Seminars in Ophthalmology, 2014; 29(5–6): 312–318 ! Informa Healthcare USA, Inc. ISSN: 0882-0538 print / 1744-5205 online DOI: 10.3109/08820538.2014.962181
REVIEW
Complications of Emulsified Silicone Oil after Retinal Detachment Repair John B. Miller, Thanos D. Papakostas, and Demetrios G. Vavvas
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Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
ABSTRACT Intraocular silicone oil has several important indications in vitreoretinal surgery, particularly the repair of complicated retinal detachments. Emulsification is a clinically significant complication of using silicone oil tamponade. There are several factors that can promote or prevent silicone oil emulsification after retinal detachment repair, including protein surfactants, contaminants, and shear forces. However, the duration of tamponade remains the most significant one. After emulsification has occurred, keratopathy and glaucoma are the most common complications. However, recent work has shown that emulsification can also affect the retina, optic nerve, and even extraocular structures. Limiting the amount of time the silicone oil remains in the eye is the most important factor in reducing its complications. Keywords: Emulsification, glaucoma, keratopathy, retinal detachment, silicone oil
INTRODUCTION
the postoperative period. Although not proven (or disproven) to be superior, most physicians will use silicone oil tamponade in retinal detachments at high risk for repair failure, including cases involving viral retinitis, proliferative vitreoretinopathy (PVR), giant retinal tears, and tractional retinal detachments.6
Silicone oil was first used for retinal detachments in the 1960s, providing internal tamponade by intravitreal injection.1 Both Machemer2 and Scott3 believed that silicone oil could dissect preretinal membranes and work against retinal traction as a stand-alone therapeutic agent. Using Scott’s technique to dissect membranes with an intravitreal injection of silicone oil without vitrectomy, others also reported good results.4,5 With Machemer’s later development of pars plana vitrectomy, silicone oil use became even more widespread, particularly for complicated retinal detachments. There are several indications for silicone oil in specific clinical situations, many of which can be explained by silicone oil’s advantages over intraocular gas. Since silicone oil’s volume does not change over time, it is thought to require less strict positioning compared to intraocular gas, making it preferable for children or other patients unable to position optimally postoperatively. Unlike gases, its volume is not affected much by variation in atmospheric pressure; thus, it is preferred in patients that have to fly during
MOLECULAR PROPERTIES Silicone is a man-made synthetic substance made of the chemical element silicon (Si) (no terminal e), the fourteenth element of the periodic table and the most abundant element on earth’s crust after oxygen. Silicone oil is the liquid form of silicone, a term used to classify repeating units of siloxane (-Si-O-). This is the same substance that, in its solid form, is used for scleral buckling elements.7 Silicone oil (SO) has a specific gravity lighter than water. Siloxane mixed with alkenes (an unsaturated chemical compound containing at least one carbon–carbon double bond) has higher specific gravity than water and sometimes is improperly referred as ‘‘heavy’’ silicone oil. With a specific gravity above water and aqueous, these
Received 25 August 2014; revised 27 August 2014; accepted 2 September 2014; published online 1 October 2014 Correspondence: John B. Miller, MD, Retina Service, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. E-mail: [email protected]
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Emulsified Intraocular Silicone Oil Complications heavier SOs sink within the eye and are used for cases requiring inferior tamponade. Surface and interfacial tension are two important factors that greatly affect the intraocular interactions of silicone oil. Surface tension is equal to the sum of attractive and repulsive forcers between molecules, collectively known as the Van der Waal forces.7 In a drop of water in air, the central water molecules are equally attracted to each other, while those at the periphery are only attracted to adjacent peripheral molecules. The total effective force (surface tension) of this surface energy is to pull peripheral molecules inward, thus reducing the total surface area of the bubble. Likewise, interfacial tension represents a similar molecular force, but only applies when the interface is between two liquid materials. Thus, interfacial tension is defined as the force required to keep a bubble intact within another liquid. Viscosity refers to the ability of a fluid to resist deformation by shear or extensional stress. In this way, a higher shear stress force is required to deform silicone oil of higher viscosity, typically silicone oils with siloxane of longer chain length. Conversely, a lower viscosity silicone oil can be more easily deformed or dispersed. In addition to shear stress, liquids can also be deformed by extensional forces, which can stretch the material so thin that the strand actually breaks up to form small droplets. The splitting of a liquid into small bubbles is known as dispersion. These small, dispersed bubbles have higher intrinsic surface tension than large bubbles due to their shorter radius, which predisposes to coalescing with the larger bubble. It is only when the small bubbles are unable to coalesce with the larger bubble that we classify the change as emulsification. This is an important distinction between emulsification and dispersion, as the terms are often confused and sometimes used interchangeably. In the case of emulsification, and according to the surface tension theory, emulsification takes place by reduction of interfacial tension between two phases that prevent the smaller bubbles from joining the larger bubble. There are two other major theories about emulcification. (1) The repulsion theory suggests that an emulsifying agent creates a film over one phase that forms globules which repel each other, not allowing them to join. This repulsive force causes the small bubbles to remain suspended in the dispersion medium (aqueous). (2) The viscosity modification theory suggests that emulsifying agents exist or form in the medium that increase the viscosity of the medium (aqueous), which helps create and maintain the suspension of globules of dispersed phase (the silicone oil). The emulsion of ‘‘oil-in-water’’ is the observed phenomenon in silicone oil emulsification, hardly ever seeing ‘‘water-in-oil’’ emulsions in the clinical setting. This is because it is not the relative volume of !
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oil and water which will determine the ‘‘oil-in-water’’ or ‘‘water-in-oil’’ emulsion, but rather, like the Bancroft rule states, ‘‘The phase in which an emulsifier is more soluble constitutes the continuous phase.’’ For example, proteins (surfactants/emulsifiers) dissolve better in aqueous than in oil, and so they tend to form oil-in-water emulsions by promoting the dispersion of silicone oil droplets through the continuous phase of aqueous.
FACTORS AFFECTING SILICONE OIL EMULSIFICATION There are several factors affecting silicone oil emulsification discussed in the literature. Early work examined the role of different biochemical properties, particularly viscosity and molecular weight. Higherviscosity silicone oil is more resistant to deformation and thus less likely to disperse and eventually emulsify.8 Likewise, higher-molecular-weight silicone oil, with its higher viscosity, has also been shown to be more resistant to emulsification.9 Lower-molecularweight silicone oils are thought to move more freely, making them more prone to emulsification. Using an in-vitro model, Crisp confirmed these concepts, showing that emulsification was more likely in both lower-viscosity and lower-molecular-weight silicone oils.10 It is important to note that these studies most often cannot distinguish clearly between emulsification and short-term dispersion. Surfactants (surface active agents) work to decrease a given liquid’s surface tension within a medium, thus increasing the risk of emulsification. As it pertains to intraocular silicone oil, there are several intrinsic surfactants, including serum, fibrin, fibrinogen, and LDLs.9 These surfactants can be present at higher levels in inflammatory, infectious, and hemorrhagic conditions. These three intraocular conditions are actually quite common in the perioperative setting, given the common indications for silicone oil. However, they can also be modified by the use of postop drops or specific intraoperative interventions (e.g., photocoagulation, antibiotics, or antiinflammatories). Like the intrinsic surfactants discussed earlier, it is also possible to have extrinsic surfactants or contaminants promote emulsification. These can come from a variety of locations in the surgical process, whether in the operating room or the instrument room prior to surgery. Dresp et al. examined cleaned and sterilized vitreoretinal surgical equipment deemed ready for use.11 Their study found both detergents and silicone oil contaminants on several vitreoretinal surgical components. Sterilization detergents, which also represent surfactants for silicone oil emulsification, were found in greatest concentrations on the vitrectomy tubing, cutter, and fundus lens. Silicone oil remnants
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314 J. B. Miller et al. or contaminants were found most commonly on the sclerotomy cannula.11 The biggest factor for emulsification is the duration of the silicone oil tamponade. Toklu et al. examined the average time to silicone oil emulsification in a retrospective study in 32 eyes.12 They first noted signs of emulsification between five and 24 months with a mean of 13.2 months. It was only in cases deemed to be at high risk of retinal detachment that extended silicone oil tamponade was used, consistent with practice standards. These results reinforce the findings of a previous study by Federman and Schubert that found some emulsification in all eyes with intraocular silicone oil for at least one year.13 While most eyes follow the typical time course described earlier, there is at least one described condition that has been shown to accelerate emulsification. Yilmaz and Guler showed that patients with underlying nystagmus develop silicone oil emulsification much more quickly than previous reports in the literature.14 They noted emulsification in all eight eyes with nystagmus one to three months postoperatively. It is thought that the repetitive shear force applied to the silicone oil by the ongoing nystagmus makes emulsification more likely. This highlights the general rule that common emulsions are inherently unstable and, over time, they want to revert to a more stable state that is made of the two phases comprising the emulsion. Thus, energy input—through stirring, shaking, homogenizing, etc.—is needed to form and keep the emulsion (one can think of the vinaigrette emulsion, which unless continuously shaken reverts to the two separate phases). There are exceptions to this rule of inherent instability of emulsions. In particular, microemulsions, which are formed by oil, water, salt, and surfactants, are thermodynamically stable, and form upon simple mixing without the need of shear forces. In addition to inherent patient characteristics, there are some surgical adjuncts that can promote emulsification. Heavy liquids, such as perfluorocarbon (PFO), are often used to assist in the repair of complex retinal detachments. Dresp found that turbulence at the interface of the PFO and SO can increase the chance of emulsification.15 He concluded that minimizing the duration of contact and turbulence at the interface by performing an efficient, but controlled, fluid exchange can help prevent emulsification.15 Others have asked whether the presence of an encircling band affects rates of emulsification. de Silva constructed an experimental model to examine this clinical scenario, confirming that an encircling scleral buckle decreases the risk of emulsification.16 This was a promising result, given the frequency of combined scleral buckle and vitrectomy for complicated retinal detachments. This same experimental model was also used to examine how the silicone oil fill affects
emulsification.16 Their experiments found that a more complete fill reduced emulsification. The authors proposed that, with a more complete fill, there is less aqueous in the posterior chamber and thus a smaller interface between the silicone oil and aqueous to create friction and ultimately emulsification.16 Others examined whether additional surgical procedures could affect emulsification. One group found that both extended phacoemulsification power use and high-speed vitrectomy in the presence of intraocular silicone oil increase the risk of emulsification.17 Like the ultrasound power used to break up the lens, the extended application of phacoemulsifcation likely disrupts the silicone oil by the intraocular distribution of the phaco power. The increased risk of emulsification with high-speed vitrectomy can likely be explained by creating more turbulence within the silicone oil, similar to the conditions described previously during fluid-fluid exchange with PFO and SO. Fortunately, phacoemulsification and high-speed vitrectomy are rarely used with silicone oil already in the eye. Typically, fresh silicone oil tamponade is added at the conclusion of the surgery, with a few notable exceptions. While higher-viscosity silicone oils are less likely to emulsify, they are more difficult to inject and remove from the eye using small-gauge cannulas. With the advent and more widespread use of small-gauge vitrectomy, the greater speed of instillation and removal of lower-viscosity silicone oils has made them preferable. Given this preference, some have set out to identify ways to decrease emulsification while still using lower-viscosity silicone oils. Williams et al. found that by adding high-molecular-weight polymers to the silicone oil, they could significantly reduce the risk of emulsification.18 Because their experiments were in an in-vitro model, further work is needed to examine potential toxicity and ensure efficacy before clinical application.
COMPLICATIONS OF SILICONE OIL EMULSIFICATION There are several known complications of emulsified silicone oil. Our review found that the literature does not distinguish well between complications of silicone oil and those specifically related to emulsification. However, it can be reasonably concluded that many of the complications are indeed secondary to emulsification, as these separated droplets of emulsified silicone oil infiltrate intraocular tissues in both the anterior and posterior segments. The most common occur in the anterior segment, so we will first focus on the keratopathy and glaucoma that can result from silicone oil emulsification. Seminars in Ophthalmology
Emulsified Intraocular Silicone Oil Complications
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Cornea Corneal decompensation frequently occurs if the silicone oil touches the corneal endothelium. There are several reports regarding this silicone-associated keratopathy, with the majority occurring in aphakic eyes.13,19–22 The histopathology of silicone-oil-induced keratopathy includes retrocorneal membrane, stromal hypercellularity, superficial stromal calcification and vascularization, decreased endothelial cell density, and attenuation of endothelial cell borders leading to bullous keratopathy.23–25 McCuen et al. reported corneal decompensation in 29% of 164 eyes in their retrospective case series.26 It occurred in 35% of aphakic eyes, 26% of pseudophakic eyes, and 20% of the eyes that remained phakic at the end of the follow-up. Chan reported siliconeinduced keratopathy in 41 out of 407 eyes treated with silicone oil tamponade.22 Forty of those 41 eyes that developed keratopathy were aphakic. In Haut’s cohort of 200 eyes, 37 developed keratopathy, with silicone-cornea touch in 34 cases.27 Casswell identified 11 eyes with keratopathy after silicone oil tamponade in a series of 85 eyes.28 In the 11 eyes with keratopathy, nine were aphakic and two were phakic. A penetrating keratoplasty was required in two eyes at the time of silicone oil removal and the corneas remained clear at the six-month follow-up visit. Interestingly, the Silicone Study Report 7 on corneal abnormalities reported an incidence of 27% at 24 months, which did not differ between those treated with gas versus silicone oil tamponade.29 Sternberg evaluated the clinical and morphologic changes in the corneas of 14 rabbits and seven cats with silicone oil in the anterior chamber.23 After six days, specular microscopy showed a 40% reduction in endothelial density in the area of the silicone oil bubble in both groups. The rabbit corneas exhibited progressive stromal thinning and retrocorneal membrane formation. On the other hand, peripheral vascularization, persistent corneal edema, and irregular plaques on the endothelium occurred in the cat eyes. Yang demonstrated that silicone oil is cytotoxic on cultivated human endothelial cells.30 In addition, they showed that the high-viscosity oil (5,000 centistokes) suppresses cell cycle significantly more than the low-viscosity oil (1,000 centistokes). Green showed that contaminants found in crude silicone oil preparations can be responsible for the silicone-oil-induced keratopathy.31 Since direct contact between the cornea and silicone oil is presumed to lead to the keratopathy, prevention is centered on keeping the silicone oil away from the cornea. To this end, an inferiorly placed peripheral iridectomy allows the free passage of aqueous fluid into the anterior chamber, preventing pupillary block and aiding in displacing silicone oil from the anterior chamber. In a cohort of 62 eyes !
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with prophylactic inferior PI, only 6.5% of the eyes had silicone oil in the anterior chamber.32 Additional work by the same group examined 12 patients who underwent penetrating keratoplasty for corneal opacification induced by silicone oil.33 During the 13.7 months after their corneal transplant, four of the 11 grafts failed while one case was lost to follow-up. Another group reported a mean graft survival of 25 months in 14 eyes that underwent penetrating keratoplasty.34 Not surprisingly, the graft failure rate was lower when silicone oil was removed at the time of keratoplasty (25% vs 67% when SO retained). Karel et al. performed penetrating keratoplasty in 13 eyes with bullous keratopathy secondary to silicone oil.35 At the last follow-up examination, a clear graft was found in six out of 13 eyes (46%). The six clear grafts were found in the 10 eyes where silicone oil had been removed before keratoplasty. The graft became opaque in all three eyes in which silicone oil had not been removed. Lee reported on 24 penetrating keratoplasties in 17 patients from 1991 to 2000.36 Silicone oil was removed before or during the time of initial penetrating keratoplasty in nine patients (52.9%) and left in situ in eight patients (47.1%). Ten out of 24 grafts survived (41.7%). At final follow up (median duration 33 months), the number of patients with a clear graft who had oil removed before or during the time of penetrating keratoplasty was seven out of 10 (70.0%). Given the graft failure rate, some have considered the Boston Keratoprosthesis (KPro) for silicone-oilrelated keratophty. Iyer et al. reviewed eight eyes that received a Boston KPro, noting anatomic retention and visual improvement in seven eyes (87.5%).37 The visual acuity improved to 20/200 or better in six eyes (66.67%). However, it should be noted that silicone oil in the setting of a KPro can be associated with severe retro-KPro membrane formation.
Glaucoma Glaucoma after silicone oil injections can be divided into two major categories: acute intraocular pressure (IOP) spikes and intermediate- or late-onset glaucoma. Only the latter category can occur as a result of silicone oil emulsification. The acute pressure spike seen postoperatively most commonly occurs as result of silicone oil overfill or pupillary block. Our review will focus on the late-onset glaucoma as a result of silicone oil emulsification. The mechanisms by which emulsification contributes to glaucoma can be divided into two general classifications: inflammation and direct infiltration of angle structures.22,25,26,38 Regarding the incidence of glaucoma after silicone oil injection, there have been variable reports in the literature, ranging from 11%39,40 up to 56%41.
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TABLE 1. Reports of incidence of glaucoma after silicone oil injection. Author
Chan
Laqua
de Corral
Burk
Riedel
Henderer
Al-Jazzaf
Year Published Total patients Glaucoma
1986 407 16.8%
1986 500 11%
1987 48 56%
1988 100 50%
1990 415 13%
1999 532 29.3%
2005 450 11%
A summary of the results in the literature is included in Table 1.22,38–43 The variable rate can be explained by the different IOP criteria for glaucoma and length of follow-up in the published studies. Emulsified silicone oil droplets can migrate into the anterior chamber and cause inflammation in the trabecular meshwork, thus impeding outflow of aqueous humor. The viscosity and purity of silicone oil may be important factors that determine the propensity of silicone oil to cause IOP spikes. Petersen found that 1000 centistoke oil was more likely to cause glaucoma compared to 5000 centistoke oil.44 However, in another study by Stinson, there was no difference found.45 The duration of silicone oil tamponade was not found to be a causative factor for IOP rises. When the IOP cannot be controlled medically, surgical removal of the silicone oil, with or without glaucoma surgery, is recommended. Jonas et al. showed that 93.4% of patients with glaucoma secondary to silicone oil achieved normal IOP after removal of the silicone oil alone.46 Budenz et al. reported success, defined by IOP522 and no additional glaucoma surgeries, in 69% of the 43 eyes reviewed at six months after surgery, dropping to 48% at 36 months.47 A total of 26% of the patients required further glaucoma surgery in addition to silicone oil removal. Trabeculectomy is technically difficult, given the presence of scarring from the previous vitreo-retinal surgery and, in general, carries a poor prognosis. Shunting procedures may be a better option. Al-Jazzaf et al. showed a cumulative success rate of 86% at six months and 76% at one year after implantation of an Ahmed Glaucoma shunt in patients with secondary glaucoma related to silicone oil.39
Retina The literature is less defined regarding the complications of emulsified silicone oil in the retina. Early investigators were concerned that extended contact of silicone oil with the retina could cause toxicity. Using rabbit and monkey models, Lee et al. reported vacuolization of the ganglion cell and photoreceptor layers, loss of the ganglion cell layer, and swelling of the nerve fiber layer via light microscopy after silicone oil injection.48 Additional work by the same group
also noted similar histopathology findings in additional animal models along with diminished ERG findings.49,50 Given the lack of definitively proven clinical silicone oil retinopathy in the years after these animal experiments, many questioned whether these changes were really related to silicone oil toxicity. Doubt was also raised by the lack of controls in the prior animal studies. Ryan’s group repeated these experiments in a rabbit model with controls, finding no evidence of silicone oil toxicity at six months.51 This study used clinical exam, histopathology, and ERG recordings compared to operative controls to verify that there was no evidence of damaging effects. Until recently, we lacked technology to properly identify emulsified silicone oil within the retina in vivo. All of the previous studies discussed in this section took place in animal models or histopathology sections after surgical removal and processing of the eye. As a result, it can be difficult to decipher true silicone oil toxicity from a secondary effect related to surgical manipulation or specimen processing. With the advancement of retinal imaging techniques, we are better able to identify emulsified silicone oil within the retina and optic nerve. Using OCT, Spaide was able to identify silicone oil droplets within the retina of a patient after macular hole repair with internal limiting membrane (ILM) peeling and silicone oil tamponade.52 In the postoperative period, the patient was noted to have early silicone oil emulsification. The authors hypothesized that the defects in the ILM provided an entryway for the emulsified silicone oil to enter the intraretinal space. Eleven years later, Spaide used even more advanced generation OCT (Swept Source) and adaptive optics to identify vacuoles of silicone oil within the retina and optic nerve head of a patient with history of multiple retinal detachment repairs.53 The patient had undergone silicone oil removal 11 years prior, just six months after it was placed. He presented with complaints of decreased vision and patchy central visual field defects. The authors suggest that our more advanced multimodal imaging may allow us to better detect direct silicone oil toxicity or a secondary impairment on retinal function due to chronic inflammation from retained silicone oil. Earlier reports implicated high intraocular pressure as a possible mechanism for silicone oil infiltration into the retina and optic nerve.54,55 More work needs to further Seminars in Ophthalmology
Emulsified Intraocular Silicone Oil Complications explore this mechanisms.
potential
toxicity
and
associated
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Extraocular Extension The complications of emulsified intraocular silicone oil are actually not limited to only the eye. There have been multiple case reports of extraocular extension of silicone oil into the brain. In 1999, Williams et al. first reported the presence of intraventricular silicone oil as seen on the MRI of a patient 15 months after retinal detachment repair with silicone oil in the setting of CMV retinitis.56,57 Since that first report, there have been four additional case reports of intraventricular silicone oil after retinal detachment repair.58–61 Interestingly, all four of these subsequent case reports involved patients with a history of diabetic retinopathy. Given the few clinical reports of intraventricular silicone oil, one radiology group examined 19 patients after silicone oil with MRIs of the brain, finding no intraventricular silicone oil.62 It is, however, important to recognize that the average follow-up was only 115 days and there was a small number of cases examined for such a rare finding.
CONCLUSIONS Silicone oil is an important clinical tool for the vitreoretinal surgeon, particularly for complicated retinal detachments and in certain patient populations. Silicone oil emulsification is a clinically significant complication that can occur with intraocular silicone use. Contaminants, protein surfactants, low molecular weight and viscosity, and adjunctive surgical procedures contribute to the incidence. However, duration of tamponade is the single most important factor in promoting silicone oil emulsification. The most well-documented complications of silicone oil emulsification are glaucoma and keratopathy. Fortunately, there has been reasonable surgical success for the treatment of both silicone-oil-related glaucoma and keratopathy. Given recent advancements in retinal and optic nerve imaging, we can better detect posterior complications of silicone oil emulsification. Further work is needed to explore these potential late complications of emulsified silicone oil. Limiting the amount of time the silicone oil remains in the eye is the most important factor in reducing its complications.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. !
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318 J. B. Miller et al. 23. Sternberg P, Hatchell DL, Foulks GN, Landers MB. The effect of silicone oil on the cornea. Arch Ophthalmol 1985; 103:90–94. 24. Foulks GN, Hatchell DL, Proia AD, Klintworth GK. Histopathology of silicone oil keratopathy in humans. Cornea 1991;10:29–37. 25. Ni C, Wang W-J, Albert DM, Schepens CL. Intravitreous silicone injection: histopathologic findings in a human eye after 12 years. Arch Ophthalmol 1983;101:1399–1401. 26. McCuen BW, de Juan E, Landers MB, Machemer R. Silicone oil in vitreoretinal surgery. Part 2: results and complications. Retina 1985;5:198–205. 27. Haut J, Ullern M, Chermet M, Van Effenterre G. Complications of intraocular injections of silicone combined with vitrectomy. Ophthalmologica 1980;180:29–35. 28. Casswell AG, Gregor ZJ. Silicone oil removal. I. The effect on the complications of silicone oil. Br J Ophthalmol 1987;71: 893–897. 29. Abrams GW, Azen SP, Barr CC, et al. The incidence of corneal abnormalities in the silicone study: silicone Study Report 7. Arch Ophthalmol 1995;113(6):764–769. 30. Yang C-S, Chen K-H, Hsu W-M, Li Y-S. Cytotoxicity of silicone oil on cultivated human corneal endothelium. Eye 2008;22:282–288. 31. Role of toxic ingredients in silicone oils in the induction of increased corneal endothelial permeability. Lens Eye Toxic Res 1992;9:377–384. 32. Beekhuis WH, Ando F, Zivojnovic R. Basal iridectomy at 6 o’clock in the aphakic eye treated with silicone oil: prevention of keratopathy and secondary glaucoma. Br J Ophthalmol 1987;71(3):197–200. 33. Beekhuis WH, van Rij G, Zivojnovic R. Silicone oil keratopathy: indications for keratoplasty. Br J Ophthalmol 1985;69:247–253. 34. SW N, GN F, BW M. Results of penetrating keratoplasty associated with silicone oil retinal tamponade. Ophthalmology 1991;98:1186–1189. 35. Karel I, Kalvodova´ B, Kuthan P. Results of penetrating keratoplasty in bullous silicone oil keratopathy. Graefe’s Arch Clin Exp Ophthalmol 1998;236(4):255–258. 36. Lee GA, Shah P, Cooling RJ, Dart J. Penetrating keratoplasty for silicone oil keratopathy. Clin Experiment Ophthalmol 2001;29(5):303–306. 37. Iyer G, et al. Boston keratoprosthesis for keratopathy in eyes with retained silicone oil: a new indication. Cornea 2011;30:1083–1087. 38. Riedel KG, Gabel VP, Neubauer L, et al. Intravitreal silicone oil injection: complications and treatment of 415 consecutive patients. Graefes Arch Clin Exp Ophthalmol 1990; 228:19–23. 39. Al-Jazzaf AM, Netland PA, Charles S. Incidence and management of elevated intraocular pressure after silicone oil injection. J Glaucoma 2005;14(1):40–46. 40. Laqua H, Lucke K, Foerster M. Results of silicone oil surgery. Jpn J Ophthalmol 1986;31(1):124–131. 41. de Corral LR, Cohen SB, Peyman GA. Effect of intravitreal silicone oil on intraocular pressure. Ophthalmic Surg 1987; 18(6):446–449. 42. Burk LL, Shields MB, Proia AD. Intraocular pressure following intravitreal silicone oil injection. Ophthalmic Surg 1988;19(8):565–569.
43. Henderer JD, Budenz DL, Flynn HW Jr, et al. Elevated intraocular pressure and hypotony following silicone oil retinal tamponade for complex retinal detachment: incidence and risk factors. Arch Ophthalmol 1999;17(2): 189–195. 44. Petersen J, Ritzau-Tondrow U. Chronic glaucoma following silicone oil implantation: a comparison of 2 oils of differing viscosity. Fortschritte der Ophthalmologie 1987; 85(6):632–634. 45. Stinson WG, Small KW. Glaucoma after surgery on the retina and vitreous. Semin Ophthalmol 1994;9(4):258–265. 46. Jonas JB, Rank RM, Hayler JK, Budde WM. Intraocular pressure after homologous penetrating keratoplasty. J Glaucoma 2001;10:32–37. 47. Budenz DL, Taba KE, Feuer WJ, et al. Surgical management of secondary glaucoma after pars plana vitrectomy and silicone oil injection for complex retinal detachment. Ophthalmology 2001;108(9):1628–1632. 48. Lee PF, Donovan RH, Mukai N, Schepens CL. Intravitreous injection of silicone: an experimental study. I. Clinical picture and histology of the eye. Ann Ophthalmol 1972;4(4): 273–287. 49. Mukai N, Lee PF, Schepens CL. Intravitreous injection of silicone: an experimental study. II. Histochemistry and electron microscopy. Ann Ophthalmol 1972;4(4):273–287. 50. Lee PF, Oguri M, Schepens CL. A long-term evaluation of silicone retinopathy in monkeys. Canadian J Ophthalmol 1975;(3):391–402. 51. Ober RR, et al. Experimental retinal tolerance to liquid silicone. Retina 1983;3:77–85. 52. Chung J, Spaide R. Intraretinal silicone oil vacuoles after macular hole surgery with internal limiting membrane peeling. Am J Ophthalmol 2003;136:766–767. 53. Mrejen S, Sato T, Fisher Y, Spaide RF. Intraretinal and intraoptic nerve head silicone oil vacuoles using adaptive optics. Ophthalmic Surg Lasers Imaging Retina 2014;45:71–73. 54. Wenkel H, Naumann G. Retrolamina¨re infiltration des nervus opticus durch als intraokulare tamponade verwendetes silikono¨l. Klin Monbl Augenheilkd 1999;214(2):120–122. 55. Knecht P. Is silicone oil optic neuropathy caused by high intraocular pressure alone? A semi-biological model. Br J Ophthalmol 2007;91:1293–1295. 56. Williams RL, Beatty RL, Kanal E, Weissman JL. MR imaging of intraventricular silicone: case Report 1. Radiology 1999;212(1):151–154. 57. Eller AW, Friberg TR, Mah F. Migration of silicone oil into the brain: a complication of intraocular silicone oil for retinal tamponade. Am J Ophthalmol 2000;129(5):685–688. 58. Tatewaki Y, Kurihara N, Sato A, Suzuki I. Silicone oil migrating from intraocular tamponade into the ventricles: case report with magnetic resonance image findings. J Comput Assist Tomogr 2011;35(1):43–45. 59. Yu JT, Apte RS. A case of intravitreal silicone oil migration to the central nervous system. Retina 2005;25(6):791–793. 60. Fangtian D, Rongping D, Lin Z, Weihong Y. Migration of intraocular silicone into the cerebral ventricles. Am J Ophthalmol 2005;140:156–158. 61. Chang C-C, Chang H-S, Toh CH. Intraventricular silicone oil. J Neurosurg 2013;118:1127–1129. 62. Kiilgaard JF, Milea D, Løgager V, la Cour M. Cerebral migration of intraocular silicone oil: an MRI study. Acta Ophthalmol 2011;89:522–525.
Seminars in Ophthalmology
REVIEW
Complications of Emulsified Silicone Oil after Retinal Detachment Repair John B. Miller, Thanos D. Papakostas, and Demetrios G. Vavvas
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Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA
ABSTRACT Intraocular silicone oil has several important indications in vitreoretinal surgery, particularly the repair of complicated retinal detachments. Emulsification is a clinically significant complication of using silicone oil tamponade. There are several factors that can promote or prevent silicone oil emulsification after retinal detachment repair, including protein surfactants, contaminants, and shear forces. However, the duration of tamponade remains the most significant one. After emulsification has occurred, keratopathy and glaucoma are the most common complications. However, recent work has shown that emulsification can also affect the retina, optic nerve, and even extraocular structures. Limiting the amount of time the silicone oil remains in the eye is the most important factor in reducing its complications. Keywords: Emulsification, glaucoma, keratopathy, retinal detachment, silicone oil
INTRODUCTION
the postoperative period. Although not proven (or disproven) to be superior, most physicians will use silicone oil tamponade in retinal detachments at high risk for repair failure, including cases involving viral retinitis, proliferative vitreoretinopathy (PVR), giant retinal tears, and tractional retinal detachments.6
Silicone oil was first used for retinal detachments in the 1960s, providing internal tamponade by intravitreal injection.1 Both Machemer2 and Scott3 believed that silicone oil could dissect preretinal membranes and work against retinal traction as a stand-alone therapeutic agent. Using Scott’s technique to dissect membranes with an intravitreal injection of silicone oil without vitrectomy, others also reported good results.4,5 With Machemer’s later development of pars plana vitrectomy, silicone oil use became even more widespread, particularly for complicated retinal detachments. There are several indications for silicone oil in specific clinical situations, many of which can be explained by silicone oil’s advantages over intraocular gas. Since silicone oil’s volume does not change over time, it is thought to require less strict positioning compared to intraocular gas, making it preferable for children or other patients unable to position optimally postoperatively. Unlike gases, its volume is not affected much by variation in atmospheric pressure; thus, it is preferred in patients that have to fly during
MOLECULAR PROPERTIES Silicone is a man-made synthetic substance made of the chemical element silicon (Si) (no terminal e), the fourteenth element of the periodic table and the most abundant element on earth’s crust after oxygen. Silicone oil is the liquid form of silicone, a term used to classify repeating units of siloxane (-Si-O-). This is the same substance that, in its solid form, is used for scleral buckling elements.7 Silicone oil (SO) has a specific gravity lighter than water. Siloxane mixed with alkenes (an unsaturated chemical compound containing at least one carbon–carbon double bond) has higher specific gravity than water and sometimes is improperly referred as ‘‘heavy’’ silicone oil. With a specific gravity above water and aqueous, these
Received 25 August 2014; revised 27 August 2014; accepted 2 September 2014; published online 1 October 2014 Correspondence: John B. Miller, MD, Retina Service, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. E-mail: [email protected]
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Emulsified Intraocular Silicone Oil Complications heavier SOs sink within the eye and are used for cases requiring inferior tamponade. Surface and interfacial tension are two important factors that greatly affect the intraocular interactions of silicone oil. Surface tension is equal to the sum of attractive and repulsive forcers between molecules, collectively known as the Van der Waal forces.7 In a drop of water in air, the central water molecules are equally attracted to each other, while those at the periphery are only attracted to adjacent peripheral molecules. The total effective force (surface tension) of this surface energy is to pull peripheral molecules inward, thus reducing the total surface area of the bubble. Likewise, interfacial tension represents a similar molecular force, but only applies when the interface is between two liquid materials. Thus, interfacial tension is defined as the force required to keep a bubble intact within another liquid. Viscosity refers to the ability of a fluid to resist deformation by shear or extensional stress. In this way, a higher shear stress force is required to deform silicone oil of higher viscosity, typically silicone oils with siloxane of longer chain length. Conversely, a lower viscosity silicone oil can be more easily deformed or dispersed. In addition to shear stress, liquids can also be deformed by extensional forces, which can stretch the material so thin that the strand actually breaks up to form small droplets. The splitting of a liquid into small bubbles is known as dispersion. These small, dispersed bubbles have higher intrinsic surface tension than large bubbles due to their shorter radius, which predisposes to coalescing with the larger bubble. It is only when the small bubbles are unable to coalesce with the larger bubble that we classify the change as emulsification. This is an important distinction between emulsification and dispersion, as the terms are often confused and sometimes used interchangeably. In the case of emulsification, and according to the surface tension theory, emulsification takes place by reduction of interfacial tension between two phases that prevent the smaller bubbles from joining the larger bubble. There are two other major theories about emulcification. (1) The repulsion theory suggests that an emulsifying agent creates a film over one phase that forms globules which repel each other, not allowing them to join. This repulsive force causes the small bubbles to remain suspended in the dispersion medium (aqueous). (2) The viscosity modification theory suggests that emulsifying agents exist or form in the medium that increase the viscosity of the medium (aqueous), which helps create and maintain the suspension of globules of dispersed phase (the silicone oil). The emulsion of ‘‘oil-in-water’’ is the observed phenomenon in silicone oil emulsification, hardly ever seeing ‘‘water-in-oil’’ emulsions in the clinical setting. This is because it is not the relative volume of !
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oil and water which will determine the ‘‘oil-in-water’’ or ‘‘water-in-oil’’ emulsion, but rather, like the Bancroft rule states, ‘‘The phase in which an emulsifier is more soluble constitutes the continuous phase.’’ For example, proteins (surfactants/emulsifiers) dissolve better in aqueous than in oil, and so they tend to form oil-in-water emulsions by promoting the dispersion of silicone oil droplets through the continuous phase of aqueous.
FACTORS AFFECTING SILICONE OIL EMULSIFICATION There are several factors affecting silicone oil emulsification discussed in the literature. Early work examined the role of different biochemical properties, particularly viscosity and molecular weight. Higherviscosity silicone oil is more resistant to deformation and thus less likely to disperse and eventually emulsify.8 Likewise, higher-molecular-weight silicone oil, with its higher viscosity, has also been shown to be more resistant to emulsification.9 Lower-molecularweight silicone oils are thought to move more freely, making them more prone to emulsification. Using an in-vitro model, Crisp confirmed these concepts, showing that emulsification was more likely in both lower-viscosity and lower-molecular-weight silicone oils.10 It is important to note that these studies most often cannot distinguish clearly between emulsification and short-term dispersion. Surfactants (surface active agents) work to decrease a given liquid’s surface tension within a medium, thus increasing the risk of emulsification. As it pertains to intraocular silicone oil, there are several intrinsic surfactants, including serum, fibrin, fibrinogen, and LDLs.9 These surfactants can be present at higher levels in inflammatory, infectious, and hemorrhagic conditions. These three intraocular conditions are actually quite common in the perioperative setting, given the common indications for silicone oil. However, they can also be modified by the use of postop drops or specific intraoperative interventions (e.g., photocoagulation, antibiotics, or antiinflammatories). Like the intrinsic surfactants discussed earlier, it is also possible to have extrinsic surfactants or contaminants promote emulsification. These can come from a variety of locations in the surgical process, whether in the operating room or the instrument room prior to surgery. Dresp et al. examined cleaned and sterilized vitreoretinal surgical equipment deemed ready for use.11 Their study found both detergents and silicone oil contaminants on several vitreoretinal surgical components. Sterilization detergents, which also represent surfactants for silicone oil emulsification, were found in greatest concentrations on the vitrectomy tubing, cutter, and fundus lens. Silicone oil remnants
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314 J. B. Miller et al. or contaminants were found most commonly on the sclerotomy cannula.11 The biggest factor for emulsification is the duration of the silicone oil tamponade. Toklu et al. examined the average time to silicone oil emulsification in a retrospective study in 32 eyes.12 They first noted signs of emulsification between five and 24 months with a mean of 13.2 months. It was only in cases deemed to be at high risk of retinal detachment that extended silicone oil tamponade was used, consistent with practice standards. These results reinforce the findings of a previous study by Federman and Schubert that found some emulsification in all eyes with intraocular silicone oil for at least one year.13 While most eyes follow the typical time course described earlier, there is at least one described condition that has been shown to accelerate emulsification. Yilmaz and Guler showed that patients with underlying nystagmus develop silicone oil emulsification much more quickly than previous reports in the literature.14 They noted emulsification in all eight eyes with nystagmus one to three months postoperatively. It is thought that the repetitive shear force applied to the silicone oil by the ongoing nystagmus makes emulsification more likely. This highlights the general rule that common emulsions are inherently unstable and, over time, they want to revert to a more stable state that is made of the two phases comprising the emulsion. Thus, energy input—through stirring, shaking, homogenizing, etc.—is needed to form and keep the emulsion (one can think of the vinaigrette emulsion, which unless continuously shaken reverts to the two separate phases). There are exceptions to this rule of inherent instability of emulsions. In particular, microemulsions, which are formed by oil, water, salt, and surfactants, are thermodynamically stable, and form upon simple mixing without the need of shear forces. In addition to inherent patient characteristics, there are some surgical adjuncts that can promote emulsification. Heavy liquids, such as perfluorocarbon (PFO), are often used to assist in the repair of complex retinal detachments. Dresp found that turbulence at the interface of the PFO and SO can increase the chance of emulsification.15 He concluded that minimizing the duration of contact and turbulence at the interface by performing an efficient, but controlled, fluid exchange can help prevent emulsification.15 Others have asked whether the presence of an encircling band affects rates of emulsification. de Silva constructed an experimental model to examine this clinical scenario, confirming that an encircling scleral buckle decreases the risk of emulsification.16 This was a promising result, given the frequency of combined scleral buckle and vitrectomy for complicated retinal detachments. This same experimental model was also used to examine how the silicone oil fill affects
emulsification.16 Their experiments found that a more complete fill reduced emulsification. The authors proposed that, with a more complete fill, there is less aqueous in the posterior chamber and thus a smaller interface between the silicone oil and aqueous to create friction and ultimately emulsification.16 Others examined whether additional surgical procedures could affect emulsification. One group found that both extended phacoemulsification power use and high-speed vitrectomy in the presence of intraocular silicone oil increase the risk of emulsification.17 Like the ultrasound power used to break up the lens, the extended application of phacoemulsifcation likely disrupts the silicone oil by the intraocular distribution of the phaco power. The increased risk of emulsification with high-speed vitrectomy can likely be explained by creating more turbulence within the silicone oil, similar to the conditions described previously during fluid-fluid exchange with PFO and SO. Fortunately, phacoemulsification and high-speed vitrectomy are rarely used with silicone oil already in the eye. Typically, fresh silicone oil tamponade is added at the conclusion of the surgery, with a few notable exceptions. While higher-viscosity silicone oils are less likely to emulsify, they are more difficult to inject and remove from the eye using small-gauge cannulas. With the advent and more widespread use of small-gauge vitrectomy, the greater speed of instillation and removal of lower-viscosity silicone oils has made them preferable. Given this preference, some have set out to identify ways to decrease emulsification while still using lower-viscosity silicone oils. Williams et al. found that by adding high-molecular-weight polymers to the silicone oil, they could significantly reduce the risk of emulsification.18 Because their experiments were in an in-vitro model, further work is needed to examine potential toxicity and ensure efficacy before clinical application.
COMPLICATIONS OF SILICONE OIL EMULSIFICATION There are several known complications of emulsified silicone oil. Our review found that the literature does not distinguish well between complications of silicone oil and those specifically related to emulsification. However, it can be reasonably concluded that many of the complications are indeed secondary to emulsification, as these separated droplets of emulsified silicone oil infiltrate intraocular tissues in both the anterior and posterior segments. The most common occur in the anterior segment, so we will first focus on the keratopathy and glaucoma that can result from silicone oil emulsification. Seminars in Ophthalmology
Emulsified Intraocular Silicone Oil Complications
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Cornea Corneal decompensation frequently occurs if the silicone oil touches the corneal endothelium. There are several reports regarding this silicone-associated keratopathy, with the majority occurring in aphakic eyes.13,19–22 The histopathology of silicone-oil-induced keratopathy includes retrocorneal membrane, stromal hypercellularity, superficial stromal calcification and vascularization, decreased endothelial cell density, and attenuation of endothelial cell borders leading to bullous keratopathy.23–25 McCuen et al. reported corneal decompensation in 29% of 164 eyes in their retrospective case series.26 It occurred in 35% of aphakic eyes, 26% of pseudophakic eyes, and 20% of the eyes that remained phakic at the end of the follow-up. Chan reported siliconeinduced keratopathy in 41 out of 407 eyes treated with silicone oil tamponade.22 Forty of those 41 eyes that developed keratopathy were aphakic. In Haut’s cohort of 200 eyes, 37 developed keratopathy, with silicone-cornea touch in 34 cases.27 Casswell identified 11 eyes with keratopathy after silicone oil tamponade in a series of 85 eyes.28 In the 11 eyes with keratopathy, nine were aphakic and two were phakic. A penetrating keratoplasty was required in two eyes at the time of silicone oil removal and the corneas remained clear at the six-month follow-up visit. Interestingly, the Silicone Study Report 7 on corneal abnormalities reported an incidence of 27% at 24 months, which did not differ between those treated with gas versus silicone oil tamponade.29 Sternberg evaluated the clinical and morphologic changes in the corneas of 14 rabbits and seven cats with silicone oil in the anterior chamber.23 After six days, specular microscopy showed a 40% reduction in endothelial density in the area of the silicone oil bubble in both groups. The rabbit corneas exhibited progressive stromal thinning and retrocorneal membrane formation. On the other hand, peripheral vascularization, persistent corneal edema, and irregular plaques on the endothelium occurred in the cat eyes. Yang demonstrated that silicone oil is cytotoxic on cultivated human endothelial cells.30 In addition, they showed that the high-viscosity oil (5,000 centistokes) suppresses cell cycle significantly more than the low-viscosity oil (1,000 centistokes). Green showed that contaminants found in crude silicone oil preparations can be responsible for the silicone-oil-induced keratopathy.31 Since direct contact between the cornea and silicone oil is presumed to lead to the keratopathy, prevention is centered on keeping the silicone oil away from the cornea. To this end, an inferiorly placed peripheral iridectomy allows the free passage of aqueous fluid into the anterior chamber, preventing pupillary block and aiding in displacing silicone oil from the anterior chamber. In a cohort of 62 eyes !
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with prophylactic inferior PI, only 6.5% of the eyes had silicone oil in the anterior chamber.32 Additional work by the same group examined 12 patients who underwent penetrating keratoplasty for corneal opacification induced by silicone oil.33 During the 13.7 months after their corneal transplant, four of the 11 grafts failed while one case was lost to follow-up. Another group reported a mean graft survival of 25 months in 14 eyes that underwent penetrating keratoplasty.34 Not surprisingly, the graft failure rate was lower when silicone oil was removed at the time of keratoplasty (25% vs 67% when SO retained). Karel et al. performed penetrating keratoplasty in 13 eyes with bullous keratopathy secondary to silicone oil.35 At the last follow-up examination, a clear graft was found in six out of 13 eyes (46%). The six clear grafts were found in the 10 eyes where silicone oil had been removed before keratoplasty. The graft became opaque in all three eyes in which silicone oil had not been removed. Lee reported on 24 penetrating keratoplasties in 17 patients from 1991 to 2000.36 Silicone oil was removed before or during the time of initial penetrating keratoplasty in nine patients (52.9%) and left in situ in eight patients (47.1%). Ten out of 24 grafts survived (41.7%). At final follow up (median duration 33 months), the number of patients with a clear graft who had oil removed before or during the time of penetrating keratoplasty was seven out of 10 (70.0%). Given the graft failure rate, some have considered the Boston Keratoprosthesis (KPro) for silicone-oilrelated keratophty. Iyer et al. reviewed eight eyes that received a Boston KPro, noting anatomic retention and visual improvement in seven eyes (87.5%).37 The visual acuity improved to 20/200 or better in six eyes (66.67%). However, it should be noted that silicone oil in the setting of a KPro can be associated with severe retro-KPro membrane formation.
Glaucoma Glaucoma after silicone oil injections can be divided into two major categories: acute intraocular pressure (IOP) spikes and intermediate- or late-onset glaucoma. Only the latter category can occur as a result of silicone oil emulsification. The acute pressure spike seen postoperatively most commonly occurs as result of silicone oil overfill or pupillary block. Our review will focus on the late-onset glaucoma as a result of silicone oil emulsification. The mechanisms by which emulsification contributes to glaucoma can be divided into two general classifications: inflammation and direct infiltration of angle structures.22,25,26,38 Regarding the incidence of glaucoma after silicone oil injection, there have been variable reports in the literature, ranging from 11%39,40 up to 56%41.
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TABLE 1. Reports of incidence of glaucoma after silicone oil injection. Author
Chan
Laqua
de Corral
Burk
Riedel
Henderer
Al-Jazzaf
Year Published Total patients Glaucoma
1986 407 16.8%
1986 500 11%
1987 48 56%
1988 100 50%
1990 415 13%
1999 532 29.3%
2005 450 11%
A summary of the results in the literature is included in Table 1.22,38–43 The variable rate can be explained by the different IOP criteria for glaucoma and length of follow-up in the published studies. Emulsified silicone oil droplets can migrate into the anterior chamber and cause inflammation in the trabecular meshwork, thus impeding outflow of aqueous humor. The viscosity and purity of silicone oil may be important factors that determine the propensity of silicone oil to cause IOP spikes. Petersen found that 1000 centistoke oil was more likely to cause glaucoma compared to 5000 centistoke oil.44 However, in another study by Stinson, there was no difference found.45 The duration of silicone oil tamponade was not found to be a causative factor for IOP rises. When the IOP cannot be controlled medically, surgical removal of the silicone oil, with or without glaucoma surgery, is recommended. Jonas et al. showed that 93.4% of patients with glaucoma secondary to silicone oil achieved normal IOP after removal of the silicone oil alone.46 Budenz et al. reported success, defined by IOP522 and no additional glaucoma surgeries, in 69% of the 43 eyes reviewed at six months after surgery, dropping to 48% at 36 months.47 A total of 26% of the patients required further glaucoma surgery in addition to silicone oil removal. Trabeculectomy is technically difficult, given the presence of scarring from the previous vitreo-retinal surgery and, in general, carries a poor prognosis. Shunting procedures may be a better option. Al-Jazzaf et al. showed a cumulative success rate of 86% at six months and 76% at one year after implantation of an Ahmed Glaucoma shunt in patients with secondary glaucoma related to silicone oil.39
Retina The literature is less defined regarding the complications of emulsified silicone oil in the retina. Early investigators were concerned that extended contact of silicone oil with the retina could cause toxicity. Using rabbit and monkey models, Lee et al. reported vacuolization of the ganglion cell and photoreceptor layers, loss of the ganglion cell layer, and swelling of the nerve fiber layer via light microscopy after silicone oil injection.48 Additional work by the same group
also noted similar histopathology findings in additional animal models along with diminished ERG findings.49,50 Given the lack of definitively proven clinical silicone oil retinopathy in the years after these animal experiments, many questioned whether these changes were really related to silicone oil toxicity. Doubt was also raised by the lack of controls in the prior animal studies. Ryan’s group repeated these experiments in a rabbit model with controls, finding no evidence of silicone oil toxicity at six months.51 This study used clinical exam, histopathology, and ERG recordings compared to operative controls to verify that there was no evidence of damaging effects. Until recently, we lacked technology to properly identify emulsified silicone oil within the retina in vivo. All of the previous studies discussed in this section took place in animal models or histopathology sections after surgical removal and processing of the eye. As a result, it can be difficult to decipher true silicone oil toxicity from a secondary effect related to surgical manipulation or specimen processing. With the advancement of retinal imaging techniques, we are better able to identify emulsified silicone oil within the retina and optic nerve. Using OCT, Spaide was able to identify silicone oil droplets within the retina of a patient after macular hole repair with internal limiting membrane (ILM) peeling and silicone oil tamponade.52 In the postoperative period, the patient was noted to have early silicone oil emulsification. The authors hypothesized that the defects in the ILM provided an entryway for the emulsified silicone oil to enter the intraretinal space. Eleven years later, Spaide used even more advanced generation OCT (Swept Source) and adaptive optics to identify vacuoles of silicone oil within the retina and optic nerve head of a patient with history of multiple retinal detachment repairs.53 The patient had undergone silicone oil removal 11 years prior, just six months after it was placed. He presented with complaints of decreased vision and patchy central visual field defects. The authors suggest that our more advanced multimodal imaging may allow us to better detect direct silicone oil toxicity or a secondary impairment on retinal function due to chronic inflammation from retained silicone oil. Earlier reports implicated high intraocular pressure as a possible mechanism for silicone oil infiltration into the retina and optic nerve.54,55 More work needs to further Seminars in Ophthalmology
Emulsified Intraocular Silicone Oil Complications explore this mechanisms.
potential
toxicity
and
associated
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Extraocular Extension The complications of emulsified intraocular silicone oil are actually not limited to only the eye. There have been multiple case reports of extraocular extension of silicone oil into the brain. In 1999, Williams et al. first reported the presence of intraventricular silicone oil as seen on the MRI of a patient 15 months after retinal detachment repair with silicone oil in the setting of CMV retinitis.56,57 Since that first report, there have been four additional case reports of intraventricular silicone oil after retinal detachment repair.58–61 Interestingly, all four of these subsequent case reports involved patients with a history of diabetic retinopathy. Given the few clinical reports of intraventricular silicone oil, one radiology group examined 19 patients after silicone oil with MRIs of the brain, finding no intraventricular silicone oil.62 It is, however, important to recognize that the average follow-up was only 115 days and there was a small number of cases examined for such a rare finding.
CONCLUSIONS Silicone oil is an important clinical tool for the vitreoretinal surgeon, particularly for complicated retinal detachments and in certain patient populations. Silicone oil emulsification is a clinically significant complication that can occur with intraocular silicone use. Contaminants, protein surfactants, low molecular weight and viscosity, and adjunctive surgical procedures contribute to the incidence. However, duration of tamponade is the single most important factor in promoting silicone oil emulsification. The most well-documented complications of silicone oil emulsification are glaucoma and keratopathy. Fortunately, there has been reasonable surgical success for the treatment of both silicone-oil-related glaucoma and keratopathy. Given recent advancements in retinal and optic nerve imaging, we can better detect posterior complications of silicone oil emulsification. Further work is needed to explore these potential late complications of emulsified silicone oil. Limiting the amount of time the silicone oil remains in the eye is the most important factor in reducing its complications.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. !
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