dry%20eye%20syndrome
DRY EYE SYNDROME

Dry eye syndrome is a clinical condition wherein the patient experiences ocular and conjunctival irritation due to decreased tear production and/or excessive tear evaporation.
It is associated with increased osmolarity of the tear film and inflammation of the ocular surface.

Goal of treatments are to relieve symptoms of patients, to improve visual acuity & quality of life of patients, to restore ocular surface & tear film to normal homeostatic state and to correct the underlying defect.

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
  • 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
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