Proposing a Neurotropic Etiology for Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Chorioretinitis

Abstract

PurposeTo reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection.MethodsNarrative review.ResultsLiterature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch’s membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model.ConclusionsThe neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC.

Atypical case of acute posterior multifocal placoid pigment epitheliopathy with intraretinal fluid

“…APMPPE is a rare inflammatory chorioretinopathy of unclear cause, which mainly affects young adults. Although its physiopathology is unclear, recent studies report that ischaemia occurring in the choriocapillaris results in hypoperfusion of the RPE and photoreceptors and consequent atrophy of the outer retinal layers 8. The case we described consisted of a male patient in his 20s with initial complaints of sudden unilateral vision loss.…”

Atypical case of acute posterior multifocal placoid pigment epitheliopathy with intraretinal fluid

“…APMPPE is a rare inflammatory chorioretinopathy of unclear cause, which mainly affects young adults. Although its physiopathology is unclear, recent studies report that ischaemia occurring in the choriocapillaris results in hypoperfusion of the RPE and photoreceptors and consequent atrophy of the outer retinal layers 8. The case we described consisted of a male patient in his 20s with initial complaints of sudden unilateral vision loss.…”

Refractory acute retinal necrosis presenting as peripapillary choroiditis – A diagnostic and therapeutic challenge

“…Such lesions have been noted in cases of acute posterior multifocal placoid pigment epitheliopathy proposing a neurotrophic and viral etiology. [ 7 ] This can also be confused with recently described angular sign of Henle’s hyper-reflectivity. [ 8 ]…”

Sequential multimodal imaging of varicella-zoster virus-associated acute retinal necrosis: Insights supporting a neurotropic hypothesis

“…Similar undulations which increased in number and amplitude in the days preceding areas of vertical outer nuclear layer hyperreflectivity in the sequential eye involvement of a case of relentless placoid chorioretinitis have been reported. 23 The spoke-like arrangement of the inner retinal folds around the fovea (Figure 2A) appears perpendicular to the arcuate anatomical trajectory of the ganglion cell axons that form the retinal nerve fibre layer (RNFL). We hypothesise a contractile force within this layer may account for the undulations potentially due to a disruption in axoplasmic flow.…”

“…While no histological confirmation of their aetiology currently exists, we hypothesisedbased on their anatomical orientationthat both continuous and beaded VHRS, including those aligned with the Henle fibre layer, may represent structural consequences of viral propagation along photoreceptor axons and/or Müller cell processes. It has previously been hypothesised that the beaded appearance may represent the formation of axonal spheroids, 23 secondary to disrupted axoplasmic flow, 26 which can occur as a consequence of neuronal viral infection. 27 The occurrence of serous detachments in ARN has also been previously observed.…”

Atypical case of acute posterior multifocal placoid pigment epitheliopathy with intraretinal fluid

“…APMPPE is a rare inflammatory chorioretinopathy of unclear cause, which mainly affects young adults. Although its physiopathology is unclear, recent studies report that ischaemia occurring in the choriocapillaris results in hypoperfusion of the RPE and photoreceptors and consequent atrophy of the outer retinal layers 8. The case we described consisted of a male patient in his 20s with initial complaints of sudden unilateral vision loss.…”

Refractory acute retinal necrosis presenting as peripapillary choroiditis – A diagnostic and therapeutic challenge

“…Such lesions have been noted in cases of acute posterior multifocal placoid pigment epitheliopathy proposing a neurotrophic and viral etiology. [ 7 ] This can also be confused with recently described angular sign of Henle’s hyper-reflectivity. [ 8 ]…”

Sequential multimodal imaging of varicella-zoster virus-associated acute retinal necrosis: Insights supporting a neurotropic hypothesis

“…Similar undulations which increased in number and amplitude in the days preceding areas of vertical outer nuclear layer hyperreflectivity in the sequential eye involvement of a case of relentless placoid chorioretinitis have been reported. 23 The spoke-like arrangement of the inner retinal folds around the fovea (Figure 2A) appears perpendicular to the arcuate anatomical trajectory of the ganglion cell axons that form the retinal nerve fibre layer (RNFL). We hypothesise a contractile force within this layer may account for the undulations potentially due to a disruption in axoplasmic flow.…”

“…While no histological confirmation of their aetiology currently exists, we hypothesisedbased on their anatomical orientationthat both continuous and beaded VHRS, including those aligned with the Henle fibre layer, may represent structural consequences of viral propagation along photoreceptor axons and/or Müller cell processes. It has previously been hypothesised that the beaded appearance may represent the formation of axonal spheroids, 23 secondary to disrupted axoplasmic flow, 26 which can occur as a consequence of neuronal viral infection. 27 The occurrence of serous detachments in ARN has also been previously observed.…”

Atypical case of acute posterior multifocal placoid pigment epitheliopathy with intraretinal fluid

“…APMPPE is a rare inflammatory chorioretinopathy of unclear cause, which mainly affects young adults. Although its physiopathology is unclear, recent studies report that ischaemia occurring in the choriocapillaris results in hypoperfusion of the RPE and photoreceptors and consequent atrophy of the outer retinal layers 8. The case we described consisted of a male patient in his 20s with initial complaints of sudden unilateral vision loss.…”

Refractory acute retinal necrosis presenting as peripapillary choroiditis – A diagnostic and therapeutic challenge

“…Such lesions have been noted in cases of acute posterior multifocal placoid pigment epitheliopathy proposing a neurotrophic and viral etiology. [ 7 ] This can also be confused with recently described angular sign of Henle’s hyper-reflectivity. [ 8 ]…”

Sequential multimodal imaging of varicella-zoster virus-associated acute retinal necrosis: Insights supporting a neurotropic hypothesis

“…Similar undulations which increased in number and amplitude in the days preceding areas of vertical outer nuclear layer hyperreflectivity in the sequential eye involvement of a case of relentless placoid chorioretinitis have been reported. 23 The spoke-like arrangement of the inner retinal folds around the fovea (Figure 2A) appears perpendicular to the arcuate anatomical trajectory of the ganglion cell axons that form the retinal nerve fibre layer (RNFL). We hypothesise a contractile force within this layer may account for the undulations potentially due to a disruption in axoplasmic flow.…”

“…While no histological confirmation of their aetiology currently exists, we hypothesisedbased on their anatomical orientationthat both continuous and beaded VHRS, including those aligned with the Henle fibre layer, may represent structural consequences of viral propagation along photoreceptor axons and/or Müller cell processes. It has previously been hypothesised that the beaded appearance may represent the formation of axonal spheroids, 23 secondary to disrupted axoplasmic flow, 26 which can occur as a consequence of neuronal viral infection. 27 The occurrence of serous detachments in ARN has also been previously observed.…”