Interstitial keratitis (IK) is a broad, descriptive term that has become synonymous with syphilitic disease. Although syphilis remains the leading cause of IK, various bacterial, viral, parasitic, and autoimmune causes of IK exist.
By definition, IK is a nonsuppurative inflammation, which is characterized by cellular infiltration of the corneal stroma. In general, no primary involvement of the corneal epithelium or endothelium occurs. Inflammation may be either the direct result of an infectious process or, more commonly, secondary to an immunologic response to a specific foreign antigen. This immunological response may take the form of antigen-antibody complex deposition, complement-mediated disease, or a delayed-type hypersensitivity reaction.
IK generally is seen in the context of syphilis and, less commonly, in the context of herpes and Cogan syndrome.
In various countries in which mycobacterial diseases (eg, tuberculosis, leprosy) are endemic, these and other parasitic causes of IK may be seen with greater frequency.
Ocular morbidity generally is in the form of corneal scarring, which can interfere with visual acuity.
No known racial predilection exists.
No gender predilection exists.
IK generally is a disease that manifests in the third to fifth decades of life.
In the acute phase, IK typically causes decreased vision, photophobia, tearing, pain, and blepharospasm. Late phase symptoms consist of decreased visual acuity but little ocular discomfort.
Congenital syphilis tends to cause acute symptoms in childhood. Patients may give a history of one or both eyes being red and painful for months as a child. They may remember being admitted to the hospital or confined to bed, and they may not have been allowed to go to school for many months. They may give a history of prolonged intravenous antibiotics or multiple shots as treatment.
Clinically, IK is characterized by areas of dense, white, stromal necrosis and vascularization in the acute phase, which may be either diffuse or focal and typically results in scarring and thinning in the later phases of inflammation.
The active vascularization contributes to the pinkish color of the cornea and is termed the salmon patch of Hutchinson. These vessels often regress, leaving behind remnants known as ghost vessels.
Once the initial inflammation has resolved, which may take many months, the cornea may exhibit mild-to-severe scarring and thinning. The scarring tends to be in the mid to posterior corneal stroma.
IK may be attributed to a number of systemic illnesses, including bacterial, viral, and parasitic infections, as well as Cogan syndrome, which can be associated with various systemic vasculitides.
Syphilis: IK in syphilis may be due to an immune-mediated reaction to an unknown treponemal antigen. IK may be seen in congenital and acquired syphilis.
IK due to congenital syphilis is commonly a late finding. Most cases of IK develop in patients aged 5-20 years. Acute IK may be triggered by ocular surface inflammation and following intraocular surgery. Corneal inflammation most often affects the deep stromal layers either as multifocal infiltrates or as a diffuse process. Corneal stromal edema may result from the inflammation, resulting in the ground glass cornea. Variable corneal stromal neovascularization depending on the severity of the inflammation may be present. Typically, the neovascularization begins at the corneal limbus and may occur in the level, although it most commonly is seen in the deeper stromal layers. Stromal inflammation overlying the vessel often causes the salmon-colored patch due to the pinkish color imparted by the stromal vessels. Intrastromal hemorrhage also may occur.
IK may progress to the regression phase, during which scarring of the corneal stromal and collagen remodeling occur. The superficial vessels resorb, and the deeper vessels may constrict, resulting in the ghost vessels that are seen as a late finding of syphilitic IK.
Congenital syphilitic IK is typically bilateral in 80% of cases. However, the two eyes are very rarely involved simultaneously; usually, the contralateral eye is affected after an interval of time, which may be as short as 2 months or as long as 15 years, following inflammation of the first eye.
Corneal disease in acquired syphilis is rare, although IK may be seen. Typically, IK is unilateral in the context of acquired syphilis. IK may occur relatively soon following the primary general infection, but it more often occurs many years later with the onset of pain, photophobia, tearing, and blurred vision, similar to the symptoms seen in acute IK in congenital syphilis. In general, the symptoms are less severe and of shorter duration.
Clinical findings of IK in acquired syphilis very closely resemble those seen in IK in congenital syphilis. Late findings of IK in acquired syphilis include opacification of the stroma with ghost vessels and thinning. Endothelial changes in the form of redundant basement membrane at the level of the Descemet membrane also may be present. Endothelial decompensation may follow, resulting in central corneal edema later in life.
Mycobacterial infections: Tuberculosis and leprosy are two mycobacterial infections that may be causative agents in the pathogenesis of IK.
Internationally, tuberculosis remains an important public health issue, and, in the United States, tuberculosis has become a relevant topic due to increased immigration from endemic areas, as well as due to the human immunodeficiency virus (HIV). Although primary tuberculosis infection of the eye is extremely rare, IK may be associated with pulmonary tuberculosis. Even in this setting, it is extremely rare and, when present, usually is unilateral. In keeping with the other types of IK, the pathogenesis seems to be an immune reaction to tuberculous antigens within the cornea. Clinical findings are similar to IK due to other disorders.
Leprosy is caused by Mycobacterium leprae and characteristically infects the skin and peripheral nerves. Two forms of leprosy exist, tuberculous and lepromatous. IK also may be an ocular finding of leprosy (Hansen disease), and, in contrast to that seen in tuberculosis, lepromatous IK usually is bilateral. Another distinguishing characteristic of lepromatous IK is that the organisms have been found throughout the stroma, implying that a direct infectious etiology may occur, in contrast to an immunologic etiology. Clinical findings of IK are similar to that in tuberculous IK; however, prognosis may be poor due to the widespread involvement of the corneal nerves in lepromatous IK.
Lyme disease: The causative organism in Lyme disease is the spirochete Borrelia burgdorferi and typically is transmitted by the deer tick vector, Ixodes.
Lyme disease clinically is distinguished by 3 stages, and ocular involvement typically occurs in stage 2 and stage 3. Stage 1 represents the viral prodrome with a flulike illness and the typical bull’s eye lesions on the skin, erythema chronicum migrans. Stage 2 is characterized by neuro-ophthalmologic manifestations.
Keratitis along with uveitis and vasculitis may occur in stage 3. Keratitis is a rare feature of Lyme disease, but, when present, it carries a typical finding of IK with the exception of stromal edema, which is not a common factor in Lyme IK. Lyme keratitis also can appear as large nummular infiltrates in various levels of the stroma without corneal neovascularization.
Parasitic infections: Parasitic infections are rare causes of IK commonly seen in the United States.
Acanthamoeba is a free-living amoeba, which may cause a severe keratitis, especially in patients with a history of contact lens wear and more typically contact lens abuse. In prior decades, the use of homemade saline solutions was found to be a cause of Acanthamoeba keratitis. The use of contact lenses while swimming, typically in a fresh water environment, also is another risk factor. Acanthamoeba keratitis may have a variety of presenting characteristics, but the most significant symptom is pain out of proportion to clinical findings. Although epitheliopathy may exist, primary stromal involvement, including inflammation edema, may be seen, which resembles IK. In typical Acanthamoeba keratitis, stromal neovascularization is not an early finding.
Onchocerciasis (river blindness) is the result of infection by the nematode Onchocerca volvulus. Ocular involvement is the result of the migration of the microfilariae to the ocular tissues. IK caused by onchocerciasis has been described as beginning in the peripheral cornea, followed by progressive spread centripetally. Vascularization and complete opacification of the cornea may result, but corneal thinning is not a significant feature in this condition.
Leishmania is a protozoan agent commonly seen in Asia, Africa, and South America. It is carried by the sand fly vector and is divided into cutaneous and visceral forms. Typically, 2 types of keratitis are seen. Necrotizing keratitis may progress to corneal necrosis and perforation. However, a second presentation is that of typical IK with late corneal scarring and thinning.
Trypanosoma cruzi is responsible for the American form or Chagas disease, and Trypanosoma brucei is responsible for the African form, also known as African sleeping sickness. IK may be seen in the African form with the typical features described previously.
Microsporidia are small intracellular protozoans, which have been isolated from patients with acquired immunodeficiency syndrome (AIDS) who had developed superficial keratoconjunctivitis. They are rare causes of keratitis in immunocompetent individuals.
Herpetic infections of the cornea comprise a myriad of clinical findings. A complete discussion is beyond the scope of this section. Herpetic stromal disease may take the form of IK and represents an important entity in the differential diagnosis. Typical findings of IK may be present along with an immune ring, which may be diagnostic.
Epstein-Barr virus also belongs to the herpes family of viruses and may have variable presentation in corneal disease. Unilateral or bilateral, multifocal or discrete infiltrates may be present, which may benefit from topical corticosteroids.
Mumps typically causes lacrimal gland inflammation, but cornea involvement may occur with a variable presentation, ranging from punctate epithelial keratopathy to nummular keratitis.
Cornea involvement in measles typically is a superficial keratitis and generally is self-limiting. However, measles has been associated with vitamin A deficiency in malnutrition, and the combination of these factors may promote stromal infiltration and perforation.
The triad of nonsyphilitic IK, vestibuloauditory disease, and associated autoimmune vasculitis is known as Cogan syndrome and was first described in 1945. In this condition, a sudden onset of vestibuloauditory symptoms (eg, tinnitus, vertigo, nausea, vomiting) occurs, along with corneal inflammation and often an association with autoimmune disorders (eg, polyarteritis nodosa, Wegener granulomatosis, rheumatoid arthritis). In contrast to the deafness associated with syphilitic IK, the hearing loss in Cogan syndrome also has the vestibular symptoms described earlier. Although the exact pathogenesis is unknown, the disease process probably represents an immune reaction against the common antigen found in the cornea and in the inner ear.
Corneal findings are very similar to those seen in syphilitic IK, with lymphocytic infiltration of the deep stroma with variable neovascularization.