Visualization in Vitrectomy: An Update

In addition to stains and dyes, light filters are enabling more effective intraoperative views.

KINNAR MERCHANT, FRCOphth

Vitreoretinal surgery is evolving with the times. New methods of tackling retinal surgical pathology are developing. These developments have been helped by newer, finer, and faster instrumentation and improvements in internal tamponading agents and visualization of the pathology.

This article will attempt to cover advances in visualization, which have been crucial in understanding and treating pathology better and in refining outcomes, as well as to provide an update on the topic since this publication last did.¹ There are three aspects to improving visualization during vitrectomy:

1. Clear media;

2. Better illumination and viewing systems; and

3. Improved visual differentiation of the various tissues during surgery.

CLEAR MEDIA

Clear media naturally improve our ability to distinguish between normal and diseased tissues. This clarity is vital in vitreoretinal surgery. Ideally, a clear view is required through the cornea, lens, and vitreous.

Cornea

Injury, infection, or scarring may cloud the cornea. The management of corneal opacity is determined by the underlying pathology. Corneal edema from previous surgery may be addressed with simple preoperative measures such as treatment with topical steroids. It is advisable to remove corneal sutures from primary repair of trauma or keratoplasty if possible.

In cases of endothelial cell failure, corneal epithelial removal alone, or combined with corneal dehydrating agents, can sometimes improve the fundal view. Large corneal scars can be dealt with by optical iridectomies, simultaneous penetrating keratoplasty (PK) with vitrectomy, and temporary keratoprostheses² or (rarely) using an open sky vitrectomy technique.

Open sky vitrectomy, while mainly being of historical interest, can occasionally be used in simple cases or in certain specific situations, but it is accompanied by the risk of globe collapse and intraocular hemorrhage.

Endoscopic vitrectomy is an option in such cases, but it is not universally available. Use of an endoscope eliminates the need for combining posterior-segment surgery with corneal grafting. Endoscopes can also be potentially useful in retinal reattachment surgery in eyes with permanent keratoprostheses.³

A temporary keratoprosthesis may be used, but it is also fraught with complications, such as instability during surgery, condensation impeding the view, and deterioration in optical quality with use.

Combined PK with retinal detachment repair increases the risks of graft failure. Silicone oil and heavy liquid are toxic to the cornea and have been associated with corneal decompensation and band-shaped keratopathy.

Recently, deep anterior lamellar dissection of the cornea has also been used to aid visualization during vitrectomy. The primary purpose of this technique is to preserve Descemet’s membrane in eyes with a healthy corneal endothelium.

However, deep anterior lamellar dissection also offers the vitreoretinal surgeon a clear view of the anterior and posterior segments through the bared Descemet’s membrane.⁴

Pupils

Poorly dilating pupils or ectopic pupils constitute another impediment to a clear fundal view. The techniques used to rectify these problems intraoperatively are similar to those used for cataract surgery, and they include the use of intracameral phenylephrine, iris stretching, sphincterotomies, iris hooks, or the Malyugin ring (MicroSurgical Technology, Redmond, WA).

Crystalline or Intraocular Lenses

Lenticular opacities can also hamper visualization during surgery, and they can even develop during vitrectomy, particularly if lens damage with instruments occurs. Approximately 75% of phakic eyes⁵ develop cataracts during follow-up after vitrectomy,⁶ which can impair follow-up.

Today, many surgeons prefer combined cataract surgery and vitrectomy. The advantages are:

• Improved visualization of the peripheral retina (facilitated by removal of any opacities in the anterior segment);

• A wider view that aids internal searching for obscure retinal breaks⁷;

• Better gas fill, improving success rates, particularly in cases of macular hole surgery⁸; and

• Combined surgery eliminates the risk of lens damage during vitrectomy.

Posterior capsulectomy in conjunction with combined surgery can prevent future loss of vision from capsular opacification, especially when intraocular gas is used at the end of vitrectomy.^9,10 However, it can also destabilize the anterior segment and allow tamponading agents to migrate into the anterior chamber.

A dislocated intraocular lens can distort the view and therefore is usually repositioned or explanted before vitrectomy. During fluid/air exchange, condensation occurring on the posterior surface of the IOL can limit the surgeon’s view of the retina.

This limitation can be alleviated by coating the back of the IOL with viscoelastic, which alters the surface properties of the IOL¹¹ and produces a film-like condensation, instead of droplet condensation, which does not alter the view.

Sometimes using warmed irrigating fluid through irrigating contact lenses also clears the view by modifying the physical environment (ie, humidity or temperature) in the anterior segment of the eye.

Vitreous

Vitreous hemorrhage is one of the major indications for vitrectomy. In itself, hemorrhage in the vitreous may obscure the view significantly. Recently, the use of anti-VEGF treatment preoperatively has been introduced to reduce intraoperative and postoperative bleeding in certain high-risk cases.

Rizzo et al¹² randomized 22 eyes with severe proliferative diabetic retinopathy and tractional retinal detachment either to intravitreal bevacizumab (Avastin, Genentech, South San Francisco, CA) or to sham injection five to seven days before vitrectomy. They showed that complications in the surgical procedure were reduced in the bevacizumab group.¹³

Clinical studies using intravitreal thrombin have shown a significant reduction in both the bleeding time after cutting vascularized membranes and the overall rate of intra- and postoperative bleeding. Given the lack of toxicity, postoperative hemostasis can be maintained for up to one week if the intravitreal thrombin is not washed out.

Heparin has a similar advantage but a very limited evidence base. Although tissue plasminogen activator has been a popular choice for this purpose, there have been reports of retinal toxicity.

BETTER ILLUMINATION AND VIEWING SYSTEMS

Illumination

The most common methods of illumination are the fiberoptic “light pipe,” chandelier lighting, and illuminated instruments.

Modern wide-angled beveled light pipes allow for 100º of fundal illumination and protect the surgeon from glare when the bevel faces down. However, it makes visualization of the vitreous and some other structures less satisfactory.¹⁴ With the advent of brighter light sources, it has been possible to develop finer-gauge chandelier illumination (23-, 25-, 27-gauge). This allows for truly bimanual surgery even with narrow-gauge instruments, which is always more helpful.

Light sources have become more powerful. The challenge is to enable their use for longer durations safely. Intense light usually causes more retinal phototoxicity; hence, the newer sources feature short wavelength filters (at least <420 nm), which cut off hazardous ultraviolet and blue light.

The DORC Bright Star (Dutch Ophthalmic Research Center, Zuidland, the Netherlands) and the Stellaris PC (Bausch + Lomb, Rochester, NY) vitrectomy machines have in-built filters that offer different colors of fundus-viewing environments by changing the lower-wavelength filters with a xenon light source (Figures 1 and 2, page 40).

Figure 1. Xenon light source without filter.
CREDIT: BAUSCH + LOMB

Figure 2. Xenon light source with green filter.
CREDIT: BAUSCH + LOMB

Recently introduced mercury vapor bulbs have much greater output. Their illumination is green-yellow and has two advantages: (1) it complements blue dyes to provide better contrast; and (2) its fundal reflection does not cause undue glare on the surgeon’s eyes.

LED light sources have now been introduced on the newer models of some vitrectomy machines.

The new brighter light sources have also revived the use of chandelier endoillumination, which can illuminate from a greater distance than conventional light sources. This ability makes them much safer. Besides the obvious safety of such systems, they also allow the surgeon to work bimanually, which helps a great deal.¹⁵

Currently available illuminated vitrectors, forceps, scissors, and picks are very bright, but they do not seem to be able to provide adequate illumination in the right place, and they cause considerable glare.

In contrast, illuminated directional laser probes are a welcome addition. They can remain straight when entering the eye, eliminating the risk of lens damage, as well as providing the ability to work around the posterior pole.

Their ability to curve is extremely beneficial when the surgeon needs to reach the periphery of the eye. A three-function tissue manipulator, combining light, aspiration, and cautery, has also been well received by surgeons.¹³

Wide-angle Viewing Systems

Wide-angle viewing systems (WAVs) are useful fundus observation devices for vitreous surgery, based on the indirect ophthalmoscopic principle. They allow for a panoramic view of the fundus and the location of retinal pathologies, without requiring excessive rotation of the globe during surgery.

WAVs can be of the contact and noncontact types. Contact WAVs are compatible with most microscopes, they have a wider view in comparison to noncontact systems, they eliminate distortion from optical aberrations or astigmatism, and they provide a similar wide angle of view under both fluid- and air-filled conditions. Such systems require an assistant or a sewn-on lens to keep the lens on the cornea. Blood/air bubbles tend to hamper the view. The best view is with the eye in the primary position.

Noncontact WAVs do not require a skilled assistant or sewn-on lens. Stereoscopic viewing is possible even with gaze movements, and they have a comfortable working distance, which allows for easy instrument exchange due to simultaneous port visualization at low zoom. On the down side, they do not neutralize corneal astigmatism, they have a steep learning curve, and water droplets on the lens may obscure a clear view.¹⁶

The Preferences and Trends survey, conducted by the ASRS, reveals that the BIOM (Oculus, Wetzlar, Germany), one of the original wide-angle viewing systems, is the most commonly used wide-angle viewing system among vitreoretinal surgeons.¹⁷ Since its introduction, the BIOM system has evolved. The reinverter (mounted on the microscope to make the image upright) is now foot-controlled, along with the focusing systems.

A disposable system, BIOM Ready, was introduced in early 2014. It is similar to the regular BIOM. However, the advantage is that there are no “water marks” or scratches that can occur with the sterilization of reusable lenses. It also reduces the down time necessary for sterilization.

It has been claimed that an additional BIOM HD Disposable Lens provides depth perception not seen before with wide-angle viewing. The Optical Fiber Free Intravitreal Surgery System (OFFISS; Topcon, Oakland, NJ) is similar to the BIOM, except that it can be mounted only on the OMS-800 Operation Microscope (Topcon). The OFFISS system has illumination incorporated into the microscope, with which the fundus can be viewed without using a light pipe. Therefore, this technology allows surgeons to perform bimanual surgery.

Other systems, such as the EIBOS 2 (Haag-Streit Surgical, Köniz, Switzerland) and the Peyman-Wessels-Landers 132 D Upright Vitrectomy Lens (Ocular Instruments, Bellevue, WA), have an integrated inverter, which keeps the microscope short and flips away if not needed.¹⁸

Vitrectomy Under Air

In vitrectomy under air, it is suggested that premature air-fluid exchange be performed so that the vitrectomy can be performed under air, rather than balanced salt solution. The view under air is wider due to the difference in refractive index (1.00 for air and 1.33 for BSS).

With this technique, the air-vitreous interface facilitates the performance of complete vitrectomy, potentially improving surgical success. The retinal surface tends to be more stable under air while shaving closely at the vitreous base.

Surgeons should be wary about inflow vs outflow mismatch (due to reduced outflow impedance with air). This limitation can be mitigated by interrupting the vitreous base dissection with brief periods without aspiration, to allow the infusion to catch up with the high rate of outflow.

Inflow vs outflow mismatch can also be apparent at the induction of an air-fluid exchange. An air block that impedes infusion while outflow continues via aspiration at the vitreous cutter can lead to sudden hypotony. In a pseudophakic eye with a disrupted posterior capsule, air can fog the IOL and compromise the view.¹⁹

Another technique for vitrectomy under air described an aphakic eye filled with air to approximately two-thirds of the anterior chamber. An erect image of the fundus of the aphakic human eye can be visualized clearly during vitrectomy, enabling the surgeon to operate without the need for vitrectomy lenses.²⁰ This technique has not become very popular.

Three-dimensional Microscopes

In March 2014, retinal surgery was performed and demonstrated, under a microscope (Leica Microsystems, Wetzlar, Germany) with three-dimensional technologies (True Vision 3D technology; TrueVision, Inc., Santa Barbara, CA), for the first time by Prof. Claus Eckardt of the Klinikum Frankfurt Höchst.

The evident advantages are as follows.

1. The surgeon operates in a “heads-up” manner, looking at a large screen, rather than through the traditional microscope oculars, which is a more ergonomic experience.

2. There is a more immersive visualization experience for the surgeon.

3. The operating team and those watching for learning purposes see the same field of view as the surgeon, thereby enhancing their understanding.

3. The low-intensity light, required for viewing ocular structures due to digital amplification of the camera signal, reduces overall phototoxicity.

The main disadvantages so far are:

1. A steep learning curve;

2. Expensive equipment; and

3. Lack of wide use and therefore limited available feedback.

INTRAOPERATIVE OCT

Intraoperative OCT is one of the latest additions to the retinal surgeon’s armamentarium. It brings to light the immediate changes that occur within the retinal layers as a result of surgical manipulation. This information is available in real time, which may help in surgical decision-making.

The full functional significance of intraoperative OCT is not absolutely clear. The Prospective Intraoperative and Perioperative Ophthalmic Imaging with Optical Coherence Tomography (PIONEER) study evaluated the feasibility, safety, and utility of intraoperative OCT for use during ophthalmic surgery. Images were qualitatively and quantitatively assessed for microarchitectural alterations, and according to the study authors, the results were encouraging. Subclinical architectural changes in the outer retina and geometric changes (especially during macular hole surgery) were noted.²¹

With the help of this technology, a surgeon should be able to determine whether an epiretinal membrane has been completely removed from the retinal surface, potentially reducing the risk of postoperative recurrence. It may lead to more insights into tackling surgical retinal entities.

Microscope-mounted OCT is already commercially available. However, the current metallic instrumentation causes shadowing on the OCT, and its light-scattering properties limits visualization. In light of these shortcomings, new instruments are being designed that will overcome these disadvantages.^22,23

IMPROVED VISUAL DIFFERENTIATION OF THE VARIOUS TISSUES DURING SURGERY

Chromovitrectomy

The process of using stains to ease the visualization and differentiation of preretinal tissues and membranes during vitrectomy procedures is known as chromovitrectomy. One or another form of staining has been used since 2000. An ideal dye should be one that is selective in its staining, is safe, and is easily eliminated.

The three main tissues of interest for staining purposes are the posterior hyaloid membrane, the epiretinal membrane, and the internal limiting membrane. Although most dyes, except for triamcinolone acetonide (TA), can stain ERM and the ILM, they have preferential staining for one of these tissues, as shown in the Table (page 41).

Indocyanine green is a dye that has affinity for extracellular components and therefore stains the ILM best. There have been some reports indicating dose- and duration-dependent toxicity toward photoreceptor and retinal pigment epithelial cells. However, the dosages and durations used for in vitro studies are not a reflection of real-life situations, in which the drug remains in the eye for a very short duration.

In response, the safer infracyanine green was introduced. It has lower toxicity because it is synthesized without sodium iodine, which damages the cornea and retina. In contrast, infracyanine green is not water-soluble, requiring it to be dissolved in 5% glucose. It is perhaps for this reason that it has not caught on in popularity among retinal surgeons.

Trypan blue has an affinity for dead glial cells and hence is able to stain ERMs very well. As is well known, it initially found use in ophthalmology to stain the anterior capsule during phacoemulsification surgery. It is commercially available as Membrane Blue (DORC) in a 0.15% solution to stain the ERMs. Incidentally, its name is derived from its property to destroy trypanosomes, which are the causative agents for sleeping sickness.

Brilliant blue G was introduced as a dye with no in vivo toxicity. This lack of toxicity was explained by its water solubility, which leads to easy washing away of the dye and poor penetration through cell membranes. It does not stain ERMs and hence aids differentiation between both tissues.

Newer blue dyes, such as Patent blue and Bromophenol blue, have also undergone trials, and they claim to have very little toxicity, but their clinical advantage over the other dyes is not yet clear.²⁴

Efficient excision of vitreous was previously aided by 0.6% sodium fluorescein, but it has been replaced by TA. This steroid has been used to identify vitreous because its particles adhere to acellular vitreous strands. These particles also precipitate on the ILM and help in identifying it.

The disadvantages of TA are:

1. TA crystals are found in the eye up to 40 days after macular hole surgery, which could potentially slow healing; and

2. TA is toxic to RPE cells.

3. After reports of infectious and noninfectious end-ophthalmitis following ophthalmic use of TA, it was concluded that the inflammatory reaction was due to the preservative (benzyl alcohol) or other excipients in nonpreserved TA. Triesence (Alcon, Fort Worth, TX) is the only commercially available, preservative-free TA licensed for visualization during vitrectomy.

Dyes and Light Sources

Dyes on the retinal surface or those that have inadvertently seeped into the subretinal space potentially carry the risk of phototoxicity by photosensitization and the release of free radicals to the neuroretina when stimulated by light of wavelengths greater than 450 nm.

Vital dyes have shown variable osmolarity and pH in saline solution and glucose 5%. Dyes dissolved in water have lower osmolarity. Spectral overlap between the absorbance of vital dyes and the endoillumination emission spectrum could cause or enhance retinal toxicity. Appropriate selection of both dye and light is a desirable way to minimize the risk of phototoxic effects.²⁵

In this regard, the mercury vapor light sources were found to be the safest among the variety available, while the lowest overlap values among the dyes were observed with indocyanine green prepared in BSS.²⁶

Dye Injection Techniques

The two main techniques of dye injection into the vitreous cavity are:

1. “Air-filled” – when dye is dripped onto the posterior pole after fluid/air exchange; and

2. “Fluid-filled” – when dye is injected in the presence of fluid (usually BSS).

The former has the advantage of a greater concentration of dye and staining of the tissue, but it can also be more toxic to the posterior retina. The latter, in contrast, is less toxic and faster, but at the same time, it does not stain so intensively.

There are ongoing research projects on the possibility of the introduction of dyes made from natural products, such as acai fruit, turmeric, paprika, indigo, and so on. The best capability for ILM staining was obtained with acai fruit extract, cochineal, and chlorophyll extract from alfalfa.²⁷

A new combination dye, comprised of lutein/zeaxanthin crystals 0.3% and Brilliant blue 0.025%, was tested recently. The advantage was its ability to stain the posterior hyaloid/vitreous base with the lutein/zeaxanthin crystalline component and the ILM with the Brilliant blue dye, thus providing better differentiation. Theoretically, this dye has a good safety profile, but further trials are needed.

CONCLUSION

The patient’s visual outcome depends on the surgeon’s view of the pathology in question, both literally and metaphorically. Visualization can be improved by clearing the path of light, or on the contrary, aiding the visualization of transparent structures such that one can be differentiated from the other.

Better optics (WAVs), improved illumination, novel techniques (eg, use of air-vitreous interface), new technology (3D endoscopy, intraoperative OCT), and better staining techniques facilitate our view of areas of the retina that were previously nearly impossible to see.

Much of the research these days also has emphasized safety and ease of use. Researchers try to find ideal dyes that can be used in their lowest concentrations to achieve good staining almost instantaneously and that cause minimal harm to the ocular structures.

Surely, as more fundamental research comes to light and is translated into practical application, our understanding of pathology, and thus, the techniques to confront it will be refined. RP

REFERENCES