Novel OCT Angiography Features, von Hippel-Lindau Disease Association, and Genetic Characterization of Juxtapapillary Retinal Capillary Hemangiomas

Abstract

Purpose: To present new clinical features of juxtapapillary retinal capillary hemangiomas (JRCHs), assess the risk of von Hippel-Lindau (VHL) disease, and explore the genotype-phenotype correlations in patients with JRCH.

Methods: Fifty patients with JRCH were included. Multimodal retinal imaging including optical coherence tomography angiography (OCTA), visual acuity, presence of peripheral RCHs, affected lateralities, systemic evaluation for VHL disease, and underlying VHL variants were reviewed.

Results: Of 59 eyes, 48 had classic JRCHs, whereas 11 had atypical JRCHs (type B, if it broke through the inner limiting membrane: 3 eyes; type A, if not: 8 eyes). Compared with atypical type A, which was indolent, type B might warrant surgical interventions. Better final visual acuity (P < 0.0001), fewer peripheral RCHs (P = 0.02), and lower prevalence of large peripheral RCHs (>1.5 mm) (P = 0.027) were observed in eyes with atypical JRCHs than classic JRCHs. VHL was diagnosed clinically in 72% of patients, and 22 VHL variants were identified, including 5 novel variants. Patients with truncating variants had a higher prevalence of atypical JRCHs than those with single amino acid substitution/deletion variants (P = 0.009). Patients with bilateral VHL-JRCHs were more likely to have large peripheral RCHs (P = 0.02) and less likely to harbor β-domain single amino acid substitution/deletion variants (P = 0.066) than those with unilateral VHL-JRCHs.

Conclusions: Atypical JRCHs, with distinctive OCTA characteristics and favorable visual outcomes, are less complicated by peripheral RCHs and more relevant to truncating variant genotypes. JRCH monitoring should incorporate OCTA classification and genotype analysis.

Figure 1.

Identification of an occult classic JRCH with OCT angiography (OCTA). (A) Fundus photograph and (B) en face OCTA image of the total retina showing apparently normal optic disc and adjacent retina (case 1). (C) Avascular slab identifying a nodular JRCH (white arrow) on the superior side. (D) Corresponding B scan taken along the level of the yellow dashed line in (C) demonstrating blood flow in the exophytic JRCH (yellow arrow). (E) Fluorescein angiography image showing hyperfluoresence of the lesion.

Figure 2.

Atypical JRCHs without breaking through the ILM (atypical type A). (A) Fundus photograph showing a nearly invisible JRCH at the nasal disc border, which is hyperfluorescent on fluorescein angiography (B, case 3). (C) En face retinal OCTA identifying a tiny vascular focus (red arrow). (D) Along the yellow dashed line in (C), the B-scan verifying blood signal of the atypical JRCH (white arrow), in the superficial layer of the retina. Thirty-two months later, the atypical JRCH remains stable on the en face retinal OCTA image (E, red arrow) and corresponding B scan (F, white arrow). (G–I) Reddish lacy vascularity around bifurcation of the upper retinal vein is shown in fundus photograph (G), en face OCTA scan (H), and B scan (I, white arrows; OCT as shown in the inset, case 4). (J–L) The lesion is demonstrated to grow with increasing blood signal and shadowing effects (L, white asterisk) after 42 months of follow-up.

Figure 3.

Atypical JRCHs breaking through the ILM (atypical type B). (A) Fundus photograph showing a faint red lesion at the temporal disc border (white arrow, case 5). Along the yellow dashed line in en face retinal OCTA image (B), the atypical JRCH breaking through the ILM (C, white arrow) and attaching to the posterior hyaloid membrane (C, white asterisk). (D) The OCTA B-scan shows weak blood flow inside. (E, F) Twenty-one months later, the lesion grows along the posterior hyaloid membrane (E), exerting tractional effects on the retina (E, yellow arrow) with enhancement of blood flow signal (F). However, the BCVA remains 20/20. (G–I) En face retinal OCTA scans at baseline with BCVA of 20/30 (G, the red arrow indicates the lesion), thirteen months later with BCVA of 20/50 (H), and 4 months after the surgery with BCVA of 20/25 (I, case 6). (J–L) Corresponding B scans demonstrating the fibrovascular lesion adhering on the posterior hyaloid membrane (J, white asterisk) with lamellar macular hole; the formation of a full-thickness hole (K) and macular hole healing after surgical removal of the lesion (L).

Figure 4.

Overview of patients with JRCHs and follow-up information. (A) The pie chart illustrates the distribution of 50 patients with JRCHs according to the association with VHL disease and genetic results. (B) The spectrum of VHL variants along the length of the VHL gene among patients with VHL–JRCHs. The subtypes of JRCHs and affected lateralities are also marked for a certain VHL variant.