Multicolor Imaging for the Detection of Inner Nuclear Layer Microcysts Secondary to Optic Nerve Atrophy

Inner nuclear layer (INL) microcysts have been reported in diseases affecting the optic nerve. The new ocular imaging techniques detect minimal structural alterations at the macula and correlate these findings to different etiologies with less invasive procedures. The relationship between ganglion cells distribution at the macula and chiasmal nerve fibers enables the diagnosis and location of neurological lesions by new generation optical coherence tomography (SD-OCT) imaging devices. We report the evaluation of a patient with a history of optic nerve trauma and macular INL microcysts with multicolor SD-OCT technology that shows a pattern that localizes the lesion to the left optic nerve and proximal segment of the chiasm.

Photo Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Multicolor Imaging for the Detection of Inner Nuclear Layer Microcysts Secondary to Optic Nerve Atrophy Belen Jimenez-Rolando, MD, Ester Carreño, MD, PhD, Miguel A. Alonso-Peralta, MD, Maria I. Lopez-Molina, MD, Guillermo Fernandez-Sanz, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 05/04/2022 FIG. 1. T2 cranial MRI showing spared occipital lobes (A). Patient’s right eye 30-2 visual field demonstrates temporal hemianopsia (B). Left eye visual field could not be performed because patient’s visual acuity was no light perception. Abstract: Inner nuclear layer (INL) microcysts have been reported in diseases affecting the optic nerve. The new ocular imaging techniques detect minimal structural alterations at the macula and correlate these findings to different etiologies with less invasive procedures. The relationship between ganglion cells distribution at the macula and chiasmal nerve fibers enables the diagnosis and location of neurological lesions by new generation optical coherence tomography (SDOCT) imaging devices. We report the evaluation of a patient with a history of optic nerve trauma and macular INL microcysts with multicolor SD-OCT technology that shows a pattern that localizes the lesion to the left optic nerve and proximal segment of the chiasm. Journal of Neuro-Ophthalmology 2021;41:e107–110 doi: 10.1097/WNO.0000000000000976 © 2020 by North American Neuro-Ophthalmology Society A 33-year-old man was admitted after severe head trauma. Computed tomography (CT) showed multiple cranial fractures involving the posterior orbital vortex and the optic foramen of the left eye preserving the optic nerve size Department of Ophthalmology (BJ-R, EC, MAA-P), Fundacion Jimenez-Diaz University Hospital, Madrid, Spain; Centro Oftalmologico Integrado (MIL-M), Madrid, Spain; and Department of Ophthalmology (GF-S), Clínica Universidad de Navarra, Madrid, Spain. The authors report no conflicts of interest. Address correspondence to Belen Jimenez-Rolando, MD, Department of Ophthalmology, Fundacion Jimenez-Diaz, Madrid 28040, Spain; E-mail: [e-mail] Jimenez-Rolando et al: J Neuro-Ophthalmol 2021; 41: e107-e110 and morphology. Cranial MRI showed no lesions in occipital lobes (Fig. 1A). Two weeks after trauma, the patient complained of complete visual loss in his left eye and presented a relative pupillary afferent defect. Fundus examination disclosed a pale left optic disc compatible with optic nerve atrophy. Throughout a follow-up for 6 months, the patient’s best-corrected visual acuity was 20/20 in the right eye and no light perception in the left eye, persisted relative afferent pupillary defect in the left eye and the right eye visual field showed a temporal hemianopsia (Fig. 1B). In a follow-up 5 years later, macular optical coherence tomography (OCT) (Heidelberg Engineering, Heidelberg, Germany) revealed microcysts in the inner nuclear layer (INL) at the parafovea with concentric distribution in the nasal hemimacula in the right eye and surrounding the whole fovea in the left eye (Fig. 2A). OCT multicolor images displayed a hyporeflective shadow along the nasal hemimacula respecting the vertical meridian in the right eye and along the whole parafovea in the left eye better defined in the blue and green reflectance images (Figs. 3 and 4). Layer segmentation analysis showed the same vertical pattern in the INL, inner plexiform layer (IPL), and ganglion cell layer (GCL) in the right eye (Fig. 2B). Fundus autofluorescence was normal. After considering the history of severe optic nerve trauma and correlating it with a neurological pattern of the diverse images, the diagnosis of INL microcysts secondary to optic nerve and anterior chiasmal segment atrophy was established. e107 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay FIG. 2. A. Spectral domain OCT B-scan revealing the presence of multiple INL microcysts (arrowheads) along the nasal parafoveal and perifoveal area in the right eye (image on the left side) and nasal and temporal left eye parafovea and perifovea (image on the right side). B. Representation of intraretinal layer segmentation images displaying hemimacula nasal defects respecting the vertical meridian in the INL, IPL, and GCL in the right eye. GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; OCT, Optical coherence tomography. INTERPRETATION OF THE FINDINGS The association of INL microcysts with optic nerve atrophy, chiasmal lesions, or multiple sclerosis is largely established (1,2). SD-OCT allows its noninvasive detection and detailed assessment, especially with the combination of the new multicolor laser imaging, which topographically highlights 3 different depths of the retina (3). When macular cysts are detected in a patient, a differential diagnosis with cystoid macular edema (CME) is mandatory. Fluorescence angiography (FA) is an invasive technique that usually shows macular leakage when CME is present. In cases without leakage, it is assumed that the CME is composed of optically empty spaces named cysts or cavitation (4). Here, we report the multimodal evaluation of INL microcysts secondary to optic nerve trauma. FA was discarded in our case for considering it an invasive test not required since the shape and distribution of the microcysts established the diagnosis. The presence of microcysts in the INL related to optic nerve atrophy and chiasmal lesions is known since 1963 when Van Buren described them in primate histological samples in which the chiasm was sectioned 20 months earlier (1). Trans-synaptic retrograde degeneration was proposed as the main mechanism but later on some authors suggested that other mechanisms must be involved because they are not present in every patient with optic nerve damage history (5). Anatomical reasons are behind it because more than 50% of ganglion cells are located in the macula, most of them related to the parvocellular system. FIG. 3. A well-defined hyporeflective shadow throughout the nasal hemimacula in the right eye in a multicolor (A), blue reflectance (B), green reflectance (C), and infrared reflectance (D) display. e108 Jimenez-Rolando et al: J Neuro-Ophthalmol 2021; 41: e107-e110 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay FIG. 4. Multicolor imaging showing a hyporeflective shadow covering the hole macula with shallow intensity because of poor fixation. Multicolor (A), blue reflectance (B), green reflectance (C), and infrared reflectance (D). Parvocellular ganglion cells are connected individually to bipolar cells along 2 mm in the parafovea and through the nerve fibers, they get to the lateral geniculate body where parvocellular fibers are predominant comparing to magnocellular fibers (6). In addition, the macular area and specially the parafoveal region have stronger vitreous attachment that after GCL and INL atrophy may keep vertical forces that prevent the area to collapse and create empty cystic spaces (5). When evaluated by SD-OCT, INL microcysts are small hyporeflective multiple spaces with verticalized shape circumferentially scattered at the parafoveal region with an annular or “C” distribution pattern. Small hyperreflective dots in the INL have also been described (5,7). This patient showed multiple small microcysts ranging from 20 to 60–100 mm with verticalized shape present at the parafoveal region of nasal macula with an inverted “C” distribution in the right eye and along the whole parafovea in the left eye (Fig. 2A, C). GCL atrophy has also been proved in histological studies and can be now detected by layer segmentation analysis. Multicolor laser imaging achieved with OCT uses 3 different lasers: blue (486 nm), green (518 nm), and infrared (815 nm) to explore diverse depths of the retina and generating an integrated image of it. The blue reflectance image scans better the inner layers of the retina like retinal nerve fiber layers and ganglion cells (3). Multicolor different imaging options showed in the patient a well-defined hyporeflective shadow in the nasal hemimacula with a clear respect of the vertical meridian reminding neuro-ophthalmological patterns. The blue reflectance image provided a better detailed visualization of the lesion. GCL, IPL, and INL segmentation analysis showed separately signs of atrophy in the nasal parafovea overlapping the presence of microcysts (Fig. 2B). Several studies support the topographical association between the GCL at the macula and the chiasm classically established by typical visual field patterns but OCT GCL analysis has already Jimenez-Rolando et al: J Neuro-Ophthalmol 2021; 41: e107-e110 proven to be more sensitive than visual field (8–11). In this regard, a clear correlation between the INL microcyst distribution and the visual field defect was seen in our case. The OCT and multicolor images together with the early CT report defined that the starting point of the neurological damage was placed at the anterior segment of the chiasm affecting both the left optic nerve and the nasal fibers in the right eye. Alternatively, a left retrochiasmal visual pathway damaged cannot be discarded because topographically related changes in the left eye related to this may be masked by the left-sided optic neuropathy. Although the presence of INL microcysts secondary to optic nerve atrophy is not common, its accurate assessment with different OCT devices is essential to confirm or rule out neurological damage and spares the use of invasive tests such as FA. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: B. Jimenez-Rolando and E. Carreño; b. Acquisition of data: B. Jimenez-Rolando, M. I. LopezMolina, and G. Fernandez-Sanz; c. Analysis and interpretation of data: B. Jimenez-Rolando, M. A. Alonso-Peralta, and M. I. LopezMolina. Category 2: a. Drafting the manuscript: B. JimenezRolando, E. Carreño, and G. Fernandez-Sanz; b. Revising it for intellectual content: B. Jimenez-Rolando, E. Carreño, M. A. AlonsoPeralta, M. I. Lopez-Molina, and G. Fernandez-Sanz. Category 3: a. Final approval of the completed manuscript: B. Jimenez-Rolando, E. Carreño, M. A. Alonso-Peralta, M. I. Lopez-Molina, and G. Fernandez-Sanz. REFERENCES 1. Pitzer Gills J, Wadsworth J AC. 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Macular ganglion cell-inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian. Graefes Arch Clinexpophthalmol. 2014;252:1501–1507. Jimenez-Rolando et al: J Neuro-Ophthalmol 2021; 41: e107-e110 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.