Curved single-plane clear corneal incision made under anterior chamber collapse by aqueous humor aspiration prevents leakage after cataract surgery.

PURPOSE: To evaluate the self-sealing on curved single-plane clear corneal incisions (CCIs) after cataract surgery. The collapse of the anterior chamber was made by aspirating the aqueous humor in order to make curved single-plane CCI. METHODS: A retrospective study was conducted at Asai Hospital in Japan. There were 189 eyes of 132 patients scheduled from February to April 2017 for single-plane CCI. There were 175 eyes of 128 patients from February to April 2018 for curved single-plane CCI. Curved single-plane CCIs were made with aqueous humor aspiration via aqueous humor pipette, and single-plane CCIs were made without the aspiration. In case of leakage of aqueous humor from the CCI at the end of surgery, sutures were used. The main outcome measure was the proportion of sutures for CCI. Secondary outcomes included CCI length and surgically induced astigmatism (SIA) magnitude. RESULTS: The proportions of suture in single-plane CCI and in curved single-plane CCIs were 25.4% (48/189) and 0% (0/175), respectively (p < 0.001). The length of curved single-plane CCI (2.06 ± 0.18 mm) was significantly greater than that of single-plane CCI (1.66 ± 0.12 mm; p < 0.001). The median postoperative SIAs of single-plane and curved single-plane CCIs were 0.64 D (n = 89) and 0.73 D (n = 85) for nasal incision, and 0.46 D (n = 100) and 0.47 D (n = 90) for temporal incision at examination 3 months after surgery, respectively, without significant change (p = 0.12 for nasal incision and p = 0.37 for temporal incision). CONCLUSION: The curved single-plane CCI achieved by only aqueous humor aspiration showed significant effectiveness in self-sealing. TRIAL REGISTRATION: UMIN clinical trials registry UMIN000032480, retrospectively registered on 6 May 2018.

The Versican G1 Fragment and Serum-Derived Hyaluronan-Associated Proteins Interact and Form a Complex in Granulation Tissue of Pressure Ulcers.

The hyaluronan (HA)-rich extracellular matrix plays dynamic roles during tissue remodeling. Versican and serum-derived HA-associated protein (SHAP), corresponding to the heavy chains of inter-α-trypsin inhibitor, are major HA-binding molecules in remodeling processes, such as wound healing. Versican G1-domain fragment (VG1F) is generated by proteolysis and is present in either remodeling tissues or the mature dermis. However, the macrocomplex formation of VG1F has not been clarified. Therefore, we examined the VG1F-containing macrocomplex in pressure ulcers characterized by chronic refractory wounds. VG1F colocalized with SHAP-HA in specific regions of the granulation tissue but not with fibrillin-1. A unique VG1F-SHAP-HA complex was isolated from granulation tissues using gel filtration chromatography and subsequent cesium chloride-gradient ultracentrifugation under dissociating conditions. Consistent with this molecular composition, recombinant versican G1, but not versican G3, interacted with the two heavy chains of inter-α-trypsin inhibitor. The addition of recombinant VG1 in fibroblast cultures enhanced VG1F-SHAP-HA complex deposition in the pericellular extracellular matrix. Comparison with other VG1F-containing macrocomplexes, including dermal VG1F aggregates, versican-bound microfibrils, and intact versican, highlighted the tissue-specific organization of HA-rich extracellular matrix formation containing versican and SHAP. The VG1F-SHAP-HA complex was specifically detected in the edematous granulation tissues of human pressure ulcers and in inflamed stages in a mouse model of moist would healing, suggesting that the complex provides an HA-rich matrix suitable for inflammatory reactions.

Influence of upper and temporal transconjunctival sclerocorneal incision on marginal reflex distance after cataract surgery.

BACKGROUND: Ptosis incidence following cataract surgery is reduced with a recently developed phacoemulsification technique using a small incision. However, it remains uncertain whether an upper transconjunctival sclerocorneal incision can cause minor blepharoptosis. In the present prospective study, patients underwent cataract surgery with either an upper or temporal 2.4-mm transconjunctival sclerocorneal incision. We measured the marginal reflex distance 1 (MRD1) preoperatively and postoperatively, and compared these measurements between the two different incision types. Further we explored the risk factors of the postoperative MRD1 reduction. METHODS: The study population included patients who underwent cataract surgery on both eyes at Aichi Medical University between October 2013 and September 2015. In each patient, one eye was operated using an upper 2.4-mm transconjunctival sclerocorneal incision, and the other with a temporal incision. We prespecified that an MRD1 difference of ≥0.5 mm between the pre- and post-surgical measurements indicated postoperative ptosis, which was a strict criterion. MRD1 was measured using digital photography, and we calculated the difference between the preoperative and postoperative MRD1 values. This change in MRD1 was compared between the groups with different incision locations. The change in MRD1 was analyzed by using the multivariate regression model including incision position (temporal or upper), preoperative MRD1, and preoperative distance between medial and lateral canthi. RESULTS: We assessed data from a total of 34 patients. The mean change in MRD1 from pre-operation to post-operation measurements was -0.26 ± 0.93 with the temporal incision and -0.24 ± 0.86 with the upper incision. The mean difference in the change in MRD1 between the different two incision types was -0.02, with a 95 % CI of -0.24 to 0.20, establishing equivalence between these incision types. The multivariate regression analysis showed that the preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery (p = 0.034). CONCLUSIONS: Cataract surgery using upper and temporal 2.4-mm transconjunctival sclerocorneal incisions are clinically equivalent with regards to change in MRD1, and neither incision type caused critical postoperative ptosis. The longer preoperative MRD1 was significantly associated with the reduction of MRD1 after surgery. TRIAL REGISTRATION: Current Controlled Trials UMIN000022310 . Retrospectively registered 14 May 2016.

Bimatoprost, latanoprost, and tafluprost induce differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases.

BACKGROUND: Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension. The purpose of this study was to investigate differences in the expression profiles of MMPs and TIMPs induced by the prostaglandin analogs bimatoprost, latanoprost, and tafluprost in human non-pigmented ciliary epithelial cells (HNPCECs). METHODS: HNPCECs were cultured for 24 h with 0, 10, 100, or 1000 µM of the free acid forms of bimatoprost, latanoprost, and tafluprost. We measured the expression levels of MMPs and TIMPs using real-time polymerase chain reaction, and compared the results. Enzyme activities of MMP-2 and -9 in conditioned media were measured by gelatin zymography. RESULTS: All prostaglandin analogs we examined dose-dependently increased expression levels of MMP-1, -2, -3, -9, and -17, whereas expression levels of TIMP-1 and -2 decreased with increasing concentrations of each analog. Each prostaglandin analog induced different levels of increases in MMPs and decreases in TIMPs. CONCLUSIONS: Unique expression profiles of MMPs and TIMPs induced by bimatoprost, latanoprost, and tafluprost, as shown in HNPCECs, may contribute to clinically different effects on intraocular pressure decreases in patients with glaucoma or ocular hypertension.

Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia.

BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogenesis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31 °C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

Homotypic versican G1 domain interactions enhance hyaluronan incorporation into fibrillin microfibrils.

Versican G1 domain-containing fragments (VG1Fs) have been identified in extracts from the dermis in which hyaluronan (HA)-versican-fibrillin complexes are found. However, the molecular assembly of VG1Fs in the HA-versican-microfibril macrocomplex has not yet been elucidated. Here, we clarify the role of VG1Fs in the extracellular macrocomplex, specifically in mediating the recruitment of HA to microfibrils. Sequential extraction studies suggested that the VG1Fs were not associated with dermal elements through HA binding properties alone. Overlay analyses of dermal tissue sections using the recombinant versican G1 domain, rVN, showed that rVN deposited onto the elastic fiber network. In solid-phase binding assays, rVN bound to isolated nondegraded microfibrils. rVN specifically bound to authentic versican core protein produced by dermal fibroblasts. Furthermore, rVN bound to VG1Fs extracted from the dermis and to nondenatured versican but not to fibrillin-1. Homotypic binding of rVN was also seen. Consistent with these binding properties, macroaggregates containing VG1Fs were detected in high molecular weight fractions of sieved dermal extracts and visualized by electron microscopy, which revealed localization to microfibrils at the microscopic level. Importantly, exogenous rVN enhanced HA recruitment both to isolated microfibrils and to microfibrils in tissue sections in a dose-dependent manner. From these data, we propose that cleaved VG1Fs can be recaptured by microfibrils through VG1F homotypical interactions to enhance HA recruitment to microfibrils.

Comparative analysis of hyaluronan's affinity for antivascular endothelial growth factor agents.

BACKGROUND: Differences in the efficacy of bevacizumab, an antivascular endothelial growth factor (VEGF) agent, against retinopathy with neovascularization when injected into the vitreous cavity of vitrectomized and nonvitrectomized eyes suggests the involvement of hyaluronan, a major component of the vitreous body. This study aimed to compare the affinities of hyaluronan for anti-VEGF agents in vitro. METHODS: We examined the affinities of hyaluronan for 3 anti-VEGF agents (bevacizumab, pegaptanib and ranibizumab). Tritium [(3)H]-labeled hyaluronan was incubated separately with each anti-VEGF agent. The ratio of bound and unbound hyaluronan measured using solid and liquid phase methods was calculated. RESULTS: Hyaluronan demonstrated a significantly greater affinity for bevacizumab than for pegaptanib or ranibizumab. CONCLUSIONS: The absence or presence of hyaluronan may be associated with the clinical efficacy of bevacizumab injected into the vitreous cavity due to the affinity of hyaluronan for bevacizumab.

A useful technique of starting internal limiting membrane peeling from the edge of the internal limiting membrane defect in epiretinal membrane surgery.

Clinicians should be aware that internal limiting membrane (ILM) defects may occur concurrently with epiretinal membrane, and starting ILM peeling at the ILM defect margin may be useful in such cases. Abstract: We describe a useful surgical technique for the treatment of idiopathic epiretinal membrane with concurrent internal limiting membrane (ILM) defect, in which ILM peeling was started from the ILM defect margin. A dissociated optic nerve fiber layer-like appearance on fundus examination and optical coherence tomography may suggest an ILM defect.

Visual Prognostic Factors in Eyes with Subretinal Fluid Associated with Branch Retinal Vein Occlusion.

We investigated whether foveal ellipsoid zone (EZ) status affects visual prognosis in eyes with subretinal fluid (SRF) associated with branch retinal vein occlusion (BRVO). We included 38 eyes retrospectively and classified those with or without a continuous EZ on the SRF of the central foveola on the vertical optical coherence tomography (OCT) image at the initial visit as intact (n = 26) and disruptive EZ (n = 12) groups, respectively. In addition, we classified the intact EZ eyes into clear (n = 15) and blurred (n = 11) EZ groups according to whether EZ on the SRF was observed distinctly or not. Multiple regression analyses showed that baseline EZ status significantly correlated (p = 0.0028) with the 12-months logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), indicating that baseline intact EZ significantly improves visual prognosis. The 12-months logMAR BCVA of the intact EZ group was significantly better (p < 0.001) than that of the disruptive EZ group, and did not differ significantly between the clear and blurred EZ groups. Thus, baseline foveal EZ status on vertical OCT images can be a novel biomarker for visual prognosis in eyes with SRF associated with BRVO.

Effects of Low-Concentration Nitrous Oxide Anesthesia on Patient Anxiety During Cataract Surgery: A Retrospective Cohort Study.

Purpose: We investigated the effects of 30% low-concentration nitrous oxide (N2O) anesthesia on anxiety, pain, and vital signs and the patient population that would benefit from low-concentration N2O anesthesia during cataract surgery. Patients and Methods: Sixty-three patients who underwent cataract surgery due to visual impairment from cataracts were included in this single-center retrospective cohort study conducted at the Ophthalmology Department of Shinseikai Toyama Hospital, Japan. Fifty eyes of 39 patients received a combination of local and N2O anesthesia (N2O group), and 30 eyes of 24 patients received local anesthesia without N2O anesthesia (Air group). The primary outcome measures were visual analogue scale (VAS) scores for patient anxiety, pain, and vital signs. The secondary outcome measures were the patient population. Results: The change in the VAS scores for anxiety and pain decreased significantly (p = 0.002 and p = 0.014, respectively) in the N2O group (-15.6 ± 22.9 and 12.4 ± 14.9, respectively) compared with that in the Air group (1.2 ± 20.6 and 24.2 ± 22.4, respectively). The systolic and diastolic blood pressure changes did not significantly differ between both groups (p = 0.093 and p = 0.23, respectively). The change in heart rate decreased significantly (p = 0.001) in the N2O group (-4.8 ± 4.8 bpm) compared with that in the Air group (-0.6 ± 5.8 bpm). Multivariate analyses demonstrated that the change in anxiety level in the N2O group correlated significantly with patient age (p = 0.045) and preoperative VAS score for anxiety (p = 0.0001), whereas the change in anxiety level in the Air group did not correlate with any factor. Conclusion: Low-concentration N2O anesthesia showed beneficial effects on intraoperative anxiety and pain during cataract surgery; this may aid the stabilization of intraoperative vital signs. Moreover, low-concentration N2O anesthesia during cataract surgery could benefit young patients and patients with high levels of preoperative anxiety.

Rapid Progression of Polypoidal Choroidal Vasculopathy following Third BNT162b2 mRNA Vaccination.

The study aimed to describe a case of rapid progression of polypoidal choroidal vasculopathy (PCV) following the third administration of the Pfizer-BioNTech (BNT162b2) mRNA vaccine. A 79-year-old Japanese man visited our hospital with a 1-week history of blurred vision in the left eye 16 h following the administration of the third BNT162b2 mRNA vaccine. The clinical examinations and imaging tests revealed massive submacular hemorrhage (SMH) and excessive subretinal fluid (SRF), owing to PCV in the left eye. No ocular abnormality was observed in the right eye. His medical history included diabetes and ocular history included cataracts, nonproliferative diabetic retinopathy, glaucoma in both eyes, and irregular retinal pigment epithelium elevation in the left eye. Since he received a single intravitreal injection of aflibercept approximately 2 years ago for the treatment of diabetic macular edema in the left eye, the left eye was stable. We performed an intravitreal injection of bevacizumab and combined phacoemulsification with pars plana vitrectomy with gas, including subretinal injection of tissue plasminogen activator to displace the SMH. Thirteen days after the surgery, the SMH and SRF decreased. Although rare, mRNA COVID-19 vaccine administrations could be associated with PCV deterioration.

Acute Onset of Dense Vitreous Hemorrhage Associated with Retinal Arterial Macroaneurysm on the Optic Disc.

We present a rare case of acute onset of dense vitreous hemorrhage (VH) associated with ruptured retinal arterial macroaneurysm (RAM) on the optic disc. A 63-year-old Japanese man had undergone phacoemulsification combined with pars plana vitrectomy (PPV) including internal limiting membrane peeling in the right eye for a macular hole approximately 1 year before presentation. His decimal best-corrected visual acuity (BCVA) in the right eye was stable at 0.8 with no recurrence of macular hole. He visited our hospital emergently prior to his regular postoperative visit for a sudden decrease in visual acuity in the right eye. Clinical examinations and imaging tests revealed dense VH in the right eye, and we could not observe the fundus. B-mode ultrasonography of the right eye showed dense VH without retinal detachment and a bulge on the optic disc. His BCVA decreased to hand movement in the right eye. He had no medical history of hypertension, diabetes, dyslipidemia, antithrombotics, or ocular inflammation in both eyes. Accordingly, we performed PPV on the right eye. During vitrectomy, we found a RAM on the optic disc with retinal hemorrhage on the nasal side. We carefully reviewed the preoperative color fundus photographs and noticed that RAM was not present on the optic disc at the time of his visit 4 months earlier. After surgery, his BCVA improved to 1.2, the color of the RAM on the optic disc changed to grayish yellow, and optical coherence tomography images showed a shrunken RAM. RAM on the optic disc could cause VH early after its onset.

Acute Retinal Pigment Epitheliitis following Vaccination.

We present a rare case of acute retinal pigment epitheliitis (ARPE) following vaccination. An 18-year-old Japanese man visited our hospital with a 5-day history of a central scotoma in the right eye. He had received the second dose of coronavirus disease 2019 vaccination (BNT162b2 mRNA, Pfizer-BioNTech) 1 month prior, following which he developed a low-grade fever of 37.3-37.5°C for 2 days accompanied by joint pain. Although he had received influenza vaccination 5 days prior to this presentation, no systemic symptoms other than injection site pain were observed. Blood test results were unremarkable. Ophthalmological examination revealed a decimal best-corrected visual acuity (BCVA) of 0.8 and 1.2 in the right and left eyes, respectively. Intraocular pressure was 15 mm Hg in both eyes. Intraocular inflammation was not observed. Fundus examination revealed a localized lesion of pigment stippling associated with yellowish hypopigmentation in the fovea. Fluorescein angiography revealed slight transmission hyperfluorescence without leakage. Optical coherence tomography (OCT) revealed disruption of the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). We diagnosed the patient with ARPE in the right eye. The patient was followed up without treatment. Five weeks after onset, the central scotoma in the right eye disappeared, and patient's BCVA in the right eye improved to 1.5. OCT showed improvement in ELM and EZ continuity in the right eye, but IZ remained disruptive. Although the exact pathophysiology of the association between ARPE and these vaccinations is unclear, ARPE may develop after the vaccination.

A case of bilateral uveitis associated with seminoma/germinoma in thymus and pineal glands, two primary lesions.

Purpose: To report a case of bilateral ocular paraneoplastic syndrome by seminoma/germinoma in thymus and pineal glands, two primary lesions. Observations: A 18-year-old male presented at a local clinic complaining of just floaters in left eye without any other clinical signs and symptoms. The treating ophthalmologist found bilateral uveitis, and referred to our hospital. Bilateral retinal periphlebitis and optic disc swelling were shown. Vitreous opacity was found in left eye. We started ocular and systemic examinations to identify the cause of the uveitis, and also initiated oral steroid therapy. The survey using aqueous humor and blood samples showed no specific results for his uveitis. Computer tomography (CT) and magnetic resonance imaging (MRI) detected tumors in thymus and pineal glands. Five months after his first visit, the tumor in his thymus was resected, and was diagnosed as a seminoma/germinoma by pathological examination. Three months later, the tumor in the pineal gland was diagnosed as a germinoma by biopsy followed by chemotherapy and focal radiotherapy. Finally no abnormal ocular finding but slight optic disc atrophy was ascertained. Conclusions and importance: This is a case of ocular paraneoplastic syndrome induced by seminoma/germinoma in thymus and pineal glands, two primary lesions. Systemic screening by CT and MRI enables prompt diagnosis, treatment and favorable clinical course for such pathogenesis.

Foveal Intraretinal Fluid Localization Affects the Visual Prognosis of Branch Retinal Vein Occlusion.

We investigated whether baseline foveal intraretinal fluid (IRF) localization affects the visual prognosis of branch retinal vein occlusion (BRVO). Fifty eyes from 50 patients were included in this retrospective study. We classified the eyes with IRF involving and not involving the central foveola on the vertical optical coherence tomography (OCT) image at the initial visit into both-sides (n = 17) and one-side IRF (n = 33) groups, respectively. Multiple regression analyses demonstrated that not only the baseline logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) but also the IRF localization significantly correlated with the 12-month logMAR BCVA (p = 0.04 and p = 0.001, respectively), indicating that eyes with better baseline logMAR BCVA and one-side IRF have a significantly better visual prognosis in BRVO. The foveal ellipsoid zone band was significantly more disrupted (p < 0.001) in the both-sides IRF (47.1%) group than in the one-side IRF (3.0%) group. No eyes with decimal BCVA less than 0.5 were detected in the one-side IRF group at 12 months. Thus, baseline foveal IRF localization on vertical OCT images can be considered a novel biomarker for the visual prognosis of BRVO.

Direct Photocoagulation for Treating Microaneurysms with Hyperreflective Ring in Eyes with Refractory Macular Edema Associated with Branch Retinal Vein Occlusion.

Microaneurysms (MAs) with hyperreflective rings are sometimes detected in eyes with refractory macular edema (ME) associated with branch retinal vein occlusion (BRVO) for more than 12 months after onset when examined using optical coherence tomography (OCT). We proposed that these MAs could result in refractory ME secondary to BRVO and hypothesized that OCT-guided direct photocoagulation of MAs could result in a reduction in refractory ME. Eleven eyes (from eleven different patients) with refractory ME associated with BRVO for more than 12 months following initial treatment were included. The mean number of MAs in each eye at baseline was 3.5 ± 2.0 (range, 1-8). The mean central subfield thickness, central macular volume, and parafoveal macular volume significantly decreased 6 months following initial direct photocoagulation when compared with those at baseline (baseline = 378.7 ± 61.8 µm, post-treatment = 304.2 ± 66.7 µm, p = 0.0005; baseline = 0.3 ± 0.049 mm3, post-treatment = 0.24 ± 0.053 mm3, p = 0.001; and baseline = 2.5 ± 0.14 mm3, post-treatment = 2.28 ± 0.15 mm3, p = 0.001, respectively). Moreover, the mean best-corrected visual acuity significantly improved 6 months following initial direct photocoagulation when compared with that at baseline (baseline = 0.096 ± 0.2 logarithm of the minimum angle of resolution (logMAR), post-treatment = 0.0077 ± 0.14 logMAR, p = 0.031). Direct photocoagulation could be suggested as a treatment option for refractory ME associated with BRVO in MAs with a hyperreflective ring on OCT.

Long-term remission of ocular and extraocular manifestations in Behçet's disease using infliximab.

OBJECTIVES: To investigate the long-term effect of infliximab on ocular and extraocular manifestations in patients with Behçet's disease. METHODS: Seven patients with active Behçet's disease and treated with infliximab at Aichi Medical University Hospital for more than 18 months were included in the study. We evaluated visual acuity, the average number of uveitis attacks involving the posterior segment, and general disease activity every 2 months. The Behçet's Disease Current Activity Form (BDCAF) was used for an overall index of disease activity. Anti-infliximab antibody levels were examined in the patients' sera. RESULTS: The follow-up period after initial introduction of infliximab ranged from 19 to 40 months (mean ± SD, 32 ± 8.7 months). The number of infliximab infusions ranged from 12 to 24 (19 ± 4.4). By the 2-month follow-up, the frequency of uveitis attacks involving the posterior segment and the BDCAF scores were significantly improved compared to the 2 months before introducing infliximab. Anti-infliximab antibodies were detected in the sera of all examined patients. CONCLUSIONS: Significant long-term improvement in both the frequency of uveitis attacks involving the posterior segment and overall disease activity was provided by the administration of infliximab to patients suffering from Behçet's disease, despite the presence of anti-infliximab antibodies.

Increase in matrix metalloproteinase-2 level in the chicken retina after laser photocoagulation.

BACKGROUND AND OBJECTIVE: We investigated the levels of matrix metalloproteinase-2 (MMP-2), which has been implicated in various vitreoretinal diseases, in the retina after laser photocoagulation (LPC). MATERIALS AND METHODS: The time course of MMP-2 expression in 2-day-old chicken retinas before and 6 hours, 12 hours, 1 day, 2 days, 4 days, 8 days, 16 days, and 32 days after LPC was determined by real-time PCR and gelatin zymography. The basal level of MMP-2 in the retina and vitreous was also measured by gelatin zymography. MMP-2 localization in the retina was examined by immunohistochemistry. The localization of MMP-2 mRNA was determined by fluorescent in situ hybridization. The internal limiting membrane (ILM) was observed by scanning electron microscopy. RESULTS: MMP-2 mRNA expression in the retina peaked at day 4, but gelatin zymography showed that MMP-2 peaked 6 hours after LPC and the significant increase in the level of active MMP-2 lasted for more than 4 days. The concentration of MMP-2 in the vitreous was significantly higher than that in the retina. A distinct MMP-2 signal around the ILM was identified 6 hours after LPC, but MMP-2 mRNA was not detected there. Electron microscopy showed a damaged retinal surface after LPC. CONCLUSION AND OUTLOOK: The significant increase in retinal MMP-2 which lasted for more than 4 days after LPC may be induced by influx from the vitreous into the retina. This MMP-2 dynamics may contribute to pathological processes in the retina after LPC.

Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization.

Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets for the treatment of AMD. We recently reported that activator of G-protein signaling 8 (AGS8), a receptor-independent Gßγ regulator, is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. AGS8 knockdown in cultured choroidal EC inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. A mouse model of laser-induced CNV, created to analyze the roles of AGS8 in vivo, demonstrated that AGS8 mRNA was significantly upregulated in choroidal lesions and AGS8 was specifically expressed in the neovasculature. Local AGS8 knockdown in intravitreal tissue significantly inhibited laser-induced AGS8 upregulation and suppressed CNV, suggesting that AGS8 knockdown in the choroid has therapeutic potential for AMD. Together, these results demonstrate that AGS8 plays critical roles in VEGF-induced CNV.

Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials.

PURPOSE: Report global adalimumab safety and efficacy outcomes in patients with non-infectious uveitis. METHODS: Adults with non-infectious intermediate, posterior, or panuveitis were randomized 1:1 to receive placebo or adalimumab in the VISUAL I (active uveitis) or VISUAL II (inactive uveitis) trials. Integrated global and Japan substudy results are reported. The primary endpoint was time to treatment failure (TF). RESULTS: In the integrated studies, TF risk was significantly reduced (hazard ratio [95% CI]) with adalimumab versus placebo (VISUAL I: HR = 0.56 [0.40-0.76], p < 0.001; VISUAL II: HR = 0.52 [0.37-0.74], p < 0.001). In Japan substudies, no consistent trends were observed between groups (VISUAL I: HR = 1.20 [0.41-3.54]; VISUAL II: HR = 0.45 [0.20-1.03]). Adverse event rates were similar between treatment groups in both studies (854 to 1063 events/100 participant-years). CONCLUSIONS: Adalimumab lowered time to TF versus placebo in the integrated population; no consistent trends were observed in Japan substudies. Safety results were consistent between studies.