ICE
|
ARS
|
|
Manifestation
|
Unilateral
|
Bilateral
|
Endothelium
|
Dystrophy
|
Normal
|
Angle
|
Goniosynechiae
|
Iris strands
|
Iris stroma
|
Abnormal
|
Abnormal
|
Ectropion uveae
|
+
|
+
|
Glaucoma
|
100% cases
|
60% cases
|
Age
|
20-30 years
|
Congenital
|
Sex
|
Mostly females
|
Equal distribution
|
Inheritance
|
Sporadic
|
Autosomal dominant
|
Saturday, May 26, 2018
Saturday, May 19, 2018
Aerie Pharmaceuticals Submits New Drug Application to U.S. Food and Drug Administration for RoclatanTM (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%
The expected FDA review period for RoclatanTM NDA is only ten months instead of twelve months because Aerie’s submission is filed under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act, since RoclatanTM is a fixed dose combination of two previously approved drugs in the United States .
“The RoclatanTM NDA filing represents another significant achievement for Aerie this year, on top of our recent commercial launch of Rhopressa® in the United States . Since RoclatanTM is being filed through the 505(b)(2) regulatory pathway, in which both active ingredients, netarsudil and latanoprost, are already approved in the United States , we expect a ten-month FDA review. We believe, if approved, RoclatanTM has the potential to be the most efficacious therapy in the market for the reduction of IOP, which makes this submission all the more exciting for our valued employees, eye care professionals, and most importantly, patients who suffer from glaucoma or ocular hypertension,” said Vicente Anido, Jr. , Ph.D., Chief Executive Officer and Chairman at Aerie.
Wednesday, May 16, 2018
IRIDOCORNEAL ENDOTHELIAL SYNDROMES: A primer
Iridocorneal Endothelial Syndromes (ICE) are characterized by the following:
Common features of the three ICES:
1. Corneal endothelial dystrophy
2. Distorted pupil
3. Ectropion uveae
4. Goniosynechiae
5. Secondary synechial glaucoma
Characteristics which distinguish between the three ICES:
1. Iris naevus syndrome (Cogan-Reese)=
Multiple small or a few larger iris nodules.
2. Chandler’s Syndrome=
Corneal oedema at normal or mildly elevated IOP.
3. Essential iris atrophy=
Progressive iris atrophy with iris hole formation (opposite to the side of goniosynechiae).
Wednesday, May 9, 2018
GLAUCOMA LASER TRIAL
The Glaucoma Laser Trial (GLT) was conducted during 1984-87 to assess the effectiveness of Argon Laser Trabeculoplasty (ALT) in newly diagnosed primary open angle glaucoma patients.
271 patients in the trial randomly underwent ALT in one eye and standard topical treatment in the other eye. The GLT-Followup Study (GLTFS) was a followup study of 203 of the 271 patients who had earlier been enrolled in the GLT. By the end of GLTFS, the patients had been under followup for a median duration of 7 years since the diagnosis of POAG. In GLT each half of the trabecular meshwork was treated with 45-55 laser burns in 2 sessions, 1 month apart. If the IOP was not controlled on followup the medications were changed in the treatment arm or added in the laser group. Further management including surgery was advised on further followup.
As compared with the treated eyes, those which underwent ALT had 1.2 mmHg greater reduction in IOP (P <0.001) and 0.6 dB greater improvement in visual fields (P <0.001). The C:D ratio also showed slightly more worsening [-0.01] (P=0.005) in the treatment group.
In conclusion, ALT was atleast as efficacious as initial treatment with topical medication.
Sunday, May 6, 2018
LASER TRABECULOPLASTY
INTRODUCTION:
A number of lasers have been used to
target the anterior chamber angle and achieve reduction in IOP. This laser induced modification
of the angle is known as Laser Trabeculoplasty (LTP). Some of
the lasers which have been used for LTP include: the argon (peaks at 488 nm and
514 nm); krypton (647.1 or 568.2 nm); diode (810 nm); and the continuous wave,
frequency doubled Nd:YAG (532 nm) laser. The Glaucoma Laser Trial and the
Glaucoma Laser Trial-Follow-up Study showed that eyes initially treated with
argon laser trabeculoplasty (ALT) had lower IOP and better visual field and
optic disc status than their fellow eyes treated initially with topical
treatment.
ARGON LASER TRABECULOPLASTY (ALT):
ALT was first described by Wise and
Witter in 1979. Usually 50 spots over 1800 of 50 micron spot size,
0.1 second duration and an average power ranging from 400-600 mW are given.
The precise mechanism by which LTP
works is not known. It has been suggested that the ALT scars induce tightening
of the trabecular beams around the scar with widening of the spaces between
them, thus enhancing outflow. In ALT, light energy enters the tissue faster
than it can dissipate, resulting in a rise of temperature and thermal energy
which spreads from the beam focus. ALT also destroys a viable area of the
trabecular meshwork (TM), creates a crater in this tissue and causes depopulation of
all normal structures. Studies have shown that ALT causes increased division of
trabecular cells and remodeling of the juxtacanalicular extracellular matrix.
However, over time the biological changes lead to the formation of a
fibrocellular membrane over the trabecular meshwork, resulting in decreased
aqueous outflow and failure of LTP.
Previous LTP also increases the
probability of bleb encapsulation following subsequent trabeculectomy. ALT
produces significant tissue disruption and coagulative damage to the TM. This
limits the reapplication of LTP again in an effective manner. Complications
reported with ALT include: transient IOP spikes (6.3-54%), peripheral anterior
synechiae (12-47%) and uveitis.
SELECTIVE LASER TRABECULOPLASTY:
In 1995 Latina and Park reported
that a 532 nm, frequency-doubled Q-switched Nd:YAG laser could selectively
cause cytotoxicity and cell death of TM cells without any apparent changes in
the adjacent non-pigmented cells. This came to be known as Selective Laser
Trabeculoplasty (SLT).
SLT is based on the principle of
“selective thermolysis”, whereby only pigmented trabecular cells are targeted
by the laser. There is no associated structural or coagulative damage to the
TM. Selective thermolysis is effective as it targets intracellular chromophore
(melanin) sparing the nonpigmented cells. Transmission electron microscopy following
SLT demonstrated fracture of melanin granules, rupture of lysosomal membranes
in pigmented cells and absence of ultrastructural damage in neighboring
nonpigmented cells. In the areas where the SLT laser had struck, beams of TM
were intact except for rare crack-like defects between preserved beams. There
was total absence of coagulative damage. The endothelium was intact, with a few
vacuolated cells. Many pigmented trabecular cells contained disrupted,
fragmented intracytoplasmic pigment granules and others also had intact
granules in their cytoplasm.
SLT delivers light energy in
extremely short nanosecond pulses, 8 orders of magnitude shorter than that of
ALT. Cooling from dissipation does not occur and temperature rise is very
rapid. This causes disintegration of a small volume of tissue into a collection
of ions and electrons called "plasma". Vaporization of water around melanosomes
at temperatures around 1500C causes formation of small, short
duration microbubbles which disintegrate cellular structures by micro-explosions in the region of pigmented TM cells.
SLT also causes increased secretion
of cytokines by TM endothelial cells. This could theoretically be linked to the
IOP lowering effect of SLT. Other mechanisms suggested for SLT include:
proliferation of trabecular endothelial cells, release of cytokines, inflammation
(recruitment of macrophages) and phagocytosis. SLT causes nuclear translocation
of transcription factors and an induction of vasoactive agents (e.g. cytokines)
followed by macrophage recruitment. IOP then decreases even as the repair
process begins.
Following SLT there is also
significant elevation in the aqueous concentration of lipid peroxide. Such free
oxygen radicals can cause inflammation and prove to be a double edged sword
during SLT.
SLT uses a 532 nm,
frequency-doubled, Q-switched Nd:YAG laser with a 3 nanosecond pulse and 400µ beam diameter. The size of the aiming beam is
much larger than the typical 50µ size ALT beam. This allows the SLT beam to
cover the entire width of the TM, thus accurate aiming is less critical. The TM
is a strip of tissue approximately 44 mm long and 0.3 mm wide. The larger spot
size is less harmful to ocular tissue because the energy is not concentrated in
a small area. The low fluency of energy safely and effectively diffuses over a
large area.
The energy density of a typical ALT
pulse of 800 mW, 0.1 second and 50 micron spot size is roughly 4 million
mJ/cm2. Contrarily, an SLT pulse of 0.8 mJ and 400 microns spot size delivers
energy of 637 mJ/cm2. This shows that each SLT pulse delivers less than 0.1% total
energy compared to ALT.
The procedure with the diode laser
is similar: a 50–75-µm laser beam is focused through a goniolens with a power
setting of 600–1000 mW and duration of 0.1 second.
The patient is pre-treated with an
alpha-agonist to prevent post-laser spike in IOP. Topical anesthesia and a
Goldmann 3-mirror or Latina SLT Lens is used. A low power beam is focused at
the pigmented TM. Power is usually set at 0.8 mJ per pulse initially. In
heavily pigmented eyes, it can be lowered further. About 50 non-overlapping
spots are applied to 180 degrees of the angle circumference. Unlike ALT where
blanching or large vaporization bubbles are produced, the endpoints of SLT are
more subtle. Some authors increase the energy to obtain small “champagne
bubbles” and then decrease power by 0.1 mJ without any subsequent visible
changes. Others strive to achieve these tiny bubbles during 50% or more of
applications.
Post-laser anti-Glaucoma medications
are continued until the IOP becomes stable. Topical steroids/NSAIDs are also
added to control inflammation. However, some suggest that postlaser
inflammation might help in lowering of IOP.
Some practitioners apply 100 shots
over 3600. However, studies have shown that success rates do not
differ significantly between 1800 and 3600 SLT. However,
900 of SLT is not as effective as 1800. Studies report
latanoprost to be more effective than 1800 SLT.
Compared to ALT, SLT is better
tolerated with less discomfort and post-laser inflammation.
However, Samples et al performed a
meta analysis of 145 papers and concluded there is no evidence of superiority
of any particular form of LTP.
Indications for SLT include:
1. In medically non-compliant
patients.
2. Those who cannot tolerate
medications.
3. As an adjuvant treatment to
reduce the number of anti-Glaucoma medications.
4. Those with uncontrolled IOP
despite previous ALT.
5. As a primary modality to treat
OAG, pxg, pigmentary Glaucoma, NTG, OHT, juvenile glaucoma,
aphakic/pseudophakic Glaucoma.
Side effects of SLT:
1. Post-laser IOP spike (0-27%)
2. Hyphema
3. Upto 50% pts show mild-moderate
uveitis lasting for about 24 hours and managed with steroid/NSAID topically
4. Corneal edema (resolved with
topical anti-inflammatory agents)
5. Transient corneal endothelial
changes.
Results:
IOP reductions following SLT ranged
from 2.1-10.6 mmHg with follow-up ranging from 4 weeks to 72 months. Reductions
in IOPs ranging from 18-40% over a 6 to 12 month follow-up have been reported.
Most of the IOP lowering effect has been reported in the first week with some
additional effect during the next 4-6 weeks.
Success rates in African-American
and white subjects were similar.
Baseline IOP was positively
associated with better IOP reduction following SLT.
Patients with thinner corneas
(<555m) also demonstrated better IOP control atleast for the first 30 months
after SLT.
Pigmentation of the angle, type of
Glaucoma, age, sex, past history of ocular surgery, phakic status, diabetes
were not associated with effectiveness of the procedure.
Chen did report an early better
reduction of IOP associated with pigmentation and pseudoexfoliation.
Cross-over effect of SLT:
SLT appears to have a statistically
significant IOP lowering effect in the contralateral untreated eye. An, as yet
known, biologic effect could be responsible.
In case IOP is lowered in the
treated eye, it gives a probability of SLT being effective in the other eye
too. However, these effects have not been studied well.
Retreatment of SLT:
Retreatment is defined as treatment
over a previously treated area of TM. As the SLT laser beam bypasses
surrounding tissue (since it targets pigmented cells only) leaving it
undamaged, theoretically SLT can be repeated several times in eyes in which the
IOP has risen to pretreatment levels or has not met the target IOP goal.
Studies have found that repeat SLT treatment is associated with further IOP
lowering and is safe and effective.
The "SLT/MED study" was conducted to compare SLT with medications.IOP reduction was similar in both arms after 9 to 12-months
follow-up. More treatment steps were necessary to maintain target IOP in the
medication group, although there was not a statistically significant difference
between groups. These results support the option of SLT as a safe and effective
initial therapy in open-angle glaucoma or ocular hypertension.
MICROPULSE DIODE LASER
TRABECULOPLASTY:
In this technique, 200 ms long
bursts comprising of 100 micropulses are applied to 200 µm spots on the TM.
There is an interval of 1.7 ms between each micropulse. About 70 spots are
applied over 1800. With this procedure, an IOP lowering of more than
20% was achieved in 60% eyes after 1 year of follow up.
PATTERNED LASER TRABECULOPLASTY:
PLT is based on the PASCAL
technology for retinal photocoagulation. The PASCAL system has an aiming beam
of 633 nm and therapeutic laser of 532 nm. Continuous wave light laser is directed
to the TM by the Latina gonio-lens. 10 ms pulses are used to produce blanching
of the TM. The procedure is started from the inferior quadrant which has the
maximum pigment. Subsequently the power is maintained but the pulse duration is
reduced to half (5 ms from 10 ms). Ophthalmoscopically invisible spots are
achieved at the TM with this reduced pulse energy. The pattern consists of
several arcs composed of multiple laser spots. Each arc contains 3 rows of 22
spots (total:66 spots). Each arc covers around 22.50 so that 8
applications for 1800 or 16 applications for 3600 are
used. Thus, more than 1000 spots of 100 micron diameter are applied over 3600.
The IOP was lowered by an average of 24% over 6 months of follow up in 60%
eyes.
The PASCAL Streamline 577 uses
yellow wavelength of 577 nm. A study by Nozaki showed a 31% IOP reduction over
6 months of follow up.
Looking at almost similar results
with PSLT and SLT, the only advantage of PSLT appears to be a faster delivery
time.
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