Ocular manifestations of syphilis ntroduction Background Syphilis is caused by an infection with a spirochete, Treponema pallidum, a thin, tightly wound,

relatively stiff, spiral-shaped parasite measuring 10-13 m. Schaudinn and Hoffman of Hamburg discovered T pallidum in 1905. This disease has been a source of social stigma, morbidity, and mortality for centuries, and it was notably notorious in the early 1900s for infectious chorioretinitis. The term "syphilis" came from a poem written in 1530 by the Italian poet Hiero Fracastor. His main character, in the poem, was an infected shepherd named Syphillus. Syphilis was first described at the end of the 15th century by an Italian physician, Nicolaus Leonicenus, at the same time of the return of the first European explorers from the New World. When Charles VIII of France invaded Naples with mercenaries from all over Europe, spread of this disease was noted on both war camps and was termed French Pox and Neopolitan Pox, respectively. Syphilis can be congenital or acquired. The acquired form usually is sexually transmitted, chronic, and systemic. Although the introduction of penicillin in the 1940s decreased the epidemiology, there has been a resurgence of the disease, over the past two decades, especially among nonwhites, male homosexuals, and intravenous drug users.

Bacterial resistance, poor socioeconomic backgrounds, increased high-risk sexual activity, and immunodepressing diseases have contributed to this resurgence. Syphilis has been given titles, such as "the great imitator, the great mimic, and the great masquerader!" of ocular inflammatory conditions. It lacks pathognomonic signs and often presents similar to other ocular inflammatory conditions. Syphilis is associated with the following ocular diseases: interstitial keratitis, episcleritis, scleritis, iritis, iris papules, chorioretinitis, papillitis, retinal vasculitis, and exudative retinal detachment. Pathophysiology Primary syphilis The predominant lesion of primary syphilis is a chancre at the inoculation site, which usually is at the genitalia region. Chancres are erythematous papules at the inoculation site that later erode to form painless ulcers. They may occur at multiple sites. Spirochetes fill the serous fluid from these lesions. The lesions appear 4 weeks after the initial infection and heal spontaneously in 1-2 months. After T pallidum penetrates the skin or mucous membrane, the organism enters the lymphatics and blood stream and disseminates shortly after contact. If left untreated, primary syphilis leads to secondary syphilis. Secondary syphilis

The systemic treponemal load is largest in secondary syphilis. Generalized maculopapular (or pustular rash), and lymphadenopathy are the characteristic lesions in this stage. These lesions appear 4-10 weeks after the initial manifestation. Lesions usually present at the flexor and volar body surfaces (ie, palms, soles). Resolution occurs without scarring, although hyperpigmentation or hypopigmentation may occur. Papules (condylomata lata) at the mucocutaneous junctions, and in moist areas of the skin, appearing as dull pink or gray hypertrophic lesions, are common. Constitutional symptoms of fever, malaise, headache, nausea, anorexia, and joint pains often are present. The liver, kidneys, and/or GI tract may or may not be involved. Ocular involvement has been reported in 10% of cases, and cerebrospinal fluid (CSF) pleocytosis has been seen in a few cases. Latent syphilis Latent syphilis follows secondary syphilis and is divided into 2 groups, early latent and late latent. These subgroups occur within and beyond 1 year after initial infection, respectively. Most cases have been reported to stay at the latent stage with 30% converting to the next stage. Tertiary syphilis Tertiary syphilis is divided into 3 groups (ie, benign tertiary, cardiovascular, neurosyphilis). Benign tertiary syphilis characteristically presents with gummatous lesions

that are actually granulomas, histologically, in the skin and the mucous membranes. The lesions may occur in the choroid, ciliary body, and iris. Cardiovascular syphilis presents with involvement of the coronary arteries or the aorta. Neurosyphilis may manifest with tabes dorsalis or general paresis. The CNS is affected via the vascular pathways or via direct involvement of parenchyma. Quaternary syphilis Quaternary syphilis has been disregarded for some time now; however, with the advent of AIDS-related syphilis cases, this stage is being reintroduced. Some authors use it to describe an aggressive form of neurosyphilis, where there is necrotizing encephalitis in patients with the acute immunodeficiency syndrome. Frequency United States Occurrence is higher in the southern and southwestern United States. It is higher in large urban populations. In 1940, prior to the introduction of antibiotics, the incidence of primary and secondary syphilis was about 100,000 cases. In 1956, with antibiotic therapy, incidence declined steadily to 10,000 cases. In the early 1980s, the incidence of syphilis rose to about 35,000. In 1988, 40,275 new cases of primary and secondary syphilis were reported.

In 1990, as a result of intravenous drug and crack cocaine abuse, as well as illegal prostitution, the incidence went up to more than 45,000 cases. In 1995, 16,500 cases were reported in the Summary of Notifiable Diseases. International In Seville, Spain, a report indicates that enhanced opportunity for spread accounts for clustering of syphilis in some towns. In Singapore, special political and sociologic factors, including prostitution, reduced prescribing of penicillin for gonorrhea because of the emergence of penicillin-resistant strains of Neisseria gonorrhoeae, and loss of "herd" immunity, resulted in an increase of early infectious syphilis from 1980-1984. Mortality/Morbidity Morbidity from primary and secondary syphilis ranges from the irritation brought about by the primary lesion to the more significant symptoms of secondary syphilis.

Infant deaths resulting from syphilis and new admissions of patients with syphilitic psychoses have fallen 99% in the United States since 1940. The total number of cases of late and latent syphilis has fallen 98% in the United States since 1943. Congenital syphilitic cases have decreased by 98% since 1941.

Race Incidence is greater among nonwhites. Sex

Incidence is greater in males than in females. Garfinkel and colleagues noted that women are screened less frequently for syphilis among emergency department patients with suspected sexually transmitted diseases (STDs).1 This raises a flag of concern about the underdiagnosis of women.

Age

Frequency is greater in young adults during the years of peak sexual activity. Most new cases occur in persons of both sexes aged 15-39 years, with the highest infection rates in individuals aged 20-29 years.

Clinical History It is essential for the physician to pay close attention to the patient's clinical history. A high index of suspicion, combined with an excellent history, leads to a streamlined list of differentials prior to examination.

Elicit a sexual history (ie, sexual intercourse, oral sex, anal sex). o Transmission of T pallidum is almost exclusively sexual.

Transmission through skin requires a break in the skin, but T pallidum can penetrate intact mucous membranes. Transplacental transmission from an infected mother to an infant accounts for infantile syphilis. Prior to modern donor screening procedures and blood banking, blood transfusions were another route for transmission. Spread by transfusion of fresh blood is still possible. Intravenous drug abuse contributes to the rising cases of syphilis. Syphilis can be spread by accidental contact with an infected lesion. The patient may complain initially of nonspecific symptoms, such as photophobia, eye redness, and blurring of vision.
o

Physical Syphilis may be congenital or acquired.

Congenital syphilis o Manifestations of the disease affect approximately 70% of infected newborn infants. o Congenital syphilis can present with a variety of ocular findings that include the following: Acute and chronic iritis Characteristic corneal lesion (see Interstitial keratitis) Scleritis Chorioretinitis "Salt and pepper" fundus

Pseudoretinitis pigmentosa (pseudo-RP) Retinal periphlebitis Optic neuritis Optic nerve pallor Secondary cataract Anterior uveitis o Unilateral in 56% of cases o Granulomatous with mutton-fat keratic precipitates on the corneal endothelium in 50% of cases o Iris nodules Iritis roseata (small, dilated collections of capillaries in the iris) Iritis papulosa (iritis roseata increasing in size to resemble a papule) Iritis nodosa (iritis papulosa increasing in size forming a yellow-red nodule) Treponemal emboli may cause vascular tortuosity and dilatation, which account for the iris nodules. Intermediate uveitis Posterior uveitis o Posterior uveitis (9-18%) o Panuveitis (27-47%) o Vitreal cells are typical. o Vasculitis with or without vascular occlusion, macular edema, stellate maculopathy, disciform macular detachment, serous macular/retinal detachment (pseudohypopyon), pseudo-RP, retinal detachment, neuroretinitis, papillitis, diffuse chorioretinitis, uveal effusion, central

retinal vein occlusion (CRVO), subretinal neovascular membrane (SNVM) formation, and retinal necrosis (big blind spot syndrome) o Syphilitic posterior placoid chorioretinitis Present in individuals who are HIV positive Large, flat, dry, yellowish, or gray (with baited centers); macular or juxtapapillary placoid lesions at the retinal pigment epithelium (RPE) layer Leopard spot hypofluorescence on fluorescein angiography Conjunctiva o Chancre in primary syphilis o Nonspecific conjunctivitis in secondary syphilis o Gumma in tertiary/late syphilis Scleritis/episcleritis o Nodular or diffuse o Usually present in secondary syphilis Interstitial keratitis o Nonulcerative and nonsuppurative inflammation of the corneal stroma o May form stromal neovascularization if untreated o Diffuse or localized o Congenital (90%) - Commonly appears between the sixth and twelfth years. Corneal edema and infiltrates are present with lacrimation and photophobia. Vascularization of the corneal stroma is characteristic and may give the cornea a pink salmon-patch appearance. The condition generally begins unilaterally and becomes bilateral in 90% of cases.

Acquired (10%) - Active interstitial keratitis shows stromal inflammation, especially in the peripheral cornea. Marginal infiltrates of the anterior stroma may be present, usually in association with anterior uveitis. When the uveal inflammation subsides, corneal scarring appears. Evidence of stromal neovascularization just anterior to the Descemet membrane may be present. Neuro-ophthalmic manifestations o Papillitis o Optic neuritis o Optic perineuritis o Papilledema Lids/eyebrows o Chancre rarely occurs in the primary stage. o Brow loss at its temporal aspect has been reported in secondary and tertiary syphilis. o Tarsitis or lid abscess rarely occurs in the tertiary stage. o Pseudoepitheliomatous hyperplasia also has been reported, as a rare occurrence, related to the gumma of tertiary syphilis. These lesions generally are elevated, and they have an uneven surface that is either ulcerated or crusty, which appears similar to squamous cell carcinoma or basal cell carcinoma. Others o Cataract has been seen in syphilis cases; however, it is not fully known whether the
o

development is caused by T pallidum or from the uveitis associated with the disease. Glaucoma almost always is associated with uveitic inflammation. In congenital syphilis, interstitial keratitis is associated with adult secondary glaucoma in 15-20% of patients. The glaucoma develops an average of 27 years after the initial episode of interstitial keratitis has subsided. Clinical evidence has shown 2 different forms of late glaucoma, a deep-chamber, openangle type, and a shallow-chamber, narrow-angle type. Both types occur with equal frequency and present with characteristic changes of congenital syphilis, such as corneal scarring with ghost vessels and chorioretinal atrophy.

Causes Spirochete T pallidum

The only known natural host is Homo sapiens. Its origin is unknown. The entire genome of T pallidum has been determined. There are 1.1 million base pairs, containing 1041 open reading frames. The study of these open reading frames and their protein products help scientists study the virulence factors, develop a method of culture, develop a vaccine, and develop specific and sensitive diagnostic tests.

Differential Diagnoses

Acute Multifocal Placoid Pigment Epitheliopathy Episcleritis HIV Keratitis, Interstitial Ocular Manifestations of HIV Papilledema Psoriasis Retinal Detachment, Exudative Sarcoidosis

Scleritis Stevens-Johnson Syndrome Tuberculosis Uveitis, Anterior, Granulomatous Uveitis, Classification Uveitis, Evaluation and Treatment

Other Problems to Be Considered Iritis Chorioretinitis Retinal vasculitis Papillitis Iris papules Neurosyphilis Genital warts Condyloma acuminata Lymphogranuloma venereum Chancroid Traumatic superinfected lesions Carcinoma Mycotic infection Granuloma inguinale Lichen planus

Fungal infection Venereal chlamydial infections Drug eruptions Pityriasis rosea Viral exanthem Workup Laboratory Studies

Serologic nontreponemal tests include Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR). o Nontreponemal tests detect antibodies directed against cardiolipin (lecithin) cholesterol antigens. o It is simple and convenient for routine screening at the local level. It is a frequent local requirement for premarital and prenatal serology. The false-positive rate for pregnant women is 12%. o A minimum of 1-3 weeks must pass from the onset of infection for the test to turn positive. It usually is positive in primary syphilis and invariably positive in secondary syphilis. o A high titer (>1:16) usually indicates active disease. Biologic false-positive tests (usually <1:8) occur in intravenous drug users, in many acute infections (eg, infectious mononucleosis, mycoplasmal infection, malaria, leprosy), in a variety of chronic disorders (eg, systemic lupus erythematosus), and possibly pregnancy.

Quantification of VDRL always should be performed before onset of treatment. o Nontreponemal test titers should decrease by 4fold within 3 months of adequate treatment of primary or secondary disease, and they should decrease by 8-fold within 6 months following therapy for early latent disease. o The cerebrospinal fluid (CSF) titer also should diminish with adequate therapy for neurosyphilis; however, the serum nontreponemal test titer may not change in patients with late latent syphilis. o The VDRL titer reflects the systemic activity of the disease. Its major value is in monitoring the response to treatment. o A persistent fall in VDRL titers after treatment provides essential evidence of an adequate response to therapy. o Reactive and weakly reactive tests should be confirmed with fluorescent treponemal antibody absorption (FTA-ABS). Serologic treponemal tests include microhemagglutination T pallidum (MHA-TP), FTA-ABS, T pallidum particle agglutination (TPA). o Their greatest value is in distinguishing falsepositive from true-positive reagin test results and in diagnosing late syphilis when blood and CSF reagin test results may be negative. o These are highly sensitive and specific tests. o Titers are not correlated with clinical activity.
o

The FTA-ABS test is not useful in monitoring response to therapy because it typically remains positive for life. The FTA-ABS test is 98% sensitive, even in latent syphilis. FTA-ABS test and TPA test are preferred over MHA-TP.

Other Tests

Dark-field immunofluorescence microscopy (direct technique) o Fluorescein-labeled anti-T pallidum antibodies are used in an immunofluorescence analysis of exudate or samples are taken from a lesion suggestive of syphilis. o The antibody attaches to syphilitic organisms displaying a motile apple-green, corkscrewshaped T pallidum. Electron microscopy: T pallidum organisms can be seen in interstitial and perivascular spaces. Ganzfeld electroretinogram (ERG) o Ganzfeld ERG was markedly reduced in a case of acute syphilitic posterior placoid chorioretinitis. o Multifocal ERG in the affected area was not recordable. Indocyanine green (ICG) angiography o ICG angiography may be a valuable tool in the assessment of patients with active ocular syphilis. o ICG angiography can help identify retinal and choroidal vascular anomalies that would

otherwise go undetected by funduscopy and/or fluorescein angiography. ICG angiography can also be useful in monitoring antitreponemal therapy. The following 2 types of anomalies were observed: Late-phase scattered hyperfluorescent spots Persistent staining of retinal vessels

Procedures

Lumbar puncture o Evaluation for asymptomatic neurosyphilis o Patients with positive syphilitic serologic tests should have their CSF examined for VDRL titers, total protein, and cell counts, including a differential count. o An elevated WBC count with a predominance of lymphocytes in the CSF or an elevated total protein level, even without a positive CSF VDRL test, is indicative of neurologic involvement, and the patient should be treated accordingly, as for neurosyphilis. HIV evaluation o Patients with ocular syphilis should be evaluated for HIV and vice versa. o Reports indicate that young adult patients who are HIV positive often have ocular syphilis. o Patients who have HIV may experience an aggressive course of syphilis, rendering standard

therapy for primary and secondary syphilis inadequate. Polymerase chain reaction o Diagnostic role in unusual or atypical ocular inflammation o Aqueous or vitreous specimens

Histologic Findings The organisms usually are superficial in epithelial lesions. A diffuse or focal lymphocytic infiltration is characteristic, particularly perivascularly. The tissue reaction is notable for stenosing intimal fibroplasia of small arteries and arterioles (eg, onion-skinning, obliterative endarteritis), as well as perivascular plasma infiltrate with some lymphocytes and macrophages. It may be found in the iris, ciliary body, or choroid. Chronic granulomatous inflammation containing epithelioid histiocytes and multinucleated giant cells is present. Overlying epidermal changes in skin can be hyperplastic (eg, condylomata lata) or ulcerating (eg, chancre). In tertiary disease, gummas are present (ie, areas of coagulative necrosis surrounded by lymphocytes, plasma cells, and possibly giant cells), and organisms are more abundant. Warthin-Starry silver stain, a specialized direct staining technique, sometimes is used. Treatment Medical Care Patients with ocular syphilis should be treated the same as patients with neurosyphilis.

The treatment regimen is the same even without CSF evidence of neurosyphilis. The blood-ocular barrier is similar to the blood-brain barrier in terms of decreasing the penetration of drugs. Patients with syphilitic ocular inflammation may have CNS syphilis without a VDRL-positive CSF. According to the Morbidity and Mortality Weekly Report (MMWR) No. RR-14, which is the most recent guideline for the treatment of syphilis, the treatment of neurosyphilis is as follows: o Administer aqueous crystalline penicillin G, 2-4 million U IV q4h for 10-14 days. Alternatively, give procaine penicillin IM qd plus probenecid, 500 mg PO qid both for 10-14 days. o In addition to the MMWR treatment guidelines for neurosyphilis, the administration of benzathine penicillin is preferred, 2.4 million U IM for 3 weeks, following either of the regimens to achieve a duration of therapy comparable to that of other forms for late syphilis.

Surgical Care In cases of interstitial keratitis, rehabilitative interventions include a penetrating keratoplasty. Consultations

Collaboration with an infectious disease specialist is ideal in cases of suggestive of syphilis. A lumbar puncture may be performed to exclude the possibility of neurosyphilis.

An allergologist consult may be warranted in cases of penicillin allergy.

Medication The goal of pharmacotherapy is to eradicate the infection, to prevent complications, and to reduce morbidity. Parenteral penicillin is DOC for all stages of syphilis. T pallidum is extremely sensitive to penicillin. Since T pallidum resistance to penicillin has not surfaced, the need for alternative drugs in treating syphilis is reserved for penicillin-allergic cases. Doxycycline, erythromycin, or tetracycline has been suggested for patients allergic to penicillin. Nonpenicillin regimen has been shown to be less effective in the treatment of neurosyphilis; therefore, attempts at penicillin desensitization may be worthwhile. Antibiotics Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Penicillin G aqueous, benzathine (Pfizerpen, Bicillin LA) Bactericidal against penicillin-susceptible microorganisms during stage of active multiplication. Inhibits biosynthesis of cell wall mucopeptide, rendering the cell wall osmotically unstable. Not active against penicillinase-

producing bacteria, which include many staphylococcal strains.

Dosing Interactions Contraindications Precautions

Adult 2-4 million U of aqueous crystalline penicillin G IV q4h for 10-14 d, followed by 2.4 million U of benzathine penicillin G IM qwk for 3 wk Pediatric Dose depends on age and stage of disease; suggested dosages are as follows: Syphilis <1 year: 50,000 U/kg IM once; not to exceed 2.4 million U Syphilis > 1 year: 50,000 U/kg IM qwk for 3 doses; not to exceed 2.4 million U

Dosing Interactions Contraindications Precautions

Probenecid can increase penicillin effectiveness by decreasing clearance; coadministration with tetracyclines and other bacteriostatic antibiotics can decrease effectiveness of penicillin

Dosing Interactions Contraindications Precautions

Documented hypersensitivity

Dosing Interactions Contraindications Precautions

Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions Caution in impaired renal function and patients with history of significant allergies and/or asthma

Doxycycline (Bio-Tab, Doryx, Vibramycin, Doxy) Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing Interactions Contraindications Precautions

Adult 100-200 mg/d PO qd or divided bid Pediatric <8 years: Not recommended >8 years: 2-5 mg/kg/d qd or divided bid; not to exceed 200 mg/d

Dosing Interactions Contraindications Precautions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Dosing Interactions Contraindications Precautions

Documented hypersensitivity; severe hepatic dysfunction

Dosing Interactions Contraindications

Precautions

Pregnancy D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus Precautions Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Erythromycin (E.E.S., E-Mycin, Ery-Tab) Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNAdependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Dosing Interactions Contraindications

Precautions

Adult 250 mg erythromycin stearate/base (or 400 mg ethylsuccinate) PO q6h, or 500 mg q12h (1 h ac or 2 h pc) Alternatively, 333 mg PO q8h; increase to 4 g/d depending on severity of infection Pediatric 30-50 mg/kg/d (15-25 mg/lb/d) PO divided q6-8h; double dose for severe infection

Dosing Interactions Contraindications Precautions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis

Dosing Interactions Contraindications Precautions

Documented hypersensitivity; hepatic impairment

Dosing Interactions

Contraindications Precautions

Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Tetracycline (Sumycin) Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

Dosing Interactions Contraindications Precautions

Adult 250-500 mg PO q6h Mild-to-moderate infections: 500 mg PO bid or 250 mg PO

qid for 7-14 d Severe infections: 500 mg PO qid for 7-14 d Pediatric <8 years: Not recommended >8 years: 25-50 mg/kg/d (10-20 mg/lb) PO qid

Dosing Interactions Contraindications Precautions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants

Dosing Interactions Contraindications Precautions

Documented hypersensitivity; severe hepatic dysfunction

Dosing Interactions Contraindications Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus Precautions Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines Uricosuric agents Used primarily to elevate and prolong plasma levels of penicillin.

Probenecid The generic name is 4-[(dipropylamine-)sulfonyl)]benzoic acid. Inhibits tubular secretion of penicillin, and usually increases penicillin plasma levels by any route the antibiotic is given. A 2-fold to 4-fold elevation has been demonstrated for various penicillins. Used in treatment of hyperuricemia associated with gout and gouty arthritis. Also used as an adjuvant to therapy with penicillin or ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whichever route the antibiotic is given.

Dosing Interactions Contraindications Precautions

Adult 500 mg PO qid 10-14 d Pediatric Initial: 25 mg/kg body-weight or 0.7 g/m2 body surface Maintenance: (next 9-13 d) 40 mg/kg body-weight or 1.2 g/m2 body surface divided qid

Media file 1: Ocular manifestations of syphilis. Interstitial keratitis in a patient with ocular syphilis.

Ocular manifestations of syphilis. Interstitial keratitis in a patient with ocular syphilis.

Ocular manifestations of syphilis. Syphilis chorioretinitis in a 30-year-old patient who is mentally retarded.

A 73-year-old female patient with syphilis. Note the optic atrophy, arteriolar narrowing, pigment loss, and clumping.

Retinal vasculitis in a patient with ocular syphilis.

Fluorescein angiography of same patient as in Media file 5.

Ocular manifestations of syphilis. Chorioretinitis of ocular syphilis.

cular manifestations of syphilis. Retinal vasculitis of ocular syphilis as seen on fluorescein angiography.