Peripheral Exudative Hemorrhagic Chorioretinopathy

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Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is an uncommon degenerative condition of the retina and choroid. This condition was first described by Reese and Jones in 1961 as peripheral hematomas under the retinal pigment epithelium (RPE), and the current name was subsequently coined by Annesley in 1980. Other terms that have been used to describe this entity include eccentric retinal degeneration, extramacular disciform, and peripheral age-related retinal degeneration.^1,2

Even though PEHCR is a relatively rare entity, it is important for all ophthalmologists to understand the diagnosis and management of this con­dition because it can mimic several other diagnoses. In particular, PEHCR is frequently mistaken for choroidal melanoma, which has very different management and prognostic implica­tions. Key aspects of the epidemiology, clinical presentation, and imaging findings can aid the ophthalmologist in the diagnosis, management, and, when warranted, timely referral to the appropriate subspecialist.

Epidemiology

PEHCR has been described mostly in White patients, with a mean age at presentation between 70 and 80 years and a female predominance of 60% to 70%.^1-5 Almost all patients reported in large case series have been White.^1-4 However, the condition has been reported uncommonly in African American and Asian patients, and some authors have suggested that the disease course may be more severe in non-White patients.⁶ Possible risk factors for the exudation and/or hemorrhage in­clude hypertension and use of systemic antiplatelet or anticoagulant drugs.^1-3

PEHCR OVER TIME. (1A) Widefield color fundus photograph of a temporal PEHCR lesion characterized by a hemorrhagic PED (white arrow) with adjacent intraretinal hemorrhage inferiorly (blue arrow). Concurrent macular RPE changes can be seen (black arrow). (1B) Same eye nine months later, showing inferior shifting of the PEHCR lesion (white arrow) leaving areas of RPE atrophy and hyperplasia (yellow arrow).

Pathophysiology

The pathophysiology of PEHCR is unclear. Initially, the condition was thought to be a peripheral variant of age-related macular degeneration (AMD), given the similar clinical characteristics of hemorrhage and ex­udation, as well as findings of macular drusen and RPE changes in a subset of cases.^1,2 Subsequently, the identification of abnormal choroidal vascular net­works and polyp-like telangiectasias on indocyanine green angiography (ICGA) raised the possibility that PE­HCR may be related to polypoidal cho­roidal vasculopathy.^7,8 A recent study using enhanced-depth imaging OCT suggests that PEHCR may belong to the pachychoroid spectrum of diseases.⁹

Clinical Presentation

Up to 60% of patients with PEHCR may be asymptomatic.⁴ Those who are symptomatic most commonly present with decreased vision, floaters, or flash­es. Less commonly, PEHCR may cause metamorphopsia, scotomas, visual field deficits, or pain. The mean BCVA at presentation ranges from 20/40 to 20/100, although around one-fifth of patients may present with BCVA worse than 20/200.^1,2,5 Causes of decreased vision at presentation include vitreous hemorrhage, subretinal hemorrhage, subretinal fluid, and lipid exudation involving the macula.^1-5

On fundus examination, PEHCR lesions are typically found in the tem­poral periphery between the equator and the ora serrata, especially infero­temporally, and are bilateral in 9% to 43% of cases.^1-5 They most often appear as elevated subretinal hemorrhages or hemorrhagic pigment epithelial detach­ments (PEDs) mimicking tumorlike masses (Fig. 1A).^1-5 Associated findings include subretinal fluid, serous PEDs, lipid exudation, subretinal fibrosis, RPE hyperplasia or atrophy (Fig. 1B), and vitreous hemorrhage.^1-5 Macular findings consistent with those seen in AMD, including drusen and RPE changes, have been reported in up to two-thirds of cases.^1-5

Diagnosis

The diagnosis of PEHCR is based on clinical examination aided by multimodal imaging. On ultrasonography, PEHCR presents as a dome- or plateau-shaped lesion with variable echogenicity and internal reflectivity. It can be associated with a clot retraction cleft between the subretinal/sub-RPE blood and choroid but typically does not exhibit intrinsic vascular pulsations or choroidal excavation, both of which can be seen with choroidal melano­ma.^1-3

On fluorescein angiography (FA), PEHCR is characterized by blockage from subretinal/sub-RPE blood, hyper- or hypofluorescence in areas of RPE at­rophy or hyperplasia, pooling in serous PEDs, and possible leakage from cho­roidal neovascularization (reported in 3%-26% of cases).^1-4 Findings on ICGA include polyps (0%-59%), a pathologic choroidal network (30%-84%), and late hypercyanescence or leakage of uncer­tain etiology (60%-62%).^2-4

It may be difficult to directly image PEHCR lesions with OCT due to their peripheral location, but these lesions can be characterized by subretinal fluid or PEDs over Bruch’s membrane, without infiltration into the underlying choroid. OCT of the macula may reveal macular extension of subretinal fluid, exudates, or development of macular fibrosis.^3-5

Differential Diagnosis

The differential diagnosis of PEHCR includes chorioretinal mass lesions such as choroidal melanoma or hemangi­oma, as well as other causes of sub­retinal/sub-RPE hemorrhage such as macroaneurysm, Coats disease, and traumatic choroidal rupture. Choroi­dal melanoma was the most common referring diagnosis for PEHCR in multiple case series, and PEHCR was second only to choroidal nevi as a cause of “pseudomelanoma” seen at a large tertiary referral center, highlighting the importance of differentiating these two entities.^1-3

Choroidal melanoma. Clinical findings and multimodal imaging characteristics can help differentiate PEHCR from choroidal melanoma, although none of these features is pathognomonic for either condition (Table 1). PEHCR typically presents in older patients, with a slight female pre­dominance, while choroidal melanoma presents over a wider age range and has a slight male predominance. PEHCR can present bilaterally, while choroidal melanoma is rarely bilateral (<1%).¹

While PEHCR lesions are typically located between the equator and the ora serrata, choroidal melanoma can be located anywhere in the uvea, including anterior to the ora serrata. This can be appreciated clinically by transillumi­nating the globe; lesions whose shadow extends anterior to the ora serrata into the pars plana are more concerning for choroidal melanoma.¹

On ultrasound, the choroid underly­ing a PEHCR lesion should be normal, although there can be a clot retraction cleft separating the subretinal or sub-RPE clot from the underlying choroid. In contrast, a mushroom-shaped lesion or the presence of intrinsic vascular pulsations are both more suggestive of choroidal melanoma, as neither of these features was seen in any cases of PEHCR in a large series.¹ Similarly, intrinsic vascularity characterized by a “double circulation” pattern (fluores­cence from vessels within the tumor as well as from the overlying intact retinal vasculature) is more characteristic of choroidal melanoma and has not been reported with PEHCR.¹

Table 1. Clinical Findings and Imaging Characteristics of PEHCR and Choroidal Melanoma

Management and Prognosis

No randomized trials have been con­ducted on the treatment of PEHCR, and management is based on case series and expert opinion. Observation is a reasonable option for stable peripheral lesions. Shields and colleagues report­ed a series of 90 patients with PEHCR managed with observation; over a mean follow-up period of 15 months, 89% of patients demonstrated stability or regression, and 11% showed pro­gression.¹ However, aggressive lesions can cause significant peripheral vision loss and can extend into the macula.⁸ Cases of PEHCR exhibiting rapidly progressive massive subretinal hem­orrhage with acute loss of vision have been reported, including two of five cases in Asian patients, highlighting the importance of close surveillance and return precautions.⁶

Treatment options for PEHCR lesions that demonstrate progression include intravitreal anti-VEGF therapy, laser photocoagulation, photodynamic therapy, and cryotherapy. Of these, anti-VEGF therapy is the most commonly used and has shown favorable out­comes in small case series.^5,10 Vitrecto­my is usually reserved for nonclearing vitreous hemorrhage.^3,6,10

Mean final BCVA in large PEHCR series ranged from 20/40 to 20/200 at mean follow-up periods of more than two years.^3-5 Vitrectomy for nonclear­ing vitreous hemorrhage was the only treatment modality associated with statistically significant improvements in visual acuity.³

Conclusion

PEHCR is an uncommon but poten­tially vision-threatening condition affecting older adults. It can mimic other causes of retinal hemorrhage or chorioretinal mass lesions, particularly choroidal melanoma, and accurate diagnosis requires careful clinical examination aided by multimodal imaging. Patients with an unclear diagnosis should be referred promptly (e.g., within one week) to a retina specialist, given the potential urgency associated with other entities in the differential diagnosis. Although most cases of PEHCR demonstrate stability or spontaneous regression, some severe cases can cause vision loss due to exten­sive peripheral hemorrhage, macular involvement, or vitreous hemorrhage. Thus, patients with PEHCR should be monitored carefully and given clear return precautions to reduce the risk of vision-threatening complica­tions.

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1 Shields CL et al. Ophthalmology. 2009;116(3):529-535.

2 Mantel I et al. Am J Ophthalmol. 2009;148(6):932-8.e1.

3 Vandefonteyne S et al. Br J Ophthalmol. 2020;104(6):874-878.

4 Zicarelli F et al. Br J Ophthalmol. 2021;105(10):1410-1414.

5 Safir M et al. PLoS One. 2022;17(9):e0275163.

6 Kim YT et al. Jpn J Ophthalmol. 2010;54(3):227-231.

7 Mantel I et al. Am J Ophthalmol. 2012;153(5):910-922.e2.

8 Goldman DR et al. Retina. 2013;33(1):48-55.

9 Shroff D et al. Retina. 2021;41(7):1518-1525.

10 Seibel I et al. Graefes Arch Clin Exp Ophthal­mol. 2016;254(4):653-659.

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Dr. Liu is an ophthalmology resident, and Dr. Kim is an assistant professor of ophthalmology; both are at the Scheie Eye Institute at the Uni­versity of Pennsylvania in Philadelphia. Relevant financial disclosures: None.

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