Immunophenotypic profiles in chalazion and pyogenic granuloma associated with chalazion.

PURPOSE: To evaluate immunophenotypic profiles of infiltrating cells in surgically excised tissues of chalazion and pyogenic granuloma associated with chalazion. METHODS: Eighty-two surgical specimens from 74 consecutive patients newly diagnosed with chalazion or chalazion-associated pyogenic granuloma at Tokyo Medical University Hospital between 2016 and 2022 were studied. Sixty specimens were chalazion lesions and 22 specimens were pyogenic granuloma lesions (from 15 men and 7 women, mean age 36.6 ± 14.4 years). All patients were immunocompetent Asian Japanese adults. Specimens were analyzed by immunohistochemistry and flow cytometry. Flow cytometry was performed using the following antibodies: CD3, CD4, CD8, CD11b, CD11c, CD16, CD19, CD20, CD23, CD25, CD34, CD44, CD56, CD69, and CD138. RESULTS: In flow cytometric analysis, the proportion of cells expressing the T cell marker CD3 was significantly higher compared with other immune cells expressing specific markers (p < 0.0001), and the proportion of CD4-positive T cells was significantly higher than that of CD8-positive T cells (p < 0.0001), in both chalazion and pyogenic granuloma specimens. The chalazion and pyogenic granuloma lesions shared similar immunophenotypic profile characterized by predominant T cell infiltration, and CD4 T cells dominating over CD8 cells. The pattern of expression of CD4 and CD8 in the specimens was confirmed by immunohistochemistry. CONCLUSION: The present study demonstrates immunophenotypic features of chalazion and chalazion-associated pyogenic granuloma. Although various inflammatory cells are involved in the pathology of chalazion and pyogenic granuloma, a significantly higher proportion of CD4-positive T cells may be closely related to the pathological mechanisms of both lesions.

Vitreous Humor Proteomic Profile in Patients With Vitreoretinal Lymphoma.

Purpose: Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Methods: Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. Results: In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. Conclusions: This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.

Immune Mediators Profiles in the Aqueous Humor of Patients with Simple Diabetic Retinopathy.

Various immune mediators identified to date are associated with the development of advanced forms of diabetic retinopathy (DR), such as proliferative DR and diabetic macular edema, although the exact pathophysiological mechanisms of early stages of DR such as simple DR remain unclear. We determined the immune mediator profile in the aqueous humor of eyes with simple DR. Fifteen eyes of fifteen patients with simple DR were studied. Twenty-two eyes of twenty-two patients with cataracts and no DR served as controls. Undiluted aqueous humor samples were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 32 immune mediators comprising 13 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated on activation, normal T cell expressed and secreted (RANTES), monokine induced by interferon-γ, basic fibroblast growth factor (bFGF), Fas ligand, granzyme A, granzyme B, interferon-inducible T-cell alpha chemoattractant (ITAC), fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), vascular endothelial growth factor (VEGF), angiogenin, tumor necrosis factor-α, and CD40 ligand. Among the 32 immune mediators, 10 immune mediators, including bFGF, CD40 ligand, fractalkine, G-CSF, IL-6, IL-8, MIP-α, MIP-1ß, and VEGF, showed significantly higher aqueous humor concentrations and the Fas ligand had significantly lower concentration (p < 0.05) in eyes with simple DR compared with control eyes. Of these 10 cytokines with significant concentration alteration, protein-protein interaction analysis revealed that 8 established an intricate interaction network. Various immune mediators may contribute to the pathogenesis of simple DR. Attention should be given to the concentrations of immune mediators in ocular fluids even in simple DR. Large-scale studies are warranted to assess whether altered aqueous humor concentrations of these 10 immune mediators are associated with an increased risk of progression to advanced stages of DR.

Resuming anti-TNF therapy after development of miliary tuberculosis in Behcet's disease-related uveitis: a case report.

PURPOSE: There is no consensus concerning restarting anti-tumour necrosis factor (TNF)-α therapy for uveitis after treatment for active tuberculosis (TB). We report a case of Behcet disease (BD) in which treatment with TNF inhibitor was successfully resumed after treatment for miliary TB. CASE REPORT: A 48-year-old Japanese male was treated for uveitis of unknown aetiology in the left eye at a general ophthalmology clinic. He was referred to Department of Ophthalmology, Tokyo Medical University Hospital because of macula oedema (ME) not responding to prednisolone (PSL) 20 mg. BD was diagnosed based on fluorescein angiographic findings of diffuse retinal vasculitis characteristic of BD, recurrent oral aphthous ulcer, erythema nodosum-like rash in his legs, and HLA-A26 positivity. After a screening test, adalimumab (ADA) was started as steroid-sparing therapy. Eight months after starting ADA, the patient was diagnosed with miliary TB. ADA and PSL were discontinued immediately due to TB. Anti-TB treatment was completed after 6 months based on clinical improvement, although T-SPOT.TB was still positive. Infliximab with isoniazid was started due to relapse of ME, worsened vitreous haze, and worsened visual acuity in his left eye. Subsequently, his ocular symptoms subsided and there was no relapse of TB. CONCLUSION: This case suggests that in patients with BD who have discontinued anti-TNF therapy due to miliary TB, restarting anti-TNF therapy may be a therapeutic option after TB has been treated appropriately with careful monitoring for relapse.

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

Comparative evaluation of 16S rRNA metagenomic sequencing in the diagnosis and understanding of bacterial endophthalmitis.

OBJECTIVE: To evaluate the usefulness of metagenomic analysis in the search for causative organisms of bacterial endophthalmitis. METHODS AND ANALYSIS: Twenty-one consecutive treatment-naïve patients (13 men and 8 women; mean age, 60.8±19.8 years) with suspected endophthalmitis were recruited. Vitrectomy was performed to diagnose and treat endophthalmitis. Bacterial culture and metagenomic analysis of the vitreous body were performed. Extracted DNA was analysed using 16S rRNA sequences, and libraries were sequenced on an Illumina MiSeq sequencer. To compare the bacterial composition in each case, α and ß diversities were determined. RESULTS: Patients were categorised into three groups: endophthalmitis cases with matching predominant organisms according to metagenomic analysis and bacterial culture, those with negative results for bacterial culture and those with negative results in both cases. In 7 of 15 culture-negative cases, results from metagenomic analysis could detect pathogens. The diversity of bacterial populations was significantly lower in the group with positive results for predominant bacteria according to culture and metagenomic analysis. All patients with uveitis were included in the group for which the causative pathogen could not be determined by culture or metagenomic analysis. The structures of bacterial populations significantly differed between the positive and negative groups by culture and metagenomic analysis. CONCLUSIONS: Metagenomic analysis could be useful for prompt detection of causative pathogens, for precise diagnosis of infection, and as a marker of inflammation processes such as uveitis.

Association Between Torque Teno Virus and Systemic Immunodeficiency in Patients With Uveitis With a Suspected Infectious Etiology.

PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis. RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein-Barr virus-positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P = .008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P = .01), but no correlations between ocular TTV and age, gender, or viral pathogenic type. CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.

Changes in Density of Peripapillary and Intrapapillary Capillaries on OCT Angiography in Acute Retinal Necrosis Treated by Pharmacotherapy Alone without Surgery.

PURPOSE: To analyze radial peripapillary capillaris (RPC) and intra-papillary capillaris (IPC) using optical coherence tomography angiography (OCTA) in acute retinal necrosis (ARN) with good outcome. METHODS: RPC and IPC were analyzed by OCTA in patients diagnosed with ARN and treated with pharmacotherapy alone without surgery at the Tokyo Medical University Hospital. RESULTS: A total of 13 patients were studied. Ophthalmoscopic examination showed no abnormality in the optic disc in 12 of the 13 patients. However, OCTA findings of the affected eye compared with the unaffected fellow eye revealed morphological abnormalities in RPC in nine cases (69%) and decrease in capillary network in RPC or IPC in eight cases (62%). CONCLUSION: In ARN, RPC and IPC were impaired even in eyes that were healed with medical treatment only without requiring surgical intervention and had no abnormal findings on ophthalmoscopic examination. This result suggests the presence of some degrees of optic neuropathy even in mild cases with good visual prognosis.

COVID-19 Developed During Systemic Steroid Therapy for Vogt-Koyanagi-Harada Disease: A Case Report.

PURPOSE: The use of immunomodulatory therapy in the setting of coexistence of uveitis and coronavirus disease (COVID-19) remains controversial. We report a case of COVID-19 during systemic steroid therapy for Vogt-Koyanagi-Harada disease (VKH). CASE REPORT: A 43-year-old female was diagnosed with VKH and started on steroid pulse therapy (1,000 mg/day) followed by high-dose oral corticosteroids. Two weeks after discharge from the hospital, she was readmitted to the intensive care unit with severe acute respiratory syndrome due to SARS-CoV-2 infection confirmed by PCR test, and fortunately both VKH and COVID-19-induced respiratory disease improved. CONCLUSION: Given the absence of international agreement on how to manage COVID-19 patients with steroid-dependent VKH, existing clinical guidelines should be reviewed thoroughly to formulate useful strategies for managing VKH patients on steroid treatment who contract COVID-19. Furthermore, the outcomes of patients with steroid-dependent autoimmune uveitis including VKH who develop COVID-19 should be analyzed.

Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role.

BACKGROUND: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. PURPOSE: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. METHODS: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. RESULTS: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. CONCLUSION: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

Ten-year follow-up of infliximab treatment for uveitis in Behçet disease patients: A multicenter retrospective study.

Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Design: Retrospective longitudinal cohort study. Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study. Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). Main outcome measures: 10-year IFX continuation rate and change in LogMAR VA. Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.

Prevalence of Merkel Cell Polyomavirus in Primary Eyelid Merkel Cell Carcinomas and Association With Clinicopathological Features.

PURPOSE: Merkel cell polyomavirus (MCPyV) infection is a known to be a critical risk factor for the development of Merkel cell carcinoma (MCC). Various reports on cutaneous MCC have shown that the differences in clinicohistopathological characteristics depend on the presence of MCPyV, but the situation in eyelid MCC is unknown. This study aimed to assess the prevalence of MCPyV in patients with eyelid MCC and examine the clinicohistopathological characteristics of MCPyV-associated eyelid MCC. DESIGN: Retrospective observational case series with laboratory investigations. METHODS: Ten patients treated for eyelid MCC were included. Histopathological characteristics were examined by immunohistochemical staining using 12 antibodies. MCPyV infection was evaluated by PCR using primer sets targeting large T antigens of the MCPyV genome and by immunohistochemical staining using CM2B4 and Ab3 monoclonal antibodies. The MCPyV viral load was also quantified by PCR using 3 primer sets. RESULTS: All patients (4 males and 6 females) were Japanese with mean age of 79 (range: 63 to 87) years. One patient died due to distant metastasis 8 months after surgery for MCC. Immunohistochemical studies showed typical MCC findings in all cases, including CK20 and neuroendocrine marker positivity. PCR and immunohistochemistry with CM2B4 and Ab3 detected MCPyV antigen in all tumors. Quantitative PCR using sT, LT4, and TAg primers yielded 0.94, 1.72, and 1.05 copies per cell, respectively. CONCLUSION: Clinical and histopathological characteristics of 10 patients with eyelid MCC were elucidated. MCPyV infection was detected in all eyelids. These results provide insight for understanding the tumorigenesis of eyelid MCC.

A multicenter study of ocular inflammation after COVID-19 vaccination.

PURPOSE: To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. STUDY DESIGN: Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. RESULTS: Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. CONCLUSIONS: COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.

Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.

Aim: To investigate the causes of low prevalence of Fuchs' uveitis syndrome (FUS) in Japan. Methods: Medical records of 160 patients diagnosed with FUS at 14 uveitis specialty facilities in Japan were reviewed retrospectively. Results: In 160 FUS patients, mean follow-up period before referral to our uveitis facilities was 31.6 ± 50.9 months. The most common reason for referral was idiopathic uveitis (61.9%), followed by cataract (25.0%), high intraocular pressure (IOP) including glaucoma (16.3%), and FUS (14.4%). Unilateral involvement was 96.9%. The most frequent ocular finding of FUS was anterior inflammation (91.9%), followed by stellate-shaped keratic precipitates (88.1%), cataract/pseudophakia (88.1%), diffuse iris atrophy (84.4%), vitreous opacity (62.5%), heterochromia (53.1%) and high IOP including glaucoma (36.3%). As treatments of these ocular findings, cataract surgery was performed in 52.5%, glaucoma surgery in 10.6%, and vitrectomy in 13.8%. Mean logMAR VA was 0.28 ± 0.59 at the initial visit, and decreased significantly to 0.04 ± 0.32 at the last visit. Proportions of FUS patients with BCVA <0.1 and 0.1 to <0.5 decreased, while that of ≥0.5 increased at the last visit compared with the initial visit. Conclusions: Ocular findings of FUS in Japanese FUS patients were consistent with the characteristic features. The low prevalence of FUS in Japan may be a result of being overlooked and misdiagnosed as mild idiopathic uveitis, cataract, and/or glaucoma.

Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases.

Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway analysis was performed. The candidate biomarker proteins for ocular sarcoidosis were validated using enzyme-linked immunosorbent assay. A total of 1590 proteins were identified in all samples. Of these, 290 and 174 DEPs were detected in vitreous of ocular sarcoidosis compared with controls and VRL, respectively. Enrichment pathway analysis revealed that pathways related to the immune system were most upregulated. Validation of two candidate biomarkers for ocular sarcoidosis, neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB), confirmed upregulated NGAL and JAMB protein expressions in ocular sarcoidosis compared to controls and VRL. The results of this study revealed that altered vitreous protein expression levels may discriminate ocular sarcoidosis from other uveitis diseases. Vitreous NGAL and JAMB are potential biomarkers and may serve as an auxiliary tool for the diagnosis of ocular sarcoidosis.

Epidemiological characteristics of malignant eyelid tumors at a referral hospital in Japan.

PURPOSE: To clarify the incidence and demographic characteristics of malignant eyelid tumors diagnosed in a single institute in Japan. STUDY DESIGN: Retrospective, observational case series METHODS: Patients with malignant eyelid tumors diagnosed histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were reviewed retrospectively. The incidence and demographic profile of malignant eyelid tumors were analyzed. The number of benign eyelid tumors diagnosed histopathologically during the same period was also counted. RESULTS: A total of 412 patients with histopathologically proven malignant eyelid tumors were included. The most common malignant eyelid tumor was sebaceous carcinoma (n = 180, 44%), followed by basal cell carcinoma (n = 148, 36%), squamous cell carcinoma (n = 35, 9%), lymphoma (n = 28, 7%), Merkel cell carcinoma (n = 11, 3%) and others (n = 10, 2%). Mean age of all patients with malignant eyelid tumor at the time of diagnosis was 71.0 ± 13.0 years. For sebaceous carcinoma, the proportion of female patients was significantly higher than that of male patients (P = 0.0283) and the proportion of involvement of upper eyelid was significantly higher than that of lower eyelid (P = 0.0001). On the other hand, there was no sex predominance in basal cell carcinoma and squamous cell carcinoma. The proportion of involvement of lower eyelid was significantly higher than of upper eyelid in basal cell carcinoma (P = 0.001) and squamous cell carcinoma (P = 0.0012). There were 1433 patients with benign eyelid tumors accounting for 78% of all eyelid tumors during the study period. CONCLUSIONS: Sebaceous carcinoma is the major malignant eyelid tumor in Japan and is more frequent in women than in men. Epidemiology of malignant eyelid tumors may be affected by the trend of population age structure associated with the recent population aging.