Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

En Face OCT of Type 2 Neovascularization:A Reappraisal of the Pitchfork Sign

Khalil Ghasemi Falavarjani, MD; Adrian Au, MD; Pasha Anvari, MD; Saber Molaei, MD; Shahriar Ghasemizadeh, BS; Aditya Verma, MD; Irena Tsui, MD; Srinivas Sadda, MD; David Sarraf, MD

Abstract

BACKGROUND AND OBJECTIVES:

To describe a new en face optical coherence tomography (OCT) imaging feature of type 2 choroidal neovascularization (CNV) and illustrate the OCT angiographic (OCTA) findings in these eyes.

PATIENTS AND METHODS:

Multimodal images of patients with type 2 CNV who displayed the typical “pitchfork” sign with cross-sectional OCT were reviewed. Corresponding en face structural OCT and OCTA images were analyzed to correlate the finding before and after anti-vascular endothelial growth factor (VEGF) therapy.

RESULTS:

Five eyes of five patients, including two females and three males with a median age of 13 years (range: 8 years to 84 years), were studied. The etiology for type 2 CNV was laser-induced maculopathy in two eyes, idiopathic in two eyes, and age-related macular degeneration in one eye. None of the eyes had evidence of inflammatory ocular disease. En face OCT displayed a characteristic wreath-like pattern of hyperreflective spikes surrounding the type 2 neovascular membrane that originated from the ellipsoid zone and extended into the outer nuclear layer. Wreath-like spikes resolved with intravitreal anti-VEGF injection with good visual outcomes and transformation of the neovascular lesion from a type 2 to type 1 morphology.

CONCLUSIONS:

Type 2 CNV associated with the pitchfork sign with cross-sectional OCT displayed a characteristic wreath-like pattern of hyperreflective spikes with en face OCT that resolved with anti-VEGF therapy. This form of type 2 neovascularization may occur in eyes with different underlying etiologies and without signs of intraocular inflammation and is not limited to pediatric patients.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:719–725.]

Abstract

BACKGROUND AND OBJECTIVES:

To describe a new en face optical coherence tomography (OCT) imaging feature of type 2 choroidal neovascularization (CNV) and illustrate the OCT angiographic (OCTA) findings in these eyes.

PATIENTS AND METHODS:

Multimodal images of patients with type 2 CNV who displayed the typical “pitchfork” sign with cross-sectional OCT were reviewed. Corresponding en face structural OCT and OCTA images were analyzed to correlate the finding before and after anti-vascular endothelial growth factor (VEGF) therapy.

RESULTS:

Five eyes of five patients, including two females and three males with a median age of 13 years (range: 8 years to 84 years), were studied. The etiology for type 2 CNV was laser-induced maculopathy in two eyes, idiopathic in two eyes, and age-related macular degeneration in one eye. None of the eyes had evidence of inflammatory ocular disease. En face OCT displayed a characteristic wreath-like pattern of hyperreflective spikes surrounding the type 2 neovascular membrane that originated from the ellipsoid zone and extended into the outer nuclear layer. Wreath-like spikes resolved with intravitreal anti-VEGF injection with good visual outcomes and transformation of the neovascular lesion from a type 2 to type 1 morphology.

CONCLUSIONS:

Type 2 CNV associated with the pitchfork sign with cross-sectional OCT displayed a characteristic wreath-like pattern of hyperreflective spikes with en face OCT that resolved with anti-VEGF therapy. This form of type 2 neovascularization may occur in eyes with different underlying etiologies and without signs of intraocular inflammation and is not limited to pediatric patients.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:719–725.]

Introduction

Choroidal neovascularization (CNV) may be classified according to the spectral-domain optical coherence tomography (OCT) location of the proliferating vessels.1 Type 1 CNV is identified under the retinal pigment epithelium (RPE), whereas type 2 CNV is noted above the RPE in the subretinal space.2 Type 3 CNV is intraretinal and originates from the deep retinal capillary plexus.3–5

Type 2 CNV is an infrequent complication of exudative age-related macular degeneration (AMD) more likely to develop in younger patients with myopia or multifocal choroiditis.6 This has been attributed to a more adherent basement membrane of the retinal pigment epithelium (RPE) in younger patients.2 Clinically these lesions may display a subretinal pigmented halo around the neovascular lesion.7 With OCT, a band of subretinal hyperreflective material (SHRM) may be noted in the subretinal space.1 However, other OCT features have also been described.8,9 Hoang et al.9 reported the “pitchfork sign” as a distinct finding of type 2 CNV specifically in eyes with inflammatory related multifocal choroiditis.

En face structural OCT imaging is acquired through reconstruction of the high-density, three-dimensional raster scans and provides depth-resolved visualization of the various retinal and/or choroidal slabs presented in the coronal plane. Several studies have demonstrated the benefit of en face OCT imaging in the evaluation of retinal and choroidal disorders.10,11 The aim of this study was to describe a new en face OCT imaging feature of type 2 CNV and illustrate the OCT angiography (OCTA) findings in these eyes before and after anti-vascular endothelial growth factor (VEGF) therapy. This paper will broaden the scope of disease associated with the pitchfork sign and improve our understanding of this finding and provide explanations for its development on the basis of the novel en face features presented.

Patients and Methods

Institutional review board approval was obtained from the respective coauthor institutions and the study adhered to the principles of the Declaration of Helsinki. Informed consents were obtained.

Inclusion criteria for the study included patients with new onset active choroidal neovascularization as determined by clinical examination and multimodal retinal imaging. All patients required high-quality baseline spectral-domain B-scan OCT, as well as en face OCT and OCTA imaging, to be included in the study. Eyes with type 2 neovascularization and the “pitchfork sign” as identified with cross sectional B scan OCT were collected and evaluated with en face OCT and OCTA. Exclusion criteria were any eyes with type 1 or type 3 CNV.

Complete ocular examination including slit-lamp biomicroscopy and indirect ophthalmoscopy was performed in all patients. Multimodal imaging included fluorescein angiography (FA) and cross-sectional spectral-domain OCT (SD-OCT) (Spectralis HRA; Heidelberg, Heidelberg, Germany). En face structural OCT and OCTA imaging was performed in all patients at baseline using either the Avanti RTVue XR (Optovue, Fremont, CA) or the Zeiss PlexElite devise (Carl Zeiss Meditec, Dublin, CA) device. Automated segmentations of the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), avascular retina, and choriocapillaris were performed using the built-in software for each instrument. In addition, the en face images from a customized slab extending from the outer plexiform layer (OPL) to an area 50 μm under the ellipsoid zone (EZ) were obtained.

Results

Five patients (two females and three males ranging in age from 8 years to 84 years) were included. Median age was 13 years. Table 1 displays the patient demographic details. The etiology for CNV included laser-induced maculopathy due to laser pointer injury in two eyes, idiopathic in two eyes, and AMD in one eye. Best-corrected visual acuity (BCVA) at baseline presentation ranged from 20/40 to 20/400. Visual acuity (VA) improved in all eyes after intravitreal anti-VEGF injection. Final BCVA ranged from 20/20 to 20/50.

Characteristics of the Patients With Spiked-Wreath Sign on En Face OCTand Pitchfork on Structural OCT

Table 1:

Characteristics of the Patients With Spiked-Wreath Sign on En Face OCTand Pitchfork on Structural OCT

Cross-sectional OCT B-scan analysis and OCTA displayed a type 2 neovascular lesion, located in the subretinal space above the RPE, in all five patients (Figures 15). In the two older patients (cases No. 4 and 5; Table 1), FA images additionally illustrated classic CNV (Figures 4 and 5). None of the eyes exhibited evidence of inflammation in the posterior segment. Specifically, there was no evidence of vitritis, choroiditis or chorioretinal scars by clinical examination or multimodal imaging in any patient.

Color fundus photography (A), optical coherence tomography (OCT) (B, C), en face OCT angiography (OCTA) (D, E), and en face structural OCT (F, G) images from an 8-year-old girl with laser-induced choroidal neovascularization (CNV). Radial hyperreflective lines (ie, the “pitchfork” sign, dashed white arrow in B and dashed black arrow in G) extending from the type 2 neovascular membrane, identified as subretinal hyperreflective material (SHRM), are noted with the baseline cross-sectional OCT B-scan (B); these linear lesions resolved after intravitreal bevacizumab therapy (C). Note the evolution into a type 1 CNV lesion after intravitreal anti-vascular endothelial growth factor therapy. The type 2 CNV lesion is identified with en face OCTA (D) but a corresponding flow signal for the radial spikes is absent (E). The linear lesions (solid black arrows in G) are more clearly visible in the baseline 6 mm x 6 mm en face OCT image with segmentation of the outer retina (G) and display a remarkable spiked-wreath pattern.

Figure 1.

Color fundus photography (A), optical coherence tomography (OCT) (B, C), en face OCT angiography (OCTA) (D, E), and en face structural OCT (F, G) images from an 8-year-old girl with laser-induced choroidal neovascularization (CNV). Radial hyperreflective lines (ie, the “pitchfork” sign, dashed white arrow in B and dashed black arrow in G) extending from the type 2 neovascular membrane, identified as subretinal hyperreflective material (SHRM), are noted with the baseline cross-sectional OCT B-scan (B); these linear lesions resolved after intravitreal bevacizumab therapy (C). Note the evolution into a type 1 CNV lesion after intravitreal anti-vascular endothelial growth factor therapy. The type 2 CNV lesion is identified with en face OCTA (D) but a corresponding flow signal for the radial spikes is absent (E). The linear lesions (solid black arrows in G) are more clearly visible in the baseline 6 mm x 6 mm en face OCT image with segmentation of the outer retina (G) and display a remarkable spiked-wreath pattern.

Color fundus photography (A), optical coherence tomography (OCT) (B, C), en face OCT angiography (OCTA) (D, E), and en face structural OCT (F) images from a 10-year-old boy with laser-induced choroidal neovascularization (CNV). Linear hyperreflective lesions (ie, “pitchfork” sign) are noted with the baseline cross-sectional OCT (B; F, dashed arrows) but display a remarkable spiked-wreath pattern with the baseline en face OCT segmented at the level of the outer retina (F, solid arrows). The radial hyperreflective spikes resolved after intravitreal bevacizumab therapy (C). Note the evolution into a type 1 CNV lesion (C). Type 2 CNV is identified with en face OCTA (D). No vascular flow signal is noted corresponding to the hyperreflective spikes with the baseline en face OCTA image (E).

Figure 2.

Color fundus photography (A), optical coherence tomography (OCT) (B, C), en face OCT angiography (OCTA) (D, E), and en face structural OCT (F) images from a 10-year-old boy with laser-induced choroidal neovascularization (CNV). Linear hyperreflective lesions (ie, “pitchfork” sign) are noted with the baseline cross-sectional OCT (B; F, dashed arrows) but display a remarkable spiked-wreath pattern with the baseline en face OCT segmented at the level of the outer retina (F, solid arrows). The radial hyperreflective spikes resolved after intravitreal bevacizumab therapy (C). Note the evolution into a type 1 CNV lesion (C). Type 2 CNV is identified with en face OCTA (D). No vascular flow signal is noted corresponding to the hyperreflective spikes with the baseline en face OCTA image (E).

Pseudocolor fundus image (A), fundus autofluorescence (B), optical coherence tomography (OCT) (C, D), en face OCT angiography (OCTA) (E), and en face structural OCT (F) from a 13-year-old girl with idiopathic choroidal neovascularization (CNV). Pitchfork spikes associated with subretinal hyperreflective material are noted with the baseline cross-sectional OCT (C; F, dashed arrow) and resolved after two intravitreal ranibizumab injections. The type 2 CNV lesion confirmed with OCTA evolved to a type 1 lesion (D). Note the remarkable spiked-wreath pattern of the lesion with baseline en face OCT (F, solid arrow) with segmentation adjusted to the outer retina.

Figure 3.

Pseudocolor fundus image (A), fundus autofluorescence (B), optical coherence tomography (OCT) (C, D), en face OCT angiography (OCTA) (E), and en face structural OCT (F) from a 13-year-old girl with idiopathic choroidal neovascularization (CNV). Pitchfork spikes associated with subretinal hyperreflective material are noted with the baseline cross-sectional OCT (C; F, dashed arrow) and resolved after two intravitreal ranibizumab injections. The type 2 CNV lesion confirmed with OCTA evolved to a type 1 lesion (D). Note the remarkable spiked-wreath pattern of the lesion with baseline en face OCT (F, solid arrow) with segmentation adjusted to the outer retina.

Multicolor fundus image (A), fluorescein angiography (B), en face optical coherence tomography angiography (OCTA) (C, F), OCT (D, E), and en face structural OCT (G) images from a 52-year-old man with idiopathic choroidal neovascularization (CNV). Radial hyperreflective spikes are noted with the en face structural OCT and corresponding pitchfork spikes are present with the OCT B-scan at baseline (black arrow and dashed white arrow, respectively, G). A vascular flow signal is absent in the en face OCTA image (F) corresponding to the radial spikes (G).

Figure 4.

Multicolor fundus image (A), fluorescein angiography (B), en face optical coherence tomography angiography (OCTA) (C, F), OCT (D, E), and en face structural OCT (G) images from a 52-year-old man with idiopathic choroidal neovascularization (CNV). Radial hyperreflective spikes are noted with the en face structural OCT and corresponding pitchfork spikes are present with the OCT B-scan at baseline (black arrow and dashed white arrow, respectively, G). A vascular flow signal is absent in the en face OCTA image (F) corresponding to the radial spikes (G).

Fundus autofluorescence (A), fluorescein angiography (B), optical coherence tomography (OCT) (C, D), en face OCT angiography (OCTA) (E), and en face structural OCT (F) images from an 84-year-old man with type 2 CNV secondary to age-related macular degeneration. Linear extensions (ie, “pitchfork” sign) are noted with the baseline cross-sectional OCT (C, F, dashed arrow), and these resolved after intravitreal bevacizumab therapy (D). Note the evolution into a type 1 neovascular lesion (D). Type 2 CNV is present with en face OCTA (E). The hyperreflective spikes are more clearly identified with baseline en face OCT segmentation of the outer retina (solid arrows, F) in a radial or wreath-like pattern.

Figure 5.

Fundus autofluorescence (A), fluorescein angiography (B), optical coherence tomography (OCT) (C, D), en face OCT angiography (OCTA) (E), and en face structural OCT (F) images from an 84-year-old man with type 2 CNV secondary to age-related macular degeneration. Linear extensions (ie, “pitchfork” sign) are noted with the baseline cross-sectional OCT (C, F, dashed arrow), and these resolved after intravitreal bevacizumab therapy (D). Note the evolution into a type 1 neovascular lesion (D). Type 2 CNV is present with en face OCTA (E). The hyperreflective spikes are more clearly identified with baseline en face OCT segmentation of the outer retina (solid arrows, F) in a radial or wreath-like pattern.

All eyes displayed the classic hyperreflective spikes in a pitchfork pattern with cross-sectional B-scan OCT. With en face OCT, a remarkable wreath-like distribution of hyperreflective spikes (spiked-wreath sign) was noted in a pattern surrounding the type 2 neovascular membrane with custom segmentation at the level of the outer retina and subretinal space. Co-localization of the radial spikes with en face OCTA analysis failed to display any evidence of vascular flow signals associated with the radial lesions. All spikes originated from the EZ and extended to the outer nuclear layer (ONL). The ONL and overlying OPL were thickened in the area above the CNV and associated with subretinal fluid, especially in the area of the hyperreflective spikes. After intravitreal anti-VEGF injections, the hyperreflective lesions in the spiked-wreath pattern resolved and the CNV lesions evolved from a type 2 to type 1 NV morphology.

Discussion

In this study, we noted the characteristic pitchfork sign, as identified with cross sectional B-scan OCT, in five eyes with type 2 CNV associated with disparate underlying etiologies, including laser-induced maculopathy and AMD. With en face OCT, a remarkable spiked-wreath pattern was appreciated, a finding not previously reported in patients with type 2 neovascularization. OCTA imaging confirmed the presence of type 2 NV and failed to display vascular flow within the radial hyperreflective spikes. Hoang et al.9 originally suggested that the pitchfork sign may be specific for inflammatory mediated CNV; however, we did not find any evidence of intraocular inflammation in our patients. Specifically, none of the patients in our study exhibited any findings of multifocal choroiditis panuveitis syndrome. Although all patients in the Hoang et al.9 series were young (age range: 16 years to 31 years), our series displayed a wide range of ages, from 8 years to 84 years. Therefore, the pitchfork sign is not limited to young patients.

The pathogenesis of pitchfork spikes associated with CNV is unknown. Hoang et al.9 attributed these lesions to inflammatory material such as fibrin. We noted that the hyperreflective spikes extended from the outer retinal layers (ie, the EZ or the external limiting membrane, overlying the neovascular tissue) without evidence of vascular flow with OCTA imaging. We speculate that there may be traction associated with the type 2 neovascular complex leading to dragging of the overlying outer retinal tissue. Alternatively, these lesions may be the result of Müller cell activation as can occur in various other retinal disorders including outer retinal tubulation and AMD.12,13

In this study, type 2 CNV at baseline regressed to a type 1 pattern in all eyes with resolution of the radial spikes and very good improvement in VA after anti-VEGF therapy. This pattern of regression was first reported by Dolz-Marco et al.14 The radial spikes were noted early in the course of the development of type 2 CNV in our study and may represent a favorable prognostic outcome after anti-VEGF therapy.

Two children in our series presented with laser-induced CNV following exposure to laser pointer instruments. In these two cases and in another child with idiopathic CNV, the neovascular lesion was detected by OCTA, without the need to acquire FA. OCTA may provide a more rapid, less-invasive, and more practical option for the detection of CNV in the pediatric population.

In conclusion, we described a novel en face OCT feature of radial hyperreflective lesions in a spiked wreath pattern associated with type 2 CNV. The radiating spikes did not show vascular flow with OCTA imaging and may be attributed to traction on the outer retina or activation of Müller cells. Future studies are needed to elucidate the histopathological correlate of these remarkable lesions.

References

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Characteristics of the Patients With Spiked-Wreath Sign on En Face OCTand Pitchfork on Structural OCT

Patient No.AgeGenderCause of CNVInitial BCVAFinal BCVATreatmentFollow-Up Time
18FemaleLaser maculopathy20/40020/20IVB3 months
210MaleLaser maculopathy20/40020/40IVB3 months
313FemaleIdiopathic20/4020/20IVR (two injections)3 months
452MaleIdiopathic20/8020/25IVB (two injections)12 months
584MaleAMD20/15020/50IVA (two injections)2 months
Authors

From the Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran (KGF, PA, SM, SG); Stein Eye Institute, David Geffen School of Medicine at University of California Los Angeles, Los Angeles (AA, IT, SS, DS); Doheny Eye Institute, University of California Los Angeles, Los Angeles (AV, SS); and Greater Los Angeles VA Healthcare Center, Los Angeles (DS).

Supported by Research To Prevent Blindness, New York (DS), and the Macula Foundation, New York (DS).

Dr. Sadda has received personal fees from Centervue, Optos, Allergan, Roche/Genentech, Amgen, Heidelberg, Novartis, and Bayer as well as grants from Zeiss outside the submitted work. Dr. Sarraf has received personal fees from Optovue, Amgen, Bayer, Genentech, and Novartis, as well as grants from Heidelberg, Regeneron, and Topcon outside the submitted work. The remaining authors report no relevant financial disclosures.

Address correspondence to David Sarraf, MD, 100 Stein Plaza, Los Angeles, CA 90095; email: sarraf@jsei.ucla.edu, dsarraf@ucla.edu.

Received: December 19, 2018
Accepted: March 26, 2019

10.3928/23258160-20191031-07

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