Publications by authors named "Kenichi Namba"

126 Publications

[DIAGNOSIS AND TREATMENT OF SEASONAL ALLERGIC CONJUNCTIVITIS BY POLLEN].

Arerugi 2022 ;71(5):353-358

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

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http://dx.doi.org/10.15036/arerugi.71.353DOI Listing
July 2022

Efficacy and Safety of Adalimumab for Exacerbation or Relapse of Ocular Inflammation in Patients with Vogt-Koyanagi-Harada Disease: A Multicenter Study.

Ocul Immunol Inflamm 2022 Jun 24:1-9. Epub 2022 Jun 24.

Centre for Ophthalmic Specialized Care, Lausanne, Switzerland.

Purpose: We investigated efficacy and safety of adalimumab (ADA) treatment for exacerbation or recurrence of Vogt-Koyanagi-Harada (VKH) patients.

Methods: Medical records of 70 VKH patients who received ADA treatment for more than 6 months were retrospectively investigated.

Results: The mean age of VKH patients was 54.8 ± 15.1 years, and male/female ratio was 34/36, and sunset glow fundus was observed in 71.4%. Subfoveal choroidal thickness, indocyanine green angiography scores, and corticosteroid and cyclosporine doses were significantly reduced by ADA treatment for 6 months compared to baseline, while LogMAR and flare counts were also improved without being statistically significant. Adverse events were observed in 17.1%, in which tuberculosis was at 7.14% and psoriasis was at 2.86%; however, ADA treatment was continued in 91.4%.

Conclusions: ADA was shown to be effective to achieve remission of VKH disease refractory to conventional treatments and was generally well tolerated with few serious adverse events.
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http://dx.doi.org/10.1080/09273948.2022.2092007DOI Listing
June 2022

Clinical features of ocular sarcoidosis: severe, refractory, and prolonged inflammation.

Jpn J Ophthalmol 2022 Jun 21. Epub 2022 Jun 21.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Purpose: To clarify the proportion of ocular sarcoidosis with severe, refractory, and prolonged inflammation and their association with ocular complications and visual prognosis.

Study Design: Multicenter, retrospective, longitudinal cohort study.

Methods: Three hundred and twenty-three eyes of 164 patients (45 men; 119 women) with ocular sarcoidosis who visited Hokkaido University Hospital and Yokohama City University Hospital from 2010 to 2015. We newly defined severe, refractory, and prolonged inflammation in ocular sarcoidosis, and investigated their proportions, ocular complications and final visual acuity from medical records of our sarcoidosis patients.

Results: The eyes with severe inflammation numbered 72/323 (22.3%), with refractory inflammation, 80/323 (24.8%), and with prolonged inflammation, 91/323 (28.2%). The number of eyes having neither severe, refractory, nor prolonged inflammation (defined as none) was 114/323 (35.3%). The numbers of eyes that reached irreversible visual dysfunction were 6/72 (8.3%) of those with severe inflammation, 10/80 (12.5%) with refractory inflammation, 12/91 (13.2%) with prolonged inflammation, and 4/114 (6.2%) with none. As complications, cataract (62.2%), glaucoma (28.5%), epiretinal membrane (24.1%), cystoid macular edema (22.6%), vitreous hemorrhage (2.8%), choroidal atrophy (2.5%), macular degeneration (1.2%), macular hole (0.9%) and retinal detachment (0.3%) were identified. Among them, secondary glaucoma (16 eyes) and macular degeneration (4 eyes) were major complications related to irreversible visual dysfunction.

Conclusions: Although most of the patients with ocular sarcoidosis had a relatively good visual prognosis, some developed severe, refractory, and/or prolonged inflammation related to the development of ocular complications, that resulted in poor visual prognosis.
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http://dx.doi.org/10.1007/s10384-022-00927-yDOI Listing
June 2022

Use of systemic corticosteroids in patients newly registered at a claims database with a diagnosis of non-infectious uveitis: results from a real-world claims database analysis.

Jpn J Ophthalmol 2022 Jul 7;66(4):394-404. Epub 2022 Jun 7.

Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.

Purpose: To investigate the real-world dose of systemic corticosteroids in the treatment of non-infectious uveitis (NIU) in Japan.

Study Design: A retrospective, observational study.

Methods: Patients newly registered at the Japan Medical Data Center health insurance claims database with a diagnosis of NIU who received systemic corticosteroids were identified, and their systemic corticosteroid dose (prednisolone equivalent) was assessed over 12 months of treatment (data extraction period: January 2008 to May 2017).

Results: The mean cumulative systemic corticosteroid dose in 12 months in 1641 new patients with NIU who received systemic corticosteroids was 593.7 mg. The mean systemic corticosteroid dose was highest at month 1 (10.7, 218.1, 16.7, and 23.0 mg/day in Behçet's disease [BD]-associated NIU [n = 19], Vogt-Koyanagi-Harada [VKH] disease-associated NIU [n = 49], sarcoidosis-associated NIU [n = 27], and "undifferentiated NIU" [NIU without specific primary disease information, n = 1545], respectively) and decreased over time. Systemic corticosteroids were prescribed at month 12 to 68.4%, 22.4%, 44.4%, and 5.6% of patients with BD-associated NIU, VKH disease-associated NIU, sarcoidosis-associated NIU, and undifferentiated NIU, respectively (mean dose, 6.0-14.3 mg/day). Multivariate regression analysis identified female sex, middle age (30 to < 40 years), VKH disease, and immunosuppressive agent use as background factors associated with higher systemic corticosteroid dose.

Conclusions: The systemic corticosteroid dose was highest at month 1 and decreased over time in all disease categories. This database research revealed that some patients with NIU continued being prescribed systemic corticosteroids for at least 1 year.
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http://dx.doi.org/10.1007/s10384-022-00923-2DOI Listing
July 2022

Long-term Outcomes of Modified 360-Degree Suture Trabeculotomy for Uveitic Glaucoma Compared With Primary Open Angle Glaucoma.

J Glaucoma 2022 08 2;31(8):682-688. Epub 2022 Jun 2.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Prcis: A Kaplan-Meier survival curve analysis showed no significant differences in success rates between uveitic glaucoma (UG) and primary open angle glaucoma (POAG) 120 months after modified 360-degree suture trabeculotomy, which was effective for both groups in the long term.

Purpose: The aim of this study was to examine the outcomes of modified 360-degree suture trabeculotomy in patients with UG as compared with those with POAG.

Patients And Methods: This was a retrospective, nonrandomized, and comparative case series study. Modified 360-degree trabeculotomy using a 5-0 nylon suture (S-LOT) was performed on 51 eyes of 51 patients (54.4±13.4 y) with UG between October 2005 and January 2012 at Hokkaido University Hospital. Age-matched patients with POAG who underwent S-LOT during the same period were enrolled as controls. Written informed consent was obtained from all patients enrolled in the present study. Surgical success was defined as an intraocular pressure (IOP) <18 mm Hg with similar or lower doses of antiglaucoma medications. Kaplan-Meier survival curves of surgical failure were analyzed and compared between UG and POAG.

Results: The mean follow-up periods (±SD) for UG and POAG were 104.8±44.0 and 98.1±36.3 months ( P =0.23), respectively. Mean preoperative IOP in UG and POAG were 34.9±11.0 and 25.3±9.4 mm Hg ( P <0.001), respectively. After surgery, mean IOP in UG and POAG decreased to 12.0±4.1 and 13.8±3.2 mm Hg, respectively, at 60 months, and 12.1±5.6 and 12.4±1.8 mm Hg ( P =0.86), respectively, at 120 months. The Kaplan-Meier survival curve analysis showed no significant differences in success rates between UG and POAG at the end of the follow-up (Log-rank test, P =0.13). Success rates in UG and POAG were 70.0 and 62.5% at 60 months, and 67.5 and 41.2% at 120 months, respectively.

Conclusion: These results suggest that S-LOT is effective for UG and POAG alike.
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http://dx.doi.org/10.1097/IJG.0000000000002057DOI Listing
August 2022

Clinical Features of Primary Vitreoretinal Lymphoma: A Single-center Study.

Cancer Diagn Progn 2021 May-Jun;1(2):69-75. Epub 2021 May 3.

Department of Ophthalmology, Faculty of Medicine andGraduate School of Medicine, Hokkaido University, Sapporo, Japan.

Background/aim: This study aimed to demonstrate the clinical outcomes of primary vitreoretinal lymphoma (PVRL).

Patients And Methods: Seventeen patients with PVRL who had been treated at Hokkaido University Hospital were enrolled in this study. They were diagnosed based on their cytology, interleukin-10/-6 ratio, and immunoglobulin heavy chain (IgH) gene rearrangement.

Results: Diagnostic tests detected cytological malignancy among 14 cases (82.3%), high interleukin-10/-6 ratios among 16 cases (94.1%), and IgH monoclonality in 13 cases (76.5%). Systemic corticosteroids were given to seven (41.2%) patients before their diagnosis of PVRL. Treatments after diagnosis comprised intravitreal methotrexate injection, local radiation, and intravenous chemotherapy for 11, seven, and five cases, respectively. Central nervous system and systemic involvements were observed in nine and one case, respectively, and these complications occurred at 3 to 43 months (mean=16 months) after initial ocular presentation.

Conclusion: Many of our patients did not receive any systemic intervention, and almost half of patients with PVRL developed central nervous system involvement during their follow-up period.
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http://dx.doi.org/10.21873/cdp.10010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962760PMC
May 2021

Long-Term Safety and Effectiveness of Adalimumab in Japanese Patients with Noninfectious Intermediate, Posterior, or Panuveitis: Post-Marketing Surveillance of 251 Patients.

Ophthalmol Ther 2022 Jun 19;11(3):1147-1161. Epub 2022 Mar 19.

Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.

Introduction: The aim of this nationwide, prospective post-marketing surveillance was to assess the safety and effectiveness of up to 52 weeks of adalimumab treatment in patients with noninfectious intermediate, posterior, or panuveitis in Japanese clinical practice.

Methods: This post-marketing surveillance was conducted at 60 medical facilities in Japan from October 2016 to June 2020. Patients with noninfectious intermediate, posterior, or panuveitis who were administered adalimumab (Humira, AbbVie Inc.) for the first time were eligible. Subcutaneous adalimumab was initially administered at 80 mg, followed by 40 mg 1 week later, then 40 mg every 2 weeks. Safety measures included the incidence of adverse events (AEs) and adverse drug reactions (ADRs; primary endpoint). Effectiveness measures included visual acuity, anterior chamber cell grade, vitreous haze, macular edema, foveal retinal thickness, uveitis recurrence rate, and oral corticosteroid dose. Health-related quality of life was evaluated using the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25).

Results: During 52 weeks of surveillance, AEs and ADRs occurred in 70 (27.9%) and 47 (18.7%) of 251 patients, respectively. The most common ADR was infection (21/251 patients; 8.4%), including serious infections in eight (3.2%) patients. ADRs were more frequent in patients ≥ 65 years of age, those with concurrent diseases, and those with past medical history. Four patients developed tuberculosis. The uveitis recurrence rate was 24.8% (61/246 patients). All effectiveness measures tended to improve from baseline to week 52, and mean corticosteroid doses decreased. Clinically meaningful changes were observed for most VFQ-25 subscales.

Conclusions: The safety profile of adalimumab was generally consistent with previous reports, and no new safety concerns were identified.

Trial Registration: ClinicalTrials.gov: NCT02916017.
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http://dx.doi.org/10.1007/s40123-022-00493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114192PMC
June 2022

Diagnostic Accuracy of Cell Block Preparations and Clinical Features Affecting It in Vitreoretinal Lymphoma.

J Clin Med 2022 Mar 3;11(5). Epub 2022 Mar 3.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.

Purpose: The purpose of this study was to examine the diagnostic accuracy of the cell block (CB) method and clinical features affecting it in patients with vitreoretinal lymphoma (VRL).

Methods: This study enrolled 38 eyes in 33 VRL patients, and 7 eyes in 7 patients with idiopathic uveitis who underwent diagnostic vitrectomy. Medical records including the results of CB cytology, interleukin (IL)-10/-6 concentrations, and immunoglobulin heavy chain gene (IgH) rearrangement were retrospectively searched.

Results: Patients with VRL comprised 16 women and 17 men, and the age of onset ranged from 44 to 85 years (mean: 70 years). CB preparations detected large malignant cells in 35 eyes (92%), whereas the other 3 VRL eyes were negative. Two of the latter three eyes showed subretinal infiltrates, which existed in 7 of 35 CB-positive eyes. Intravitreal IL-10 and -6 concentrations were 1866 ± 4088 pg/mL and 98 ± 139 pg/mL, respectively, and the rate of IL-10/-6 >1 was 86.9%. The presence of IgH monoclonality was 63.2%. In patients with uveitis, CB specimens revealed no atypical but small inflammatory cells. IL-6 concentration was 311.1 ± 240 pg/mL, whereas IL-10 was undetectable in six eyes, and the IL-negative rate was 85.7%. Six eyes (85.7%) with uveitis showed no IgH monoclonality.

Conclusions: Diagnostic accuracy of CB preparations in VRL could achieve an equivalent outcome to IL ratio calculation and IgH monoclonality detection. The appearance of subretinal infiltrates may diminish the CB positivity.
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http://dx.doi.org/10.3390/jcm11051391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911042PMC
March 2022

The Steroid-Sparing Effect of Adalimumab in the Treatment for the Recurrent Phase of Vogt-Koyanagi-Harada Disease.

Ocul Immunol Inflamm 2022 Feb 25:1-5. Epub 2022 Feb 25.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: To reveal the steroid-sparing effect of adalimumab (ADA) in the treatment for the chronic recurrent phase of Vogt-Koyanagi-Harada (VKH) disease.

Cases And Methods: Thirty-six eyes from 18 cases of the recurrent phase of VKH disease treated with ADA over 12 months were examined retrospectively. Before the introduction of ADA, 4 cases received prednisolone (PSL) monotherapy and other 14 cases received PSL and cyclosporine A (CYA) combination therapy.

Results: In cases treated with PSL and CYA, CYA was discontinued when ADA was introduced. The minimum dose of PSL to control intraocular inflammation (min dose of PSL) could be reduced in all cases after the introduction of ADA (from 16.9 ± 7.9 mg to 6.3 ± 3.1 mg). No serious adverse events were observed in the observational periods.

Conclusion: By comparing the min dose of PSL before and after the introduction of ADA, the steroid-sparing effect of ADA was confirmed.
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http://dx.doi.org/10.1080/09273948.2022.2037657DOI Listing
February 2022

A case of Epstein-Barr virus acute retinal necrosis successfully treated with foscarnet.

Am J Ophthalmol Case Rep 2022 Mar 29;25:101363. Epub 2022 Jan 29.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: Epstein-Barr virus (EBV) is a herpes virus known to cause infectious mononucleosis and several other human disorders. Ocular EBV infections that have been reported include uveitis, retinal vasculitis, and acute retinal necrosis (ARN). ARN is usually caused by herpes simplex virus (HSV) or varicella-zoster virus (VZV). ARN that is caused by EBV (EBV-ARN) is rarely seen, and only a few cases have been reported. The visual prognosis for EBV-ARN is poor, and no treatment strategy has been established. We report on a patient who was treated successfully for EBV-ARN.

Observation: An 80-year-old female who had been treated with prednisolone at 5 mg/day and methotrexate at 2 mg/week for rheumatoid arthritis visited our hospital because of blurred vision in her left eye. Her left visual acuity was 20/50, and extensive white-yellowish retinal lesions at the temporal periphery with retinal hemorrhages were seen through vitreous haze. The DNA sequence of EBV, but not of HSV, VZV, or cytomegalovirus, was detected by a polymerase chain reaction (PCR) assay in the aqueous humor (4.2 × 10 copies/ml), with EBV also being positive in serum (3.5 × 10 copies/ml). The patient received 2 mg of intravitreal ganciclovir injections twice with a 3-day interval and intravenous infusion of acyclovir at 750 mg/day for 7 days; however, the retinal white lesions expanded rapidly, then dose of prednisolone was increased (40 mg/day) and vitrectomy was performed 10 days after the initial visit. After the surgery, the retinal lesion continued to enlarge. Vitreous samples showed high copies of EBV (1.2 × 10 copies/ml). Following treatment with intravenous foscarnet (4800 mg/day), which replaced the acyclovir application, the retinal white lesions gradually diminished, leaving retinal scars. To date, the patient has developed no retinal detachment and shows visual acuity over 6/60 in the left eye along with silicone oil.

Conclusions: We experienced a case of EBV-ARN that was refractory to systemic acyclovir and topical ganciclovir but responded effectively to systemic foscarnet after vitrectomy. Although the clinical management remains challenging in this disease, foscarnet is considered to be one of the candidate drugs for EBV infections.
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http://dx.doi.org/10.1016/j.ajoc.2022.101363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818534PMC
March 2022

Posterior scleritis with anti-neutrophil cytoplasmic antibody-associated vasculitis utilizing rituximab therapy to maintain remission: A case report.

Am J Ophthalmol Case Rep 2022 Mar 22;25:101333. Epub 2022 Jan 22.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis syndrome characterized by the destruction of small vessels, leading to various organ disorders. Here, we report a case of posterior scleritis with AAV successfully treated with prednisolone and rituximab (RTX) combination therapy.

Observations: A 69-year-old female suffered from ocular pain and redness in her left eye for 2.5 years. She had been diagnosed with idiopathic otitis media before a year. At her initial visit, scleral injection with nodular elevated scleral lesions, vitreous haze, and serous retinal detachment (SRD) in the inferior periphery were observed in the left eye. Enhanced computed tomography revealed the enhancement and thickening of the left sclera. The results of laboratory analysis were positive for myeloperoxidase ANCA. Accordingly, she was diagnosed with AAV. Owing to the exacerbation of vitreous haze and SRD, topical treatment and steroid pulse therapy were initiated. Following therapy, anterior and posterior scleritis improved, and additional RTX was administered to maintain the remission. Following treatment, the patient has maintained remission with 10 mg/day prednisolone to date.

Conclusions And Importance: We encountered a case of posterior scleritis with AAV in which inflammatory manifestations subsided with RTX and glucocorticoid combination therapy. RTX administration likely contributed to the maintenance of remission.
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http://dx.doi.org/10.1016/j.ajoc.2022.101333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802867PMC
March 2022

Multicenter, retrospective, observational study for the Treatment Pattern of systemic corticoSTERoids for relapse of non-infectious uveitis accompanying Vogt-Koyanagi-Harada disease or sarcoidosis.

Jpn J Ophthalmol 2022 Mar 19;66(2):130-141. Epub 2022 Jan 19.

Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan.

Purpose: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice.

Study Design: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390).

Methods: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression).

Results: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes).

Conclusion: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.
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http://dx.doi.org/10.1007/s10384-021-00897-7DOI Listing
March 2022

Optic Nerve Head Microcirculation in Eyes with Vogt-Koyanagi-Harada Disease Accompanied by Anterior Ischemic Optic Neuropathy.

Case Rep Ophthalmol 2021 Sep-Dec;12(3):899-908. Epub 2021 Nov 8.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Anterior ischemic optic neuropathy (AION) is infrequently complicated with Vogt-Koyanagi-Harada (VKH) disease. We quantitatively examined sequential changes in the morphology and circulation hemodynamics, using a C-scan of optical coherence tomography (OCT) and laser speckle flowgraphy (LSFG) in a patient with VKH disease accompanied by AION. A 65-year-old female complained of blurred vision in both of her eyes. The patient presented with optic disc swelling and remarkable choroidal thickening detected by OCT bilaterally. The diagnosis of VKH disease was established based on the presence of pleocytosis detected in the cerebrospinal fluid and hypofluorescent dark dots scattered all around the fundus, detected by indocyanine green angiography. Goldmann perimetry detected visual field defects, similar to superior altitudinal hemianopsia in the right eye and similar to inferior altitudinal hemianopsia in the left eye. The patient was suspected to have developed AION in both eyes. The patient received methylprednisolone pulse therapy, followed by oral prednisolone. With these treatments, the optic disc swelling disappeared. However, optic disc atrophy with visual field defects remained in both eyes. An OCT C-scan showed the ganglion cell complex (GCC) and circumpapillary retinal nerve fiber layer (cpRNFL) thickness getting thinner below the normal range, and LSFG showed the decrease in optic nerve head (ONH) tissue microcirculation. These results supported the occurrence of AION in this patient with VKH disease. The analysis of GCC and cpRNFL thickness and ONH microcirculation would be useful for supporting the occurrence of AION in a case of VKH disease.
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http://dx.doi.org/10.1159/000520036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647108PMC
November 2021

The Expression of Matrix Metalloproteinases in Eyes with Intraocular Lymphoma.

Ocul Immunol Inflamm 2021 Aug 11:1-5. Epub 2021 Aug 11.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL).

Methods: Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions.

Results: In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%.

Conclusions: MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.
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http://dx.doi.org/10.1080/09273948.2021.1957122DOI Listing
August 2021

Macrophage-like iPS-derived Suppressor Cells Reduce Th1-mediated Immune Response to a Retinal Antigen.

Curr Eye Res 2021 12 19;46(12):1908-1916. Epub 2021 Jul 19.

Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Purpose: To investigate the immunotherapeutic effects of macrophage-like induced pluripotent stem (iPS) cell-derived suppressor cells (SCs) in ocular immune response and experimental autoimmune uveoretinitis (EAU).

Methods: The genes of , and were transferred to B cells enriched from the spleen cells of C57BL/6 mice by using retrovirus vectors. Transferred B cells were cultured for 17 days to obtain colonies of iPS cells. Through additional steps, iPS-SCs were induced. An antigen-specific T cell proliferation assay was performed with CD4 T cells collected from draining lymph nodes of the mice immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide and co-cultured with iPS-SCs. Cytokine concentrations in the culture supernatant were examined. Mice were immunized with hIRBP peptide to induce EAU. The iPS-SCs were administered into the mice one day before the induction of EAU.

Results: The iPS-SCs decreased hIRBP-specific T cell proliferation depending on the number of cells. Productions of tumor necrosis factor-α and interferon-γ were significantly decreased; however, transforming growth factor-β1, nitric oxide, interleukin (IL)-13, IL-17A, and IL-17 F levels were elevated in the supernatant when the collected T cells were co-cultured with iPS-SCs. The iPS-SCs had immunosuppressant effects even without cell-to-cell contact, and their effects were non-specific to the antigen preloaded on iPS-SCs. EAU was significantly milder in the mice administered iPS-SCs prior to immunization.

Conclusions: Macrophage-like iPS-SCs reduced Th1 immune response to a retinal antigen and Th1-mediated EAU in mice. These results showed the possibility of the application of iPS technology to the treatment of noninfectious ocular inflammation, endogenous uveitis, in the future.
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http://dx.doi.org/10.1080/02713683.2021.1952605DOI Listing
December 2021

Prevalence and incidence rates and treatment patterns of non-infectious uveitis in Japan: real-world data using a claims database.

Jpn J Ophthalmol 2021 Sep 28;65(5):657-665. Epub 2021 Jun 28.

Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.

Purpose: To estimate the nationwide, longitudinal prevalence and incidence rates and assess treatment patterns of non-infectious uveitis (NIU) in Japan.

Study Design: A retrospective study.

Methods: Health insurance claims' data of patients with NIU were extracted from the Japan Medical Data Center (JMDC) database and analyzed descriptively (data extraction period, January 2011 to May 2017). Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, and sarcoidosis were selected as the primary diseases of NIU.

Results: From 2011 to 2016, the mean and median age of patients increased. Most (> 90%) patients were categorized as "undifferentiated NIU" (NIU without specific primary disease information after excluding BD-, VKH disease-, and sarcoidosis-associated NIU). Over 60% of patients with NIU were treated at non-hospital clinics, while the rest were treated at university, public, or other hospitals. The estimated prevalence rate of NIU was 386.5 per 100,000 persons (95% confidence interval [CI], 374.5-398.6) in 2011 and 439.3 per 100,000 persons (95% CI, 432.3-446.3) in 2016; the estimated incidence rate was 189.7 per 100,000 persons (95% CI, 181.2-198.5) in 2012 and 207.8 per 100,000 persons (95% CI, 202.2-213.5) in 2016. Most patients' prescribed uveitis drugs were ophthalmic drops over the first 6 months after patient presentation and entry into the JMDC database, followed by systemic corticosteroids.

Conclusion: The estimated prevalence of NIU in Japan in recent years was approximately 400 with incidence of 200 per 100,000 persons.
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http://dx.doi.org/10.1007/s10384-021-00850-8DOI Listing
September 2021

Surgical Outcomes of Trabeculectomy in Uveitic Glaucoma: A Long-Term, Single-Center, Retrospective Case-Control Study.

J Ophthalmol 2021 21;2021:5550776. Epub 2021 May 21.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: To evaluate the long-term outcomes of trabeculectomy with mitomycin C (MMC-TLE) in patients with uveitic glaucoma (UG). This was a retrospective, nonrandomized case series study. MMC-TLE was performed on 50 eyes with UG between February 2001 and January 2015 at Hokkaido University Hospital. Age- and sex-matched patients with primary open angle glaucoma (POAG) who underwent MMC-TLE were matched by age and sex and enrolled as controls. Surgical success was defined as an intraocular pressure (IOP) less than 18 or 15 mmHg. The Kaplan-Meier survival curves for surgical failure were analyzed.

Results: The mean preoperative IOP in UG and POAG was 27.6 ± 10.6 and 18.0 ± 4.5 mmHg, respectively. After the surgery, the mean IOP in UG and POAG was reduced to 11.7 ± 4.2 and 12.2 ± 3.8 mmHg at 12 months, 11.9 ± 7.0 and 12.1 ± 3.1 mmHg at 36 months, and 13.0 ± 5.2 and 10.6 ± 1.2 mmHg at 120 months, respectively. The success rates (IOP <18 mmHg, IOP reduction >20%) in UG and POAG were 91.7% and 88.0% at 12 months, 82.2% and 75.6% at 36 months, and 66.5% and 61.8% at 120 months, respectively. The success rates (IOP <15 mmHg) in UG and POAG were 64.0% and 58.0% at 12 months, 55.1% and 45.5% at 36 months, and 47.9% and 37.8% at 120 months, respectively. There was no significant difference in the success rate between UG and POAG at 120 months after surgery by either definition of surgical success.

Conclusions: MMC-TLE effectively reduced IOP in both UG and POAG. There was no significant difference in the success rate between UG and POAG. Following sufficient inflammation suppression, surgical outcomes of UG may be comparable with those of POAG.
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http://dx.doi.org/10.1155/2021/5550776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163556PMC
May 2021

Distinguishing Features of Anterior Uveitis Caused by Herpes Simplex Virus, Varicella-Zoster Virus, and Cytomegalovirus.

Am J Ophthalmol 2021 07 25;227:191-200. Epub 2021 Mar 25.

Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo (H.T, N.H, M.I, M.M). Electronic address:

Purpose: To determine distinguishing features of the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV).

Design: Retrospective, multicenter case series.

Methods: Consecutive patients with herpetic AU examined at 11 tertiary centers in Japan between January 2012 and December 2017 and who were followed for ≥3 months were evaluated. Diagnosis was made by polymerase chain reaction (PCR) for HSV, VZV, or CMV in the aqueous humor, or classical signs of herpes zoster ophthalmicus.

Results: This study enrolled 259 herpetic AU patients, including PCR-proven HSV-AU (30 patients), VZV-AU (50), and CMV-AU (147), and herpes zoster ophthalmicus (32). All HSV-AU and VZV-AU patients were unilateral, while 3% of CMV-AU patients were bilateral. Most HSV-AU and VZV-AU patients were sudden onset with an acute clinical course, while CMV-AU had a more insidious onset and chronic course. There were no significant differences for all surveyed symptoms, signs, and complications between HSV-AU and VZV-AU. However, significant differences were detected for many items between CMV-AU and the other two herpetic AU types. Ocular hyperemia and pain, blurring of vision, ciliary injection, medium-to-large keratic precipitates (KPs), cells and flare in the anterior chamber, and posterior synechia significantly more often occurred in HSV-AU and VZV-AU vs CMV-AU. In contrast, small KPs, coin-shaped KPs, diffuse iris atrophy, elevated intraocular pressure, and glaucoma surgery were significantly more frequent in CMV-AU vs HSV-AU and VZV-AU.

Conclusion: This multicenter, retrospective study identified distinguishing features of HSV-AU, VZV-AU, and CMV-AU.
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http://dx.doi.org/10.1016/j.ajo.2021.03.020DOI Listing
July 2021

Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey.

Jpn J Ophthalmol 2021 Mar 11;65(2):184-190. Epub 2021 Mar 11.

Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan.

Purpose: To investigate the epidemiology of uveitis in Japan and assess its changes over time.

Study Design: Retrospective multicenter study METHODS: Sixty-six hospitals in Japan with uveitis specialty clinics participated in this retrospective nationwide survey. A questionnaire was sent to each hospital to survey the total number of patients who made a first visit to the outpatient uveitis clinic of each hospital between 1 April 2016 and 31 March 2017. The diagnosis of uveitis was based on guidelines when available or on commonly used diagnostic criteria.

Results: In 2016, new patients with uveitis accounted for 3.2% of the total number of new patients with ophthalmic diseases. A total of 5378 patients were enrolled in the survey; 3408 cases could be classified with a specific uveitis entity, and 1970 cases were described as unclassified intraocular inflammation. Among the classified cases, the most frequent disease was sarcoidosis (10.6%), followed by Vogt-Koyanagi-Harada disease (8.1%), herpetic iritis (6.5%), acute anterior uveitis (5.5%), sclerouveitis (4.4%), Behçet's disease (4.2%), malignant disease (2.6%), acute retinal necrosis (1.7%), Posner-Schlossman syndrome (1.7%), and diabetic iritis (1.4%). The rates of sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet's disease were similar; however, the rate of herpes iritis increased (4.2-6.5%) when compared with the 2009 survey.

Conclusions: Some changes were observed between the previous nationwide surveys (2002 and 2009) and the present survey. It must be valuable to continue such nationwide epidemiologic surveys at regular intervals.
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http://dx.doi.org/10.1007/s10384-020-00809-1DOI Listing
March 2021

Recent Clinical Features of Intraocular Inflammation in Hokkaido, Japan - Comparison with the Previous Decade.

Ocul Immunol Inflamm 2021 Feb 11:1-7. Epub 2021 Feb 11.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Purpose: This study aimed to investigate the clinical features of intraocular inflammation (uveitis) in Hokkaido and to assess the etiology trends in comparison with those of our previous survey.

Methods: We retrospectively reviewed the medical records of 1,616 new referral uveitis patients (1,020 females and 596 males) in Hokkaido University Hospital between 2004 and 2014.

Results: Sarcoidosis was the most frequent etiology (17.4%), followed by Vogt-Koyanagi-Harada disease (8.1%), Behçet's disease (4.5%), and human leukocyte antigen B27 -associated uveitis (2.5%). The etiologies in 48.7% of the patients were unclassified. Compared to the previous survey between 1994 and 2003, the rate of Behçet's disease decreased and that of sarcoidosis increased. The rates of infectious uveitis and vitreoretinal lymphoma increased.

Conclusion: Although the order of the top four etiologies was the same in the two surveys, the rate of sarcoidosis increased and that of Behçet's disease decreased.
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http://dx.doi.org/10.1080/09273948.2020.1836565DOI Listing
February 2021

Validation of systemic parameters for the diagnosis of ocular sarcoidosis.

Jpn J Ophthalmol 2021 Mar 9;65(2):191-198. Epub 2021 Jan 9.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.

Purpose: Ocular sarcoidosis is diagnosed based on suggestive intraocular findings and systemic investigations. In this study, we assessed the clinical usefulness of systemic parameters in the diagnosis of ocular sarcoidosis.

Study Design: A retrospective study.

Methods: This study included 79 cases (19 men, 60 women) with ocular sarcoidosis who visited Hokkaido University Hospital from 2011 to 2015 and were followed up for more than one year. The control group was 91 cases of other uveitis (38 men, 53 women). All cases underwent blood examination for the measurement of angiotensin-converting enzyme (ACE), Krebs von den Lungen-6 (KL-6), soluble interleukin-2 receptor (sIL-2R), and calcium (Ca) levels. Bilateral hilar lymphadenopathy (BHL) was also examined by plain chest X-ray and contrasting chest computed tomography (CT).

Results: The sensitivity for sIL-2R (76.4%) was higher than for ACE (37.7%), KL-6 (26.3%), and Ca (11.8%), although all showed high specificity: ACE (97.5%), KL-6 (96.2%), sIL-2R (93.8%), and Ca (95.1%). From these results, the Youden index of sIL-2R (0.70) was higher than that of ACE (0.35), KL-6 (0.26), and Ca (0.07). Imaging tests revealed better detection of BHL by contrasting chest CT (82.7%) than by plain chest X-ray (29.5%).

Conclusion: The present findings indicate that the systemic parameters, particularly serum sIL-2R levels and BHL on contrasting chest CT, are useful biomarkers for the diagnosis of ocular sarcoidosis.
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http://dx.doi.org/10.1007/s10384-020-00793-6DOI Listing
March 2021

Alteration of oral flora in Mongolian patients with Behçet's disease: a multicentre study.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):80-85. Epub 2020 Dec 10.

Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo and Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Objectives: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS).

Methods: DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora.

Results: Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group.

Conclusions: The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.
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December 2020

Correction to: Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy.

Graefes Arch Clin Exp Ophthalmol 2021 Apr;259(4):1083

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

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http://dx.doi.org/10.1007/s00417-020-05038-3DOI Listing
April 2021

Japanese guidelines for allergic conjunctival diseases 2020.

Allergol Int 2020 Jul 25;69(3):346-355. Epub 2020 Apr 25.

Department of Ophthalmology, Tsurumi University School of Dental Medicine, Kanagawa, Japan.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.
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http://dx.doi.org/10.1016/j.alit.2020.03.005DOI Listing
July 2020

Development of cytomegalovirus retinitis after negative conversion of cytomegalovirus antigenemia due to systemic antiviral therapy.

Graefes Arch Clin Exp Ophthalmol 2021 Apr 13;259(4):971-978. Epub 2020 Nov 13.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Purpose: Cytomegalovirus (CMV) antigenemia assays have been widely used as adjunct tests to diagnose tissue invasive CMV diseases, including cytomegalovirus retinitis (CMVR). In this study, we examined CMVR cases to assess the presence of CMV in sera and aqueous humor and antiviral therapy received prior to the onset of CMVR.

Methods: A total of 37 eyes from 26 different cases of CMVR in patients who visited Hokkaido University Hospital between 2007 and 2015 were enrolled. The diagnosis of CMVR was established based on characteristic ophthalmoscopic findings and the presence of local and/or systemic CMV infection. Among the 26 cases, 3 cases (12%) were HIV-positive, while the other 23 cases (88%) were HIV-negative. The records of clinical and laboratory results were reviewed from clinical charts retrospectively.

Results: CMV antigenemia was positive at the onset of CMVR in 14 cases (53.8%) and negative in the other 12 cases. In 9 cases among the antigenemia-negative cases (75.0%), the antigenemia had been previously positive and had turned negative before the onset of CMVR. In 12 of the 14 antigenemia-positive cases (85.7%) and in 8 of the 9 antigenemia-negative cases (88.9%) that were previously positive, systemic antiviral therapies had never been used or had been used before but had been discontinued prior to the onset of CMVR.

Conclusion: Even if viremia turns negative, the risk of developing CMVR exists for more than several weeks after the completion of systemic therapy.
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http://dx.doi.org/10.1007/s00417-020-05011-0DOI Listing
April 2021

Multiple evanescent white dot syndrome and panuveitis: a case report.

J Ophthalmic Inflamm Infect 2020 Oct 29;10(1):26. Epub 2020 Oct 29.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Nishi 7, Kita 15, Kita-ku, Sapporo, 060-8638, Japan.

Aim: To report a patient with multiple evanescent white dot syndrome (MEWDS) complicated by iridocyclitis and vitritis.

Case Description: A 70-year-old woman developed multiple subretinal white dots, iritis, and diffuse vitreous opacity. Angiographic and macular morphological features were consistent with those of MEWDS. Inflammatory findings including the white dots improved following only topical dexamethasone within 1 month after the initial visit. Best-corrected visual acuity recovered to 1.0 with restored photoreceptor structure.

Conclusion: The presence of iridocyclitis and vitritis, atypical to MEWDS, indicates the concurrent development of panuveitis associated with MEWDS. These results suggest that MEWDS is a clinical entity of uveitis.
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http://dx.doi.org/10.1186/s12348-020-00221-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596130PMC
October 2020

Reduced steroid-induced intraocular pressure elevation in tacrolimus-treated refractory allergic ocular diseases.

Jpn J Ophthalmol 2020 Nov 7;64(6):568-576. Epub 2020 Oct 7.

Department of Ophthalmology, Tsurumi University Dental Hospital, Yokohama, Kanagawa, Japan.

Purpose: To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation.

Study Design: Open cohort post hoc analysis study.

Methods: Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids.

Results: The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006).

Conclusions: Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.
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http://dx.doi.org/10.1007/s10384-020-00774-9DOI Listing
November 2020

Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.

Ocul Immunol Inflamm 2022 Jan 18;30(1):48-53. Epub 2020 Sep 18.

Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis.: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis.: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis.: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.
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http://dx.doi.org/10.1080/09273948.2020.1789179DOI Listing
January 2022

Genetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis.

Commun Biol 2020 08 21;3(1):465. Epub 2020 Aug 21.

Department of Ophthalmology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.
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http://dx.doi.org/10.1038/s42003-020-01185-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442816PMC
August 2020

Epidemiological aspects of allergic conjunctivitis.

Allergol Int 2020 Oct 9;69(4):487-495. Epub 2020 Jul 9.

Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Tottori, Japan.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.
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http://dx.doi.org/10.1016/j.alit.2020.06.004DOI Listing
October 2020
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