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Protecting the corneal endothelium during cataract surgery

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Richard L. Lindstrom, MD: Ophthalmic viscosurgical devices are used to protect the endothelium and deepen the anterior chamber to maintain ample surgical space during phacoemulsification and IOL insertion. As a result, ophthalmologists enhance patient outcomes because ocular structures remain in place during surgery and endothelial damage is minimized.

Please discuss the key functions of an ophthalmic viscosurgical device (OVD).

Steve A. Arshinoff, MD, FRCSC: Historically, OVDs have had two roles. Their first recognized role was and continues to be to facilitate all types of intraocular surgical maneuvers by creating space, inducing pressure, and stabilizing tissues and anything else placed in the eye. In the early development of OVDs, it was noted that because of their barrier effect, OVDs protect delicate intraocular tissues, particularly the corneal endothelium, and can partition single spaces. OVDs have received FDA approval for cataract surgery, but they are useful in other intraocular surgeries, such as penetrating keratoplasty and glaucoma filtering procedures, as well as provide corneal epithelial protection in surgery and keratitis sicca.

Thierry Amzallag, MD: Since the 1980s, OVDs have been mandatory and specific tools for cataract surgery. An OVD should be easy to inject, effective at creating and maintaining space in the anterior chamber, transparent, and effective at protecting the endothelium and tissue during various maneuvers. They also should be easy to remove at the end of the procedure and effective at controlling IOP.

Lindstrom: An OVD can also prevent a nuclear fragment from moving and can maintain position of a prosthesis while suturing it to the iris or sclera. In addition, many ophthalmologists are beginning to use OVDs to protect the ocular surface during surgery.

Edward J. Holland, MD: Epithelium protection is also important, and spreading an OVD on the ocular surface, whether during corneal transplantation or ocular surface transplantation, will protect the tissue sufficiently.

OVD material and classification

Lindstrom: What are the types of materials used to make OVDs?

Arshinoff: The rheologic properties of OVDs are based on the OVD content of the three biopolymers: sodium hyaluronate, chondroitin sulfate, and hydroxypropyl methylcellulose (HPMC). These polymers differ greatly from each other in the rheologic action they confer on the finished OVD. They even differ significantly within different preparations using the same biopolymer, but of different origin and molecular mass average and distribution. Hence, unlike drugs, it is important when referring to an OVD to use its trade name, rather than its generic name, because different preparations of apparently generically similar products often perform in a dramatically different manner in surgery.

Amzallag: Chondroitin sulfate combined with sodium hyaluronate enhances an OVD’s surface properties. During surgery, these OVDs remain in the anterior chamber for a longer period. They are slightly more difficult to remove and seem to protect the corneal endothelium and intraocular tissues more effectively than other OVDs.

Lindstrom: In my experience, sodium hyaluronate is more effective at maintaining space during surgery than HPMC.

What are the different categories of OVDs?

Ivan Ossma, MD, MPH, MSc: OVDs are classified based on zero shear viscosity and cohesive-dispersive behavior in a two-dimensional matrix (Table).¹ With the advent of new combinations or molecular weights, new categories have been created such as viscous dispersive and viscoadaptive. Viscoadaptive OVDs such as Healon5 (sodium hyaluronate 2.3%; Advanced Medical Optics, Inc. [AMO]) perform differently based on the amount of flow or shear used during surgery.

Lindstrom: Which type of OVD is considered a more effective coating and protecting agent. Which type is considered more effective for maintaining space?

Holland: Different surgeons have different preferences depending on their techniques and phacoemulsification procedures. Cohesive OVDs tend to be effective for maintaining space. However, as clinicians learned more about the damage from free radicals in phacoemulsification and protecting the endothelium, dispersive OVDs became more prominent because they are superior coating agents, are better retained in the anterior chamber and along the endothelial layer, and provide greater protection.

Hiroko Bissen-Miyajima, MD, PhD: Although dispersive OVDs are retained more effectively, they are difficult to remove from the eye at the end of surgery. It is preferable to use an OVD composed of material that is well retained inside the eye but that is also easy to remove. The new generation of OVDs is easier to remove, even with a high rate of cohesion or high molecular weight. In the past, surgeons often used high vacuum and flow rates during traditional phacoemulsification. With smaller-incision surgeries, however, phacoemulsification settings are lower, and cohesive OVDs can be better retained.

Benjamin G. Cabrera, MD: Ophthalmic surgery has evolved significantly over the years, and OVDs have played an important role in altering the way ophthalmologists perform surgery. Previously, surgeons were primarily concerned with maintaining space and being able to manipulate inside the anterior chamber. Coating and creating space were considered adequate protection for the endothelium. Over the past decade, however, surgeons realized that other factors must be considered, such as tissue protection, which is vital to corneal function. Studies show that dispersive OVDs maintain the protective mechanism for the endothelium,^2,3 and they, as well as improved equipment and different phacoemulsification settings, have changed the way ophthalmologists perform surgery in an effort to minimize damage to tissues.

Amzallag: The coating ability reflects the adhesion capacity of OVDs. Coating ability is measured by the angle between the OVD and a solid support. Lowness of the angle correlates with greater coating ability of the OVD. This ability reflects the lubricant capacity of the OVD. Theoretically, HPMC-based OVDs have the most coating ability. However, in current practice, dispersive sodium hyaluronates (especially those containing chondroitin sulfate, such as Viscoat [chondroitin sulfate, sodium hyaluronate; Alcon Laboratories, Inc.]c) are the most widely used. It is important to distinguish between the ability to create space and the ability to maintain space. These abilities do not correspond to the same physical and chemical properties. Cohesive OVDs, which have high molecular weights and low concentrations, are more suitable for creating space because of their high viscosity and elasticity.

Arshinoff: When OVDs were first classified, viscoadaptive and viscous dispersive OVDs had not yet been developed, and thus the classification included only higher-viscosity cohesive OVDs and lower-viscosity dispersive OVDs. The higher-viscosity cohesives, such as Healon GV (1.4% sodium hyaluronate, AMO) and Healon, are most effective at creating, pressurizing, and maintaining spaces, whereas lower-viscosity dispersives exhibit prolonged retention in the anterior chamber despite irrigation and enable partitioning of spaces.

Protection of delicate tissues is difficult to evaluate because the creation of additional space is protective to the endothelial cells by preventing their contact with instruments or devices placed in the eye. However, during the turbulence of phacoemulsification and irrigation/aspiration, the enhanced retention of dispersive OVDs gives additional protection of the endothelial surface with the presence of a barrier layer of OVD. Coating may not be an appropriate term because it implies continued presence of the OVD adjacent to a surface by way of chemical interaction with that surface. Usually, any chemical interaction with the delicate cell membranes of endothelial cells is detrimental, and OVDs reside adjacent to endothelial cells by their charge, resistance to movement due to their viscosity, and their content of hyaluronic acid that interacts harmlessly with the normal hyaluronic acid boundary layer found on endothelial cells. This function is not exactly the same as the general meaning of the term “coating.”

Properties of OVDs

Lindstrom: OVDs composed of sodium hyaluronate can be long-chain or short-chain substances, and they can have slightly different characteristics in terms of viscosity and cohesion. They can be used in various concentrations and also can be combined with other agents. To date, Viscoat and DisCoVisc (4% sodium chondroitin sulfate, 1.65% sodium hyaluronate; Alcon Laboratories, Inc.) are the only OVDs composed of a combination of sodium hyaluronate and chondroitin sulfate. Viscoat and DisCoVisc have different characteristics because they have different concentrations of the two materials, and their hyaluronic acid moiety is of a different molecular weight.

How do you select an OVD for a clinical application? What properties are important to you in an OVD for cataract surgery?

Ossma: The option of using one effective agent for all functions is important. For the majority of my patients, I use a viscous dispersive OVD, DisCoVisc, because I can perform routine and complex procedures without having to switch products. However, I still rely on specific characteristics of other OVDs for some cases. For example, in patients with extremely shallow chambers in which a significant amount of space is required, I would use a high-viscosity OVD.

Holland: Typically, during cataract surgery, I use two OVDs, such as with the DuoVisc system (ProVisc [1% sodium hyaluronate] and Viscoat [3% sodium hyaluronate, 4% chondroitin sulfate]; Alcon Laboratories, Inc.). As a corneal surgeon, I believe effective endothelial protection during phacoemulsification is the most valuable feature in an OVD. I find that the combination of sodium hyaluronate and chondroitin sulfate in Viscoat is the most effective in protecting the endothelium, and studies show that Viscoat’s retention along the endothelial layer is valuable (Figure 1).⁴ Chondroitin sulfate, which is negatively charged, binds to the endothelium, which is positively charged. An OVD with chondroitin sulfate will bind easily to the endothelium.

Chondroitin Sulfate vs. Hyaluronate OVDs using in vivo Confocal Microscopy Figure 1. A study by Petroll et al showed that viscous-dispersive OVDs provided the greatest residual thickness post phacoemulsification, adherent OVD thickness to endothelium measures its retention post phacoemulsification, and endothelial cell damage after phacoemulsification is less when the OVD is retained.4 Source: Alcon Laboratories, Inc.

During the latter phase of cataract surgery, when surgeons focus on implanting the IOL, maintaining space is a priority. I use ProVisc as the second agent to create space for implanting an IOL.

Cabrera: Sodium hyaluronic acid and chondroitin sulfate combined provides three negative charges and attaches well to the endothelium. In certain cases, such as during the soft-shell surgical technique, I prefer to use Viscoat to ensure that the endothelium is well coated. The combination of Viscoat and ProVisc may not be ideal for brunescent, hard nuclear fragments because some of the fragments remain in the anterior chamber toward the angle on top of the iris. With DisCoVisc, however, the surgeon can manipulate the fragments with a small amount of the side port fluid or the phaco tip and move the fragments toward the center of the surgical field. The surgeon can move the fragments back into the phaco tip without much manipulation.

Holland: If small fragments remain in the chamber, it is clear that the endothelium is being protected, because there must be viscoelastic remaining.

Amzallag: During capsulorrhexis and phacoemulsification, the dispersive abilities of Viscoat provide good anterior chamber stability, good capsular tear control, and a visible presence of the OVD along the endothelium throughout the ultrasound phase. During implantation, the expansion abilities and ease of removal of cohesive OVDs are most important. Therefore, using an OVD such as DuoVisc is logical. DisCoVisc retains the advantages of cohesive OVDs while providing some dispersive properties. DisCoVisc is an innovative product and represents a different approach for OVDs. It is the first higher-viscosity OVD made from sodium hyaluronate associated with chondroitin sulfate.

Bissen-Miyajima: DisCoVisc may not always be appropriate for a hard nucleus. Compared with Viscoat, DisCoVisc is more likely to be aspirated if the surgeon starts to move the phaco tip upward. Viscoat, under high flow, remains in the endothelium and is safe to use. When using DisCoVisc, the surgeon should also keep the phaco tip at the level of the iris plane, not in the shallow anterior chamber, or use the bevel down technique.

Properties of OVDs also include substance clarity. DisCoVisc, which is a clear substance, is sometimes difficult to see inside the eye. Viscoat, however, is visible under a microscope.

Lindstrom: Chondroitin sulfate coats well and binds to the endothelium, and it is also a cell membrane stabilizer. In some cases, a stressed cell that might be near death can be preserved if it is coated with chondroitin sulfate. Chondroitin sulfate is also a free radical scavenger. It has been reported that phacoemulsification generates a significant amount of free radicals.⁵ Chondroitin sulfate may be useful because free radicals can damage cells indirectly (Figure 2).⁵

Free Radical Short Exposure Test Summary Figure 2. An OVD with chondroitin sulfate may be useful because free radicals can damage cells indirectly.5 Source: Alcon Laboratories, Inc.

Bissen-Miyajima: Researchers in Japan published a study on free radicals and the amount of OVD in the anterior chamber. Viscoat was shown to prevent damage in this area.^6,7

Arshinoff: Chondroitin sulfate OVDs have made an impact because of their dispersive nature and prolonged retention in the anterior chamber, yielding more effective endothelial protection during prolonged phacoemulsification and irrigation/aspiration. Surgeons can never achieve as many varied surgical environments with a single OVD as they can with two. Also, the more different the two OVDs, the better the partitioning of the surgical spaces created. DisCoVisc is effective for routine cases, but soft-shell techniques are more effective for complex cases, and modifications of ultimate soft shell (USS) and soft shell, using Viscoat, Healon5, and balanced salt solution (BSS) are most effective for the most complex cases. I use different OVDs and combinations for different situations and use more than one for the more complex cases. I recommend using a viscoadaptive OVD to create, pressurize, and maintain a space, and I find that Viscoat is the most effective OVD to protect endothelial cells from turbulence. When both functions are necessary, OVD combinations are best using variations of the soft-shell technique.

Current research

Lindstrom: Viscoat has a slightly higher osmolality than other OVDs. Viscoat can be used to maintain a thin cornea during corneal preservation because it has a deturgescent capability due to the chondroitin sulfate and its osmolarity. Endothelial cell counts may not be similar, but corneas are thinner, and thinner corneas usually correlate with better visual acuity measurements on postoperative day 1.

What has been your experience with current OVDs and their ability to protect the endothelium?

Arshinoff: Achieving clear corneas on day 1 is important, but it is really the long-term endothelial cell loss that is important and not the transient corneal deturgescence as a result of an osmotic effect.

Bissen-Miyajima: To increase the accuracy of the corneal endothelial cell count, my colleagues and I try to count more than 100 cells in the captured picture of specular microscopy. The current phacoemulsification technique is acceptable for most OVDs. However, the soft-shell technique will protect the corneal endothelium more effectively and help produce a clear cornea on postoperative day 1.

Cabrera: Data show that using a sodium hyaluronate-only OVD will result in endothelial cell loss of approximately 10% to 15%.⁸ Using a sodium hyaluronate/chondroitin sulfate combination OVD will result in an approximate 6% to 8% loss of endothelial cells. To further minimize endothelial cell damage in brunescent cataracts, I use a crater and crush technique. I create a 4-mm bowl in the center of the nucleus, mimicking a doughnut shape. Then I crush the nuclear rim between the phaco tip and the chopper, concentrating on linear opposing forces rather than a slicing tangential chop motion. This keeps the large nucleus practically immobile and avoids the spinning vectors created by a regular chop technique. The crushing does not use a significant amount of ultrasonic power but rather relies on mechanical blunt forces. The nuclear fragments are then brought to the center of the bowl and torsional phacoemulsification can be applied. After about half of the nucleus has been removed, it is essential to pause and add another coating of Viscoat to protect the endothelium before removing the remainder of the nucleus.

Surprisingly, patients who are 80 to 90 years old with dense cataracts who undergo this technique achieve visual acuity of 20/40 and 20/30 on postoperative day 1. In addition, corneas are clear, and swelling is minimal. Recoating midway through the procedure is crucial to reducing endothelial cell loss.

Ossma: Study data show that chondroitin sulfate is favorable for protecting the endothelium. Aguilera et al performed a prospective study comparing five OVDs.⁸ The results showed that patients with hard nuclei who underwent cataract surgery with OVDs containing chondroitin sulfate had thinner corneas at days 1, 7, 30, and 60, and they experienced less endothelial cell loss. The use of chondroitin sulfate OVDs resulted in less than 10% of endothelial cell loss, whereas the use of sodium hyaluronate-only OVDs resulted in losses of approximately 26% (Figure 3). The study investigators subcategorized the patient groups and found that patients with the hardest cataracts who underwent surgery with sodium hyaluronate-only OVDs had more endothelial cell loss than patients who underwent surgery with OVDs containing chondroitin sulfate.

Percent of ECC Loss Pre- to 2 Months Postoperatively Figure 3. F. Aguilera, MD, showed that the use of chondroitin sulfate OVDs resulted in less than 10% of endothelial cell loss.8 Source: Aguilera F

In a masked study, Vasavada et al compared two OVDs that contain chondroitin sulfate: DisCoVisc and DuoVisc.⁹ Study investigators found no statistical differences between these two OVDs in endothelial cell counts, postoperative IOP, and pachymetry values.

Amzallag: An objective measurement of endothelial protection is not easy to determine. Endothelial cell count is not always sufficient, and results may vary. However, my clinical experience convinces me that dispersive OVDs that contain chondroitin sulfate and that are used during phacoemulsification and removed completely at the end of the procedure provide more effective outcomes. Osmolality certainly plays a role. Although it has not been clearly clinically demonstrated yet, the visible maintenance along the endothelium may also be protective.

Clinical pearls and techniques

Lindstrom: What advice would you give surgeons who have never used an OVD that contains chondroitin sulfate?

Ossma: Surgeons can perform the soft-shell technique with an OVD such as DuoVisc, which combines a cohesive, space-generating OVD (ProVisc), with a dispersive, protecting-type OVD (Viscoat). Surgeons also could use DisCoVisc because it will allow them the same amount of space without losing the ability to protect the endothelium (Figure 4).⁹

Mean Endothelial Cell Density Figure 4. A study by Praveen et al showed no statistical difference in endothelial cell density between DuoVisc and DisCoVisc preoperatively and 3 months postoperatively. Also, no difference was found in coefficient of variation between the groups.9 Source: Alcon Laboratories, Inc.

Amzallag: Chondroitin sulfate increases the protective abilities of sodium hyaluronate. DuoVisc can be used sequentially (Viscoat for the capsulorrhexis and Provisc for the implantation) or simultaneously. Surgeons should note that these OVDs remain in the anterior chamber longer than OVDs without chondroitin sulfate. To improve control, I recommend that the capsulorrhexis be performed with a forceps rather than with a bent needle.

Lindstrom: Please describe how you perform the soft-shell technique.

Cabrera: First, I put a globule of Viscoat directly on top of the nucleus of the lens, and then I inject ProVisc in the center of the Viscoat bleb that I just made. The ProVisc will push the Viscoat up toward the periphery and toward the endothelium and produce that coating across the endothelial surface. The ProVisc, which is now in the center, will provide the surgeon with the space and ability to maneuver and start the capsulorrhexis.

The soft-shell technique also clears the interface between the aqueous and the Viscoat so that the surgeon can manipulate the capsulorrhexis properly and see it clearly during hydrodissection.

Arshinoff: For surgeons who have not used chondroitin sulfate-containing OVDs and are accustomed to higher zero shear viscosity sodium hyaluronate-containing OVDs, the soft-shell technique allows them to maintain the high anterior chamber stability to which they are accustomed while incorporating the additional endothelial protection added by Viscoat.

Lindstrom: Will the surgeon notice any changes when making the capsulorrhexis? Should they make any adjustments when performing phacoemulsification?

Bissen-Miyajima: A surgeon may need to adjust the technique depending on the amount of Viscoat inserted into the anterior chamber. Surgeons who use a cystotome instead of capsulorrhexis forceps will likely have difficulty making the capsulorrhexis because they will find more resistance when switching from a cohesive OVD to Viscoat or DisCoVisc. I recommend that surgeons using a cystotome who want to switch from a cohesive OVD to a dispersive OVD practice first using pig eyes.

I think the amount of Viscoat and cohesive ProVisc used is also important. I do not use a significant amount of Viscoat at the beginning of phacoemulsification. I use approximately 0.1 mL, and then I use cohesive ProVisc. The cohesive OVD inserted into the anterior chamber is approximately 5 mm to 6 mm in diameter and is visible, as is the ring. Furthermore, I use this ring as the leading line to create the capsulorrhexis.

Lindstrom: I also use a cystotome to create the capsulorrhexis. I sometimes place a layer of Viscoat directly under the endothelium, and then I use the sodium hyaluronate OVD under it. In other cases, I fill the anterior chamber with Viscoat or sodium hyaluronate alone. I have noticed that using sodium hyaluronate on the capsule makes the capsulorrhexis easier to create. Sodium hyaluronate is also useful for pupils that require viscodilation. Adding more Viscoat may be necessary for a patient with an unhealthy endothelium or if the surgeon wants to enhance space maintenance. The nuclear pieces should be able to move around, though, so the surgeon should avoid placing too much Viscoat over the iris and in the angle because it may act like glue and trap particles.

Arshinoff: After pushing the Viscoat in the anterior chamber up against the endothelium with a sodium hyaluronate-containing OVD such as ProVisc, the capsulorrhexis can be made more easily if a thin layer of BSS is injected onto the surface of the lens capsule before proceeding. This combines the concepts of USS technique (using BSS) with soft shell (Figure 5).

Soft-shell Technique Figure 5. Capsulorrhexis is easier to perform when BSS is injected over the capsule, after OVD injection when using the soft-shell technique, or any cohesive OVD by itself. Source: Arshinoff SA

Holland: To protect the cornea, I tend to use more Viscoat in the anterior chamber initially. Although surgeons may experience a learning curve in creating the capsulorrhexis, they should feel comfortable after performing the procedure a few times.

Also, at the beginning of the procedure, I put Viscoat on the corneal epithelium because it coats well and reduces the need to instill drops in the eye. Surgeons can put Viscoat on the corneal epithelium in patients who have epitheliopathy to facilitate visibility of the anterior chamber. When the epithelium is slightly dry or if the patient has epithelial basement membrane degeneration, applying Viscoat in the epithelium can help the surgeon better see the anterior chamber.

In my experience, the most common postoperative complication after a penetrating or deep anterior lamellar keratoplasty is traumatized epithelium. To protect the epithelium, surgeons can coat it with an OVD such as Viscoat as soon as the donor cornea is placed in the wound.

Amzallag: The dispersive and cohesive OVDs, such as in the DuoVisc system, can be used successively but also simultaneously. During the first phase, the dispersive OVD can be injected as usual to enable the creation of volumes and to protect the endothelium. The injection of a cohesive OVD layer between the anterior capsule and the dispersive OVD creates a more pseudoplastic space facilitating the capsulorrhexis. Then the cohesive OVD can be used to expand the capsular bag during the implantation. There again, it is used as customary. The dispersive OVD then can be injected along the corneal endothelium. The removal of the two OVDs is made easier by the anterior location of the dispersive OVD in front of the IOL.

Lindstrom: Does the technique for phacoemulsification change when using DisCoVisc?

Bissen-Miyajima: My colleagues and I performed a clinical study in which we asked surgeons to compare the ease of cataract surgery technique using DisCoVisc or other cohesive OVDs (H. Bissen-Miyajima, MD, et al, unpublished data, July to October 2006). Most surgeons found that creating the capsulorrhexis was slightly different. I recommend that surgeons practice the procedure because, like Viscoat, DisCoVisc is sticky. With practice, surgeons can control the size of the capsulorrhexis more easily with a viscous dispersive agent than with a cohesive OVD.

Surgeons also reported good visibility with DisCoVisc and that the agent is easy to remove at the end of surgery.

Cabrera: Technique does not change significantly when using DisCoVisc, and the agent maintains flap positioning. During removal at the end of the procedure, however, the surgeon may need to increase flow rate slightly to aspirate.

Ossma: The ability to determine capsulorrhexis size is important when implanting premium IOLs. With DisCoVisc, the surgeon has more control and can implant a premium IOL with adequate overlap and perfect centration compared with using a cohesive-only OVD.

Arshinoff: The capsulorrhexis is more difficult with DisCoVisc because of the OVD’s higher viscosity and dispersive nature, but the accuracy of the capsulorrhexis sizing is more effective with higher viscosity.

Amzallag: DisCoVisc has both viscous and dispersive qualities, because of the blend of higher molecular weight hyaluronic acid with chondroitin sulfate. Its high pseudoplasticity enables an easy injection with a thin cannula (27 g) through a tiny incision. The creation, as well as the maintenance, of space in the anterior chamber makes the capsulorrhexis easier to perform in standard or difficult cases. Due to the presence of chondroitin sulfate, DisCoVisc remains along the endothelium during phacoemulsification, even if most of the OVD is washed out at the beginning of the ultrasound phase. The capacity of expansion of DisCoVisc enables the creation of space in the capsular bag as well as in the anterior chamber before implantation. DisCoVisc is easier to remove than Viscoat, but it requires a specific technique to be as easy to aspirate as ProVisc. I suggest a bi-instrumental aspiration technique to facilitate the removal of DisCoVisc. The irrigation/aspiration handpiece through the incision is associated with a micromanipulator through the side port incision. The settings are vacuum, 600 mm Hg; flow rate, 40 mL/min; and bottle height, 90 cm. First, the product is aspirated in front of the IOL with high vacuum levels. Then, the optic is slightly luxated by the manipulator to enable product aspiration behind the optic.

High-risk patients

Lindstrom: Please discuss your recommendations for treating a high-risk patient, such as an 80-year-old patient with a 4+ brunescent nucleus, cornea guttata, and pachymetry measurement of 640 µm.

Holland: Traditionally, cataract surgeons would have deferred surgery for approximately 6 months because this patient is at a high risk for decompensation. With the availability of endothelial keratoplasty instead of penetrating keratoplasty, surgeons have the confidence to intervene earlier. If the cornea decompensates, the surgeon can perform endothelial keratoplasty several weeks after phacoemulsification and achieve good outcomes.

To determine which patients would benefit from a simultaneous endothelial transplant and phaco procedure, the surgeon must first determine whether the patient has corneal edema. I ask whether the patient’s vision changes throughout the day because morning blur is a hallmark of endothelial dysfunction and corneal edema. The surgeon should also look for stromal folds and haze. Also, if the surgeon can move the epithelium with a needle or forceps, the patient likely has epithelial edema, which is a sign of early corneal decompensation.

The surgeon must then determine the patient’s vision demands. Acuity of 20/40 may be useful and satisfactory for an elderly patient, and the patient can avoid a corneal transplant. Most patients, however, demand excellent visual acuity. For the patient who has early corneal edema, I recommend a combination phacoemulsification and endothelial keratoplasty procedure.

Cabrera: For a high-risk patient with a compromised endothelium, I would coat the endothelium with Viscoat initially and then use DisCoVisc under to facilitate manipulations. I would also periodically recoat, which is an essential step. Traditionally, surgeons were taught to finish the procedure as quickly as possible with the least amount of manipulation. If the surgeon feels that he or she is taking too long or manipulating too much, I recommend stopping and recoating. I find that a slower and more controlled procedure produces better outcomes.

Bissen-Miyajima: For a patient with a compromised cornea or an endothelial cell count of 500 to 600, I would use the soft-shell technique (Figure 6).^10,11 I would use Viscoat to try to prevent the nucleus from moving up toward the endothelium. If the lens begins to move upward, I may add a small amount of Viscoat. My results show that these high-risk patients do not require corneal transplantation and maintain clear corneas even at 1 year postoperatively.

Pre- vs. Postoperative Changes in CCT Figure 6. Tarnawska et al found that patients treated with DuoVisc had smaller increases in CCT at all time points measured compared with patients treated with sodium hyaluronate alone.10 Poyer et al speculate that the protective effect of Viscoat results from its coating properties.11 Source: Alcon Laboratories, Inc.

Ossma: For patients at high risk, when the cumulative dissipated energy measure on the Infiniti OZil machine (Alcon Laboratories, Inc.) reaches 10, I recommend recoating. Surgeons should also prevent BSS from flowing toward the endothelium. They must work gently but quickly to avoid significant turbulence and flow of BSS into the anterior chamber.

Holland: If a patient’s pupil is marginal, I am more apt to use iris hooks in a hard lens to maximize space. Posterior phacoemulsification is also important. I manipulate deeper to keep lens pieces, the phaco tip, and energy away from the endothelium. In this case, I would use Viscoat at the start and perform torsional phacoemulsification. To allow me to manipulate deeper, I may chop the nucleus into smaller pieces, such as eight pieces instead of four or six. With a large piece, the surgeon may move too close to the endothelium, but with smaller pieces of the hard lens, the surgeon can remain posterior.

Arshinoff: This type of high-risk patient is not unusual. First, I make tight incisions that will decrease turbulence during surgery. I inject Viscoat onto the lenticular surface, then push the Viscoat up against the endothelium with Healon5, a viscoadaptive OVD. Next, I inject a layer of BSS onto the lenticular surface beneath the OVDs. I then decrease turbulence by lowering the aspiration rate to 20 cc/min, the vacuum limit to 200 mm Hg, and the bottle height to 80 cm above the patient’s head. I use Ozil and try to keep all phacoemulsification and irrigation/aspiration confined to the capsular bag. At the end of the procedure, I remove the Healon5 but leave the Viscoat layer protecting the endothelium. I place carbachol 0.2% drops in the conjunctival cul de sac, which is excellent to keep the pupil miotic for 24 hours and to prevent postoperative IOP spikes.

Amzallag: For this patient, an endothelial cell count is mandatory. If there are no visible cells in the central area and most of the peripheral areas, the surgeon must inform the patient of the risk of postoperative corneal edema, which may lead to the need for a corneal graft.

The quality of an OVD’s endothelial protection is important. With the DuoVisc system, Viscoat is supposed to protect the endothelium well because of the better maintenance in the anterior chamber, its presence along the endothelium, and its coating properties. With DisCoVisc, the chondroitin sulfate improves its maintenance in the anterior chamber and along the endothelium compared with a standard cohesive OVD. The OZil technology seems less traumatic and more mechanically effective.

Lindstrom: What are some other high-risk situations?

Holland: Patients with dense lenses, regardless of a good endothelial cell count, are also at risk for corneal endothelium damage. Surgeons will spend more time and use more power and irrigation fluid on a dense lens. Previous trauma and history of iridocyclitis are also risk factors.

Lindstrom: Which type of OVD do you prefer for patients with small pupils or with intraoperative floppy iris syndrome (IFIS)?

Ossma: Pupil dilation will always be optimal with use of a cohesive OVD. First, I would try an extremely viscous OVD, such as ProVisc or DisCoVisc, or a viscoadaptive OVD, such as Healon5. The next option is to perform surgical maneuvers to enlarge the pupil. For patients with IFIS, I recommend using hooks or a ring to dilate the pupil to avoid reducing pupil size during phacoemulsification.

Holland: The decision to use an OVD in patients with small pupils depends on the density of the nucleus. I am more likely to use hooks or a ring for a patient with a hard lens.

Cabrera: I find using a cohesive OVD sufficient in patients with pupils of approximately 4 mm to 4.5 mm. For IFIS, I use one iris hook inserted into a stab incision placed beneath the main keratome incision. This keeps the iris from repeatedly prolapsing through the main incision and allows almost routine phacoemulsification, albeit with lowered parameters.

Bissen-Miyajima: Patients with poor endothelium often present with small pupils as well. I use Viscoat to protect the endothelium and a cohesive OVD to dilate the pupil. If the pupil size decreases during surgery, I insert the cohesive OVD again to enlarge the pupil, allowing me to see the remainder of the nucleus or cortex. I maneuver under the iris and aspirate from there, performing phacoemulsification in the center, and I repeat this process.

Arshinoff: For very dense lenses, the goal is to minimize turbulence and exposure of endothelial cells to surgical trauma. I would treat patients with dense lenses in the same manner as I treat patients who have marginal endothelium. For patients with small pupils, the surgeon must first determine whether the pupil is small because of previous inflammation and, if so, remove the fibrous pupillary ring. If the pupil is fibrotic, I stretch it with Arshinoff hooks. In patients with IFIS, I use my modified soft-shell-USS technique,¹² whereby incisions are kept tight, the iris oscillations are tamponaded with Viscoat, the anterior chamber is bridged with Healon5, the capsulorrhexis is kept small, and all work is performed in the capsular bag. I use intracameral phenylephrine preceding the OVDs to maximize pupil dilation, which helps most of the time.

Lindstrom: I think that cohesive OVDs are the best option for viscodilation, but the manner in which they are inserted is important. The surgeon should place the OVD on the posterior capsule in the center of the pupil to push out on the iris margin and enlarge the pupil. In some patients with IFIS, a dispersive OVD can allow the surgeon to push a floppy iris back and hold it posterior to the nucleus when using a supracapsular phacoemulsification technique.

Holland: The goal for treating patients with IFIS is to protect iris function and to prevent the iris from coming out of the wound because once the iris is damaged, it does not function optimally. I find that early intervention with iris hooks is the safest approach for patients with IFIS.

Cabrera: Surgeons may not be able to manipulate the nuclear fragments or residual cortex subincisionally in patients with challenging features, such as small pupils. Using an OVD, the surgeon can push the residual cortex away and viscodissect a ring or quadrant. The subincisional tissues, such as cortext or nucleus can then be rotated toward the surgical zone.

Amzallag: For patients with small pupils, a cohesive OVD such as ProVisc makes the creation of space in the anterior chamber and the treatment of synechias easier. For patients with shallow anterior chambers or strong posterior pressure, Viscoat is more suitable because it maintains the anterior chamber under difficult surgical conditions more effectively. DisCoVisc combines the capabilities of creating and maintaining space, increasing the pupil dilation, and preserving it during the different maneuvers.

Regarding intumescent cataracts, due to the hyperpressure inside the capsular bag, in addition to transparency and visibility, maintenance of the anterior chamber and presence of the OVD along the endothelium are of major importance. For those cases, Viscoat or DisCoVisc is more suitable.

For extremely hard nuclei, transparency and endothelial protection are necessary (Figure 7).¹³ For patients with subluxated lenses, many different situations require different types of OVDs, both dispersive and cohesive. Dispersives OVDs are useful to push and maintain the crystalline back or to control the vitreous in the anterior chamber during the procedure. Cohesive OVDs are suitable for creating space in the anterior chamber, removing the remaining cortex with a thin cannula, and placing a capsular tension ring with either forceps or an injector. For patients with severely subluxated lenses, the simultaneous use of dispersive and cohesive viscoelastics can help.

Refractive Index of OVDs Figure 7. Tested OVDs have equivalent clarity (1.3362-1.3435 refractive index).13 Source: Alcon Laboratories, Inc.

Avoiding IOP spikes

Lindstrom: The primary negative side effect of OVDs is a postoperative IOP spike. How can surgeons avoid these spikes?

Ossma: The different types of OVDs perform differently. Surgical time must be tailored to the type of OVD used. A cohesive OVD is easy to remove. The surgeon can remove a cohesive OVD approximately 20 seconds after implanting the IOL and 20 seconds after irrigation/aspiration. I would risk an IOP spike, especially in a high-risk case, over damaging the endothelium.

Viscous dispersives such as DisCoVisc are similar to cohesive OVDs during removal. Given adequate flow parameters, viscous dispersive OVDs can be removed in 30 to 40 seconds.

Holland: Much of the retained OVD is found behind the IOL. When I insert an IOL, I use a cyclodialysis spatula that stabilizes the posterior chamber lens. When I remove the OVD, I tilt up the posterior chamber lens and put the irrigation/aspiration tip behind the lens to ensure that I do not retain OVD behind the IOL.

For me, the phacoemulsification technique has changed more than the type of OVD used. With torsional phacoemulsification, less fluid is used. Therefore, a significant amount of OVD can remain in the anterior and posterior chamber. I carefully ensure that all of the OVD is removed from each quadrant of the anterior chamber as well as from behind the IOL.

Cabrera: The introduction of torsional phacoemulsification changed my technique and reduced the amount of DuoVisc I use. Although the surgeon will use less OVD in a routine torsional procedure, meticulous removal of most if not all of the OVD should be attempted to minimize the potential for IOP spikes, especially when implanting premium IOLs. The surgeon can use a rock-and-roll technique or tilt the lens to remove OVD. By tilting the lens, the inflow of fluid moves across to the other side and pushes the OVD out.

Bissen-Miyajima: I do not use any prophylactics, and I usually check the IOP 24 hours postoperatively. In the clinical study my colleagues and I performed, we found that IOP was not significantly high 5 hours postoperatively, although it has been said that IOP increase is the highest at 5 hours.¹⁴ I think IOP spikes are dependent on the technique and amount of OVD used.

Lindstrom: I use medical therapy, such as dilute carbachol, to achieve a small pupil postoperatively, which also helps reduce IOP spikes. I also instill one drop of beta blocker on the eye. Surgeons should note that when using a dispersive OVD such as Viscoat, the goal is not complete removal. I describe the procedure as a core viscectomy. The surgeon will want to remove the primary bolus of viscoelastic, but it is unnecessary and almost impossible to remove it all.

Arshinoff: In the late 1990s, my colleagues and I performed a study with the FDA that reviewed postoperative IOP spikes (unpublished data). We determined that all OVDs, if left in the eye, cause IOP spikes, with the spikes from longer-chain OVDs occurring slightly later. The peak of IOP spikes is at approximately 6 to 12 hours postoperatively, which is usually at night when no one measures IOP. All drugs that reduce aqueous production were found to be completely ineffective in preventing or reducing postoperative IOP spikes, and many of them worsened the spikes, presumably by delaying OVD washout until the peak spike time. The most effective agents were those that increase outflow, such as cholinergics. I use topical carbachol 0.2% in all postoperative cataract patients to prevent IOP spikes. Prostaglandin agents are also effective.

Holland: Ophthalmic viscosurgical devices must be removed completely from patients implanted with toric IOLs, however. Retained OVD can be the cause of a toric IOL moving from the original axis of placement.

Amzallag: It is most important to remove as much of the OVD as possible from the anterior chamber, both in front of and behind the IOL, using a proper technique. A local treatment also should be used in patients with symptomatic IOP spike approximately 5 to 8 hours postoperatively. At 24 hours postoperatively, most of the hyper-IOP has disappeared.

Hydrodissection vs viscodissection

Lindstrom: Viscodissection is a useful procedure. I perform supracapsular phacoemulsification, and at times, I am unable to tip the nucleus. Often, I will use a dispersive OVD to pop the nucleus up with viscodissection (Figure 8).¹⁵

Cadaver Eye: Viscodissection vs. Hydrodissection Figure 8. Vasavada et al showed that viscodissection with DisCoVisc created a larger space than hydrodissection alone and that hydrodissection creates only a cleavage plane but not space.15 Source: Vasavada A

Holland: The viscodissection technique described by Richard Mackool and his son, Richard Mackool, Jr, has been shown in their large series of patients to be effective at reducing capsular rupture in routine cases (Figure 9).¹⁶

Viscodissection Study Figure 9. Mackool et al performed hydrodissection without viscodissection in 759 consecutive patients (group 1).16 Hydrodissection followed by viscodissection (Viscoat) was performed in 725 consecutive patients (group 2). Results showed that viscodissection significantly reduced the incidence of posterior capsule rupture during phacoemulsification. Source: Alcon Laboratories, Inc.

Amzallag: For congenital posterior polar cataracts, I inject a cohesive viscoelastic such as ProVisc under the posterior opacity to reduce the risk of posterior capsule hole.

Ossma: The surgeon can also perform viscodissection for the rare posterior polar cataract that has an increased tendency to pop during hydrodissection. Another indication for viscodissection is when cortical material is retained subincisionally. In this case, the surgeon can attempt to viscodissect the cortical material using any OVD.

Cabrera: I perform viscodissection also in patients who require a capsular tension ring (CTR). The surgeon should remove a little bulk of the nucleus and create a space using viscodissection to place the CTR without creating too much tension between the tissues so that the CTR can slide in easily.

Bissen-Miyajima: A resident in training may have difficulty rotating the nucleus or manipulating from the side and may perform a viscodissection to make the procedure easier.

Lindstrom: Please discuss your experience with extremely cohesive agents such as Healon5 and Healon GV (AMO). How do you remove extremely cohesive OVDs?

Bissen-Miyajima: To remove Healon5, I use the behind-the-lens technique at the end of surgery. For other OVDs, the rock-and-roll technique is sufficient.

Arshinoff: Highly viscous OVDs are easy to remove using the rock-and-roll technique. I prefer to use the USS technique, which avoids placement of Healon5 behind the lens, to the two-compartment technique.

Lindstrom: I participated in one of the early clinical trial evaluations of Healon GV, and I used my routine rock-and-roll removal technique. I push down on the optic and roll left and roll right a few times, which is similar to how I remove other cohesive OVDs such as Amvisc Plus (Bausch & Lomb) or ProVisc. In my evaluation, however, with Healon GV, this approach resulted in more patients with an elevated IOP the next day. I believe that the surgeon must be more compulsive in removing the OVD from under the lens if using Healon GV to prevent a significant IOP spike.

Arshinoff: It is relatively easy to leave behind an unobserved chunk of Healon5 or Healon GV. However, the surgeon does not need to go behind the IOL for Healon GV. I recommend briefly irrigating in each quadrant to ensure that no pieces are left. As surgeons move to smaller, tighter incisions with less leakage, OVD removal will become a more critical issue.

Holland: In my practice, we perform cataract surgery on many patients with congenital aniridia. Capsulorrhexis in these patients is difficult to perform. I use Healon GV or Healon5 to maintain space in patients with aniridia to assist in the management of weak zonules, abnormal capsule, and the tendency for the lens to move anteriorly. However, all OVD must be removed.

Future of OVDs

Lindstrom: What properties or features would you want in an ideal OVD? What do you see for the future of OVDs?

Bissen-Miyajima: The ideal OVD would be able to remain in the eye without causing an increase in IOP, be absorbed faster, and be easy to remove.

Arshinoff: It would be ideal if OVDs spontaneously broke down in the anterior chamber within 1 hour of surgery and did not cause IOP spikes, so surgeons could leave them in the eye. In the future, I think OVDs will be incorporated into irrigating solutions and that OVDs will require only covering incisions with them, leaving most of the anterior chamber filled with BSS. That would make surgery easier and removal simpler. OVDs also will be designed to instill pharmacologic agents into the eye.

Cabrera: Occasionally, it would be ideal to leave a small amount of OVD in the eye at the end of surgery, such as when treating patients with IFIS and the iris prolapses more than once. The surgeon may want to use a small amount of OVD to make the pupil round and seal in the iris.

Holland: It is possible to safely leave a small amount of Viscoat in the eye. When surgeons performed the triple procedure in the past, including penetrating keratoplasty, cataract extraction, and posterior chamber lens implantation, they did not want to reenter the anterior chamber to avoid damaging the new endothelium. The surgeon would instead place a small amount of Viscoat on the IOL and put the penetrating keratoplasty tissue in place. Leaving this small amount of Viscoat does not increase IOP.

Current OVDs provide enhanced space maintenance, but endothelial protection is a more critical feature. In the future, OVDs will be composed of materials and substances that promote endothelial function or protect the endothelium.

Amzallag: The ideal OVD would be contained in only one syringe; enable the surgeon to work in a completely stable anterior chamber; protect ocular tissues more effectively, especially the corneal endothelium; and be able to remain at the end of the procedure without any consequences such as postoperative IOP spikes or posterior capsule opacification. An OVD could be combined with active functions such as anesthetic, antibiotic, anti-inflammatory, and anti-proliferation of remaining capsule epithelial cells.

Lindstrom: Ophthalmologists often focus on the endothelium, uveal tract, posterior capsule, and space maintenance, but they should also strive to protect the ocular surface. Furthermore, in addition to being able to remain in the eye in small amounts, future OVDs should protect and restore the endothelium. Instead of resulting in 4% to 8% of endothelial cell loss, future OVDs should result in a 0% loss of cells. An OVD with an anesthetic is already available, and perhaps soon there will be an OVD engineered with some anti-inflammatory effects and the capability to inhibit bacterial growth.

I thank Ocular Surgery News Europe/Asia-Pacific Edition for organizing this panel and Alcon Laboratories, Inc., for its sponsorship. I also thank the faculty for participating in this discussion.

References

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