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[Treatment of neovascular glaucoma by anterior retinal cryotherapy and trabeculectomy].

OBJECTIVE: To investigate the efficacy of anterior retinal cryotherapy (ARC) for treatment of neovascular glaucoma (NVG). METHODS: 12 eyes (11 patients) with open angle NVG were treated by ARC only, 22 eyes (22 patients) with closed angle NVG were treated by ARC combined with trabeculectomy, and 32 eyes (31 patients) with closed angle NVG were treated by either ARC or cyclocryotherapy as controls. The follow-up period were 6-26 months. RESULTS: Iris new vessels (INV) regressed or disappeared with normal intraocular pressure (IOP) in 92% (11/12) of the eyes with open angle NVG treated simply by ARC. In comparison with closed angle NVG treated by the same method, there was a significant difference in IOP (P < 0.05). The combination of ARC and trabeculectomy showed markedly better results than either ARC or cyclocryotherapy for treatment of closed angle NVG (P < 0.01). In the eyes with closed angle NVG, INV regressed or disappeared with normal IOP in 86% (19/22), 90% (18/20) achieved a marked relief from pain and the visual acuity was better or unchanged in 67% (8/12) that was significantly different from the eyes treated by cyclocryotherapy (P < 0.05). CONCLUSION: The results indicate that ARC is suitable for treatment of NVG at early stage, and ARC combined with trabeculectomy, at later stage.

Adult↗

Indocyanine green angiography. American Academy of Ophthalmology.

The purpose of the Committee on Ophthalmic Procedures Assessment is to evaluate on a scientific basis new and existing ophthalmic tests, devices, and procedures for their safety, efficacy, clinical effectiveness, and appropriate uses. Evaluations include examination of available literature, epidemiological analyses when appropriate, and compilation of opinions from recognized experts and other interested parties. After appropriate review by all contributors, including legal counsel, assessments are submitted to the Academy's Board of Trustees for consideration as official Academy policy.

Choroid↗

RPE transplants stabilize retinal vasculature and prevent neovascularization in the RCS rat.

Previous reports indicate that in the Royal College of Surgeons (RCS) rat a decline in the retinal vessel density accompanies the loss of the normal architecture of the deep bed. This begins at about three months with neovascularization that originates in the deep vessel bed and develops in the direction of the retinal pigment epithelial (RPE) cells by four months. A surgical technique has been developed recently for the transplantation of healthy RPE cells into the subretinal space of the RCS rat, resulting in the rescue of photoreceptor cells. This permits evaluation of the possibility that such transplants also protect the retinal vessels. We report for the first time: (1) the stabilization of the normal retinal vasculature by maintenance of the density and architecture of the deep vessel bed; and (2) prevention of neovascularization of the RPE by the surgical transplantation of healthy RPE cells into the subretinal space of the RCS rat. More specifically, we show a maintenance of the deep vessel bed density under the transplant in contrast to a significant reduction in the vessel density that had taken place in corresponding areas in nongrafted and sham injected controls at four months of age. The vessel density in the transplanted group is statistically different from the nongrafted and the sham injected groups. We also report a significant decline in the number of neovascularization profiles around the transplant site of the RPE-grafted RCS retina. We also note that the pathological changes in the vasculature of the RCS rat occur in a predictable central to peripheral gradient.

Animals↗

Familial spastic paraplegia and maculopathy with juxtafoveolar retinal telangiectasis and subretinal neovascularization.

PURPOSE: To describe a previously unreported condition involving familial spastic paraplegia and a peculiar type of maculopathy. METHODS: Two pairs of siblings were studied. All four cases underwent serial clinical examinations, fundus photography, and fluorescein angiography. Two siblings had extensive investigations. RESULTS: Characteristics of the four cases include spastic paraplegia diagnosed in the first decade of life and visual loss at about age 9 due to a maculopathy with an abnormal vascular complex. In the early stages, parafoveal dilatation of the capillary network was noted. The later stages were characterized by cystic macular degeneration, and seven of eight eyes developed fibrovascular scars with retinochoroidal anastomoses, pigment migration, and atrophic changes. In two siblings, electro-oculographic findings were subnormal, whereas results of electroretinography, magnetic resonance imaging of the brain and spinal cord, and metabolic and karyotype studies were normal. These siblings were an Indonesian girl and boy; the other siblings were white males. There was no consanguinity of the parents and family history was unremarkable. CONCLUSIONS: This study suggests that the two pairs of siblings have an identical familial and probably recessive disorder with neurodegenerative changes that have caused paraplegia and a peculiar maculopathy associated with anomalous retinal vascular complexes, retinochoroidal anastomoses, and subretinal neovascularization.

Adolescent↗

Vitreous: an inhibitor of retinal extract-induced neovascularization.

One of the major problems in assessing neovascularization in mammalian experimental animal models is the immunologic response of the host to stimuli from nonautologous species. Hence, crude bovine vitreous and retinal extracts may produce a complex immune reaction when tested in the rabbit. To circumvent this problem, the chicken chorioallantoic membrane (CAM) assay is most appropriate. In this study the CAM assay for angiogenesis has been modified to study antiangiogenic substances. The modified assay is described in detail and used to demonstrate for the first time the inhibition by adult bovine vitreous of neovascularization induced by extracts of adult bovine retina. In addition to vitreous, three common glycosaminoglycans (keratan sulfate, chondroitin sulfate C, and hyaluronic acid) were assayed for antiangiogenic activity. The results indicate that vitreous inhibition of retinal extract-induced neovascularization is dose dependent, while the sulfated glycosaminoglycans tested had no antiangiogenic activity. A commercial preparation of bovine vitreous hyaluronic acid exhibited a slight, but not statistically significant, inhibitory activity. When vitreous extracts were digested with hyaluronidase, no loss of antiangiogenic activity occurred. These results suggest that the inhibitor of angiogenesis from adult vitreous is probably not a common glycosaminoglycan. The results are consistent with the hypothesis that antiangiogenic substance(s) in vitreous and angiogenic components from retina may act as natural antagonists in controlling the process of retinal neovascularization.

Animals↗

[Effect of pan-retinal photocoagulation in iris neovascularization].

The authors were able to produce experimental rubeosis iridis in the rhesus monkey's eye on 5 days following occlusion of the major retinal vessels and persistent ocular hypotony. Histopathological examination revealed true neovascularization. This experiment attempted to see whether laser pan-retinal photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis or not. We first performed laser pan-retinal photocoagulation, and at the same time performed occlusion of the major retinal vessels and persistent hypotony to aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At 14 days, histological examination revealed vessels on the surface of the iris following pan-retinal photocoagulation treatment were covered by fibroblast and melanocyte, and their endothelial cells showed no fenestrations. This means that clinical rubeosis iridis is not true neovascularization, but dilatation of the iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits development of iris neovascularization.

Animals↗

Experience with photocoagulation in Behçet's disease.

Between 1973 and 1987 we examined both eyes of 300 patients with the uveoretinitis-type lesions characteristic of Behçet's disease. Of the 556 eyes whose fundus could be examined, 38 eyes (6.8%) in 33 patients (11%) had developed retinal capillary nonperfusion, branch retinal vein occlusion, or retinal or disc neovascularization. These eyes were treated by photocoagulation, primarily to forestall vitreous hemorrhage and the development of neovascular glaucoma, as well as to decrease the macular edema resulting from vein occlusion. The treatment, which was well tolerated, was successful in closing retinal capillary nonperfusion areas and eliminating retinal neovascularization. Disc neovascularization was resolved completely in some cases, and partially in others.

Behcet Syndrome↗

Transient exposure of rat pups to hyperoxia at normobaric and hyperbaric pressures does not cause retinopathy of prematurity.

We have shown that hyperoxia reduces brain damage in a rat model of hypoxia-ischemia. The purpose of this study was to examine the possibility of hyperoxia in inducing vision-threatening retinopathy. Two different experiments were conducted in this study. PART 1: seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 degrees C). Pups were treated with 100% oxygen at 1 ATA, 1.5 ATA, and 3.0 ATA for a duration of 1 h. PART 2: Newborn rat pups were exposed to 100% oxygen at 1, 1.5, or 3.0 ATA for 1 h, the same treatment protocol used for brain protection after hypoxia-ischemia. Retinopathy was evaluated by the degree of neovascularization (measuring retinal vascular density), by the structural abnormalities (histology) in the retina, and by the expression of hypoxia-hyperoxia sensitive proteins including hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at 24 h, 1, 2, and 10 weeks after hyperoxia exposure. Hyperoxic treatment at all pressures administered significantly reduced the hypoxia-ischemic-induced reduction in brain weight. Retinal vascular density measurements revealed no signs of neovascularization after hyperoxia exposure. There were also no abnormalities in the structure of the retina and no changes in the protein expression of HIF-1alpha and VEGF following hyperoxia exposure. Exposure to hyperoxia for 1 h at normobaric or hyperbaric pressures did not result in the structural changes or abnormal vascularization that is associated with retinopathy of prematurity, suggesting that hyperoxia is a safe treatment for hypoxic newborn infants.

Analysis of Variance↗

Neovascularization of the RPE: temporal differences in mice with rod photoreceptor gene defects.

Neovascularization (NV) of the retinal pigment epitheium (RPE) by retinal capillaries following degeneration and loss of photoreceptor cells is a widely recognized phenomenon in rodents. NV of the RPE usually occurs several weeks to months after the loss of photoreceptor cells. We have observed that NV of the RPE occurs much earlier in a line of P23H mutant rhodopsin transgenic mice than in most other mice and rats that have been previously examined. To compare the temporal course of RPE NV in P23H mice with that of two other retinal degeneration mutants with the same time course of photoreceptor cell loss, we have quantified the number of retinal capillaries in the RPE of P23H and Q344ter mutant rhodopsin transgenic mice and retinal degeneration (rd/rd) mice at ages ranging from postnatal day (P) 20-400. Retinal capillary profiles located within the RPE were already present as early as P20 in the P23H retinas, and although these usually were located where most photoreceptor nuclei were missing, they occasionally were found where 1-2 rows of photoreceptor nuclei were still present. The maximal incidence was found in P23H retinas at P100. By contrast, NV of the RPE in rd/rd and Q344ter mice occurred much later. In rd/rd, a significant number of capillary profiles was not seen in the RPE until about P130, and not until about P180 in Q344ter. Both showed maximal incidence at about P240. In all three mutants, an apparent regression of the capillaries occurred following the peak, with that in the P23H mice preceeding the other two mutants. The findings suggest that the P23H mutant rhodopsin transgenic mouse may be a useful model for studying the regulation of NV in the outer retina.

Aging↗

Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome).

BACKGROUND: One of the largest series of patients with incontinentia pigmenti who have undergone detailed ophthalmologic examination is reported here, including previously unrecognized findings with visually disabling consequences. METHODS: Thirteen females with incontinentia pigmenti from eight unrelated families were evaluated. The diagnosis of incontinentia pigmenti had been established previously by a referring pediatrician or dermatologist in 12 patients and by the authors in one other patient on the basis of retinal findings and history of characteristic skin manifestations. RESULTS: Abnormalities of the eye, central nervous system, skeleton, teeth, and hair develop in a majority of patients. The authors describe the evolution of retinal vascular abnormalities, and, for the first time, document foveal hypoplasia (in 4 of their 13 patients). The authors also provide the first report of a child with a normal brain shown on computed tomographic scan at 3 days old, which evolved to devastating cerebral ischemia, edema, and cortical blindness beginning at 6 days old. CONCLUSIONS: Incontinentia pigmenti should be included in the differential diagnosis of patients with peripheral retinal vascular nonperfusion, preretinal neovascularization, infantile retinal detachment, or foveal hypoplasia, particularly if there is evidence of characteristic dermatologic or other systemic manifestations. In infants with incontinentia pigmenti, retinal vascular anomalies are best detected by examination under anesthesia using fluorescein angiography.

Adolescent↗

[Value of indocyanine green angiography in localization of occult choroid neovascularization].

PURPOSE: To determine the role of Indocyanin Green (ICG) angiography in localizing occult new vessels associated with age-related macular degeneration (ARMD) and assess the possibilities of ICG guided laser photocoagulations. PATIENTS AND METHODS: Fluorescein and ICG angiographies (IMAGEnet system) of 62 patients with occult new vessels (ONV), serous (SPED) or vascular (VPED) pigment epithelium detachment have been studied. RESULTS: Based on fondoscopic examination and fluorescein angiography, 43 eyes (69%) disclosed ONV, 8 (13%) SPED and 11 (18%) VPED. Choroidal neovascularisation was confirmed by ICG angiography in 37 ONV cases (86%), in 8 (72%) VPED cases, but in no SPED. Conversion of ONV in classical neovascular membranes was possible in 19 ONV cases (44%) and in 6 (54%) VPED cases, making a laser photocoagulation possible in 9 eyes (36%). CONCLUSION: ICG angiography plays an important role in the evaluation, classification and laser treatment of patients with ONV secondary to ARMD.

Aged↗

Neovascularisation: has the angiogenic factor already been found?

Recently many soluble growth factors capable of influencing neovascularisation (angiogenesis) have been isolated and molecularly cloned. As such they are now available in a highly purified and active form. One or several of these already quite well known molecules may be of importance in the control of ocular neovascularisation. This article reviews what is presently known about growth factor control of neovascularisation with particular emphasis on both the eye and those factors that have already been molecularly cloned. In addition several recently reported inhibitors of neovascularisation are discussed. Such research is of particular interest to the ophthalmologist as knowledge gained in this area may allow for the use of both growth factors as well as growth factor inhibitors in the management of several ocular diseases involving neovascularisation.

Angiogenesis Inducing Agents↗

Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures.

Chorioretinal neovascular membranes are a recognised but rare cause of late visual loss in eyes suffering contusional injuries. A series of eight cases is presented all with indirect choroidal ruptures involving the perifoveal region. Two main patterns of 'at risk' rupture were noted: a temporally situated rupture passing almost directly through the fovea, and a rupture which curves inferior or superior to the optic disc stopping just short of the fovea. In six of eight cases there was only a partial thickness rupture of the choroid. These neovascular membranes may present at any time after the original injury, either early (within six months of the injury), which could be related to persistence of the normal reparative neovascular response, or late (at least one year after the injury), which are more likely to have resulted from a secondary breakdown of the outer blood-retina barrier.

Adolescent↗

Technology evaluation: pegaptanib, Eyetech/Pfizer.

Eyetech Pharmaceuticals and Pfizer are co-developing the anti-vascular endothelial growth factor aptamer, pegaptanib, as an angiogenesis inhibitor for the potential treatment of age-related macular degeneration and diabetic macular edema, in addition to other ocular diseases. Gilead was previously investigating the aptamer for the potential treatment of cancer, however, no data have been published for this indication since 1999.

Angiogenesis Inhibitors↗

Angioblasts in adult and its role in ocular disorders due to neovascularization.

Blood vessel formation includes vasculogenesis and angiogenesis. Traditionally vasculogenesis is believed to occur in embryo, forming blood vessels by the differentiation of angioblasts, while angiogenesis is defined as the formation of new blood vessels that originate from pre-existing vessels, which happens both in embryo and adult. However, recent studies on angioblasts have shown that new blood vessel formation due to angioblast differentiation, once was believed to happen exclusively in embryo, also occurs in adult. These findings not only help us to understand the pathogenesis of new blood vessel formation, but also provide some new clues to investigate new therapeutic target for the treatment of angiogenesis.

Adult↗