John T. Thompson

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.

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 with 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.

TRANSFORMING GROWTH FACTOR-β2 SIGNIFICANTLY ENHANCES THE ABILITY TO FLATTEN THE RIM OF SUBRETINAL FLUID SURROUNDING MACULAR HOLES: Preliminary Anatomic Results of a Multicenter Prospective Randomized Study

Previous studies of treatment of full-thickness macular holes have effected resolution of the surrounding subretinal fluid cuff in 58%-71% of cases. An initial report has found 330 ng and 1,330 ng transforming growth factor-beta 2 to be successful in effecting resolution of the surrounding subretinal fluid cuff in 100% of cases. A randomized, masked, controlled, prospective, multicenter study of 90 patients with full-thickness macular holes was performed to assess the efficacy of the local application of TGF-beta 2 at the time of vitrectomy surgery. Eligibility criteria included: (1) best corrected visual acuity of 20/80 or worse; (2) duration of macular hole for less than 1 year; and (3) absence of other ocular disorders that might interfere with vision. Patients were evenly randomized to receive placebo, 660 ng transforming growth factor-beta 2, or 1,330 ng transforming growth factor-beta 2. The treatment assignment was unmasked at the examination 3 months after treatment only if the macular hole failed to close. If the initial treatment had been placebo, patients were offered crossover to 1,330 ng transforming growth factor-beta 2 during a reoperation. It can be deduced that resolution of the subretinal fluid cuff occurred in 16 of 30 placebo-treated eyes, 53 of 58 eyes treated with transforming growth factor-beta 2, and in 9 of 13 cases (69%) initially treated with placebo that subsequently underwent repeat surgery under the crossover option.(ABSTRACT TRUNCATED AT 250 WORDS)

COMPARISON OF RECOMBINANT TRANSFORMING GROWTH FACTOR-BETA-2 AND PLACEBO AS AN ADJUNCTIVE AGENT FOR MACULAR HOLE SURGERY

OBJECTIVE This study aimed to compare the visual and anatomic results of macular hole surgery in eyes treated with recombinant transforming growth factor-beta-2 (TGF-beta2) or placebo. DESIGN The design was a prospective, multicenter, randomized, double-masked, placebo-controlled clinical study. PARTICIPANTS One hundred thirty eyes with idiopathic macular holes of 1 year or less and a refracted Early Treatment Diabetic Retinopathy Study visual acuity of 20/80 or worse were treated with 1.1 microg recombinant TGF-beta2 or placebo to the macular hole after fluid-gas exchange. INTERVENTION The effect of recombinant TGF-beta2 as an adjunctive agent for macular hole surgery was evaluated. MAIN OUTCOME MEASURES Closure of the macular hole and change in visual acuity at 3 months were measured. RESULTS The 3-month visits were completed for 120 eyes. The macular hole was closed at 3 months in 35 (61.4%) of 57 eyes treated with placebo and 49 (77.8%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.08). The mean visual acuity gain was +6.4 letters in eyes receiving placebo and +8.9 letters in eyes treated with recombinant TGF-beta2 (P = 0.27). Visual acuity improved 2 or more lines in 23 (40.4%) of 57 eyes treated with placebo and 30 (47.6%) of 63 eyes treated with recombinant TGF-beta2 (P = 0.42). Intraocular pressure elevation greater than 30 mmHg was more common 2 weeks after surgery in eyes treated with recombinant TGF-beta2 (P < 0.001). CONCLUSIONS Recombinant TGF-beta2 resulted in a similar proportion of successful closure of macular holes as placebo. There was no statistically significant visual acuity benefit with the use of recombinant TGF-beta2 for the treatment of macular holes.

Assessment of Vision in Idiopathic Macular Holes with Macular Microperimetry Using the Scanning Laser Ophthalmoscope

BACKGROUND Visual loss in eyes with full-thickness macular holes has been thought to be due to the absence of retinal function in the area of neurosensory defect as well as loss or reduction of retinal function in the surrounding area of neurosensory retinal detachment. With the advent of surgical techniques to treat macular holes, it is increasingly important to better characterize this visual dysfunction. METHODS Thirty eyes of 30 patients with full-thickness idiopathic macular holes were evaluated with microperimetry using the scanning laser ophthalmoscope to detect and quantitate absolute and relative scotomata within the central 40 degrees of visual field. A log 2 scale of test stimulus intensities was established. Results of microperimetry were compared with best-corrected visual acuities as measured on the logarithmic Early Treatment of Diabetic Retinopathy Study chart as well as duration of symptoms. RESULTS All 30 eyes showed an absolute scotoma in the area of neurosensory defect as well as surrounding relative scotomata in the area of neurosensory detachment. Best-corrected visual acuity was correlated with the size of the absolute and relative scotomata (P < 0.002). The sizes of the scotomata were correlated with the duration of symptoms of the macular holes (P < 0.05). CONCLUSION Microperimetry using the scanning laser ophthalmoscope demonstrates that the visual loss associated with macular holes is related to the reduction of retinal function in the area of the surrounding neurosensory detachment as well as the absence of retinal function in the area of neurosensory defect. The size of the scotomata, determined by microperimetry, is correlated with the patients visual acuity as well as the duration of symptoms of the macular hole.

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.

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 surgeons 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.

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.

Prognostic Indicators of Success and Failure in Vitrectomy for Diabetec Retinopathy

Results of pars plana vitrectomy for complications of diabetic retinopathy were analyzed by logistic regression analysis in 1007 eyes to determine the preoperative and intraoperative factors associated with visual success or failure. Preoperative factors associated with a poorer visual outcome (final visual acuity less than 5/200) include preoperative iris neovascularization, cataract, visual acuity less than 5/200 and traction or rhegmatogenous retinal detachment. Intraoperative factors associated with a greater chance of a poor visual result include use of intravitreal gas or air and creation of an iatrogenic retinal break or detachment. The presence of any one of these factors resulted in a 1.5 to 3.9 times greater risk of a poor final visual result. The regression coefficients may be combined to predict the likelihood of obtaining final acuity greater than or equal to 5/200 in eyes with various preoperative characteristics.

Results of Vitrectomy for Proliferative Diabetic Retinopathy

The authors treated 1007 eyes with vitrectomy for complications of proliferative diabetic retinopathy. Indications for surgery were: vitreous hemorrhage, 353 eyes (35%); traction retinal detachment, 360 eyes (36%); combined traction-rhegmatogenous retinal detachment, 172 eyes (17%); and other progressive fibrovascular proliferation 122 eyes (12%). During the study period, the frequency of vitreous hemorrhage as an indication for surgery decreased from 42 to 25%, and other progressive fibrovascular proliferation increased from 5 to 22%. The frequency of traction and traction/rhegmatogenous retinal detachments did not change. The results of surgery varied according to the indication. Seventy-nine percent of eyes with vitreous hemorrhage obtained final vision of 5/200 or better. Similar results were obtained in 64% of eyes with traction detachment, 56% of eyes with rhegmatogenous detachment, and 81% of eyes with progressive fibrovascular proliferation. The percentage of eyes achieving final vision of 20/100 or better are as follows: vitreous hemorrhage, 48%; traction detachment, 27%; rhegmatogenous detachment, 24%; and progressive fibrovascular proliferation, 46%. The success rate improved in each anatomic category during the last 3 years of the study.