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Betty Dylan* was concerned about the vision in her left eye. The 74-year-old was still making a living as an interior decorator and, like many in her profession, was well known for her attention to detail. But details were now beginning to trouble her. Two or three months before she requested an eye exam, she noticed that straight lines appeared to have a curved quality when viewed with her left eye, particularly when she looked at the edges of doorways and counters. She also complained that the vision of that eye was becoming gradually blurred, and that the blurring was now a constant problem.
Ms. Dylan had undergone cataract surgery in both eyes about seven years before we saw her; other than that, her ocular history was normal. She had hypertension and hypothyroidism and took atenolol, levothyroxine and aspirin daily. She also used artificial tears two or three times a day in both eyes. With regard to her family history, one brother had died from a stroke.
We Get a Look
When we examined her, Ms. Dylan’s BCVA was 20/30 in her right eye and 20/50 in her left, and her IOP was 15 mmHg in the right and 17 mmHg in the left. Her pupils reacted briskly to light, and we noted no relative afferent pupillary defect. Her extraocular movements and visual fields to confrontation were normal bilaterally.
During the slit-lamp exam, we noted scarring on her eyelids from previous blepharoplasties and lax skin surrounding her eyes. Her conjunctivae were white and quiet bilaterally, the corneas were clear and her anterior chambers were deep and quiet. Her irises had small nevi, and her posterior chamber IOLs were in the appropriate position with open posterior capsules.
The dilated fundus exam showed a clear vitreous with posterior vitreous detachment in both eyes and normal retinal vessels. Each optic nerve had a cup-to-disc ratio of 0.3 and both were flat, sharp and pink. She had linear streaks of retinal pigment epithelial atrophy, which radiated peripherally from both optic nerves and quickly tapered to points (Figs. 1 and 2). The macula of the right eye was remarkable for retinal pigment epithelial irregularities temporally, while the macula of the left eye demonstrated a gray neovascular membrane superonasally, with similar RPE irregularities temporally. An intraretinal hemorrhage was seen adjacent to the membrane. The retinal periphery of the right eye demonstrated a hemorrhage superior to the optic nerve, while the periphery of the left eye was unremarkable.
Ocular coherence tomography of the macula of the right eye showed a retina with normal foveal contour and no subretinal or intraretinal fluid. The macular OCT of the left eye demonstrated several intraretinal cysts with macular edema superonasal to the center of the macula (Fig. 3).
Red-free photography demonstrated white streaks radiating from the optic nerves in both eyes. Fluorescein angiography demonstrated window defects in the location of the linear streaks emanating from both optic discs (Fig. 4). In addition, the left eye demonstrated the presence of a neovascular membrane in the superonasal macula, which was associated with one of the hyperfluorescent streaks (Fig. 5). The lesion demonstrated early staining and late leakage.
Angioid streaks are irregular, jagged lines at the level of Bruch’s membrane that extend from the peripapillary area toward the periphery. These streaks are typically narrow and taper down to a point a few millimeters from the optic disc.1 The lesions typically are bilateral and range in color from light to dark brown, but they occasionally appear red.
Angioid streaks correspond to breaks in Bruch’s membrane that have been associated with the calcification and thickening of the membrane. The histologic appearance of these lesions is consistent, regardless of the underlying systemic cause.
The characteristics of these lesions during fluorescein angiography depend on the degree of overlying atrophy. If there is atrophy of the retinal pigment epithelium, early hyperfluorescence will occur secondary to a window defect. The hyperfluorescence will gradually fade as the fluorescein is washed out of the choroid. If the choriocapillaris has become separated from Bruch’s membrane, however, hyperfluorescence will occur along the margins of the streaks without central staining.
The most severe complication from angioid streaks is choroidal neovascularization, which is anatomically associated with a streak. Breaks in Bruch’s membrane allow for fibrovascular ingrowth into the RPE and neurosensory retina. These membranes may lead to serous or hemorrhagic RPE detachment and resemble membranes associated with exudative AMD.
The Leading Suspect
Although the differential diagnosis of angioid streaks is extensive, pseudoxanthoma elasticum is the most common cause for these lesions.
PXE is a systemic condition that primarily affects the skin, eyes and cardiovascular system. It is believed to be predominantly inherited in an autosomal recessive manner and has been linked to a mutation in the ABCC6 gene in chromosome 16.2 This gene encodes for a protein that is an active transmembrane transporter. The exact function of this protein, however, remains unknown.
The analysis of skin specimens from PXE patients has found an increased rate of synthesis and degradation of elastin. Pathologically, the disease is characterized by calcification of elastic fibers. The skin is typically redundant and may show small yellow-white papules on the neck or the flexor areas of the arms and legs. Indeed, when we examined Ms. Dylan, we observed excessive elasticity in the skin around her neck (Fig. 6). The absence of skin findings, however, does not exclude a diagnosis of PXE, and the presence of any specific skin finding is not pathognomonic for the disease.
The disease may also affect the cardiovascular system, leading to hypertension, cardiomyopathy, valvular dysfunction, early atherosclerosis, or even cardiac failure and death. Blood vessels throughout the body are characterized by premature calcification. Damage to the blood vessels of the heart, brain or gastrointestinal tract may lead to life-threatening bleeding.
In addition to angioid streaks, ocular findings in patients with PXE include a diffuse mottling of the temporal macular RPE, often referred to as peau d’orange. This is typically the first ocular manifestation of the disease and usually precedes the development of angioid streaks by a few years.2 Optic disc drusen and small chorioretinal atrophic lesions also have been linked to PXE. The atrophic lesions are typically found in the midperiphery and have RPE atrophic edges, which curtail to a point that is directed toward the posterior pole.