Efficacy and safety of abatacept for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan. RESULTS: Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases. CONCLUSIONS: Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.

Efficacy and safety of tumor necrosis factor inhibitors for systemic juvenile idiopathic arthritis: a systematic review.

OBJECTIVES: This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA). METHODS: Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies. RESULTS: One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%. CONCLUSIONS: Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.

Vascular tortuosity analysis in eyes with epiretinal membrane imaged by optical coherence tomography angiography.

BACKGROUND: This study aimed to evaluate macular vessel tortuosity using optical coherence tomography angiography (OCTA) and its association with visual outcomes in eyes undergoing surgery for epiretinal membrane (ERM). METHODS: The study included 22 consecutive patients who underwent vitrectomy for ERM between May 2019 and July 2020 and OCTA at Osaka University Hospital. All patients underwent ophthalmologic examinations, including swept-source OCTA. Standard vitrectomy was performed, and the patients were followed up for 6 months postoperatively. Distortion of retinal vessels was calculated using two parameters: the actual vessel length in the vessel section (VL) and the direct vessel branching point distance (BD) in the three quadrants (nasal, temporal, and superior-inferior) of the macula. We analyzed the correlation between these parameters and visual outcomes. RESULTS: Significantly longer VL was found at 1, 3, and 6 months postoperatively (p = 0.006, 0.008, and 0.022, respectively) in the temporal quadrant compared to baseline temporal VL. Significantly shorter VL was found in nasal quadrants at 1 and 3 months (p = 0.046 and p = 0.018) in the comparison of nasal baseline VL. VL/BDs were correlated with the same postoperative best-corrected visual acuity (BCVA) at 1, 3, and 6 months (p = 0.035, 0.035, and 0.042, respectively) in the superior-inferior quadrant. A significant association of changes in VL and BCVA was found at 3 and 6 months postoperatively in the nasal quadrant (p = 0.018 and 0.0455, respectively). CONCLUSIONS: Changes in vascular distortion after ERM surgery can be measured using OCTA. The change in vessels around the macula became more linear; this was associated with visual outcomes after surgery.

Corneal Opacity Induced by Light in a Mouse Model of Gelatinous Drop-Like Corneal Dystrophy.

Gelatinous drop-like corneal dystrophy (GDLD) is a severe inherited corneal dystrophy characterized by subepithelial corneal amyloid deposition. We had previously succeeded in identifying the responsible gene, TACSTD2, and subsequently found that the epithelial barrier function is significantly decreased. As with GDLD patients, the knockout mice showed severe loss of tight junction, progressive opacity, and neovascularization in the cornea. We devised an easy method to confirm the loss of the corneal barrier function even before corneal opacity is observed. Furthermore, by using knockout mice, we were able to verify clinical findings, such as the wound healing delay and light-induced acceleration of the disease. This mouse model should prove to be a highly useful tool for investigating the pathology of GDLD and for developing new therapies.

Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during regular infusion of tocilizumab: a case report.

BACKGROUND: Filamentous fungi are ubiquitous in plants, water, and soil. The predominant fungi that infect the human cornea include Fusarium and Aspergillus species. The onset of fungal endophthalmitis is indolent, and typically takes weeks to months to develop after corneal infection. We report a case of Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during intravenous tocilizumab therapy. CASE PRESENTATION: A 65-year-old female patient was referred to our department due to pain and decreased vision in her left eye. Slit-lamp examination showed a white focus on the upper peripheral cornea, hypopyon, anterior chamber fibrin formation, marked ciliary hyperemia, and whole corneal epithelial defects. As the corneal scraping smear was positive for filamentous fungi and Fusarium species were detected by aqueous humor polymerase chain reaction, anti-fungal therapy was started. Although the initial response to anti-fungal therapy was good, we observed corneal infiltration, worsening hypopyon, and vitreous opacity after tocilizumab infusion. Given that the infection continued to progress despite conservative therapy, we performed penetrating keratoplasty combined with vitrectomy. After removal of the white focus beneath the intraocular lens, a temporary corneal prosthesis was mounted and the dense vitreous opacity was removed. Finally, a frozen donor graft was sutured in place. The corneal infiltration, hypopyon, and vitreous opacity all disappeared after the operation. CONCLUSION: The rapid progression of Fusarium keratitis to endophthalmitis in a patient who was receiving a regular infusion of tocilizumab demonstrates that ocular condition should be closely monitored during systemic tocilizumab administration due to increased risk of infection.

Endogenous endophthalmitis caused by group B streptococcus; case reports and review of 35 reported cases.

BACKGROUND: Group B streptococcus (GBS), a gram-positive coccus that occasionally causes neonatal sepsis or invasive infection in the elderly, has been considered a rare cause of endogenous bacterial endophthalmitis (EBE). However, the number of invasive GBS infections is increasing, particularly in elderly patients with underlying conditions such as diabetes mellitus (DM), cardiovascular disease and cancer. We report 6 cases of EBE caused by GBS and review the literature. METHODS: Retrospective case series and literature review. RESULTS: In the current case series, 6 eyes of 6 patients developed EBE caused by GBS. The average age was 73.5 years. The focus of infection included the urinary tract, cellulitis, arthritis, peritonitis, catheter-associated infection and endocarditis. Four patients had DM. While all 6 strains were sensitive to ß-lactams (penicillins and cephems), 4 strains were resistant to levofloxacin (no data for 1 isolate). Each case was treated with the systemic antibiotic to which the individual strain was sensitive. All cases showed poor visual acuity at presentation (decimal visual acuity: less than 0.03). Vitrectomy with intravitreal antibiotics injection was performed in 4 cases. Visual acuity recovered in 4 cases and did not recover in 2 cases, even after vitrectomy. The literature review of 53 eyes of 41 patients revealed that 60% of eyes finally lost all vision, and death occurred in 2 cases. Initial visual acuity of less than counting fingers was associated with a final outcome of lost vision. Of 41 patients, 13 (32%) had DM as an underlying medical condition. The most common extra-ocular infection focus was endocarditis (37%). CONCLUSIONS: DM is common in patients with EBE caused by GBS. While the 4 cases in the current report had a relatively good visual acuity outcome, despite poor initial visual acuity, the literature review indicated that EBE caused by GBS is generally a severe condition with a poor prognosis. The current study also indicates the importance of considering the possibility of endocarditis on encountering EBE caused by GBS.

STAT3 signaling maintains homeostasis through a barrier function and cell survival in corneal endothelial cells.

The cornea protects the eye from inflammation, which is one of the leading causes of blindness. Severe inflammation in the anterior chamber disrupts the barrier function of corneal endothelial cells (CECs) leading to severe visual loss. However, the mechanism by which such inflammation affects CEC function and survival is unknown. Activation of STAT3 signaling regulates various intracellular responses through inflammation and generally mediates expression of the barrier function marker zonula occludens-1 (ZO-1). In this study, we investigated the relationship between the corneal endothelial barrier function and activation of STAT3 signaling through a variety of cytokines in human CECs. Phosphorylated STAT3 (pSTAT3) was expressed in human and mouse CECs. Inhibition of pSTAT3 remarkably decreased the expression of the ZO-1 protein, reduced the trans-endothelial electric resistance, and induced cell apoptosis. The expression level of ZO-1 mRNA was correlated with that of STAT3 mRNA in the human corneal endothelium. pSTAT3 was increased with the addition of LIF, IL-6, and IFN-γ. LIF expressed in CECs suppressed pSTAT3 activation as observed experimentally using an anti-LIF antibody. Promoter regions of ZO-1 and SOCS3 were directly regulated by transcriptional activation of STAT3. These findings suggest that regulation of the STAT3 pathway is essential for corneal endothelial homeostasis via barrier function and may protect from various inflammatory factors.

Fourier Analysis of Corneal Irregular Astigmatism Due to the Anterior Corneal Surface in Dry Eye.

OBJECTIVES: To evaluate corneal irregular astigmatism due to the anterior corneal surface using Fourier harmonic analysis with a Placido ring-based corneal topographer (Placido-based topographer) and three-dimensional anterior segment optical coherence tomography (OCT) in dry eyes. METHODS: Forty-four eyes of 44 subjects with dry eye and 20 eyes of 20 normal control subjects were enrolled. Corneal topographic data were obtained using a Placido-based topographer and OCT. Dioptric data from the central 3-mm zone of the anterior corneal surface were decomposed using Fourier harmonic analysis. Spherical, regular astigmatism, and irregular astigmatism (asymmetry and higher-order irregularity) refractive error components of the cornea from the two imaging modalities were compared. RESULTS: Both asymmetry and higher-order irregularity values were significantly greater in dry eyes than in control eyes for both the Placido-based topographer and OCT measurements (all P<0.05). In dry eyes, measured values of asymmetry and higher-order irregularities were significantly smaller when obtained with OCT than with the Placido-based topographer (both P<0.001). By contrast, these parameters were not significantly different between the two devices in control eyes. In dry eyes, severity of superficial punctate keratopathy in the central corneal region was correlated with irregular astigmatism. CONCLUSIONS: The amount of corneal irregular astigmatism, quantified using Fourier harmonic analysis, was significantly higher in dry eyes than in normal eyes. Measurements obtained with OCT and the Placido-based topographer differed in subjects with dry eyes. Therefore, caution should be practiced when trying to use these measurements interchangeably.

Catching the therapeutic window of opportunity in early initial-onset Vogt-Koyanagi-Harada uveitis can cure the disease.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune granulomatous choroiditis that begins in the choroidal stroma. The aim of this review was to gather a body of evidence for the concept of a window of therapeutic opportunity, defined as a time interval following initial-onset disease during which adequate treatment will substantially modify the disease outcome and possibly even lead to cure, similar to what has been described for rheumatoid arthritis. METHODS: We reviewed the literature and consulted leading experts in VKH disease to determine the consensus for the notion of a therapeutic window of opportunity in VKH disease. RESULTS: We found a substantial body of evidence in the literature that a therapeutic window of opportunity exists for initial-onset acute uveitis associated with VKH disease. The disease outcome can be substantially improved if dual systemic steroidal and non-steroidal immunosuppressants are given within 2-3 weeks of the onset of initial VKH disease, avoiding evolution to chronic disease and development of "sunset glow fundus." Several studies additionally report series in which the disease could be cured, using such an approach. CONCLUSIONS: There is substantial evidence for a therapeutic window of opportunity in initial-onset acute VKH disease. Timely and adequate treatment led to substantial improvement of disease outcome and prevented chronic evolution and "sunset glow fundus," and very early treatment led to the cure after discontinuation of therapy in several series, likely due to the fact that the choroid is the sole origin of inflammation in VKH disease.

Diagnosing superinfection keratitis with multiplex polymerase chain reaction.

PURPOSE: To report the potential usefulness of multiplex polymerase chain reaction (mPCR) for diagnosing superinfection keratitis caused by herpes simplex virus-1 (HSV-1), bacteria and fungus. METHODS: Case series. Corneal scrapings were analyzed with mPCR for human herpes virus 1-8, bacterial 16S ribosomal DNA (rDNA) and fungal 28S rDNA. RESULTS: Case 1 was a 69-year-old man who presented with refractory infectious keratitis. PCR examination was positive for bacterial 16S rDNA and negative for fungal 28S rDNA. HSV-1 was not examined at this time. A geographic ulcer arose after 2 months of intensive antibacterial treatment. Herpes simplex keratitis (HSK) was suspected; PCR analysis was positive for HSV-1. Corneal scrapings obtained at the initial visit were re-analyzed and found to be HSV-1 positive. Thus, it turned out that this was a case of superinfection keratitis caused by bacteria and HSV-1. Case 2 was a 60-year-old man with corneal ulcer who had received unsuccessful treatment with antibiotics. mPCR analysis was positive for HSV-1, bacterial 16S rDNA and fungal 28S rDNA. The patient was diagnosed with superinfection keratitis caused by HSV-1, bacteria and fungus. Case 3 was an 82-year-old woman who had been treated for HSK and then developed bacterial keratitis during treatment. mPCR analysis was positive for HSV-1 and bacterial 16S rDNA. The patient was diagnosed with superinfection keratitis caused by HSV-1 and bacteria. CONCLUSION: Superinfection keratitis is hard to diagnose because of its atypical manifestation. mPCR has the potential to allow prompt diagnosis and appropriate treatment in these cases.

Endogenous Fusarium Endophthalmitis During Treatment for Acute Myeloid Leukemia, Successfully Treated with 25-Gauge Vitrectomy and Antifungal Medications.

Endogenous fungal endophthalmitis (EFE) caused by disseminated fusariosis is a rare condition that generally has a poor outcome, even with intensive therapy. Here, we describe a case in which this type of EFE was diagnosed with vitreous sampling and was successfully treated with 25-gauge vitrectomy and antifungals, including liposomal amphotericin B and voriconazole. A 16-year-old male patient undergoing treatment for acute myeloid leukemia complained of eye pain and blurred vision in his right eye. Treatment was initiated for a vitreous opacity, possibly associated with herpetic retinitis, but the patient worsened and he was referred to us. Right-eye visual acuity was limited to light perception. We suspected endogenous endophthalmitis and performed 25-gauge vitrectomy with antibiotic perfusion of ceftazidime, vancomycin, and voriconazole. Vitreous culturing revealed the presence of Fusarium solani species complex, and enhanced computed tomography revealed disseminated fusariosis lesions in the lung, spleen, and the soft tissue of the left upper arm. The patient received antifungal treatment with liposomal amphotericin B and voriconazole, and these conditions were eliminated. Visual acuity recovered to 20/400 after additional vitrectomy for tractional retinal detachment and was maintained at this level during the 6-month follow-up period. The success of our treatment allowed the capture of optical coherence tomography images of the retina during fusarium-associated endogenous endophthalmitis and the follow-up period. Furthermore, this case showed that immediate vitrectomy for suspected EFE and intensive treatment can lead to a good clinical outcome.

Endophthalmitis associated with Purpureocillium lilacinum during infliximab treatment for surgically induced necrotizing scleritis, successfully treated with 27-gauge vitrectomy.

PURPOSE: To report a case of endophthalmitis associated with Purpureocillium lilacinum (P. lilacinum) during infliximab treatment for surgically induced necrotizing scleritis, successfully treated with 27-gauge vitrectomy. METHODS: A single case report. RESULTS: A 71-year-old man who had undergone immunosuppressive therapy, including infliximab, for surgically induced necrotizing scleritis (SINS) in his left eye complained of visual disturbance and eye pain in the eye. He had a past history of surgery for recurrent pterygium: pterygium excision, amnion transplantation with mitomycin C and limbal transplantation. Visual acuity in the left eye was counting fingers at 30 cm, and intraocular pressure was 3.0 mmHg. Slit-lamp examination revealed the presence of anterior chamber cells (3+), and a B-mode ultrasound scan showed a vitreous opacity. We made a diagnosis of endophthalmitis and performed 27-gauge microincision vitrectomy surgery (27GMIVS) with antibiotic perfusion of ceftazidime, vancomycin and voriconazole. Intraoperative findings included a fungus-like ball-shaped opacity in the vitreous, and a close-to-normal retinal appearance. A vitreous body culture identified the presence of P. lilacinum. After 2 months of antibacterial and antifungal therapy, inflammation decreased and visual acuity recovered to 20/100. CONCLUSIONS: This is the first report of a case of endophthalmitis associated with P. lilacinum during infliximab treatment for SINS. Scleral thinning due to necrotizing scleritis, especially during immunosuppressive therapy, is a risk factor for endophthalmitis. We found that 27GMIVS was a useful strategy for such a challenging clinical situation.

Characteristics of cases needing advanced treatment for intractable Posner-Schlossman syndrome.

BACKGROUND: In Posner-Schlossman syndrome (PSS), which is characterized by recurrent unilateral attacks of ocular hypertension. Surgical treatment is sometimes necessary because intraocular pressure (IOP) cannot be controlled with anti-glaucoma medications. To identify the clinical features of Posner-Schlossman syndrome (PSS) indicative of the need for intraocular pressure (IOP)-controlling surgery. METHODS: This study was a retrospective case-series analysis of the clinical charts of 33 patients diagnosed with PSS, who underwent surgery to control IOP or received medication only. Various clinical factors were compared between the surgical and medication groups. RESULTS: The surgical group had a higher corneal endothelial cell (CEC) density loss (p < 0.05), higher maximum IOP (p < 0.01), greater visual field loss (p < 0.01) and higher positive number for cytomegalovirus (CMV) (p < 0.001) than the non-surgical group. Eighteen of the 33 patients had a high CEC reduction ratio. Of these 18, 16 required glaucoma surgery. CONCLUSIONS: PSS patients with a higher CEC reduction ratio, higher maximum IOP, greater visual field loss and higher positive number for CMV in the aqueous humor tended to be more likely to require progressive treatment, such as glaucoma surgery.

Stage-specific reference genes significant for quantitative PCR during mouse retinal development.

Developing mouse retina has been serving as an ideal model for investigating the molecular mechanism of neural development and angiogenesis, because several significant events associated with these physiological phenomena are drastically occurring in conjunction with retinal development. However, as many genes are influencing on each other to establish mature retina within 21 days from E10 to P12, we must carefully design the experiments, such as in the case of quantitating the amount of altered gene expression toward the establishment of retina by quantitative PCR. As we have seen considerable variations of quantitative results in different developmental stages of retina depending on the reference genes used for compensation, we here attempted to determine a reliable reference gene to accurately quantitate the target genes in each stage. According to the results of in silico prediction and comparison with a database of SAGE, we found that the most stable gene from early to late stages was Sdha, whereas one of the most popular housekeeping genes, Actb, was the one that could mislead the quantitative results even in the adult stage. Consequently, we pointed out the importance of selecting an appropriate reference gene, especially to quantitate the amount of gene expression in the developmental stages of a certain tissue.

The association between systemic oxidative stress and ocular blood flow in patients with normal-tension glaucoma.

PURPOSE: To evaluate the association between ocular blood flow and biomarkers of systemic oxidative stress, as well as the potential of these biomarkers to assess normal-tension glaucoma (NTG). METHODS: This study included 73 eyes of 73 patients with NTG. We assessed ocular blood flow by measuring mean blur rate (MBR) in the optic nerve head using laser speckle flowgraphy, both overall and separately in the vessel and tissue areas. We also measured urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and skin autofluorescence (SAF), and lastly, determined correlations between these measurements and with other clinical parameters. RESULTS: SAF was correlated with age, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), mean deviation (MD), and overall MBR (P = 0.003, P = 0.013, P = 0.015 and P = 0.006, respectively). SAF and 8-OHdG were both correlated with tissue-area MBR (P = 0.006 and P = 0.010, respectively). Visual acuity, cpRNFLT, mean deviation and tissue-area MBR had a significant tendency to change with NTG severity (P = 0.014, P < 0.001, P < 0.001 and P = 0.006, respectively). Multiple regression analysis revealed that cpRNFLT and 8-OHdG were independent contributing factors to MD (P < 0.001 and P = 0.040, respectively), and that cpRNFLT and 8-OHdG were independent contributing factors to tissue-area MBR (P = 0.005 and P = 0.028, respectively). CONCLUSIONS: We found a close relationship between cpRNFLT, MD, tissue MBR, SAF and 8-OHdG, suggesting that systemic oxidative stress is associated with decreased ocular blood flow and may be involved in the pathogenesis of NTG.

Topical ocular dexamethasone decreases intraocular pressure and body weight in rats.

BACKGROUND: Recently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats. RESULTS: Ten-week old Sprague Dawley (SD) rats (N = 12) were used to evaluate the effect of topical 0.1% dexamethasone (50 µl) administered 3 times daily for 4 weeks. Sodium chloride (0.9%) was used in another group of rats (N = 12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3 ± 1.3 mmHg in the treated eyes, compared to 14.8 ± 2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P = 0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P < 0.001) and alanine transaminase (P = 0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment. CONCLUSIONS: In contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose.

Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression.

Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-ß/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1 (ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation.

Quantification of the filtering bleb's structure with anterior segment optical coherence tomography.

BACKGROUND: The aim of the study is to determine the relationship between post-trabeculectomy bleb structure evaluated using anterior segment optical coherence tomography (AS-OCT) and postoperative intraocular pressure (IOP). DESIGN: Rretrospective is showed for the design of this study. PARTICIPANTS: There are twenty-seven eyes of 27 trabeculectomy patients. METHODS: We drew contour lines for the bleb and cleft on 8-radius-scanned AS-OCT images, and determined correlations of AS-OCT measurements to postoperative IOP at 6 months. MAIN OUTCOME MEASURES: The parameter used in this study is an anterior segment optical coherence tomography measurements of bleb structure, including cleft volume, wall volume, and the brightness of the bleb wall. RESULTS: We found significant correlations between postoperative IOP at 6 months and cleft volume at 3 and 6 months (r = -0.56, P = 0.007 and r = -0.82, P <0.001), bleb wall volume at 6 months (r = -0.48, P = 0.042), bleb vertical brightness at 3 and 6 months (r = 0.73, P < 0.001 and r = 0.49, P = 0.040), and bleb horizontal brightness at 1 week, 2 weeks, 3 months and 6 months (r = 0.49, P = 0.016, r = 0.65, P < 0.001, r = 0.52, P = 0.013 and r = 0.71, P = 0.001). A stepwise multiple regression analysis of bleb structural measurements made ≤2 weeks postoperatively showed that the strongest independent factor indicating postoperative IOP at 6 months was bleb horizontal brightness at 2 weeks (ß = 0.50, P = 0.006). CONCLUSIONS: Early postoperative AS-OCT measurements of blebs, especially horizontal brightness of the bleb wall, were associated with postoperative IOP at 6 months. AS-OCT measurements of blebs may be useful predictors of trabeculectomy outcomes.