PEER REVIEWED
Advances
in Visualization During Vitrectomy Surgery
KRISTIE
L. LIN, MD, & HOWARD F. FINE, MD, MHSc
INTRODUCTION
Visualization
is crucial in surgery, and ophthalmology is no exception. However, vitrectomy surgery
poses a number of unique challenges: many of the tissues involved are nearly transparent,
the globe is relatively small in size, and special optical systems are necessary
before a view is possible. Even then, some structures are optically inaccessible
without special manipulation, and just a few drops of blood in the surgical field
can completely obscure the view.
Improved visualization during vitrectomy therefore remains an
ongoing quest for vitreoretinal surgeons. Several innovations have allowed this.
Wide-angle viewing systems and the use of endoscopy during vitrectomy provide unfettered
admission to areas that were previously inaccessible — namely the peripheral
retina and vitreous base, wherein lies a vast amount of vitreoretinal pathology.
The advent of smaller gauge, sutureless vitrectomy has also prompted the need for
improved endoillumination through smaller instruments or from an additional fourth
sclerotomy site. Tissue dyes are also employed to improve visualization and accurately
remove thin and transparent tissue. One such use is staining of the internal limiting
membrane (ILM) during macular hole repair and epiretinal membrane removal. Intraoperative
hemorrhage can be a major problem by obscuring the view during vitrectomy.
Various pharmaceutical agents and instruments are used to decrease
hemorrhage and improve visualization. For example, preoperative bevacizumab (Avastin,
Genentech) is used to decrease intraoperative hemorrhage during tractional retinal
detachment repair in proliferative diabetic retinopathy. Intraoperative thrombin
and use of an end-aspirating endoilluminator (Alcon Laboratories, Fort Worth, Texas)
also decrease bleeding. This article will review these modalities to facilitate
visualization: wide angle viewing systems, endoillumination, tissue staining, and
the use of pharmaceutical agents to promote intraoperative hemostasis. Both bevacizumab
and thrombin are used here in an off-label capacity.
WIDE-ANGLE VITRECTOMY LENS SYSTEMS
Lens systems for vitrectomy initially employed planoconcave or
biconcave lenses, which afforded only a 20� to 35� view.1
The retinal periphery was difficult to visualize, as even prism lenses could not
provide visualization much past 60�.2
Wide-angle viewing systems were introduced and took advantage of the same principle
on which the indirect ophthalmoscope is based: the astronomical telescope. In this
system, the cornea and lens act together as the objective and the high-plus condensing
lens as the eyepiece. This produces a real inverted aerial image of the retina and
vitreous. However, performing bimanual surgery in an inverted fashion is counterintuitive
for humans. Stereoscopic image inversion systems solve this problem typically with
the use of 2 adjoining but orthogonally oriented prisms that can be moved into or
out of the viewing path of the microscope3
in either a manual or mechanized manner.
Two types of wide-angle viewing systems for vitrectomy surgery
exist: noncontact systems and contact systems. Each type has advantages and disadvantages.
Contact systems typically provide a wider field of view with fewer aberrations and
reflections. This is because the lens is directly coupled to the cornea via a viscous
agent such as viscoelastic (eg, Healon, Advanced Medical Optics, Santa Ana, Calif)
or hydroxypropyl methylcellulose (ie, Goniosol, Novartis). However, either a lens
ring must be sewn on or a skilled assistant will be required to maintain the image
quality. Contact lens systems include those produced by: Advanced Visual Instruments,
Inc. (New York); Volk Optical, Inc. (Mentor, Ohio); and Ocular Instruments, Inc.
(Bellevue, Wash).
Noncontact systems do not require a skilled assistant, and they
cause less trauma to the corneal epithelium. Scleral depression is typically easier
and manipulation of the microscope foot pedal remains consistent whether or not
the image is inverted. The Insight Instruments binocular indirect ophthalmomicrosope
(Stuart, Fla) employs a stereo inverter above the microscope objective, while the
Moeller erect indirect binocular ophthalmic system, or (Hamburg, Germany), uses
an inverter below the objective.
Wide-angle
viewing systems have revolutionized vitrectomy procedures because surgeons now have
access to the peripheral retina and vitreous base, the site of a vast amount of
vitreoretinal pathology.
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Figure
1. Triamcinolone acetonide assisted pars plana vitrectomy. A. The arrowhead shows
that the posterior hyaloid can be separated from the retina by a silicone-tipped
needle. B. The case of rhegmatogenous retinal detachment. C. The arrow shows that
the island of the thin posterior hyaloid membrane stained with triamcinolone acetonide
granulates on the macula. D. This membrane was removed by internal limiting membrane
forceps (arrowhead) easily in the case of proliferative diabetic retinopathy.
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ILLUMINATION SYSTEMS
The introduction of wide-angle viewing systems was coupled with
the development of more powerful light sources. While increased power allows for
improved illumination, it is also associated with a higher risk of retinal phototoxicity.
Retinal toxicity is thought to be secondary to photochemical exposure to shorter
wavelength light, particularly ultraviolet and visible blue light.4
This can disrupt the blood-retinal barrier function and hence blue-light–blocking
filters are used.5-7
Phototoxicity thresholds have been studied extensively to maximize
exposure time and minimize risk when developing light sources for vitrectomies.
Standard light sources available on a 20-gauge fiberoptic light probe include tungsten-halogen
and metal halide available as the Alcon Accurus (Fort Worth, Texas) and Bausch &
Lomb Millennium (Rochester, NY). These light sources typically have a maximum illumination
of 10 lumens, which is roughly halved when used with lighted instruments, wide-angle
probes, and chandelier systems through a standard 20-g light probe, leading to a
significant drop in illumination.8
The recent development of xenon light sources provides increased power output, with
increased illumination in smaller gauge probes and chandelier systems. To reduce
the risk of retinal phototoxicity, safety measures have been advocated. These include
the recommended use of a
475 μm long pass filter to block blue light, the
lowering of the power output, and perhaps most importantly, increasing the distance
between the light probe and the retina.9
Xenon light has been shown to have similar safety profiles in comparison to tungsten-halogen
and improved safety relative to metal halide light sources.10,11
One of the advantages of a xenon light source is the option to
use it as an ancillary light in combination with wide-angle illuminators and instruments
such as forceps or tissue manipulators. Another major advantage is that it can be
used as the sole light source in a chandelier system, allowing bimanual surgery
helpful in proliferative vitreoretinopathy (PVR) membrane dissection or peripheral
and anterior vitreous base dissection (see Figure 6 in "Evolutionary and Revolutionary
Trends in Vitreoretinal Surgery" by P Bhatnagar, HF Fine, and I-V Ho on p.
27). These also offer a wider angle of illumination, which is useful in 360-degree
scleral depression. Given the increased working distance from the retina, this can
significantly decrease retinal phototoxicity.9
Some currently available options include the Tornambe Torpedo (Insight Instruments,
Buffalo, NY), the 25-g Awh Chandelier (Synergetics, O'Fallon, Mo), and fourth-port
25-g plug-in chandeliers such as the DORC Neptune Dual Chandelier (Kingston, NH).
Vitreoretinal Endoscopes
Wide-angle viewing systems and powerful light sources allow access
to the far peripheral retina and ciliary body, but they often require scleral depression.
Ophthalmic endoscopes can provide complete assessment of the pars plana in its natural
state without scleral depression, and they can extend surgical control where standard
microscopic views are limited. In complicated cases of proliferative vitreoretinopathy
and iris neovascularization, where a small pupil, hyphema, or opaque posterior capsule
can prevent complete visualization — even with standard and panoramic contact
lenses — ophthalmic endoscopy can augment control in the retroirideal area.12
When used in conjunction with intraoperative fluorescein angiography, vitreoretinal
endoscopy can identify pathologic areas in the pars plana and aid in intraoperative
evaluation and further surgical treatment of complicated diabetic retinopathy.13,14
Endoscopy can also facilitate the management of complications of cataract surgery.
It is used to visualize retained lens fragments that can be embedded in the vitreous
base and to provide precise haptic placement in posteriorly dislocated intraocular
lens implants.15,16 The learning
curve can be steep as the surgeon's view is via television screen and therefore
lacks stereopsis. However, new technology with high-definition televisions and 3-D
software can now provide high-resolution stereoscopic views.17
VISUALIZATION AGENTS
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Figure
2. Operating microscope view demonstrating the continuous ILM peel in progress.
A triangular flap of ILM is seen being peeled by forceps. Arrowheads indicate the
area of ILM peeled in contrast with the unpeeled trypan blue stained ILM.
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Visualization of the ILM
Another advance in visualization during vitreoretinal surgery
is the use of tissue dyes for selective staining of the ILM during removal. Various
substances such as indocyanine green (ICG), trypan blue, and triamcinolone acetonide
can be used. Note that all of these substances are used for this purpose off-label.
Kadonosono et al reported the use of ICG to facilitate removal of the transparent
ILM (see Figure 1 in "Evolutionary and Revolutionary Trends in Vitreoretinal Surgery" by
P Bhatnagar, HF Fine, and I-V Ho on p. 25).18
Augmenting visibility of the ILM allows for effective and safe removal with less
risk of retinal damage.
Many
authors report positive outcomes in ILM removal with the use of ICG. Recent studies
have shown equivalent anatomic and visual outcomes with and without the use of adjunctive
ICG in ILM removal.19-24
Mavrofrides et al showed that ICG usage during macular hole surgery was not associated
with worse visual outcome and that possible toxic side effects reported were not
clinically significant.19
Kumagai et al reported decreased rates of macular hole reopening with ILM removal.21-22
However, the use of ICG has been controversial, given reports of toxicity to the
retinal pigment epithelium (RPE). While the exact etiology of ICG-related retinal
toxicity is unclear, experimental in vitro studies have suggested a cytotoxic mechanism
with induced apoptosis of the RPE.25,26
Rabbit and mouse studies in vivo have been correlated with alterations in electroretinograms
and histology.27-29
Clinical reports of poor visual acuity and visual field defects post-ICG application
with ILM peeling were attributed to ICG-related toxicity.30-35
Notably, visual field defects have also been documented in cases of macular hole
surgery without ILM removal.36
The deleterious effects of ICG appear to be compounded with increases
in phototoxicity. Expression of apoptosis genes is upregulated in a dose-dependent
manner when ICG is applied to human RPE cells. This effect was more pronounced with
the direct application of endoillumination.27,37
While some argue that ICG phototoxicity is exacerbated most with light exceeding
wavelengths of 620 μm,30
others noticed no change when applied in conjunction with a halogen light source
for 15 minutes.38
Long-term intravitreal ICG in rat eyes caused ICG-related toxicity
to retinal ganglion cells that was amplified when endoillumination was simulated.27
However, in this experimental model, the dye was left inside the eye for 1 month.
This does not mirror clinical practice, in which ICG is typically applied for only
10 to 60 seconds and then immediately removed. With recent reports of persistence
of intraocular ICG for anywhere from 1 to 8 months, this could become a potential
source of concern.39-41 Given
the continued dichotomy between theory and practice, the judicious use of ICG for
ILM staining is currently advocated by many in ILM removal for macular hole surgery.
Triamcinolone Acetonide
Triamcinolone acetonide is a corticosteroid suspension that is
commonly injected in an off-label fashion into the vitreous for the treatment of
a wide variety of disorders, including retinovascular disease and macular degeneration.
The crystals adhere to the vitreous gel, effectively highlighting the vitreous.
This property can be extremely helpful in determining the location and attachments
of the vitreous. For instance, intravitreal triamcinolone is useful while inducing
a posterior vitreous separation intraoperatively or for highlighting peripheral
vitreous when shaving the anterior vitreous base. Triamcinolone has been proposed
as an alternative to ICG to enhance visualization of the internal limiting membrane.42-44
Triamcinolone is typically much less expensive than ICG and avoids toxicity to the
RPE associated with ICG. Histological specimens collected at the time of removal
confirm successful identification and delamination of the ILM with the use of triamcinolone.43
While it does not selectively stain the ILM, it improves visualization by dusting
the ILM and providing a map for the surgeon to see what remains to be peeled (Figure
1). There is a large published experience with intravitreal triamcinolone in the
literature, and well-documented side effects include steroid-induced glaucoma and
cataract, typically at much higher concentrations than what remains after assistance
for ILM peeling. A recent study using an in vivo rabbit model did not show histologic
changes in the retina at triamcinolone concentrations of 0.5 mg or 1 mg, but it
did note a dose-dependent retinal toxicity of the photoreceptor outer segments and
RPE at higher triam-cinolone doses of 4 mg, 8 mg, and 20 mg.45
Trypan
Blue
Trypan blue stains basement membranes and first gained widespread
use in ophthalmology to stain the anterior lens capsule in preparation for capsulorhexis.46,47
Trypan blue has also successfully been used as an alternative dye to stain and assist
in ILM and epiretinal membrane (ERM) removal (Figure 2).48
In vitro studies on human RPE cell lines have demonstrated no trypan blue dye related
cell toxicity at concentrations as high as 1.5 mg/mL (stock solution). Clinically,
doses are typically given at a concentration of 0.075 mg/mL (one-twentieth of stock
solution).49 A retrospective
study using trypan blue at a concentration of 0.06% during pars plana vitrectomy
with ILM delineation and removal reported no toxic or adverse effects after 1 year.50
As it has become increasingly accepted that ILM removal improves
anatomic and visual outcomes, new dyes have been investigated to facilitate ILM
staining and removal while minimizing retinal toxicity. Brilliant blue G has been
suggested as a safer alternative tissue dye.51
Haritoglou et al have evaluated novel vital dyes, such as light green SF yellowish,
copper (II) phthalocyanine-tetrasulfonic acid, bromophenol blue, and Chicago blue,
for intraocular surgery.52
MINIMIZING BLEEDING
Preoperative Bevacizumab to Decrease Intraoperative Hemorrhage
Intraoperative hemorrhage can be a major obstacle during vitrectomy
for sequelae of proliferative diabetic retinopathy (PDR), such as tractional retinal
detachment. Vascular endothelial growth factor (VEGF) has been implicated in the
pathogenesis of PDR, and vitreous levels of VEGF are markedly elevated in PDR. Bevacizumab
is a humanized murine monoclonal antibody that binds VEGF. Bevacizumab was developed
and approved by the FDA for the treatment of metastatic colorectal cancer.53
Intravitreal bevacizumab has been used extensively to retard intraocular angiogenesis
and vascular permeability. Early experience with intravitreal bevacizumab suggested
that it might reduce hemorrhage associated with neovascularization. Intravitreal
bevacizumab was injected in 2 patients with severe PDR complicated by vitreous hemorrhage
and resulted in rapid regression of both the neovascularization and vitreous hemorrhage.54
Given these promising results, it was hypothesized that using bevacizumab preoperatively
in patients with severe PDR and tractional retinal detachments could cause regression
of neovascularization and decrease the risk of intraoperative hemorrhage.55
Bevacizumab was then given intravitreally 2 weeks preoperatively with significant
regression of neovascularization seen on fundus photography.
Preoperative regression of neovascularization allows for more
straightforward removal of fibrotic tractional membranes with minimal bleeding during
segmentation and delamination.
Intravitreal Thrombin
Another adjuvant used to minimize intraoperative hemorrhage is
intravitreal thrombin. In vivo and clinical studies have shown a significant reduction
in both bleeding time after cutting vascularized membranes and overall rate of intra-
and postoperative bleeding.56,57
Toxicity studies show no effect on the lens, corneal endothelium, or visual acuity.58,59
Electroretinograms demonstrated normal b-wave amplitudes, but decreased sensitivity
has been noted.60 Given the
lack of toxicity, postoperative hemostasis can be maintained for up to 1 week if
the intravitreal thrombin is not washed out.59
CONCLUSIONS
Improved visualization during vitrectomy surgery is one of the
major factors that has improved surgical outcomes and allowed retinal physicians
to approach more and more difficult cases. Wide-angle viewing has afforded surgeons
a three-dimensional intraoperative view of the peripheral retina, vitreous base,
ora serrata, pars plana and pars plicata, and ciliary body. Illumination systems
have evolved along with smaller-gauge surgery, and newer light sources allow for
bimanual surgery, wider-angle viewing to visualize anterior ocular structures, and
improved contrast for detecting subtle membranes and the ILM. Ophthalmic endoscopy
can provide complete assessment of the retroirideal space in its natural state without
scleral depression and extend surgical control where standard microscopic views
are limited. Tissue-staining techniques have provided methods to better illuminate
vitreous gel, aiding in posterior vitreous separations and anterior vitreous shaving,
as well as highlighting membranes and the ILM to improve the ability of surgeons
to perform peeling procedures. Finally, therapeutics designed to reduce intraoperative
bleeding simplify surgical cases and improve outcomes. Future advances in the field
of vitrectomy surgery will undoubtedly include further improvements in visualization.
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Kristie
L. Lin, MD, practices ophthalmology at the St. Vincent Catholic Medical Center in
New York. Howard F. Fine, MD, MHSc, is a postdoctoral clinical fellow with the Harkness
Eye Institute of the Columbia University College of Physicians and Surgeons in New
York and practices ophthalmology at Vitreous Retina Macula Consultants of New York.
Neither author has any financial interest in any of the information contained in
this article. Dr. Lin can be contacted at (212) 604-8041.
Retinal Physician, Issue: November 2006