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Lamina Puncture
Pars Plana Optic Disc Surgery for Central Retinal Vein Occlusion
Eugene S. Lit, MD;
Miltiadis Tsilimbaris, MD;
Eustratios Gotzaridis, MD;
Donald J. D'Amico, MD
Arch Ophthalmol. 2002;120:495-499.
ABSTRACT
Objective To determine the feasibility of creating a perivascular space adjacent
to the central retinal vein at the level of the lamina cribrosa as a potential
method of reestablishing perfusion in central retinal vein occlusion.
Methods Various designs for a puncture instrument, or lamina puncture lancet,
were investigated in cadavers, pigs that had undergone enucleation, and in
vivo rabbit eyes.
Results A lancet with a sharp cutting edge on one side and an opposing blunt
edge is repeatedly able to create a perivascular space with limited optic
nerve fiber damage.
Conclusions Lamina puncture is technically feasible, and evaluation in carefully
selected patients appears warranted.
INTRODUCTION
CENTRAL RETINAL vein occlusion (CRVO) remains a difficult and often
frustrating disease for both the patient and the ophthalmologist. Although
some younger patients with nonischemic forms may recover, most patients with
CRVO are left with poor vision; in patients with widespread capillary nonperfusion,
less than 10% maintain a visual acuity better than 20/400 OU.1
No treatment has proved useful in improving vision, and ophthalmic care is
supportive with observation for the development of iris neovascularization
and the need for intervention with retinal ablation.2
Histological studies suggest that regardless of the level of perfusion,
most or all cases of CRVO result from thrombus formation in the central retinal
vein at or just posterior to the lamina cribrosa.3
Anatomically, the luminal diameter of the central retinal vein is narrowest
at this level, resulting from the relatively denser connective tissue that
makes up the lamina cribrosa encircling the retinal vessels. The development
of CRVO is undoubtedly multifactorial, including the resultant increased turbulence
in blood flow, possible concomitant endothelial cell damage, and possible
systemic factors, and results in a wide variety of CRVO forms with variable
degrees of perfusion. Nevertheless, the mechanical constriction of the central
retinal vein at the lamina cribrosa predisposes this location to thrombus
formation.
We postulated that it might be possible to restore normal perfusion
to the central retinal vein if a surgical technique could be developed to
release the constriction of the central retinal vein by the surrounding connective
tissue at the level of the lamina cribrosa. The resulting increase in luminal
diameter of the central retinal vein might allow the passage of a thrombus.
Alternatively, the increased intraluminal diameter might permit sufficient
blood flow at the level of the lamina cribrosa to allow for increased perfusion
of the retina, even if the thrombus was not dislodged or expressed mechanically.
We tried to determine the feasibility of transvitreal optic disc surgery
to create a perivascular opening in the lamina cribrosa, which we termed lamina puncture, as a prelude to considering such an intervention
in patients with CRVO.
MATERIALS AND METHODS
Initial experiments were performed on human cadaver eyes and enucleated
pig eyes; the latter were chosen for their anatomical similarity to human
eyes. Lamina puncture was performed in enucleated eyes after removing the
anterior segment, including both the vitreous and the vitreous base. This
preparation permitted direct visualization of the posterior eye cup and optic
disc using a dissecting microscope. Subsequent experiments used intact Dutch-belted
rabbits in a transvitreal approach. These experiments were reviewed and approved
by the animal review committee at our hospital. After anesthesia with 3 to
5 mL of a mixture (1:1) of intramuscular ketamine hydrochloride (100 mg/mL)
and xylazine hydrochloride (20 mg/mL), the animals were placed under a dissecting
microscope, and adequate anesthesia was confirmed. Following a localized peritomy,
a 1.5-mm superior sclerotomy was performed approximately 1.5 mm posterior
to the limbus. The lamina puncture lancet was introduced through this sclerotomy
without removal of the vitreous. A contact lens and operating microscope were
used for visualization and illumination. The various lancets were moved across
the vitreous and into the optic disc. The rabbits were euthanized, and the
eyes were enucleated after 3 to 4 minutes of observation for hemorrhage and
confirmation of retinal vascular perfusion. All tissues were processed for
light microscopy using conventional techniques.
The instruments were initially shaped from copper and molten glass.
These 2 materials were selected for their ductility, relative strength, and
ability to be used in areas with small dimensions, all of which facilitated
frequent early changes.
Subsequent modifications were refined on instruments made of surgical
stainless steel. Lamina puncture lancets were evaluated for each instrumental
design on the basis of the following parameters: the ability to create a perivascular
space around the central retinal vein, the presence and degree of damage to
the vessel wall, the amount of residual connective tissue adjacent to the
vessel wall, and the amount of damage done to nerve fibers.
RESULTS
Initial experiments on enucleated eyes were encouraging because the
vessel wall of the central retinal vein appeared to be much stronger than
the connective tissue fibers of the lamina cribrosa, and consequently it was
possible to selectively disrupt the lamina cribrosa without violating the
integrity of the central retinal vein. Although blunt lamina puncture lancets
in combination with multiple passes and a slightly roughened surface were
very effective in stripping away connective tissue from around the central
retinal vein, these instruments caused significant collateral damage to the
optic nerve fiber tissue (Figure 1).
Puncture instruments with a sharp cutting edge were superior to blunt instruments
in minimizing the area of damage to optic nerve fibers, but this cutting edge
created damage in the central retinal vein wall if directed against the vessel
(Figure 2).
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Figure 1. The optic nerve in an enucleated
pig eye after lamina puncture using a blunt lancet. The vessel wall remains
intact, but there is significant collateral damage to the adjacent neural
tissue (hematoxylin-eosin; original magnification x 20).
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Figure 2. The optic nerve in an enucleated
pig eye after lamina puncture using a sharp lancet. Although there is little
damage to the adjacent neural tissue, the vessel wall integrity has been violated
(hematoxylin-eosin; original magnification x 20).
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As a result, puncture instruments were created that combined a slightly
roughened blunt side with a cutting edge on the opposite side. These lancets
were passed through the optic nerve head with the cutting edge directed away
from the vessel wall. This design required little force to allow a relatively
small puncture to be made through the lamina cribrosa, especially when the
instrument was angled so that the cutting edge entered the nerve head first.
At the same time, the roughened blunt side did not damage the vein wall and
was able to completely strip away the connective tissue of the lamina cribrosa
from the vessel wall with only a few consecutive passes. This final version
was 300 to 400 µm in width, with a sharp portion about 60 µm in
length and a relatively blunt tip (Figure
3). The shaft diameter was equivalent to 20 gauge, allowing it to
be passed through a standard sclerotomy. Small (300- to 400-µm diameter)
puncture wounds were achievable immediately adjacent to the vessel walls,
with no wall damage and minimal optic nerve fiber damage (Figure 4).
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Figure 3. The optic nerve in an enucleated
pig eye after lamina puncture using the final instrument design. There is
little damage to the adjacent neural tissue, and the vessel wall integrity
is maintained (hematoxylin-eosin; original magnification x 20).
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Figure 4. The final instrument design: the
lance tip is blunt, and the surface facing the vessel wall is blunt and slightly
roughened. The opposite edge is sharp, reducing the amount of neural tissue
damage caused during tissue entry. The sharp edge flares out slightly to a
blunt surface and pushes neural tissue aside, further minimizing collateral
damage.
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This final lancet design was then used to create lamina punctures in
8 consecutive in vivo rabbit eyes. In 7 of the 8, there was no bleeding and
grossly normal perfusion after the puncture. The vein wall was intact on histological
examination in all cases (Figure 5).
In the sole eye in which there was bleeding, the amount of blood was minimal,
and hemostasis occurred spontaneously after about 20 seconds. Although the
central retinal vein was intact on histological examination, a small branching
vessel on the optic disc had been severed, accounting for the hemorrhage.
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Figure 5. The optic nerve in an in vivo
rabbit eye after lamina puncture using the final instrument design. There
is little collateral tissue damage with an intact vessel wall (hematoxylin-eosin;
original magnification x 20).
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COMMENT
Although many questions may be raised about the possibility of effective
therapy for an acutely compromising event such as CRVO, the development of
a thrombus at the site of constriction by the lamina cribrosa appears central
to this disease. Consequently, attempts to relieve vascular compromise and
restore blood flow are consistent with the underlying pathophysiologic characteristics
of CRVO. Lamina puncture may relieve constriction on the central retinal vein
and permit thrombus migration or bypass by creating a potentially enlarged
vascular diameter. Furthermore, it is also possible that mechanical compression
of the vein during the procedure might result in clot dislodgment unrelated
to vascular diameter, but this mechanism cannot be evaluated from the available
animal models.
In addition to other concerns regarding the visual efficacy of reestablishing
blood flow by any means, 2 potential limitations to lamina puncture are the
failure of the technique to reestablish perfusion and the possibility of excessive
collateral optic nerve damage. The latter seems unlikely, however, given the
anatomy of the optic nerve head. Macular fibers enter the optic nerve head
along the periphery. With the puncture adjacent to the central retinal vein
and with damage therefore limited to the central portion of the nerve, it
seems reasonable that any reduction in central vision associated with the
puncture would be minimal. Furthermore, for CRVO in patients older than 65
years, the extremely poor natural history for visual recovery suggests that
optic nerve head trauma would not be a significant limiting factor in the
initial evaluation of the procedure. Until further in vivo experiments are
performed, it is not possible to determine if releasing constriction of the
central retinal vein at the level of the lamina cribrosa will allow for mobilization
of the thrombus and reperfusion of the retina.
There have been many previous attempts to develop treatments for CRVO.
Early approaches such as the use of cholesterol-lowering agents4
or x-rays5 did not take into account the cause
of the disease; namely, the formation of a thrombus at the level of the lamina
cribrosa. More recent approaches have been based on this pathogenesis.
Rather than reperfusion of the retina via the central retinal vein,
McAllister, Vijayasekaran, et al,6-8
created a new venous outflow route by forming a chorioretinal venous anastomosis
through the use of high-energy argon lasers. They showed the feasibility of
such anastomosis in both dog and rat models. McAllister and colleagues showed
that similar chorioretinal venous anastomosis could be created in 8 of 24
patients in a small pilot study. Encouragingly, in those 8 patients, not only
was retrograde venous flow demonstrated with some degree of visual improvement,
but the anastomosis seemed to remain patent for the duration of the study,
ranging from 1 to 3 years. Although approximately 40% of the sites with attempts
at anastomosis creation developed hemorrhages, these were all visually insignificant
and resolved spontaneously. Nevertheless, the potential for a significant
hemorrhage exists, as does the development of preretinal and subretinal fibrosis.
A larger multicenter trial is under way to determine the efficacy of this
treatment. The fact that the limited reperfusion achieved in the 33% of patients
in whom an anastomosis could be successfully created was associated with visual
improvement, whereas not statistically significant, is encouraging for our
current study. It suggests that if lamina puncture is successful in improving
retinal venous outflow, there is the potential for visual improvement.
Thrombolytic agents are also used to dissolve a thrombus at the level
of the lamina cribrosa. Early studies using systemic streptokinase9 showed statistically improved vision in patients who
were taking the drug. However, in 3 of 20 patients, severe vitreous hemorrhage
occurred leading to functional blindness. A more recent study used tissue-type
plaminogen activator (tPA), which has a better safety profile than streptokinase,
has a shorter circulating half-life, is less antigenic, and carries less risk
of creating a fibrinolytic state leading to significant systemic hemorrhage.
A pilot study using tPA by Elman10 in 1996
had encouraging results. Fifty-nine percent of the 89 patients with sufficient
follow-up (of an original 96 patients) had 3 or more lines of visual improvement.
However, 3 patients developed intraocular bleeding, and 1 patient had a fatal
hemorrhagic stroke. A decreased risk of extraocular hemorrhage might be achieved
with localized delivery of tPA via retinal vein cannulation. Weiss11 showed that this is technically feasible and was
able to achieve modest improvement in 4 of 8 eyes, with no catastrophic adverse
effects.
Although pharmacologic dissolution of a thrombus may restore blood flow,
this therapeutic strategy does not relieve the constriction of the central
retinal vein at the level of the lamina cribrosa. In addition, endothelial
cell proliferation following venipuncture may further limit lumen size if
constriction around the vessel is not relieved. Nevertheless, the results
of current clinical trials may demonstrate the efficacy of pharmacologic clot
lysis. It may be of interest to explore the combination of local delivery
of a thrombolytic agent with lamina puncture, as both are directed at the
same pathophysiologic dysfunction.
E. Mitchel Opremcak, MD (oral communication, May 2001), has performed
a similar maneuver using an unmodified microvitreoretinal blade and cutting
part of the optic nerve near the central retinal vein as well as the adjacent
peripapillary sclera and retina. In his technique, a single radial incision
is made using a microvitreoretinal blade following vitrectomy. He reports
that he has operated on more than 40 patients using this technique, with an
increase in perfusion of the central retinal vein in most patients and no
cases of significant visual loss. His method appears very similar to our earlier
techniques in which a sharp instrument was used, and for the reasons stated
previously, we believe that our final instrument design may result in less
hemorrhage. Nevertheless, it is encouraging that in his group of patients,
no significant visual loss occurred.
The idea of cutting the sclera surrounding the optic nerve was first
proposed by Vasco-Posada,12 although he did
not have access to modern vitrectomy techniques and used an external approach.
Although one other study13 reports using this
technique, the external approach was not further developed. Because subsequent
histopathologic studies have localized the thrombus to the level of the lamina
cribrosa, an internal approach that can reach the proper anatomical level
seems more direct.
Surgery to enlarge the perivascular tissue in the lamina cribrosa via
a pars plana approach is technically feasible and potentially applicable to
patients with CRVO. A lancet with a sharp cutting edge on one side and a roughened
blunt side placed adjacent to the central retinal vein was repeatedly able
to produce a significant perivascular space with limited collateral nerve
fiber damage. Although the potential efficacy and complications of this procedure
in patients with CRVO are unknown, our study's promising results and the dismal
visual prognosis in certain subgroups of patients with CRVO suggest that lamina
puncture should be evaluated in a select group of patients.
AUTHOR INFORMATION
Submitted for publication October 11, 2001; final revision received
January 6, 2002; accepted January 18, 2002.
Supported in part by the Vitreoretinal Research Fund (Dr D'Amico), Boston,
Mass.
Corresponding author and reprints: Donald J. D'Amico, MD, Massachusetts
Eye & Ear Infirmary, 243 Charles St, Boston, MA 02114 (e-mail: djdamico{at}meei.harvard.edu).
From the Retina Service of the Massachusetts Eye & Ear Infirmary
and the Department of Ophthalmology, Harvard Medical School, Boston, Mass.
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