Dry%20eye%20syndrome Treatment
Principles of Therapy
- Therapy is based on the severity of patient’s symptoms & is adjusted depending on the response
- Medication’s efficacy & safety, & patient’s convenience should be taken into consideration when subjecting the patient to long-term treatment
Goals:
- To relieve symptoms of patients
- To improve visual acuity & quality of life of patients
- To restore ocular surface & tear film to normal homeostatic state
- To correct the underlying defect
Pharmacotherapy
Tear Supplementation (Lubricants or Artificial Tears)
- Hypotonic or isotonic solutions that contain electrolytes, surfactants, & different types of viscosity agents
- Ideally, should be preservative-free, contains potassium, bicarbonate & other electrolytes, & have polymeric system that increases retention time
- Non-BAK (benzalkonium chloride) preserved drops may still be used in mild to moderate dry eye syndrome (DES)
- Mainly used to lubricate the ocular surface through their viscosity & mucoadhesive properties
- Replace tear volume
- Provide short-term, palliative relief of dry eye symptoms
- Do not replace the cytokines & growth factors, & have no anti-inflammatory properties but aids in decreasing inflammation by diluting or washing away inflammatory agents
- In general, do not alter ocular pathology
- Studies have shown that regular use improves tear break up time & eliminate dry spots, implying a reparative effect on superficial corneal epithelial cells & their glycocalyx
- Selected based on concentration & choice of electrolytes, osmolarity & type of viscosity or polymeric system, presence & type or absence of preservative
- No evidence yet has shown that any agent is superior to another
Preservative-free Lubricants
- May be used more frequently w/o thinking about possible toxic effects of preservatives
- Preservatives [eg benzalkonium chloride (BAK), disodium (EDTA)] can irritate the eye & aggravate dry eye symptoms
- Toxicity of BAK depends on its concentration, dosing frequency, tear secretion level, & ocular surface disease severity
- May be tolerated by patients w/ mild DES when used for ≤4-6x/day
- Preservatives [eg benzalkonium chloride (BAK), disodium (EDTA)] can irritate the eye & aggravate dry eye symptoms
- More important characteristic of lubricants to consider when managing patients w/ moderate to severe DES than the type of polymeric agent used
- BAK toxicity may be high in patients w/ moderate to severe DES due to reduced tear secretion & turnover
- Highly recommended in patients w/ severe dry eye w/ ocular surface disease & impaired lacrimal gland secretion, & in patients on various preserved topical medications for chronic eye disease
- Maybe available as liquid drops, gels, ointments, or ocular inserts
- Gels contain high molecular weight cross-linked polymers that have longer retention times than liquid preparations
- Ointments contain mineral oil & petrolatum that have longer retention times but produce more significant effects on vision than gels, hence should be applied at bedtime
- Ocular inserts are long-acting slow-release ocular rods of hydroxypropyl cellulose that is used to decrease repeated instillation of artificial tears; however, is limited by the discomfort of placing a foreign body in the inferior conjunctival sac
Electrolyte- or Ion- (eg Potassium, Bicarbonate) containing Lubricants
- Shown to be useful in treating ocular surface damage caused by dry eye
- Potassium is vital in maintaining corneal thickness
- Bicarbonate promotes the recovery of epithelial barrier function in damaged corneal epithelium & helps in maintaining normal epithelial ultrastructure
- Also maintains the mucin layer of the tear film
- Most artificial tears do not have the same composition as human tears, although some new formulations mimic the human tears’ electrolyte component
Hypo-osmotic Lubricants
- Important since increased tear film osmolarity (crystalloid osmolarity), which is commonly seen in patients w/ dry eyes, causes morphological & biochemical changes to the corneal & conjunctival epithelium, & is pro-inflammatory
- Solutes like glycerin, erythritol, & levocarnitine were added in ophthalmic drops to protect against high osmolarity adverse effects w/ the theory that it:
- Distribute between the tears & intracellular fluids which may help protect against cellular damage due to hyperosmolar tears
- Also, lubricants w/ high colloidal osmolality may be of value because addition to damaged cell surface may cause deturgescence which may lead to return of normal cell physiology
- Colloidal osmolality difference affects the net flow of water across membranes
Viscosity Agents of Lubricants
- Eg Carboxymethylcellulose (CMC), hydroxymethylcellulose (HMC), polyvinyl alcohol, polyethylene glycol, glycol 400, propylene glycol HMC, hydroxypropyl cellulose
- Macromolecular components added to tear supplements that cause increase in residence time which provide longer interval of patient’s comfort
- CMC was shown to bind & be retained by human epithelial cells
- Helps protect the ocular surface epithelium
- HMC coats & protects the surface epithelium, or helps restore protective effect of mucins
- CMC was shown to have cytoprotective properties that may promote re-epithelialization of corneal wounds
- Viscoelasticity of lubricant drop is important
- Must be viscous enough to remain on the corneal surface, w/o being washed away
- At the same time, it has to be elastic enough to maintain a coating on the ocular surface w/o breaking up due to the action of the opening & closing of the eyelids
- Another important property is “lubricity” or the ability of the lubricant to decrease the friction that occurs between the ocular surface & the eyelid margin as it goes up & down over the eye during blinking
- Blurring of vision, caking & drying on eyelashes are the limiting factors of high molecular weight viscous agents especially for patients w/ mild to moderate dry eye
- Castor oil or mineral oil are used to restore or increase the lipid layer of the tear film
- Hyaluronic acid (0.2%) was shown by studies to have longer ocular surface residence time than HPMC (0.3%) or polyvinyl alcohol (1.4%)
Anti-Inflammatories
- Indicated in patients w/ corneal disease who have persistent symptoms despite extensive use of artificial tears
Corticosteroids (Ophthalmic)
- Inhibit inflammatory response w/ fast onset of action
- Improves signs & symptoms of patients w/ or w/o Sjogren syndrome
- Studies have shown improvement of symptom severity scores, reduction of fluorescein & rose bengal staining, decrease in human leukocyte antigen-DR-positive cells, & increase in the number of goblet cells after 2-4 weeks of treatment of patients w/ moderate to severe dry eye
- Should not be recommended for long-term use due to its possible serious side effects
- Pulse therapy may be given to control exacerbations
Cyclosporine
- Inhibits T lymphocyte activation but does not affect activated T lymphocytes
- Reduces fluorescein staining of the cornea & increases basal & reflex tear secretion
- Alleviates symptoms of blurred vision, decreases need for artificial tears, & improves evaluation of global response to treatment
- Requires 2-4 weeks of continuous administration before significant improvement in symptoms is noted
- Improvement was noted for ≥6 months even when medication has been stopped
- An effective & less toxic alternative to ophthalmic corticosteroids
- When combined w/ ophthalmic corticosteroids, produces a faster anti-inflammatory response by stimulating lymphocyte apoptosis
- Optimizes ocular surface to prevent or reduce severity of LASIK-associated dry eye when used w/ lubricants & nutritional supplements in patients who are candidates for refractive surgery w/ dry eye
- May also improve corneal nerve regeneration or nerve sensitivity, & promote better & faster recovery of visual acuity
Tetracyclines
- Eg Doxycycline, Minocycline
- May help improve dry eye symptoms of patients w/ ocular rosacea or meibomian gland dysfunction
- Reduce inflammatory cytokines’ production (interleukin-1 & tumor necrosis factor α), restrain collagenase & matrix metalloproteinases’ activity, & have antiangiogenic properties
- Also reduce the load of bacteria on the eyelids
Secretagogue
Pilocarpine
- Muscarinic agonist used to stimulate production & secretion of tears & saliva in patients w/ Sjogren syndrome
- Noted to be more effective for dry mouth than for dry eye symptoms
- Dry eye symptom improvement was seen after 6-12 weeks of treatment
- May cause transient increase in numbers of goblet cells
- Reserved for patients w/ moderate to severe symptoms who can tolerate its cholinergic side effects
Biological Tear Substitutes
Autologous Serum
- Contains fibronectin, vitamin A, cytokines, growth factors, & anti-inflammatory substances
- Shown to be beneficial in patients w/ Sjogren syndrome, graft-vs-host disease, Stevens-Johnson syndrome, cicatricial pemphigoid, etc
- Improves dry eye symptoms, tear film break-up time (TFBUT) & rose-bengal staining scores as evidenced by studies compared to artificial tears
Salivary Gland Autotransplantation
- May replace deficient mucin & aqueous tear film phase
- Recommended only in patients w/ end-stage DES w/ absolute tear deficiency, conjunctivalized surface epithelium, & persistent severe pain despite punctal occlusion & hourly application of preservative-free lubricants
- Causes significant improvement in Schirmer test, TFBUT, & rose bengal staining
- Reduces discomfort & need of pharmaceutical ophthalmic lubricants
Non-Pharmacological Therapy
Punctal Plugs
- Recommended in patients w/ symptomatic dry eyes, Schirmer test (w/ anesthesia) <5 mm at 5 minutes, & has evidence of ocular surface dye staining
- Studies have shown significant decrease in tear production in patients w/ normal tear production for up to 2 weeks after plug insertion
- Should be avoided by patients w/ allergy to components of the plug, punctal ectropion, pre-existing nasolacrimal duct obstruction, untreated clinical ocular surface inflammation, or in patients w/ acute or chronic lacrimal canaliculus or sac infection
- Complications may include spontaneous plug extrusion, internal migration of a plug, biofilm formation or infection, or pyogenic granuloma formation
Moisture Chamber Spectacles
- Alleviates ocular discomfort due to dry eye
- Shown to increase interblink intervals
Contact Lenses
- Eg hydrophilic bandage contact lenses
- May be used to protect & hydrate the corneal surface in patients w/ severe dry eye syndrome (DES)
- Have been shown to improve visual acuity & comfort, decrease corneal epitheliopathy, & heal persistent corneal epithelial defects
- May be associated w/ small risk of corneal vascularization & corneal infection when used by patients w/ dry eyes