Incidence and Management of
`Glaucoma after lntravitreal
`Silicone Oil Injection for
`Complicated Retinal
`Detachments
`
`Quang H. Nguyen, MD, Mary Ann Lloyd, MD, Dale K. Heuer, MD,
`George Baerveldt, MD, Don S. Minckler, MD,
`John S. Lean, MD, Peter E. Liggett, MD
`
`Background:
`lntravitreal silicone oil injection used for managing complicated retinal
`detachments can be associated with elevated intraocular pressure (IOP). This study
`was undertaken to determine the incidence of glaucoma in patients who underwent
`silicone oil injection, as well as to evaluate the effectiveness of medical and surgical
`therapy in patients in whom glaucoma developed.
`Methods: The postoperative courses of 50 eyes of 4 7 consecutive patients who
`underwent pars plana vitrectomy and silicone oil injection for the management of com(cid:173)
`plicated retinal detachments were reviewed retrospectively. The outcomes of patients
`who underwent silicone oil removal and/or glaucoma surgery also were evaluated.
`Results: The mean overall postoperative IOP before any glaucoma surgery was
`16. 7 ± 9.3 mmHg (range, 0 to 45 mmHg), with a mean follow-up of 16.6 ± 12.1 months
`(range, 2 to 51 months). Twenty-four (48%) eyes had postoperative IOPs of at least 25
`mm Hg and IOP elevations of at least 1 O mmHg above the preoperative levels. Twenty(cid:173)
`one (42%) eyes underwent complete removal of silicone oil and/or glaucoma surgery
`to effect IOP control. The IOPs were controlled to 21 mmHg or less (but > 5 mmHg) in
`8 of 14 eyes that underwent removal of silicone oil alone, in 3 of 5 eyes that underwent
`Molteno implantation, and in 1 eye that underwent Nd:YAG transscleral cyclophoto(cid:173)
`coagulation, but not in 1 eye that underwent a modified Schocket procedure (mean
`follow-up, 13.5 ± 11 .0 months; range, 0.2 to 33 months).
`Conclusion:
`lntraocular pressure elevation is a common occurrence after intravitreal
`silicone oil injection. The underlying mechanism may often be multifactorial in nature.
`Patients in whom uncontrolled IOP develops may benefit from aggressive medical and/
`or surgical treatment with silicone oil removal, glaucoma implants, or cyclodestructive
`procedures. Ophthalmology 1992;99: 1520- 1526
`
`Originally received: April 2, 1992.
`Revision accepted: June 12. 1992.
`From the Department of Ophthal mology, University of Southern Cal(cid:173)
`iforn ia School of Medici ne and the Doheny Eye Institute, Los Angeles.
`Dr. Lloyd is now also with the Department of Veterans Affairs Outpatient
`Clinic, Los Angeles.
`Dr. Lean is now in private practice in Santa Ana.
`Dr. Liggett is now with the Department of Ophthalmology, Yale Uni(cid:173)
`versity School of Medicine, New Haven.
`Presented in part as a poster at the American Academy of Ophthalmology
`An nual Meeting, Anaheim, October 1991.
`
`Supported in part by the Foundation for G laucoma Research, San Fran(cid:173)
`cisco, California, Natio nal Glaucoma Research, a program of the Amer(cid:173)
`ican Health Assistance Foundation, Beltsville, Maryland, and Research
`to Prevent Blindness, Inc, New York, New York.
`The authors have no financial interest in Molteno implants.
`Dr. Baerveldt does have a financial interest in another glaucoma implant
`manufactured by another company.
`
`The views expressed herein arc those of the authors and d o not reflect
`the oflkial policy or position of the U.S. Government.
`Reprint requests to Mary Ann Lloyd, MD, Doheny Eye Institute, 1450
`San Pablo St, Los Angeles, CA 90033.
`
`1520
`
`Novartis Exhibit 2288.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Nguyen et al · Int ravitreal Silicone Oil Injection
`
`lntravitreal silicone oil injection can be useful in the
`management of complicated retinal detachments. Because
`silicone oil can internally tamponade the retina, it can
`effect anatomic reattachment even in the presence of pro(cid:173)
`liferative vitreoretinopathy. However, intravitreal silicone
`oil injection has been associated with a high incidence of
`complications, one of the most common of which is a
`transient or sometimes permanent intraocular pressure
`(IOP) elevation.
`We retrospectively reviewed the postoperative I0P
`courses of patients who underwent intravitreal silicone
`oil injection after complete pars plana vitrectomy. This
`study was undertaken to determine the incidence of glau(cid:173)
`coma and the outcomes of medical and surgical glaucoma
`therapy in patients who underwent silicone oil injection.
`Possible mechanisms underlying the development of
`glaucoma after silicone oil injection are discussed.
`
`Subjects and Methods
`
`Forty-seven consecutive patients underwent pars plana
`vitrectomy and silicone oil injection for the management
`of complicated retinal detachments as participants in the
`Adatomed Silicone Oil Study at the Doheny Eye Institute
`between November 11, 1986 and January 4, 1991. Three
`patients underwent bilateral pars plana vitrectomy and
`silicone oil injection; results of both eyes have been in(cid:173)
`cluded in this report. The retinal surgeries were performed
`by two surgeons (JSL or PEL), and the glaucoma proce(cid:173)
`dures were performed by three surgeons (GB, DKH, or
`DSM). All patients gave informed consent. The silicone
`study protocol was approved by the Los Angeles County/
`University of Southern California Medical Center Insti(cid:173)
`tutional Review Board (research protocol #05741).
`All patient records were retrospectively reviewed for
`patient demographic, preoperative, intraoperative, and
`postoperative data, the most current postoperative data
`being obtained from the referring ophthalmologists' offices
`for patients who could not return to the Doheny Eye In(cid:173)
`stitute for evaluation. Elevated I0P was defined before
`reviewing the charts as any postoperative l0P of at least
`25 mm Hg that also was at least IO mmHg above the pre(cid:173)
`operative I0P level. For those patients who underwent
`surgery to control their I0Ps, the categories for surgical
`outcome were also defined prior to reviewing the charts
`(Table 1 ). The final postoperative visual acuities and IOPs
`were those from each patient's most recent examination.
`
`For those patients who lost light perception, the final dates
`were recorded when the patients were first noted to have
`lost light perception.
`
`Surgical Procedures
`
`All patients underwent standard three-port pars plana vi(cid:173)
`trectomy, membrane segmentation, and additional pro(cid:173)
`cedures (such as scleral buckling) as appropriate for the
`retinal pathology, followed by silicone oil injection. Before
`silicone oil injection, inferior peripheral iridectomies were
`created in those patients with aphakia and pseudophakia
`who had sufficient iris present. Glaucoma surgical pro(cid:173)
`cedures performed included one- or two-stage single-plate
`Molteno implantation, modified Schocket procedure, and
`Nd:YAG transscleral cyclophotocoagulation.
`The basic procedure for Molteno implantation has been
`described previously, 1 with a few modifications added in
`this group of patients. A peritomy was performed at the
`limbos, and blunt dissection was used to free space pos(cid:173)
`teriorly between the rectus muscles. In eyes that had scleral
`buckles in place, the Molteno plates were secured to the
`sclera or bands with 5-0 polyester fiber suture through
`the two anterior fixation holes. Implantations were most
`frequently perfonned inferiorly with the tubes (which were
`ligated with absorbable suture during one-stage proce(cid:173)
`dures) inserted through 22- or 23-gauge needle tracts at
`the inferior limbus (rather than the pars plana) to mini(cid:173)
`mize postoperative silicone drainage through the tubes.
`Donor glycerin-preserved scleral grafts were applied over
`the ends of the tubes adjacent to the limbus, and con(cid:173)
`junctiva and Tenon's capsule were closed at the limbus
`with 7-0 or 8-0 polyglactin mattress sutures that were
`run posteriorly, closing the relaxing incisions in a single
`layer. Dexamethasone phosphate ( 12 mg), gentamicin
`sulfate (20 mg), and (in some cases) vancomycin hydro(cid:173)
`chloride (20 mg) were injected subconjunctivally at the
`conclusion of the procedures; postoperatively, patients
`were treated with topical I% prednisolone acetate or
`phosphate for several months and topical antibiotics for
`l to 2 weeks.
`The modified Schocket procedure was performed
`through a fornix-based conjunctiva! opening. Blunt dis(cid:173)
`section was used to free conjunctiva and Tenon's layers
`from the previously placed 280 band in the inferior tem(cid:173)
`poral quadrant. The capsule surrounding the encircling
`element was incised and a 23-gauge needle was used to
`
`Table 1. Categories of G laucoma ,Surgical Outcome
`
`Complete Success
`Q ualified Success
`Qualified Failure
`Complete Failure
`
`6 mmHg s IOP s 21 mmHg without medication
`6 mmHg s IOP s 21 mmHg with medication
`IOP > 21 mmHg
`Further glaucoma surgery (or recommendation thereof), hypotony, devastating
`complication, or loss of light perception
`
`IOP = intraocular pressure.
`
`1521
`
`Novartis Exhibit 2288.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Ophthalmology Volume 99, Number 10, October 1992
`
`Table 2. Data Summary (50 Eyes of 47 Patients)
`
`Age (yrs):
`Range
`Mean ±SD
`Lens Status:
`Aphakic
`Phakic
`Retinal Detachment Associated with:
`Proliferative vitreoretinopathy (PVR)
`Cyromegalovirus retinitis
`Proliferative diabetic retinopathy (non-PVR)
`G iant retinal tear
`Coloboma
`Massive choroidal hemorrhage
`Recurrent retinal detachment
`Glaucoma Antedating Any Ocular Surgery
`Congenital
`Open-angle
`Angle-closure
`Neovascular
`Preoperative IOP (mmHg):
`Range
`Mean ±SD
`Preoperative Antiglaucoma Medication
`1 Medication
`2 Medications
`Prior Pars Plana Vitrectomy with Gas and/or Oil Injection
`Surgical Procedures:
`Pars plana vitrectomy with silicone oil
`Sciera! buckle (including those placed previously)
`Peripheral iridectomy
`Length of Follow-up (mos)":
`Range
`Mean ±SD
`Postoperative IOP (mmHg)*:
`Range
`Mean ± SD
`Postoperative IOP Elevationt
`Postoperative Antiglaucoma Medication:
`T emporaryt
`1 Medication
`2 Medications
`3 Medications
`Chronic§
`1 Medication
`2 Medications
`3 Medications
`Visual Outcome:
`Eyes without IOP elevation
`Betted
`Same11
`Worse"
`Eyes with IOP elevationtt
`Better
`Same
`Worse
`Complications:
`Phthisis bulbi
`Corneal decompensation
`Oil infiltrating anterior chamber
`Rubeosis iridis
`
`1522
`
`7-80
`47.6 ± 21.3
`
`37 (74%)
`13 (26%)
`
`35 (70%)
`7 (14%)
`2 (4%)
`2 (4%)
`2 (4%)
`1 (2%)
`1 (2%)
`6 (12%)
`2(4%)
`2 (4%)
`1 (2%)
`1 (2%)
`
`1-22
`10.7 ± 5.1
`9 (18%)
`6 (12%)
`3 (6%)
`20(40%)
`
`50 (100%)
`32 (64%)
`21 (42%)
`
`2-51
`16.6 ± 12.1
`
`0-45
`16.7 ± 9.3
`24 (48%)
`
`32 (64%)
`13 (26%)
`14 (28%)
`5 (100/o)
`16 (32%)
`11 (22%)
`4 (80/o)
`1 (2%)
`
`26 (52%)
`10 (200/o)
`9 (18%)
`7 (14%)
`24 (48%)
`8 (16%)
`8 (16%)
`8 (16%)
`
`7 (14%)
`6(12%)
`6 (12%)
`3 (6%)
`
`Novartis Exhibit 2288.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Nguyen et al · lntravitreal Silicone Oil Injection
`
`Table 2.
`
`(continued)
`
`SD = standard deviation; PVR = proliferative vitreoretinopathy; IOP = intraocular pressure.
`• Before silicone oil removal or glaucoma surgery.
`t Postoperative IOP at least 25 mmHg and elevated at least 10 mmHg above preoperative level.
`t Duration of glaucoma therapy was at least one to five weeks.
`§ Duration of glaucoma therapy was the entire course of follow-up or until surgery was performed to lower the
`IOP.
`N Postoperative visual acuity at least two lines better than preoperative visual acuity.
`1 Postoperative visual acuity within one line of preoperative visual acuity.
`•• Postoperative visual acuity at least two lines worse than preoperative visual acuity.
`tt Visual acuities for those eyes that underwent surgery to lower the IOPs are final acuities after surgery was
`performed.
`
`create a tract in the capsule through which a silicone tube
`was passed and secured to the buckling element. The cap(cid:173)
`sule was closed with 8-0 polyglactin suture, and irrigation
`of the potential space i"nside the capsule was performed
`through the tube. The tube insertion, donor scleral graft,
`conjunctival closure, subconjunctival medications, and
`postoperative medications were similar to those with
`Molteno implantation.
`Nd:YAG transscleral cyclophotocoagulation was per(cid:173)
`formed on one patient. A Shields lens was placed after
`the patient had received retrobulbar anesthesia, and a total
`of 36 spots were applied approximately 1.0 to 1.5 mm
`posterior to the limbus over 360°, sparing the 1 clock
`hour around both the 3-o'clock and 9-o'clock positions.
`The patient received a topical combination of tluoro(cid:173)
`metholone and sulfacetamide sodium for several weeks
`after surgery.
`
`Results
`
`Demographic, preoperative, intraoperative, and postop(cid:173)
`erative data are summarized in Table 2. The patients'
`ages ranged from 7 to 80 years (mean ± standard devia(cid:173)
`tion, 47.6 ± 21.3 years). The mean overall follow-up for
`patients before their having undergone silicone oil removal
`or glaucoma surgery was 16.6 ± 12.1 months (range, 2 to
`51 months), and the mean follow-up for those patients
`who underwent surgical procedures to lower their IOPs
`was 13.5 ± 11.0 months (range, 0.2 to 33 months). The
`follow-up periods for five patients were limited by their
`deaths from human immunodeficiency virus infection or
`other causes unrelated to their eye surgeries.
`All patients had complicated retinal detachments that
`were associated with the following conditions: 35 (70%)
`eyes with proliferative vitreoretinopathy, 7 (14%) eyes with
`cytomegalovirus retinitis, 2 ( 4%) eyes each with severe
`proliferative diabetic retinopathy, giant retinal tears, and
`colobomas, and I (2%) eye each with massive choroidal
`hemorrhage and recurrent retinal detachment. Thirty(cid:173)
`seven eyes were aphakic, and 20 eyes had undergone pre(cid:173)
`vious pars plana vitrectomy with gas-fluid exchange or
`silicone oil injection in attempts to effect retinal reattach-
`
`ment. Eighteen (36%) eyes had previously placed scleral
`buckles, and 14 (28%) eyes underwent scleral buckling at
`the time of silicone oil injection. Inferior peripheral iri(cid:173)
`dectomies were performed at the time of oil injection in
`21 (42%) eyes.
`Six ( 12%) eyes of 6 patients had a diagnosis of glaucoma
`antedating silicone oil injection (2 patients each had con(cid:173)
`genital glaucomas and open-angle glaucomas, and 1 pa(cid:173)
`tient each had neovascular and secondary angle-closure
`glaucomas); 3 other patients who had elevated IOPs with(cid:173)
`out diagnoses of glaucoma also were using antiglaucoma
`medications preoperatively. Twenty-four (48%) eyes
`overall had postoperative IOPs of at least 25 mmHg and
`IOP increases of at least IO mm Hg above the preoperative
`levels. The preoperative IOPs ranged from I to 22 mmHg
`(mean ± standard deviation, 10.7 ± 5.1 mmHg), and the
`final IOPs before silicone oil removal or glaucoma surgery
`ranged from Oto 45 mmHg (mean± standard deviation,
`16.7 ± 9.3 mmHg). Thirty-two (64%) eyes received an(cid:173)
`tiglaucoma medications at least temporarily (from I to 5
`weeks after surgery), and 16 of those eyes chronically re(cid:173)
`ceived medications (for the duration of follow-up or until
`glaucoma surgery was performed) to control IOP.
`Silicone oil removal alone was performed on 14 eyes,
`and glaucoma surgery (with or without oil removal) was
`performed on 7 eyes with medically uncontrollable IOP.
`The outcomes of these eyes are presented in Table 3.
`Among the eyes that had silicone oil removal alone, IOP
`was controlled in eight eyes, and among the eyes that
`underwent a glaucoma procedure (with or without oil re(cid:173)
`moval), IOP was controlled in four eyes. Of the nine eyes
`receiving antiglaucoma medications before silicone oil
`injection, one eye had no postoperative IOP elevation,
`two eyes had transient postoperative IOP elevations, three
`eyes received chronic antiglaucoma medical therapy, and
`three eyes underwent Molteno implantation (two of these
`eyes were categorized as qualified successes and one eye
`as a qualified failure).
`In our series overall, the postoperative visual acuities
`remained within I line of the preoperative visual acuities
`or improved in 35 (70%) eyes. Among the 24 eyes with
`IOP elevations (including the eyes on which glaucoma
`surgery was performed), the final postoperative visual
`
`1523
`
`Novartis Exhibit 2288.004
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Ophthalmology Volume 99, Number 10, October 1992
`
`Table 3. Data Summary of Eyes Undergoing
`Surgery for Glaucoma (21 Eyes of 18 Patients)
`
`Surgical Procedures to Control IOP
`Silicone oil removal alone*
`Glaucoma procedurest
`Molteno implantation
`Modi.lied Schocket procedure
`Nd:Y AG laser cyclophotocoagulation
`Preoperative IOP (mmHg):
`Range
`Mean ±SD
`Postoperative IOP (mmHg):
`Range
`Mean ±SD
`Length of Follow-up (mos):
`Range
`Mean ±SD
`Surgical Outcome:
`Complete silicone oil removal alone
`Success
`Complete
`Qualified
`Failure
`Qualified
`Completet
`Molteno implantation
`Success
`Complete§
`Qualiliedll
`Failure
`Qualified11
`Complete**
`Modi.lied Schocket procedure
`Qualified failure tt
`Nd:YAG transscleral cyclophotocoagulation
`Complete success
`
`21 (42%)
`14 (28%)
`7 (14%)
`5 (10%)
`1 (2%)
`1 (2%)
`
`15- 45
`27.0 ± 7.3
`
`4- 31
`15.8 ± 7.7
`
`0.2-33
`13.5 ± 11.0
`
`14 ( lQOO/o)
`8 (57%)
`7 (50%)
`1 (7%)
`6 (43%)
`0 (00/o)
`6 (43%)
`5 (lOOo/o)
`3 (60%)
`1 (20%)
`2 (40%)
`2 (40%)
`1 (20%)
`1 (20%)
`1 (100%)
`1 (100%)
`1 (lOOo/o)
`1 (100%)
`
`IOP = intraocular pressure; SD = standard deviation.
`• All eyes had oil removed within three months of injection.
`t One eye each that underwent Molteno implantation, modified Schocket
`procedure, and Nd: Y AG transscleral cyclophotocoagulation also had sil(cid:173)
`icone oil removed previously.
`t Three eyes underwent glaucoma procedures, and three eyes lost light
`perception because of retinal redetachment associated with cytomega(cid:173)
`lovirus retinitis.
`§ The eye underwent one-stage single-plate Molreno implantation.
`II Both eyes underwent one-stage single-plate Molteno implantations.
`11 The eye underwent two-stage single-plate Molreno implantation. The
`final IOP was 23 mmHg but considered adequately controlled in this
`eye.
`.. The eye underwent two consecutive two-stage single-plate Molteno
`implantations and lost light perception because of retinal necrosis asso(cid:173)
`ciated with severe proliferative diabetic retinopathy.
`tt The final IOP was 23 mrnHg but considered adequately controlled in
`this eye.
`
`acuities remained the same or improved in 16 eyes. All
`patients who lost light perception did so primarily because
`of retinal redetachment, ischemia, or necrosis rather than
`uncontrolled I0P.
`The complications of silicone oil in this group of pa(cid:173)
`tients are summarized in Table 2. Seven ( 14%) eyes be(cid:173)
`came phthisical. Six (12%) eyes developed corneal de(cid:173)
`compensation after undergoing silicone oil injection, and
`penetrating keratoplasty was subsequently performed on
`them. Oil infiltrated the anterior chambers of 6 (12%)
`eyes, none of which developed glaucoma. Three eyes (6%)
`developed postoperative rubeosis iridis, but not neovas(cid:173)
`cular glaucoma. One eye that underwent two consecutive
`two-stage single-plate Molteno implantations developed
`a massive anterior chamber fibrin reaction that occluded
`one tube, which was subsequently cleared by intracameral
`tissue plasminogen activator. One patient who underwent
`one-stage single-plate Molteno implantation had oil in
`the tube tip that did not impair aqueous flow.
`
`Discussion
`
`Although the anatomical and visual results obtained from
`intravitreal silicone oil injection used to manage compli(cid:173)
`cated retinal detachments can be encouraging, late com(cid:173)
`plications may preclude satisfactory long-term out(cid:173)
`comes.2·3 Although glaucoma is the second most common
`postoperative adverse occurrence after silicone oil injec(cid:173)
`tion (ranging from 15% to 22%),4
`7 the mechanisms un(cid:173)
`-
`derlying its development remain controversial.
`deCorral and colleagues8 have shown that IOP eleva(cid:173)
`tion associated with silicone oil injection is independent
`of systemic conditions such as diabetes mellitus. In 1967,
`Watzke2 described the occurrence of postoperative glau(cid:173)
`coma after silicone oil injection and indicated that visible
`oil in the anterior chamber need not necessarily be present
`when the IOP is elevated. The mechanism for I0P ele(cid:173)
`vation is indeed unclear, as Laroche and co-workers9 noted
`normal I0Ps even when silicone globules were present in
`the angle. As Sugar and 0kamura10 also pointed out, el(cid:173)
`evated I0P in the presence of silicone oil may be masked
`by ciliary body detachment from cyclitic membranes.
`Weinberg and colleagues• 1 reported elevated I0P after
`pars plana vitrectomy alone, attributing it to neovascu(cid:173)
`larization, erythroclasis, hemorrhage, hemolysis, or pba(cid:173)
`colysis. Intraocular pressure elevation also may be due to
`peripheral anterior synechiae and/or inflammation.8 In
`addition, we have seen that silicone oil may become
`emulsified and enter the anterior chamber (Fig I), and
`postulate that it may sometimes impede the drainage of
`aqueous through the trabecular meshwork.
`Twenty-four (48%) eyes that underwent pars plana vi(cid:173)
`trectomy with silicone oil injection in our series had post(cid:173)
`operative I0Ps of at least 25 mmHg and I0P increases
`of at least 10 mmHg above the preoperative levels, oc(cid:173)
`curring as early as the first postoperative day. Thirty-two
`
`1524
`
`Novartis Exhibit 2288.005
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Nguyen et al · Intravitreal Silicone Oil Injection
`
`managing glaucoma in patients with intravitreal sili(cid:173)
`cone oil.
`Among the 21 eyes in this series on which surgery was
`performed to manage elevated IOPs, all eyes either had
`scleral buckles and/or lacked intraoperative peripheral ir(cid:173)
`idectomies (because the eyes were phakic or had inade(cid:173)
`quate amounts of iris present). Although the role of these
`factors in the development of glaucoma in our patients
`is uncertain, we re-emphasize the need for performing
`inferior peripheral iridectomies in aphakic and pseudo(cid:173)
`phakic eyes undergoing intravitreal silicone oil injection,
`as Ando 12 has suggested, because they may prevent pu(cid:173)
`pillary block by allowing silicone in the anterior chamber
`to return to the posterior chamber, and aqueous to flow
`from the posterior to the anterior chamber. In addition,
`a scleral buckle can impede outflow from the episcleral
`veins, thereby contributing to inadequate drainage of
`aqueous from Schlemm's canal, as well as inadequate ve(cid:173)
`nous drainage of the ciliary body, making it edematous
`and more likely to obstruct the angle.
`A variety of postoperative complications, including
`phthisis bulbi, occurred in this series, both in eyes that
`underwent glaucoma surgery and those that did not. Be(cid:173)
`cause these eyes frequently had complex pathology, the
`complications were often difficult to attribute to one
`etiology. Corneal edema, one of the most frequent adverse
`occurrences in our series, also has been reported to be the
`third most common complication in other series6 and is
`believed to be the result of corneal endothelial decom(cid:173)
`pensation. All six of our patients who had corneal decom(cid:173)
`pensation had oil in contact with the endothelium. Haut
`and co-workers 13 reported that approximately 40% of pa(cid:173)
`tients who developed glaucoma associated with silicone
`oil injection had oil in the anterior chamber. In our series,
`12% of eyes had silicone oil infiltrating the anterior cham(cid:173)
`ber, but none of them developed glaucoma. Three eyes
`in our series developed rubeosis iridis, but none of them
`developed neovascular glaucoma, which is consistent with
`deCorral and colleagues' report.8 Fourteen percent of the
`eyes in our series became phthisical; this rate is also some(cid:173)
`what consistent with a report by Weinberg et al 11 in which
`I of 5 eyes (20%) became phthisical after silicone oil in(cid:173)
`jection. Glaucoma surgery itself was associated with rel(cid:173)
`atively few complications and did not appear to contribute
`to ophthalmic morbidity overall.
`In summary, IOP elevation is a common occurrence
`after intravitreal silicone oil injection used in the man(cid:173)
`agement of complicated retinal detachments. The under(cid:173)
`lying mechanism is often unclear, and may frequently be
`multifactorial in nature. Patients should be monitored
`closely for the development of elevated postoperative IOP,
`especially if they have a history of elevated preoperative
`IOP, and they may benefit from aggressive medical and/
`or surgical treatment of glaucoma with silicone oil re(cid:173)
`moval, glaucoma implants, or cyclodestructive procedures
`to avoid additional optic nerve damage.
`Acknowledgment. The authors thank Thomas Chu, MD,
`PhD, for providing the photograph.
`
`1525
`
`Figure 1. Emulsified silicone oil in the anterior chamber after intravitreal
`injection for repair of a complicated retinal detachment.
`
`(64%) eyes were receiving antiglaucoma medications for
`at least I to 5 weeks after surgery to control the IOPs; 16
`of those eyes required chronic medications. Our incidence
`of glaucoma is higher than those previously reported; the
`reasons for this finding are unclear but may be related to
`our patients having had more complex pathology or our
`definition of glaucoma differing from those in other stud(cid:173)
`ies. In any case, given the relatively high incidences of
`glaucoma after intravitreal silicone oil injection noted in
`several studies, patients should be closely monitored for
`postoperative IOP spikes. IfIOP elevation occurs, it should
`probably be treated aggressively to prevent further isch(cid:173)
`emia to the retina and optic nerve. As 8 of 9 (89%) eyes
`treated for elevated preoperative IOP had some amount
`of postoperative IOP elevation (3 of these eyes later un(cid:173)
`derwent glaucoma surgery), our data suggest that patients
`with elevated IOPs before undergoing silicone oil injection
`may be particularly at risk for developing elevated post(cid:173)
`operative IOP.
`In our series, 14 (28%) eyes with uncontrolled post(cid:173)
`operative IOPs underwent complete silicone oil removal.
`Furthermore, seven patients (including three who previ(cid:173)
`ously had silicone oil removed) underwent glaucoma sur(cid:173)
`gery to attempt IOP control. Because traditional filtering
`surgery is technically difficult because of conjunctival
`scarring from the retinal surgery and carries a poor prog(cid:173)
`nosis in eyes having had multiple surgeries, artificial
`drainage devices or cyclodestructive procedures may be
`the most appropriate means to lower medically uncon(cid:173)
`trollable IOPs associated with intravitreal silicone oil.
`Three of the five eyes that underwent•Molteno implan(cid:173)
`tation and the one eye that underwent Nd:YAG trans(cid:173)
`scleral cyclophotocoagulation achieved IOP control; the
`one eye that underwent a modified Schocket procedure
`did not achieve a final IOP of2 l mmHg or less. However,
`relatively few patients underwent glaucoma procedures
`in our series, and additional studies are needed to deter(cid:173)
`mine which treatment modalities are most effective in
`
`Novartis Exhibit 2288.006
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Ophthalmology Volume 99, Number 10, O ctober 1992
`
`References
`
`I. Minckler DS, Heuer DK, Hasty B, et al. Clinical experience
`with the single-plate Molteno implant in complicated glau(cid:173)
`comas. Ophthalmology 1988;95:1181-8.
`2. Watzke RC. Silicone retinopiesis for retinal detachment. A
`long-term clinical evaluation. Arch Ophthalmol 1967;77:
`185-96.
`3. Kanski JJ, Daniel R. lntravitreal silicone injection in retinal
`detachment. Br J Ophthalmol I 973;57:542-5.
`4. Alexandridis E, Daniel H. Results of silicone oil injection
`into the vitreous. Dev Ophthalmol l981;2:24-7.
`5. Grey RHB, Leaver PK. Results of silicone oil injection in
`massive preretinal retraction. Trans Ophthalmol Soc UK
`I 977;97:238-4 1.
`6. Leaver PK, Grey RHB, Garner A. Complications following
`silicone-oil injection. Mod Prob! Ophthalmol 1979;20:
`290-4.
`7. Ni C, Wang W-J, Albert OM, Schepens CL. Intravitreous
`
`silicone injection. H istologic findings in a human eye after
`12 years. Arch Opbthalmol 1983;101:1399-1401.
`8. deCorral LR, Cohen SB, Peyma n GA. Effect ofintravitreal
`silicone oil on intraocular pressure. Ophthalmic Surg
`1987; 18:446-9.
`9. Laroche L, Pavlakis C, Saraux H, Orcel L. Ocular findings
`following intravitreal silicone injection. Arch Ophthalmol
`1983;101: 1422-5.
`10. Sugar HS, Okamura ID. Ocular findings six years after in(cid:173)
`travitreal silicone injection. Arch Ophthalmol 1976;94:
`612-5.
`I I. Weinberg RS, Peyman GA, Huamonte FU. Elevation of
`intraocular pressure after pars plana vitrectomy. Albrecht
`Von Graefes Arch KJin Exp Opbthalmol 1976;200: 157-6 1.
`12. Ando F. lntraocular hypertension resulting from pupillary
`block by silicone oil [letter]. Am J Ophthalmol 1985;99:
`87-8.
`13. Haut J, Ullern M, Chermet M , Van Effenterre G. Compli(cid:173)
`cations of intraocular injections of silicone combined with
`vitrectomy. Ophthalmologica 1980; 180:29-35.
`
`1526
`
`Novartis Exhibit 2288.007
`Regeneron v. Novartis, IPR2021-00816
`
`