WHITE DOT SYNDROMES

Clinical Features

The white dot syndromes are a group of disorders characterized by multiple whitish yellow inflammatory lesions located at the level of the retinal pigment epithelium (RPE) and choroid. Symptoms associated with the inflammatory white dot syndromes include blurred vision, visual field loss (blind spot enlargement), photopsias, nyctalopia, and floaters.

The majority of individuals with white dot syndromes are younger than 50 years, with the exception of birdshot chorioretinitis and serpiginous choroiditis, which may affect middle-aged and older adults. Multiple evanescent white dot syndrome (MEWDS), birdshot chorioretinopathy, and multifocal choroiditis with panuveitis are more commonly observed in women. The white dot syndromes may be unilateral or bilateral, depending on the etiology.

Vitritis is usually mild except in cases of birdshot chorioretinopathy and multifocal choroiditis with panuveitis. The white dots may be subtle or prominent, depending on the condition. For example, MEWDS is characterized by faint white dots located in the mid-

peripheral or posterior fundus, whereas multifocal choroiditis with panuveitis is notable for more prominent inflammatory lesions. The white dot lesions may be discrete (MEWDS, multifocal choroiditis, birdshot chorioretinopathy, diffuse unilateral subacute neuroretinitis [DUSN]) or more placoid in appearance (acute posterior multifocal placoid pigment epitheliopathy [APMPPE] and serpiginous choroiditis).

Differential Diagnosis

The classic white dot syndromes include APMPPE, MEWDS, multifocal choroiditis with panuveitis, DUSN, serpiginous choroiditis, and birdshot chorioretinopathy. Other conditions associated with white dot lesions include sarcoidosis, ocular lymphoma, presumed ocular histoplasmosis syndrome, Pneumocystis choroidopathy, Behçet’s disease, toxoplasmosis, sympathetic ophthalmia, tuberculosis, and syphilis.

Noninflammatory white dot lesions include drusen, Stargardt disease, and other fleck retinal dystrophies, fundus albipunctatus, and early laser photocoagulation burns.

Clinical Features

White-centered retinal hemorrhages (Roth spots) were historically described as septic emboli in patients with subacute bacterial endocarditis. However, evidence suggests that they are nonspecific and may be found in a variety of disease states.

Most patients are asymptomatic or have visual loss related to the underlying disease process. White-centered retinal hemorrhages may be isolated or more numerous, depending on the association.

White-centered hemorrhages most likely result from localized capillary rupture from any anoxic insult or sudden elevation in venous pressure. The white center is a fibrin platelet aggregate that results during the physiologic healing process. Previous theories concerning the etiology of the white center have included bacterial infiltrates producing microabscesses (subacute bacterial endocarditis) and collections of abnormal white blood cells (leukemia).

Differential Diagnosis

The differential diagnosis for white-centered retinal hemorrhages is broad. The most common underlying factors are anemia and thrombocytopenia. Conditions in which white-centered hemorrhages have been described include subacute bacterial endocarditis, leukemia, diabetic retinopathy, hypertensive retinopathy, human immunodeficiency virus (HIV) retinopathy, toxoplasmosis, shaken baby syndrome, childbirth, intracranial hemorrhage, anoxia, and carbon monoxide poisoning.

It is important to note that anemia is a common association of subacute bacterial endocarditis, leukemia, and HIV/acquired immunodeficiency syndrome. Anemia may be the underlying factor that links this diverse group of conditions.

SELECTED REFERENCES

Bull’s Eye Maculopathy

1.Kempen JH. Drug-induced maculopathy. Int Ophthalmol Clin. 1999;39:67–82.

2.Stone TW, Jaffe GJ. Reversible bull’s-eye maculopathy associated with intravitreal fomivirsen therapy for cytomegalovirus retinitis. Am J Ophthalmol. 2000;130:242–243.

2.Rossetti L, Autelitano A. Cystoid macular edema following cataract surgery. Curr Opin Ophthalmol. 2000;11:65–72.

3.Schumer RA, Camras CB, Mandahl AK. Latanoprost and cystoid macular edema: Is there a causal relation? Curr Opin Ophthalmol. 2000;11:94–100.

Cherry Red Spot

1.Brown GC, Eagle RC, Shakin EP, Gruber M, Arbizio VV. Retinal toxicity of intravitreal gentamicin. Arch Ophthalmol. 1990;108:1740–1744.

2.Brady RO. Ophthalmologic aspects of lipid storage diseases. Ophthalmology. 1978;85:1007–1013.

3.Federico A, Battistini S, Ciacci G, de Stefano N, Gatti R, Durand P, et al. Cherry-red spot myoclonus syndrome (type I sialidosis). Dev Neurosci. 1991;13:320–326.

Chorioretinal Folds

1.Cohen SM, Gass JD. Bilateral radial chorioretinal folds. Int Ophthalmol. 1994;18:243–245.

2.Leahey AB, Brucker AJ, Wyszynski RE, Shaman P. Chorioretinal folds. A comparison of unilateral and bilateral cases. Arch Ophthalmol. 1993;111:357–359.

Drusen

1.Abdelsalam A, Del Priore L, Zarbin MA. Drusen in agerelated macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression.

Surv Ophthalmol. 1999;44:1–29.

2.Bressler NM. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina. 1994;14:130–142.

Flecked Retina Syndromes

1.Armstrong JD, Meyer D, Xu S, Elfervig JL. Long-term follow-up of Stargardt’s disease and fundus flavimaculatus. Ophthalmology. 1998;105:448–457.

Foveal Yellow Spot

1.Gass JD. Reappraisal of biomicroscopic classification of stages of development of a macular hole. Am J Ophthalmol. 1995;119:752–759.

Choroidal Neovascularization

1.Campochiaro PA, Soloway P, Ryan SJ, Miller JW. The pathogenesis of choroidal neovascular neovascularization in patients with age related macular degeneration. Mol Vis. 1999;5:34.

2.Cohen SY, Laroche A, Leguen Y, Soubrane G, Coscas GJ. Etiology of choroidal neovascularization in young patients. Ophthalmology. 1996;103:1241–1244.

3.Marano F, Deutman AF, Leys A, Aandekerk AL. Hereditary retinal dystrophies and choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol.

2000;238:760–764.

Cotton Wool Spot

1.Brown GC, Brown MM, Hiller T. Cotton wool spots. Retina. 1985;5:206–214.

2.McLeod D, Kohner EM. Cotton wool spots and giant cell arteritis. Ophthalmology. 1996;103:701–702.

3.Shami MJ, Uy RN. Isolated cotton wool spots in a 67- year-old woman. Surv Ophthalmol. 1996;40(5):413–415.

Cystoid Macular Edema

1.Gass JDM, Norton EWD. Cystoid macular edema and papilledema following cataract extraction: a fluorescein funduscopic and angiographic study. Arch Ophthalmol. 1966;76:646–661.

Intraretinal Hemorrhages

1.Kivlin JD, Simons KB, Lazoritz S, Ruttum MS. Shaken baby syndrome. Ophthalmology. 2000;107:1246–1254.

2.Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol. 1998;116:83–89.

Lipid Exudates

1.Chew EY. Diabetic retinopathy and lipid abnormalities.

Curr Opin Ophthalmol. 1997;8:59–62.

2.Duker JS, Jalkh AE. Lipid exudates in age-related macular degeneration. Am J Ophthalmol. 1993;116:140–147.

Macular Atrophy

1.Marmor MF, McNamara JA. Pattern dystrophy of the retinal pigment epithelium and geographic atrophy of the macula. Am J Ophthalmol. 1996;122:382–392.

2.Sunness JS, Gonzalez-Baron J, Applegate CA, Bressler NM, Tian Y, Hawkins B, et al. Enlargement of atrophy and visual acuity loss in the geographic atrophy form of age-related macular degeneration. Ophthalmology. 1999;106:1768–1779.

Macular Disc Edema with Macular Star

1.Dreyer, RF, Hopen, G, Gass, JD, Smith, JL. Leber’s idiopathic stellate neuroretinitis. Arch Ophthalmol. 1984;102:1140–1145.

2.Ormerod, LD, Dailey, JP. Ocular manifestations of catscratch disease. Curr Opin Ophthalmol. 1999;10:209–216.

3.Solley WA, Martin DF, Newman NJ, King R, Callanan DG, Zacchei T, et al. Cat scratch disease: posterior segment manifestations. Ophthalmology. 1999;106:1546–1553.

Retinitis

1.Forster DJ, Dugel PU, Frangieh GT. Rapidly progressive outer necrosis in the acquired immune deficiency syndrome. Am J Ophthalmol. 1990;110:341–348.

2.Walters G, James TE. Viral causes of the acute retinal necrosis syndrome. Curr Opin Ophthalmol.

2001;12:191–195.

Peripheral Pigmentation

1.Bastek JV, Siegel EB, Straatsma BR, Foos RY. Chorioretinal juncture. Pigmentary patterns of the peripheral fundus. Ophthalmology. 1982;89(12):1455–1463.

2.Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th ed. St. Louis: Mosby, Inc; 76–77.

Rubeosis

1.Brown GC, Magargal LE. The ocular ischemic syndrome: clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol. 1988;11:239–251.

2.Sivak-Callcott JA, O’Day DM, Gass JDM, et al. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Opthalmology. 2001;108:1767–1778.

Pigment Epithelial Detachment

1.Macular Photocoagulation Study Group. Subfoveal neovascular lesions in age-related macular degeneration: Guidelines for evaluation and treatment in the Macular Photocoagulation Study. Arch Ophthalmol. 1991;109:1242–1257.

2.Tornambe, PE. Treatment of retinal pigment epithelial detachments. Ann Ophthalmol. 1984;16:884–886.

Pigmented Lesions

1.Shields GL, Shields JA, Kiratli H, De Potter P, Cater JR. Risk factors for growth and metastasis of small choroidal melanocytic lesions. Ophthalmology. 1995;102:1351–1361.

2.Tiret A, Parc, C. Fundus lesions of adenomatous polyposis. Curr Opin Ophthalmol. 1999;10:168–172.

Preretinal Hemorrhage

1.Guyer DR, Schachat AP, Vitale S, Markowitz JA, Braine H, Burke PJ, et al. Leukemia retinopathy: relationship between fundus lesions and hematologic parameters at diagnosis. Ophthalmology. 1989;96:860–864.

Subretinal Fluid

1.Gass JDM, Little HL. Bullous retinal detachment and multiple retinal pigment epithelial detachments in patients receiving hemodialysis. Ophthalmology. 1995;75:810–821.

Tumors

1.Collaborative Ocular Melanoma Study Report No. 5. Factors predictive of growth and treatment of small choroidal melanoma. Arch Ophthalmol. 1997;115:1537–1544.

Vasculitis

1.Graham EM, Stanford MR, Whitcup SM. Retinal vasculitis. In: Prepose JS, Holland GN, Wilhemus KR, eds. Ocular Infection and Immunity. St. Louis: MosbyYear Book Inc; 1996:538–551.

2.Stanford MR, Verity DH. Diagnostic and therapeutic approach to patients with retinal vasculitis. Int Ophthalmol Clin. 2000;40:69–83.

Retinal Crystals

1.Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy: a clinicopathologic report. Ophthalmology. 1981;88:89–93.

2.Moisseiev J, Lewis H, Bartov E, Fine SL, Murphy RP. Superficial retinal refractile deposits in juxtafoveal telangiectasis. Am J Ophthalmol. 1990;109:604–605.

Vitelliform Lesions

1.Dubovy SR, Hairston RJ, Schatz H, et al. Adult-onset foveomacular pigment epithelial dystrophy: clinicopathologic correlation of three cases. Retina. 2000;20:638–649.

2.Gass JDM. Autosomal dominant pattern dystrophies of the pigment epithelium. In: Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. St Louis: Mosby-Year Book, Inc; 1997:314–325.

Retinal Neovascularization

1.Jampol LM, Goldbaum MH. Peripheral proliferative retinopathies. Surv Ophthalmol. 1980;25:1–14.

2.Kinyoun JL, Lawrence BS, Barlow WE. Proliferative radiation retinopathy. Arch Ophthalmol. 1996;114:1097–1100.

Vitreous Hemorrhage

1.Davis, M. Vitreous contraction in proliferative retinopathy. Arch Ophthalmol. 1965;74:741–751.

Vitreous Opacity

1.Akiba J, Ishiko S, Yoshida A. Variations of Weiss’s ring. Retina. 2001;21:243–246.

2.Gill MK, Jampol LM. Variations in the presentation of primary intraocular lymphoma: case reports and a review. Surv Ophthalmol. 2001;45:463–471.

3.Moss SE, Klein R, Klein BE. Asteroid hyalosis in a population: the Beaver Dam eye study. Am J Ophthalmol. 2001;132:70–75.

3.Shah GK, Kleiner RC, Augsburger JJ, Gill MK, Jampol LM. Primary intraocular lymphoma seen with transient white fundus lesions simulating the multiple evanescent white dot syndrome. Arch Ophthalmol.

2001;119:617–620.

White Dot Syndromes

1.Brown J Jr, Folk JC. Current controversies in the white dot syndromes. Multifocal choroiditis, punctate inner choroidopathy, and the diffuse subretinal fibrosis syndrome. Ocul Immunol Inflamm. 1998;6:125–127.

2.Polk TD, Goldman EJ. White dot chorioretinal inflammatory syndromes. Int Ophthalmol Clin. 1999;39:33–53.

White-Centered Retinal Hemorrhages

1.Duane TD, Osher RH, Green WR. White-centered hemorrhages: their significance. Ophthalmology. 1980;87:66–69.

2.Ling R, James B. White-centered retinal hemorrhages (Roth spots). Postgrad Med J. 1998;74:581–582.