Integument: Glaucoma Lecture

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1

Glaucoma

  • Damage in the optic nerve - optic disc and nerve fibers - with defects in visual field.
  • Decreased peripheral vision and blindness if undiagnosed and not treated appropriately.
2

Open Angle

  • Chronic, develops over several years, most common type of glaucoma
3

Angle Closure

  • Acute or chronic, may be undiagnosed until routine eye exam or an acute event
4

Normal Tension

  • Changes in the eye consistent with glaucoma despite IOPs < 21 (treated as open angle unless surgery is required)
  • Some patients have normal IOP but have pathology in the eye that are indicative of glaucoma. Diagnosed as Open Angle.
5

Secondary (type of Glaucoma)

  • Use of anticholinergic drugs or long-term use of steroids (treat as open angle)
6

Angle Closure Glaucoma

  • Trabecular network is blocked by the iris. Characterized by a rapid increase in IOP. Majority of cases are chronic and asymptomatic until discovered during eye exam.
  • Treatment is prophylactic iridotomy followed by the same medications used to treat OAG if pressure remains high.
7

Risk Factors for Angle Closure Glaucoma

  • Increased age
  • Female gender
  • Family history
  • Shallow anterior chamber causing a narrow angle between the cornea and iris or tight contact between the iris and lens
  • Farsightedness
  • Certain medications
8

Medications that may precipitate Angle Closure Glaucoma

  • Anticholinergics/Antihistamines (ocular or systemic) - 1st generation antihistamine (Benadryl, Ditropan or Oxybutynin, Tolterodine (Detrol))
  • Tricyclic Antidepressants - Amitriptyline (most anticholinergic), Nortriptyline
  • SSRIs/SNRIs - Celexa/Effexor XR, Strattera
  • Decongestants - PSE, phenylephrine
  • Antipsychotics - Haloperidol, Risperdal and Seroquel (atypicals - weight gain symptoms), Zyprexa, Abilify
9

Acute Angle Closure Glaucoma

  • Very rapid increase in IOP
  • Symptoms: blurred vision, halos around the eyes reddening of the eye, severe pain and headache
  • Signs: dilated pupils, hazy cornea
  • Ocular emergency
  • Action needed - rapid decrease in IOP
  • Treatment: iridotomy by laser or surgery in affected eye and other eye
  • Medications - a combination of medications used to treat open angle glaucoma
10

Open Angle Glaucoma (OAG)

  • Patients often have no symptoms, but ocular examination reveals pathology indicative of glaucoma.
  • Most patients have increased IOP, but some have normal IOP with ocular changes associated with increased IOP.
  • If untreated, patient has optic damage followed by peripheral vision loss and then general vision loss.
  • Lowering IOP reduces disease progression and preserves vision
11

Risk Factors for Developing Open Angle Glaucoma

  • IOP > 21 or 22 mmHG
  • Aging
  • Family History - If your mother or father had glaucoma, they need regular eye exams 10 years after they were diagnosed
  • Ethnicity - African Americans and Hispanics have a greater risk OAP
  • Hypotension - Not getting enough blood flow
  • Corticosteroid use long term - Example: Prednisolone eye drops (long term use of ocular/oral steroids)
  • Severe myopia
  • Ocular trauma, optic nerve damage, optic disk hemorrhage (Car or motorcycle accident)
  • Reduced blood flow to the optic nerve
  • Increased susceptibility of optic nerve to ischemia
  • Increased vertical cup to disk ratio (>0.5)
  • Thin central cornea thickness (<555um)
12

Goals of Therapy for Open Angle Glaucoma

  • Decrease IOP from about 20-30% from baseline in both eyes
  • Decrease IOP <20 or 21 mmHg for most patients (Important to decrease so there is no further damage to the eye)
13

Lantanoprost (Xalatan) (0.005%)

One drop in each eye at bedtime (1 gtt ou qd hs)

14

Betaxolol (Betoptic S) (0.25%)

One drop in each eye twice a day (1 gtt ou bid)

15

Brimonidine (Alphagan P) (0.1%)

One drop in each eye twice a day (1 gtt ou bid)

16

Nasolacrimal Occlusion

  • After administration of the eye drop, they press their eye near the tear duct.
  • Wait for 1 to 2 minutes
17

Eyelid closure technique

  • Gently close eyelid and keep head tilted back
  • Do NOT immediately look down or squeeze eyes shut
18

Pharmacotherapy for Open Angle Glaucoma

First Line Medications

  • Ocular Prostaglandin analogues
  • Ocular Beta-blockers
19

Pharmacotherapy for Open Angle Glaucoma

Second-line medications*

*May be used 1st line in patients with contraindications to a Beta-blocker or a Prostaglandin Analogue

  • Ocular Alpha 2 adrenergic agonist Brimonidine
  • Ocular Carbonic anhydrase inhibitors
20

Pharmacotherapy for OAG

Third-line

  • Comination Products
21

Pharmacotherapy for OAG

Fourth-line Medications (rarely used)

  • Ocular Cholinergic (Miotic) agents
  • Systemic carbonic anhydrase inhibitors
  • Used often in acute angle closure glaucoma to rapidly decrease IOP
22

Ocular Prostaglandin analogues

  • MOA: improves uveoscleral outflow, and to a lesser amount, trabecular outflow, of aqueous humor to reduce IOP by 25-35%
  • Compared to Beta-blockers: Greater 24-hour IOP reduction, once a day administration, better control of nocturnal IOP, fewer systemic side-effects
  • Bimatoprost may be slightly more effect than other Prostaglandin Analogues (PAs)
23

Prostaglandin Analogues and modified Prostaglandin Analogue

  • Latanoprost (Xalatan) - 1 gtt ou qd hs
  • Bimatoprost (Lumigan) - 1 gtt ou qd hs
  • Travoprost (Travatan Z) - 1 gtt ou qd hs
  • Tafluprost (Zioptan) - 1 gtt ou qd hs (preservative free)
  • Lantanoprostene bunod - Vyzulta (modified prostaglandin analogue) - 1 gtt qd hs
    • Marginally effective compared than latanoprost and much more expensive
24

Ocular Prostaglandin Analogues

  • Advantages
    • No change in pupil size or accommodation
    • Lack of systemic side-effects for slightly possibility of headache
    • Good IOP reduction and good nocturnal control of IOP
    • Available as generic products
    • Administer 1 gtt ou qd nightly
25

Ocular Prostaglandin Analogues

  • Contraindications:
    • Macular Edema
    • History of Herpetic Keratitis (Herpes infection in the eye)
    • History of problematic or unwanted side-effects
    • Modified prostaglandin analogue, Vyzulta, has same advantages and contraindications; disadvantage - it is much more expensive than Prostaglandin Analogues
26

Side Effects of Prostaglandin Analogues and latanoprost bunod (Vyzulta)

  • Eyelid skin darkening and redness
  • Ocular inflammation and edema - they need to stop taking this drug
  • Stinging and Foreign body sensation upon administration
  • Loss of periorbital fat - eyes look sunken in and is irreversible
  • Dry eye, especially if using > 1 eye drop medication
  • Allergic conjunctivitis
  • Iris pigmentation - increases - light green and light blue eyes affected (irreversible)
  • Eyelash darkening - darkens eyelashes and causes them to grow (Latisse)
  • Eyelash overgrowth (hypertrichosis)
27

Ocular Beta-blockers

Mechanism of Action: Reduce IOP by reducing aqueous humor production by the ciliary body to reduce IOP by 20-30%

28

Ocular Beta-blocker

  • Advantages
  • Available as generic products
  • Do not affect pupil size or accommodation - miotics shrink pupils
  • Low incidence of ocular side-effects - need to do nasolacrimal occlusion or eye closure technique
  • BID dosing for most, QD dosing for some
29

Ocular Beta-blocker

  • Disadvantages
  • Systemic side effects if you do not do techniques to prevent these
  • Compliance
30

Ocular Beta-blockers

  • Timolol maleate (Timoptic) - 1 gtt bid or qd
  • Timoptic XE gelling solution - 1 gtt qd
  • Levobunolol HCl (Betagan) - 1 gtt bid
    • Cardioselective - best for individuals who have a pulmonary condition
  • Metipranolol - Optipranolol - 1 gtt bid
  • Carteolol - 1 gtt bid
  • Rel. Beta-1 (Cardioselective): Betaxolol HCl (Betoptic) and (Betoptic S - suspension) - 1 gtt bid
31

Ocular Beta-blockers

  • Systemic Side-effects if there is systemic absorption

Worsening or precipitation of:

  • Asthma, COPD, bronchospasm, respiratory depression
  • Bradycardia, hypotension, heart blockage
  • Masks signs of hypoglycemia in diabetes
32

Ocular Beta-blockers

  • Cautions and Contraindications for Use
  • Asthma, COPD, bronchospasm
  • Bradycardia, HF, heart block, atherosclerosis
  • Diabetes
  • Myasthenia Gravis
33

Ocular Beta-Blockers

  • Local Side Effects - very low incidence*
  • Stinging upon administration
  • Dry eye, especially if using > 1 eye drop medication
  • Ocular irritation
  • Allergic conjunctivitis
  • Blurred vision upon administration
34

Ocular Beta-Blockers

  • Patient counseling points:
  • Nasolacrimal occlusion or eye closure technique to avoid systemic absorption/side effects
  • They should not be using an ocular beta-blocker for glaucoma while taking an oral beta-blocker
  • Use proper administration technique to prevent systemic effects/absorption. Hypotension could worsen.
35

Ocular Alpha-2 Adrenergic Agonist

  • MOA: reduce aqueous humor production and increase in outflow with Brimonidine
  • Decrease IOP approx. 20-25% at peak effect 5 hours after administration
  • Brimonidine (Alphagan P) 1 gtt bid to tid - considered an alternative to BB or PA
  • Purite preservative causes fewer local side-effects than preservative benzalkonium chloride (does not cause as much dry eye)
  • Generics available
  • Apraclonidine (Iopidine) - 1 gtt bid to tid . Used post eye surgery to decrease IOP; Not effective for long term use; NOT USED FOR GLAUCOMA.
36

Ocular Alpha 2 Adrenergic Agonists

  • Side Effects

Local Side-Effects:

  • Eye irritation, itching, ocular edema
  • Allergic conjunctivitis
  • Foreign body sensation in eye
  • Dry eye, especially if using > 1 eye drop medication
  • Dry mouth

Systemic Side-Effects (if no or poor NLO or ELC):

  • Dizziness
  • Fatigue and Somnolence
  • Dry mouth
  • Dry nose
  • Headache
  • Bradycardia, Hypotension
  • Caution : Avoided in people who have cerebrovascular disease, impaired renal function, diabetes and cardiovascular disease.
37

Ocular Carbonic anhydrase inhibitors

  • MOA - decrease aqueous humor production to reduce IOP
  • Reduce IOP 15-25%
  • Considered an alternative to a PA or a BB
  • Dorzolamide (Trusopt) - 1 gtt bid to tid
  • Brinzolamide (Azopt) - 1 gtt bid to tid
38

Ocular CAIs

  • Side effects

Ocular (Local) side effects:

  • Ocular burning and stinging - common
  • Dry eye
  • Transient blurred vision; tearing
  • Allergic conjunctivitis
  • Rare - severe conjunctivitis, allergic dermatitis of the lids, corneal edema, photophobia

Systemic side effects (rare with ocular agents):

  • Exception:
    • Even if they do NLO and ECT: metallic or sour taste in their mouth occurs
    • Allergic conjunctivitis varies with this drug
39

Systemic (oral) CAIs

  • MOA - decrease aqueous humor production to decrease IOP
  • Reduce IOP by 25-40%
  • Used very short term in angle closure glaucoma to lower IOP
  • Acetazolamide, Methazolamide
  • Not normally used in Open angle glaucoma due to potential for serious systemic side effects: hypokalemia, anemia, diarrhea, kidney stones and systemic acidosis-fatigue, anorexia, weight loss, etc.
  • Relative contraindication with sulfonamide allergy
40

Netarsudil (Rhopressa)

  • Rho Kinase Inhibitor
  • MOA: increases aqueous humor outflow
  • Dosage regimen: 1 gtt qd pm
  • Place in therapy not completely determined
  • Considered an addition to first line therapy
  • More effective in patients with lower pre-treatment IOP so role may evolve to be useful in patients with progression of their glaucoma despite normal IOP
  • Side effects:
    • Pain during instilling
    • Hemorrhages (broken blood vessels)
41

Combination Products

  • Advantage - ease of administration, increased adherence; disadvantage cost (approximately $150+)
  • Responsible for drug ingredients and dosage regimens for combination products
42

Combination Products

  • Timolol and Dorzolamide (Cosopt and Cosopt PF) - 1 gtt bid
  • Timolol and Brimonidine (Combigan) - 1 gtt bid
  • Timolol and Latanoprost (Xalacom) - 1 gtt qd (available outside the U.S.)
  • Brinzolamide and Brimonidine (Simbrinza) - 1 gtt tid
  • Travoprost/Timolol, Timolol/Brinzolamide (Available outside of the USA)