Woman experiences decline in vision over 2 years
Dilated fundus exam found bilateral, yellow lesions in both maculae.
A 44-year-old healthy woman was referred to New England Eye Center because of a gradual decline in vision over the last 2 years. She noticed that her vision was stable until 2 years ago when she began to experience some difficulty with her reading and distance vision. Both eyes appeared to be affected. On a recent evaluation by optometry, the patient’s vision was unable to be improved significantly with refraction.
Ocular history was remarkable for an unknown eye condition she was diagnosed with in 1997. She was otherwise healthy and took only vitamins. She had no medication allergies and denied tobacco use. She was employed as a dog groomer. Family history was remarkable for age-related macular degeneration and the same unknown eye condition affecting the patient. Her review of systems was unremarkable.
Examination revealed a visual acuity of 20/40+2 with –1.25 +0.50 × 90 in the right eye and 20/60-2 with –1.00 sphere in the left eye. Pupils, extraocular movements, color testing, tonometry, anterior slit lamp examination and alignment were all within normal limits, as were Humphrey 30-2 visual fields in both eyes.
On dilated fundus exam, the patient was noted to have bilateral, yellow, yolk-like lesions in both maculae (Figures 1a and 1b). Standard optical coherence tomography (OCT) was obtained, which showed macular thicknesses to be within normal limits, but ultra-high resolution OCT showed subretinal deposits causing disruption of the retinal pigment epithelium and photoreceptor inner and outer segments (Figures 2a and 2b). A multifocal electroretinogram showed mild central signal decrease with a small loss of the central peak in the right eye and more diffuse and significant signal decrease in the left eye (Figures 3a and 3b).
Images: Balderas I, Hedges TR
What is your diagnosis?
Decline in vision
Best’s disease and adult vitelliform degeneration were considered the most likely possibilities given the fundus appearance of bilateral macular “egg-yolk” lesions.
Adult vitelliform degeneration is characterized by a symmetrical, yellowish foveal lesion that resembles Best’s disease. It is a rare macular dystrophy that has no characteristic inheritance pattern. It differs from Best’s disease in that the electrooculogram (EOG) is generally normal or only mildly reduced, and onset is presumed to be in adulthood. In our patient, although an EOG was not obtained, a diagnosis of Best’s disease was made based on clinical presentation and family history.
Best’s disease is a rare, autosomal-dominant disorder that classically presents in childhood with a yellow or orange yolk-like lesion in the macula. The first pedigree was described in 1905 by Franz Best. The lesions evolve through several stages over many years, increasing the potential for vision loss. The hallmark of this disease is an abnormal EOG in all stages of the disease and in phenotypically normal carriers. There are no systemic associations with this disease.
The actual incidence is unknown, and the clinical expression is highly variable. There is a “carrier” state in which patients have no clinical findings of Best’s but have an abnormal EOG and can transmit the disease to offspring. The usual age of onset is thought to be between 3 and 15 years, but it is usually not detected for many years until visual decline is noted. The atrophic stage of the disease typically begins after age 40.
The genetic defect has been localized to chromosome 11, the q13 locus, which codes for bestrophin (VDM2). Several groups have been able to localize the protein product to the basolateral plasma membrane of the retinal pigment epithelium (RPE), and it is believed to be a calcium-sensitive chloride channel involved in generating the light peak. Several mutations involving the VDM2 gene have been identified in association with Best’s and adult vitelliform macular degeneration.
Progression of Best’s disease can be described in several stages. Stage one (previtelliform) has a relatively normal appearing macula with 20/20 vision and an abnormal EOG. Stage two disease (vitelliform) is characterized by the classic egg-yolk lesion with 20/20 to 20/50 vision. The pseudohypopyon (stage three) occurs when breaks in the RPE lead to accumulation of subretinal fluid in cystic spaces. An “air-fluid” level can be appreciated on fundus exam. This most often occurs in the teenage years when observed, and vision can range from 20/20 to 20/50. Stage four (vitelliruptive) is characterized by breakup of the yolk lesion (“scrambled egg”) with pigment clumping and atrophic changes. Vision can range from 20/20 to 20/100. An atrophic lesion is seen in stage five, where the yellow lesions disappear and RPE atrophy remains. Vision is usually less than 20/200 at this stage. Stage six occurs if choroidal neovascularization is present, proceeded by formation of a whitish subretinal fibrous scar.
Early disease is easily diagnosed by the pathognomonic egg-yolk appearance of the retina. Longstanding cases or those with a normal fundus appearance are diagnosed by an abnormal EOG. The majority of carriers and affected individuals will manifest a severe decrease in light response, reflected by an Arden ratio of 1.1 to 1.5 (normal is at least 1.8). No correlation has been found between EOG result and disease stage, visual acuity or patient age. The EOG is usually symmetric for both eyes, and the full-field ERG is usually within normal limits. A focal or multifocal ERG may reveal some abnormality. This is the only disease with a relatively normal ERG and abnormal EOG. Genetic testing for several mutations of the VDM2 gene is also available and has become an important tool in genetic counseling.
Carriers never phenotypically express the disorder, and many affected individuals maintain 20/40 or better vision, never progressing beyond the early disease stages. Mohr and Fine followed 91 patients and found that 77% maintained 20/40 or better visual acuity and that 19% with atrophic or fibrous scars lost two or more lines. Deterioration of vision is usually slow and occurs after age 40.
There is currently no treatment for Best’s disease. Several case reports and small observational studies have been done looking at photodynamic therapy for the treatment of subfoveal CNV complicating Best’s disease. Andrade and colleagues reported a case of a 43-year-old with Best’s and subfoveal CNV treated with PDT who demonstrated regression of the lesion and resolution of exudation 3 weeks later.
Chung and colleagues described 14 eyes of 12 patients with subretinal hemorrhage associated with a clinical diagnosis of Best’s disease. All patients had visual loss at presentation (median 20/100). All patients were observed. Median final visual acuity was found to be 20/50 with a median follow-up of 48.5 months. Eleven of 14 eyes were found to have scarring or RPE atrophy while three of 14 eyes were noted to have subretinal hemorrhage at final follow-up.
Our patient continues to function fairly well with strong reading glasses and is followed on a periodic basis.
For more information:
- Isabel Balderas, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.
- Edited by Shazia Ahmed, MD, and My Hanh T. Nguyen, MD. Drs. Ahmed and Nguyen can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Ahmed and Nguyen have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
- Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease. Am J Ophthalmol. 2003;136(6):1179-1181.
- Chung MM, Oh KT, et al. Visual outcome following subretinal hemorrhage in Best disease. Retina. 2001;21(6):575-580.
- Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. 4th ed. St. Louis: CV Mosby; 1997:304-319.
- Marmorstein LY, McLaughlin PJ, et al. Bestrophin interacts physically and functionally with protein phosphatase 2A. J Biol Chem. 2002;277(34):30591-30597.
- Mohler CW, Fine SL. Long-term evaluation of patients with Best’s vitelliform dystrophy. Ophthalmology. 1981;88(7):688-692.
- Yanoff M, Duker JS, Dresner K, Small KW. Macular dystrophies. In: Ophthalmology. 2nd ed. St. Louis: CV Mosby; 2004:824-827.