Syphilitic Keratitis

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 by Christina Moon, M.D. on September 4, 2023.

Syphilitic keratitis results from congenital or late acquired syphilis. The incidence of disease has decreased dramatically since the penicillin era, however, it has not been eradicated, and is seen disproportionally in developing nations. It is still seen rarely in the developed world throughout the 21st century and is therefore still important to consider in a patient presenting with bilateral stromal keratitis, especially with other systemic symptoms. Prevention is best achieved by treating syphilis positive patients who are pregnant with penicillin in their second semester or earlier. Treatment for syphilitic keratitis is topical corticosteroids with cyclosporine or tacrolimus used for refractory or recurrent cases and penetrating keratoplasty for surgical management.


Syphilitic keratitis is a non-ulcerative interstitial keratitis that typically manifests as a late sequela of congenital or acquired syphilis. Syphilitic keratitis is seen more commonly in patients with congenital syphilis than in those who acquire syphilis later in life. In congenital syphilis, keratitis is typically bilateral in up to 80% of cases and presents as late congenital syphilis in children or adolescents most often between ages 5 and 15. Involvement of the second eye is typically seen within a few weeks following onset of disease in the first eye, but may also occur simultaneously. Syphilitic keratitis can be the only manifestation of late congenital syphilis, but oral pathology (misshapen teeth) is seen in 50% of cases as well.[1] The deep stroma of the cornea is primarily involved in syphilitic keratitis and manifests clinically as a stromal haze or focal infiltrate. The inflammation appears most commonly in the superior cornea and can lead to corneal thickening. Neovascularization of the cornea often occurs after the onset of stromal haze and edema. Neovascularization occurs as extensions of both the limbal and anterior ciliary vessels often coinciding with increased lymphatic extension into the peripheral cornea.[1] The combination of neovascularization and lymphatic extension leads to the classic salmon-colored patch seen in the disease. Treatment is important in the active stage of the disease to limit the neovascularization and lymphatic extension by inhibiting the inflammatory response. After appropriate treatment, recurrence occurs in 5-15% of patients.[1]

Syphilitic keratitis is uncommon in patients with acquired syphilis. When it does occur in acquired syphilis, presentation is typically with a unilateral keratitis in 60% of cases and presents most commonly in late latent phase of infection.[2] Syphilitic keratitis has similar pathologic manifestations in acquired syphilis as in congenital syphilis with a few noted exceptions. Besides the unilateral preference, acquired syphilis is usually more localized and with less corneal neovascularization. When bilateral involvement occurs in acquired syphilis, the second eye typically has less severe involvement.[1]


Prior to the era of Penicillin, syphilitic keratitis was estimated to have a prevalence of >1million individuals worldwide, placing 1 in every 1,000 newborns at risk of acquiring the disease.[1] While overall disease prevalence has decreased exponentially since the development of penicillin, syphilitic keratitis is still an ophthalmic condition seen not uncommonly in the developing world. Prevention is focused on decreasing the incidence of congenital syphilis, as pregnant women conventionally undergo screening and treatment during the second trimester of pregnancy.[1] This has shown to be effective with syphilitic keratitis incidence decreasing 22% per year between 1990 and 1999.2 Rates of congenital syphilis remain high, however with an estimated incidence of 14.5 cases per every 100,000 live births in 1999.[3] With new efforts and initiatives by the CDC, the rate of congenital syphilis decreased to 8.8 cases per 100,000 in 2004. While becoming increasingly rare, congenital syphilis presents a public health challenge to improve and expand prenatal care to further decrease rates and sequelae of the disease including keratitis.


The pathophysiology of syphilitic keratitis is not completely understood. While laboratory studies have shown that Treponema pallidum can attach to keratocytes and can also enter the eye via hematogenous spread, the inability to find these spirochetes in eyes with syphilitic keratitis has led to other theories on the mechanism of disease.[1] The prevailing theories focus on an auto-inflammatory response to Treponema pallidum, not Treponema pallidum itself, as the mechanism of disease in syphilitic keratitis.[1] This is supported by the lack of treatment response of the disease to antibiotics and the response to treatment by corticosteroids and cyclosporine. The findings of mononuclear cells and angiogenesis in the disease also point to an immune-mediated response. The prevailing theories are that the immune-mediated process is triggered by a response to hidden antigens and molecular mimicry of self-antigens leading to syphilitic keratitis.[1]


Prevention is best achieved by treating syphilis positive patients who are pregnant with penicillin in their second semester or earlier.

Physical examination

Clinical exam findings reported include corneal opacification, chronic edema, astigmatism, amyloid degeneration, and calcific band keratopathy.[1] On exam, syphilitic keratitis can be classified as active or inactive based on findings with active disease showing stromal inflammation without ulceration. This typically coincides with an anterior uveitis. Inactive syphilitic keratitis presents with stromal scarring and thinning as well as ghost vessels and deposition of collagenous material on Descemet membrane.[4] Complications of syphilitic keratitis include glaucoma, cataracts, and choroidal atrophy.[1][5] Hemorrhagic Descemet membrane detachment as a result of syphilitic keratitis has also been reported.[6] Classically, ghost vessels are also seen on exam which appear as phantom vessels that weave through the stroma. While these ghost vessels are most often phantom vessels, some of the ghost vessels are patent and can carry red blood cells.[7]

Diagnostic procedures and Laboratory test

Diagnostic testing is a combination of clinical exam and laboratory findings. Laboratory testing centers on treponemal and nontreponemal serologic tests. Classically algorithms have suggested starting with a nontreponemal test and following it with a treponemal test if the former is positive. However, because nontreponemal serologic titers decrease over time, it has been suggested that for latent syphilis and syphilitic keratitis the testing should start with a treponemal test.[1]


The preferred treatment of all stages of syphilis is penicillin. However, syphilitic keratitis requires a multistep approach. Antibiotics have shown to be ineffective at treating the corneal manifestations of syphilis and this observation is one of the reasons the pathogenesis of syphilitic keratitis has been thought to be an inflammatory response.[7] First-line treatment of syphilitic keratitis is topical corticosteroids. Topical corticosteroids shorten the duration of the keratitis and lead to improved vision in the large majority of cases. For patients who fail topical corticosteroid treatment, evidence shows immunosuppression therapy with cyclosporine or tacrolimus is an alternative and effective treatment.[8] In addition to this, antibiotics are used, not to treat syphilitic keratitis, but to treat latent or tertiary syphilis if there is laboratory evidence of infection or a history of not being treated. Antibiotic treatment can treat systemic syphilis before tertiary or neurosyphilis sequela present. It has been argued that any ocular manifestations of syphilis should be treated with a neurosyphilis regimen of penicillin therapy (14 days of penicillin G) to prevent further systemic or ocular complications including optic neuritis and Argyll Robertson pupils.[1][9]

Orsoni, et al. argues for immunosuppression therapy (oral cyclosporine) over topical corticosteroids for recurrent syphilitic keratitis due to the risk of cataracts and glaucoma with chronic corticosteroid use. Additionally, the efficacy of immunosuppressive agents is superior in recurrent syphilitic keratitis at preventing relapses.[8] Finally, protocols for immunosuppression and their safety profile have already been developed and studied for multiple other conditions including uveitis.[8] Surgical treatment for severe syphilitic keratitis presenting with corneal opacity is penetrating keratoplasty.[1][10] Penetrating keratoplasty can also be combined with cataract surgery if this complication is present. The outcomes of penetrating keratoplasty have shown that at 10-year follow-up the graft survival rate is just under 80%. Penetrating keratoplasty results in increased visual acuity in most patients, however, 20/20 vision is not always achieved. It is theorized that in patients not achieving normal vision early syphilitic keratitis causes some level of amblyopia.[10]


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 Wilhelmus KR. Syphilitic stromal keratitis. In: Mannis MJ, Holland EJ, ed. Cornea. United States: Elsevier Inc; 2017: 996-1012. Print.
  2. Aldave AJ, King JA, Cunningham ET. Ocular syphilis. Curr Opin Ophthalmol. 2001;12:433–441.
  3. Centers for Disease Control and Prevention. Together we can. The National Plan to Eliminate Syphilis from the United States. Atlanta, GA: US Department of Health and Human Services, May 2006.
  4. Schwartz GS, Harrison AR, Holland EJ. Etiology of immune stromal (interstitial) keratitis. Cornea 1998;17:278–81.
  5. Bodh SA, et al. Inflammatory glaucoma. Oman J Ophthalmol. 2011 Jan-Apr; 4(1): 3–9. doi: 10.4103/0974-620X.77655.
  6. Höllhumer R, Zairani Mz A, Watson S. Hemorrhagic Descemet Membrane Detachment Following Syphilitic Interstitial Keratitis. Cornea. 2016 Sep;35(9):1255-6.
  7. 7.0 7.1 Lee ME, Lindquist TD. Syphilitic Interstitial Keratitis. JAMA. 1989; 262(20):2921. doi:10.1001/jama.1989.03430200169047.
  8. 8.0 8.1 8.2 Orsoni JG, Zavota L, Manzotti F, Gonzales S. Syphilitic interstitial keratitis: treatment with immunosuppressive drug combination therapy. Cornea. 2004 Jul;23(5):530-2.
  9. Gaudio PA. Update on ocular syphilis. Curr Opin Ophthalmol, 2006;17(6), 562-566.
  10. 10.0 10.1 Goegebuer A, Ajay L, Claerhout I, et al. Results of penetrating keratoplasty in syphilitic interstitial keratitis. Bull Soc Belge Ophtalmol 2003; 290:35–9.
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