiments in an animal model, or an indirect effect due to the near-normalization of the glucose levels by rhIGF-I warrants further investigations. Finally, this work points to an important caveat regarding the therapeutic use of rhIGF-I in this patient population.

Acanthosis Nigricans↗
PubMedDate not supplied

Altered endothelial/pericyte ratio in Goto-Kakizaki rat retina.

The Goto-Kakizaki (GK) rat represents a model of hereditary non-insulin-dependent diabetes mellitus (NIDDM), characterized by nonobesity, mild hyperglycemia from early life, impaired glucose tolerance test results, and a markedly defective insulin response to glucose. The rats develop signs of both nephropathy and neuropathy, but, to our knowledge, retinal changes have not been reported so far in this model of NIDDM. Hence, the aim of the present study was to assess whether morphological vascular changes could be demonstrated in retinal vessel preparations of GK rats. The endothelial/pericyte ratio was found to be higher in GK rats aged 8 months as well as after 24-30 months compared to their matched controls (2.3 +/- 0.2 versus 2.0 +/- 0.1; p < 0.01, and 2.6 +/- 0.2 versus 1.9 +/- 0.1; p < 0.001, respectively). Furthermore, in 24 to 30-months-old GK rats, the endothelial/pericyte ratio was higher than in 8 month old GK rats (p < 0.05). Thus, the GK rat appears to be a suitable model for experimental studies of chronic complications, including diabetic retinopathy, in NIDDM.

Age Factors↗
PubMed1976

The central vascular pattern of the eyeground in children with drusen of the optic disk.

In a series of 50 children with optic disk drusen the anomaly was found to be associated with unusual properties. A cilioretinal artery was more frequent in the series with drusen than in a control series of the same age. The emergence and course of the central retinal vessels were studied in the right-sided fundi of 46 of the children and in two control series (the fundi of the "better" eyes of 46 strabismic children and the fundi of one of the eyes of 10 children or young adults with papilledema). Analysis of the measurements indicated that early branching of the central vessels and vascular tortuosity are so frequently associated with optic disk drusen that they can be considered features of the anomaly. On the other hand, the fundal vascular features in papilledema seem to be distinguishable by the method used from those associated with optic disk drusen. When the peripapillary choroidal vascular pattern was studied by fluorescein angiography, choriocapillaris filling was delayed in about the half of the angiograms. The aberrant vascular features found on and around optic disks with drusen can be explained by an embryonic affection of the developing vascular system at the optic nerve head. In this respect the anomaly seems to resemble congenital disorders of mesodermal origin.

Adolescent↗
PubMed2005

Severe ocular involvement in disseminated intravascular coagulation complicating meningococcaemia.

BACKGROUND: Disseminated intravascular coagulation (DIC) is characterized by inappropriate widespread activation of coagulation leading to extensive microvascular thrombosis and haemorrhage. Ocular involvement typically manifests as fibrin-platelet clots in the choroidal vessels of the posterior pole with overlying serous retinal detachment and sparing of the retinal vessels. METHODS: Case report. RESULTS: An 18-year-old female with meningococcal septicaemia and DIC developed bilateral dense vitreous haemorrhage. At vitrectomy multiple areas of sub-internal limiting membrane haemorrhage were evacuated and silicone oil injected. The patient developed bilateral large macular holes with inferior tractional retinal detachment. Two years later, final visual acuity was 6/36 OD and count fingers OS. CONCLUSION: Ocular involvement in DIC can be more extensive than choroidal vascular occlusion alone. Previous reports suggest that DIC associated with sepsis (especially meningococcaemia) may present with more severe manifestations. This may be due to sub-clinical endophthalmitis or haemorrhagic ischemia. Visual prognosis can be poor.

Adolescent↗
PubMed1983

Ophthalmoscopic findings in Leber's hereditary optic neuropathy. II. The fundus findings in the affected family members.

Eighteen men and four women had Leber's disease. Fundus photographs obtained in three cases showed the following: Peripapillary microangiopathy, present from the beginning, slowly increased during the presymptomatic stage. At the end of the presymptomatic stage, the nerve fiber layer became swollen. During the acute stage, retinal vessels on and around the disc were dilated, tortuous, and telangiectatic. Nerve fiber layer hemorrhages occurred in two eyes. As atrophy appeared first in the papillomacular bundle and then in the remaining retina, the vascular bed involuted, leaving a capillary-poor retina with attenuated arterioles and a pale optic disc. The final degree of atrophy varied. Fifteen of the affected persons were blind with severe optic atrophy, but in seven optic atrophy was only partial, causing less visual handicap. Our results suggest that Leber's disease is primarily an intraocular, not a retrobulbar, optic neuropathy. It should be redesignated as Leber's hereditary neuroretinopathy.

Adolescent↗
PubMed1998

Expression of vascular endothelial growth factor and its receptor, KDR, following retinal ischemia-reperfusion injury in the rat.

PURPOSE: There is considerable evidence that vascular endothelial growth factor (VEGF) mediates ocular neovascularization in retinal vascular diseases. We investigated the time-dependent changes in the expression of VEGF and its receptor KDR/ Flk in a transient retinal ischemia-reperfusion injury model. METHODS: Transient retinal ischemia was induced by increasing the intraocular pressure in albino rats eyes for 45 min. In situ hybridization was used to identify the retinal cells synthesizing VEGF mRNA and KDR mRNA at various times following reperfusion. Immunohistochemical analysis was also carried out to detect VEGF immunoreactivity. RESULTS: In the control, non-ischemic retinas, signals for VEGF mRNA and KDR mRNA were observed in the cells of the ganglion cell layer. Immunoreactivity to VEGF was also found in the nerve fiber layer, the ganglion cell layer, and the retinal pigment epithelial (RPE) cell layer. Immediately and 6 h after reperfusion, VEGF and KDR mRNA expression was markedly decreased, but recovered by 24 h to the levels observed in normal retinas. Immunoreactivity for VEGF was also decreased immediately and 6 h after reperfusion, and was detected in the endothelial cells of the retinal vessels after 24 h. Immunoreactivity to VEGF recovered by 48 h after reperfusion. CONCLUSIONS: The hybridization pattern of VEGF and KDR mRNA in the ganglion cell layer strongly suggests that the ganglion cells are the major source of this growth factor. The decrease of VEGF mRNA, KDR/Flk mRNA and VEGF protein levels after ischemia and recovery after reperfusion suggest that transient hypoxia might mediate short-term down-regulation of VEGF and KDR mRNA.

Animals↗
PubMed2003

The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration.

AIM: To comprehensively evaluate the effects of dorzolamide on the choroidal and retinal circulation in patients with age related macular degeneration (AMD). METHODS: In this randomised, double masked, parallel study, 36 non-exudative AMD patients were randomised in a 2 to 1 fashion to placebo versus topical dorzolamide and underwent assessment of their choroidal and retinal circulation. Scanning laser ophthalmoscope indocyanine green angiograms (ICGA) were analysed by a new area dilution analysis technique. Four areas in the perifoveal region and two areas in the temporal peripapillary region were evaluated by plotting intensity of fluorescence of each area over time. The means of the choroidal filling times and the heterogeneity of the filling times were assessed. Scanning laser ophthalmoscope fluorescein angiography (FA) was evaluated for retinal arteriovenous passage (AVP) times by plotting intensity of fluorescence of retinal vessels over time. Assessment was performed at baseline and at 4 months. RESULTS: Compared to placebo, AMD patients treated with dorzolamide showed a significantly increased rapidity of choroidal filling in the superior and inferior peripapillary regions (p=0.007, p=0.02, respectively). No significant difference in choroidal filling times was found in any of the perifoveal areas (p=0.9). Also, on FA assessment, treatment with dorzolamide showed no statistical differences in AVP times (p=0.19). CONCLUSIONS: Dorzolamide may increase peripapillary choroidal perfusion in non-exudative AMD patients. Further studies are merited.

Aged↗
PubMed1975

The role of oxygen in retrolental fibroplasia.

The effects of oxygen in the immature or incompletely vascularized retina are conveniently divided into an initial vasoconstrictive and obliterative stage and a secondary vasoproliferative response that occurs after removal of the subject from an enriched oxygen environment. Vasoproliferation starts at the zone of perfused and nonperfused retina. The incompletely vascularized retina is uniquely responsive to these oxygen-induced changes. After vascularization is complete and the retinal vessels reach the ora, the susceptibility to hyperoxia disappears. The vessels in the temporal periphery of the retina have a peculiar susceptibility to the primary and secondary effects of hyperoxia on the immature retina. Ophthalmoscopic examination of the temporal periphery therefore should always be done carefully in the premature infant or in older individuals giving a history of prematurity. The indirect ophthalmoscope provides the most satisfactory instrument for examination. The incidence of retrolental fibroplasia has been greatly reduced following the incrimination of oxygen as its principal cause. Further studies are still required to determine precise blood oxygen levels that are safe for the premature retina and to discover other factors that may play a role in the pathogenesis or RLF.

Animals↗
PubMed1992

Degeneration of astrocytes in feline retinopathy of prematurity causes failure of the blood-retinal barrier.

This study addresses the role of astrocytes in the genesis of retinopathy of prematurity, examined in the feline model of this condition. Evidence is presented that the hypoxia of retinopathy of prematurity, in addition to inducing vasoproliferation, damages the retina directly. Retinal neurons survive the hypoxia, but the astrocytes, which are involved in the formation of the glia limitans of the retinal vessels, degenerate. Astrocytes subsequently recolonize the retina after a delay that matches the period of leakiness of the proliferative vasculature (described in the companion article). Given the evidence from other studies that the barrier properties of vessels are induced by their glia limitans, the authors suggest that the initial lack of barrier properties in the new vasculature is caused by the degeneration of astrocytes and that the subsequent formation of those properties is induced by the astrocytes that recolonize the retina some days later. The observation that astrocytes are more sensitive to hypoxia than neurons, at least in developing tissue, was unexpected. The literature reporting on the damage caused to central nervous tissue by hypoxia is consistent in assessing neurons as more sensitive and glial changes as a reaction to neuronal damage. The sensitivity of astrocytes found in this study and earlier in vitro research suggests that degenerated astrocytes can be replaced and their structural and functional relationships reestablished.

Animals↗
PubMed1991

Isoxsuprine in nonproliferative diabetic retinopathy: effect on human retinal circulation assessed by fluorescein angiography--a pilot study.

The retinal vessel filling time of 10 patients with early nonproliferative diabetic retinography was measured by fluorescein angiography. Initially, the reproducibility of the authors' standardized fluorescein angiography was assessed by control angiograms on two different dates in each patient. Thereafter, prolonged use (six months) of isoxsuprine sustained release (80 mg/day) led to a nearly 50% reduction of the arterial filling time and a nearly 25% reduction of the arteriovenous filling time, whereas no changes were seen in control patients. This effect of isoxsuprine might be explained by an increase of red cell deformability and, concomitantly, a decrease of platelet adherence in the microcirculation of patients with diabetic mellitus.

Adult↗
PubMed2001

Ocular complications of paediatric patients with nephrotic syndrome.

PURPOSE: To investigate ocular complications arising from nephrotic syndrome and/or its treatments in children. METHODS: A cross-sectional study was conducted in a teaching hospital. A total of 31 paediatric patients with nephrotic syndrome were studied. Comprehensive ophthalmic assessments on best-corrected visual acuity, intraocular pressure, slit-lamp and fundus examination were taken. Information regarding histological diagnosis of nephrotic syndrome and its treatment regimen in each patient was reviewed and analysed. RESULTS: Bilateral posterior subcapsular cataracts were detected in three of 29 patients (10.3%) who received steroid therapy. Two had normal vision while one had visual acuity reduced to 6/15 in both eyes. The age of onset of the nephrotic syndrome in these three patients was 2 years, which was significantly younger than those without cataract (5.4 +/- 3.2 years, P < 0.001). Three patients (9.7%) had isolated asymptomatic fundal findings of tortuous and dilated retinal vessels. Hypertensive retinopathy was found in one patient (3.2%). No steroid-induced glaucoma, uveitis, ocular infection, or other eye complications related to the use of steroids or other immunosuppressive agents were noted. CONCLUSIONS: Children who have nephrotic syndrome often require prolonged, intermittent high dose of systemic corticosteroid therapy. Paediatricians should be aware of the potential risk of developing steroid-related complications, especially posterior subcapsular cataract. It appears to have a higher risk when steroid therapy is used in very young patients. Early detection would help to prevent amblyopia development, particularly in the group of immature eyes.

Adolescent↗
PubMed2003

The effect of arteriovenous sheathotomy on cystoid macular oedema secondary to branch retinal vein occlusion.

BACKGROUND: Arteriovenous (AV) sheathotomy, a potential treatment for branch retinal vein occlusion (BVO), surgically separates retinal vessels at an AV crossing. Relief of the aetiological obstruction, with resolution of cystoid macular oedema (CMO), may result in improved visual acuity. METHODS: A retrospective review of consecutive cases of AV sheathotomy for BVO was undertaken. Eyes were categorised as having resolution (group 1), reduction (group 2), or persistence (group 3) of CMO. Intergroup comparisons were made with regard to preoperative, intraoperative, and postoperative parameters. Preoperative and postoperative visual acuities were compared within each group. RESULTS: Of the 27 eyes identified, eight (29.6%) had resolution, 14 (51.8%) had reduction, and five (18.6%) had persistence of CMO. Median preoperative visual acuity was similar in all groups (1.0, 1.0, 1.3, respectively; p = 0.29). Overall median follow up was 12.0 months (Q1 = 12.0, Q2 = 22.5). Eyes in group 1 had significantly better median postoperative visual acuity than eyes in groups 2 and 3 (0.6, 1.0, 2.0 respectively; p = 0.01). A significantly higher proportion of eyes in group 1 had visual acuity improvement compared with eyes in the other groups (87.5% v 35.7% and 20.0%; p = 0.03). Median postoperative visual acuity was significantly better than median preoperative visual acuity in group 1 eyes only (p = 0.02). A higher percentage of group 1 eyes had evidence of postoperative retinal perfusion (83.0% v 21.43% and 40.0%; p = 0.16). Postoperative retinal detachment occurred in three eyes (11.1%). CONCLUSION: Complete resolution of CMO after AV sheathotomy occurred in one third of patients, and postoperative vision improved significantly in this group. However, in the majority of cases, despite an improvement in CMO, there was no improvement in vision after AV sheathotomy.

Aged↗
PubMed1997

Fluorescein angiography of peripheral retina and pars plana during vitrectomy for proliferative diabetic retinopathy.

PURPOSE: To evaluate the extreme peripheral retina and pars plana during vitrectomy in patients with proliferative diabetic retinopathy. METHODS: In a prospective study using a modified ophthalmic endoscopic system and an intraocular light source, we performed fluorescein angiography during pars plana vitrectomy in 12 eyes of 10 patients with proliferative diabetic retinopathy. Vitrectomy had been performed previously in two patients, and the subsequent surgery was necessary because of recurrent vitreous hemorrhage in one patient and silicone oil removal in the other. RESULTS: All 12 eyes of 10 patients demonstrated a wide avascular area in the peripheral retina anterior to the previous photocoagulation scar. At the ora serrata in two eyes, a fibrovascular ridge of peripheral retinal vessels with fluorescein leakage that resembled the demarcation line in retinopathy of prematurity was noted; one eye had developed neovascular glaucoma 4 weeks after vitrectomy with maximum augmentation of endolaser photocoagulation, and the other eye had neovascular glaucoma that had been treated with photocoagulation 1 year before vitrectomy. In the two eyes that had undergone previous pars plana vitrectomy, fluorescein leakage was apparent at the fibrous scar of the sclerotomy site. CONCLUSION: Intraoperative fluorescein angiography using an endoscope disclosed unusual findings in the extreme peripheral retina and pars plana of patients with proliferative diabetic retinopathy. Intraoperative fluorescein angiography may aid intraoperative evaluation and treatment of proliferative diabetic retinopathy.

Adult↗
PubMed1993

Uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis in the Lewis rat: an ultrastructural study.

The histopathological features of uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis (EAE) were investigated using light and electron microscopy. Lewis rats were immunized by spinal cord homogenate, complete Freund's adjuvant and Bordetella pertussis. The eyes of rats with EAE exhibited vasculitis in the iris, trabeculitis and endothelial abnormalities in the retinal vessels; vasculitis was observed in the optic nerve and brain. Endothelial cells in the vessels in the iris, retina, optic nerve and central nervous system were noted to be elevated (high endothelial-like venules, or HELV). Inflammatory cells in the vascular lumen were attached to the surface of endothelial cells in abnormal areas in the iris. By comparison with the findings in the iris and retina, there were no significant changes in the vessels of the ciliary body and choroid. The ultrastructural features indicated that anterior uveitis in acute EAE resulted from vasculitis in the iris due to changes of the endothelial cells and was not due to a reaction against the myelinated nerves or any other particular components of the iris. In addition, our results suggested that vasculitis in the iris was consequent upon specialized changes of the endothelial cells similar to HELV which were responsible for the transcellular emigration of lymphocytes in other inflammatory diseases or in experimental models. HELV change plays an important role in the perivascular inflammatory process in the iris, retina, optic nerve and central nervous system in EAE and possibly in multiple sclerosis.

Animals↗
PubMed1999

Angioscotoma detection with fundus-oriented perimetry. A study with dark and bright stimuli of different sizes.

Fundus-oriented perimetry (FOP) was used to evaluate the effectiveness of different-sized bright and dark stimuli in detecting and quantitatively measuring angioscotoma. The foveolas and optic disks of digitized fundus images were aligned with their psychophysical counterparts to construct individual grids of perimetric stimuli. Each grid included a linear set of test point locations crossing a retinal vessel. Angioscotomas immediately became visible in nine of 13 healthy normal volunteers tested with FOP. Additional mathematical processing of local loss of differential light sensitivity (dls) disclosed an angioscotoma for at least one stimulus condition in all persons tested. The angioscomas were usually deeper for small (12) targets than for large (32') ones. On the other hand, the overall noise at dls thresholds was generally higher for small than for large stimuli regardless of whether the stimuli were bright or dark. No noteworthy differences were found in detection rates or signal-to-noise ratios under different stimulus conditions (dark/bright/small/large). FOP permits the individual arrangement of stimuli for specific morphological conditions and is thus capable of detecting even minute visual field defects such as angioscotomas.

Adult↗
PubMed1989

["Morning glory syndrome" and "Handmann's anomaly" in congenital macropapilla. Extreme variants of "confluent optic pits"?].

Seventeen optic disks with morning glory syndrome were measured in absolute and relative size units (millimeters and parapapillary retinal vessel caliber) in 5 and 12 eyes, respectively. Their respective mean areas were 7.47 +/- 2.63 mm2 and 7.84 +/- 4.96 mm2. They were significantly (Mann-Whitney test) larger than 457 unselected normal optic nerve heads (2.69 +/- 0.70 mm2; p less than 0.0001) and 15 optic disks with pits (4.84 +/- 1.42 mm2; p less than 0.001). They are the largest optic nerve heads, probably with constant postnatal size, measured so far, and form part of a spectrum of optic disk anomalies and diseases whose frequency correlates with the size of the optic disk. This spectrum includes abnormally small optic nerve heads with increased prevalence of drusen, pseudopapilledema and nonarteritic anterior ischemic optic neuropathy, asymptomatic macrodisks with physiologic, "pseudoglaucomatous" macrocups, symptomatic macrodisks with pits and, finally, optic nerve heads with morning glory syndrome. The last-mentioned may be considered an extreme variation of optic disks with pits which have combined to form a single macropit covering the entire optic nerve head.

Fluorescein Angiography↗