Original release: April 1, 2017

last review: March 20, 2017

expiratiOn: April 30, 2018

in GlaucomaChallenging CasesManaging

The Pressure’s ON!

CME MONOGRAPH

This continuing medical education activity is jointly provided by New York Eye and Ear Infirmary of Mount Sinai and MedEdicus LLC.

This continuing medical education activity is supported through an unrestricted educational grant from Bausch & Lomb Incorporated.

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Faculty

DaviD S. GreenfielD, MDJeffrey M. liebMann, MDrobert n. Weinreb, MD

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LEARNING METHOD AND MEDIUMThis educational activity consists of a supplement and ten (10) study questions. The participant should, in order, read the learning objectives contained at the beginning of this supplement, read the supplement, answer all questions in the post test, and complete the Activity Evaluation/Credit Request form. To receive credit for this activity, please follow the instructions provided on the post test and Activity Evaluation/Credit Request form. This educational activity should take a maximum of 1.5 hours to complete.

CONTENT SOURCEThis continuing medical education (CME) activity captures content from a CME regional meeting series.

ACTIVITY DESCRIPTIONDespite the variety of treatments available for glaucoma, some patients continue to have vision-threatening intraocular pressure (IOP) levels. New drugs, new fixed combinations of existing drugs, and new procedures constantly challenge the traditional treatment paradigm and are showing promise in lowering IOP and slowing disease progression by multiple mechanisms of action. The purpose of this activity is to update ophthalmologists on the current state of the art and science for treating patients with glaucoma.

TARGET AUDIENCEThis educational activity is intended for ophthalmologists.

learning OBJeCtivesUpon completion of this activity, participants will be better able to:• Assess traditional and emerging risk factors, such as ocular perfusion pressure and cerebrospinal fluid pressure, in the global risk assessment of glaucoma• Describe the mechanism of action of current and emerging topical glaucoma therapies• Evaluate the clinical relevance of safety and efficacy data for emerging topical therapies for the treatment of glaucoma• Develop treatment plans to achieve evidence-based target IOP in patients with glaucoma

ACCREDITATION STATEMENTThis activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of new York eye and Ear Infirmary of Mount Sinai and MedEdicus LLC. The new York eye and ear Infirmary of Mount Sinai is accredited by the ACCME to provide continuing medical education for physicians.

AMA CREDIT DESIGNATION STATEMENTThe New York Eye and Ear Infirmary of Mount Sinai designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

GRANTOR STATEMENTThis continuing medical education activity is supported through an unrestricted educational grant from Bausch & Lomb Incorporated.

DISCLOSURE POLICY STATEMENTIt is the policy of New York Eye and Ear Infirmary of Mount Sinai that the faculty and anyone in a position to control activity content disclose any real or apparent conflicts of interest relating to the topics of this educational activity, and also disclose discussions of unlabeled/unapproved uses of drugs or devices during their presentation(s). New York Eye and Ear Infirmary of Mount Sinai has established policies in place that will identify and resolve all conflicts of interest prior to this educational activity. Full disclosure of faculty/planners and their commercial relationships, if any, follows.

DISCLOSURESMurray Fingeret, OD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Allergan; and Bausch & Lomb Incorporated.

David S. Greenfield, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Aerie Pharmaceuticals, Inc; Alcon; Allergan; Bausch & Lomb Incorporated; and Quark.

Jeffrey M. Liebmann, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Alcon; Allergan; Bausch & Lomb Incorporated; Carl Zeiss Meditec, Inc; ForSight VISION5; Heidelberg Engineering, Inc; Reichert, Inc; Sustained Nano Systems, LLC;

and Valeant; Contracted Research: Allergan; Bausch & Lomb Incorporated; Heidelberg Engineering, Inc; Tomey Corporation; Topcon Corporation; and Valeant; Ownership Interest: Diopsys, Inc; SOLX, Inc; and Sustained Nano Systems, LLC.

Robert N. Weinreb, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Aerie Pharmaceuticals, Inc; Alcon; Allergan; Bausch & Lomb Incorporated; ForSight VISION5; Nemus Bioscience, Inc; Unity; and Valeant; Contracted Research: Genentech, Inc; and Quark.

NEW YORK EYE AND EAR INFIRMARY OF MOUNT SINAI PEER REVIEW DISCLOSUREJoseph F. Panarelli, MD, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Allergan; and Aerie Pharmaceuticals, Inc..

EDITORIAL SUPPORT DISCLOSURESTony Realini, MD, MPH, had a financial agreement or affiliation during the past year with the following commercial interests in the form of Consultant/Advisory Board: Alcon; Bausch & Lomb Incorporated; Inotek Pharmaceuticals Corporation; and Smith & Nephew; Contracted Research: Alcon; and F. Hoffmann-La Roche Ltd.

Diane McArdle, PhD; Cynthia Tornallyay, RD, MBA, CHCP; Kimberly Corbin, CHCP; Barbara Aubel; and Michelle Ong have no relevant commercial relationships to disclose.

DISCLOSURE ATTESTATIONThe contributing physicians listed above have attested to the following:1) that the relationships/affiliations noted will not bias or otherwise influence their involvement in this activity;2) that practice recommendations given relevant to the companies with whom they have relationships/affiliations will be supported by the best available evidence or, absent evidence, will be consistent with generally accepted medical practice; and3) that all reasonable clinical alternatives will be discussed when making practice recommendations.

OFF-LABEL DISCUSSIONThis CME activity includes discussion of unlabeled and/or investigative uses of drugs. Please refer to the official prescribing information for each drug discussed in this activity for FDA-approved dosing, indications, and warnings.

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New York Eye and Ear Infirmary of Mount Sinai Privacy & Confidentiality Policieshttp://www.nyee.edu/health-professionals/cme/enduring-activities

CME Provider Contact InformationFor questions about this activity, call 212-979-4383.

tO OBtain AMA PRA CATEGORY 1 CREDIT™To obtain AMA PRA Category 1 Credit ™ for this activity, read the material in its entirety and consult referenced sources as necessary. Complete the evaluation form along with the post test answer box within this supplement. Remove the Activity Evaluation/Credit Request page from the printed supplement or print the Activity Evaluation/Credit Request page from the Digital Edition. Return via mail to Kim Corbin, Director, ICME, New York Eye and Ear Infirmary of Mount Sinai, 485 Madison Avenue, 17th Floor, New York, NY 10022 or fax to (212) 353-5703. Your certificate will be mailed to the address you provide on the Activity Evaluation/Credit Request form. Please allow 3 weeks for Activity Evaluation/Credit Request forms to be processed. There are no fees for participating in and receiving CME credit for this activity.

Alternatively, we offer instant certificate processing and support Green CME. Please take this post test and evaluation online by going to http://tinyurl.com/ThePressuresOnCME. Upon passing, you will receive your certificate immediately. You must score 70% or higher to receive credit for this activity, and may take the test up to 2 times. Upon registering and successfully completing the post test, your certificate will be made available online and you can print it or file it.

ACKNOWLEDGMENTThe authors wish to thank Murray Fingeret, OD, and David S. Greenfield, MD, for contribution of the cases for this review. DISCLAIMERThe views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of New York Eye and Ear Infirmary of Mount Sinai, MedEdicus LLC, Bausch & Lomb Incorporated, or Ophthalmology Times.

In July 2013, the Accreditation Council for Continuing Medical Education (ACCME) awarded New York Eye and Ear Infirmary of Mount Sinai “Accreditation with Commendation,” for six years as a provider of continuing medical education for physicians, the highest accreditation status awarded by the ACCME.

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in GlaucomaChallenging CasesManaging

The Pressure’s ON! faculty

DaviD S. GreenfielD, MDProfessor of OphthalmologyDouglas R. anderson chair in Ophthalmologyco-Director, Glaucoma ServiceBascom Palmer Eye Instituteuniversity of Miami Miller School of MedicineMiami, Florida

Jeffrey M. liebMann, MDShirlee and Bernard Brown Professor of OphthalmologyVice chair, Department of OphthalmologyDirector, Glaucoma ServiceEdward S. Harkness Eye Institutecolumbia university Medical centerNew york, New york

robert n. Weinreb, MDDirector, Shiley Eye InstituteDistinguished Professor and chair of OphthalmologyDistinguished Professor of BioengineeringDirector, Hamilton Glaucoma centeruniversity of california, San Diegola Jolla, california

cMe revieWer for neW yorK eye anD ear infirMary of Mount Sinai

JoSeph f. panarelli, MDassistant Professor of OphthalmologyIcahn School of Medicine of Mount Sinaiassociate Residency Program DirectorNew York Eye and Ear Infirmary of Mount SinaiNew york, New york

IntroductionThe science of glaucoma evaluation and management is progressing. New risk factors to guide clinical decision making are emerging, and new drugs with novel mechanisms of action have been evaluated in phase 3 clinical trials with promising results. In this series of cases, new relevant information and key decisions in the evaluation and clinical management of patients with suspected or established glaucoma will be discussed.

Case 1. Assessing the Need for Treatment in Ocular Hypertension

A 36-year-old African American male presents for a comprehensive eye examination complaining of blurred vision. His last eye examination was 2 years ago. His medical and family histories are unremarkable.

On examination, his visual acuity is 20/20 OU, with a -1.00 D spherical correction in each eye. Anterior segment examination is unremarkable. Goldmann tonometry at 9 am is 28 mm Hg in the right eye and 29 mm Hg in the left eye. Pachymetry reveals a corneal thickness of 520 and 510 μm in the right and left eye, respectively. The angles are open on gonioscopy. Figure 1 shows his optic nerves, optical coherence tomography (OCT) imaging, and visual fields.

Q: What is this patient’s diagnosis? The visual field in the right eye (Figure 1C) has a superior paracentral defect that could be glaucomatous or spurious. This was the patient’s first visual field test, and the right eye was tested first. Both the healthy appearance of the optic nerve (Figure 1A) and the normal retinal nerve fiber layer (RNFL) OCT image (Figure 1B) support this being a potential artifact; thus, confirmation of an abnormality by a second visual field test should be done prior to making clinical decisions. The visual field test was repeated and showed bilateral normal results.

It is noteworthy that visual field loss is not required to make the diagnosis of primary open-angle glaucoma (POAG). The 2015 edition of the American Academy of Ophthalmology’s (AAO’s) Preferred Practice Pattern for Primary Open-Angle Glaucoma defines POAG as “a chronic, progressive optic neuropathy in adults in which there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an open anterior chamber angle by gonioscopy.”1

This CME activity is copyrighted to MedEdicus LLC ©2017. All rights reserved. d.

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The development and progression of glaucoma occur in a continuum (Figure 2).2 The disease state begins when an unknown factor or factors accelerate the rate of apoptosis in a previously healthy eye, leading to early loss of retinal ganglion cells and their axons. These factors may include elevated intraocular pressure (IOP), ischemia, inflammation, aberrant immunity, or other potential factors (Figure 3).3 Current

technology to assess both structure and function in glaucoma lacks the sensitivity to identify very early changes, so the disease is undetectable in this early stage. With further retinal ganglion cell death and axonal loss, RNFL damage becomes clinically evident and early visual field defects will appear, even though the patient may remain asymptomatic at this time. If undiagnosed or undertreated, the disease can progress to a symptomatic stage and, ultimately, can result in significant functional impairment or even blindness.

As can be seen in the glaucoma continuum (Figure 2), there is a stage in the glaucoma disease process in which the disease exists but is undetectable. Distinguishing this stage of early POAG from simple ocular hypertension is not possible using current technology. Patients with either entity may have elevated IOP, with normal appearing optic nerve heads and normal visual fields. The natural history of these 2 entities is vastly different. Most patients with POAG will progress to worse POAG over time,4 whereas most patients with ocular hypertension will not develop POAG.5

The most liberal approach would be to treat all of these patients, even though many will be treated unnecessarily. The most conservative approach would be to treat none of them, observe them closely over time, and treat those who progress to detectable disease. Ideally, a middle ground should be followed, in which patients who would most benefit from therapy, that is, those with the highest risk of developing visual dysfunction, would be identified and treated.

Q: How do we identify these patients?A comprehensive risk assessment is a process by which

Figure 3. Multifactorial pathophysiology of primary open-angle glaucoma3

Reprinted from The Lancet, 363, Weinreb RN, Khaw PT, Primary open-angle glaucoma, 1711-1720, Copyright 2004, with permission from Elsevier.

Figure 2. Glaucoma continuum covering the spectrum from early, undetectable disease to advanced disease with visual dysfunction2

Abbreviation: VF, visual field.

Reprinted from American Journal of Ophthalmology, 138, Weinreb RN, Friedman DS, Fechtner RD, et al, Risk assessment in the management of patients with ocular hypertension, 458-467, Copyright 2004, with permission from Elsevier.

UnDe

teCt

aBle

Dise

ase

asYMptOMatiC Disease

FUnCtiOnal iMpairMent

Figure 1. Clinical data from the patient presented in Case 1. (A) Color optic nerve photographs. (B) Optical coherence tomography results. (C) Visual field results.Images courtesy of Murray Fingeret, OD

C

a

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observation is prudent.2 For a risk between 5% and 15%, the decision to treat or observe should follow an informed discussion with the patient. For a risk in excess of 15%, treatment should be encouraged. Applying the risk calculator to the patient in Case 1 reveals an 18.5% probability that this patient will develop POAG within the next 5 years (Table). Accordingly, treatment was recommended, and the patient agreed.

Q: What is the optimal first-line therapy for prophylactic treatment of patients with ocular hypertension?According to the findings of the Ocular Hypertension Treatment Study, a 20% reduction in IOP confers a significant reduction in the risk of progressing from ocular hypertension to POAG.5 Based on efficacy, tolerability, convenience of dosing, and cost, daily prostaglandin analogue therapy is a reasonable choice. For patients who cannot tolerate or do not adequately respond to prostaglandin analogue therapy, daily beta-blocker therapy can also be effective in the absence of relevant contraindications (eg, restrictive pulmonary disease, second-degree heart block, and bradycardia).

Topical medical therapy is generally well tolerated, and minor side effects are typically well accepted by patients with POAG who face the risk of vision loss and possibly blindness without therapy. When offering prophylactic therapy to a patient with ocular hypertension, the risk-benefit analysis is considerably different. This type of patient does not have a potentially blinding disease; therapy is offered for risk modification rather than for treatment of glaucoma. For this reason, the threshold for tolerating the negative effects of therapy—including side effects, the inconvenience of daily dosing, and the cost of medications—may be lower. Selective laser trabeculoplasty (SLT) is an effective and safe alternative to daily medical therapy18 that minimizes issues related to side effects, daily dosing, and cost.

Case 2. Initial Therapy for Newly Diagnosed Primary Open-Angle Glaucoma

A 68-year-old Hispanic male with diabetes mellitus presents for an eye examination to screen for diabetic eye disease. He has no personal history of any eye problems. His family history includes a brother with open-angle glaucoma. His medical history is significant for non–insulin-dependent diabetes mellitus diagnosed 10 years ago, which is well controlled with oral metformin. His recent HbA1c was 5.8%. He also has hyperlipidemia, which is controlled with simvastatin, and systemic hypertension, which is controlled with atenolol and hydrochlorothiazide.

known risk factors for glaucoma are carefully considered, weighed appropriately, and synthesized into an easily interpreted measure of long-term risk of visual field loss. Many risk factors for glaucoma are known and should be included in this process. Elevated IOP is perhaps the best-known risk factor for POAG.6 Other well-established risk factors include corneal biomechanical parameters such as central corneal thickness and hysteresis, increasing age, glaucoma family history/genetics, race (there is a higher risk in African Americans and Hispanics than in whites), and high myopia.1 Two potential risk factors have emerged in recent years: ocular perfusion pressure (OPP) and cerebrospinal fluid pressure (CSFP).

Ocular Perfusion PressureOcular perfusion pressure is the difference between systemic blood pressure and IOP, and represents the relative pressure of blood perfusing the eye. Numerous epidemiologic studies have demonstrated a higher prevalence of POAG in subjects with low OPP than in those with normal or high OPP.7-11 A role for OPP in the development of POAG is biologically plausible because low OPP indicates reduced perfusion of ocular tissues, which may contribute to hypoxia/ischemia of optic nerve tissue. Importantly, IOP is typically highest at night when systemic blood pressure is typically lowest, resulting in low OPP.12 Ambulatory 24-hour blood pressure monitoring is readily available, and, recently, the US Food and Drug Administration (FDA) approved the Triggerfish contact lens–based continuous IOP monitor, which was designed for 24-hour IOP assessment.13 Coupling these monitoring strategies can provide insight into circadian OPP in appropriate patients. Ocular perfusion pressure is also potentially modifiable, and this can be most easily achieved by adjusting antihypertensive medications to avoid periods of hypotension.

Cerebrospinal Fluid Pressure Cerebrospinal fluid pressure is relevant at the level of the lamina cribrosa in the optic nerve head, and likely leads to optic nerve damage in concert with elevated IOP. The lamina is acted on by 2 opposing forces: IOP on the prelaminar side and CSFP on the retro-laminar side. The configuration of the lamina—bowed forward, bowed backward, or in a neutral position—is determined by the translaminar pressure, which is represented by the difference between IOP and CSFP. Two studies—1 retrospective and 1 prospective—have demonstrated that eyes with POAG have lower CSFP than healthy eyes, suggesting that imbalances in translaminar pressure can contribute to glaucoma, possibly by impeding axoplasmic flow.14,15 It is difficult to measure CSFP, but noninvasive methods are under development. Importantly, CSFP can be modified pharmacologically and represents a potential novel therapeutic target for glaucoma.

Risk Calculator Many of these risk factors were identified in a pair of major clinical trials: the Ocular Hypertension Treatment Study6 and the European Glaucoma Prevention Study.16 The combined results of these 2 trials produced a validated risk calculator that considers the most well-established risk factors, weighs them accordingly, and generates the probability of progressing to POAG with reproducible visual field loss within 5 years.17 This tool is available without charge online at http://ohts.wustl.edu/risk/calculator.html. The calculator does not consider emerging risk factors, such as OPP and CSFP, which have come to light in the years since these 2 landmark trials. Expert consensus supports the following treatment guidelines based on risk level. If the risk is below 5%,

FACTORS

Age 36 RIGHT EYE MEASUREMENTS

LEFT EYE MEASUREMENTS

1st 2nd 3rd 1st 2nd 3rdUntreated Intraocular Pressure

(mm Hg)28 27 28 29 30 28

Central Corneal Thickness(μm)

520 522 516 510 505 505

Vertical Cup to Disc Ratio by Contour 0.45 0.45Pattern Standard DeviationHumphrey Octopus loss variance (dB) (dB)

1.7 1.6 1.4 1.4

Reprinted with permission.

Table. Risk Assessment Using the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study Risk Calculator for the Patient in Case 1

The patient’s estimated 5-year risk (%) of developing glaucoma in at least 1 eye18.5%

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On examination, his visual acuity is 20/20 in each eye, with a small hyperopic correction. Intraocular pressure, measured at 9 am with Goldmann tonometry, is 17 and 16 mm Hg in the right and left eye, respectively. Central corneal thickness is 545 and 540 μm in the right and left eye, respectively. Gonioscopy revealed angles open to the ciliary body band in both eyes. Figure 4 shows his optic nerves, RNFL, OCT, and visual fields.

Q: What is the diagnosis?Careful inspection of the optic nerve photographs (Figure 4A) reveals thinning of the inferior neuroretinal rim in the right eye, with an associated RNFL bundle defect. A similar

inferior RNFL bundle defect can be seen in the left eye. OCT imaging of the RNFL confirms thinning inferotemporally in both eyes (Figure 4B). The visual field in the right eye has a corresponding superior arcuate defect, whereas the left visual field remains essentially full (Figure 4C). Thus, this patient has functional loss in the right eye, which correlates with the structural damage evident both clinically and on OCT imaging. In the left eye, however, there is no evident visual field loss on standard automated perimetry. On the basis of these observations, the patient was diagnosed with POAG.

Historically, the classic findings of POAG in an eye with normal IOP would be considered normal-tension glaucoma (NTG). It is unclear, however, whether NTG is a distinct entity from POAG or a subset of POAG. Given that no pathognomonic finding distinguishes NTG from POAG other than IOP, it is likely that they are the same disease and that POAG exists across the full spectrum of IOP.

This patient has only been examined once. Intraocular pressure is a dynamic biologic parameter that exhibits significant variation throughout the day and from day to day in both healthy and glaucomatous eyes.19,20 Unless the clinical setting necessitates urgent IOP reduction, there is value in delaying the initiation of therapy to permit multiple assessments to more fully characterize IOP. After initiating therapy, multiple on-therapy measurements may be necessary to fully characterize the therapeutic response to treatment.21 The patient was asked to return for a repeat IOP assessment 2 weeks before starting therapy. At this visit, IOP was 17 mm Hg OU at 2 pm. The diagnosis of POAG with normal IOP was made. A target IOP of 13 mm Hg (25% reduction) was established.

Q: What is the best first-line therapy for this patient?The choice of therapy should consider treatment goals. The AAO Preferred Practice Pattern for POAG recommends an initial 25% IOP reduction for POAG, citing numerous lines of evidence that this degree of IOP lowering can slow progression of the disease.1 Other considerations when selecting therapy include safety, tolerability, convenience of dosing, and cost.

Prostaglandin analogues provide the optimal features of a first-line intervention for POAG. Alternatives include topical beta-blockers and SLT. Of note, topical beta-blockers have reduced efficacy in subjects on systemic beta-blockers (such as this patient), presumably because of a partial therapeutic effect from systemic administration.22 Surgical interventions are very effective for achieving low IOP, but with a less favorable safety profile, and are not typically considered for first-line therapy in early or moderate glaucoma.

In Case 2, generic latanoprost was prescribed for evening dosing OU. One month later, the patient returned with an IOP of 15 mm Hg OU. Two weeks later, IOP was 16 mm Hg OU. The patient has responded suboptimally to prostaglandin analogue therapy.

Q: What is the next best therapeutic step?Beta-blockers are a reasonable alternative first-line therapy in many patients, but several contraindications exist, including bradycardia, heart block, and pulmonary disease.23 Also, as discussed previously, beta-blockers provide reduced efficacy in patients using systemic beta-blockers22; therefore, SLT is a reasonable alternative for this patient. Numerous studies have

Figure 4. Clinical data from the patient presented in Case 2. (A) Right and left optic nerve photographs; green arrows indicate retinal nerve fiber layer bundle defects. (B) Optical coherence tomography images of the retinal nerve fiber layer. (C) Visual fields.

Images courtesy of Murray Fingeret, OD

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SS 24-2 SS 24-2

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demonstrated that SLT provides IOP reduction comparable to that of prostaglandin analogue therapy.18,24

This case demonstrates that there is a significant unmet need for medical therapies that provide equivalent or superior efficacy, safety, and dosing convenience to prostaglandin analogues for patients who have contraindications to, cannot tolerate, or exhibit suboptimal efficacy with prostaglandins. Several promising drugs are in late-stage development, including latanoprostene bunod (LBN) and netarsudil mesylate, which have multiple modes of action (Figure 5).

Latanoprostene BunodLatanoprostene bunod is a nitric oxide (NO)-donating form of latanoprost. Disease states in which NO is a therapeutic target include angina pectoris, pulmonary hypertension, erectile dysfunction, and, more recently, glaucoma. Nitric oxide relaxes smooth muscle, thus promoting vasodilation. In the trabecular meshwork, NO activates the cyclic guanosine monophosphate signaling pathway, resulting in trabecular relaxation and increased conventional outflow.25 Coupled with the effect of latanoprost on increasing uveoscleral outflow, LBN would be expected to provide a greater IOP reduction than latanoprost alone. In the phase 2 VOYAGER trial comparing LBN in various doses to latanoprost in 413 subjects, LBN, 0.024%, daily lowered IOP 1 to 1.5 mm Hg more than did latanoprost, 0.005%, daily.26 The most common adverse event associated with LBN was pain upon instillation. Conjunctival or ocular hyperemia rates were similar with LBN (7%) and latanoprost (8.5%). A pair of phase 3 trials—APOLLO and LUNAR—compared the IOP reduction of LBN, 0.024%, with that of timolol, 0.5%, twice daily.26,27 In the APOLLO trial, LBN was superior to timolol, providing a significantly lower IOP at all 9 diurnal time points (8 am, 12 pm, and 4 pm at weeks 2, 6, and 12).27 In the LUNAR trial, LBN was found to be noninferior to timolol, lowering IOP significantly more than did timolol at 8 of the 9 time points.28 Across the 2 studies, mean IOP reduction ranged from 7.5 to 9.1 mm Hg with LBN and from 6.6 to 8.0 mm Hg with timolol.26,27 Other NO-donating molecules are in earlier stages of development, including formulations of bimatoprost as well as dorzolamide and brinzolamide.29,30

Another product in late-stage development is netarsudil mesylate, a drug with a dual mechanism of action. This molecule inhibits both rho-kinase and the norepinephrine transporter. Inhibition of the enzyme rho-kinase results in both increased trabecular outflow and reduced episcleral venous pressure, both of which would contribute to IOP reduction.31 Inhibition of the norepinephrine transporter increases adrenergic activity, which in turn reduces the rate of aqueous

production, also a contributor to IOP reduction. Phase 3 studies of netarsudil mesylate have produced mixed results and remain unpublished to date.

Several novel delivery systems for existing glaucoma drugs are also in development. Among these are a punctal plug32 and an intraocular implant33 delivering travoprost, as well as an intraocular implant34 and a conjunctival ring35 delivering bimatoprost. Several of these products are in late-stage development, and the role of these products in current management practice patterns has yet to be established.

Case 3. Glaucoma Progression Despite Low Intraocular Pressure

A 70-year-old white female with a 20-year history of POAG presents for a scheduled follow-up visit. She has advanced POAG and lost fixation in her right eye 10 years ago. Her current treatment regimen includes latanoprost OU at bedtime and dorzolamide OU twice daily. She reports excellent adherence to therapy. Her medical history is remarkable for migraine headache, hyperlipidemia controlled with simvastatin, and hypertension controlled with atenolol.

On examination, her visual acuity is counting fingers in the right eye and 20/40 in the left eye (due to moderate cataract). Her IOP is 13 mm Hg in the right eye and 14 mm Hg in the left eye. Of note, her pretreatment IOP level was 24 mm Hg in the right eye and 32 mm Hg in the left eye, and her IOP on therapy has never been above 15 mm Hg in the past 10 years. Central corneal thickness in the right and left eye is 499 and 497 μm, respectively. Her angles are open on gonioscopy. Figure 6 shows the left optic nerve photograph and OCT and visual field results that demonstrate progression.

Q: Why is this patient progressing with intraocular pressure in the low teens?When confronted with any patient with glaucoma whose disease is progressing, the first question to ask is whether IOP has been adequately lowered from untreated baseline. In this case, the patient’s left eye IOP has been consistently reduced from 32 to 14 mm Hg, a 56% reduction. This magnitude of IOP reduction would be expected to halt, or at least dramatically slow, glaucoma progression.

An additional consideration is whether the patient is adherent to therapy. Some patients use their medications only in the days preceding office visits, which presents a misleading appearance of adequate IOP control to the physician. Such patients are unlikely to admit to such behavior, and ophthalmologists are generally unable to identify patients who are most likely to be nonadherent.36 This patient consistently reports excellent adherence to therapy, but such behavior is difficult to verify objectively.

Central corneal thickness can contribute to artifact in the measurement of IOP by applanation tonometry. Specifically, thin corneas—which tend to be flatter and less rigid—applanate with less force than thicker corneas and can lead to underestimation of true IOP. This patient’s corneas are quite thin—less than 500 μm—which is likely associated with a clinically relevant underestimation of IOP. Although the ocular hypotensive response to therapy appears to be adequate, her true absolute IOP level may be considerably higher than the 14 mm Hg value measured with Goldmann tonometry, and a lower target IOP may be appropriate in light of her recent progression.

Figure 5. Sites and mechanisms of action of current and emerging intraocular pressure–lowering medications.

Abbreviation: LBN, latanoprostene bunod.

Netter illustration used with permission of Elsevier, Inc. All rights reserved. www.netterimages.com.

Decrease trabecular outflow resistanceLBN (nitric oxide) Netarsudil

Open angle by mechanical tensionMiotics

Aqueous suppressionBeta-blockersCarbonic anhydrase inhibitorsAlpha-receptor adrenergic agonistsNetarsudil

Increase uveoscleral outflow

Prostaglandins

Alpha-receptor adrenergic agonists

LBN (prostaglandin analogue)

Lower episcleral venous pressure

Netarsudil

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This patient’s IOP has consistently been 15 mm Hg or lower when measured during routine office hours, yet IOP tends to

peak at night when lying down asleep. This is because IOP is higher in the supine position than in the sitting position and also because IOP tends to rise at night as part of its own circadian rhythm.37 Routine clinical assessment of 24-hour IOP is impractical because of the lack of safe, affordable, and user-friendly home tonometry devices.

Coupled with the known rise of IOP at night, systemic blood pressure tends to dip at night.12 This can be particularly significant in patients who take blood pressure medications, especially those who dose their antihypertensive therapy in the evening before bed. The concurrence of high IOP and low systemic blood pressure during the nocturnal period may result in a significant reduction in OPP. As discussed previously, OPP is an emerging risk factor for the development of glaucoma and may represent a risk factor for glaucoma progression related to aberrant perfusion of the optic nerve.

Q: Is any additional workup appropriate for this patient?This patient is progressing despite a 50% reduction in baseline IOP to the low teens. An additional diagnostic evaluation might be warranted. Ambulatory 24-hour blood pressure monitoring may reveal nocturnal dips. Likewise, 24-hour IOP monitoring using the Triggerfish system may reveal IOP fluctuation throughout the day and night.38 Nocturnal IOP peaks may be reduced by sleeping with an extra pillow or 2 to elevate the head.39,40 Dips in nocturnal blood pressure might be mitigated by reducing the dose of systemic antihypertensive medication, using morning dosing rather than evening dosing, or having the patient ingest salty snacks (such as tomato juice or potato chips) before bed to raise blood pressure. There are no data from epidemiologic studies or trials to support salt loading in this setting.

A simpler approach to 24-hour blood pressure assessment is to obtain blood pressure measurements during office-based glaucoma visits. Routine daytime blood pressure measurements in all patients is expensive, cumbersome, and may be of limited value. Selecting patients at high risk for progression (eg, patients who report a history of low blood pressure or eyes with optic disc hemorrhage) may provide a snapshot and reveal systemic hypotension, which may be more pronounced at night. These patients might benefit the most from adjustment of the dose or time of administration of antihypertensive therapy by the primary care physician.

Q: What is the next therapeutic step for this patient?This patient is progressing by both structural and functional criteria, despite having an IOP in the low teens on 2 glaucoma medications (prostaglandin analogue and carbonic anhydrase inhibitor). Additional IOP lowering is necessary to halt disease progression. A reasonable goal would be an additional 15% to 20% reduction in IOP (approximately 10-11 mm Hg). One therapeutic approach is to add a third topical medication, such as a beta-blocker or adrenergic agonist, to achieve the target IOP and continue close surveillance.

Other, invasive, options include proceeding directly with laser trabeculoplasty or incisional surgery. Selective laser trabeculoplasty can lower IOP in patients on multidrug regimens. However, in patients with confirmed progression

Figure 6. Clinical data from the patient presented in Case 3. (A) Color optic nerve photograph. (B) Optical coherence tomography data showing a decline in retinal nerve fiber layer thickness over time. (C) Visual field data showing progression of visual field loss over time.

C

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Images courtesy of David S. Greenfield, MD

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who require a very low target IOP, traditional glaucoma surgery, such as trabeculectomy or tube-shunt implantation, may be the preferred approach.41 Because this patient also has a visually significant cataract and is functionally monocular, she may be a good candidate for a combined cataract and glaucoma procedure. Lastly, a new generation of minimally invasive glaucoma surgery has emerged in recent years, and these procedures may be acceptable in eyes with coexisting cataract and mild-to-moderate open-angle glaucoma. It should be noted that cataract surgery alone often lowers IOP by several points in eyes with elevated IOP.42-44

Case 4. A Young Patient With a High Risk for Vision Loss

A 47-year-old African American male with a 6-year history of POAG presents for a scheduled follow-up. His current medical regimen includes latanoprost OU at bedtime and a dorzolamide/timolol fixed combination OU twice daily. He is in excellent health.

On examination, his visual acuity is 20/20 OU. His IOP is 13 mm Hg OU; his untreated baseline IOP was 29 mm Hg OU. Pachymetry reveals thin corneas (520 μm OU), and his angles are open on gonioscopy. Figure 7 shows his optic nerve photographs, OCTs, and visual fields. This patient has advanced POAG. A careful examination of Figure 7A reveals little residual neuroretinal rim in the right eye; further thinning may not be easily detected on clinical examination. In addition, Figure 7B reveals a very thin residual RNFL in both eyes. Further small reductions in RNFL thickness may not be readily apparent by OCT. As demonstrated in Figure 7C, however, a significant residual intact visual field remains, which provides the best opportunity to detect changes over time.

Q: What is an appropriate target IOP for this patient?Determination of a target IOP requires a careful evaluation of the risk factors for progression. In this patient’s case, there are several important factors to consider. He is a young man and will likely live with glaucoma for many decades. Therefore, the goal of treatment should be to halt, rather than slow down, the rate of progression. He is also African American, which is an independent risk factor for glaucoma progression and blindness.45 Further, he has advanced glaucoma, as evidenced by the fixation-threatening visual field defects in both eyes. The AAO guidelines suggest an initial IOP reduction in excess of 25% for this high-risk patient.1 His current IOP reduction is 55%, which is entirely reasonable, but to be sure this is enough, he should be monitored carefully for evidence of progression.

Q: What is the best strategy for monitoring this patient for future progression?Progression can manifest by structural change, functional change, or both. Therefore, the ongoing surveillance for progression of glaucoma must include periodic evaluations of both the appearance and function of the optic nerve. The relative importance of structural and functional assessment varies, however, with the stage of the disease. In early disease, structural changes are more likely to appear while function is preserved. In late-stage glaucoma, small changes in structure may not be apparent, given extensive structural loss and limited residual neuroretinal rim, whereas functional testing may be better suited to detecting changes in the central visual field.

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Figure 7. Clinical data from the patient presented in Case 4. (A) Color optic nerve photographs. (B) Optical coherence tomography results. (C) Visual field results.

Images courtesy of Murray Fingeret, OD

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1. American Academy of Ophthalmology. Preferred Practice Pattern® Guidelines. Primary Open-Angle Glaucoma. San Francisco, CA: American Academy of Ophthalmology; 2015.2. Weinreb RN, Friedman DS, Fechtner RD, et al. Risk assessment in the management of patients with ocular hypertension. Am J Ophthalmol.

2004;138(3):458-467.3. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363(9422): 1711-1720.4. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early

Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.5. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment

Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.6. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment

Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):714-720.7. Memarzadeh F, Ying-Lai M, Chung J, Azen SP, Varma R; Los Angeles Latino Eye

Study Group. Blood pressure, perfusion pressure, and open-angle glaucoma: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. 2010;51(6):2872-2877.8. Leske MC, Wu SY, Nemesure B, Hennis A. Incident open-angle glaucoma and

blood pressure. Arch Ophthalmol. 2002;120(7):954-959.9. Bonomi L, Marchini G, Marraffa M, Bernardi P, Morbio R, Varotto A. Vascular

risk factors for primary open angle glaucoma: the Egna-Neumarkt Study. Ophthalmology. 2000;107(7):1287-1293.10. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113(2):216-221.11. Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol. 2001;119(12):1819-1826.12. Costa VP, Jimenez-Roman J, Carrasco FG, Lupinacci A, Harris A. Twenty-four- hour ocular perfusion pressure in primary open-angle glaucoma. Br J Ophthalmol. 2010;94(10):1291-1294.13. U.S. Food and Drug Administration. FDA permits marketing of device that senses optimal time to check patient’s eye pressure. http://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm489308.htm. Published March 4, 2016. Accessed February 1, 2017. 14. Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117(2):259-266.15. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5): 763-768.16. Miglior S, Pfeiffer N, Torri V, Zeyen T, Cunha-Vaz J, Adamsons I; European Glaucoma Prevention (EGPS) Group. Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study. Ophthalmology. 2007;114(1):3-9.17. Gordon MO, Torri V, Miglior S, et al; Ocular Hypertension Treatment Study Group; European Glaucoma Prevention Study Group. Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114(1):10-19.18. Katz LJ, Steinmann WC, Kabir A, Molineaux J, Wizov SS, Marcellino G; SLT/ Med Study Group. Selective laser trabeculoplasty versus medical therapy as initial treatment of glaucoma: a prospective, randomized trial. J Glaucoma. 2012;21(7):460-468.19. Realini T, Weinreb N, Wisniewski S. Short-term repeatability of diurnal intraocular pressure patterns in glaucomatous individuals. Ophthalmology. 2011;118(1):47-51.20. Realini T, Weinreb RN, Wisniewski SR. Diurnal intraocular pressure patterns are not repeatable in the short term in healthy individuals. Ophthalmology. 2010;117(9):1700-1704.21. Realini T. Assessing the effectiveness of intraocular pressure-lowering therapy. Ophthalmology. 2010;117(11):2045-2046.22. Schuman JS. Effects of systemic beta-blocker therapy on the efficacy and safety of topical brimonidine and timolol. Brimonidine Study Groups 1 and 2. Ophthalmology. 2000;107(6):1171-1177.23. Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidence- based assessment. Am J Ophthalmol. 2002;134(5):749-760.24. McIlraith I, Strasfeld M, Colev G, Hutnik CM. Selective laser trabeculoplasty as initial and adjunctive treatment for open-angle glaucoma. J Glaucoma. 2006;15(2):124-130.

25. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of endothelin-1-induced trabecular meshwork cell contractility by latanoprostene bunod. Invest Ophthalmol Vis Sci. 2015;56(6):4108-4116.26. Weinreb RN, Ong T, Scassellati Sforzolini B, Vittitow JL, Singh K, Kaufman PL; VOYAGER Study Group. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2015;99(6):738-745.27. Weinreb RN, Scassellati Sforzolini B, Vittitow J, Liebmann J. Latanoprostene bunod 0.024% versus timolol maleate 0.5% in subjects with open-angle glaucoma or ocular hypertension: the APOLLO Study. Ophthalmology. 2016;123(5):965-973.28. Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of latanoprostene bunod 0.024% and timolol maleate 0.5% in open-angle glaucoma or ocular hypertension: the LUNAR Study. Am J Ophthalmol. 2016;168:250-259.29. Impagnatiello F, Toris CB, Batugo M, et al. Intraocular pressure-lowering activity of NCX 470, a novel nitric oxide-donating bimatoprost in preclinical models. Invest Ophthalmol Vis Sci. 2015;56(11):6558-6564.30. Huang Q, Rui EY, Cobbs M, et al. Design, synthesis, and evaluation of NO-donor containing carbonic anhydrase inhibitors to lower intraocular pressure. J Med Chem. 2015;58(6):2821-2833.31. Bacharach J, Dubiner HB, Levy B, Kopczynski CC, Novack GD; AR-13324- CS202 Study Group. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology. 2015;122(2):302-307.32. Ocular Therapeutix, Inc. Phase 2b study evaluating safety and efficacy of OTX-TP compared to timolol drops in the treatment of subjects with open angle glaucoma or ocular hypertension. ClinicalTrials.gov Web site. https://clinicaltrials.gov/ct2/ show/NCT02312544. Updated December 13, 2016. Accessed February 1, 2017.33. Glaukos Corporation. Study comparing travoprost intraocular implants to timolol ophthalmic solution. ClinicalTrials.gov Web site. https://clinicaltrials.gov/ct2/show/ NCT02754596. Updated April 27, 2016. Accessed February 3, 2017.34. Lewis RA, Christie WC, Day DG, et al; Bimatoprost SR Study Group. Bimatoprost sustained-release implants for glaucoma therapy: 6-month results from a phase I/II clinical trial Am J Ophthalmol. 2017;175:137-147.35. Brandt JD, Sall K, DuBiner H, et al. Six-month intraocular pressure reduction with a topical bimatoprost ocular insert: results of a phase II randomized controlled study. Ophthalmology. 2016;123(8):1685-1694.36. Okeke CO, Quigley HA, Jampel HD, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-199.37. Liu JH, Zhang X, Kripke DF, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis Sci. 2003;44(4):1586-1590.38. 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;130(12):1534-1539.39. Buys YM, Alasbali T, Jin YP, et al. Effect of sleeping in a head-up position on intraocular pressure in patients with glaucoma. Ophthalmology. 2010;117(7): 1348-1351.40. Malihi M, Sit AJ. Effect of head and body position on intraocular pressure. Ophthalmology. 2012;119(5):987-991.41. Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL; Tube Versus Trabeculectomy Study Group. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol. 2012;153(5):789-803.e2.42. Mansberger SL, Gordon MO, Jampel H, et al; Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology. 2012;119(9):1826-1831.43. Poley BJ, Lindstrom RL, Samuelson TW, Schulze R Jr. Intraocular pressure reduction after phacoemulsification with intraocular lens implantation in glaucomatous and nonglaucomatous eyes: evaluation of a causal relationship between the natural lens and open-angle glaucoma. J Cataract Refract Surg. 2009;35(11):1946-1955.44. Shingleton BJ, Laul A, Nagao K, et al. Effect of phacoemulsification on intraocular pressure in eyes with pseudoexfoliation: single-surgeon series. J Cataract Refract Surg. 2008;34(11):1834-1841.45. Racette L, Wilson MR, Zangwill LM, Weinreb RN, Sample PA. Primary open-angle glaucoma in blacks: a review. Surv Ophthalmol. 2003;48(3):295-313.

In most stable patients, practice patterns consist of annual visual field testing. In this high-risk patient, a more frequent testing interval—as often as every 6 months—might be appropriate. Also, because his visual field loss is central and threatens fixation, using a 10-2 strategy might reveal small but relevant changes close to fixation that would indicate the need for a lower target IOP.

SummaryGlaucoma evaluation and management are evolving. New risk factors enable better evaluation of the value of treatment in glaucoma suspects and better understanding of the complex pathophysiology of glaucoma. New treatments will soon come to market, offering novel ways to lower IOP. Each of these advances improves clinicians’ ability to ensure that patients with glaucoma maintain their sight and preserve their quality of life.

References

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CME Post Test QuestionsTo obtain AMA PRA Category 1 Credit ™ for this activity, complete the CME Post Test by writing the best answer to each question in the Answer Box located on the Activity Evaluation/Credit Request form on the following page. Alternatively, you can complete the CME Post Test online at http://tinyurl.com/ThePressuresOnCME.

See detailed instructions at To Obtain AMA PRA Category 1 Credit™ on page 2.

For instant processing, complete the CME Post Test online http://tinyurl.com/ThePressuresOnCME

1. A 66-year-old man with POAG has IOP readings consistently in the low teens, but his visual field continues to progress. Which of the following is NOT a reasonable explanation for this clinical scenario? a. His peak IOP is occurring outside of office hours b. He has a thin cornea and his IOP readings are underestimates of his true IOP c. He has elevated CSFP causing progressive optic nerve damage d. He takes his medications only during the week before each of his follow-up visits

2. Ocular perfusion pressure is lowest when: a. IOP is elevated and blood pressure is elevated b. IOP is reduced and blood pressure is elevated c. IOP is elevated and blood pressure is reduced d. Both IOP and blood pressure are reduced 3. The translaminar pressure difference is the difference between: a. IOP and systemic blood pressure b. CSFP and diastolic blood pressure c. IOP and CSFP d. IOP and diastolic blood pressure

4. Beta-blockers lower IOP by: a. Reducing the production of aqueous humor b. Increasing trabecular outflow of aqueous humor c. Increasing uveoscleral outflow of aqueous humor d. Decreasing episcleral venous pressure

5. Latanoprostene bunod is in late-stage clinical development for the reduction of IOP in eyes with ocular hypertension or glaucoma. By what dual mechanisms does this drug reduce IOP? a. Reducing aqueous production and increasing uveoscleral outflow b. Reducing aqueous production and increasing trabecular outflow c. Reducing episcleral venous pressure and increasing trabecular outflow d. Increasing uveoscleral outflow and increasing trabecular outflow

6. All of the following are important steps in the development of a treatment plan for a patient with newly diagnosed ocular hypertension, EXCEPT: a. Assess known risk factors for progression to glaucoma b. Estimate progression risk using an online calculator c. Establish a target IOP d. Always start with prostaglandin analogue monotherapy

7. Which of the following is the correct pairing of drug class and mechanism of action? a. Carbonic anhydrase inhibitors: increase trabecular outflow b. Beta-blockers: increase uveoscleral outflow c. Adrenergic agonists: decrease aqueous production d. Prostaglandin analogues: increase trabecular outflow

8. You are considering the use of topical timolol to manage a patient’s glaucoma. When taking the patient’s medical history, use of which of the following systemic hypertension medications might prompt you to select a different IOP-lowering agent? a. Angiotensin-converting enzyme inhibitor b. Beta-blocker c. Thiazide diuretic d. Angiotensin receptor blocker

9. Nitric oxide plays an important role in many areas of human health. In glaucoma, NO can lower IOP by: a. Increasing trabecular outflow b. Reducing aqueous production c. Increasing uveoscleral outflow d. Increasing episcleral venous pressure

10. When initiating IOP-lowering therapy in a newly diagnosed patient with early POAG and a baseline IOP of 20 mm Hg, what is a reasonable target IOP? a. 15% reduction b. < 21 mm Hg c. 25% reduction d. < 18 mm Hg

Activity Evaluation/Credit Request THE PRESSURE’S ON! MANAGING CHALLENGING CASES IN GLAUCOMATo receive AMA PRA Category 1 Credit ™, you must complete this Evaluation form and the Post Test. Record your answers to the Post Test in the Answer Box located below. Mail or Fax this completed page to New York Eye and Ear Infirmary of Mount Sinai–ICME, 485 Madison Avenue, 17th Floor, New York, NY 10022 (Fax: 212-353-5703). Your comments help us to determine the extent to which this educational activity has met its stated objectives, assess future educational needs, and create timely and pertinent future activities. Please provide all the requested information below. This ensures that your certificate is filled out correctly and is mailed to the proper address. It also enables us to contact you about future CME activities. Please print clearly or type. Illegible submissions cannot be processed.PARTICIPANT INFORMATION (Please Print) ☐ Home ☐ OfficeLast Name ___________________________________________________________ First Name ____________________________________Specialty ____________________Degree ☐ MD ☐ DO ☐ OD ☐ PharmD ☐ RPh ☐ NP ☐ RN ☐ PA ☐ OtherInstitution __________________________________________________________________________________________________________Street Address ______________________________________________________________________________________________________City _________________________State _________________ ZIP Code ________________Country_______________________________E-mail _________________________________________ Phone ___________________________Fax_______________________________

Please note: We do not sell or share e-mail addresses. They are used strictly for conducting post-activity follow-up surveys to assess the impact of this educational activity on your practice.Learner Disclosure: To ensure compliance with the US Centers for Medicare and Medicaid Services regarding gifts to physicians, New York Eye and Ear Infirmary of Mount Sinai Institute for CME requires that you disclose whether or not you have any financial, referral, and/or other relationship with our institution. CME certificates cannot be awarded unless you answer this question. For additional information, please call NYEE ICME at 212-979-4383. Thank you.☐ Yes ☐ No I and/or my family member have a financial relationship with New York Eye and Ear Infirmary of Mount Sinai and/or refer Medicare/Medicaid patients to it.☐ I certify that I have participated in the entire activity and claim 1.5 AMA PRA Category 1 Credits™.

Signature Required ____________________________________________________Date Completed _____________________________OUTCOMES MEASUREMENT☐ Yes ☐ No Did you perceive any commercial bias in any part of this activity? IMPORTANT! If you answered “Yes,” we urge you to be specific about where the bias occurred so we can address the perceived bias with the contributor and/or in the subject matter in future activities.____________________________________________________________________________________________________________________

Circle the number that best reflects your opinion on the degree to which the following learning objectives were met:5 = Strongly Agree 4 = Agree 3 = Neutral 2 = Disagree 1 = Strongly DisagreeUpon completion of this activity, I am better able to: • Assess traditional and emerging risk factors, such as ocular perfusion pressure and cerebrospinal fluid pressure, in the global risk assessment of glaucoma• Describe the mechanism of action of current and emerging topical glaucoma therapies• Evaluate the clinical relevance of safety and efficacy data for emerging topical therapies for the treatment of glaucoma• Develop treatment plans to achieve evidence-based target IOP in patients with glaucoma

1. Please list one or more things, if any, you learned from participating in this educational activity that you did not already know. ____________________________________________________________________________________________________________________2. As a result of the knowledge gained in this educational activity, how likely are you to implement changes in your practice? 4 = definitely will implement changes 3 = likely will implement changes 2 = likely will not implement any changes 1 = definitely will not make any changes Please describe the change(s) you plan to make: ___________________________________________________________________________________________________________________________________________________________________________________________3. Related to what you learned in this activity, what barriers to implementing these changes or achieving better patient outcomes do you face?_____________________________________________________________________________________________________4. Please check the Core Competencies (as defined by the Accreditation Council for Graduate Medical Education) that were enhanced for you through participation in this activity. ☐ Patient Care ☐ Practice-Based Learning and Improvement ☐ Professionalism ☐ Medical Knowledge ☐ Interpersonal and Communication Skills ☐ Systems-Based Practice5. What other topics would you like to see covered in future CME programs? _______________________________________________

ADDITIONAL COMMENTS _____________________________________________________________________________________________

pOst test answer BOx

Original Release: April 1, 2017Last Review: March 20, 2017

Expiration: April 30, 2018

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