Blurred vision, floaters, flashing lights, dark spot in vision.

Critical

Lesions can range from focal to multifocal, unilateral or bilateral, and can be retinal, chorioretinal, or choroidal in location.

Other

Associated vitreous cell, macular edema, retinal vasculitis.

Diagnostic Categories

• White dot syndromes

  • APMPPE

  • Multiple evanescent white dot syndrome (MEWDS)

  • Birdshot chorioretinopathy

  • Multifocal choroiditis (MFC)

  • Punctate inner choroidopathy (PIC)

  • Serpiginous choroiditis

• Inflammatory

  • Sarcoidosis

• Infectious

  • Toxoplasmosis

  • TB

  • Syphilis

• Neoplastic

  • Primary choroidal lymphoma

  • Metastasis

  • Amelanotic choroidal melanoma

Types of White Dot Syndromes

• APMPPE: Acute visual loss in young adults, often after a viral illness. Multiple, creamy yellow-white or gray, plaque-like subretinal lesions in both eyes (see Figure 12.8.1). Lesions block early and stain late on IVFA. Usually spontaneously improves over weeks to months without treatment. May be associated with a cerebral vasculitis (consider MRA if the patient has a headache or other neurologic symptoms), in which case, systemic steroids are indicated.

  Figure 12.8.1: Creamy placoid lesions in a patient with acute posterior multifocal placoid pigment epitheliopathy.

  

• MEWDS: Typically unilateral photopsias and visual loss, often after a viral illness and usually in young women. May have a shimmering scotoma. Uncommonly bilateral, sequential, or recurrent. Characterized by multiple, faint, small white  lesions deep in the retina or at the level of the RPE with foveal granularity and occasionally vitreous cells. Fluorescein angiography may show a classic perifoveal “wreath-like” pattern. There is often an enlarged blind spot on formal visual field testing. Vision typically returns to normal within 6 to 8 weeks without treatment.

• Birdshot chorioretinopathy: Usually middle-aged patients with multiple bilateral, oval, creamy-yellow spots deep to the retina, approximately 1 mm in diameter, scattered throughout the fundus but most prominent in the nasal quadrants (see Figure 12.8.2). A mild-to-moderate vitritis is typically present. Retinal vasculitis, CME, and optic nerve edema may be present. ICGA shows characteristic hypofluorescent spots. IVFA often shows retinal phlebitis and CME. Positive HLA-A29 in 95% to 100% of patients. Early systemic immunosuppression is often recommended.

  Figure 12.8.2: Deep, creamy, ovoid choroidal lesions typical of a patient with birdshot chorioretinopathy.

  

• MFC: Visual loss in young myopic women more often than men, typically bilateral. Multiple, small, round, and pale inflammatory lesions are located at the level of the pigment epithelium and choriocapillaris. Vitritis is a characteristic feature (unlike presumed ocular histoplasmosis syndrome). The lesions can occur in the macula and midperiphery and frequently respond to oral or periocular steroids, but typically recur with tapering. Immunosuppressive therapy is often necessary. CNV occurs in about one-third of patients, so patients should return for urgent evaluation if they have decreased vision or metamorphopsia (see Figure 12.8.3).

  Figure 12.8.3: Inactive multifocal choroiditis.

  

• PIC: Blurred vision, paracentral scotoma, and/or photopsias, usually in young myopic women. Multiple, small round yellow-white spots predominantly in posterior pole with minimal intraocular inflammation. Typically bilateral. Lesions become well-demarcated atrophic scars within weeks. CNV may develop in up to 40% of patients (see Figure 12.8.4). Systemic immunosuppression is usually indicated.

  Figure 12.8.4: Punctate inner choroiditis complicated by a choroidal neovascular membrane.

  

• Serpiginous choroiditis: Typically bilateral, recurrent chorioretinitis characterized by acute lesions (yellow-white subretinal patches with indistinct margins) bordering old atrophic scars. The chorioretinal changes usually extend from the optic disc outward; however, one-third may begin in the macula. Patients are typically aged 30 to 60 years. CNV may develop. Systemic immunosuppression is usually indicated. Must be  distinguished from the “serpiginous” pattern of tuberculous chorioretinitis (see Figure 12.8.5).

  Figure 12.8.5: Inactive serpiginous choroiditis.

  

• Masquerades.

  • Sarcoidosis: Pleomorphic uveitis. Posterior manifestations include focal or multifocal chorioretinal lesions that are initially creamy-appearing choroidal granulomas that progress to atrophic punched-out appearing lesions.

  • Syphilis: Pleomorphic uveitis. Must be ruled out in the setting of suspected MEWDS, APMPPE.

  • Toxoplasmosis: Classically an area of white retinitis adjacent to a prior chorioretinal scar (reactivation) but can be multifocal and bilateral.

  • TB: Pleomorphic uveitis. Must be ruled out in the setting of suspected serpiginous choroiditis as tuberculous serpinous-like choroiditis may present similarly.

  • Presumed ocular histoplasmosis syndrome: Multifocal peripheral punched-out chorioretinal scars, peripapillary atrophy. Frequently complicated by CNV. Vitreous cells are absent. See 11.24, Ocular Histoplasmosis.

  • Neoplasms.

    • Primary choroidal lymphoma: Multifocal, deep, hypopigmented choroidal lesions which can be unilateral or bilateral. May masquerade birdshot chorioretinopathy. B-scan US may show a retrobulbar hypoechoic lesion associated with this mucosa-associated lymphoid tissue (MALT) lymphoma.

    • Others: Metastasis, amelanotic choroidal melanoma.

1. Obtain a thorough history and review of systems. In particular ask about a history of sexually transmitted diseases, high-risk sexual activity, history of exposure to cats, rash, difficulty breathing, travel, neurologic symptoms (deficits or headaches).

2. Complete ocular examination, including an IOP check and a dilated fundus examination.

3. Consider OCT to determine lesion location (intraretinal, subretinal, choroidal) and associated CME.

4. Consider fundus photography to tract lesions for disease progression.

5. Consider FAF to help differentiate between white dot syndromes and to watch for disease progression.

6. Consider an IVFA to help differentiate between white dot syndromes and assess for associated vasculitis.

7. Consider ICGA to help differentiate between white dot syndromes and assess for subtle choroidal lesions.

8. Focused serologic testing based on history and examination:

   • Treponemal test (syphilis EIA, FTA-ABS, TP-PA), followed by confirmatory nontreponemal test (RPR, VDRL). See 12.10, Syphilis.

   • Interferon gamma releasing assay (IGRA, QuantiFERON Gold) and/or PPD. Consider chest imaging (CXR or CT chest) to assess for signs of active or prior pulmonary disease. 

     • In those at risk for TB (e.g., immigrants from high-risk areas such as India, HIV-positive patients), homeless patients, or prisoners.

     • If considering immunosuppressive therapy (especially biologics).

   • HLA-A29 testing is both sensitive and specific for the diagnosis of birdshot chorioretinopathy.

   • Serologic testing for antibodies against HSV, VZV, CMV, and toxoplasmosis can be useful in ruling out a disease as the causative etiology (IgG and/or IgM negative). The presence of positive IgG titer is not necessarily indicative of active disease, but rather prior exposure. Very elevated IgG titers may make you more suspicious for active disease, and a positive IgM indicates recent infection, but again are not fully diagnostic.

   • ACE, lysozyme, and chest imaging (CXR or CT chest).

9. Consider an AC paracentesis to detect DNA for toxoplasmosis-associated disease. See Appendix 13, Anterior Chamber Paracentesis.

10. Consider MRI of the brain and orbits with and without gadolinium contrast to evaluate for CNS lesions in the setting of suspected APMPPE.

11. Consider referral to an ocular oncologist in the setting of suspected primary choroidal lymphoma or other neoplasm for further evaluation and possible biopsy.

Remember that the natural history of MEWDS and APMPPE is self-resolution without treatment and may be observed closely for resolution.

1. Consider topical prednisolone acetate 1% or difluprednate 0.05% q1–2h while awaiting workup results

2. Treat infectious etiologies with appropriate antimicrobials prior to using local long-acting steroids or systemic steroids.

   • For syphilis treatment, see 12.10, Syphilis.

   • For toxoplasmosis treatment, see 12.9, Toxoplasmosis.

   • For TB treatment, refer the patient to an internist, infectious disease specialist, or public health officer for consideration of systemic treatment. Patients with ocular TB frequently have no pulmonary disease but still require systemic four-drug antituberculous therapy. Concomitant oral steroids or steroid-sparing immunosuppression may be necessary.

3. Consider a trial of oral steroids after appropriate negative infectious workup.

4. Consider local steroid injection, particularly if the disease is unilateral, the eye is pseudophakic, and there is no history of steroid response ocular hypertension.

5. If the disease becomes persistent consider long-acting local steroids (0.19 mg or 0.59 mg fluocinolone acetonide implants) versus systemic steroid-sparing immunosuppression (e.g., antimetabolites, calcineurin inhibitors, and anti-TNF agents).