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Ocular System

Dry eye disease (DED)

Multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film (deficiency of the aqueous layer or excessive evaporation), and accompanied by ocular symptoms.

Multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film (deficiency of the aqueous layer or excessive evaporation), and accompanied by ocular symptoms.


Etiology

Tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiologic roles.

Aqueous-deficient DED/Keratoconjunctivitis sicca (KCS) (10% cases)

Characterized by inadequate tear production.
  • Sjogren Syndrome (primary or secondary)
  • Lacrimal gland deficiencies
  • Lacrimal duct obstructions
  • Systemic drugs affecting tear production

Hyperevaporative DED (> 80% cases)

Characterized by increased tear film evaporation
  • Meibomian gland dysfunction (M/C)
    • Meibomian glands line the eyelid margins and secrete oils that become the lipid layer of the tear film and reduce the evaporation of tears.
  • Poor blinking (low rate, incomplete lid closure)
  • Disorders of the lid aperture
  • Environmental factors (low humidity, high airflow)

Pathophysiology

Tear film:

  • 2-5 µm thick layer over cornea
  • Composed of three main components:

I. Lipid layer (M/superficial):

Produced by the meibomian glands of the eyelids
  • Functions to reduce the evaporation of tears

II. Middle aqueous layer (thickest component):

Produced by lacrimal glands (in the orbits), and accessory lacrimal glands (glands of Krause and Wolfring) in the conjunctiva

III. Basal layer

Composed of mucins, or glycoproteins, and is predominantly produced by conjunctival goblet cells.
  • Mucins enhance the spread of the tear film over the corneal epithelium through the regulation of surface tension.

Vicious circle: Hallmark of dry eye disease

Hyperosmolarity of the tear film damages the ocular surface directly/indirectly by inciting inflammation which may further decrease tear film stability

Presentation

  • Redness
  • Burning
  • Stinging
  • Foreign body sensation
  • Pruritus
  • Photophobia

Diagnosis

Eyelid examination:

  • Blink rate: Blinking is important to distribute the tear fluid over the ocular surface, and supports secretion from the meibomian glands.
  • Lid incongruity (e.g., ectropion, entropion)
  • Insufficient lid closure (e.g., facial nerve palsy)
  • Eyelid margin: Identify inflammation cause or any dysfunction of the meibomian glands with associated hyperevaporative disorder.

Noncontact infrared meibography:

Examination of the eyelid margins and meibomian gland orifices with expression of meibomian secretion
Meibomian gland dysfunction
Meibomian gland dysfunction: (a) Meibomian gland orifices on the eyelid margin blocked by thickened meibomian secretion; (b) Appearance of healthy meibomian glands on meibography | Messmer E. M. (2015). The pathophysiology, diagnosis, and treatment of dry eye disease. Deutsches Arzteblatt international, 112(5), 71–82. https://doi.org/10.3238/arztebl.2015.0071

Conjunctival examination:

  • Temporal lid-parallel conjunctival folds (LIPCOFs) in straight gaze: Result of increased friction between the lids and the conjunctiva.
Lid-parallel conjunctival folds
Lid-parallel conjunctival folds (grade 1) | Höh H, Schirra F, Kienecker C, Ruprecht KW. Lid-parallel conjunctival folds are a sure diagnostic sign of dry eye. Ophthalmologe. 1995;92:802–808.

Ocular surface examination:

Ocular surface staining with fluorescein/lissamine green:
  • Fluorescein stains both the precorneal tear film and epithelial erosions in the conjunctiva and cornea.
  • Lissamine green highlights superficially damaged cells with a defective mucin layer

Slit lamp examination:

Examination of the tear film
  • Tear film meniscus: Height of the tear film meniscus observed during slit lamp examination can provide clues about the presence of hyposecretory dry eye
  • Tear film break-up time (TFBUT): Describes the stability of the tear film.
    • It is determined after instillation of unpreserved fluorescein drops without topical anesthesia using a slit lamp with a cobalt blue filter
    • Normal values are between 20 and 30 seconds. Values below 10 seconds are definitely pathological.
Measuring tear film break-up time to assess tear film stability
Measuring tear film break-up time to assess tear film stability: (a) Invasive method, using fluorescein and the slit lamp with a cobalt blue filter; (b) Noninvasive method, without fluorescein, using a keratograph. The exact time and area of break-up are determined | Messmer E. M. (2015). The pathophysiology, diagnosis, and treatment of dry eye disease. Deutsches Arzteblatt international, 112(5), 71–82. https://doi.org/10.3238/arztebl.2015.0071

Schirmer test with/without anesthesia:

Measures the secretions of the lacrimal gland
Schirmer test to measure tear secretion
Schirmer test to measure tear secretion

Diagnosing Sjögren’s syndrome:

Patients with xerostomia in addition to dry eye must be investigated for the possible presence of Sjögren’s syndrome (SS).

Management

Artificial tears:

Mainstay of therapy for all severity grades of dry eye

Eyelid hygiene:

Consistent eyelid hygiene is the basic treatment for meibomian gland dysfunction
  • Hot compresses
  • Eyelid warming masks/goggles
  • Infrared heaters
  • Eyelid massage

Anti-inflammatory treatment:

To break the vicious circle of surface damage and inflammation, anti-inflammatory treatment is required in patients with moderate to severe dry eye disease.
  • Topical corticosteroids
  • Topical cyclosporine A: Immunosuppressant that inhibits the calcineurin–phosphatase pathway
  • Tacrolimus/pimecrolimus: Used in patients who cannot tolerate cyclosporine A
  • Tetracyclines: Bacteriostatic antibiotics with anti-inflammatory effect
  • Azithromycin: Antibiotic effect + anti-inflammatory capacities
  • Omega fatty acids: For ocular surface homeostasis

Punctal plugs:

Temporary occlusion of the tear ducts by small collagen or silicone plugs (punctal plugs) is effective in patients with severe aqueous-deficient dry eye disease.

Severe ocular surface disease:

  • Bandage contact lenses
  • Scleral lenses

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