Efficacy of subthreshold micropulse laser in the treatment of diabetic macular edema is influenced by pre-treatment central foveal thickness.

PURPOSE: To determine if the severity of diabetic macular edema influences the effectiveness of subthreshold micropulse (STMP) laser treatment. METHODS: A total of 63 eyes of 58 patients with diabetic macular edema were divided into two groups based on their initial central foveal thickness (CFT). Group 1 had CFT ≤400 µm, group 2 had CFT >400 µm. The change from baseline in CFT and visual acuity were compared at 3, 6 and 12 months follow-up. Patients were considered for retreatment with micropulse laser at 3 months if macular edema had not improved. Patients were considered for rescue anti-VEGF injections if there was clinically significant macular edema at 6 months follow-up. Number of laser retreatments, injections, and any adverse effects from STMP laser were recorded. RESULTS: Group 1 (n=33) experienced an average of 55 µm reduction in CFT and 0.2 log MAR gain in visual acuity at 12 months (P<0.001). No patient required rescue anti-VEGF injections. Group 2 (n=30) experienced no significant change in CFT or visual acuity by 6 months despite retreatment with STMP in 19 eyes. From 6 to 12 months follow-up, all the patients in group 2 received rescue Bevacizumab injections that resulted in 307 µm reduction in CFT and 0.3 log MAR improvement in visual acuity (P<0.001). No adverse effects from STMP laser were recorded. CONCLUSION: Severity of edema can influence the effects of STMP laser. STMP monotherapy is safe and effective in treating edema of mild to moderate severity.

Scleral outfolding for macular translocation.

PURPOSE: To report experimental study and clinical observation of scleral outfolding for macular translocation. METHODS: In six human cadaver eyes, circumferential mattress sutures to create sclera infoldings were compared with radial-interrupted mattress sutures to create scleral outfoldings. In a 75-year-old man with macular degeneration and choroidal neovascular membrane, radial-interrupted mattress sutures were used for macular translocation. RESULTS: In the human cadaver eyes, circumferential mattress sutures for scleral infolding created an average decrease in corresponding internal anteroposterior retinal contour of 0.36 mm. Radial-interrupted mattress sutures for scleral outfoldings created an average decrease in the corresponding internal anteroposterior retinal contour of 4. 61 mm. The statistical significance of the difference between infoldings of the sclera versus outfoldings of the sclera had a P value of.0001. CONCLUSIONS: Initial experimental and clinical study suggests that radial-interrupted mattress sutures may generate more shortening of the internal scleral surface and greater macular translocation than circumferential mattress sutures. Additional studies are needed to evaluate the long-term effects of radial-interrupted mattress sutures and macular translocation for treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

Clinicopathologic correlation of an untreated macular hole and a macular hole treated by vitrectomy, transforming growth factor-beta 2, 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 patient's 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.

Increased intraocular pressure after macular hole surgery.

PURPOSE: To determine the incidence and timing of increased intraocular pressure in eyes with an idiopathic macular hole treated with bovine transforming growth factor-beta 2 (TGF-beta 2) with different intraocular gas concentrations, recombinant TGF-beta 2, or placebo. METHODS: Intraocular pressure was measured preoperatively and two days, two weeks, six weeks, and three months postoperatively in two prospective studies of the treatment of idiopathic macular hole with vitrectomy. Group 1 consisted of 95 eyes treated with bovine TGF-beta 2. Eyes in this group were treated with different concentrations of air and perfluoropropane (C3F8) intraocular gas bubbles. Fifteen eyes were treated with air, 15 eyes with 5% perfluoropropane, 15 eyes with 10% perfluoropropane, and 50 eyes with 16% perfluoropropane. Group 2 consisted of 29 eyes treated with recombinant TGF-beta 2. Twenty-six eyes were treated with placebo in a double-masked, randomized, placebo-controlled study evaluating recombinant TGF-beta 2 with a 16% perfluoropropane intraocular gas bubble. RESULTS: At the two-week examination, the intraocular pressure in Group 1 eyes was > 30 mm Hg in four (26.7%) of 15 eyes treated with air, two (13.3%) of 15 eyes treated with 5% perfluoropropane, one (8.3%) of 12 eyes treated with 10% perfluoropropane, and nine (19.1%) of 47 eyes treated with 16% perfluoropropane. There was no statistically significant difference in the risk of increased intraocular pressure in eyes treated with short-, intermediate-, or long-duration gas tamponade using bovine TGF-beta 2. The intraocular pressure in Group 2 was > 30 mm Hg at the two-week examination in 11 (39.3%) of 28 eyes receiving recombinant TGF-beta 2 compared with one (4.3%) of 23 eyes receiving a placebo (P = .006). CONCLUSIONS: Some eyes develop increased intraocular pressure after vitreous surgery for macular hole, and the increase occurs most frequently between two days and two weeks postoperatively. The risk of increased intraocular pressure is somewhat increased in eyes treated with bovine TGF-beta 2 but is markedly increased in eyes in which recombinant TGF-beta 2 is used as an adjunctive agent for macular hole surgery. Intraocular injection of growth factors produced by similar recombinant DNA techniques may result in potentially dangerous increased intraocular pressure several weeks after surgery. Impurities in the recombinant TGF-beta 2 may explain the relatively high risk of increased intraocular pressure.

Reoperation after failed macular hole surgery.

PURPOSE: The authors determined the anatomic and visual success rates of vitrectomy in patients who have failed previous macular hole surgery. METHODS: Standardized Early Treatment Diabetic Retinopathy Study (ETDRS)-style best-corrected visual acuity was measured in each patient pre- and postoperatively. Surgery was performed at two centers using a standardized protocol, as previously reported, using 1330 ng bovine-derived transforming growth factor-beta 2 (TGF-beta 2) and 16% perfluoropropane internal gas tamponade. Endpoint analyses were conducted for anatomic closure of the hole, visual improvement of three or more ETDRS lines, and final visual acuity of > or = 20/63 and > or = 20/40. RESULTS: Forty-eight failing macular hole surgery were reoperated. The anatomic results showed closure of the hole in 40 (83%) cases at the end of the mean follow-up interval of 7.4 months. The visual acuity improved in greater than or equal to three lines in 52%, was > or = 20/63 in 54%, and was > or = 20/40 in 25% of reoperated eyes. The only factor associated with a better final visual acuity was preoperative visual acuity better than 20/80. Nuclear sclerosis leading to cataract extraction was observed in 13 (30%) of 43 initially phakic eyes. CONCLUSIONS: Macular hole closure was induced in this subset of reoperated patients. Visual improvement occurred often, although in a lower percentage than has been reported for primary surgical eyes. Repeat vitrectomy should be considered in patients with persistent macular hole after failure of primary surgery.

Intraocular tamponade duration and success of macular hole surgery.

PURPOSE: The authors compare the success of macular hole surgery with a short duration tamponade using 5% perfluoropropane (C3F8), intermediate duration tamponade using 10% C3F8, or a long duration tamponade using 16% C3F8 in a prospective consecutive clinical trial at two institutions. METHODS: Vitrectomy and fluid-gas exchange was performed in 29 eyes treated with 5% C3F8 and 1 week of prone positioning, 30 eyes treated with 10% C3F8 and 2 weeks of prone positioning, and 90 eyes treated with 16% C3F8 and 2 weeks of prone positioning 90% of time, followed by 2 weeks of prone positioning 50% of time. RESULTS: The macular hole was closed successfully in 19 of 29 eyes (65.6%) treated with 5% C3F8, 19 of 30 eyes (63.3%) treated with 10% C3F8, and 85 of 90 eyes (94.4%) treated with 16% C3F8 at 3 months (P = 0.00017 for 5% vs. 16% C3F8, P = 0.00006 for 10% vs. 16% C3F8). The visual acuity improvements measured by refraction using the Early Treatment Diabetic Retinopathy Study (ETDRS) acuity charts paralleled the success of macular hole closure. The acuity improved a mean improvement of + 9.6 ETDRS letters for eyes treated with 5% C3F8, + 6.4 ETDRS letters for eyes treated with 10% C3F8, and + 13.1 ETDRS letters in eyes treated in 16% C3F8. CONCLUSIONS: A long duration intraocular gas tamponade with 16% C3F8 gives a substantially higher success rate for macular hole surgery than a short (5% C3F8) or intermediate duration (10% C3F8) intraocular gas tamponade.

Vitrectomy, fluid-gas exchange and transforming growth factor--beta-2 for the treatment of traumatic macular holes.

PURPOSE: To evaluate whether vitreous surgery is successful in closing full-thickness traumatic macular holes and whether there is subsequent improvement in visual acuity. METHODS: Twelve eyes from 12 consecutive patients with traumatic macular holes underwent vitrectomy, fluid-gas exchange and instillation of bovine or recombinant transforming growth factor (TGF)-beta-2. Three of four eyes underwent repeat vitrectomy with TGF-beta-2 after the initial procedure failed to close the macular hole. RESULTS: Eleven (92%) of 12 eyes had closure of the macular hole. Follow-up ranged from 3 to 33 months. Visual acuity improved by 2 or more lines in 8 (67%) of 12 eyes. Six (50%) of 12 eyes improved to 20/40 or better. All 3 eyes that underwent reoperation had successful closure of the macular hole and achieved 2 or more lines of visual improvement. CONCLUSION: Treatment of full-thickness traumatic macular holes with vitrectomy, fluid-gas exchange, and TGF-beta-2 may result in successful anatomic closure and visual improvement.

Full-thickness macular hole formation in eyes with a pre-existing complete posterior vitreous detachment.

BACKGROUND: Tangential macular traction by the posterior vitreous cortex has been widely accepted as the major causative factor in the development of idiopathic macular holes. Separation of the posterior cortical vitreous should relieve this vitreoretinal traction. METHODS: The authors report five patients with idiopathic full-thickness macular hole formation that occurred in the presence of a well-documented pre-existing complete posterior vitreous detachment. RESULTS: Of five eyes, three underwent pars plana vitrectomy and instillation of transforming growth factor-beta. No residual prefoveal cortical vitreous was present at the retinal surface at the time of surgery. Additionally, clinically identifiable epiretinal membranes were present in three of five eyes, but these epiretinal membranes were extremely thin, transparent, induced minimal traction, and did not warrant surgical peeling. CONCLUSION: It is likely that, in these five patients, some mechanism other than tangential traction by prefoveal vitreous cortex is responsible for idiopathic full-thickness macular hole formation.

Distribution of iatrogenic retinal breaks in macular hole surgery.

BACKGROUND: Intraoperative peripheral iatrogenic retinal breaks can be a serious complication of vitreous surgery. This study was undertaken to determine whether vitreous surgical techniques used for macular hole surgery were associated with a different incidence or distribution of retinal breaks. METHODS: The authors prospectively evaluated a series of 181 consecutive eyes undergoing macular hole surgery. Contemporaneous reporting of intraoperative and postoperative retinal breaks and postoperative retinal detachments was performed. Comparison was made to historic controls of two case series of patients undergoing vitreous surgery for other indications. RESULTS: Of 181 eyes, 10 (5.5%) had 15 intraoperative retinal breaks. Of the 15 breaks, 3 (20%) were in the quadrant near the surgeon's right-hand sclerotomy, 9 (60%) were in the two inferior quadrants, and 11 (73%) were in the two temporal quadrants. By comparison to previously reported case series, tears in our series were less likely to be near the right-hand sclerotomy (P = 0.00055) and more likely to occur in the two inferior retinal quadrants (P = 0.00015) and two temporal retinal quadrants (P = 0.0042). Two patients (1.1%) of 181 had postoperative retinal detachments. CONCLUSIONS: Patients undergoing vitreous surgery for macular hole have a similar incidence but different location of iatrogenic retinal breaks when compared with patients undergoing pars plana vitrectomy for other indications. These breaks are not distributed near sclerotomy sites and tend to be in the inferior and temporal retina. This establishes the need for greater intraoperative surveillance in these areas.

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.

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.

Efficacy of fluid-air exchange during pars plana vitrectomy.

PURPOSE: Vitreous fluid that remains trapped in the peripheral vitreous cavity after vitrectomy with fluid-air exchange can result in a smaller than desired intravitreal gas bubble size. To evaluate the effectiveness of a single fluid-air exchange in dehydrating the vitreous cavity, we measured the rate and volume of posterior vitreous fluid migration after an initial fluid-air exchange. METHODS: Thirty-eight eyes undergoing vitrectomy for macular hole closure had measurements of posterior vitreous fluid accumulation at either 5, 10, 15, or 20 minutes after fluid-air exchange. RESULTS: An average of 0.38 ml of fluid accumulated posteriorly within 10 minutes after the initial fluid-air exchange compared to 0.22 ml that accumulated after 5 minutes (P = 0.0003). A mean of 0.04 ml accumulated during each 5-minute interval between 10 and 20 minutes after the initial fluid-air exchange. CONCLUSION: Fluid composing 10% of the vitreous volume may migrate and accumulate posteriorly within 10 minutes of an apparently complete fluid-air exchange. Fluid aspiration after a 10-minute wait after the initial fluid-air exchange helps maximize vitreous cavity dehydration and should be employed when a large gas bubble is required after vitrectomy.

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.

Effects of intraocular bubble duration in the treatment of macular holes by vitrectomy and transforming growth factor-beta 2.

PURPOSE: To compare the effect of a long-acting (16% perfluoropropane [C3F8]) versus a short-acting (air) intraocular gas tamponade on visual outcome and macular hole closure rate after vitrectomy and intravitreal instillation of transforming growth factor-beta 2 (TGF-beta 2) on the macula. METHODS: Vitrectomy with removal of the posterior hyaloid fluid-gas exchange with instillation of TGF-beta 2 was performed in 15 eyes treated with air and 37 eyes treated with 16% C3F8 using identical surgical techniques (mean follow-up, 5.6 months). RESULTS: The macular hole was closed successfully in 36 (97%) of 37 eyes treated with 16% C3F8 and in 8 (53.3%) of 15 eyes treated with air (P = 0.00007). The visual acuity improved by a mean of 3.1 lines on the Early Treatment of Diabetic Retinopathy Study chart for eyes treated with 16% C3F8 and 1.3 lines for eyes treated with air (P = 0.003). CONCLUSIONS: A longer duration intraocular gas tamponade from 16% C3F8 gives a much higher rate of successful closure of macular holes and improved visual acuity using vitrectomy and TGF-beta 2 than does air.

Effects of TGF-beta and TGF-beta neutralizing antibodies on fibroblast-induced collagen gel contraction: implications for proliferative vitreoretinopathy.

PURPOSE: The main cause of failure after retinal reattachment surgery is proliferative vitreoretinopathy (PVR), in which contractile fibrocellular membranes form on the retinal surface and vitreous base. Recently, elevated levels of transforming growth factor-beta 2 (TGF-beta 2) were measured in the vitreous of patients with PVR, suggesting a possible association with the disease. Because neutralizing TGF-beta may prove useful in controlling this blinding disease process, the authors examined the effect of anti-TGF-beta 1 and TGF-beta 2 antibodies in TGF-beta-mediated fibroblast-induced collagen gel contraction. METHOD: Rabbit dermal fibroblasts were combined with type I collagen in an in vitro model of collagen gel contraction. The authors evaluated the effect of TGF-beta 1, TGF-beta 2, and their antibodies on fibroblast-induced gel contraction. RESULTS: TGF-beta 1 and TGF-beta 2 equally enhanced gel contraction to an average of 6% to 7% of the control area by day 4. In contrast, gels without TGF-beta contracted only to an average of 38% of the control gels. Several anti-TGF-beta antibodies neutralized this TGF-beta-enhanced contraction, whereas control IgGs had no effect. A dose-dependent response was detected with TGF-beta 1, TGF-beta 2, and anti-TGF-beta. CONCLUSION: Because TGF-beta levels have been shown to correlate with the severity of PVR, the neutralizing action of anti-TGF-beta on TGF-beta-mediated contraction may offer further insights into the structure and function of PVR membranes and may provide clues to possible therapeutic solutions for controlling this disease process.

Fluorescein angiographic characteristics of macular holes before and after vitrectomy with transforming growth factor beta-2.

We evaluated the fluorescein angiographic features of full-thickness macular holes before and after vitrectomy, fluid-gas exchange, and instillation of transforming growth factor beta-2 in 43 eyes in a masked fashion to evaluate the angiographic characteristics of macular holes preoperatively and the changes that occur with successful and unsuccessful closure of the macular hole. Hyperfluorescence was present in the base of the macular hole preoperatively in 34 of 43 eyes (79.1%), was questionable in eight of 43 eyes (18.6%), and was definitely absent in only one of 43 eyes (2.3%). The hyperfluorescence in the base of the macular hole disappeared in 19 of 20 eyes (95%) with successful closure of the macular hole (P < .00001) and appeared to be caused by blocked fluorescence at the site of the macular hole. The photographic features of eyes with unsuccessful closure of the macular hole changed little, except that the size of the cuff of neurosensory detachment around the hole increased and was associated with decreased postoperative visual acuity. These angiographic changes support the presence of a glial tissue plug bridging a small defect in the fovea of eyes with successful closure of a macular hole.

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.

Indocyanine green angiography in multiple evanescent white-dot syndrome.

Using indocyanine green angiography we examined two patients with multiple evanescent white-dot syndrome. Both patients had unilateral loss of vision and a fundus appearance typical of multiple evanescent white-dot syndrome. Fluorescein angiography in both patients disclosed a patchy hyperfluorescent pattern at the level of the retinal pigment epithelium. Using indocyanine green angiography, we observed multiple deep, small, round hypofluorescent lesions that appeared early and persisted into the late phases. The spots appeared to block the underlying choroidal pattern. These hypofluorescent spots were clearly visible and present throughout the posterior pole. Many more spots were seen on indocyanine green angiography than were visible by clinical examination or angiography. After follow-up examinations, there was a rapid resolution of the spots over four to six weeks with return of vision. Our findings show that indocyanine green angiography can be a valuable tool in the recognition and further understanding of multiple evanescent white-dot syndrome.

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.

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.