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Shedding New Light on the Trabecular MeshworkNATHAN HESEMANN, MD

COLUMBIA, MO

Disclosure

I have no financial interests or relationships to discloseHarry S

Truman VA Chief of Ophthalmology

Columbia Eye Consultant Optometry

University Of Missouri – Mason Eye Institute.

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Aqueous Outflow

What we know in 2020

IOP reduction is the only treatment option in glaucoma

Elevated IOP is secondary to impaired aqueous outflow

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Aqueous Outflow

Current terminology:

Trabecular pathway (conventional outflow)

Pressure sensitive – outflow changes with pressure

Nontrabecular pathway (uveoscleral outflow)

Pressure insensitive – outflow stays about the same

Nontrabecular Outflow

Previously and commonly called uveoscleral outflow

Outflow that includes uveoscleral, uveovortex and uveolymphaticrouts.

Small amount of fluid passing through the cornea, iris and retina is insignificant under physiologic conditions.

Mostly passage of fluid through the anterior face of the ciliary muscle and into the supraciliary and suprachoroidal spaces

This fluid then diffuses through the tissue of the sclera, choroid and lymphatics.

Role of lymphatics remains uncertain.

Nontrabecular outflow

Main resistance is muscle bundles and connective tissue of the ciliary body.

Driven by pressure and osmotic gradient.

Very hard to measure nontrabecular outflow.

Maybe 10-70% of total outflow.

Apparently we have no idea.

Probably 50% of outflow is nontrabecular but this flow declines in glaucoma.

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Nontrabecular outflow

Relatively unaffected by IOP

TM

Uveal

Corneoscleral

Juxtacanalicular – outermost, forms the inner wall of Schlemm’s canal.

Trabecular outflow

Aqueous flows through the TM into Schlemm’s canal

Juxtacanalicular TM tissue – outmost layer next to Schlemm’s forms the inner wall of Schlemm’s.

Aqueous crosses the inner wall of Schlemm's through pores or microtubules.

Then into the collector channel entrances to aqueous, episcleral and conjunctival veins.

Proximal system - TM and Juxtacanalicular tissue

Distal system – everything down stream from Schlemm’s.

Many people think trabecular outflow resistance in glaucoma is 50% proximal, 50% distal.

50% nontrabecular

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Trabecular outflow

Late 1950s and early 1960s

Grant showed that IOP control and loss of control is secondary to outflow problems and not aqueous overproduction.

Cadaver eyes were pressurized and the TM was removed layer by layer

When the inner wall of SC and juxtacanalicular tissue was removed the IOP dropped by about 75%.

Two Erroneous conclusions not taught by Grant but still propagated today.

75% of outflow is through the TM

Trabecular outflow resistance is localized to the juxtacanalicular and Schlemm’s.

Reality: making a hole anywhere increases outflow in a pressurized system.

Juxtacanalicular TM is still thought to be the major site of resistance, but its role has been reconsidered.

Passive Model

Assumes outflow resistance is only a function of TM permeability.

Doesn’t explain the complex anatomy of the TM

A lot of unused parts doesn’t seem right.

Trabecular Outflow

Grant and Ellingsen continued to publish papers that showed resistance is more than just the TM

Left the TM alone and removed outer wall of SC and the sclera. This also eliminated 75% of the outflow resistance

Only 25% attributed to TM

Paradoxical result

So removing either the inner wall or outer wall of SC eliminates 75% of the resistance.

Hypothesis that IOP is the interaction of the inner wall (JXC TM) and outer wall of SC.

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TM Outflow.

Grants studies were done at high pressures (30mmHg)

Grant thought that SC can collapse as IOP rises and TM is forced into Schlemm’s

This closure increases resistance and leads to higher pressures which spiral out of control.

Fast Forward

New in vivo studies show that the TM is not as compact as we originally thought on histology and the spaces are too big to account for all the outflow resistance.

IOP dependent collapse of the SC by TM apposition has been confirmed by many studies – OCT and Ultrasound

SC closure occurs at “normal” pressures.

Tension in the ciliary body pulls on the scleral spur and adds tension to the TM

Keeps the TM from closing SC.

May also increase the permeability of the TM

More to the story

SC closure is an important factor and explains why resistance increases as IOP rises.

TM still passively resists outflow.

“It is self-evident that TM permeability and TM motion must be coexistent phenomena, as only tissues resisting a force undergo deformation.” – Andrew, Surv. Ophth 2020.

Resistance downstream from SC is a significant factor in low-normal IOPs

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Have you ever seen pulsating mires on applanation?

Dynamic Model of the TM

The trabecular meshwork is a “biomechanical pump” that is powered by the ocular pulse, blinking and eye movements.

All the parts have a use.

During systole the TM moves outward from the AC and compresses SC, moving fluid into the collector channels.

During diastole the TM recoils and sucks aqueous into SC

The ocular pulse generates approximately 3mmHg of drive

Blinking and eye movement can generate 10mmHg

TM as a pump

The pumping mechanism of the TM is dependent on elasticity and tension

The movement of the TM is increased at higher pressures until SC closure occurs.

Short term IOP changes alter the pump mechanism – self regulation

Higher pressures increase the movement of TM and volume pumped...up to the point where SC closes then self-regulation is lost.

Long term the pump mechanism is degraded by loss of elasticity.

Basement membranes in TM thicken over time.

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Glaucoma

The TM becomes less elastic in glaucoma

The TM moves less

IOP increases

The TM is pushed outward (into Schlemm’s)

Schlemm's Canal collapses.

Pressure goes up.

This happens in normal eyes also, but normal eyes rebound.

The more this happens the more this happens

TM loses function and we have persistently elevated IOP.

Schlemm's Canal – aqueous outflow is segmental.

SC is not a smooth oval structure – not like a pipe or hose.

Its rough and irregular – aqueous outflow is segmental.

Mostly nasal? Handy for MIGS?

The collector channels have collagen flaps at the entrances.

Yet to be proved these function as valves

More like a lymphatic vessel than a vein.

Summary

The TM is probably a pump that doesn’t work as well in POAG

The TM is the best target for therapy.

Direct Treatment of the problem.

Of note it was not until 1942 that Karl Ascher demonstrated aqueous veins and proved that aqueous was produced and absorbed.

Prior to this we thought aqueous was stagnant.

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Questions

The TM is here to PUMP YOU UP.

POAG epidemiology

70% of Caucasian glaucoma patients have primary open-angle glaucoma

Sounds like a high percentage.

30% of Caucasian patients do NOT have POAG!

If you see 4 glaucoma patients, one of them does not have POAG.

Rest have PDS, PXF, CACG

Gonioscopy is the only way to find out.

Gonioscopy

All glaucoma patients should have a documented gonioscopy.

All patients with a “narrow angle” by screening – such as von Herrick should have a gonioscopy, even with normal IOPS.

Gonioscopy should be preformed every 1-5 years

Indicated repeat gonio: Progressive disease, change in treatment plan, refractory disease, prior results difficult to interpret.

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Gonioscopy

2009 Centers for Medicare and Medicaid

2-3% of eye exams bill for gonioscopy.

CPT 92020 – reimbursement about $20.

About 2-3% of the population has glaucoma.

Gonioscopy – complaints.

Takes time

Patients uncomfortable.

Not easy!

Variations in anatomy

Compression gonio is difficult to master.

Where’s the gonio lens?

I can’t see anything.

Not possible on some patients (rare)

Up your game for Gonioscopy.

Basically everyone needs to get better.

Admit that you know nothing.

Use the resources on-line

Practice, practice

Take your time.

Teaching points:

Pseudophakic patients

3 mirror (not 4 mirror) – tour the angle.

Corneal wedge

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Importance of gonioscopy.

Several years of new studies focused on the angle.

MIGS, SLT, Eagle study.

Providers must be good at gonioscopy.

Eagle: Effectiveness of early lens extraction for the treatment of PACG

“Lens extraction should be first line treatment for advanced angle-closure disease” Tanner, Eye (London) 2020

“CLE is an option in the initial treatment of some patients with PACG as its superiority has been demonstrated against LPI.” Pose-Bazarra Curr OpinOphthal 2018.

30% of your patients don’t have POAG.

How far we have come - 1993

Rossetti et al Randomized clinical trials on medical treatment of glaucoma: are they appropriate to guide clinical practice? Arch Ophthalmol. 1993;11196- 103

“practicing ophthalmologists should be aware that the effectiveness of pressure-lowering agents in the treatment of primary open angle glaucoma is still to be determined"

Noted that controlled trials with functional endpoints and sufficient duration were urgently needed.

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Glaucoma Concepts

A multifactorial progressive optic neuropathy for which intraocular pressure is a major risk factor. IOP is the only modifiable risk factor.

Age/race are the other big risk factors.

Lowering IOP does not “cure” glaucoma. Does IOP lowering “stop” RNFL loss?

No! There is normal age-related loss of RNFL. Vianna JR et al. Ophthalmology. 2015;122(12):2394-2400.

Parikh, RS et al. Ophthalmology, 2007; 114; (5):921-926

The goal of lowering IOP is to reduce RNFL loss to insignificant and hopefully undetectable levels (normal levels)

Target IOP

American Academy of Ophtho Preferred Practice Pattern:

Definition: “a range of IOP adequate to stop progressive pressure-induced injury”

World Glaucoma Association:

Definition: “an estimate of the mean IOP at which the risk of decreased vision-related quality of life due to glaucoma exceeds the risk of the treatment.”

Quality of life with treatment is better than quality of life without treatment.

Disease is worse

than cure

Cure is worse than

disease

Targ

et

IOP

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Understanding Target pressure: We must first understand the untreated state.

Natural History of OAG/OHT

Little prospective data exists because we have no untreated patients

Ocular Hypertension Study.

Collaborative Normal Tension Glaucoma Study

Early Manifest Glaucoma Trial

½ of patients randomized to untreated control group.

Probably not going to see any more trials with an untreated control group.

Progression was defined as reproducible field deterioration or increased cupping as read by the masked grading center.

Ex: 3 depressed points that show up on 3 fields – fields repeated when new points appeared.

Repeat the field Remember that even in reliable visual fields the defects often go

away on repeat testing.

Was it actually real?

Think about glaucoma patients who have “good days and bad days”

Maybe those neurons flicker before they go out?

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Confirmation of Visual Field Abnormalities in the Ocular Hypertension Treatment Study

Keltner, Arch Ophthalmol. 2000;118(9):1187-1194.

Looked at all 21,603 regular follow-up visual fields.

703 were reliable and showed a new abnormality.

In 604 (85.9%) of the 703 the abnormality was not confirmed on the next test which was given 1day to 8 weeks later.

Seeing a new defect in a previously normal eye means very little.

Prescribe another field, not latanoprost.

Ocular HTN Study – Kass et al.

IOPs between 24 - 32 with no evidence of glaucoma

Treatment goal was to reduce IOP 20% and get IOP below 24.

At 5 years

4.4% of treatment group developed POAG

9.5% of observation group developed POAG

2010 analysis of patients 13 years later – those that received treatment from the start did better than those who received treatment after the initial 5 year observation.

Natural History OAG

EMGT: At 6 years 80 of 118 untreated eyes showed progression in the mean deviation (MD)

POAG >21mmHg: -1.31dB/year

NTG (POAG <21mmHg): -0.39dB/year

PXF: -3.31dB/year

Large variability among patients, such that individual progression could not be predicted. - don’t expect any patient to be average.

“other patients probably progressed but did not meet progression criteria of the study”

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Collaborative Normal Tension Glaucoma Study.

79 eyes were untreated controls.

50% showed no progression at 5 years. Mean IOP 16.

Effect of pressure lowering

The Collaborative Normal Tension Study Group: 30% IOP reduction decreased rate of progression from 35% in the observation group to 12% in the treated group.

The Early Manifest Glaucoma Trial (EMGT): IOP reduction by 25% reduced progression from 62 % to 45% in the treated vs untreated.

Ocular Hypertension Treatment: IOP by 20% and get IOP below 24 reduced progression from 9.5% to 4.4% at 5 years.

Generally accepted to set an initial target of 20-30% IOP reduction

Individual goals are more important and target pressure needs adjusted.

Effect of commonly used glaucoma drugs.

Van der Valk 2005 Ophthalmology

Meta-analysis of RTCS.

Placebo: 5% reduction – regression to the mean.

PGAs & Timolol > brimonidine, CAIs & betaxolol,

30-17% reduction depending on peak and trough levels.

differences between PGAs and timolol are less than 1 point

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Questions

SLT: How we got here.

1970 – Goniopuncture with laser – didn’t work that well, but what can you say, it was the 1970s and we had lasers. Seemed like a great idea.

Selective Thermolysis: process by which radiation energy is absorbed by a pigmented cell population within a tissue to cause local damage

Argon Laser Trabeculoplasty (ALT)

Energy selectively absorbed by melanin causes localized damage.

But the duration of 0.1s does not allow for thermal relaxation (cool down)

Heat is diffused into the surrounding tissues.

Thermal relaxation time of melanin is one MICROsecond.

ALT

Theoretically laser caused contraction of tissue and “opening “ of the TM

But the IOP does not go down immediately after laser

Must be some secondary remodeling pathway.

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ALT

Generally, the initial IOP reduction is around 25%-30%

Retreatment does not work that well. Richter repeated ALT in eyes with history of ALT and only 1/3 decreased

3 mmHg or more.

Transient IOP spikes, later development of peripheral anterior synechiae, anterior uveitis

Glaucoma Laser Trial Research Group: ALT as initial treatment is superior to medication through 2 years, but inferior at 5 years.

Selective Laser Trabeculoplasty

Latina and Park 1995

532nm with pulse duration of 3 NANOseconds.

3 orders of magnitude shorter than the relaxation time of melanin.

6 orders of magnitude shorter than ALT

Good for selective thermolysis.

So how does SLT work?

Very hard to study.

Can be done in cadaver eyes – but can only study the anatomical response.

in vivo we would have to image the TM at the cellular level - not quite there yet.

As we discussed in the opening slides, we have a lot to learn about the TM, much less SLT effect on the TM.

Hard to define effect of SLT when we do not exactly know what is going on in normal eyes.

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SLT Mechanism

Limited structural damage on histopathology (vs ALT)

Studies show multiple mechanisms Cytokines, interleukins, matrix metalloproteinase

Monocytes, macrophages.

Cell division.

John, Paul, George and Ringo.

Notable that both PGAs and SLTs may interrupt intercellular junctions and increase aqueous permeability. Alvarado AJO 2010.

SLT increases outflow by a uncertain mechanism.

How its done.

Seated at laser, much like an examination.

Pre-procedure pilocarpine and or brimonidine optional.

Proparacaine

Gonioscopy lens

Takes about 2-5 minutes

Some blurry vision after

Patients may feel mild ache or discomfort.

Not painful

SLT does not correct vision.

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BREAK

Questions?

What we knew before LiGHT trial.

Clinical efficacy

Prior to LiGHT trial various trials showed such a wide range of results that it is hard to make a conclusion

Example: 20% reduction in IOP

66.7 to 75% eyes at 6 months

58 to 94% at 12 months

40 to 85% at 2 years

38 to 74% at 3 years

38 to 68% at 4 years

11.1 to 31% at 5 years

See Gazzard et al. Eye 2018

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SLT in Treatment Naïve vs Replacement.

McIlraith et al. Journal of Glaucoma 2006

Treatment naïve-group 8.1mmHg drop

PGA 4 week washout group 6.4 mmHg Statistically significant difference

Is 4 weeks adequate washout time

Or is SLT more effective in treatment naïve patients

Would be good to know as many patients started on PGA just before referral.

Are we decreasing the clinical effectiveness of SLT by starting patients on PGA?

Adjunct Therapy

Woo et al

Patients taking 0-3 glaucoma medicines were given SLT (N= 206)

Average reduction 21-29% at 6 months across all groups

24-26% reduction at 5 years across all groups (N=55 remaining)

Similar findings in other smaller studies.

24 hour control

IOP changes over a 24 hour period (diurnal variation)

24 hour contact lens sensors show less diurnal variation after SLT in POAG and OHT patients.

2 small studies

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Repeat Laser

SLT effect diminishes with time.

Multiple studies – prior to LiGHT trial SLT repeated as short a 6 months.

Possibly repeat treatments last longer than initials treatments.

Success of repeat is similar to initial therapy.

Repeat often achieves the same pressure point as first treatment, but the percentage reduction is often less.

Secondary treatments are usually tried at lower pressures.

1st treatment: 24mmHg to 17mmHg

Repeat treatment: 22mmHg to 17mmHg

SLT in Chronic Angle closure

Has been studied and it worked.

I suggest phaco.

Eagle Study – PI vs phaco

PXF, Pigmentary, NTG

Success is more limited.

Patients with pigmentary glaucoma may have more pain and inflammation afterward.

IOP spikes more common.

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Complications and adverse events

AC reaction in 80% of patients.

Pred QID x 5 days. (SALT Trial)

Rarely CME, Peripheral anterior synechiae.

Transient corneal edema can be seen

Rare reports of permanent corneal changes.

Song J. Complications of selective laser trabeculoplasty: a review. Clin Ophthalmol 2016;10:137–143.

Notable trials comparing IOP lowering effect of SLT to drops as initial treatment. Studies like these paved the way for the LiGHT trial.

Showed safety and effectiveness in IOP control in smaller populations over shorter time periods.

Notable SLT vs Drops Studies

Nagar M, A randomized, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. Br J Ophthalmol. 2005;89(11):1413-1417.

Katz LJ, Steinmann WC, Kabir A, et al. Selective laser trabeculoplasty versus medical therapy as initial treatment of glaucoma: a prospective, randomized trial. J Glaucoma. 2012;21(7):460-468.

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LiGHT Trial - How is it different.

Compares OAG and OHT

Health related quality of life

Clinical effectiveness

Cost electiveness

Robust treatment-escalation protocol to minimize risk of bias.

Longer Follow-up

HVF data – did not just look at IOPs.

Laser in Glaucoma and Ocular Hypertension Trial. LiGHT Trial.

Purpose: establish whether initial treatment with SLT is superior to topical medication in POAG and OHT.

718 patients at 6 centers in the UK enrolled 2012-2014

Treatment arms

Initial SLT followed by conventional medical therapy as needed

Initial conventional medical therapy

Trial was not masked, but treatment was on done by algorithm.

Testing was masked (optometrist/technician taking IOP, getting the OCT or administering the visual field did not know the treatment)

Patient Characteristics

Does the LiGHT trial apply to my population?

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LiGHT Trial Participants

Newly diagnosed, never treated patients with OHT, POAG, PXF and NTG

Mean Deviation Not worse than -12.0dB in the good eye or -15 in the bad eye.

Patients unable to use topicals or be seated at the laser could not be randomized and were not enrolled

Patient with history of uveitis (contraindication to SLT)

Patient with previous surgery, except for uncomplicated phacomore than one year prior, were excluded.

Patient Characteristics.

718 patients

41% had bilateral POAG

13% POAG and OHT

22% POAG and healthy fellow eye

17% bilateral OHT.

5% OHT and healthy fellow eye.

POAG average 68 years old

OHT averaged 58 years old.

70% Caucasian

20% African heritage

30% +FH

Exclusion Criteria

Advanced POAG

Visual acuity worse than 6/36 (20/120)

Inability to use topical meds

Visually significant cataract

Treatment for other eye conditions.

AMD, pregnancy

Diabetic retinopathy.

Cataract surgery within the preceding year.

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Management

Clinical monitoring intervals and treatment decisions were guided by a computer algorithm.

Intake exam

Visual acuity

HVF 24-2 SITA standard

Heidelberg optic disc imaging

IOP by Goldman applanation

CCT

DFE

Questionnaires

Quality of whole life questionnaire (EQ-5D-5L)

Glaucoma Utility index: glaucoma health outcomes such as near and distance vision, mobility activities of daily living

Glaucoma Symptom Scale: Burning, stinging, tearing, dryness, soreness, blurry vision, dim vision, hard to see in dim or bright lights, halos.

Glaucoma Quality of Life-15: Reading, walking on uneven ground, dim and bright lights, tripping, falling, crossing road, finding items.

Client Receipt Service Inventory: patient costs and service utilization

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Standardized Disease Treatment

Computer based algorithm was used to determine severity and determine target IOP.

Canadian Target IOP WorkshopTraditional Classification

Suspect

IOP above 22

0.2 asymmetry

Suspicious rim

Suspicious HVF 24-2

Early

HVF not within 10 degrees

0.65 C/D

Moderate

HVF not within 10 degrees

C/D 0.7-0.85

Severe

HVF within 10 degrees

More than 0.85 CD

Classification for the LiGHT Trial

OHT: healthy nerve with no HVF defect

Mild OAG: nerve changes with 0 to -6.0dB MD – no point within 5 degrees of fixation.

Moderate: nerve changes with -6.0 to -12dB or points within 5 degrees of fixation

Severe: nerve changes and <-12dB or both hemifields have points within 5 degrees of fixation.

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Algorithm Targets

OHT

IOP <25 and >20% reduction (based on OHTS study)

POAG

Mild: <21mmHg & >20% reduction (based on CIGTS and expert opinion)

Moderate: <18mmHg & >30% reduction ( based on CNTGS and AGIS)

Severe: <15mmHg & >30% reduction (based on AGIS and expert opinion)

Similar to Canadian Target IOP workshop in 2003.

Laser Arm

SLT first

Retreatment with SLT if there was a response to the first laser.

After two SLT treatments patients started on medical therapy.

If there were complications of first treatment, start medical therapy.

SLT Application

100 Shots of laser (25 per quadrant)

360 degrees

50% bubbles

0.3 to 1.4mJ

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Medical therapy Arm.

Start with prostaglandin analogues

Second drug: Beta blockers

Third and Fourth: CAI & alpha-agonists.

Combo drops allowed.

Max medical therapy

If patients met any of the 3 criteria they were offered Trabeculectomy

Could not tolerate drops necessary to meet target IOP.

Use of 3 medications

5 drop doses per day

Disease progression

3 points that get worse on 3 fields.

“likely progression” on Glaucoma progression analyses on HVF software.

OCT images with rim area loss >1% of baseline per year.

If patients progressed treatment was increased, regardless of IOP.

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Target IOP and Management

2-4 mmHg above target without progression – raise target & monitor more closely.

2-4 mmHg above target with progression – intensify treatment to get them to target

4mmHg above target – do not consider progression – intensify treatment to get them to target.

Progression at the initial target pressure

Decrease target pressure 20% with increased treatment and begin intensive monitoring

For patients on MMT

2mmHg above target watch closely if they progress offer surgery.

Glaucoma IOP management– on one slide.

Base the target pressure on untreated pressure and disease severity.

OHTN: IOP <24 & 20% reduction.

POAG

Mild: <21mmHg & >20% reduction

Moderate: <18mmHg & >30% reduction

Severe: <15mmHg & >30% reduction

Keep lowering pressure until patient is <4mmHg from initial target.

Then watch for progression - low threshold to repeat field.

No progression – OK

Progression – reduce further 20%

Questionnaires Re-Evaluated at 36 months.

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Design

Both the treating providers and the patients knew what treatment arms they were in

No Placebo.

However, test administration, OCT, HVF were all masked and decisions were made by computer algorithm.

First trial to compare SLT with medicine in previously untreated patients.

Personalized IOP Target, Objectively defined IOP Target

HVF and Quality of life measures as and endpoint, not just IOP lowering effect.

LiGHT Trial Results

718 Patients

356 SLT first

362 Medications first

Note that throughout the results presentation the numbers will occasionally be slightly different. This is because protocol was broken or incomplete results during that portion of the analysis.

IOPs

OHT averaged 26mmHg (21 -32 defined)

POAG averaged 24mmHg

24% of POAG were 19mmHg or below.

Note POAG < OHT IOP: That’s because the NTG pull down the average for POAG. No such thing as normal tension ocular hypertension.

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Analysis available at the 36 month end-point

536 eyes in 314 patients that received SLT

536 eyes in 312 patients that received drops.

Primary Outcome: Quality of Life

At 36 months there was not a significant difference in overall quality of life between the two groups.

Not surprising considering glaucoma is an asymptomatic disease.

Glaucoma related quality of life measures suggested better quality of life in the SLT group with one questionnaire reaching statistical significance.

IOPS at 36 months

509 of 536 (95%) eyes treated with Selective laser trabeculoplasty were at target IOP at 36 months. (with or without additional meds)

Target IOP was achieved without medications in 419/536 (78.2%)

76.6% received only one treatment

499 of 536 (93%) eyes treated with medications were at target pressure

Target IOP was achieved in 64.6% with use of only PGA

SLT patients were below target at 93% of visits.

Medication patients were below target at 91% of visits.

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In Case you missed that.

76% of patients were at target pressure at 36 months with a single SLT treatment.

Another way to look at it.

100% of your glaucoma patients on drops or 25% for the next 3 years?

Office Banter.

Drops. Do you have refills?

You changed pharmacies?

Travatan is preferred.

Purple drop or blue drop.

Light green at night, yellow in morning.

You stopped your drops before the exam to see how the pressure would be.

My wife does my drops.

The burning means its working.

Patrick Mahomes doesn’t throw interceptions based on your eye drops, please use them.

SLT Your pressure is 18 today, that’s down

from 24. Very good.

You pressure may creep back up in a few visits, if that happens we can repeat the laser.

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Efficacy of Repeat SLT in Medication-Naive OAG and OHT in the LiGHT Trial

Anurag Ophthalmology 2020

Patients receiving repeat 360 degree SLT within 18 months.

Retreatment initiated by IOP or progression.

115 eyes in 90 patients received repeat SLT within 18 months.

34 eyes were early treatment failures (<2 months) Actually 158 of 611 (25%) of Light trial eyes received repeat SLT, but only

repeats in the first 18months were analyzed to allow for comparison of duration between first and second treatments.

67% of 115 eyes were drop free after second SLT.

The effect and duration repeat SLT was at least as good as the first SLT.

Additive Effect

Patients with higher starting pressures have greater absolute reductions

The untreated pressure is going to be higher than the pressure that triggers a repeat SLT.

Controlling for difference between pre-treatment IOP in the primary vs repeat groups, the repeat groups have a statistically significant greater reduction in IOP.

The second SLT also had a longer duration of effect

SLT vs Drops

SLT outperformed drops in all groups except severe OAG.

25 patients in eye drop group needed phaco.

13 patients in the SLT group needed phaco.

Numbers of clinic visits was the same for both groups after subtracting the mandated 2 week IOP check after SLT. Only 6 eyes had a rise of >5mmHg on day of SLT. One required

treatment.

1 day one treated pressure spike in 776 SLT treatments.

Pressure check at 2 weeks “appears unnecessary”

10-day global period.

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Severity

Both drops and SLT had more failures as disease severity increased.

Lower target pressure goals in these patients.

Progression

36 eyes progressed on HVF in the eye drops group

23 eyes progressed on HVF in the SLT Group

5 eyes in the medication group had trabeculectomy

Zero eyes in the slt group had trabeculectomy

Side effects

73 patients reported medication side effects.

34% of SLT patients reported transient discomfort, blurred vision, photophobia and hyperemia.

No vision threatening events.

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Cost

The study was done in the UK, hard to say how that converts to dollars

Patients saved money.

At 36 months laser group

74% drop free.

Better IOP control.

More visits at the target pressure.

More economical

Less intense drops

No glaucoma surgeries.

Why was laser better

Better compliance.

Probably works even better in the real world where compliance is even worse

Clinical trial participants are more compliant

Clinical trial participants get medicines as part of trial

SLT has no “peak and trough” (diurnal variation)

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Conclusion of LiGHT

“Selective laser trabeculoplasty should be offered as a first-line treatment for open angle glaucoma and ocular hypertension, supporting a change in clinical practice.” -Gazzard.

What Do Ophthalmologist think?

L. Jay Katz, Wills Eye, Journal of Glaucoma 2020

SLT is a safe and effective first line treatment for glaucoma that is underutilized.

Developed and educational program for ophthalmologists to increase consideration of selective laser trabeculoplasty earlier in the glaucoma treatment paradigm.

Prior to educational program

28% of ophtho prefer SLT as first line therapy.

52% said <10% of patients actually received SLT as first line therapy.

SLT Volumes

FDA approval in 2001

75,000 procedures in 2001

142,000 procedures in 2012

Medicare beneficiaries Arora 2015

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Barriers to utilization

Uncertain about patient selection

Lack of evidence

Availability/time

Patient hesitancy

Drops are easy to explain

SLT requires referral

Drug companies have nice dinners.

Nudges – not just a great book.

We are all “choice architects”

How we present SLT matters.

Key points: SLT works most, but not all of the time.

SLT is a relatively safe procedure.

SLT does not cure glaucoma, but provides a temporary pressure reduction that will hopefully last years. It may need to be repeated.

SLT does not correct vision.

Patients may return to activities the same day

The eye may feel uncomfortable for a few hours after surgery, symptoms are usually gone in 1-2 days.

Management of SLT patients

Identify patients that need treatment.

Still an ‘art’

There will be disagreements between providers given the many glaucoma options

Life expectancy, quality of life, severity of glaucoma or OHT.

1/3 of newly diagnosed patients live <10 years.

Average life expectancy about 13 years. – Quigley. AJO 2006

Sharma, Ten‐year outcomes in newly diagnosed glaucoma patients: mortality and visual function, BJO 2007.

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Work together, put ego away.

If the ophthalmologist does SLT every time for every patient you send him or her, that’s probably a bad sign.

You want an ophthalmologist that independently considers the risks and benefits.

You want a colleague that uses their brain.

No two providers agree on everything 100% of the time – especially glaucoma

Avoid telling the patient that they “need” or “will have” SLT.

Yes, most of the time they do.

Disagreement between providers on therapy?

Glaucoma is a slow disease. There is time to think it though.

Like most disagreements, there often is a lack of full information or communication.

Repeat testing, careful monitoring can solidify the picture.

SLT

Ophthalmologist would/should like to look at the visual fields themselves.

Ultimate responsibility as to the appropriateness of procedure.

Can be difficult to share pressures, OCTs and VFs for review.

We need to get better at that

Guest EMR logins?

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Management.

Day of SLT – may or may not have IOP check.

SALT Trial – 4-5 days of anti-inflammatories may increase effectiveness and increase comfort.

IOP Recheck at 2 weeks may or may not be necessary.

10 day global period.

IOP check at 6-8 weeks

OK to stay on existing glaucoma drops

May start to wean off drops as IOP responds.

Sending for repeat SLT as appropriate.

Summary

The TM is probably a pump

You have to know gonioscopy

When in doubt repeat the testing. (pressure, field, OCT mismatch)

SLT as first line achieves target pressure in 75% of patients without drops at 3 years. – LiGHT

Results of the LiGHT trial should cause a shift in our management.

Citations.

Pose-Bazarra S, Azuara-Blanco A. Role of lens extraction and laser peripheral iridotomy in treatment of glaucoma. Curr Opin Ophthalmol. 2018;29(1):96-99.

Tanner L, Gazzard G, Nolan WP, Foster PJ. Has the EAGLE landed for the use of clear lens extraction in angle-closure glaucoma? And how should primary angle-closure suspects be treated?. Eye (Lond). 2020;34(1):40-50.

van der Valk R, Webers CA, Schouten JS, Zeegers MP, Hendrikse F, Prins MH. Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials. Ophthalmology. 2005;112(7):1177-1185.

McAlinden C. Selective laser trabeculoplasty (SLT) vs other treatment modalities for glaucoma: systematic review. Eye (Lond). 2014;28(3):249-258. doi:10.1038/eye.2013.267

Katz LJ, Steinmann WC, Kabir A, et al. Selective laser trabeculoplasty versus medical therapy as initial treatment of glaucoma: a prospective, randomized trial. J Glaucoma. 2012;21(7):460-468.

Richter CU, Shingleton BJ, Bellows AR, Hutchinson BT, Jacobson LP. Retreatment with argon laser trabeculoplasty. Ophthalmology 1987;94:1085–1089

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Arora KS, Robin AL, Corcoran KJ, Corcoran SL, Ramulu PY. Use of various glaucoma surgeries and procedures in medicarebeneficiaries from 1994 to 2012. Ophthalmology 2015;122:1615–1624.

Groth SL, Albeiruti E, Nunez M, Fajardo R, Sharpsten L, Loewen N, Schuman JS, Goldberg JL. SALT Trial: Steroids after Laser Trabeculoplasty: Impact of Short-Term Anti-inflammatory Treatment on Selective Laser Trabeculoplasty Efficacy. Ophthalmology. 2019 Nov;126(11):1511-1516. doi: 10.1016/j.ophtha.2019.05.032. Epub 2019 Jun 6. PMID: 31444008; PMCID: PMC6810843.

Woo DM, Healey PR, Graham SL, Goldberg I. Intraocular pressure-lowering medications and long-term outcomes of selective laser trabeculoplasty. Clin Exp Ophthalmol 2015;43:320–327.

Parikh, Normal Age-Related Decay of Retinal Nerve Fiber Layer Thickness,Ophthalmology,Volume 114, Issue 5,2007,Pages 921-926

Mills RP, Budenz DL, Lee PP, Noecker RJ, Walt JG, Siegartel LR, Evans SJ, Doyle JJ. Categorizing the stage of glaucoma from pre-diagnosis to end-stage disease. Am J Ophthalmol. 2006 Jan;141(1):24-30. doi: 10.1016/j.ajo.2005.07.044. PMID: 16386972.

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