教育演講1:與全身性疾病相關的眼疾--診斷與治療
Ocular Manifestations and Treatments of Eye diseases related to Systemic Disrders

程 序 表

E1-2
Dry Eye and Systemic Diseases
侯育致
臺大醫院眼科部

  Dry eye is a multifactorial disease of the tears and ocular surface with symptoms of discomfort, visual disturbance, and tear film instability. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Dry eye is recognized as a disturbance of the Lacrimal Functional Unit, comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves. The major classes of dry eye are aqueous tear-deficient dry eye (ADDE) and evaporative dry eye (EDE). ADDE has 2 subclasses: Sjogren syndrome (SS) and non SS. Primary SS consists of ADDE with symptoms of dry mouth, in the presence of autoantibodies (anti–SS-A and/or anti–SS-B, rheumatoid factor, ANA), evidence of reduced salivary secretion and with a positive focus score on minor salivary gland biopsy. Early markers of SS include autoantibodies to salivary protein-1(SP1), parotid secretory protein (PSP), and carbonic anhydrase VI (CA6). Secondary SS consists of the features of primary SS together with the features of an overt autoimmune connective disease, such as rheumatoid arthritis, which is the most common, or systemic lupus erythematosis, polyarteritis nodosa,Wegener’s granulomatosis, systemic sclerosis, primary biliary sclerosis, or mixed connective tissue disease. The most common non SS is age-related dry eye (keratoconjunctvitis sicca). EDE causes can be intrinsic (meibomian gland dysfunction), or extrinsic (contact lens wearing).
  Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by swelling, tenderness, and destruction of at least 1 synovial joint. Dry eye is the most common ocular manifestation. Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem disease which may affect eyes. Dry eye is common in SLE. Wegener’s granulomatosis (WG) is a systemic vasculitis and ocular involvement occurs in 30-50% of patients. Lacrimal gland involvement leads to dry eyes. Stevens-Johnson syndrome is an acute, generally self-limited, inflammatory disorder of skin and mucous membranes (vasculitis). Toxic epidermal necrolysis may cause conjunctival scarring and symblepharon, keratinized, vascularized cornea, and severe dry eye. Cicatricial pemphigoid is an autoimmune reaction at basement membrane blisters of skin and mucous membrane. It may progress to subconjunctival fibrosis, symblepharon, ankyloblepharon, keratinizated conjunctiva and cornea, and corneal perforation.
  Endocrine system disorders can cause dry eye including diabetes mellitus (DM), thyroid disorders. Decrease corneal sensation and tear secretion (neurotrophic keratopathy) in DM cause corneal erosion, delayed epithelial wound healing, and dry eye (53%). The pathophysiology of Graves' ophthalmopathy is lymphocytic infiltration of orbital tissues, antoantibodies against TSH receptor, causing exophthalmos, lid retraction, and EDE.
  Rosacea is an inflammatory facial skin disorder (telangiectasias, erythema,, hypertrophic sebaceous glands, and rhinophima). Its prevalence rate ranges from 1.3% to 2.1% (33% ocular rosacea). Ocular rosacea may manifest meiboniam gland orifice obstruction, excessive seborrheic secretion, and collarettes around the eyelashes, causing dry eye and meibomian gland loss. Prevalence of psoriasis is 2 % of population and 10 % of psoriasis patients has blepharitis, conjunctivitis, keratitis and xerosis.
  Graft-versus-host disease (GVHD) is T-cell mediated processes derived as a result of allogeneic hematopoietic stem cell transplantation. Lacrimal gland showed a prominent fibrosis and an increase in CD34+ stromal fibroblasts in the glandular interstitium in addition to infiltration of Tcells into the periductal areas. Dry eye is the most frequent ocular complication in chronic GVHD. Meibomian gland dysfunction is frequently associated with severe dry eye.
  Dry eye increases with age; women are more frequently affected than men and dry eye is considerably more prevalent in women postmenopause. Women with low levels of 17b-estradiol (estradiol), estrone, and testosterone had more severe dry eye. Serum oestrogen appears to be a key factor in meibomian gland dysfuction. Postmenopausal women, particularly oestrogen-only therapy is associated with an increased risk of dry eye.
  Rare dry eye in healthy children. Dry eye is a potential indicator of systemic diseases. 15% of children with type 1 diabetes 11% of patients with juvenile rheumatoid arthritis had dry eye symptoms. Dry eye in a pediatric patient warrants a systemic work-up.
  When patients present with ocular complications that are caused by a systemic disease, you must not only treat the ocular symptoms, but also manage the underling condition. Dry eye treatments include artificial tear substitutes, gels and ointments, moisture chamber spectacles, punctual plugs occlusion, anti-inflammatory agents (topical cyclosporine A, corticosteroids, 0.03% tacrolimus (FK-506), 5.0% lifitegrast? and oral tetracycline or doxycycline, and omega-3 fatty acids), autologous serum, secretogogues (pilocarpine, cevilemine, 2% diquafosol, and rebamipide). Surgical treatments for dry eye include amniotic membrane transplantation, tarsorrhaphy, lid surgery, and salivary gland autotransplantation. More advanced cases that involved manifestations of retinopathy and scleritis may need systemic immunosuppression.