Ultrasound biomicroscopy outcomes after laser peripheral iridotomy in narrow occludable angles
Mary Ruth M. Quilendrino, MD, Patricia M. Khu, MD, Margarita Lat-Luna, MD
GLAUCOMA is a major cause of ocular morbidity
worldwide. In the Philippines, it is the third leading cause
of bilateral blindness and the leading cause of irreversible
bilateral blindness.
1
Among Asians, primary angle-closure
glaucoma (PACG) is the most common type,
2
with the
prevalence among Southeast Asians lower than that of the
Chinese but higher than that of Indians.
3-4
Eyes with appositional closure or occludable angles are
at risk for progressing into synechial angle closure and
angle-closure glaucoma. There are few published data on
the natural history of primary angle-closure suspects
(PACS). A population-based study in Alaska reported 35%
progression to primary angle closure (PAC) or PACG over
10 years.
5
Another population-based study in South India
reported progression of PACS to PAC in 22% in the
absence of treatment, and progression of PAC to PACG
in 28.5% over 5 years.
6
Laser peripheral iridotomy (LPI) remains the standard
prophylactic management for angle closure, eliminating
pupillary block and causing an increase in angle width. It
has, however, not been demonstrated to be an effective
prophylaxis in gonioscopically narrow angles. In a retrospective analysis of post-LPI patients in India, no eye with
PACS progressed to PAC or PACG in nearly 4 years,
showing how LPI can favorably alter its natural course.
7
However, it has been argued that because of the large
number of patients affected with PACS and their relatively
lower risk of progression, LPI may not be indicated for all
diagnosed patients. Some studies suggested that unless
there was a risk factor that could be identified, LPI may
not be warranted.
6 To better understand PACS and the role LPI plays in it,
several studies have utilized various imaging modalities
that allow documentation of anterior-chamber-angle
anatomy in eyes with PACS. Ultrasound biomicroscopy
(UBM) is one such modality capable of giving reproducible images of angle anatomy and detecting small changes
in response to other stimuli, both qualitatively and
quantitatively. Some studies have demonstrated through
UBM significant angle widening in occludable angles
treated with LPI.
8-9 However, one prospective interventional study conducted in Singapore reported that 20%
of eyes had residual angle closure as determined by
gonioscopy, and 59% of eyes with patent iridotomy were
found to have iridotrabecular contact as documented by
UBM even after LPI.
8 This brought about suggestions that
the presence of narrow angles is related not only to
pupillary block, but to mixed mechanisms in which
nonpupil block coexists with pupil block. Factors involved
in causing nonpupil block are not well understood. Few
studies have correlated ciliary body
10
and iris properties
11
to presence of occludable angles.
This study was conducted to characterize the features of NOA or PACS using UBM before and after LPI. It
specifically aimed to describe qualitative and quantitative
UBM findings in NOA or PACS in Filipino eyes and to
determine the degree of angle opening achieved by LPI
using UBM.
METHODOLOGY
This is a prospective interventional study involving
patients 40 to 80 years old who were seen at the glaucoma
clinic of the Department of Ophthalmology and Visual
Sciences, University of the Philippines–Philippine General
Hospital from October 2007 to September 2008 and
diagnosed with NOA or PACS at the time of initial
screening. NOA or PACS was defined as appositional
contact between peripheral iris and posterior trabecular
meshwork (PTM), with ≥ 180 degrees of the PTM and
scleral spur (SS) not visualized on primary gaze during
gonioscopy and intraocular pressures (IOP) ≤ 21 mm Hg.
6
Excluded were patients with established peripheral
anterior synechiae (PAS) and/or IOP > 21 mm Hg,
established glaucomatous optic neuropathy, significant
cataract of nuclear sclerosis greater than +3, ocular
medication use for the past 2 weeks, any ocular condition
hampering visualization and examination of the anteriorchamber angles (e.g. corneal opacity), history of previous
intraocular surgery or trauma, health conditions
precluding proper performance of the procedures and
follow-up.
All eligible patients underwent baseline ophthalmologic examination, including visual acuity (VA), IOP,
and slitlamp examination. VA was obtained using the
standard Snellen E chart. Best-corrected VA was determined using results of manifest refraction. Three consecutive IOP measurements alternating between 2 eyes were
taken using the Goldmann applanation tonometer, and
the mean for each eye was determined. Slitlamp examination to estimate limbal-chamber depth (LCD) was done
using the Van-Herick method at 25x magnification.
Slitlamp gonioscopy was carried out using a Goldmann
4-mirror goniolens at 25x magnification by a single
experienced gonioscopist in a dimly lit room. A narrow,
short slit beam light was used in examining the inferior,
superior, nasal, and temporal quadrants. Care was taken
to avoid passing the light through the pupil to prevent
false opening of a closed angle. Large, unsteady movements
were avoided to prevent undue pressure on the globe.
The angles were graded according to Shaffer’s classification. Dynamic gonioscopy using the same Goldmann
lens was performed after static gonioscopy of all quadrants.
Biometry was done using OTI-Scan 3D/B/A Scan 1000
(Ophthalmic Technologies, Ontario, Canada). Axial
length, lens thickness, and anterior-chamber depth were
recorded.
UBM was performed using OTI-Scan (Ophthalmic
Technologies,Toronto, Canada) by a single trained and
experienced sonologist under standard lighting
conditions with the room lights off. After instillation of
topical proparacaine as anesthetic, a plastic eyecup was
used to gently part the lids; saline solution was used as a
coupling agent. Images of the 4 quadrants of the anteriorchamber angles were taken while the subjects fixated on
5 standard-distance targets on the ceiling to minimize
variations in accommodation. The images were recorded
in a computer and the required parameters were
measured from the images.
The eyes included in the study were subjected to
neodynium/yttrium-aluminum-garnet (Nd:Yag) LPI by a
second- or third-year resident. Prior to LPI, 2% topical
pilocarpine every 15 minutes for 3 doses and topical
proparacaine were instilled. An Abraham lens with
coupling gel was used. The LPI was placed at the superior
quadrant of the peripheral third of the iris, where the iris
was thinnest. The Nd:Yag laser was initially set at 2 mJ,
then increased up to 6 mJ until the full thickness of the
iris was perforated. The minimum target size of iridotomy
was set at 0.3 mm. The baseline IOP, number of laser
applications, and energy settings were recorded. IOP was
measured 1 hour after the procedure, and any increase
of more than 5 mm Hg was treated with a topical alpha
agonist, topical beta-blocker, and/or topical or oral
carbonic anhydrase inhibitor. All patients were given
prednisolone acetate 1 drop hourly for the first 24 hours,
then every 6 hours for 5 days after the procedure.
Two weeks after LPI, the subjects were required to
return for examination. VA, IOP, gonioscopy, and UBM
were performed as described above.
The following were the outcome measures: gonioscopic
grading of angles before and after LPI, and UBM
qualitative characteristics and quantitative parameters
before and after LPI. Qualitative characteristics noted
were whether each quadrant of the angle and the entire
angle remained closed or opened up after LPI, whether
the iris was inserted anteriorly, and whether the ciliary
body was rotated anteriorly. Anterior iris insertion was
defined as insertion of the iris at the base of the ciliary
process or more anterior to it. Anterior ciliary-body
rotation was considered if the apex of the ciliary process
was found more central than the axial plane of the scleral
spur. Quantitative parameters included the following:
• Angle-opening distance (AOD) was the distance from
the corneal endothelium to the anterior iris perpendicular
to a line drawn along the trabecular meshwork at 250 µm
(Figure 1A) and 500 µm (Figure 1B) from the scleral spur.
It was measured in all four quadrants.
• Iris thickness was the shortest distance between the
anterior and posterior surfaces of the iris measured at 750µm (Figure 2A) and 1000 µm (Figure 2B) from the scleral
spur.
• Iridocorneal angle (Figure 3) was the angle formed by
a line along the posterior cornea and another line along
the anterior iris plane. It was measured in all four
quadrants.
• Ciliary-body thickness was the widest distance between
the anterior and posterior surfaces of the ciliary body
(Figure 4).
• Anterior-chamber depth (ACD) and lens thickness were
measured using the biometric feature of the UBM as the
distance between the spike from the posterior corneal
endothelium to the spike from the anterior capsule, and
as the distance between the anterior and posterior lens
capsule, respectively.
Descriptive statistics, including mean and standard
deviation, were used for continuous variables, and
percentage frequency distribution for categorical data. All
variables measured pre- and post-LPI were analyzed using
paired student t-test or Wilcoxon signed-rank test, where
applicable. Subject eyes were categorized into open or
closed angle after LPI, and variables under each were
compared using chi square test and independent t-test
for qualitative and quantitative variables, respectively. All
statistical analyses were two-tailed. A p value of less than
or equal to 0.05 was considered statistically significant.
Data were analyzed using Statistical Package for Social
Sciences for Windows version 16.0.
Written, informed consent was obtained from all study
participants. The research followed the tenets of the
Declaration of Helsinki and was approved by the Ethics
Review Committee of the Expanded Hospital Research
Office of the Philippine General Hospital.
RESULTS
A total of 22 out of 33 eligible patients were enrolled
into the study. Eleven declined to participate. The
outcomes from 34 eyes were included in the final analysis.
The mean age of the patients was 62 ± 8 years with range
of 44 to 77 years. Nine out of 10 were females. Fourteen
(14) were diagnosed with bilateral NOA or PACS, while 8
had angle closure in the other eye distributed as primary
angle closure (PAC) in 2 eyes, primary angle-closure
glaucoma (PACG) in 3 eyes, absolute glaucoma secondary
to uncontrolled PACG in 2 eyes, and phacomorphic
glaucoma in 1 eye. Baseline characteristics of the study
population are described in Table 1.
Almost half of the eyes studied had a Van-Herick LCD
grade of 2 (47%); 32% and 21% had grades 1 and 3,
respectively. On gonioscopy, no angle structures were seen
on primary gaze in all 4 quadrants of 25 (73.5%) eyes, in
3 quadrants of 5 (14.7%) eyes, and 2 quadrants of 4
(11.8%) eyes. The most commonly closed quadrant was superior (94%), followed by the inferior (85%), the nasal
(82%), and the temporal (74%) quadrants.
LCD increased significantly after LPI (Table 2, p < 0.0001).
The proportion of eyes with Van-Herick grade of 1
decreased from 32% before LPI to 0% after LPI. The
proportion of eyes with narrow LCD (Van Herick grade
below 4) decreased by 17%. Eighteen percent of eyes
appeared to have normal LCD after LPI.
The Shaffer angle grading on static gonioscopy widened
significantly in all quadrants after LPI (Table 3, p < 0.05).
The largest change in angle width was noted in the inferior
quadrant (30%), followed by the superior (24%), nasal
(20%), and temporal (14%) quadrants. On dynamic
gonioscopy, only the superior quadrant had a significant
change (24%) in Shaffer angle grading after LPI (p < 0.05).
After classifying the angles into open or closed based
on Shaffer angle grading during static gonioscopy after
LPI, the presence of anterior ciliary-body displacement
(12 out of 34 eyes) and anterior iris insertion (8 out of 34
eyes) were only found in eyes with closed angles. The
absence of these characteristics in study eyes with open
angles, however, was not statistically significant.
Of the quantitative UBM characteristics noted in the
study, AOD 250, AOD 500, and ICA widened significantly
(Tables 4 and 5; p < 0.0001) after LPI. The greatest amount
of AOD widening was noted in the nasal quadrant.
Iridocorneal angle increase was largest in the superior
quadrant. There were no statistically significant changes
in ACD, lens thickness, ciliary-body thickness, and iris
thickness after LPI.
Comparing the UBM quantitative variables between eyes
with open angles and eyes with closed angles based on
Shaffer angle grading during static gonioscopy (Table 6),
there was no statistically significant difference in any of the
parameters except for the temporal ICA, which appeared
wider in eyes that remained closed after LPI (p = 0.027)
DISCUSSION
Results showed that a greater
proportion of narrow occludable
angles occur in females and in older
age groups. This finding has been
documented in previous studies.
12-13
The narrowing of the angles in
females is thought to be due to their
overall smaller ocular dimensions—
shorter axial lengths and shallower
ACD—but this cannot be proved by
this study for lack of comparison of
biometric data with those of the
normal population. The higher
occurrence of occludable angles in
the older age groups is thought to be
due to the increase in thickness and
slight anterior movement of the lens
with age; however, this cannot be
proved in the study because changes
in lens properties were not compared
with those of the normal population.
The narrowest angle by Shaffer
grade was found at the superior
quadrant. This finding has been well
known from previous studies.
13
Since
the test is performed in an upright
position, gravity plays a role in making
the superior quadrant appear
narrower.
Comparison of Van-Herick LCD
grade and Shaffer angle grade before
and after LPI showed a statistically
significant increase in LCD grade and
in angle width in all quadrants. The
largest change in Shaffer angle grade
was noted at the inferior quadrant.
This may be because of the effect of
gravity, making the inferior quadrant
appear wider than the rest of the angles. Similar angle widening after
LPI was reported in the Liwan Eye
Study, where LCD increased from 15
to 25% of peripheral corneal
thickness, and iridotrabecular angle
measured gonioscopically increased
from 10 to 30 degrees in the inferior
quadrant.
1 4
Other studies
9
also
demonstrated similar findings. This
increase or widening in Van-Herick
LCD and Shaffer angle grades,
however, should not be equated with
actual opening up of the angles.
Comparison of mean Shaffer grades
of angles before and after LPI showed
that only 4 out of 34 eyes actually
opened up. The 30 eyes appeared
clinically closed despite significant
widening of quadrant angles.
This study documented a significant increase in AOD at both 250
and 500 microns from the scleral spur
in all quadrants, which was also shown
in similar UBM studies.
8-9
The angle
widening was greatest in the nasal
quadrant, but the reason for this
proportionate increase is not understood. Studies correlating location of
LPI and greatest area or quadrant of
angle opening, as well as studies
determining whether LPI causes focal
or diffuse angle opening may help in
understanding this .
Previous studies reported the
greatest proportionate amount of
angle opening after LPI at the
superior quadrant,
8
being the most
narrow quadrant at baseline. A
significant increase in ICA, greatest
superiorly, was also documented by
UBM in this study. The discrepancy
in location of greatest angle widening
between AOD and ICA can be
explained by the dissimilarity of area
measured by the 2 variables. This is
best demonstrated in eyes with
plateau iris configuration, wherein a
wide ICA does not necessarily mean
that AOD is also wide.
As in previous studies,
9
ACD did
not significantly increase after LPI in
this study. Other quantitative UBM
parameters pertaining to the ciliary body and iris did not show significant
change as was demonstrated in earlier
studies. The Liwan Eye Study
reported significant increase in iris
thickness, which was attributed to the
relief of stretch forces placed on the
iris by buildup of posterior-chamber
pressure in relative pupillary block.
8
Thickening of ciliary body, which
suggests posterior displacement of
ciliary processes and hence posterior
movement of the lens and deepening
of the anterior chamber, has not been
demonstrated in any study yet.
Anterior ciliary-body rotation and
anterior iris insertion were only noted
in eyes that remained closed after LPI,
although its absence in eyes that
opened up after LPI was not
significant. These characteristics may
partly be responsible for the nonpupil
block mechanism in PACS that may
not be addressed by LPI alone.
Further studies are needed to shed
light on this.
Previously reported difference in
quantitative UBM characteristics
between eyes that opened up after
LPI and eyes that remained closed
after LPI
8
have not been shown to be
significant in this study. No trend of
angle widening has been demonstrated between clinically closed and
open angles after LPI. This may mean
that clinical assessment using
gonioscopy does not always correlate
with objective UBM measurements.
Angles that appear closed after LPI
may actually have significant angle
opening that can only be demonstrated by UBM.
The study is limited by its sample
size. Having more subjects for analysis
may show more significant trends in
UBM characteristics. Long-term
follow-up of these patients will help
determine whether those with
residual angle closure will have a
different outcome compared with
those whose angles opened up after
LPI.
In summary, although LPI does not
always result in clinically open angles,
UBM demonstrates that there is
significant increase in angle width in
patients with NOA or PACS.
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