Ординатура / Офтальмология / Английские материалы / Retinal and Vitreoretinal Diseases and Surgery_Boyd, Cortez, Sabates_2010

In January 1987 (Experimental Vitreous Replacement with Perfluorotributylamine,Am. J Ophthalmology. 103: 29-37) I described the ideal physical and chemical attributes of a perfluorocarbon liquid suitable for use in vitreoretinal surgery as 1) high specific gravity, 2) optically clear, 3) immiscible with water or blood or other common organic compounds, 4) low viscosity, 5) a high interfacial tension in saline, 6) high vapor pressure rate 7) a refractive index significantly different from aqueous and 8) a significant tamponading effect. Today, those parameters remain essential for the utility of perfluorocarbon liquids in vitreoretinal surgery.

Similarities in names of the various perfluorocarbon liquids have even contributed to some confusion encountered in discussions of the merits of the several compounds for use in vitreoretinal surgery. For instance, perfluoro-n-octane and perfluorooctane are often confused. Perfluoro-n-octane is composed of essentially pure (99.91%) straight chain octadecafluoro-n-octane, without isomeric impurities or fluoro-olefin impurities, as confirmed by gas chromatographic analysis. Perfluorooctane is produced as an industrial product, with several industrial applications. This is a material containing a large mixture of isomers such as C6, C7 and C8 perfluorocarbons, and impurities such as ethers), and non-fully fluorinated structures.

In a published paper of perfluorocarbon heavyliquids,RobertBourkeandPeterCooling point out that “although safe for intraoperative

use, most studies have shown that long-term tamponade (> 2 weeks) is associated with retinal changes that may be ascribed to two mechanisms – chemical toxicity or mechanical effects. Mechanical compression causes atrophic changes in dependent retina, whereas chemical toxicity is manifested as a macrophage and fibroblastic (PVR and epiretinal membrane) response.”

Retinal changes include displacement of photoreceptor nuclei into the rod and cone layer (photoreceptor drop down), distortion of photoreceptor outer segments, narrowing of the outer plexiform layer, and ultimately retinal pigment epithelial hypertrophy. These changes are confined to the dependent retina. This probably represents a mechanical effect as analogous changes have been noted in the superior retina following prolonged retinal contact with silicone oil. Other findings that might be mechanical in origin include corneal endothelial damage and mild lens opacification following prolonged contact with perfluorocarbon liquids. This may again be equivalent to the effects of silicone oil, where a relatively inert substance blocks normal metabolic access to the lens or corneal endothelium.

ERG changes, including decreased b wave, a wave amplitude and increased latency, might be altered electrical conductivity rather than toxicity, since serial ERG’s following removal of perfluorocarbon liquids, demonstrate recovery of the retinal function at one week after removal of the liquid.

Biologic intolerance manifests as preretinal membrane formation and vitreous infiltration consisting of foamy macrophages that contain ingested emulsified perfluorochemical. Preretinal fibrosis may ensue, and emulsification associated with macrophage ingestion may result in trabecular obstruction and subsequent elevation of intraocular pressure.

Fibroblasts may proliferate, contributing to epiretinal membrane formation and PVR.

When I introduced these high, specific gravity, low viscosity, immiscible, optically clear liquids to the world as an adjunct to the successful treatment of proliferative vitreoretinopathy and giant retinal tear(s), I demonstrated the value of these physical properties over those of previously existing retinal tamponade systems.

Physical Properties

High Specific Gravity

The most surgically significant physical characteristic of these heavy liquid compounds would certainly seem to be their high specific gravity. This property enables perfluorocarbon liquids to gently but uniformly flatten the detached retina by displacing subretinal fluid. As the perfluorocarbon is slowly introduced over the optic disc, its heavier-than-water specific gravity permits it to sink to the posterior retina immediately (Figure 2). As more material is added, the displaced subretinal fluids are forced anteriorly ahead of the meniscus of the perfluorocarbon liquid

until they exit into the vitreous cavity through the pre-existing anterior retinal breaks. In this manner, perfluorocarbon liquids initially reattach the posterior retina and continue to re-appose anterior retina in a what Bourke and Cooling describe as a “sequential manner”. This mechanism of anterior displacement may eliminate the need for a posterior drainage retinotomy in many cases. Often, subretinal fluids are trapped posteriorly by the use of lighter-than-water tamponading agents such as gas or silicone oil, which force fluids posteriorly as they are introduced into the vitreous cavity. The ability of perfluorocarbon liquids to naturally descend to the most posterior retina also makes them ideal for use in engaging the rolled anterior flap of a giant retinal tear, facilitating the accurate repositioning of the tear.

Optical Clarity

All perfluorocarbon liquids tend to be optically clear and relatively free of sources of reflection or optical aberration, as can be the case with other retinal tamponades. The ability to flatten the retina effectively intraoperatively, and the optical clarity of material allows the application of laser energy to the attached retina during the surgical procedure, thus ensuring adequate laser treatment. Since they do not absorb visible light and have a higher boiling point than the thermal burn, perfluorocarbon liquids are considered a safe medium for the delivery of laser energy. In a study conducted by Bourke and Cooling, they found that the intraoperative use of laser and diathermy tended to raise the

local temperature of preretinal perfluorocarbon liquids to between 35o and 50o C under in-vitro conditions.

Immiscible with Intraocular Fluids

Perfluorocarbon liquids vary slightly in their miscibility with water. The ability of the material to resist incursion by blood or intraocular fluids makes it a valuable aide in improving visibility in cases involving heavy or uncontrolled bleeding. Perfluorocarbon liquids can also be used as a “unit”, making them helpful in retrieving intraocular or crystalline lenses by floating them off the retina and up into the pupillary space.

Interfacial Tension

Perfluorocarbon liquids have a relatively low surface tension (14–17 dynes/cm) and correspondingly high interfacial tension in water. This property makes the occurrence of subretinal perfluorocarbon liquid somewhat less likely than with silicone oil due to a higher perfluorocarbon-water interfacial tension than that of silicone-water.

Viscosity

Perfluorocarbon liquids vary greatly intheir viscosity. The ideal material for intraocular use should have a very low viscosity, making it easy to inject and remove completely at the end of the procedure. Having a perfluorocarbon with a low viscosity also makes the

management of subretinal migration much easier and safer to remove in the event that this should occur.

Refractive Index

The ability to accurately control intraoperative perfluorocarbon liquid is dependent in large part on the surgeon’s ability to visualize the material in the eye. Perfluorocarbons vary widely in their refractive index. Some, like perfluoro-n-octane, have an index significantly different than aqueous (1.27 vs. 1.33). A distinct interface between the perfluorocarbon liquid and aqueous can be clearly visualized. With other perfluorocarbon liquids, such as perfluorophenanthrene, the refractive index is similar to water (1.33) and visualization of the interface is poor. The inability to clearly see the perfluorocarbon-saline interface also makes it very difficult to be sure that all the remaining perfluorocarbon liquid has been removed at the conclusion of surgery.

Vapor Pressure

Just as with the refractive index, the vapor pressure rates (volatility) of the various perfluorocarbon liquids differ greatly. During the process of removal, it is a distinct advantage to have a material with high vapor pressure (perfluoro-n-octane). During fluid-air exchange, any residual layer of perfluoro-n-octane will usually evaporate

after aspiration of all visible perfluorocarbon liquid. The vaporized liquid exits with air via the sclerotomy sites. Perfluorocarbon liquids with lower vapor pressure rates are less volatile, and extensive irrigation of the retina with saline is necessary to insure that all the material has been removed at the conclusion of the surgery.

Tamponade Force

Perfluorocarbon liquids have a tamponade force greater than that of silicone oil. This force has been described as a “third hand”, providing a hydrokinetic tool for opening a narrow or closed funnel retinal detachment with PVR, or for stabilizng the retina during peeling of epiretinal membranes. However, it is important that the tamponade force not be too great, particularly in procedures involving an atrophic retina where iatrogenic breaks could easily occur.

The chemical and physical properties of perfluorocarbon liquids offer a major technical advance in the area of vitreoretinal surgery. Although not appropriate as a long-term vitreous replacement, the clinical study and subsequent FDAapproval of one such material PERFLUORON (purified perfluoro-n-octane liquid-Alcon Laboratories), has established the safety and efficacy of this particular perfluorocarbon liquid for the management of retinal detachments associated with trauma, proliferative vitreoretinopathy and/or giant retinal tear.

WORKING WITH

PERFLUOROCARBON

LIQUIDS

The physical and chemical properties of certain types of perfluorocarbon liquids makes them ideal surgical tools in vitreoretinal surgery. As our clinical experience has grown, we have come to realize that its usefulness may someday only be limited by the ability of the retina to regain function. Listed below are some of the “tips” that we have learned, along with several things that need to be considered when working with perfluorocarbon liquids.

Preparation and Handling of

Perfluorocarbon Liquids

The unique physical (immiscibility) and chemical (volatility) properties of perfluorocarbon liquids (PFCL’s) make them extremely difficult to adequately sterilize. PFCL’s are commercially sterilized and re-sterilization should not be attempted. The 0.22 micron disc filters that are routinely used in surgery are not adequate to handle large (5 ml or more) volumes, and thus are not intended for that use. These filters are included in some approved perfluorocarbon liquid packaging to trap and remove any “cored” stopper material that might accidentally be drawn up into the PFCL syringe. Also, as we all know, these filters do not address the problem of viral contamination, since viruses are smaller than the filter pore size.

The filter material in the disc filters tends to trap from 0.3 to 0.5 ml of fluid as the perfluorocarbon liquid is filtered, so if the surgeon is concerned about not having an adequate volume of PFCL to complete the case, the filter might not be used.

After the PFCL is drawn up and transferred to the sterile field, there are a few precautions that can be taken to avoid the loss of any PFCL prior to its infusion. The use of a small cannula (25 ga. or smaller) will avoid evaporation through the tip, and make slow controlled infusion much easier to achieve. During storage of the syringe and cannula, always elevate the tip of the cannula to avoid having the material flow out the end. This can easily be done by laying it across another instrument on the Mayo stand. Never expose perfluorocarbon liquids to extreme heat, and store the vials at room temperature.

Surgical Instrumentation

When Using Perfluorocarbon

Liquids

For best results, it is wise to use perfluorocarbon liquids in conjunction with “Wide Field” viewing systems whenever possible. These systems provide a panoramic view of the eye, even when the pupil is partially constricted, allowing visualization of the peripheral retina and the expanding margin of the PFCL bubble (Figure 3).

Breaks in the peripheral retina can be seen, and traction can be relieved more thoroughly with such systems. Visibility under air in phakic or pseudophakic eyes is also greatly enhanced. With the opportunity to see the peripheral retina more completely, consideration should also be given to the type of light source to be used.

For controlled administration of the PFCL, many surgeons have found that either a small gauge “soft-tipped” extrusion needle or the Chang dual-bore cannula provide the best results. The Chang Cannula helps control intraocular pressure during the infusion of

PFCL’s by the use of a side-by-side cannula design that removes BSS or aqueous from the eye in a volume equal to the amount of PFCL infused. Soft-tip cannulas and lighted picks may also be useful in the management of a bullous detachment.

Finally, to take advantage of the ability to perform laser endophotocoagulation under PFCL’S, a multipurpose laser probe, such as Chang Aspirating Laser Probe (with or without soft tip), permits easy and accurate placement of laser energy in the peripheral retina (Figure 4).

Administration of

Perfluorocarbon Liquids

Always administer perfluorocarbon liquids slowly, keeping the tip of the cannula just within the meniscus of the expanding bubble, and centered over the optic disc if it is visible.

A small bubble of PFCL will flatten and stabilize the posterior retina, allowing time to evaluate and control the retina anterior to

the PFCL before continuing with membrane removal if necessary.

Continue to administer the PFCL slowly as needed, constantly monitoring the position of the PFCL meniscus as it spreads. Avoid forceful infusion of PFCL, as this may cause retinal breaks.

As the PFCL reaches the anterior portion of the vitreous cavity, reduce the flow of the active infusion line to avoid dispersion and the creation of many tiny PFCL bubbles.

Since PFCL is not miscible with water. If necessary, turn off the infusion line at this point, or lower the bottle height to reduce turbidity.

Sometimes, despite our best efforts, small bubbles of PFCL will form. If they appear beside the larger bubble, wait for a minute or so, and they will often merge on their own. If this doesn’t happen, you may encourage their coalescence by gently stroking the surface of the bubbles together with an instrument such as a soft-tip extrusion needle. Be sure to remove any small bubbles before beginning epiretinal mem-

brane removal. Residual membranes can be removed under PFCL, although it is usually preferable to peel membranes anterior to the PFCL bubble (Figure 5). If working beneath PFCL, care should be taken not to lift the retina or tear it.

The low surface tension and correspondingly high interfacial tension of some PFCL’S, such as perfluoro-n-octane, will permit their use over small retinal breaks without fear of subretinal migration, so long as the retina is completely mobile and free of any residual traction.

Remove all retinal traction before increasing the PFCL fill level above any retinal break, paying particular attention to anterior traction. Subretinal membranes tend to become more visible under PFCL’S, but they should be removed anterior to the PFCL bubble only. If residual subretinal traction is noted under PFCL, the PCFL should first be removed by aspiration before attempting to do subretinal membrane removal.

PFCL’s may also be useful in helping you locate posterior retinal breaks that have not been previously visualized. Infuse the PFCL slowly, and as the bubble expands, monitor the peripheral meniscus carefully. Stop infusion of the PFCL when a break is reached by the meniscus, and remove all retinal traction before continuing to fill the eye. If PFCL slips beneath the retina at the break, the PFCL is usually aspirated through the same break it migrated through, using a soft-tip extrusion needle.

Since they are not miscible with blood or other organic compounds, PFCL’s can be used in cases involving active bleeding, such as PDR or vitreous hemorrhage, to improve intraoperative visibility or to contain fresh blood. The blood can be “swept” back from the operative field off of the surface of the PFCL bubble.

Avoiding and/or Managing PFCL Complications

The main complications of perfluorocarbon liquids are subretinal migration and residual

droplets. Subretinal migration occurs when traction on a retinal break is unrelieved, and the level of the PFCL rises above it. As epiretinal membranes surrounding the break are peeled, the lifting of the retina may result in subretinal migration. This can be avoided by careful monitoring of the level of the PFCL as it is injected and rises close to the retinal break.

Always try to keep the PFCL meniscus posterior to the break. A panoramic viewing system can be helpful in visualizing the meniscus as it rises in the periphery. If membrane dissection around a break flattened under PFCL is required, the pulling forces to free the membrane should be exerted tangentially so that the retina is not lifted as membranes are peeled.

Removal of subretinal PFCL is usually done by removing at least part of the preretinal PFCL, and then tilting the globe over so that the subretinal bubble will roll near a retinal hole. A soft silicone-tip flute needle can be used to aspirate the PFCL. With a large retinotomy or giant tear, subretinal PFCL can easily be aspirated from under the retinal flap.

Residual droplets of PFCL can be avoided by good visualization during the fluid-air or fluid-silicone exchange. With perfluoro- n-octane, the vapor pressure is high, and any residual layer of PFCL will evaporate as air flushes through the eye. However, it is generally preferable to dry the surface of the retina several times during fluid-air exchange. With low vapor pressure PFCLs such as perfluorodecalin or perfluorophenanthrene,

the residual layer of PFCL must be irrigated from the surface of the retina under air. A small amount of balanced saline is injected over the retinal surface to allow the residual liquid to form small bubbles which can be aspirated.

Postoperatively, one or two small bubbles of PFCL may occasionally be seen rolling on the retina. These are generally well-tolerated and often become trapped in the ciliary processes.

Larger amounts of residual PFCL (0.5 ml or more), should be removed surgically, since they may cause epiretinal membranes. Bubbles of PFCL in the anterior chamber postoperatively may cause endothelial decompensation and localized inferior microcystic edema or keratic precipitates. These drops can be aspirated using a 30 gauge cannula at the slit lamp under topical anesthetic.

Substantial subretinal retention of perfluorocarbon liquid (PFCL) after vitreoretinal surgery can have drastic consequences on visual outcome in the case of subfoveal location because of its potential direct toxic effects on retinal pigment epithelium (RPE) and photoreceptor cells.14-18 Most authors recommend that subfoveal PFCL persisting after vitreoretinal surgery be removed when central visual acuity is substantially reduced.15-20

Several techniques have been described. Some authors attempted to perform pneumo displacement by injecting intravitreal gas,18

direct aspiration of PFCL droplets using a 36-gauge,18 39-gauge,19 or 49-gauge cannula20 via retinotomy adjacent to the droplets on the extrafoveal facing has been also attempted. Irreversible alterations of the pigment epithelium of the macula have been reported as a potential complication of this surgical aspiration procedure.20

INDICATIONS AND

TECHNIQUES

Beginning with my first description in 1987 of the utility in vitreous surgery of perfluorocarbon liquids, and continuing with the February 29, 1996 FDA approval based on the data derived from the clinical trials of one such compound (perfluro-n-octane), ophthalmicliteraturehasextensivelychronicled the effectiveness of perfluorocarbon liquids in the intraoperative atraumatic manipulation of intraocular tissues and the displacement of fluids, lens nuclei and intraocular lenses. Several literatures has suggested the following potential applications for the short-term physical and chemical properties of perfluorocarbon liquids:

•Giant Retinal Tear

•Proliferative Vitreoretinopathy (PVR)

•Traumatic Retinal Detachment with Vitreous Hemorrhage and Anterior Retinal Tear

•Management of Dislocated Lens Nuclei

•Management of Dislocated IOL

•Retinal Detachment Associated with Dislocated Crystalline or Intraocular Lenses