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

Abstract

Acute posterior multifocal placoid pigment epitheliopathy is a rare inflammatory chorioretinopathy, classified as a white dot syndrome, in which ischaemia of the choriocapillaris leads to atrophy of the external retinal layers, including the retinal pigment epithelium.

A male patient in his 20s presented with sudden severe loss of vision in the left eye. Funduscopy revealed with yellow placoid lesions in the macula and near periphery. Spectral-domain optical coherence tomography and fluorescein angiography revealed the presence of central intraretinal fluid in the left eye and multiple areas of macular ischaemia bilaterally. Treatment with oral corticosteroids was initiated, and the anatomical changes, including the intraretinal fluid, improved steadily over the following weeks.

Although rare, the presence of subretinal or intraretinal fluid should not decrease the suspicion of acute posterior multifocal placoid pigment epitheliopathy. Reabsorption of the fluid is usually accompanied by the improvement of the remaining anatomical changes and the visual function.

Background

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory chorioretinopathy, first described by Gass in 1968.¹ It is classified as a white dot syndrome and has an estimated incidence of 0.15 cases per 100 000 people.^{2 3} The most common presentation is bilateral. It affects males and females equally, often in the 2nd–4th decade of life. Its pathophysiology is not clearly understood, and the primarily affected region of the retina is unclear.^{4 5} Initially, it was thought that the disease primarily involved inflammation in the retinal pigment epithelium (RPE),^{6 7} producing the characteristic placoid lesions. Other hypotheses consider ischaemia in the choriocapillaris, due to occlusive vasculitis, possibly due to inflammatory or autoimmune processes, resulting in hypoperfusion of the RPE and photoreceptors.⁸ The most accepted theory at present refers to a primary affectation of the choriocapillaris, leading to secondary injury of the RPE and outer retina, resulting in the atrophy of the choriocapillaris, RPE and photoreceptors. Approximately 33% of the patients report preceding influenza-like symptoms before APMPPE’s onset.⁹ The disease has also been described as associated with cases of systemic vasculitis, sarcoidosis, ulcerative colitis, thyroiditis, other viral and bacterial infections, and postvaccination.^10–12 Genetic associations have been reported involving the HLA-B7 and HLA-DR2 haplotypes.¹³

The diagnosis of APMPPE is made based on the clinical presentation, retinoscopy findings and complementary imaging tests, such as spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, fluorescein angiography (FA) and indocyanine green angiography.^{3 5} The most common ophthalmological complaint is a bilateral, usually asymmetric, rapid onset of blurred vision associated with central or paracentral localised scotomas. Best-corrected visual acuities (BCVAs) may range from 6/10 to count fingers, and photopsia and metamorphopsia may also develop. Systemic symptoms such as influenza-like syndrome and headache may be present concomitantly. The anterior segment evaluation is usually normal, but anterior cell reaction may develop. Mild vitritis is reported in 50% of the cases. Fundus examination often shows white-yellow placoid lesions at the level of the RPE and choroid.⁴ Papillitis may occur, but cystoid macular oedema is uncommon. The most typical acute findings in SD-OCT include hyper-reflectivity in the outer retinal layers and the absence of the ellipsoid zone.^{14 15} FA usually exhibits early hypofluorescence corresponding to the placoid lesions, followed by late hyperfluorescent staining. The early hypofluorescence may represent poor perfusion of the choriocapillaris or blockage due to the overlying outer retina and RPE thickening.¹⁶ IGCA manifests early and late hypofluorescence, due to the poor perfusion of the choriocapillaris.

The natural history of APMPEE is usually self-limited, with partial or complete resolution of the visual symptoms after 4–8 weeks. Most patients achieve a BCVA of 6/12 or better. Foveal involvement confers a worse prognosis.⁵ Other factors which may also lead to a worse prognosis include patients older than 60 years, unilaterality and an interval of 6 months before the involvement of the second eye.¹⁷ There is no current consensus regarding the treatment and its impact on the final visual result. Steroids are anecdotally used when the macula is involved. The recurrence of the disease is uncommon and generally predicts a worse prognosis.³ All patients with a new diagnosis of APMPEE should receive full neurological and systemic workup to evaluate for CNS vasculitis and other associated systemic conditions such as autoimmune and infectious diseases.

Case presentation

A male patient in his early 20s presented in the emergency department with severe left eye (OS) vision loss for 4 days. He did not report any other ocular symptoms, such as red eye or pain. He denied trauma or any other precipitating factors. His medical history was unremarkable, and he did not take any medication. There was no history of recent disease or influenza-like symptoms. His BCVA was 6/6 and 6/30 on his right and left eyes, respectively. The slit-lamp examination showed a normal anterior segment, with the absence of anterior chamber reaction. Funduscopy revealed macular yellowish placoid lesions, occupying a large portion of the macula and the near periphery. He underwent an SD-OCT (figure 1) and FA (figures 2–5), which showed the presence of central intraretinal fluid dispersed in an atypical pattern, on the OS, and multiple areas of macular ischaemia bilaterally, with late central and paracentral diffusion. A systemic study with infectious and immunological markers was requested that came out negative. Neurological examination was also unremarkable. After ruling out an infectious cause, an initial dose of 80 mg of prednisolone was started.

Figure 1.

SD-OCT of the left eye at presentation, showing the presence of intraretinal fluid and disruption of the ellipsoid zone. The arrowmarks correspond to the orientation of the scan in the OCT's printout document. SD-OCT, spectral-domain optical coherence tomography.

Figure 2.

Colour fundus photography of the right eye at presentation, showing mild white/yellow placoid-like lesions, occupying part of the central and superior macula.

Figure 3.

Colour fundus photography of the left eye at presentation, showing severe yellow placoid lesions, occupying a large portion of the macula and near periphery.

Figure 4.

Fluorescein angiography of the right eye at presentation, showing ischemia in the superior macula.

Figure 5.

Fluorescein angiography of the left eye at presentation, showing multiple areas of central and paracentral macular ischaemia.

Three days after the initial presentation, the patient was reevaluated. His OS BCVA had improved to 6/12, the anterior chamber still had no inflammatory reaction and the funduscopy appearance was similar. The SD-OCT was repeated, which showed a reduced volume of intraretinal fluid. Given the improvement of the clinical picture, treatment was maintained. He was again evaluated 1 week after onset, showing a similar BCVA of 6/12 on his OS, but this time the intraretinal fluid had completely disappeared on the SD-OCT. A progressive weaning of the oral corticosteroid was started, and his BCVA progressively improved during the following weeks. During the last observation, 8 weeks after the initial presentation, the patient had a BCVA of 6/7.5 on his OS. Funduscopy revealed a marked improvement of the posterior pole lesions, with some regions of cicatricial pigmentary changes (figures 6–9). SD-OCTs repeated during each examination showed the absence of intraretinal or subretinal fluid (SRF), with mild anatomical changes in the outer layers of the retina (figure 10).

Figure 6.

Colour fundus photography of the right eye, 3 months after the initial presentation, showing improvement of the placoid lesions with corresponding cicatricial pigmentary atrophy.

Figure 7.

Colour fundus photography of the left eye at presentation, 3 months after the initial presentation, showing improvement of the placoid lesions, with cicatricial pigmentary atrophy.

Figure 8.

Fluorescein angiography of the right eye, 3 months after the initial presentation, showing an improvement in macular ischaemia, with corresponding patches of atrophy.

Figure 9.

Fluorescein angiography of the left eye, 3 months after the initial presentation, showing an improvement in macular ischaemia, with corresponding patches of atrophy.

Figure 10.

SD-OCT of the right eye, 5 weeks after the initial presentation, showing the absence of intraretinal or subretinal fluid, and mild disruption of the central outer retinal layers. SD-OCT, spectral-domain optical coherence tomography.

Investigations

The imagological study included SD-OCT, retinography and FA).

SD-OCT was performed at baseline and at each follow-up visit. Initially, they showed the presence of central intraretinal fluid distributed in an atypical pattern, on the OS, which decreased significantly in volume after 3 days, and disappeared completely after 1 week. The macula remained dry in all scans performed after the first week of follow-up.

Retinography and FA were performed at baseline, and 8 weeks after the initial presentation. At baseline, the retinography and FA showed macular yellowish placoid lesions in a large portion of the macula and near periphery, and multiple areas of macular ischaemia bilaterally, with late central and paracentral diffusion. After 8 weeks, there was marked improvement of the lesions, with areas of cicatricial pigmentary changes.

A systemic investigation with infectious and immunological markers was also requested, to exclude infectious and inflammatory causes, which was negative.

Treatment

Treatment was started with oral prednisolone (Lepicortinolo) after infectious causes had been ruled out. The initial dose was 80 mg/day for 1 week, which was then slowly tapered over the following weeks, and fully discontinued after 8 weeks.

Outcome and follow-up

During the first week after presentation, the intraretinal fluid had completely disappeared and did not relapse at subsequent visits. OS BCVA improved steadily over the following weeks, with a BCVA of 6/7.5 8 weeks after the initial presentation. Funduscopy showed an improvement of the posterior pole lesions, with the presence of areas of cicatricial pigmentary changes.

Discussion

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. Although the subjective complaints were unilateral, imaging studies showed a bilateral, asymmetrical involvement. It was therefore a case with bilateral structural anatomic changes, with unilateral functional manifestations, probably since the pathological process was more severe on the OS, therefore having a greater functional impact. Those findings were similar to most described cases of APMPPE, where asymmetric bilateral changes are present.⁶ Although many cases are preceded by systemic symptoms like inflenza-like syndrome,⁹ our patient did not have any history of recent systemic disease. Headache or other neurological manifestations were also not present. In all cases, a full neurological and systemic study must be performed to rule out the existence of complications, namely cerebral vasculitis, which is associated with this disease in some cases.^{18 19} The initial OS BCVA of 6/30 matched the values described in the literature for this disease, which may range from 6/12 to count fingers. Funduscopy appearance, consisting of yellowish plaques involving the macula and the near periphery were also typical.⁴ However, the presence of intraretinal fluid constitutes a rare finding, scarcely reported throughout the literature. Birnbaum et al described a small series of cases including some with SRF and intraretinal fluid (IRF) shown in SD-OCT. They hypothesised that a mildly reflective layer forms above the RPE, likely representing inflammatory debris or degenerative material, giving the impression that the fluid is intraretinal, although it is subretinal. They also stated that the quick and substantial recovery of visual acuity supports the presence of SRF, rather than IRF.²⁰ Nonetheless, even though it is rare, SRF or apparent IRF is a possible finding in APMPPE, and should not decrease the suspicion of the diagnosis. The resolution of fluid usually accompanies the improvement of the visual function and is typically rapid.

Regarding the treatment, the evidence is unclear. Most studies report that structural and functional improvement is usually fast and occurs spontaneously, without any treatment.³ However, many authors consider treatment with oral corticosteroids when the lesions affect the fovea.¹⁷ When central nervous system vasculitis is present, therapy is mandatory and can be life-saving. A recurrent form of APMPPE may represent a different clinical entity called relentless placoid chorioretinitis, a disease that shares features with APMPPE and serpiginous choroidopathy. It has a high recurrence rate and longer periods of activity. In those cases, immunomodulatory therapy may be necessary.^{21 22} In our case, the patient was promptly treated with oral corticosteroids as soon as an infectious cause was ruled out. The structural changes, namely the presence of intraretinal fluid improved rapidly, within 1 week, while the BCVA steadily, and almost completely improved during the 8 weeks following the onset of the disease. It was not possible to conclude whether the use of corticosteroids had an impact on the improvement of the anatomical and functional outcomes.

Conclusion

This report presented a case of APMPPE with atypical imagiological findings, namely the presence of intraretinal fluid. Despite being a rare, scarcely reported finding, in this disease, the presence of foveal SRF or IRF should not lessen the degree of suspicion of this disease. The reabsorption of the fluid is usually spontaneous and fast, accompanying the improvement of the visual function. There is insufficient evidence to conclude that active treatment with corticosteroids influences the rate of improvement of the intraretinal fluid, in this condition.

Learning points.

• Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) may present with sudden, severe vision loss, in the absence of red eye, pain or anterior segment inflammation.

• Although many cases of APMPPE are preceded by systemic influenza-like symptoms, those symptoms may be absent.

• Despite being a rare, scarcely reported finding, the presence of foveal or intraretinal fluid should not lessen the degree of suspicion of APMPPE.

• The reabsorption of the fluid is usually spontaneous and fast, accompanying the improvement of the visual function.

• There is insufficient evidence to conclude that active treatment with corticosteroids influences the rate of improvement of the intraretinal fluid, in this condition.

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