Beyond the conventional paradigm: perspectives from COVID-19, hepatitis C therapy, and cases associated with pregnancy on Vogt-Koyanagi-Harada disease, a narrative review

Introduction

Background

Vogt-Koyanagi-Harada (VKH) is a complex autoimmune disorder, which, in its advanced stage, is characterized by bilateral granulomatous uveitis accompanied by involvement of other systems, including significant changes to the skin and disturbances in the nervous or auditory systems. The condition acquires its eponym from three distinguished physicians—Alfred Vogt [1906], Einosuke Harada [1926], and Yoshizo Koyanagi [1929]—each of whom independently characterized pivotal aspects of the syndrome, including intense intraocular inflammation, marked neurological sequelae, and distinctive dermatological changes. These distinct clinical observations were methodically integrated to form the cohesive nosological construct now designated as VKH disease (1). VKH disease may initially present with a persistent headache, even in the absence of clear eye-related symptoms (2). VKH primarily affects races with darker skin tones, but it is also uncommon in Africans, indicating that skin pigmentation is not the only etiologic factor in its Patho development (3). Early posterior uveitis and, if left untreated, recurrent granulomatous anterior uveitis are the hallmarks of VKH in Chinese patients (4). In a retrospective cohort study conducted by Bykhovskaya et al. at a single academic center, 79% of the patients were female (5). Similarly, a study from Turkey—where VKH is relatively uncommon—also reported a higher prevalence among women, accounting for 71.1% of the cases (6). Most cases in Turkey were diagnosed in the chronic stage, frequently as incomplete or probable VKH, with complications like pigment clumping and sunset-glow fundus, most likely because of delayed referrals (6). Likewise, in Iran, the ‘probable’ form of VKH predominated, with ocular signs like Chorioretinal scars and sunset-glow fundus, while integumentary findings were uncommon (7). About 25% of people with VKH disease in the Japanese cohort experience recurrent episodes of inflammation. Recurrent inflammation was found to primarily manifest as posterior uveitis in 8 and anterior uveitis in 6 of the 55 Japanese patients with VKH disease complicated by exudative retinal detachment (8). In North Africa, VKH continues to be a major cause of uveitis, ranking as the fourth most common overall and the second leading cause of panuveitis during the study period (9). Given the virulent nature of the disease and its effects on various organ systems, early detection based on clinical suspicion is essential for better long-term prognoses and optimal management, particularly in populations at higher risk. VKH disease has been linked in recent years to several clinical settings, including immunological changes during pregnancy, antiviral treatments [most notably interferon-alpha (IFN-α) for hepatitis C], and viral infections [especially coronavirus disease 2019 (COVID-19)]. These situations present challenges for diagnosis and treatment that deviate from the usual manifestations of diseases and approaches to their treatment.

Rationale and knowledge gap

This review is the first to look at VKH cases that might be linked to COVID-19 (either from the infection or vaccination), pregnancy, and IFN-α treatment for hepatitis C all at the same time. By combining these topics, we gain a wider understanding of how different immune-related factors might trigger or worsen VKH. We also gathered 14 recent COVID-related VKH case reports into an updated summary table (Table 1). Comparing these three situations side by side helps us see common immune system problems, difficulties in diagnosis during different stages, and important points for adjusting treatment. This review fills an important gap by giving a broad and connected view of VKH, going beyond earlier reviews that looked at these issues separately.

Objective

This review attempts to summarize new data from these specific settings and investigate how they deepen our knowledge of the pathophysiology of VKH and its responses to treatment. We present this article in accordance with the Narrative Review reporting checklist (available at https://aes.amegroups.com/article/view/10.21037/aes-25-26/rc).

Methods

A narrative review methodology was used to examine VKH disease in relation to COVID-19, hepatitis C therapy, and pregnancy. PubMed was the primary database, with supplementary searches in Google Scholar. No time limits were applied; the last search was completed in April 2025. Search terms included “Vogt-Koyanagi-Harada disease”, “Vogt-Koyanagi-Harada syndrome”, “VKH”, “COVID-19”, “SARS-CoV-2”, “Hepatitis C”, and “Pregnancy”, combined using Boolean operators. Eligible studies were limited to English-language, peer-reviewed publications reporting original clinical data, case reports, or observational studies. Non-peer-reviewed material was excluded. Study selection was performed independently by two reviewers (M.S. and M.S.). Titles, abstracts, and full texts were screened, and any discrepancies were resolved through consensus (Table 2).

Importance of early diagnosis

Early detection of VKH is essential to avoiding long-term complications and irreversible vision loss. VKH may present as other conditions in atypical situations, such as pregnancy, recent vaccination or infection, and co-occurring hepatitis C. Human leukocyte antigen (HLA) typing, lumbar puncture, and multimodal imaging could help refine the diagnosis. When overlapping systemic changes obscure standard presentation, these tools become even more crucial.

Mechanism and pathophysiology

The hallmark of VKH is an autoimmune reaction that specifically targets melanocytes in the tissues of the eyes. It has been demonstrated that melanocyte-specific antigens like tyrosinase and gp100 are recognized by ocular-infiltrating CD4⁺ T cells. These T cells frequently have a Th1 cytokine profile, which is linked to their function in promoting intraocular inflammation and aiding in the disease’s etiology (24). Tyrosinase peptides and cytomegalovirus (CMV) antigens, particularly the CMV envelope glycoprotein H (CMV-egH), exhibit cross-reactivity in patients with VKH. This interaction suggests that one of the key mechanisms supporting the start of the autoimmune response may be molecular mimicry (25). Shindo et al. demonstrated a robust association between VKH and the HLA-DR4 allele, especially the DRB10405 subtype. According to PCR-RFLP genotyping, all VKH patients had either DRB10405 or DRB10410, which share a serine residue at position 57 in the antigen-binding groove and may also increase susceptibility to the disease (26). Likewise, a study in Japanese patients confirmed a highly significant association between DRB10405 and VKH, while no significant links were found with polymorphisms in the tyrosinase gene family (TYR, TYRP1, and DCT), underscoring the dominant role of HLA class II genes in VKH pathogenesis (27). Tyrosinase-related proteins, particularly TRP-1 and TRP-2, which are expressed in the central nervous system (CNS) as well as in skin and eye melanocytes are the main target of the autoimmune response in VKH. With both ocular and extraocular inflammation seen in animal models, such as the immunization of Lewis rats with TRP-1 and TRP-2, which replicates the clinical features of the human disease, this cross-reactivity points to a possible involvement of the CNS in the pathophysiology of VKH (28). There may be common pathogenic mechanisms behind Behçet’s disease (BD) and VKH, as microRNA-182 (miR-182) has been identified as a potential genetic susceptibility factor for both conditions. Although no significant correlation was found between BD or VKH risk and miR-27a, FoxO1, or IL2RA SNPs, a study by Yu et al. [2014] demonstrated that miR-182 contributes to the genetic susceptibility of both BD and VKH (29). The role of small extracellular vesicles (sEVs), which transport microRNAs that control immune responses, has been investigated in more detail. For instance, it has been demonstrated that sEVs derived from plasma from VKH patients inhibit T cell proliferation by means of microRNA-410-3p. This microRNA shapes the inflammatory environment and regulates the CXCL5 axis, offering information about possible treatment approaches that target immune tolerance in VKH (30). A localized immune response in the cerebrospinal fluid (CSF) is caused by melanocytes in the CNS expressing different surface antigens than those in other tissues in VKH disease. This is corroborated by research showing that CSF leukocytes have distinct immune cell markers from peripheral blood leukocytes and exhibit less cytotoxic activity against melanoma cells. According to these variations, meningeal melanocytes might have distinct antigens that contribute to the compartmentalized inflammation observed in VKH (31). Furthermore, the existence of melanocytic antigens in the CNS is further supported by the presence of melanin-loaded macrophages in the CSF. This implies that the inflammation and pleocytosis seen in the early stages of VKH syndrome are caused by a localized immune response that targets melanocytes in the meninges (32). However, Abad et al. reported that T cells are isolated from the CSF of VKH patients were unable to identify shared melanocytic antigens (33). These results highlight how intricate the pathophysiology of the illness is. Important gaps still exist despite tremendous progress in identifying important antigens and genetic predispositions. Although suggestive, the evidence for molecular mimicry is still circumstantial, and it is unclear exactly how vaccination and viral infections contribute to the development of autoimmunity in VKH. Moreover, it is still unclear why only a small percentage of genetically predisposed people experience VKH after COVID-19 or interferon therapy. These open questions underscore the necessity of additional immunogenetic and epidemiological research.

The four classical phases

Prodromal phase: not just headache and meningismus

Meningeal irritation is one of the prodromal symptoms, which frequently appear suddenly. headache, Meningismus, tinnitus and nausea are some of the symptoms of aseptic meningitis (34-36). However, Khairallah et al. demonstrated a patient with a headache alone, devoid of any other meningitis symptoms (37). According to Andreoli and Foster, neurological symptoms such as headache, meningismus, encephalitis, and cranial nerve palsies can manifest during the prodromal stage of VKH. These symptoms may be initially disregarded because they frequently resemble those of viral syndromes. The disease’s systemic neuroinflammatory nature is highlighted by the fact that CSF analysis often shows lymphocytic pleocytosis one to two weeks before the onset of ocular symptoms (38).

Uveitic phase: are multimodal imaging findings shifting diagnostic timelines?

This stage is marked by papillitis, vitritis, and choroiditis along with bilateral vision blurring. One to three days may pass between the involvement of both eyes. The characteristic thickening seen on ultrasonography is caused by inflammatory cell infiltration into the choroid (3). The retina separates from the retinal pigment epithelium (RPE) during the uveitic stage. The subretinal detached region exhibits an eosinophilic exudate that contains proteinaceous material. Multinucleated giant cells and focal aggregates of epithelioid histiocytes are among the lymphocytes that have diffusely infiltrated the choroid (39). Additionally, optic nerve head (ONH) swelling has been linked to reduced retinal blood flow, lower oxygen levels in retinal venules, and an increased difference in oxygen saturation between arterioles and venules (40). Fundus photography and fundus fluorescein angiography (FFA) have historically been used to diagnose VKH. However, more precise visualization of subretinal fluid and lesions has been made possible by more recent imaging techniques like optical coherence tomography (OCT). Comparing OCT to FFA, OCT showed a greater percentage of patients with subretinal fluid, indicating that OCT is more sensitive in identifying acute VKH changes that may not yet be apparent on fundoscopy (41). This increased sensitivity may facilitate earlier diagnosis and treatment, although further research is needed to determine its impact on long-term outcomes (41). In addition to a thickened choroid in the acute stage and possibly a thinned choroid in the chronic stage, OCT features of VKH include intraretinal edema in the outer retinal layers, subretinal membranous structures, and subretinal hyperreflective dots (42). In the non-acute uveitic stage, choroidal bulging—an enhanced depth imaging (EDI)-OCT finding that may reflect ongoing inflammation—can serve as a useful indicator for monitoring treatment response and disease activity (43).

Chronic convalescent phase

Signs of depigmentation in integumentary and/or uveal tissue are indicative of this stage. The most prevalent symptom of choroid depigmentation at this stage is sunset glow fundus (4). Latent choroidal inflammation during the convalescent stage of VKH may be the cause of the thinner choroid and larger peripapillary atrophy areas, which were correlated with the extent of depigmentation or the length of the disease (44).

Recurrent phase

The chronic recurrent stage is characterized by mild panuveitis with recurrent episodes of anterior uveitis. This stage is usually considered to be the result of inadequate or delayed treatment with corticosteroids for the disease (34). Subretinal fibrosis, glaucoma, choroidal, and chorioretinal atrophy are among the vision-threatening complications that are known to arise during this phase of VKH disease (45). In a study by Ahn et al. the ciliary body and pars plana were significantly involved in the recurrent phase of VKH disease, but there were no supraciliary effusions (46). The iris may develop Busacca nodules, which are round, whitish, and well-circumscribed nodules. Systemic corticosteroid therapy frequently fails to alleviate these recurrent episodes of inflammation (3). Despite receiving high-dose treatment within 30 days of the onset of the disease and a gradual taper of prednisone, 79% of patients in the Brazilian cohort with VKH disease developed chronic-recurrent disease (47).

Treatment strategies

Corticosteroid therapy

Systemic corticosteroids, administered in high doses either orally or through intravenous pulse therapy, are the primary treatment for acute VKH disease due to their strong anti-inflammatory effects (48-50). In addition, the use of corticosteroids during the acute phase of VKH has been linked to improved visual acuity and the resolution of intraocular inflammation (51) (Table 3). Although systemic corticosteroids are still first-line treatments, long-term use of these medications can cause serious side effects like glucose intolerance, hypertension, and osteoporosis. Prednisolone is usually regarded as safe in pregnant patients because of its low placental transfer; nevertheless, monitoring for fetal growth restriction is recommended.

Immunosuppressive therapy

Immunosuppressive medications such as methotrexate (MTX) and azathioprine (AZA) are also used either alone or in conjunction with corticosteroids (85,86). In 6–9 months, corticosteroids are gradually decreased, and immunosuppressive medications should be taken continuously until inflammation is completely under control and does not recur (58). Mycophenolate mofetil, MTX, and AZA are examples of immunosuppressive medications that are good steroid-sparing choices for patients who need long-term control or who are having steroid-related side effects (54,66,87). Immunomodulatory treatment, when started early, is associated with better visual results and fewer relapses (64). In cases of refractory or chronically relapsing VKH, biologic therapies—specifically, tumor necrosis factor-alpha (TNF-α) inhibitors like adalimumab and infliximab—have shown promise as treatments (71,81). Although infliximab and adalimumab are used more frequently in refractory cases, they are contraindicated in patients who need to be screened for tuberculosis and have active infections. There is little information on their use during pregnancy, although it appears that there is little transplacental transfer during the first two trimesters. A study supports the use of adalimumab combined with immunosuppressants as an alternative to conventional corticosteroid-based regimens, even in treatment-naïve patients who cannot tolerate corticosteroids (74). Combination therapies may provide better control than corticosteroids alone in acute VKH, according to Concha-Del Río et al. (67). According to Dai et al., cyclosporine-corticosteroids (CSA-CS) continue to be the more economical option for most patients with VKH, even though adalimumab-corticosteroids (ADA-CS) provide modest improvements in quality-adjusted life-years (82). In complex VKH cases, triple-agent immunosuppressive protocols have also been documented to produce positive results (52). Despite being teratogenic in animal models, AZA has been used with caution during pregnancy. Because of its abortifacient effects, MTX should not be used. Mycophenolate should be avoided because it has a high risk of birth defects. Immunosuppressant and antiviral medication use in hepatitis C patients’ needs to be closely watched for hepatic function.

Local ocular treatment

According to Karacorlu et al., intravitreal injections of triamcinolone acetonide could be used as an extra treatment option for VKH (53) (Table 3). Fluocinolone acetonide and other local corticosteroid implants have shown satisfactory safety profiles and long-term results in the treatment of chronic VKH (65). Triamcinolone acetonide administered intravitreally is usually saved for chronic VKH patients whose inflammation does not resolve with systemic treatment. It is particularly helpful in patients who require rapid control of localized inflammation or in whom systemic corticosteroids are contraindicated.

The viral hypothesis: potential causative factor, trigger, or coincidental finding?

VKH after COVID-19 infection or vaccination: is there an association?

Reactivation or de novo onset of VKH disease following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination has been documented in several case reports since the start of the COVID-19 pandemic (11-13).

Several theories have been put forth in the literature to explain a potential connection between VKH and COVID-19 infection or immunization. Following an infection or vaccination, one theory proposes that the immune system may change from a T-helper 2 (Th2)-dominant to a Th1-dominant response, potentially revealing a latent autoimmune predisposition (14) (Table 1). Cross-reactive immune responses may arise from molecular mimicry, another theory that has been put forth. This mechanism involves structural similarities between host antigens and viral proteins (88). The spike glycoprotein from mRNA vaccines has also been hypothesized to function as an immunological potentiator, potentially causing VKH-like uveitis, particularly in genetically susceptible individuals like those with HLA-DR4 (16) (Table 1). It is crucial to stress that these suggested mechanisms are not the findings of this paper; rather, they represent the viewpoints of the cited authors. It will take epidemiological research to ascertain whether there is a real correlation between VKH illness and COVID-19 infection or vaccination. The large variability in timing between COVID-19 infection or vaccination and the onset of VKH symptoms, which ranged from concurrent to four months later, does not support a strong association. Moreover, the evidence currently available does not support a causal relationship because of the enormous number of vaccinations and infections in comparison to the comparatively small number of case reports.

VKH disease in pregnancy

Gestation orchestras a complex immunological response, characterized by a shift toward a Th2-dominant immune phenotype, which supports maternal immune tolerance of the semi-allogeneic conceptus, thereby allowing its prolonged intrauterine presence (89). The immune changes that occur during pregnancy can temporarily reduce Th1-driven autoimmune responses, which may alter the progression of autoimmune conditions like VKH disease. Notably, Sugita et al. (90) documented a rapid resolution of subretinal fluid in a pregnant patient with VKH disease, achieved without the administration of high-dose corticosteroids. VKH can appear during pregnancy and have a clinical course comparable to that of nonpregnant women (91). To treat VKH during pregnancy, maternal health and fetal safety must be balanced. When used appropriately, high-dose systemic corticosteroids like prednisolone are widely used and generally regarded as safe. The ocular symptoms of a 26-year-old pregnant woman who received high dose corticosteroids after 18 weeks of pregnancy improved. Nevertheless, the baby was born underweight and with congenital defects such as preauricular appendages and epibulbar dermoids. Rather than being brought on by the corticosteroid treatment, these abnormalities were probably inherited. Although more research is required, high-dose corticosteroids for VKH during pregnancy do not seem to raise the risk of abortion or severe malformations (92). sub-Tenon injection of triamcinolone acetonide should be taken into consideration for the initial treatment of new-onset VKH disease during pregnancy, according to Nakamura et al. No signs of chronic or recurrent inflammation were found during the 13-month follow-up period, and there were no systemic effects on the pregnancy over the fetus (93). If standard therapies are ineffective, immunosuppressive agents such as AZA can be an option. Despite being a category D drug, it has been used carefully during early pregnancy under close supervision, with Ingolotti et al. reporting positive outcomes (94). In a case report by Ueyama et al. [2024], a gravid patient diagnosed with VKH disease demonstrated favorable clinical outcomes after the administration of steroid pulse therapy. This underscores the critical significance of an individualized therapeutic strategy when managing VKH disease during pregnancy (95). However, even in the later stages of pregnancy, VKH can manifest for the first time. A headache should not be written off as a harmless ailment because it can occur before any ocular symptoms, especially if it is severe and persistent. Such presentations may cause diagnostic confusion and delay, which could lead to irreversible visual loss, as demonstrated by Matsubara et al. Therefore, when headache and visual disturbances occur during pregnancy, obstetricians and clinicians should keep a high index of suspicion and seek an ophthalmologic evaluation as soon as possible (96).

VKH in hepatitis C patients receiving interferon therapy: could IFN-α be double-edged sword?

Ribavirin and IFN-α have been the most widely used treatments for chronic hepatitis C (97). The type 1 interferon family member IFN-α is essential for the Host’s immune system to defend against viral and malignant diseases (98). On the other hand, Ribavirin and interferon-α have been connected to the reactivation of VKH disease in susceptible individuals. In a case described by Soma et al., a 60-year-old woman with a 17-year history of inactive VKH had a relapse three weeks after starting pegylated interferon-α and ribavirin for chronic hepatitis C. The relapse was characterized by blurred vision, eye discomfort, and worsening hearing loss. Her symptoms went away entirely after the antiviral medication was stopped and corticosteroid therapy was started, and she was able to see normally again without any lingering ocular inflammation (99). This highlights the paradoxical role of IFN-α, which acts as a powerful antiviral treatment for hepatitis C while also potentially triggering autoimmune conditions. Many studies have documented instances in which the initiation of interferon therapy, both as a standalone treatment and in conjunction with ribavirin, has catalyzed the onset of VKH in individuals with hepatitis C who were previously asymptomatic. Prominent cases, as reported by Duan et al. (100), Al-Muammar et al. (101), and other researchers (102), highlight the intricate nature of IFN therapy in this patient population. These observations underscore the dual nature of IFN-α, which, while efficacious in viral clearance, can simultaneously provoke immune responses that may lead to the manifestation of VKH. The autoimmune side effects of interferon therapy and its role in inciting inflammatory conditions like VKH were highlighted by Sylvestre et al. (103) when they reported VKH in a patient following this regimen. Additionally, similar cases of patients with chronic hepatitis C developing VKH after receiving interferon therapy were examined by Touitou et al. (104), who hypothesized that the immune response triggered by interferon might aggravate or uncover latent autoimmune predispositions. These results highlight the need for close observation in patients receiving interferon-based treatments, especially those with chronic hepatitis C who may be more susceptible to developing VKH.

Conclusions

This review highlights the challenges and insights associated with VKH disease in unusual settings. Genetically predisposed people may have latent autoimmunity that is revealed by COVID-19 infection or vaccination. Pregnancy-related immunological changes can modify the course of VKH, necessitating a careful evaluation of the risks and benefits of various treatments. Paradoxically, IFN-α treatment for hepatitis C patients may trigger a recurrence of the illness. These situations highlight the need for specialized treatment plans that are based on the patient’s comorbidities, immunological status, and clinical context. More research is needed to clarify management algorithms in these unconventional presentations.

Strengths and limitations

This review provides a comprehensive overview of VKH disease, highlighting both established and novel treatments. It also includes comprehensive tables on available treatments and VKH cases associated with COVID-19. It also looks at less discussed situations like VKH during pregnancy and following viral infections. However, generalizability is limited by the fact that most recent data originate from case reports or small studies. Large-scale studies and more randomized clinical trials are required to validate treatment effectiveness and gain a better understanding of disease triggers.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aes.amegroups.com/article/view/10.21037/aes-25-26/rc

Peer Review File: Available at https://aes.amegroups.com/article/view/10.21037/aes-25-26/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aes.amegroups.com/article/view/10.21037/aes-25-26/coif). H.A. serves as an unpaid editorial board member of Annals of Eye Science from June 2024 to December 2025. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Herbort CP, Mochizuki M. Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan. Int Ophthalmol 2007;27:67-79. [Crossref] [PubMed]
2. Kosma KK, Kararizou E, Markou I, et al. Headache as a first manifestation of Vogt-Koyanagi-Harada disease. Med Princ Pract 2008;17:253-4. [Crossref] [PubMed]
3. Damico FM, Kiss S, Young LH. Vogt-Koyanagi-Harada disease. Semin Ophthalmol 2005;20:183-90. [Crossref] [PubMed]
4. Yang P, Ren Y, Li B, et al. Clinical characteristics of Vogt-Koyanagi-Harada syndrome in Chinese patients. Ophthalmology 2007;114:606-14. [Crossref] [PubMed]
5. Bykhovskaya I, Thorne JE, Kempen JH, et al. Vogt-Koyanagi-Harada disease: clinical outcomes. Am J Ophthalmol 2005;140:674-8. [Crossref] [PubMed]
6. Tugal-Tutkun I, Ozyazgan Y, Akova YA, et al. The spectrum of Vogt-Koyanagi-Harada disease in Turkey: VKH in Turkey. Int Ophthalmol 2007;27:117-23. [Crossref] [PubMed]
7. Hedayatfar A, Hosseini SM, Karimi N, et al. The spectrum of Vogt-Koyanagi-Harada disease in Iran. Int Ophthalmol 2018;38:443-9. [Crossref] [PubMed]
8. Iwahashi C, Okuno K, Hashida N, et al. Incidence and clinical features of recurrent Vogt-Koyanagi-Harada disease in Japanese individuals. Jpn J Ophthalmol 2015;59:157-63. [Crossref] [PubMed]
9. Khairallah M, Zaouali S, Messaoud R, et al. The spectrum of Vogt-Koyanagi-Harada disease in Tunisia, North Africa. Int Ophthalmol 2007;27:125-30. [Crossref] [PubMed]
10. Eatz T, Charles JH. Vogt-Koyanagi-Harada syndrome in the setting of COVID-19 infection. Clin Case Rep 2023;11:e6617. [Crossref] [PubMed]
11. Yepez JB, Murati FA, Petitto M, et al. Vogt-Koyanagi-Harada Disease Following COVID-19 Infection. Case Rep Ophthalmol 2021;12:804-8. [Crossref] [PubMed]
12. Zou H, Zhang K, Chen X, et al. Vogt-Koyanagi-Harada disease after SARS-CoV-2 infection: Case report and literature review. Immun Inflamm Dis 2024;12:e1250. [Crossref] [PubMed]
13. Anthony E, Rajamani A, Baskaran P, et al. Vogt Koyanagi Harada disease following a recent COVID-19 infection. Indian J Ophthalmol 2022;70:670-2. [Crossref] [PubMed]
14. Ikuno Y, Yamaguchi A, Takahashi T, et al. Vogt-Koyanagi-Harada Syndrome Following COVID-19 mRNA Vaccination: Th2 to Th1 Transition-related Molecular Machinery. Acta Derm Venereol 2024;104:adv21502. [Crossref] [PubMed]
15. De Domingo B, López M, Lopez-Valladares M, et al. Vogt-Koyanagi-Harada Disease Exacerbation Associated with COVID-19 Vaccine. Cells 2022;11:1012. [Crossref] [PubMed]
16. Sato T, Nihei R, Sora D, et al. Case report: Bilateral panuveitis resembling Vogt-Koyanagi-Harada disease after second dose of BNT162b2 mRNA COVID-19 vaccine. Front Immunol 2022;13:967972. [Crossref] [PubMed]
17. Xu K, Gao B, Li J, et al. Clinical features, diagnosis, and management of COVID-19 vaccine-associated Vogt-Koyanagi-Harada disease. Hum Vaccin Immunother 2023;19:2220630. [Crossref] [PubMed]
18. Yamaguchi C, Kunikata H, Hashimoto K, et al. De novo Vogt-Koyanagi-Harada disease after vaccination for COVID-19, successfully treated with systemic steroid therapy and monitored with laser speckle flowgraphy. Am J Ophthalmol Case Rep 2022;27:101616. [Crossref] [PubMed]
19. Rujkorakarn P, Patamatamkul S. Vogt-Koyanagi-Harada disease following ChAdOx1 nCoV-19 and mRNA-1273 vaccination. J Fr Ophtalmol 2023;46:207-10. [Crossref] [PubMed]
20. Chen X, Wang B, Li X. Acute-onset Vogt-Koyanagi-Harada like uveitis following Covid-19 inactivated virus vaccination. Am J Ophthalmol Case Rep 2022;26:101404. [Crossref] [PubMed]
21. Muto T, Sakamoto M, Imaizumi S, et al. Reactivation of previously controlled Vogt-Koyanagi-Harada disease more than 46 years following COVID-19 vaccination: a case study. J Int Med Res 2024;52:3000605231221081. [Crossref] [PubMed]
22. Ding X, Chang Q. Probable Vogt-Koyanagi-Harada Disease after COVID-19 Vaccination: Case Report and Literature Review. Vaccines (Basel) 2022;10:783. [Crossref] [PubMed]
23. Han R, Xu G, Ding X. COVID-19 Vaccine-Related Vogt-Koyanagi-Harada Disease Complicated by Central Serous Chorioretinopathy during Treatment Course: Case Report and Literature Review. Vaccines (Basel) 2022;10:1792. [Crossref] [PubMed]
24. Sugita S, Takase H, Taguchi C, et al. Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens. Invest Ophthalmol Vis Sci 2006;47:2547-54. [Crossref] [PubMed]
25. Sugita S, Takase H, Kawaguchi T, et al. Cross-reaction between tyrosinase peptides and cytomegalovirus antigen by T cells from patients with Vogt-Koyanagi-Harada disease. Int Ophthalmol 2007;27:87-95. [Crossref] [PubMed]
26. Shindo Y, Inoko H, Yamamoto T, et al. HLA-DRB1 typing of Vogt-Koyanagi-Harada's disease by PCR-RFLP and the strong association with DRB1*0405 and DRB1*0410. Br J Ophthalmol 1994;78:223-6. [Crossref] [PubMed]
27. Horie Y, Takemoto Y, Miyazaki A, et al. Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients. Mol Vis 2006;12:1601-5.
28. Yamaki K, Kondo I, Nakamura H, et al. Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats. Exp Eye Res 2000;71:361-9. [Crossref] [PubMed]
29. Yu H, Liu Y, Bai L, et al. Predisposition to Behçet's disease and VKH syndrome by genetic variants of miR-182. J Mol Med (Berl) 2014;92:961-7. [Crossref] [PubMed]
30. Li B, Sun N, Yang F, et al. Plasma-Derived Small Extracellular Vesicles From VKH Patients Suppress T Cell Proliferation Via MicroRNA-410-3p Modulation of CXCL5 Axis. Invest Ophthalmol Vis Sci 2023;64:11. [Crossref] [PubMed]
31. Norose K, Yano A, Aosai F, et al. Immunologic analysis of cerebrospinal fluid lymphocytes in Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci 1990;31:1210-6.
32. Nakamura S, Nakazawa M, Yoshioka M, et al. Melanin-laden macrophages in cerebrospinal fluid in Vogt-Koyanagi-Harada syndrome. Arch Ophthalmol 1996;114:1184-8. [Crossref] [PubMed]
33. Abad S, Wieërs G, Colau D, et al. Absence of recognition of common melanocytic antigens by T cells isolated from the cerebrospinal fluid of a Vogt-Koyanagi-Harada patient. Mol Vis 2014;20:956-69.
34. Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol 1995;39:265-92. [Crossref] [PubMed]
35. Rajendram R, Evans M, Rao NA. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin 2005;45:115-34. [Crossref] [PubMed]
36. Beniz J, Forster DJ, Lean JS, et al. Variations in clinical features of the Vogt-Koyanagi-Harada syndrome. Retina 1991;11:275-80. [Crossref] [PubMed]
37. Khairallah AS. Headache as an initial manifestation of Vogt-Koyanagi-Harada disease. Saudi J Ophthalmol 2014;28:239-42. [Crossref] [PubMed]
38. Andreoli CM, Foster CS. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin 2006;46:111-22. [Crossref] [PubMed]
39. Rao NA. Pathology of Vogt-Koyanagi-Harada disease. Int Ophthalmol 2007;27:81-5. [Crossref] [PubMed]
40. Abu El-Asrar AM, AlBloushi AF, Gikandi PW, et al. Acute uveitic phase of Vogt-Koyanagi-Harada disease: optic nerve head swelling, ocular blood flow and retinal oxygen metabolism. Eye (Lond) 2023;37:1432-8. [Crossref] [PubMed]
41. Wu H, Hu L, Tang W, et al. Clinical Comparative Study of Different Fundus Imaging Methods in the Acute Phase of Vogt-Koyanagi-Harada Disease. Evid Based Complement Alternat Med 2022;2022:5812090. [Crossref] [PubMed]
42. da Silva FT, Sakata VM, Nakashima A, et al. Enhanced depth imaging optical coherence tomography in long-standing Vogt-Koyanagi-Harada disease. Br J Ophthalmol 2013;97:70-4. [Crossref] [PubMed]
43. Sakata VM, da Silva FT, Hirata CE, et al. Choroidal bulging in patients with Vogt-Koyanagi-Harada disease in the non-acute uveitic stage. J Ophthalmic Inflamm Infect 2014;4:6. [Crossref] [PubMed]
44. Takahashi H, Takase H, Ishizuka A, et al. Choroidal thickness in convalescent vogt-koyanagi-harada disease. Retina 2014;34:775-80. [Crossref] [PubMed]
45. Ohno S, Minakawa R, Matsuda H. Clinical studies of Vogt-Koyanagi-Harada's disease. Jpn J Ophthalmol 1988;32:334-43.
46. Ahn JK. Morphologic changes in the anterior segment in patients with initial-onset or recurrent Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm 2010;18:314-8. [Crossref] [PubMed]
47. Sakata VM, da Silva FT, Hirata CE, et al. High rate of clinical recurrence in patients with Vogt-Koyanagi-Harada disease treated with early high-dose corticosteroids. Graefes Arch Clin Exp Ophthalmol 2015;253:785-90. [Crossref] [PubMed]
48. Nakayama M, Keino H, Watanabe T, et al. Clinical features and visual outcomes of 111 patients with new-onset acute Vogt-Koyanagi-Harada disease treated with pulse intravenous corticosteroids. Br J Ophthalmol 2019;103:274-8. [Crossref] [PubMed]
49. Yamanaka E, Ohguro N, Yamamoto S, et al. Evaluation of pulse corticosteroid therapy for vogt-koyanagi-harada disease assessed by optical coherence tomography. Am J Ophthalmol 2002;134:454-6. [Crossref] [PubMed]
50. Abu El-Asrar AM, Al Tamimi M, Hemachandran S, et al. Prognostic factors for clinical outcomes in patients with Vogt-Koyanagi-Harada disease treated with high-dose corticosteroids. Acta Ophthalmol 2013;91:e486-e493. [Crossref] [PubMed]
51. Zhang C, Wang Y, Chen Y, et al. Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China. BMC Ophthalmol 2023;23:199. [Crossref] [PubMed]
52. Agarwal M, Ganesh SK, Biswas J. Triple agent immunosuppressive therapy in Vogt-Koyanagi-Harada syndrome. Ocul Immunol Inflamm 2006;14:333-9. [Crossref] [PubMed]
53. Karacorlu M, Arf Karacorlu S, Ozdemir H. Intravitreal triamcinolone acetonide in Vogt-Koyanagi-Harada syndrome. Eur J Ophthalmol 2006;16:481-3. [Crossref] [PubMed]
54. Paredes I, Ahmed M, Foster CS. Immunomodulatory therapy for Vogt-Koyanagi-Harada patients as first-line therapy. Ocul Immunol Inflamm 2006;14:87-90. [Crossref] [PubMed]
55. Read RW, Yu F, Accorinti M, et al. Evaluation of the effect on outcomes of the route of administration of corticosteroids in acute Vogt-Koyanagi-Harada disease. Am J Ophthalmol 2006;142:119-24. [Crossref] [PubMed]
56. Moreker MR, Lodhi SA, Pathengay A. Role of intravitreal triamcinolone as an adjuvant in the management of Vogt-Koyanagi-Harada disease. Indian J Ophthalmol 2007;55:479-80. [Crossref] [PubMed]
57. Wang Y, Gaudio PA. Infliximab therapy for 2 patients with Vogt-Koyanagi-Harada syndrome. Ocul Immunol Inflamm 2008;16:167-71. [Crossref] [PubMed]
58. Lai TY, Chan RP, Chan CK, et al. Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease. Eye (Lond) 2009;23:543-8. [Crossref] [PubMed]
59. Cuchacovich M, Solanes F, Díaz G, et al. Comparison of the clinical efficacy of two different immunosuppressive regimens in patients with chronic vogt-koyanagi-harada disease. Ocul Immunol Inflamm 2010;18:200-7. [Crossref] [PubMed]
60. Khalifa YM, Bailony MR, Acharya NR. Treatment of pediatric vogt-koyanagi-harada syndrome with infliximab. Ocul Immunol Inflamm 2010;18:218-22. [Crossref] [PubMed]
61. Dolz-Marco R, Gallego-Pinazo R, Díaz-Llopis M. Rituximab in refractory Vogt-Koyanagi-Harada disease. J Ophthalmic Inflamm Infect 2011;1:177-80. [Crossref] [PubMed]
62. Zmuda M, Tiev KP, Knoeri J, et al. Successful use of infliximab therapy in sight-threatening corticosteroid-resistant Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm 2013;21:310-6. [Crossref] [PubMed]
63. Jeroudi A, Angeles-Han ST, Yeh S. Efficacy of adalimumab for pediatric Vogt-Koyanagi-Harada syndrome. Ophthalmic Surg Lasers Imaging Retina 2014;45:332-4. [Crossref] [PubMed]
64. Urzua CA, Velasquez V, Sabat P, et al. Earlier immunomodulatory treatment is associated with better visual outcomes in a subset of patients with Vogt-Koyanagi-Harada disease. Acta Ophthalmol 2015;93:e475-e480. [Crossref] [PubMed]
65. Heo JW, Cho BJ, Goldstein DA, et al. Fluocinolone acetonide implant for Vogt-Koyanagi-Harada disease: three-year outcomes of efficacy and safety. Retina 2016;36:2124-31. [Crossref] [PubMed]
66. Shen E, Rathinam SR, Babu M, et al. Outcomes of Vogt-Koyanagi-Harada Disease: A Subanalysis From a Randomized Clinical Trial of Antimetabolite Therapies. Am J Ophthalmol 2016;168:279-86. [Crossref] [PubMed]
67. Concha-Del Río LE, Gómez L, Arellanes-García L. Corticotherapy vs. Corticotherapy Plus Immunosuppressive Therapy in Acute Vogt-Koyanagi-Harada Disease. Arch Soc Esp Oftalmol (Engl Ed) 2018;93:225-30. [Crossref] [PubMed]
68. Couto C, Schlaen A, Frick M, et al. Adalimumab Treatment in Patients with Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm 2018;26:485-9. [Crossref] [PubMed]
69. Budmann GA, Franco LG, Pringe A. Long term treatment with infliximab in pediatric Vogt-Koyanagi-Harada disease. Am J Ophthalmol Case Rep 2018;11:139-41. [Crossref] [PubMed]
70. Su E, Oza VS, Latkany P. A case of recalcitrant pediatric Vogt-Koyanagi-Harada disease successfully controlled with adalimumab. J Formos Med Assoc 2019;118:945-50. [Crossref] [PubMed]
71. Takayama K, Obata H, Takeuchi M. Efficacy of Adalimumab for Chronic Vogt-Koyanagi-Harada Disease Refractory to Conventional Corticosteroids and Immunosuppressive Therapy and Complicated by Central Serous Chorioretinopathy. Ocul Immunol Inflamm 2020;28:509-12. [Crossref] [PubMed]
72. Kwon HY, Woo SJ. A Case of Recurrent Vogt-Koyanagi-Harada Disease Successfully Treated with Adalimumab in Young Female Adult Patient. Korean J Ophthalmol 2020;34:92-3. [Crossref] [PubMed]
73. Dutta Majumder P, Shah A, Kaushik V. Tofacitinib in Vogt-Koyanagi-Harada disease. Indian J Ophthalmol 2020;68:1938-9. [Crossref] [PubMed]
74. Yang S, Tao T, Li Z, et al. Systemic glucocorticoid-free therapy with adalimumab plus immunosuppressants versus conventional therapy in treatment-naïve Vogt-Koyanagi-Harada disease patients. Ann Transl Med 2022;10:699. [Crossref] [PubMed]
75. Ono T, Goto H, Sakai T, et al. Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt-Koyanagi-Harada disease. Jpn J Ophthalmol 2022;66:119-29. [Crossref] [PubMed]
76. Hiyama T, Harada Y, Kiuchi Y. Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease. Front Med (Lausanne) 2021;8:730215. [Crossref] [PubMed]
77. Takeuchi M, Nakai S, Usui Y, et al. Adalimumab treatment for chronic recurrent Vogt-Koyanagi-Harada disease with sunset glow fundus: A multicenter study. Saudi J Ophthalmol 2022;36:380-6. [Crossref] [PubMed]
78. Yang S, Tao T, Huang Z, et al. Adalimumab in Vogt-Koyanagi-Harada Disease Refractory to Conventional Therapy. Front Med (Lausanne) 2021;8:799427. [Crossref] [PubMed]
79. Zhong Z, Dai L, Wu Q, et al. A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease. Nat Commun 2023;14:3768. [Crossref] [PubMed]
80. Fushitsu R, Ishibazawa A, Murono M, et al. Outcomes of patients with acute Vogt-Koyanagi-Harada disease treated with intravenous corticosteroid pulse followed by the slow tapering of oral corticosteroid therapy. Int Ophthalmol 2023;43:431-40. [Crossref] [PubMed]
81. Feng H, Chen W, Yang J, et al. Predictive factors and adalimumab efficacy in managing chronic recurrence Vogt-Koyanagi-Harada disease. BMC Ophthalmol 2024;24:238. [Crossref] [PubMed]
82. Dai L, Zhong Z, Wu Q, et al. Cost-Effectiveness Analysis of Adalimumab Versus Cyclosporine for Vogt-Koyanagi-Harada Disease: A Randomized Controlled Study. Curr Eye Res 2024;49:1080-8. [Crossref] [PubMed]
83. Acharya NR, Rathinam SR, Thundikandy R, et al. Outcomes in Patients With Vogt-Koyanagi-Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial. Am J Ophthalmol 2024;267:100-11. [Crossref] [PubMed]
84. Almerri S, Behbehani R. A complicated Vogt-Koyanagi-Harada presenting with bilateral papillitis in a 5-year-old- case report. J Ophthalmic Inflamm Infect 2025;15:27. [Crossref] [PubMed]
85. Lu Y, Pan Y, Chen Y, et al. Outcomes of Corticosteroids Combined with 15 Mg/Week Methotrexate as Initial Treatment for Acute Vogt-Koyanagi-Harada Disease. Ocul Immunol Inflamm 2025;33:897-904. [Crossref] [PubMed]
86. Kim SJ, Yu HG. The use of low-dose azathioprine in patients with Vogt-Koyanagi-Harada disease. Ocul Immunol Inflamm 2007;15:381-7. [Crossref] [PubMed]
87. Rao NA. Treatment of Vogt-Koyanagi-Harada disease by corticosteroids and immunosuppressive agents. Ocul Immunol Inflamm 2006;14:71-2. [Crossref] [PubMed]
88. Oldstone MB. Molecular mimicry and autoimmune disease. Cell 1987;50:819-20. [Crossref] [PubMed]
89. Raghupathy R, Makhseed M, Azizieh F, et al. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod 2000;15:713-8. [Crossref] [PubMed]
90. Sugita K, Mizumoto K, Kato N, et al. Early resolution of subretinal fluid without high-dose corticosteroids in a pregnant patient with Vogt-Koyanagi-Harada disease: a case report. J Ophthalmic Inflamm Infect 2015;5:20. [Crossref] [PubMed]
91. Cherukuri N, Murthy SI, Tyagi M. Effects of pregnancy on the clinical course and treatment outcomes of Vogt-Koyanagi-Harada disease. Indian J Ophthalmol 2025;73:S158-63. [Crossref] [PubMed]
92. Doi M, Matsubara H, Uji Y. Vogt-Koyanagi-Harada syndrome in a pregnant patient treated with high-dose systemic corticosteroids. Acta Ophthalmol Scand 2000;78:93-6. [Crossref] [PubMed]
93. Nakamura T, Keino H, Okada AA. Sub-tenon triamcinolone acetonide injection in a pregnant patient with Vogt-Koyanagi-Harada disease. Retin Cases Brief Rep 2018;12:375-8. [Crossref] [PubMed]
94. Ingolotti M, Schlaen BA, Roig Melo-Granados EA, et al. Azathioprine During the First Trimester of Pregnancy in a Patient with Vogt-Koyanagi-Harada Disease: A Multimodal Imaging Follow-Up Study. Am J Case Rep 2019;20:300-5. [Crossref] [PubMed]
95. Ueyama K, Kakinuma T, Mori K, et al. Managing Vogt-Koyanagi-Harada disease during pregnancy with steroid pulse therapy: A case report. World J Clin Cases 2024;12:6493-9. [Crossref] [PubMed]
96. Matsubara S, Kuwata T, Ohkawara Y, et al. Headache in late pregnancy: a symptom for Vogt-Koyanagi-Harada disease. Arch Gynecol Obstet 2011;283:1423-5. [Crossref] [PubMed]
97. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998;339:1485-92. [Crossref] [PubMed]
98. Müller U, Steinhoff U, Reis LF, et al. Functional role of type I and type II interferons in antiviral defense. Science 1994;264:1918-21. [Crossref] [PubMed]
99. Soma M, Hirata A, Takahashi T, et al. Relapse of Vogt-Koyanagi-Harada Disease during Interferon-α and Ribavirin Therapy in a Case of Chronic Viral Hepatitis C. Case Rep Ophthalmol 2011;2:5-9. [Crossref] [PubMed]
100. Duan J, Wang Y, Liu D, et al. Induction of Vogt-Koyanagi-Harada Disease by Interferon-Alpha and Ribavirin Treatment in Patients with Hepatitis C: A Case Report and Review of the Literature. Ocul Immunol Inflamm 2019;27:229-34. [Crossref] [PubMed]
101. Al-Muammar AM, Al-Mudhaiyan TM, Al Otaibi M, et al. Vogt-Koyanagi-Harada disease occurring during interferon-alpha and ribavirin therapy for chronic hepatitis C virus infection. Int Ophthalmol 2010;30:611-3. [Crossref] [PubMed]
102. Kasahara A, Hiraide A, Tomita N, et al. Vogt-Koyanagi-Harada disease occurring during interferon alpha therapy for chronic hepatitis C. J Gastroenterol 2004;39:1106-9. [Crossref] [PubMed]
103. Sylvestre DL, Disston AR, Bui DP. Vogt-Koyanagi-Harada disease associated with interferon alpha-2b/ribavirin combination therapy. J Viral Hepat 2003;10:467-70. [Crossref] [PubMed]
104. Touitou V, Bodaghi B, Cassoux N, et al. Vogt-Koyanagi-Harada disease in patients with chronic hepatitis C. Am J Ophthalmol 2005;140:949-52. [Crossref] [PubMed]