glaucoma advances
TRANSCRIPT
What’s the future
Glaucoma management!
Innovative solutions
Perimetry
Diagnostics
• Signal : Noise ratio –Extraction of better signal from noise
CHALLENGES OF VF ANALYSIS
• 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
HFA
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
Gen X PerimetrySmart 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
VF Easy App
• Similar to 24-2 SITA• Grey scale
representation• <3.5 minutes per eye
test• Future:– Fewer testing locations– Shorter testing time
Micro-perimetry: MPOCT 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
ADVANCES IN IMAGINGBeyond OCT
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
OCTStructural 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
Structure Function correlate
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
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
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
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
TONOMETRYIs Goldman a Gold standard?
Accurate TONOMETRY: Obstacles
• GAT: ?? Gold standard–NO!!!• CCT• Myopia• Keratoconus• Children• Corneal scarring• Nystagmus
Improvements
• Riechert– Pneumotonometer– Tonopen XL– ORA
• PASCAL dynamic• Why GAT– No expense: Gravity– Economical– Fits on S/L– Easy to understand
PHARMACOTHERAPYRocking RhoKinase
DISTAL
PROXIMAL
Phase 3 pipeline
• Histiric
–Miotics
– Β blockers: selective
– Selective α adrenergic agonists
– CAI
– PGA
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
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
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
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
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
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
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
ROCLATAN
• Phase 2b trail: 34 % decrease in IOP
• Fixed combination of Rhopressa and
Latanoprost
– 4 actions
– Combination exceeds PGA alone efficacy
– Combination less hyperemia
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
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
SURGICAL ASPECTSAre you still doing Trab?
Aqueous outflow: Segmental and distal flow
Supra choroidall spacePHYSIOLOGIC 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
Newer Surgical procedures
None of these procedures has been shown to re-
duce IOP to the degree achieved by trabeculectomy
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
Update on MIGS
• Safe even in early and moderate disease
• Ab Interno micro incision, Less trauma
• High safety profile
• Rapid recovery
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
Currently available MIGS
• Trabectome
• iStent
• Goniscopy assisted transluminal
trabeculotomy
• Ab interno canaloplasty
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
iStent
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
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
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
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
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
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
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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