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.

Clinico-epidemiological analysis of 1000 cases of orbital tumors.

PURPOSE: To clarify the incidence, demography and clinical features of orbital tumors diagnosed in a single institute in Japan. STUDY DESIGN: Retrospective, observational case series. METHODS: Patients with primary orbital tumors including tumor-like lesions diagnosed clinically or histopathologically at Tokyo Medical University Hospital between 1995 and 2019 were analyzed. Incidence of all orbital tumors, demographic profile and clinical features of major benign and malignant tumors were reviewed retrospectively. RESULTS: Totally 1000 cases of primary orbital tumor were diagnosed clinically or histopathologically during the study period. Benign tumors accounted for 72% and malignant tumors 28%. 55% of benign tumors and 99% of malignant tumors were proven histopathologically. The most common benign orbital tumor was idiopathic orbital inflammation (27%), followed by IgG4-related ophthalmic disease (17%), cavernous venous malformation (13%) and pleomorphic adenoma (9%). The most common malignant tumor was lymphoma (70%), followed by adenoid cystic carcinoma (7%) and solitary fibrous tumor (5%). CONCLUSIONS: Epidemiology of orbital tumors has changed by the improvement of imaging techniques, establishment of novel clinical and histopathological criteria, and changes in population age structure associated with the aging society. Currently, lymphoproliferative diseases including lymphoma and IgG4-related ophthalmic diseases form the major orbital tumors in Japan.

Clinical features and symptoms of IgG4-related ophthalmic disease: a multicenter study.

PURPOSE: The aim of this study was to elucidate the clinical features and symptoms of IgG4-related ophthalmic disease (IgG4-ROD). STUDY DESIGN: Retrospective, multicenter study. METHODS: The medical charts of 378 patients with IgG4-ROD diagnosed at 9 hospitals in Japan were reviewed. The demographic profiles, clinical findings, and ocular symptoms of the patients were analyzed. RESULTS: On the basis of the diagnostic criteria for IgG4-ROD, the diagnosis was definite in 261 patients (69%), probable in 45 patients (12%), and possible in 72 patients (19%). The patients' mean age at the time of diagnosis was 60.6 ± 13.9 years; 195 (52%) were male. The mean IgG4 serum level at the time of the initial diagnosis was 578.9 mg/dL. Imaging studies showed pathologic lesions as follows: lesions in the lacrimal glands (86%), extraocular muscles (21%), trigeminal nerve (20%), and eyelids (12%); isolated orbital mass (11%); diffuse orbital lesion (8%); lesion in the perioptic nerve (8%); and lesion in the sclera (1%). The ophthalmic symptoms included dry eye (22%), diplopia (20%), decreased vision (8%), and visual field defects (5%). IgG4-ROD with extraocular lesions was observed in 182 patients (48%). CONCLUSION: Although the lacrimal glands are well known to be the major pathologic site of IgG4-ROD, various ocular tissues can be affected and cause ophthalmic symptoms including visual loss.

Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma.

PURPOSE: Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. METHODS: A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. RESULTS: A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. CONCLUSIONS: Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.

Clinical features and prognosis of sebaceous carcinoma arising in the eyelid or conjunctiva.

PURPOSE: The aim of this study was to clarify the demographics, clinical features, and outcomes of Japanese patients with sebaceous carcinoma of the eyelid or conjunctiva. STUDY DESIGN: Retrospective study. METHODS: One hundred twenty-five patients with sebaceous carcinoma of the eyelid or conjunctiva diagnosed at Tokyo Medical University Hospital between 1994 and 2017 were reviewed. The outcomes of the 116 patients who were treated and followed for at least 24 months at our hospital were investigated. RESULTS: The patients reviewed comprised 52 men and 74 women. The average age at diagnosis was 70.6 ± 13.8 (range 31-96) years. The main lesion was located in the upper eyelid in 51% of the patients; in the lower eyelid in 38% of the patients; and in other regions in 11% of the patients. Treatments included surgical resection with or without eyelid reconstruction in 108 cases (93%), orbital exenteration in 5 cases (4%), and radiation therapy in 3 cases (3%). Local recurrence was detected in 11 cases (9%). Metastasis to the regional lymph nodes was confirmed in 10 cases (9%). Four patients (3%) died because of direct intracranial invasion of the tumor. Risk of local recurrence and metastasis was significantly related to larger tumor size. CONCLUSION: Proper diagnosis and treatment at the optimal timing is critical to improve the outcome of sebaceous carcinoma of the eyelid or conjunctiva. Long-term follow-up is required because local recurrence and metastasis may occur several years after treatment.

Effectiveness of prophylactic intravitreal bevacizumab injection to proliferative diabetic retinopathy patients with elevated preoperative intraocular VEGF in preventing complications after vitrectomy.

PURPOSE: This study aimed to elucidate the effects of intravitreal bevacizumab (IVB) injections for the prevention of post-vitrectomy complications in proliferative diabetic retinopathy (PDR) patients with elevated vitreous vascular endothelial growth factor (VEGF) concentration. DESIGN: Prospective case series. METHODS: Thirty-three patients (42 eyes) with PDR who underwent primary vitrectomy in the Department of Ophthalmology, Tokyo Medical University Hospital were studied. We measured VEGF concentrations in vitreous humor collected at the time of vitrectomy using ELISA. IVB injections were performed after vitrectomy in patients with vitreous VEGF levels exceeding 1,000 pg/mL. New bleeding occurring within 1 month of vitrectomy was defined as early vitreous hemorrhage (VH). MAIN OUTCOME MEASURE: The incidence of complications after vitrectomy including postoperative early VH. RESULTS: IVB injections were administered to 11 eyes (26%) with vitreous VEGF concentrations exceeding 1,000 pg/mL. None of the 11 eyes that received an IVB injection developed early VH. Among 31 eyes (74%) with vitreous VEGF concentrations lower than 1,000 pg/mL, two eyes (6%) developed early VH after vitrectomy. CONCLUSIONS: Prophylactic IVB injections administered to patients with elevated preoperative intraocular VEGF concentrations were effective in preventing post-vitrectomy early VH.

Evaluation of focal damage in the retinal pigment epithelium layer in serous retinal pigment epithelium detachment.

The purpose of this study was to evaluate focal damage in the retinal pigment epithelium (RPE) layer in serous retinal pigment epithelium detachment (PED) with multi-contrast optical coherence tomography (OCT), which is capable of simultaneous measurement of OCT angiography, polarization-sensitive OCT and standard OCT images. We evaluated 37 eyes with age-related macular degeneration that had serous PED. Focal RPE damage was indicated by hyper-transmission beneath the RPE-Bruch's membrane band in standard OCT images. Distribution of RPE melanin was calculated using the dataset from multi-contrast OCT. Twenty-four points with hyper-transmission were detected in 21 of the 37 eyes. Standard OCT images failed to show disruption of the RPE-Bruch's membrane band at 5 of the 24 hyper-transmission points. Conversely, multi-contrast OCT images clearly showed melanin defects in the RPE-Bruch's membrane band at all points. Areas of melanin defects with disruption of the RPE-Bruch's membrane band were significantly larger than those without disruption. The volume of intraretinal hyper-reflective foci was significantly larger in eyes with hyper-transmission than that in eyes without hyper-transmission. Multi-contrast OCT is more sensitive than standard OCT for displaying changes at the RPE-Bruch's membrane band when there are small areas of RPE damage.

Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid tissue lymphoma from benign lymphoproliferative tumors.

PURPOSE: To evaluate novel immunophenotypic profiles of patients with orbital lymphoproliferative tumors. METHODS: From 2006 to 2014, surgical biopsies from consecutive patients with newly diagnosed orbital mucosa-associated lymphoid tissue (MALT) lymphoma and IgG4-related ophthalmic disease (IgG4-ROD) were collected from Tokyo Medical University Hospital. A total of 44 tumors from 44 patients were analyzed, including 21 with orbital MALT lymphoma (11 men and 10 women, mean age 67.8 ± 13.4 years) and 23 with definitive IgG4-ROD (9 men and 14 women, mean age 60.5 ± 15.1 years). Patients with secondary orbital MALT lymphoma and MALT lymphoma with IgG4-ROD were excluded. All patients were immunocompetent Asian adults. Samples were analyzed by immunohistochemistry and flow cytometric analysis. Flow cytometry was performed with the following antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, CD25, CD30, CD34, and CD56 lambda and kappa chains. RESULTS: Expression of CD25 and CD19 was higher in patients with orbital MALT lymphoma compared to patients with IgG4-ROD (p < 0.001). In contrast, expression of CD3, CD4, and CD23 was higher in patients with orbital IgG4-ROD compared to those with MALT lymphoma (all p < 0.01). The presence of CD23 and CD25 in the specimens was confirmed by immunohistochemistry. CONCLUSION: The present study elucidated the novel immunophenotypic features of orbital MALT and benign lymphoproliferative disorders such as IgG4-ROD. Among them, CD23 and CD25 have shown a disease-specific expression pattern.

PERSISTENT OVERPRODUCTION OF INTRAOCULAR VASCULAR ENDOTHELIAL GROWTH FACTOR AS A CAUSE OF LATE VITREOUS HEMORRHAGE AFTER VITRECTOMY FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: The purpose of this study was to investigate whether vitreous levels of vascular endothelial growth factor (VEGF) predict late vitreous hemorrhage (VH) after vitrectomy for proliferative diabetic retinopathy, and how VEGF level changes in patients with postoperative late VH. METHODS: Eighty-five eyes of 68 patients with proliferative diabetic retinopathy who underwent vitrectomy were analyzed retrospectively. Vitreous samples were collected from eyes undergoing primary vitrectomy and from eyes with late VH undergoing second vitrectomy. Vitreous VEGF levels were measured using enzyme-linked immunosorbent assay. The relationship between VEGF level and late VH (>4 weeks) occurring during follow-up as well as clinical findings, and changes in VEGF level in eyes with late VH undergoing second vitrectomy were analyzed. RESULTS: Late VH occurred in 20 (24%) of 85 eyes, and 9 eyes required second vitrectomy. Vitreous levels of VEGF were significantly higher (median: 1,945 pg/mL; P < 0.0001) in eyes with late VH than in those without. Preexisting iris neovascularization (P < 0.0001), hypertension (P = 0.002), and proteinuria (P = 0.040) were also significant risk factors of late VH. Multivariate logistic regression analysis showed that a higher vitreous VEGF level was independently associated with a risk of postoperative late VH in patients with proliferative diabetic retinopathy (odds ratio: 20.8, 95% confidence interval: 2.72-159.47; P = 0.003). Vitreous VEGF level at second vitrectomy in patients with late VH was significantly lower compared with that at primary vitrectomy, but remained elevated (median: 1,610 pg/mL; P = 0.023). CONCLUSION: In patients with proliferative diabetic retinopathy, high intraocular VEGF level at primary vitrectomy was identified as an independent risk factor of postoperative late VH. Persistent overproduction of intraocular VEGF may be associated with postoperative late VH.

Clinical Analysis of Uveal Melanoma.

Purpose: To clarify clinical features of patients with uveal melanoma. Method: We analyzed 125 eyes of 125 patients diagnosed as uveal melanoma from 1992 to 2014 retrospectively. Results: The mean age of the patients at the time of diagnosis was 58.1±14.4 years. Tumors were originated in the choroid (93%), ciliary body (4%) and iris (3%). The main reasons leading to diagnosis included decreased vision (27%), visual field loss (17%), and no significant symptoms (16%). Average tumor size of the choroidal melanoma was 10.4 mm in largest basal diameter and 7.2 mm in height. Treatment included enucleation of eyeball (53 cases), local resection of the tumor (4 cases), heavy particle beam therapy (18 cases), and brachytherapy (4 cases). Extraocular metastasis was detected in 22% of the patients, and 89% of them died within 5 years. Five-year survival rate was 20% in 6 cases (13.6%) in whom histopathologic studies revealed extrascleral invasions. Conclusions: Prognosis of patients with metastatic uveal melanoma is extremely poor. Early diagnosis and treatment, and establishment of follow-up system after local treatment are critical. Further development and dissemination of novel treatment for metastatic melanoma is desired.

A Case of Choroidal Melanoma Resulted in Eyeball Enucleation 2 Years after Carbon Ion Radiotherapy Due to Local Recurrence.

Background: Recently, carbon ion radiotherapy (CIR) has become the standard therapy for choroidal melanoma to preserve the eyeballs in Japan. We report a case of choroidal melanoma resulting in eyeball enucleation 2 years after carbon ion radiotherapy due to local recurrence. Case: A 64-year-old man was referred to Tokyo Medical University hospital with a diagnosis of choroidal tumor. Intraocular tumor was located at the equator of temporal area in ocular fundus. After systemic work-up, clinical diagnosis of choroidal melanoma was made and CIR was applied. After CIR, the intraocular tumor was stable for 2 years. However, 2 years and 3 months after CIR, local recurrence of the tumor was detected. Eventually, the eyeball was enucleated. Histopathologically, the original lesion was composed of melanoma cells containing abundant melanin pigments, and these cells were positive for HMB-45, Melan-A and S-100 protein. In contrast, the recurrent lesion showed lack of melanin pigment and proved less positive for HMB-45, Melan-A and S-100 protein. Four months after enucleation, the patient developed liver metastasis and received the appropriate supportive care. Conclusions: Even after CIR with remission, choroidal melanoma can recur. Recurrent lesions of the tumor may reveal alternative histopathological findings compared to the original lesion.

Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

BACKGROUND: To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors. METHODS: Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L. RESULTS: Aqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p < 0.05). CONCLUSIONS: Angiogenin, IL-8, and MCP-1 levels in aqueous humor may be potential markers for distinguishing malignant uveal melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.

Immunoglobulin G4-Related Ophthalmic Disease Involving the Sclera Misdiagnosed as Intraocular Tumor: Report of One Case.

AIMS: Immunoglobulin G4 (IgG4)-related disease is known to have diverse clinical manifestations. We report a case of IgG4-related ophthalmic disease misdiagnosed as intraocular tumor. METHODS: Case report. RESULTS: A 41-year-old man was referred to our department with a diagnosis of intraocular tumor, presumably choroidal melanoma. Although MR imaging was compatible with choroidal melanoma, he had been observed periodically without treatment because fundus findings were not typical of melanoma and visual function was preserved. He was again referred to us 15 years later due to increased tumor size and visual field disturbance. Transscleral biopsy of the intraocular tumor was attempted to make a histopathological diagnosis. During the biopsy procedure, thick placoid tissue adhering to the sclera was found at a location consistent with the site of the elevated intraocular lesion. Histopathological examination of this extraocular material revealed proliferation of dense fibrous tissue with follicular proliferation of lymphocytes and plasmacytes. The plasmacytes were diffusely positive for IgG and IgG4. Serum IgG4 level was slightly elevated and no extraocular lesion was detected. Despite administration of systemic corticosteroids after biopsy, the intraocular mass was not reduced. Visual acuity of 20/20 has been maintained as of the last follow-up. CONCLUSION: IgG4-related disease should be included in the differential diagnosis of intraocular elevated lesion.

Global metabolomics reveals metabolic dysregulation in ischemic retinopathy.

Proliferative diabetic retinopathy (PDR) is the most severe form of diabetic retinopathy and, along with diabetic macular edema, is responsible for the majority of blindness in adults below the age of 65. Therapeutic strategies for PDR are ineffective at curtailing disease progression in all cases; however a deeper understanding of the ocular metabolic landscape in PDR through metabolomic analysis may offer new therapeutic targets. Here, global and targeted mass spectrometry-based metabolomics were used to investigate metabolism. Initial analyses on vitreous humor from patients with PDR (n = 9) and non-diabetic controls (n = 11) revealed an increase of arginine and acylcarnitine metabolism in PDR. The oxygen-induced-retinopathy (OIR) mouse model, which exhibits comparable pathological manifestations to human PDR, revealed similar increases of arginine and other metabolites in the urea cycle, as well as downregulation of purine metabolism. We validated our findings by targeted multiple reaction monitoring and through the analysis of a second set of patient samples [PDR (n = 11) and non-diabetic controls (n = 20)]. These results confirmed a predominant and consistent increase in proline in both the OIR mouse model and vitreous samples from patients with PDR, suggesting that over activity in the arginine-to-proline pathway could be used as a therapeutic target in diabetic retinopathy.

Genome-Wide Analysis of Ocular Adnexal Lymphoproliferative Disorders Using High-Resolution Single Nucleotide Polymorphism Array.

PURPOSE: We identified the genomic signature of ocular adnexal lymphoproliferative disorders (LPDs), especially ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma, IgG4-related ophthalmic disease (IgG4-ROD), reactive lymphoid hyperplasia (RLH), and diffuse large B-cell lymphoma (DLBCL). METHODS: We included 52 subjects with ocular adnexal LPDs (13 orbital MALT lymphomas, 16 conjunctival MALT lymphomas, 13 IgG4-RODs, 4 RLHs, and 6 DLBCLs) who had been treated at the Tokyo Medical University Hospital from 2008 to 2012. Genomic DNA was extracted from the tumor tissues and subjected to high-resolution single nucleotide polymorphism array (SNP-A) karyotyping using GeneChip Human Mapping 250K SNP arrays. The array data were investigated using Copy Number Analysis for GeneChips (CNAG) software. RESULTS: In ocular adnexal MALT lymphomas, the most frequent copy number (CN) gain region was trisomy 3 detected in 31% (9/29), followed by trisomy 18 in 17% (5/29), and 6p and 21q in 14% (4/29). The most frequent CN loss regions were 6q and 9p, detected in 7% (2/29). Uniparental disomy was detected on 6q in 14% (4/29), followed by 3q in 10% (3/29). Copy number variations (CNVs) were not detected in IgG4-RODs and RLHs. Conversely, CNVs were more frequent in DLBCLs than in ocular adnexal MALT lymphomas. Copy number variations were detected in 77% (10/13) of orbital MALT lymphomas and in 67% (11/16) of conjunctival MALT lymphomas. CONCLUSIONS: High-resolution single nucleotide polymorphism array is a useful method for discriminating ocular adnexal lymphomas from benign LPDs. The differences in the chromosomal abnormality patterns may reflect the activity of ocular adnexal LPDs.

[Adenoid cystic carcinoma of the lacrimal gland: clinicopathological study].

PURPOSE: To clarify the clinicopathologic features including outcome of adenoid cystic carcinoma arising from the lacrimal gland. SUBJECTS AND METHODS: Background of patients, TNM classification, treatments, histopathological findings and the outcome were examined for 10 patients with adenoid cystic carcinoma of the lacrimal gland diagnosed at Tokyo Medical University Hospital. RESULTS: Patients included 6 men and 4 women and the average age was 49.5 years old. Four patients (40%) developed distant metastases and 5 patients (50%) showed local recurrence. Three patients died or progressed to palliative care, and the 5 year survival rate was 55.5% (Kaplan-Meier). The patients with progression of more than T3 in TNM classification and solid pattern in histopathological findings suggested poor outcome. Although heavy ion radiotherapy was performed in 4 patients, 2 patients died or progressed to palliative care. CONCLUSION: Prognosis of patients with adenoid cystic carcinoma of the lacrimal gland is related to TNM classification and histological type. Medical treatment including heavy ion radiotherapy was performed, the outcome was poor.

Peroxisome proliferator-activated receptor-γ agonist pioglitazone suppresses experimental autoimmune uveitis.

Peroxisome proliferator-activated receptor (PPAR)-γ agonists are clinically used as anti-diabetes agents. Recent research has discovered that an anti-inflammatory effect of PPAR agonist may have the potential to treat autoimmune disease. In the present study, we investigated the anti-inflammatory effects of PPAR-γ agonist, pioglitazone, on murine model of endogenous uveitis. Experimental autoimmune uveoretinitis (EAU) was induced by immunizing C57BL/6 mice with human interphotoreceptor retinoid binding protein-derived peptide (1-20). Pioglitazone or vehicle was injected intravenously from day -1 (whole phase treatment) or day 8 (effector phase study) until day 20. Severity of EAU was assessed clinically and pathologically on day 21. Immunological status was assessed by measuring intraocular inflammatory factors, and activation and regulatory markers of CD4(+) T cells in draining lymph nodes (LNs). Treatment with pioglitazone suppressed both whole-phase and effector-phase of EAU. In effector-phase treatment, intraocular concentrations of TNF-α and IL-6 were significantly suppressed, and CD4(+)Foxp3(+) regulatory T cells and CD4(+)CD62L(high) naïve T cells increased in draining LNs, although there were no differences in CD4(+)CD44(high) effector T cells and IL-17 producing CD4(+) T cells between pioglitazone- and vehicle-treated mice. Administration of pioglitazone before and after the onset of EAU significantly reduced disease severity. The present results suggest that pioglitazone may be a novel therapeutic agent for endogenous uveitis.

A case of orbital sebaceous gland carcinoma developing in an anophthalmic socket 65 years after enucleation.

Although conjunctival squamous cell carcinoma is known to develop as a result of chronic irritation from wearing an ocular prosthesis, orbital sebaceous gland carcinoma arising in an anophthalmic pocket is extremely rare. We report a 68-year-old female who developed a sebaceous gland carcinoma 65 years after her right eye was enucleated (at the age of three years) due to congenital glaucoma. The patient had noticed increasing discharge and swelling of her right eyelid. Incisional biopsies of an underlying orbital mass revealed poorly differentiated sebaceous gland carcinoma. The sebaceous gland carcinoma in this case could have been caused by chronic irritation as a result of long-standing use of a poorly fitted ocular prosthesis. The current case of a malignant tumor occurring 65 years after enucleation emphasizes the importance of long-term clinical surveillance to monitor for tumor formation. Careful examination of the anophthalmic socket should be part of the physical examination.

Angiolymphoid hyperplasia with eosinophilia occurring in bilateral eyelids.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign lesion, primarily occurring in the head and neck. ALHE arising from the ocular adnexa is rare, and the bilateral presentation is especially rare in the eyelids. CASE PRESENTATION: A 64-year-old Japanese man presented with tearing. Multiple nodules, approximately 5 mm in size, were observed in bilateral upper and lower eyelids. Surgical excisions of the both eyelids masses were performed. Histopathological examination of the excised masses demonstrated proliferated blood vessels lined by plump endothelial cells together with a lymphoid and eosinopilic infiltrate, compatible with a diagnosis of ALHE. Flow cytometry studies showed that the mass consisted of mostly CD3-positive cells. During two-year follow-up, no recurrence of the mass was observed and the patient had no subjective symptom of tearing CONCLUSION: ALHE may occur in the bilateral eyelids. The cause of ALHE remains uncertain, but our results of flow cytemetry suggest that T cells are related to the pathogenesis of this disease.

Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy.

PURPOSE: To investigate whether vitreous and aqueous humor concentrations of vascular endothelial growth factor (VEGF) predict postoperative complications after vitrectomy for proliferative diabetic retinopathy (PDR). METHODS: Sixty eyes of 52 patients with PDR who underwent vitrectomy were enrolled. Vitreous and aqueous humor were obtained from eyes with PDR during primary vitrectomy and the levels of VEGF were measured using a commercial flow cytometer. Patients were followed for more than 6 months after surgery. Demographic data and both intraoperative and postoperative findings were recorded. The relationship between VEGF levels in ocular fluids and the main postoperative complications of early vitreous hemorrhage (VH) and neovascular glaucoma (NVG) occurring during follow-up was analyzed. Logistic regression analyses were performed to examine risk factors related to postoperative complications. RESULTS: Early VH occurred in 25%, and NVG occurred in 8% of 60 eyes. The vitreous levels of VEGF were significantly higher (P = 0.015) in eyes with early VH than in those without. The aqueous humor and vitreous levels of VEGF were significantly higher (P = 0.005 and P = 0.001, respectively) in eyes with NVG than in those without. Axial length was significantly shorter in eyes with early VH than in those without (P = 0.028). Multivariate logistic regression analysis showed that the higher vitreous VEGF level was associated with a risk of early VH after vitrectomy for PDR (odds ratio, 5.1; P = 0.020). CONCLUSIONS: High intraocular VEGF level at the time of primary vitrectomy in patients with PDR was identified as a significant risk factor for postoperative early VH.