Henry J. Kaplan

Clinical Experience with the Surgical Removal of Subfoveal Neovascular Membranes: Short-term Postoperative Results

BACKGROUNDnSevere 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.nnnMETHODSnPatients 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThese 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.

Fas ligand (CD95 ligand) controls angiogenesis beneath the retina

A principal cause of blindness is subretinal neovascularization associated with age-related macular degeneration. Excised neovascular membranes from patients with age-related macular degeneration demonstrated a pattern of Fas+ new vessels in the center of the vascular complex, surrounded by FasL+ retinal pigment epithelial cells. In a murine model, Fas (CD95)-deficient (lpr) and FasL-defective (gld) mice had a significantly increased incidence of neovascularization compared with normal mice. Furthermore, in gld mice there is massive subretinal neovascularization with uncontrolled growth of vessels. We found that cultured choroidal endothelial cells were induced to undergo apoptosis by retinal pigment epithelial cells through a Fas–FasL interaction. In addition, antibody against Fas prevented vascular tube formation of choroidal endothelial cells derived from the eye in a three-dimensional in vitro assay. Thus, FasL expressed on retinal pigment epithelial cells may control the growth and development of new subretinal vessels that can damage vision.

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.

Vaso-occlusive Retinopathy Associated with Anti-phospholipid Antibodies (lupus anticoagulant retinopathy)

The authors observed three cases (6 eyes) of vaso-occlusive retinopathy associated with the lupus anticoagulant and the related antiphospholipid antibody anticardiolipin. The disease occurred in patients who had no definable autoimmune disease such as systemic lupus erythematosus (SLE) and was characterized by severe bilateral retinal vascular occlusion. There was profound visual loss from intraretinal ischemia as well as vitreous hemorrhage from preretinal neovascularization. Results of laboratory testing showed a prolonged partial thromboplastin time (PTT) in two patients, and the presence of the lupus anticoagulant in all. Treatment with panretinal photocoagulation appeared to stabilize the neovascularization. The role of systemic anticoagulation and immunosuppressive therapy is uncertain.

Retinal pigment epithelial cell transplantation after subfoveal membranectomy in age-related macular degeneration: Clinicopathologic correlation

PURPOSEnTo report the histopathology after retinal pigment epithelial cell transplantation and subfoveal membranectomy in age-related macular degeneration.nnnMETHODSnAn 85-year-old white woman with bilateral choroidal neovascularization underwent subfoveal membranectomy combined with transplantation of a sheet of human adult retinal pigment epithelium (retinal pigment epithelium) under the foveal center in the right eye. The patient was immunosuppressed postoperatively with prednisone, cyclosporine, and azathioprine. The patient died from congestive heart failure 114 days after surgery.nnnRESULTSnA patch of hyperpigmentation was visible at the transplant site under the foveola after surgery. Mound-like clusters of individual round, large densely pigmented cells were present in the subretinal space and outer retina in this area. There was loss of the photoreceptor outer segments and native retinal pigment epithelium in the center of the transplant bed, with disruption of the outer nuclear layer predominantly over regions of multilayered pigmented cells. Cystic spaces were present in the inner and outer retina. A residual intra-Bruchs membrane component of the original choroidal neovascular complex was present under the transplant site.nnnCONCLUSIONSnThe transplant site contained clusters of round, pigmented cells that did not form a uniform monolayer in most areas. The morphology at the transplant site is consistent with the lack of visual improvement seen after surgery in this patient.

Retinal Pigment Epithelial Debridement as a Model for the Pathogenesis and Treatment of Macular Degeneration

PURPOSEnTo determine the effects of the absence of the retinal pigment epithelium on the choriocapillaris and outer retina by performing retinal pigment epithelial cell debridement with mitomycin C to inhibit cell proliferation pharmacologically in the porcine eye.nnnMETHODSnA pars plana vitrectomy was performed in 12 eyes, and two neurosensory retinal detachments per eye were created by injecting 10(-3) mg/ml mitomycin C and 0.25% edetic acid into the subretinal space. Twenty minutes later, the retinal pigment epithelium was debrided, and the retina was reattached with a fluid-gas exchange.nnnRESULTSnBruchs membrane was devoid of native retinal pigment epithelium, and the choriocapillaris was patent immediately after debridement. No proliferation of the retinal pigment epithelium occurred 1 week after debridement, and choriocapillaris atrophy was present beneath areas of Bruchs membrane that were devoid of retinal pigment epithelium. Four weeks postsurgery, choriocapillaris atrophy persisted in all debrided blebs, although unpigmented retinal pigment epithelium repopulated portions of Bruchs membrane in one of three blebs. Outer retinal atrophy was present in areas of Bruchs membrane with no retinal pigment epithelium and no choriocapillaris 4 weeks postsurgery. The choriocapillaris was patent in areas of mitomycin C injection without debridement.nnnCONCLUSIONnAbsence of the retinal pigment epithelium leads to atrophy of the choriocapillaris within 1 week after surgery. This finding provides an animal model to study transplantation of retinal pigment epithelium onto bare patches of Bruchs membrane in age-related macular degeneration and other diseases and provides insight into the pathogenesis of nonexudative age-related macular degeneration.

Distribution of Growth Factors in Subfoveal Neovascular Membranes in Age-related Macular Degeneration and Presumed Ocular Histoplasmosis Syndrome

PURPOSEnWe performed a histopathologic and immunohistologic study to determine the macromolecular and cellular components of subfoveal neovascular membranes removed at the time of submacular surgery.nnnMETHODSnSubfoveal 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.nnnRESULTSnMost 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.nnnCONCLUSIONSnSubfoveal 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.

Triple Agent Immunosuppression in Serpiginous Choroiditis

Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective.

Correlation between Scanning Laser Ophthalmoscope Microperimetry and Anatomic Abnormalities in Patients with Subfoveal Neovascularization

PURPOSEnThe purpose of the study is to identify the anatomic abnormalities associated with an absolute scotoma and the location and stability of fixation in patients with subfoveal neovascularization in age-related macular degeneration, presumed ocular histoplasmosis syndrome, and other disorders.nnnMETHODSnScanning laser ophthalmoscope microperimetry was superimposed on color fundus photographs and fluorescein angiograms of 21 eyes with subfoveal neovascular membranes secondary to age-related macular degeneration (14 eyes) and presumed ocular histoplasmosis syndrome (7 eyes). The authors determined the location and the area occupied by the absolute scotoma and each of the following subretinal lesions: subretinal hemorrhage, neurosensory retinal detachment, retinal pigment epithelial (RPE) atrophy, RPE hyperplasia, atrophy of the choriocapillaris, hard exudates, and the subfoveal neovascular membrane. The area of absolute scotoma determined by scanning laser ophthalmoscope microperimetry was superimposed on the anatomic lesions. The authors calculated the relative risk ratio (RR) of an absolute scotoma occurring in regions corresponding to each anatomic abnormality, and determined the preferred location and stability of fixation in each eye.nnnRESULTSnAn absolute scotoma was present in areas of chorioretinal scar (RR = 107.61), RPE atrophy (RR = 9.97), subretinal hemorrhage (RR = 2.88), and the neovascular membrane (RR = 1.86). Fixation was stable in all patients with presumed ocular histoplasmosis syndrome but only 29% of patients with age-related macular degeneration. Fifty-five percent of patients with stable fixation fixated over an area of RPE hyperplasia.nnnCONCLUSIONnThe relative risk of an absolute scotoma is highest over areas of chorioretinal scars, RPE atrophy, subretinal hemorrhage, and the neovascular membrane. Fixation is more stable in patients with subfoveal neovascularization from presumed ocular histoplasmosis syndrome than with age-related macular degeneration and frequently is present over an area of RPE hyperplasia.

Photoreceptor transplantation in retinitis pigmentosa: short-term follow-up

PURPOSEnTo explore the use of adult human photoreceptor transplantation as a treatment for advanced retinitis pigmentosa (RP).nnnDESIGNnProspective noncomparative case series.nnnPARTICIPANTSnEight patients with advanced RP.nnnINTERVENTIONnTransplantation of adult human cadaver photoreceptor sheets harvested with the excimer laser. No immunosuppression was used postoperatively. Patients were followed for 12 months postoperatively.nnnMAIN OUTCOME MEASUREnVisual acuity and retinal function measured by psychophysical, electrophysiologic, and clinical testing.nnnRESULTSnBest-corrected visual acuity (Bailey-Lovie chart), median reading speed, contrast sensitivity, and visual fields for the operated eye were not statistically significantly improved postoperatively. The amplitude and latency of the maculoscope electroretinogram, as well as the log threshold for dark adaptation, did not change between the operated and control (unoperated) eye. There was no detectable homograft reaction on slit-lamp biomicroscopy or fluorescein angiography. The only adverse effect observed was one patient who complained of monocular diplopia after retinal transplantation and subsequent cataract surgery.nnnCONCLUSIONSnAllogeneic adult human photoreceptor transplantation is feasible in RP but was not associated with rescue of central vision or a delay in visual loss. However, any possible slowing in the rate of retinal degeneration will take many years to determine.