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University of Verona
Department of Neurological and Visual Sciences
Eye Clinic
Head: Prof. G. Marchini
Pneumo trabeculoplasty (PNT)
Clinical studies
and study for FDA
Giorgio Marchini
SFO – 8 May 2007
Correlation LASIK-IOP
• 8113 consecutive eyes operated by LASIK
• Data extrapolated from a theoretic zero D correction show
1.36 mmHg decrease in IOP suggesting an independent
component from laser ablation (additional constant)
Is the constant induced by the suction?
DH Chang, R. Doyle Stulting. Change in Intraocular Pressure Measurements after LASIK. Ophthalmology 112, 2005
PNeumoTrabeculoplasty (PNT)
•
•
•
•
•
Perilimbal ring (sterile packing)
3 tubes, 1 silicon tube and the controller
Homogeneous perilimbal depression
Suction pump checked by a microprocessor
Digital timer for length of the treatment
PNT procedure
•
•
•
•
•
•
Topical anaesthesia (4%-lidocaine)
Patient supine
Ring centred on the cornea
60 seconds treatment
5 minutes interval
Repetition of 60 sec. treatment
• Re-treatment after 1 week
• Re-treatment after 3 months
• Therapy with NSAID and vasoconstrictor-drugs for 7 days
The trabeculum: is it the future
of antiglaucoma therapy?
The most resistance to the aqueous outflow
is located into the juxtacanalicular trabeculum
Resistance to the aqueous outflow
Extracellular matrix
accumulation into juxtacanalicular tissue of the
trabecular meshwork is
related to an increase in
resistance to the aqueous
outflow in POAG eyes
Mechanisms of PNT
• Not yet known
• Possible target is the trabecular meshwork
- Mechanical effect: trabecular stretching
- Biochemical effect: increase in permeability
involving metalloproteinases
Mechanical opening of trabecular pores
The trabecular “stretching” is associated with a
reduction of the extracellular matrix, an increase
of the outflow and a subsequent reduction in IOP
Even though PNT can
determine trabecular
stretching there is no
clinical evidence that it
determines cyclodialysis.
Furthermore after PNT
treatment no patient
showed inflammatory
cells in the anterior
chamber.
Possible side effect due to the suction ring
Central vein and artery occlusion
• External pressure >45-50 mmHg may induce temporary
vessels occlusion but…
• …LASIK experience shows that it is possible to apply
suction rings for 1-4 minutes and give rise to IOP of 65
mmHg (90 mmHg with modern microkeratoms)
• PNT procedure determines
- lower IOP increase than LASIK
- shorter treatment length than LASIK
Possible side effect due to the suction ring
Visual field defects (glaucoma)
• External pressure >45-50 mmHg may induce ischemic
optic nerve damage but…
• …LASIK is not a contraindication in glaucoma patients
(Suction device approved by FDA)
• Severe visual field defects and advanced glaucoma
remain excluded from treatment protocols with PNT
Possible side effect due to the suction ring
Vitreo-retinal complications and high myopia
• External pressure >45-50 mmHg may induce
mechanical vitreo-retinal damage but…
• …LASIK is performed in myopic patients up to
-8 D and more
• The incidence of vitreo-retinal complications in
29916 LASIK procedures is 0.06%
Agudelo LM et al.: Changes in intraocular pressure after LASIK for myopia, hyperopia, and astigmatism. J Refract Surg. 2002;18:472-4
• Rhegmatogenous retinal degenerations and
Myopia > 6 D are exclusion criteria for PNT
treatment
PNT - Indications
• Primary Open Angle Glaucoma
• Ocular Hypertension
• Pseudoexfoliative Glaucoma
• Pigmentary Glaucoma (?)
• With / Without antiglaucoma medical therapy
PNT- Contraindications
•
•
•
•
•
•
•
Sicca syndrome (severe)
Keratitis
Penetrating keratoplasty
Uveitis
Diabetic retinopathy (rubeosis iridis)
Macular degeneration
Myopia > 6 D and rhegmatogenous retinal deg.
•
•
•
•
Advanced glaucomatous visual field defects
Conjunctival bleb (trabeculectomy)
Angle-closure glaucoma
Neovascular glaucoma
Clinical studies
6 studies of case series
1 prospective controlled study
1) Marchini-Marraffa-Ceruti Study
(Verona University)
• Primary aim: IOP lowering effect of PNT
• Secondary aim: UBM variations induced by PNT
• Observation time: 140 days
• Procedure: 2 sessions (1 week interval)
2 treatment in each session (5 min. interval)
one eye: treated - contralateral eye: control
• 14 POAG pts. under topical medical treatment
ARVO 2006
IOP during follow-up
24
PNT eyes
Control eyes
mmHg
22
20
18
16
0 1
8
14
30
60
Days
120
Results
Significant IOP lowering effect (p<0.05) from
base-line: 22.8  1.7 mmHg
IOP  SD
Day
2=
8=
14 =
30 =
60 =
120 =
19.8  1.7 mmHg
18.0  1.8 mmHg
19.0  1.4 mmHg
18.9  1.5 mmHg
19.0  1.4 mmHg
20.0  1.4 mmHg
Δ%
13.2%
21.0%
16.6%
16.7%
16.6%
13.8%
Results
Control Chart: DAY1
25,5
25,9
24,1
23,1
22,7
20,3
21,3
17,5
Mean
Mean
Control Chart: PRE1
19,9
trattato
Treated
controllo
Control
14,7
trattato
Treated
controllo
Control
Results
Control Chart: DAY8
25,5
22,4
24,1
20,7
22,7
19,0
21,3
17,3
Mean
Mean
Control Chart: PRE1
19,9
trattato
Treated
controllo
Control
15,6
trattato
Treated
controllo
Control
Ultrasound Bio-Microscopy
B-scan ultrasonographic immersion procedure
Qualitative evaluation - Quantitative biometry
This research is based on the assumption that morphological
evaluation in a clinical setting may prove useful for investigating
functional mechanisms
Technical characteristics of the UBM
• 50 MHz: frequency
• 5 mm: focus of the us beam
• 50 microns: axial resolution
• 50 microns: lateral resolution
• 5 mm: exploration depth
• Linear scanning mode
Qualitative evaluation
5 x 5 mm high-definition images of the anterior segment
Anatomic changes of different structures and their relationship
Scleral
spur
Anterior chamber
Pupil
diameter
Iris-lens contact
Angle
Iris
PC
Lens
Zonule
Ciliary
process
Quantitative UBM parameters (1)
500
µ
SD
Scleral spur

ID1 (Iris th.)
TCPD
ICPD (Sulcus)
IZD (Post. Ch.)
ILCD
(Contact)
ACD

Trabec.-ciliary proc. distance: TCPD

Sulcus ciliaris: ICPD

Posterior chamber: IZD

Iris-lens contact: ILCD

Iris thickness: ID1, ID2, ID3

Scleral thickness: SD

Anterior chamber depth: ACD
Quantitative UBM parameters (2)
SCPA

500
µ
Scleral spur
ACA
AOD AOD
250 500

Anterior chamber angle: ACA (ß 1)

Angle opening distance: AOD 250
and AOD
500

Iris-lens angle: ILA (ß 2)

Scleral-iris angle: SIA (ß 3)

Scleral-cil.proc. angle: SCPA (ß 4)

Iris-cil.proc.angle: ICPA
ICPA
SIA
ILA
Reliability of the measurements
Agreement

Same observer, same image
Good-Excellent

Different observers, same image
Sufficient

Same observer, different images
Good-Sufficient

Different observers, different images
Unacceptable
Marchini G. et al., Docum Ophthalmol 1997
Coefficients of variation (%)
Tello et al. (1994)
ACD
ACA
TCPD
AOD 500
ID 1
ICPD
IZD
ILCD
SCPA
SIA
0.3 - 0.5
4.5 - 11.1
1.8 - 4.7
5.1 - 9.2
3.7 - 8.3
3.7 - 6.7
2.6 - 7.1
2.9 - 3.3
not reported
not reported
Marchini et al. (1997)
1.4
12.4
5.9
8.0
10.5
15.6
6.6
14.2
8.6
7.5
UBM Study after PNT
• UBM examination at day 0 and day 8
• Anterior Chamber Depth (ACD)
• Sclera - Ciliary Process Angle (SCPA)
• Ciliary body thickness at different distances
from the scleral spur
Ciliary Body Thickness (CBT)
and latanoprost-0.005%
Baseline
After 1 week

+72 
CBT1 604 ±172
676 ±178
CBT2 434 ±140
536 ±127* +102 
CBT3 319 ±103
412 ±100*
+93 
*p<0.01
The differences in the control group were not significant.
These data indirectly support the mechanism of uveoscleral outflow and are in agreement
with the biochemical hypothesis of the passage of the aqueous flow through the extracellular
spaces of the ciliary muscle.
Marchini G. et al., J Glaucoma 2003
Results after PNT
Thickness reduction of ciliary processes
post PNT (p<0.05%) at 1 mm from the SS
659 ±158 
593 ±152 
- 66 
Results after PNT
Increase in uveal reflectivity after PNT
(Suction effect?)
11/14 (78.6 %)
Results after PNT
No significant variations in ACD and SCPA
between base-line and after PNT
SCPA
ACD
2.735 µ ±0.372
vs
2.781 µ ±0.365
45.5° ± 6.5
vs
46.7° ± 4.7
Conclusion
1. Max IOP lowering effect at day 8 (-21 %)
2. Significant IOP reduction until month 4 (-15.8 %)
3. Reduction in ciliary body thickness
and increase in uveal reflectivity
4. “Stretching” of the trabeculum ?
2) Bucci et al. Study
(“Tor Vergata” University - Rome)
• Aim: IOP lowering effect of PNT, without medical therapy
• Procedure: 2 sessions (1 week interval)
2 treatment in each session (5 min. interval)
control eye treated after 30 days
• Observation time: 120 days
• IOP measurements: day 0, 1, 7, 14, 30, 37, 60, 90 e 120
• 37 POAG or OH patients:
–
–
–
–
–
Wash-out from previous topical drugs
IOP 22-28 mmH before treatment (base line)
Difference between two eyes < 5 mmHg
Age >18 years
No concomitant ocular pathology
Bucci MG et al. Pilot Study to Evaluate Efficacy and Safety of Pneumatic Trabeculoplasty (PNT)
in Glaucoma and Ocular Hypertensive Eur.J.Ophthal., 2005; 15: 347-352
Mean IOP variation (n=27)
IOP (mmHg)
Control - PNT at day 30
Treated – PNT at day 0
Days
% IOP reduction (n=27)
% IOP
reduction
Days
Treated
Control
Patients responders
% IOP reduction
Pts. “responder”
Days
Treated
Control
Days
Treated
Control
Results
• Max. IOP lowering effect
– Day 60
-4.2 mmHg
– Day 90
-5.2 mmHg
– Day 97
-5.7 mmHg
– Day 120
-5.4 mmHg
The control eye, treated at day 30, shows an IOP lowering
effect, without hypertensive peak.
Possible explanations could be:
- sympathetic effect due to autonomic nervous system
- remodelling of trabecular meshwork with systemic release of
mediators affecting fellow eyes
Side effects
• Mild discomfort post-PNT
• Small conjunctival hemorrhages
• Conjunctival edema
All mild side effects (no clinical significance)
3) Avalos-Li Vecchi Study (pilot study)
• Primary aim: IOP lowering effect of PNT
• Secondary aim: Reduction of concomitant medications
• Observation time: 180 days
• Procedure: 2 sessions (1 week interval)
2 treatment in each session (5 min. interval)
• 177 POAG or OH patients (320 eyes): + PDS, PEX, traum. Gl.
– Pts. with topical medical therapy
– Age: 65.3 years
– Follow up:23.5 months
– No concomitant ocular pathology
Bores L., Avalos G., LiVecchi JT. Pneumatic Trabeculoplasty (PNT) – A new method to treat primary open-angle glaucoma (POAG) and reduce the number of concomitant
medications Ann. Ophthalmol. 2005;37:37-46
Results
• Primary aim: IOP reduction of
6.3 mmHg
• Secondary aim:
Therapy
No medications
BetaBlockers
BB+Pilocarpine
BB+Pilo+Adrenergic
BB+Pilo+Adren+CAI
Before (n)
8
33
68
24
44
Post-PNT (n)
65
34
33
14
31
4) Brogioni-Borgia Study
(Chieti University)
• Primary aim: IOP lowering effect of PNT
• Secondary aim: UBM variations induced by PNT
• Additional aim: Reduction of IOP fluctuations
• Observation time: 30 days
• Procedure: 2 sessions (1 week interval)
2 treatment in each session (5 min. interval)
• 20 POAG patients:
– Age: 60.4 ±6.8 years
– 10 pts. treated with prostaglandine analogues
– 10 pts. treated with beta-blockers
Boll. Oculistica 3, 2006
Results
IOP base-line
IOP at day 30
after PNT
Primary aim: 17 % reduction in IOP
Additional aim: 33% reduction in IOP fluctuations
(from 3.6 ±0.62 to 2.4 ±0.5 mmHg)
Results
Significant increase in Anterior Chamber Angle
(ACA) between base-line and after PNT
ACA
28.6° ±1.4
vs
32.6° ±1.4 (+13.8 %)
5) Offermann-Augustin Study
(Karlsruhe University)
• Primary aim: IOP lowering effect of PNT
• Observation time: 120 days
• Procedure: 3 sessions at days 0 - 7 - 90
2 treatment in each session (5 min. interval)
• 20 POAG patients:
– Age: 67 years (41-80)
– Pts. treated with latanoprost
– No concomitant ocular pathology
DOC, 27 May 2006
Results
IOP
PNT
mmHg
PNT
PNT
Days
IOP reduction of 3.65 mmHg (-18.1%, p<0.01)
6) Balacco Gabrieli Study
“La Sapienza” University - Rome
• Primary aim: IOP lowering effect of PNT
• Observation time: 180 days
• Procedure: 3 sessions at days 0 - 7 - 30
2 treatment in each session (5 min. interval)
• 16 POAG patients (30 eyes):
– Age: 55.7 ±14.1 years
– IOP 20-25 mmHg (difference between eyes </= 5 mmHg)
– Topical medical monotherapy
– No concomitant ocular pathology
SOI 2006
Results
1
After
PNT1
8
After
PNT2
31
After
PNT3
90
120
150
180
Days
The efficacy and safety
of pneumatic trabeculoplasty:
results of a 6-month,
multicenter study
Fogagnolo P (1), Rossetti L (2), Marraffa M (3),
Rolando M (4), Ciancaglini M (5), Calabria G (4),
Mastropasqua L (5), Orzalesi N (2), Marchini G (3)
(1) G.B. Bietti Foundation for the Study and Research in Ophthalmology, IRCCS, Rome, Italy
(2) Eye Clinic, San Paolo Hospital, University of Milan, Italy
(3) Eye Clinic, Department of Neurological and Vision Science, University of Verona, Italy
(4) Department of Ophthalmology, University of Genoa, Italy
(5) Ophthalmic Clinic, University of Chieti, Italy
Accepted ARVO 2007 – Submitted BJO
Introduction
• Pneumatic trabeculoplasty (PNT) is a
novel device for the treatment of OHN
and POAG
• Few clinical data are up-to-now
available
Purpose
To evaluate the efficacy
and safety of PNT
in patients with
OHT and POAG
Methods
Worse eye of 63 patients - 4 Italian academic sites
Inclusion Criteria
• Diagnosis of OHT or POAG
• IOP = 20-25 mmHg (treated & untreated - no washout)
Exclusion Criteria
• MD worse than 12 dB
• Past intraocular surgery or inflammation
• Significant eye diseases
Scheduled Visits
• Baseline: (day - 0)
• PNT treatment: day 0, day 7
• Safety visits: day 1, day 8
• Follow-up visits: month 1, 2, 3, 4, 5, 6
Daytime IOP curve (8, 10 am, 2, 4 pm)
The procedure
• Tetracaine-0.5% or Lidocaine-4%
• Lids are gently spread by the physician using his fingers
• PNT ring (sterile) is centered on the cornea
• Moderate downward pressure to facilitate the initial
attachment of the ring
• Vacuum of 20 inches Hg is applied to the ring
• 60 seconds - rest of 5 minutes - 60 seconds treatment
• Topical antibiotic + NSAID eyedrops (QID)
Patients characteristics
Age at inclusion
mean ± SD (range)
66 ± 10 years (42-87)
Race, %
Caucasian / Black
98% / 2%
Male / Female, %
Iris, %
57% / 43%
Pigmented / Not pigmented
74% / 26%
Study discontinuations, n (%)
8 (13%)
PNT eye
Not-PNT eye
OD / OS
60% / 40%
40% / 60%
POAG / OHT
40% / 60%
56% / 44%
None
21%
17%
Prostaglandin analogues
49%
25%
Beta-blockers
35%
29%
Others
3%
5%
Treatment, n
Results
23
22
IOP (mmHg)
21
20
19
18
17
1
2
NON PNT
3
4
PNT (responders)
5
6
PNT (intent to treat)
7
Results
• Mean IOP decrease from baseline: 17.9% 19.1%
• Mean IOP decrease in responders: 23.0% 18.2%
• Rate of non-responders (≤ 5%): 23-32%
Trend for better responses in the group using prostaglandin
analogues compared to beta-blockers
22.8% ±16.0%
vs
11.0% ±14.9%
P = 0.17
Results
70
Percentage of patients
60
50
40
30
20
10
0
30
60
90
120
150
IOP reduction
< 5%
6 - 14%
> 15%
> 20%
> 25%
180
Side effects
SIDE EFFECTS
N (%)
DURATION, mean ± SD (range)
Conjunctival hyperaemia
31 (49%)
12 ±20 days (1; 90)
Foreign body sensation
11 (17%)
10 ±13 days (1; 45)
Punctuate keratitis
8 (13%)
7 ±0 days
Blurred vision
7 (11%)
1 ±2 hours (15 mins – 5 hours)
Subconjunctival haemorrhage
5 (8%)
5 ±6 days (1; 14)
Burning
4 (6%)
6 ±6 days (1; 14)
Dry eye sensation
3 (5%)
10 ±6 days (1; 14)
Corneal abrasion
1 (2%)
7 days
Corneal oedema
1 (2%)
7 days
IOP increase to 40 mmHg
1 (2%)
1 day
Photophobia
1 (2%)
1 day
Conclusions
• Effective: 17-20 % IOP lowering effect
• Safe: mild side effects
• Rate of non-responders: ¼
Unresolved questions
• Mechanism of action?
• Synergic to PG?
• Repetitions: how often? Are they effective?
Why PNT ?
• Not surgical technique
• No retro- or peri-bulbar anaesthesia
• Safe procedure
• IOP reduction of 2-10 mmHg in 75% of POAG
patients
• IOP lowering effect persists for 3-4 months
• Less antiglaucoma topical medications
• PNT treatment can be repeated
• PNT can postpone medical treatment
Thank you
for
the attention