Asymptomatic patient has hypopigmented spots in the retina
A 59-year-old man was referred to our clinic for evaluation of multiple hypopigmented spots within the peripheral retina in both eyes. The patient was asymptomatic with no complaints of vision loss, floaters, pain or discomfort.
The patient’s medical history was positive for hypertension and type 2 diabetes. He reported taking glipizide, metformin, furosemide, lisinopril, Trulicity (dulaglutide, Eli Lilly), the men’s multivitamin Osteo Bi Flex, aspirin, fish oil and vitamin C. Family ocular and medical history was unremarkable. The patient reported a drug allergy to penicillin. Social history was negative for the use of drugs, alcohol and tobacco. The patient was oriented to time, person and place with appropriate mood and affect. Ocular history was positive for blepharitis and mild cataract in both eyes.
Vision was 20/25+2 in the right eye and 20/20+1 in the left eye. Confrontation visual fields, pupils and extraocular motilities were normal. IOP was 20 mm Hg OD and 17 mm Hg OS as measured by Goldmann applanation tonometry.
The patient had 1+ nuclear sclerotic and trace cortical age-related cataracts in both eyes. All other anterior segment findings were unremarkable in both eyes. The anterior chamber was deep and quiet in both eyes. There was a diffuse epiretinal membrane in the right eye. Rare white blood cells and haze were present in the anterior vitreous in both eyes. Multiple creamy-white choroidal lesions were present. The spots were most concentrated around the optic nerve and extended into the periphery in all quadrants.
OCT showed multiple discrete areas of mild retinal pigment epithelium (RPE) atrophy and intermittent loss of the ellipsoid zone surrounding the nerve and near the arcades in both eyes. No cystoid macular edema was present. Fundus autofluorescence showed scattered areas of hypofluorescence surrounding the optic nerve. Visual field 30-2 testing and fundus photos were also obtained.
What’s Your Diagnosis?
Pigmented spots
When a patient presents with multiple white dots in the fundus, the differential diagnosis includes several entities that fall under the umbrella of white dot syndromes. The differential can be narrowed by characterizing the appearance of the fundus, the presence or absence of anterior segment inflammation and whether the findings are unilateral or bilateral.
Conditions that fall under the category of white dot syndromes include presumed ocular histoplasmosis syndrome, acute posterior multifocal placoid pigment epitheliopathy, multiple evanescent white dot syndrome, multifocal choroiditis and panuveitis syndrome, punctate inner choroidopathy, serpiginous chorioretinopathy and birdshot chorioretinopathy.
Due to the presence of lesions within the choroid, other inflammatory and infectious causes of choroidal inflammation should also be considered in a patient with multiple white choroidal lesions. Laboratory work-up could include testing to rule out sarcoidosis (angiotensin converting enzyme, chest X-ray), tuberculosis (PPD skin testing) or syphilis (rapid plasma reagin or venereal disease research laboratory test, fluorescent treponemal antibody absorbed). Vitreous biopsy should be performed if primary central nervous system lymphoma is suspected.
Birdshot chorioretinopathy (BSCR) can be differentiated from other white dot syndromes because it has the unique fundus finding of multiple ill-defined choroidal cream-colored lesions that extend into the periphery in both eyes. BSCR is also the only white dot syndrome with a strong association with the tissue type HLA-A29.
Based on fundus appearance and clinical findings, the patient was tentatively diagnosed with birdshot chorioretinopathy. HLA-A29 testing was ordered. The decision was made to observe the patient with no additional testing because the patient denied ocular and systemic symptoms. HLA-A29 testing was positive, which helped further establish the diagnosis.
Characteristics of birdshot chorioretinopathy
Birdshot chorioretinopathy is a rare bilateral chronic posterior uveitis. Due to its rarity, the exact prevalence of BSCR is unknown, but has been estimated to be somewhere in the range of 0.1 to 0.6 per 100,000 (Minos et al.). Median age of onset is 53 years, with a slight predilection for women (Shah et al.). The cause of BSCR is poorly understood but believed to be autoimmune in nature (Kuiper et al.).
The hallmark of BSCR is the development of ill-defined creamy-colored ovoid or round lesions that are visible on funduscopy. They commonly occur in a radial pattern around the nerve extending into the periphery resembling the appearance of scattered birdshot from a shotgun.
Mild vitritis is believed to be present in nearly all cases of BSCR. Anterior segment inflammation is a rare finding but is often mild if present. Retinal vasculitis and retinal neovascularization have also been reported in patients with the condition. Visual acuity loss occurs most commonly because of cystoid macular edema but may also occur due to global retinal dysfunction that affects the macula or optic atrophy in late stages of the disease.
Studies show that 85% to 98% of patients with BSCR test positive for HLA-A29. Approximately 7% of the Caucasian population will also test positive for HLA-A29, indicating that the presence of the genetic marker is not pathognomonic for the disease and that testing should not be performed unless clinical suspicion for BSCR is high (Baarsma et al.). The diagnostic criteria defined by the International Conference for Birdshot Chorioretinopathy held in 2012 (Levinson et al.) is as follows:
Required characteristics: Bilateral, at least three peripapillary birdshot lesions (cream-colored, irregular or elongated choroidal lesions radiating from the optic disc); 1+ anterior vitreous cells 2+ vitreous haze.
Suggestive findings: HLA-A29 positive, retinal vasculitis, cystoid macular edema.
Exclusion criteria: Keratic precipitates, posterior synechiae, other identified etiology (infection, neoplasm or inflammation).
Two disease phases
Patients with birdshot chorioretinopathy often experience two phases of the disease. The first is a subacute phase that involves good central vision, often with complaints of floaters, paracentral scotoma, night blindness and blurry vision. Patients typically present with complaints despite 20/20 vision, which may be attributed to loss of contrast sensitivity, metamorphopsia and color vision changes. Symptoms can occur even with subtle fundus findings, often leading to misdiagnosis.
Patients in the chronic phase of the condition will experience chronic inflammation that leads to global photoreceptor loss. Inflammation waxes and wanes, causing significant vision loss in some cases; however, retinal function is often lost without affecting visual acuity. One review reported that the final visual acuity in the better eye was 20/40 or better in 75.1% of patients and 20/200 or worse in 9.8% of patients with BSCR (Shah et al.).
Testing to monitor disease progression can include electroretinogram and 30-2 visual field testing to measure retinal function. OCT aids in the diagnosis and treatment of CME and also shows areas of patchy ellipsoid zone atrophy, disrupted RPE and outer-retinal thinning corresponding to areas of retinal atrophy. Indocyanine green (ICG) fluorescent imaging is considered more helpful than fluorescein angiography to monitor disease activity. ICG reveals hypofluorescent areas often distributed along choroidal vasculature. Fundus autofluorescence shows hyporeflectivity that corresponds to areas of RPE atrophy that are often not visible on funduscopy.
Treatment, outcome
Due to the rareness of the disease and variability in patient symptoms and the extent of retinal involvement, no long-term treatment protocol has been established for patients with BSCR. Treatment often involves systemic immunosuppression with steroids, cyclosporine or other steroid-sparing immunomodulatory therapies to decrease ocular inflammation. Some uveitis specialists advocate aggressive treatment to prevent progressive vision loss, even in asymptomatic patients. However, it is suggested that up to 20% of patients with BSCR have self-limiting disease (Gasch et al.).
The patient in this case was asymptomatic despite very prominent fundus changes, an unusual presentation for BSCR. A uveitis specialist was consulted regarding the details of the case. After an extensive discussion with the patient regarding management options and treatment, we elected to defer treatment with immunosuppressive agents and monitor the patient every 3 months with 30-2 visual field testing, OCT and fundus autofluorescence. The patient is currently stable.
References:
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For more information:
Rachel Obrock, OD, practices at the Retinal Institute in Fort Wayne, Ind. She can be reached at robrock@myretinalinstitute.com.