In this study, we describe FVL as a specific morphological finding on structural SD-OCT and discuss its differential diagnosis in a case series of 10 eyes of 10 patients.

The study findings revealed that FVL could be identified through SD-OCT in various settings. FVL was not only associated with tractional disorders of the vitreoretinal interface or accompanying fluid resorption but also in the context of inflammation, macular telangiectasia, AMD, diabetic retinopathy, and scarring. No FVL-specific pattern, isolated from broader morphological elements or the clinical context, was found to characterize any of those conditions.

Analyzis of those specific cases, in their proper clinical context, enables us to describe various conditions in which FVL may appear.

In their landmark study of hyperreflective stress lines and macular holes, Scharf et al. described FVL as an early OCT marker for FTMH development. [2] They retrieved FVL in 6 over 12 eyes (50%) that underwent OCT before the development of FTMH and, post-surgically, in 26 over 51 eyes (51%) in which pars plana vitrectomy was performed with anatomical success defined as closure. They also analyzed 88 eyes with lamellar macular holes and noticed FVL in 22 (25%). The authors postulated that in this context, FVL might be a sign of central foveal dehiscence owing to disruption of the Muller cell cone. The common denominator in all cohorts may be the presence of a naturally existing cleavage plane or seam in the central fovea that is either being pulled apart or pulled together in these three clinical situations. [2]

Whatever the etiology of macular edema, its resorption may be accompanied and followed by FVL.

Two mechanisms may explain the appearance of FVL in this setting: on the one hand, the deposition of lipidic and proteinaceous material similar to hard exudates, favored by the predisposing existence of relatively decreased resistance at the very center of the fovea; on the other hand, the activation of cellular inflammatory processes that include activation of the local microglia and recruitment of macrophages. [8]

Hasegawa et al. reviewed 59 eyes with resolved macular edema related to branch retinal vein occlusion and found FVL in 21 (36%). [1] They noticed that FVL were associated with a disrupted external limiting membrane before the resolution of macular edema and, after the resolution of macular edema, with an interruption of the ellipsoid zone, therefore making FVL a marker of damage to the photoreceptors.

To our knowledge, FVL has not yet been systematically studied in diabetic macular edema, the most common cause of macular edema. However, subretinal fluid and foveal plaque [9] are well-known markers of chronicity and severity in diabetic macular edema. FVL might be closely related to the pathophysiology of those conditions. In retinal vein occlusion, for instance, FVL has been described as a track of the passage through which intraretinal fluid within the cystoid spaces flows into the subretinal space. [9]

Besides just described OCT observable phenomena related to the resorption of intraretinal fluid, inflammatory mechanisms can result in FVL.

Bolz et al. described hyper-reflective foci in diabetic retinopathy. Those are punctate lesions scattered throughout the retina. [10] Whatever their exact nature, still controversial but intimately associated with inflammation (activated microglial cells, degenerated photoreceptor cells, anteriorly migrated retinal pigment epithelium (RPE), vascular components), those should be differentiated from hard exudates. [11] However, in the fovea, they could combine with those later and adopt different patterns [12], including vertically linear, to display FVL on OCT.

MacTel 2 can be divided into non-proliferative and proliferative stages, with neovascularization in the advanced disease. [13] In the non-proliferative stage of MacTel 2, a hyperreflective middle retinal layer from capillary leakage can be noted on imaging. Findings of irregular fovea and hyperreflective RPE clumps are common in the advanced stage of MacTel 2 with poor vision.Combined with inner and outer retinal hyporeflective cavities accentuating the contrast, retinal crystals seen as hyperreflective spots in the superficial layers of the retina and outward turning of the inner retinal layers, those can result in the appearance of FVL, in possible further association with the hyperreflective elements related to the neovascular complication. [14]

Hyperreflective dots have been described in several forms of intraocular inflammation. We have already mentioned their common presence in diabetic macular edema. They have also been observed in infectious[15] and non-infectious uveitis[16], after uncomplicated cataract surgery[17], in neurological conditions such as multiple sclerosis [18] as a marker of inflammation in retinitis pigmentosa[19] as well as in von Hippel-Lindau disease[20] or with Covid-19. [20] It should be noticed that hyperreflectivity displayed on averaged volumetric scans can exhibit a linear pattern, appearing as FVL. Cohen’s team hypothesized that FVL could correspond to a previously unrecognized reaction to various photoreceptor, Müller cell, and/or RPE damage [4, 6].

Deep hyperreflective dots were described early in OCT studies of age-related macular degeneration. [21]

Hyperreflective dots were generally believed to represent anteriorly migrating RPE cells and possible disaggregated photoreceptors. [22] It is currently admitted that those foci may also represent microglia migrating from the inner to the outer retinal layers engorged by lipid droplets or cholesterol. [23] Balaratnasingam et al., studying the RPE behavior in AMD by multimodal ex vivo imaging including SD-OCT and high-resolution histology, defined several histology-OCT correlations in D-PED: small and large hyperreflective intraretinal foci represent fully pigmented and nucleated RPE cells that migrate anteriorly either singly or in groups; hyperreflectivity internal to the RPE-BL band resembling vitelliform lesions represent subretinal plaques of RPE organelles mixed with outer segment debris and sometimes also RPE cell bodies; punctate hyperreflective foci in the D-PED interior represent refractile material among the lipid pools. Microglial activation is mainly related to neovascular disease. [23] Those hyperreflective structures have variable morphological characteristics such as size, migration, and clumping. They can eventually adopt a linear pattern. [23]

Subretinal hyper-reflective material (SHRM) is a morphological feature seen on OCT as hyper-reflective material located external to the retina and internal to the RPE. SHRM may be attributed to a heterogeneous group of lesions, including gray exudative fluid, hemorrhage, vitelliform material, or type 2 CNV. [24] It may represent many elements, from neovascular tissue to fibrin, blood, and lipids.

Hyperreflective dots located above the external limiting membrane, often co-localized with a drusenoid pigment epithelial detachment, can also represent a nascent type 3 macular neovascularization, often characterized by vertical growth. [25]

Fibrosis, appearing as a hyperreflective structure, is the end-stage complication of many destructive chorioretinal pathologic processes, AMD being the most frequent. Alone or in combination with other disease markers, it can adopt a vertical pattern, displaying the features of FVL on OCT [26].

There are obvious limitations to our study. Its observational design, retrospective nature, and relatively small sample size may limit the findings' generalizability. We cannot pretend to dress an exhaustive list of etiologies for FVL but enhance awareness of these unique features revealed by SD-OCT. Further research with larger cohorts is warranted to validate these observations, establish the prevalence of FVL in different etiologies, and describe its long-term behavior and prognostic significance. Histologic studies would be required to determine the cellular correlation of this reflectivity pattern in selected conditions. It is essential to acknowledge that patients can present with FVL and that recognizing it, with the help of other orienting clues, is capital in determining the correct diagnoses and offering the most accurate treatment.

In conclusion, in this study, we describe and identify FVL as a specific morphological finding on SD-OCT in patients with various ophthalmic conditions. The comprehensive discussion of the differential diagnoses associated with FVL aids ophthalmologists in making accurate diagnoses and implementing appropriate treatment strategies. Further studies with larger sample sizes are necessary to evaluate more etiologies for FVL and the clinical implication of this yet underestimated phenomenon.

Examples of FVL as revealed by SD-OCT in different clinical settings: A: Inflammation; B: Mechanical; C: Resorption of fluids;D: Macular telangiectasia; E: AMD; F: Diabetic retinopathy; G: Scar