20 - Ocular Toxicity

Question 1

What are the 2 separate vascular systems of the eye?

Answer 1

• Uveal blood vessels

- Retinal vessels

Question 2

Purpose of cornea

Answer 2

• Transparent protective membrane (must remain transparent, allows light rays to reach the retina)
• Avascular (corneal epithelium, stroma, and endothelium)

Question 3

Purpose of lens

Answer 3

• Avascular and transparent

- Focus, accommodation

Question 4

What effect can chlorpromazine have on the eye?

Answer 4

• Pigmentation ranging from white to yellow to tan (5 stages)
• • Begins on anterior surface of the lens
• • Cornea is involved when lenticular pigmentation reaches grade 3

Question 5

What determines the effect of chlorpromazine on the eye?

Answer 5

• Dependent on cumulative dose
• • Unlikely to show if total dose < 500g
• • 90% of px w/ total cumulative dose > 2500g show ocular changes
• Px on high doses or on long-term low-dose regimens w/ chlorpromazine should have eyes checked annually

Question 6

What effect can corticosteroids have on the eye?

Answer 6

• Systemic, topical, nasal, inhaled steroids cause posterior subcapsular cataracts (PSC)
• MOA –> altered lens epithelium electrolyte balance and binding to protein of lens
• Generally reversible

Question 7

What determines the effect of corticosteroids on the eye?

Answer 7

• Unlikely in px who receive < 10 mg prednisone (or treated for < 1 year)
• Px on long-term oral steroid therapy should have eyes examined q6months

Question 8

What effect can quetiapine have on the eye?

Answer 8

• Manufacturer recommends eye exam at baseline and q6months throughout therapy
• Cataract development observed in dog model
• Some px have developed lens changes but no cataracts

Question 9

Aqueous humour is equivalent to ____

Answer 9

CSF

Question 10

Where is the aqueous humour found?

Answer 10

Flows between posterior surface of iris and anterior lens surface

Question 11

Normal intraocular pressure?

Answer 11

10-22 mmHg

Question 12

What can intraocular pressure > 28-30 mmHg cause?

Answer 12

Ischemic damage of the optic nerve causing glaucoma

Question 13

Sx of open-angle glaucoma

Answer 13

• Absence of pain
• Slow loss of peripheral visual field
• Often unnoticed by pt

Question 14

Causes of closed-angle glaucoma

Answer 14

• Happens to individuals that are genetically susceptible
• Narrow anterior chamber angle
• Caused by anything that dilates the pupil

Question 15

Which drugs affect intraocular pressure?

Answer 15

• Corticosteroids
• Phenothiazines (chlorpromazine)
• TCAs

Question 16

Affect of corticosteroids on IOP?

Answer 16

• Increased resistance to aqueous humour outflow
• Topical ophthalmic agents more likely than oral agents to increase IOP
• Prolonged continuous use (1600 mg beclomethasone or budesonide/day for 3 months or longer)

Question 17

Which drugs increase tear production?

Answer 17

• Cholinergics (pilocarpine)

- Adrenergic agonist (ephedrine)

Question 18

Which drugs are excreted in tears?

Answer 18

Oral erythromycin and rifampin (orange coloured tears)

Question 19

What is the uvea?

Answer 19

Iris, ciliary body, and choroid

Question 20

Sx of anterior uveitis

Answer 20

• Eye pain
• Conjunctival redness
• Photophobia and blurred vision
• Pupil small and responds sluggishly to light

Question 21

Which drugs are associated w/ anterior uveitis?

Answer 21

• Rifabutin

- Bisphosphonates

Question 22

Chloroquine and hydroxychloroquine effect on retina

Answer 22

• Accumulation in the choroid, RPE (retina pigment epithelium), ciliary body and iris
• Irreversible retinopathy
• Doses < 400 mg/day of hydroxychloroquine appear safe even after prolonged therapy

Question 23

Digoxin and digitoxin effect on retina

Answer 23

• Visual sx -> dyschromatopsia, flickering or flashes of light, coloured spots surrounded by coronas, snowy vision, hazy or blurred vision, glare sensitivity
• Vision disturbances can also occur at therapeutic doses of digoxin
• Inhibition of Na+K+ATPase (cone receptor function)
• Reversible w/in few weeks after dose reduction or discontinuation

Question 24

Which drugs affect the retina?

Answer 24

• Chloroquine and hydroxychloroquine
• Digoxin
• Indomethacin
• Tamoxifen
• Retinoids
• Quinine

Question 25

Indomethacin effect on retina

Answer 25

- Chronic administration of 50-200 mg/day for 1-2 years produces corneal opacities, paramacular depigmentation, decreased visual acuity, altered visual fields, blue-yellow colour deficits, and increased threshold for dark adaptation - MOA of retinotoxicity unknown - Colour disturbances return to normal after d/c

Question 26

Tamoxifen effect on retina

Answer 26

- Chronic high-dose therapy (180-240 mg/day for 3 years) = axonal degeneration in the macular and perimacular areas - Permanent decrease in visual acuity and abnormal visual fields - Crystallizes in the retina

Question 27

Retinoids effect on retina

Answer 27

- Poor night vision - Glare sensitivity - Problems w/ colour detection

Question 28

Quinine effect on retina

Answer 28

- Neurotoxic injury to retinal ganglion cells (permanent loss) and optic nerve - Retinal vasoconstriction - Blurred vision, central and peripheral scotomata, and complete blindness - Sudden visual loss can occur as late as 14 h after OD

Question 29

Purpose of optic nerve

Answer 29

Carries visual info from retina to several distinct areas of the CNS

Question 30

Ethambutol effect on optic nerve

Answer 30

- Decreased contrast sensitivity and colour vision - Dose-related alterations = blue-yellow and green-red dyschromatopsia - Optical neuropathy (central scotoma, visual field loss, decreased visual acuity) - 10% of px receiving 25-50 mg/kg/day show loss of vision between 1-7 months; reversible upon discontinuation

Question 31

What is a normal pupil size?

Answer 31

- 3-4 mm | - Equal to each other

Question 32

What causes pupil constriction (miosis)?

Answer 32

- Cholinergic agents - Opiates - Phenothiazines - Sedative hypnotics

Question 33

What causes pupil dilation (mydriasis)?

Answer 33

- Anticholinergics - Anti-depressants - Sympathomimetics

Question 34

Which drug causes jerk nystagmus?

Answer 34

Phenytoin

Question 35

What is the most common nystagmus?

Answer 35

Jerk nystagmus

Question 36

Which drugs can cause vertical nystagmus?

Answer 36

- Ketamine - Dextromethorphan - Phencyclidine

Question 37

What are some ocular complications of drug abuse?

Answer 37

- Quinine amblyopia (IV use of quinine-containing heroin) - Talc retinopathy - Infectious complications -> fungal & bacterial endophthalmitis - HIV-related retinitis - Cocaine -> diffuse vasospasm = retinal ischemia and blindness - “Crack eye” (corneal defects)