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Pneumo trabeculoplasty (PNT) Clinical studies and study for FDA

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

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Pneumo trabeculoplasty (PNT) Clinical studies and study for FDA

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  1. 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

  2. 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

  3. 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 PNeumoTrabeculoplasty (PNT)

  4. 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 vaso-constrictor-drugs for 7 days PNT procedure

  5. The trabeculum: is it the future of antiglaucoma therapy? Trabecular meshwork

  6. The most resistance to the aqueous outflow is located into the juxtacanalicular trabeculum JCT

  7. Resistance to the aqueous outflow Extracellular matrix accumulation into juxta-canalicular tissue of the trabecular meshwork is related to an increase in resistance to the aqueous outflow in POAG eyes

  8. Mechanisms of PNT • Not yet known • Possible target is the trabecular meshwork - Mechanical effect: trabecular stretching - Biochemical effect: increase in permeability involving metalloproteinases

  9. Mechanical opening of trabecular pores

  10. 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.

  11. 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

  12. 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

  13. 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% • Rhegmatogenous retinal degenerations and Myopia > 6 D are exclusion criteria for PNT treatment Agudelo LM et al.: Changes in intraocular pressure after LASIK for myopia, hyperopia, and astigmatism. J Refract Surg. 2002;18:472-4

  14. PNT - Indications • Primary Open Angle Glaucoma • Ocular Hypertension • Pseudoexfoliative Glaucoma • Pigmentary Glaucoma (?) • With / Without antiglaucoma medical therapy

  15. 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

  16. Clinical studies • 6 studies of case series • 1 prospective controlled study

  17. 1) Marchini-Marraffa-Ceruti Study (Verona University) • Primary aim: IOP lowering effect of PNT • Secondary aim:UBMvariations 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

  18. IOP during follow-up 24 22 20 18 16 PNT eyes Control eyes mmHg 0 1 8 14 30 60 120 Days

  19. Results Significant IOP lowering effect (p<0.05) from base-line: 22.8  1.7 mmHg IOP  SD Δ % Day 2 = 19.8  1.7 mmHg 13.2% 8 = 18.0  1.8 mmHg 21.0% 14 = 19.0  1.4 mmHg 16.6% 30 = 18.9  1.5 mmHg 16.7% 60 = 19.0  1.4 mmHg 16.6% 120 = 20.0  1.4 mmHg 13.8%

  20. Results Treated Control Treated Control

  21. Results Treated Control Treated Control

  22. 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

  23. 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

  24. Qualitative evaluation 5 x 5 mm high-definition images of the anterior segmentAnatomic changes of different structures and their relationship Scleral spur Anterior chamber Angle Iris Pupil diameter Ciliary process PC Iris-lens contact Lens Zonule

  25. Quantitative UBM parameters (1) SD 500 µ • 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  Scleral spur TCPD ID1 (Iris th.) ICPD (Sulcus) IZD (Post. Ch.) ACD ILCD (Contact)

  26. Quantitative UBM parameters (2) SCPA • 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 500 µ  Scleral spur AOD 250 AOD 500 ACA ICPA SIA ILA

  27. 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

  28. Coefficients of variation(%) Tello et al. (1994) Marchini et al. (1997) ACD 0.3 - 0.5 1.4 ACA 4.5 - 11.1 12.4 TCPD 1.8 - 4.7 5.9 AOD 500 5.1 - 9.2 8.0 ID 1 3.7 - 8.3 10.5 ICPD 3.7 - 6.7 15.6 IZD 2.6 - 7.1 6.6 ILCD 2.9 - 3.3 14.2 SCPA not reported 8.6 SIA not reported 7.5

  29. 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

  30. Ciliary Body Thickness (CBT)and latanoprost-0.005% BaselineAfter 1 week  CBT1 604 ±172 676 ±178 +72  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

  31. Results after PNT Thickness reduction of ciliary processes post PNT (p<0.05%) at 1 mm from the SS 593±152  659 ±158  -66

  32. Results after PNT Increase in uveal reflectivity after PNT (Suction effect?) 11/14 (78.6 %)

  33. 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

  34. Conclusion • Max IOP lowering effect at day 8 (-21 %) • Significant IOP reduction until month 4 (-15.8 %) • Reduction in ciliary body thickness • and increase in uveal reflectivity • “Stretching” of the trabeculum ?

  35. 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

  36. Mean IOP variation(n=27) IOP (mmHg) Control - PNT at day 30 Treated – PNT at day 0 Days

  37. % IOP reduction(n=27) % IOP reduction Days Treated Control

  38. Patients responders % IOP reduction Pts. “responder” Days Days Treated Control Treated Control

  39. 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 effectdue to autonomic nervous system • remodelling of trabecular meshwork with systemic release of mediators affecting fellow eyes

  40. Side effects • Mild discomfort post-PNT • Small conjunctival hemorrhages • Conjunctival edema All mild side effects (no clinical significance)

  41. 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

  42. Results • Primary aim: IOP reduction of 6.3mmHg • Secondary aim: Therapy Before (n) Post-PNT (n) No medications 8 65 BetaBlockers 33 34 BB+Pilocarpine 68 33 BB+Pilo+Adrenergic 24 14 BB+Pilo+Adren+CAI 44 31

  43. 4) Brogioni-Borgia Study (Chieti University) • Primary aim: IOP lowering effect of PNT • Secondary aim: UBMvariations 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

  44. 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)

  45. 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 %)

  46. 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

  47. Results PNT IOP mmHg PNT PNT Days IOP reduction of 3.65mmHg (-18.1%, p<0.01)

  48. 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

  49. Results 1 After PNT1 8 After PNT2 31 After PNT3 90 120 150 180 Days

  50. 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) • 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

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