Bert M. Glaser

Transforming Growth Factor-β2 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-β 2 (TGF-β 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-β 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-β 2 in eyes with a fullthickness 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-β 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-β 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-β 2 on visual improvement ( P = 0.003).

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.

Clinicopathologic Correlation of an Untreated Macular Hole and a Macular Hole Treated by Vitrectomy, Transforming Growth Factor-β2, and Gas Tamponade

PURPOSE To study the clinicopathologic features of an untreated macular hole in the right eye and a macular hole in the left eye treated by vitrectomy, application of transforming growth factor-beta 2, and gas tamponade. METHODS The patient, a 73-year-old man with bilateral macular holes, was studied clinically before and after surgical treatment of the macular hole in his left eye. The patients eyes were obtained postmortem and serially step-sectioned through the macula and optic nerve head for electron microscopy. RESULTS Examination of 1-micron thick plastic-embedded sections through the macula of the right eye disclosed a 0.6-mm macular hole with rounded gliotic margins, a thin epiretinal membrane, and parafoveal cystic changes. Examination of 1-micron thick plastic-embedded sections through the macula of the left eye disclosed a 0.25-mm defect in the fovea, which was bridged by glial cells. The glial cells were continuous with a thin hypocellular epiretinal membrane without contraction features on both sides of the defect. The ultrastructural features of the glial cells were consistent with Mueller cells. CONCLUSIONS Treatment of a macular hole with vitrectomy, transforming growth factor-beta 2, and gas tamponade was followed by complete closure of the macular hole by Mueller cell proliferation.

Resolution of an Absolute Scotoma and Improvement of Relative Scotomata After Successful Macular Hole Surgery

Visual loss in eyes with full-thickness macular holes is thought to be caused by the absence of retinal function in the area of the neurosensory defect as well as reduction in retinal function in the surrounding area of neurosensory retinal detachment. To improve characterization of the visual function of eyes after successful macular hole surgery, we studied six eyes preoperatively and postoperatively with macular microperimetry using the scanning laser ophthalmoscope. Best-corrected visual acuity was improved postoperatively in all eyes. Microperimetry performed preoperatively demonstrated an absolute scotoma that corresponded to the neurosensory defect in all eyes, with surrounding concentric isopters of relative scotomata. No detectable absolute scotoma was found in any eye postoperatively. All eyes showed partial or complete resolution of the surrounding relative scotomata. Improvements in visual acuity after successful macular hole surgery may be related to disappearance of a detectable absolute scotoma as well as improvement in the surrounding retinal function.

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.

Cryotherapy during Surgery for Giant Retinal Tears and Intravitreal Dispersion of Viable Retinal Pigment Epithelial Cells

BACKGROUND Retinal pigment epithelial (RPE) cells are a major component of contractile cellular membranes in proliferative vitreoretinopathy (PVR). Displacement of viable RPE cells into the vitreous cavity is necessary for membrane formation. This study examines the effect of cryotherapy during surgery for giant retinal tears on the dispersion of viable cells into the vitreous cavity. METHODS A total of seven eyes undergoing vitrectomy and retinal reattachment surgery were studied. Vitreous fluid from three eyes was aspirated immediately after cryotherapy; fluid from four eyes was aspirated after scleral indentation with the cryoprobe, but without cryotherapy. Colonies of pigmented cells routinely grew in flasks inoculated with fluid from eyes treated with cryotherapy. In contrast, flasks inoculated with fluid from eyes not treated with cryotherapy contained significantly fewer viable cells. CONCLUSION Cryotherapy performed during retinal reattachment surgery in eyes with giant retinal tears is likely to enhance intravitreal dispersion of viable RPE cells. The findings in this study suggest that possible harmful effects of cryotherapy should be evaluated further and that alternative methods of creating a chorioretinal adhesion should be considered in cases with an especially high risk of PVR.

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.

Retreatment of full-thickness macular holes persisting after prior vitrectomy. A pilot study.

PURPOSE Vitrectomy with fluid-gas exchange has been shown to close more than one half of full-thickness macular holes, with improvement in visual acuity. By adding the appropriate dose of transforming growth factor-beta 2, a higher success rate has been reported. However, there still remain cases of macular holes that fail to close after vitreous surgery. The current pilot study is designed to determine whether reoperation may have a role in the management of cases that fail after vitreous surgery. METHODS Twelve eyes with persistent full-thickness macular holes that failed to close after an initial vitrectomy underwent reoperation using 1330 ng transforming growth factor-beta 2. RESULTS After the second operation, closure occurred in 12 (100%) of 12 eyes. Follow-up ranged from 8 to 16 months. Visual acuity also improved by two or more lines in 5 (42%) of 12 patients. Increased nuclear sclerosis occurred in nine (90%) of the ten phakic eyes. Of the five eyes showing visual improvement, four required cataract extraction and intraocular lens implantation. CONCLUSION Retreatment of persistent full-thickness macular holes with transforming growth factor-beta 2 appears to have a beneficial effect on both neurosensory retinal flattening and visual outcome.

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.