Pediatric peripapillary choroidal neovascularization secondary to ocular sarcoidosis: a long-term follow-up case

Pediatric peripapillary choroidal neovascularization secondary to ocular sarcoidosis: a long-term follow-up case | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Pediatric peripapillary choroidal neovascularization secondary to ocular sarcoidosis: a long-term follow-up case Yuan Zong, Keyan Wang, Ting Zhang, Gezhi Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6591051/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jul, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 12 You are reading this latest preprint version Abstract Background: To describe a boy with probable ocular sarcoidosis and bilateral peripapillary choroidal neovascularization (PCNV). Case presentation: We report a case of a 14-year-old boy with a 2-month history of floaters and gradual vision loss in both eyes. Examination revealed bilateral granulomatous uveitis with peripapillary subretinal lesions. Level of serum angiotensin-converting enzyme was elevated. Positron emission tomography demonstrated increased metabolic activity in the nasopharynx and small intestine, consistent with diagnosis of sarcoidosis. Despite resolved vitreous cells and retinal vasculitis, the PCNV progressed slowly in the left eye, which was controlled with combined treatment of immunomodulatory regiment and multiple intravitreal anti-vascular endothelial growth factor injections over a prolonged period. Conclusions: This case highlights the need for a multidisciplinary approach and long-term follow-up in pediatric ocular sarcoidosis with PCNV. Sarcoidosis Choroidal Neovascularization Uveitis Pediatric Anti-vascular Endothelial Growth Factor Immunosuppressive Agents Figures Figure 1 Figure 2 Figure 3 Background Sarcoidosis is a multisystemic and granulomatous inflammatory disease of unknown cause. Pediatric sarcoidosis is a rare condition with a higher incidence in patients aged 13 to 15 years. Ocular involvement is the presenting symptom in nearly 30%-60% patients[ 1 ]. Choroidal neovascularization (CNV) was a severe sight-threatening complication of both infectious and non-infectious uveitis[ 2 ]. Peripapillary choroidal neovascularization (PCNV) account for 10% of all CNV[ 3 ], which was previously reported in adult ocular sarcoidosis. Here we described a unique case of pediatric sarcoidosis with bilateral PCNV. Case presentation A 14-year-old boy was referred to our hospital with a 2-month history of floaters and gradual vision loss in both eyes. He was born with congenital hypothyroidism and had no history of trauma or infection. On examination, the best-corrected visual acuity (BCVA) was 20/400 in the right eye (RE) and 20/80 in the left eye (LE). Intraocular pressure (IOP) was 14.1 mmHg RE and 17.3 mmHg LE. Slit-lamp examination revealed anterior chamber flares in both eyes. Fundus examination exhibited diffuse vitreous cells and perivenous infiltrates which resembled “candle-wax drippings” (Fig. 1 A and 1 B). Fundus fluorescein angiography (FFA) demonstrated diffuse hyperfluorescent leakage along the retinal veins and staining of the peripapillary subretinal lesions (Fig. 1 C and 1 D). Hyper-reflective peripapillary subretinal lesions were detected by enhanced-depth imaging optical coherence tomography (EDI-OCT) in both eyes (Fig. 1 E and 1 F). Laboratory tests, including complete blood count, erythrocyte sedimentation rate, C-reactive protein level, and autoimmune antibody tests, revealed no abnormalities. Syphilis and Toxoplasma serology test results were negative. serum angiotensin-converting enzyme (ACE) level was elevated (114.4 U/L; reference range 6–86 U/L). Polymerase Chain Reaction test of the aqueous humor RE revealed no viral or Bartonella infections. Both the tuberculin skin test and the interferon-gamma release assay were negative. No skin nodules were observed. The ultrasonographic findings of the thyroid, liver, spleen, and kidneys were normal. Magnetic resonance imaging (MRI) of the brain and chest computed tomography (CT) of the chest revealed no abnormalities. Positron emission tomography (PET) throughout the body revealed increased metabolism of 18F-fluorodeoxyglucose (18F-FDG) in the nasopharynx, in the duodenal bulb and several segments of the small intestine. A diagnosis of probable ocular sarcoidosis was made based on the presence of elevated serum ACE levels and abnormal 18F-FDG PET imaging findings in conjunction with compatible granulomatous uveitis (including signs of string of pearls vitreous opacities, segmental periphlebitis, and bilateral inflammation) according to the revised criteria of the International Workshop on Ocular Sarcoidosis (IWOS)[ 4 ]. The patient was prescribed oral prednisone (50 mg per day). Although a relatively low loading dose of oral corticosteroids (nearly 0.6 mg/kg/d, his body weight was 90 kg) was used, his IOP increased two weeks post treatment. Oral prednisone was tapered and stopped after two months. Oral methotrexate (MTX, 15 mg every week) and subcutaneous injections of adalimumab (40 mg every two weeks) were administered as part of the therapeutic regimen in consultation with the pediatric rheumatology department. The vitreous cells and vasculitis resolved gradually over the 4-month treatment period, and his BCVA improved to 20/25 in both eyes. However, the PCNV in the left eye grew slowly towards the macular region (Fig. 2 ). Intravitreal injection of anti-vascular endothelial growth factor (VEGF) was recommended; however, due to the COVID − 19 pandemic, the injection was interrupted, and the patient was lost to follow - up for 17 months. The patient was treated with oral methotrexate (MTX; 15 mg weekly) and subcutaneous injections of adalimumab (40 mg every two weeks). In addition, he had not received any COVID-19 vaccination. At 22 months of follow-up, the patient’s BCVA LE had worsened to 20/100. Fundus examination revealed no vitreous cells in either eye; however, the PCNV LE grew closer to the fovea, and the outer layer of the fovea was disrupted (Fig. 3 A, 3 B, 3 C). Repeated FFA showed patchy hyperfluorescent leakage of PCNV in both eyes. Three intravitreal injections of LE aflibercept were administered. The growth of PCNV was controlled (Fig. 3 D). Subcutaneous injections of adalimumab (40 mg every two weeks) were tapered to 40 mg every four weeks after two years of treatment. At 33 months (5 months after adalimumab tapering), OCT angiography (OCTA) revealed PCNV growth with increased subretinal fluid LE (Fig. 3 E). A fourth intravitreal aflibercept injection was administered to the left eye. At 41 months (12 months post adalimumab tapering), OCTA revealed recurrent PCNV growth in both eyes. Intravitreal injection of aflibercept was repeated in both eyes, and subcutaneous injections of adalimumab were adjusted back to biweekly dosing with consultations from the rheumatology department. Serum uric acid (546 µmol/L) was raised two years after immunomodulatory treatment and was treated accordingly. Routine magnetic resonance imaging (MRI) of the brain and chest CT scan were negative. The echocardiogram results were normal. PCNVs in both eyes was controlled with the BCVA at 20/20 RE and 20/60 LE (Fig. 3 F). Biweekly subcutaneous injections of adalimumab were still maintained. Currently, the patient is undergoing regular follow-ups and observation. Discussion and conclusions This case presents a 14-year-old boy with persistent peripapillary choroidal neovascular membrane associated with probable ocular sarcoidosis related uveitis. The PCNV grew very slowly toward the macula in one eye despite systemic immunosuppressant treatment, which is a rare complication of ocular sarcoidosis. The gold standard for diagnosis of sarcoidosis is histopathologic confirmation from tissue biopsy. However, biopsy not done for our patient, and he was negative for bilateral hilar lymphadenopathy, thus a probable diagnosis of sarcoid uveitis was made in accordance with the IWOS criteria. The goals of treatment for pediatric uveitis include controlling intraocular inflammation, preventing recurrence of inflammation, and reducing ocular complications and vision loss[ 5 ]. However, there are no standardized treatment protocols for pediatric non-infectious uveitis. In our case, we prescribed oral corticosteroids and steroid-sparing anti-rheumatic drug MTX was added timely. A long-term use of an anti-tumor necrosis factor agent adalimumab was also recommended to our patient by rheumatology department, which was consistent with previous research that patients under long-term adalimumab therapy were likely to achieve disease control[ 6 ]. Meanwhile the PCNV at initial presentation was another indication for the prompt immune-modulatory therapy for our patient, which was still not fully controlled through the follow up. The PCNV in his left eye slowly but persistently grew towards the macula, resulting the vision decrease LE. It is interesting that the PCNV evolved into fibrosis around the papilla except that part of PCNV at the macula portion was comprised of vascular signals, suggesting the relatively higher metabolic environment resulting higher VEGF level at that macula. The intravitreal anti-VEGF treatment could partially reduce the growth of the inflammatory CNV, which was consistent with other studies[ 3 , 7 ]. However, the PCNV was not totally controlled with four injections of anti-VEGF drug. The subcutaneous injection of adalimumab was tapered to 40mg every four weeks might be an explanation. In a recent study of Airaldi’s, the inflammatory CNV secondary to idiopathic multifocal choroiditis was better controlled by immunomodulatory therapy[ 8 ]. As a result, we advised the patient to switch back to the every-two-week dosing of adalimumab. At the last visit, his PCNV showed no signs of further development. There is limited literature regarding the duration of follow-up for ocular sarcoidosis. Pediatric uveitis can lead to long-term vision impairment if not appropriately treated and followed[ 9 ]. A case of bilateral subretinal fibrosis ten years after first presentation with chronic ocular sarcoidosis in a child was sobering[ 10 ]. In addition, inflammatory CNV was found much more frequently (both at initial presentation and throughout follow-up) in cases of posterior and panuveitis[ 2 ], which is another reason for the need of long-term follow up for pediatric uveitis. In summary, a multidisciplinary approach and long-term follow-up for pediatric ocular sarcoidosis with PCNV was necessary. Abbreviations CNV: choroidal neovascularization; PCNV: peripapillary choroidal neovascularization; BCVA: best-corrected visual acuity; RE: right eye; LE: left eye; IOP: intraocular pressure; FFA: fundus fluorescein angiography; EDI-OCT: enhanced-depth imaging optical coherence tomography; ACE: angiotensin-converting enzyme; CT: computed tomography; PET: positron emission tomography; 18F-FDG: 18F-fluorodeoxyglucose; IWOS: the international workshop on ocular sarcoidosis; MTX: methotrexate; VEGF: anti-vascular endothelial growth factor; OCTA: OCT angiography. Declarations Ethics approval and consent to participate This case report adhered to the Declaration of Helsinki and was approved by the Institutional Review Board of the Eye and Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China. Consent for publication Written informed consent for publication of clinical details and clinical images was obtained from the parents of the patient. Availability of data and materials All data generated or analysed during this study are included in this published article. Competing interests None of the authors has any conflicting interests to disclose. Funding This study was supported by the 2024 Clinical Scientists Programme of Shanghai Medical School, Shanghai Hospital Development Center Foundation (SHDC12023116) and the National Natural Science Foundation of China (82201204). Authors' contributions YZ and TZ performed the investigation and data collection, while KW and GX provided resources and validated the findings. YZ and TZ wrote the original draft, and all authors (YZ, TZ, and KW) participated in manuscript review and editing. References Ma SP, Rogers SL, Hall AJ, Hodgson L, Brennan J, Stawell RJ, Lim LL: Sarcoidosis-related Uveitis: Clinical Presentation, Disease Course, and Rates of Systemic Disease Progression After Uveitis Diagnosis. Am J Ophthalmol 2019,198(3): 30-36. Baxter SL, Pistilli M, Pujari SS, Liesegang TL, Suhler EB, Thorne JE, Foster CS, Jabs DA, Levy-Clarke GA, Nussenblatt RB et al: Risk of choroidal neovascularization among the uveitides. Am J Ophthalmol 2013, 156(3):468-477. Jutley G, Jutley G, Tah V, Lindfield D, Menon G: Treating peripapillary choroidal neovascular membranes: a review of the evidence. Eye (Lond) 2011, 25(6):675-681. Mochizuki M, Smith JR, Takase H, Kaburaki T, Acharya NR, Rao NA, International Workshop on Ocular Sarcoidosis Study G: Revised criteria of International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis. Br J Ophthalmol 2019, 103(10):1418-1422. Sood AB, Angeles-Han ST: An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis. Curr Treatm Opt Rheumatol 2017, 3(1):1-16. Nott K, Nott V, Lever E, Deakin C, Galloway J, Fisher C, Compeyrot-Lacassagne S: Pediatric Sarcoidosis: Retrospective Analysis of Biopsy-Proven Patients. J Rheumatol 2023, 50(7):924-933. Woronkowicz M, Niederer R, Lightman S, Tomkins-Netzer O: Intravitreal Antivascular Endothelial Growth Factor Treatment for Inflammatory Choroidal Neovascularization in Noninfectious Uveitis. Am J Ophthalmol 2022, 236:281-287. Airaldi M, Monteduro D, Tondini G, Pichi F, De Simone L, Cornish E, Casalino G, Zicarelli F, Oldani M, Staurenghi G et al: Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis. Am J Ophthalmol 2024, 262:62-72. Kim L, Li A, Angeles-Han S, Yeh S, Shantha J: Update on the management of uveitis in children: an overview for the clinician. Expert Rev Ophthalmol 2019, 14(4-5):211-218. Mavris N, Jaouni T, Amer R: Subretinal Fibrosis Developing 10 Years After First Presentation with Chronic Ocular Sarcoidosis in a Child. Ocul Immunol Inflamm 2024:1-4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Jul, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 30 Jun, 2025 Reviews received at journal 29 Jun, 2025 Reviews received at journal 16 Jun, 2025 Reviewers agreed at journal 15 Jun, 2025 Reviews received at journal 14 Jun, 2025 Reviewers agreed at journal 08 Jun, 2025 Reviewers agreed at journal 06 Jun, 2025 Reviewers invited by journal 06 Jun, 2025 Editor assigned by journal 04 Jun, 2025 Editor invited by journal 14 May, 2025 Submission checks completed at journal 11 May, 2025 First submitted to journal 11 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6591051","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":468140055,"identity":"ae257d67-e728-43f7-a853-d5852edf24af","order_by":0,"name":"Yuan Zong","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Zong","suffix":""},{"id":468140056,"identity":"8f375ab7-660a-4018-8a32-17cec0ae76d5","order_by":1,"name":"Keyan Wang","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Keyan","middleName":"","lastName":"Wang","suffix":""},{"id":468140057,"identity":"fe643d74-fa03-4e85-b4bf-f831e67fab75","order_by":2,"name":"Ting Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5UlEQVRIie3PIQvCQBTA8XccbOV0dWLwKzwZTMPUr6IcLBn8AIaBoEWw+iEMV23Th0uCdcFsMiwuKDgVtO0WBe8Pd6+8H9wBmEy/GH/dcXHYIs8w6GuF+BIeN9aTUOoJfIg1bIpszyIdGdi1XQbTc6vjbNALMOZg00GVP6wuXUgu7e36inKM5zqIMEzLicDmPSKm0iPSGC8cXOHriJeziAYFac+6SCyqQHy3ICN1mksOlQgJvwsJSZXyhC0xlJbuL/bq6KUwpZ467eaQ34K+Y1NSSr65w/e0qq0/c+LquyaTyfRfPQBCJ0m1zZN96gAAAABJRU5ErkJggg==","orcid":"","institution":"Fudan University","correspondingAuthor":true,"prefix":"","firstName":"Ting","middleName":"","lastName":"Zhang","suffix":""},{"id":468140058,"identity":"48d73d8d-ee3e-490f-baec-456b3a16f109","order_by":3,"name":"Gezhi Xu","email":"","orcid":"","institution":"Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Gezhi","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-05-05 04:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6591051/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6591051/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12886-025-04266-7","type":"published","date":"2025-07-23T15:57:19+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84306335,"identity":"6b7091c8-d727-4a4d-a523-697244d06466","added_by":"auto","created_at":"2025-06-10 11:24:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5821541,"visible":true,"origin":"","legend":"\u003cp\u003eInitial presentations in both eyes. (A and B) Ultra-field optos funduscopy showing diffuse vitreous cells and perivenous infiltrates that resemble “candle-wax drippings” in both eyes. (C and D) Fundus fluorescein angiography showing diffuse hyperfluorescent leakage along the retinal veins and staining of the peripapillary subretinal lesions. (E and F) Optical coherence tomography showing hyperreflective peripapillary subretinal lesions.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6591051/v1/efe5a112845ddd0d5d439175.png"},{"id":84306351,"identity":"3784b4a4-7eb3-41fe-b918-0b1f7a916d31","added_by":"auto","created_at":"2025-06-10 11:24:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5564095,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in peripapillary choroidal neovascularization (PCNV) in both eyes one month (A and B), two months (C and D), three months (E and F) and four months (G and H) after systemic anti-inflammatory treatment. The PCNV in the left grew slowly towards the macular region despite resolution of vitreous cells and retinal vasculitis.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6591051/v1/0a3fba963991f1f70147315c.png"},{"id":84306251,"identity":"b168351c-6ccd-4c1d-a9fc-8e2e848a12f6","added_by":"auto","created_at":"2025-06-10 11:24:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":9051725,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in peripapillary choroidal neovascularization (PCNV) before and after anti-VEGF treatment in the left eye. (A) Color funduscopy, (B) red-free funduscopy and (C) optical coherence tomography angiography (OCTA) showing PCNV growing towards the macula and outer layers of the fovea were disrupted at month 22. (D) OCTA showing shrinkage of PCNV after three injections of anti-VEGFs at month 26. (E) OCTA showing reactivation of PCNV with subretinal fluid at month 33. (F) OCTA showing shrinking of PCNV again after the fifth injection of anti-VEGFs and subcutaneous adalimumab was switched back to a biweekly regiment. The PCNV remained stable at the last follow-up at month 46.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6591051/v1/0e0c46097992ff71bb3840f6.png"},{"id":87756687,"identity":"46cdac07-db23-4c81-9d45-ea7138b33f39","added_by":"auto","created_at":"2025-07-28 16:07:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":20220967,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6591051/v1/38cfe129-acf8-4a89-8873-7d4219bf73d8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric peripapillary choroidal neovascularization secondary to ocular sarcoidosis: a long-term follow-up case","fulltext":[{"header":"Background","content":"\u003cp\u003eSarcoidosis is a multisystemic and granulomatous inflammatory disease of unknown cause. Pediatric sarcoidosis is a rare condition with a higher incidence in patients aged 13 to 15 years. Ocular involvement is the presenting symptom in nearly 30%-60% patients[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Choroidal neovascularization (CNV) was a severe sight-threatening complication of both infectious and non-infectious uveitis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Peripapillary choroidal neovascularization (PCNV) account for 10% of all CNV[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], which was previously reported in adult ocular sarcoidosis. Here we described a unique case of pediatric sarcoidosis with bilateral PCNV.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 14-year-old boy was referred to our hospital with a 2-month history of floaters and gradual vision loss in both eyes. He was born with congenital hypothyroidism and had no history of trauma or infection.\u003c/p\u003e \u003cp\u003eOn examination, the best-corrected visual acuity (BCVA) was 20/400 in the right eye (RE) and 20/80 in the left eye (LE). Intraocular pressure (IOP) was 14.1 mmHg RE and 17.3 mmHg LE. Slit-lamp examination revealed anterior chamber flares in both eyes. Fundus examination exhibited diffuse vitreous cells and perivenous infiltrates which resembled “candle-wax drippings” (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). Fundus fluorescein angiography (FFA) demonstrated diffuse hyperfluorescent leakage along the retinal veins and staining of the peripapillary subretinal lesions (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). Hyper-reflective peripapillary subretinal lesions were detected by enhanced-depth imaging optical coherence tomography (EDI-OCT) in both eyes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eE and \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eLaboratory tests, including complete blood count, erythrocyte sedimentation rate, C-reactive protein level, and autoimmune antibody tests, revealed no abnormalities. Syphilis and Toxoplasma serology test results were negative. serum angiotensin-converting enzyme (ACE) level was elevated (114.4 U/L; reference range 6–86 U/L). Polymerase Chain Reaction test of the aqueous humor RE revealed no viral or Bartonella infections. Both the tuberculin skin test and the interferon-gamma release assay were negative. No skin nodules were observed. The ultrasonographic findings of the thyroid, liver, spleen, and kidneys were normal. Magnetic resonance imaging (MRI) of the brain and chest computed tomography (CT) of the chest revealed no abnormalities. Positron emission tomography (PET) throughout the body revealed increased metabolism of 18F-fluorodeoxyglucose (18F-FDG) in the nasopharynx, in the duodenal bulb and several segments of the small intestine. A diagnosis of probable ocular sarcoidosis was made based on the presence of elevated serum ACE levels and abnormal 18F-FDG PET imaging findings in conjunction with compatible granulomatous uveitis (including signs of string of pearls vitreous opacities, segmental periphlebitis, and bilateral inflammation) according to the revised criteria of the International Workshop on Ocular Sarcoidosis (IWOS)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe patient was prescribed oral prednisone (50 mg per day). Although a relatively low loading dose of oral corticosteroids (nearly 0.6 mg/kg/d, his body weight was 90 kg) was used, his IOP increased two weeks post treatment. Oral prednisone was tapered and stopped after two months. Oral methotrexate (MTX, 15 mg every week) and subcutaneous injections of adalimumab (40 mg every two weeks) were administered as part of the therapeutic regimen in consultation with the pediatric rheumatology department.\u003c/p\u003e \u003cp\u003eThe vitreous cells and vasculitis resolved gradually over the 4-month treatment period, and his BCVA improved to 20/25 in both eyes. However, the PCNV in the left eye grew slowly towards the macular region (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Intravitreal injection of anti-vascular endothelial growth factor (VEGF) was recommended; however, due to the COVID − 19 pandemic, the injection was interrupted, and the patient was lost to follow - up for 17 months. The patient was treated with oral methotrexate (MTX; 15 mg weekly) and subcutaneous injections of adalimumab (40 mg every two weeks). In addition, he had not received any COVID-19 vaccination.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAt 22 months of follow-up, the patient’s BCVA LE had worsened to 20/100. Fundus examination revealed no vitreous cells in either eye; however, the PCNV LE grew closer to the fovea, and the outer layer of the fovea was disrupted (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). Repeated FFA showed patchy hyperfluorescent leakage of PCNV in both eyes. Three intravitreal injections of LE aflibercept were administered. The growth of PCNV was controlled (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSubcutaneous injections of adalimumab (40 mg every two weeks) were tapered to 40 mg every four weeks after two years of treatment. At 33 months (5 months after adalimumab tapering), OCT angiography (OCTA) revealed PCNV growth with increased subretinal fluid LE (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eE). A fourth intravitreal aflibercept injection was administered to the left eye. At 41 months (12 months post adalimumab tapering), OCTA revealed recurrent PCNV growth in both eyes. Intravitreal injection of aflibercept was repeated in both eyes, and subcutaneous injections of adalimumab were adjusted back to biweekly dosing with consultations from the rheumatology department.\u003c/p\u003e \u003cp\u003eSerum uric acid (546 µmol/L) was raised two years after immunomodulatory treatment and was treated accordingly. Routine magnetic resonance imaging (MRI) of the brain and chest CT scan were negative. The echocardiogram results were normal. PCNVs in both eyes was controlled with the BCVA at 20/20 RE and 20/60 LE (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eF). Biweekly subcutaneous injections of adalimumab were still maintained. Currently, the patient is undergoing regular follow-ups and observation.\u003c/p\u003e "},{"header":"Discussion and conclusions","content":"\u003cp\u003eThis case presents a 14-year-old boy with persistent peripapillary choroidal neovascular membrane associated with probable ocular sarcoidosis related uveitis. The PCNV grew very slowly toward the macula in one eye despite systemic immunosuppressant treatment, which is a rare complication of ocular sarcoidosis.\u003c/p\u003e\u003cp\u003eThe gold standard for diagnosis of sarcoidosis is histopathologic confirmation from tissue biopsy. However, biopsy not done for our patient, and he was negative for bilateral hilar lymphadenopathy, thus a probable diagnosis of sarcoid uveitis was made in accordance with the IWOS criteria. The goals of treatment for pediatric uveitis include controlling intraocular inflammation, preventing recurrence of inflammation, and reducing ocular complications and vision loss[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, there are no standardized treatment protocols for pediatric non-infectious uveitis. In our case, we prescribed oral corticosteroids and steroid-sparing anti-rheumatic drug MTX was added timely. A long-term use of an anti-tumor necrosis factor agent adalimumab was also recommended to our patient by rheumatology department, which was consistent with previous research that patients under long-term adalimumab therapy were likely to achieve disease control[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMeanwhile the PCNV at initial presentation was another indication for the prompt immune-modulatory therapy for our patient, which was still not fully controlled through the follow up. The PCNV in his left eye slowly but persistently grew towards the macula, resulting the vision decrease LE. It is interesting that the PCNV evolved into fibrosis around the papilla except that part of PCNV at the macula portion was comprised of vascular signals, suggesting the relatively higher metabolic environment resulting higher VEGF level at that macula. The intravitreal anti-VEGF treatment could partially reduce the growth of the inflammatory CNV, which was consistent with other studies[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the PCNV was not totally controlled with four injections of anti-VEGF drug. The subcutaneous injection of adalimumab was tapered to 40mg every four weeks might be an explanation. In a recent study of Airaldi’s, the inflammatory CNV secondary to idiopathic multifocal choroiditis was better controlled by immunomodulatory therapy[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. As a result, we advised the patient to switch back to the every-two-week dosing of adalimumab. At the last visit, his PCNV showed no signs of further development.\u003c/p\u003e\u003cp\u003eThere is limited literature regarding the duration of follow-up for ocular sarcoidosis. Pediatric uveitis can lead to long-term vision impairment if not appropriately treated and followed[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A case of bilateral subretinal fibrosis ten years after first presentation with chronic ocular sarcoidosis in a child was sobering[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition, inflammatory CNV was found much more frequently (both at initial presentation and throughout follow-up) in cases of posterior and panuveitis[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], which is another reason for the need of long-term follow up for pediatric uveitis.\u003c/p\u003e\u003cp\u003eIn summary, a multidisciplinary approach and long-term follow-up for pediatric ocular sarcoidosis with PCNV was necessary.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCNV: choroidal neovascularization; PCNV: peripapillary choroidal neovascularization; BCVA: best-corrected visual acuity; RE: right eye; LE: left eye; IOP: intraocular pressure; FFA: fundus fluorescein angiography; EDI-OCT: enhanced-depth imaging optical coherence tomography; ACE: angiotensin-converting enzyme; CT: computed tomography; PET: positron emission tomography; 18F-FDG: 18F-fluorodeoxyglucose; IWOS: the international workshop on ocular sarcoidosis; MTX: methotrexate; VEGF: anti-vascular endothelial growth factor; OCTA: OCT angiography.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report adhered to the Declaration of Helsinki and was approved by the Institutional Review Board of the Eye and Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of clinical details and clinical images was obtained from the parents of the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone of the authors has any conflicting interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the 2024 Clinical Scientists Programme of Shanghai Medical School, Shanghai Hospital Development Center Foundation (SHDC12023116) and the National Natural Science Foundation of China (82201204).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYZ and TZ performed the investigation and data collection, while KW and GX provided resources and validated the findings. YZ and TZ wrote the original draft, and all authors (YZ, TZ, and KW) participated in manuscript review and editing.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMa SP, Rogers SL, Hall AJ, Hodgson L, Brennan J, Stawell RJ, Lim LL: Sarcoidosis-related Uveitis: Clinical Presentation, Disease Course, and Rates of Systemic Disease Progression After Uveitis Diagnosis. Am J Ophthalmol 2019,198(3): 30-36.\u003c/li\u003e\n\u003cli\u003eBaxter SL, Pistilli M, Pujari SS, Liesegang TL, Suhler EB, Thorne JE, Foster CS, Jabs DA, Levy-Clarke GA, Nussenblatt RB et al: Risk of choroidal neovascularization among the uveitides. Am J Ophthalmol 2013, 156(3):468-477.\u003c/li\u003e\n\u003cli\u003eJutley G, Jutley G, Tah V, Lindfield D, Menon G: Treating peripapillary choroidal neovascular membranes: a review of the evidence. Eye (Lond) 2011, 25(6):675-681.\u003c/li\u003e\n\u003cli\u003eMochizuki M, Smith JR, Takase H, Kaburaki T, Acharya NR, Rao NA, International Workshop on Ocular Sarcoidosis Study G: Revised criteria of International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis. Br J Ophthalmol 2019, 103(10):1418-1422.\u003c/li\u003e\n\u003cli\u003eSood AB, Angeles-Han ST: An Update on Treatment of Pediatric Chronic Non-Infectious Uveitis. Curr Treatm Opt Rheumatol 2017, 3(1):1-16.\u003c/li\u003e\n\u003cli\u003eNott K, Nott V, Lever E, Deakin C, Galloway J, Fisher C, Compeyrot-Lacassagne S: Pediatric Sarcoidosis: Retrospective Analysis of Biopsy-Proven Patients. J Rheumatol 2023, 50(7):924-933.\u003c/li\u003e\n\u003cli\u003eWoronkowicz M, Niederer R, Lightman S, Tomkins-Netzer O: Intravitreal Antivascular Endothelial Growth Factor Treatment for Inflammatory Choroidal Neovascularization in Noninfectious Uveitis. Am J Ophthalmol 2022, 236:281-287.\u003c/li\u003e\n\u003cli\u003eAiraldi M, Monteduro D, Tondini G, Pichi F, De Simone L, Cornish E, Casalino G, Zicarelli F, Oldani M, Staurenghi G et al: Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis. Am J Ophthalmol 2024, 262:62-72.\u003c/li\u003e\n\u003cli\u003eKim L, Li A, Angeles-Han S, Yeh S, Shantha J: Update on the management of uveitis in children: an overview for the clinician. Expert Rev Ophthalmol 2019, 14(4-5):211-218.\u003c/li\u003e\n\u003cli\u003eMavris N, Jaouni T, Amer R: Subretinal Fibrosis Developing 10 Years After First Presentation with Chronic Ocular Sarcoidosis in a Child. Ocul Immunol Inflamm 2024:1-4.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sarcoidosis, Choroidal Neovascularization, Uveitis, Pediatric, Anti-vascular Endothelial Growth Factor, Immunosuppressive Agents","lastPublishedDoi":"10.21203/rs.3.rs-6591051/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6591051/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: To describe a boy with probable ocular sarcoidosis and bilateral peripapillary choroidal neovascularization (PCNV).\u003c/p\u003e\n\u003cp\u003eCase presentation: We report a case of a 14-year-old boy with a 2-month history of floaters and gradual vision loss in both eyes. Examination revealed bilateral granulomatous uveitis with peripapillary subretinal lesions. Level of serum angiotensin-converting enzyme was elevated. Positron emission tomography demonstrated increased metabolic activity in the nasopharynx and small intestine, consistent with diagnosis of sarcoidosis. Despite resolved vitreous cells and retinal vasculitis, the PCNV progressed slowly in the left eye, which was controlled with combined treatment of immunomodulatory regiment and multiple intravitreal anti-vascular endothelial growth factor injections over a prolonged period.\u003c/p\u003e\n\u003cp\u003eConclusions: This case highlights the need for a multidisciplinary approach and long-term follow-up in pediatric ocular sarcoidosis with PCNV.\u003c/p\u003e","manuscriptTitle":"Pediatric peripapillary choroidal neovascularization secondary to ocular sarcoidosis: a long-term follow-up case","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-10 11:24:27","doi":"10.21203/rs.3.rs-6591051/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-06-30T05:41:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-29T21:49:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-16T14:58:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106322788993900342020775223369187448088","date":"2025-06-15T22:16:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-14T06:08:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"297686530520664511730627597494293276768","date":"2025-06-08T12:26:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229037696170474105075201352361688586715","date":"2025-06-06T14:21:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-06T10:04:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-04T07:09:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-14T07:21:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-11T08:17:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-05-11T08:16:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"890d3b30-585d-426c-91a6-72feb0a485d8","owner":[],"postedDate":"June 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T16:00:23+00:00","versionOfRecord":{"articleIdentity":"rs-6591051","link":"https://doi.org/10.1186/s12886-025-04266-7","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-07-23 15:57:19","publishedOnDateReadable":"July 23rd, 2025"},"versionCreatedAt":"2025-06-10 11:24:27","video":"","vorDoi":"10.1186/s12886-025-04266-7","vorDoiUrl":"https://doi.org/10.1186/s12886-025-04266-7","workflowStages":[]},"version":"v1","identity":"rs-6591051","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6591051","identity":"rs-6591051","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}