1. Jane Goodwin BSc, MSc Nurse Practitioner
Drugs and the Eye

2. A&P

3. A & P

4. Pharmacology
A solution is a liquid vehicle for drug delivery to the eye.
Solutions have a shorter contact time.
Drops drain into lacrimal apparatus, into the nose and are absorbed systemically.

6. Drops needs to be sterile therefore free from bacteria, viruses, and fungi.
Preservatives are added to inhibit the multiplication of organisms.
Some solutions oxidise when exposed to air which can alter their chemistry.
The shelf life of drops are 1 month

7. Preservative free drops are supplied in single
dose units ‘Minims’ and used once
Most eye solutions are expressed as ‘per cent’. This translate to grams / 100ml.
EG – 0.5% Chloramphenicol = 500mg of Chloramphenicol in 100ml of solution.

8. Advantages of administering the drug locally is that is delivers the agent directly to the site of action.
Its effects are more immediate.
Smaller doses are used.
Systemic side effects are minimised.

9. Administration
Locally – direct into lower eye lid.

10. Subconjunctival injection – space between conj and sclera

11. Retrobulbar Injection - into muscle cone behind the eye

12. Peripubulbar – into space around the eye
Intraocular – into the eye eg Anterior Chamber
Intraocular Lens

13. Contact lens – impregnated and placed on cornea
Edge of lens

14. Absorption Drugs applied topically enter the eye through the cornea
There are 5 layers to the
Cornea
Descemet’s Membrane
Internal Layer
Endothelium

15. The outer most layer have a high lipid content (lipophilic)
The innermost layer have a high water content (Hydrophilic)
Drugs therefore have to require both lipophilic and Hydrophilic properties
PH of eye drops range between 3.5 – 10.5 which is to aid absorption
Factors that can influence absorption include trauma to the cornea – increasing the amount absorbed
Drugs can also bind to contact lenses therefore reducing their effectiveness and cause damage to the contact lens

16. Other factors affecting absorption
Drops can be lost from the eye before they cross the cornea.
Occlude Inner Canthus

17. Types Antibiotics Antihistamines Anti-virals
Mydriatics – dilation of pupil 2 types – parasympatholytic & Sympathomimetic
Miotics – constrict the pupil
Glaucoma drugs -Carbonic anhydrase inhibitors, Beta-blockers, Alpha 2 agonists
Steroids
Local anaesthetics
Diagnostic
Tear Replacement

18. Mydriatics - are used to dilate the pupil for the following reasons
To examine the retina
To maintain dilatation of the pupil in uveitis, with corneal ulcers, severe corneal abrasions and after surgery
To break down posterior synaechiae in uveitis
To allow a cataract to be extracted and retinal surgery
Refraction in children

19. 2 types
Parasympatholytics – which cause mydriasis and cycloplegia (relaxing circular iris muscle causing paralysis of the ciliary muscles)
E.g. atropine, tropicamide and cyclopentolate
Sympathomimetics - mydriasis (stimulating the radial muscle of the iris to contract causing the pupil to dilate)
E.g. adrenaline and phenylephine

20. Side Effects and Cautions
Causes blurred vision therefore driving not advised
Systemic absorption can occur causing anticholinergic effects such as tachycardia, dizziness, dry mouth, constipation and hypertension
Due to risk of systemic absorption should be used with caution in people with hypertension, heart disease and thyrotoxicosis
Can cause a rise in intra ocular pressure (IOP)
Contraindicated in glaucoma especially narrow angle glaucoma
Contra-indicated with MAOI’s (monoamine oxidase inhibitors) – risk of hypertensive crisis

21. Miotics
Miotic drugs constrict the pupil and ciliary muscle which opens up the drainage channel for aqueous flow. It main use is in the treatment of Acute Glaucoma
Pilocarpine 1% 2% and 4% (most common)

22. Acute Glaucoma IS SIGHT THREATENING!
Is a sudden rise in intra ocular pressure. This is caused by an acute blockage in the drainage system – stopping the aqueous humour drain from the eye. Symptoms include a red painful eye, reduced vision, nausea, headache and can be in one or both eyes.

23. Normal Flow
Acute blockage

24. Miotics - Cautions
Causes - Headache/browache in long term use.. Usual burning itchy and sensitivity with drops.
Blurred vision and restricted vision -
Patient on long term treatment need monitoring for field s and IOP’s.
Avoid in conditions where a miosed pupil would be undesirable ie Iritis and Uvietis

25. Chronic Open Glaucoma
The angle is open – but other parts of the drainage system can be affected.
Slow onset, irreversible sight loss, hereditary, more common in elderly and Afro-Caribbean's
Caused by a persistent low grade rise in intraocular pressures (normal readings are between mmHg). Therefore readings above mmHg may require monitoring and treatment.
It causes damage to the retinal nerve fibres known as cupping of the disc making the disc pale and a change in shape.

26. Circulation of Aqueous
= problem with aqueous drainage

27. Other Glaucoma Drugs Carbonic anhydrase inhibitors Beta blockers
Alpha 2 agonists
Prostaglandin analogues
Sympathomimetics
Combinations of the above i.e. Carbonic anhydrase inhibitors and Beta blockers

28. Carbonic anhydrase inhibitors
Carbonic anhydrase is an enzyme necessary for the production of aqueous. These drugs therefore reduce the production of aqueous.
Uses - Acute, Chronic and secondary Glaucoma
Ocular SE – Local eye irritation and taste disturbance
Systemic SE –drowsiness, GI, nausea, upset potassium levels and is a weak diuretic
Types – Oral and IV -Acetazolamide (Diamox) not used long term mostly in acute cases
Examples - Topical – Dorzolamide (Trusopt) and Brinzolamide (Azopt)

29. Beta Blockers
Are relatively safe, efficacious and usually first line treatment.
Work by affecting the production of aqueous in the ciliary body and increase the outflow of aqueous in trabeculae meshwork
Uses – primary open angle glaucoma
Ocular SE – dry eyes, blurred vision, eye irritation
Systemic SE – bronchospasm in asthmatics, bradycardia and can mask manifestations of hypoglycaemia
Examples – Timolol (Timoptil), Betaxolol (Betoptic), Carteolol (Teoptic) and Levobunolol (Betagan).

30. Alpha 2 Agonists
Is used as add on therapy when beta blockers are not enough to reduce IOP or when B’blockers are contra-indicated.
Works by enhancing drainage from the eye and decreasing production of aqueous.
Uses – primary open angle glaucoma and pre op
Ocular SE – dry eyes, blurred vision, eye irritation and stinging
Systemic SE – Headache, changes in heart rate, rhythm an BP as well as anxiety and tremor
Examples – Apraclonidine (Iopidine) and Brimonidine (Alphagan)

31. Prostaglandin Analogues
Work by increasing uveoscleral outflow
Uses – open angle glaucoma and *ocular hypertension
Ocular SE – brown colour changes in the iris and lengthening of the eyelashes
Examples – Bimatoprost (Lumigan) and Latanoprost (Xalatan)
*NB – ocular hypertension is when the IOP is normal but there is signs of the disease from the visual field tests and optic disc defects.

32. Sympathomimetics
Dipivefrine is a pro drug of adrenaline. It is claimed to pass more rapidly than adrenaline through the cornea and is then converted to the active form.
Works by increasing the outflow of aqueous through the trabecular meshwork.
It is contra indicated in angle closure glaucoma because it is a mydriatic (dilating drug)
Ocular SE – severe smarting and stinging
Systemic SE – caution with pt’s with hypertension and heart disease.

33. Tunnel Vision

34. Coffee Time !

35. Microbiology of the eye
Micro-organisms can gain access as a result of:-
Direct Contact e.g. Herpes simplex
Air-Bourne infections
Insect-Bourne infections e.g. Trachoma
Migration of bacteria from nasopharynx
Trauma
Infected contact lenses
Infected eye drops and lotions
Infected instruments

36. Conjunctivitis – most common cause of Red Eye
Types of conjunctivitis
Bacterial
Viral
Allergic
Secondary
Chronic

37. Bacterial Conjunctivitis
Acute onset
Bilateral
Red, gritty, sore, puffy lids and purulent discharge
Resolves within 5-10 days
Rx G.Chlor or Fusidic acid

38. Viral Acute onset Related to other URTI Likely to be Unilateral
Red, gritty sore, Watery discharge
Corneal staining with Fluorescien
Diagnosis difficult in Primary Care therefore refer a unilateral red eye if no improvement within 48hrs of Rx
Last for 3 -4 weeks

39. Allergic Acute onset Bilateral Hx of exposure to allergens
Hx Atopy or Fhx
Sx – very itchy,watery, chemosis (jelly like) of conj, puffy lids, follicles on Tarsal Plate (under eye lid)
Responds to antihistamines, remove from cause
Should respond immediately to Rx
Prophylactic treatment recommended.

40. Drugs for allergic conjunctivitis
Topical antihistamine drops (H1 antagonists) – antazoline, azelastine and levocabastine provide rapid relief and can be used for up to 4/52.
If prolonged relief is required a mast cell stabiliser eg lodoxamide, nedocromil and sodium cromoglycate
Start their use ideally 1/12 before allergy season
Diclofenac is also licensed and steroids can be used only after examination on a slit lamp and seen by an ophthalmologist
Eye sx alone are best treated topically, however if a pt has other sx oral antihistamines are recommended

41. Secondary Herpes – Dendritic Ulcer Corneal Abrasion
Corneal Ulcer, with pus in AC
Corneal Foreign Body

42. Chlamydia Serotypes D-K are genital
Serotypes A-C causes Trachoma – worlds leading cause of blindness
It attacks mucous membranes & inhibits host cell protein synthesis
Topical Rx tetracycline ointment QDS 6/52
Systemic - Doxycycline, Tetracycline or Erythromycin
Under surface of eye lid (sub tarsal plate)

43. Chloramphenicol Broad Spectrum Abx with least overall resistance
It is a bacteriostatic and inhibits bacterial syntheses by reversibly binding to ribosome's which disrupts peptide bond formation and protein synthesis
Acts on Gram +ve and –ve organisms
MUST be stored in the fridge
Bathe away discharge before use
Regime – 2 hourly in severe cases for 24 hours then QDS for 5 – 7 days.

44. Side Effects/Cautions
Stinging, local discomfort
Greater chance of allergy than Fusidic acid
Aplastic anaemia (bone marrow suppression) check FHx and GH
Gray Baby syndrome
Avoid in pregnancy, breast feeding and with caution in under ones
Check bloods regularly if using long term
Not sensitive to Pseudomonas

45. Fusidic Acid
Is a bacteriostatic and bactericidal agent with a steroid-like structure of no glucocorticoid activity.
Inhibits bacterial protein synthesis and prevents elongation of the peptide chain.
It is chemically unrelated to any other antibacterial in clinical use
There is no cross-resistance nor cross sensitivity between Fusidic acid and other antibacterials
It is microcrystalline giving it sustained release properties therefore concentration is maintained for 12 hours in lacrimal fluid and aqueous humour (BD dose regime)

46. Side Effects/Cautions
Stinging, local discomfort, burning redness and watering on initial instillation
Allergic reactions are less than Chloramphenicol
Not known to be harmful in pregnancy
Is excreted in breast milk – not known to be harmful – weigh up risks/benefits.
Can be local variations of resistance

47. Antibiotic efficacy against common ocular pathogens
* Known Activity
Fusidic Acid
Chloramphenicol
Staph’ Aureus *
Staph’ epidermis
Strep’ pyogenes
Sensitive
Strep pneumoniae
Gonorrhoea
Escherichia coli
Resistant
Haemophilus influenzae
Pseudomonas

48. OTC products for conjunctivitis
Brolene and Golden Eye are antiseptic not antibiotic
They are of little use
They commonly cause an allergic reaction which compounds the patients symptoms
They are used in acanthamoeba keratitis (organism grown on contact lenses)
Chloramphenicol is now OTC

49. Advice to patients
Conjunctivitis is self limiting and will resolve without Rx in mild cases
Clean eyes with cooled boiled water
Avoid touching and rubbing eyes
Wash hands after touching eyes
Avoid sharing towels/face cloths
Throw away make up that may be contaminated
Contact Lenses SHOULD NOT be worn due episode and leave for 48hours after finishing Rx

50. Contact Lenses
Types include soft, hard (gas permeable) disposable and extended wear.
Should not be worn during infections
Strict hygiene, cleaning and maintenance should be encouraged at all times
Soft CL are not compatible with drops that contain preservatives
Soft CL absorb Fluorescein and permanently stain

51. Instilling eye medication
Drops contain preservatives to prevent micro-bacterial growth
1/12 shelf life-throw out after
Clean discharge away first
Wash hands
Pull on lower eyelid to make a ‘well’ – drop solution or squeeze ointment into eye.
Avoid touching the tip of the bottle with the eye

52. Anti-virals
Herpes Simplex and Zoster

53. Acyclovir (Zovirax) comes in tablet and oral form and used for both types of herpes. Ointment is used 5 x a day and compliance is essential to ensure disruption of the DNA synthesis.
Pt’s should be monitored by an ophthalmologist as corneal scarring will occur
Side effects from topical Rx include irritation, stinging, itching, inflammation, pain and photophobia

54. Oral & Topical Steroids
Overdose or prolonged use can exaggerate some of the normal physiological actions of corticosteroids leading to mineralocorticoid and glucocorticoid side effects

55. Adrenal suppression amongst many things can cause Conjunctivitis.
Suppression of infection - therefore masks sx and exacerbates infections e.g. bacterial, viral and fungal
Causes – next slide

56. Cataract
Systemic steroids have a high risk (75%) of inducing a cataract

57. Glaucoma

58. Papilloedema
Sclera Thinning

59. Amiodarone Used in Rx for arrhythmias
Has a very long half life extending to several weeks.
SE’s can cause reversible corneal deposits (causes night glare), Optic neuritis – causing blindness
Treatment MUST be stopped and expert advice taken

60. Amiodarone
Blurred Vision
Optic Neuritis
Corneal Deposits

61. Antimalarials
Hydroxychloraquine and chloroquine are also used to treat Rheumatoid arthritis and SLE
CAUSES
Ocular Toxicity
Retinal damage & Keratopathy
(Corneal Deposits)

62. Royal College of Ophthalmologists
Recommend regular ophthalmic examination
Arrangement should be made locally between prescriber and ophthalmologist and agreed management plan for those on long term treatment of 5 yrs or more.
Va - distance and near recorded before, during and after Rx
Any visual impairment needs to be assessed and recorded before, during and after Rx
Any deterioration in vision MUST be assessed by ophthalmologist
Children receiving treatment for Juvenile Arthritis should be screened for Uveitis

63. TB Drugs
Ethambutol is included in a Rx regime when there is resistance to other TB drugs
SE’s – Loss of VA
Colour Blindness
Reduction and restriction in Visual Field
The dark patches show loss of vision

64. Side effects are more common when given in excessive doses
The drug should be stopped at the earliest presentation of ocular toxicity
Always advise pt’s to stop Rx and seek medical and ophthalmic help
Eye sight is nearly always restored if discontinuation of drug is early enough
Pt’s who may not understand warnings about visual sx should be given an alternative TB drug if possible
Children under 5 may not be able to report changes

65. Visual Acuity should be tested before starting treatment

66. Other Systemic Drugs Tamoxifen – oestrogen antagonist
Causes visual disturbances including corneal changes, cataracts and Retinopathy
Digoxin Toxicity – causes visual disturbance
MAOI’s (monoamine oxidase inhibitors) – causes blurred Va, Nystagmus and interacts with Sympathomimetics e.g. Phenylephrine (drug used to dilate pupil)
Retinopathy

67. Diagnostic Drops Fluorescein – Orange die
Stains conjunctival and corneal epithelial damage e.g. corneal ulcers, erosions, and conjunctival or corneal abrasions

68. Assessment of dry eye
Tonometry

69. Fluorescein is available as drops or as paper strips
Fluorescein grows pseudomonas therefore is always used in single dose units

70. It is also used IV so photographs can be taken of retinal blood vessels, optic disc and macula
Scar

71. Rose Bengal
Stains dead conjunctival and corneal epithelium in dry eye syndrome.
It causes pain and stinging on instillation
Dead Corneal epithelium

72. Dry Eyes
3 Layers of Tear Film

73. Artificial Tears
Are used for dry eyes and must be used as often as possible to keep the eyes feeling comfortable.
Can be as often as every hour
Once diagnosed – drops will be necessary for life
Dry, hot, windy conditions exacerbate sx also reading, using PC (Starring for long periods)

74. Types Drops include – Hypromellose, Tears Naturelle, Liquifilm
Gel tears – ‘Viscotears’ – bind with own natural tears and stay in eye for longer
Ointments – used at night, stay in eye for longer, can cause blurring of vision.

75. List 3 things you’ve learnt1 2 3
Try and remember them!!!!

76. Resources http://www.goodhope.org.uk/departments/eyedept/dropsfor.htm
Maclean H (2002) The Eye in Primary Care, Butterworth Heinmann.
Galbraith et al (1999) Fundamentals of Pharmacology, Addison Wesley Longman Ltd
Spalton et al (2006) Atlas of Clinical Ophthalmology 3rd Ed, Elsevier Mosby

77. Any Questions