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`Section 3
`
`Special Adjuncts to Treatment
`
`Chapter
`
`Silicone Oil in Vitreoretinal Surgery
`Ron P. Gallemore
`Brooks W Mccuen II
`
`I
`
`INTRODUCTION
`
`Since the US FederaJ Drug Administration approved the use of
`silicone oil as an intraocular tamponade in 1996, this agent has
`been used with increasing frequency in the USA and elsewhere
`as an adjunct in vitreoretinal surgery. Silicone oil has been used
`most commonly in the management of complex rhegmatogenous
`retinal detachments due to severe proliferative vitreoretinopathy
`(PVR), giant retinal tears, viral retinitis, trauma, and proufera(cid:173)
`tive diabetic retinopathy (PDR). Additional applications now
`include idiopathic, myopic, and traumatic macular holes, colobo(cid:173)
`matous retinal detachments, and chronic uveitis with severe
`hypotony. In this chapter, we review the unique surgical tech(cid:173)
`niques associated with silicone oil usage, the clinical settings in
`which silicone oil tamponade may be used, the advantages and
`disadvantages of silicone otl compared with other tamponades
`and the complications associated with its use.
`
`HISTORICAL PERSPECTIVE
`
`Based on the experimental work of Stone1 and Armaly,Z Paul
`Cibis3-6 introduced liquid silicone oil for use in retinal reattach(cid:173)
`ment surgery in the early 1960s. This initial clinical application of
`silicone oil came before the advent of modem pars plana vitreous
`surgery.7 Utilizing both its relatively high interracial tension with
`water as well as its hydraulic capabilities, Cibis envisioned silicone
`oil both as an extended intraocular tamponade as well as a surgical
`instrument. Silicone was utilized as a tamponade for pushing
`back the retina against the force of preretinal membranes8 and
`as an intrument to separate preretinal membranes. With these
`approaches, previously inoperable retinal detachments could be
`treated with significant anatomical and visual success.
`Despite initial success and excitement with the use of liquid
`stlicone oil, the combination of the untimely death of Cibis in
`1965 and the increasing reports of complications associated
`with prolonged silicone tamponade9-17 led to near abandonment
`of the use of silicone oiJ in retinal surgery. Only a few retinal
`surgeons, most notably John Scott in England, IK--Z l continued to
`use liquid silicone oil, thus extending the work of Cibis and
`providing additional experience with silicone oil as a long-acting
`tamponade.
`With the advent of modern vitreous microsurgery in the
`1970s, several investigators, including Jean Haut in France,22- 26
`
`Relja Zivojnovic in the Netherlands, 27-m and Peter Leaver in
`England, 30-Js successfully combined pars plana vitrectomy
`techniques with the use of silicone oil as an internal tamponade.
`As the use of silicone oil spread, other advances, such as the
`inferior peripheral iridectomy39,40 and relaxing retinotomy4 1-"3
`in selected cases reduced the complication rates and further
`increased the likelihood of successful retinal reattachment.«-W
`While in Europe silicone oil was used with increasing frequency
`in the treatment of complex retinal detachments, retinal surgeons
`in the USA focused their attention on improving fluid-gas
`exc.hange techniques10-73 and on the development of longer-acting
`gases74,75 for extended intraocular tamponade ( see Chapter 127
`for review). By the mid- l 980s, the relative safety and efficacy
`of these two tamponades had not been defined. Uncontrolled
`clinical studies suggested that the guaranteed and extended nature
`of the silicone oil tamponade might improve the anatomic
`results for complex cases, but that the ultimate visual results
`might be compromised by complications related to its use.76
`Thl!.IS was born the SiJicone Study, organi7.ed by Stephen Ryan,
`which sought to compare the safety and efficacy of stlicone oil
`to long-acting gas as a tamponade in the repair of complex
`rhegmatogenous retinal detachments with severe PVR. 76.77
`
`INDICATIONS FOR SILICONE OIL TAMPONADE
`
`Silicone oil tamponade is now utilized in the management of a
`wide variety of vitreoretinal problems. Here we review some
`specific indications for the use of silicone oil.
`
`Retinal detachment complicated by severe
`proliferative vitreoretinopathy
`The Silicone Study was a prospective, multicentered, randomized,
`controlled clinical trial comparing silicone oil and long-acting
`gases in the management of eyes with severe PVR. 76 In this
`study, eyes were divided into two groups: group 1 ( eyes with no
`previous history of vitreous surgery) and group 2 ( eyes with a
`previous history of at least one vitrectomy with gas for PVR).
`This study concluded that overall, siJicone oil was superior to
`sulfur hexafluoride gas78 and roughly equivalent to perfluoro(cid:173)
`propane (C:iF8) gas79,so in the management of retinal detachment
`with severe PVR. Despite their overall equivalence, however,
`certain subgroups of eyes appeared to do better with silicone oil
`
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`
`

`

`2212
`
`Surgical Retina
`Section 3 Special Adjuncts to Treatment
`
`than with C3F8. Relative indications for the use of silicone oil
`include the need to travel by air or on land to higher elevations
`and anticipated difficulty with postoperative prone positioning
`(children, and those who are mentally or physically impaired).81,82
`Eyes with severe anterior PVR also did better with silicone oil
`than with C3F8.83 In group 1, patients undergoing relaxing
`retinotomy, whose eyes were treated with silicone oil did better
`both anatomically and visually than eyes receiving C3F8 gas.84
`Relative indications for the use of gas rather than silicone oil
`include: a high probability of corneal tamponade touch (such as
`when there is a poor iris diaphragm); the presence of superior
`retinal breaks on the posterior slope of a high scleral buckle (since
`gas conforms better than silicone to the slopes of the buckle);
`and the presence of a silicone intraocular lens with an open
`posterior capsule (see Complications, below).82 An interesting
`cost–benefit analysis revealed that silicone oil was slightly more
`cost-effective than C3F8 gas in eyes with PVR without previous
`vitrectomy, whereas C3F8 gas was more cost-effective than
`silicone oil with previous vitrectomy and PVR.85 The study also
`concluded that PVR surgery on eyes with either tamponade
`was cost-effective when compared with other widely accepted
`intravitreal therapies across diverse medical specialties.
`
`Complications of severe proliferative diabetic
`retinopathy
`The use of silicone oil in the management of patients with severe
`PDR remains controversial. In Europe, silicone oil is often used
`during the initial vitrectomy for severe diabetic traction retinal
`detachment as well as for recurrent diabetic vitreous hemor-
`rhage following previous vitrectomy surgery.86–89 The rationale
`for silicone oil use in PDR is based on a potential reduction in
`postoperative hemorrhage, a more rapid recovery of visual
`function (for example, in one-eyed patients, in contrast with gas
`tamponade) and reduced postoperative positioning require-
`ments.90–93 A downside of the use of silicone oil in diabetic
`patients is the necessity for a second operation to remove it.
`Unlike in eyes with PVR, there has been no prospective, ran-
`domized clinical trial comparing silicone oil with extended gas
`tamponade in eyes with severe PDR.
`Silicone oil may be of potential use in diabetic patients with
`severe anterior-segment neovascularization or anterior hyaloidal
`fibrovascular proliferation.94,95 A silicone oil tamponade may
`suppress anterior-segment neovascularization by impeding the
`movement of vasoproliferative factors from the posterior segment
`to the anterior segment or by increasing oxygen tension in the
`aqueous by preventing diffusion of oxygen-enriched aqueous to
`the posterior segment.96,97 In an uncontrolled series, we per-
`formed revision of vitrectomy and silicone oil injection in 18
`eyes that developed advanced iris neovascularization or anterior
`hyaloidal fibrovascular proliferation complicated by retinal detach-
`ment or media opacity after vitrectomy for the complications
`of PDR.95 Stabilization or regression of the anterior ocular
`neovascular changes was noted in 83% of the eyes. Sustained
`retinal reattachment was achieved in 56% of eyes, with visual
`acuity improving to 20/400 or better in 28% of eyes. Posterior-
`segment vascular or avascular reproliferation was the main cause
`
`for anatomic failure, while generalized retinal vascular ischemia
`was felt to be the main cause for poor visual results despite
`retinal reattachment.
`Douglas et al.98advocate the use of pars plana resection, vitrec-
`tomy, and silicone oil in eyes with severe PDR and combined
`traction/rhegmatogenous retinal detachment involving the macula.
`In a retrospective, noncomparative consecutive series of 22 eyes
`in 22 patients, the authors observed macular attachment in
`91% of eyes at the final follow-up visit (average of 15 months).
`In the 64% of patients who underwent silicone oil removal,
`visual acuity of 20/400 or better was found in 93% of cases. In
`contrast, in those patients who did not undergo silicone oil removal,
`only one case (8.3%) achieved a visual acuity of 20/400.
`We also advocate the use of silicone oil after failure of con-
`ventional vitreous surgery for PDR due to the development of
`severe PVR.99 While these eyes have a very poor anatomical and
`visual prognosis, at least some could be salvaged by reoperation with
`a silicone oil tamponade. A randomized, controlled clinical trial
`would be required to assess the relative contribution of silicone
`oil to the success or failure in these complicated diabetic cases.
`
`Selected cases of macular hole
`Silicone oil tamponade has been used in the repair of macular
`holes in several settings: retinal detachment caused by macular
`holes, idiopathic macular holes, and traumatic macular holes.
`Macular holes causing retinal detachments usually occur in eyes
`with pathologic myopia, often in patients of Asian or Middle
`Eastern descent. Modern pars plana vitrectomy techniques,
`accompanied by the use of a gas tamponade and prone posi-
`tioning, have been of value in the management of these macular
`hole-detachment cases.100–102 Silicone oil may be advantageous
`in patients for whom postoperative positioning is impaired by
`physical or psychological factors or in whom traveling at high
`altitudes is required. In addition, silicone oil remains a reasonable
`approach in eyes failing attempts with a gas tamponade.100,103
`Its principal disadvantage with respect to gas is the necessity for
`a second operation to remove the oil 4 to 8 weeks after the
`initial surgery.
`In an initial study of silicone oil as a temporary tamponade in
`eyes with idiopathic macular holes, results were promising.104
`In this retrospective consecutive series including 40 eyes and
`employing autologous serum but no internal limiting membrane
`peeling, we found that 80% of the holes could be sealed with
`one operation and that the overall success rate increased to
`92.5% with a second procedure. Visual acuity improved an
`average of 2.6 lines in all eyes. More recently, Lai et al. found a
`lower anatomic macular hole closure rate with silicone oil com-
`pared with gas.105 The rate of hole closure with one operation
`was 65% with oil versus 91% with gas. The reoperation rate was
`also significantly higher with oil: 35% versus 4% with gas. The
`final closure rate with more than one operation was not statis-
`tically significant between the two groups: 90% with oil versus
`96% with gas (P = 0.628). The final median visual acuity, however,
`was significantly better for gas than oil (20/50 versus 20/70,
`respectively. There were no differences in the prevelance of
`internal limiting membrane peeling or the use of indocyanine
`
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`

`

`Chapter 130
`Silicone Oil in Vitreoretinal Surgery
`
`2213
`
`green dye between the two groups. Factors proposed to account
`for the greater success rate with gas versus oil include the greater
`buoyancy force with gas, the unproven possibility of silicone oil
`toxicity, and a glial response with gas which has not yet been
`evaluated for silicone oil. Other factors could include the higher
`surface tension of gas versus oil which may facilitate isolation of
`the hole from fluid currents as it heals, and the occurrence of
`emulsification with oil which may lead to droplets in the hole
`itself impeding hole closure.
`While our enthusiasm for silicone oil has waned, we still con-
`sider the use of silicone oil for selected cases in the treatment
`of idiopathic macular holes when problems with postoperative
`positioning are anticipated, rapid return to normal function is
`required, air travel is necessary, or the patient is monocular.
`The use of silicone oil in traumatic macular hole repair may
`also be considered. Again, the ability and willingness to maintain
`face-down postoperative positioning is of primary importance.
`Traumatic holes occur more often in young males and children
`in whom postoperative positioning may be less reliable. Overall,
`gas remains our tamponade of choice for nearly all cases of
`macular hole.
`Silicone oil allows clear visualization of the macula and we
`have observed the time course and properties of macular hole
`closure utilizing optical coherence tomography.106 By the first
`postoperative day, the macular hole was flat with resolution of
`parafoveal cysts. Complete hole closure was observed at 1 month
`in successful cases. Persistent retinal separation at 1 month was
`indicative of failure in all cases.
`
`Giant retinal tears
`Silicone oil may be used in the repair of giant retinal tears in
`two different ways: (1) as an instrument to facilitate unfolding
`and flattening of the retinal detachment and tear; and (2) as a
`long-term tamponade. The advent of liquid perfluorocarbons
`(PFCs) has allowed less traumatic flattening of retinal detach-
`ments caused by giant retinal tears and has led to PFCs largely
`replacing silicone oil techniques for intraoperative flattening of
`the retina.
`The use of silicone oil in cases of giant retinal tear without PVR
`remains controversial. It is still widely used for this purpose in
`Europe, while extended intraocular tamponade with gas remains
`more popular in the USA. Reports of excellent anatomical and
`visual success with either technique are available,34,35,38,107–109
`but there are no randomized controlled studies directly comparing
`results with silicone to gas. We may select oil over gas when
`positioning is a concern, particularly when the tear extends to
`the 6 o’clock position.
`
`Retinal detachment associated with choroidal
`coloboma
`A choroidal coloboma is a congenital lesion characterized by
`absence of the normal retina, retinal pigment epithelium, and
`choroids. These lesions are most commonly located in the infero-
`nasal fundus and are associated with an incidence of retinal
`detachment of 23 to 42%.110,111 Colobomatous retinal detach-
`ments are often caused by small, atrophic retinal breaks located
`
`in or near the base of the coloboma. Scleral buckling techniques
`for the repair of these detachments result in low rates of
`success of 35 to 55%,110.,111 but it is still advocated for select
`patients by some authors.112 Vitrectomy surgery has increased
`the success rate of repair of these rare and unusual detachments
`and is often used in combination with long-term silicone oil
`tamponade.113–115 We achieved retinal reattachment in five of
`five eyes with choroidal colobomas utilizing silicone oil as an
`extended intraocular tamponade.114 Adjunctive surgical techniques
`to vitrectomy included retinectomy in two eyes and cyanoacry-
`late retinopexy in one eye. In four of the five eyes, the silicone
`oil was removed after several months. Retinal redetachment was
`observed following silicone oil removal in one eye, suggesting
`the need for prolonged intraocular tamponade in at least some
`of these cases.
`
`Chronic uveitis with profound hypotony
`Hypotony associated with chronic, intractable uveitis can be an
`important cause of severe vision loss in these patients. Vitreous
`surgery has been used to clear the ocular media, to remove
`inflammatory byproducts, and for diagnostic purposes.116–121 We
`hypothesized that the space-occupying and compartmentalizing
`qualities of silicone oil might provide additional benefits in eyes
`with profound hypotony associated with scleral infolding
`and/or serous retinal detachment and reported on our use of
`vitrectomy with silicone oil tamponade in a series of five such
`eyes.122 The silicone oil facilitated anatomic reattachment in
`three of five eyes, improved visual acuity in all five eyes, and
`increased intraocular pressure in four of five eyes at 6 months.
`At the final follow-up, the intraocular pressure was still improved
`or maintained in four eyes and the visual acuity, though poor,
`was improved over the baseline level in three eyes. Overall, the
`use of silicone oil appeared at least partially to benefit these
`extremely poor prognosis eyes.
`
`Infectious retinitis
`Silicone oil has been used with increasing frequency for the
`management of complex retinal detachments associated with
`infectious retinitis. The most common scenario is rhegmatoge-
`nous detachment associated with retinitis due to cytomegalovirus
`infection in immunologically compromised patients.107,123–129 In
`these patients, the widespread and occult nature of the pathology,
`together with the potential for recurrence, make the use of a
`permanent silicone oil tamponade attractive.
`Long-lasting ganciclovir implants, combined with silicone oil
`tamponade, have also been effective for some patients with
`cytomegalovirus-related retinal detachments (DF Martin,
`personal communication). In these cases, the implant is placed
`in a dependent quadrant to maximize access of the drug to the
`aqueous phase. A detailed review of the management of these
`detachments, with and without silicone oil, is provided in
`Chapter 156.
`
`Trauma
`Pars plana vitreous surgical techniques have increased the rate
`of successful repair of severely traumatized eyes. Silicone oil
`
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`

`

`2214
`
`Surgical Retina
`Section 3 Special Adjuncts to Treatment
`
`has been used as an adjunct to vitreoretinal surgery in severe
`cases of penetrating ocular trauma, both as part of the initial
`vitrectomy and in later reoperations after initially unsuccessful
`surgery. Advocates of the use of silicone oil during the initial
`vitrectomy for severe penetrating ocular trauma believe that
`silicone oil helps to minimize intra- and postoperative hemor-
`rhage, which are known risk factors for the development of
`PVR.130 The extended nature of the silicone oil tamponade may
`also help to maintain retinal reattachment and avoid phthisis in
`such severely traumatized eyes.
`In a recent retrospective case series, Spiegel and colleagues131
`reviewed the outcomes of severe ocular trauma managed with
`primary vitrectomy and silicone oil within 24 h of injury. Of
`435 eyes with severe trauma, only 13 patients underwent imme-
`diate intervention with vitrectomy and silicone oil. This approach
`was restricted to eyes with extensive retinal lacerations greater
`than 4 disc diameters, retinal detachment, and/or substantial
`intraocular bleeding that had occurred during surgery. After a
`mean follow-up of 30 months, 11 eyes achieved a visual acuity
`ranging from 20/25 to 20/200. Silicone oil was removed in 11
`of 13 eyes at an average of 6 months. Recurrent PVR developed
`in two eyes. While these results are encouraging and suggest
`that early vitrectomy with silicone oil may be of value in the
`recently injured eye, the study is uncontrolled. In addition, it is
`very hard to match eyes undergoing vitrectomy for trauma accu-
`rately because of the great degree of variability from case to case;
`consequently, assessing the actual benefits of silicone oil over
`modern gas techniques in primary trauma is extremely difficult.
`When conventional vitreous surgery fails in cases of severe
`penetrating ocular trauma, repeat vitrectomy with long-term
`silicone oil tamponade may be used to improve the anatomic and
`visual outcomes.27,56,132–134 Despite reasonable initial anatomic
`and functional success, ultimate visual and anatomic outcomes
`are often quite poor in these eyes. We utilized a silicone oil tam-
`ponade after failed primary vitreous surgery with intraocular
`gas in 42 cases of complicated retinal detachment following
`severe ocular trauma.132 At 6-month follow-up, we achieved
`successful reattachment of the macula in 50% of cases and 28%
`of eyes had a visual acuity of 5/200 or better. By 2-year follow-
`up, however, only 33% were still completely attached posterior
`to the scleral buckle and only 12% were 5/200 or better. The
`high failure rate with long-term follow-up is often due to recurrent
`retinal detachment following silicone oil removal. We believe
`that the proliferative process associated with penetrating ocular
`trauma continues for a longer period of time than in eyes with
`nontraumatic retinal detachment. When conventional vitreous
`surgery has failed to rehabilitate these severely traumatized
`eyes, the ultimate prognosis is generally quite poor, even with
`reoperation and the use of silicone oil.
`
`Complicated pediatric retinal detachment
`Silicone oil tamponade has been advocated for use in the repair
`of selected complicated retinal detachments in the pediatric
`population. The rationale for the choice of silicone as the
`intraocular tamponade includes the high incidence of trauma in
`these cases as well as the potential poorer compliance with posi-
`
`tioning instructions. We reported the results of 48 consecutive
`cases of complex retinal detachments in children 16 years old
`or younger managed with pars plana vitrectomy and silicone oil
`tamponade.135 Forty-two percent of patients had a history of
`trauma and 35 of the eyes had undergone at least one previous
`retinal surgery. Of the 48 cases, only eight (17%) were count-
`fingers vision or better postoperatively and only two eyes
`achieved a visual acuity of 20/200 or better. Thirty-five percent
`were successfully reattached at long-term follow-up but signifi-
`cant complications included corneal opacification (62%) and
`hypotony (58%). In a recent series of patients with pediatric
`retinal detachments, Weinberg and colleagues136 also observed
`poor outcome in those patients requiring silicone oil at the time
`of surgery. They also observed a high incidence of trauma and
`identified a “new” predictor of poor visual outcomes – the
`inability of the clinician to determine the preoperative visual
`acuity confidently.
`
`Endophthalmitis
`There is increasing evidence that silicone oil can suppress
`bacterial growth. With this in mind, several investigators have
`treated severe cases of endophthalmitis, unresponsive to initial
`antibiotic therapy (“tap and inject”) with vitrectomy and silicone
`oil tamponade.137–139
`In a prospective randomized controlled study by Azad and
`colleagues138of posttraumatic endophthalmitis, only one of 12
`patients who failed conventional tap-and-inject therapy achieved
`vision greater than 20/200 when treated with vitrectomy alone
`compared with seven of 12 (58%) when treated with vitrec-
`tomy and silicone oil. Immediate postoperative detachments
`occurred in 33% of vitrectomy-only patients versus 0% of those
`treated with silicone oil. Mechanisms by which silicone may be
`useful include increased concentration of intravitreal antibiotics,
`innate bactericidal properties of silicone oil, and stabilization of
`atrophic retina minimizing the occurrence of retinal detachment.
`Select cases of endophthalmitis may benefit from silicone oil
`tamponade and further studies will be required to determine
`the appropriate timing and cases for its use.
`
`GENERAL SURGICAL TECHNIQUES
`
`While silicone oil has been used with some success as an instru-
`ment for actual membrane dissection,21 it is now used primarily
`as an intraocular tamponade. The main physical properties of
`silicone oil that determine its clinical applications are its surface
`(interfacial) tension, specific gravity, and viscosity (Table 130-1).
`The two most commonly used silicone oils are classified based
`on their viscosity. The lower-viscosity (1000 cs) silicone oil was
`selected for use in the Silicone Oil Study while the higher-
`viscosity (5000 cs) silicone oil was the first one approved by the
`Federal Drug Administration for use in the USA. Now both are
`commercially available worldwide. As reviewed in Chapter 129,
`higher-viscosity silicone oil has a lower tendency to emulsify,
`i.e., to break up into tiny bubbles postoperatively.140–143 This
`may be advantageous, since some of the complications related
`to silicone oil use, reviewed later in this chapter, may relate to
`
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`

`Chapter 130
`Silicone Oil in Vrtreoretinal Surgery
`
`2215
`
`Table 130-1 Chemical properties of rommony used i1traowar tm,ponades
`
`Substance
`
`Molecular
`wegrt*
`
`Viscosity (cs}
`
`Slrlacetensiont
`(dyn/cm}
`
`Spedfk:
`17avity
`
`Siicone oil (HXXl)
`
`Siicone oil (5000)
`
`25 ODO
`
`50000
`
`1000
`
`5000
`
`Perfluoropmpane gas
`
`Sulfur hexa11uoride gas
`
`PJr
`
`Physiologic saline
`
`Water
`
`Perfluo-n--octane:j:
`
`188
`
`146
`
`29
`NA
`
`18
`
`438
`
`NA
`
`NA
`
`NA
`
`1.0
`
`1.0
`
`0.8
`
`21.2
`
`21.3
`
`70
`
`70
`
`70
`
`NA
`
`NA
`
`14
`
`0.971
`
`0.973
`
`<0.0001
`
`<0.0001
`
`<0.0001
`
`1.0064
`
`1.0000
`
`1.76
`
`'MolecUar weights for silicorJG oil can vary slgrificantly, as discussed in Chapter 129.
`tsurfaca tension occurs at tll8 intertace of a liquid and mother immlscbla Uqlid (rnterfacial surface tension) or
`gas. llle silicone od su"face tensions r(ll(lrted hem am values measLrnd in vitro (soo Chapter 129). They are much
`IOWQ'" than the theoretical value of -50 due to Impurities in the oil Itself. A further lowering of SIJface tension has
`been r(llOrted In vivo c1Je to tll8 presence of proteins and surtactants within the eye.
`:f:Pllrlluornn brand of ~ iquid, chemical formula C,.F ,..
`NA, not applicabl9.
`
`the degree of emulsification. Another determinant of oil emul(cid:173)
`sification, however, may be the presence of impurities in the oil,
`so maximally purified silicone oil is preferred for clinical use.
`The commercially available preparations of I 000 cs and 5000 cs
`silicone oil are of high-grade purity and a clinically significant
`difference in emulsification has not been reported. The main
`advantage of using the 1000 cs is quicker infusion and removal
`compared to 5000 cs oil.
`Of note, clinical studies are currently underway in Europe
`evaluating "heavy silicone oil" as an internal tamponade for com(cid:173)
`plicated retinal detachments. The silicone oil-RMN3 mixture,
`for example, has a density of 1.03 and viscosity of 3800 cs. A
`recent prospective study of the silicone oil-RMN3 mixture
`found that the oil was well tolerated. 144 We await the results of
`further studies to determine if heavy silicone oils or PFC liquids
`may be useful for postoperative tamponade agents.
`The relationship between the viscosity of silicone oil and its
`surface tension remains a common cause of confusion in under(cid:173)
`standing how silicone oil works as an internal tamponade. 145
`Despite marked viscosity differences, the l 000 cs and 5000 cs
`silicone oils have nearly identical surface tensions. Therefore,
`each silicone oil will have the same tendency to tamponade a
`retinal break (desired result) as well as to pass through holes in
`the retina under traction (unwanted result) .146 The surface tension
`of silicone oil relative to water is much less than that of gas
`relative to water (21 versus 70 dyn/cm: Table 130-l). Silicone
`will therefore pass through retinal breaks still under traction
`more readily than will gas.
`Silicone oil has important physicochemical differences from
`long-acting gases, PFC liquids, air, and physiologic saline solu(cid:173)
`tions. Both the 1000 cs and 5000 cs silicone oils have a specific
`
`gravity just less than 1.0 and are, therefore, "lighter than water."
`As shown in Table 130-l, the relative specific gravity for each
`of these tamponades is: air - gas < < silicone oil > water - saline
`< PFC liquids. This is of primary importance in two similar but
`different surgical maneuvers: (1 J when utilizing the tamponade
`for the purpose of retinal flattening; and (2) when a temporary
`tamponade is exchanged for silicone oil. In the sections that
`follow, we consider the technical aspects of infusing silicone oil
`into the eye, including exchanging silicone oil with various
`temporary tamponades.
`
`Infusion of silicone oil
`Due to the high viscosity of silicone oil, relatively high pressures
`are required to infuse silicone into the eye in comparison to
`other substances. Special methods have been developed. to
`minimize the infusion pressure required.27·55•57•61 The silicone oil
`is placed in a relatively large syringe (e.g., 20 ml syringe for 5 to
`10 ml of silicone oil) which can handle the high pressures
`necessary for injection (plastic is preferable to glass for safety
`reasons). The injection pressures are highest near the silicone(cid:173)
`containing syringe, and it is important to be certain that reliable
`connections (Luer-lok) will prevent the lines from coming apart
`at this point. According to Poiseuille's law, the flow of a fluid in
`a tube is proportional to the fourth power of the radius of the
`tube and inversely proportional to the length of the tube. In order
`to decrease the resistance to injection of silicone oil, we have
`found it helpful to modify the infusion line by keeping it as
`short as possible, while at the same time increasing its diameter.
`It is also helpful to use a relatively nondistensible material for
`silicone infusion tubing, such as polyethylene, since the high
`pressures that are necessary for silicone oil injection cause the
`
`Novartis Exhibit 2317.006
`Regeneron v. Novartis, IPR2021-0