Download PNeumatic Trabeculaplasty (PNT)

PNeumatic Trabeculoplasty
(PNT)
An Alternative Approach for the Long Term
Management of POAG and OH Patients
John W. Sharkey, Ph.D.
President – Ophthalmic International
Management Team
 G. Richard Smith – CEO Over 25 years in development and manufacturing
of ophthalmic devices and co-inventor of PNT
 John W. Sharkey, Ph.D. – President. 20 years experience in global health
care industry
 Francesco Aspes, M.D. – Head of Europe. 25 yeas experience in global
health care industry
Glaucoma
 World Health Organization found glaucoma to be second
leading cause of blindness worldwide, second only to cataracts
 Glaucoma is leading cause of visual field loss in people over
age 55, followed by stroke
 Approximately 62% of patients discontinue and 18% change
their initial glaucoma medication within 18 months of diagnosis
 Surgical intervention does not eliminate need for
pharmaceutical treatments
 Glaucoma is a progressive disease and patients progress to
multiple medications and surgery over time
What is Glaucoma?
 Glaucoma is a group of neurodegenerative eye diseases
 The Optic Nerve is damaged
 Several forms of glaucoma have associated with them
Elevated Intraocular Pressure (IOP)
 It is an asymptomatic disease that is significantly under
diagnosed
 The disease is typically associated with aging and there is no
cure
Glaucoma Market
 Treatments for glaucoma account for almost half of the present
market for ophthalmic pharmaceuticals
 Global ophthalmic marketplace is approximately USD $ 4
billion and is expected to grow to USD$ 7 billion by 2009
 In excess of 1% of the U.S. population is estimated to have
glaucoma
 It is estimated that only 50% of U.S. glaucoma patients are
diagnosed and therefore eligible for treatment
Market Drivers
 Aging population – Incidence of glaucoma increases with age
 More aggressive diagnosis – with growing recognition of the
long term consequences of untreated glaucoma, several
initiatives underway world-wide to improve diagnosis and
initiate treatment
 Improved Compliance – recognition that poor patient
compliance is a major component of poor medical outcomes
What is Ocular Hypertension?
 Ocular Hypertension (OH)
 Intraocular Pressure (IOP) is elevated but
 Optic Nerve is normal therefore no visual deterioration
 4-10% of the U.S. population over 40 years of age have
elevated IOP.
 The Ocular Hypertension Treatment Study (OHTS)
estimated patients risk at 10% to develop glaucoma within a
5 year period.
 Risk can be reduced to 5% with active IOP control
Why OH Is Not Aggressively Treated
 Many physicians hesitate medically treating OH since
Most OH patients will not develop glaucoma
Side effect profile for ocular anti-glaucoma medications
are not benign and treatment is life-long
Therefore a large number of physicians will monitor and if
glaucoma develops will then try to manage
The OH market represents an equally large market for a
safe, effective treatment with minimal side effects
Origins of PNT
 Relationship between corneal thickness and measured IOP
has been known for over 50 years
 Several studies have shown that following PRK and LASIK
procedures there is a drop on measured IOP which correlates
to the amount of material removed
Goldmann H, Schmidt T. Über Applanationstonometrie.
Ophthalmologica 1957;134:221–42.
Emara B, Probst LE, Tingey DP, et al. Correlation of intraocular pressure and central
corneal thickness in normal myopic eyes and after laser in situ keratomileusis. J
Cataract Refract Surg 1998;24:1320–5.
Relationship Between Pachymetry
and IOP
 A significant number of patients exhibit a reduction of the IOP
after refractive surgery
 The explanation most frequently used was that the reduction
was a secondary artifact to the change of rigidity of the cornea
due to interrupting Bowman membrane
 A number of studies proposed that that the reduction of the IOP
post-LASIK was a real event and not fully attributable to
changes in the thickness of the cornea
What happens to corneal thickness
following Lasik and PRK
 The study was designed to determine changes in the corneal
thickness and IOP following LASIK (25 patients) or PRK (20
patients)
 Near-sighted patients between -6.00 and -8.00 diopters.
Examinations carried out at 1, 3, 6, 12, 36 months
 Exams included
– Topography
– Corneal pachymetry
– Tonometry
Hjortdal JO, Moller-Pedersen T, Ivarsen A, Ehlers N. Corneal power,
thickness, and stiffness: results of a prospective randomized controlled
trial of PRK and LASIK for myopia. J Cataract Refract Surg. 2005
Jan;31(1):21-9
Results
 Near term IOP is lowered more following LASIK versus PRK
even though corneal thickness decreased significantly less in
LASIK eyes than in PRK eyes
 Long term (3 years) the corneal thickness is the same in two
groups but the IOP is significantly lower in LASIK patients
 This would support that the difference in IOP following corneal
surgery is not a result of changes in corneal thickness
Correlation LASIK-IOP
 A study on 8113 consecutive eyes following LASIK
 Regression analysis demonstrated a reduction of 0.12 mm Hg per diopter of
refractive change which theoretically would be related to changes in corneal
thickness
 Extrapolation to “zero” diopters shows a reduction of 1.36 mmHg which cannot
be related to the change in corneal thickness
 Data supports an additional mechanism, independent of corneal thinning,
which leads to an IOP reduction
DH Chang, R. Doyle Stulting. Change in Intraocular Pressure Measurements
after LASIK. Ophthalmology 112,6,June 2005
Additional Change in IOP
Exact Relationship of Corneal
Thickness to IOP is Unknown
 It is accepted measurements underestimate IOP with thinner corneas and
overestimate IOP with thicker corneas
 It is unknown whether the relationship between corneal thickness and IOP in
the general population is linear or non-linear across the range of naturally
occurring thicknesses
 It is unknown whether a cornea thinned by LASIK has the same implications in
terms of tonometric artifacts as does a naturally thinned cornea
Samuelson TW. Refractive surgery in glaucoma. Curr Opin
Ophthalmol. 2004 Apr;15(2):112-8
PNT Procedure
Indications
 Patients 18 years of age or older
 Patients with:
– Primary open angle glaucoma (POAG)
– Pigmentary glaucoma (PG)
– Glaucoma secondary to pseudoexfoliation of the lens capsule (PXG)
– Eyes with moderate ocular hypertension (OHT), defined as any nonglaucomatous eye with an IOP in the range of 22-25 mm Hg
– With or without concomitant medication
Contraindications
 Chronic iritis/uveitis in either or both eyes
 History of secondary glaucoma in one or both eyes
 History of penetrating keratoplasty (corneal transplants), diabetes with rubeosis
iridis, severe cupping (90% to complete; excavation), narrow angles and/or
moderate to extensive visual field changes (i.e., only a central island of vision
(advanced visual field loss within 10 degrees of central fixation as determined by
automated perimetry) in either or both eyes.
 Moderate visual field defect
 Macular degeneration (wet or dry) in either or both eyes
 Patients who have undergone a surgical trabeculectomy. Prior ATL and SLT
procedures are not considered to be contraindications
 Patients with keratitis
 Patients whose angles are not fully open (i.e. narrow angle, atypical angle, closed
angle).
 Patients with severe dry eye syndrome associated with Fuch's Corneal Dystrophy
 Patients with corneal abnormalities or corneal disorders
 High Myopia defined as myopsis in excess of 6 diopters
The Equipment
 A patented 3-port design allows for equal vacuum to be applied
throughout the perimeter, essential for achieving consistent IOP
reduction
 The ring is single use, prepackaged as sterile and ready for use
 The ring is connected to a microprocessor controlled vacuum
pump which is activated using a unique barcode
PNT Procedure
 topical anesthesia
 60 sec application
 5 minutes off
 repeat 60 sec application
 re-treat at 1 week
 start reduction of meds at
3-4 weeks
 re-treat in 3-4 months
Summary of Clinical Experience
Clinical Trials
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Bucci
Avalos and LiVecchi
Bores
Ceruti-Marchini-Marraffa
Brogioni-Borgia
Dorigo-Bandello-Roman
Prigione-Rolando-Calabria
Offermann-Augustin
Monotherapy Trial
Pilot Study to Evaluate Efficacy and
Safety of Pneumatic Trabeculoplasty
(PNT) in Glaucoma and Ocular
Hypertensive
Principle Authors:
Prof. Massimo G. Bucci, M.D.
Marco Centofanti, M.D.
Francesco Oddone, M.D.
Mariacristina Parravano, M.D.
Prof. Corrado Balacco Gabrieli, M.D.
José Pecori-Giraldi, Ph.D.
Aloisa Librando, M.D.
Emanuele Paone, M.D.
Leo D. Bores, M.D.
Eur. J. Ophthal., 15(3), 2005 pp 347-352.
Bucci Trial Design
 Purpose: To independently determine the IOP lowering effect of
PNT
 Prospective, open-label fellow eye trial in POAG and OH
patients performed in 2 glaucoma centers in Italy
 Patients on glaucoma medication willing to stop treatment and
undergo adequate washout
 IOP between 22-28 mm Hg on Day 0
 Extensive ocular examinations and safety monitoring
 Duration of trial 120 days
Mean Change in IOP
For In-Study Subjects
Italian Monotherapy Trial
% IOP Reduction
Result From Monotherapy Trial
 73% (27/37) showed a PNT (pressure lowering) response and
completed study
 Four of the 10 dropouts were due to issues not associated
with PNT procedure
 No patients withdrew due to intolerability of procedure
 A 15% reduction in IOP was achieved by approximately 50% of
patients during the study period
 No significant adverse events observed. All events resolved
without medical intervention
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PNT – Combination Therapy and
Ability to Reduce Medication
Requirements
 “Pneumatic Trabeculoplasty
(PNT) – A new method to treat
primary open-angle glaucoma
(POAG) and reduce the number
of concomitant medications”
 G. Avalos Urza, M.D.
John T. LiVecchi, M.D.
Leo Bores, M.D.,
Ann. Ophthalmol. 2005; 37(1),
pp. 37-46.
Compilation of data from two separate trials
involving PNT
 Drs. Avalos and LiVecchi – First studies were performed at Dr.
Avalos’s clinic to evaluate the potential of PNT to lower IOP in
patients on existing medication
 Dr. Bores – Study was performed at the Arizona Glaucoma
Institute, to evaluate the potential of PNT to reduce medication
requirements while maintaining IOP control
Study By Avalos and LiVecchi
 Purpose: To test hypothesis that PNT can provide a clinically
significant decrease in IOP
177 patients; 320 eyes treated
 Duration of trial 6 months
 Outcomes in PNT patients were compared to a historical
cohort of patients, during the same time period, who were on
meds alone
Summary of IOP Results
Avalos and LiVecchi
Mean Age
65.3
Mean follow-up (months)
23.5
Pre-Treatment IOP range (mm Hg)
19-36
Post-Treatment IOP range (mmHg)
13-32
Mean Pre-Treatment IOP (mm Hg)
23.4
Mean Post-Treatment IOP (mm Hg)
17.1
Mean IOP Drop (mm Hg)
6.3
Observed Reduction in Medication
Avalos and LiVecchi
# of patients
Medications
Study Initiation Post-PNT
(at mean followup)
No Medications
8
65
1 Med: [Beta blockers (BB)]
33
34
2 Meds: [BB + pilocarpine (pilo)]
68
33
3 Meds: [BB + pilo + andrenergic (adr)]
24
14
4 Meds: [BB + pilo + adr + diamox]
44
31
19 eyes went on to require filtering procedures, 5 of these being those
with capsular exfoliation and 1 with recessed angle due to trauma
Comparison of Medication Requirements
Avalos/LiVecchi
M edication requirements Prior to PNT
68
70
70
60
60
50
50
40
34
33
30
24
20
# of Patients
# of Patients
M edication requirements Following PNT
65
40
34
33
31
30
20
14
10
8
10
0
0
No meds
b-blocker
b-blocker + pilo b-blocker + pilo b-blocker + pilo
+ adr
+ adr + diamox
Medications
Pre-PNT
No meds
b-blocker
b-blocker + pilo b-blocker + pilo b-blocker + pilo
+ adr
+ adr + diamox
Medications
Post-PNT
Observed Side Effect
Avalos and LiVecchi
 Side Effects from PNT procedure were generally considered
minor, resolved without medical intervention and included
 Mild conjunctival edema and injection
 Subconjunctival hemorrhage
 Mild discomfort
 No serious sight threatening complications and no visual field
deterioration or retinal nerve damage were observed (VF
analysis)
Arizona Glaucoma Institute
 Study was undertaken by Leo D. Bores, M.D., beginning in the
fall of 1997
 320 eyes (165 patients)
 Mean follow-up was 14 months (Longest was 24 months)
 Outcomes compared to a historical cohort of patients
treated during the same period at the same institution
Summary of IOP Results
Bores
Initial IOP 16 – 48 mm HG
Patients (N)
144
Mean follow-up (months)
9
Pre-Treatment IOP range (mm Hg)
16-48
Post-Treatment IOP range (mmHg)
15-20
Mean Pre-Treatment IOP (mm Hg)
19.2
Mean Post-Treatment IOP (mm Hg)
15.8
Mean IOP Drop (mm Hg)
3.4
Reduction in Study Medication
Bores @ 3 months
 Again, a shift towards fewer
number of concomitant meds
was observed post-PNT
 Majority of patients required
0 or 1 medication following
PNT to maintain safe IOP
Observations From Results Observed In
Avalos/LiVecchi and Bores Studies
 PNT can achieve good IOP control with a significant reduction
or elimination of concomitant medications
 The PNT effect is ‘reproducible’. When IOP drifts upwards in a
patient who has responded to PNT a repeat application will
again reduce the IOP
 No safety issues were observed which would prevent using
PNT in the glaucoma or ocular hypertension patient
Efficacy of Pneumatic Trabeculoplasty in Primary
Open Angle Glaucoma
 Dr. P. Ceruti, et.al., Department of Neurological and Visual Sciences,
University of Verona, Verona, Italy
 Presented – 2006 Annual Meeting of the Association for Research in Vision
and Ophthalmology (ARVO)
 The Study – Prospective 14 patient study, 120 days in duration, to
determine the IOP lowering effect of PNT in patients not adequately
controlled on anti-glaucoma medication. All patients received
comprehensive ophthalmic monitoring, including Ultrasound Biomicroscopy
examinations. Starting IOP was 22 ± 1.8 mm Hg
 Results: A statistically significant reduction of greater than -15%, with a
maximum -21% on day 8, was observed for the entire study. UBM analysis
supports the apparent mechanism of action being the restoration of
trabecular outflow.
UBM
 Examinations performed pre and post PNT
– ACD (Anterior Chamber Depth)
– SCPA (Scleral Ciliary Process Angle)
– CBT (Ciliary Body Thickness)
UBM Parameters
SCPA
1000
UBM Results

ACD and SCPA: No significant variation pre and post PNT
SCPA
ACD
Results of UBM

Reduction in Ciliary Body Thickness (CBT) following PNT (p<0.05) a 1000
µm from the scleral spur
sperone sclerale
sperone sclerale
2500 2000 1500 1000
2500 2000 1500 1000
Results

Increase in uveoscleral reflectivity following PNT
Efficacy of Pneumatic Trabeculoplasty in Primary
Open Angle Glaucoma
 Brogioni, C. et. al., Dip.di Medicina e Scienze dell’Invecchiamento
Università di Chieti
 Published – Boll. Ocul, 85 (3), 2006, pg 253-256
 The Study – Prospective 20 patient study, 120 days in duration, to determine the
IOP lowering effect of PNT in patients not adequately controlled on prostaglandins
(10) or beta-blockers (10). All patients received comprehensive ophthalmic
monitoring, including Ultrasound Biomicroscopy examinations. Starting IOP was 22
± 1.8 mm Hg
 Results: 17% drop in IOP observed for both groups. 33% reduction in “oscillations”
from 3.6 +/- 0.62 to 2.4 +/- 0.5 mm Hg. UBM results consistent with those of Ceruti
et. al.
Change in Angle following PNT
Change in Mean IOP
Dorigo-Bandello-Roman
(part of multicenter trial )
Università di Padova
 Primary objective: To verify the reduction in IOP
 Secondary objective: to determine impact on Central Vision,
RNFL and C/D ratio
 PNT Treatments on days 0 and 7. Additional visits on 1, 8, 14,
30, 60, 90 and 120
 10 patients with POAG
 Follow up 12 months for final pathology
Results
 Mean IOP reduction: 4.0 mmHg
 Mean % Reduction: 20%
Mean post-treatment IOP
25
20
15
10
5
0
0
1
7
8
14
30
60
90 120
V ISUAL FIELD
pre-PNT and post-PNT
mean MD
8
mean PSD
6.38
6.08
6
4
2
dB
0
PRE-PNT
-2
POST-PNT
4 months
-4
-6
-8
-6.78
-6.41
OCT Results
Mean RNFL (Retinal Nerve Fiber Layer)
micron
68
67.96
p=ns
M ean Cup / Disk
0.452
0.45
67.95
0.45
67.9
0.448
0.446
67.85
0.444
67.8
0.442
67.75
0.44
67.72
0.44
67.7
0.438
67.65
0.436
67.6
0.434
pre-PNT
post-PNT
pre-PNT
post-PNT
Evaluation of Pneumatic Trabeculoplasty (PNT) on
Intraocular Pressure with Different Treatment Sequences in
Primary Open Angle Glaucoma

A. Librando, E. Pacella, A. Gabrielli, S. D’Angelo, S. De Gaetano, J. Percori
Giraldi
 Published: Boll Ocul 85(4) 2006 pgs 279 – 288
 The Study: Thirty eyes suffering from Primary open-angle Glaucoma and Ocular
Hypertension (IOP between 20-25 mm Hg) were treated by means of a sequence of
three treatments of PNT. All patients IOP’s were under control with on Day 7 with
monotherapy (either beta-blockers, carbonic anhydrase inhibitors or prostaglandins)
 Results: A further reduction in IOP (maximum of 18%) was obtained following PNT
(days 0, 7,30). No significant undesirable side-effects were observed, except for a
moderate conjunctival hyperemia, which disappeared within 2-3 days. A prolong
duration of the effect was demonstrated (16.5% @ Day 150, 9.3% @ Day 180)
Safety and Efficacy of Pneumatic Trabeculoplasty in
African population
 Dr. Guido Prigione, et. al.; Clinica Oculistica, Department of Neurological
Sciences, Ophthalmology, Genetic, University of Genoa, Italy
 Presented – 2006 Annual Meeting of the Association for Research in Vision
and Ophthalmology (ARVO)
 The Study – A study, carried out in Ghana, involving 82 glaucomatous
eyes were consecutively included in this study. All the eyes were diagnosed
primary open angle glaucoma. The mean pre-PNT IOP was 25.71 + 5.02
mmHg.
 Results - Following 2-PNT treatments, a week apart, the IOP was reduced
by 3.89 mm Hg (-15.13%). 87.7% response rate. No significant sideeffects were found, except for 16 cases (19.51%) of subconjunctival
haemorrhages which resolved without medical intervention
Results
Effect of PNT on IOP in Patients Suffering From
Primary Open Angle Glaucoma.
 Drs. Indre Offermann and Albert Augustin; Department of
Ophthalmology, Klinikum Karlsruhe, Karlsruhe, Germany
 Presented at the 2006 German Ophthalmic Surgeons (DOC) Meeting,
Nuremburg, Germany
 The Study: 20 patients with POAG who were poorly controlled with
Latanoprost. Baseline intraocular pressure (IOP) ranged between 18 to 24
mmHg. 20 eyes were treated with PNT at day 0, 7 and 90, 180 (treatment
group). Comprehensive visual assessments were performed 1 day, 1 month
and 3 month after treatment
 Results: Treatment group mean IOP at baseline was 20.15 mmHg and was
reduced to 16.5 mm Hg at Day 120 (-3.65 mm Hg; -18.1%). They concluded
that PNT seems to be a safe and effective treatment to decrease IOP in
patients suffering from POAG.
Results
Mean reduction in IOP of 3.65 mmHg (-18.1%,
p<0.01)
Mechanism of Action
The Problem is the Trabecular
Meshwork
Most of the resistance to the flow occurs in the
juxtacanalicular trabecular meshwork and the inner
wall of Schlemm's canal
Outflow Resistance
Excessive accumulation of extracellular
matrix material in the woven juxtacanalicular
trabecular meshwork is the suspected cause
for increased resistance to outflow in the
eyes with POAG
Dorigo 2006
Gentle “Stretching" of the Trabecular Meshwork
Helps Eliminate Excessive Matrix Extracellular
Material, Improve Outflow and Reduce IOP
Why PNT?
 Broad Efficacy– Approximately 80% of POAG patients will
exhibit a lowering of their IOP following the PNT procedure
 Duration – The reduction in IOP usually last, on average, 3-4
months
 Reproducibility – Responders typically respond in a similar
fashion with follow up PNT treatments
 Improved Compliance – For the non-compliant patients, has
the potential to offer some long term IOP reduction
 Medication Reduction – PNT reduces, and often eliminates,
the number of medications necessary for IOP control
 Delay Initiation of Medication – PNT has the potential to
postpone the introduction of IOP lowering medication
 MOA appears to be physiological restoration of trabecular
outflow
Intellectual Property
 Patents have been granted,
covering both the equipment and
procedure
– US #5,601,548
Issued Feb.11, 1997
– EP #0 790 803 B1 Issued
Feb.19, 2003
coverage in Japan, China, etc
has also been obtained
 Additional patents are being
pursued
Current Status
 Device is registered as a 2a medical device within the
European Economic Community (EEC)
 Sales, Marketing and Distribution agreements covering Italy,
Spain, Portugal, France and Poland are in place
 Advanced discussions covering distribution in additional
territories within the EEC
 Exclusive Sales, Marketing and Distribution agreement in
place covering the Peoples Republic of China
Strategy Going Forward
– Leverage additional device registrations using our CE mark
as the basis for accelerated approvals
– Continue forward with U.S. registration activities
– Where feasible, utilize government reimbursement
mechanism to gain access to government hospitals/clinics
– Continued KOL development via our and our distributors
sponsoring several smaller trials in multiple countries
– Initiate a 1-year, prospective, multi-center trial of PNT versus
additional medical intervention in a well defined group of
early POAG patients
Thank you for your attention