Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

British Journal of , 1977, 61, 693-698

Unusual ocular presentation of acute DARRELL WILLERSON, JR., THOMAS M. AABERG, FREDERICK REESER, AND TRAVIS A. MEREDITH From the Medical College of Wisconsin, Eye Institute, Milwaukee, USA

SUMMARY Four patients with toxoplasmosis are reported with unusual presenting ocular lesions. One patient had an active lesion that appeared to involve the as well as focal toxoplas- mosis at the macula. A second patient had a pale optic nerve in association with the classical chorioretinal scars of toxoplasmosis. The third patient had toxoplasmosis chorioretinitis of the macula with subretinal neovascularisation. The fourth patient had a branch artery occlusion complicating acute .

Our report includes 4 patients with unusual mani- mutton-fat keratic precipitates (kp) OD, but not OS. festations of toxoplasmosis. and/or The anterior chamber had 2+ cells OD and 1+ optic atrophy was present in 2 patients. A sub- flare. The vitreous had 1 to 2+ cells anteriorly and retinal neovascular frond was present in a third 3 to 4+ posteriorly. An elevated, one disc diameter, patient. The fourth individual had a branch artery intraretinal exudative lesion of the macula was occlusion involving a vessel which passed through an present with overlying vitreous cells (Fig. 1). The area of acute toxoplasmosis chorioretinitis. disc was oedematous; at the temporal margin there Although retinitis occurring at the macula, the copyright. retinal periphery, or even in a juxtapapillary position occurs commonly, optic nerve involvement in toxo- plasmosis is rare (Hogan et al., 1964). In addition, we are not aware of a previous report in which either subretinal neovascularisation or a branch artery obstruction has been reported in association with acute toxoplasmosis chorioretinitis. Since these com- plications can add confusion to the diagnosis of http://bjo.bmj.com/ acute toxoplasmosis, we believe they warrant documentation. Case reports

PATIENT 1 A 15-year-old Caucasian male awoke 3 weeks prior on September 24, 2021 by guest. Protected to examination with decreased visual acuity in the right eye (OD). He denied other symptoms and had been in good health. Family pets included 5 new kittens and 1 dog. Ophthalmological examination 5 years previously documented visual acuity of 20/20 in both eyes (OU). On examination at the Medical College of Wisconsin (MCOW) his visual acuity was Fig. I Patient 1: Venous phase offluorescein angiogram 10/200 OD and 20/20 in the left eye (OS). A positive OD which demonstrates dye leaking from the active Marcus-Gunn pupillary response (i.e., afferent con- lesion at the (open arrows). There is duction defect) was present OD. There were obstruction offluorescence by the acute retinitis at the macula except at the margins of the lesions. There is a Address for reprints: Dr Thomas M. Aaberg, Medical suggestion ofa subretinal neovascularfrond present at College of Wisconsin, 8700 West Wisconsin Avenue, 1 o'clock in the perifoveal area (white arrow), but it is Milwaukee, Wisconsin 53226, USA beyond the resolution of the photographs 693 Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

69fy4 Darrell Willerson, Jr., Thomas M. Aaberg, Frederick Reeser, and Travis A. Meredith was intraretinal exudation and sheathing of the (Fig. 4). The peripheral scars blocked fluorescence retinal vessels, and there were many cells in the except at their margins, where staining occurred. vitreous overlying the optic disc. The periphery of At 30 minutes there was diffuse staining of the disc the right eye was normal. There were no abnor- as well as the adjacent . The patient was next malities of the left eye. Fluorescein angiogram showed dye actively leaking from three separate foci on the disc and extending beyond the margins (Fig. 1). In the late views the optic nerve head was completely obscured by fluorescein leakage (Fig. 2). The macular lesion blocked fluorescence centrally but leaked progressively at the margins. There was a suggestion of subretinal neovascularisation (Figs. 1 and 2, perifoveal area at 1 o'clock), but a definite frond could not be identified. The Sabin-Feldman dye titre was 1:32 and the indirect immunofluor- escence antibody titre for toxoplasmosis was 1:256. Complement fixation titre was 1:8. Skin test for was negative. At follow-up examina- tions over a 6-month period his visual acuity remained 20/200 OD, and the Marcus-Gunn pupillary response persisted. Comment: This patient illustrates acute optic neuritis associated with an active toxoplasmic lesion involving the macula. The optic nerve oedema and fluorescein angiography characteristics appear to be due to intrinsic inflammation within the nerve

head, not to the macular lesion, evidenced by the Fig. 2 Patient 1: Late frame offluorescein angiogram copyright. persistent afferent pupillary response defect after OD. Note the increase in fluorescein leakage from the quiescence of the inflammation. disc (open arrows)

PATIENT 2 An 18-year-old female had optic neuritis diagnosed in her left eye at age 16, accompanied by visual loss and bitemporal and occipital headaches. Approxi- mately 1 year later blurring of vision recurred OS, with a mild, right temporal headache. Her ophthal- http://bjo.bmj.com/ mologist noted retinal scars suggestive of ocular toxoplasmosis, and she was given treatment for toxoplasmosis. Vision fluctuated over the next 3 months, at which time she was seen in consultation at MCOW and noted to have visual acuity of 20/20 OD and 20/20-2 OS. A definite positive Marcus-

Gunn pupillary response was present OS. An on September 24, 2021 by guest. Protected atrophic chorioretinal scar with pigment at its margins was present superonasal to the disc OS (Fig. 3). Vitreous condensation extended from the side of the lesion to the disc and into the vitreous body. Inferonasal to the disc was another punched- out area of chorioretinal atrophy, with a large choroidal vessel visible (Fig. 3). Neither of these lesions appeared active. The disc was pale. The macula was normal, and there was no vascular attenuation. The fundus of the right eye appeared normal. Fluorescein angiography showed some Fig. 3 Patient 2: Kodachrome taken with red-free light dilated capillaries on the disc OS with a peripapil- OS demonstrates typical toxoplasmosis chorioretinal lary rim of atrophy, but no dye leaking from the disc scars and pale optic disc Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

Unusual ocular presentation of acute toxoplasmosis 695 Fluorescein angiography demonstrated subretinal neovascularisation at the macula (Fig. 6), with dye leaking progressively from the neovascular frond into the subretinal space (Fig. 7). Indirect immuno- fluorescence titre for toxoplasmosis was 1:16. The patient underwent treatment with prednisone, pyrimethamine, and sulphadiazine. One year later the macular lesion was inactive and the disc ap- peared normal. An afferent conduction defect pupillary response was no longer present.

Fig. 4 Patient 2: Venous phase offluorescein angiogram OS demonstrates dilated capillaries on the disc with peripapillary hyperfluorescence, but no dye leaking from the disc surface copyright. seen 1 j years later with an active, recurrent satellite lesion. Visual acuity was 20/25 OS. One month later her visual acuity had returned to 20/20 + 2 OS, but the afferent nerve conduction defect remained Fig. 5 Patient 3: Kodachrome using red-free light OS present. demonstrates the retinitis at the macula with retinal Comment: This patient has typical chorioretinal striae extending from it (white arrow) lesions of toxoplasmosis and a history of optic neuritis evidenced by a Marcus-Gunn

pupillary http://bjo.bmj.com/ response and pallor of the optic disc.

PATIENT 3 A healthy 15-year-old male on no medications com- plained of blurred vision OS for 4 weeks. He had no previous history of ocular disease, and visual acuity had been normal 5 months earlier. Examination showed a visual acuity of 20/20 OD and 10/200 OS. on September 24, 2021 by guest. Protected A positive Marcus-Gunn pupillary response OS was present. The anterior chamber was clear OU. The anterior vitreous was clear OD, but had 2+ cells OS. Indirect showed a normal fundus OD. The disc margin OS was oedematous and slightly elevated, with a dusky pigmentation from the 6-12 o'clock position. The macula had a sub- retinal white, round, elevated lesion (Fig. 5), with A retinal striae extending nasally and temporally from the lesion. Vitreous precipitates were present on the back of the retracted vitreous face. Amsler- Fig. 6 Patient 3: Early venous phase offluorescein Grid revealed an absolute central which angiogram OS demonstrating the subretinal neovascular extended 10' vertically and 12' horizontally, frond (white arrow) Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

696 Darrell Willerson, Jr., Thomas M. Aaberg, Frederick Reeser, and Travis A. Meredith which can obscure the inflammatory focus, should alert the ophthalmologist to the possibility of under- lying toxoplasmosis chorioretinitis when present in a young patient with cellular infiltrate in the vitreous. Discussion 4 a Ocular toxoplasmosis is caused by a non-motile ~~~~obligate~~~~~ intracellular parasite, Toxoplasma gondii. It may occur in either a congenital or acquired form ~~~Clinically-~~~~~~~- the ocular lesion in either form usually

Fig. 7 Patient 3: Late venous phase offluorescein angiogram OS demonstrating dye leaking from subretinal neovascular frond (white arrow)

Comment: The patient had subretinal neovascu- larisation as shown by fluorescein angiography, associated with toxoplasmosis chorioretinitis. Al-

though the disc was originally oedematous with an copyright. afferent conduction defect of the nerve, the inflam- mation apparently was secondary to the macular lesion, since later examination revealed neither optic Fig. 8 Patient 4: Kodachrome taken with red-free light atrophy nor persistent conduction defect. OS which demonstrates the area of acute retinitis with the attenuated arteriole passing through it (dark arrow) PATIENT 4 A 17-year-old male had no visual difficulties until 10 days prior to consultation at the MCOW, when OS was noted. On examination http://bjo.bmj.com/ visual acuity was 20/15 OD and 20/200 OS. Small, white keratic precipitates were present OS withwt, 1+ cellular reaction and flare in the anterior // chamber. The and anterior chamber OD were clear and the fundus examination was normal. Fundus examination OS revealed an intense retinitis

in the superior portion of the macula (Fig. 8) with on September 24, 2021 by guest. Protected subretinal fluid along the inferior margin. There was localised intraretinal haemorrhage and a branch '! artery obstruction of an arteriole passing through the area of retinitis. Fluorescein angiogram showed the area of non-perfusion resulting from the branch artery obstruction as well as fluorescein leakage in the area of retinitis (Fig. 9). The Sabin-Feldman dye titre was 1:256. He was treated with sulphadiazine, Fig 9 Patient 4: Arterial phase offluorescein angiogram pyrimethamine, folinic acid, and prednisone, with OS which demonstrates that the attenuated arteriole resolution of the acute chorioretinitis. passing through the acute retinitis does not fill with dye, Comment: This case showed a branch artery oc- with complete obstruction of the arteriolar branch at the clusion originating at the locus of acute toxoplas- bifurcation (open arrow) and surrounding areas of mosis chorioretinitis. Branch vascular occlusion, capillary non-perfusion (dark arrows) Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

Unusual ocular presentation ofacute toxoplasmosis 697

presents as a focal necrotising chorioretinitis. Re- toxoplasmosis include periphlebitis with or without currences are common as satellite lesions adjacent venous insufficiency, concomitant periphlebitis and to an old atrophic scar or in an area of previously periarteritis, and rarely segmental periarteritis alone normal-appearing . The inflammation may be (Schwartz, 1977; Wise et al., 1971). Patient 4 self-limited or in some instances fulminating, result- presented with a branch artery obstruction as the ing in (Duke-Elder, 1966; Gass, vessel passed through a localised area of acute 1970). Juxtapapillary lesions are less common. retinitis (Figs. 8, 9). An active lesion in the optic nerve is rare (Walsh Serological tests for toxoplasmosis include the and Hoyt, 1969). Sabin-Feldman dye test, indirect fluorescent anti- While cranial nerve involvement has been des- body test, complement fixation test, precipitin test, cribed (Koch, 1943) and papilloedema may be and haemagglutination test. A skin test has also been secondary to lesions in the CNS (Koch, 1943), the used but may not become positive until as long as optic nerve of Patient 1 appears to have been 6 months after infection (Hogan et al., 1964; directly affected as well as there being a classical O'Connor, 1957; Huldt, 1958; Jacobs and Lunde, lesion involving the macula (Figs. 1, 2). There were 1957; Scott, 1974). A Sabin-Feldman dye titre of no CNS symptoms or signs to suggest secondary 1:16 or greater has been considered positive (Hogan papilloedema. In addition the disturbance of the et al., 1964; Scott, 1974). Hogan et al. reported an optic disc was unilateral, the visual acuity was unusual patient with a positive dye titre only in un- acutely and severely decreased, and a Marcus-Gunn diluted serum but who had toxoplasma organisms pupillary response was present and persisted. in his eye at necropsy (Hogan et al., 1964). Others Patient 2 had a pale optic disc in association with have found equally low Sabin-Feldman dye titres in typical chorioretinal scars (Figs. 3, 4). An attack of histologically proved cases, including 1 case which recurrent acute inflammation occurred as a satellite was seronegative (Zscheile, 1964; Franceschetti and lesion, which is characteristic of toxoplasmosis. It is Engelbrecht, 1964). There has been good agreement possible that the patient had both toxoplasmosis (95 %) between the Sabin-Feldman dye test and the chorioretinitis and a separate cause of the pale disc. indirect fluorescent antibody test regarding their Zimmerman, however, noted Toxoplasma gondii in specificity and sensitivity (Scott, 1974; Walton et al., copyright. the optic nerve in a case of ocular toxoplasmosis 1966). Positive titres in either test can exist for years, (Zimmerman, 1961). Others have suggested that and it has been suggested that variations in serum some cases of optic neuritis in young adults may be titres tend to reflect proliferative activities of the caused by toxoplasmosis (Hogan et al., 1964; Frenkel parasite in the reticuloendothelial organs more than and Jacobs, 1958; Frezzotti and Guerra, 1963). the activity of eye lesions (Scott, 1974; O'Connor, Patient 3 presented acutely with subretinal neo- 1973). Patient 1 had a dye titre of 1:16 and an in- vascularisation (Figs. 5, 6, 7). Patient 1 also had the direct fluorescent antibody titre of 1:64. Patient 2

appearance of subretinal neovascularisation in the did not have serological testing but had classical http://bjo.bmj.com/ chorioretinitis which occurred at the macula (Figs. peripheral chorioretinal scars associated with toxo- 1, 2), but photographic resolution did not permit plasmosis. Patient 3 had an indirect fluorescent absolute identification of the frond. Retinociliary antibody titre of 1:16. Patient 4 had a Sabin- anastomotic vessels have been previously reported in Feldman dye titre of 1:256. None of our patients had chorioretinal scars due to toxoplasmosis (Gass, evidence of systemic lupus erythematosus, which 1970; Saari et al., 1975; Kennedy and Wise, 1971). may cause a false positive immunofluorescent test In a addition, racemose angioma of the retina has for toxoplasmosis. on September 24, 2021 by guest. Protected been described in association with toxoplasmosis The 2 cases in this report with optic nerve in- (Stucchi et al., 1972) as well as preretinal fibro- volvement emphasise the need to include toxoplas- vascular proliferans extending from the disc to a mosis in the differential diagnosis of any patients chorioretinal lesion (Saari et al., 1975; Maumenee, presenting with optic neuritis. In addition they 1961). We are unaware of a previous case in which a suggest the importance of carefully testing patients neovascular frond was present like that in Patient 3. with peripheral toxoplasmosis chorioretinitis for a The patient had no history of trauma, was not Marcus-Gunn pupillary response to rule out con- myopic, and had no peripheral scars such as are seen comitant occult optic nerve involvement. The third in presumed ocular histoplasmosis. He did not have patient indicates that toxoplasmosis should be angioid streaks. Although the possibility of Toxocara included in the differential diagnosis of subretinal canis was considered, the clinical appearance and neovascularisation, particularly in the young. reactive immunofluorescence antibody titre seemed Finally, the fourth patient demonstrates that branch to confirm the diagnosis of toxoplasmosis. artery occlusion may complicate toxoplasmosis Retinal vascular lesions previously reported in chorioretinitis. Br J Ophthalmol: first published as 10.1136/bjo.61.11.693 on 1 November 1977. Downloaded from

698 Darrell Willerson, Jr., Thomas M. Aaberg, Frederick Reeser, and Travis A. Meredith

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ciation, 122, 1267. Zscheile, F. B. (1964). Recurrent toxoplasmic retinitis with copyright. Maumenee, A. E. (1961). Toxoplasmosis, p. 736. Williams weakly positive methylene blue dye test. Archives of and Wilkins: Baltimore. Ophthalmology, 71, 645-648. http://bjo.bmj.com/ on September 24, 2021 by guest. Protected