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Neutrophils and leucocyte adhesion molecules in sickle cell retinopathy.

AIMS: The expression of the adhesion molecules ICAM-1, VCAM-1, and P-selectin, and the distribution and number of polymorphonuclear leucocytes (PMNs) were investigated in sickle cell retinopathy (SCR) and compared to the normal retina. METHODS: Postmortem ocular tissue was obtained from five subjects (16, 21, 28, 40, and 41 years of age) with sickle haemoglobinopathies and from one control subject. Tissue was cryopreserved, and streptavidin peroxidase immunohistochemistry was performed with antibodies against ICAM-1, VCAM-1, and P-selectin. Immunohistochemical reaction product was scored, and PMN numbers were counted in sections stained with non-specific esterase. RESULTS: Increased ICAM-1, VCAM-1, and P-selectin immunoreactivities were observed in sickle cell subjects compared to the control subject. The highest ICAM and P-selectin immunoreactivity was associated with intraretinal vessels adjacent to the preretinal neovascular formation in subjects with proliferative retinopathy. This was not the case with VCAM-1 immunoreactivity, which was highest in intraretinal vessels adjacent to the sea fan when the sea fan was still "in statu nascendi." Fully formed, "older" sea fans had the highest levels of VCAM-1. The increase in adhesion molecule immunoreactivity was paralleled by an increase in intraretinal PMNs. The number of intraretinal PMNs increased with progression of the disease and the numbers surpassed those in control subjects by threefold. In the sea fan with the greatest VCAM-1 immunoreactivity, there were 20 times more PMNs were observed than in the rest of the retina in the same subject. CONCLUSION: These data suggest that adhesion molecule mediated leucocyte adhesion might play an important part in the vaso-occlusive phase of sickle cell retinopathy and in autoinfarction of sea fan formations.

Adolescent↗

Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate.

BACKGROUND: Lesions resembling those of human retinopathy of prematurity can be provoked in newborn Wistar rats by exposure to an FiO2 of 80% for the first 5 days of life followed by 5 days recovery under room-air conditions. METHODS: We evaluated the effects of moderate hyperbarism (+60.75 kPa, i.e. 455 mmHg or 0.6 atm) and topical administration of 0.25% timolol maleate on oxygen-induced retinopathy (OIR) in this experimental model. RESULTS: OIR (including neovascularization in most cases) was observed in 100% of the retinas of normobaric oxygen-reared ratlings that did not receive timolol. OIR was less frequent in oxygen-reared ratlings treated with hyperbarism (60%) or timolol (65%). Hyperbaric oxygen supplementation combined with timolol treatment during both the hyperoxic and room-air phases reduced the incidence of OIR to 30%. There was no sign of vasoproliferation in any of the retinas from the latter three groups. CONCLUSIONS: The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery.

Administration, Topical↗

A new model of subretinal neovascularization in the rabbit.

PURPOSE: To establish a new model of subretinal neovascularization (SRN) in the rabbit by implanting basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres beneath the retina. METHODS: Basic fibroblast growth factor-impregnated gelatin microspheres were prepared by forming a polyion complex between gelatin and bFGF. The microspheres, containing 2.5 micrograms of bFGF, were injected into the subretinal space of rabbit eyes (n = 29). Control eyes (n = 10) received bFGF-free gelatin microspheres. Eyes were followed up for 3 days to 8 weeks by ophthalmoscopy, photography, fluorescein angiography, light microscopy, and transmission electron microscopy. RESULTS: Twenty of 24 experimental eyes (83%) showed fluorescein leakage from SRN 2 weeks after implantation of the bFGF-impregnated microspheres. This leakage continued for 2 to 6 more weeks. In striking contrast, control eyes showed no fluorescein leakage. Histologic examination revealed SRN in all the experimental eyes but in none of the control eyes. CONCLUSIONS: Subretinal implantation of bFGF-impregnated gelatin microspheres induces reproducible SRN in the rabbit.

Animals↗

Pericytes of newly formed vessels in experimental subretinal neovascularization.

OBJECTIVE: To examine the role of pericytes in the progression of subretinal neovascularization in a primate model. METHODS: Subretinal neovascularization was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 3, 7, 14, and 21 days after photocoagulation and were studied with light and electron microscopy. RESULTS: Three days after photocoagulation, newly formed vessels were observed in the choroid and subretinal space. Although most of these vessels had an immature appearance and consisted only of endothelial cells that formed narrow lumens, mitotic figures of pericytes were occasionally found near the endothelial cells. Seven days after photocoagulation, all of the newly formed vessels possessed pericytes. Fourteen days after photocoagulation, many vessels appeared to be mature. Many sites of pericyte-endothelial cell contact were observed. These contacts were composed of cytoplasmic interdigitation and membrane apposition. By 21 days after photocoagulation, the mature vessels had increased in number, and the endothelial cells had many fenestrations with diaphragms. The pericyte coverage of the endothelial cells was less at this stage than at 14 days after photocoagulation, and sites of pericyte-endothelial cell contacts were observed only rarely. CONCLUSION: Pericytes are involved in maturation of the endothelial cells that form subretinal new vessels.

Animals↗

Visual field defect after pars plana vitrectomy.

OBJECTIVE: This study aimed to report the occurrence of visual field defects after pars plana vitrectomy (PPV) for the treatment of each of the following conditions: macular hole (MH), subretinal neovascular membrane (SRNVM), and epiretinal membrane proliferation (EMP). This study also aimed to speculate on the pathogenic mechanisms for the observed field defects. DESIGN: Noncomparative case series. PARTICIPANTS: The study included 48 subjects (50 eyes). Twenty-one of the 50 eyes had stage III MH, 13 eyes had SRNVM, and 16 eyes had EMP. TESTING: Goldmann kinetic perimetry was performed postoperatively. MAIN OUTCOME MEASURE: Visual field defects. RESULTS: Nine (18%) of the 50 eyes had visual field defects. Four (19%) of the 21 eyes with MH and 5 (38%) of the 13 eyes with SRNVM had visual field defects. Of the 16 patients who had epiretinal membrane peeling, none had a visual field defect. An air-fluid exchange had been performed in all patients found to have a postvitrectomy field defect. The difference in rate of visual field defects in eyes that had air-fluid exchange (EMP group) was statistically significant (P < 0.05, chi-square). No significant correlation was found between visual field defect and preoperative intraocular pressure, postoperative intraocular pressure, patient's age, and iatrogenic detachment of the vitreous cortex. The field defects identified were altitudinal (2 eyes), baring of the blind spot (1 eye), inferotemporal (3 eyes), inferonasal (2 eyes), and superonasal (1 eye). CONCLUSIONS: Central and peripheral visual field defects may occur after PPV for the treatment of MHs or SRNVMs. Air-fluid exchange procedure was the common denominator in all of the patients found to have visual field deficit. The etiology is likely to be trauma to the optic nerve region during the air-fluid exchange procedure.

Adult↗

Electroretinographic findings in iris neovascularization due to acute central retinal vein occlusion.

Electroretinograms (ERGs) were recorded in 94 patients with central retinal vein occlusion (CRVO). Of these 94, 11 had neovascularization of the iris (NVI) at the time of testing, 25 later developed NVI, and 58 did not develop NVI during a follow-up period that varied from 1 1/2 to 5 years. The ERG recorded at the patient's presentation visit predicted the occurrence of NVI in these patients with high sensitivity and specificity. The most predictive ERG parameters were the semi-saturation constant from intensity-response analysis (log K), and the implicit times of the scotopic a- and b-waves and the scotopic 30-Hz flicker response. These parameters were highly correlated, suggesting that the functional mechanism that places eyes at risk for NVI in CRVO is unidimensional. Paradoxically, the most likely candidate for this mechanism is photoreceptor sensitivity loss due to ischemia.

Acute Disease↗

Distribution of growth factors in subfoveal neovascular membranes in age-related macular degeneration and presumed ocular histoplasmosis syndrome.

PURPOSE: We performed a histopathologic and immunohistologic study to determine the macromolecular and cellular components of subfoveal neovascular membranes removed at the time of submacular surgery. METHODS: Subfoveal neovascular membranes were surgically removed from ten patients (seven with age-related macular degeneration and three with presumed ocular histoplasmosis syndrome). Tissues obtained were examined by light and electron microscopy to identify structural components. Immunohistochemical staining was then performed with monoclonal antibodies to various growth factors, including transforming growth factor-beta 1, basic fibroblast growth factor, platelet-derived growth factor, and epidermal growth factor, as well as antibodies against procollagen 1 and phosphotyrosine residues. RESULTS: Most cells in subfoveal neovascular membranes are retinal pigment epithelial cells and cells resembling fibroblasts, with some vascular endothelial cells, lymphocytes, and macrophages. Basic fibroblasts growth factor was found in the extracellular matrix and in endothelial cells. Transforming growth factor-beta 1 was found in endothelial cells, fibroblasts, and retinal pigment epithelial cells. Procollagen 1 was found in protein-synthesizing fibroblasts, and phosphotyrosine residues were detected within fibroblasts, endothelial cells, and retinal pigment epithelial cells. CONCLUSIONS: Subfoveal neovascular membranes are neovascular complexes composed of retinal pigment epithelial cells, fibroblasts, vascular endothelial cells, and chronic inflammatory cells. Furthermore, transforming growth factor-beta 1 and basic fibroblast growth factor are present within the major cell types, which suggests a possible pathogenic role in the development of the neovascular complex.

Adult↗

Retinal toxicity secondary to intraocular gentamicin injection.

The authors present five cases of severe retinal ischemia associated with gentamicin injection. In three of the cases massive doses of gentamicin were erroneously injected into the eye; in two of the cases the authors presume that gentamicin toxicity occurred. The sequence of clinical findings was similar in all five cases. The prominent findings included early superficial and intraretinal hemorrhages, opaque and edematous retina, cotton-wool infarcts, arteriolar narrowing, and venous beading. Fluorescein angiography revealed severe retinal vascular nonperfusion. Chronic findings included rubeosis irides, neovascular glaucoma, retinal pigmentary degeneration, and optic atrophy. Of the documented cases of massive intraocular gentamicin injection, two patients had no light perception (NLP) vision and one had bare light perception. Of the two cases of presumed gentamicin toxicity, one had 20/400 vision and one had count fingers vision. Strict precautions are necessary to prevent the catastrophic events resulting from inadvertent gentamicin injection; such precautions should include precise labeling of all injectable solutions on the surgical field, waiting to draw up injectable antibiotics until the time they are needed, and drawing up injectable antibiotics under direct physician observation. All intravitreal injections should be performed slowly, in the anterior vitreous, with the needle bevel up.

Adult↗

Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease.

Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal rat, vascular pruning began centrally and extended peripherally, leaving behind a less dense, smaller-caliber vasculature. The pruning was correlated with retinal vascular expression of intercellular adhesion molecule-1 (ICAM-1) and coincided with an outward-moving wave of adherent leukocytes composed in part of cytotoxic T lymphocytes. The leukocytes adhered to the vasculature through CD18 and remodeled it through Fas ligand (FasL)-mediated endothelial cell apoptosis. In a model of oxygen-induced ischemic retinopathy, this process was exaggerated. Leukocytes used CD18 and FasL to obliterate the retinal vasculature, leaving behind large areas of ischemic retina. In vitro, T lymphocytes isolated from oxygen-exposed neonates induced a FasL-mediated apoptosis of hyperoxygenated endothelial cells. Targeting these pathways may prove useful in the treatment of retinal ischemia, a leading cause of vision loss and blindness.

Animals↗

[Radiotherapy of occult neovascularization in senile macular degeneration: initial results of a pilot study].

BACKGROUND: AMD is the leading cause of legal blindness in people aged of more than 50 in industrialized countries. Occult neovascularization accounts for more than 70% of all exsudatives forms of AMD. Radiotherapy has been proposed as a possible treatment for retrofoveal neovascularization. We present the first results of a pilot study actually ongoing at the AMD Center in Creteil. PATIENTS AND METHODS: 44 patients (46 eyes) presenting occult choroidal neovascularization involving the fovea, aged of > 50 years and with a minimal visual acuity of at least 0.1 were included. They received a total dose of 16 Gy in 4 sessions of 4 Gy. All the patients were checked after 3 months. RESULTS: Visual acuity was globally maintained (> 0.1 in 93% of the eyes). Only one eye suffered a significant loss of vision (> 6 lines) and 11% suffered a moderate loss of vision (> 3 lines). Moreover 67% of eyes still had a near vision of 0.5 or more with reading glasses. On fluorescein angiography 17.5% of the eyes experienced an increase of the size of the occult neovascularization of > 0.5 Disk Area (DA), 76% showed no modification and 6.5% demonstrated a decrease in size of > 0.5 DA. CONCLUSIONS: As it has been shown that the antimitotic action of radiotherapy is most effective after 3 months, the present results suggest better evolution than natural history. However, as occult choroidal neovascularization is a slow-evolving disease further follow-up is needed to confirm it.

Aged↗

Laser photocoagulation in preproliferative retinopathy of incontinentia pigmenti.

Incontinentia Pigmenti is a rare, X-linked, dominant disorder in which affected female infants develop characteristic abnormalities of the skin, central nervous system, hair, teeth, and eyes. Ocular abnormalities occur in about 35% of patients and consist of proliferative vitreoretinopathy, retinal detachment, strabismus, cataract, microphthalmia, optic nerve atrophy, and iris hypoplasia. Retinal vascular abnormalities, ranging from peripheral retinal avascularity to neovascular and fibrous proliferation with traction retinal detachment, are the primary cause of severe visual dysfunction in patients. Therapeutic intervention with laser photocoagulation and cryotherapy for the proliferative vitreoretinopathy of incontinentia pigmenti has met with variable success. We report a case in which laser photocoagulation was used at the onset of retinopathy with subsequent resolution of the vasculopathy.

Female↗

Ocular angiogenesis: the role of growth factors.

Ocular angiogenesis, the formation of new vessels from the existing vascular tree, is a major cause of severe vision loss. It can affect different structures in the eye, including the retina, choroid and cornea. During the last decade our knowledge in the mechanisms underlying ocular angiogenesis has increased dramatically. We have witnessed the identification of key molecules. Many are classified as growth factors due to their biological properties, regulating angiogenesis. This knowledge has propelled the development of a new group of therapeutic tools, the antiangiogenic agents. This review gives an update on the role of growth factors in ocular angiogenesis from both a basic and a clinical perspective.

Animals↗

[Characteristics of retinal vascular involvement in systemic lupus erythematosus].

Retinal vascular abnormalities were studied in 194 patients with systemic lupus erythematosus (SLE). All patients fulfilled the American Rheumatism Association criteria for SLE. The mean age of patients was 31.9 +/- 9.7 years (17-63 years), women falling ill 5 times more often than men. Retinal vascular abnormalities were found in 67 (34.5%) patients and were as follows: retinal angiopathy (80.6%), cotton-wool spots (10.4%), occlusion of central vein or its branches (3%), occlusion of a retinal artery branch (4.5%), and retinal vasculitis with extensive peripheral capillary nonperfusion and neovascularization (3%). In general, retinal vascular occlusions were found in 6.7% of all SLE patients and in 19.4% of SLE patients with retinal vascular changes. Retinal vascular occlusions in SLE patients were associated with the antiphospholipid syndrome. Retinopathy did not depend on systemic hypertension or duration of SLE but correlated with disease activity. Small retinal vessels were involved more often than large vessels (p < 0.0395) and arteries more often than veins (p = 0.0338). Visual outcomes were better in patients with cotton-wool spots than in those with severe retinal vaso-occlusive disease (0.92 +/- 0.09 and 0.15 +/- 0.13, respectively, p < 0.0000).

Adolescent↗