Limited efficacy of adalimumab in the acute phase of serpiginous choroiditis refractory to corticosteroid and cyclosporine, a case report.

BACKGROUND: The optimal treatment of serpiginous choroiditis is not established. While recent reports indicate the efficacy of adalimumab, there is limited evidence. We present a case of serpiginous choroiditis refractory to steroids, immunosuppressants, and adalimumab. CASE PRESENTATION: An 18-year-old woman presented with severe vision loss in both eyes. A fundus examination revealed a foveal grayish-white lesion, and optical coherence tomography revealed outer retinal damage. She was diagnosed with serpiginous choroiditis and treated with steroid pulse therapy, but the disease progressed continuously. The addition of sub-Tenon's injection of triamcinolone and oral cyclosporine did not change the disease course. We also administered subcutaneous injections of adalimumab, but even with the intensive treatment, the retinal lesions and subsequent atrophy progressed. Her right and left visual acuity declined from 20/22 to 20/66 and 20/200, respectively, during the 9 months of follow-up. CONCLUSION: Here, we report a case of serpiginous choroiditis refractory to corticosteroids, immunosuppressants, and adalimumab. Further studies are needed to establish the optimal treatment for such cases.

Long-term follow-up of a bilateral acute posterior multifocal placoid pigment epitheliopathy following COVID-19 infection: a case report.

BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory eye disorder that is characterized by the presence of multiple placoid lesions in the posterior pole of the eye. Relentless placoid chorioretinitis (RPC) is an inflammatory chorioretinopathy that combines clinical features of APMPPE and serpiginous chorioretinitis, which is a progressive condition with a high risk of visual disability. Patients with COVID-19 can develop various ocular manifestations, however, there have been limited reports of APMPPE and RPC associated with the infection. We report a case of a patient who developed APMPPE after a COVID-19 infection and subsequently progressed into RPC. CASE PRESENTATION: A 17-year-old male presented with a one-week history of painless gradual visual loss in both eyes. Two months prior to the visual symptoms, the patient had a SARS CoV-2 infection, confirmed by polymerase chain reaction test. Clinical findings with fundoscopy, optical coherence tomography and fluorescein angiography were consistent with APMPPE. Due to the severely affected vision in both eyes, the patient was started on 50 mg oral prednisolone daily, after which vision began to improve rapidly. Two months after symptom onset during steroid taper, the impression of continued inflammatory activity and new lesions in the retinal periphery of both eyes suggested RPC. Adalimumab 40 mg every other week was initiated with 12.5 mg prednisolone daily followed by slow tapering. Vision improved and five months after the start of the adalimumab treatment, the steroid was discontinued and there were no signs of active inflammation. The patient has been followed for a total of 21 months since presentation, had full visual recovery and good tolerance of the immunosuppressive treatment. CONCLUSION: COVID-19 might cause long-lasting activity of APMPPE. The scarcity of reports compared with the number of confirmed COVID-19 infections worldwide suggests a rare entity. The association of APMPPE with a variety of infections may suggest a common immunological aberrant response that might be triggered by various factors. Further examinations and case reports are needed to understand the role of biological therapy in the treatment of such cases.

Relentless placoid chorioretinitis: A review of four cases in pediatric and young adult patients with a discussion of therapeutic strategies.

Introduction: Relentless placoid chorioretinitis (RPC) is a rare, bilateral disease of the retinal pigment epithelium. The clinical course is prolonged and relapsing. No standard treatment has been established to date. The purpose of this case series is to report four cases of RPC in pediatric and young adult patients in which varying treatments were used, comparing them to previously published cases. Methods: A literature review was conducted to investigate currently published presentations and treatment options for RPC. A multicenter retrospective chart review was also performed on four consecutive patients. These patients were diagnosed with RPC because of new chorioretinitis lesions continuing to appear without or despite therapy for 5-36 months (2 patients), with a clinical course prolonged and relapsing, or because of the atypical location of the multiple lesions (>50) extending from the posterior pole to the equator and mid-peripheral retina (all four patients), which were not consistent with other entities like acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. Results: All four cases of RPC received oral or IV steroids acutely, and three of these patients were transitioned to a steroid-sparing agent and biologic therapy: anti-TNF alpha or anti-IL-6. Quiescence of the chorioretinitis lesions was obtained after 7 months, 1 month, and 36 months; however, the latter had issues with treatment adherence. Mycophenolate mofetil was insufficient to control the disease in one patient, but tocilizumab and infliximab thereafter were effective after cessation of adalimumab due to side effects. Adalimumab when started the first month after the presentation was effective in controlling the disease in one patient. After the failure of interferon-alpha-2a, one patient displayed long-term control with infliximab. One patient did not require a steroid-sparing agent after oral prednisone taper as there was no evidence of progression or recurrence. Conclusion: This case series adds to the current knowledge regarding potential treatments for RPC, specifically the use of anti-TNF-alpha treatment and anti-IL-6 tocilizumab. In this case study, relapses of RPC were found among patients on mycophenolate mofetil and interferon-alpha-2a, and one case did not relapse on oral steroids without a steroid-sparing agent. Our findings suggest that adalimumab, infliximab, and tocilizumab may be useful medications to obtain quiescence of RPC.

Bilateral Relentless Placoid Chorioretinitis Following Pfizer-BioNTech COVID-19 Vaccination: Specific Antigenic Trigger or Nonspecific Immune Activation?

PURPOSE: To report bilateral relentless placoid chorioretinitis following Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine administration. CASE REPORT: A 55-year-old Caucasian New Zealand-born woman presented with progressive left eye vision loss and bilateral photopsias and floaters occurring 10 days after receiving the Pfizer-BioNTech COVID-19 vaccination. She had a similar self-limiting episode of photopsias and floaters without vision loss 1 year prior after receiving the influenza vaccine. Snellen visual acuity (VA) was 20/25 in the right eye, and count fingers at 2 m in the left eye. Bilateral, active, creamy, plaque-like lesions were present at the level of the retinal pigment epithelium and choroid, suggestive of relentless placoid chorioretinitis. Commencement of 100 mg oral prednisolone and 3 g mycophenolate daily resulted in recovery of the foveal ellipsoid layer with VA of 20/25 in each eye after 8 weeks. Subsequent activations occurred following COVID-19 infection and respiratory infection. CONCLUSION: This is the first reported case of relentless placoid chorioretinitis occurring as a potential side-effect of the Pfizer-BioNTech COVID-19 vaccine. Vaccination, and not infection, could be assumed to be the likely trigger. Subsequent flares following COVID-19 and a nonspecific respiratory infection during periods of inadequate immunosuppression suggest that a COVID-19 antigen or general immune activation could also be the trigger.

Clinical Outcomes of Observed and Treated Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Chorioretinitis.

PURPOSE: To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC). METHODS: Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC. RESULTS: There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids. CONCLUSIONS: While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.

[Acute posterior multifocal placoid pigment epitheliopathy, serpiginous choroiditis and related diseases]. / Épithéliopathie en plaque, choroïdite serpigineuse et leurs formes frontières.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) and serpiginous choroiditis are two diseases classified as "white spot syndromes." Both are inflammatory/autoimmune diseases with suspected primary involvement of the choriocapillaris. The former usually has an excellent prognosis, while the latter can rapidly induce legal blindness. Whereas these diseases are well defined and well known, other entities (such as persistent placoid maculopathy or ampiginous choroiditis) with features of both APMPPE and serpiginous choroiditis have been described more recently. This review aims to describe demographic characteristics and multimodal imaging features to help differentiate between these four diseases.

Systemic combined with intravitreal methotrexate for relentless placoid chorioretinitis: A case report.

BACKGROUND: We describe a case of relentless placoid chorioretinitis (RPC) that progressed despite administration of peribulbar and systemic corticosteroids, and was resolved by systemic combined with intravitreal methotrexate. CASE SUMMARY: A 16-year-old male reported painless blurred vision and a temporal scotoma in his right eye for one week. Due to widespread distribution and continuous enlargement, multimodal imaging of the lesions led to the diagnosis of RPC. Lesions in the right eye extended despite peribulbar injection of triamcinolone acetonide, but the progression was immediately terminated by a single dose of intravitreal methotrexate. A new fresh lesion occurred in the contralateral eye despite systemic prednisolone but was resolved by oral methotrexate. CONCLUSION: Systemic immunosuppressants should be given upon RPC diagnosis. Intravitreal methotrexate immediately halted progression and may be considered for sight-threatening cases as part of the initial therapy.

Relentless Placoid Chorioretinitis With Branch Retinal Vein Occlusion and Secondary Peripheral Retinal Neovascularization.

Purpose: We report a case of relentless placoid chorioretinitis (RPC) that developed branch retinal vein occlusion and peripheral retinal neovascularization in one eye. Methods: A case report is presented. Results: A 33-year-old healthy man presented with decreased visual acuity (20/150) in both eyes. Slit-lamp examination revealed anterior chamber and vitreous inflammation. Multiple yellow-white lesions were evident in the macula and scattered throughout the fundus. Following workup, a diagnosis of RPC was made. The patient was started on Pred Forte (prednisolone acetate 1%) and atropine drops. Three months later, visual acuity improved to 20/70 and 20/100 in the right and left eyes, respectively. At this time, fundus examination and fluorescein angiography revealed peripheral retinal neovascularization. Sectoral scatter laser photocoagulation was performed in the areas of nonperfusion. Conclusions: We describe a novel presentation of RPC associated with branch retinal vein occlusion and retinal neovascularization. Although the pathophysiology of RPC is believed to be primarily a choroidal vasculitis, retinal vascular changes may also occur, as observed in other white dot syndromes.

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

Purpose: To 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. Methods: Narrative review. Results: Literature 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. Conclusions: The 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.

Cyclosporine and prednisolone combination therapy as a potential therapeutic strategy for relentless placoid chorioretinitis.

PURPOSE: Relentless placoid chorioretinitis (RPC) is a new disease concept that was proposed by Jones et al. in 2000. Some cases of RPC have been reported; however, a treatment strategy has not yet been established. We report herein four cases of patients diagnosed with RPC. OBSERVATIONS: We experienced four cases of RPC in patients aged 24-51 years. All patients exhibited retinal lesions similar to that seen in acute posterior multifocal placoid pigment epitheliopathy or serpiginous choroiditis from the posterior pole to the surrounding region. Although patients underwent systemic prednisolone (PSL) therapy, recurrence was observed and the retinal scar formation was progressive; they were then diagnosed with RPC. In all cases, cyclosporine (CyA) was administered in addition to PSL, no recurrence was observed thereafter. CONCLUSIONS AND IMPORTANCE: RPC is a rare disease, and a treatment strategy has not yet been established. CyA and PSL combination therapy is considered to be effective in the treatment of RPC.

Relentless Placoid Chorioretinitis: A Case Series of Successful Tapering of Systemic Immunosuppressants Achieved with Adalimumab.

BACKGROUND: Adalimumab, a human anti-tumor necrosis factor-ɑ monoclonal antibody, was recently reported to be effective in lowering the risk of recurrence of noninfectious uveitis. This is the first case series of adalimumab administrations for relentless placoid chorioretinitis (RPC) patients. CASE PRESENTATION: We report 2 cases of RPC where successful treatments were achieved with adalimumab. A 34-year-old woman developed conjunctival hyperemia, mild iridocyclitis, and multiple atrophic retinal lesions, along with exudative changes that were widespread from the posterior pole to peripheral retina in both eyes. The diagnosis of RPC was made based on the characteristic recurrences of choroiditis despite systemic corticosteroid and cyclosporine. Adalimumab therapy was introduced to the patient, and thereafter no recurrence was observed while tapering the immunosuppressive agents. The second case was a 22-year-old man with visual deterioration in both eyes who exhibited widespread multiple chorioretinal atrophic lesions. We diagnosed the case as RPC based on characteristic clinical findings and recurring chorioretinitis during tapering of systemic corticosteroids. Adalimumab therapy was administrated, and immunosuppressant dosage was successfully reduced without any recurrences. CONCLUSIONS: In the current two RPC cases, adalimumab was quite effective and useful to reduce the dosages of systemic immunosuppressants. Further study is necessary to confirm the effectiveness of adalimumab in RPC patients.

Multi-modal imaging and anatomic classification of the white dot syndromes.

The white dot syndromes (WDS) are a diverse group of posterior uveitidies that share similar clinical findings but are unique from one another. Multimodal imaging has allowed us to better understand the morphology, the activity and age of lesions, and whether there is CNV associated with these different ocular pathologies. The "white dot syndromes" and their uveitic masqueraders can now be anatomically categorized based on lesion localization. The categories include local uveitic syndromes with choroidal pathology, systemic uveitic syndromes with choroidal pathology, and multifocal choroiditis with outer retinal/choriocapillaris pathology with uveitis and without uveitis. Neoplastic and infectious etiologies are also discussed given their ability to masquerade as WDS.

A Case of Ampiginous Choroiditis.

PURPOSE: Presentation of a case report of a unilateral ampiginous choroiditis. METHODS: This is an observational case report. RESULTS: A 70-year-old woman was referred to us with unilateral scattered chorioretinal lesions. The multifocal pattern of the lesions and the angiographic features led to the diagnosis of ampiginous choroiditis. CONCLUSION: Ampiginous choroiditis is a primary inflammatory choriocapillaropathy with characteristics of both acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis.

Macular retinal and choroidal thickness in unilateral relentless placoid chorioretinitis analyzed by swept-source optical coherence tomography.

BACKGROUND: The purpose of this study is to evaluate the retinal and choroidal thickness of the macular region in patients with unilateral relentless placoid chorioretinitis (RPC) and macular involvement. Patients diagnosed with RPC affecting only one eye underwent a comprehensive ophthalmologic examination including best-corrected visual acuity (BCVA), axial length (AL) measurement, slit-lamp examination, and color fundus and autofluorescence photography. The macular region was scanned by swept-source optical coherence tomography in the 1,050-nm wavelength. Automated segmentations of the retina and the choroid were used to obtain the corresponding thickness values. RESULTS: A total number of three patients (two men and one woman; age range 17 to 62 years) were included. Eyes with clinically evident RPC had a mean AL of 24.62 ± 0.11 mm, whereas in the clinically healthy fellow eyes, the mean AL was 24.65 ± 0.03 (p = 0.70). The mean BCVA was 0.93 ± 0.16 in eyes with RPC, and 1.0 in all the fellow eyes (p = 0.70). Slit-lamp examination did not reveal any sign of vitreous inflammation in any cases. The mean macular retinal thickness was 288.10 ± 10.22 µm in eyes with RPC, and 300.30 ± 7.17 µm in the healthy fellow eyes (p = 0.20). The mean central choroidal thickness was 260.70 ± 140.60 µm in eyes with RPC, and 262.30 ± 123.10 µm in the fellow eyes (p = 0.99). The mean macular choroidal thickness was 248.60 ± 128.40 and 255.10 ± 123.60 µm, respectively (p = 0.99). CONCLUSIONS: The pathogenesis of RPC remains unknown. No changes in the retinal and choroidal thickness were observed in the macular area of eyes diagnosed with RPC with macular involvement compared with the asymptomatic healthy fellow eyes. Further prospective studies are warranted in order to investigate the role of the choroid in cases of RPC.