Best’s disease

DEFINITION/OVERVIEW

Best’s disease, also known as vitelliform macular dystrophy type 2 (VMD2), is a degenerative disorder of the central macula named for its ‘egg-yolk’-like (vitelliform) appearance seen in the early stages. It is most commonly a bilateral disorder. In later stages, this condition causes

retinal degeneration and atrophy leading to bilateral loss of central vision (177).12,13

ETIOLOGY

Best’s disease is an AD-inherited macular dystrophy that begins with an ‘egg-yolk’-like accumulation of material underneath the central macula, which later leads to degeneration and atrophy in this area and subsequent central vision loss. The gene responsible for this condition is found on Chr 11q13 and was only recently discovered (1998).14 The gene, known as bestrophin, codes for a calcium-sensitive chloride channel protein within the retinal pigment epithelium (the cell layer underneath the retina that aids in metabolism and removal of waste products).

CLINICAL PRESENTATION

Patients with Best’s disease frequently first present with mildly decreased vision or are sometimes diagnosed incidentally on a routine ophthalmologic examination. The initial presentation of this condition can be quite variable. In the early stages, a dilated fundus examination reveals a yolk-like (vitelliform) elevated, subretinal accumulation of yellowish material (lipofuscin) within the central macula of both eyes (178).

DIFFERENTIAL DIAGNOSIS

The diagnosis of Best’s disease should be differentiated from other macular dystrophies including Stargardt disease, Sorsby’s macular dystrophy, Doyne’s honeycomb dystrophy, and butterfly macular dystrophy. Other nondegenerative macular diseases such as subretinal fluid (central serous chorioretinopathy) and infections (toxoplasmosis) should also be included in the differential; however, these conditions rarely present with bilateral involvement.

DIAGNOSIS

The diagnosis of Best’s disease is simpler when the characteristic vitelliform lesion is seen in the early stages. In the later stages when macular atrophy is seen, the diagnosis is more difficult due to an appearance similar to other macular degenerations. ERG generally shows a normal full field retinal response, because this is a localized disease of the central macula (ERG results are a summation of the entire retinal response). The ERG readings are usually abnormal in other retinal degenerative disorders such as Stargardt disease.

The definitive test for Best’s disease is an electro-oculogram (EOG). This test examines the change in voltage across the retina as the eye moves horizontally from one extreme of gaze to the other. In most degenerative retinal diseases, when the EOG results are abnormal, the ERG results are also abnormal. Best’s disease is the only known retinal condition that demonstrates a normal ERG and an abnormal EOG.

MANAGEMENT/TREATMENT AND PROGNOSIS

There are no known treatments that improve the vision in patients with Best’s disease. An important intervention that can be very helpful for patients with Best’s disease and their families is low-vision therapy and social services referrals for the blind if vision falls below 20/200.

The vitelliform lesion may remain stable for years without causing significant vision loss. Over time, the material within the lesion may settle inferiorly, resulting in a fluid level superiorly. In the later stages of Best’s disease, the lipofuscin is gradually absorbed, resulting in an appearance described as ‘scrambled eggs’. These changes lead to thinning and dysfunction of the overlying retina, and ultimately atrophy of the central macula. In these later stages, central vision is slowly but progressively lost. The vision ranges depending on the stage of involvement, but final visual acuity is often in the range of 20/100–20/200.

Persistent fetal vasculature

DEFINITION/OVERVIEW

Persistent fetal vasculature (PFV), previously known as persistent hyperplastic primary vitreous (PHPV), is congenital persistence of normal ocular vasculature that would normally be reabsorbed prior to full-term birth.

ETIOLOGY

The etiology of this disorder is not known. As its former name implies, the primary vitreous forms the initial fetal vasculature of the eye during the 3rd–6th weeks of embryological development. The term PFV was coined in 1997 by Dr. Morton Folk Goldberg, who proposed that the term was more descriptive of the anatomic and developmental changes seen in the condition.15 The primary vitreous is composed of mesenchymal vasoproliferative cells and ectoderm that fill the cavity between the fetal lens and retina. During this time, the hyaloid artery extends from the dorsal ophthalmic artery through the fetal fissure anteriorly to reach the lens. This artery, aided by mesenchymal elements from the primary vitreous, then forms a network of vessels, known as the tunica vasculosa lentis, that surround and nourish the developing lens.

The secondary adult vitreous begins to form during the 9th week, and is composed of sodium hyaluronic acid, hyalocytes, and collagen fibrils. The development of secondary vitreous causes regression and displacement of the primary vitreous. At full term, the vasculature that once enveloped the lens and extended from the optic nerve anteriorly, has regressed, leaving only avascular adult vitreous.

Failure of this fetal vasculature to regress is seen in only 3% of full-term infants, but is commonly seen (95%) in varying degrees of severity in patients born prior to 36 weeks gestational age. PFV is a spontaneous disorder, but several cases of genetic linkage have been reported in some families.

CLINICAL PRESENTATION

Patients with PFV are frequently diagnosed soon after birth when the pediatrician, using a direct ophthalmoscope in the nursery or office, discovers a dim red reflex or frank leukocoria. The majority of patients with PFV have unilateral disease (>90%);16 however, careful examination of the contralateral eye may reveal clinically insignificant evidence of persistent vasculature (Mittendorf’s dot or pupillary strands). The findings of PFV may be categorized according to their location of involvement: 25% of cases involve only the anterior segment, 12% of cases involve only the posterior segment, and the remaining 63% involve both anterior and posterior segments. However, significant abnormalities of the posterior segment are only present in about 10%.

The anterior form of PFV commonly shows a plaque of white, opaque fibrovascular tissue posterior to the lens (retrolental tissue) (179, 180). Occasionally only a small lens opacity is present, but this often progresses over time. Amblyopia is common in the setting of unilateral cataracts, warranting careful observation and treatment. Untreated PFV can lead to shallowing of the anterior chamber and angle-closure glaucoma.

The posterior form of PFV (181) does not involve anterior segment structures, but the posterior fibrovascular tissue commonly leads to folds or detachments of the retina (70%). Other abnormalities include poor macular development and optic nerve hypoplasia. Other ocular abnormalities seen in PFV patients include microphthalmia and strabismus.

DIFFERENTIAL DIAGNOSIS

The most important diagnoses to distinguish from PFV include retinoblastoma, retinopathy of prematurity, uveitis, and ocular toxocariasis, because these diagnoses require different and urgent treatments. Other conditions that may be confused with PFV include Norrie’s disease, incontentia pigmenti, familial exudative vitreoretinopathy, and simple unilateral congenital cataract.17

DIAGNOSIS

Any infant with an abnormal red reflex should be referred for a complete ophthalmologic exam. PFV is diagnosed by careful direct visualization by indirect ophthalmoscopy and slit-lamp examination, as well as b-scan ultrasonography if the fundus is difficult to view. An examination under anesthesia may be required in order to establish the diagnosis and perform the appropriate treatment.

MANAGEMENT/TREATMENT

The management of PFV is surgical, specifically lens removal (lensectomy), membrane removal (membranectomy), and vitreous removal (vitrectomy). The goal of treatment in anterior PFV is to remove the cataractous lens and fibrovascular tissue that obstruct the visual axis, and to relieve any contractures that may be shallowing the anterior chamber. Management should be instituted soon after diagnosis.

PROGNOSIS

Patients who undergo early surgery for unilateral cataracts associated with PFV have a guarded visual prognosis. In the study by Anteby et al., approximately 12% of patients ultimately showed visual acuity of 20/70–20/200, 47% showed visual acuity of 20/350 light perception, and 30% showed no light perception.18 However, cases that are left untreated do not develop useful vision, and other complications such as severe glaucoma may develop as soon as 3 months after birth, and eventually, phthisis bulbi.