Reducing the Pressure on Glaucoma Decision-Making

Transcription

1 Reducing the Pressure on Glaucoma Decision-Making Ron Melton, OD, FAAO Randall Thomas, OD, MPH, FAAO Financial Disclosure Dr. Ron Melton and Dr. Randall Thomas are consultants to, on the speakers bureau of, on the advisory committee of, or involved in research for the following companies: Allergan, Icare, Shire, and Valeant. The Strength of Optometric Glaucoma Care Although highly desirable, physicianpatient communication is an often overlooked but essential element in engaging patients in their own care. When physicians communicate well, adherence rates are 19% higher than for patients whose physicians communicate less effectively. Who can spend more time with their patients, those seeing 20-some patients daily or those seeing 40-some patients daily? It s simple arithmetic! Ophthalmology. July Page 1

2 Underdiagnosis of POAG Population studies suggest over half of all glaucoma patients have not been diagnosed From the Baltimore Eye Study: One-half of all people who were found to have glaucoma had seen an eye doctor within the past year and were unaware they had glaucoma! Despite all the progress being made in the field, it is sobering that ophthalmologists fail to diagnose more than 50% of cases of glaucoma. (Quigley, Ophthalmology Times) Risk Factors For POAG Suspicious ONH cupping Elevated or increasing IOP Subnormal central corneal thickness (CCT) Advancing age (particularly after 50) African or Hispanic origin onset earlier (about 10 years), damage more severe, treatment less successful Positive family history (age at Dx?) Diurnal fluctuation? High myopia Does Blood Pressure Affect Glaucoma? Non-traditional risk factors include low blood pressure or perfusion pressure and other vascular factors Traditional Risk Factors for Glaucoma Include elevated eye pressure, family history, age, and individuals of African, Asian, or Hispanic descent. Most people with elevated eye pressure do not have and may never develop glaucoma. 40% of those who develop glaucoma have eye pressures that are in the normal range Other Risk Factors for Glaucoma Ocular perfusion pressure is a strong risk factor for glaucoma. Ocular perfusion pressure is the relationship between the eye pressure and the blood pressure What Can We Do Today? Low ocular perfusion pressure may be improved by lowering eye pressure and/or by increasing blood pressure Reference: Louis B. Cantor, MD. Does Blood Pressure Affect Glaucoma? Gleams From Glaucoma Research Foundation. January Page 2

3 Diastolic Blood Pressure Ocular Perfusion Pressure and Glaucoma OPP = diastolic BP IOP Theory: OPP <50mmHg is a risk factor for glaucoma, and glaucoma progression Examples: DBP of 65 and an IOP of 15 DBP of 85 and an IOP of 35 These two patients may be at equal risk because they have same theorized OPP of 50mmHg Take home message: Begin to check blood pressures on your glaucoma and glaucoma suspect patients, especially those with lower IOPs. Reference: Quaid, P et al, IOVS, Jan 2013 Under-Appreciation of Systemic Hypotension As It Relates To Ocular Perfusion OPP: IOP minus the diastolic blood pressure Ocular perfusion pressure: may be the single biggest risk factor for glaucoma onset and progression Reference: Liebmann JM. Optometric Glaucoma Society, Boston, October Diastolic Blood Pressure Ocular Perfusion Pressure and Glaucoma The driving force for ocular blood flow is the ocular perfusion pressure (OPP), defined as the ocular artery pressure minus the IOP. Large cross-sectional prevalence studies in different populations found a significant association between low diastolic OPP and the prevalence of OAG. The greater incidence of progression in patients with lower blood pressure, seen mainly in patients with lower IOP, suggests a vascular risk factor for progression independent of IOP. Low blood pressure... may be the most important vascular risk factor for glaucoma progression. Reference: AJO. May 2010 Page 3

4 OHTS Summary of Practice Implications Risk for progression of ocular hypertension to POAG can be assessed - Age, IOP, vertical C/D ratio, CCT CCT should be measured in all patients with ocular hypertension and all glaucoma suspects Patients at high risk should be treated Therapy should be selected based on efficacy, tolerability, and likelihood of patient compliance Treatment of Ocular Hypertension In the end, the physician is stuck with the persistent problem of whom to treat and whom to watch. It probably still makes sense that young patients with lots of high risk factors should receive prophylaxis, while elderly patients with few risk factors should not. The endless symposia and debates on how to best manage patients with ocular hypertension will probably continue unabated. Reference: Sommer A. Editorial. Treatment of Ocular Hypertension. Archives of Ophthalmology. March, Delaying Treatment of Ocular Hypertension In summary, the second phase of OHTS allows us to draw some important conclusions about the management of patients with OHT. Early medical treatment decreases the cumulative incidence of POAG. The absolute effect is greatest in high-risk individuals. Conversely, there is little absolute benefit of early treatment in individuals with OHT at low risk of developing POAG. Reference: Klass M et al. Delaying Treatment of Ocular Hypertension. Archives of Ophthalmology. March, Page 4

5 Perspective on Central Corneal Thickness (CCT) CCT has become standard-of-care in the POAG (or suspect) work-up Thinner corneas are a strong risk factor for POAG because true IOP is actually higher than the measured IOP. Some patients with measured ocular hypertension may simply have a thicker CCT, thus reducing POAG risk because the true IOP is actually less than the measured IOP CCT is the most heritable aspect of ocular structure (more than refraction, axial length, or optic disc size), suggesting that it is under exquisite genetic control. (Ophthalmology, Nov. 2007) Correction values for applanation tonometer readings according to corneal thickness Calculation based on data of Ehlers et al (1975) Modified from Stodtmeister (1998) Arithmetic mean of corneal thickness in healthy subjects: 545 µm (Doughty and Zaman 2000) Correction values according to corneal thickness of 545 µm Role of CCT and Glaucoma Thinner CCT may be a significant, independent risk factor for open-angle glaucoma among persons with ocular hypertension. It is unclear whether the impact of CCT as a risk factor for glaucoma is mediated largely through its role in determining measured IOP, or whether the thickness of the cornea is a surrogate for greater susceptibility of the eye to damage. Reference: AJO, May, 2006 Page 5

6 The general clinical evaluation of a new glaucoma suspect / patient This clinical evaluation builds upon a careful family history, personal medical history, current health status, and medication(s) Best corrected vision Document pupil size and reactivity Careful slit lamp biomicroscopy noting A/C depth, any iris abnormalities such as pigment dispersion, retroillumination defects, pseudo exfoliation, corneal guttata, etc. Applanation tonometry, noting time Pachymetry to determine CCT Clinical Perspective on Rebound Tonometry The advantages of rebound tonometry include portability, lack of dependence on slit lamp mounting or even an external electrical source (battery powered), no need for topical anesthetic, ease of use, suitability for use by non-medically trained personnel, and toleration by young children and non-cooperative adults. These characteristics make it quite useful in screening situations. In my practice, this is our go to instrument for children as young as 3 years, for the intellectually challenged adults, and those with blepharospasm. Reference: R. Stamper, MD, Optometry and Vision Science. January 2011 Glaucoma Work-Up (continued) Baseline gonioscopy (4-mirror preferred) looking for PAS, angle recession, angle pigmentation, and the anatomic patterns of the angle anatomy Thorough BIO to r/o any peripheral pathology Stereoscopic evaluation of the optic nerve heads (60D, 78D, or Hruby lens); glaucoma detected most often through dilated pupils Baseline static threshold visual fields Image analyzer of optic nerve head Optic disc photographic documentation Page 6

7 Breakthrough on Gonioscopic Training A most wonderful website exists to help teach superb gonioscopic anatomy and technique Please seek and study: Optic Nerve Head Evaluation Cup depth is critical - Stereopsis! Are cup walls steep or sloping? Note rim translucency and vertical elongation of the cup Is the cup concentric with the disc, or is the cup displaced? Is the neuroretinal rim thinned more at certain clock hours than others? Especially look for any accentuated erosion of the inferotemporal or superotemporal regions. Is the disc generally pink, yellowish, or pale? ISN T Helpful diagnostic observation in ONH evaluation Normal neuroretinal rim anatomy follows the ISN T rule - Inferior rim should be thickest - Superior rim is slightly less thick - Nasal rim is slightly less thick - Temporal rim should be the thinnest Most ONH s are round or slightly vertically oval ISN T rule may not hold if ONH horizontally oval Page 7

8 Optic Disc Size and Glaucoma Bergtson (25 yrs ago) Normal small discs have small cups Normal large discs have large cups. Average disc diameter 1.5 mm Disc Diameter Mean C/D Upper Limit Small mm Medium mm Large mm Implications for glaucoma diagnosis and management A high ratio may not be pathologic C/D s for large discs change by a smaller amount C/D changes caused by glaucoma occur more slowly in large discs than in small discs (baseline photos large discs especially important C/D asymmetry is not always pathological Sizing the Optic Nerve Head There is poor agreement between slit lamp ophthalmoscopy, HRT, and OCT in classifying disk size as small, average, or large. Jonas proposed that in routine practice, the clinician conduct a quick, crude estimate of whether the disk in question is average-sized (medium), smaller-than-average, or larger-thanaverage. Reference: AJO, September, 2006, pp ONH Hemorrhage Highly specific for glaucoma RNFL/disc hemorrhages tend to be most common ST or IT. Prevalence higher in NTG (20-35%) Disc hemorrhages may precede a VF defect or a change in nerve head Common, but often missed, sign in glaucoma patients Associated with aspirin use and diabetes (Ophthalmology 09/04) Among glaucomatous eyes receiving treatment, those with a larger baseline VF defects and older age had a faster rate of VF loss after a DH developed. There is no association between CCT and the later development of DH. Recurrence of DH during follow-up was not associated with a fast rate of VF loss in this study. (Ophthalmology, January 2010) Page 8

9 Glaucoma - Visual Fields Program Strategies Perspectives on Perimetry Visual Field Interpretation Foundational guidelines Catch trials Grey scale Total and Pattern deviation Glaucoma hemifield test Global indices Summary Plaquenil Visual Field Testing SITA-Standard vs SITA-Fast Detecting VF progression is far from straightforward, with significant potential for detecting false change or failing to defect definite change. Because variability differences between the two tests were low at near-normal thresholds, the shorter test times associated with SITA-Fast may be preferable in glaucoma suspects or patients with early VF loss. Bottom Line: Either test works equally well. Reference: JAMA-Oph. January 2015 Debunking Myths Once thought rare, optic disc hemorrhages occur in most glaucoma patients. It has been proposed that IOP fluctuations represent a key risk factor for glaucoma progression, however, there is no clear evidence to support this concept. Another myth is that selective perimetric testing (such as SWAP or FTD) can detect VF loss before standard white-on-white perimetry. Reference: International Glaucoma Review of the World Glaucoma Association, Vol. 10, 2008 Page 9

10 Regarding Visual Field Changes Within patient variability in the VF test is a wellknown phenomenon. In 3 major trials of glaucoma and ocular hypertensive treatment, 3 consecutive VF tests were required to confirm a defined change in VF. If there is any doubt, especially if the VF defect does not correlate to your studious observation, always repeat the VF test. This is usually done in 1-3 months, depending upon the doctor s discretion. AJO, July 2014 Ultrasummary A combined cerebral assessment of: Pattern Deviation probability plots as compared to Total Deviation probability plots Pattern Standard Deviation probability values These probability plots give the greatest VF data guidance to the functional status of the patient s optic nerves Remember: ALWAYS CORRELATE THE CLINICAL FINDINGS WITH THE VISUAL FIELD STUDIES! Optic Nerve Head Image Analyzers GDX-VCC, OCT-3, HRT, RTA, etc. Can be helpful in early diagnosis Limited value in advanced glaucoma Excellent for detection of progression A COMPONENT of the glaucoma evaluation Not a litmus test for glaucoma Page 10

11 Nerve Fiber Layer Analyzers in Perspective These so-called objective nerve fiber layer scanning devices are only relatively objective compared to highly subjective perimetry. Looking at this next series of GDx scans very nicely demonstrates this clinical truth. Imaging vs VF to Assess Glaucoma Evidence indicates that RNFL and optic disc assessment by imaging technologies may not provide adequate sensitivity to follow-up patients who manifest severe glaucomatous change. In this situation, visual field testing losses are still the best method to quantify the effect of the disease and monitor its progression. More succinctly: There is an inverse relationship between disease severity and the ability to detect change with imaging devices. Reference: Archives of Ophthalmology, September 2012 Treatment Goals For POAG Establish a target IOP below which optic nerve damage is unlikely to occur Maintain an IOP at or below this target level with appropriate therapy Monitor VF's and ONH appearance to refine the adequacy of the target IOP Optimally balance the benefits of therapy with any side effects Educate and engage patients in the management of their disease Page 11

12 When to Treat? Patients with normal optic disc and visual field could tolerate an IOP of 30 mmhg for many years without need of treatment. What it comes down to is... treat young patients who are in the high-risk group, and it is worth watching the elderly in a low-risk group. The problem remains what to do for those in the middle. Reference: A Sommer / Johns Hopkins Univ. Ophthalmology Times. January Melton-Thomas: All glaucoma doctors struggle with the decision of whom to treat, and when. Remember: medical care is an art, and equally well-trained doctors commonly differ in clinical decision-making. Factors Regarding Treatment Initiation Use of a risk calculator, and lack of glaucoma specialty training were associated with physicians being more likely to treat ocular hypertension 2 / 58 glaucoma specialists and 4 / 118 ophthalmologists reported treating all patients with an IOP >21 mmhg Most critical factors: IOP, C/D ratio, and CCT (both groups) Rational estimation of risk of conversion to OAG is essential for proper clinical decision-making Treatment by default or faulty decision-making remains a healthcare crisis in glaucoma patient care management Reference: AJO, October, 2011 Target Pressure: Use and Abuse Despite recent breakthroughs in our knowledge of risk of progression, we still are making educated guesses. At all but the highest pressures, not all patients will progress. Some patients may have non-pressure dependent optic neuropathies that are beyond our current understanding and treatment capabilities. Around half of patients with normal tension glaucoma will not progress even without treatment. Reference: Werner M. Ophthalmology Web. March 12, Page 12

13 Glaucoma Follow-Up Most controlled glaucoma patients are seen every 3 to 4 months for monitoring of the IOP and ONH status Visual Fields and/or a scan are done as frequently as necessary, and at least once yearly A dilated stereoscopic view of the optic nerve should be performed at least yearly, however, a quick look should be done at each visit. If control is felt inadequate, more aggressive follow-up is in order until adequate control of the patient is achieved Glaucoma Treatment Options Prostaglandin Analogs Beta-Adrenergic Blockers Prostaglandin / Beta-Blocker combinations Adrenergic Agonists Adrenergic Agonist / Beta-Blocker combination Carbonic Anhydrase Inhibitors (CAI s) CAI / Beta-Blocker combination Pilocarpine derivatives Epinephrine derivatives Laser Trabeculoplasty Surgical Trabeculoplasty Marijuana? Marijuana For Glaucoma - NOT The American Academy of Ophthalmology does not recommend marijuana for the treatment of glaucoma No scientific evidence is found that marijuana is an effective long-term treatment for glaucoma, particularly when compared to the wide variety of prescription medication and surgical treatments available Initial studies in the 1970 s reported that smoking marijuana did lower IOP for 3 to 4 hours but there is no evidence to date that proves it alters the long-term course of the disease Marijuana lowers blood pressure throughout the body, resulting in the potential to lower the blood flow to the optic nerve which can lead to vision loss No research exists to date that demonstrates that marijuana can deliver a level of efficacy compared to medicated eye drops or surgery. Reference: American Academy of Ophthalmology Reiterates Position That Marijuana Is Not Proven Treatment for Glaucoma. July 3, 2014 Page 13

14 Prostaglandin Receptor Agonists Latanoprost (Xalatan and generic) 0.005% Travoprost (Travatan Z and generic) 0.004% Bimatoprost (Lumigan) 0.01%, and generic 0.03% Tafluprost (Zioptan) % Prostaglandins Pharmacology: prostaglandin analog Mechanism: enhances uveoscleral outflow Dosage: once daily, usually in the evening Effectiveness: 30% reduction in IOP Potential side effects: Iris darkening, hypertrichosis, CME, iritis, HSK activation, migraine headache, inflammatory bowel disease (IBS) Xalatan 0.005% by Pfizer (and generic), Travatan (Z) 0.004% by Alcon, Lumigan 0.01% by Allergan, and Zioptan % by Merck Tafluprost Ophthalmic Solution FDA approved February 2012 First preservative-free prostaglandin Reduces IOP similarly to the other prostaglandins Dosage: once daily, preferably in the evening Most common side-effect conjunctival hyperemia Available in unit dose containers Marketed as Zioptan % ophthalmic solution by Merck / Akorn (Health Care Providers Request Samples) Page 14

15 The Efficacy and Safety of Once-Daily Versus Once-Weekly Latanoprost Treatment for Increased Intraocular Pressure Latanoprost treatment for ocular hypertension or early glaucoma once-weekly was as effective as once-daily after 3 months of follow-up, and there were fewer, and only minor, side effects with this protocol. Reference: S. Kurtz, MD and G. Shemesh, MD. Journal of Ocular Pharmacology and Therapeutics, November 2004 Lumigan-Induced Periocular Skin Changes Time to onset: 3 to 15 months Time to resolution following discontinuation: 3-9 months Reversibility of prostaglandin-induced periocular hyperpigmentation is in contrast to the irreversible or very slow reversible nature of prostaglandin-induced iris hyperpigmentation. Mechanistic explanation: dermal melanocytes are continent relative to melanin granules, whereas iris melanocytes are incontinent Switching to another prostaglandin may or may not evoke a lessened expression Reference: Ophthalmology, November 2006 Prostaglandin-Associated Periorbitopathy A more newly recognized side effect of prostaglandin therapy Periorbital fat atrophy gives rise to marked deepening of the superior lid sulcus, which can result in ptosis and enophthalmos Beyond the obvious cosmetic concerns, such altered lid/orbital anatomy can make applanation tonometry quite challenging Probably expressed more in middle-aged patients than in older patients Tends to be at least partially reversible over a few months. Advanced Ocular Care. July-August Page 15

16 Nitric Oxide (NO)-Donating Glaucoma Medication Latanoprostene bunod, first NO-donating PGF2a analog for potential treatment of glaucoma and ocular hypertension Phase 3 studies in US and Japan Has shown superiority to latanoprost in clinical trials Dual mechanism of action affecting conventional outflow and uveoscleral outflow Worldwide licensing agreement with Bausch & Lomb and Nicox Topical Beta-Andrenergic Receptor-Blocking Drugs * Timolol (Timoptic and Timoptic XE /Betimol) 0.25% and 0.5%; (Istalol) 0.5% * Levobunolol (Betagan) 0.25% and 0.5% Metipranolol (Optipranolol) 0.3% Carteolol (Ocupress) 1.0% Betaxolol (Betoptic-S 0.25%) * Have longer half-lives than other beta-blockers Topical Beta-Blockers Decrease aqueous production Reduces IOP.25%; no response 15% R/O asthma Recommend monocular trial with lowest concentration once daily Possible diminished effect if used with systemic beta-blockers No advantage to gel-forming solution Page 16

17 Beta Blockers and Chronic Heart failure Unless there is a specific contraindication, all patients with stable heart failure with reduced ejection fraction should receive a beta blocker in addition to an ACE inhibitor A recent observational cohort study in patients with heart failure with preserved ejection fraction found that use of a beta blocker was associated with a rate of all-cause mortality. Reference: The Medical Letter, Vol. 57 (1460). January 19, 2015 Adrenergic Receptor Agonists Brimonidine Apraclonidine Dipivefrin Epinephrine Brimonidine Tartrate Alpha-2 adrenergic agonist; tid FDA approval Acts by reducing aqueous production with some enhancement of uveoscleral outflow Reduces IOP similar to timolol 0.5% bid Side effects: fatigue and dry mouth most common side effects; uveitis reported; may reduce systolic BP 10 mmhg Less tachyphylaxis or allergy development than the other alpha-2 agonists Neuro-protective potential unknown Alphagan (0.2%) by Allergan, and generic Alphagan P (0.15%) by Allergan and generic, and Alphagan P (0.1%) by Allergan Page 17

18 Neuroprotection Despite the long list of neuroprotective candidates, clinicians lack a proven neuroprotective agent with which to manage glaucoma. Glaucoma Today. November/December Combigan Ophthalmic Solution Combination of 0.2% brimonidine and 0.5% timolol With ANY combination drug, always try one of the component drugs as monotherapy, and only use the combination product if or when the monotherapy drug comes close, but does not achieve target IOP Remember, most all drugs have a non-response rate of about 10%, so there is a 20% chance that one of the components of any combination drug is not performing The IOP lowering effect, when administered twice daily, has been found to be slightly less than that seen with the concomitant use of 0.5% timolol bid and 0.2% brimonidine tid. Ocular Surgery News, Nov. 15, 2007 Combigan Ophthalmic Solution If using timolol and not quite to target IOP, then trying Combigan would be rational If using brimonidine and not quite to target IOP, then rational to try Combigan If a prostaglandin does not reach target IOP, then try a once daily beta-blocker like timolol. If this two drop therapy approaches, but does not achieve target IOP, then trying a combination drug is rational Marketed as Combigan by Allergan in 5, 10, and 15 ml opaque white bottles, preserved with BAK.005% Page 18

19 Topical CAI s Dorzolamide 2% sol. and Brinzolamide 1% susp. Mechanism: decreases aqueous humor secretion Reduces IOP approximately 15% FDA dosage: tid, practical dosage bid Contraindications: Allergy to sulfa and/or history of blood dyscrasias Side effects: minimal; some burning, bitter taste, rare allergic reaction Most all patients controlled with oral acetazolamide were successfully controlled with a topical CAI Azopt 1% susp-alcon; Trusopt 2% sol-merck Dorzolamide Hydrochloride 2% Timolol Maleate.5% (Cosopt) Both components decrease IOP by reducing aqueous humor secretion Because of the CAI, must be used bid, which results in excessive beta-blocker therapy Contraindications: patients with asthma, heart disease, or allergy to sulfa drugs Ocular side effects: burning/stinging and perversion in taste Marketed as Cosopt by Merck bottle and PF and generic Simbrinza (brinzolamide 1.0% and brimonidine 0.2% combination) Combination drug without a beta blocker where both ingredient drugs are dosed the same (b.i.d.) Combines 1% brinzolamide (Azopt ophthalmic suspension) with 0.2% brimonidine Offers a wide range of treatment possibilities due to its strong efficacy and ability to decrease elevated IOP by 21-35% Marketed by Alcon under the brand name Simbrinza suspension Page 19

20 Contemporary Glaucoma Medication Flow 1st Tier: Prostaglandin q d or timolol q am 2nd Tier: Topical CAI or brimonidine 3rd Tier: 4th Tier: Combigan, Cosopt, Simbrinza, or Prostaglandin/beta-blocker combination Pilocarpine Oral CAI (preferably methazolamide) ALT vs SLT Selective laser trabeculoplasty almost certainly led to a marked increase in the use of trabeculoplasty in the first years of the 21st Century. However, careful, longitudinal trials suggest that it is no better than the argon laser. Ophthalmology, July 2015 Help for Non-Adherent Patients Demonstrate to patients exactly how to instill an eyedrop! Inability to competently instill eyedrops is a key reason for non-adherence Forgetfulness is a second major reason for nonadherence Brainstorm with patients Set a timer if necessary Skepticism about glaucoma causing vision loss, or skepticism about glaucoma medicines mitigating that risk may be yet another reason for non-adherence Doctor-patient communication!! Ophthalmology, July OVS, May Page 20

21 Alert on Topiramate (Topamax) Approved for seizure disorders Unapproved: Migraine HA, weight loss, depression, bipolar disorder Mechanism of action is unknown Because of a topiramate-associated risk for oral clefts, the FDA has now designated topiramate as a pregnancy category D drug. Numerous reported cases of acute, bilateral, simultaneous angle-closure glaucoma Onset usually within first 2 weeks of therapy Most common presenting symptom: blurred vision Exact mechanism of increased IOP is unknown Tx: Stat consult with prescribing physician to begin to reduce topiramate dosage; then aqueous suppressants, oral CAI, cycloplegia (retracts ciliary body) - no miotics IOP normalizes in 1-4 days, no laser treatment indicated Topiramate (Topamax) and Vision Uses: anticonvulsant, migraine prevention, bipolar disorder, obesity, OCD, IIH, neuropathic pain, essential tremor, post-herpetic neuralgia, and other esoteric uses. Topiramate is a sulfa derivative (like CAI s) Idiosyncratic ciliochoroidal effusion is the most common ocular side effect, and most always results in a myopic shift with or without increased IOP This rare event usually occurs within 2 weeks of initiation (or doubling) of dosing First described in % are female Tx: D/C the medicine; use (PRN) beta-blocker, brimonidine, or, in refractory case, oral prednisone or IV methylprednisolone. Also, instill cycloplegic agent, and do not use pilocarpine. Reference: Clinical Ophthalmology. January 2012 Qsymia: Potential for Decreased Weight and Increased Risk of Angle Closure New drug for weight loss patients who are overweight or obese and also have at least one weight-related condition such as high blood pressure, diabetes or high cholesterol. Combination of two older drugs Phentermine (appetite suppressant) Topiramate (feeling of satiation) Lesser dosages of each component drug tend to act synergistically On average, patients lose about 10% of their body weight over one year Marketed by Vivus Inc (Mountain View, California) FDA approval July 17, 2012 Page 21