Causes of Blindness

A. Epidemiology

World Health Organization (WHO) data estimate ~40 million "blind" in 1990s
Low vision in another ~110 million persons in 1990s
Definitions
1. WHO blindness definition: visual acuity <20/400
2. USA blindness definition: best visual acuity <20/200
3. Low vision is <20/40 in USA, <20/60 by WHO
Worldwide, 80% of blindness considered preventable or curable
90% of blindness occurs in developing world

B. Four Causes of Visual Loss

Refractive Error
1. Check with pinhole; needs refraction
2. Glasses, contacts, surgery
Media Opacities
1. Cataracts
2. Chemical/physical trauma
3. Hemorrhage
4. Keratitis
Macular Disease
1. Age Related Macular Degeneration (ARMD)
2. Diabetic edema
Optic Nerve Disease
1. Neuritis
2. Compression - including glaucoma
3. Nerve transection
4. Inherited disorders
5. Metabolic disorders

C. Main Causes of Blindness in USA

Age-Related Macular Degeneration (AMD) [4]
1. Leading cause of visual impairment over age 50 in white persons
2. Affects retina, macula and choroid
3. Current therapy is only mildly effective
Glaucoma [2]
1. Leading cause of blindness in blacks
2. Important cause of blindness in whites
3. Causes an optic neuropathy due to compression of optic nerve
4. Elevated intraocular pressure causing the compression is detectable and treatable
Cataracts [3]
1. Main cause of low vision (but not blindness) in USA
2. Blindness usually preventable by surgery
Diabetes [4]
1. Leading cause of blindness in working age Americans, especially blacks
2. Overall, blindness is 25 fold more common in diabetics versus non-diabetics
Trauma

D. Worldwide Causes of Blindness

Cataracts
1. Leading cause of blindness worldwide
2. Responsible for ~50% all cases
Trachoma [5]
1. Caused by Chlamydia trachomatis serotypes A, B, Ba and C
2. Repeat infections with these serotypes is required for clinical disease
3. Occasionally, genital serotypes D-K can cross into the eye and cause trachoma
4. Corneal scarring 10-20 years after infection
5. Treatment of infection completely prevents scarring and blindness
6. Infection is endemic in many parts of developing world (main cause of blindness)
7. Azithromycin 1-3 doses clears >93% of infections and prevents blindness
8. Azithromycin is more effective with better compliance than topical tetracycline
Onchoceriasis
1. "River Blindness" vector is black fly
2. Reaction to dead worms damages ocular structures
Xerophthalmia (vitamin A deficiency)
1. Night Blindndess
2. Dry eye with Bitots spots on conjunctiva; leads to corneal ulceration
HIV Infection
1. Affects lacrimal gland, cornea, choroid, retina, optic nerve
2. Increasing epidemic in developing countries

E. Blindness Prevention in Developed Countries [10,11]

Routine visual screening in primary care setting has not been shown to benefit
Routine eye professional screening for glaucoma is strongly advocated
Timely identification of eye diseases is critically important to prevent blindness
Optimizing Management of Systemic Diseases
1. Critically important for long term blindness prevention
2. Diabetes mellitus is most important
3. Hypertension and hyperlipidemia also important
Certain types of macular degeneration may benefit from anti-oxidants

F. Vitreous Hemorrhage [6]
[Figure]: "Schematic of the Eye"

Hemorrhage into the vitreous humor
Incidence of spontaneous vitreous hemorrhage is ~7 per 100,000 persons per year
Causes
1. Diabetic Retinopathy (~30%)
2. Retinal Tear (~30%)
3. Retinal Vein Occlusion with proliferative retinopathy (~10%)
4. Posterior vitreous detachment (<10%)
Pathogenesis of Bleeding
1. Pathologic disruption of normal vessels
2. Bleeding from diseased retinal vessels
3. Bleeding from new-vessels (neo-vascularization vessels are typically abnormal)
Consequences of non-clearing vitreous hemorrhage
1. Hemosiderosis bulbi
2. Glaucoma - ghost cell, hemolytic, and hemosiderotic types
3. Main problem is difficulty clearing blood cell debri
Current treatment of non-clearing vitreous hemorrhage is pars plana vitrectomy

G. Keratitis [7]

Causes
1. Neurotrophic Keratopathy - nerve palsy, often trigeminal and/or facial nerve
2. Dry Eyes - without or with (Sjogren Syndrome) systemic symptoms, contact lenses
3. Rheumatoid Arthritis - includes direct inflammatory component
4. Corneal infection - chlamydia, bacterial (contact lenses), fungal, trauma
5. Bacterial (Pseudomonas, >90%) and fungal (Fusarium, <5%) keratitis associated with contact lens wear [12]
Pathogenesis
1. The cornea is normally bathed in tears
2. Tears contain corneal epithelial growth and repair factors
3. Bioactive molecules include various growth factors and cytokines
4. Stimulation of normal tear function is partially mediated by the trigeminal nerve
5. Normal tearing requires eyelid sensation, also the trigeminal nerve
6. Substance P, a transmitter of the trigenimal nerve, may play a role
7. Substance P + IGF-1 stimulate integrin receptors (alpha-5 and ß1; see below)
Usually presents as reduced vision with pain, often with red eye
Physical Exam
1. Corneal epithelial erosion - direct visualization and abnormal fluorescein pattern
2. Hypolacrimation and/or hyperemia commonly found
Treatment [8]
1. Insulin-like growth factor 1 (IGF-1) helps heal cornea
2. Substance P is synergistic with IGF-1 for healing of neurotrophic keratopathy [8]

H. Retinitis Pigmentosa (RP)

Hereditary peripheral retinopathy
Affects about 1.5 million persons worldwide
Genetic Disease
1. Autosomal dominant, recessive, and X-linked forms
2. Seven gene mutations have been found associated with RP
Genes associated with RP
1. Rhodopsin
2. Alpha and ß subunits of rod cGMP phosphodiesterase
3. Rod cGMP cation-gated channel protein alpha subunit
4. Peripherin/RDS gene
5. TULP1 and TULP 2 genes
Slowly progressive retinal degeneration

I. Leber's Congenital Amaurosis (LCA) [13,14]

J. Leber's Hereditary Optic Neuropathy (LHON) ,

First disease in humans linked to heritable point mutations in mitochondrial DNA
Most common form of blindness in otherwise healthy young men
1. Males affected 4 to 1 over females
2. Average onset at 23 years of age; 90% affected by age 40
3. Progression in weeks to months
Painless, subacute, bilateral visual loss
Central scotomas and abnormal color vision
Visual recovery can occur, mainly in patients with T14484C mutation
Dystonia may be present, usually with optic atrophy [15]
Four different mutations have been identified

References