Syphilis and the Eye

Syphilis, caused by Treponema pallidum, can involve the eye at any stage, earning the name "the great imitator". Ocular syphilis has increased in incidence, especially in men who have sex with men and in people with HIV, and can cause permanent blindness if undiagnosed.

• Stages and ocular involvement:
  • Primary: chancre of the eyelid or conjunctiva (rare).
  • Secondary: uveitis (anterior, intermediate, posterior, panuveitis), retinitis, retinal vasculitis, scleritis, optic neuritis and perineuritis; most ocular disease occurs in the secondary and early latent stages.
  • Tertiary: gumma of the uveal tract or orbit, Argyll Robertson pupils, optic atrophy, cranial nerve palsies, and chorioretinitis.
  • Congenital: interstitial keratitis (5 to 20 years of age), salt-and-pepper chorioretinopathy, optic atrophy, glaucoma, and Hutchinson triad (interstitial keratitis, notched incisors, deafness).
• Syphilitic posterior placoid chorioretinopathy (yellow placoid lesion at the level of the retinal pigment epithelium) is a characteristic form.
• Every patient with ocular syphilis is presumed to have central nervous system involvement, so CSF examination is performed and the neurosyphilis regimen is used whatever the CSF result.

• Any uveitis pattern: granulomatous or non-granulomatous anterior uveitis with iris roseolae, vitritis, retinitis (necrotising or punctate inner retinitis), retinal vasculitis and vascular occlusion, placoid chorioretinopathy, macular oedema, and disc swelling.
• Painless bilateral blurred vision, photophobia, floaters, red eye, and field loss; ocular signs sometimes the only sign.
• Optic neuropathy: acute or subacute loss with disc swelling and relative afferent pupillary defect.
• Argyll Robertson pupils: small irregular pupils with light near dissociation.
• Interstitial keratitis in congenital syphilis: sectoral or diffuse stromal haze, deep vascularisation ("salmon patch"), photophobia, and later "ghost vessels".
• Systemic: rash on palms and soles, mucous patches, lymphadenopathy, headache, hearing loss, and cognitive changes.

• Serological tests: treponemal tests (enzyme immunoassay, Treponema pallidum particle agglutination, or fluorescent treponemal antibody absorption) with non-treponemal tests (rapid plasma reagin or VDRL with titres); a reactive treponemal test with a high or rising non-treponemal titre indicates active disease; non-treponemal titres may be negative in 1 to 2 percent (prozone) and late disease.
• HIV test (all patients); screening for other sexually transmitted infections.
• Lumbar puncture for CSF white cell count (above 5 cells per microlitre), protein, CSF VDRL, and treponemal tests, particularly with neurological or ocular posterior segment disease.
• Ocular imaging: slit lamp, dilated fundus examination, optical coherence tomography (outer retinal changes), fluorescein angiography (leakage, vasculitis, delayed filling), fundus autofluorescence, and B-scan.
• Polymerase chain reaction of aqueous or vitreous in difficult cases.

• Use the neurosyphilis regimen even when the CSF is normal: aqueous benzylpenicillin 18 to 24 million units daily, given as 3 to 4 million units IV every 4 hours (or continuous infusion), for 10 to 14 days. Alternative: procaine penicillin 2.4 million units IM once daily with probenecid 500 mg four times daily, both for 10 to 14 days. Penicillin allergy: desensitise where possible, or ceftriaxone 2 g IV daily for 10 to 14 days; doxycycline 200 mg twice daily for 28 days if no other option.
• Jarisch-Herxheimer reaction (after the first doses): prednisolone 20 to 40 mg daily for 3 days starting the day before or on the day of penicillin to reduce inflammation; topical steroids and cycloplegia for anterior uveitis (prednisolone acetate 1 percent every 2 to 4 hours, cyclopentolate 1 percent three times daily); oral prednisolone 1 mg/kg daily for posterior uveitis and optic neuritis after antimicrobial cover is established, tapered over 2 to 4 weeks.
• HIV co-infection: start or optimise antiretroviral therapy; treat partners.
• Congenital syphilis: aqueous benzylpenicillin 50,000 units/kg IV every 8 to 12 hours for 10 days; topical steroids for interstitial keratitis.
• Follow up: repeat non-treponemal titres at 3, 6, 12 and 24 months (a fourfold fall within 12 months indicates response); repeat CSF at 6 months until cells normalise; ocular review at 1 to 2 weeks, 4 weeks, and then every 3 months.
• Complications requiring treatment: macular oedema (intravitreal triamcinolone), retinal detachment (vitrectomy), neovascularisation (laser), glaucoma, and cataract.
• Partner notification, safe sex counselling, and repeat screening for reinfection.