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Glaucoma advances

What future advavces to expect

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Glaucoma advances

  1. 1. • Evolution – Manual Kinetic Automated Static • Automated: 24 or 30 -2; 50 t0 80 locations – Bayesian test strategies: SITA – VF sensitivity values – Normative data: Age, Sex, Location adjusted – Multivariate statistical & Mathematical analysis – Alignment monitoring – Different visual functions: white, Blue on Yellow
  2. 2. HFA limitations • Central only – No far periphery – Beyond 30° radius may harbor glaucomatous functional loss – Limited macular testing • SLO and OCT revealed damaged macula • Time consuming
  3. 3. Gen X Perimetry Smart phone and Tablet based technology • VF Easy App: George kong – High spatial and temporal resolution – Dynamic intensity range – Accurate calibration – Light weight – Inexpensive; ! free – No need for continuous power
  4. 4. VF Easy App • Similar to 24-2 SITA • Grey scale representation • <3.5 minutes per eye test • Future: – Fewer testing locations – Shorter testing time
  5. 5. Micro-perimetry: MP OCT proved structure function association • Currently MP use limited to macula • Compass MP Center vue – Central 30° radius – Better functional assessment • Current Structure Function testing at different times – Ideal simultaneous • Improves alignment • Registration • Localization
  6. 6. ADVANCES IN IMAGING Beyond OCT
  7. 7. Advances in imaging • Evolution – Analog to Digital – Disc photography: • Subjective • Qualitative changes – Stereoscopic Imaging of ONH: flicker photography • Inter-observer variation in estimating neural rim width – Digital OCT • ONH, RNFL
  8. 8. OCT Structural precedes over Functional • Current usages – Disc area – Rim area – Vertical /horizontal rim thickness – C/D ratio: Vertical – Termination of Brusch membrane ( software, algorithm) • Useful in tilted/ oblique discs • Early glaucomatous changes – Thickness of GC-IPL • Ganglion cell density • Inner plexiform layer thickness • Average Peri-papillary RNFL, thickness • Minimum GC-IPL thickness
  9. 9. Structure Function correlate
  10. 10. OCT Future parameters • Capture speed – Scan speed: > 70, 000 (100,000 A scans) – Resolution (Tissue Depth) 3 μ (3.8 – 5 μ) • Global RNFL thickness measurement – @95% Specificity • Sensitivity 65-6 Ziess; 62.1 optiVue
  11. 11. SS SD - OCT • Short cavity swept source • Tunable wavelength • 100,000 a scans • Faster acquisition – Wide angle view • All in one scan: Posterior pole, ONH, Macula • Less susceptible to artifacts, centering error
  12. 12. OCT physiological changes • Lamina Cibriosa (LC): – Primary site of axonal injury • Bowing of LC: Axonal damage due to ischaemia • OCT finding: In glaucoma – Displacement of LC: • Occurs prior to visible Onh changes – Thinning of LC
  13. 13. OCTA: SSADA • Split spectrum amplitude decorrelation angiography – Quantitative measure of local circulation in ONH – Differences in disc flow index • Normal versus Glaucomatous • Safer than invasive FFA which also evaluates disc flow
  14. 14. TONOMETRY Is Goldman a Gold standard?
  15. 15. Accurate TONOMETRY: Obstacles • GAT: ?? Gold standard –NO!!! • CCT • Myopia • Keratoconus • Children • Corneal scarring • Nystagmus
  16. 16. Improvements • Riechert – Pneumotonometer – Tonopen XL – ORA • PASCAL dynamic • Why GAT – No expense: Gravity – Economical – Fits on S/L – Easy to understand
  17. 17. PHARMACOTHERAPY Rocking RhoKinase
  18. 18. Phase 3 pipeline • Histiric – Miotics – Β blockers: selective – Selective α adrenergic agonists – CAI – PGA
  19. 19. What’s in store • Directly acting on tissue of pathology –Trabecular meshwork • Rho Kinase inhibitors: Rhopresa, Rocklatan • Adenosine agonists: trabodenoson • NO donors: Latanopreston bunod, NCX 667
  20. 20. ROLE OF EXTRACELLULAR MATRIX CELL MORPHOLOGY WITHIN THE TRABECULAR MESHWORK Increase in actin stiffness and the development of crosslinked actin networks Cells assume a rigid shape and outflow has been shown to decrease Ethacrynic acid, latrunculins, and Rho-kinase inhibitors induce changes in cell shape, increasing outflow around cells and decreasing IOP
  21. 21. Rho Kinase inhibitor • Rhopressa: IOP lowering – Action 3 cooperative mechanisms • 1. ROCK inhibition: – Increase aqueous outflow through trabecular meshwork • 2. Reduce episcleral venous pressure • 3. Nor-epinephrine transport inhibitor – Decreases total amount of fluid produced • Complements PGA (increase uveoscleral outflow
  22. 22. Rhopressa: Once Daily • Less effective than latanoprost – 1 mm of Hg at 0.01 or 0.02 % compared to PGA – More hyperemia • But decreases upto 5.7 mm of Hg @ 0.02 % – Phase 2b trails • Superior to timolol, non inferior – ROCKET 2 phase 3 registration
  23. 23. Adonosine agonists: TRABODENOSON • 4 Adenosine receptors in Human Trabecular mesh work – In combination A1, A2, A3 reduce IOP – Alone A3 increases IOP – Decrease of 7 mm of Hg IOP – No detectable systemic side effects – Less hyperemia – Once Daily
  24. 24. A2A agonist • OPA 6566 – Increases AQ humor outflow via • Trab mesh • Schlemm’s canal – Not by UVEOSCLERAL PATHWAY as by PGA • ATL313 – No study details out yet
  25. 25. Modulation of NO: NO DONORS • NICOX: Latanoprostene bunod – Prostaglandin F2 analog • IOP regulation • Neuroprotective • Better than Timolol • Once daily • NCX 667: preclinical studies – Better than nicox • Less Dosing issues, less side effects
  26. 26. ROCLATAN • Phase 2b trail: 34 % decrease in IOP • Fixed combination of Rhopressa and Latanoprost – 4 actions – Combination exceeds PGA alone efficacy – Combination less hyperemia
  27. 27. Improving Adherence • Positive reinforcement – Praise pt if IOP in target range • Owernership and Parternership – Why they need to continue – Their responsibility • Education – Missinga day in a week adds upto 6 weeks a year – One page handout glaucoma, eye drops
  28. 28. Compliance • Reeducation – Spend time reeducating if not adhering – Show and explain VF, OCT, Discuss progression • Creativity – Schedule dosing to suit daily activities • Explain stage of glaucoma, make them understand treatment plan
  29. 29. SURGICAL ASPECTS Are you still doing Trab?
  30. 30. Aqueous outflow: Segmental and distal flow
  31. 31. Supra choroidall space PHYSIOLOGIC RATIONALE Aqueous humor that enters the suprachoroidal space exits the eye via the uveoscleral outflow system This normal physiologic route of aqueous drainage consists of flow from the anterior chamber along the ciliary muscle into the suprachoroidal space and out through the sclera into connective tissue of the orbit Uveoscleral pathway responsible for up to 50% of total outflow Most effective pharmacologic therapies for reducing IOP act by increasing uveoscleral outflow
  32. 32. Newer Surgical procedures None of these procedures has been shown to reduc e IOP to the degree achieved by trabeculectomy
  33. 33. Primary surgical interventions • Trabeculectomy or an aqueous tube shunt: Complication profile –Sub conjunctival scarring –fibrous encapsulation –bleb leaks –hypotony –choroidal hemorrhages – blebitis –endophthalmitis –ptosis – diplopia
  34. 34. Update on MIGS • Safe even in early and moderate disease • Ab Interno micro incision, Less trauma • High safety profile • Rapid recovery
  35. 35. Why MIGS? Greater safety and fewer complications Minimise the invasiveness of traditional trabeculectomy Eliminates removal of sclera and iris during the procedure The Express glaucoma filtration device Stainless steel, 400 mm, biocompatibile, no surrounding tissue inflammation MRI safe and compatible to 4 tesla Do not achieve the dramatic intraocular pressure (IOP) reduction typical of what can be seen with the gold standard of trabeculectomy
  36. 36. Currently available MIGS • Trabectome • iStent • Goniscopy assisted transluminal trabeculotomy • Ab interno canaloplasty
  37. 37. Trabectome • Trabeculoplasty via internal approach • Uses electrocautery to remove strip of Trab mesh, unroof schlemm’s canal – Allows Aq to flow freely out of eye • Treat 120° through single incision – If larger areas are needed extend incision
  38. 38. iStent
  39. 39. Gonioscopy assisted transluminal trabeculotomy • Goniotomy • Canulating schlemm’s canal 360° – Passing a suture or – Microcatheter • Retrive the suture – catheter at distal end • Externalize to complete trabeclotomy – Removes the tissue that is contributing to the resistance
  40. 40. Ab Interno canaloplasty • Similar to gonioscopy assisted transluminal trabeculotomy – Goniotomy – Schlemm’s canal cannulated with microcatheter – Pass through 360° of the canal – Viscodilation of the canal dilates – Collector channel system restored – Aq flows into distal drianage system
  41. 41. Future MIGS Devices: Trabecular meshwork • Second generation istent: Injectable • Phase 3 trails • Titanium, 360μm long, different shape • Narrow lumen • Apical head with 4 inlets • Flange base secures and allows passage of Aq into schlemm”s canal • No sideways sliding • Two stents preloaded
  42. 42. Hydrus (Nitinol) • 8 mm flexible • Dual mechanism – Has Snorkel, allows Aq into schlemm’s canal – Due to long length, allows it to dilate and support schlemm’s canal upto 3 clock hours • Dilation allows Aq to flow through Trab meshwork, placing Trab mesh work under tension – As collector channels are segmented, Hydrus disrupts tissue bridges, accessing more collector channels
  43. 43. Kahook Dual blade • Similar to trabectome • Uses blades in stead of electro cautery • Blade has tapered tip – First blade – Easy entry into schlemm’s canal – Then into trab meshwork – Second blade • Blade in canal lifts and streches meshwork • Safely cuts tissue • Minimum collateral damage
  44. 44. Future devices: Suprachoroidal space • Cypass Micro – stent – Polyimide 6 mm long , 300 μm lumen – Allows Aq from AC to Suprachoroidal space – Stent placed under gonioscopy – Target located between SS and ciliary body – Stent enters the potential space between inner scleral wall and ciliary body, and choroid • Istent supra ; Under trail – Uveoscleral outflow pathway gbvvv
  45. 45. Future devices: sub conjunctiva • Xen45: ?? MIGS. FDA 510(K) in 2017 – Soft tubular porcine gelatin cross linked with glutaraldehyde – 6 mm long: lumen size 3 sizes; 45,63, and 140 μm – The tube in 27 G needle under conjunctiva is inserted through anterior meshwork and sclera – This allows Aq to pass through the tube, delivering Aq into sub conj space – Bleb is formed without external cutting and suturing

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    Feb. 9, 2016
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What future advavces to expect

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