NEI Clinical Studies
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Silicone Study, The
- To compare, through a randomized, multicenter surgical trial, the postoperative tamponade effectiveness of intraocular silicone oil with that of an intraocular long-acting gas (initially sulfur hexafluoride [SF6], later perfluoropropane [C3F8]) for the management of retinal detachment complicated by proliferative vitreoretinopathy (PVR), using vitrectomy and associated techniques.
- To evaluate the ocular complications that result from the use of silicone oil and gas.
The treatment of retinal detachment complicated by PVR remains controversial. Although some cases are managed successfully by pars plana vitrectomy and with temporary tamponade provided by intraocular gas, others eventually redetach with this technique. Preliminary reports indicate that prolonged tamponade with liquid silicone results in improved anatomical success, but the eventual visual outcome may be prejudiced by silicone-related complications, particularly glaucoma and keratopathy. The addition of hydraulic reattachment by simultaneous fluid/gas exchange to vitrectomy surgery has proved to be an important development. Although complications are few with these procedures, subsequent redetachment is frequent.
The Silicone Study was a randomized trial to investigate the relative merits of silicone oil or gas as tamponade modalities. All study patients underwent vitrectomy and were randomized intraoperatively either to silicone oil or to gas. Two groups of eyes were entered into the study: eyes that had not had a prior vitrectomy (Group 1) and those that had undergone previous vitrectomy outside the study (Group 2).
A critical element in the study was a standardized surgical procedure for PVR. This surgical procedure, intended to relieve retinal traction with vitrectomy techniques, was followed by assessment of the relief provided by an intraocular air tamponade. The eye was randomized to silicone oil or gas only after completion of the entire surgical procedure to eliminate investigator bias that might develop through knowledge of the treatment modality. Patients were examined 5 to 14 days following the randomization and again at 1, 3, 6, 12, 18, 24, and 36 months after that date. Repeated surgery was permitted for either treatment modality. The Fundus Photograph Reading Center staff processed and analyzed photographs taken at all the clinics, graded the preoperative severity of PVR on the basis of baseline visit photographs, and confirmed the macular status at followup visits.
End points of the study were visual acuity of 5/200 or greater and macular reattachment for 6 months following the final surgical procedure. The successful outcomes and complication rates of the two modalities were compared.
Eligibility criteria included but were not limited to PVR of Grade C-3 or greater according to the Retina Society Classification and visual acuity of light perception or better.
Patient Recruitment Status
Completed. Recruitment began on September 1, 1985, and was completed June 30, 1991. A total of 151 eyes were randomized to receive either SF6 gas or silicone oil (113 in Group 1 and 38 in Group 2). Four hundred and four eyes were randomized to receive either C3F8 gas or silicone oil (232 and 172 in Groups 1 and 2, respectively).
Current Status of Study
Results and Implications for Clinical Practice Outcomes Comparing Group 1 Versus Group 2:
Previous reports have stressed the perceived differences in pathologic anatomy and outcomes in eyes undergoing primary vitrectomy (Group 1 eyes) compared with eyes that have already failed at least one prior vitrectomy for PVR (Group 2 eyes). In those nonrandomized retrospective studies, Group 2 eyes have had poorer anatomic and visual results than Group 1 eyes. In the Silicone Study, anatomic and vision results and prevalence of complications suggest that the differences in outcomes between Groups 1 and 2 were not as great as previously believed.
Intraocular pressure (IOP) abnormalities were a common postoperative complication in eyes with PVR. Chronically elevated IOP was found in 5 percent of the eyes; chronic hypotony was found in 24 percent of the eyes. Chronically elevated IOP was more prevalent in silicone oil eyes than in C3F8 gas eyes. Chronic hypotony was more prevalent in C3F8 gas eyes than in silicone oil eyes, more prevalent in eyes with anatomical failure, and correlated with poor postoperative vision, corneal opacity, and retinal detachment. The presence of diffuse contraction of the retina anterior to the equator should alert the vitrectomy surgeon that the eye is likely to be hypotonous postoperatively.
Retinotomy in the Silicone Study:
Using data from the Silicone Study, we compared the cohort of eyes that underwent relaxing retinotomy with the cohort of eyes that did not in regard to preoperative and intraoperative findings and to visual and anatomic outcomes and complications. We concluded that eyes undergoing vitreous surgery for the first time for the treatment of PVR can be treated successfully in most instances by conventional techniques without the need for relaxing retinotomy. Retinotomy may be required more frequently in patients undergoing repeat vitreous surgery for PVR. In those patients, silicone oil and C3F8 gas appeared to be equally effective tamponade modalities. In eyes undergoing retinotomy that have not been previously vitrectomized, silicone oil may initially increase the likelihood of visual success and may decrease the likelihood of hypotony at 6 months; however, long-term observations at 24 months suggested a trend toward worsening in silicone oil-filled eyes and improvement in gas-filled eyes.
Outcomes After Silicone Oil Removal:
Because the advisability of silicone oil removal from these complex eyes remains controversial, we used data from the Silicone Study to compare visual and anatomic outcomes in the cohort of eyes from which oil was removed with visual and anatomic outcomes in the cohort of eyes in which oil was retained. Compared with the oil-retained eyes evaluated at a comparable time after silicone oil injection, oil-removed eyes at the examination before oil removal were more likely to have attached retinas, have visual acuity 5/200, and not be hypotonous. Eyes with attached retinas at the time of oil removal generally showed improvement in visual acuity at the last followup examination. In a matched-pair cohort analysis comparing oil-removed eyes with oil-retained eyes, there was an increased risk of recurrent retinal detachment at the last followup examination in the oil-removed eyes. However, in oil-removed eyes with attached retinas at the last followup examination, overall visual acuity improved and the incidence of complications decreased.
Corneal Abnormalities in the Silicone Study:
The Silicone Study was the first study to document that the postoperative incidence rates of corneal abnormalities are equivalent between oil and gas. The incidence of corneal abnormalities in eyes randomized to gas was higher than expected, and the incidence of corneal abnormalities in eyes randomized to silicone oil remained high in spite of the use of an inferior iridectomy. Successful surgical repair of the retinal detachment with a single operation and prevention and early management of silicone oil-corneal touch should help to prevent corneal abnormalities. If rubeosis iridis or severe aqueous flare is present, preoperative treatment with intense topical and possibly periocular steroids might help to reduce preoperative and postoperative inflammation, which may mediate corneal damage.
Postoperative Macular Pucker in the Silicone Study:
Macular pucker is a term that describes wrinkles and folds in the central retina resulting from contraction of an epiretinal membrane. A limited manifestation of PVR, macular pucker is observed within 6 months in 4 to 13 percent of eyes after successful conventional surgery for retinal detachment without PVR. Using data from the Silicone Study, we found that the 6-month point prevalence rate of postoperative macular pucker was 15 percent. The occurrence of macular pucker following successful surgery for retinal detachments complicated by severe PVR was not influenced by the choice of intraocular tamponade.
Prognosis Using the Silicone Study Classification System:
As part of the study, a Silicone Study classification system for PVR was developed based on the characteristic patterns of retinal distortion produced by the contraction of proliferative membranes on the retina or within the vitreous base. This classification was designed to document the extent and anatomic distribution of PVR present preoperatively and to help standardize the surgical treatment. Using data from the Silicone Study, we demonstrated that identification of the anteroposterior extent of the PVR was prognostic of visual acuity and hypotony at 24 months. The joint knowledge of the location of PVR (using the Silicone Study classification system) and the tightness of the funnel for retinas with 9 to 12 clock hours involved by fixed folds (using the Retinal Study classification system) has prognostic utility for eyes presenting with anterior plus posterior PVR.
Comparison of Outcome in Anterior Versus Posterior PVR in the Silicone Study:
Using the Silicone Study classification system, we compared preoperative and intraoperative findings, and vision and anatomic outcomes and complications, in the cohort of eyes with anterior PVR and the cohort of eyes with only posterior PVR. We found that anterior PVR was more prevalent in these Silicone Study eyes than was posterior PVR and had a worse prognosis. Eyes with anterior PVR and clinically significant posterior PVR changes had a better visual prognosis if silicone oil rather than C3F8 gas was used.
Long-Term Outcome in the Silicone Study:
At the time of study closeout (June 30, 1991), the National Eye Institute funded an extension of the Silicone Study to provide long-term followup in the cohort of eyes (randomized to silicone oil or long-acting gas) with attached maculas at the 36-month followup examination. During 6 years of followup, attachment of the macula was maintained for all eyes. No significant differences in the rates of complete retinal attachment, visual acuity greater than 5/200 or glaucoma were found between treatment groups. In contrast, gas-treated eyes had more hypotony. Success in the first operation for PVR is paramount in obtaining better visual results. Overall, surgery for PVR had a high likelihood of retinal reattachment, and if anatomically and visually successful at 3 years, there is an excellent chance that the results will be maintained over the long term.
Abrams GW, Azen SP, McCuen BW, Flynn H, Lai MY, Ryan SJ, Silicone Study Group: Vitrectomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy: Results of additional long-term follow-up (Silicone Study Report #11). Archives of Ophthalmology 115: 335-344, 1997.
Diddie KR, Azen SP, Freeman HM, Boone DS, Aaberg TM, Lewis H, Radtke NA, Ryan SJ, Silicone Study Group: Anterior proliferative vitreoretinopathy in the Silicone Study (Silicone Study Report #10). Ophthalmology 107: 1092-1099, 1996.
Lean J, Azen SP, Lopez P, Qian D, Lai MY, McCuen B, Silicone Study Group: The prognostic utility of the Silicone Study Classification System (Silicone Study Report #9). Arch Ophthalmol 114: 286-292, 1996.
Abrams GW, Azen SP, Barr CC, Lai MY, Hutton WL, Trese MT, Irvine A, Ryan SJ, Silicone Study Group: The incidence of corneal abnormalities in the Silicone Study (Silicone Study Report #7). Arch Ophthalmol 113: 764-769, 1995.
Cox MS, Azen SP, Barr CC, Linton KLP, Diddie KR, Lai MY, Freeman HM, Irvine A, Silicone Study Group: Macular pucker after successful surgery for proliferative vitreoretinopathy (Silicone Study Report #8). Ophthalmology 102: 1884-1891, 1995.
Hutton WL, Azen SP, Blumenkranz MS, Lai MY, McCuen BW, Han D, Flynn HW, Ramsey RC, Ryan SJ, Silicone Study Group: The effects of silicone oil removal (Silicone Study Report #6). Arch Ophthalmol 112: 778-785, 1994.
McCuen BW, Azen SP: Reply to the editor: The letter from Peyman, Greve, Millsap. Arch Opthalmol 112: 729, 1994.
Azen SP, Ryan SJ: Reply to the editor: The letters from Clement K. Chan and Yannick Le Mer. Arch Ophthalmol 111: 428-429, 1993.
Barr CC, Lai MY, Lean JS, Linton KLP, Trese M, Abrams G, Ryan SP, Azen SP, Silicone Study Group: Postoperative intraocular pressure abnormalities in the Silicone Study (Silicone Study Report #4). Ophthalmology 100: 1629-1635, 1993.
Blumenkranz MS, Azen SP, Aaberg TM, Boone DC, Lewis H, Radtke N, Ryan S, Silicone Study Group: Relaxing retinotomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy (Silicone Study Report #5). Am J Ophthalmol 116: 557-564, 1993.
McCuen II BW, Azen SP, Stern W, Lai MY, Lean JS, Linton KLP, Ryan SJ, Silicone Study Group: Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy (Silicone Study Report #3). Retina 13: 279-284, 1993.
Lean JS, Boone DC, Azen SP, Lai MY, Linton KLP, McCuen B, Ryan SJ, Silicone Study Group: Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy. Results of a randomized clinical trial (Silicone Study Report #1). Arch Ophthalmol 110: 770-779, 1992.
McCuen B, Azen SP, Boone DC, Lai MY, Linton KLP, Lean J, Ryan SJ, Silicone Study Group: Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy. Results of a randomized clinical trial (Silicone Study Report #2). Arch Ophthalmol 110: 780-792, 1992.
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Barlow W, Azen SP, Silicone Group: The effect of therapeutic treatment crossovers on the power of a clinical trial. Controlled Clin Trials 11: 314-326, 1990.
Azen SP, Irvine AR, Davis M, Stern W, Lonn L, Hilton G, Schwartz A, Boone D, Quillen-Thomas B, Lyons M, Silicone Study Group: The validity and reliability of photographic documentation of proliferative vitreoretinopathy. Ophthalmology 96: 352-357, 1989.
Boone DC, Lai M, Azen S, Silicone Study Group: Clinical judgment and centralized data management. Controlled Clin Trials 10: 339, 1989.
Irvine AR: Photographic documentation and grading of PVR, in Freeman HM, Tolentino FI (eds). Proliferative Vitreoretinopathy, New York, Springer-Verlag 105-109, 1989.
Lean JS, Stern WH, Irvine AR, Azen SP, Silicone Study Group: Classification of proliferative vitreoretinopathy used in the silicone study. Ophthalmology 96: 765-771, 1989.
Stern WH, Lean JS, Silicone Study Group: Intraocular silicone oil versus gas in the management of proliferative vitreoretinopathy (PVR): A multicenter clinical study, in Freeman HM, Tolentino FI (eds). Proliferative Vitreoretinopathy, New York, Springer-Verlag, 1989.
Glaser BM, Silicone Study Group: Silicone oil for proliferative vitreoretinopathy: Does it help or hinder?. Arch Ophthalmol 106: 323-324, 1988.
Lean JS: Changing attitudes in the United States to the use of intravitreal silicone. Jpn J Ophthalmol 31: 132-137, 1987.
The Silicone Study Group: Proliferative vitreoretinopathy [Editorial]. Am J Ophthalmol 99: 593-595, 1985.
Stephen J. Ryan, M.D.
Estelle Doheny Eye Institute
University of Southern California School of Medicine
1355 San Pablo Avenue
Los Angeles, CA 90033
Telephone: (213) 342-6444
Fax: (213) 342-6442
Stanley P. Azen, Ph.D.
Division of Biometry
Department of Preventive Medicine
University of Southern California School of Medicine
1540 Alcazar Street CHP 218
Los Angeles, CA 90033
Telephone: (213) 342-1810
Fundus Photograph Reading Center
Alexander R. Irvine, M.D.
University of California at San Francisco Medical Center
400 Parnassus Avenue
San Francisco, CA 94143
Telephone: (415) 476-4142
Donald Everett, M.A.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528
Last Updated: 10/22/99