Etiology of OAG

-        Specific cause of optic nerve damage unknown

-        Vision loss varies with IOP

-        Normal or low tension

-        Visual field loss increases with increasing IOP

-        Low IOP slows progression of loss 

Clinical presentation of OAG   (picture above)

-        Typical disk changes or vision loss = Glaucoma à slow and progressive vision loss

-        IOP < 21 mm Hg + typical disk changes and/or vision loss = Normal or low tension glaucoma à 30% of population

-        IOP > 21 mm Hg + disk and/or visual field changes = Open angle glaucoma

-        IOP > 21 mm Hg + no disk or visual field changes = Ocular hypertension à 5 to 7% of population; some progress to glaucoma 

Symptoms: 

-        Discomfort    

-        Halo vision

-        Loss of peripheral vision      

-        Scotomas à dark spot in the middle of vision (picture on right);

o   But floaters are due to break down of aqueous humor

§ Direct examination of the optic nerve (Optic nerve degeneration, Trabecular meshwork degeneration, Retinal nerve atrophy)

§ Visual field testing

§ IOP measurement (~22-40 mm Hg) à don’t see IOP greater than 40 in OAG

§ Other useful diagnostic tests

•  
  • Newer imaging technologies (GDx, OCT, HRT)
  • Pachymetry

Ocular HTN

• Whot to treat
• Goal of tx
• Monitoring

-        Who to treat?

o   4-20% will develop visual field defects within 5 years

o   Risk factors:   IOP > 25 mm Hg

                                                Vertical cup:disk ratio >0.5

                                                Central corneal thickness < 555 μm

o   Patient risks:               Family history of glaucoma               Black ethnicity

                    Severe myopia                                                One eye

-        Goal of therapy – reduce IOP à want at least 20% reduction in IOP

-        Monitoring – measure IOP, assess optic disk, visual field checks, ADRs and compliance

OAG 

• who to treat
• goal of tx

-        Who to treat?

o   All patients with optic nerve and visual field changes MUST be treated.

-        Therapy – stepwise, start with low concentrations of well-tolerated topical

-        Goal of therapy

o   Usually 30 to 40 % IOP reduction                

§  Reduction in mean IOP to < 10-12 mm Hg

§  As low as you need to go to stop progression

o   Control of diurnal IOP fluctuation throughout the day

o   High rate of response

o   No tachyphalaxis or long term drift à starts to go down and then back up

Pharmacologic tx of OAG

• what to start off with
• what to monitor
• when to change tx
• what to change tx

-        Start as single topical agent in 1 eye

o   Unless very high IOP or advanced vision loss

-        Monitor in 4-6 weeks to see response in IOP, 6 months for visual field and disk changes

o   Adjust and recheck in 4 to 6 weeks

o   Once at goal, check every 3-4 months

-        Visual field and disk changes – 6 months for the first year or two and then annually

If IOP control insufficient…

-        SUBSTITUTE different topical monotherapy

-        Add “adjunctive” topical therapy or switch to combination topical therapy

-        Add therapies until IOP is “controlled”

- If IOP control still insufficient

-        Perform laser trabeculoplasty (ALT/SLT), may be repeated à control IOP for 5 to 6 years and then it starts to wear off; It may be repeated once or twice depending on the therapy

- If IOP control still insufficient

-        Perform trabeculectomy and/or insert drainage device

β Blockers

• MOA
• ADRs
• Cautions/CI
• Common Agents

-        Mechanism of action: unclear, appears to be decreased aqueous humor production/ secretion

-        Only class proven in multiple placebo controlled trials to impact visual field

-        No activity on pupil or ciliary muscles

o   Should not cause blurred vision or night blindness         

-        Well tolerated: burning in eyes and dry eyes

-        Was first line agent

-        Dose BID in most cases

-        Cautions: Only use β₁ selective agents in patients with COPD, asthma

-        All – contraindicated in CHF

o   Nonselective: contraindicated in asthma, CHF and COPD

o   Selective: contraindicated in CHF

Nonselective: Carteolol, Levobunolol, Metipranolol, Timolol (Gold Std)

Selective: Betaxolol, Levobetaxolol

Sympathomimetics

• MOA
• ADRS
• Place in Tx
• Agents
• Cautions

Sympathomimetics

-     α₂ adrenergic agonists

-   Mechanism of action: dual action - appears to be decreased aqueous humor production and increase uveoscleral outflow à increasing the clearance of the aqueous humor

-   No activity on pupil or ciliary muscles                    

-   Well tolerated

-   Commonly first line agents

-        Alphagan 0.2% - benzalkonium chloride preservative

o   Soft contact lenses may absorb benzalkonium à contact lenses must be out of the eye for at least 15 minutes or else preservative can destroy the contact

o   Higher incidence of burning and allergic reactions

-        Alphagan P 0.15% - purite preservative 

o   More neutral pH

o   Less allergic reaction (reduced by 41%)

-        These are not interchangeable because different percentages! 

Brimonidine (Alphagan)

Apraclonidine (Iopidine)

PG analagues

• MOA
• agents
• ADRs
• Place in tx
• Products

-        Increase the outflow of the aqueous humor

-        PG F2-alpha

o   Latanoprost – prostanoid selective FP receptor agonist

o   Travoprost – synthetic prostaglandin F_2α analog – selective FP prostanoid receptor agonist

-        PG analogue

o   Bimatoprost – prostamide, synthetic structural analog of prostaglandin

-        Eye pigment changes, changes in eyelashes à MAJOR SIDE EFFECT

o   Makes light eyes (blue) into brown eyes

o   May be in one eye, not reversible à can change color in one eye only! Not bilateral! Pigmentation of iris is NOT reversible

o   Coloring turn brown due to melanin deposits

o   Latanoprost : 12% in US;  as high as 50% in Japan

§  Blue brown – 20%

§  Hazel, green-brown – 50%

o   Travoprost: 5% eye color changes; 60-70% lashes

o   Bimatoprost: 1-2 % eye color changes; 12-35% lashes

o   Bimatoprost (Latisse) topical gel: apply to lash line

o   Latanoprost – study demonstrated more effective at bedtime than even BID dosing

-        Bimatoprost (Lumigan vs. Latisse)

-        Have become first line

-        Good as monotherapy but most patient need more than one

-        Latanoprost: BAK preservative, #1 agent used, generic in 2011 possibly

-        Travaprost: Reformulated with sofZia, less ocular surface disease

-        Bimatprost: may have little better efficacy, hyperemia 

CAI

• MOA
• Cautions
• Agents

-        Mechanism – carbonic anhydrase catalyzes the reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. Inhibition in the ciliary processes of the eye decreases aqueous humor secretion.

-        May improve ocular perfusion – increased ocular blood flow and improved regulation

-        Dosed BID- TID à compliance problem

-        Sulfonamide agents

-        No effect on pupil or ciliary muscles

-        Similar reduction in IOP (3-5 mm Hg)

-        May be more effective as adjunctive therapy

-        Caution: dorzolamide and brinzolamide – sulfonamides

·       Dorzolamide – burning

·       Brinzolamide – foreign body sensation 

Symptoms:

-        Unilateral:

o   Red eye                                  

o   Opaque cornea           

o   Painful eyes

-        Prodromal symptoms 1-2 hours prior:

o   Halos around lights

o   Blurring/sudden loss of vision          

o   Nausea, vomiting, diarrhea

o   Bradycardia

      Signs: 

            Acute rapid increase in IOP > 40 mm Hg (40-90)                

    Corneal edema

Closed angle, narrow anterior chamber                    

Hyperemic conjunctiva

Edematous and hyperemic optic disk                                   

Pupil – semidilated and fixed

Treatment

-        Goal – rapid reduction in IOP to preserve vision

-        Protection of non-affectedd eye

-        Iridectomy is definitive treatment 

Pharmacologic therapies

o   Secretory inhibitor: Systemic CAI (Acetazolamide IV and/or PO 500 mg) 

o   Hyperosmotic

§  For most rapid IOP reduction

§  Parental Agents –

·       Mannitol  

o   Route: IV, preferred parental osmotic agent; Dose: 1-2 g/kg

o   ADR: Nausea, vomiting, headache, confusion, volume overload

o   Limit free water

·       Urea         

§  Oral Agents         

·       Glycerin→ ADR: Nausea, vomiting, hyperglycemia in diabetics

·       Isosorbide→ ADR: Nausea, vomiting, better tolerated than glycerin,

o   Pilocarpine

§  Parasympathetic mimicking agent

§  Increases out flow

§  Produces miosis which may worsen angle closure by increasing papillary block. (hold until IOP starts dropping)

§  1-2% q 5 minutes x 3 doses, then q 15-30 minutes until angle open.

§  Once affected eye stable- 1% q 6 hours, Contralateral eye - 1% q 6 hours

o   Dapiprazole (Rev-Eyes)→alpha-adrenerigc agent used to reverse mydriasis

§  effective for reversing mydriasis in patient whose pupils are dilated and does not increase papillary block or worsening the angle.

§  Not routinely used for CAG

o   Topical corticosteroids→Reduces ocular inflammation, reduces development of synechiae (adhesion)

o   Agent to additionally lower IOP (neuroprotectant)

§  β blocker (timolol)

§  α₂-agonist (brimonidine)

§  prostaglandin F_2α analog (latanoprost)