Complications Associated
`with the Use of Silicone Oil in
`150 Eyes after Retina-vitreous
`Surgery
`
`JAY L. FEDERMAN, MD, HERMANN D. SCHUBERT, MD
`
`Abstract: Complicated retinal detachments (RDs) were successfully managed
`in 150 eyes of 170 consecutive patients by one surgeon (JLF) using silicone oil
`in conjunction with modern pars plana vitrectomy. Long-term postoperative
`complications were observed between 6 months and 5 years of follow-up .
`Cataracts developed in all phakic eyes and all corneas with oil-endothelial
`touch showed band keratopathy within 6 months. Recurrent detachments were
`noted in 22% of eyes during silicone oil tamponade and occurred in 13% of
`eyes after the oil had been removed. Other complications associated with the
`use of oil for vitreous surgery included pupillary block glaucoma (3%), closure of
`the inferior iridectomy ( 14 % ), fibrous epiretinaJ and subretinal proliferations
`(15%), pain (5%), and subconjunctivaJ deposits of oil (3%). Wrthout exception,
`within a period of 1 year the intraocular silicone oil showed some degree of
`emulsification, suggesting that the physicochemical characteristics of the oil
`injected may be an important variable in long-term complications. [Key words:
`complications, silicone oil, vitrectomy.] Ophthalmology 95:870-876, 1988
`
`Complications and difficulties associated with the
`mere injection of silicone oil to repair complicated reti(cid:173)
`nal detachments (RDs) led to its disuse in the 1960s. 1•2
`Despite these discouraging early reports, the combina(cid:173)
`tion of silicone oil with microsurgical vitrectomy tech(cid:173)
`niques improved the rate of anatomic reattachment of
`the retina where other procedures had failed. 3•4 In con(cid:173)
`junction with sophisticated vitrectomy, the use of sili-
`
`cone oil tamponade has found increasing acceptance
`over the past few years, and its role and limitations have
`been the subject of many publications.s-3-0 In this report,
`we describe the postoperative complications observed in
`150 eyes with complicated vitreoretinal problems. Most
`of these difficuJties are due to the proliferative nature of
`the underlying disease, some to technique and altered
`intraocular physiology, and last, but not least, some may
`be due to the characteristics and purity of the specific oil
`used.3'
`
`Originally received: November 8, 1987.
`Revision accepted: February 18, 1988.
`
`MATERIALS AND METHODS
`
`From the Retina Service, Wills Eye Hospital, Philadelphia.
`
`Presented at the Annual Meeting of the American Academy of Ophthal(cid:173)
`mology, Dallas, November 1987.
`
`Reprint requests to Jay L. Federman, MD, Wills Eye Hospital, 9th &
`Walnut Sis, Philadelphia, PA 19107.
`
`We reviewed the patient records of 150 eyes of 170
`consecutive cases with complicated RDs which were
`successfully anatomically reattached combining silicone
`oil tarnponade with modern pars plana vitrectomy tech(cid:173)
`niques. All surgery was performed by one surgeon (JLF)
`
`870
`
`Novartis Exhibit 2287.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`FEDERMAN ANO SCHUBERT
`
`• COMPLICATIONS OF SILICONE Oil
`
`Table 1. Frequency of Preoperative Diagnoses in 150 Cases
`of Complicated Retinal Detachment
`
`No. of Patients
`
`PVR C3 or worse
`103
`PDR with traction RD
`32
`Giant retinal tear
`8
`Expulsive choroidal hemorrhage
`3
`2
`Uveitis and ocular hypotension
`Foreign body with RD and PVR
`2
`PVR = proliferative vitreoretinopathy; PDR = proliferative diabetic
`retinopathy; RD = retinal detachment.
`
`using the techniques and principles described by Zivoj(cid:173)
`novic et al. 13• 14 The preoperative diagnosis was prolifera(cid:173)
`tive vitreoretinopathy (PVR) C3 or worse on 103 eyes
`and proliferative diabetic retinopathy (PDR) with trac;.
`tion RD and PVR in 32 eyes. The remaining compli(cid:173)
`cated RDs were due to giant retinal tears in eight eyes
`expulsive choroidal hemorrhages in three, uveitis with
`?Cular hypotension in two, and intraocuJar foreign body
`in two (Table I). The mean age of the diabetic patients
`was within the fourth decade, whereas the mean age of
`the remaining patients was within the sixth decade. The
`patients were followed from 6 months to 5 years (mean
`follow-up, 31.6 months).
`All eyes had complete preoperative examinations, in(cid:173)
`cluding visual acuity, applanation tonometry, biomicro(cid:173)
`scopic examination, and binocular indirect ophthalmos(cid:173)
`copy. Postoperative follow-up evaluations took place at
`2 weeks and 1, 2, 3, and 6 months, and then every 6
`months thereafter. At each follow-up visit, a complete
`ocular evaluation was performed, including visual
`acuity testing, measurement of intraocular pressure
`slit-lamp examination with and without contact lens:
`and binocular indirect ophthalmoscopy.
`
`VISUAL FUNCTION
`
`In general, optimal visual acuity was reached at 3
`months and, in agreement with other authors, usually
`
`temained stable or decreased thereafter. 5•7•29 In order to
`relate visual function to the presence or absence of sili(cid:173)
`cone oil, the visual acuities of 77 eyes with greater than
`30 months of follow-up were evaluated at 30 months.
`Two groups were formed: 42 eyes in which intraocular
`silicone oil was present (Table 2), and 35 eyes in which
`the oil had been removed between 3 and 6 months after
`the initial surgery (Table 3). In more than half of the
`eyes of each group, there was an obvious explanation
`why the visual function had not improved. Cataracts,
`pupillary block glaucoma, recurrent RDs, macular
`pathology, and band keratopathy were the reasons for
`the lack of visual improvement after the 3-month visit in
`22 of the eyes with intraocular oil (Table 2). Cataracts,
`recurrent detachments, macular pathology, and chronic
`uveitis with macular edema were the reasons for lack of
`visual improvement in 21 eyes in the group where the oil
`was removed (Table 3).
`In the 20 eyes with oil present, where there was no
`apparent reason for the visual acuity not to improve the
`visual function decreased slightly during the period of
`follow-up (Table 2). In the 14 eyes of the 35 where the
`oil had been removed and where there was no obvious
`pathology to explain a decrease in vision, the visual
`acuity either stabilized or showed a slight trend toward
`improvement (Table 3).
`In comparing these two groups of no apparent pathol(cid:173)
`ogy, the slight difference in favor of removal of silicone
`oil could be due to the refractive qualities of the silicone
`or to actual oil-tissue interactions leading to progressive
`dysfunction as a result of prolonged retinal exposure to
`oil. It is also possible that the 14 eyes in which the oil was
`removed had the potential for better visual function ini(cid:173)
`tiaUy. We cannot make a conclusion from our some(cid:173)
`what arbitrary samples.
`Visual function variability was described by some of
`the aphakic patients. Those with a visual acuity of 6/60
`or better complained of subjective changing of vision
`several times during the day. We attributed this phe(cid:173)
`nomenon to the constantly changing shape of the oil(cid:173)
`aqueous interface at the pupillary opening in those
`aphakic eyes that did not have a total fill.
`
`Table 2. Visual Acuity in Eyes with lntraocular Oil Present to the 30-month Follow-up
`
`Obvious Reason for Decrease in Visual Acuity (n = 22)
`
`No Apparent Reason for Decrease in Visual Acuity (n = 20)
`
`Visual
`Acuity
`
`Postoperative
`
`Postoperative
`
`Preoperative
`
`3 Mos
`
`12 Mos
`
`30 Mos
`
`Preoperative
`
`3 Mos
`
`12 Mos
`
`30 Mos
`
`46%
`36%
`9%
`9%
`
`4%
`46%
`27%
`23%
`
`18%
`46%
`23%
`130/o
`
`4%
`NLP
`23%
`LP
`15%
`36%
`HM
`40%
`10%
`200/o
`CF
`23%
`10%
`6/120
`15%
`4%
`6/60+
`n = number of patients; NLP = no light perception; LP = light perception; HM = hand motions; CF = counting fingers.
`
`60%
`25%
`15%
`
`5%
`20%
`30%
`25%-
`10%
`10%
`
`5%
`20%
`30%
`20%
`15%
`10%
`
`871
`
`Novartis Exhibit 2287.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`OPHTHALMOLOGY
`
`• JULY 1988
`
`• VOLUME 95
`
`• NUMBER 7
`
`Obvious Reason for Decrease in Visual Acuity (n = 21)
`
`Table 3. Visual Acuity in Eyes without Oil to the 30-month Follow-up
`No Apparent Reason for Decrease in Visual Acuity (n = 14)
`
`Postoperative
`
`Postoperative
`
`Preoperative
`
`3 Mos
`
`12 Mos
`
`30 Mos
`
`Preoperative
`
`3 Mos
`
`12 Mos
`
`30 Mos
`
`38%
`43%
`14%
`5%
`
`14%
`19%
`24%
`24%
`19%
`
`24%
`28.5%
`28.5%
`
`190/o
`
`14%
`19%
`28.5%
`28.5%
`5%
`5%
`
`36%
`36%
`21%
`7%
`
`14%
`36%
`14%
`36%
`
`14%
`29%
`14%
`43%
`
`14%
`29%
`14%
`43%
`
`Visual
`Acuity
`
`NLP
`LP
`HM
`CF
`6/120
`6/60+
`
`n = number of patients; NLP = no light perception; LP = light perception; HM = hand motions; CF = counting fingers.
`
`EMULSIFICATION
`
`Like other authors, we use the term emulsification to
`describe tiny intraocular droplets of silicone. The fre(cid:173)
`quency with which these have previously been noted
`varies from 5 to 25%.3•5•7•12•16•18•25•26 In our cases, they
`were seen floating freely in the anterior chamber, on the
`corneal endothelium, infiltrating the iris stroma, in the
`superior angle, in the posterior chamber, on the poste(cid:173)
`rior surface of the iris and on the anterior lens capsule,
`on the zonules, on and between the ciliary processes, on
`the posterior capsular surface, on the posterior surface of
`the oil bubble, on the epiretinal surface, and in some
`cases with detached retina, on the retroretinal surface.
`At 1 month, 1% of eyes showed emulsification, at 2
`months 6%, at 3 months 11 %, and by 6 months 85% of
`the eyes showed tiny intraocular droplets. The mean
`time for the development of emulsification in this group
`was 5 months and at the I-year follow-up examination
`I 00% of the eyes with an oil fill showed some degree of
`emulsification. In most of the eyes in which the oil was
`permanently removed, oil droplets were found moving
`(like cells) throughout the aqueous and vitreous com(cid:173)
`partment.
`
`CATARACT
`
`cular glaucoma developed 6 weeks after oil removal in
`the other patient who was a diabetic.
`
`PAIN
`
`In seven patients, pain was a significant complaint, as
`also noted in other reports. 16,29 Subconjunctival oil was
`found in four of these eyes resulting from extravasation
`through the sclerotomy. The pain was relieved after re•
`pair of the sclerotomy and removal of the subconjuncti•
`val oil. Removal of subconjunctival silicone is difficult,
`because the oil becomes multiloculated and elicits a
`lipogranulomatous response in the episcleral connective
`tissue spaces. We used a cotton-tipped applicator, apply(cid:173)
`ing pressure over the infiltrated areas to mechanically
`express the oil. The other three patients experienced re(cid:173)
`lief of pain only after complete removal of intraocular
`silicone oil. T apical atropine and steroids did not relieve
`the pain in these three cases. Five of the painful eyes had
`a diagnosis of PVR, one eye was in a patient with uveitis
`and one was in a patient with diabetes. Tbe diabetic and
`uveitis patients had subconjunctival extrusion of sili(cid:173)
`cone after removal of which the pain was relieved. We
`could not explain the reason for the pain. There was no
`evidence of inflammation, increased pressure, or kera(cid:173)
`topathy.
`
`Thirty-three of the 150 eyes were phakic after success(cid:173)
`ful reattachment of the retina. Cataracts developed in all
`of the phakic eyes. The rate of formation of the cataract
`was directly proportional to the duration of lenticular
`contact with the oil, an observation shared by other au(cid:173)
`thors. 5·7·25 Posterior subcapsular changes were most
`common and were seen to occur earlier in the diabetic as
`compared with the nondiabetic patients. The mean time
`for cataract development was 3 months in the diabetic
`group as opposed to 6 months in the remaining patients.
`In two eyes, the silicone oil was removed while the
`lens was clear. Cortical and nuclear changes developed
`within 6 months in one patient who had a giant retinal
`tear. Blood staining of the cornea secondary to neovas-
`
`SILICONE OIL KERATOPATHY
`
`Band keratopathy occurred in all 20 eyes that showed
`silicone oil- corneal endothelial touch, agreeing with
`other reports. 2•3·5•7•10 In six eyes of diabetic patients with
`oil-endothelial touch, the mean time for the appearance
`ofkeratopathy was 3 months, whereas in the 14 remain(cid:173)
`ing eyes the mean time for development of keratopathy
`was 5 months. All of these eyes were aphakic at the time
`of silicone instillation; 15 had a total fill (including the
`aqueous compartment) due to insufficient iris tissue,
`whereas the inferior iridectomy closed in the other five
`eyes, resulting in forward displacement of the oil.
`
`872
`
`Novartis Exhibit 2287.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`FEDERMAN AND SCHUBERT
`
`• COMPUCA TIONS OF SILICONE OIL
`
`Table 4. Ocular Complications Associated with Silic-0ne Oil
`Combined with Vitreoretlnal Surgery
`
`Complication
`
`EmtJlsificalion
`Cataract
`Oil keratopathy
`Flare and cell
`After oil removal
`With o ii present
`Postoperative RO
`After oil removal
`With intraocular oil
`Silicone oil replacement
`Fibrous proliferation
`Inferior iridectomy closure
`Glaucoma
`Chronic glaucoma
`Pupillary block
`Clumped pigment inferior angle
`Pain
`Macular pucker
`Pupillary membrane
`Separate anterior chamber oil bubble
`Subconjunclival oil
`Subretinal hemorrhage
`Rubeosis with oil
`Hyphema with oll-rubeosis
`Endophthalmitis
`
`RD = retinal detachment.
`
`Percentage
`
`100.0
`100.0
`100.0
`
`48.3
`6.7
`
`13.3
`22.0
`16.7
`15.3
`14.3
`
`10.0
`3.3
`7.3
`4.7
`3.3
`2.7
`2.7
`2.7
`1.3
`t3
`1.3
`0.7
`
`CLOSURE OF THE INFERIOR IRIDECTOMY
`
`An inferior iridectomy was performed whenever there
`was adequate iris tissue in aphakic and pseudophalcic
`patients. Of the 105 eyes with inferior iridectomies, 90
`remained patent and functioning, whereas 15 closed
`( 14.3%). In 10 of the 15 that closed, the oil was removed
`before keratopathy developed, and in all of these there
`was forward displacement of oil. Closure of the iridec(cid:173)
`tomy was believed to be due to inflammation, rubeosis
`and/or pigment eel] proliferation in the inferior angle.
`
`FLARE AND CELL-CHRONIC UVEITIS
`Of the 150 eyes with a silicone oil fill, only 10 (6.7%)
`showed evidence of flare and cells at I month postopera(cid:173)
`tively. Eight of these eyes had PVR, two of which had
`chronic uveitis preoperatively and the additional two
`were eyes of diabetic patients. Iritis had also been noted
`by other authors. 16•18•28
`A much larger percentage of eyes appeared with flare
`and cells after silicone oil removal. The oil was removed
`in 60 of the 150 eyes, and 29 of these eyes (48 .3%)
`showed persistent flare and cells for more than I month
`postoperatively.
`
`SILICONE OIL REINSTILLA TION
`It was necessary to replace the silicone oil in IO of the
`60 eyes (16.7%) in which the oil was removed. Nine of
`
`these eyes had PVR and the other had PDR. The causes
`for oil reinstillation could be grouped into three catego(cid:173)
`ries: ( 1) six eyes with recurrent RD in which the oil was
`replaced within 6 months of removal, (2) two eyes in
`which rubeosis developed after a 360° peripher&l RD
`necessitating replacement of oil within 2 months of re(cid:173)
`moval, and (3) three eyes that required oil replacement
`within 3 months of removal due to the development of
`intense flare (4+) and cells (I+) associated with hypo(cid:173)
`tension. All ten of these eyes were stable after the oil was
`replaced and the detachments were repaired; the ru(cid:173)
`beosis regressed and adequate pressure was maintained
`in otheiwise quiet eyes.
`
`GLAUCOMA
`
`There were 15 eyes ( I 0%) with chronically elevated
`intraocular pressure as compared with an incidence of 2
`to 40% in other reports.2•7•10•12• 14•18•23,2.1 , 2s,29 The glau(cid:173)
`coma was controlled postoperatively with topical medi(cid:173)
`cations alone in 11 eyes, controlled with topica1 medica(cid:173)
`tions and oral drugs in 3, and with cryoablation of cili(cid:173)
`ary body in 1. We could not definitely attribute the
`glaucoma to the presence of silicone oil because all of
`these eyes had had multiple previous procedures result(cid:173)
`ing in anterior synechiae, pigment in the angle, rubeosis,
`or a combination of these findings. Only two eyes had
`massive emulsification; however, removal of the oil did
`not change the need for topical medications.
`Pupillary block related to the silicone oil developed in
`five eyes (3. 3%) after the initial instillation of silicone oil.
`In each case, the silicone was behind the plane of the iris
`at the conclusion of surgery. Postoperatively, varying
`between 24 hours and 3 weeks, the silicone oil bubble
`moved forward resulting in pupillary block. In four of
`these eyes, this complication occurred within 72 hours
`of surgery. Two eyes had a large subretinal and prereti(cid:173)
`nal hemorrhage which forced the silicone forward (1 in a
`phakic eye). The other two eyes had large choroidal de(cid:173)
`tachments forcing the silicone forward (aphakic eyes).
`Tbe fifth case of postoperative pupillary block occurred
`3 weeks after surgery and was thought to be due to clo(cid:173)
`sure of the inferior iridectomy. The two eyes with intra(cid:173)
`ocular hemorrhage eventually became phthisical: the
`two eyes with choroidal detachments were successfully
`managed by removing the oil and using a long-acting
`gas. Surgical readjustment of the oil volume and reopen(cid:173)
`ing of the iridectomy successfully managed the last case.
`
`POSTOPERATIVE RETINAL DETACIIMENT
`
`Recurrent RDs occurred in 33 eyes (22%) with intra(cid:173)
`ocular silicone oil present. The overall redetachment
`rate reported ranges from 11 to 53%. 2 •3•5•6 •10, 11 , 16, 18,_
`19-23 - 27 •2 9 "Late" redetachments range from 45 to
`53%.6•19 In our study, the majority (23 eyes) showed
`peripheral detachments which were most commonly
`present within 3 months after oil instillation. Nineteen
`of these eyes were inferior peripheral detachments,
`
`873
`
`Novartis Exhibit 2287.004
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`OPHTHALMOLOGY
`
`• JULY 1988
`
`• VOLUME 95
`
`• NUMBER 7
`
`whereas four were found in the superior periphery. Four
`of these peripheral detachments were not apparent until
`12 months after silicone injection. Total detachments
`developed in eight eyes within 6 months of silicone in(cid:173)
`stillation. The earliest total detachment was seen within
`2 weeks; most were present within 3 months. In two
`eyes, a shallow detachment of the posterior pole was
`present within 3 months of oil instillation.
`The silicone oil was removed in 60 eyes and recurrent
`RDs occurred in 8 of these eyes ( 13.3%) which agrees
`with the experience of other authors. 29 Five of these
`detachments involved the posterior pole, whereas three
`were peripheral only. In two of the eyes with peripheral
`detachments that developed after oil removal, rubeosis
`developed within a few weeks. Most of the recurrent
`detachments occurred within 6 months of oil removal.
`In all cases, the retina could be reattached when the oil
`was replaced. Rubeosis, if present, showed signs of re(cid:173)
`gression.
`
`POSTOPERATIVE FIBROUS PROLIFERATION
`
`Epiretinal fibrous proliferation was seen in 23 eyes
`( 15 .3%) of the 150 with silicone oil fill. The reported rate
`of recurrent proliferation ranges from 3 14 to 71 %. 26 In
`seven of our eyes, subretinal fibrosis in the form of
`bands and/or sheets was also found. In almost all in(cid:173)
`stances, the epiretinal fibrosis occurred at the edge of
`large retinotomies and appeared to conform to the pos(cid:173)
`terior surface of the silicone bubble. Subretinal fibrosis
`was only found in those eyes with persistent subretinal
`fluid and typically occurred in locations where fluid was
`present.
`
`PUPILLARY MEMBRANES
`
`Inflammatory pupillary membranes occurred in four
`eyes (2.7%). These may have been the result of heavy
`pbotocoagulation; however, in most cases it was be(cid:173)
`lieved to be related to the silicone. In one case, the
`membrane resolved spontaneously, another was opened
`with the Y AG laser and the other two were so dense that
`they were surgically excised at the time of silicone oil
`removal.
`
`ENDOPHTHALMITIS
`
`Endophthalmitis developed in one eye (0.7%) within
`2 weeks of silicone oil instiJlation.
`
`SEPARATE ANTERIOR CHAMBER OIL BUBBLE
`
`the main posterior oil bubble. 1n the pseudophakic and
`phakic eyes, the oil had to be removed surgically.
`
`MACULAR PUCKER
`
`A macular pucker developed in five eyes (3.3%) after
`silicone oil removal, and occurred within 2 months in all
`cases as also noted by other authors. 14
`17
`•
`
`CLUMPED PIGMENT IN THE INFERIOR ANGLE
`
`Clumps of pigment were found in the inferior angle in
`11 eyes (7.3%) with PVR. Pigment in the inferior angle
`was not found in eyes of diabetic patients. These clumps
`of pigment and pigmented membranes were similar in
`appearance to the pigment seen on the surface of the
`retina in advanced PVR. The amount of pigment seen
`in these eyes did not appear to increase. over time and
`was believed to be debris from the surgery that settled
`into the inferior aqueous compartment (i.e., the inferior
`angle). The silicone oil tamponade of the vitreous com(cid:173)
`partment appeared to concentrate debris in the anterior
`chamber. Even though there must have been fluid be(cid:173)
`tween the silicone oil bubble and the peripheral retina in
`more cases than we were aware of, clumped pigment
`was not appreciated biomicroscopically in this area.
`
`RUBEOSIS IN OIL-FILLED EYES
`
`The development of rubeosis or an increase of already
`present rubeosis was found to occur in two eyes (1.3%)
`while silicone was present. These were eyes of diabetic
`patients, and all had rubeosis before surgery. In one of
`these eyes, a peripheral detachment was present and this
`was thought to be the cause of the increased rubeosis. An
`intense fibroproliferative/ neovascular response devel(cid:173)
`oped in the second eye with increased rubeosis despite
`massive photocoagulation and a flat retina. In two eyes
`of diabetic patients in which rubeosis was present before
`the instillation of oil, hyphemas developed postopera(cid:173)
`tively. We were not impressed with the development
`and progression of a neovascular response in the fluid(cid:173)
`filled cavities of the diabetic eyes after the injection of
`silicone oil. As a matter of fact, there were five eyes of
`diabetic patients in this series with aggressive rubeosis
`preoperatively which showed regression of rubeosis and
`stabilization after surgical reattachment of the retina
`with pars plana vitrectomy and instillation of silicone
`oil. Of the remaining 23 diabetic eyes, there was no
`evidence of the development of rubeosis as long as the
`oil was present. In two of these eyes, rubeosis became
`apparent within 2 weeks after oil removal.
`
`A separate silicone oil bubble was found in the ante(cid:173)
`rior chamber of four eyes (2.7%); two of these were
`aphakic, one was pseudophakic, and one was phakic. By
`having the aphakic patient's head placed in a prone po(cid:173)
`sition, the anterior chamber oil bubble connected with
`
`SUBCONJUNCTIV AL SILICONE OIL
`
`Extravasation of silicone oil through the sclerotomy
`into the subconjunctival space was found in four eyes
`(2. 7%). All four patients presented symptomatically
`with pain, and a delle developed in one of the patients.
`
`874
`
`Novartis Exhibit 2287.005
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`FEDERMAN AND SCHUBERr • COMPLICATIONS OF SILICONE OIL
`
`DISCUSSION
`
`Cataract formation and oil keratopathy were found
`much more frequently in our patients than in previous
`reports, reflecting the greater length of folJow-up. We
`also noted a high incidence of emulsification ( l 00%) and
`chronic uveitis in 6.7% of oil-filled eyes and 48.3% of
`eyes after oil removal. These complications are possibly
`caused by the presence of silicone oil. There is no doubt
`that the silicone oils used in several reports differ in
`origin and therefore diffe.r in their chemical and physical
`properties.31 Since as a rule only the viscosity of the
`liquid silicone and not the origin of the oil is disclosed, it
`is difficult to determine whether such complications are
`related to mechanical oil-tissue interactions or differing
`properties of the oils. We believe that more attention
`needs to be given to the physicochemical properties of
`the various oils with regard to incidence and severity of
`complications.
`In our series, the fibrous proliferation, closure of the
`inferior iridectomy, pain, and the immediate postopera(cid:173)
`tive appearance of pupillary membranes in a smaU num(cid:173)
`ber of cases may all be related to low-grade inflamma(cid:173)
`tion. Gabel et al31 reported the presence of low molecu(cid:173)
`lar weight components capable of diffusing into
`surrounding tissues to incite a toxic and/or inflamma(cid:173)
`tory reaction. It is possible that variations in the beat
`sterilization of the oils at the different clinical centers
`may result in undesirable low molecular weight frac(cid:173)
`tions which incite an inflammatory response depending
`on their concentration. We used the same source of oil
`for all cases; however, the different incidences in which
`the presumed oil-related inflammation occurred may be
`due to variations in heat sterilization.3 1
`Our incidence of recurrent RD is low compared with
`several previous reports. This may reflect the technique
`of extremely complete silicone-fluid exchange during
`pars plana vitrectomy via an automated oil pump, acti(cid:173)
`vated by a foot pedal. We believe this technique affords
`a more complete interna] drainage of subsilicone and
`subretinal fluid, thus allowing a more complete oil fill.
`In addition, we use extensive endolaser photocoagula(cid:173)
`tion in all cases under direct clear view through the
`silicone, ensuring closure of all holes and retinotomies.
`The low incidence of fibrous proliferation may be re(cid:173)
`lated to the extensive laser treatment, and also to the fact
`that in the absence of an extra silicone fluid space there
`may be less movement between the surface of the retina
`and tbe surface of the silicone.
`Improvements in surgical techniques have lessened
`the incidence of complications ascribed to the mechani(cid:173)
`cal effects of silicone. 1- 30 The physicochemical proper(cid:173)
`ties that characterize the biocompatibility of the silicone
`may be much more important than viscosity or me(cid:173)
`chanical intraoperative considerations. 31
`As has been observed by other authors, many of the
`complications reported here did not occur until after the
`3-montb follow-up visit. If the oil is to be removed, we
`suggest this be done within 3 months of the initial pro(cid:173)
`cedure of instillation. If oil is to be used as a permanent
`
`tamponade, then a highly biocompatible oil must be
`used. Clinical studies comparing tissue effects of oils
`from various origins would be useful in determining
`biocompatibility. We believe silicone oil is an important
`adjunct in the treatment of complicated vitreoretinal
`problems and because of its optical clarity and high sur(cid:173)
`face tension, is often an indispensable tool in meticulous
`microsurgery of the retina.
`
`REFERENCES
`
`1 . Cibis PA, Becker B. Okun E. The use of liquid silicone in retinal
`detachment surgery. Arch Ophthalmol 1962; 68:590-9.
`2. Okun E. lntravitreal surgery utilizing liquid silicone. A long term fol•
`lowup. Trans Pac C-Oast Ophthalmol Soc 1968; 52:141-59.
`3. Cockerham WO, Schepens CL, Freeman HM. Silicone injection in
`retinal detachment Arch Ophthalmol 1970; 83:704-12.
`4. Scott JD. Treatment of the detached immobie retina. Trans Ophthal(cid:173)
`mol Soc UK 1972; 92:351-7 .
`5. Grey RHB, Leaver PK. Results of silicone oil injection in massive
`preretinal retraction. rrans Ophthalmol Soc UK 1977; 97:238-4 1.
`6. Grey RHB, Leaver PK. SUiC-One oil in the treatment of massive prereti·
`nal retraction. I. Results in 105 eyes. Br J Ophthalmol 1979; 63:355-
`60.
`7. Leaver PK, Grey RHB, Garner A. Silicone oil injection in the treatment
`of massive preretinal relfaction. II. Late complications in 93 eyes. Br J
`Ophthalmol 1979: 63:361-7.
`8. Leaver PK, Grey RHB, Garner A. Complications following silicone-oil
`injection. Mod Prob! Ophthalmol 1979; 20:290-4.
`9. Haul J, Chermet M, Van Effenterre G, Robert P. 1 echnique et resul•
`tats de !'injection de silicone liquide combinee a la vitrectomie dans le
`traitement des inversions retiniennes. Bull Soc Ophtalmot Fr 1980;
`80:517-8.
`10. Haut J. Ullem M, Chermet M, Van Effenterre G. Complications des
`injections intra·oculaires de silicone. Bull Soc Ophtalmol Fr 1980;
`80:519-23.
`11 . Haut J, Van Effenterre G, Ullern M, Cl1ermet M. Traitement chirurgical
`des decollements de reine avec trou maculaire par la technique de la
`vitrectomie associee a !'injection de silicone liquide. J Fr Ophtalmol
`1980: 3:115- 8.
`12. Haut J, Ullern M, Chermet M, Van Effenterre G. Complications of
`intraocular injections of silicone combined with vitreclomy. Ophthal•
`mologica 1980; 180:29-35.
`13. i ivojnovic R, Mertens DAE, Baarsma GS. Das flussige Siikon in der
`Amotiochirurgie. Bericht Ober 90 FWle. Klin Monatsbl Augenheilkd
`1981 : 179:17- 22.
`14. iivojnovic R, Mertens DAE, Peperkamp E. Das flGssige Silikon in der
`Amotiochirurgie (II) Bericht Ober 280 F!ille- weitere Entwicklung der
`Technik. Klin Monatsbl Augensheilkd 1982; 181:444-52 .
`15. Gonvers M. Temporary use of lntraocular silicone oil in the treatment
`of detachment with massive periretinal proliferation : p<elimina,y re(cid:173)
`port. Ophlhalmologica 1982: 184:210-8.
`16. Mouilleau D, Sourdille Ph, Baikoff G. et al. Complications des lnjec•
`lions intra-oculaires d'huile de silicone. Bull Soc Ophtalmol Fr 1983;
`83:461-4 .
`17. Leaver PK, Cooling RJ, Feretis EB, et al. Vitrectomy and fluid/sili(cid:173)
`cone-oil exchange for giant retinal tears: results at six months. Br J
`Ophthalmol 1984; 68:432-8.
`18. Roussat 8, Ruellan YM. Tra1tement du decoUement de reline par
`vitrectomie et injection d'huie de silicone. Resultats a long terme et
`complications dans 105 cas. J Fr Ophtalmol 1984; 7:11-8.
`19. Barthelemy F, Chauvaud D, Frota A. Utilisation de l'huile de silicone
`en tamponnement transito~e dans le traitement des decollements de
`reline avec retraction vilreo-retinienne. Premiere partie: Resultats an-
`
`875
`
`Novartis Exhibit 2287.006
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`OPHTHALMOLOGY • JULY 1988
`
`• VOLUME 95
`
`• NUMBER 7
`
`atomiques et fonctionnels a court et long terrnes sur 110 cas. J Fr
`Ophtalmol 1984; 7:273-7
`20. Chauvaud D, Barthelemy F, Frota A. Utilisation de l'huile de silicone
`en tamponnement transitoire dans le traitement des decollements de
`reline avec retraction vitreo-retinienne. Deuxieme partie: Aspects,
`prevention et traitement des complications. J Fr Ophtalmol 1984;
`7:279-84.
`21 , Gnad H, Skorpik Ch, Paroussis P, et al. Funktioneele und anato(cid:173)
`mische Resultate nach temporiirer Silikonolimplantation. Klin Mon(cid:173)
`atsbl Augenheilkd 1984; 185:364-7.
`22. Faulbom J. lndikation zur Silikonotimplantation bei fortgeschrittener
`proliferativer diabetischer Retinopathie. Klin Monatsbl Augenheilkd
`1984; 185:362-3.
`23. Mccuen BW II, De Juan E Jr, Landers MB Ill, Machemer R. SUicone oil
`in vttreoretinal surgery Part 2: results and complications. Retina 1985;
`5:198- 205.
`24. Heimann K, Dimopoulos St, Paulmann H. Silikonolinjektion in der
`Behandlung komplizierter NetzhautabRisungen. Klin Monatsbl Au(cid:173)
`genheilkd 1984; 185:505-8.
`25. Dimopoulos St, Heimann K. Spiitkomplikationen nach Silikon<ilinjek-
`
`lion. Langzeitbeobachtungen an 100 Flilen. Klin Monatsbl Augen(cid:173)
`heilkd 1986; 189:223- 7.
`26. Stern WH, Johnson RN, Irvine AR, et al. Extended retinal tamponade
`in the treatment of retinal detachment with proliferative vitreoretinopa(cid:173)
`thy. Br J. Ophthalmol 1986; 70:91 1-7.
`27. Abellan P, Raspiller A, Hachet E, Berrod JP. L'huile de silicone dans
`la chirurgie du decollement de la reline. Bull Soc Ophtalmol Fr 1986;
`86:693-6.
`28. Pang MP, Peyman GA, Kao GW. Early anterior segment complica(cid:173)
`tions after silicone oii injection. Can J Ophthalmol 1986; 21 :271- 5.
`29. Sell CH, McCuen BW II, Landers MB Ill, Machamer R. Long-term
`results of successful vitrectomy with silicone oil for advanced prolifer(cid:173)
`ative vitreoretinopathy. Am J Ophthalmol 1987; 103:24-8.
`30. Peyman GA, Kao GW, de Corral LR. Randomized clinical trial of
`intraocular silicone vs. gas in the management of complicated retinal
`detachment and vitreous hemo