Clinical features and visual outcomes of ocular sarcoidosis at a tertiary referral center in Tokyo.

BACKGROUND: To analyze clinical features, treatment, complications, and visual outcomes of ocular sarcoidosis at a tertiary center in Tokyo. METHODS: Clinical records of 53 patients with ocular sarcoidosis ("definite" or "presumed") presenting between 2013 and 2018 to the Kyorin Eye Center were retrospectively reviewed. Diagnosis was based on the revised criteria of the International Workshop on Ocular Sarcoidosis. RESULTS: Definite (biopsy-proven) disease was present in 87% of patients and presumed disease in 13%. The mean age at presentation was 58 years (13-81 years) and 68% were women. The mean follow-up was 34 months (6-70 months). Forty-five patients (85%) had panuveitis, and the most common ocular clinical sign suggestive of ocular sarcoidosis was bilaterality (92%). Ocular complications were observed in 93 eyes (85%), most commonly cataract (73%), epiretinal membrane (24%), macular edema (24%) and glaucoma (19%). Thirty-one eyes (30%) underwent cataract surgery and 12 eyes (12%) underwent pars plana vitrectomy. Ten patients (19%) received systemic corticosteroid therapy and 33 eyes (32%) received periocular corticosteroid injections. The best-corrected visual acuity was 1.0 or better in 51% of eyes at presentation, 57% at 6 months, 50% at 12 months, and 58% at 36 months. CONCLUSIONS: The majority of ocular sarcoidosis patients were women, had bilateral disease and panuveitis involvement. Most eyes maintained good visual acuity, although surgical interventions for cataract and epiretinal membrane were common.

Circulating Vitreous microRNA as Possible Biomarker in High Myopic Eyes with Macular Hole.

High myopia is a major cause of irreversible visual impairment globally. In the present study, we investigated the microRNA (miRNA) profile in the vitreous of macular hole (MH) and high myopic MH. We performed miRNA analysis using TaqMan® Low Density Arrays (Thermo Fisher Scientific, Waltham, MA, USA) to investigate the circulating vitreous miRNA profile from patients with MH (axial length < 26.5 mm, n = 11) and high myopic MH (axial length ≥ 26.5 mm, n = 11) who underwent pars plana vitrectomy. The vitreous inflammatory cytokine signature was examined in high myopic MH eyes using a multiplex assay. A miRNA-Array analysis revealed that let-7c was significantly up-regulated and miR-200a was significantly down-regulated in high myopic MH eyes compared to those in MH eyes. The bioinformatics analysis for up-regulated miRNA targeted gene identified 23 pathways including mitogen-activated protein kinase (MAPK) and several inflammatory signaling pathways, whereas the bioinformatics analysis for down-regulated miRNA targeted genes showed 32 enriched pathways including phosphoinositide 3-kinase/protein kinase B (PI3K/AKT). The levels of inflammatory cytokines including IP-10, IFN-γ, and MCP-1 were significantly higher in the vitreous of high myopic MH eyes. These results suggest that specific miRNAs expressed in the vitreous may be associated with the pathological condition of high myopic MH and the above mentioned miRNAs may contribute to the development of inflammatory status in the vitreous of high myopic eyes.

Vitrectomy and scleral imbrication in patients with myopic traction maculopathy and macular hole retinal detachment.

PURPOSE: To determine the outcomes of vitrectomy with scleral imbrication in highly myopic eyes with either myopic traction maculopathy (MTM) or macular hole retinal detachment (MHRD). METHODS: The medical records of 17 patients who had undergone vitrectomy with internal limiting membrane (ILM) peeling and scleral imbrication for MTM or MHRD were reviewed. The best-corrected visual acuities (BCVAs), the axial length, the macular hole (MH) closure rate, and the shape of the posterior segment determined by optical coherence tomography were evaluated. Three-dimensional magnetic resonance imaging (3D-MRI) was also performed on five eyes. RESULTS: The postoperative BCVA improved significantly from 0.76 ± 0.39 logarithm of the minimum angle of resolution (logMAR) units to 0.53 ± 0.35 logMAR units (P = 0.0004). The axial length decreased from 29.42 ± 1.81 mm to 27.97 ± 1.71 mm at 1 month. The MTM was resolved or decreased in all eyes. The MH was closed in 44 % of the MHRD eyes, and the retina was reattached in all of the MHRD eyes. The horizontal distance between the optic disc and the bottom of the posterior staphyloma was significantly decreased at 1 month (P = 0.012) but not at later times. The 3D-MRI images showed a reduction in the distance between the bottom of the posterior staphyloma and the center of the eye (P = 0.029) and a flattening of the posterior staphyloma (P = 0.010). CONCLUSIONS: Vitrectomy with ILM peeling and scleral imbrication may be helpful in treating MTM and MHRD by reducing the degree of curvature of the posterior staphyloma.

MACULAR DETACHMENT ASSOCIATED WITH INTRACHOROIDAL CAVITATION IN NONPATHOLOGICAL MYOPIC EYES.

PURPOSE: To report the characteristics of a macular detachment associated with peripapillary intrachoroidal cavitation (ICC) and the outcomes of vitrectomy. METHODS: The medical records of 69 eyes of 61 patients who underwent vitrectomy for macular detachment or macular retinoschisis but without vitreomacular traction or optic disc pit were reviewed. Optical coherence tomography was used to determine the morphology of the ICC. The outcomes of vitrectomy including the creation of a posterior vitreous detachment and internal limiting membrane peeling were evaluated. RESULTS: An ICC was detected in 3 of 3 eyes without pathologic myopia but none in 66 eyes with pathologic myopia (P < 0.0001). Myopic peripapillary conus was present in all 3 eyes, tilted disc in 2 eyes (67%), posterior staphyloma in 1 eye (33%), and no preoperative posterior vitreous detachment in all eyes. Optical coherence tomography detected a connection between the vitreous cavity and the ICC in two eyes with pit-like splitting and between the subretinal space and the ICC in two eyes. The macular detachment was resolved 5 months to 6 months postoperatively with improvement of vision. CONCLUSION: A macular detachment with ICC can be present in nonpathological myopic eyes. Vitreous surgery to create a posterior vitreous detachment with internal limiting membrane peeling may help resolve the macular detachment.

Levofloxacin susceptibility of Staphylococci from conjunctiva in patients with atopic dermatitis.

PURPOSE: The ocular surface in patients with atopic dermatitis (AD) is known to harbor an abundance of gram-positive cocci, particularly Staphylococcus aureus (S. aureus). This study reviewed the results of microbial cultures from the conjunctiva in AD patients, with special attention to the levofloxacin susceptibility of Staphylococci. STUDY DESIGN: Retrospective, single-center study. METHODS: This study involved 131 eyes of 112 Japanese patients with AD (87 men and 25 women, mean age: 40.4 ± 12.2 years) who underwent ocular surgery at Kyorin University Hospital. Bacterial isolates were collected from the conjunctival sacs in the preoperative period. Drug resistance to methicillin and levofloxacin was judged using the minimal inhibitory concentrations of oxacillin and levofloxacin determined by the broth dilution method. RESULTS: One hundred and fifty-seven strains were identified in 103 of the 131 eyes examined. S. aureus was isolated from 74 eyes (56.5%), followed by Staphylococcus epidermidis (S. epidermidis). In S. aureus, 11 strains (14.9%) were methicillin-resistant, and 18 (24.3%) were levofloxacin-resistant. In S. epidermidis, 15 strains (26.8%) were methicillin-resistant, and 17 (30.4%) were levofloxacin-resistant. No significant differences were observed in levofloxacin susceptibility with age, sex, previous ocular surgery, or duration of previous surgery. However, logistic multivariate analysis revealed that levofloxacin-resistant Staphylococci were concurrently resistant to methicillin, suggesting multidrug resistance. CONCLUSION: Distinctive bacterial distribution and drug resistance need consideration in the managing of ocular disorders among patients with AD.

A COVID-19 Risk Reduction Strategy for the Treatment of Acute Vogt-Koyanagi-Harada Disease Utilizing the Antiviral Potential of Cyclosporine.

PURPOSE: To report on the successful treatment of patients with acute Vogt-Koyanagi-Harada (VKH) disease utilizing the antiviral potential of cyclosporine during the COVID-19 pandemic. STUDY DESIGN: Case series. METHODS: Clinical records were retrospectively reviewed of 4 patients presenting with new-onset acute VKH disease who elected to receive initial treatment consisting of bilateral sub-Tenon injection of triamcinolone acetonide combined with immediately starting oral cyclosporine without the use of systemic corticosteroids. RESULTS: The mean follow-up was 17.0 months. Choroidal thickness decreased to normal with recovery of bilateral best-corrected visual acuity (BCVA) of 1.2 in 3 patients. One elderly patient had decreased BCVA (OD 0.5, OS 0.8) due to cataract progression and mild epiretinal membrane. No recurrences of intraocular were observed in any patients. Mild renal dysfunction developed in 2 elderly patients, but importantly no patients developed COVID-19 disease. CONCLUSIONS: Oral cyclosporine as the initial systemic treatment of acute VKH disease, in combination with sub-Tenon injection of triamcinolone acetonide, lead to favorable clinical outcomes. Due to the known antiviral properties of cyclosporine, we suggest that this may represent a good treatment strategy for patients during the COVID-19 pandemic.

Clinical Features, Treatment, and Visual Outcomes of Japanese Patients with Posterior Scleritis.

Purpose: The purpose of this study is to describe clinical features and visual outcomes of Japanese patients with posterior scleritis.Methods: Clinical records of 10 patients (13 eyes) presenting between 2006 and 2016 were retrospectively reviewed.Results: The mean age was 50.1 ± 20.8 years; 50% were women, and three patients had bilateral disease. Associated anterior scleritis (11 eyes, 85%) and serous retinal detachment (8 eyes, 62%) were common at presentation. Treatment consisted of corticosteroids (all patients) and immunosuppressive agents (seven patients). The mean subfoveal choroidal thickness was significantly reduced over follow-up [611 µm at baseline, 298 µm (p < 0.01) at 1 month, and 238 µm (p < 0.01) at 1 year]. Recurrent inflammation was observed in six patients. A best-corrected visual acuity of 0.8 or better was achieved in all 13 eyes at 3 years and 71% of eyes at 5 years.Conclusion: Although 60% of patients with posterior scleritis had recurrence, visual outcomes were favorable.

Anti-Inflammatory Effect of Dehydroxymethylepoxyquinomicin, a Nuclear factor-κB Inhibitor, on Endotoxin-Induced Uveitis in Rats In vivo and In vitro.

Purpose: To determine the anti-inflammatory effects of dehydroxymethylepoxyquinomicin (DHMEQ), a nuclear factor-κB (NF-κB) inhibitor, on endotoxin-induced uveitis (EIU) in rats.Methods: EIU was induced by a subcutaneous injection of lipopolysaccharide (LPS) in Lewis rats. DHMEQ was injected intraperitoneally concurrently with the LPS. Aqueous humor was collected 24 h after the LPS injection. Isolated peritoneal exudate cells (PECs) were exposed to LPS with or without DHMEQ to determine the production of TNF-α, IL-6, and MCP-1.Results: DHMEQ significantly reduced the number of infiltrating cells, and the concentrations of proteins, TNF-α, and IL-6 in the aqueous humor. DHMEQ suppressed the production of TNF-α, IL-6, and MCP-1 from PECs. Immunochemistry revealed a reduction in the translocation of the NF-κB p65 into the nuclei in DHMEQ-exposed PECs.Conclusions: The results indicate that DHMEQ has anti-inflammatory effects on EIU and may be a promising agent to treat intraocular inflammation.

Anti­inflammatory effects of the NF­κB inhibitor dehydroxymethylepoxyquinomicin on ARPE­19 cells.

The retinal pigment epithelium (RPE) is a polarized, monolayer of pigmented cells that forms the outer retinal layer. A key function of the RPE is to maintain the integrity of the photoreceptors mainly via phagocytosis and recycling of the digested photoreceptor outer segments. Moreover, RPE cells are a major source of inflammatory cytokines and chemokines, which play important roles in the activation of other immune cells under inflammatory conditions in the posterior segment of the eye. Dehydroxymethylepoxyquinomicin (DHMEQ) is a NF­κB inhibitor and its structure is related to that of epoxyquinomicin C, which is an antibiotic. The present study evaluated the anti­inflammatory effects of DHMEQ on a human retinal pigment epithelial cell line (ARPE­19). It was revealed that high concentrations of DHMEQ (100 µg/ml) induced apoptosis and necrosis of tumor necrosis factor (TNF)­α­stimulated ARPE­19 cells. Furthermore, the percentage of intercellular adhesion molecule 1 (ICAM­1)­positive TNF­α­stimulated cells was significantly reduced in the presence of DHMEQ (10 µg/ml), as determined by flow cytometry. It was also demonstrated that DHMEQ exposure significantly decreased the levels of interleukin (IL)­8 and monocyte chemoattractant protein­1 (MCP­1) in the supernatant of cultured ARPE­19 cells as determined by ELISA. Moreover, the protein expression levels of IL­8 and MCP­1 were significantly reduced in ARPE­19 cells exposed to DHMEQ compared with cells exposed to dexamethasone. PCR array analysis revealed that DHMEQ reduced the expression levels of MCP­1, ICAM­1, IL­6, Toll­like receptor (TLR)2, TLR3 and TLR4. Therefore, the present results indicated that DHMEQ has anti­inflammatory effects on TNF­α­stimulated ARPE­19 cells. Thus, DHMEQ may have therapeutic potential for TNF­α­mediated inflammatory disorders of the eye.

Asymmetrical recovery of cone outer segment tips line and foveal displacement after successful macular hole surgery.

PURPOSE: To determine whether the photoreceptor outer segments recover symmetrically after successful macular hole surgery, and whether the recovery is correlated with the degree of foveal displacement. METHODS: This was a retrospective, interventional case series. The medical records of 35 patients (n = 35 eyes) with a surgically closed macular hole were reviewed. Spectral-domain optical coherence tomography (SD-OCT) was used to obtain cross-sectional images across the fovea horizontally and vertically. The lengths of cone outer segment tips (COST) line defect in the temporal, nasal, superior, and inferior sectors of the fovea, the best-corrected visual acuity (BCVA), and the papillofoveal distance were measured before and at 6 and 12 months after the surgery. RESULTS: The temporal COST line defect was significantly longer than the nasal length defect preoperatively (P = 0.031), at 6 months (P < 0.001), and at 12 months (P = 0.038) postoperatively. The length of the temporal COST line defect was significantly correlated with the BCVA preoperatively (P = 0.014) and at 6 months postoperatively (P = 0.001). The papillofoveal distance was significantly shorter at 6 months (P = 0.029) and 12 months (P = 0.043) postoperatively than at the baseline. The center of the COST line defect was located further temporally from the fovea postoperatively, and the distance was shorter than the nasal foveal displacement at 6 months (158.8 ± 167.0 µm, P = 0.13) and 12 months (244.8 ± 172.7 µm, P = 0.008). CONCLUSIONS: The restoration of the temporal COST line was delayed after successful macular hole surgery. In addition, the fovea was displaced more nasally than the center of the COST line defect which recovered centripetally. (ClinicalTrials.gov number, NCT01959776.).