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MEDICAL MANAGEMENT OF GLAUCOMA

California Optometric Association Monterey 2018

Leo Semes, OD, FAAO

Disclosures

Commercial Interest

Nature of Relevant Financial Relationship

Maculogix Honorarium Speaker Science Based Health Honorarium Speaker OptoVue Honorarium Speaker B&L Honorarium Advisor Allergan

Genentech

Regneneron

Shire

ZeaVision

Reichert/Ametek

HPO

Honorarium

Honorarium

Honorarium

Honorarium

Honorarium

Honorarium

Stock options

Advisor

Advisor

Speaker

Speaker

Advisor

Speaker

Advisor

“Half of what you learn during your training will be shown to be either dead wrong or out of date within five years of your graduation; . . .

NOBODY can tell which half! And . . . the most important thing to learn is how to learn

on your own.” –David Sackett, MD. 1934-2015

IOP 4

u Elevated IOP is the greatest risk factor for developing glaucomatous damage 

u Lowering IOP is the only means currently of managing glaucoma

u Topical drops to lower iop are the prefered initial

means to “treat” glaucoma

  u  Issues in measuring IOP

u  How is baseline IOP established? u  What are the influences on an IOP measurement? u  What is the “sampling rate” of IOP?  u  The future of IOP monitoring

A pinhole view of IOP 5

Our working definition of POAG

POAG is a progressive, chronic optic neuropathy in adults in which

intraocular pressure (IOP) and other currently unknown factors contribute to damage and in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons in the presence of an gonioscopically open anterior chamber angle. –ala AAO PPP, AOA CPG

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There are some other good reasons… There are some other good reasons…

There are some other good reasons… And just last year. . . 10

Issues in “treating” glaucoma 11

How much to lower IOP when Glaucoma or OHT is diagnosed

¤  Risk of progression indices

Medical Therapy

¤  Cost and side effects issues ¤  Adherence issues ¤  Optimize and maximize protection to match risk

Initial therapy

¤  Topical PGA

  ¤  ? SLT

Advancing topical therapy ¤  tCAI ¤  beta-blocker ¤  alpha-agonist ¤  fixed-combination (FC) drop

Recent publications regarding IOP-lowering influences

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¨  Week's Best Articles: Glaucoma

¨  One week in October

Comparison of surgical outcomes between phacocanaloplasty and phacotrabeculectomy at 12 months’ follow-up: a longitudinal cohort study

Journal of GlaucomaOcular surface disease in glaucoma: effect of polypharmacy and preservatives

Optometry and Vision SciencePupillary responses to high-irradiance blue light correlate with glaucoma severity

OphthalmologyTrabeculectomy vs. EX-PRESS shunt vs. Ahmed valve implant: short-term effects on corneal endothelial cells

American Journal of OphthalmologyMeta-analysis of selective laser trabeculoplasty versus topical medication in the treatment of open-angle glaucoma

BMC Ophthalmology   ||   Full Text   ||   Evidence-Based MedicineRisk factors for a severe bleb leak following trabeculectomy: a retrospective case-control study

Journal of GlaucomaThe macula in pediatric glaucoma: quantifying the inner and outer layers via optical coherence tomography segmentation

Journal of AAPOSHow glaucoma patient characteristics, self-efficacy and patient-provider communication are associated with eye drop technique

International Journal of Pharmacy PracticeAssociation between glaucoma medication usage and dry eye in Taiwan

Optometry and Vision ScienceA survey on the preference of sustained glaucoma drug delivery systems by Singaporean Chinese patients: a comparison between subconjunctival, intracameral, and punctal plug routes

Journal of Glaucoma

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Case example 13

Mid -50s WM

¨  First seen at UAB Eye Care 4/24/2014

¨  54 WM Engineer is referred to UAB Eye Care as a “glaucoma suspect.”

Past Medical History Conditions Hernia Sx, Tinnitus Details Hernia Sx - couple years ago, all okay now.

Past Hx of bad rxn to Penicillin Past Hx of Tinnitus Pt. thinks he has Sleep apnea? *

*SAS ruled out – new Dx = heart murmur (cardiac ultrasound) No medications

Past / Present Ocular History   Date Diagnosed

Glaucoma Negative  

Cataracts Negative  

Age-Related Macular Degeneration Negative  

Eye Injury Negative  

Retinal Disease Lattice Degeneration OU  

Other Disease Negative  

Blindness Negative  

Strabismus Negative  

Amblyopia Negative  

Diabetes Negative  

Dry Eye Negative  

Refractive Glasses Full-time  

Other H/o transient dipl/intermittent dipl, resolved (spectacle adjustment)

 

Social History Drugs None Alcohol None Occupation Engineer (currently unemployed) Hobbies Writer, Musician, Woodworker Tobacco Quit smoking 3 yrs ago, uses Nicotine lozenges Smoking Status Former smoker

Family History Glaucoma Negative Cataracts Mother, Father ARMD Negative Eye Injury Negative Retinal Disease Negative Other Disease Negative Blindness Negative Strabismus Sister - DV, wears prism in glasses Amblyopia Negative Diabetes Negative Cancer MGM - skin Heart Disease Negative Hypertension Negative High Cholesterol Negative Kidney Disease Negative Stroke Negative

Medications Date Name Strength Form S

IG

4/21/2014 Advil       6/9/2010 Ibruprofen       4/24/2014 Zyrtec 10 mg Add'l Sig  

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Ophthalmic findings

¨  BSCVA 20/20 20/20 -2.25 – 0.50 X 090 -2.50-0.75X 090 ¨  Pupils – normally reactive w/o RAPD ¨  IOP history (Goldmann)

¤ 13/14 (4/24/2014) ¤ 16/15 (7/22/2014)

¨  Pachymetry: 587u, 586u ¨  Anterior segment – unremarkable ¨  ACA – open; AC - D&Q

Ophthalmic findings

¨  Lens (LOCSIII) : NO 1 / NC2 CS 0 PSC 0 (OD = OS)

¨  Optic disc

¨  VF

¨  OCT

¨  What do you expect?

Reliable data? (Where’s the blind spot?) GHT, PSD, PD significance

Good scan quality Note segmentation markers

⇐ Symmetry Ave RNFL thickness ONH size C/D!

⇐ Disc margin Note RNFL defects. RNFL profile And, RNFL average sectors are within reference range, But clock hour IT OS, OS show thinning.

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Excellent scan quality Note the island of GCC thinning IT OD that corresponds to RNFL defect. AND, the raphe respect. And, RNFL average sectors are within reference range.

What are our next steps?

¨  Reviewing the data ¤ Good VA ¤  (-) family history of glaucoma ¤ ? SAS / (+) heart murmur // no beta-blocker meds. ¤ Normal IOP

¨  Apparently clean VF ¨  Evidence of ONH / RNFL damage

Diagnostic labeling

¨  Glaucoma suspect ¨  Glaucoma ¨  Pre-perimetric glaucoma ¨  ?

Repeated visual field !!!

Reliable data? GHT, PSD, PD significance

Reliable data? GHT, PSD, PD significance

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Reconciling the data-OD Correlating the data-OS

Management

¨  Critical questions ¤ Degree of damage ¤ Burden of treatment ¤ Life span

Management

¨  Critical questions ¤ Degree of damage ¤ Burden of treatment ¤ Life span

Alternatives ¨  No treatment at this time ¨  Follow, repeating all tests X 6 mo ¨  ? Other ?

Most recent visit

¨  IOP = 19/20

¨  Updated disrupted sleep status – diagnosed with SAS and using CPAP device. Reportedly, “…feeling much better.”

¨  Does this change our thinking?

June 23, 2015

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June 23, 2015

Source: http://www.reviewofoptometry.com/cmsdocuments/2015/7/0715_reicherti.pdf

Remember: Risk increases as IOP increases & Risk is compounded with lower CH

Would CH be a useful diagnostic data point?

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“TheEffectofIOPonratesofprogressionwasdependentupon

CornealHysteresis”

•  IOPof30isnotsobadwithaCHof11.

•  IOPof20isverybadwithaCHof6

Corneal Hysteresis in Glaucoma Predictive of Progression in Prospective, Longitudinal Study (DIGS)

Medeiros FA et al. Ophthalmology. 2013;120:1533-1540.

Percentage per year change in VFI

What about complementary techonologies?

42

¨  How would OCT-A influence your management?

¨  What about electrodiagnostic testing?

Vessel density (OCTA) and VF loss correlation in glaucoma

Yarmohammadi A, et al., Relationship between Optical Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma.Ophthalmology 2016;123:2498-2508

Considerations in management

¨  Does the patient understand the risks and benefits of treatment?

¨  What is the risk of vision/sight loss over his lifetime? (25 years?)

¨  What is his likelihood of adherence to treatment if offered/accepted?

¨  What would be his “target IOP”? ¨  With what would be the initial treatment

option?

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“To treat or not to treat and if so, how?”

Another example 45

RB 9/24/1938 (AA/F)

¨  ONH (5/2006) PACHYMETRY: 642/591)

VF Series – 1: 2004 (baseline) VF Series – 2: 2005

RB 9/24/1938 (AA/F) - IOP Range

¨  17-24 (OD) ¨  15-21 (OS)

¨  PACHYMETRY: 642/591

Frequency Doubling Technology (FDT) Perimetry Results (4/6/05)

“Threshold” No flags (OD, OS)

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(4/6/05)

Retest! (OS) Dilemma? or Direction?

RB 9/24/1938 (AA/F)

¨  VA 20/20 to 20/20- with mild NS changes ¨  BP good ¨  PR: 60

¨  4/08 As OHT (IOP range 17-24, 15-21): ¨  Risk calculation (1-5% - low)

VF Series – 3: 2/19 2010 (Bad day or progression? Fundus photos 4/5/2006

5/10/2011 Repeat the VF! (5/10/2011)

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Change analysis

OS OD

5/10/2011 –look closely

5/10/2011 –look closely Treat or not?

Need more evidence?

¨ OCT ¤ RNFL ¤ MRNFL (GCC) ¤ ONH

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5/10/2011 –look closely

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Update

¨  11/11 – IOP: 18/13 Switch to Lumigan 0.01% ¨  12/11 – IOP: 20/14 Continue L. 0.01% ¨  1/12 – IOP: 21/15 Switch to T-Z ¨  2/ 12 – IOP unchanged: Switch to Combigan qAM ¨  3/12 – IOP unchanged: Switch to Azopt tid ¨  5/12 – no IOP response = SLT recommendation ¨  6/13 – IOP = 17 mm Hg OD, OS. ¨  6/14 – IOP 17/15 mm Hg OD, OS ¨  6/15 – IOP 14/15 mm Hg OD, OS

Choosing an initial “treatment” strategy 70

* Realini T, Fechtner R. Ophthalmology (editorial) 2002; 109: 1955-1956.

The trouble with the world is that the stupid are cocksure and the intelligent are full of doubt. ~Bertrand Russell

*

Guidance on initiating therapy - Delphi Panel

71

Singh K, Lee BL, Wilson MR; Glaucoma Modified RAND-Like Methodology Group. A panel assessment of glaucoma management: modification of existing RAND-like methodology for consensus in ophthalmology. Part II: Results and interpretation. Am J Ophthalmol. 2008 Mar;145(3):575-581.

Which PA is best?

�  It depends!

�  Alasbali T, Smith M, Geffen N, Trope GE, Flanagan JG, Jin Y, Buys. Discrepancy between results and abstract conclusions in industry- vs nonindustry-funded studies comparing topical prostaglandins. Am J Ophthalmol. 2009 Jan;147(1): 33-38.

�  Meta Analyses suggest slight superiority of bimatoprost. (e.g., Aptel F, Cucherat M, Denis P. Efficacy and tolerability of prostaglandin-timolol fixed combinations: a meta-analysis of randomized clinical trials. Eur J Ophthalmol. 2011 May 19:0.

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Considerations in the medical management of glaucoma/ OHT

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¨  “Baseline” IOP? ¨  Target IOP ¨  Severity of damage at initial presentation ¨  Burden of treatment

¤ Ocular surface ¤ Side-effects / Systemic issues ¤ Cost of medications ¤ Likelihood of adherence to regimen*

¨  Potential lifespan

Adherence . . . for the long term 74

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Adherence . . . for the long term 75

Factors influencing IOP

Physiological factors ¤  CCT ¤  Diurnal variation

¤  Arterial (pulse) pressure ¤  Posture

¤  Blood Flow ¤  Exercise

¤  Accommodation ¤  Axial length / refractive error

¤  Corneal dystrophies ¤ 

¤  ¤ 

Situational influences on IOP

¨  Eye rubbing ¨  Necktie ¨  Head position ¨  Fluid intake ¨  Medications ¨  Weight lifting ¨  Scleral indentation ¨  Wind instrument

playing ¨  ¨  ¨  + spontaneous

Sambala sirsasana

Extraneous influences on IOP

Journal of Glaucoma

Extraneous influences on IOP

And . . . 80

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An additional confounder surrounding IOP and our “sampling”

81

QUESTION: How many seconds elapse in the quarterly interval from one visit to the subsequent one for a patient whom you are monitoring for glaucoma progression? ANSWER: about 8,000,000. [8 million]

An Implantable Intraocular Pressure Transducer 82

An Implantable Intraocular Pressure Transducer 83

>/= 3 measurements (each device)

Image credit: http://www.google.com/imgres?um=1&hl=en&sa=N&biw=1101&bih=538&tbm=isch&tbnid=vYr8xY3etZh4CM:&imgrefurl=http://www.behance.net/gallery/Continuous-Intraocular-Pressure-Monitoring/2045171&docid=WSm-sv0wMjQpnM&imgurl=http://behance.vo.llnwd.net/profiles12/607447/projects/2045171/f7b82ec1e4716d0a05f6123713e8735d.JPG&w=600&h=400&ei=rdPOT_rcA9GtgQf1qOWoDA&zoom=1&iact=hc&vpx=274&vpy=108&dur=84&hovh=183&hovw=275&tx=158&ty=80&sig=109544038664839131986&page=2&tbnh=146&tbnw=182&start=9&ndsp=15&ved=1t:429,r:6,s:9,i:109

Example

53 yo treated glaucoma patient (PGA qhs + timolol/tCAI comb); excellent reproducibility for two overnights blue & yellow.

Mansouri K, Medeiros FA, Tafreshi A, Weinreb RN. Continuous 24-Hour Monitoring of Intraocular Pressure Patterns With a Contact Lens Sensor: Safety, Tolerability, and Reproducibility in Patients With Glaucoma. Arch Ophthalmol. 2012; 13:1-6.

Example

52 YO Asian female glaucoma suspect (PGA qhs Rx’d but may have been noncompliant); good reproducibility pattern for two overnights blue & yellow.

Mansouri K, Medeiros FA, Tafreshi A, Weinreb RN. Continuous 24-Hour Monitoring of Intraocular Pressure Patterns With a Contact Lens Sensor: Safety, Tolerability, and Reproducibility in Patients With Glaucoma. Arch Ophthalmol. 2012; 13:1-6.

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Example

Poor reproducibility in a 20 GS for two overnights with spikes (n.b., pt has poor sleep habits). [app on your iPhone]

Mansouri K, Medeiros FA, Tafreshi A, Weinreb RN. Continuous 24-Hour Monitoring of Intraocular Pressure Patterns With a Contact Lens Sensor: Safety, Tolerability, and Reproducibility in Patients With Glaucoma. Arch Ophthalmol. 2012; 13:1-6.

LS

Sensimed Triggerfish FDA cleared 88

¨  FDA News Release ¨  FDA permits marketing of device that senses

optimal time to check patient’s eye pressure

¨  Increased eye pressure is associated with nerve damage common in glaucoma

¨  For Immediate Release

¨  March 4, 2016

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Home tonometry- more frequent data gathering but not continuous.

News / 03.22.2017 FDA Cleared Icare® HOME, An Innovative Device Poised To Revolutionize IOP Self-Monitoring.

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Baseline IOP

¨  Establishing a baseline IOP with several measurements guards against making the wrong call.

For example, a single IOP of 34mmHg might suggest the need for a treatment recommendation and encourage a reduction to 20mmHg (>30%)

when that initial measurement may be an aberration.

So, baseline IOP is critical to establish.

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Practical Considerations

¨  Establish the diagnosis ¤ Use multiple IOP measurements to determine a baseline

IOP

¤ Consider charting a diurnal IOP pattern

¤ Use all data available (History, medications, vocational and avocational activities, physical findings including stereo photos and digital imaging as well as VF testing.)

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Recent thoughts on baseline IOP

¨  Asymmetry is damped with MULTIPLE IOP measurements.

¨  Predictions of efficacy are impossible but may be more accurate when more data are gathered.

King AJ, Uppal S, Rotchford AP, Lakshumanan A, Abedin A, Henry E. Monocular trial of intraocular pressure-lowering medication: a prospective study. Ophthalmology. 2011 Nov;118(11):2190-5.

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Baseline IOP suggestions – “measure twice, cut once”

King AJ, Uppal S, Rotchford AP, Lakshumanan A, Abedin A, Henry E. Monocular trial of intraocular pressure-lowering medication: a prospective study. Ophthalmology. 2011 Nov;118(11):2190-5.

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Studyvisits Determining “Target” IOP 96

Target IOP Defined 97

≡ the pressure at which the patient shows stabilization (i.e., no progression)

Canadian Perspective

98

“Target IOP is a dynamic concept, needing constant reevaluation.” “What is lacking are established guidelines for determining the target IOP range that can be used in general …practice.”

Damji KF, Behki R, Wang L; Target IOP Workshop participants. Canadian perspectives in glaucoma management: setting target intraocular pressure range. Can J Ophthalmol. 2003 Apr;38(3):189-97.

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An alternative suggestion (‘market IOP’) What it means:

99

Singh K, Shrivastava A. Early aggressive intraocular pressure lowering, target intraocular pressure, and a novel concept for glaucoma care. Surv Ophthalmol. 2008 ;53 Suppl1:S33-8.

If there is a relatively lower risk of vision loss, then there is greater emphasis on guarding against the risks of therapy.

With a high risk of vision loss, the emphasis on lowering IOP increases.

Alternative target IOP guidance

100

¨  Target IOP needs to be individualized as progression is highly variable and IOP is only partly responsible.

¨  Once rate of progression has been determined (by a sufficient # of VFs) and treatment advanced accordingly. [e.g, slower progression for NTG but faster for PXG]

Rossetti L, Goni F, Denis P, Bengtsson B, Martinez A, Heijl A. Focusing on glaucoma progression and the clinical importance of progression rate measurement: a review. Eye 2010; 24: s1-s7.

Hyman L, et al. Natural History of IOP in the EMGT. Arch Ophthalmol. 2010;128(5):601-607.

What about advancing therapy? 101

¨ Options include ¤  Switching to an alternative topical

therapy or adding additional topical drops

¤  SLT ¤  Trabeculectomy

What about advancing therapy by adding another medication?

102

¨ Single agent? ¤ Consensus guideline suggests tCAI

¨ A constellation of drops? ¤ Using additional dosages is likely to

decrease adherence

¨ Fixed combination drop? Beta-blocker containing or BB-free?

Ophthalmic Generics 103

Consider this scenario

The pharmacist calls you and asks, “Can I give your patient a generic equivalent of this PGA?” Your response would be: A.  Sure, they are bioequivalent B.  No, they only have the same active ingredient as

the original product C.  Go ahead, we’ll see how it performs D.  No, my child is on a

NAMEYOURFAVORITEPHARMA scholarship at Vanderbilt

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Ophthalmic generic qualifications ala FDA 105

“Generic ophthalmic medications contain the same active ingredients as their brand-name predecessors.”

Ophthalmic generic qualifications ala FDA 106

“Generic ophthalmic medications contain the same active ingredients as their brand-name predecessors.”

¨  But, is the bioavailability the same? (i.e., what is the other 99.995%?)

What influences bioavailability? 107

¨  Excipients ¤ Buffers ¤ Antioxidants ¤ Thickening agents

¨  pH ¨ Preservatives ¨ Tonicity ¨ Drop size ¨ Bottle composition

108

https://www.google.com/search?q=coca+cola&hl=en&tbo=d&source=lnms&tbm=isch&sa=X&ei=HBQVUcLvL5OO9ASlooHQDw&ved=0CAcQ_AUoAA&biw=1126&bih=633#imgrc=ynYqmoO2GbB76M%3A%3BAjPa_BSl75wi9M%3Bhttp%253A%252F%252Fwww.thetimes.co.uk%252Ftto%252Fmultimedia%252Farchive%252F00374%252FVIDEO_Coca-cola_add_374157a.jpg%3Bhttp%253A%252F%252Fwww.thetimes.co.uk%252Ftto%252Fhealth%252Fnews%252Farticle3658262.ece%3B1024%3B576

http://www.google.com/imgres?imgurl=http://manfoodblog.files.wordpress.com/2011/04/p4071906.jpg&imgrefurl=http://manfoodblog.wordpress.com/2011/04/08/store-brand-cola-shootout/&h=1536&w=2048&sz=1343&tbnid=Am6yxEXN7ckZrM:&tbnh=90&tbnw=120&zoom=1&usg=__c2jLtVQyrU4bBmsFWEjTAKSQYm4=&docid=5vjRaELR8NGEkM&hl=en&sa=X&ei=IRUVUfjtBIze8ATUxoDICw&ved=0CDAQ9QEwAA&dur=0

Which would you choose?

Issues with generics 109

¨  $/Pharmacy substitution ¨  Insurance coverage ¨  Medicare part D vs. Private Pay

Approaching the generic substitution issue with patients

110

¨  Some patients prefer a branded product

¨  When $ is a consideration, discuss the situation

¨  Generics may not have equivalent bioavailability, so monitor more closely/frequently

Ask patients to bring their bottles to visits

¨  Have the dispensing pharmacist understand why what you have prescribed for the patient

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Approaching the generic substitution issue with patients

111

¨  Consider options ¤  Pharmaceutical manufacturers’

plans/coupons ¤  Other classes of drugs ¤  Fewer doses / day, and other off-

label options, etc.

Impact of generic latanoprost 112

Impact of the Introduction of Generic Latanoprost on Glaucoma Medication Adherence. Stein, JD, et al. Am J. Ophth.Published Online: February 10, 2015

Conclusions Given that cost can significantly deter adherence, switching patients to generic medications may help improve patients' drug-regimen adherence. A considerable number of patients discontinued glaucoma drug use altogether when generic latanoprost became available. [We] should work with insurers and pharmacists to prevent such discontinuation of use as generic forms of other PGA agents become available.

Lipid Family Receptors

114

Lipid Family Receptors

Cannabinoids Prostaglandins Prostamides

What about weed? 115

Information is current as of Sept. 14, 2017.

State with legal medical marijuana

State with decriminalized marijuana possession laws

State with both medical and decriminalization laws

AGS position statement

¨  Treatment modalities (to lower IOP) ¤ Medication ¤ Laser ¤ Surgery

¨  Marijuana as an alternative ¤ Frequent dosing

¤ SEs ¤ Inadequate topical formulations

¤ May be neuroprotective

116

Jampel H. American glaucoma society position statement: marijuana and the treatment of glaucoma. J Glaucoma. 2010 Feb;19(2):75-6.

AGS position statement

¨  Bottom line: NO scientific evidence for its use to treat glaucoma .

117

Jampel H. American glaucoma society position statement: marijuana and the treatment of glaucoma. J Glaucoma. 2010 Feb;19(2):75-6.

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Nocturnal hypoperfusion as a glaucoma risk factor

Perfusion to the ONH 119

Example comparing DOPP and mean OPP 120/80 IOP = 20; DOPP = 60 [ 80-20] What IOP do we measure? diastolic

Significant difference between DOPP and MOPP Which to use???

Perfusion to the ONH 120

Example comparing DOPP and mean OPP 120/80 IOP = 20; DOPP = 60 [ 80-20] What IOP do we measure? diastolic

Comparing DOPP to MOPP calculation

MOPP = 2/3[DBP = 1/3 (SBP-DBP)- IOP 2/3[80 + 1/3 (40)] – 20 results in 42

2014 (monkeys)

122

*Recent association between nocturnal BP dips and ODH in NTG

Kwon J, Lee J, Choi J, Jeong D, Kook MS. Association Between Nocturnal Blood Pressure Dips and Optic Disc Hemorrhage in Patients With Normal-Tension

Glaucoma. Am J Ophthalmol. 2017 Apr;176:87-101. doi: 10.1016/j.ajo.2017.01.002. Epub 2017 Jan 12.

over-dippers = progressors

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*Recent association between nocturnal BP dips and ODH in NTG

Kwon J, Lee J, Choi J, Jeong D, Kook MS. Association Between Nocturnal Blood Pressure Dips and Optic Disc Hemorrhage in Patients With Normal-Tension

Glaucoma. Am J Ophthalmol. 2017 Apr;176:87-101. doi: 10.1016/j.ajo.2017.01.002. Epub 2017 Jan 12.

è

over-dippers = progressors

How should glaucoma be managed comprehensively?

¨  First, lower IOP

125

New directions in glaucoma treatment

¨  Yes, treatment ¨  Beyond IOP reduction, regulation of blood flow . . .

¤  Systemically (regulating blood pressure and monitoring perfusion pressure)

¤  Locally – endothelial-cell activity by modulating Nitric Oxide (NO) This is the NEXT BIG THING! n Regulation of aqueous dynamics at the trabecular

meshwork by vascular modulation

n In addition, the application of NO-donating compounds for the lowering of IOP directly

Nov. 2, 2017. . .

Future options for medical management – targeting the site of glaucoma, the TM

128

¨ Rho-kinase inhibitors (Rhopressa and Roclatan, (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, Aerie) ¤ Completed 12-month safety evaluation, Rocket (Canada) ¤ Completed 3-month efficacy study (USA), Mercury

¤ FDA-Approved December 2017

Future options for medical management – targeting the site of glaucoma, the TM

129

¨  Rho-kinase inhibitors (Rhopressa and Roclatan, (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005%, Aerie) ¤  Completed 12-month safety evaluation, Rocket (Canada) ¤  Completed 3-month efficacy study (USA), Mercury ¤  FDA-approved December 2017

¨  *MOAs ¤  increase fluid outflow through the trabecular meshwork, (10

drainage) ¤  increase fluid outflow through the uveoscleral pathway, (20

drainage) ¤  reduce fluid production in the eye, and ¤  reduce episcleral venous pressure (EVP).

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Other future directions for medical management of glacuoma

130

¨  Drug delivery (continuous, episodic)

¨  “Neuroprotection” & Neuroregeneration

How should glaucoma be managed comprehensively? ¨  Second, consider increasing perfusion (may be a

consequence of lowered IOP) ¤ Topical treatments? (betaxolol, brimonidine,

brinzolamide, ¤ Gingko Biloba) ¤ Exercise, weight loss ¤ Lower cholesterol, blood sugar levels ¤ Treat underlying vascular disorders (HT, SAS, CVD) ¤ Etc.

131

Anti-oxidant/Supplement formulation 132

HarrisA,GrossJ,MooreN,etal.Theeffectsofantioxidantsonocularbloodflowinpatientswithglaucoma.ActaOphthalmol.2017Aug3.doi:10.1111/aos.13530.[Epubaheadofprint]

Study design 133

¨  45 patients with confirmed glaucoma on IOP-lowering treatment (placebo controlled, X-over)

¨  Baseline and post-administration (@ 1 month) measurements ¤  IOP ¤ OPP ¤ Retrobulbar (ultrasound) and retinal capillary (Doppler)

blood flow

Results 134

¨  Increased peak systolic and/or end diastolic velocities among the active group (but not placebo)

¨  Reduced vascular resistance in central retinal and short posterior ciliary arteries

¨  Increased superior and inferior temporal retinal artery mean blood flow

¨  Enhanced retinal capillary density

SO, what were they given? 135

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SO, what were they given? 136

How should glaucoma be managed comprehensively?

¨  Third, reduce oxidative stress (Ca++ blockade [BUT, not systemic β-blockers] , supplements)

137

NON-SELECTIVE Beta-blockers: Significant additional precaution

Topical β-blockers administered at night to those taking systemic β-blockers may reduce perfusion to the ONH plus β-blocker therapy to reduce IOP is ineffective at night.

Which brings us to . . .

138

Hayreh SS. Effect of nocturnal blood pressure reduction on retrobulbar hemodynamics in glaucoma. Graefes Arch Clin Exp Ophthalmol. 2002; 240: 867-8.

Consider this:

¨  Is glaucoma AION that happens over a lifetime?

OR ¨  Is AION glaucoma that happens overnight?

Liu C-H, et al. Comparison of the Retinal Microvascular Density Between OAG and nAION. IOVS. 2017;58:3350–3356. DOI: 10.1167/iovs.17-22021

Remember . . . 141

¨  Adherence and life span are increasingly parts of our management paradigm.

¨  Technology is allowing us better diagnostic (earlier) and progression (monitoring) algorithms.

¨  A number of options for initial and advancing treatment are available and considerations include systemic and financial factors.

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Thank you!