virus infection. Whether our cases were congenital oracquired cannot be determined. In the literature, ocularmanifestations of lymphocytic choriomeningitis virusinfection have been noted to mimic those of toxoplas-mosis. Our observations support the need to test forlymphocytic choriomeningitis virus infection in pa-tients with chorioretinal scars and negative toxoplasmagondii serologic tests.

REFERENCES

1. Daffos F, Forestier F, Capella-Pavlovsky M, et al. Prenatalmanagement of 746 pregnancies at risk for congenital toxo-plasmosis. N Engl J Med 1988;318:271–275.

2. Rousseau MC, Saron MF, Brouqui P, Bourgeade A. Lympho-cytic choriomeningitis virus in southern France: four casereports and a review of the literature. Eur J Epidemiol.1997;13:817–23.

3. Wright R, Johnson D, Neumann M, et al. Congenital chorio-meningitis virus syndrome: a disease that mimics congenitaltoxoplasmosis or cytomegalovirus infection. Pediatrics 1997;100:e9.

4. Bechtel RT, Haught KA, Mets MB. Lymphocytic choriomen-ingitis virus: a new addition to the TORCH evaluation. ArchOphthalmol 1997;115:680–681.

5. Ackerman R, Kalter SS, Heberling RL, et al. Fetal infection ofthe baboon (Papio cynocephalus) with lymphocytic chorio-meningitis virus. Arch Virol 1979;60:311–23.

Choroidal Neovascularization WithGranulomatous Inflammation inOcular Histoplasmosis SyndromeEric S. Mann, MD, PhD, Steven J. Fogarty, MD,and Marilyn C. Kincaid, MD

PURPOSE: To report pathologic examination of an excisedchoroidal neovascular membrane in a patient with ocularhistoplasmosis syndrome that demonstrated granuloma-tous inflammation.METHOD: Case report. A 50-year-old woman with suddenvision loss in her left eye demonstrated clinical andfluorescein angiographic findings characteristic of choroi-dal neovascularization secondary to ocular histoplasmosissyndrome.RESULTS: Histopathologic examination of the surgicallyexcised choroidal neovascular membrane disclosed gran-ulomatous inflammation.

Accepted for publication March 14, 2000.From the Departments of Ophthalmology (E.S.M., S.J.F., M.C.K.), and

Pathology (M.C.K.), Saint Louis University Health Sciences Center, StLouis, Missouri.

Inquiries to Eric S. Mann, MD, PhD, Saint Louis University EyeInstitute, 1755 S Grand Blvd, St Louis, MO 63104; e-mail:manne4@slu.edu

FIGURE 2. Fundus photograph of the left eye of patient 2, demonstrating pseudotoxoplasmic, multiple, macular, chorioretinalscars.

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CONCLUSIONS: This case suggests an important role ofmononuclear phagocytic cells as primary mediators ofangiogenesis or modifiers of choroidal neovasculariza-tion. This association of choroidal neovascularizationwith granulomatous inflammation did not respond totreatment with systemic corticosteroids. (Am J Oph-thalmol 2000;130:247–250. © 2000 by Elsevier ScienceInc. All rights reserved.)

SUBFOVEAL CHOROIDAL NEOVASCULARIZATION SEC-

ondary to the ocular histoplasmosis syndrome fre-quently results in profound visual loss with no benefit fromlaser photocoagulation. Surgical removal of subfoveal cho-roidal neovascularization in ocular histoplasmosis syn-drome is currently being evaluated as a treatmentalternative in the randomized, controlled SubmacularSurgery Trial. Though the pathogenesis of choroidal neo-vascularization is poorly understood, histopathology re-ports of such surgically excised membranes have providedinsight into the underlying pathogenesis.1–5

A 50-year-old woman was examined because of suddenvision loss in her left eye. The patient had no history ofprevious granulomatous disease but had resided in an area

endemic for histoplasmosis all her life. Ocular examinationshowed a best-corrected visual acuity of RE: 20/30 and LE:20/200. Results of slit-lamp examination were unremark-able in both eyes. There was no evidence of intraocularinflammation, and there was no vitreous cell or posteriorvitreous separation in either eye. Fundus examinationshowed peripapillary atrophy with chorioretinal scars inthe midperiphery and macula of both eyes. The left eyedemonstrated a serous neurosensory retinal detachmentwith subretinal hemorrhage suggestive of choroidal neo-vascularization (Figure 1, top). The clinical macula of botheyes showed no drusen. Fluorescein angiography confirmedsubfoveal choroidal neovascularization (Figure 1, bottomleft and right).

Systemic corticosteroid therapy with oral prednisone(60 mg daily) for more than 1 month was of no benefit infacilitating regression of the choroidal neovascularizationor in improving vision. The patient elected submacularsurgery to excise the subfoveal choroidal neovasculariza-tion but declined enrollment in the Submacular SurgeryTrial. Pathologic examination of the excised subfovealchoroidal neovascularization with light microscopy dem-onstrated fibrovascular proliferation with granulomatous

FIGURE 1. Fundus photograph (top) of the left eye shows peripapillary atrophy, chorioretinal macular scar, and choroidalneovascularization with subretinal hemorrhage and a serous neurosensory retinal detachment. Early (bottom left) and late (bottom right)phases of the fluorescein angiogram demonstrate subfoveal choroidal neovascularization (arrow) and subretinal hemorrhage (arrowhead).

AMERICAN JOURNAL OF OPHTHALMOLOGY248 AUGUST 2000

inflammation (Figure 2). Retinal pigment epithelial cellswere seen within the surgical specimen, but a monolayer ofretinal pigment epithelium was not found. No microorgan-isms were seen with Gomori methenamine-silver, acid-fast,or periodic acid–Schiff stains. Results of a systemic evalu-ation for granulomatous disease were negative.

Best postoperative visual acuity was LE: 20/60 untilrecurrent juxtafoveal choroidal neovascularization neces-sitated focal laser treatment. Recurrent subfoveal choroidalneovascularization 9 weeks after surgery resulted in loss ofvisual acuity to 20/200. Oral prednisone failed to improvevision, and the patient declined further surgery.

Granulomatous inflammation with choroidal neovascu-larization has been reported in whole eyes and surgicallyexcised membranes with age-related macular degenera-tion2,3 and in surgically excised choroidal neovasculariza-tion thought to be idiopathic or “an incompletemanifestation of the ocular histoplasmosis syndrome.”4

This case demonstrates granulomatous inflammation in asurgically excised choroidal neovascular membrane froman eye with typical ocular histoplasmosis syndrome.

Most previous histopathologic studies of excised choroi-dal neovascular membranes by light and electron micros-copy and by immunohistochemistry show a nonspecific,localized stereotypic wound repair response similar togranulation tissue.1 The clinical and fluorescein angio-graphic findings in this case are characteristic of choroidalneovascularization in ocular histoplasmosis syndrome, yetthe surgically excised specimen is morphologically differ-

ent from in previous reports, with epithelioid cells andattenuated vascular channels.

The significance of mononuclear phagocytic cells in thepathogenesis of choroidal neovascularization is unknown.The presence of giant cells in choroidal neovascularmembranes of whole eyes and in surgically excised mem-branes in both age-related macular degeneration andocular histoplasmosis syndrome may suggest an importantrole of mononuclear phagocytic cells as primary mediatorsof angiogenesis or modifiers of choroidal neovasculariza-tion through their release of cytokines, expression of celladhesion molecules (integrins), and degradation of theextracellular matrix (metalloproteinases). Inflammatorychorioretinal lesions do indeed recur in patients withocular histoplasmosis syndrome and may precede choroidalneovascularization.6 Perhaps the association between cho-roidal neovascularization and subretinal granulomatousinflammation reflects a particular response to or a pathwayof breakdown of Bruch membrane, as suggested in age-related macular degeneration.5

REFERENCES

1. Saxe SJ, Grossniklaus HE, Lopez PF, et al. Ultrastructuralfeatures of surgically excised subretinal neovascular mem-branes in the ocular histoplasmosis syndrome. Arch Oph-thalmol 1993;111:88–95.

2. Penfold PL, Killingsworth MC, Sarks SH. Senile maculardegeneration: the involvement of immunocompetent cells.Graefes Arch Clin Exp Ophthalmol 1985;223:69–76.

FIGURE 2. Surgically excised choroidal neovascular membrane (arrow) showing granulomatous inflammation with pale-stainingepithelioid cells (arrowheads), surrounded by lymphocytes (hematoxylin-eosin, 3440).

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3. Hutchinson AK, Grossniklaus HE, Capone A. Giant-cellreaction in surgically excised subretinal neovascular mem-brane. Arch Ophthalmol 1993;111:734–735.

4. Pavan PR, Margo CE. Submacular neovascular membraneand focal granulomatous inflammation. Ophthalmology1996;103:586–589.

5. Dastgheib K, Green WR. Granulomatous reaction to Bruch’smembrane in age-related macular degeneration. Arch Oph-thalmol 1994;112:813–818.

6. Callanan D, Gish GE, Anand R. Reactivation of inflamma-tory lesions in ocular histoplasmosis. Arch Ophthalmol1998;116:470–474.

Chorioretinal Involvement in PrimarySystemic Nonfamilial AmyloidosisAlfredo Pece, MD, Lawrence Yannuzzi, MD,Carmen Sannace, MD,Baldo Scassellati Sforzolini, MD, andRosario Brancato, MD

PURPOSE: To report a case of primary systemic nonfamil-ial amyloidosis studied by fluorescein angiography andindocyanine green angiography.METHODS: Case report. A 59-year-old woman with pri-mary systemic nonfamilial amyloidosis presented bilat-eral diffuse deep hemorrhages and pigmentary mottling atthe posterior pole.RESULTS: On fluorescein angiography bilateral diffuseareas of hypofluorescence were present. Indocyaninegreen angiography showed large hypofluorescent areaswith hypofluorescent lines in the midperiphery and hy-perfluorescent streaks in the peripapillary area.CONCLUSIONS: In this case of primary systemic nonfamil-ial amyloidosis, diffuse bilateral chorioretinal abnormal-ities included hemorrhages and pigmentary mottling atthe posterior pole, with hypofluorescent areas on fluo-rescein angiography and indocyanine green angiography,as well as hypofluorescent lines in the midperiphery.(Am J Ophthalmol 2000;130:250–253. © 2000 byElsevier Science Inc. All rights reserved.)

PRIMARY SYSTEMIC NONFAMILIAL AMYLOIDOSIS OR SO-

called AL amyloidosis is a systemic disorder character-ized by an aberrant deposition in single or multiple organsystems of insoluble chains of polypeptides derived from a

portion of the light chain of immunoglobulins. Nephroticsyndrome, congestive heart failure, and peripheral neurop-athy are the most common severe complications of thisdisease.1 We describe a case of primary systemic nonfamil-ial amyloidosis with severe chorioretinal involvement andabnormal findings on fluorescein angiography and indocya-nine green angiography.

A 59 year-old woman presented in 1998 with a 6-monthhistory of bilateral visual loss and metamorphopsia. Thepast medical history was significant for primary systemicnonfamilial amyloidosis with renal involvement since1990 and peritoneal dialysis for renal failure since 1995.The visual acuity was RE: 20/40 and LE: 20/32; the Amslertest confirmed the metamorphopsia in both eyes. Anteriorsegment and intraocular pressure were normal. Ophthal-moscopy showed bilateral, diffuse, deep hemorrhages in-volving the posterior pole with pigmentary mottling in themacular area (Figures 1 and 2, top left). On fluoresceinangiography diffuse areas of hypofluorescence, partiallyoverlapping with the hemorrhages seen on ophthalmos-copy, were observed. These hypofluorescent areas persistedunchanged in the late phases. Hyperfluorescent streakswere also present in the peripapillary area. Large hypofluo-rescent areas with “salt and pepper” pigmentary mottlingwere visible both on fluorescein angiography and indocya-nine green angiography. In the periphery choroidal vesselsappeared as hypofluorescent lines on indocyanine greenangiography. Hyperfluorescent streaks radiating from theoptic disk could be observed in the late frames of indocya-nine green angiography (Figures 1 and 2). After 1 year offollow-up the clinical status and the angiographic findingswere unchanged.

Ocular involvement in primary systemic nonfamilialamyloidosis has been infrequently reported.2 Purcell3 de-scribed a patient presenting with recurrent subconjunctivalhemorrhages. Histologically, amyloid deposits were foundin the conjunctiva with involvement of blood vessels.Ts’o4 reported a case of primary systemic nonfamilialamyloidosis with diffuse occlusion of the choriocapillaris.Amyloid substance was found around and inside the vesselsas well. Vitreous deposits of amyloid are found in primaryfamilial amyloidosis but are only sporadically reported inprimary systemic nonfamilial amyloidosis.2,5 Amyloid de-posits have sometimes been associated with retinal perivas-culitis and hemorrhages.2,5

In our case hypofluorescent areas masking the back-ground choroidal fluorescence were observed on bothfluorescein and indocyanine green angiography. The exactnature of these areas is not known. However, these areascould represent amyloid deposits. They could also be theresult of previous intraretinal and subretinal hemorrhages.The hypofluorescent streaks visualized by indocyaninegreen angiography in the midperipheral retina probablyrepresent either choroidal vascular occlusion or intravas-cular and/or perivascular amyloid deposits. The assumption

Accepted for publication Mar 24, 2000.Department of Ophthalmology and Visual Sciences, San Raffaele

Hospital, University of Milano (A.P., C.S., R.B.), Milan, Italy; andLuEsther T. Mertz Retinal Research Department, Manhattan Eye, Ear,and Throat Hospital (L.Y., B.S.S.), New York, New York.

Inquiries to Rosario Brancato, MD, Department of Ophthalmology andVisual Sciences, San Raffaele Hospital, University of Milano, ViaOlgettina 60, 20132 Milano, Italy.

AMERICAN JOURNAL OF OPHTHALMOLOGY250 AUGUST 2000