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Leonardo Mastropasqua – [email protected]
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GLAUCOMA
Trans-scleral outflow
Current glaucoma treatments do not fully exploit the trans-scleral
outflow pathway
Courtesy of Leonardo Mastropasqua MD
by Roibeard O’hEineachain in Milan
Figure 1: Planar reconstruction of the superior bulbar
conjunctiva in an eye with ocular hypertension. Microcysts appear
as optically clear spaces within the conjunctival epithelium
of the bulbar conjunctiva, indicating the trans-scleral
aqueous humour passage
“I
n the near future, improving the
trans-scleral outflow of aqueous
humour could represent an
important strategy for reducing
intraocular pressure (IOP) in patients with
glaucoma,” said Leonardo Mastropasqua MD,
director of the Excellence Eye Centre at the
University G d’Annunzio of Chieti-Pescara,
Chieti, Italy.
During his keynote speech at the Glaucoma
Day sessions at the XXX Congress of the
ESCRS, Prof Mastropasqua stated: “Transscleral outflow is the last step of the uveoscleral outflow pathway and plays a key role
in ocular hydrodynamics. In fact, the sclera
has a good hydraulic conductivity and offers
poor resistance to aqueous humour passage.
The sclera is also a very accessible structure
for surgery.” He also noted that the human
eye has two main pathways for aqueous
outflow: the trabecular and the uveo-scleral
outflow pathway. The first accounts for 80 per
cent of aqueous outflow and the second for
20 per cent, on average, with measurements
ranging from 12 per cent to 54 per cent.
He explained how the aqueous humour
that flows out from the anterior chamber
through the uveo-scleral pathway first
passes between the ciliary muscle bundles
into the supraciliary and suprachoroidal
spaces. Hence, aqueous humour drains
either towards the choriocapillaris, reaching
the blood circulation, or externally, passing
through the sclera and conjunctiva. From
here, final aqueous humour resorption is
guaranteed by lymphatics vessels and veins,
or by trans-conjunctival passage towards the
ocular surface. All these terminal outflow
pathways bring aqueous to extra-orbital
tissue. Adding that uveo-scleral outflow
EUROTIMES | Volume 18 | Issue 2
Figure 2: Slit-lamp image showing a cystic/diffuse functioning filtering bleb (A). In vivo confocal microscopy the conjunctiva shows
numerous and wide fluid-filled hyporeflective microcysts, indicating the aqueous humour passage through the bleb-wall (B)
tends to decrease with age because of an
accumulation of fibrillar extracellular material
in the ciliary muscle and ciliary processes.
Improving uveo-scleral pathways
At present there are both medical and
surgical approaches to increase uveo-scleral
outflow in eyes with glaucoma. For example,
prostaglandin analogues improve this
pathway by widening and decompressing
the connective tissue in the ciliary muscle
and remodelling the extracellular matrix
by increasing the secretion of matrix
metalloproteinases.
Among surgical procedures, cyclodialysis
increases both the rate of uveo-scleral (by
a factor of four) and trans-scleral outflow.
However, the procedure has a high frequency
of complications, which can themselves result
in a high rate of failure and elevated IOP.
Another surgical possibility is to place a
shunt between the suprachoroidal space and
the anterior chamber, Prof Mastropasqua
said. Although the treatment is effective at
first, the lumen of these implants are prone
to encapsulation and obstruction of flow with
fibrous connective tissue.
Improving trans-scleral pathways
Another possibility is treatments focusing
specifically on enhancing the trans-scleral
portion of the uveo-scleral outflow, Prof
Mastropasqua said. Laboratory studies have
shown that the potential outflow of aqueous
through the sclera is two to three times higher
in vitro than it normally is in vivo, in the eye
of a patient.
Interestingly, in patients affected with
untreated ocular hypertension or medically
treated open angle glaucoma, trans-scleral
outflow is two to five times greater than in
healthy subjects, probably representing an
adaptive mechanism for overcoming the
increased trabecular resistance to aqueous
outflow. (Ciancaglini et al. Invest Ophthalmol
Vis Sci. 2008; 49(7):3042-8. Agnifili et
al. Acta Ophthalmol. 2012;90(2):e132-7.
doi: 10.1111/j.1755-3768.2011.02255.x.).
Exploiting that potential through surgical or
medical approaches could represent a useful
strategy for IOP reduction, alternative to the
current fistulasing procedures.
Besides in vitro measurements, transscleral outflow may also be measured in vivo,
by using laser scanning confocal microscopy
to evaluate the density and surface of
conjunctival epithelial microcysts. These
microcysts represent the hallmark of the
trans-conjunctival passage of the aqueous
humour, as reported by Ciancaglini and
Mastropasqua in 2008 (1. Ciancaglini et al.
Invest Ophthalmol Vis Sci. 2008; 49(7):30428) (Figure 1). These structures were first
described within the bleb wall of functioning
trabeculectomy (Figure 2). Prof Mastropasqua
and his associates reported epithelial
microcysts were greater in both size P=0.017)
and number (P=0.014) in the successful blebs
when compared to failed blebs (Ciancaglini et
al. J Glaucoma. 2008. 17(4):308-17.).
As is the case with uveo-scleral outflow in
general, there are already both medical and
surgical techniques that specifically enhance
trans-scleral aqueous outflow, he noted. For
example, prostaglandin analogues increase
the trans-scleral permeability by increasing
the secretion of matrix metalloproteinases,
which lead to remodeling of collagen fibres .
Surgical procedures that thin the sclera
may potentially lead to a significant
enhancement of the trans-scleral aqueous
humour outflow. This was originally reported
in the partial thickness laminar dissection of
the sclera, he said.
Currently, different surgical approaches
work by also reducing the scleral thickness.
Canaloplasty, a standardised treatment that
improves the trabeculo-canalicular outflow,
appears to increase aqueous outflow also
through the sclera and conjunctiva. Unlike
trabeculectomy, a conjunctival bleb is not
created since a watertight suture at the site
of surgery is mandatory. However, like
trabeculectomy it does increase the size
and concentration of epithelial microcysts;
probably because the sclera is thinned at the
surgical site. In a study involving a series of 30
patients who underwent canaloplasty, there
was a four-fold increase from baseline in the
number of conjunctival microcysts in the 27
eyes in which the procedure was successful,
but the microcyst concentration did not
increase significantly in the eyes in which the
procedure was unsuccessful (Mastropasqua et
al. Br J Ophthalmol 2012; 96:634-639).
New techniques Other techniques now
in the pre-clinical phase of investigation
include the creation of intrascleral canals
injected with non-animal stabilised
hyaluronic acid (NASHA). A study involving
porcine eyes showed that the scleral canals
had a significantly higher rate of aqueous
outflow than control eyes (Mavrakanas et al.
Invest Ophthalmol Vis Sci. 2009; 50: 37593762).
Techniques that create intrascleral canals
with femtosecond lasers may be even more
promising. A three-dimensional finite
element model indicated that creating partial
thickness intrascleral channels may reduce
IOP from 67.2 per cent to 80.6 per cent (Chai
et al. Lasers Surg Med. 2008;40:188-195).
In addition, an in vivo study showed
that rabbit eyes that had undergone scleral
channel creation with a femtosecond
laser had significantly lower IOP than the
contralateral control eyes. The IOP reduction
appeared to result from an increase in
aqueous humour outflow through the sclera
(Chai et al. Lasers Surg Med. 2010; 42(7):647651). The investigators used a titanium/
sapphire laser system tuned to the wavelength
of 1.7 microns with an optical parametric
amplifier. They scanned the femtosecond
laser beam along a rectangular raster pattern
to create partial thickness subsurface drainage
channels in the sclera.
Prof Mastropasqua concluded, “Scleral
thinning with a femtosecond laser represents
a valuable field of research in glaucoma
surgery and may enhance trans-scleral
outflow while avoiding sub-conjunctival
aqueous humour percolation and bleb
formation.”
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