Physician describes characteristics of white-dot chorioretinal inflammatory syndromes

Fundus fluorescein angiography and indocyanine green videoangiography are helpful in diagnosing the conditions.

Amar Agarwal

Introduction

White-dot chorioretinal inflammatory syndromes are a group of unrelated conditions that present with scattered white or yellow spots in the retina, with or without an associated posterior uveitis and sometimes preceding nonspecific flu-like systemic disease. My special guest in this column is J. Fernando Arevalo from the Arevalo-Coutinho Foundation for Research in Ophthalmology, Caracas, Venezuela, who will discuss these interesting conditions.

– Amar Agarwal, MS, FRCS, FRCOphth
OSN Complications Consult Editor

The white-dot chorioretinal inflammatory syndromes include acute posterior multifocal placoid pigment epitheliopathy (APMPPE), multifocal evanescent white-dot syndrome (MEWDS), birdshot chorioretinopathy or vitiliginous chorioretinitis, multifocal choroiditis with panuveitis, punctate inner choroidopathy and diffuse subretinal fibrosis syndrome.

Although there is a superficial similarity in the fundus appearance of these conditions, they are different, and their fluorescein and indocyanine green angiograms are different (Table 1). Fundus fluorescein angiography (FFA) and indocyanine green videoangiography (ICG-V) are important tools to help diagnose these conditions.

Acute posterior multifocal placoid pigment epitheliopathy

This syndrome can cause transient visual loss in young patients, is commonly bilateral, as opposed to asymmetric in MEWDS, and consists of focal, flat, gray-white lesions at the level of the retinal pigment epithelium (RPE). The ocular lesions evolve fairly rapidly, changing from gray-white to partly depigmented. Typically, these lesions resolve spontaneously over weeks, with a delayed but reliable improvement in visual acuity to a subnormal level.

FFA: APMPPE lesions are considerably larger and block fluorescence early in the fluorescein angiogram, as opposed to early hyperfluorescence in MEWDS. More pigment disruption develops with APMPPE than with MEWDS. Therefore, the early phase FFA of APMPPE shows irregular areas of blocked fluorescence characteristic of acute lesions. At the arteriovenous phase, acute lesions still block fluorescence and are well-demarcated. Mid- and late-phase angiograms demonstrate diffuse, even staining of the acute lesions. The lesions may involve the fovea; even with foveal involvement, the prognosis for a return of a good visual acuity is favorable. In the recovery phase of APMPPE, the lesions are primarily simple pigment epithelial window defects. These lesions have the same map-like contours of acute lesions, with no leakage or staining.

ICG-V: This tool demonstrates, especially in the late phases, the dark lesions that exactly correspond to the lesions that block fluorescence and stain late on FFA. In healed APMPPE, more clearly delineated areas of hypofluorescence persist. There is some controversy regarding if there is blockage of fluorescence by inflammatory debris at the RPE cells or if there is transient occlusion of the choroidal arterioles in APMPPE. Because the hypofluorescence persists on ICG after the healed phase and patients usually recover good visual acuity, the more accepted theory is a partial choroidal vascular occlusion (Figure 1).

Figure 1. Acute posterior multifocal placoid pigment epitheliopathy. A) Early phase fluorescein angiography in APMPPE shows irregular areas of blocked fluorescence characteristic of acute lesions. B) At the arteriovenous phase, acute lesions still block fluorescence and are well-demarcated. C and D) Mid- and late-phase angiograms demonstrate progressive, diffuse, even staining of the acute lesions. Image: Arevalo JF

Multifocal evanescent white-dot syndrome

This is an acute, multifocal, usually unilateral retinopathy predominantly seen in young women with blurred central vision, bothersome photopsias, paracentral scotomas or enlargement of the blind spot, and headache that usually resolves spontaneously over 2 months. The condition is manifested by small white dots (100 µm to 200 µm) seen at the level of the RPE or outer sensory retina. The white dots are mostly concentrated in the paramacular area, usually sparing the fovea itself, and are less prominent and numerous beyond the mayor vascular arcades. In addition, there is often a granular appearance to the macula, vitreal cells, retinal venous sheathing, blurring of the disc margins and abnormalities shown on electroretinography during the acute phase.

FFA: The white dots in the acute phase show early hyperfluorescence and late staining. Each lesion consists of a cluster of hyperfluorescent dots surrounding a relatively dark center in the arteriovenous stage of the angiogram. These lesions superficially resemble photocoagulation scars. Some window defects may be seen in the macula at the site of the irregular granularity. These lesions usually resolve in about 7 weeks on average, and vision returns to normal.

Figure 2. Multiple evanescent white dot syndrome. A) Fundus examination reveals small and large spots scattered through the fundus in the left eye. B) Fluorescein angiography shows punctate hyperfluorescence. C) Indocyanine green video-angiography demonstrates small and large hypofluorescent spots. A diagnosis of MEWDS was made. D) One month later, the spots in the fundus had disappeared, and visual acuity recovered. Image: Ciardella A

ICG-V: The acute phase is characteristic with numerous hypofluorescent spots throughout the posterior pole and periphery at about 10 minutes. These spots are larger than those seen on FFA. In some patients, there is a ring of hypofluorescence around the optic nerve that seems to correlate with the presence of blind-spot enlargement (Figure 2).

Birdshot chorioretinopathy

The most distinctive sign of birdshot chorioretinopathy is the presence of depigmented spots, which are usually cream-colored at the level of RPE or deeper. The lesions radiate outward from the disc in a linear pattern that seems to follow the choroidal vessels. There is no noticeable thinning or atrophy of the retina and choroid at the site of these lesions. It is seen in middle-aged healthy patients, usually bilaterally, and it usually demonstrates significant vitreous reaction and retinal vascular leakage in an eye that appears externally quiet. Acute onset is not characteristic of birdshot chorioretinopathy, and HLA-A29 is frequently found positive in these patients. Retinal vascular abnormalities, such as hyperpermeability of capillaries with resultant cystoid macular edema, diffuse narrowing of retinal arterioles, perivascular hemorrhages in the nerve fiber layer, tortuosity of vessels and optic disc swelling, are common findings in birdshot chorioretinopathy. Although the precise etiology of the disease remains unknown, an immune-mediated process is strongly implicated.

FFA: This usually demonstrates an increase in the retinal circulation time, and the retinal vessels may leak fluorescein in the active stage. The angiographic characteristics of the spots depend on their stage in the disease. Early, when there is choroidal infiltration with minimal RPE atrophy, the spots are hypofluorescent in the transit phase of the study and become mildly hyperfluorescent in the later phases as dye from the choriocapillaris stains the extrachoroidal vascular space. This is consistent with a deep-seated inflammatory focus that gradually accumulates fluorescein. As RPE atrophy ensues, the spots may show an early alteration of fluorescence or a hyperfluorescent window defect, followed by late staining, expected from choriocapillary atrophy or depigmentation of the RPE, respectively. In many instances, the lesions are more apparent by ophthalmoscopy than by angiography.

Figure 3. Birdshot chorioretinopathy. A and B) Color fundus photo of right and left eye, respectively. C) Early fluorescein angiography with choroidal infiltration and minimal retinal pigment epithelium atrophy. The spots are hypofluorescent. D) The lesions become mildly hyperfluorescent in the late phases of the study as dye from the choriocapillaris stains the extrachoroidal vascular space. Image: Arevalo JF

ICG-V: This demonstrates a characteristic early pattern of scattered hypofluorescence (within 5 minutes of dye injection) and well-delineated round to oval spots often located between large choroidal vessels. The early appearance of the spots differentiates these lesions from the late spots seen with multifocal choroiditis. In contrast to the hyperfluorescent spots of FFA, the hypofluorescent spots of ICG-V exceed the number of depigmented lesions seen clinically; they persist throughout the study and the convalescence phase of birdshot chorioretinopathy, making for a useful diagnostic clue. The focal loss of choroidal tissue may explain the persistence and expansion of hypofluorescent areas in long-standing disease (Figure 3).

Other conditions

These are similar in that they affect young and middle-aged women predominantly; are characterized by scattered yellow-gray choroidal and RPE lesions, which lead to round pigmented chorioretinal scars; often cause scotomas, which are much larger than would be expected on the basis of the number and distribution of chorioretinal scars; and are characterized by moderate visual loss.

Summary

FFA and ICG-V may provide information on the pathophysiology of some ocular inflammatory diseases, may be useful to monitor the effect of therapeutic interventions and may show disease recurrence before the development of the classical ocular fundus changes.

References:

• Agarwal A. Fundus Fluorescein and Indocyanine Green Angiography: A Textbook and Atlas. Thorofare, NJ; SLACK Incorporated; 2007.
• Agarwal A. Handbook of Ophthalmology. Thorofare, NJ: SLACK Incorporated; 2005.
• Agarwal S, Agarwal A, Agarwal A. Four volume textbook of ophthalmology. India: Jaypee; 2000.

• Amar Agarwal, MS, FRCS, FRCOphth, is director of Dr. Agarwal’s Eye Hospital and Eye Research Centre. Prof. Agarwal is the author of several books published by SLACK Incorporated, publisher of Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery and Presbyopia: A Surgical Textbook. He can be reached at 19 Cathedral Road, Chennai 600 086, India; fax: 91-44-28115871; e-mail: dragarwal@vsnl.com; Web site: www.dragarwal.com.
• J. Fernando Arevalo, MD FACS, can be reached at Clinica Oftalmologica Centro Caracas, Edif. Centro Caracas PH-1, Av. Panteon, San Bernardino, Caracas 1010, Venezuela; 58-212-576-8687; fax: 58-212-576-8815; e-mail: arevalojf2020@gmail.com.