Relentless Placoid Chorioretinitis (RPC) is a rare bilateral inflammatory choroidal disease first reported in 20001).
It shows intermediate features between acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC). RPC presents with multiple placoid lesions like APMPPE, but differs in taking a chronic relapsing course like SC. Since the first report, it remains a rare disease with few cases worldwide1).
Age of onset is mainly 20–60 years, but onset in children and young adults has also been reported1). Prodromal viral symptoms occur in about 33% of cases1). Additionally, multiple cases after COVID-19 infection have been reported1, 2), and associations with thyroiditis and cerebral vasculitis have been noted1).
It is characteristic that 50 or more multiple disc-shaped lesions appear bilaterally 1, 4). The lesions show different imaging findings in the acute and scar stages.
Acute Lesions
Fundus findings: Cream-colored to gray-white disc-shaped lesions. Multiple lesions from the posterior pole to the periphery.
FAF (Fundus Autofluorescence): Acute lesions show hyperautofluorescence 2, 3).
FA (Fluorescein Angiography): Pattern of early hypofluorescence and late hyperfluorescence. Early hypofluorescence reflecting choroidal ischemia is characteristic 1, 4).
ICG Angiography: Hypofluorescent spots throughout all phases. It is an indicator of active choroiditis 1, 5).
Chronic and Scar Stage
FAF: Scarred chronic lesions show hypoautofluorescence 2, 3).
OCT: Hyperreflective changes in the outer retina, RPE irregularity, and damage to the photoreceptor layer are observed 1).
OCT-A: Can detect decreased blood flow in the choriocapillaris layer 6). The inner choroid is considered the main site of damage 6).
Scar lesions: Remain as RPE atrophy, pigmentation, and aggregation.
It has been reported that leakage from the disc (optic disc fluorescein leakage) is observed in the acute phase in approximately 70% of cases5).
The characteristics of various imaging tests are shown below.
| Test | Acute phase findings | Chronic phase findings |
|---|---|---|
| FAF | Hyperautofluorescence | Hypoautofluorescence |
| FA | Early hypofluorescence | Late hyperfluorescence |
| ICG | Hypofluorescence throughout all phases | Hypofluorescent spots |
According to reports, there are cases where new lesions continue to appear for 5 to 24 months1). This is the basis for calling RPC “prolonged” and is also an essential difference from acute posterior multifocal placoid pigment epitheliopathy.
The specific etiology of RPC has not been elucidated. It is thought to be primarily an immune-mediated choroidal vasculitis.
Prodromal infection symptoms: About 33% of cases have prodromal symptoms suggestive of viral infection1). The specific pathogen has not been identified.
COVID-19-related onset: Several cases of RPC developing after COVID-19 infection have been reported1, 2). Immune abnormalities after COVID-19 may have been a trigger.
Autoimmune mechanism: A T-cell-mediated autoimmune reaction is thought to be involved3). Responsiveness to immunosuppressive therapy supports this.
Systemic complications: Cases complicated by thyroiditis and cerebral vasculitis have been reported1). It is necessary to keep in mind the possibility of a systemic inflammatory disease with extraocular involvement.
Choriocapillaris ischemia: Ischemia at the level of the choriocapillaris is considered the main pathogenesis of onset6). For details, see the section “Pathophysiology and Detailed Mechanism of Onset”.
Diagnostic criteria for RPC have not been established. Clinical diagnosis is made based on a combination of the following features.
Diagnostic points:
A wide variety of diseases must be differentiated from RPC. Detailed differentiation from 12 diseases has been reported2).
| Differential Diagnosis | Key Differentiating Points |
|---|---|
| APMPPE | Spontaneous resolution, not persistent |
| Serpiginous choroiditis | Geographic progression, tendency for monocular involvement |
| Vogt-Koyanagi-Harada disease | Systemic symptoms, sunset glow fundus |
Other differential diagnoses include multiple evanescent white dot syndrome (MEWDS), birdshot retinochoroidopathy, infectious choroiditis (toxoplasmosis, tuberculosis, syphilis), and sarcoidosis-associated choroiditis2).
Perform syphilis serology (RPR/TPHA), QuantiFERON-TB (tuberculosis), toxoplasma antibody, chest X-ray/CT, and ACE (sarcoidosis) 1, 2).
Multimodal imaging evaluation with FA, ICG, FAF, OCT, and OCT-A is essential for diagnosis and disease activity assessment 1, 5, 6).
There is no established standard treatment protocol for RPC. Currently, immunosuppressive therapy is the mainstay of treatment.
Systemic steroids are used as first-line therapy 1). Oral prednisolone is commonly initiated. However, steroid monotherapy often fails to achieve sufficient effect, and addition of immunosuppressive agents is necessary.
Cyclosporine + Prednisolone: A combination used even in pediatric and young adult cases 1).
Azathioprine: Reported to be used in 96.2% of cases, widely used as maintenance therapy 1).
Methotrexate (MTX) 15 mg/week: Used as maintenance therapy after cyclophosphamide pulse therapy 3).
In a report of 4 refractory RPC cases, intravenous cyclophosphamide pulse therapy at 10 mg/kg significantly improved BCVA from 20/125 to 20/32 (P < 0.001) 3). Side effects were minimal. MTX 15 mg/week was used as maintenance therapy 3).
In post-COVID-19 RPC cases, a case has been reported in which remission was achieved for 6 months with triple therapy (triple IMT) consisting of cyclosporine, mycophenolate mofetil (MMF), and methylprednisolone2).
Bombuy Gimenez J et al. (2025) reported achieving 6-month remission in a 51-year-old male with RPC following COVID-19 infection using triple IMT (cyclosporine + MMF + methylprednisolone)2). The diagnosis was made after detailed differentiation from 12 diseases.
Cases have been reported in which adalimumab, infliximab, and tocilizumab were used for refractory or recurrent cases1). The use of tocilizumab has attracted attention as the first reported case worldwide (see “Latest Research and Future Prospects” section for details).
In cases complicated by retinal vein occlusion (RVO) and peripheral retinal neovascularization, sector scatter laser photocoagulation has been performed4).
There is a report of sub-Tenon triamcinolone (IVTA) used in a pregnant RPC case1).
The main pathology of RPC is believed to be ischemia of the choriocapillaris 6).
Choriocapillaris ischemia: OCT-A studies have confirmed reduced blood flow in the choriocapillaris layer, with the inner choroid being the primary site of damage 6). This ischemia secondarily damages the overlying retinal pigment epithelium (RPE) and outer retina.
Choroidal vasculitis: Immune-mediated choroidal vasculitis is considered the underlying mechanism 4). The features of FA and ICG findings are common with acute posterior multifocal placoid pigment epitheliopathy, suggesting that inflammation at the choroidal vessel level causes circulatory disturbances.
Spread to retinal vessels: In the world’s first reported case complicated by retinal vein occlusion and peripheral retinal neovascularization, it was suggested that choroidal vasculitis may have spread to adjacent retinal vessels 4). Leukostasis is hypothesized as the mechanism of retinal vein occlusion 4).
Gupta RR et al. (2021) reported the world’s first case of a patient with RPC having more than 50 lesions complicated by branch retinal vein occlusion (BRVO) and peripheral retinal neovascularization 4). This was described as a finding supporting choroidal vasculitis as the main pathology.
Significance of OCT findings: Hyperreflectivity of the outer retina in the acute phase is thought to reflect damage to the photoreceptor-RPE complex due to ischemia 1).
The use of tocilizumab for pediatric and young adult RPC has attracted attention as the world’s first report 1).
In the report by Zaheer HA et al. (2023), a 17-year-old RPC patient received tocilizumab but experienced recurrence; after switching to infliximab, a final visual acuity of 20/15 was achieved 1). IL-6 inhibitors (tocilizumab) are expected as a new treatment option for RPC.
In a case series of 4 patients, intravenous cyclophosphamide 10 mg/kg significantly improved visual acuity (BCVA) from 20/125 to 20/32 (P < 0.001) with minimal side effects 3). It is evaluated as a promising treatment option for refractory RPC.
Pedroza-Seres et al. (2025) administered cyclophosphamide IV pulse therapy at 10 mg/kg to 4 cases, achieving significant improvement in BCVA (20/125 → 20/32, P < 0.001) 3). MTX 15 mg/week was used as maintenance therapy 3).
Elucidating the mechanism of RPC onset after COVID-19 infection is an important future challenge 1, 2). Further research is needed on how post-infection immune abnormalities trigger choroidal vasculitis.
As the first report worldwide, its use in one case has been reported 1), but currently the evidence is limited to case report level. A case with recurrence that achieved a good outcome after switching to infliximab has also been reported 1). Further accumulation is needed to establish it as standard treatment.
