Benign Lobular Inner Nuclear Layer Proliferations of the Retina Associated with Congenital Hypertrophy of the Retinal Pigment Epithelium

Abstract

Purpose: To report the clinical and imaging findings of 4 patients with benign intraretinal tumors, 2 of which were associated with retinal pigment epithelium (RPE) hypertrophy. To our knowledge, this condition has not been described previously and should be distinguished from retinoblastoma and other malignant retinal neoplasms.

Design: Retrospective case series.

Participants: Four patients from 3 institutions.

Methods: Four patients with intraretinal tumors of the inner nuclear layer (INL) underwent a combination of ophthalmic examination, fundus photography, fluorescein angiography, OCT, OCT angiography, and whole exome sequencing.

Main outcome measures: Description of multimodal imaging findings and systemic findings from 4 patients with benign intraretinal tumors and whole exome studies from 3 patients.

Results: Six eyes of 4 patients 5, 13, 32, and 27 years of age were found to have white intraretinal tumors that remained stable over the follow-up period (range, 9 months-4 years). The tumors were unilateral in 2 patients and bilateral in 2 patients. The tumors were white, centered on the posterior pole, and multifocal, with some consisting of multiple lobules with arching extensions that extended beyond the central tumor mass. OCT demonstrated these lesions to be centered within the INL at the border of the inner plexiform layer. In addition, 2 patients demonstrated congenital hypertrophy of the RPE (CHRPE) lesions. Three of 4 patients underwent whole exome sequencing of the blood that revealed no candidate variants that plausibly could account for the phenotype.

Conclusions: We characterize a novel benign tumor of the INL that, in 2 patients, was associated with separate CHRPE lesions. We propose the term benign lobular inner nuclear layer proliferation to describe these lesions.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: Congenital hypertrophy of the retinal pigment epithelium; Inner nuclear layer; Retinal mass; Retinal tumor; Retinoblastoma.

Figure 1.

Multimodal imaging of the right eye of Case 1. A, Color fundus montage showing a collection of white intraretinal tumors located temporal to the fovea consisting of lobules with thin, arching extensions. B, SD-OCT line scan corresponding to the green dotted line in A, shows a homogenous, hyper-reflective lobular mass lesion compressing the adjacent outer retinal and inner retinal layers. A magnified inlay clearly shows the lateral extension of the tumor residing completely within the INL. C, En face structural OCT with slab through the INL again demonstrates the morphology of the tumor. D-E, OCT-A with slab through the INL shows no intrinsic vascularity, and no identifiably feeder vessels.

Figure 2.

Multimodal imaging of Case 2. A, Color fundus photo of the right eye showing clinically normal appearing optic nerve, macula and vasculature. B, Color fundus montage of the left eye demonstrates a large, lobular appearing white intraretinal tumor superior to the fovea with subtle, arching lateral extension emanating from the nasal border. A second, round white lesion is present inferior to the fovea. A third lesion within the maculopapular bundle is difficult to observe because of the prominent ILM sheen. Multiple grouped CHRPE lesions are present within the inferotemporal quadrant. C, SD-OCT through the fovea of the right eye appears normal. D, SD-OCT through the fovea of the left eye demonstrates a normal foveal depression with a subtle linear hyper-reflective lesion extending from the nasal INL across the foveal center to the temporal INL. E-F, High magnification color images show the intraretinal masses in greater detail. The colored dotted lines correspond to SD-OCT line scans. E’, SD-OCT line scan through the lesion in E show two homogenous, round hyper-reflective masses compressing the adjacent retinal layers. These lesions are likely connected by a very thin extension adjacent to the IPL which is slightly hyper-reflective compared to the IPL. F’-F”’, Three SD-OCT line scans through the lesion shown in F show the tumor clearly located within the INL and causing varying degrees of compression to the adjacent tissue layers. G, OCT-A taken at the level of the superficial vascular plexus shows artifactual hyper-reflectivity within the tumors. H, En face structural OCT at the level of the intermediate vascular plexus highlights the morphology of the smaller tumor with thin linear extensions. The superior extension crosses the foveal plane, and can be seen in panel D. I-I’, Magnified color images of the grouped CHRPE lesions and corresponding SD-OCT showing typical findings of CHRPE.

Figure 3.

Multimodal imaging of Case 3. A, Widefield pseudocolor photography of both eyes showing a white intraretinal tumor involving the fovea and superior macula consisting of lobules with thin extensions in the right eye. Superonasally, there are multiple lobular areas of retinal whitening corresponding to lesions similar to those in the macula. In addition, there are numerous CHRPE lesions of different sizes seen in both eyes, predominately in the right eye. B, Widefield fundus autofluorescence of both eyes showing hypoautoflourescence corresponding to the areas of CHRPE lesions in both eyes. C, Midphase widefield fluorescein angiography of both eyes shows areas of blocked florescence corresponding to the areas of CHRPE lesions in both eyes. D, SD-OCT testing through the fovea of the right eye show multiple temporal homogenous, hyper-reflective lobular lesions residing in the INL compressing the adjacent outer retinal and inner retinal layers, including the RPE. E, SD-OCT testing through the lesion at the superior macula of the right eye shows a homogenous, hyper-reflective INL mass lesion compressing the adjacent outer retinal and inner retinal layers. F, Higher magnification SD-OCT line scans through the lesion shown in panel D (green bar) and E, (orange bar) show the tumor clearly located within the INL and causing varying degrees of compression to the adjacent tissue layers.

Figure 4.

Multimodal imaging of Case 4. A-B, Color fundus photo of the right and left eye shows subtle gray-white intraretinal reticular lesions composed of linear extensions criss-crossing the posterior pole. C-D, En Face structural OCT highlights the web-like morphology, and accompanying OCT-A deep retinal slab demonstrates absence of the foveal avascular zone and avascularity of the INL lesions. E-F, SD-OCT shows the tumors localize and extend throughout the INL. Note the absence of a normal foveal depression and central preservation of inner retinal layers. G-H, Combination fluorescein and indocyanine green angiography are unremarkable except for the reduced size of the foveal avascular zones. I-J, The tumors are silent on fundus autofluorescence and without associated RPE lesions.