Multizonal outer retinopathy and retinal pigment epitheliopathy (MORR) with a chronologically divergent presentation- a case report

Abstract

Purpose: Acute zonal occult outer retinopathy (AZOOR) is a rare inflammatory disease of the outer retina, often presented with subtle early findings. A specific subtype, termed Multizonal Outer Retinopathy and Retinal Pigment Epitheliopathy (MORR), is characterized by distinct progression pattern (Ramtohul et al. Retina 43:1890–1903, 2023) in multiple zones of the outer retina and retinal pigment epithelium. This case report aims to illustrate the chronologically divergent presentation, a phase-shifting disease progression and the complex clinical course of MORR, and to discuss the diagnostic challenges posed by its phase‑shifted timeline as well as potential therapeutic options.

Methods: A case of a 52-year-old female patient with initially unilateral, inactive posterior uveitis was retrospectively analyzed. Over thirteen years, progressive functional impairment developed in the fellow eye. Findings were assessed using multimodal imaging (Optical Coherence Tomography [OCT], Fundus Autofluorescence [FAF], Fluorescein and Indocyanine Green Angiography [FFA/ICGA]) and electrophysiological examinations (multifocal ERG, full-field ERG, EOG, VEP). Additional rheumatologic and neurologic assessments were conducted, and an infectious workup was performed.

 Results: The patient demonstrated chronologically divergent bilateral involvement with extensive damage to the retinal pigment epithelium (RPE) and photoreceptors. Fundus autofluorescence revealed a tri- to multizonal pattern in the better eye, while the fellow eye already exhibited diffuse atrophic areas devoid of any autofluorescence. Electrophysiological, the better eye showed selectively prolonged latencies on multifocal electroretinography (multifocal ERG) but preserved amplitudes, whereas the more severely affected eye displayed substantial functional loss. Despite various therapeutic interventions, including high-dose corticosteroids and immunosuppressive agents, progressive visual impairment ensued, driven by increasing macular involvement.

Conclusions: This case highlights the marked heterogeneity and diagnostic complexities of Multizonal Outer Retinopathy and Retinal Pigment Epitheliopathy (MORR), a newly recognized progressive variant of Acute Zonal Occult Outer Retinopathy (AZOOR). The disease course can present with chronologically divergent manifestations in both eyes. While initial stages may exhibit only subtle funduscopic changes, structural and functional deficits can progress rapidly, episodically and in a phase-shifted manner. Multimodal imaging is essential to delineate the disease trajectory and to distinguish MORR from diseases affecting outer retina. Currently, no definitive treatment is available; although immunomodulatory therapies may stabilize the condition in certain cases, their efficacy remains inconsistent. Consequently, early low-vision management and close interdisciplinary collaboration are of particular importance.

Keywords: Acute zonal occult outer retinopathy; Course; Multimodal imaging; Multizonal outer retinopathy and retinal pigment epitheliopathy.

Fig. 1

Fundus autofluorescence (FAF; Spectralis, Heidelberg Engineering, Heidelberg: a-c, a´-c, Clarus 500, Zeiss, Oberkochen, Germany). Both eyes over time (Upper row, a-d, right eye, lower row, a’-d’, left eye) The figure shows a peripapillary lesion with a trizonal autofluorescent pattern in the right eye: linear to spotty flaring hyperautofluorescent border between MORR lesion and normal retina (Zone I), speckled hyperautofluorescence within the MORR lesion (Zone II) and hypoautofluorescent area corresponding to RPE to choroidal atrophy (Zone III), with a progressive course over the years (upper row). At the 12th year of presentation, centripetal spread from inferior with mild speckled hyperfluorescent border is seen (white triangle). At the 13th year of presentation, the centripetal multizonal spread formed a subtotal circular pattern with confluent areas and showed speckled hyperautofluorescence at the margin at the transition to normal retina. The periphery showed confluent hypoautofluorescence corresponding to the extensive RPE atrophy (white triangle). The left eye shows similar absent autofluorescence over the years due to central retinal to choroidal atrophy. Individual patchy hypo- to isoautofluorescent lesions correspond to the inhomogeneously distributed pigment clumping (lower row)

Fig. 2

Correlation of FFA, ICGA and SD-OCT for photoreceptor, RPE and choriocapillaris atrophy zones The white arrows show three border transitions in the right eye (a, c): (I) from normal anatomical outer retinal structures and choriocapillaris to (II) RPE and photoreceptor degeneration/remodeling with reticular-like drusenoid deposits in OCT and corresponding hypo- or hyperfluorescent appearance in fluorescence angiography depending on their position in relation to the pigment layer of the retina and the amount of lipids and proteins they contain, missing drusen fluorescence in RPE atrophy. Subsequently (III) complete RPE loss and limiting to absent visualization of the choriocapillaris with decrease of peripapillary choroidal thickness in OCT, corresponding window defect and simultaneously hypofluorescent in FFA, as well as peripapillary vessel density decrease (yellow arrows) of the choroid in ICG

Fig. 3

∆: SD-OCT progression over 13 years

Fig. 4

∆: Fundus photographs demonstrating progressive atrophy and pigment changes in both eyes over time