A 6-year-old boy presents with leukocoria in the right eye. Dilated fundoscopy under anesthesia reveals the findings shown in the diagram. The structures marked **A** are telangiectatic light-bulb aneurysms. Which of the following best describes the PRIMARY PATHOPHYSIOLOGIC mechanism responsible for the formation of these aneurysms in Coats disease?
A. Congenital persistence of primitive hyaloid vasculature with abnormal regression during fetal development
B. Retinal ischemia from capillary non-perfusion triggering neovascularization and abnormal vessel growth
C. Breakdown of the inner blood-retinal barrier due to retinal endothelial cell dysfunction, leading to plasma leakage and compensatory vascular dilation
D. Genetic mutation in the RB1 gene causing uncontrolled endothelial proliferation and aneurysm formation
Explanation
Why option 1 is right
The primary pathophysiologic defect in Coats disease is a breakdown of the inner blood-retinal barrier caused by dysfunction of retinal endothelial cells. This barrier failure leads to plasma leakage into the retina and subretinal space, which triggers compensatory vascular dilation and telangiectasia, culminating in the characteristic "light-bulb" aneurysms marked A in the diagram. This is the foundational mechanism that distinguishes Coats disease from other causes of leukocoria and drives all downstream pathology (lipid deposition, exudative detachment). (Shields JA. Coats Disease Classification; AAO BCSC Pediatric Ophthalmology)
Why each distractor is wrong
Option 2 (Persistent hyaloid vasculature): This describes persistent fetal vasculature (PFV), a different cause of leukocoria in infants. PFV is congenital and involves abnormal regression of the hyaloid system, not endothelial barrier breakdown. It is a key differential diagnosis but does not explain the telangiectasia and aneurysm formation in Coats disease.
Option 3 (Retinal ischemia and neovascularization): While capillary non-perfusion is indeed present on fluorescein angiography in Coats disease, it is a SECONDARY finding, not the primary mechanism. The primary defect is endothelial barrier failure; ischemia and neovascularization follow, not precede, the telangiectasia.
Option 4 (RB1 mutation): RB1 mutations cause retinoblastoma, the most important differential diagnosis of leukocoria. Retinoblastoma presents with a calcified intraocular mass on imaging and may have family history. Coats disease is idiopathic, non-hereditary, and shows NO calcification—it is a vascular disorder, not a malignancy.
High-YieldNEET PG
Coats disease = primary endothelial barrier breakdown → telangiectasia → aneurysms → exudation → lipid deposition → exudative RD. No calcification, no family history, no RB1 involvement.
