A WHITE DOT SYNDROME CASE: SERPIGINOUS CHOROIDITISAMANDA S LEGGE, B.S.

ABSTRACTCASE REPORT: A 52-year-old white male was diagnosed with early serpiginous choroiditis, refused anti-inflammatory treatment, and was then lost to follow up. Six years later the patient returned with a chief complaint of severe blurred vision O.U. The serpiginous lesions progressed into the maculae of both eyes. The patient requested to proceed with an anti-inflammatory regimen to preserve the remaining vision.DISCUSSION: Serpiginous choroidopathy is considered a variant of the many white dot syndromes and must be differentially diagnosed from these as well as other choroid and retinal pigment epithelium degenerations. Careful dilated fundus exam, fluorescein angiography, indocyanine green angiography, and fundus autofluorescence reveal distinct characteristics of serpiginous choroidopathy. These techniques can also determine whether the serpiginous lesions are active or inactive thereby dictating treatment considerations.

Serpiginous choroiditis is one of many white dot syndromes that affect the posterior pole. It is differentiated from the other syndromes by its classic geographic and helicoid destruction pattern of the choroid and retinal pigment epithelium. Reactivation is common causing progressive foveal scarring and damage to Bruch’s membrane allowing for choroidal neovascularization1,2. Treatment is based on anti-inflammatory regimens; however no standard of care has been established to date3.

The following case report illustrates the progression of serpiginous choroiditis and the potential management options of this diagnosis.

CASE REPORT

HISTORY

The patient is a 52-year-old white male diagnosed with serpiginous choroiditis at a previous examination in 2006. At that time the patient’s chief complaint was blurred vision O.S. His visual acuity was 20/20 O.D. and 20/30 O.S. Fundus examination showed classic, inactive serpiginous lesions O.S. greater than O.D. Fundus photographs were taken and a fluorescein angiogram was performed at that visit. The patient was educated about the diagnosis and a regimen of oral steroids was recommended. The patient declined steroid management at that time and was lost to follow up.

Figure 1. Atrophic scars are present prominently O.S. and nasal to the optic disc O.D. No areas of active inflammation are evident during this visit.

Figure 2. Magnified images of the atrophic scars present O.D., O.S. These lesions are inactive.

Figure 3. Fluorescein angiography illustrating early hypofluorescence followed by late hyperfluorescent borders without evidence of choroidal neovascularization.

DIAGNOSTIC DATA

Six years later the patient presented to the office with a chief complaint of increasingly blurry vision O.U. at distance and near for the past 12 months. He denied floaters or photopsia, diplopia, pain, or discomfort.

The patient’s aided visual acuity was 20/40 O.D. and 20/80 O.S. without pinhole improvement. Pupils were round, equal, and reactive to light with no relative afferent defect. Extraocular motility testing found no restrictions of muscle movement. Confrontation visual fields were full to finger counting O.D., O.S.

Intraocular pressures were measured to be 16 mmHg O.D. and 18 mmHg O.S. Anterior segment evaluation was unremarkable O.U.

Amsler grid showed new scotomas present O.D., O.S. No sign of metamorphopsia O.U. was noted.

Posterior segment examination of the right eye revealed serpiginous, helicoid lesions mostly temporal to the macula with active lesions in the fovea. A scar nasal to the disc was also noted at approximately the same size as 2006. The left fundus showed diffuse posterior pole helicoid scarring without active inflammation

Figure 4. Fundus photographs illustrating the progression of serpiginous choroiditis in a six-year period without intervention. Active lesions are seen superiorly and inferiorly to the fovea O.D.

Figure 5.Red-free photograph

Fluorescein angiography performed at this exam revealed classic early hypofluorescence of the active sites O.D. with late staining of the

serpiginous borders O.U. No sign of choroidal neovascularization was present.

Figure 5.Early phase fluorescein angiography demonstrating the classic presentation of serpiginous choroiditis as well as early blockage from the active lesions O.D.

Figure 6.Late phase fluorescein angiography demonstrating the classic late staining of serpiginous lesions.

DIAGNOSIS AND MANAGEMENT

The severe progression of serpiginous choroiditis was identified as the sole cause of the patient’s decreased vision O.U. At this time the patient inquired about the possibility of starting a corticosteroid treatment regimen. After discussing possible adverse effects, the patient was started on a 60mg dose for two weeks followed by a slow taper over a 6 week period.

The patient was advised that because of the extensive scarring O.U. prednisone would likely not improve his vision but would help to stabilize it. He is scheduled to return at the end of his corticosteroid treatment to reassess the active areas O.D. and to modify treatment as necessary.

An Amsler grid was dispensed. The patient was educated to return if any changes in vision are noted. A low vision consultation was recommended to improve reading function.

DISCUSSION

Serpiginous choroiditis (SC) is a chronic, and progressive inflammatory condition of the choroid and retinal pigment epithelium (RPE).

Fundus findings are characterized by geographic, helicoid lesions that typically originate near the optic nerve and progress centrifugally along the vascular arcades.

Active serpiginous lesions present as irregular gray-white subretinal infiltrates. Over four to six weeks active lesions become atrophic and form inactive scars with variable pigment accumulation1,2. Although active inflammation resolves over the course of a few weeks, gradual degenerative extension occurs up to 9 months4. Recurrences of active lesions are common and may occur weeks to years after the initial event5.

The resulting chorioretinal atrophy involves the fovea and causes irreversible vision loss approximately 50% of the time when left untreated6. Choroidal neovascularization, retinal vasculitis, and retinal vein occlusions have also been documented to cause visual impairment in SC7,8,9. Visual outcome is directly related to the involvement of para-fovea and fovea by scarring or neovascularization4.

Multiple etiologies have been proposed including autoimmunity, infection, vasculopathy, and exposure to a variety of toxins. Immune responses to HLA-B7, HLA-A210,

retinal S antigen11, and factor VIII-von Willebrand12 have been identified in several case series. Proposed infectious etiologies include varicella zoster virus, herpes simplex virus13, ocular tuberculosis14, and Candida spp. infections4,15. Although the precise etiology of SC is debated, clinicopathology is known. Vasculitis and lymphocytic infiltration of the choriocapillaris causes an inflammation of the choroid and RPE with fibroglial tissue formation around Bruch’s membrane2,4.

Moderate to severe SC is easily diagnosed from its unique clinical picture; however early or variant forms of SC must be differentially diagnosed from other choroidal infectious and inflammatory diseases that affect the posterior pole. This includes toxoplasmosis, presumed ocular histoplasmosis syndrome (POHS), ocular tuberculosis, acute multifocal placoid pigment epitheliopathy (AMPPE), and multifocal choroiditis.

In any stage of severity, SC has distinct features on fluorescein angiography (FA), indocyanine green angiography (ICGA), and fundus autofluorescence (FAF) that can distinguish this diagnosis from the differentials. FA of inactive scarring shows early, dark, hypofluorescence of geographic atrophy. Mild hyperfluorescence of the borders are seen which become increasingly stained with dye throughout the angiogram. Granular staining in a brush fire pattern is seen in late phases which represent diffusion of dye from the healthy surrounding choriocapillaris16.

Active lesions are also hypofluorescent in early FA phases; however this is thought to be due from an opaque, inflamed, RPE rather than atrophy17. Active lesions become hyperfluorescent in later phases.

ICGA in SC shows extensive hypofluorescence representing nonperfusion of the choriocapillaris. There is no late hyperfluorescence. Although ICGA does not significantly contribute to the diagnosis of SC, it is more sensitive than FA in determining the extent and appearance of new lesions18. Because SC is primarily a choroidal disease, ICGA shows larger areas of hypofluorescence than FA in active sites indicating late perfusion or non-perfusion of the choriocapillaris.

FAF is an imaging technique used for the evaluation of diseases affecting the chorioretinal interface. Therefore, it is useful in SC for initial diagnosis as well as long-term management. Hyperautofluorescence is seen two to five days after the appearance of new inflammatory lesions19. This relates to the buildup of lipofuscin because of a dysfunctional RPE. As the resolution and progressive scarring occurs the autofluorescence decreases and become deeply hypoautofluorescent as the RPE and overlying retina atrophies.

Although exact etiology of SC is yet to be determined, it is known to be an inflammatory disease. Anti-inflammatories and immunosuppressants are therefore the most common treatment approach at this time. Alkylating agents, interferon therapy, and antituberculosis treatment has also been attempted. Anti-fungals are another consideration15; however no long-term studies have shown any efficacy as a sole treatment modality.

Systemic corticosteroids are the mainstay of treatment for new, active lesions. Oral corticosteroids have been shown to reduce the

duration of inflammation thereby decreasing the visual deficit when scarring and atrophy ensues. The typical regimen for oral prednisone is 1mg/kg/d until the choroiditis is controlled followed by an appropriate taper20. Active lesions may not respond to oral corticosteroid treatment for up to two weeks. If a lesion is threatening the foveal avascular zone, intravenous methylprednisolone at 1 gram for 3 days is recommended for an earlier response21.

Intravitreal triamcinolone has also been used to treat active lesions when systemic administration of corticosteroids is contraindicated. Intravitreal injection of triamcinolone lowers systemic steroid adverse effects while still maintaining a therapeutic dosage at the choroidal level. Steroids alone do resolve active lesions; however they do not decrease the recurrence of the disease22.

Several studies have shown a decrease in the rate of recurrence when using immunosuppressive agents such as methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine A23. Commonly triple agent therapy is utilized as a combination

of prednisone (1mg/kg/d), azathioprine (1.5mg/kg/d), and cyclosporine (5mg/kg/d) with a slow taper over 6 months. This initial study demonstrated a statistically significant difference between patients treated with triple agent therapy and those treated with corticosteroids alone24. Studies since that time have found mixed results.

Other combinations of immunosuppressive agents25 and other therapy options have been investigated. Alkylating agents such as cyclophosphamide and chlorambucil26, interferon therapy with alpha-2A27, and antituberculosis treatment have been considered. These must be interpreted with caution as large studies with control groups have not been performed because of the rarity of this disease.

Prompt diagnosis and appropriate management with corticosteroids or immunosuppressive agents is necessary to preserve central vision and decrease recurrences of active inflammation. Frequent monitoring may be necessary to detect recurrent episodes as symptoms are uncommon until the fovea is involved.

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