glaucoma advances

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

gbvvv

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