Case of the Month
Edited by Robert N. Johnson, MD
Case #103, Jan, 2018
Presented by Judy Chen, MD
A 51-year old woman presents with blurred vision in both eyes and a blind spot in the left eye.
Figure 1: Fundus photograph of the right eye revealed angioid streaks (inset), retinal pigment mottling and geographic atrophy within the macula, a peau d’orange stippling of the temporal macula, and multiple comet-shaped hypopigmented spots in the midperiphery
Figure 2: Fundus photograph of the left eye showed angioid streaks (inset), pigment mottling, a larger area of geographic atrophy in the macula, peau d’orange stippling, and comet spots.
A 51-year-old Caucasian female presented with a prolonged history of worsening vision in both eyes and a large blind spot in her left eye. She described intermittently receiving injections in both eyes 7-10 years ago, although none recently. She felt the blind spot in the left eye had slowly enlarged over the last several years. Her past medical history, past ocular history, and family history was otherwise unremarkable.
On examination, her best-corrected visual acuity was 20/25 in the right eye and 20/50 in the left eye. There was no relative afferent pupillary defect and ocular motility was normal in both eyes. Intraocular pressures were 14 and 16 in the right and left eyes, respectively. Anterior segment examination was unremarkable in both eyes. The posterior segment examination of the right eye (Figure 1) revealed many red curvilinear angioid streaks emanating from the disc, retinal pigment mottling and geographic atrophy within the central and nasal macula, a peau d’orange stippling of the temporal macula, and multiple comet-shaped hypopigmented spots in the midperiphery. Fundus examination of the left eye (Figure 2) showed similar changes to the right eye.
Fundus autofluorescence of the right eye (Figure 3) and left eye (Figure 4) were significant for several large, well circumscribed areas of hypoautofluorescence consistent with geographic atrophy as well as many punctate hyperautofluorescent dots in the peripapillary region corresponding to retinal pigment epithelial hypertrophy and clumping. Optical coherence tomography (OCT) scans of the right eye (Figure 5) and left eye (Figure 6) showed patchy loss of the ellipsoid line and increased signal transmission corresponding to areas of geographic atrophy. OCT angiography (OCT-A) scans of the right eye (Figure 7) revealed a few small nets of residual choroidal neovascularization within the choriocapillaris.
Figure 3: Wide-field fundus autofluorescence of the right eye reveals areas of hypoautofluorescence consistent with geographic atrophy and punctate hyperautofluorescent dots centered around the optic nerve.
Figure 4: Wide-field fundus autofluorescence of the left eye reveals more extensive areas of hypoautofluorescence consistent with geographic atrophy in the macula and punctate hyperautofluorescent dots centered around the optic nerve.
Figure 5: SD-OCT scan through the macula. Note disruption of the EZ band, and areas of RPE atrophy.
Figure 6: SD-OCT scan through the macula. Note disruption of the EZ band, and areas of RPE atrophy.
Figure 7: OCT-A of the right macula. Areas of atrophy are noted with loss of the choriocapillaris, but also areas of persistent CNV
What is your Diagnosis?
Ehlers-Danlos syndrome, Paget’s disease, Marfan syndrome, acromegaly, senile elastosis, sickle cell hemoglobinopathies, thalassemia, acanthocytosis, hereditary spherocytosis, facial angiomatosis, neurofibromatosis, pseudoxanthoma elasticum
Additional Case History
Examination of the skin around the neck (Figure 8) and flexural surfaces of the arm (Figure 9) revealed innumerable coalescent yellowish papules and plaques in a reticular pattern. A presumed diagnosis of pseudoxanthoma elasticum was made. The patient was referred back to her primary care physician for appropriate workup and monitoring of cardiovascular manifestations.
Figure 8: Color photography of the patient's neck. Note pattern of coalescent yellowish plaques in a reticular pattern.
Figure 9: Color photography of the patient's antecubital fossa. Note a similar pattern of coalescent yellowish plaques in a reticular pattern present on her neck.
Angioid streaks were first described by Doyne in 1889 as irregular radiating lines extending from the optic nerve to the peripheral retina found in eyes with retinal hemorrhages after blunt trauma.1 Histopathologically, they have been found to be due to irregular, well delineated breaks in Bruch’s membrane.2 Most patients with angioid streaks remain asymptomatic until they develop complications such as choroidal neovascularization, which often carries a poor prognosis.
Pseudoxanthoma elasticum (PXE) is the most common systemic disorder associated with angioid streaks. PXE is an inherited disorder characterized by fragmentation and degeneration of elastic tissues within the skin, gastrointestinal tract, cardiovascular system, and the eyes with subsequent calcium deposition.2 Our case demonstrates many of the characteristic ocular findings in PXE, including angioid streaks, peau d’orange stippling of the retina, pigmentary changes within the macula, geographic atrophy, comet-shaped chorioretinal atrophy in the mid periphery which are considered pathognemonic for PXE, and secondary choroidal neovascularization.3 Optic disc drusen, another common ocular finding in PXE, was not present in our patient.
Systemic manifestations of PXE mainly affect the skin, the heart, and the brain. Cutaneous lesions are small, discrete, yellowish papules most commonly found on the neck, axillae, and anticubital and popliteal fossae, which can increase in number and coalesce into larger plaques.5 Cardiovascular manifestations include angina pectoris, reduced pulse amplitude, arterial hypertension, restrictive cardiomyopathy, and mitral valve prolapse or stenosis with sudden cardiac failure.3 Cerebrovascular complications can include transient ischemic attacks or acute infarctions of the brain due to narrowing of the cerebral arteries and aneurysm formation.4
The causative mutation for PXE has been localized to the ABCC6 gene transporter protein on chromosome 16, of which over 300 mutations linked to PXE patients have been described. More recently, ENPP1 has also been described to cause a PXE-like syndrome.5 Diagnostic criteria for PXE includes either homozygosity or compound heterozygosity for a known disease-causing mutation in the ABCC6 gene or the presence of one or two major eye findings (angioid streaks > 1 disc diameter, peau d’orange) in addition to one or two characteristic skin findings (classical pseuxanthomatous skin plaques, positive skin biopsy).5
Treatment of the ocular manifestations of PXE is not needed until secondary neovascular complications develop. Options for treatment of CNV include laser photocoagulation, transpupillary thermotherapy and photodynamic therapy, macular translocation surgery, and anti-vascular endothelial growth factor (anti-VEGF) injections. Although no randomized controlled trials for CNV secondary to PXE have been performed, a systematic review of ten case series describing the use of bevacizumab or ranibizumab in a total of 49 eyes of 45 patients under either maintenance or as needed regimens concluded favorable results in stabilizing or improving final visual acuity.6 Additionally, because the calcification of Bruch’s membrane may lead to breaks from mild head or eye injuries, resulting in severe subretinal hemorrhages, PXE patients are advised to refrain from contact sports. No specific treatment for the systemic findings of PXE is currently available.
Take Home Points
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