GlaucomaIN REVIEW 360 Annual Gala New Horizons Forum CME Symposium

The Catalyst Award

New Horizons in Glaucoma Drug Delivery Shaffer-Hetherington-Hoskins Lecture

PUBLISHED AS A SUPPLEMENT TO ADD SIMBRINZA® Suspension to a PGA for Even Lower IOP1*

INDICATIONS AND USAGE SIMBRINZA® (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2% is a fixed combination indicated in the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Dosage and Administration The recommended dose is one drop of SIMBRINZA® Suspension in the Up to 5.6† mm Hg affected eye(s) three times daily. Shake well before use. SIMBRINZA® Suspension may be used concomitantly with other topical ophthalmic drug 7.1 mm Hg additional mean products to lower intraocular pressure. If more than one topical ophthalmic additional IOP diurnal IOP drug is being used, the drugs should be administered at least five (5) minutes apart. reduction from lowering observed baseline when from baseline when IMPORTANT SAFETY INFORMATION added to a PGA1 added to a PGA1 Contraindications SIMBRINZA® Suspension is contraindicated in patients who are hypersensitive to any component of this product and neonates and infants under the age of 2 years. Warnings and Precautions Sulfonamide Hypersensitivity Reactions—Brinzolamide is a sulfonamide, and although administered topically, is absorbed sys. temically Sulfonamide attributable adverse reactions may occur. Fatalities have occurred due to severe reactions to sulfonamides. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation. IOP Daily Time Points (mm Hg)‡ Corneal Endothelium—There is an increased potential for developing Treatment Arm 8 AM 10 AM 3 PM 5 PM corneal edema in patients with low endothelial cell counts. ® Baseline§ 24.5 22.9 21.7 21.6 ® PGA + SIMBRINZA Severe Hepatic or Renal Impairment (CrCl <30 mL/min)—SIMBRINZA (N=88) Suspension has not been specifically studied in these patients and is Suspension Week 6 19.4 15.8 17.2 15.6 not recommended. PGA + Vehicle Baseline§ 24.3 22.6 21.3 21.2 Contact Lens Wear—The preservative in SIMBRINZA® Suspension, (N=94) Week 6 21.5 20.3 20.0 20.1 benzalkonium chloride, may be absorbed by soft contact lenses. Contact ‡D ifferences (mm Hg) and P-values at Week 6 time points between treatment groups were: -2.14, lenses should be removed during instillation of SIMBRINZA® Suspension P=0.0002; -4.56, P<0.0001; - 2.84, P<0.0001; -4.42, P<0.0001. but may be reinserted 15 minutes after instillation. §Baseline (PGA Monotherapy) Severe Cardiovascular Disease—Brimonidine tartrate, a component of SIMBRINZA® Suspension, had a less than 5% mean decrease in blood Mean Diurnal IOP (mm Hg)|| pressure 2 hours after dosing in clinical studies; caution should be Treatment Arm exercised in treating patients with severe cardiovascular disease. Baseline¶ 22.7 PGA + SIMBRINZA® Suspension (N=88) Adverse Reactions Week 6 17.1 SIMBRINZA® Suspension Baseline¶ 22.4 PGA + Vehicle (N=94) In two clinical trials of 3 months’ duration with SIMBRINZA® Suspension, Week 6 20.5 the most frequent reactions associated with its use occurring in approximately ||Differences (mm Hg) and P-values at Week 6 between treatment groups were -3.44, P<0.0001. 3-5% of patients in descending order of incidence included: blurred vision, ¶Baseline (PGA Monotherapy) eye irritation, dysgeusia (bad taste), dry mouth, and eye allergy. Adverse reaction rates with SIMBRINZA® Suspension were comparable to those of Study Design: A prospective, randomized, multicenter, double-blind, parallel-group study of 189 patients with open-angle glaucoma and/or ocular hypertension receiving the individual components. Treatment discontinuation, mainly due to adverse treatment with a PGA. PGA treatment consisted of either travoprost, latanoprost, reactions, was reported in 11% of SIMBRINZA® Suspension patients. or bimatoprost. Patients in the study were randomized to adjunctive treatment with SIMBRINZA® Suspension (N=88) or vehicle (N=94). The primary efficacy endpoint was Prescribe SIMBRINZA® Suspension as adjunctive mean diurnal IOP (IOP averaged over all daily time points) at Week 6 between treatment groups. Key secondary endpoints included IOP at Week 6 for each daily time point therapy to a PGA for appropriate patients (8 AM, 10 AM, 3 PM, and 5 PM) and mean diurnal IOP change from baseline to Week 6 between treatment groups.1 ® SIMBRINZA Suspension should be taken at least five * PGA study-group treatment consisted of either travoprost, latanoprost, or bimatoprost. (5) minutes apart from other topical ophthalmic drugs †95% Confidence Interval: -6.23 to -5.06. Learn more at myalcon.com/simbrinza

For additional information about SIMBRINZA® Suspension, please see Brief Summary of full Prescribing Information on adjacent page. Reference: 1. Data on file, 2014

© 2014 Novartis 10/14 SMB14121JAD BRIEF SUMMARY OF PRESCRIBING INFORMATION ritis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, potential benefit justifies the potential risk to the fetus. INDICATIONS AND USAGE ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular Nursing Mothers - In a study of brinzolamide in lactating rats, decreas- SIMBRINZA® (brinzolamide/brimonidine tartrate ophthalmic suspension) pruritus and rhinitis. es in body weight gain in offspring at an oral dose of 15 mg/kg/day (150 1%/0.2% is a fixed combination of a carbonic anhydrase inhibitor and The following adverse reactions were reported at an incidence below times the recommended human ophthalmic dose) were observed during an alpha 2 adrenergic receptor agonist indicated for the reduction of el- 1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, dip- lactation. No other effects were observed. However, following oral evated intraocular pressure (IOP) in patients with open-angle glaucoma lopia, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, administration of 14C-brinzolamide to lactating rats, radioactivity was or ocular hypertension. keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or found in milk at concentrations below those in the blood and plasma. In DOSAGE AND ADMINISTRATION sticky sensation, nausea, pharyngitis, tearing and urticaria. animal studies, brimonidine was excreted in breast milk. The recommended dose is one drop of SIMBRINZA® Suspension in the Brimonidine Tartrate 0.2% - In clinical studies of brimonidine tartrate It is not known whether brinzolamide and brimonidine tartrate are affected eye(s) three times daily. Shake well before use. SIMBRINZA® 0.2%, adverse reactions occurring in approximately 10 to 30% of the excreted in human milk following topical ocular administration. Because Suspension may be used concomitantly with other topical ophthalmic subjects, in descending order of incidence, included oral dryness, many drugs are excreted in human milk and because of the potential for drug products to lower intraocular pressure. ocular hyperemia, burning and stinging, headache, blurring, foreign serious adverse reactions in nursing infants from SIMBRINZA® (brinzol- If more than one topical ophthalmic drug is being used, the drugs body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic amide/brimonidine tartrate ophthalmic suspension) 1%/0.2%, a decision should be administered at least five (5) minutes apart. reactions, and ocular pruritus. should be made whether to discontinue nursing or to discontinue the DOSAGE FORMS AND STRENGTHS Reactions occurring in approximately 3 to 9% of the subjects, in drug, taking into account the importance of the drug to the mother. Suspension containing 10 mg/mL brinzolamide and 2 mg/mL brimo- descending order included corneal staining/erosion, photophobia, eyelid Pediatric Use - The individual component, brinzolamide, has been nidine tartrate. erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory studied in pediatric glaucoma patients 4 weeks to 5 years of age. CONTRAINDICATIONS symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, The individual component, brimonidine tartrate, has been studied ® ocular irritation, gastrointestinal symptoms, asthenia, conjunctival in pediatric patients 2 to 7 years old. Somnolence (50-83%) and Hypersensitivity - SIMBRINZA Suspension is contraindicated in ® patients who are hypersensitive to any component of this product. blanching, abnormal vision and muscular pain. decreased alertness was seen in patients 2 to 6 years old. SIMBRINZA Suspension is contraindicated in children under the age of 2 years [see ® The following adverse reactions were reported in less than 3% of Neonates and Infants (under the age of 2 years) - SIMBRINZA Contraindications]. Suspension is contraindicated in neonates and infants (under the age of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, 2 years) see Use in Specific Populations insomnia, conjunctival discharge, depression, hypertension, anxiety, Geriatric Use - No overall differences in safety or effectiveness have palpitations/arrhythmias, nasal dryness and syncope. been observed between elderly and adult patients. WARNINGS AND PRECAUTIONS Sulfonamide Hypersensitivity Reactions - SIMBRINZA® Suspension Postmarketing Experience - The following reactions have been OVERDOSAGE contains brinzolamide, a sulfonamide, and although administered identified during postmarketing use of brimonidine tartrate ophthalmic Although no human data are available, electrolyte imbalance, devel- topically is absorbed systemically. Therefore, the same types of adverse solutions in clinical practice. Because they are reported voluntarily from opment of an acidotic state, and possible nervous system effects may reactions that are attributable to sulfonamides may occur with topical a population of unknown size, estimates of frequency cannot be made. occur following an oral overdose of brinzolamide. Serum electrolyte administration of SIMBRINZA® Suspension. Fatalities have occurred due The reactions, which have been chosen for inclusion due to either levels (particularly potassium) and blood pH levels should be monitored. to severe reactions to sulfonamides including Stevens-Johnson syn- their seriousness, frequency of reporting, possible causal connection Very limited information exists on accidental ingestion of brimonidine in drome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulo- to brimonidine tartrate ophthalmic solutions, or a combination of these adults; the only adverse event reported to date has been hypotension. cytosis, aplastic anemia, and other blood dyscrasias. Sensitization may factors, include: bradycardia, hypersensitivity, iritis, keratoconjuncti- Symptoms of brimonidine overdose have been reported in neonates, recur when a sulfonamide is re-administered irrespective of the route vitis sicca, miosis, nausea, skin reactions (including erythema, eyelid infants, and children receiving brimonidine as part of medical treatment of administration. If signs of serious reactions or hypersensitivity occur, pruritus, rash, and vasodilation), and tachycardia. of congenital glaucoma or by accidental oral ingestion. Treatment of an discontinue the use of this preparation [see Patient Counseling Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, oral overdose includes supportive and symptomatic therapy; a patent Information] lethargy, pallor, respiratory depression, and somnolence have been airway should be maintained. Corneal Endothelium - Carbonic anhydrase activity has been observed reported in infants receiving brimonidine tartrate ophthalmic solutions PATIENT COUNSELING INFORMATION in both the cytoplasm and around the plasma membranes of the corneal [see Contraindications]. Sulfonamide Reactions - Advise patients that if serious or unusual oc- endothelium. There is an increased potential for developing corneal ede- DRUG INTERACTIONS ular or systemic reactions or signs of hypersensitivity occur, they should ma in patients with low endothelial cell counts. Caution should be used Oral Carbonic Anhydrase Inhibitors - There is a potential for an discontinue the use of the product and consult their physician. when prescribing SIMBRINZA® Suspension to this group of patients. additive effect on the known systemic effects of carbonic anhydrase Temporary Blurred Vision - Vision may be temporarily blurred follow- ® inhibition in patients receiving an oral carbonic anhydrase inhibitor and ing dosing with SIMBRINZA® Suspension. Care should be exercised in Severe Renal Impairment - SIMBRINZA Suspension has not ® been specifically studied in patients with severe renal impairment (CrCl brinzolamide ophthalmic suspension 1%, a component of SIMBRINZA operating machinery or driving a motor vehicle. Suspension. The concomitant administration of SIMBRINZA® Suspension < 30 mL/min). Since brinzolamide and its metabolite are excreted Effect on Ability to Drive and Use Machinery - As with other drugs ® and oral carbonic anhydrase inhibitors is not recommended. predominantly by the kidney, SIMBRINZA Suspension is in this class, SIMBRINZA® Suspension may cause fatigue and/or not recommended in such patients. High-Dose Salicylate Therapy - Carbonic anhydrase inhibitors drowsiness in some patients. Caution patients who engage in hazardous Acute Angle-Closure Glaucoma - The management of patients with may produce acid-base and electrolyte alterations. These alterations activities of the potential for a decrease in mental alertness. were not reported in the clinical trials with brinzolamide ophthalmic sus- acute angle-closure glaucoma requires therapeutic interventions in Avoiding Contamination of the Product - Instruct patients that ocular ® pension 1%. However, in patients treated with oral carbonic anhydrase addition to ocular hypotensive agents. SIMBRINZA Suspension has not solutions, if handled improperly or if the tip of the dispensing container been studied in patients with acute angle-closure glaucoma. inhibitors, rare instances of acid-base alterations have occurred with high-dose salicylate therapy. Therefore, the potential for such drug contacts the eye or surrounding structures, can become contaminat- ® Contact Lens Wear - The preservative in SIMBRINZA Suspension, interactions should be considered in patients receiving SIMBRINZA® ed by common bacteria known to cause ocular infections. Serious benzalkonium chloride, may be absorbed by soft contact lenses. Contact Suspension. damage to the eye and subsequent loss of vision may result from using lenses should be removed during instillation of SIMBRINZA® Suspension contaminated solutions [see Warnings and Precautions ]. Always CNS Depressants - Although specific drug interaction studies have replace the cap after using. If solution changes color or becomes cloudy, but may be reinserted 15 minutes after instillation [see Patient ® Counseling Information]. not been conducted with SIMBRINZA Suspension, the possibility of an do not use. Do not use the product after the expiration date marked additive or potentiating effect with CNS depressants (alcohol, opiates, on the bottle. Severe Cardiovascular Disease - Brimonidine tartrate, a component of barbiturates, sedatives, or anesthetics) should be considered. SIMBRINZA® Suspension, has a less than 5% mean decrease in blood Intercurrent Ocular Conditions - Advise patients that if they have Antihypertensives/Cardiac Glycosides - Because brimonidine tartrate, ocular surgery or develop an intercurrent ocular condition (e.g., trauma pressure 2 hours after dosing in clinical studies; caution should be ® exercised in treating patients with severe cardiovascular disease. a component of SIMBRINZA Suspension, may reduce blood pressure, or infection), they should immediately seek their physician’s advice caution in using drugs such as antihypertensives and/or cardiac concerning the continued use of the present multidose container. Severe Hepatic Impairment - Because brimonidine tartrate, a compo- glycosides with SIMBRINZA® Suspension is advised. nent of SIMBRINZA® Suspension, has not been studied in patients with Concomitant Topical Ocular Therapy - If more than one topical hepatic impairment, caution should be exercised in such patients. Tricyclic Antidepressants - Tricyclic antidepressants have been report- ophthalmic drug is being used, the drugs should be administered at ed to blunt the hypotensive effect of systemic clonidine. It is not known least five minutes apart. Potentiation of Vascular Insufficiency - Brimonidine tartrate, a whether the concurrent use of these agents with SIMBRINZA® Suspen- ® ® component of SIMBRINZA Suspension, may potentiate syndromes sion in humans can lead to resulting interference with the IOP lowering Contact Lens Wear - The preservative in SIMBRINZA Suspension, associated with vascular insufficiency. SIMBRINZA® Suspension should benzalkonium chloride, may be absorbed by soft contact lenses. Contact effect. Caution is advised in patients taking tricyclic antidepressants ® be used with caution in patients with depression, cerebral or coronary which can affect the metabolism and uptake of circulating amines. lenses should be removed during instillation of SIMBRINZA Suspen- insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or sion, but may be reinserted 15 minutes after instillation. thromboangiitis obliterans. Monoamine Oxidase Inhibitors - Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine tartrate ©2013 Novartis Contamination of Topical Ophthalmic Products After Use - There and potentially result in an increased systemic side-effect such as U.S. Patent No: have been reports of bacterial keratitis associated with the use of mul- hypotension. Caution is advised in patients taking MAO inhibitors which 6,316,441 tiple-dose containers of topical ophthalmic products. These containers can affect the metabolism and uptake of circulating amines. ALCON LABORATORIES, INC. have been inadvertently contaminated by patients who, in most cases, USE IN SPECIFIC POPULATIONS Fort Worth, Texas 76134 USA had a concurrent corneal disease or a disruption of the ocular epithelial 1-800-757-9195 surface [see Patient Counseling Information]. Pregnancy - Pregnancy Category C: Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/ [email protected] ADVERSE REACTIONS day (20, 60, and 120 times the recommended human ophthalmic dose) Clinical Studies Experience - Because clinical studies are conducted produced maternal toxicity at 6 mg/kg/day and a significant increase under widely varying conditions, adverse reaction rates observed in the in the number of fetal variations, such as accessory skull bones, which clinical studies of a drug cannot be directly compared to the rates in the was only slightly higher than the historic value at 1 and 6 mg/kg. In rats, clinical studies of another drug and may not reflect the rates observed statistically decreased body weights of fetuses from dams receiving oral in practice. doses of 18 mg/kg/day (180 times the recommended human ophthal- SIMBRINZA® Suspension - In two clinical trials of 3 months duration mic dose) during gestation were proportional to the reduced maternal 435 patients were treated with SIMBRINZA® Suspension, and 915 were weight gain, with no statistically significant effects on organ or tissue treated with the two individual components. The most frequently report- development. Increases in unossified sternebrae, reduced ossification ed adverse reactions in patients treated with SIMBRINZA® Suspension of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were occurring in approximately 3 to 5% of patients in descending order of not statistically significant. No treatment-related malformations were incidence were blurred vision, eye irritation, dysgeusia (bad taste), dry seen. Following oral administration of 14C-brinzolamide to pregnant rats, mouth, and eye allergy. Rates of adverse reactions reported with the radioactivity was found to cross the placenta and was present in the individual components were comparable. Treatment discontinuation, fetal tissues and blood. ® mainly due to adverse reactions, was reported in 11% of SIMBRINZA Developmental toxicity studies performed in rats with oral doses of 0.66 Suspension patients. mg brimonidine base/kg revealed no evidence of harm to the fetus. Dos- Other adverse reactions that have been reported with the individual ing at this level resulted in a plasma drug concentration approximately components during clinical trials are listed below. 100 times higher than that seen in humans at the recommended human Brinzolamide 1% - In clinical studies of brinzolamide ophthalmic ophthalmic dose. In animal studies, brimonidine crossed the placenta suspension 1%, the most frequently reported adverse reactions reported and entered into the fetal circulation to a limited extent. in 5 to 10% of patients were blurred vision and bitter, sour or unusual There are no adequate and well-controlled studies in pregnant women. taste. Adverse reactions occurring in 1 to 5% of patients were blepha- SIMBRINZA® Suspension should be used during pregnancy only if the © 2014 Novartis 10/14 SMB14121JAD GUnitingLAU research,CO industry,MA philanthropy 360 Innovation, science take center stage–striving for one goal: A cure!

cientific advancement and The Visionary Award was shared by innovation shared the spot- Nobel Laureate Shinya Yamanaka, MD, light at the 4th Annual Glau- PhD, and Masayo Takahashi, MD, PhD, Scoma 360 meeting, presented who was 2014 Stem Cell Person of the by the Glaucoma Research Founda- Year. Both researchers were honored tion (GRF). The meeting brought to- for their work to improve global health- gether leaders in research, industry, care and treating blinding eye disease. ophthalmology, and philanthropy with Paul P. Lee, MD, presented both the one goal–to find a cure for glaucoma. Drs. Henry and Frederick Sutro Memo- Adrienne Graves, PhD, and Andrew Iwach, MD The three-day event, co-chaired by rial Lecture and the Shaffer-Hether- were co-chairpersons and hosts for the 2015 Glaucoma 360 meeting, presented by GRF. Andrew Iwach, MD, and Adrienne ington-Hoskins Lecture at this year’s Graves, PhD, centered around the Glacuoma 360. Dr. Lee’s lectures ad- GLAUCOMA 360 Glaucoma 360 Annual Gala, the New dressed ophthalmic challenges and exclusive video Horizons Forum, and the CME Sym- opportunities and offered a different Andrew Iwach, MD, welcomes posium. Glaucoma 360 was held Feb. insight to patient care. readers to the Glaucoma 360 5-7, in San Francisco. This special report from Ophthal- coverage. http://bit.ly/1GsQMCJ The Glaucoma 360 Annual Gala fea- mology Times, “the official partner tured the presentation of the 2015 Cata- and media sponsor” for Glaucoma lyst Award and Visionary Award. 360, highlights the presentations of The Catalyst Award was presented to the meeting. Readers are encouraged Adrienne Graves, PhD, a global oph- to download the Ophthalmology Times thalmic leader who has dedicated her app and experience the Glaucoma 360 career to advancing innovative concepts meeting through the on-line exclusives, so patients could preserve their vision. videos, and podcasts. ◗ (insets) unney rish T Glaucoma 360 Annual Gala T The “Glaucoma 360 Annual Gala” raises money for GRF research and education. The gala includes a reception, auction, dinner, entertainment, and awards. For a glimpse of the Gala festivities, go to: www.ophthalmologytimes.com/gala2015 ectors / mfto(background) ; P hoto by ision V (top and bottom) unney rish T T

CATALYST AWARD WINNER Richard L. LIVE AUCTION RAISES FUNDS Auctioneer OPERATIC PERFORMANCE Italian tenor Lindstrom, MD, and Gena Harper (right) pre- Chad Carvey rallies for bids during the Live Auc- Pasquale Esposito entertained and dazzled An- sented the 2015 Catalyst Award to Adrienne L. tion at the Gala. The auction raised $210,000 nual Gala attendees with his music that focused Graves, PhD, at the Glaucoma 360 Annual Gala. with a record total over $500,000 at the event. on “operatic pop” with traditional opera. THIS PAGE: P hotos by THIS PAGE: G etty I mages /D igital V COVER:

4 GLAUCOMA 3 6 0 NEW HORIZONS FORUM EyeMDs must change to meet future opportunities, challenges

By Laird Harrison Along with demographic changes in the population as a whole are coming phthalmologists must changes in the eye-care workforce, change the way they use Dr. Lee said. He cited a report by the data in order to meet the American Academy of Ophthalmol- Omounting challenges fac- ogy finding that the United States ing their profession, said Paul P. Lee, will face a shortage of ophthalmolo- MD, JD, in the Drs. Henry and Fred- gists and a surplus of optometrists erick Sutro Memorial Lecture. in the future. “We know there are certain mega- In addition, he said, there are gen- trends out there that we have to deal erational differences in the approaches with,” said Dr. Lee, professor and that practitioners bring to their work. chairman, Department of Ophthal- The health-care system is changing mology, and director, W.K. Kellogg as well, Dr. Lee said. He outlined four Pail P. Lee, MD, cited shifting demographics, a Eye Center, University of Michigan, alternative scenarios for the future changing workforce, and the growing pressure to Ann Arbor. based on an analysis by the Robert improve health care as challenges for the future. Dr. Lee, who has written exten- Wood Johnson Foundation (RWJF). sively on glaucoma and eye-care de- On one extreme, we could move into minants of health, personalization of livery, identified multiple challenges “health if you can get it.” care, health education, prediction of for ophthalmologists: In this disorganized system of growing health states, stem cell transplants, ◗ shifting demographics, desperation, “people who have money widespread use of bio-monitoring, ◗ a changing workforce, and get really great care,” Dr. Lee said. “Peo- integration of health systems lever- ◗ pressure to improve the quality ple on the bottom are trying to figure aging big data clouds, and commu- of care in the face of costs. out what they can do to survive.” nity-centered health homes. The second possible scenario—which Aging and diverse population Dr. Lee called the “conventional path- ‘Culture of health’ An aging and growing population way”— is “slow reform, better health.” The fourth scenario laid out by the will need more eye care, he said. At In this scenario, health care is gradu- RWJF is a “culture of health” in which the same time, the population is be- ally becoming more centralized and optimal health care is delivered equi- coming more diverse. big data is starting to play a role. tably, efficiently, and economically. “The ethnic makeup of the United As an example, he cited a drive by To realize this ideal future will call States is changing, and changing very the Centers for Medicare and Med- for rapid innovation, Dr. Lee said. Al- quickly,” Dr. Lee said. “California is icaid Services to pay providers by ready the dissemination of medical already a state where there is not a quality or value of care. As part of discoveries is speeding up, he said, majority by ethnicity, and the same this initiative, it expects to pay half pointing out that it took 264 years to will soon be true of the rest of the of providers through accountable-care implement the knowledge that citrus country.” organizations and bundled payments fruits could prevent scurvy.

unney This diversity can offer an oppor- by the end of 2018. Today, it takes 15 to 17 years for a

rish T tunity to ophthalmologists who un- The third scenario is “big data, big confirmed evidence-based therapy T derstand the data about the needs of health gains.” This scenario entails a to penetrate to the marketplace, he SUTRO MEMORIAL LECTURE Page 6 P hoto by subgroups, he said. focus on prevention and social deter- See on

GLAUCOMA 3 6 0 5 NEW HORIZONS FORUM Early neuronal changes may be biomarkers for glaucoma

By Laird Harrison GLAUCOMA 360 podcast team of researchers may Listen as Andrew Hubeman, soon be able to catch glau- PhD, provides an update on the coma cases early by spotting research of the Catalyst for a Cure Research Biomarker Initiative. nerve damage, said Andrew A http://bit.ly/1R1iJ7S D. Huberman, PhD, as he provided an update on the work of the Glau- nia, San Diego. “We have called this coma Research Foundation’s Catalyst effort ‘the canary in the coal mine.’” for a Cure Biomarker Initiative at the Traditionally, clinicians have used Glaucoma 360 New Horizons Forum. such techniques as eye charts and “Our goal is to better monitor dis- computed tomography to monitor Andrew Huberman, PhD, outlines how “off” ease progression,” said Dr. Huberman, glaucoma. These approaches, how- ganglions are impacted in glaucoma models. who is assistant professor, Depart- ever, do not reveal much about retinal ment of Neurosciences, Division of ganglion cell damage, which plays “You can’t see the ganglion cells Biological Sciences, Department of a key role in the disease, Dr. Huber- because the resolution of traditional Ophthalmology, University of Califor- man said. See CATALYST FOR A CURE on Page 8

From SUTRO MEMORIAL LECTURE on Page 5 His own institution has started to use GLAUCOMA 360 geospacial information mapping. As a exclusive podcast & video said. This process can be accelerated. first step, researchers have created a Listen as Paul P. Lee, MD, To speed up this process will require map of strabismus for the United States. delivers the Drs. Henry and structural changes, Dr. Lee said. For “We can tell you which states are Frederick Sutro Memorial Lecture in its example, setting protocols that allow underdiagnosed by the Medicare sys- entirety. http:// bit.ly/1GcXOeP patients to send photographs of their tem,” he said. eyes to their ophthalmologists could help Such a map for glaucoma might determine when they need to be seen. overlay glaucoma diagnoses with a variety of risk factors, including the Home monitoring location of grocery stores and neigh- “We know that telemedicine does im- borhood crime statistics. prove access to care,” he said. “If you’re not in a safe neighbor- Another promising innovation is a de- hood, you can’t go out for a walk, Watch as Paul P. Lee, MD, vice patients can use at home to monitor so you’re not going to get your exer- outlined the challenges and their own neovascularization, he said. cise,” Dr. Lee said. opportunities facing ophthalmology “Home monitoring, if we have things Finally, he called on practitioners to as presented in his Drs. Henry and Frederick Sutro Memorial Lecture.

that work, would be very helpful for make room for “the genius in the ga- unney Dr. explained that while there are

what we do,” he said. rage.” “It’s going to take someone who rish T

challenges, there are many new T Dr. Lee praised the use of algorithms challenges the existing orthodoxy to discoveries that will help ophthalmic ◗ http://bit.ly/1cEmTUa that can predict the course of an illness. really make things better,” he said. patients. P hoto by

6 GLAUCOMA 3 6 0

NEW HORIZONS FORUM

From CATALYST FOR A CURE on Page 6 As a next step, the team is trying to GLAUCOMA 360 determine whether human patients exclusive video imaging just isn’t there yet,” he said. with glaucoma experience a change in Watch as Andrew Huberman, “We need to be able to see the cells.” the way they perceive dimming lights. PhD, explains early neuronal If they could count the cells at dif- At the same time, the researchers changes as biomarkers for glaucoma ferent points in time, ophthalmolo- have noticed that the “off” cells place in his update on the work of the gists could tell whether they were their connections within a different Glaucoma Research Foundation’s dying, he said. depth in the retina than the “on” cells. Catalyst for a Cure Biomarker Initiative. http://bit.ly/1FyfyTc In a mouse model of glaucoma, Specifically, they are located in the researchers used genetics to make same layer as the microvasculature. ganglions glow green, allowing the “We’re wondering if this is the scientists to observe them, Dr. Hu- issue,” Dr. Huberman said. “Vascu- berman said. lar cells close to these ganglion cells “We have asked this question: ‘Are may be—may be—the primary insult there any ganglion types that are im- in glaucoma.” pacted first in glaucoma?’” he posed. As for observing the ganglions them- In answer to this question, Dr. Hu- selves, the researchers are struggling berman and his team identified “off” to overcome a fundamental problem. use of adaptive optics, a technique of ganglions, which fire when lights dim. “Unfortunately or fortunately, na- correcting ocular aberrations, which In the glaucoma model in mice, these ture designed the ganglion cells to are distortions in the light wavefront cells appear to die earlier than “on” gan- be clear so that light can pass to the passing through the pupil. Adaptive glions that fire when lights brighten. back of the eye,” Dr. Huberman said. optics can greatly enhance the reso- “This is an important discovery in “So they are very difficult to image.” lution of an image. our biomarker initiative,” he said. His team has high hopes for the “That’s where we are headed, and we definitely feel this is a goal that’s online exclusive within reach,” Dr. Huberman said. GLAUCOMA 360 Success in imaging the retinal gan- New FDA guidances to benefit development The FDA wants glion cells could lead to insights into to help drug and device developers get their products approved and on the U.S. market faster and earlier. A series of new programs and other diseases besides glaucoma, such guidances appear to be working, http://bit.ly/1cNFeOv as Alzheimer’s disease, because reti- nal ganglion cells are linked to the Palliative care, support vital for patients losing vision rest of the nervous system, he added. Robert Stamper, MD, explains why it is important for ophthalmologists to He said the Catalyst for a Cure owes prepare and to support patients who lose vision while in their care. its success to a multidisciplinary ap- Then, watch as Dr. Stamper explains what physicians should do when their best efforts in treating patients fail. http://bit. proach. He works closely with Jeff ly/1Gq4XZm Goldberg, MD, PhD, professor of oph- thalmology at the University of Cali- Laser treatment mainstay for angle closure glaucoma fornia, San Diego; Vivek Srinivasan, Laser-based options for treating angle closure glaucoma include laser PhD, assistant professor of biomedical iridotomy, laser iridoplasty, and endocycloplasty. Only laser iridotomy has a defi nitive role, said Shan C. Lin, MD. http://bit.ly/1IPYFlY engineering at the University of Cali- fornia, Davis; and Alfredo Dubra, PhD, Economic profiling can affect ophthalmic practices Ruth assistant professor of ophthalmology D. Williams, MD, outlines how insurers are economic-profi ling patients by at the Medical College of Wisconsin. funneling them to providers based on cost and quality data, which may “We look forward to this stuff being not always be accurate. used in patients very soon,” he said. Watch as Dr. Williams provides more details behind economic profi ling and what effects it has on the ophthalmic practice. “We’re happy with our progress, but http://bit.ly/1LmCkfy we’re certainly not satisfied.” ◗

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By Fred Gebhart months, said CEO John Maroney, matching the typical medical visit irst-line treatment for glau- schedule for glaucoma. coma has changed little since Phase I data shows the early 20th Century. Cli- a 6.7 mm Hg reduc- nicians have more drug op- tion in IOP over 3 F months. The most fre- tions today, but topical medications quent adverse events intended to reduce IOP remain the pri- were hyperemia, mary treatment modality. Sustained- similar to or less than release drug delivery devices offer levels reported with promise to transform glaucoma care. prostaglandin drops, “At the end of the day, we will have and slightly elevated mucus. Phase II a way, or ways, to take the patient out Each panelist in the New Horizons in Drug Delivery session presented technologies that feature a sustained- or controlled-release component. showed sustained of the equation and allow the drug IOP lowering over to exert its maximum effectiveness,” topical drops and full adherence. 6 months. The company is planning a predicted Robert Fechtner, MD, direc- “The ophthalmologist can take direct phase III trial for 2016. tor of Glaucoma Division at Rutgers control of treatment and address the GrayBug New Jersey Medical School, Newark. poor adherence that is typical with eye drops,” Gillissen said. GrayBug is developing micro- and “Sustained release or controlled re- nanoparticle-controlled release vehicles lease is a very important component Envisia Therapeutics for injection. The particles are at the in- for driving effective drug delivery.” Envisia Therapeutics borrowed from jection site and remain outside the visual Dr. Fechtner co-moderated “New microelectronics to print micro- and axis, said Justin Hanes, PhD, founder and Horizons in Dr ug Deliver y” with Eliot nano-sized polymers that can be filled chief scientific officer. Drug is released with active ingredient and injected or as the particles erode at a controlled Lazar, MD, president of elCon Medi- inserted into the appropriate ocular rate and are absorbed. The company is cal. Eight companies presented four site. The company is in phase IIa on a working with glaucoma drugs for both drug delivery technologies: solid im- 6-month, biodegradable, rod-shaped for- neuroprotection and IOP-lowering. plants, punctal plugs, injectable gels, mulation of travoprost for glaucoma, said The neuroprotective agent targets and implantable pumps. Several de- Chief Scientific Officer Benjamin Yerxa, DLKinase, a key initiator of neuron death PhD. Future plans include an IND for in glaucoma. “Our particles form a mass, vices are in phase II trials and some biodegradable steroid formulations for which allows for more drug to be implant- are moving toward phase III. post-cataract inflammation and extended ed,” Hanes said. “We can package small release formulations of biologic agents. molecules and macromolecules and they DSM Biomedical Yerxa said he hoped to have human all stay wherey the are injected.” DSM Biomedical uses injectable amino data to report in 2016. acid-based polyesteramide (PEA) fibers “The drug is available 24/7 at the Mati Therapeutics containing latanoprost for glaucoma. PEA optimal concentration,” Yerxa said. “The Mati Therapeutics is nearing its first phase can be fabricated into fibers, rods, films, rod is fully biodegradable and nothing is III trial of The Evolute, a punctal plug that micro- and nano-particles and coatings, left in the eye at six months. This puts elutes latanoprost. The device has been said Mirian Gillissen, program manager treatment in the hands of the clinician, tested in nearly 700 patients across 10 for drug delivery. not the patient.” clinical trials with more than 6 months of A single fiber injected into the conjunc- treatment exposure in some patients, said tiva delivers a steady dose of latano- ForSight VISION5 Bob Butchofsky, founder and CEO. unney

prost. The drug-eluting fiber showed a 6 ForSight VISION5 is developing Helios, Punctal plug delivery gives less overall rish T T mm Hg reduction in IOP over 6 months. a flexible prostaglandin-eluting ring that drug exposure compared to drops with The IOP reduction is similar to eye drops fits beneath the eyelids. The target drug more drug actually delivered, he said. P hoto by with fewer adverse events compared to delivery and replacement cycle is six See DRUG DELIVERY on Page 12

10 GLAUCOMA 3 6 0 WHAT DO YOUR PEERS SAY ABOUT ICARE?

DR. SANJAY G. ASRANI, MD, USA

Do you find the Icare easy to use? Do you find the Icare to correlate I feel that the Icare rebound tonometer well with Goldman? is very easy to use and handle and so Yes, as we have shown in the study do my technicians. recently published in Journal of Glaucoma Feb 2011. Other studies Have you found that patients prefer have also shown a good correlation. it over other tonometry methods? Most patients prefer it because they Would you recommend the Icare do not need to get anesthetic eye to colleagues? drops and have realized that their Absolutely! The Icare rebound dry eye does not get worse after the tonometer is a great instrument. eye examination.

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By Fred Gebhart in IOP Monitoring, Diagnostics and Digital Health.” ay good-bye to periodic test- “The first place we will see this ing and say hello to data change is with our approach to IOP streams–Big Data streams. and continuous monitoring,” he said. SFrom glaucoma testing to “Over the next five years, I see the diagnostics, treatment monitoring, paradigm changing. New devices and practitioner and practice benchmark- new data will improve our under- ing and clinical research, masses of standing of the disease.” data are changing the face of glau- Start with diagnosis. Glaucoma is coma care. a major cause of irreversible blind- “The future is one in which we will ness worldwide. People lose their vi- Panel members address questions about big be reacting to streams of data,” said sion because they don’t get treated, data during the New Horizons in IOP Monitoring, Diagnostics and Digital Health session. Robert Weinreb, MD, chairman and said George Spaeth, MD, Esposito Re- distinguished professor of ophthal- search Professor at Wills Eye Hos- of people with glaucoma never get mology and director of the Shiley pital/Thomas Jefferson University, diagnosed,” Dr. Spaeth said. “We can Eye Center at the University of Cali- Philadelphia. They don’t get treated address that diagnosis gap using con- fornia, San Diego. Dr. Weinreb mod- because they don’t get diagnosed. trast sensitivity testing.” erated a session on “New Horizons “In some parts of the world, 80% See BIG DATA on Page 13

From DRUG DELIVERY on Page 10 mation, is in phase III, said Art Driscoll, “Our vehicle can be made in almost vice president of product development. any physical confi guration–gels, wafers, The latest phase II U.S. trial showed a Phase IIa results show robust, clinical- rods, fi bers–to fi t the target tissue and consistent 5 mm Hg to 6 mm Hg reduc- ly signifi cant IOP reduction at 3 months. delivery method,” DeVore said. “It can be tion in IOP over 3 months, at which point Plugs are well tolerated by patients with the plug is replaced. Trials show the loaded with almost any drug and shows no change in hyperemia, no excessive standard latanoprost adverse events, stead state distribution with both hydro- tearing, and no serious adverse events. but conjunctival hyperemia is only 7.6%, philic and hydrophobic agents.” about half the rate seen with eye drops. Euclid Systems Replenish Ocular Therapeutix Euclid Systems is developing collagen- Replenish is developing the world’s small- based vehicles. Viscous formulations Ocular Therapeutix loads its punctal plug est, refi llable, implantable pump. The pump are injected through a 30-gauge cannula with prostaglandin. The plug is dry when is inserted into the vitreous, where it both or needle and form homogenous beads inserted, then softens and expands upon measures IOP hourly and delivers daily within one minute. Films and wafers can contact with tears. The plug is in phase drug doses of 200 nL to 10 uL. The physi- be designed to degrade from a few hours IIb trials while the same system, loaded cian reads IOP data remotely and changes to six months and longer and implanted. with steroid for post-op pain and infl am- drug dosing as appropriate, reported said Collagen is already used in FDA- Sean Caffey, MD, co-founder and chairman. approved or cleared ophthalmic devices, The pump is invisible from the outside said Chief Scientifi c Offi cer Dale DeVore, GLAUCOMA 360 and holds six months of drug. The res- PhD. It can be manipulated into different

podcast unney physical forms with controlled biore- ervoir is cleaned and refi lled in the clinic using a proprietary 31-gauge needle Listen as each of the eight sporption characteristics. In vitro studies rish T T companies present their drug using gel formulation and rabbit studies system. A rabbit model shows a single delivery technologies at the New show steady state delivery of latanoprost infusion directly next to the ciliary body P hoto by Horizons Forum. http://bit.ly/1F2jNRv for 180 days. causes sustained IOP lowering. ◗

12 GLAUCOMA 3 6 0 NEW HORIZONS FORUM

From BIG DATA on Page 12 GLAUCOMA 360 adverse events, but the size of the podcast implant caused pupil distortion and other Wills researchers have developed problems. A smaller iteration appears Listen as Implanta Ophthalmic to have addressed the issues, said CEO an automated contrast sensitivity test, Products and Sensimed outline Max Ostermeier, MBA, and more detailed SPARCS, that evaluates visual resolu- their IOP-monitoring devices during data will be discussed at the World Glau- tion and acuity, motion perception, on- the New Horizons in IOP Monitoring, coma Congress 2015 in June. off changes, and defects in the visual Diagnostics and Digital Health “This device allows you to take IOP session. http://bit.ly/1R4ghgV field. The five-minute test is based on readings anytime,” added Ostermeier. “It allows the physician to monitor the pa- contrast gratings in five areas of the tient long term, and it allows the patient visual field, using a standard computer rich resources for clinical research. to monitor their own IOP, which empowers monitor to score contrast sensitivity to “IRIS is a game changer for innova- and involves them in treatment. Long- assess and localize vision loss. tion,” Dr. Park said. “We are trying to term, continuous monitoring is the way SPARCS can distinguish glaucoma, reduce undesirable variation in practice treatment will be guided and assessed.” and improve the outcomes of care.” macular degeneration, diabetic reti- Sensimed nopathy, and cataract from vision. The Once glaucoma has been identified, Sensimed has a CE-marked device, goal, Dr. Spaeth said, is to put SPARCS IOP monitoring is the next step. The Trigger sh, which uses a contact lens online for self-administration and re- current standard of care, measuring sensor to measure changes in ocular ferral for clinical evaluation as needed. IOP at office visits, is far from ideal. volume. “What if the real IOP is lower and “We see 24-hour IOP monitoring as a continuum of care,” said Sensimed CEO we are measuring peaks of pressure?” Data registry David Bailey. “The contact lens solution Continuous monitoring is also how Dr. Weinreb asked. “Or what if we are is minimally invasive screening and treat- ophthalmologists and ophthalmo- measuring troughs and the actual pres- ment management tool that is applicable logic practices will be guided and sure is much higher? Continuous IOP to a very broad population. The implant assessed. IRIS, the data registry es- monitoring would give us better infor- is a targeted solution for a select popula- tion. The two together will bene t the tablished by the American Academy mation for making clinical decisions.” entire spectrum of glaucoma treatment.” of Ophthalmology (AAO), has already Two approaches to continuous IOP Trigger sh uses a circular strain gauge recorded more than 20 million pa- monitoring are being developed, tem- to measure dimensional changes in the tient visits, representing more than porary external sensors and perma- eye. Changes are transmitted wirelessly 7 million unique patients since the nent implantable sensors. to a receiver that can be  tted to the official launch in 2014. face for sleeping or into eyeglasses for daytime use. “We anticipate the numbers are Implandata Ophthalmic Products Implandata Ophthalmic Products’ There is a strong correlation between going to rise substantially to over implantable sensor directly measures changes in ocular volume and IOP, but 100 million patient visits within the IOP, but the device has not yet been the correlation has not yet been mapped, next couple of years,” said AAO’s CEO approved for marketing. A pilot study Bailey said. The company is using a data- David Park II, MD. “That is big data. in patients undergoing cataract surgery registry, user groups, and an advisory board to better de ne the clinical utility And in today’s world, data is the key showed no narrowing of the anterior chamber and no device-related severe of ocular volume changes. ◗ currency to demonstrate patient out- comes, navigate payer systems, ease online exclusive maintenance of certification and li- GLAUCOMA 360 Drugs with new MOA race to NDA submission Physicians cense renewal, benchmark and im- have been waiting 20 years for new molecules with novel mechanisms of prove your performance, and conduct action to treat glaucoma. That drought may be over. clinical research.” Then watch as Gary Novack, PhD, president of PharmaLogic Individual practitioners and practices Development, outlines the state of glaucoma pharmaceuticals and can use IRIS to benchmark their own where the future is headed. http://bit.ly/1PusSww. performance and guide improvements. New devices add dimension for treatment Nine companies, Experience in cardiology and other spe- with four broad out ow strategies, presented their latest glaucoma cialties have shown that registries are devices and data. http://bit.ly/1Fk7ulC

GLAUCOMA 360 13 CME SYMPOSIUM Science and art combine for improved patient outcomes

By Laird Harrison The ophthalmologists ranged in accuracy from 61% to 94%. The re- ew technology can help oph- searchers concluded that common thalmologists care for their imaging devices outperform most patients if they combine clinicians. Nit with a personal touch, “The reading centers are at least as said Paul P. Lee, MD, JD, in the Shaf- good as the physicians,” Dr. Lee said. fer-Hetherington-Hoskins Lecture. “Physicians tend to underestimate “Wisdom comes from a combina- the severity of disease as compared tion, in one way of looking at the with the reading centers.” world, of combining the science that Dr. Lee also urged his audience we have with the art of medicine,” to look very closely at visual field said Dr. Lee, professor and chairman, changes. Department of Ophthalmology, and He pointed out that Early Manifest director, W.K. Kellogg Eye Center, Glaucoma Trial (EMGT) and Collab- Paul Lee, MD, said in his Shaffer-Hetherington- University of Michigan, Ann Arbor. orative Initial Glaucoma Treatment Hoskins Lecture that lessons can be learned by combining science with the art of medicine. One lesson from science that oph- Study (CIGTS) criteria both show more thalmologists can apply is that early change than Advanced Glaucoma In- GLAUCOMA 360 glaucoma entails no visual field loss. tervention Study (AGIS) criteria for podcast So ophthalmologists must assess the the same fields. Listen as Paul Lee, MD, delivers nerve and nerve fiber layer carefully. That makes sense because AGIS the 2015 Shaffer-Hetherington- In the European Optic Disc Assess- is intended for advanced glaucoma, Hoskins Lecture in its entirety. ment Trial, ophthalmologists from “so to find the change it’s got to be http://bit.ly/1PRj22D 11 European countries classified 40 a big change,” Dr. Lee said. healthy eyes and 48 glaucomatous However, he cautioned practitioners getting worse. Don’t overact and eyes with varying severity on ste- to “use one method; don’t bounce change something because today’s reoscopic slides. back and forth.” visual field is getting worse.” At the same time, changes in vi- Another way clinicians can measure GLAUCOMA 360 sual field should not govern a treat- the progression of a patient’s glau- exclusive video ment plan. Instead, ophthalmologists coma is to look at test results over a Watch as Paul Lee, MD, should study and apply Bayes’ Theo- long period. He urged the audience explains how to improve patient rem, a mathematical formula used to go back to field tests from 5, 10, outcomes by combining science and art. http://bit.ly/1PRhpBW for calculating conditional probabili- or even 15 years in the past. ties, he said. Once you find that someone’s glau- One insight from the theorem is coma is worsening, look for factors that one positive test result does not that could explain the change, Dr. prove the presence of a disease. Lee suggested. “This is a really important concept Many surprising factors can increase for all of us,” Dr. Lee said. “There pressure, including yoga positions in L indsey A nthony have to be at least two independent which the patient spends time upside SCIENCE AND ART Page 15 pieces of evidence that someone is See on P hoto by

14 GLAUCOMA 3 6 0 CME SYMPOSIUM Unraveling glaucoma genetics for potential future therapies

By Cheryl Guttman Krader ular degeneration, should be avoided until treatment or surveillance strate- enetic testing to identify gies are proven useful in prospective susceptibility for adult- randomized trials. Additionally, it onset primary open angle is important to use approved Clini- Gglaucoma (POAG) or pseu- cal Laboratory Improvement Amend- doexfoliation (PXF) glaucoma has a ments (CLIA) labs and be cautious of ver y limited role in clinical practice at direct-to-consumer testing services this time, said Robert T. Chang, MD. until FDA approved. Dr. Chang cited a consensus rec- “Identifying someone who carries a ommendation from the 2014 Ameri- gene-conferring susceptibility to glau- can Academy of Ophthalmology Task coma only indicates he or she is at Force on Genetic Testing. The group increased risk, but does not predict if concluded that routine testing for ge- the person will actually get the dis- Robert Chang, MD, said that genetics research netically complex disorders, which is helpful in understanding glaucoma and ease,” said Dr. Chang, assistant pro- includes POAG and age-related mac- possible potential future therapies. See Genetics on Page 16

From SCIENCE AND ART on Page 14 ten to the patients and hear what’s “If you do a good job of taking care of bothering them?” he asked. yourself and working with your doc- down, sleep position, tight neckties, In one survey, patients rated techni- tor, we have every confidence that you isometric exercises, the Valsalva ma- cal expertise as the fourth most im- will not go blind by the time you pass.” neuver, playing a wind instrument, portant skill in a practitioner, after He also exhorted ophthalmologists periodic water spikes, blood loss, honesty, diagnosis and prognosis, to learn cultural sensitivity and to be syphilis, methanol, and hypoten- and clear language. aware of widespread illiteracy. sion, he added. “Take the last year of school com- “So many of our patients are being Offer assurance pleted, and subtract five grade lev- treated for hypertension,” Dr. Lee said. After receiving a diagnosis of glau- els to get someone’s level of literacy,” “Try to keep the pressure from get- coma, patients worry about blind- he said. “We know that people with ting too low.” ness, even if they don’t express that poor literacy have poorer adherence Finally, Dr. Lee urged his audience fear, Dr. Lee said. and poorer results.” to address patients’ expectations. He suggested that physicians can Conversations with patients can re- “Do we take the time to really lis- respond by offering this assurance: veal early warning signs that they might be thinking of switching to an- GLAUCOMA 360 online exclusive other ophthalmologist, Dr. Lee said. Changing trends that may alter glaucoma practices “All of us are here because we love to take care of individual patients, Andrew Iwach, MD, reports rapid changes in the pharmaceutical and by taking care of individual pa-

L indsey A nthony industry. Many of these changes will have an impact on practices. Then, watch as Dr. Iwach outlines the impact of the changing tients we can improve the health of http://bit.ly/1AakcVx ◗ P hoto by landscape. our population,” he said.

GLAUCOMA 3 6 0 15 CME SYMPOSIUM

From GENETICS on Page 15 is performed in large families who demonstrate disease inheritance in GLAUCOMA 360 fessor, Byers Eye Institute, Stanford almost every generation, SNP analy- exclusive video University, Stanford, CA. “This is dif- ses compare the frequency of many Watch as Robert Chang, MD, ferent from single-gene disorders with alleles in large populations of dis- differentiates the fact from fi ction in glaucoma genetics. high penetrance, where the likelihood ease subjects versus unaffected con- http://bit.ly/1FoleNM of disease expression is very high.” trols to identify new genes associated with disease. Genetic associations LOXL1 is a strong risk factor for Trabecular meshwork inducible glu- PXF glaucoma, originally identified cocorticoid response (TIGR, a.k.a. by Thorleifsson, et al. in a study in- myocilin) was the first gene associ- volving Icelandic persons with glau- ated with POAG and was identified coma and normal controls. However by Polansky, et al. in 1997 through PXF glaucoma is multifactorial, which genetic-linkage analysis. However, is why some PXF syndrome patients myocilin, together with the two other do not go on to develop glaucoma. type of glaucoma, Dr. Chang said. original glaucoma genes identified “Being a carrier of a high-risk LOXL1 by genetic linkage analysis—WDR36 Other studies allele does not mean a person will con- and OPTN—only account for a small Subsequent studies have associated vert from PXF syndrome to PXF glau- percentage of glaucoma. LOXL1 in different ethnic popula- coma,” Dr. Chang said. “These indi- LOXL1, discovered in 2007, was tions and even revealed that LOXL1 viduals may have a genetic predisposi- the first glaucoma gene identified risk variants are also common in un- tion, but it appears they also must be using the new method of searching affected controls, rendering genetic exposed to some environmental factor.” for unique, single-nucleotide poly- testing less useful. In addition, the morphisms (SNPs) in a genome-wide available evidence shows no associa- Multiple mutations association (GWAS) study. In contrast tion between LOXL1 and POAG, indi- Since 2010, GWAS studies have found to genetic linkage analysis, which cating that exfoliation is a secondary multiple different genetic mutations related to common glaucoma risk fac- tors, including increased vertical cup- online exclusive GLAUCOMA 360 to-disc ratio, optic disc area, high Evidence supports move to more drainage devices Weight IOP, and low central cornea thickness, of evidence from clinical trials over 20 years supports the greater use of as well as genes involved in TGF- glaucoma drainage devices, said Kuldev Singh, MD. beta signaling and endothelial nitric Then, watch as Dr. Singh outlines how devices are implemented. http://bit.ly/1A6JWBW ox ide. Many publications have come out from the collaboration of the NEI Initial results for MIGS devices encouraging Several new Glaucoma Human Genetics Collabo- MIGS devices offer promise in lowering early mean postoperative IOP to ration (NEIGHBOR) led by Wiggs, et the mid-to-high teens, reported Steven Vold, MD. http://bit.ly/1c0eXvC al. and Gene-Environment Interac- How to optimize outcomes after trab, tube shunts Careful tions in Glaucoma (GLAUGEN) Re- attention to detail can optimize refractive outcomes in trabeculectomy search Consortium. and shunts, reported Cynthia Mattox, MD. http://bit.ly/1LdGo1N “Genetics research is helping us to understand a complex, multifactorial Technology provides advantage in tough surgical cases disease and to explain existing clini- New technology can improve outcomes for complex cataract cases in cal signs with their associated mo- glaucomatous eyes, according to Alan Crandall, MD. He outlines the advantages of the latest medical gadgets. lecular components,” said Dr. Chang. Then, watch as Dr. Crandall discusses complexities encountered “This is important in terms of look- with cataract surgery in glaucoma patients. http://bit.ly/1S8hXHQ ing for potential future therapies.” ◗

16 GLAUCOMA 3 6 0 5th ANNUAL

NEW HORIZONS FORUM SAVE THE DATE January 29, 2016 San Francisco, CA

Speeding the development of new therapies and diagnostics for glaucoma patients

“Excellent forum for compelling new technology in glaucoma.” John Maroney, CEO, ForSight Vision5

“Informative annual meeting that captures the essence of the state of glaucoma.” Eliot Lazar, MD, President, elCON Medical

“The best meeting to take the pulse on the future of glaucoma treatment.” George Marcellino, PhD

251 Post Street, Suite 600, San Francisco, CA 94108 (415) 986-3162 www.glaucoma.org

www.glaucoma360.org CME SYMPOSIUM Environmental risks emerging in XFS development, growth

By Cheryl Guttman Krader the anterior portion of the eye in up to 30% xfoliation syndrome (XFS) of people over age 60, was first described nearly a and XFS accounts for be- century ago and represents tween 5% and 25% of Ethe most common, recog- all open-angle glaucoma nizable cause of secondary open- worldwide, depending angle glaucoma. Only recently has on the population. XFS received the level of attention “Although first de- it deserves, and now a new concept scribed in Finland, ex- about XFS development and progres- foliation glaucoma oc- Terri Pickering, MD, provided an overview of exfoliation syndrome sion has emerged that may provide curs in populations in and its changing role as a disease of environmental risk factors targets for intervention, reports Terri all continents that have in the progression of secondary open-angle glaucoma. Pickering, MD. been studied,” she said. “XFS is now considered a disease Observational studies on XFS showed glass-use during the summer between of environmental risk factors among that it was prevalent among people peak sun hours (10 a.m. to 4 p.m.). genetically pre-disposed people,” said who spend a lot of time outdoors, Increased time spent outdoors dur- Dr. Pickering, in private practice, Glau- including the Navajo, Aborigines, ing youth also seemed to be associ- coma Center of San Francisco, San Bantu, fisherman, and farmers in ated with an increased risk of XFS. Francisco. “We know that age and the Adriatic islands. A recent study Looking at latitude of residence, the variants of the lysyl oxidase-like 1 conducted in the United States and researchers found the risk of XFS in- (LOXL1) gene may be involved. How- Israel showed an association with his- creased by 11% for every degree of ever, other genes have also been as- tory of sun exposure and residential latitude lived away from the equator. sociated with XFS, and the common latitude with the risk being higher The information on time spent out- denominator seems to be an associ- the further north from the equator. doors and sunglasses points to a role ation with extracellular matrix and for UV exposure, and that is further trabecular function. Study confirm theory supported by data showing that indi- Dr. Pickering added that there is The study, repor ted by Pasquale et al. viduals who worked over water or snow evidence that increased ultraviolet [JAMA Ophthalmol. 2014;132(12):1439- had a four-fold increased risk of XFS. (UV) exposure, altitude, and lower 1445], investigated a population com- “Wearing a hat in those conditions ambient temperature have a role in prised of white adults over age 60. It was not protective because it does not disease onset, while disease progres- found that the risk of XFS increased prevent exposure from the reflected sion is affected by ox idative stress and by 4% for each hour, per week spent UV rays,” Dr. Pickering said. the actions of profibrotic growth fac- outdoors during the summer aver- Another study analyzed data from tors and matrix metalloproteinases. aged over a lifetime and decreased participants in the Nurses’ Health by 2% for every 1% of lifetime sun- See XFS EVIDENCE on Page 19 Epidemiology Dr. Pickering pointed out that XFS GLAUCOMA 360 online exclusive is more common than many people Development

Fact or fiction about stem cells and glaucoma L indsey A nthony realize. According to some studies, of stem cell treatments for glaucoma faces big hurdles, but researchers are making rapid progress, said Yvonne Ou, MD. http://bit.ly/1HpPgTr

exfoliative deposits can be found in P hoto by

18 GLAUCOMA 3 6 0 CME SYMPOSIUM Neuroprotective drug in future is not an impossible dream

By Cheryl Guttman Krader that has demonstrated safety and perhaps some efficacy in a pilot he idea that a neuroprotec- clinical study. tive agent for glaucoma will The study population would be available within the next have to be tightly defined, which Tdecade is wishful thinking, would allow for a trial with ad- but not unrealistic, according to Rob- equate power to detect what may ert N. Weinreb, MD. be a moderate treatment effect Dr. Weinreb said that with selection with a smaller sample size. Dr. of an appropriate drug and implemen- Weinreb suggested proper can- Robert Weinreb, MD, is optimistic that a neuro- tation of new testing paradigms, there didates would be patients whose protective agent will available in five to 10 years. is a likelihood that a trial of a neu- glaucoma is rapidly progressing roprotective agent could achieve its on standard therapy or who have sig- desired level of improvement to be clinical endpoints within a reasonable nificant risk factors for progression. provided by the treatment. Dr. Wein- time period and at a reasonable cost. reb said it might be possible to de- “I am optimistic that within five to Detecting benefit sign trials enrolling a few hundred 10 years, we will have a neuroprotec- “Using these inclusion criteria would patients treated for less than 1 year, tive agent that would slow the rate of reduce the ability to generalize the and perhaps even 6 months. How- glaucoma damage,” said Dr. Weinreb, results and would also make recruit- ever, endpoint selection is critical. distinguished professor and chairman, ment more difficult,” Dr. Weinreb “The detection of progressive glau- Department of Ophthalmology, and added. “However, since change is more comatous injury and the definition of director of the Shiley Eye Institute, likely in these patients, the likelihood study endpoints have been problematic,” University of California, San Diego. of detecting benefit with a neuropro- Dr. Weinreb said. “Regulatory agencies Dr. Weinreb explained that an “ap- tective agent would be improved.” equate glaucoma progression with stan- propriate drug” could be one that has The sample size will depend on the dard achromatic visual field loss and been shown to have neuroprotective rate of worsening of the outcome mea- have not embraced structural alterations activity in an experimental model and sures in untreated patients and the See NEUROPROTECTIVE AGENT on Page 20

From XFS EVIDENCE on Page 18 living in the middle latitudes of the However, XFS is a systemic condi- United States and about 75% lower tion, and exfoliative material is found Study and the Health Professionals for residents of southern-tier states. in many other organs of the body. Follow-up Study, focusing on individu- In the eye, cells of the iris, epithe- “XFS has been associated with hear- als who lived in the same geographic lium, and endothelium make exfo- ing loss, renal artery stenosis, hyper- tier of the United States their entire life liative material. In addition to caus- tension, stroke, angina, myocardial [Ophthalmology. 2012;119(1):27-35]. ing glaucoma, which tends to be a infarction, and Alzheimer’s Disease Using persons dwelling in northern- severe form, XFS has been associ- among other extraocular conditions,” tier states as a reference group, that ated with breakdown of the blood- Dr. Pickering said. “So far, there is L indsey A nthony study found the population risk of XFS aqueous barrier and damage to the no clear evidence that it increases ◗

P hoto by was nearly 50% lower among people retinal vasculature and optic nerve. the risk for mortality.”

GLAUCOMA 3 6 0 19 CME SYMPOSIUM MIGS options bring balance to cataract-glaucoma surgery

By Cheryl Guttman Krader tional impairment,” said Thomas W. Samuelson, MD, adjunct associate pro- he need for cataract surgery fessor of ophthalmology, University of has often been the tipping Minnesota, Minneapolis, and attending point for proceeding with sur- surgeon, Minnesota Eye Consultants, Tgical management of glau- Minneapolis. “Today, combined sur- coma, but in 2015, surgeons are better gery is performed in a broader pop- able to tailor their intervention based ulation thanks to the availability of on where the patient lies along the alternatives that are far less likely to spectrum of glaucoma. cause iatrogenic vision loss.” “After the drug renaissance of the Dr. Samuelson said that while cat- late 1990s and early 2000s, combined aract surgery is not a cure for glau- cataract surgery with a filtering or tube coma, it is an important management Thomas Samuelson, MD, urged surgeons to pick procedure began to be reserved for option that can result in significant at least one MIGS procedure as an alternative to glaucoma patients at high risk for func- See MIGS on Page 21 trabeculectomy or tube procedures.

From NEUROPROTECTIVE AGENT on Page 19 in glaucoma neuroprotection studies– estimates retinal ganglion cell loss since structural change is an objec- using data from SD-OCT imaging of in optic nerve as primary endpoints.” tive measure and often occurs before the retinal nerve fiber layer, func- He acknowledged that preservation functional change. Furthermore, with tional results from standard perim- of visual function and vision-related current spectral-domain optical co- etry, and age-related change. quality of life is the ultimate goal in herence tomography (SD-OCT) sys- The CSFI is considerably more sensitive the clinical management of glaucoma tems, the imaging is patient-friendly. than mean deviation, visual field index, patients. However, these are subjec- and OCT average thickness for detect- tive endpoints. Imaging adds benefits ing progressive glaucomatous damage Addressing visual field loss, Dr. “OCT imaging is done through an un- [Am J Ophthalmol. 2012;154:814-24]. Weinreb said it is an insensitive mea- dilated pupil and data acquisition is Looking to the future, Dr. Weinreb sure early in the disease, variable (par- very fast, which enables repeat test- proposed two indications for a neu- ticularly late in disease), and not pa- ing,” Dr. Weinreb said. “The ability roprotective drug for glaucoma. One tient-friendly. He suggested that the to easily collect a sufficient number use would serve as complementary ability to detect change with standard of endpoints would allow a study that therapy, where the agent is added to perimetry could be improved by in- has a smaller sample size, shorter medical treatment or used after sur- creasing the frequency of testing at duration, and lower cost.” gery in patients who achieve IOP- baseline and the end of the trial. Oth- Using an endpoint that combines lowering, but are still experiencing erwise, demonstrating preservation of structure and function testing is an- progressive loss of visual function. visual function would depend on the other approach. The combined struc- The second would serve as an alter- development of a more objective test. ture-function index (CSFI), developed native therapy for patients in whom L indsey A nthony Use of a structure-related endpoint is by Felipe A. Medeiros, MD, and col- IOP-lowering agents are not tolerated ◗

more attractive for assessing efficacy leagues at the Shiley Eye Institute, or ineffective. P hoto by

20 GLAUCOMA 3 6 0 CME SYMPOSIUM

From MIGS on Page 20 fact that we are overusing them in GLAUCOMA 360 some patients and that ocular sur- exclusive video IOP reduction. Therefore, he consid- face toxicity is rampant. With MIGS Watch as Thomas Samuelson, ers phacoemulsification alone useful we can successfully convert patients MD, outlines how he manages for patients needing cataract surgery from an unrealistic, unsustainable patients with cataracts and who have untreated ocular hyper- medication schedule to a reasonable glaucoma. http://bit.ly/1L9fTub tension or are glaucoma suspects. regimen of just one or two drops per Patients with mild-to-moderate day, a regimen that is minimally in- glaucoma are candidates for phaco- trusive, and sustainable.” emulsification plus “enhanced micro- He added that in the future, the invasive glaucoma surgery (MIGS),” introduction of sustained, delivery- which would involve ab interno tra- drug systems might take MIGS with beculectomy (Trabectome, NeoMe- MIST to the next level. dix), a trabecular microbypass stent (iStent, Glaukos), or endoscopic cy- Gearing up for MIGS clophotocoagulation plus some post- Dr. Samuelson noted that while it may Dr. Samuelson said the reflux of operative medication. be unrealistic for surgeons to adopt all blood when the stent first enters Trabeculectomy or a tube proce- MIGS procedures, they should pick one Schlemms canal is a nice sign that dure remains an important option so that they will be able to offer an al- the stent is properly placed. How- to combine with phacoemulsification ternative to trabeculectomy or tube pro- ever, blood reflux does not always for patients who need cataract sur- cedures. Dr. Samuelson said he chose occur or it may not be seen until all gery and are at high risk for func- the trabecular microbypass stent, and of the viscoelastic is removed from tional impairment (patients with se- he offered a few tips for success. the eye. Blood coming out through vere glaucoma, poor compliance, ex- First, Dr. Samuelson advised sur- the snorkel following placement is a treme IOP, medication intolerance, or geons to master intraoperative gonios- tell-tale sign the device is communi- aggressive progression). copy–since excellent visualization is cating with the episcleral vasculature, critical to achieve accurate placement but it will only be visualized when Enhanced MIGS of the device. When implanting the the eye is soft and below episcleral Explaining the rationale for enhanced stent, he recommended approaching venous pressure. MIGS, Dr. Samuelson said that while the trabecular meshwork at a slight highly safe, the current MIGS op- angle and to be definitive when pen- Continue medical therapy tions have modest efficacy. Use of etrating the trabecular meshwork. Dr. Samuelson also suggested that con- one or two topical medications after “You want to be steep enough with tinuous medical therapy after MIGS MIGS provides patients with addi- your line of attack so that you will should be established with patients tional IOP-lowering effect in, what get to the back wall of the canal, and during a preoperative discussion. That Dr. Samuelson terms, “minimally in- use enough force to push the stent approach will avoid the frustration trusive sustainable therapy (MIST).” through the juxtacanalicular mesh- of the patient to ask in the recovery Continued use of medication in this work,” Dr. Samuelson pointed out. room, “What should I do with my manner should not be viewed as sur- “Being too superficial with stent place- glaucoma medications?” gery failure, he added. ment was the most common error I “Better to make the immediate post- “The ability of a surgical procedure made in my early cases.” op medication decisions preoperatively to completely eliminate medications Once the device is in Schlemms so the patient knows which glaucoma is a laudable goal, but does not have canal, the insertion is completed by medications to stop and which to con- to be achieved to consider the proce- flattening the angulation, dropping tinue after surgery,” Dr. Samuelson dure a success,” Dr. Samuelson ex- the heal or lifting the toe of the de- said. “This avoids somewhat arbitrary, plained. “It is a fact that we have su- vice, while maintaining full visual- on-the-fly, glaucoma medication deci- perb glaucoma drugs, but it is also a ization the entire time. sions in the recovery room.” ◗

GLAUCOMA 3 6 0 21 CME SYMPOSIUM Limited medical therapy drives impetus for product development

By Cheryl Guttman Krader prost 0.004% with sofZia (Travatan Z, Alcon Laboratories). In addition, ecent innovations have ad- there are three preservative-free op- dressed some limitations of tions: tafluprost 0.0015% (Zioptan, medical treatment for glau- Merck), single-use dorzolamide HCl Rcoma, but unmet needs re- 2%/timolol maleate 0.5% (Cosopt PF, main, said Sunita Radhakrishnan, MD. Akorn), and single-use timolol ma- Discussing the current status of med- leate 0.5% (Timoptic in Ocudose, ical therapy for glaucoma, Dr. Rad- Bausch + Lomb). hakrishnan cited newer formulations For patients whose IOP cannot be that are more ocular surface friendly controlled on a single medication, the and the first beta blocker-free, fixed fixed-combination category recently combination as useful advances. Items was expanded by the addition of the on her “medical therapy wish list” brinzolamide 1%/brimonidine 0.2% Sunita Radhakrishnan, MD, presented her included products with better drug combination (Simbrinza Suspension, “medical therapy wish list” for glaucoma. delivery systems and options acting Alcon), the only beta-blocker-free, via alternate mechanisms of action. fixed-combination. tration of BAK, which improves drug Dr. Radhakrishnan noted that rel- delivery through the cornea, bimato- Progress for safety, adherence ative to its individual components, prost 0.01% has the same IOP-lower- The potential for chronically used the brinzolamide/brimonidine fixed- ing effect as its predecessor, bimato- topical medications to damage the combination has a similar side-effect prost 0.03%, but is associated with a ocular surface is an often-ignored profile and greater IOP-lowering ef- lower rate of conjunctival hyperemia. issue. However, it is an important ficacy. The magnitude of IOP reduc- The availability of a medication pro- concern that underscores the value tion provided by the brinzolamide/ viding a different mechanism of action of medications that limit preserva- brimonidine fixed-combination is than existing options would also be tive-related toxicity. about the same as that provided by a welcome addition for patients, Dr. “We know from patient reports and monotherapy with a prostaglandin. Radhakrishnan said. Today’s most many studies that ocular surface dis- commonly used, IOP-lowering drugs ease is highly prevalent among glau- Future developments either act as aqueous suppressants coma patients being treated with medi- Several companies are working to de- (beta-blockers, alpha agonists, and cal therapy,” said Dr. Radhakrishnan, velop novel technology for delivering carbonic anhydrase inhibitors) or in- in private practice at Glaucoma Cen- medication to the eye. Better drug- crease uveoscleral outflow (prosta- ter of San Francisco. “We also know delivery systems could allow for treat- glandin analogues, alpha agonists). that the preservative benzalkonium ment regimens using a lower dose of Increasing trabecular outflow is an- chloride (BAK) contributes to the dis- the active medication that could mini- other mechanism for lowering IOP, ruption of the ocular surface.” mize side effects without compromis- but it is only provided by pilocarpine, Currently, there are two branded ing IOP-lowering efficacy. The 0.01% which has limited use because of its products formulated with non-BAK formulation of bimatoprost (Lumigan side effects. However, agents acting preservatives, brimonidine tartrate 0.01%, Allergan/Actavis) offers a good as rho kinase inhibitors may aug- L indsey A nthony 0.1% and 0.15% with Purite (Alpha- illustration of that concept. ment the group of trabecular outflow ◗

gan P, Allergan/Actavis) and travo- Reformulated with a higher concen- medications in the future. P hoto by

22 GLAUCOMA 3 6 0