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Retinal Physician

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UVEITIS CORNER: Interpreting Optical Coherence Tomography Findings of Retinal Whitening

The finding occurs in infectious, inflammatory, and ischemic retinal disease.

By: Jacob Fondriest, MD, Veena Raiji, MD
Retinal Physician April 1, 2023 Vol 20, Issue April 2023 Page(s): 40-45

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Retinal whitening occurs secondary to a multitude of causes — ischemic, infectious, inflammatory, traumatic, neoplastic, therapeutic, and idiopathic. A patient’s history, demographics, and comorbid medical conditions help inform the diagnosis. Optical coherence tomography (OCT) is a key component of making a diagnosis and prognostication. This article reviews intralesional OCT findings of various etiologies of retinal whitening, using the proposed lexicon for retinal layers from the 2014 International Nomenclature for Optical Coherence Tomography Panel.1 This review will include several causes of retinal whitening, with an emphasis on clinically pertinent infectious, inflammatory, and ischemic etiologies.

RETINAL ARTERIAL OCCLUSION

Retinal arterial circulation perfuses the inner retina. The outer plexiform layer (OPL) represents a “watershed zone” between retinal and choroidal circulation. Acute retinal arterial occlusions cause hyperreflectivity and thickening of the inner retinal layers (Figure 1). There may also be a loss of identifiable retinal layers, intraretinal fluid, and subretinal fluid.2 In chronic retinal arterial occlusions, thinning of the inner retinal layers, as well as disappearance of the ellipsoid zone (EZ), are possible (Figure 2).3

Figure 1. Acute central retinal artery occlusion with cilioretinal sparing (A). Optical coherence tomography (Heidelberg Spectralis) demonstrates thickening and hyperreflectivity from the nerve fiber layer to the inner nuclear layer.
Figure 1. Acute central retinal artery occlusion with cilioretinal sparing (A). Optical coherence tomography (Heidelberg Spectralis) demonstrates thickening and hyperreflectivity from the nerve fiber layer to the inner nuclear layer. There is preservation of retinal architecture in the area of cilioretinal sparing. Acute central retinal artery occlusion (B). Optical coherence tomography demonstrates diffuse hyperreflectivity and thickening of the inner retina. Vitreomacular adhesion is also noted.

COTTON-WOOL SPOT

Cotton-wool spots (CWS) occur from axoplasmic disruption in the retinal nerve fiber layer (RNFL) secondary to focal ischemia. They acutely present as a focal RNFL thickening and sometimes hyperreflectivity.4-6 Larger CWS may distort the adjacent retinal layers and shadow the outer retinal layers (Figure 3).7 Gomez et al showed that in patients with resolved CWS secondary to HIV, the retinal layers from the inner nuclear layer (INL) to the OPL become thin and that most of the thinning occurs in the ganglion cell layer; the outer nuclear layer (ONL) however may become thickened.6

Figure 2. Chronic central retinal artery occlusion. Optical coherence tomography (Heidelberg Spectralis) shows thinning of the inner retinal layers with preservation of the identifiable layers
Figure 2. Chronic central retinal artery occlusion. Optical coherence tomography (Heidelberg Spectralis) shows thinning of the inner retinal layers with preservation of the identifiable layers.
Figure 3. Acute and chronic cotton wool spot. Optical coherence tomography (Heidelberg Spectralis) demonstrates thickening of the retinal nerve fiber layer in the acute setting (A). One month later, there is decreasing thickness of the inner retinal layers (B). In some chronic lesions, outer nuclear layer thickening can be seen (not shown).
Figure 3. Acute and chronic cotton wool spot. Optical coherence tomography (Heidelberg Spectralis) demonstrates thickening of the retinal nerve fiber layer in the acute setting (A). One month later, there is decreasing thickness of the inner retinal layers (B). In some chronic lesions, outer nuclear layer thickening can be seen (not shown).

COMMOTIO RETINAE/BERLIN EDEMA

Commotio retinae, also called Berlin edema, is a traumatic retinopathy indicative of damage to the photoreceptors from blunt ocular trauma. In mild cases, there is hyperreflectivity of the EZ without edema, which resolves within days to weeks (Figure 4).8 In severe trauma, there can be acute loss of the EZ with thickening and hyperreflectivity of the overlying retinal layers. Cases of full-thickness retinal hyperreflectivity can progress to atrophic outer retinal layers with hyperreflective aggregates above the retinal pigment epithelium (RPE), with lasting vision impairment.9

PROGRESSIVE OUTER RETINAL NECROSIS

Forster et al in 1990 described progressive outer retinal necrosis (PORN) with a predominance of outer retinal necrosis sparing of the vasculature.10 In early PORN infection, OCT shows inner retinal hyperreflectivity, outer retinal hyporeflectivity, and total retinal thickening.11-15 Progressive outer retinal necrosis is believed to start in the outer retina and progress to involve the full retinal thickness. Margo and Friedman hypothesized that PORN may truly begin in the inner retina, contending that early PORN can resemble arterial occlusion on OCT.16 Intraretinal fluid and schisis can also be seen. Late findings show severe retinal thinning and loss of identifiable retinal layers.

Figure 4. Commotio retinae. There is mild ellipsoid zone hyperreflectivity without thickening in the area of whitening (arrows). In the bottom image (Heidelberg Spectralis), there is decreased reflectivity of the external limiting membrane and ellipsoid zone left of the leftward arrow. Vitreous hemorrhage is also noted.
Figure 4. Commotio retinae. There is mild ellipsoid zone hyperreflectivity without thickening in the area of whitening (arrows). In the bottom image (Heidelberg Spectralis), there is decreased reflectivity of the external limiting membrane and ellipsoid zone left of the leftward arrow. Vitreous hemorrhage is also noted.
Figure 5. Acute retinal necrosis. Fundus photo (A) shows initial presentation, and optical coherence tomography (B) shows the area 2 months later, after treatment. On optical coherence tomography (Heidelberg Spectralis) there is severe thinning and loss of identifiability of the outer retinal layers, as well as vitreopapillary adhesion.
Figure 5. Acute retinal necrosis. Fundus photo (A) shows initial presentation, and optical coherence tomography (B) shows the area 2 months later, after treatment. On optical coherence tomography (Heidelberg Spectralis) there is severe thinning and loss of identifiability of the outer retinal layers, as well as vitreopapillary adhesion.

ACUTE RETINAL NECROSIS

Early acute retinal necrosis (ARN) may start as mild hyperreflectivity and thickening in the inner plexiform layer.17 Over days to weeks, the hyperreflectivity and thickening extend to the entire inner retina and can progress to full-thickness retinitis.17-20 Prominent vitritis may limit image quality. Cystoid macular edema, epiretinal membranes, and serous and rhegmatogenous retinal detachments may occur. In the chronic setting, there can be hyporeflectivity, thinning, and loss of identifiability of the retinal layers (Figure 5).17

CYTOMEGALOVIRUS RETINITIS

A longitudinal study by Invernizzi et al in 2018 found 2 broad patterns in active retinitis.21 The first is full-thickness hyperreflectivity and thickening with RPE thickening and choriocapillaris changes; these retinas become thin and lose identifiability of retinal layers with time (Figure 6). The second is cavernous retinitis with inner retinal hyperreflectivity and empty space in the ONL; these are prone to retinal detachments.22 Epiretinal membranes, vitreomacular adhesions, vitreomacular traction, external limiting membrane abnormalities, and EZ zone abnormalities are nonspecific findings in cytomegalovirus retinitis.

Figure 6. Cytomegalovirus retinitis. Images (Heidelberg Spectralis) show full-thickness retinal thickening, hyperreflectivity, and loss of identifiable layers.
Figure 6. Cytomegalovirus retinitis. Images (Heidelberg Spectralis) show full-thickness retinal thickening, hyperreflectivity, and loss of identifiable layers.
Figure 7. Multiple evanescent white dot syndrome. On presentation, optical coherence tomography (Heidelberg Spectralis) shows broad ellipsoid zone and external limiting membrane hyporeflectivity in the area of whitening in the acute phase (A). Two months later, there is significant resuscitation of the normal ellipsoid zone (B). Three months after initial presentation, there is essentially complete recovery of the ellipsoid zone (C).
Figure 7. Multiple evanescent white dot syndrome. On presentation, optical coherence tomography (Heidelberg Spectralis) shows broad ellipsoid zone and external limiting membrane hyporeflectivity in the area of whitening in the acute phase (A). Two months later, there is significant resuscitation of the normal ellipsoid zone (B). Three months after initial presentation, there is essentially complete recovery of the ellipsoid zone (C).

MULTIPLE EVANESCENT WHITE DOT SYNDROME

In multiple evanescent white dot syndrome, the white dots will show patchy hyporeflectivity of the EZ (Figure 7). In recurrent cases, one can see thinning of the ONL.23 Nearly half of patients may have punctate hyperreflective change in the inner choroid on enhanced depth imaging OCT that may precede the EZ disruption.24 Small hyperreflective dots in the ONL can be noted on SD-OCT and are hypothesized to be lipofuscin or damaged photoreceptor debris translocated to the outer retina.25

ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY (APMPPE)

In acute posterior multifocal placoid pigment epitheliopathy, OCT shows hyperreflectivity which can extend from the OPL to the RPE and can have associated disappearance of the external limiting membrane and EZ (Figure 8). Over time, these changes may resolve, but permanent photoreceptor and RPE atrophy may ensue.26,27 Recovery of the EZ is correlated with improvement of visual acuity.27

MYELINATED NERVE FIBER LAYER

In a patient with myelinated nerve fiber layer, OCT will show dense nerve fiber layer hyperreflectivity in the area of retinal whitening (Figure 9). In severe cases, there can be compression of the adjacent inner retinal layers. These lesions do not change with time.28,29

INTRAOCULAR LYMPHOMA

Primary vitreoretinal lymphoma can present in any location, including intravitreal, preretinal, intraretinal, subretinal, and sub-RPE. Infiltrates are hyperreflective and can be focal or diffuse. Vitreous involvement and sub-RPE deposits are the most common, each independently seen in about two-thirds of cases.30 Serial OCT can be useful to monitor disease progression and response to treatment of these lesions.31

CHOROIDAL GRANULOMA

The differential diagnosis for choroidal granulomas can include sarcoidosis, tuberculosis, ocular toxocariasis, cat-scratch disease, focal scleral nodule, choroidal nevi, amelanotic melanoma, choroidal metastasis, and uveal lymphoma.32 They can be typically large homogenous hyporeflective lesions in the choroid, with a smooth dome-shaped change in curvature of the choroid, and can present with subretinal fluid.33-35 Enhanced depth imaging OCT is useful in detecting the change in the lesion over time, but it is not useful in differentiating the etiology of the lesion. Enhanced depth imaging OCT can help evaluate for a focal scleral nodule, which involves the sclera rather than the choroid.32

Figure 8. Acute posterior multifocal placoid pigment epitheliopathy. Upon initial presentation, there are discrete lesions of hyperreflectivity from the OPL to RPE and corresponding loss of identifiable external limiting membrane and ellipsoid zone layers (A)
Figure 8. Acute posterior multifocal placoid pigment epitheliopathy. Upon initial presentation, there are discrete lesions of hyperreflectivity from the OPL to RPE and corresponding loss of identifiable external limiting membrane and ellipsoid zone layers (A). There is partial foveal sparing. Imaging (Zeiss Cirrus HD-OCT model 5000) 8.5 weeks later shows noted resolution of the prior changes, with some persistent patchy ellipsoid zone hyporeflectivity (B).
Figure 9. Myelinated nerve fiber layer. Optical coherence tomography (Zeiss Cirrus HD-OCT model 5000) demonstrates focal hyperreflectivity with subtle thickening of the nerve fiber layer in the area of retinal whitening.
Figure 9. Myelinated nerve fiber layer. Optical coherence tomography (Zeiss Cirrus HD-OCT model 5000) demonstrates focal hyperreflectivity with subtle thickening of the nerve fiber layer in the area of retinal whitening.

CONCLUSION

The etiologies of retinal whitening are many and have distinct OCT presentations. Risk factors, clinical history, and multimodal imaging including OCT are instrumental in making the diagnosis and prognosis. RP

Jacob Fondriest, MD, is an ophthalmology resident at Rush University in Chicago, Illinois. He reports no related financial disclosures. Veena Raiji, MD, is the director of the uveitis and inflammatory disease section in the department of ophthalmology at Rush University Medical Center. She reports no related financial disclosures. Reach Dr. Fondriest at jacob_fondriest@rush.edu.

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