Multimodal imaging including optical coherence tomography angiography of benign familial fleck retina.

A 44-year-old woman presented with complaints of pain in the right eye (RE). Fundus examination revealed disc edema in the RE along with retinal flecks sparing the macula in both eyes (BE). Fundus autofluorescence demonstrated a symmetrical pattern of white flecks in BE. Spectral-domain optical coherence tomography (SD-OCT) revealed the lesions at the level of retinal pigment epithelium with impingement onto the outer retina. SD-OCT angiography through the flecks revealed hyperreflective lesions at the level of avascular retina. RE B-scan revealed a T-sign. Based on these findings, she was diagnosed with BE benign familial fleck retina (BFFR) with RE posterior scleritis. We describe the multimodal imaging features in a middle-aged patient with BFFR and provide an insight into the probable pathogenesis. Copyright:

Introduction

Flecked retina syndromes incorporate a cluster of diseases that include Stargardt's macular dystrophy, fundus albipunctatus, retinitis punctata albescens, Leber congenital amaurosis, pseudoxanthoma elasticum, Kjellin's syndrome, Alport's syndrome, Sjögren–Larsson syndrome, Bietti's crystalline dystrophy, oxalosis, and cystinosis.[123] Benign familial fleck retina (BFFR) is an autosomal recessive inherited disorder associated with a distinctive retinal appearance and no apparent visual or electrophysiological deficits.[4] Ocular fundus is characterized by the presence of retinal flecks, extending till far periphery and sparing the macula. Affected individuals are asymptomatic and hence the disease often goes unreported.[5] We report a case of a middle-aged patient who presented with posterior scleritis, and BFFR was diagnosed as an incidental finding.

Case Report

A 44-year-old woman presented with complaints of dull aching pain in the right eye (RE) for 5 days. Her best-corrected visual acuity was 20/20 in both eyes (BE). There was no history of night blindness. She had no known systemic illnesses. Anterior segment examination in BE was unremarkable. Fundus examination of BE revealed multiple yellow-white fleck-like lesions arranged in a concentric pattern sparing only the macular region. The centrally appearing flecks were small and dot like, especially near the optic disc and papillomacular region, and were appearing linear, temporal to the macula. The peripheral flecks were shaped either pisiform or oblongated. In addition, there was disc edema in the RE [Figure 1a and b]. Fundus autofluorescence (FAF) revealed hyperautofluorescence of the fleck lesions [Figure 1c and d]. Spectral-domain optical coherence tomography (SD-OCT) of BE revealed a normal foveal contour. In addition, there was presence of intraretinal cystoid spaces nasal to the fovea at the papillomacular region along with disc edema in the RE. SD-OCT line scan through the affected outer retina revealed multiple small-rounded as well as conical hyperreflective lesions seen at the level of the retinal pigment epithelium (RPE) and impinging on the photoreceptor layer in BE corresponding to the flecks. The enhanced depth imaging OCT in BE revealed normal subfoveal choroidal thickness [Figure 2a-f].

Figure 1

(a and b) Color fundus imaging of both eyes showing multiple yellow-white flecks arranged in a concentric pattern located extensively and sparing only the macular region. Additionally, right eye optic disc shows blurring of its nasal margins when compared to the left eye. (c and d) Fundus autofluorescence of both eyes showing hyperautofluorescence of the flecks

Figure 2

(a and b) Enhanced depth imaging of spectral-domain optical coherence tomography line scan through the macula right eye and left eye, respectively, showing a normal foveal contour and normal outer retina under the macula. Note the peripapillary intraretinal cystoid spaces in the right eye. The subfoveal choroidal thickness in the right eye is 294 μm and in the left eye is 261 μm. (c and d) Spectral-domain optical coherence tomography line scan through a region inferior to the fovea in the right eye and left eye, respectively, showing multiple conical hyperreflective lesions at the level of the retinal pigment epithelium and impinging on the photoreceptor layer suggestive of flecks (arrow). (e and f) Spectral-domain optical coherence tomography line scan through the optic disc of the right eye showing edema in the right eye along with peripapillary intraretinal cystoid spaces and left eye showing a normal optic disc

SD-OCT angiography (SD-OCTA) imaging of BE revealed hyperreflective interspersed linear pisiform lesions at the outer retina just above the RPE in BE, with a normal underlying choriocapillaris [Figure 3a-f]. RE B-scan was done which showed disc elevation and the presence of T-sign, thereby confirming the diagnosis of posterior scleritis [Figure 4a]. Following a systemic workup, she was initiated on oral steroid medications.

Figure 3

(a and b) Spectral-domain optical coherence tomography angiography 3 mm × 3 mm macular cube of the right eye and left eye, respectively, showing an avascular hyporeflective outer retina. (c and d) Spectral-domain optical coherence tomography angiography 3 mm × 3 mm cube through the region of flecks showing hyperreflectivity of the lesions at the avascular outer retina. (e and f) Spectral-domain optical coherence tomography angiography 3 mm × 3 mm cube through the region of flecks showing a normal choriocapillaris

Figure 4

(a) B-scan of the right eye revealing retinochoroidal scleral thickening (line) with the presence of shallow episcleral fluid and a T-sign (arrow). (b) Full-field electroretinogram of both eyes showing normal scotopic and photopic responses

An electroretinogram (ERG) was obtained which showed normal rod and cone responses in BE [Figure 4b].

Discussion

The term fleck retina was introduced by Krill and Klien to describe fundus conditions characterized by multiple yellow-white lesions of various sizes and configurations without vascular or optic nerve abnormalities.[5] BFFR was initially described by Aish and Dajani as a separate entity.[6] The diagnosis of BFFR is usually based on the characteristic fundus findings along with the patient being asymptomatic and having good vision. Multimodal imaging (MMI) helps to confirm the diagnosis. Benign fleck is a disease which is localized to the RPE layer and characterized by multiple hyaline excrescences that give it a characteristic yellowish-white fleck-like appearance.[67] These flecks are known to appear in various sizes and shapes as well as sparing the macula. Younger patients have been shown to have immature flecks when judged by the size, density, concentration, and shape of the flecks.[6] Our patient, however, had a more posterior distribution of the flecks with the ones nasal to the macula being dot like and temporal ones being more linear. Hyperautofluorescent nature of these flecks due to deposition of lipofuscin on FAF has been well documented in the literature with our findings similar to the ones reported.[7] Fluorescein angiography is shown to reveal irregular hyperfluorescence not corresponding to the distribution of the flecks suggestive of a diffuse RPE abnormality.[8]

OCT studies of the flecks have shown it to be irregularities as well as thickening of the RPE.[5] Neriyanuri et al., in their series of four patients with BFFR, described two patients who had undergone swept-source OCT to have the lesions not only limited to the RPE but also extending to the photoreceptor layer and external limiting membrane (ELM).[7] Our patient also had similar linear and conical appearing hyperreflective lesions seen at the level of RPE with extension beyond the ELM into the outer retina in BE on SD-OCT, similar to subretinal drusenoid deposits seen in age-related macular degeneration. In addition, in the RE, there was also presence of intraretinal cystoid spaces adjacent to the edematous optic disc. EDI on SD-OCT showed the choroidal thickness and vasculature to be within normal limits without attenuation of the choriocapillaris. An SD-OCTA 3 mm × 3 mm slab through the region of the flecks revealed the lesions to have a high flow signal in an otherwise hyporeflective avascular retina. There was no obvious reduction in the choriocapillaris perfusion in our case which designates this entity to be primarily a disorder of the RPE. Garcia et al. in their report of a 27-year-old woman with BFFR described the SD-OCTA findings of a normal choroidal microvasculature.[3] However, the flecks were limited to the RPE with no outer retinal involvement on OCT. Hence, the hyperreflective lesions seen in the avascular retina of our middle-aged patient may be attributed to the outer retinal projections of the flecks. This finding is different from the previous OCTA description.[3]

ERG in patients with BFFR is usually normal as seen in our case. However, other reports have shown reduced dark-adapted ERG as well as light-adapted multifocal ERG defects.[279] Neriyaneuri et al. postulated that extension of the flecks from the RPE to the photoreceptor layer can result in some functional loss like delayed dark adaptation.[7]

BFFR is usually underreported as the patient remains asymptomatic with good vision. However, our case presented with complaints of ocular pain and had associated posterior scleritis.

In summary, we describe the MMI features of BFFR. Although benign, flecks are primarily abnormality of the RPE as SD-OCT and SD-OCTA reveal outer retinal involvement, which may denote the natural evolution of flecks over time in this middle-aged woman.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.