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Case Reports and Small Case Series
April 2001

Primary Intraocular Lymphoma Seen With Transient White Fundus Lesions Simulating the Multiple Evanescent White Dot Syndrome

Arch Ophthalmol. 2001;119(4):617-620. doi:

We describe 3 patients with multifocal, white, deep retinal lesions simulating the multiple evanescent white dot syndrome (MEWDS). The retinal lesions waxed and waned in each patient. All patients were eventually proven to have primary intraocular lymphoma. Our 3 cases expand the spectrum of unusual, recognized clinical features of primary intraocular lymphoma.

Report of Cases
Case 1

A 58-year-old man had a 1-month history of decreased visual acuity in the right eye. Ocular history included a diagnosis of possible MEWDS in the left eye. Small white dots in the retina resembling MEWDS (Figure 1A) were noted. These grew into tumor-like masses. Two years later the left eye was blind and painful; enucleation was performed and revealed intraocular large cell lymphoma with optic nerve involvement. The patient received radiation treatment to the brain and orbits. The patient first visited us with a 1-month history of worsening vision in the right eye, which had a visual acuity of 20/40. Fundus examination revealed scattered gray-white granular lesions of the deep retina clustered in the midperipheral fundus (Figure 1B). These lesions resembled the lesions noted previously in the left eye. Magnetic resonance imaging of the head and orbits revealed lymphoma. On follow-up, the patient's visual acuity decreased to counting fingers. There was an increase in the number and size of white lesions present in the right fundus, which was consistent with intraocular lymphoma. The patient underwent radiation treatment in the right eye, with improvement of visual acuity to 20/30. On his most recent follow-up, 9 years after the initial visit, the patient was noted to be free of ocular or cerebral lymphoma; however, the visual acuity of the right eye was no light perception, secondary to radiation optic neuropathy and retinopathy.

Figure 1.
A, Case 1, 2 years prior to initial
visit. Photograph of the left eye reveals small, yellow-white lesions along
the inferotemporal arcade. B, Case 1 at initial visit. Note gray-white granular
lesions in postequatorial region of right eye.

A, Case 1, 2 years prior to initial visit. Photograph of the left eye reveals small, yellow-white lesions along the inferotemporal arcade. B, Case 1 at initial visit. Note gray-white granular lesions in postequatorial region of right eye.

Case 2

A 53-year-old woman had experienced worsening vision in her right eye for 1 month. Visual acuity was 20/30 OD and 20/20 OS. Examination of the right fundus revealed multiple whitish outer retinal or subretinal lesions located above the superotemporal arcade (Figure 2A). A fluorescein angiogram of the right fundus showed stippled foci of late-appearing hyperfluorescence, with a subset of lesions in a wreathlike shape corresponding to the whitish fundus spots (Figure 2B). The clinical diagnosis was MEWDS. During the next month, the fundus lesions disappeared spontaneously, and the patient's visual acuity returned to 20/20.

Figure 2.
A, Case 2 at initial visit. Photograph
of right eye shows multiple deep white retinal or subretinal lesions along
the superotemporal retinal vascular arcade. B, Late-phase fluorescein angiogram
corresponding to preceding fundus photograph shows wreathlike hyperfluorescence
of whitish lesions.

A, Case 2 at initial visit. Photograph of right eye shows multiple deep white retinal or subretinal lesions along the superotemporal retinal vascular arcade. B, Late-phase fluorescein angiogram corresponding to preceding fundus photograph shows wreathlike hyperfluorescence of whitish lesions.

One year later the patient returned with spots in her right eye. Her visual acuity was 20/20 OD and 20/15 OS. The right fundus showed numerous flat, white, outer retinal or subretinal lesions measuring 250 µm to 500 µm in diameter along the superotemporal arcade, and similar lesions associated with turbid subretinal fluid along the inferotemporal arcade (Figure 3A). Multifocal chorioretinitis was suspected, but an extensive workup was negative for this.

Figure 3.
A, Case 2, 1 year after initial
visit. Photograph of right eye shows multiple small whitish lesions along
superotemporal retinal vascular arcade and larger whitish deep retinal or
subretinal lesions and subretinal fluid along inferotemporal arcade. B, Photograph
of right eye shows enlargement and coalescence of lesions along the inferotemporal
arcade, but fading of small spots along superotemporal arcade.

A, Case 2, 1 year after initial visit. Photograph of right eye shows multiple small whitish lesions along superotemporal retinal vascular arcade and larger whitish deep retinal or subretinal lesions and subretinal fluid along inferotemporal arcade. B, Photograph of right eye shows enlargement and coalescence of lesions along the inferotemporal arcade, but fading of small spots along superotemporal arcade.

During the next month, the patient's visual acuity decreased to counting fingers OD. Examination showed an increase in the posterior subretinal fluid in the right eye, but the disappearance of the white fundus lesions along the superotemporal arcade (Figure 3B). Diagnostic vitreous biopsy results revealed neoplastic lymphoid cells consistent with the diagnosis of intraocular large cell lymphoma. The right eye was treated with radiation. After treatment, extensive macular subretinal fibrosis developed, and visual acuity decreased to hand motions OD.

Two years after ocular diagnosis and treatment, despite whole-brain radiation, the patient died of central nervous system lymphoma.

Case 3

A 53-year-old man had experienced worsening vision in his right eye for 2 weeks. Visual acuity was 20/40 OU. Fundus examination of the right eye revealed numerous small, white, deep retinal or subretinal lesions above the fovea that were consistent with MEWDS (Figure 4A). The patient was treated by his ophthalmologist with 60 mg of oral prednisone. During the next month, the white fundus lesions disappeared.

Figure 4.
A, Case 3 at initial visit. Photograph
of right eye shows multiple small whitish deep retinal or subretinal lesions
in the region of the superotemporal retinal vascular arcade. B, Macular region
of the left eye shows circumscribed area with a honeycomb appearance.

A, Case 3 at initial visit. Photograph of right eye shows multiple small whitish deep retinal or subretinal lesions in the region of the superotemporal retinal vascular arcade. B, Macular region of the left eye shows circumscribed area with a honeycomb appearance.

Three months later, the patient developed a localized area of superficial retinal infiltration with intraretinal hemorrhage in the inferotemporal region of the right eye. Infectious retinitis was suspected. The cause of the presumed retinitis was unknown. Despite his immune status being normal, he was empirically treated with intravenous ganciclovir. The retinal infiltrates resolved after 3 to 4 weeks, and the visual acuity increased to 20/25 OD. Four years after the original episode, the patient noted worsening vision in his left eye. Visual acuity was correctable to 20/25 OD, but only to counting fingers OS. Fundus examination of the left eye revealed multifocal yellow-white chorioretinal lesions in the posterior pole and superonasal region (Figure 4B). A fine-needle aspiration biopsy was performed, the results of which were consistent with the diagnosis of primary intraocular large cell lymphoma. The visual acuity in the left eye returned to counting fingers. To date, the patient is undergoing a course of external beam radiation therapy to that eye.

Comment

Primary intraocular large-cell (non-Hodgkin) lymphoma is an uncommon neoplastic disorder characterized by infiltration of the vitreous and retina by neoplastic lymphoid cells. Accumulation of large-cell lymphoma cells in geographic white to yellow-white lesions beneath the retinal pigment epithelium is the usual appearance. A variety of other presentations such as retinal infiltrates that can resemble viral retinitis; vascular sheathing; retinal vascular occlusions; and multifocal, tiny, deep retinal or superficial choroidal white lesions have been reported.1 The neoplastic lymphoid cells are almost always B cells. The disorder is frequently bilateral and can cause profound visual loss.2 Patients with primary intraocular lymphoma tend to be middle aged to elderly adults, and women seem to be affected more often than men. This disorder is usually associated with central nervous system lymphoma, which is often the cause of death in affected persons.3,4

Primary intraocular lymphoma can be difficult to diagnose, especially in patients with unusual characteristics. Our 3 patients initially visited with unilateral, multifocal, small, whitish spots at the level of the outer retina. Initially each patient was believed to have MEWDS or a variant thereof. The partial or complete resolution of the lesions in these patients prior to developing more typical manifestations of lymphoma suggested MEWDS. However, all patients were in their 50s, and 2 of the 3 were men. Although MEWDS is occasionally seen in patients in this age group, it is very unusual.5 The diagnosis of MEWDS is suspect unless the lesions are absolutely classic. The absence of the classic foveal changes of MEWDS in all cases should also have suggested another diagnosis.

The possibility of primary intraocular lymphoma during the MEWDS-like phase of the disorder in all of the patients was not initially entertained. We now believe that the multifocal, whitish fundus lesions noted at initial visit were deep retinal or subretinal lymphomatous infiltrates. The fluorescein angiographic appearance in one of the patients was similar but not identical to the angiographic changes seen in patients with MEWDS. The mechanism that can induce clinical regression of the whitish fundus spots and a prolonged quiescent interlude before more typical lesions develop is unknown.

Primary intraocular large cell lymphoma should be included in the differential diagnosis of MEWDS, especially in patients older than 50 years. Clinicians must be aware that subtle, multifocal, deep retinal or subretinal lesions that wax and wane can rarely be manifestations of primary intraocular lymphoma. Diagnostic vitrectomy, along with magnetic resonance imaging and lumbar puncture, may be useful diagnostic modalities to rule out primary intraocular lymphoma in these patients.

This work was supported in part by the Vitreoretinal Research and Education Fund, Philadelphia, Pa, the Heed Ophthalmic Foundation, Cleveland, Ohio (Dr Shah), and an unrestricted university grant from Research to Prevent Blindness Inc, New York, NY (Northwestern University).

Corresponding author and reprints: Gaurav K. Shah, MD, Barnes Retina Institute, One Barnes Hospital Plaza, East Pavilion, Suite 17413, St Louis, MO 63110 (e-mail: Shah@vision.wustl.edu).

References
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Freeman  LNSchachat  APKnow  DL  et al.  Clinical features, laboratory investigations, and survival in ocular reticulum cell sarcoma. Ophthalmology. 1987;941631- 1639Article
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Gass  JDMSever  RJGrizzard  WS  et al.  Multifocal pigment epithelial detachments by reticulum cell sarcoma: a characteristic funduscopic picture. Retina. 1984;4135- 143Article
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Lang  GKSurger  JLGreen  RW  et al.  Ocular reticulum cell sarcoma: clinicopathologic correlation of a case with multifocal lesions. Retina. 1985;579- 86Article
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Lim  JIKokame  GTDouglas  JP Multiple evanescent white dot syndrome in older patients. Am J Ophthalmol. 1999;127725- 728Article
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