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Biomedical subjects

B M Glaser

Publications and source records attributed to B M Glaser.

At least 19 recordsLinked to original sources

Progression of nuclear sclerosis and long-term visual results of vitrectomy with transforming growth factor beta-2 for macular holes.

PURPOSE: We studied the progression of cataracts and visual acuity up to 36 months after vitrectomy and instillation of transforming growth factor beta-2 for treatment of full-thickness macular holes. METHODS: Sixty-four eyes with idiopathic and two with traumatic macular holes in this prospective consecutive series were divided into the following two groups: 56 phakic eyes were treated with 70, 330, or 1,330 ng of transforming growth factor beta-2 to study the progression of cataracts, and 31 phakic or pseudophakic eyes were treated with 1,330 ng of transforming growth factor beta-2 to study the long-term visual acuity after macular hole surgery. RESULTS: Eyes in the cataract progression study had a mean preoperative nuclear sclerosis grade of 0.4, which increased to 2.4 on final lens examination at a mean of 12.4 months postoperatively. The amount of nuclear sclerosis increased progressively with duration of follow-up, and 16 (76%) of 21 eyes followed up for 24 months or more required cataract extraction. The mean preoperative posterior subcapsular cataract grade was 0.0 and increased only slightly to 0.25 on final lens examination. All eyes had initial successful closure of the macular hole, but the macular hole reopened in two eyes (between six and 12 months and at 19 months) for an overall success rate of 29 (93.5%) of 31 eyes at a mean of 19.5 months. The visual acuity increased two or more Snellen lines in 29 (93.5%) of 31 eyes. The final visual acuity was 20/40 or better in 23 (74%) of 31 eyes and the visual improvement was stable in eyes followed up for three years. CONCLUSIONS: Nuclear sclerotic cataracts progress substantially after macular hole surgery with a long-acting intraocular gas tamponade. The visual acuity often decreases 12 or more months after vitrectomy because of cataract progression, but the visual results of vitrectomy and transforming growth factor beta-2 for macular holes are excellent when the cataracts are removed.

Adolescent

Fundus photographic and fluorescein angiographic characteristics of pseudoholes of the macula in eyes with epiretinal membranes.

BACKGROUND: The fluorescein angiographic characteristics in eyes with pseudoholes of the macula associated with epiretinal membranes have not been studied extensively. METHODS: Stereo photographs and fluorescein angiograms from 83 consecutive eyes of 80 patients with pseudoholes of the macula were evaluated by two independent graders for epiretinal membrane opacity, fluorescence in the base of the pseudohole, and late perifoveal pooling of dye. RESULTS: Hyperfluorescence in synchrony with choroidal fluorescence appeared within the base of the pseudohole in 52 (63%) of the 83 eyes studied. The hyperfluorescence was smaller than the pseudohole in 37 (45%) eyes. Diffuse hyperfluorescence filled the pseudohole in 15 (18%) eyes. No fluorescence was seen in 20 (24%) eyes. Eleven (13%) eyes could not be graded due to coexistent macular disease or media opacity. Fluorescence within the area of pseudohole was less common in eyes with opaque epiretinal membranes than in eyes with visible or transparent epiretinal membranes (P = 0.002). Fluorescence within the area of the pseudohole was also less common in eyes with evidence of macular edema on fluorescein angiography (P < 0.001). The mean visual acuity was better for eyes with hyperfluorescence within the area of the pseudohole than for eyes without hyperfluorescence (P < 0.01). CONCLUSION: A common fluorescein angiographic characteristic associated with pseudoholes of the macula is early hyperfluorescence within the area of the pseudohole. This hyperfluorescence coincides with choroidal filling and appears to be a form of transmission defect rather than a blocking of surrounding choroidal fluorescence by the epiretinal membrane. This central hyperfluorescence may result in misdiagnosis of the macular pseudohole as a full-thickness macular hole.

Basement Membrane

The use of perfluoro-octane in the management of giant retinal tears without proliferative vitreoretinopathy.

PURPOSE: A technique for managing giant retinal tears without proliferative vitreoretinopathy (PVR) is presented, and visual outcome, anatomic reattachment, and postoperative complications are discussed. METHODS: A total of 25 consecutive cases of retinal detachment from giant retinal tears in eyes without PVR that had not previously undergone surgery were reviewed. A surgical technique combining pars plana vitrectomy, perfluoro-octane, and fluid-gas exchange was used. Scleral buckling was performed in 23 (92%) of 25 eyes, and pars plana lensectomy was performed in 11 (69%) of the 16 phakic eyes. A minimum follow-up period of 6 months was documented in each case. RESULTS: Of the 25 eyes, redetachment occurred in 3 (12%) after the initial procedure, and further surgery was necessary to successfully reattach the retina. A total of 9 secondary procedures were performed in 7 (28%) of the 25 eyes. Final retinal reattachment was achieved in all 25 eyes. Final Snellen visual acuity was 20/80 or better in 18 (72%) patients and 20/200 or better in 21 (84%) patients. CONCLUSION: The anatomic and visual results of this method of surgical treatment of giant retinal tears without PVR compare favorably to those achieved with techniques that use a nonbuckling approach, but with reduced ocular morbidity.

Adolescent

Transforming growth factor-beta 2 levels increase following retinal laser photocoagulation.

To determine if the levels of transforming growth factor-beta 2 (TGF-beta 2) in ocular tissues change following laser photocoagulation, pigmented rabbit eyes underwent panretinal photocoagulation using laser indirect ophthalmoscopy. The rabbits were followed for a period of either 2 or 14 days after the procedure. The eyes were then removed and samples of vitreous and aqueous humor were collected. TGF-beta 2 levels were measured using an immunoassay. When compared to control eyes, TGF-beta 2 levels in the vitreous humor of treated eyes at day 2 and day 14 were increased. Changes in TGF-beta 2 levels were also seen in the aqueous humor of the treated eyes, with increased levels seen at day 2 and day 14 compared to control eyes. The increase in both vitreous and aqueous humor in treated eyes compared to control eyes was shown to be statistically significant (p < 0.05). Our results show that intraocular TGF-beta 2 levels increase significantly following laser photocoagulation. This preliminary study suggests that TGF-beta 2 may be involved in the process of chorioretinal wound healing.

Animals

Amiloride inhibition of angiogenesis in vitro.

Angiogenesis is important to such processes as normal embryonic development and tissue growth, and is also a central feature of diseases such as diabetic retinopathy and the growth of solid tumors. Understanding the basic events governing angiogenesis has therefore attracted great interest. The ion channel blocking agent, amiloride, has been shown to inhibit angiogenesis in an in vivo model (Lansing et al., '91). This suggested a vital role for Na(+)-coupled transport processes in angiogenesis. A large number of structural analogues of amiloride have been synthesized (Kleyman and Cragoe, '88), and many of these are well characterized with respect to biological activity. These analogues present an opportunity to dissect the process of angiogenesis and identify potentially important physiological events. In this report we describe the effects of amiloride on an in vitro model for angiogenesis employing vascularized tissue explants. Amiloride inhibits capillary morphogenesis completely and reversibly at concentrations as low as 134 microM. It appears to act by blocking endothelial cell proliferation, but not migration. Inhibition is heightened by the introduction of hydrophobic groups on the terminal guanidino nitrogen atom, or on the 5-amino position. An analogue substituted at both of these positions is 30-fold more potent than the parent compound. Of amiloride's known biological activities, these results most closely correlate with the inhibition of Ca2+ transport processes, and thereby suggest an important role for Ca2+ transport in capillary morphogenesis.

Amiloride

High-performance liquid chromatographic method for quantitating plasma levels of amiloride and its analogues.

An assay for amiloride was devised for efficient use with the wide variety of analogues available. Amiloride was extracted from 1-ml plasma samples by elution from a C8 preparative column with 6% acetonitrile-45% methanol-5.4% acetic acid, adjusted to pH 4.0 with trimethylamine. Samples were lyophilized, resuspended in 50% methanol, filtered through 0.22-microns Spin-X cartridges, applied to a reversed-phase C18 column, and eluted in a 0-50% acetonitrile gradient in 0.4% acetic acid, pH 4.5 (1.2 ml/min). Detection by ultraviolet absorbance at 360 nm was linear from 1 to 1000 ng. Versatility of the method was demonstrated with the analogues benzamil, 6-hydro-, 6-iodo-, 5-hexamethylene-, and 5-chlorobenzyl-2',4'-dimethylbenzyl-amiloride.

Administration, Oral

Transforming growth factor-beta 2 for the treatment of full-thickness macular holes. A prospective randomized study.

BACKGROUND: Full-thickness macular holes generally cause a significant reduction in visual acuity, due in part to a rim of surrounding neurosensory retinal detachment and retinal thickening. Recent studies have suggested that flattening of this narrow rim of neurosensory detachment can result in improved visual acuity. However, the ability to flatten the neurosensory detachment is limited using current surgical techniques. METHODS: Transforming growth factor-beta 2 (TGF-beta 2) is a recently discovered potent stimulator of wound healing. The authors, therefore, performed a prospective randomized study of 60 patients to determine if the local application of TGF-beta 2 to the edge of the macular hole can reproducibly induce flattening of the surrounding neurosensory detachment. The results of a study designed to determine the effect of a pars plana vitrectomy, fluid-gas exchange, and intravitreal instillation of TGF-beta 2 in eyes with a full-thickness macular hole and reduced visual acuity are reported. RESULTS: After treatment, visual acuity improved 2 lines or more in 5 of 11 eyes treated with 70 ng, in 4 of 12 eyes treated with 330 ng, and in 10 of 11 eyes treated with 1330 ng of TGF-beta 2. In some eyes, hyaluronic acid was added. In these cases, visual acuity improved 2 lines or more in 0 of 9 eyes treated with 70 ng TGF-beta 2, in 2 of 8 eyes treated with 330 ng, and in 4 of 9 eyes treated with 1330 ng. CONCLUSION: Logistic regression analysis demonstrated a statistically significant beneficial effect of TGF-beta 2 on visual improvement (P = 0.003).

Adolescent

Nuclear sclerotic cataract after vitrectomy for idiopathic epiretinal membranes causing macular pucker.

We evaluated the occurrence or progression of nuclear sclerosis of the crystalline lens in 100 eyes after vitrectomy for removal of idiopathic epiretinal membranes causing macular pucker. The follow-up period ranged from six to 99 months (average, 29 months). Visually significant nuclear sclerosis was present preoperatively in three of the operated on eyes and four of the fellow eyes. The rate of occurrence or progression of visually significant nuclear sclerosis was far greater in the operated on eyes (P less than .0001). Of 100 patients, 80 operated on eyes and 24 fellow eyes had visually significant nuclear sclerosis or had undergone previous cataract extraction at the conclusion of the study. Different concentrations of glucose in the intraocular irrigating solution did not affect occurrence of later nuclear sclerosis. Patients older than 50 years of age had a far greater incidence of later nuclear sclerosis than patients younger than 50 years of age (P = .0003). Nuclear sclerosis may be caused by altered lens metabolism after removal of part of the vitreous gel, since nuclear sclerosis also occurs in other conditions associated with vitreous liquefaction.

Adolescent

Extracellular matrix of newly forming vessels--an immunohistochemical study.

During wound healing, embryological development, and solid tumor growth, the established vasculature gives rise to large numbers of new blood vessels. This neovascular response occurs at the level of the capillary bed, where endothelial cells divide rapidly, locally remodel the surrounding stroma, and migrate away from existing vessels to form capillary sprouts. In order to examine the environment of these newly forming vessels, actively growing blood vessels in neovascularized rabbit and guinea pig corneas were examined immunohistochemically using antibodies against laminin, type IV collagen, heparan sulfate proteoglycans, entactin, and factor VIII-related antigen. Sequential serial 5-microns sections taken from the unfixed frozen corneas in a plane perpendicular to the direction of vessel growth were stained with these antibodies. It was possible to follow well-defined lumenized vessels out through sequential sections to the point where they became single factor VII-R positive cells in the region of the capillary sprout. Examination of these stained sections has shown the presence of four important basement membrane components--laminin, type IV collagen, heparan sulfate proteoglycan, and entactin--associated with actively migrating and invading capillary sprouts. These results suggest that the extracellular matrix of the actively invading capillary sprouts does not differ qualitatively from that of the established vasculature.

Animals

Perfluoro-octane in the treatment of giant retinal tears with proliferative vitreoretinopathy.

Giant retinal tears complicated by proliferative vitreoretinopathy (PVR) pose one of the more complex problems in vitreoretinal surgery. The authors developed a technique using perfluoro-octane, a temporary vitreous substitute that is heavier than water, combined with vitrectomy, scleral buckling, fluid-gas exchange, and direct manipulation of the retina to treat these cases. Ten eyes with giant retinal tears and grade D-1 PVR or worse were treated. In all eyes, the retina was successfully reattached at the end of surgery. Nine of the ten retinas remained attached after 6 months of follow-up. Five eyes required a total of six reoperations for epiretinal membrane formation without retinal detachment. The one eye in which the retina did not remain reattached developed severe recurrent PVR and iris neovascularization. Visual acuity improved in 8 of 10 eyes. Final visual acuity was 20/400 or better in 8 of 10 eyes, and 20/80 or better in 4 eyes.

Adult

15-Hydroxyeicosatetraenoic acid stimulates migration of human retinal microvessel endothelium in vitro and neovascularization in vivo.

We evaluated 15-hydroxyeicosatetraenoic acid (15-HETE), a major arachidonic acid product of vascular endothelium and leukocytes, for its effect on neovascularization. In a modified Boyden chamber assay, 15-HETE (10-7 M) stimulated human retinal microvessel endothelial cell migration by 42 +/- 10% (mean +/- S.E.M., p less than 0.01). 12-HETE, a major arachidonic acid metabolite of platelets, had no such effect. Further studies in the rabbit corneal pocket assay revealed that 15-HETE stimulated neovascularization in vivo. Concentrations at which the in vivo effects were observed are within the range generated by several cell types and are achievable in human serum. 15-HETE stimulation of human endothelial cell migration in vitro and neovascularization in vivo suggests that it may play a role in vasoproliferative disorders.

Animals

Iatrogenic retinal breaks complicating pars plana vitrectomy.

To determine the current incidence and outcome of iatrogenic retinal breaks occurring during pars plana vitrectomy, the authors reviewed 404 consecutive operations done on eyes without preexisting retinal breaks. Thirteen eyes had 14 iatrogenic peripheral retinal breaks. Three other eyes had both peripheral breaks and posterior breaks. Twenty-five eyes had 43 posterior breaks. The incidence of peripheral breaks was 4% and of posterior breaks was 6%. Patients with proliferative diabetic retinopathy had a higher incidence of iatrogenic retinal breaks than those with other diagnoses. Peripheral breaks occurred most commonly just posterior to the site of insertion of the vitrectomy probe. Although six eyes required reoperation, 33 of 38 eyes had a successful anatomic outcome.

Cohort Studies

Evolving concepts in the management of posterior segment penetrating ocular injuries.

Advances in understanding the pathobiology of secondary complications after posterior segment penetrating ocular injuries along with progress in instrumentation and surgical techniques have provided a powerful means to salvage certain eyes that would otherwise be lost. Further progress will probably include the use of pharmacologic agents that interfere with fibrocellular proliferation, as well as better delineation of the methods and timing of surgery.

Animals

Miosis during vitreoretinal surgery.

Maintenance of wide pupillary dilation during vitreoretinal surgery can be important in successful completion of the operation. This study identified factors associated with intraoperative miosis. Also, flurbiprofen, a topically applied nonsteroidal anti-inflammatory agent, was evaluated for its efficacy in preventing intraoperative miosis in a prospective, randomized study of 99 consecutive patients. Factors associated with intraoperative miosis included duration of surgery greater than 90 minutes, preoperative afferent pupillary defect, and recent previous surgery. Preoperative treatment with flurbiprofen did not decrease the risk of intraoperative miosis.

Chi-Square Distribution

Surgical treatment of postoperative dilated, nonreactive pupil in eyes after combined pars plana lensectomy and vitrectomy.

Synechiae between the iris and tissue posterior to the iris can cause a markedly dilated, nonreactive pupil that is cosmetically undesirable after combined pars plana lensectomy and vitrectomy for complicated forms of retinal detachment. The authors have used a combined limbal and pars plana approach to lyse the posterior synechiae, resulting in partial pupillary constriction. The surgical technique is described, and clinical results are illustrated.

Adolescent

Scleral buckle revision to treat recurrent rhegmatogenous retinal detachment.

Recurrent rhegmatogenous retinal detachment sometimes occurs following scleral buckling surgery in the absence of advanced proliferative vitreoretinopathy (grade C-2 or greater). Such detachments can occur because: 1) the scleral buckle is not properly positioned beneath the original break; 2) the buckle is not high enough; 3) the break is elevated off the buckle due to progressive vitreous traction; 4) there are new breaks; and 5) chorioretinal adhesion is insufficient. Techniques that may be useful for reattaching the retina in these cases include: 1) adding scleral buckling material to augment the original buckle; 2) modifying the existing buckle without adding new material; 3) replacing the original buckle with other material; 4) re-treating inadequately closed breaks; and 5) combinations of these four techniques. Vitrectomy may be avoided in many cases.

Adolescent

Retinal pigment epithelium cells can influence endothelial cell plasminogen activators.

Endothelial cells from both human retinal microvessels (HME) and fetal bovine aortic endothelium (FBAE) were grown in aggregate cultures alone, or with either retinal pigment epithelium (RPE) cells or fibroblasts. The levels of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in the conditioned media of the various aggregate types were measured. High PA levels were detected in the conditioned medium of pure endothelial cell aggregates (equal to 140% and 124% of urokinase control for HME and FBAE, respectively), and high PAI levels were associated with pure RPE aggregates (inhibiting 93% of the urokinase control). The conditioned medium of pure fibroblast aggregates had very low levels of either PA or PAI. When RPE cells were aggregated with FBAE or HME cells into mixed (heterogenous) aggregates, the PA measured in the conditioned medium was equal to 22% and 30% of the urokinase control, respectively. The PA level in the conditioned medium of mixed fibroblast-FBAE cell aggregates was higher, 104% of the control, and the difference was statistically significant (P less than 0.001). Co-incubation of pure RPE aggregates with pure FBAE aggregates or with pure HME aggregates resulted in PA activity in the conditioned medium that was equal to 110% and 96% of the control, respectively. The PA level found when pure FBAE cell aggregates were co-incubated with pure fibroblast aggregates was higher, 134% of the control, and the difference was statistically significant (P less than 0.001). Our results indicate that RPE cells can reduce endothelial cell PA, probably through both direct contact between the cells and PAI production. Fibroblasts did not have this influence on endothelial cell PA.

Analysis of Variance

The surgical management of giant retinal tears with the cannulated extrusion needle.

In 18 eyes of 17 patients, we treated retinal detachment caused by a giant retinal tear by unfolding and repositioning the retina with a cannulated extrusion needle. After pars plana vitrectomy, a fluid-gas exchange was performed with the patient in the supine position. Using the cannulated extrusion needle to drain subretinal fluid posterior to the giant retinal tear, the retinal flap was manipulated into the correct anatomic position. With this technique, 18 of 18 eyes with retinal detachment caused by a giant retinal tear were successfully reattached intraoperatively. Although eight of these eyes subsequently redetached and required additional surgical procedures, 16 of 18 eyes remain attached with a mean follow-up of 11 months.

Adult