Grand RoundsGrand Rounds

Michael Rubin, MDMichael Rubin, MDDepartment of Ophthalmology Department of Ophthalmology

and Visual Scienceand Visual ScienceThe University of ChicagoThe University of Chicago

25878402587840

November 25, 2003November 25, 2003

• 40 y/o M presents for retinal 40 y/o M presents for retinal evaluation.evaluation.

• Referred by Dr. Pitrak because pt newly Referred by Dr. Pitrak because pt newly diagnosed with HIV (CD4 168)diagnosed with HIV (CD4 168)

• PMH: HIV x 1 monthPMH: HIV x 1 month

• Meds: Paxil, BactrimMeds: Paxil, Bactrim

• VA: 20/25VA: 20/25 20/3020/30

• Exam: UnremarkableExam: Unremarkable

April 26, 2005April 26, 2005

• Pt presents to ER Service with Pt presents to ER Service with pressure, pain, and clear discharge pressure, pain, and clear discharge both eyes.both eyes.

• VA CC: 20/20VA CC: 20/20 20/4020/40

• VA RX: 20/20VA RX: 20/20 20/2520/25

ExamExam

• IOP: 16 and 14IOP: 16 and 14

Anterior Exam:Anterior Exam:

• Right: 2+ injection / KPs / 4 + Cell Right: 2+ injection / KPs / 4 + Cell and Flareand Flare

• Left: 2 + injection / PEK / D&Q Left: 2 + injection / PEK / D&Q

Posterior Exam:Posterior Exam:

• UnremarkableUnremarkable

TreatmentTreatment

• Started on PF QID OU and HA BID OUStarted on PF QID OU and HA BID OU

• F/U 3 daysF/U 3 days

April 29, 2005April 29, 2005

• Pt seen by Dr. Yeh in ER ClinicPt seen by Dr. Yeh in ER Clinic

• Pt “doing better.”Pt “doing better.”

• VA CC: 20/20VA CC: 20/20 20/2520/25

ExamExam

• IOP: 15 and 15IOP: 15 and 15

Anterior Exam:Anterior Exam:

• Right: 2+ injection / KPs / 4 + Cell and Right: 2+ injection / KPs / 4 + Cell and FlareFlare

• Left: 2 + injection / PEK / tr Cell and Left: 2 + injection / PEK / tr Cell and Flare Flare

Posterior Exam:Posterior Exam:

• UnremarkableUnremarkable

TreatmentTreatment

• Cont PF QID R, decrease PF to TID L, Cont PF QID R, decrease PF to TID L, Cont HA Bid, f/u with ER Service on Cont HA Bid, f/u with ER Service on 5/35/3

May 3, 2005May 3, 2005

• Patient states he is doing betterPatient states he is doing better

• VA: 20/20VA: 20/20 20/2520/25

• Exam:Exam:

• Trace cell right, quiet leftTrace cell right, quiet left

• Taper PF to BID RE, QD LETaper PF to BID RE, QD LE

• F/U 2 weeksF/U 2 weeks

May 17 and 31, 2005May 17 and 31, 2005

• Eyes quieted down, VA remained the Eyes quieted down, VA remained the same, tapered off of PF.same, tapered off of PF.

June 14, 2005June 14, 2005

• Patient presents to Dr. Rezaei with Patient presents to Dr. Rezaei with “severe vision loss in the right eye.”“severe vision loss in the right eye.”

• VA:VA: CF at 2ftCF at 2ft 20/2520/25

Thoughts?Thoughts?

• Differential Diagnosis…Differential Diagnosis…

HistoryHistory

• PMH: HIV with CD4 of 250 and HIV RNA PMH: HIV with CD4 of 250 and HIV RNA less than 75less than 75

• Meds: Sustiva 600/1, AZT 300/2, Meds: Sustiva 600/1, AZT 300/2, Abacavir 300/2, Lamivudine 150/2, Abacavir 300/2, Lamivudine 150/2, Paxil 20/1Paxil 20/1

• All: NKDAAll: NKDA• FH: N/CFH: N/C• SH: Grad student, former heavy ETOH SH: Grad student, former heavy ETOH

use, No tobacco or IVDA useuse, No tobacco or IVDA use

EXAMEXAM

AnteriorAnterior

• Right: D4 C1 F1Right: D4 C1 F1

• Left: NormalLeft: Normal

Posterior: See Fundus PhotoPosterior: See Fundus Photo

Photo MontagePhoto Montage

Right EyeRight Eye

Right Eye Peripheral ViewRight Eye Peripheral View

Left EyeLeft Eye

Next Step…Next Step…

• What do you want to do now?What do you want to do now?

Right EyeRight Eye

LELE

FANG LEFANG LE

RightRight

Right EyeRight Eye

Treatment?Treatment?

Treatment RenderedTreatment Rendered

• IV Acyclovir 600 mg IV q8 hours then IV Acyclovir 600 mg IV q8 hours then PO for total of 10 daysPO for total of 10 days

• Pred Forte 1% q6 hoursPred Forte 1% q6 hours

• HA BIDHA BID

Labs?Labs?

LabsLabs

• WBC: 4.5WBC: 4.5

• H/H: 14.3/42.0H/H: 14.3/42.0

• PLT: 227PLT: 227

RPRRPR

• RPR 512 ( < 1)RPR 512 ( < 1)

• Treponema IFA: PositiveTreponema IFA: Positive

Spinal TapSpinal Tap

• App: ClearApp: Clear

• Cells: 20Cells: 20

• WBC: 13WBC: 13

• Glc 57 (50-70)Glc 57 (50-70)

• Protein 51 (15-45)Protein 51 (15-45)

• VDRL CSF NRVDRL CSF NR

Spinal Tap Viral LoadSpinal Tap Viral Load

• VDRL CSF 8 (VDRL CSF 8 (<1)<1)

• HSV and VZV PCR for CSF NegativeHSV and VZV PCR for CSF Negative

• CD 4 306CD 4 306

Further TreatmentFurther Treatment

• Penicillin G 4 million units IV q4 for Penicillin G 4 million units IV q4 for 10 days10 days

Right Eye After TreatmentRight Eye After Treatment

Left Eye After TreatmentLeft Eye After Treatment

DemographicsDemographics

• More than 900,000 individuals are More than 900,000 individuals are infected with HIV in the US, and close infected with HIV in the US, and close to 30 million individuals carry the to 30 million individuals carry the virus worldwide. Among the virus worldwide. Among the individuals infected with HIV, individuals infected with HIV, approximately 70-80% will be treated approximately 70-80% will be treated for an HIV-associated eye disorder for an HIV-associated eye disorder during the course of the illness. during the course of the illness.

CD 4 Counts…CD 4 Counts…

• What diseases do you see at CD4:What diseases do you see at CD4:

• < 500:< 500:

• < 250:< 250:

• <100:<100:

CD 4 CountsCD 4 Counts

• In general, CD4+ T-lymphocyte count has been used to In general, CD4+ T-lymphocyte count has been used to predict the onset of certain ocular infections in patients predict the onset of certain ocular infections in patients who are HIV positive. who are HIV positive.

• CD4+ T-cell count less than 500 cells/mm3 is CD4+ T-cell count less than 500 cells/mm3 is associated with Kaposi sarcoma, lymphoma, and associated with Kaposi sarcoma, lymphoma, and tuberculosistuberculosis

• CD4+ T-cell count less than 250 cells/mm3 is CD4+ T-cell count less than 250 cells/mm3 is associated with pneumocystosis and toxoplasmosisassociated with pneumocystosis and toxoplasmosis

• CD4+ T-cell count less than 100 cells/mm3 is CD4+ T-cell count less than 100 cells/mm3 is associated with retinal or conjunctival associated with retinal or conjunctival microvasculopathy, cytomegalovirus (CMV) retinitis, microvasculopathy, cytomegalovirus (CMV) retinitis, varicella-zoster virus (VZV) retinitis, mycobacterium varicella-zoster virus (VZV) retinitis, mycobacterium avium complex infection, cryptococcosis, avium complex infection, cryptococcosis, microsporidiosis, HIV encephalopathy, and progressive microsporidiosis, HIV encephalopathy, and progressive multifocal leukoencephalopathy. multifocal leukoencephalopathy.

HZOHZO

• Background: HZO is a painful vesiculobullous Background: HZO is a painful vesiculobullous dermatitis, which results mostly from the reactivation dermatitis, which results mostly from the reactivation of previously established primary VZV infection. of previously established primary VZV infection.

• 20% of adults with primary infection eventually show 20% of adults with primary infection eventually show clinical symptoms. clinical symptoms.

• Clinical manifestation usually begins as pain over the Clinical manifestation usually begins as pain over the involved dermatome, most commonly the first division involved dermatome, most commonly the first division of trigeminal nerve (V1), lasting for several days, of trigeminal nerve (V1), lasting for several days, followed by dermatitis in the form of vesicular rash. followed by dermatitis in the form of vesicular rash.

• Herpes zoster can involve any dermatome, particularly Herpes zoster can involve any dermatome, particularly T3 to L3 and cranial V1 (most common), V2, and V3. T3 to L3 and cranial V1 (most common), V2, and V3. When the ophthalmic division is affected with or When the ophthalmic division is affected with or without ocular involvement, it is referred to as HZO. without ocular involvement, it is referred to as HZO.

Pathopysiology of HZOPathopysiology of HZO

• Pathophysiology: HZO results from Pathophysiology: HZO results from the reactivation of latent VZV from a the reactivation of latent VZV from a previous primary infection that previous primary infection that subsequently travels down the subsequently travels down the involved nerve; the most common involved nerve; the most common nerve involved is the first division of nerve involved is the first division of cranial nerve V (trigeminal nerve). cranial nerve V (trigeminal nerve).

FrequencyFrequency

• HZO affects about 5-15% of patients HZO affects about 5-15% of patients who are infected with HIV. who are infected with HIV.

IridocyclitisIridocyclitis

• Background: Iridocyclitis in patients who are Background: Iridocyclitis in patients who are HIV positive tends to be mild and often is HIV positive tends to be mild and often is associated with retinitis due to CMV or VZV. associated with retinitis due to CMV or VZV.

• When iridocyclitis is severe, it usually is seen When iridocyclitis is severe, it usually is seen in association with ocular toxoplasmosis, in association with ocular toxoplasmosis, tuberculosis, syphilis, or bacterial or fungal tuberculosis, syphilis, or bacterial or fungal retinitis (rare). Other causes of iridocyclitis in retinitis (rare). Other causes of iridocyclitis in HIV-positive patients include medications HIV-positive patients include medications (eg, rifabutin, cidofovir). (eg, rifabutin, cidofovir).

Posterior FindingsPosterior Findings

• Disorders of the posterior segment Disorders of the posterior segment are seen in more than 50% of are seen in more than 50% of patients who are HIV positive. patients who are HIV positive.

• Common presenting complaints Common presenting complaints include floaters, flashing lights, visual include floaters, flashing lights, visual field defect, and decreased visual field defect, and decreased visual acuity. acuity.

Second Years…Second Years…

• What is the most common retinal What is the most common retinal pathology in patients who are HIV pathology in patients who are HIV positive?positive?

• How does it present?How does it present?

• What is the underlying What is the underlying pathophysiology?pathophysiology?

HIV RetinopathyHIV Retinopathy

• Background: This is the most common retinal Background: This is the most common retinal pathology in patients who are HIV positive, often pathology in patients who are HIV positive, often manifesting as cotton-wool spots. manifesting as cotton-wool spots.

• Pathophysiology: The cause of retinal Pathophysiology: The cause of retinal microvasculopathy in patients who are infected with microvasculopathy in patients who are infected with HIV is similar to those suggested for conjunctival HIV is similar to those suggested for conjunctival vascular changes; increased plasma viscosity, vascular changes; increased plasma viscosity, immune-complex deposition, and a direct cytopathic immune-complex deposition, and a direct cytopathic effect of the virus on the retinal vascular endothelium effect of the virus on the retinal vascular endothelium are believed to be involved. The arteriolar occlusion in are believed to be involved. The arteriolar occlusion in HIV microvasculopathy leads to interruption of the HIV microvasculopathy leads to interruption of the axoplasmic flow, which manifests as cotton-wool axoplasmic flow, which manifests as cotton-wool spots. spots.

• Frequency: HIV retinal microvasculopathy occurs in as Frequency: HIV retinal microvasculopathy occurs in as many as 50-70% of patients who are HIV positive. many as 50-70% of patients who are HIV positive.

HIV-Related HIV-Related RetinochoroiditisRetinochoroiditis

• Background: Viral retinitis and/or choroiditis is the Background: Viral retinitis and/or choroiditis is the most common cause of infectious retinitis and/or most common cause of infectious retinitis and/or choroiditis. The herpesvirus family is implicated choroiditis. The herpesvirus family is implicated most commonly in infections of the retina and/or most commonly in infections of the retina and/or choroid in patients who are HIV positive. choroid in patients who are HIV positive.

• CMV is the most common cause of necrotizing CMV is the most common cause of necrotizing retinitis in patients who are HIV positive. VZV and retinitis in patients who are HIV positive. VZV and HSV may cause acute retinal necrosis (ARN), with HSV may cause acute retinal necrosis (ARN), with VZV as a more common cause of such necrotizing VZV as a more common cause of such necrotizing retinitis. This necrotizing retinitis may be unilateral retinitis. This necrotizing retinitis may be unilateral or bilateral. Another form of necrotizing retinitis, or bilateral. Another form of necrotizing retinitis, progressive outer retinal necrosis (PORN), may progressive outer retinal necrosis (PORN), may occur in advanced HIV disease. To date, VZV is the occur in advanced HIV disease. To date, VZV is the only organism associated with PORN. only organism associated with PORN.

Bacterial CausesBacterial Causes

• Common bacterial causes of retinitis in Common bacterial causes of retinitis in patients who are HIV positive include patients who are HIV positive include Treponema pallidumTreponema pallidum (syphilis) and (syphilis) and Mycobacterium tuberculosisMycobacterium tuberculosis. .

• Fungal causes of retinitis and/or choroiditis Fungal causes of retinitis and/or choroiditis include include Pseudallescheria boydii, Pseudallescheria boydii, Cryptococcus neoformans, Histoplasma Cryptococcus neoformans, Histoplasma capsulatumcapsulatum, as well as , as well as Candida, Sporothrix,Candida, Sporothrix, and and AspergillusAspergillus species. Parasitic causes species. Parasitic causes include include Toxoplasma gondiiToxoplasma gondii and and Pneumocystis carinii.Pneumocystis carinii.

Acute Retinal NecrosisAcute Retinal Necrosis

• Background: ARN is a fulminant retinal vaso-Background: ARN is a fulminant retinal vaso-occlusive necrotizing retinitis that may complicate occlusive necrotizing retinitis that may complicate VZV, HSV, or, rarely, CMV infections. HIV-positive VZV, HSV, or, rarely, CMV infections. HIV-positive patients with ARN tend to have a CD4+ count patients with ARN tend to have a CD4+ count greater than 60 cells/mL, usually with an greater than 60 cells/mL, usually with an associated history of VZV or HSV dermatitis. associated history of VZV or HSV dermatitis.

• Frequency: Incidence of VZV-associated retinitis Frequency: Incidence of VZV-associated retinitis after HZO in patients who are HIV positive is 4-after HZO in patients who are HIV positive is 4-17%. For retinitis following HSV or CMV infections, 17%. For retinitis following HSV or CMV infections, the frequencies are much lower compared to the the frequencies are much lower compared to the VZV-associated retinitis. A 2:1 male-to-female VZV-associated retinitis. A 2:1 male-to-female predilection with the occurrence of ARN exists. predilection with the occurrence of ARN exists.

Progressive Outer Retinal Progressive Outer Retinal NecrosisNecrosis

• Background: PORN is a rapidly progressive, Background: PORN is a rapidly progressive, necrotizing retinitis that has been reported in necrotizing retinitis that has been reported in patients with advanced AIDS. PORN is associated patients with advanced AIDS. PORN is associated with a history of VZV infection in patients with AIDS. with a history of VZV infection in patients with AIDS.

• Pathophysiology: While the exact pathophysiologic Pathophysiology: While the exact pathophysiologic mechanism for PORN has not been elucidated mechanism for PORN has not been elucidated completely, the general consensus is that severe completely, the general consensus is that severe immunocompromise along with a previous infection immunocompromise along with a previous infection with at least VZV infection are necessary. PORN also with at least VZV infection are necessary. PORN also has been described in patients with severe has been described in patients with severe immunocompromise secondary to chemotherapy. immunocompromise secondary to chemotherapy.

• Frequency: Incidence of PORN is much lower than Frequency: Incidence of PORN is much lower than ARN. ARN.

ARNARN

• Acute retinal necrosis:Acute retinal necrosis: Patients with ARN usually Patients with ARN usually present with eye pain associated with decreased present with eye pain associated with decreased visual acuity, floaters, and history of recent HSV or visual acuity, floaters, and history of recent HSV or HZV infection. In early disease, funduscopic HZV infection. In early disease, funduscopic examination often reveals small, necrotic yellowish examination often reveals small, necrotic yellowish lesions in the periphery, which rapidly spread into a lesions in the periphery, which rapidly spread into a larger confluent white area, most often involving larger confluent white area, most often involving the entire peripheral retina, and then progress the entire peripheral retina, and then progress toward the posterior pole. In about 36% of cases, toward the posterior pole. In about 36% of cases, the second eye is involved. Associated anterior the second eye is involved. Associated anterior uveitis, retinal vasculitis, episcleritis, scleritis, or uveitis, retinal vasculitis, episcleritis, scleritis, or retinal detachment may be present.retinal detachment may be present.

Complications of ARNComplications of ARN

• Acute retinal necrosis: ARN frequently is complicated Acute retinal necrosis: ARN frequently is complicated by anterior uveitis, retinal and choroidal vasculitis, by anterior uveitis, retinal and choroidal vasculitis, vitritis, and papillitis. Episcleritis, scleritis, or optic vitritis, and papillitis. Episcleritis, scleritis, or optic neuropathy also may be present. neuropathy also may be present.

• During the initial phase of the infection, the severity of During the initial phase of the infection, the severity of the retinitis could lead to exudative retinal the retinitis could lead to exudative retinal detachment. However, following the resolution of the detachment. However, following the resolution of the retinitis, traction between the vitreous and the retinitis, traction between the vitreous and the resulting gliotic scar of the necrotic retina may occur resulting gliotic scar of the necrotic retina may occur and can cause retinal breaks at the interface between and can cause retinal breaks at the interface between the normal and necrotic retina. Subsequently, this may the normal and necrotic retina. Subsequently, this may result in RRD. As many as 75% of eyes affected by ARN result in RRD. As many as 75% of eyes affected by ARN may be complicated by RRD after 2-3 months of onset. may be complicated by RRD after 2-3 months of onset.

PORNPORN

• Progressive outer retinal necrosis:Progressive outer retinal necrosis: Patients with PORN usually present with Patients with PORN usually present with minimal anterior chamber inflammation, minimal anterior chamber inflammation, with no vitritis or retinal vasculitis. In with no vitritis or retinal vasculitis. In general, the lesions in PORN usually are general, the lesions in PORN usually are multifocal, deep to the retina, opaque, and multifocal, deep to the retina, opaque, and patchy, with a tendency to start from the patchy, with a tendency to start from the posterior pole and spread with extreme posterior pole and spread with extreme rapidity to involve the entire retina.rapidity to involve the entire retina.

Complications of PORNComplications of PORN

• Complications of PORN may include Complications of PORN may include macular retinitis, optic nerve disease, macular retinitis, optic nerve disease, acute vitreous hemorrhage, and/or acute vitreous hemorrhage, and/or retinal detachment. Up to 66% of retinal detachment. Up to 66% of patients diagnosed with PORN patients diagnosed with PORN eventually become blind within 6 eventually become blind within 6 weeks of diagnosis despite weeks of diagnosis despite aggressive treatment.aggressive treatment.

Labs for PORN and ARNLabs for PORN and ARN

• Acute retinal necrosis Acute retinal necrosis – Perform a detailed history and a complete Perform a detailed history and a complete

ophthalmologic examination with dilated ophthalmologic examination with dilated funduscopic examination for diagnosis of ARN. funduscopic examination for diagnosis of ARN.

– Check for HSV-1, HSV-2, and CMV IgG and IgM Check for HSV-1, HSV-2, and CMV IgG and IgM titers.titers.

• Progressive outer retinal necrosis Progressive outer retinal necrosis – Workup of PORN is similar to ARN, except that Workup of PORN is similar to ARN, except that

the serology focuses on HZV IgG and IgM titers. the serology focuses on HZV IgG and IgM titers. – See ARN for details.See ARN for details.

Treatment for ARN / PORNTreatment for ARN / PORN

• Start acyclovir 5-10 mg/kg/d IV in 3 divided doses for 1 week, then change Start acyclovir 5-10 mg/kg/d IV in 3 divided doses for 1 week, then change to oral acyclovir 800 mg 5 times daily for the following 1-2 months. Monitor to oral acyclovir 800 mg 5 times daily for the following 1-2 months. Monitor blood urea nitrogen and creatine levels because of the nephrotoxic effect blood urea nitrogen and creatine levels because of the nephrotoxic effect of acyclovir. of acyclovir.

• Start a slow tapering dosage of prednisone 60-100 mg PO daily 24 hours Start a slow tapering dosage of prednisone 60-100 mg PO daily 24 hours after starting acyclovir, continue for about 1-2 months. Be sure to obtain a after starting acyclovir, continue for about 1-2 months. Be sure to obtain a chest x-ray and PPD before starting the oral steroid. chest x-ray and PPD before starting the oral steroid.

• A topical steroid, such as prednisolone acetate 1%, instilled q2-6h, and a A topical steroid, such as prednisolone acetate 1%, instilled q2-6h, and a cycloplegic agent, such as homatropine 5% instilled 2-3 times daily. cycloplegic agent, such as homatropine 5% instilled 2-3 times daily.

• Add Zantac 150 mg PO twice daily for steroid-induced gastritis. Add Zantac 150 mg PO twice daily for steroid-induced gastritis. • In fulminate cases, particularly in HIV-positive patients, IV or intravitreal In fulminate cases, particularly in HIV-positive patients, IV or intravitreal

ganciclovir and/or foscarnet, or intravenous cidofovir may be considered ganciclovir and/or foscarnet, or intravenous cidofovir may be considered (see (see CMVCMV for dosage). for dosage).

• Use of retinal laser photocoagulation to surround the necrotic lesion is still Use of retinal laser photocoagulation to surround the necrotic lesion is still controversial. controversial.

• For retinal detachment, vitrectomy, membranectomy, endolaser, and For retinal detachment, vitrectomy, membranectomy, endolaser, and silicone oil infusion usually is required. silicone oil infusion usually is required.

Intravitreal Antivirals in the Management of Patients With Acquired Intravitreal Antivirals in the Management of Patients With Acquired Immunodeficiency Syndrome With Progressive Outer Retinal NecrosisImmunodeficiency Syndrome With Progressive Outer Retinal Necrosis

SyphilisSyphilis

• Pathophysiology: Syphilis is believed to result from the Pathophysiology: Syphilis is believed to result from the proliferation and subsequent infiltration of proliferation and subsequent infiltration of T pallidumT pallidum spirochetes into ocular structures. Histologic evaluation spirochetes into ocular structures. Histologic evaluation demonstrates mononuclear and polymorphonuclear cell demonstrates mononuclear and polymorphonuclear cell infiltration of the involved ocular tissue, particularly infiltration of the involved ocular tissue, particularly cornea, iris, retina, and choroid. cornea, iris, retina, and choroid.

• Frequency: Incidence of syphilis has been on the rise Frequency: Incidence of syphilis has been on the rise since 1985, with 25% of the new cases reported from since 1985, with 25% of the new cases reported from 1986-1987. This rise in the number of new cases of 1986-1987. This rise in the number of new cases of syphilis was correlated to a shift from heterosexual to syphilis was correlated to a shift from heterosexual to homosexual and bisexual males who constitute homosexual and bisexual males who constitute approximately 30-40% of all the new cases. Usually a approximately 30-40% of all the new cases. Usually a 5% rate of ocular involvement in untreated cases 5% rate of ocular involvement in untreated cases occurs with rare ocular involvement within 6 months of occurs with rare ocular involvement within 6 months of primary infection. primary infection.

SyphilisSyphilis

• Syphilis:Syphilis: The presentation of the patient The presentation of the patient depends on the stage of the disease. The ocular depends on the stage of the disease. The ocular findings in syphilis can mimic any ocular findings in syphilis can mimic any ocular inflammatory disorder, including conjunctivitis, inflammatory disorder, including conjunctivitis, interstitial keratitis, episcleritis, scleritis, interstitial keratitis, episcleritis, scleritis, choroiditis, vascular occlusion, Argyll-Robertson choroiditis, vascular occlusion, Argyll-Robertson pupil, Raeder syndrome, cranial nerve palsies, pupil, Raeder syndrome, cranial nerve palsies, optic neuritis, and optic atrophy. Most of the optic neuritis, and optic atrophy. Most of the ocular findings are seen in stage 2 (secondary) ocular findings are seen in stage 2 (secondary) and stage 3 (tertiary). Initial presentation of and stage 3 (tertiary). Initial presentation of ocular syphilis is unilateral with subsequent ocular syphilis is unilateral with subsequent contralateral eye involvement in 50% of cases. contralateral eye involvement in 50% of cases.

StagesStages

• Primary - Eyelid or conjunctival chancre Primary - Eyelid or conjunctival chancre • Secondary or tertiary - Iridocyclitis or more diffuse Secondary or tertiary - Iridocyclitis or more diffuse

intraocular inflammation is present. Other manifestations of intraocular inflammation is present. Other manifestations of secondary and/or tertiary syphilis include optic neuritis, secondary and/or tertiary syphilis include optic neuritis, active chorioretinitis, retinitis, retinal vasculitis, active chorioretinitis, retinitis, retinal vasculitis, conjunctivitis, episcleritis dacryoadenitis, dacryocystitis, conjunctivitis, episcleritis dacryoadenitis, dacryocystitis, scleritis, and monocular interstitial keratitis. Dissemination scleritis, and monocular interstitial keratitis. Dissemination of the disease in secondary syphilis may be accompanied by of the disease in secondary syphilis may be accompanied by arthralgia, headache, low-grade fever, and maculopapular arthralgia, headache, low-grade fever, and maculopapular rash. Three distinct patterns of iris findings may be seen rash. Three distinct patterns of iris findings may be seen prior or during the active stage of the disease, as follows: prior or during the active stage of the disease, as follows: (1) iris roseata in which reddish spots or engorged vascular (1) iris roseata in which reddish spots or engorged vascular tufts that resolve with treatment are present, (2) iris tufts that resolve with treatment are present, (2) iris papulosa in which the roseata spots increase in size to papulosa in which the roseata spots increase in size to resemble a papule, and (3) iris nodosa in which the area of resemble a papule, and (3) iris nodosa in which the area of iris lesion forms a large yellow-red nodule. iris lesion forms a large yellow-red nodule.

TertiaryTertiary

• Tertiary - Inadequately treated syphilis Tertiary - Inadequately treated syphilis or untreated disease sets the stage for or untreated disease sets the stage for tertiary syphilis, which includes the tertiary syphilis, which includes the development of an obliterative development of an obliterative endarteritis in about one third of the endarteritis in about one third of the patients. Optic atrophy, chorioretinitis, patients. Optic atrophy, chorioretinitis, chronic iritis, Argyll-Robertson pupil chronic iritis, Argyll-Robertson pupil also are seen in this stage.also are seen in this stage.

Labs for SyphilisLabs for Syphilis

• SyphilisSyphilis– The VDRL becomes positive 1-3 weeks after the appearance of the The VDRL becomes positive 1-3 weeks after the appearance of the

chancre. chancre. – Fluorescent treponemal antibody absorption (FTA-ABS) test or Fluorescent treponemal antibody absorption (FTA-ABS) test or

microhemagglutination microhemagglutination Treponema pallidumTreponema pallidum (MHA-TP) is highly (MHA-TP) is highly sensitive and specific in all stages of syphilis. Once reactive, these sensitive and specific in all stages of syphilis. Once reactive, these tests do not reverse to normal, and they are not helpful in assessing tests do not reverse to normal, and they are not helpful in assessing the patient's response to treatment. the patient's response to treatment.

– Lumbar puncture (LP) may be performed if the FTA-ABS test is positive Lumbar puncture (LP) may be performed if the FTA-ABS test is positive combined with neurologic or neuro-ophthalmologic signs, papillitis, combined with neurologic or neuro-ophthalmologic signs, papillitis, active chorioretinitis, or uveitis. active chorioretinitis, or uveitis.

– Diagnoses of ocular syphilis should include obtaining a specific Diagnoses of ocular syphilis should include obtaining a specific treponemal-antibody assay (FTA-ABS or MHA-TP) and nonspecific treponemal-antibody assay (FTA-ABS or MHA-TP) and nonspecific treponemal-antibody assay (Venereal Disease Research Laboratory treponemal-antibody assay (Venereal Disease Research Laboratory [VDRL] test or rapid plasma reagin [RPR]). VDRL or RPR correlates with [VDRL] test or rapid plasma reagin [RPR]). VDRL or RPR correlates with disease activity, and it is useful in monitoring response to treatment. It disease activity, and it is useful in monitoring response to treatment. It also is used for screening, but it may show a false-negative result in also is used for screening, but it may show a false-negative result in early primary, latent, or late syphilis. It is not as specific as FTA-ABS or early primary, latent, or late syphilis. It is not as specific as FTA-ABS or MHA-TP.MHA-TP.

Treatment for SyphilisTreatment for Syphilis

• All HIV-positive patients with syphilitic eye findings All HIV-positive patients with syphilitic eye findings are considered to have tertiary syphilis and are are considered to have tertiary syphilis and are treated accordingly. treated accordingly.

• Treatment of syphilis is with intravenous penicillin G Treatment of syphilis is with intravenous penicillin G (24 million U/d for 7-10 d). Relapse may occur in spite (24 million U/d for 7-10 d). Relapse may occur in spite of adequate treatment. For penicillin-allergic patients, of adequate treatment. For penicillin-allergic patients, tetracycline 500 mg 4 times per day or doxycycline tetracycline 500 mg 4 times per day or doxycycline 200 mg twice a day by mouth for 30 days or a third-200 mg twice a day by mouth for 30 days or a third-generation cephalosporin (ceftriaxone). generation cephalosporin (ceftriaxone).

• Cycloplegia with either cyclopentolate 2% or Cycloplegia with either cyclopentolate 2% or homatropine 5% 3 tid and prednisolone acetate 1% homatropine 5% 3 tid and prednisolone acetate 1% qid is recommended if anterior segment inflammation qid is recommended if anterior segment inflammation is present.is present.

Financial ConsiderationsFinancial Considerations

• Initial visit: $160Initial visit: $160

• Follow up visit x 3: $103 x 3 = $309Follow up visit x 3: $103 x 3 = $309

• Yet to collectYet to collect

Cost of Lumbar PunctureCost of Lumbar Puncture

• Lumbar Puncture Dx (CPT 62270): $ Lumbar Puncture Dx (CPT 62270): $ 600600

• Labs Associated with LP: $740Labs Associated with LP: $740

• Yet to collectYet to collect

Inpatient billingInpatient billing

Inpatient Billed: $2389.00 x 3 = $7267Inpatient Billed: $2389.00 x 3 = $7267

Insurance Pays: $1433.40 x 3 = Insurance Pays: $1433.40 x 3 = $4300.20$4300.20

Practice Based LearningPractice Based Learning

• 1. Ocular inflammation in a patient with 1. Ocular inflammation in a patient with HIV merits consideration of a broader HIV merits consideration of a broader differential diagnosis.differential diagnosis.

• 2. Multiple diseases processes could be 2. Multiple diseases processes could be implicated in HIV related implicated in HIV related chorioretinopathy.chorioretinopathy.

• 3. Laboratory evaluation early in the 3. Laboratory evaluation early in the course of the ophthalmic disease process course of the ophthalmic disease process may minimize morbidity.may minimize morbidity.

ARNARN