Introduction

One of the most common presenting symptoms in ophthalmology  is red eye .It is  the manifesting sign of many ocular diseases; can be acute or chronic, mild or severe, unilateral or bilateral. The  etiology can be infectious,  allergic,  autoimmune, inflammatory or traumatic (probably most common).  Pathologies of each of  the orbit, eyelid, conjunctiva, cornea , sclera, episclera and even the posterior uveal tract can all manifest as a red eye. 

Eyelid diseases and red eye

As a result of the intimate relationship between the lid margin and the ocular surface, pathologies affecting the eyelids are common  causes of red eye. 

Blepharitis

Symptoms of blepharitis include burning, grittiness, mild photophobia, crusting and redness of the lid margins. These symptoms are characteristically worse in the morning.( Dry eyes cause similiar symptoms but usually peak later in the afternoon). Two types of blepharitis are distinguished clinically:

-posterior blepharitis : due to meibomian gland dysfunction.(ocular rosacea).

-anterior blepharitis  :   can be divided  into 2 types :

           - staph blepharitis where hard and brittle scales are centered around the base of eyelashes forming colarretes.

           -seborrheic blepharitis where scales are soft and greasy and eyelashes are stuck together. Corynebacterium  is  
             known to contribute  to the pathogenesis .

 Treatment : Lid hygiene ( ex;  with warm compressors and baby shampoo ).
                  Antibiotic ointment ( ex; fusidic acid for anterior blepharitis  and tetracyclin for posterior blepharitis).
                  Weak topical steroids (ex; fluorometholone).
                  Tear substitutes for patients with tear film instability as in posterior blepharitis.
                  Application of warm compressors (5x /day) to thin out solidified sebum,  and  mechanical
                  expression of the inflamed meibomian glands may reduce the amount of irritating lipids within the glands.

Ectropion  of the lower eyelid is horizontal lid laxity and loss of normal apposition of the lacrimal punctum on the surface of the globe.This  results in epiphora, and, in longstanding cases,  inflamed  red and thickened conjunctiva .Types of ectropion are;

-involutional(senile)
-cicatricial (trauma, burns)
-paralytic ( secondary to facial nerve palsy)

Patients with paralytic ectropion , because of their inability to close eyelids when sleeping (lagophthalmos), are prone to  develop exposure keratopathy. Usually the inferior cornea is affected because the eye tends to rotate upward when sleeping
(physiologic Bell's phenomenom), so the inferior cornea remains exposed, gets dehydrated and the conjunctiva inflamed,
leading ultimately to red eye.

Treatment

Heavy lubrication and strapping of the lids at night is usually adequate for mild cases. Other treatment methods are injection of botulism toxin into the levator to induce temporary  ptosis .Sometimes  bandage contact lens are indicated for recurrent and chronic epithelial defects.

Entropion   is the inward rotation of the eyelid margin towards the globe causing constant rubbing of the eyelashes on the cornea causing irritation, ulceration and pannus formation. Types of entropion are;

-involutional ( senile)
-cicatricial , due to chemicals, burns or infections (trachoma of chlamydia).
-congenital , caused by improper development of the retractor aponeurosis into the inferior border of the tarsal plate.

  Treatment

- Mechanical epilation or electrocauterisation of those eyelashes rubbing on the corneal surface.
 -Blepharoplasty, tarsal fracture...

Conjunctival diseases and red eye

The conjunctiva is the  transparent connective tissue  layer covering the white of the eye .Any inflammatory response therefore,which  naturally includes vascular dilation and engorgement, will give the eye a red appearane . 

Bacterial cunjunctivitis:  Most common organisms are  staphylococcus aureus and epidermidis > streptococcus pneumonia  > H.influenzae,Moraxella
Clinical features include acute onset of redness, grittiness, burning, mucupurulent discharge, beefy red conjunctiva and crusted eyelids stuck together on waking.

Treatment

Topical antibiotics; Fusidic acid , chloramphenicol, ofloxacin, tobramycin,gentamycin, trimethoprim....
Ointments are preferably used at night because they provide a higher concentration of antibiotic for longer period than eyedrops.Their use during the day is limited because they cause blurred vision following installation.

Gonorrhea is a venereal  GU tract infection caused by  the diplococcus Neisseria gonorrhea. It should be highly suspected in young, sexually active individuals presenting with hyperacute, extremely profuse, purulent discharge. The conjunctiva shows intense hyperemia, chemosis (edema), and occasionally  a pseudomembrane. Preauricular lymphadenopathy may be prominent.
Treatment  consists of irrigation  along with topical and systemic antibiotic.

Viral conjunctivitis

Adenoviral ;  most common, causes acute onset of watery discharge, redness, discomfort and photophobia. Bilateral in about 60% of cases, typically one eye preceding the other by few days. The conjunctiva shows chemosis and follicles, more in the lower eyelids.
Clinically, two ocular syndromes caused by adenovirus are distinguished :

Pharyngioconjunctival fever (PCF); caused by serotypes 3 and 7. Typically affects children and causes URTI sxs.
Keratitis develops in 30 % of cases and is usually mild.

Epidemic keratoconjuntivitis(EKC): caused by serotypes 8 and 19. No associated systemic symptoms.
Keratitis occurs in 80 % of cases and may be severe.

Treatment

Largely symptomatic and supportive. Spontaneous resolution occurs within 2 weeks. Topical steroids are sometimes used if there is associated keratitis which is severe(stage 2-3,with subepithelial iinfiltrates),and affecting visual acuity. Steroids here will not shorten the natural course of the disease but will alleviate the symptoms, suppress  the inflammation and minimize the scarring.

 
Other  common causes of conjunctivitis and red eye  are Herpes (simplex and zoster) and Chlamydia. The latter is the most common cause of neonatal conjunctivitis. It is noteworthy that the  conjunctival reaction in neonates is papillary and not follicular because infants cannot form follicles until about the third month of life.

Adult chlamydial keratoconjunctivitis is a sexually transmitted disease and should be suspected in patients with  unilateral red eye and mucopurrulent discharge persisting for more than 3 months. Treatment include  tetracyclins and erythromycin .

Allergy and red eye

Allergic rhinoconjunctivitis:
- The most common form of eye allergy.
- Hypersensitivity reaction to specific airborne antigens( pollens, housedust mites...)
- Presentation is acute and  transient attacks of  red , itchy watery eyes, sneezing and a watery nasal discharge and      
  congestion. The eyelids may show mild edema, and the upper tarsal  conjunctiva  a milky appearance .
Treatment : Topical antihistamines and mast cell stabilizers.

Vernal keratoconjunctivits ( vernal catarrh)

- Recurrent, bilateral, external ocular inflammation affecting males between 4and 20 years of age.
- Common in warm dry climates, like the Meditarranean basin.
- 75% have associated atopy, asthma, eczema ...
- 60% have family history of atopy.
- clinical features:  Intense ocular itching, lacrimation, burning and foreign body sensation and  photophobia.
  Presentation might include ptosis and thick mucus discharge. Slit-lamp exam reveals  round gelatinous white elevations over the superior limbus called Trantas dots, composed predominantly of eosinophils. The corneal involvement may range from superficial punctate keratopathy  to macroerosions , plaques or shield-like ulcers.
Treatment :
-Antihistamines.
-Mast cell stabilizers.
-Topical steroids (mainly to treat  severe cases with keratopathy) .
-cold compressors (contribute significantly to symptomatic relief).

 
Fig. 1: Giant Papillae (Cobblestones) in the palpebral 
            conjunctiva in patients with Vernal Catarrh.

Fig. 2: Tranta's Dots

Atopic keratoconjunctivits

- Rare but serious disease typically affecting patients with atopic dermatitis, hay fever, asthma, migraine.....
-clinical features are similiar to vernal catarrh, yet  more chronic and severe ; The eyelids are red, thickened, macerated and fissured.   A  chronic staphylococcal bleparitis is  commonly associated and must be treated. The conjunctiva may have pale and featureless  appearance to become hyperemic and  chemotic with papillary hypertrophy during exacerbations .In advanced cases, cicatrization and symblepharon can form usually involving the inferior fornices.
Keratopathy is the main cause of visual impairement and includes  extensive punctate epitheliopathy , persistant epithelial defects, with shield-shaped anterior stromal ulcers and peripheral neovascularization.
Treatment
-Oral antihistamines
-Mast cell stabilizers
-Steroids for inflammatory flare-ups.

Miscellaneous conjunctival diseases causing red eye

Pinguecula and pterygia  (check anatomy lecture), can give the eye a reddish appearance especially in case of  inflammation of the degenerative  vascularized conjunctival tissue.

Fig. 3: non-inflamed pterygium, 
encroaching on the cornea nasally

Phlectenulosis is caused by  a non- specific delayed hypersensitivity reaction , (mostly to staphylococcus, Tb in the past).Clinical features include photophobia , hyperlacrimation and blepharospasm. The conjunctiva  shows a phlyctan= a small pinkish white nodule near the limbus surrounded by hyperemia. Treatment is by steroids ,  the time- tested immunologic modulators.

Acne rosacea  is a common skin disease affecting facial convexities characterized by flushing, persistant erythema  and telangiectasia. Ocular  features include  hyperemic conjunctivitis, posterior blepharitis, recurrent stye and chalazion  formation and keratitis. Ocular treatment include topical steroids , fusidic acid and systemic tetracyclin.

Dryness as cause of red eye

Keratoconjunctivitis sicca  (KCS) refers to a dry eye due mainly to aqueous tear deficiency , resulting from destructive infiltration of the lacrimal glands by mononuclear cells. KCS can be associated with xerostomia (primary Sjogren's) and systemic diseases like rheumatoid arthritis (secondary Sjogren's)

Other causes of dry eyes include meibomianitis or meibomian gland dysfunction, where the outermost lipid layer of the tear film is deficient,  leading to increased evaporation...Lid laxity in ectropion  and lagophthalmos (inability to close the eyes) in facial nerve palsy,or proptosis  in dysthyroidism, similiarly  cause increased  corneal exposure and  tear evaporation.
Tear film deficiency is also seen in sarcoidosis, familial dysautonomia, mucucutaneous syndromes like Stevens-Johnson and cicatricial pemphigoid where there is inflammation and scarring in the conjunctiva, affecting goblet cell  secretion of the mucoid layer of the tear film.
Clinical features of dry eyes include irritation, foreign body sensation , redness, and stringy mucuous discharge (common in filamentary keratitis). Special tests are::
-Schirmer : a  Whatman filter paper is installed in the lower fornix ; Normal is > 10 mm wetting  after 5 minutes.
-BUT (break-up time):  A dop of fluorescin is used to color the tear film which normally  should remain stable (confluent) for more than 10  seconds.
-Rose bengal stains, in pink, dead and devitalized cells, and shows well corneal filaments ,mucuous, plaques....

Treatment
-Tear substitutes (Tears Naturale, Viscotears..)
-Mucolytic agents( Acetylcystein 5%).
-Punctal occlusion eithar temporarily by special  collagen plugs or permanently by cauterization .

Corneal diseases and red eye

Bacterial keratitis
Few pathogens only are able to produce corneal infection in the presence of intact epithelium. These are N.Gonorrhea, Corynebacterium diphtheria, Listeria and Haemophilus. Other bacteria cause keratitis only after loss of corneal integrity ,  such as   secondary to  extended contact lens wear (pseudomonas) , herpetic disease, trauma, bullous keratopathy and exposure keratopathy ( staphylococcus and streptococcus).

 Fungal  keratitis (Aspergillus,Candida, Fusarium ), and viral (Herpes simplex and zoster), and protozoan ( Acanthamoeba in soft  contact lens wearers ) ,  can all  lead to conjunctivits and red  eye.

Uveitis and red eye

-Uveitis  referrs  to  inflammation of the middle coat of the eye (iris + ciliary body +choroid)
-Can be divided into ;
   -anterior uveitis = iritis or iridocyclitis.
   -intermediate uveitis = pars planitis.
   -posterior uveitis = choroiditis (usually associated with retinitis).
   - panuveitis = inflammation involving the whole uveal tract.

- can be acute (sudden and persists < 2 months ) or chronic (insiduous and lasts > 3 months with occasional exacerbations)
- can be due to infectious causes (toxoplasma, herpes zoster,CMV...) or associated with  systemic, inflammatory and autoimmune   diseases (spondyloarthropathies, Behcet's, sarcoidosis, juvenile rheumatoid arthritis ..), or can be merely idiopathic.  

clinical features:
- acute anterior uveitis causes pain and photophobia (due to ciliary spasm), redness and decreased vision.
   Slit lamp exam shows:
    - ciliary injection ( vascular engorgement around limbus) giving the eye a violaceous hue.
    -keratic precipitates (KP's) =  cellular deposits on the corneal endothelium. Large, greasy, mutton-fat KP's are seen   
     in granulomatous uveitis (sarcoidosis).
    -iris nodules may be present at the pupillary border (Koeppe's nodules) , or in the center of  the iris (Bussaca's).
    -  cells in the anterior chamber (mainly WBC), the quantity of which reflect the activity of the disease. Aqueous
    flare,however, which results from leakage of proteins from damaged vessels,does not necessarily reflect the activity of the    .   disease.
    -posterior synechiae =  adhesions between the inflamed iris and the anterior surface of the lens. The use of mydriatic eye   
    drops, like atropine or mydriaticum, is used prophylactically  to prevent formation of the the synechiae.
   
- intermediate uveitis   is usually insidious and chronic  and the patient may not present with pain or a red eye.
Common symptoms are floaters or decreased vision (due to cystoid macular edema).
   Slit-lamp exam shows:
    -relatively quiet anterior chamber.
    -cells  and gelatinous exudates ('snowballs)  in the anterior vitreous.
   Indirect ophthalmoscopy (with indentation) reveals snowbanking = grey white plaque  covering the inferior pars plana.
 Treatment includes steroids, cytotoxic agents and  cryotherapy.

-posterior uveitis   is posterior segment inflammation , so the  patient presents with  a red eye only if the anterior segment gets secondarily involved. Common symptoms are floaters and decreased vision if the fovea or papillomacular bundle are involved.
IT is noteworthy that 30% of posterior uveitis is idiopathic, and it appears to be an organ- specific disease mediated by T cells against specific antigens derived from the retina (ex: S-antigen),while anterior uveitis starts as an extraocular process which is secondarily  retargeted against the eye .

Fig. 4: KP's; Click to enlarge

Endophthalmitis

-massive  ocular inflammation caused by infected or injured intraocular tissue, not uncommonly leading to blindness.
-symptoms include marked pain ,visual loss, lid and conjunctival edema, corneal haze, cells and fibrinous exudates in the anterior chamber, hypopyon, vitreous cells...
- can be divided into 4 categories:

   - acute post-op  endophthalmitis : day 1-10 post- op, due  to staph. epidermidis > staph. aureus > pseudomonas >>proteus
   -delayed post-op endophthalmitis :  weeks to months after surgery, mostly due to propionobacterium acne>> s. epidermidis
   -post-traumatic endophthalmitis: worse prognosis due to marked stuctural damage and virulence of organisms( ex: bacillus )
   -endogenous endophthalmitis : the causative organisms ,usually fungi,  enter the previously intact eye  from a distant focus    
    through the posterior ocular circulation. The patients are usually immunocompromised, debilitated, on hyperalimentation...
    Most common organisms: candida >aspergillus>>bacteria 

-treatment of endophthalmitis include intravitreal ,subtenon and topical antibiotics, ex: ceftazidime, amikacin,    vancomycin...
 Steroids are used to decrease the inflammatory response. Vitrectomy is reserved with patients with LP vision
 Evisceration might also be the last resort for those unfortunate, with NLP vision .

 
 
Glaucoma and red eye 

Acute angle closure glaucoma  is  caused by  sudden and total closure of the angle, resulting in drastic elevation in the intraocular pressure  (50 -100 mm Hg ). The patient presents with  severe pain , nausea, vomitting, and  rapidly progressive decrease in vision.
Slit-lamp exam shows
-ciliary inection (red eye)
-corneal edema( due to endothelial decompensation)
-shallow anterior chamber with cells and flare (gonioscopy confirms angle closure)
- pupil fixed in mid-dilated position.

Treatment includes intravenous acetazolamide or hyperosmotic agents like mannitol.
Nd:YAG laser iridotomy is  often used to establish an opening in the iris, creating a shortcut for the aqueous to pass from the posterior to the anterior chamber.This will also  help restore a wider angle.