1

Doctors of Optometry | Course Notes

OD2 – 2CE Innovations in Glaucoma

Saturday, February 17, 2018 8:40 am – 10:40 am Plaza C – 2nd Fl

Presenter: Dr. Walt Whitley Walter Whitley, OD, MBA, FAAO serves as the Director of Optometric Services and Residency Program Supervisor at Virginia Eye Consultants in Norfolk, Virginia where his practice encompasses ocular surface disease, glaucoma, surgical co-management, clinical research and the supervision of an extensive referral network. He is a frequent lecturer and author on ocular disease, surgical comanagement and practice management topics. Dr. Whitley is the co-chief medical editor of CollaborativeEye and serves on the editorial boards for the Review of Optometry and Optometry Times. On the state level, Dr. Whitley is the current legislative chair for the Virginia Optometric Association and serves on the board of trustees. He was named the 2012 Young OD of the Year and the 2015 Keyperson of the Year for the Virginia Optometric Association.

Course Description

This course will review some of the new technologies, medications, and philosophies utilized in the treatment and management of glaucoma. Using case examples, attendees will be able to discuss issues to determine when to treat, when to use medication vs. surgery, and how to improve patient compliance.

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Doctors of Optometry | Course Notes

NOTES:

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Innovations in Glaucoma COPE#52116-GL

Walter O. Whitley, OD, MBA, FAAO Director of Optometric Services

Virginia Eye Consultants

Residency Program Supervisor

Pennsylvania College of Optometry

Virginia Eye Consultants Tertiary Referral Eye Care Since 1963

• John D. Sheppard, MD, MMSc

• Stephen V. Scoper, MD

• David Salib, MD

• Elizabeth Yeu, MD

• Thomas J. Joly, MD, PhD

• Dayna M. Lago, MD

• Constance Okeke, MD, MSCE

• Jay Starling, MD

• Samantha Dewundara, MD

• Rohit Adyanthaya, MD

• Albert Cheung, MD

• Walter O. Whitley, OD, MBA, FAAO

• Cecelia Koetting, OD, FAAO

• Christopher Kruthoff, OD, FAAO

• Jessica Schiffbauer, OD

• Kelsey Butler, OD

Disclosures

• Alcon

• Allergan

• Bausch and Lomb

• Biotissue

• Beaver-Visitec

• Carl Zeiss Meditec

• Diopsys

• Advanced Ocular Care – Co-Chief Medical Editor

• Review of Optometry – Contributing Editor

• Optometry Times – Editorial Advisory Board

Walter O. Whitley, OD, MBA, FAAO has received consulting fees, honorarium or research funding from:

• Glaukos

• J&J Vision

• Ocusoft

• Science Based Health

• Shire

• TearLab Corporation

• Tearscience

The Most Valuable Glaucoma Tool

Glaucoma: Diagnosis

• We know it when we see it

IOP: 26 OU

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• Yet not always so easy to detect

Glaucoma Diagnosis

3 YEARS

IOP: 23 IOP: 25

CCT: 450

Glaucoma Diagnosis

Glaucoma Diagnosis

• Gonioscopy

• Central corneal thickness

• Visual fields

• Fundus photography

• Scanning lasers

• Serial tonometry

• Corneal hysteresis

• Electrodiagnostics

GLAUCOMA SEVERITY SCALE DEFINITIONS

• Mild Stage: optic nerve changes consistent with glaucoma but NO visual field abnormalities on any visual field test OR abnormalities present only on short-wavelength automated perimetry or frequency doubling perimetry.

• Moderate Stage: optic nerve changes consistent with glaucoma AND glaucomatous visual field abnormalities in one hemifield and not within 5 degrees of fixation.

• Severe Stage: optic nerve changes consistent with glaucoma AND glaucomatous visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least one hemifield.

http://www.americanglaucomasociety.net/professionals/glaucoma_staging_codes_teaching_module/

Managing Glaucoma Patients

• Monitor IOP reduction: 1-2 week, 1 month

• Check IOP every 3-4 months

• Repeat VF every 6-12 months

• Disc photos every 1-2 years

• Gonioscopy every year

• Optic nerve analysis every 6-12 months

• Document everything

http://www.aoa.org/optometrists/tools-and-resources/clinical-care-publications/clinical-practice-guidelines?sso=y https://www.aao.org/guidelines-browse?filter=preferredpracticepatterns

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What We Do Know

Ocular Hypertension Treatment Study

4.4% 9.5% 5 years

Gordon, M., Beiser, J., Brandt, J., Heuer, D., Higginbotham, E., Johnson, C., & Keltner, J. (2002, June). The Ocular Hypertension Treatment

Study. Archives of Ophthalmology, 120, 714-720.

What We Do Know- OHTS

Coleman, A., Gordon, M., Kass, M., & Beiser, J. (2004, October). Baseline Risk Factors for the Development of Primary Open-Angle

Glaucoma in The Ocular Hypertension Treatment Study. American Journal of Ophthalmology, 138(4), 684-685.

Corneal Hysteresis

Corvis ST by Oculus Ocular Response Analyzer by Reichert

How ORA Works

1st IOP

Air-jet stops

2nd IOP

ORA—Signal Plot

“In” signal peak “Out” signal peak

IOP 1 IOP 2

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Start Thinking

Weak vs. Strong IOP Corneal Hysteresis

Relationship of IOP and Corneal Hysteresis

Wells AP, Garway-Heath DF, et a. Corneal hysteresis but not corneal thickness Correlates with optic nerve surface compliance in Glaucoma patients. Invest Ophthalmol Vis Sci 2008

Lower CH = More Likely to Respond to Topical Medications Higher CH = Less Likely to Respond to Topical Medication

Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141:868

Anand A, De Moraes CG, Teng CC, et al. Corneal hysteresis and visual field asymmetry in open angle glaucoma. Invest Ophthalmol Vis Sci 2010;51:6514

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More Likely to Respond to Topical Medications

Association with Progressive Field Worsening

Greater Structural Bowing of Lamina Cribrosa

Low CH

Structure Function Fundus Photograph

(Subjective) Visual Field (Subjective)

Structure Function

Optical Coherence Tomography (Objective)

ERG (Objective)

When Do I Use Electrophysiological Tests?

• Clarify Differential Diagnosis…. Is it Systemic or Trauma vs. Ocular?

• When Standard Tests are Unattainable or Unreliable

• When Other Tests are Inconsistent or Borderline Result

• To Monitor Subclinical Disease for Functional Changes and Alter Treatment and Efficacy

VEP (neuro)

PERG (retinal)

Electrophysiology objectively measures strength and speed of the visual signal to the

brain (VEP) or retina (PERG)

Healthy VF

Glaucoma OCT

Documented structural damage

PERG/VEP

Symptomatic Asymptomatic

1. Parisi V, Miglior S, Manni G, Centofanti M, Bucci MG. Clinical ability of pattern-electroretinograms and visual evoked potentials in detecting

visual dysfunction in ocular hypertension and glaucoma. Ophthalmology. 2006 Feb;113(2):216-28.

OHT

ELECTROPHYSIOLOGY DETECTS CHANGES EARLIER THAN OCT AND VISUAL FIELD1

Non structural damage documented

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Visual Evoked Potential (VEP)

• Main Indications

– Glaucoma

– Multiple Sclerosis

– Ischemic Optic Neuropathy

– Traumatic Brain Injury

– Amblyopia

– Other Neuropathies

WHY USE VEP?

• VEP is an objective, functional test when standard tests cannot provide sufficient information for diagnosis and treatment

• Many optic nerve diseases are asymptomatic because central vision is not affected until late in the disease1

• Diagnosis and management of optic nerve disorders are often based on structural or subjective visual field tests2

Pattern ERG = PERG

Main Indications

Glaucoma

Maculopathies

Can also help the clinician differentiate between retinal and optic nerve disorders when used in conjunction with Visual Evoked Potential (VEP).

How Does PERG Work?

Since the PERG (in contrast to the flash ERG) is a local response from the area covered by the retinal stimulus image, specifically GCC, it can be used as a sensitive indicator of dysfunction within the macular region and it reflects the integrity of the optics, photoreceptors, bipolar cells and retinal ganglion cells.

*Source: http://www.iscev.org/standards/pdfs/ISCEV-PERG-Standard-2013.pdf

AAO Basic Science Course 2015/2016: PERG is a useful tool for the early diagnosis

of glaucoma “In patients who are glaucoma suspects, PERG signal anticipates an equivalent loss of OCT signal by several years (as many as 8 years).”

Per NIH and Bascom-Palmer

Invest Ophthalmol Vis Sci. 2013;54:2346–2352) DOI:10.1167/iovs.12-11026

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IOP 18 mmHg IOP 18 mmHg IOP 26 mmHg Treatment initiation

Visual Assessment

IOP 26 mmHg Treatment initiation

IOP 18 mmHg IOP 18 mmHg

Dynamic Visual Function Assessment

Ganglion Cell Function Measured By ERG After IOP Reduction in POAG

• Researchers concluded that significant IOP-lowering therapy could improve RGC function measured by PERG in patients with pre-perimetric and early stages of POAG

– IOP significantly decreased avg 31%

– Increase in MOPP avg 14%

– PERG amplitude of P50 and N95 waves increased in 75% and 79% eyes

Karaśkiewicz J, Penkala K, Mularczyk M, et al. Evaluation of retinal ganglion cell function after intraocular pressure reduction measured by pattern electroretinogram in patients with primary open-angle glaucoma. Doc Ophthalmol. 2017; Feb 7. [Epub ahead of print].

Patient Work-Up

Gender Female

Age 72

Ethnicity Caucasian

Complaints/Symptoms

Presents with burning and irritated eyes, OU. History of DM.

Family History No family history

IOP (mmHg) OD 21

IOP (mmHg) OS 20

Pachymetry OD 522

Pachymetry OS 529

BCVA OD 20/25

BCVA OS 20/25

Preliminary Diagnosis

Glaucoma Suspect

Case Review – Glaucoma Suspect

Reason for test: When standard test are unreliable (Showing asymmetry)

Standard Tests

• SLE: 2+ SPK, OU • 1+ NS OU • C/D – 0.5 OD / 0.6 OS • Gonio – Open to TM 360 OU

Visual Fields

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HRT

VEP

Icare® HOME tonometer

• Handheld, battery operated device that measures intraocular pressure (IOP) without the need for topical anesthetic

• The device is intended as an adjunct for monitoring IOP of adult patients (self-use). The HOME tonometer is designed for use at home or on the go

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How it Works: Probe Mechanics Two coils are moving the probe and measuring the probe speed

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probe

probe base

coil frame

coils

IOP Fluctuation Matters

Research suggests that short-term IOP fluctuation may be an independent risk factor for the incidence, prevalence and progression of glaucoma.

Boland MV, Quigley HA. J Glaucoma. 2007;16:406-418.

Asrani S, Zeimer R, Wilensky J, et al. J Glaucoma. 2000;9:134-142.

Not only is an ideal mean target IOP needed, but also a target for IOP fluctuation.

Asrani S, Zeimer R, Wilensky J, et al. J Glaucoma. 2000;9:134-142.

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Self-Monitoring Makes a Difference

Arsani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-14

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1

5.76

0

1

2

3

4

5

6

7

Diurnal IOP Range 3.11 mm Hg Diurnal IOP Range 5.4 mm HG

Relative Risk of Disease

Progression

Why 24 Hr Monitoring?

24 hour IOP monitoring can reveal higher peaks and wider fluctuations of IOP than those found during routine office visits. Research reports a steady daily increase in IOP in some patients being treated for glaucoma.

Barkana Y, Anis S, Liebmann J, et al. Arch Ophthalmol. 2006;124:793-797.

Studies have shown IOP rises when a patient is supine; IOP peaks were measured upon awakening and declined within 30 minutes.

Barkana Y, Anis S, Liebmann J, et al. Arch Ophthalmol. 2006;124:793-797.

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Icare HOME tonometer

• IOP, date, time, eye recognition (right/left) and measurement quality are all stored in the internal memory.

• Data is transferred to a PC for further analysis by the prescribing physician.

• New features: positioning light, automatic eye recognition system, series or single measurements, new user interface panel.

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What is Triggerfish? Smart Contact Lens - A soft, disposable silicone contact lens with an embedded micro-sensor that captures circumferential changes near the corneoscleral junction

pressure

strain

gauge

contact

lens

tissue

biomechanics

Triggerfish is measuring ocular

volume change over a 24 hour

period. Ocular volume change is

associated with the eyes ability

to handle increases in pressure as

they are related to tissue

elasticity

Why is This Important?

The data has been shown that elements of the TF curve are highly correlated to glaucoma progression

Data has shown that the curve that is produced may also be indicative of glaucoma even with normal IOP

Data is wirelessly transmitted from the lens to the antenna, that is applied adhesively around the eye (2)

The data is transmitted through a wire to a recorder (3) that the patient wears (4)

The data is then downloaded to the practitioners computer for analysis

Patients maintain there regular routine and wear the lens for 24 hours, capturing the most sensitive night time activity

The lens is applied just

like a contact lens (1)

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Jonas JB, Berenshtein E, Holbach L.Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci. 2003

Dec;44(12):5189-95.

IOP

CSF

Basic Physics

Force 1 ( IOP) Force 2 (ICP)

Corneal Hysteresis May play a role

ICP effects the Nerve

Pseudotumor Glaucoma

CSF Pressure in Glaucoma

Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal

tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmology Vis Sci. 2008;49:5412-5418.

Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology.

2010;117:259-266.

Fanelli, J. (2012, December). Can Pressure Be Helpful. Review of Optometry. Allingham, R. (2015, August). Cerebrospinal Fluid a Major Player in Glaucoma? Ophthalmology Times.

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“Balance Goggles” by Equinox Glaucoma: Treatment

• Goal of treatment – Halt further visual loss – Halt further optic nerve damage

• How We Treat – Reduction of IOP slows progression of glaucoma

• Treatment options – Medications – Laser therapy – Surgical intervention

Glaucoma: Medications Ocular Science Glaucoma Drops

$25.00/ 1 month supply

$30.00/ 1 month Supply

$35.00/ 1 month supply

• 180 day shelf life

• 0.02% BAK

preservative

• Ships directly to

patient

First Line Therapy: Prostaglandins

• All active first line drugs are effective compared with placebo in reducing IOP at 3 mos

• Bimatoprost, latanoprost, and travoprost are most efficacious and within-class difference were small

• Can we say the same for generics? – Adherence – Cost – Efficacy – Drop size – Active ingredient

Tianjing Li, Lindsley K, Rouse B, et al. Comparative effectiveness of first-line medications for primary open-angle glaucoma. Ophthalmology. 2016;123(1):129-40.

Overall Compliance Rates

• 10% - 25% take none of their prescribed medication

• 25% - 35% take all of their medication as prescribed

• Majority are partially compliant

1. Weintraub M. Compliance in the elderly. Clin Geriatr Med. 1990;6:445-452. 2. Lamy PP. Compliance in long term care. Geriatrika. 1985;1(8):32. 3. Coleman TJ. Non-redemption of prescriptions: linked to poor consultations. BMJ. 1994;308(6921):135.

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How Do Patients Feel about their Drop Usage?

• 68 glaucoma pts

• 54% stated their drops were expensive

• 72% were suffering from side effects

• 91% said medical therapy represented minimal/no inconvenience

• 82% were interested in learning about procedures that could reduce or possible eliminate their need for drops

Patient Compliance and Dosing

• Literature review of 76 studies show

– Compliance increases with decreased dosage regimen and complexity1

– 79% compliance with QD regimen vs 51% for QID regimens (p=0.001)1

– Simpler, less-frequent dosing results in better compliance in a variety of therapeutic classes1

Co

mp

lian

ce

Dosing (Times/day)

1. Claxton et al. Clinical Therapeutics. 2001; 23:1296-1310.

Continuous Use

Nordstrom, Friedman, et al. Ophthalmology 2005

Poor Adherence To Glaucoma Therapy

• By one year after first eye drop Rx, less than 50% are still filling prescription

• Among New Jersey Medicaid seniors, 25% never filled the second prescription

• Average number of treated days = 70

Reardon, Schwartz, Mozaffari. Clin Therap 2003;25:1172 Gurwitz et al. Am J Public Health 1993;83:711-6.

How Adherent are Glaucoma Patients with QD Medication?

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Glaucoma: Medications

• When COMPLIANCE with drops is low

• When MEDICAL THERAPY FAILS

• When the PROGRESSION continues to WORSEN

• Treatment options

– Medications

– Laser therapy

– Surgical intervention

Glaucoma Surgical Options

• Laser Therapy – SLT – ALT – LPI

• Surgical Options – Trabeculectomy – Trabectome – Express Shunt – Tube shunt – Canaloplasty – ECP – Any many more

• Collaborative Normal Tension Glaucoma Study (NTGS)

• Advanced Glaucoma Intervention Study (AGIS)

• Collaborative Initial Glaucoma Treatment Study (CIGTS)

• Ocular Hypertensive Treatment Study (OHTS)

• Early Manifest Glaucoma Trial (EMGT)

• Glaucoma Laser Trial (GLT)

Glaucoma Clinical Trials The ABC(DE)’s of Choosing a Surgery

Ronald L. Fellman, MD

• A – Age / Angle

• B – Blood aqueous barrier

• C – Conjunctiva

• D – Disc / Discussion

• E - Expertise

Accessed on September 13, 2012 from http://revophth.com/content/d/glaucoma_management/i/2088/c/36431/

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Selective Laser Trabeculoplasty

• Non-thermal treatment which uses short pulses of relatively low energy to target and irradiate only the melanin-rich cells in the TM

http://www.youtube.com/watch?v=cU1aS5_J0gE

Selective Laser Trabeculoplasty

• IOP decrease after SLT – Primary Therapy - 28.7% – Adjunctive therapy – 19.4% – Retreatments – 12.1%

• Who responds better? – Primary eyes – Phakic – No previous PGA – Blue – Younger

SLT Procedure Video Courtesy Nate Lighthizer, OD

Selective Laser Trabeculoplasty versus Medical Therapy as Initial Treatment of Glaucoma: a

Prospective, Randomized Trial • PURPOSE: To compare outcomes of selective laser

trabeculoplasty (SLT) with drug therapy for glaucoma patients in a prospective randomized clinical trial

• RESULTS: 54 patients reaching 9 to 12-months follow-up. – SLT (29 pts) - Baseline IOP 24.5 mm Hg to 18.2 at follow up

– Med (25 pts) - Baseline IOP 24.7 mm Hg to 17.7 at follow up

– SLT group -> 11% of eyes required additional SLT

– Prostaglandin group -> 27% of eyes required additional medication

Katz, LJ, Steinmann, WC, Kabir, A. et al. J Glaucoma. 2012 Sep;21(7):460-8

N=127 eyes

Selective Laser Trabeculoplasty as Initial and Adjunctive Treatment for Open-Angle Glaucoma

• Purpose: To investigate the efficacy and safety of selective laser trabeculoplasty as an initial treatment for newly diagnosed open-angle glaucoma, and its role as adjunctive therapy

• SLT

– 31.0% reduction

– 83% responder rate

• Control

– 30.6% reduction

– 84% responder rate

McIlraith, Ian MD*; Strasfeld, Maurice MD; Colev, George MD et. Al. Journal of Glaucoma: April 2006 - Volume 15 - Issue 2 - pp 124-130

N=100 eyes

Cost Considerations

• Compared five year costs of three treatment strategies whose IOPS were not adequately controlled with two meds

– SLT = $4,838

– Medication = $6,571

– Surgery = $6,363

***5-year cumulative costs

Cantor LB et al: Economic evaluation of medication, laser trabeculoplasty and filtering surgeries in treating patients with glaucoma in the US. Curr Med Res Opin. 2008; 24(10):2905-18

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Cost Considerations

• Lee R, Hutnik CM. Projected cost comparison of selective laser trabeculoplasty versus glaucoma medication in the Ontario Health Insurance Plan. Can J Ophthalmol 2006 Aug;41(4):449-56

– Monotherapy $ 206.54

– Dual therapy $1,668.64

– Triple therapy $2,992.67

***Assumed 2 year repeat SLT rate, 6 year cumulative savings

Peripheral Iridotomy (PI)

Laser Peripheral Iridotomy Nate Lighthizer, OD, FAAO

Dysphotopsia after temporal versus superior laser peripheral iridotomy

• RESULTS - New-onset linear dysphotopsia

– Sup PI - 18 (10.7%)

– Temp PI – 4 (2.4%)

– P = .002

• CONCLUSIONS: Temporal placement of LPI is safe and was found to be less likely to result in linear dysphotopsia as compared with superior placement. Temporal iris therefore may be considered a preferred location for LPI.

Vera, V., Naqi, A., Belovay, G. Am J Ophthalmol. 2014 May;157(5):929-35.

N=169 pts

Glaucoma: Laser Treatment

• Open or Narrow Angle Glaucoma

– Transcleral Cyclophotocoagulation

Considerations for Optometry

• Laser therapy remains a viable option

• Can be used as primary or secondary treatment

• IOP lowering of 20 - 25%

• Glaucoma comanagement considerations

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Advances in Glaucoma Surgery

• Evolution of small-incision phacoemulsification techniques and small-profile IOLs – Smaller wounds, less inflammation

• Using antimetabolites to enhance filtration surgery – MMC intra-operatively

– 5-FU post-operatively with needling/injections

• Availability of novel glaucoma procedures – Non-penetrating glaucoma surgeries (Trabectome,

canaloplasty)

– Endocyclophotocoagulation

Cataract and Glaucoma

• How to position the cataract operation in the management scheme of the patient’s glaucoma condition?

• Is it better to choose one sequence and type of surgery before the other, or to combine two procedures?

• STRESS the IMPORTANCE of visual fields PRIOR to cataract surgery

The Effects of Phacoemulsification on Intraocular Pressure and Topical Medication Use

in Patients With Glaucoma

• A 12%, 14%, 15%, and 9% reduction in IOP from baseline occurred 6, 12, 24, and 36 months after phacoemulsification

• A mean reduction of 0.57, 0.47, 0.38, and 0.16 medications per patient of glaucoma medication occurred 6, 12, 24, and 36 months after phacoemulsification

Armstrong, JJ, Wasiuta, T, and Kiatos, E. et al. Journal of Glaucoma: Post Author Corrections: March 22, 2017

*3 year data analysis

IOL Choices in Glaucoma

“Yes – I would like to be free from glasses!”

STANDARD

MULTIFOCAL TORIC

TRADITIONAL GLAUCOMA SURGERY

• Traditionally done when meds and/or lasers fail to adequately control the pressure

• In advanced cases can be first line mode of treatment

• Gold Standard Surgical technique

– Long history

– Low eye pressures

– Reduce or eliminate medications and costs

Trabeculectomy

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• Optic nerve progression despite MMT and/or LT

• Visual field progression despite MMT and/or LT

• Inability to take drops adequately

• Target pressure is LOW

• Moderate/advanced disease

Candidates for Trabeculectomy

• Surgical exposure

• Conjunctival flap

• Scleral flap - +/- antifibrosis agent

• Sclerostomy

• Iridectomy – needed to prevent the iris from incarcerating into the internal ostium

• Scleral flap closure

• Conjunctival closure

Trabeculectomy Procedure

Trabeculectomy Complications

• Scar formation-failure

• Bleb leak

• Blurring of vision

• Hypotony

• Choroidal hemorrhage

• Infections

• Cataract formation

Tube Shunt and Cataract Surgery

Tube Shunt Advantages

• Safer for contact lens wearers

• More standardized post operative care

• Used when previous trabeculectomy failed

• Results comparable to trabeculectomy

Trab vs. Tube Study

• Trabeculectomy (with MMC) vs Tube study (non-valved Baerveldt)

– Prior surgery required

• Nationally the relative amount of trabs being done is decreasing

• Tube procedures are increasing

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The Tube Versus Trabeculectomy Study

• Objective: – Compare the safety and efficacy of non-valved tube shunt

surgery to trabeculectomy with mitomycin C in patients with previous intraocular surgery

• 212 participants with prior cataract or trabeculectomy surgery – Uncontrolled glaucoma with IOP of 18-40mmHg on MMT – Tube Shunt (Baerveldt) vs Trabeculectomy with mitomycin C

• Main outcome: – IOP, visual acuity, surgical complications, glaucoma medications

and treatment failure

The Tube Versus Trabeculectomy Study

• Both surgical procedures produced a significant and sustained reduction in IOP at 3 mo

• The degree of IOP reduction was similar between the two treatment groups at 5 years – IOP reduction from baseline was 10.2 mm Hg (41.4%) in the tube

group and 12.4 mm Hg (49.5%) in the trabeculectomy group

• A significant reduction in the use of medical therapy was seen in both treatment groups at 5 years – Decreased from baseline by 1.8 in the tube group and 1.7 in

trabeculectomy group

The Tube Versus Trabeculectomy Study

• A significantly higher failure rate was seen in the trabeculectomy group than the tube group after 5 years (50% vs 33%)

• A higher rate of reoperation for glaucoma was observed in the trabeculectomy group compared with the tube group (29% vs 9%)

• Significant VA decrease was observed in both groups

Filtering Surgery Alternatives: Express Shunt

Express Shunt PO

• Don’t have to worry about hypotony

• Can still scar over of bleb = increased iop

• Always have a high suspicion of endophthalmitis

Why Express Shunt over Simple Trabeculectomy?

• Trabeculectomy procedure: – A sclerostomy under the

scleral flap with two to three punches with a Kelly Descemet’s punch

– Surgical peripheral iridectomy

• Ex-PRESS implantation:

– The above steps skipped

– Instead, implant inserted through a 27g needle tract

– Less inflammation

– More standardization

– Less time

– Less early hypotony

– Fewer complications

– Similar IOP results

Maris PJG Jr, Ishida K, Netland PA. Comparison of trabeculectomy with Ex-PRESS miniature glaucoma device implanted under scleral flap. J Glaucoma. 2006;16:14-19.

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What Do You Get When You Add?

+

Great Candidate for MIGS/PHACO

“The new MIGS procedures are to trabeculectomy what phacoemulsification was to intracapsular

cataract extraction or LASIK was to RK.”

Concomitant Cataract & Glaucoma Patients

79.5% Cataract Only

20.5% Cataract +

Minimum of 1 OHT Med

3.5M US Cataract Procedures

Cataract Pts Cataract Pts w/ Glaucoma

718K

111 Centers for Medicare and Medicaid Services. 2002 – 2007. Medicare Standard Analytical File. Baltimore, MD. 2007 .

Significant Treatment Opportunity

One in five Cataracts Eyes on OHT Medication

PN: 400-0122-2013-US Rev 0

Release Date: 04/26/2013

Pathway for Trabecular Bypass Devices

• Shunting the canal – Express MiniShunt (Alcon)

• Stenting the canal – iStent (Glaukos Corp)

• Reduce aqueous production – Endocyclophotocoagulation

• Dilating the canal – Visco 360 / Ab-Interno

Canaloplasty (ABIC)

• Divert aqueous into the suprachoroidal space – Cypass Microshunt (Alcon)

• Divert aqueous into the subconjunctival space – Xen Gen Stent (Allergan)

Glaucoma Drops On the Horizon

New Drug Company Type

Latanoprostene bunod Bausch + Lomb Nitric oxide – donating prostaglandin F2-a-analogue

Rhopressa Arie Inhibits Rho kinase and norepinephrine transporter

Roclatan Arie Rhopressa + latanoprost

Trabodenoson Inotek Highly selective adenosine mimetric acting only at A1 receptor subtype

Latanoprostene bunod (Vyzulta)

• A nitric oxide-donating prostaglandin F2-a analogue that reduces IOP in patients with open angle glaucoma and ocular hypertension

• Dual Action – Latanoprost derivative –

increases uveoscleral outflow

– Nitric Oxide - relax the trabecular meshwork and ciliary muscle to increase trabecular outflow

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Latanoprostene bunod (Vyzulta)

• Improved IOP lowering profile compared to latanoprost and timolol – Phase 3 trials: reduced mean IOP by 7.5 to 9.1 mm Hg

from baseline between 2 and 12 weeks of treatment.

• The safety of latanoprostene bunod was comparable to latanoprost, with the most common adverse event’s being mild hyperemia, which occurred at a similar rate across all treatment groups

• Recently Approved Nov. 2017

Netarsudil 0.02% (Rhopressa)

http://investors.aeriepharma.com/releasedetail.cfm?releaseid=908343

Netarsudil* Causes Expansion of Trabecular Meshwork Tissue, Opening Spaces for Increased Outflow

http://aeriepharma.com/research/#Rhopressa-Disease-Modification-Potential

Rhopressa

• Finished phase 3 trials, once-daily dosing reduced IOP by 5-6mmHg

– The primary adverse event was hyperemia, which was experienced by approximately 35% of the Rhopressa patients

• 80% was reported as mild

– PDUFA Date 2/28/18

http://investors.aeriepharma.com/releasedetail.cfm?releaseid=908343

Roclatan

• Rhopressa + latanoprost = Roclatan

• “Quadruple Action”

– Reduces aqueous production

– Increases trabecular outflow

– Increases uveoscleral outflow

– Decreases episcleral venous pressure

Aerie Pharmaceuticals. Aerie Pharmaceuticals reports Roclatan phase 2b results achieve all clinical endpoints. June 25, 2014. http://investors.aeriepharma.com/releasedetail.cfm?ReleaseID=856396.

Roclatan

• Phase 3 Clinical Trials – Lowered mean diurnal IOP on day 29 by 34% from

a baseline of 25.1 to 16.5 mm Hg.

– IOP-lowering effect exceeded that of latanoprost by 1.6 to 3.2 mm Hg across each time point evaluated during the study, and these results were statistically significant at all time points.

– The most common adverse event with Roclatan was hyperemia, which was reported in 40% of patients and scored as mild for most of them.

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Trabodenoson

• Stimulation of adenosine A1 receptor in the trabecular meshwork upregulates proteases (MMP2) that digest and removes proteins that clog the trabecular meshwork

Ocular Therapeutix

• Sustained-release travoprost in an intracanalicular depot composed of polyethylene glycol hydrogel and drug-containing microparticles

– Drug elutes over 90 day period

– In Phase 3 Clinical Trials

Ocular Therapeutix. Sustained release travoprost. http://www.ocutx.com/pipeline/travoprost-punctum-plug

Travoprost Punctum Plug (OTX-TP, Ocular Therapeutix)

Ocular Therapeutix, Inc. Ocular Therapeutix TM reports on topline results of phase 2b glaucoma clinical trial. Press Release. 22 October 2016.

http:// investors.ocutx.com/phoenix.zhtml?c=253650&p=irol-newsArti- cle&ID=2100516. [Accessed 6 September 2016]

IOP

Red

uct

ion

OTX-TP timolol

4.5-5.7 mm Hg

6.4-7.6 mm Hg

0

5

10

No hyperemia in OTX-TP Retention Rates 91, 88, 48% @ days 60, 75, 90

Bimatoprost Sustained Release Implant

• Phase 2 trial comparable to topical bimatoprost qd dosing (for 4-6 months)

• Inserted into the anterior chamber

• Biodegradable

• Allergan is currently performing phase 3 clinical trials

24 Month Phase I/II Clinical Trial

75 Patients

Bimatoprost pellet (6, 10, 15, or 20 micrograms)

Topical bimatoprost 0.03%

24 Month Phase I/II Clinical Trial

Bimatoprost pellet (6, 10, 15, or 20 micrograms)

Topical bimatoprost 0.03%

4 months – IOP reduction 7.2, 7.4, 8.1, 9.5 mm Hg 92% of patients

4 months – IOP reduction of 8.4 mm Hg

Sustained at 6 mos. in 71%

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% Conjunctival Hyperemia

52% Implant group

30.7% Topical group

Side Effects

Safety Bimatoprost Ring

Goldberg I, Laganovska G, Baumane K, et al. The novel topical ocular insert (Helios) for sustained delivery of bimatoprost in glaucoma and ocular hypertension. Poster presented at: American Academy of Ophthalmology Annual Meeting; October 20, 2014; Chicago, IL.

n = 49 eyes

IOP

mm

Hg

Month

Baseline 1 mo 6 mo

23.9

18.7 18.8

0

5

10

15

20

Bimatoprost Ring

Ophthalmology 2016 123, 1685-1694DOI: (10.1016/j.ophtha.2016.04.026)

Copyright © 2016 American Academy of Ophthalmology Terms and

Conditions

Brandt J, Sall K, DuBiner H, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert. Ophthalmology. 2016;123(8):1685-1694.

Bimatoprost Ring

Retention Rate – 89%

Ophthalmology 2016 123, 1685-1694DOI: (10.1016/j.ophtha.2016.04.026)

Copyright © 2016 American Academy of Ophthalmology Terms and

Conditions

Brandt J, Sall K, DuBiner H, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert. Ophthalmology. 2016;123(8):1685-1694.

Bimatoprost Ring

Case Example – POAG / MGD

• 76YOWF – Present for follow up for Glaucoma and dry eye disease. Compliant with drops OU. Vision has been blurry and eyes irritated more in the past few months

– Previous treated with topical azithromycin

– Current Ocular Meds: Restasis BID OU, latanoprost qhs OU

– Numerous systemic meds including singulair, synthroid

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• SPEED Score: 24

• Tear Osmolarity 308 / 315

• SLE: 2+ MGD OD / 3+ MGD OS / 1+ SPK OU

• Cloud secretions OU

• MG Structure: See images

• IOP: 14/13

• HVF: Stable OU

Early to Moderate Structural Changes to Meibomian Glands

Advanced Gland Atrophy / Dropout

Post Treatment

• Post Tx Osmolarity – 300/299

• Post Lipiflow Management – Heat masks qhs OU

– Hydroeye as directed

– Restasis BID OU

– Lipid based tear BID OU

– Latanoprost qhs OU

– F/u 3 months dry eye

• Order tear osmolarity

• Order inflammadry

• SPEED Questionnaire

• 6 Weeks Post Treatment

HOW DO YOU ADDRESS HYPEREMIA AND PGAS???

OSD and Glaucoma Considerations

• Glaucoma medications significantly elevate the risk and progression of MGD1

• Preservative and dry eye2

• Glaucoma and MGD: 96% (using Prostaglandins) had obstructive MGD vs. 58% of those on non Prostaglandin Therapy.3

1. Arita R, Itoh K, Maeda S, et al. Comparison of the long-term effects of various topical antiglaucoma medications on meibomian glands. Cornea. 2012 Nov 31(11): 1229-34. 2. Baudouin, C, Labbe, A, Liang, H, et. Al. Preservatives in eyedrops: The good, the bad and the ugly, Progress in Retinal and Eye Research, Volume 29, Issue 4, July 2010, Pages 312-334 3. Mocan MC, et al. The Association of Chronic Topical Prostaglandin Analog Use With Meibomian Gland Dysfunction. J Glaucoma. 2016 Sep;25(9):770-4.

Focus on Dry Eye Prevalence

• Cataract Surgery 77%

• Penetrating Keratoplasty 60%

• Lasik 27%

• Glaucoma Surgery 78%

• Blepharoplasty 26%

Trattler, ASCRS CME Supplement, 2013 Sheppard, WCC, 2015 Azuma, BMC Research Notes, 2014 Leung, Journal of Glaucoma, 2008 Prischmann, JAMA Facial Plastic Surgery, 2013

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Conclusions

• Glaucoma Dx / Tx is constantly advancing

• Consider benefits of MIGS

• Address the ocular surface

• Anticipate continuous innovation

THANK YOU WWHITLEY@VEC2020.COM