Choriocapillaris atrophy after submacular surgery in presumed ocular histoplasmosis syndrome.
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Adult↗
Biomedical subjects
H J Kaplan
Publications and source records attributed to H J Kaplan.
Retinal pigment epithelial repopulation in monkeys after submacular surgery.
BACKGROUND: Transplantation of retinal pigment epithelium may be a treatment for retinal diseases, such as age-related macular degeneration and hereditary macular degeneration. Before transplantation studies are undertaken, questions concerning repopulation of retinal pigment epithelial cells in situ and photoreceptor repair after submacular surgery need to be addressed. METHODS: We removed the retinal pigment epithelium from Bruch's membrane in the macaque monkey in the macula and outside the vascular arcades. This model allowed the study of in situ retinal pigment epithelium regrowth and photoreceptor repair for 9 months following débridement. RESULTS: Fluorescein angiography revealed a window defect in the area of denuded retinal pigment epithelium. Histologic studies revealed repopulated nonpigmented retinal pigment epithelial cells in the denuded areas in both the early and late periods. At 9 months, the repopulated retinal pigment epithelium was associated with repaired, normal-appearing photoreceptor outer segments. Retinal pigment epithelium regrowth was observed only if Bruch's membrane was intact. CONCLUSIONS: Repopulation of retinal pigment epithelium in the adult primate can occur rapidly and can support the repair of damaged photoreceptors following submacular surgery.
Animals↗
Débridement of the pig retinal pigment epithelium in vivo.
OBJECTIVE: To study the morphologic effects of surgical débridement of the retinal pigment epithelium (RPE) in an animal model. METHODS: A pars plana vitrectomy was performed in the domestic pig, and a neurosensory retinal detachment was created by injecting the calcium-chelating agent edetic acid (commonly referred to as ethylenediaminetetraacetic acid or EDTA) into the subretinal space through a retinotomy. Twenty minutes later, the RPE was débrided by gently brushing Bruch's membrane with a soft-tip silicone catheter. Dissociated RPE was aspirated from the subretinal space, and the retina was reattached with a fluid-gas exchange. RESULTS: Light microscopic analysis confirmed that Bruch's membrane was devoid of native RPE and the choriocapillaris was morphologically intact immediately after débridement. Photoreceptor outer segments were disrupted and foreshortened immediately after RPE débridement. One to 4 weeks later, a layer of hypopigmented RPE covered most of the previously débrided areas of Bruch's membrane. The choriocapillaris was intact in areas of Bruch's membrane that were repopulated by hypopigmented RPE, and remained intact 12 weeks after débridement. Some regions of Bruch's membrane near the retinotomy remained devoid of RPE for more than 4 weeks after débridement. The choriocapillaris was atrophic and there was extensive disruption of the outer retinal layers in these areas. CONCLUSIONS: The RPE healed in most areas after surgical débridement of the RPE in the experimental animal. Atrophy of the choriocapillaris was present in areas of poor RPE healing near the retinotomy.
Animals↗
Branch retinal artery occlusion caused by a mitral valve papillary fibroelastoma.
PURPOSE: We studied clinicopathologically a branch retinal artery occlusion caused by an embolus from a mitral valve papillary fibroelastoma. METHODS: At initial examination the patient, a 37-year-old woman, had visual acuity of 20/400 in her left eye, and eight months later her visual acuity improved to 20/20. The diagnosis required echocardiographic and radiologic studies to localize the lesion. RESULTS: The mitral valve papillary fibroelastoma was successfully treated with tumor resection involving the mitral valve. CONCLUSIONS: It is important to diagnose intracardiac papillary fibroelastoma, because it can cause recurrent arterial embolization and because it responds favorably to tumor resection.
Adult↗
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↗
Branch retinal artery occlusion caused by a mitral valve papillary fibroelastoma--correction.
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Carbon Dioxide↗
Surgery for subfoveal membranes in myopia, angioid streaks, and other disorders.
OBJECTIVE: A retrospective analysis of patients who underwent surgical removal of subfoveal neovascular membranes caused by factors other than age-related macular degeneration (AMD) and presumed ocular histoplasmosis syndrome (POHS) was performed. METHODS: 17 eyes (16 patients) were identified in which subfoveal neovascularization was caused by myopic degeneration (5 eyes), angioid streaks (5 eyes of 4 patients), idiopathic neovascularization (4 eyes), punctate inner choroidopathy (1 eye), multifocal choroiditis (1 eye), or candida chorioretinitis (1 eye). RESULTS: Visual acuity remained stable after surgery in 10 of 17 eyes (59%), improved by 2 or more Snellen lines in 6 eyes (35%) and decreased in 1 eye (6%). Preoperative visual acuity was 20/80 or better in only 1 of 17 eyes (6%), but 5 of 17 eyes (29%) achieved postoperative visual acuity of 20/80 or better. Intraoperative and postoperative complications included peripheral retinal tears (1 eye), peripheral rhegmatogenous retinal detachment (1 eye), and mild cataract formation (1 eye). Subretinal neovascularization recurred after surgical removal in 4 eyes, 2 of which underwent repeat surgery. CONCLUSION: Visual acuity remained stable or improved in 94% of eyes after surgical removal of subfoveal neovascularization, but postoperative visual acuity better than 20/80 was achieved in a minority of eyes.
Adolescent↗
Intraocular viral replication after systemic murine cytomegalovirus infection requires immunosuppression.
PURPOSE: Human cytomegalovirus retinitis is the most common blinding complication of acquired immune deficiency syndrome. However, the pathogenesis of the disease is poorly understood. The authors sought to characterize intraocular viral replication after systemic murine cytomegalovirus (MCMV) infection in the normal and immunosuppressed Balb/c mouse. METHODS: Normal or immunosuppressed mice (400 rads radiation plus antilymphocyte serum) were infected intravenously with a recombinant MCMV (RM408) that carries an MCMV IE1 promoter--LacZ insert. In vivo MCMV replication and its tissue distribution were monitored by beta-gal activity with x-gal staining on frozen tissue sections of multiple organs harvested from infected mice at different time points after inoculation. RESULTS: MCMV replication within the eye can be detected in the immunosuppressed Balb/c mouse but not in the normal host. Intraocular viral replication was noted first, and most frequently, in the ciliary body and was mainly restricted to the uveal tract. Intraocular viral replication coincided with the peak of systemic viral replication; however, the neurosensory retina was spared. In contrast, supraciliary inoculation of MCMV in the immunosuppressed Balb/c mouse resulted in massive viral replication and destruction of the neurosensory retina. CONCLUSIONS: This study demonstrated that intraocular MCMV replication after systemic infection requires systemic immunosuppression. Furthermore, the ciliary body is the portal of entry for the virus within the eye. MCMV can replicate in the epithelium of the uvea and retinal pigment epithelium, but it does not replicate within the neurosensory retina. The absence of MCMV replication within the neurosensory retina is not caused by either a defect in the recombinant virus or the inability of the host tissue to support viral replication.
Animals↗
Experimental autoimmune anterior uveitis. Induction with melanin-associated antigen from the iris and ciliary body.
PURPOSE: This study was designed to investigate an animal model of uveitis that resembles anterior uveitis in humans after immunization with iris-ciliary body antigen. METHODS: Male Lewis rats 6 to 8 weeks of age were immunized with the buffer- and detergent-insoluble bovine iris-ciliary body antigen mixed with complete Freund's adjuvant and pertussis toxin. Antigen was digested with various proteolytic enzymes and tested in different rodent strains for a uveitogenic response. RESULTS: Acute iridocyclitis developed in both eyes of the Lewis rat during the second week after immunization, and the pattern of inflammation was similar to acute anterior uveitis in humans, with sudden onset, localization to the anterior uvea, and spontaneous resolution. Among the strains tested, F344 rats were susceptible to experimental autoimmune anterior uveitis but Long-Evans rats were not. Experimental autoimmune anterior uveitis did not develop in any of the mice studied, nor was it induced by immunization with synthetic melanin, amelanotic bovine tissues, pigmented bovine skin, or pigmented rat and rabbit iris-ciliary body. A soluble fraction derived from bovine melanin-associated antigen (BMAA) after digestion with the proteolytic enzyme V8 protease resulted in a disease similar to that observed with intact BMAA. CONCLUSIONS: A model of anterior uveitis has been induced in the Lewis rat after immunization with bovine uveal antigen, and it resembles the acute iridocyclitis observed in humans. These results suggest that the pathogenic antigen is a melanin-associated protein(s) present within the iris-ciliary body.
Animals↗
Histopathologic examination of vascular patterns in subfoveal neovascular membranes.
BACKGROUND: Subfoveal neovascular membranes cause significant visual loss in age-related macular degeneration (AMD) and the ocular histoplasmosis syndrome. The frequency of post-laser treatment persistence or recurrence of subfoveal membranes in AMD is as high as 51%. The reason for the high incidence of failure after laser treatment is unknown. The authors performed a histopathologic study of subfoveal membranes to determine the distribution of blood vessels within the neovascular complex, and to see if the blood vessel pattern would provide insight into the reason for laser treatment failure. METHODS: The authors used light microscopy to examine serial sections of subfoveal membranes from six patients (4 with AMD, 2 with the ocular histoplasmosis syndrome). The data from this examination were used to create detailed two-dimensional vascular maps of each membrane. RESULTS: The authors found that subfoveal membranes from patients with AMD and the ocular histoplasmosis syndrome, whether occurring de novo or after laser treatment, have a nonuniform distribution of blood vessels, and that large areas which include the membrane margin may be avascular. CONCLUSIONS: Using current laser treatment protocols, it is likely that avascular or poorly perfused peripheral areas of the neovascular complex would be left untreated after laser photocoagulation. Partial treatment of the neovascular complex may contribute to the high rate of post-laser treatment persistence or recurrence of subfoveal membranes.
Aged↗
Laser photocoagulation and fluid-gas exchange for recurrent macular hole.
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Aged↗
Endotoxin-induced uveitis in the rat is attenuated by inhibition of nitric oxide production.
PURPOSE: These experiments were undertaken to assess the role of increased nitric oxide production in the pathogenesis of vascular dysfunction associated with endotoxin-induced uveitis. METHODS: Lipopolysaccharides (LPS) (100 micrograms of Salmonella minnesota) was injected into foot-pads of Lewis rats randomly assigned to an untreated group or to a group treated with subcutaneous injections of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS). Controls included untreated and aminoguanidine-treated rats. Twenty to 24 hours later, blood flow and vascular 125I-albumin permeation were quantified in ocular tissues. Eyes were graded histologically for leukocyte infiltration into the anterior uvea and anterior chamber, and leukocyte counts were performed on aqueous fluid. Plasma nitrate levels were measured fluorometrically after enzymatic reduction to nitrite. RESULTS: Lipopolysaccharides markedly increased plasma nitrate levels and 125I-albumin permeation in aqueous fluid, retina, anterior uvea, and choroid-sclera. Blood flow was increased only in the anterior uvea. Aminoguanidine normalized plasma nitrate levels and prevented or significantly ameliorated the 125I-albumin permeation and blood flow changes in ocular tissues. The increased aqueous fluid content of lymphocytes and neutrophils in LPS-treated rats, as well as the increased histologic score of iritis, were significantly reduced by aminoguanidine. CONCLUSIONS: These results suggest that the hemodynamic and vascular permeability changes associated with endotoxin-induced uveitis are mediated in large part by increased production of nitric oxide.
Albumins↗
Differential expression of the complement regulatory proteins in the human eye.
PURPOSE: The presence of complement activation products in the human eye during infection or inflammation has been well described. During complement activation the host must be protected from attack against self tissue; this is achieved by three membrane-bound complement regulatory proteins: membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF, CD55), and membrane attack complex inhibiting protein (CD59). This study was undertaken to analyze the expression of these proteins in the normal human eye. METHODS: Tissues were sectioned by cryostat and both polyclonal and monoclonal antibodies to MCP, DAF, and CD59 were used. Control stains were performed with nonrelevant antibodies of the same immunoglobulin subclass and normal rabbit serum as well as by omission of the primary and secondary antibodies. RESULTS: All three proteins were found to be differentially expressed in the human eye. With anti-MCP, strong staining of the corneal epithelium and weak staining of the corneal keratocytes in stroma and photoreceptor cells was observed. Staining with anti-DAF was very strong in the corneal epithelium and the ciliary body and moderate in the corneal stroma (keratocytes) and iris. In contrast, anti-CD59 stained very strongly in the corneal epithelium, corneal stroma (keratocytes), iris, choroid, and all layers of the retina, and moderately in the ciliary body. CONCLUSIONS: Identification of MCP, DAF, and CD59 in the human eye provides evidence that a regulatory system exists to protect these cells from destruction by complement-activating events. It remains to be determined if other more specialized functions exist for these proteins, especially in the case of CD59 because of its extensive expression in the retina.
Adult↗
Clinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results.
BACKGROUND: Severe visual loss occurs in the presumed ocular histoplasmosis syndrome (POHS) and in age-related macular degeneration (ARMD) from subfoveal neovascularization. Although laser photocoagulation has recently been recommended for this complication in ARMD, treatment is inevitably associated with a loss of central vision. In an attempt to restore and/or preserve central vision, the authors undertook surgical removal of subfoveal neovascular membranes in these diseases. METHODS: Patients with POHS and ARMD with reduced Snellen visual acuity to 20/80 or less were selected if there was angiographic evidence of a neovascular membrane beneath the fovea. Modern vitreoretinal techniques were used to remove the subfoveal neovascular complex. RESULTS: The authors' first 15 patients with POHS and 19 patients with ARMD were followed for an average of 4 months postoperatively. Snellen visual acuity improved by 2 lines or more in 8 of 15 (53%) cases of POHS. Although similar improvements in Snellen visual acuity were not observed in cases of ARMD, 14 of 19 (74%) cases showed either slight improvement or stabilization of their vision postoperatively. Complications included recurrent neovascularization in 2 of 15 (13%) and 3 of 19 (16%) eyes with POHS and ARMD, respectively. No retinal detachment or preretinal proliferation was observed. CONCLUSIONS: These results suggest that subfoveal neovascularization can be successfully removed with preservation of foveal vision in POHS and stabilization in ARMD, at least for the short term. Visual improvement was observed in POHS even after 6 months of decreased vision. Finally, visual prognosis is most dependent on the integrity of the subfoveal RPE after removal of the membrane.
Adolescent↗
Surgical treatment of intermediate uveitis.
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Animals↗
The wavelength of light governing intraocular immune reactions.
Injection of antigen into the anterior chamber of the eye results in the induction of suppressed systemic cell-mediated responses as measured by delayed-type hypersensitivity or contact hypersensitivity (CHS). Previous studies from the author's laboratories have determined that this response is governed by exposure of the eye to visible light during the initial intraocular encounter between T cells and antigen. To more fully understand the role of light, as well as to begin to understand the molecular mediators involved, the authors chose to explore the properties of light governing the effect. Neutral density filter were used to demonstrate that the minimum amount of light required to induce suppression of CHS following anterior chamber injection of antigen is 1-2 lux (lumens/meter2). With narrow band filters, the wavelengths responsible for suppression were shown to be 500-510 nm. The results show that the effect of light extends beyond the hapten-derivatized spleen cell system to other antigens placed in the anterior chamber of the eye. Studies also show that the retina and the pineal gland, two light absorbing structures, may not be involved. The results in this report show that light of very restricted wavelengths controls intraocular immune reactions.
Animals↗
Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome.
We treated two patients with presumed ocular histoplasmosis, subfoveal neovascular membranes, and progressive visual acuity loss to 20/400. Vitreoretinal surgical techniques were used to remove the subfoveal membranes. Visual acuity returned to 20/20 with seven months of follow-up in one patient (Case 1) and to 20/40 with three months of follow-up in the other patient (Case 2). No evidence of persistent or current subretinal neovascular membranes in either patient have been noted. These preliminary results suggest that vitreoretinal surgical techniques may be successful in mechanically removing subfoveal neovascular membranes with preservation of overlying neurosensory retina and thus preservation of central visual acuity.
Adult↗
Perforating (through-and-through) injuries of the globe. Surgical results with vitrectomy.
Fifty-one eyes of 48 patients with perforating (through-and-through) injuries of the globe were treated with vitrectomy during a 12-year period. Functional success was obtained in 32 eyes (63%), anatomic success was obtained in nine eyes (17%), and treatment failed in 10 eyes (20%). In 16 eyes (32%), 20/20 to 20/100 visual acuity was obtained; in 17 eyes (33%), 20/200 to 5/200 visual acuity was obtained; and in 18 eyes (35%), less than 5/200 visual acuity was obtained. The mechanism of injury was an important prognostic indicator of final visual outcome. Eight (62%) of 13 eyes that sustained knife or nail injuries achieved a final visual acuity of 20/50 or better, while only six (16%) of 38 eyes [corrected] with missile injuries achieved a similar level of acuity. Final visual outcome correlated well with the state of the macula and was not predicted by preoperative visual acuity. Despite improvement in surgical techniques and instrumentation, no trend toward improved visual outcomes was identified during the 12-year period.
Adolescent↗