Differential Diagnosis 
Physical Signs in Cornea

ferritin line                                    
vortex keratopathy
corneal neovascularization         
band keratopathy
ghost vessels                                 
breaks in Descemet's membrane
peripheral corneal thinning        
corneal oedema
pigments on the endothelium      
keratic precipitates on the endothelium

The cornea provides a variety of signs for the slit-lamp examination. These signs are easy to detect provided you examine each layer in turn and know how to use the various slit-lamp techniques. Usually more than one sign is present in the cornea. The following provide lists of differential diagnosis of common corneal signs seen in the examination.

Ferritin lines
(This seldom occurs in isolation in the examination. It is either a coincidental finding or associated with the corneal problem.)

  • Hudson-Stahli's line (occurs in elderly and is found at the junction between the upper 2/3 and lower 1/3 of the cornea)
  • Ferry's line (found anterior to a filtering bleb)
  • Stocker's line ( found anterior to a pterygium)
  • Fleischer's ring ( found at the base of keratoconus)
  • foreign body
  • other ( diseases which distort the surface of the cornea often causes iron deposition for example recurrent erosion syndrome, radial keratotomy)

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Vortex keratopathy
(Also known as cornea verticillata; it is characterized by epithelial deposition which is arranged in a vortex fashion and usually begins just below the pupil and radiate outward. Like ferritin lines it is unlikely to be the only signs, if there is no other physical signs in the cornea ask to examine the posterior segment. For example, you may be given vortex keratopathy with tamoxifen deposition in the macula or vortex keratopathy with bull-eye maculopathy due to chloroquine toxicity.)

  • Inherited
    • Fabry's disease
  • Drug-induced
    • amiodarone
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Corneal neovascularization
(These may be superficial or deep in stroma. In the examination, the most common cases are phthisical eye, trauma, herpes simplex keratopathy, chemical burnt and ocular cicatricial pemphigoid.)
  • contact lens wear
  • trauma
  • infections
  • bacteria such as chlamydia, staphylococcus, pseudomonas
    viruses such as herpes simplex and herpes zoster
    protozoa such as onchocerca volvulus, leishmania brasiliensis
  • alkali burns
  • immunologic diseases
  • Steven-Johnson's syndrome
    graft rejection
    cicatricial ocular pemphigoid
  • degenerative disorders
  • pterygium
    Terrien's marginal degeneration
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    Band keratopathy
    (It is found in the palpebral fissure. Although it may occur singly, in the examination you are likely to be given one with underlying ocular diseases for example chronic uveitis, interstitial keratic, phthsical eye or silicone oil in the anterior chamber)
    •  Ocular causes
      • chronic inflammation (Still's disease and chronic uveitis)
        interstitial keratitis
        phthsical eye
        silicone oil in the chamber
    • Systemic disease
      • hypercalcaemia
        vitamin D intoxication
        dystrophic band keratopathy
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    Ghost vessels
    (These usually occur in deep stroma in patients with interstitial keratitis. The chronic inflammation usually leaves a thin cornea and possibly anterior or posterior synechiae. Although interstitial keratitis classically occurs in congenital syphilis in which case the condition is invariably bilateral, it can also occur in a variety of infection. The most likely case in the examination is congenital syphilis and the patient may have the typical facial features of saddle nose, deafness and Hutchinson's teeth or may be normal. Avoid using words like syphilis (in front of the patient) when asked about the diagnosis or investigation instead used terms like St. Louis's disease or serology for Treponema pallidum.
    The following is a differential diagnosis of interstitial keratitis:)
    • Bacterial disease
      • congenital syphilis
    • Viral disease
      • herpes simple
        herpes zoster
    • Parasitic disease
      • leishmaniasis
    • Unknown aetiology
      • Cogan's syndrome
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    Breaks in Descemet's membrane
    (This is a common sign in the examination and the most common cause in the examination is bulphthalmos. Therefore, look out for differences in corneal size. )
  • congenital glaucoma
  • advanced keratoconus
  • trauma (for example forcep delivery)
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    Peripheral corneal thinning
    (In the clinical examination, the most common cases will include rheumatoid arthritis, Mooren's ulcer and Terrein's marginal degeneration. However, in your differential diagnosis do not forget to mention more common condition such as bacterial infection or recurrent marginal keratitis.)

  • Infectious
  • Local immune diseases
  • marginal keratitis
    vernal keratoconjunctivitis
    Mooren's ulcer
    superior limbic keratoconjunctivitis
  • Degenerative disorders
  • Terrien's marginal degeneration
  • Systemic immune diseases
    • Collagen vascular diseases
        rheumatoid arthritis
        systemic lupus erythematosus
        relapsing polychondritis
        Wegener's granulomatosis
      Dermatologic conditions
      Inflammatory bowel diseases
        Crohn's disease
        ulcerative colitis
      Blood disorders
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    Corneal oedema
    (Another common sign in the examination. The sign may be missed if subtle unless you look at the corneal thickness and the present of clear spaces in the stroma. You must look for the underlying cause. The most common case is pseudophakic bullous keratopathy.)

    • Increased intraocular pressure
      • congenital glaucoma
        angle-closure glaucoma
        neovascular glaucoma
    • Endothelium decompensation
      • inherited
          congenital hereditary endothelial dystrophy
          posterior polymorphous dystrophy
          Fuch's dystrophy
        corneal ulcer
          chronic uveitis
          graft rejection
          iridocorneal endothelial syndrome
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    Pigments on the endothelium
    (The typical case in the examination is Krukenberg's spindle in patient with pigment dispersion syndrome. However, pigments can also occur in various conditions and a detailed examination of the anterior segment may provide the clues.)
    • pigment dispersion syndrome
    • pseudoexfoliation syndrome
    • post-cataract surgery
    • previous corneal performation in which the iris was incarcerated in the wound leaving behing pigment
    • trauma
    • idiopathic


    Keratic precipitates in the endothelium
    (The most common case is Fuch's heterochormic cyclitis in which there are multiple discrete KP evenly distributed in the endothelium. Occasionally you may be given a patient with mutton fat KP and asked to give a differential diagnosis. Possible cases include sarcoidosis (look for  nodules on the iris), toxoplasmosis (there may be chorioretinitis scar in the posterior segment) and rarely sympathetic ophthalmia (look for signs of ocular damage in the opposite eye)
    The following list is for mutton fat KP ie. granulomatous inflammation.)

    • Infectious
      • tuberculosis
        Lyme disease
        propiobacterium  acnes
    • inflammation
      • sarcoidosis
        sympathetic ophthalmia
        phacoanaphylactic uveitis
        Vogt-Koyanagi-Harada's syndrome
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