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5/16 Glaucoma Medication Lecture: Drops, drops, drops…

Alena Reznik, MD

Summary

The goal of the lecture is to review 4 established medication classes for glaucoma treatment- beta blockers, alpha agonists, prostaglandin analogues and carbonic anhydrase inhibitors. I will review indications, strength, brand/generic formulations and side effects for each class. I will outline my approach to chosing an appropriate medication for each patient and reason behind escalating therapy and using combination formulations. I will also review an emerging class of Rho-kinase inhibitors and their application to glaucoma treatment. To conclude the lecture I will present two glaucoma patients and will go through their proposed medical treatment plan.

2 Outline for lecture: Drops, drops, drops. Medical Therapy in Glaucoma – 1 hour lecture

February 13, 2017 6pm – 7pm Alena Reznik MD

1. Beta Blockers

Betaxolol (Betoptic, Lokren, Kerlone)

•Metipranolol (OptiPranolol, Betanol, Disorat, Trimepranol)

•Timolol (Betimol, Blocadren, Istalol, Timoptic, Timoptic-XE, Timoptic OcuDose) •Carteolol (Cartrol, Ocupress, Teoptic, Arteolol, Arteoptic, Calte, Carteabak, Carteol, Cartrol, Elebloc, Endak, Glauteolol, Mikelan, Poenglaucol, Singlauc) • Levobunolol (AK-Beta, Liquifilm, Betegan)

•

•ConcentrationsBetaxolol - 0.5% & andDosing 0.25%, BID

•Metipranolol - 0.1% and 0.3%, BID •Timolol - 0.5% and 0.25% (solution or gel), BID or Daily gel

•Carteolol - 2%, BID •Levobunolol - 0.25% and 0.5%, BID

• on

•Mechanism of acti •Decrease aqueous production

•Inhibit cAMP production in ciliary epithelium •Onset of action within 1 hour

•Slightly addictive effect of beta agonists- and beta antagonists •Systemic absorption, untreated eye IOP lowering

•Nonselective: metipranolol, timolol, carteolol, levobunolol •Selective B1 antagonist: betaxolol

•Efficacy

3 -

•Reduce aqueous humor secretion 20 50% (2.5 μL/min to 1.0 μL/min) -30%

•Corresponding IOP reductionr of 20 •Onset of action within 1 hou

•May persist up to 4 weeks after stopping

•Decrease-20% of aqueous patients production fail to respond more in day, less in sleep •10 -blocker

•Efficacy dampened in patients taking-term systemic drift) β •Extended use reduced effect (long

•SideOcular effects •–Blurring –Irritation –Corneal anesthesia

–Punctate keratitis –Allergy

–

Possible aggravation of myasethenia gravis

Systemic

•–Increase LDL (carteolol least) –Hypotension –Bradycardia

–Heart block –

–bronchospasmDecreased libido (betaxolol less) –C

NS depression

4 –

–Mood swings

–Reduced glucoseexercise tolerance tolerance 2. Prostaglandins

–•BrandXalatan names - Latanoprost –Lumigan - Bimatoprost

– -

–TravatanZioptan – TafluprostTravoprost

•Concentrations–Xalatan (Generic) 0.005% (has benzalkonium) –

- Lumigan (NO generic) 0.01% (has benzalkonium)

-Travatan (Generic) 0.004% (Travatan Z = benzalkonium free) Zioptan (NO generic) 0.0015% (preservative free)

•Dosing–All qhs

•Prostaglandins

•Mechanism– of Action

Increasing uveoscleral outflow (although not exactly clear)

•Efficacy–

~30% IOP lowering.

•Indications-indications

•Contra–

No true CI’s

•Prostaglandin Side Effects

–•IncreasedPermanent melanosomes change (NOT melanocytes)

5 –Frequency depends on eye color at baseline

–Up to 33% at 5 years –79% of green-

browne irides and 85% hazel vs. 8% blue irides

•Hypertrichosis, Trichiasis, Distichiasis– •HSV exacerbations + CME + Uveitis debatable. Avoid if present at baseline.

•Conjunctival– injection •Hyperemia more common w bimatoprost and travoprost

•Prostaglandin Notes

•Latanoprost/Travoprost– corneal = prodrugs. esterase hydrolize drugs

Become activeLESS after •BID dosing = effective

•Some patients- respond betteradministration. to one drug than another in the SAME class •Peak effect 10 14 hours post 3. Carbonic Anhydrase Inhibitors

•Brand names

•Chemical names •Concentrations

•Dosing

•Mechanism–Decrease aqueous of Action

•Efficacy–15% reduction in IOP

•Acetazolamide– Diamox –

•250mg PO QD QID

6 –

Diamox Sequels

•500mgethazolamidePO QDAY / BID •M–

Neptazene-

•50 100mg PO BID/TID

•Dichlorphenamide–Daranide

•50mg PO TID

•Dorzolamide–Trusopt

•2% BID •Brinzolamide–Azopt

•1% BID

•Carbonic Anhydrase Inhibitors

•Acetazolamide

•Indications-indications

•Contra-effects •Side

•Indicated when MMT is not providing adequate IOP reduction •Contraindicated in those with sulfa allergy

•Side–Hypokalemia Effects –Metabolic acidosis

7 –Kidney stones

–Depression –Diarrhea

–

–NumbnessFlat tasting / soda tingling (metallic) (hands / feet / lips) –RARE: Aplastic anemia

•Methazolamide

•Indications-indications

•Contra-effects •Side

•Indicated when MMT is not providing adequate IOP reduction

•Better tolerated in those with sulfa allergies acidosis •Side effects similar to Acetazolamide except no metabolic

•Dorzolamide (Trusopt)

•Indications-indications •Contra-effects

•Side

•IOP lowering medication •Side– Effects:

–StingBitter / taste burn/ itch –SJS (sulfa)

–Corneal edema

•More acidic and more irritating e

•Preservative free formulation availabl

8

•Brinzolamide (Azopt)

•Indications-indications •Contra-effects

•Side

•IOP lowering medication •Side– Effects:

–StingBitter / taste burn/ itch –SJS (sulfa)

–Corneal edema

•Less acidic and better tolerated

4. ALPHA AGONISTS-2 Agonist) Selective (Alpha

•Clonidine

–•Apraclonidine0.5%, 1% (Iopidine)

–•Brimonidine0.1%, 0.15%, (Alphagan) 0.2%

Combo drugs

•Simbrinza: Brimonidine/Brinzolamide

•Combigan: Brimonidine/Timolol •Mechanism

Central vs Peripheral

9

•Mechanism?1. Decreased aqueous production

-protein-coupled receptor  ↓ (additive with BB)  ↓cAMP  production •G adenylate cyclase activity

2. Increased uveoscleral outflow -adrenergic stimulation

•Increased PGA release from alpha

•Efficacy25% (2 hours and Dosing postdose) to 15% (trough 12 hours postdose) IOP reduction

TID (as monoagent) = BID (as adjunctive agent)

Equivalent to CAI and BB when used with PGA

http://www.ncbi.nlm.nih.gov/pubmed/20625041

TachyphylaxisApraclonidine > Brimonidine

•Side effects

Conjunctivitis-Most common (follicular) ocular side effect -

Apraclonidine (~40%) > brimonidine 0.2% (~15%) > brimonidine Purite (10%>)

10

•Side effects

Mydriasis-Peripheral / AlphaMiosis- 2 constricts pupils -Alpha-1 and Central Alpha-2 dilate pupils

•SideLid retraction effects -Alpha-

1 effect (weak)

•Side effects

Dry-Most eye common / Dry mouth systemic side effect

•SideRespiratory effects depression -Crosses BBB in neonates and infants (up to 5 years old)

-Decrease in sympathetic tone

•Side effects

11 Hypotension

-Decrease in sympathetic tone -Clonidine > Apraclonidine >>>> Brimonidine

5. Miotics

•Brand names •Chemical names

•Concentrations •Dosing

•Mechanism of Action •Efficacy

•Brand Names and

•Chemical Names

•Mechanism of Action: •Efficacy -30%. Add

•Lowers IOP- by 20 itive effect with BB, adrenergic agents, and CAIs. •Melanin bound, so higher doses necessary in pots with darkly pigmented irides. tolerance. •Although miotics lower IOP effectively, clinical use is limited by local ocular longer-lasting and more potent than direct agonists •Indirect muscarinic agonists are

•Direct + indirect acting muscarinic agonists = less effect than either alone •Indications

•Elevated IOP

12

•Additional uses:

•Pilocarpine: 0.12% for Adie’s (systemic uses include stimulation of bladder emptying) •Carbachol: induce miosis after IOL implantation;

•Echothiophate: accommodative esotropia

•Physostigmine: crab louse infection of eyelashes; (systemic uses include Alzheimer’s,dications delayed gastric emptying, orthostatic hypotension, myasthenia) •Contrain

•Ocular:

•Uveitic glaucoma (any significant ocular inflammation)

•Neovascular glaucoma

•Retinal breaks, RD •PSC -acting cholinesterase inhibitors) contraindicated in acute angle

•Pilo 4% (long closure;hakia, canpre rotate- CB forward and close the angle contraindications) •Ap presbyopia, concurrent use of prostaglandin analogs (relative

•Systemic:

•Asthma

•Coronary insufficiency

•Gastroduodenal ulcers

•Incontinence - increased potency and duration of action •Ester anesthetic (procaine) and succinylcholine use

•Side Effects

•Ocular:

•Brow ache - •Induced myopia /accommodative spasm (induced accommodation / move lens forward) desirable in accommodative ET

13

•Cataractogenesis (anterior subcapsular)

•Inability to dark adapt •Iris cyst formation

•Follicular conjunctivitis, allergic blepharoconjunctivitis, conjunctival injection •Lid myokymia

•Retinal detachment •Systemic: (rare)

•Excessive salivation

•Dyspepsia •Diaphoresis

•Bronchial mucus secretion •Bronchospasm

•Bradycarida •Vasodilation

•Nausea/Vomiting (physostigmine), Diarrhea

•Seizures (physostigmine) •Osmotics

•Glycerol (Osmoglyn) 50% solution- 1 g/kg- PO

•Mannitol (Osmitrol) 10%- 1 1.5 g/kg at 3 5 mL/min

•Urea (Ureaphil) 30% 2 7 mL/kg- •Isosorbide (Ismotic) 45% 1.5 2 g/kg

•Mechanism of Action  osmotic gradient  blood •Increases blood osmolality draws water from vitreous to

•Efficacy

•More the better •Transient results

14

•Careful of rebound elevation

•Indications

•Acute-op IOP IOP •Peri

•Critically-indications shallow AC •Contrafailure

•Renal

•CHF -effects •Side

•Headache, confusion •CHF, MI

•Hyperglycemia •Extravasation of infusion

15 Drops, drops, drops

Alena Reznik MD Assistant Professor of Ophthalmology Glaucoma Service Cell 310-980-6038 [email protected]

Children's 16 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Financial Disclosure

• None

• No $ from Alcon, AMO, Novartis, Allergan, Glaukos, Pfizer, Bausch/Lomb, Merck, Regeneron, and so forth and so on0/

Children's 17 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Who we are

• Glaucoma service

• Beverly Hills (Wilshire/Doheny) • Pasadena (Fair Oaks) • Arcadia • Downtown LA (Keck)

Emergency referral line : 323-442-EYES

Children's 18 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Outline

• When to treat and how to treat?

• Major groups: chemical structure and pharmacological action • Brand names/generic names • Side effects • Step wise approach in my practice

Children's 19 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Ocular HTN Treatment Study

• GS vs early POAG • Risk factors: higher IOP, CCT, age, larger C:D, family h/o • Efficacy and safety of IOP lowering: 22.5% decrease in IOP -> 9.5% to 4.4% at 5 years

• Iphone app: Glaucoma calc ($1.99)

Children's 20 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Target IOP

• Type of glaucoma: NVG vs congenital vs POAG vs CACG • Focus on POAG/CACG in this lecture • 20% from baseline • Advanced-> aggressive • Reassess: repeat HVF/OCT/frequent visits

Children's 21 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Beta Blockers

R\lSt:.11 A 1..0\111

. NOC 17478-288-11 Er """' Timolol Maleate ~ Ophthalmic Solution, USP 0.5% ~~~ .,., Maleate 6.8 mg/ml) 1lon1y 10 ml 'fAl

Children's 22 Hl~~~ITiJLES. ~ I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< • Selective: Betaxolol (Betoptic, Lokren, Kerlone) • Metipranolol (OptiPranolol, Betanol, Disorat, Trimepranol) • Timolol (Betimol, Blocadren, Istalol, Timoptic, Timoptic-XE, Timoptic OcuDose) • Carteolol (Cartrol, Ocupress, Teoptic, Arteolol, Arteoptic, Calte, Carteabak, Carteol, Cartrol, Elebloc, Endak, Glauteolol, Mikelan, Poenglaucol, Singlauc) • Levobunolol (AK-Beta, Liquifilm, Betegan)

Children's 23 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Concentrations & Dosing

• Betaxolol - 0.5% and 0.25%, BID • Metipranolol - 0.1% and 0.3%, BID • Timolol - 0.5% and 0.25% (solution or gel), BID or Daily gel • Carteolol - 2%, BID • Levobunolol - 0.25% and 0.5%, BID

Children's 24 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Mechanism of action

• Inhibit cAMP production in ciliary epithelium-> Decrease aqueous production • Onset of action within 1 hour, lasts up to 4 weeks • Systemic absorption, untreated eye IOP-lowering • Qday vs BID dosing, additive effect with others

• Nonselective B1+B2: metipranolol, timolol, carteolol, levobunolol • Selective B1 antagonist: betaxolol

Children's 25 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Efficacy

• Reduce aqueous humor secretion 20-50% (2.5 μL/min to 1.0 μL/min) • Corresponding IOP reduction of 20-30% • Decrease aqueous production more in day, less in sleep • 10-20% of patients fail to respond • Efficacy dampened in patients taking systemic β-blocker • Extended use reduced effect (long-term drift)

Children's 26 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Side effects

• Ocular • Systemic – Blurring – Increase LDL (carteolol least) – Irritation – Hypotension – Corneal anesthesia – Bradycardia – Punctate keratitis – Heart block – Allergy – bronchospasm (betaxolol less) – Possible aggravation of – Decreased libido myasthenia gravis – CNS depression – Mood swings – Reduced exercise tolerance

– Reduced glucoseChildren's tolerance 27 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Prostaglandins

• Brand names – Xalatan - Latanoprost – Lumigan - Bimatoprost -::: N – Travatan -Travoprost lN 0 – Zioptan – Tafluprost (taffuprost ophthalmic l ~ solution) ~o Z- • Concentrations 0..0015, – Xalatan (Generic) 0.005% (has benzalkonium) – Lumigan (NO generic) 0.01% (has benzalkonium) - Travatan (Generic) 0.004% (Travatan Z = benzalkonium free) - Zioptan (NO generic) 0.0015% (preservative free) • Dosing – All qhs

'28 Prostaglandins

• Mechanism of Action – Increasing uveoscleral outflow (although not exactly clear) • Efficacy – ~30% IOP lowering. • Indications – Ummm0glaucoma0/ • Contra-indications – No true CI’s – Personal: actors/actresses

Children's 29 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Prostaglandin Side Effects

• Increased melanosomes (NOT melanocytes) – Permanent change – Frequency depends on eye color at baseline – Up to 33% at 5 years – 79% of green-browne irides and 85% hazel vs. 8% blue irides • Hypertrichosis, Trichiasis, Distichiasis • HSV exacerbations + CME + Uveitis – debatable. Avoid if present at baseline. • Conjunctival injection • Hyperemia – more common w bimatoprost and travoprost

Children's 30 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Prostaglandin Notes

• Latanoprost/Travoprost = prodrugs. – Become active after corneal esterase hydrolize drugs • BID dosing = LESS effective • Some patients respond better to one drug than another in the SAME class • Peak effect 10-14 hours post administration.

Children's 31 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Carbonic Anhydrase Inhibitors

OC 0065- 0275-05 Alcon

(brin zolam ide ophthalmic suspe nsion) 1%

Children's I32 USC Eye Institute Hl~~~ITiJLES. We Treat Kids Beller Carbonic Anhydrase Inhibitors

• Brand names • Acetazolamide • Chemical names – Diamox • Concentrations • 250mg PO QD – QID – Diamox Sequels • Dosing • 500mg PO QDAY / BID • Methazolamide – Neptazene • 50-100mg PO BID/TID • Dichlorphenamide – Daranide • Mechanism of Action • 50mg PO TID – Decrease aqueous • Dorzolamide • Efficacy – Trusopt – 15% reduction in IOP • 2% BID – Onset 2-3 hours • Brinzolamide – Washout 2-3 days – Azopt • 1% BID

Children's 33 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Dorzolamide (Trusopt)

• Indications • IOP lowering medication • Contra-indications • Side Effects: • Side-effects – Sting / burn/ itch – Bitter taste – SJS (sulfa) – Corneal edema • More acidic and more irritating • Preservative free formulation available

Children's 34 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Brinzolamide (Azopt)

• Indications • IOP lowering • Contra-indications medication • Side-effects • Side Effects: – Sting / burn/ itch – Bitter taste – SJS (sulfa) – Corneal edema • Less acidic and better tolerated

Children's 35 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Acetazolamide

• Indications • Indicated when MMT is not • Contra-indications providing adequate IOP • Side-effects reduction • Contraindicated in those with sulfa allergy • Side Effects – Hypokalemia – Metabolic acidosis – Kidney stones – Depression – Diarrhea – Numbness / tingling (hands / feet / lips) – Flat tasting soda (metallic) – RARE: Aplastic anemia

Children's 36 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Methazolamide

• Indications • Indicated when MMT is • Contra-indications not providing adequate • Side-effects IOP reduction • Better tolerated in those with sulfa allergies • Side effects similar to Acetazolamide except no metabolic acidosis

Children's 37 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( ALPHA-2 AGONISTS-selective

Selective (Alpha-2 Agonist) • Clonidine • Apraclonidine (Iopidine) – 0.5%, 1% • Brimonidine (Alphagan) – 0.1%, 0.15%, 0.2%

--~~=-- Combo drugs IO:~i>''',1 ::, SLMBRINZA-- ~ .,,f • (brinz:olarnid1/ ,. , Simbrinza: brirnollidine ;• tartratt ophthalmic '-' 11 Brimonidine/Brinzolamide SIISpe!Uion) i" 116/0.2'16 j; • Combigan: Brimonidine/Timolol Sterile II!.':.':,".:==''"- 8 ml M:11111 Children's 38 Hl~~~ITiJLES. fill I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Mechanism Central vs Peripheral

0023-9321-10· ·"""° " "'°"' Alphagal(P (bnmomdinetartrate ophthalm,csohmonlDI\ 10 ;:,10ml ,,~

Clonidine

Children's 39 BBB Hl~~~ITiJLES. ~ I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Mechanism?

1. Decreased aqueous production (additive with BB) • G-protein-coupled receptor  ↓adenylate cyclase activity  ↓cAMP  production

2. Increased uveoscleral outflow • Increased PGA release from alpha-adrenergic stimulation

Children's 40 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Efficacy and Dosing

25% (2 hours postdose) to 15% (trough 12 hours postdose) IOP reduction

TID (as monoagent) = BID (as adjunctive agent)

Equivalent to CAI and BB when used with PGA http://www.ncbi.nlm.nih.gov/pubmed/20625041

Tachyphylaxis Apraclonidine > Brimonidine

Children's 41 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Side effects

Conjunctivitis (follicular) - Most common ocular side effect - Apraclonidine (~40%) > brimonidine 0.2% (~15%) > brimonidine Purite (10%>)

42 I USC Eye Institute LAC+USC 1-lf"-'-llHrAAFNfr,\'ORI< Side effects

Mydriasis / Miosis - Peripheral Alpha-2 constricts pupils - Alpha-1 and Central Alpha-2 dilate pupils

Children's 43 Hl~~~ITiJLES. ~ I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Side effects

Lid retraction - Alpha-1 effect (weak)

Children's 44 Hl~~~ITiJLES. ~ USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Side effects

Dry eye / Dry mouth - Most common systemic side effect

Children's 45 Hl~~~ITiJLES. ~ I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Side effects

Respiratory depression - Crosses BBB in neonates and infants (up to 5 years old) - Decrease in sympathetic tone

Alpha Agonists cause ApneA

Children's 46 Hl~~~ITiJLES. We Treat Kids Beller Side effects

Hypotension - Decrease in sympathetic tone - Clonidine > Apraclonidine >>>> Brimonidine

Children's 'lW47 u~c ~ye institute Hl~~~ITiJLES. We Treat Kids Beller Miotics

• Brand names • Indications • Chemical names • Contra-indications • Concentrations – Ocular – • Dosing Systemic • Side-effects • Mechanism of Action – Ocular • Efficacy – Systemic

Children's 48 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Piloc.arplne Alcon Hyd ochlorlde Miotics Oph1halmlc lsopto Solu on USP Carbachol 3%

49 ~ c+usc 34 K"AAF Nfr,\'ORI< Brand Names and Chemical Names Chemical Brand Names Concentration Dosing Name (%)

Ocusert Pilo-40 20, 40 mcg q 5-7 days Cholinergics Pilocarpine Adsorbocarpine, Akarpine, Almocarpine, Isopto Carpine, 0.12, 1, 2, 3, 4, 6 QID Miocarpine, Pilagan, Pilocar, Pilocel, Pilagan, Pilomiotin, Piloptic, Pilostat Carbachol Carbastat, Carboptic, Isopto 0.1%, 0.75, 1, 3, TID or QID Carbachol, Miochol (Ach 1%), Miostat Intraocular 5 Anti- Echothiophate Phospholine Iodide, 0.03-0.25 BID cholinesteras iodide Echodide es Physostigmine Eserine sulfate, 0.25, 0.5 QID Isopto Eserine

Demecarium Humorsol 0.03-0.25 QD or QOD bromide Tosmilen (Bulgaria, Japan)

Di isopropyl Floropryl ,,,,.. 0.01-0.1 Chlldre h's 1 instillation fluorophosphate 50 pl :(~ I USC E ve Institute H-l-~~~IT ~ELES, (lasts~ 15 d) 35 ~ We Treat K '~ r., (DFP) fd s Beller !;!\S1~r~£ Mechanism of Action: Carbachol Direct Acting Muscarinic (muscarinic + nicotinic agonist) Agonists Pilocarpine (non-specific muscarinic M3 agonist) • Iris sphincter muscle Echothiophate iodide Indirect Acting contracts (miosis)

(irreversible) Muscarinic Agonists • Longitudinal ciliary [ muscle contracts (pulls on scleral spur Di isopropyl and opens trabecular fluorophosphate (DFP) meshwork) (irreversible) • Circular ciliary muscle contracts Physostigmine (accommodation) (reversible) • Moves the lens diaphragm forward

Demecarium bromide (reversible)

51 36 Efficacy

• Lowers IOP by 20-30%. Additive effect with BB, adrenergic agents, and CAIs. • Melanin-bound, so higher doses necessary in pts with darkly pigmented irides. • Although miotics lower IOP effectively, clinical use is limited by local ocular tolerance. • Indirect muscarinic agonists are longer-lasting and more potent than direct agonists • Direct + indirect acting muscarinic agonists = less effect than either alone Children's 52 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Indications • Elevated IOP • Additional uses: • Pilocarpine. 0/12% for !die’s • Carbachol: induce miosis after IOL implantation; (systemic uses include stimulation of bladder emptying) • Echothiophate: accommodative esotropia • Physostigmine: crab louse infection of eyelashes- (systemic uses include !lzheimer’s, delayed gastric emptying, orthostatic

Children's hypotension, myasthenia)53 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC 38 We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Contraindications

• Ocular: • Uveitic glaucoma (any significant ocular inflammation) • Neovascular glaucoma • Retinal breaks, RD • PSC • Pilo 4% (long-acting cholinesterase inhibitors) contraindicated in acute angle closure; can rotate CB forward and close the angle • Aphakia, pre-presbyopia, concurrent use of prostaglandin analogs (relative contraindications) • Systemic: • Asthma • Coronary insufficiency • Gastroduodenal ulcers • Incontinence • Ester anesthetic (procaine) and succinylcholine use - increased potency and duration of action Children's 54 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC 39 We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Side Effects • Ocular: • Brow ache • Induced myopia /accommodative spasm (induced accommodation / move lens forward) - desirable in accommodative ET • Cataractogenesis (anterior subcapsular) • Inability to dark adapt • Iris cyst formation • Follicular conjunctivitis, allergic blepharoconjunctivitis, conjunctival injection • Lid myokymia • Retinal detachment • Systemic: (rare) • Excessive salivation • Dyspepsia • Diaphoresis • Bronchial mucus secretion • Bronchospasm • Bradycarida • Vasodilation • Nausea/Vomiting (physostigmine), Diarrhea Children's • Seizures (physostigmine) 55 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC 40 We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Osmotics

• Glycerol (Osmoglyn) 50% solution 1 g/kg PO • Mannitol (Osmitrol) 10% 1-1.5 g/kg at 3-5 mL/min • Urea (Ureaphil) 30% 2-7 mL/kg • Isosorbide (Ismotic) 45% 1.5-2 g/kg

Children's 56 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Mechanism of Action

• Increases blood osmolality  osmotic gradient  draws water from vitreous to blood

Children's 57 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Efficacy

• More the better • Transient results • Careful of rebound elevation

Children's 58 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Indications

• Acute IOP • Peri-op IOP • Critically shallow AC

Children's 59 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Contra-indications

• Renal failure • CHF

Children's 60 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Side-effects

• Headache, confusion • CHF, MI • Hyperglycemia • Extravasation of infusion

Children's 61 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( My approach

• Beta blocker • PGA • SLT/ALT • CAI • Combination • Alpha-2 agonists

• Surgery

Children's 62 HL~~~~~JLES. {~ I USC Eye Institute LAC+USC We Treat Kids Beller lal'JJTHrAAf NIT,\'llRI( Thank you!

• Dr. Rohit Varma • Dr. Lernik Torossian

• Cell 310-980-6038 • [email protected] • Emergency referral line : 323-442-EYES

Children's 63 Hl~~~ITiJLES. ~ I USC Eye Institute LAC+USC We Treat Kids Beller 1-lf"-'-llHrAAFNfr,\'ORI< Vision is our Mission—Preserve, Protect, Restore

Nationally top ranked ophthalmology program — 22 consecutive years and counting!

J. BRADLEY RANDLEMAN, MD Professor of Ophthalmology, Director, Cornea, PLEASE JOIN US FOR External Disease, and Refractive Surgery Service AN EDUCATIONAL EVENING WITH FRIENDS & NEIGHBORS J. Bradley Randleman, MD is one of the nation’s top corneal researchers and surgeons and an expert on everything from LASIK to the latest Private 2 Hour CME in Beverly Hills FDA approved treatments for corneal cross­linking surgery. Date: Monday, Februay 13, 2017 Time: 7:00pm Location: ALENA REZNIK, MD Maggiano's Little Italy at The Grove Assistant Professor of Clinical Ophthalmology 189 The Grove Dr. Suite Z80 Dr. Reznik specializes in early detection and treatment Los Angeles, CA 9036 of glaucoma and cataracts as well as novel surgical techniques for advanced cases. Her research RSVP: Lina Poyzner at interests are minimally invasive glaucoma surgery [email protected] and new approaches to eye emergencies. She is a principal investigator on clinical trials for glaucoma medications and surgical devices. Program: Glaucoma (Optic Nerve Cupping), DAMIEN C. RODGER, MD, PHD presented by Dr. Reznik — 1 Hour Assistant Professor of Clinical Ophthalmology Retina (OCT Reading and OCT Enigmas), Dr. Rodger’s clinical interests include diabetic retinopathy, macular degeneration, medical presented by Dr. Rodger — 30 min. retina, retinal detachment, uveitis and vitreoretinal surgery.He has conducted research on the design, fabrication, and testing of high­density Cornea (Cross Linking), microtechnologies for retinal and spinal cord presented by Dr. Randleman — 30 min. prostheses, and has been instrumental in the development of other novel bioMEMS.

USC Roski Eye Institute • 323­442­6335 • www.usceye.org • Clinics conveniently located at: Los Angeles Clinic Beverly Hills Clinic Pasadena Clinic Arcadia Clinic USC Roski Eye Institute USC Roski Eye Institute USC Roski Eye Institute USC Roski Eye Institute 1450 San Pablo Street, 4th Floor 9033 Wilshire Boulevard, Suite 360 625 S. Fair Oaks Avenue, Suite 400 65 N. First Avenue, Suite 101 Los Angeles, CA 90033 Beverly Hills, CA 90211 64 Pasadena, CA 91105 Arcadia, CA 91006 323­ 442­6335 310­601­ 3366 626­ 796­0293 626­­ 446 2122 CURRICULUM VITAE ALENA REZNIK,MD SEPTEMBER 19, 2016

PERSONAL INFORMATION: Work Home USC Eye Institute 8568 Burton Way 1450 San Pablo Street 4806 Apt 102 Los Angeles, CA 90033 Los Angeles, CA 90048

Phone:323-4426383 Citizenship: US Fax: 323-4426412 Email: [email protected]

EDUCATION AND PROFESSIONAL APPOINTMENTS

EDUCATION: 2005 BS, Summa Cum Laude,Microbiology/Immunology/Molec ular Genetics, UCLA, LA 2009 MD, Johns Hopk ins University School Of Medicine, Baltimore

POST-GRADUATE TRAINING: 2009-2010 Internship in Internal Medicine, UC Davis Medical Center, Sacramento

2010-2013 Ophthalmology Residency, UC Davis Medical Center, Sacramento

2013-2014 Glaucoma Fellowship, Jules Stein Eye Institute, UCLA, LA

HONORS, AWARDS:

65 2016 Top Doctor 2016 Pasadena Magazine 2016 Rising Star 2016 Top Doctors

2012 ARVO Travel Grant ARVO, Ft.Lauderdale, FL

2007 AFAR Research Fellow Johns Hopk ins Hospital, Baltimore, MD

2008-2009 The Roothbert Fund Fellow Johns Hopk ins Hosptal, Baltimore, MD

2008-2009 Marilyn and Marshall Butler Johns Hopk ins Hospital, Baltimore, MD Scholarship

2007-2008 William W.More, Ph.D. MemoriaJohns Hopk ins Hospital, Baltimore, MD Scholarship[ 2007-2009 HIAS Scholarship NY

2007-2009 Ruth G White PEO Scholarship Johns Hopk ins Hospital, Baltimore, MD

2007-2009 Ethel O. Gardner PEOP Johns Hopk ins Hospital, Baltimore, MD Scholarship

2007 Travel Grant AGS WA

ACADEMIC APPOINTMENTS: 2014-current Assistant Professor of USC Eye Institute, USC, LA, CA Ophthalmology

TEACHING

DIDACTIC TEACHING: Institution USC

66 2014 Femtosecond Laser in 1Hr Lecturer Glaucoma Surgery

2015 Novel Techniques in 2Hrs Lecturer Glaucoma Surgery

2015 New Treatments in 2Hrs Lecturer Advanced Glaucoma

2015 Glaucoma Curriculum (USC 12Hrs Lecturer LAC Residency)

10/2015 Wet Lab “Minimally Invasive 3Hrs Lecturer Glaucoma Surgery/Trabectome”

11/2015 Wet Lab “iStent and Angle 3Hrs Lecturer Surgery”

11/2015 Wet Lab “Trabeculectomy” 2Hrs Lecturer

3/2016 OKAP Review Lectures 4 Hrs Lecturer

3/2016 Journal Club Glaucoma 2Hrs Lecturer

POSTGRADUATE MENTORSHIP: 2015-2016 Benjamin Xu, MD, PhD PGY4 2016 Career Guidance 2014-2015 Yohk o Murak ami, MD PGY4 2015 Career Guidance

SERVICE

DEPARTMENT SERVICE: 2014-current Complaince Committee USC Eye Institute 12/2015-current Residency Selection USC Eye Institute 07/2014-current Glaucoma Fellowship Selection USC Eye Institute 07/2014-current Postgraduate Education Committee USC Eye Institute

PROFESSIONAL SOCIET Y MEMB ERS HIP S : 2010-current American Academy of Ophthalmology

2013-current American Glaucoma Society 2010-current Women In Ophthalmology 2010-current American Society of Cataract and Refractive Surgeons

RESEARCH AND SCHOLARSHIP

67 EDITORSHIPS AND EDITORIAL BOARDS: 03/2015-current Editor Elsevier Editorial System

MAJOR AREAS OF RES EARC H INTER ES T Research Areas 1. Minimally Invassive Glaucoma Surgery 2. Novel Surgical Techniques in Glaucoma

PUBLICATIONS:

REFER E ED JOURNAL ARTICLES: Klimava, A, Akpek, E. Evaluation of Patients with Dry Eye Syndrome for Associated Medical Conditions. ARVO 2007. Lecture presentation, May 2007. Published in Cornea September 2010:29(9):1072. Reznik J, Salz, J, Klimava A. Late Unilateral Corneal Ectasia After PRK With Preoperative Topography Suggestive of FFK. AAO Refractive Subspecialty Day, November 2006. Lecture presentation; Published in J Refract Surg. 2008 Oct;24(8):843-7. Nagai N, Klimava A, Wen-Hsiang L, Handa J. CTGF is increased in BasalDeposits and Regulates Matrix Production through the ERK (p42/p44map k ) MAPK and the p38 map k signaling pathways. Published in Invest Ophthalmo l Vis Sci. 2009 Apr;50(4):1903-10.

REFER E ED JOURNAL ARTICLES IN PRES S : Format: Authors, Title. Journal. Volume #(Suppl ##):Page-Page, Year. PMID#, PMCID#, Narrative describing personal contribution.

REFER E ED REVIEWS , CHAPTERS, AND EDITORIALS: Reznik, A, Varma, R. (12/2015). Ab-Interno Subconjunctival Glaucoma Implant for Advanced Open- Angle Glaucoma CLINICAL COMMUNICATION: (CAS E REP ORTS , LETT ERS ) Authors. Title. Journal Volume(Suppl ##):Page-Page, Year. PMID#, PMCID#

ON-LIN E PUBLICATIONS: Reznik A, Mukundum G, Sonu R, Lin L. Imaging in immunohistologically proven orbital tumors. Submitted for a publication in Radiographics, May 2012 BOOKS, MONOGRAPHS, AND TEXT BOOKS: Authors. Title. Publication Volume(Suppl ##):Page-Page, Year.

LETTERS TO THE EDITOR: Authors. Title. Publication Volume(Suppl ##):Page-Page, Year. PMID#, PMCID#

ABSTRACTS AND PRES EN TA T IONS: Re znik A, Keltner J. Emergency department direct ophthalmoscopy and non-mydriatic funduscopic camera as a training tool. UC Davis research Symposium 2012. Lecture presentation. Reznik A, Weber C, Telander D, Morse L, Thirkill C. Inflammatory reactions complicating exudative age- related macular degeneration. ARVO 2012. Poster presentation. Akpek E, Klimava A, Thorne J, Martin D, Lekhanont K, Ostrovsky A. Evaluation of Dry Eye Patients for Presence of Underlying Sjogren’s Syndrome. AAO 2007 meeting. Lecture presentation.

68 Gupta A, Sadeghi P, Klimava A, Akpek E. Occult thyroid eye disease in patients presenting with dry eye symptoms. Tear Film and Ocular Surface Society Annual Meeting, Taormina, Sicily, September 2007. Lecture presentation. Reznik J, Salz, J, Klimava A. Late Unilateral Corneal Ectasia After PRK With Preoperative Topography Suggestive of FFK. AAO Refractive Subspecialty Day, November 2006. Lecture presentation; Published in J Refract Surg. 2008 Oct;24(8):843-7. Klimava A, Handa J. Increased Connective Tissue Growth Factor in Basal Deposits of Bruch’s Membrane of Human Maculae. American Geriatric Society Annual Meeting, May, 2007. Poster presentation. Klimava A, Handa J. Connective Tissue Growth Factor Expression in ARMD. Johns Hopkins Summer Activities Symposium, October 2006. Poster presentation. Reznik J, Kim A, Klimava A, Akpek E, Gatifloxacin 0.3% in treatment of bacterial keratitis; ARVO 2009. Poster presentation.

69