PNEUMATIC TRABECULOPLASTY

PNEUMATIC TRABECULOPLASTY Prof. MARIA TERESA DORIGO MD ΦΡΙΣΤΟΦΟΡΟΣ ΓΚΟΥΝΤΗΣ MD VERONICA MARITAN MD University of Padova PNEUMATIC TRABECULOPLASTY (PNT) A New Treatment for Primary Open Angle Glaucoma & Ocular Hypertension PNT The purpose of this presentation is to evaluate efficacy and safety of pneumatic trabeculoplasty PNT When a patented external pneumatic suction device is applied over the perilimbal area for a specific time, a lasting decrease in the IOP is realized Changes in IOP after LASIK for myopia, hyperopia, and astigmatism. IOP decreased in myopic, hyperopic and astigmatic eyes after LASIK. The reduction was not correlated to the amount of tissue removed or to flattening or steepening of the central cornea Agueldo LM et.al J Refract Surg 2002 Changes in IOP after LASIK • IOP is measurably lower in a significant number of cases. • The decrease in IOP is real event or an artifact secondary to central thining associated with a change in cornea rigidity due to the interruption of Bowman’s membrane ? • Li Vecchi considered the possibility that the application of the ring itself may be causative. PNT device • Suction ring • Vacuum pump • Connecting tubing The pump is preset to deliver a maximum vacuum pressure corresponding to 20 inches,inducing an IOP between 45-50 mm/Hg PNT Procedure • PNT is an office-based procedure. • The patient is placed in the supine position. • Topical anesthesia is used to anesthetize the operative eye. • A wire lid speculum is placed in the eye to hold it open. PNEUMATIC TRABECULOPASTY Topical anesthesia administered Lid Speculum PNT Procedure The clinician then positions the pneumatic suction ring to clear the upper eyelid, centers it around the clear cornea, and presses it down slightly until full suction is achieved. Pneumatic suction ring placed on eye PNT Procedure • This pneumatic suction ring is left on the eye for 60 seconds. • Removed for 5 minutes • Repeated once again for 60 seconds • The wire lid speculum is removed and the patient is checked for IOP one hour postoperatively IOP Check Preliminary trials have show that a repeat of the procedure at 1 week provides a more profound and lasting decrease in IOP Three questions • What happens to an eye in whom the IOP has been raised well beyond the norm, albeit for only 60 seconds? • Are glaucoma eyes suscetible to increased pressure? • Do short-term elevations of IOP affect the health of glaucomatous eyes? The risks related to the short-term elevations of IOP to levels beyond that considered normal (14-21mmHg) during application of a vacuum fixation device to the human eye have been carefully reviewed in the literature Risk associated with suction ring application • It is well know that a pressure application in excess of 45mmHg can produce a temporary occlucion of both the central artery and vein • The application of a vacuum fixation ring in performing classical keratomileusis (IOP > 65mmHg - 4,5minutes) has resulted in a case of macular edema with loss of best corrected visual acuity after a ring application in excess of 8 minutes during LASIK • Several cases of retinal detachments have been reported following use of the vacuum fixation ring in the LASIK procedure. Acute IOP elevation and its effect on Visual Field • The visual field following acute primary angle closure. (Aung T et.al 2001) Conclusions: The frequency of visual field loss at 6 months after APAC was low at only 38%. • Visual field changes after LASIK in myopic eyes. (Ozdamar A et.al 2004) Conclusions: LASIK did not cause visual field defects in mild to moderate myopic patients who had no risk factors that might render the optic nerve vulnerable to damage Refractive surgery in glaucoma • Most studies have no changes in the RNFL or optic disk after LASIK Dementyev DD et.al 2005 • The safety of LASIK in patients with glaucoma has not been proved. • Glaucoma is not a absolute contraindication, is a relative contraindication. Samuelson TW 2004 INDICATIONS • • • • Patients 18 years of age or older POAG or OH IOP: 20-25mmHg With or without concomitant medication CONTRAINDICATIONS • Chonic iritis/uveitis • History of glaucoma secondary or angle closure glaucoma in • either or both eyes History of penetrating keratoplasty, diabetic retinopathy with rubeosis iridis and advanced visual field defects. Patients with macular degeneration (wet or dry) Patients who have udergone a trabeculectomy. Prior ALT and SLT procedures are not considered to be contraindications Patients with keratitis Patients with severe dry eyes syndrome Hight myopia ( > 6 diopters) • • • • • • 10 patients with POAG or OH were enrolled in a prospective, • • • open-label, fellow-eye, multi-center trial to determine the IOP lowering effect. All the patients kept on taking the hypotensive drugs PNT was performed at day 0 and 7. The pre-operating treatment included the use of non steroid anti-inflammatory drugs on the two days preceding the PNT. treatment, and during the week following it, with the addition of a vasoconstrictor. The IOP was always measued at 10 a.m of day 0 (I-PNT) and post-PNT days 1, 7 (II-PNT), 8, 14, 30, 60, 90 and 120. The visual field, RNFL and C/D measurements were performed before and four months after the treatment. The gonioscopy and the examination of the anterior chamber were performed before and immediatly after the treatment METHODS • • • RESULTS RESULTS Patients Mean age Mean follow-up Mean pre-treatment IOP N or % 10 56+/-10.4 SD years 12 months 20+/-4.47 SD mmHg Mean post-treatment IOP Mean IOP drop 16+/-1.73 SD mmHg 4 mmHg Mean % IOP drop -20 % Mean post-treatment IOP IOP 25 (mmHg) 20 15 10 5 0 I PNT II PNT PrePNT 0 1 7 8 14 30 60 90 120 Day post-treatment SAFETY • Visual field • OCT • Gonioscopy • Visual acuity • Biomicroscopy V ISUAL FIELD pre-PNT and post-PNT 8 6 4 2 mean MD 6,38 mean PSD 6,08 dB 0 -2 -4 -6 -8 -6,78 -6,41 OCT-Safety Mean RNFL (Retinal Nerve Fiber Layer) p=ns 0,452 0,45 0,448 0,446 0,444 Mean Cup / Disk micron 68 67,96 67,95 0,45 67,9 67,85 67,8 0,442 67,75 67,7 67,72 0,44 0,44 0,438 0,436 0,434 67,65 67,6 pre-PNT post-PNT pre-PNT post-PNT GONIOSCOPY: After the treatment Ocularcardiac Reflex The ECG revealed that only the first patient had a heart rate decreased during suction, secondary to an excessive bulbar compression, while applying the suction ring SIDE EFFECTS • • • • Mild conjunctival edema and injection Occasional subconjunctival hemorrhage Mild discomfort Foreign body sensation Complications No vascular occlusion, retinal detachments, retina holes or macular edema Probable mechanism of action The mechanism of action of PNT may involve stretching of the zonule, which produces a corresponding change in the trabecular meshwork, either physiologically, through chemical mediators, or through a mechanical opening of the trabecular pores. Mechanical opening of the TM pores The possible contribution of chemical mediators Understanding trabecular meshwork physiology: A key to the control of IOP ? Trabecular Meshwork: Future of antiglaucoma therapy? TM tissue: TM cell + ECM • ECM (collagens, proteoglycans, laminin, elastin, and fibronectin) • TM cells functions: ECM synthesis, secretion, degradation and others The primary pathway in humans for removal of aqueous humor consists of the trabecular meshwork (TM) and the canal of Schlemm (SC). The majority of resistance to outflow of aqueous humor is generated deep in the TM (juxtacanalicular region) near or at the inner wall of SC Resistance to Outflow Excessive accumulation of extracellular matrix (ECM) in the juxtacanalicular tissue (JCT) of the meshwork has been postulated to cause an increased outflow resistance in eyes with POAG Extracellular matrix (ECM) turnover is mediated by matrix metalloproteinases (MMPs) • MMP-1(collagenases), MMP-2-9(gelatinases), MMP-3 (stromelysins), MMP-7(matrilysins), MMP-12(metalloelastase), MT-MMP (membrane-type) • The activity of MMPs is regulated by specific endogenous inhibitors, the tissue inhibitors of metelloproteinases (TIMP-1-2) • Dysregulated expression of MMPs and TIMPs are likely candidates to be involved in the abnormal ECM metabolism charateristic of POAG The decreased aqueous levels of MMP-2 activity and the significantly increased concentrations of TIMP-1 and -2 may contribute to the abnormal matrix accumulation found in the JCT of POAG •MMPs and TIMPs are regulated at the transcriptional level by TGFbeta •TGFbeta1, downregulate the expression of MMP-1-3 and to upregulate the expression of MMP-2 and TIMP-1-3 •TGFbeta2, upregulate the TM expression of PAI-1,fibronectin, elastin, laminin, collagens and fibulin. Fleenor DL et.al IOVS 2006 Transforming growth factors (TGF) • TGF can inhibit epithelial cell proliferation, induce extracellular matrix protein synthesis, and stimulate mesenchymal cell growth. Elevated levels of TGF-b2 have been found in the aqueous of glaucoma eyes. • The study speculated that increased TGF-b2 levels may be responsible for the decreased cellularity of the trabecular meshwork and may lead to increased debris and resistance to outflow. Therapeutic manipulations (PNT) that to eliminate the excessive extracellular matrix should theoretically improve outflow facility and consequently lower IOP We reported 2 observations that support this hypothesis • Manipulation of TM (MMP) activity reversibly modulates outflow facility in perfused human anterior segment organ culture • Laser trabeculoplasty induces sustained MMP expressions Bradley JB IOVS 2001 TM cells sence increase in IOP as stretching or distorsion of their ECM and respond by increasing ECM turnover enzymes • TM cells respond by increasing MMP-2, MMP-14 and decreasing TIMP-2 levels • This will increase ECM turnover rates, reduce the trabecular resistance to AHO, and restore normal IOP levels. Molecular mechanism PNT: Trabecular Meshwork under stress • Induction of TGFbeta1 in the TM under cyclic mechanical stress Liton PB et.al 2005 • Induction of IL-6 expression by mechanical stress in the TM Liton PB et.al 2005 TGFbeta1 induces the contraction of TM mediated by the interaction of TM cells with extracellular collagen. The contraction of TM tissue is thought to be responsible for the outflow facility. The possible contribution of chemical mediators in this process is supported by the fact that patients who respond well to latanoprost also generally benefit from pneumatic trabeculoplasty Analysis of expression of matrix MMPs and TIMPs in human ciliar body after latanoprost • MMP-3-9 and 17 may be responsible for the alteration in the ECM with latanoprost treatment • TIMP-3 was only TIMP consistently altered by latanoprost Oh DJ et.al IOVS March 2006 Acute effects of PGF2alpha on MMP-2 secretion from human ciliary muscle cells • Prostanoid F receptor activation leads to the acute secretion of MMP-2. • MMP-2 can decrease outflow resistance in uveoscleral outflow pathways Husain S et.al IOVS 2005 CONCLUSIONS • Pneumatic trabeculoplasty can lower IOP in • • • • • • patients with POAG or OH with very low risk to the subjects Reduction in IOP could be permanent Repeatable with similar or greater effect Latanoprost patients seem especially amenable No damage to optic nerve fibers Does not accelerate/produce VF changes Non clinical significant OCT-RNFL changes Ευχαριστώ Πολύ