Resistance force for intraocular lens insertion through lens cartridges and syringe-type injectors.

PURPOSE: To measure and compare the resistance force for intraocular lens (IOL) insertion using 5 syringe-type injector systems. SETTING: Tokyo Medical University and laboratory in Kowa Co., Tokyo, Japan. DESIGN: Experimental study. METHODS: Intraocular lenses were inserted into the lens capsular bag of porcine eyes after phacoemulsification using 5 implantation systems (Groups A, B, C, D, and E). For each system, the resistance force for IOL insertion to the lens capsular bag of porcine eyes was measured using an automated force gauge system. For control, the resistance force for IOL delivery into a plastic dish was measured. Changes in the resistance force and its curve and maximum value were evaluated. The mean total area under the curve (AUC) was compared. Data were statistically analyzed. RESULTS: For all groups, the mean resistance forces were 17.2, 6.3, 4.2, 20.7, and 2.3 newtons (N), respectively, in porcine eyes, and 14.4, 5.8, 4.5, 12.6, and 2.2 N in controls. The mean sizes of the total AUC were 43 371, 8465, 6771, 30 306, and 2334 pixels in porcine eyes and 40 940, 7080, 6876, 20 710, and 2215 pixels in controls; the correlation coefficients between the resistance forces and the sizes of the total area were 0.576, 0.113, 0.346, 0.726, and 0.933 in porcine eyes and 0.707, 0.557, 0.914, 0.951, and 0.893 in controls. CONCLUSION: Resistance force and its curve were clarified in 5 IOL implantation systems. Appropriate IOL and injector selection may be achieved after clarifying resistance force and its waveform during IOL insertion. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned.

The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1ß.

Obesity is a major global public health problem, and understanding its pathogenesis is critical for identifying a cure. In this study, a gene knockout strategy was used in post-neonatal mice to delete synoviolin (Syvn)1/Hrd1/Der3, an ER-resident E3 ubiquitin ligase with known roles in homeostasis maintenance. Syvn1 deficiency resulted in weight loss and lower accumulation of white adipose tissue in otherwise wild-type animals as well as in genetically obese (ob/ob and db/db) and adipose tissue-specific knockout mice as compared to control animals. SYVN1 interacted with and ubiquitinated the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1ß, and Syvn1 mutants showed upregulation of PGC-1ß target genes and increase in mitochondrion number, respiration, and basal energy expenditure in adipose tissue relative to control animals. Moreover, the selective SYVN1 inhibitor LS-102 abolished the negative regulation of PGC-1ß by SYVN1 and prevented weight gain in mice. Thus, SYVN1 is a novel post-translational regulator of PGC-1ß and a potential therapeutic target in obesity treatment.

Cell adhesion and glistening formation in hybrid copolymer intraocular lenses.

The purpose of this study is to investigate the cell adhesion and glistening formation properties of various foldable intraocular lenses (IOLs) in vitro. Three conventional hydrophobic methacrylate acrylic (MA) IOLs, a hydrophilic hydroxyethyl methacrylate (HEMA) IOL and a hybrid MA/HEMA copolymer IOL were investigated for immunologically activated cell adhesion and for formation of glistenings resulting from cavitation, by analysis of digital images using NIH Image J PC software. The MA IOLs exhibited a low level of adhering cells but a high level of glistening formation, the HEMA IOL exhibited the reverse tendency, and the MA/HEMA IOL exhibited a low level of both, thus indicating that hybrid MA/HEMA IOLs are less susceptible than HEMA IOLs to cell adhesion and less susceptible than MA IOLs to glistening formation.

Successful closure of large blunt macular chorioretinal rupture: a case report.

The authors present a rare case of large chorioretinal rupture caused by blunt traumatic injury of the globe. A 22-year-old woman sustained a blunt injury to her left eye. The best-corrected Snellen visual acuity was 2/20 in her left eye, and hyphema and vitreous hemorrhage were noted. The day after the injury occurred the vitreous hemorrhage had disappeared. Fundus examination revealed a crescent-shaped retinal rupture three disc diameters in size near the macula, and a choroidal rupture six disc diameters in size that was over the vascular arcade. Three days after the injury, vitrectomy with internal limiting membrane peeling was performed. Postoperative prone positioning was maintained for 4 days. Five days postoperatively, closure of the ruptured retina was confirmed. The visual acuity improved to 16/20 4 months after surgery and this was maintained over a 48-month period. In conclusion, early vitrectomy with internal limiting membrane peeling after injury was effective for a case involving severe blunt chorioretinal rupture with closed globe injury.

Adhesive retention of sodium hyaluronate ophthalmic viscosurgical devices in an acrylic tube model and in porcine-eye corneal endothelium with different irrigation rates.

PURPOSE: To evaluate the influence of irrigation rates on the adhesive retention of sodium hyaluronate ophthalmic viscosurgical devices (OVDs) by observation in an acrylic tube system designed to model the epithelial wall and in a porcine-eye experiment. SETTING: Kohseichuo Hospital, Tokyo, Japan. METHODS: Commercial sodium hyaluronate OVDs differing in molecular weight were visualized with fluorescein powder. Their adhesive and kinetic characteristics at 2 irrigation rates were visually observed in the acrylic tube model and in a porcine eye under phacoemulsification and aspiration. RESULTS: In the acrylic tube model, the mean retention time of the low-molecular-weight sodium hyaluronate increased from 2.3 seconds under 78 mL/min irrigation to 27.9 seconds under 45 mL/min irrigation. In the porcine eye, phacoemulsification retention of the same OVD on the corneal endothelial cells was also longer under the low irrigation rate of a 2.2 mm incision than under the higher rate of a 3.5 mm incision. CONCLUSION: The stable retention of low-molecular-weight sodium hyaluronate in the acrylic tube model at the low irrigation rate corresponded closely with that observed in the porcine eye. This indicates that low-molecular-weight sodium hyaluronate with the low irrigation rates used in procedures such as microincision cataract surgery may effectively protect corneal endothelial cells against surgical risks.

Presumed Vogt-Koyanagi-Harada disease with unilateral ocular involvement: report of three cases.

AIM: To report three cases of presumed Vogt-Koyanagi-Harada (VKH) disease with unilateral ocular manifestations. METHODS: This retrospective study reviewed the long-term follow-up observations of three patients who attended the uveitis clinic at Tokyo Medical University Hospital. The patients were followed for 5-16 years with systemic clinical, ophthalmologic and laboratory examinations. Ophthalmoscopic findings, extraocular manifestations, visual acuity, and response to corticosteroid administration were evaluated. RESULTS: Three patients had characteristic clinical features of VKH involving only one eye, including diffuse choroiditis, serous retinal detachment, focal areas of delayed choroidal perfusion, multifocal areas of pinpoint leakage, macular oedema, and optic nerve staining. All patients received systemic corticosteroid therapy during the acute phase of the disease. During the follow-up period (5-16 years), all three patients developed sunset-glow fundus and nummular chorioretinal depigmented scars in the affected eye only, as well as systemic complications of deafness, vitiligo, and poliosis. CONCLUSION: The clinical and laboratory features of all three patients were typical of VKH disease except for the unilateral involvement. It is important for ophthalmologists to recognize unilateral VKH disease, even though it is a rare clinical variant of the disease.

Effects of dioxin on vascular endothelial growth factor (VEGF) production in the retina associated with choroidal neovascularization.

PURPOSE: Cigarette smoking is the most consistent risk factor for age-related macular degeneration (AMD), especially the choroidal neovascularization (CNV)-mediated exudative type. Dioxins and dioxin-like compounds have various effects on living organisms and are also contained in cigarette smoke. However, the effects of dioxins on the eye remain elusive. In this study, the authors examined the association between dioxins and neovascularization in the eye. METHODS: C57BL/6 mice were injected intraperitoneally with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every other day for 14 days. Messenger RNA expression of cytochrome P450 (CYP)1A1, CYP1B1, vascular endothelial growth factor (VEGF)-A and VEGF-B, and VEGF production were examined in the eyes of TCDD-treated mice and in human retinal pigment epithelial cell lines (ARPE-19) exposed to TCDD. In addition, CNV was induced by photocoagulation in mice injected with TCDD, and the volume of CNV was compared by fluorescence-labeled choroidal flat mount. RESULTS: TCDD injected intraperitoneally increased CYP1A1 mRNA expression in the iris/ciliary body and retina, indicating that TCDD acts directly on ocular tissues through the aryl hydrocarbon receptor (AhR) to promote the transcription of target genes. TCDD also promoted VEGF-A mRNA expression in the retina and the retinal pigment epithelium. TCDD-induced VEGF production at the molecular level was also observed in vivo by immunohistochemistry and in vitro using ARPE-19. Moreover, the injection of TCDD significantly exacerbated photocoagulation-induced CNV in mice. CONCLUSIONS: The authors demonstrate that dioxins are among the factors inducing abnormal vascularization in the eye through VEGF production mediated by AhR signaling.

[STD in the eye].

In this paper, we review sexually transmitted diseases (STD) involving the eye. Recently conjunctivitis due to Chlamydia trachomatis in children and adults is increasing, and that of Neisseria gonorrhoeae resistant to multiple antibiotics has attracted special attention in our country. Syphilis has many ocular manifestations such as keratitis, iridocyclitis, retinochorioiditis, and neuritis, etc. Ocular complications related to HIV infection, including HIV retinopathy, cytomegalovirus retinitis, zoster ophthalmics, and Kaposi s sarcoma in conjunctiva are increasing in Japan. Phthirus pubis infection of the eye lid, and human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis are occasionally reported. Furthermore conjunctival tumor associated with human papilloma virus (HPV) infection, acute retinal necrosis(ARN) due to herpes simplex virus type 2 (HSV-2), as well as hepatitis B virus (HVB) and hepatitis C virus (HVC) retinopathy are also mentioned in this review.

[Terminal care for one-person household].

In addition to visitor medical-examination service, Mutsumi-cho clinic (Minami-ku, Yokohama-city) started a home care service in October 2008. The number of one-person elderly house-hold is 8,483 (about 10%) out of 84,399 house-hold in Minami-ku where 200,000 people reside. We report here our experience in the terminal care of one-person elderly person who lives at home. The regional cooperation is indispensable for seeing-off of the end stage elderly patient at home. We (the physician, visiting nurse, care manager and helper were united and performed) spent a total of 10 days for a terminal care of the end stage elder patient.

The additive effects on intraocular pressure of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions: a prospective, randomized, multicenter study.

PURPOSE: To investigate the effectiveness of combining nipradilol 0.25% and latanoprost 0.005% ophthalmic solutions in improving the intraocular pressures (IOPs) in glaucoma patients. METHODS: We divided the 53 patients into two groups, those who had been treated with latanoprost and those who had been treated with nipradilol. We administered to the first group one dose of latanoprost daily for 12 weeks and to the second group one dose of nipradilol daily for 12 weeks. Each group then received both solutions for another 12 weeks; the latanoprost group received nipradilol and the nipradilol group received latanoprost. IOPs were measured at each 4-week visit. RESULTS: In the patients previously treated with latanoprost, the mean IOP was 19.6+/-2.5 mmHg at baseline, and 14.9+/-2.4 mmHg (23.7% reduction) after 12 weeks of latanoprost monotherapy. The addition of nipradilol decreased the IOP to 13.8+/-1.9 mmHg (29.0% reduction). In the group previously treated with nipradilol, the mean IOP was 20.2+/-3.1 mmHg at baseline, and 16.7+/-3.5 mmHg (17.1% reduction) after 12 weeks of nipradilol monotherapy. Addition of latanoprost decreased the IOP to 14.2+/-3.2 mmHg (29.5% reduction). CONCLUSION: Latanoprost and nipradilol are more effective as a combination therapy than each one by itself.

Preoperative disinfection of the conjunctival sac with antibiotics and iodine compounds: a prospective randomized multicenter study.

PURPOSE: To compare disinfection by povidone-iodine (PI) solution with that by polyvinyl alcohol-iodine (PAI) solution in preoperative eyewash and to assess the optimal duration of the preoperative application of 0.5% levofloxacin (LVFX) ophthalmic solution. METHODS: Two-hundred-seventy-two elderly cataract patients who had undergone phacoemulsification aspiration with intraocular lens insertion at 12 clinical facilities in Japan were randomized into three groups: 3-day, 1-day, and 1-h preoperative application of 0.5% LVFX ophthalmic solution. Each LVFX group was further divided into two subgroups; the patients in one subgroup were treated with diluted PI eyewash, and those in the second subgroup with diluted PAI eyewash, immediately before the surgery. Thus, a total of six groups were studied. Conjunctival scrapings were collected four times: before LVFX application, after LVFX application, after the eyewash with iodine compounds, and after the surgery. Samples of the aqueous humor were collected immediately after the surgery. All samples were cultured aerobically and anaerobically. RESULTS: The 3-day application of LVFX had a significantly higher disinfection rate than the 1-day or 1-h applications (P<0.05). The disinfection rate of PI was 78.0%, and that of PAI was 79.4%; PAI was not inferior to PI as a preoperative disinfectant. However, new isolates, mainly Propionibacterium acnes and Staphylococcus epidermidis, were detected after LVFX application and even after use of the eyewash with iodine compounds. CONCLUSION: Three-day administration of LVFX ophthalmic solution and use of an eyewash with diluted iodine compounds is effective for preoperative disinfection. However, complete elimination of bacteria from the conjunctival sac is difficult.

Proteomic surveillance of retinal autoantigens in endogenous uveitis: implication of esterase D and brain-type creatine kinase as novel autoantigens.

PURPOSE: Various retinal proteins are newly exposed to immune system in a process of tissue destructive endogenous uveitis. Some of such proteins could be autoantigens that extend the ocular inflammation in human endogenous uveitis. In this study, we aimed to investigate the possibility of such spreading of autoantigens in endogenous uveoretinitis using a proteomic approach. METHODS: Experimental autoimmune uveoretinitis (EAU) was induced in mice by inoculation with a peptide consisting of amino acids 1-20 (GPTHLFQPSLVLDMAKVLLP) of interphotoreceptor retinoid binding protein (IRBP). Six weeks after immunization, the presence of autoantibodies against the retinal proteins in mice with EAU were examined by two-dimensional electrophoresis followed by western blotting (2D-WB). Retinal proteins targeted by the autoantibodies were identified by mass spectrometry (MS) and their autoantigenicity in patients with endogenous uveitis, such as Behcet's disease (BD, n=36), Vogt-Koyanagi-Harada disease (VKH, n=16), and sarcoidosis (n=17) were examined by enzyme-linked immunosorbent assay. RESULTS: Six new candidate autoantigens, which were detected in mice with EAU using 2D-WD were identified by MS as beta-actin, esterase D (EsteD), tubulin beta-2, brain-type creatine kinase (BB-CK), voltage-dependent anion-selective channel protein, and aspartate aminotransferase. Among the patients with endogenous uveitis, 25% of BD and 25% of VKH patients were positive for anti-EsteD antibody, and 25% of VKH and 38.4% of sarcoidosis patients were positive for anti-BB-CK antibody. CONCLUSIONS: Autoantibodies to EsteD and BB-CK produced in EAU-induced mice were also detected in some endogenous uveitis patients, suggesting that these proteins might be autoantigens spreading in a process of endogenous uveoretinitis.

Effect of gauge thickness on wound-width measurements in microincision cataract surgery.

PURPOSE: To evaluate the effect of gauge thickness on wound-width measurement values in microincision cataract surgery (MICS). SETTING: Kosei Chuo Hospital, Tokyo, Japan. METHODS: For intraocular lens (IOL) implantation, the incision was enlarged with 1 of 2 knives of different widths. Before and after IOL insertion, the wound width was measured with a 0.15 mm thick gauge (F-gauge), which was the same thickness as both types of knife, and a commercially available 0.35 mm thick gauge (A-gauge). RESULTS: In the 2.2 mm incision group, the mean wound width before IOL insertion was 2.20 mm+/-0.03 (SD) measured with the F-gauge and 2.16+/-0.05 mm measured with the A-gauge; the difference was statistically significant (P=.002). The mean wound width after IOL insertion was 2.41+/-0.08 mm using the F-gauge and 2.35+/-0.09 mm using the A-gauge; the difference was statistically significant (P<.0001). In the 2.4 mm incision group, the mean wound width before IOL insertion was 2.39+/-0.04 mm using the F-gauge and 2.31+/-0.06 mm using the A-gauge (P<.0001); the mean wound width after IOL insertion was greater than 2.5 mm in both groups. CONCLUSIONS: In MICS, when the wound-width gauge thickness exceeded the knife thickness, the potential for measurement errors increased. Thus, a similar thickness between the 2 instruments may be preferable.

Phenoxazine derivative, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one suppresses growth of human retinoblastoma cell line Y79 in vitro and in vivo.

The aim of the study was to evaluate the in vitro and in vivo antitumor effects of the 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1) on the human retinoblastoma cell line Y79. The in vitro effects of Phx-1 on cell viability and apoptosis of the human retinoblastoma Y79 cells, were studied by using colorimetric and flow-cytometric methods. The in vivo antitumor effects of Phx-1 on the human retinoblastoma Y79 cells subcutaneously transplanted in BALB/c nude mice were studied, examining the tumor size, the adverse effects on the mice and the histopathological evaluations including hematoxylin and eosin and immunohistochemical staining in the mass of tumors of human retinoblastoma Y79 cells isolated from the mice. Phx-1 suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Phx-1 markedly reduced the growth of Y79 cells transplanted into the mice without causing bodyweight loss. Pathological findings of the tumor mass isolated from mice revealed that the tumor of Y79 cells treated with Phx-1 had a decreased mitotic index, decreased expression of Ki67 and p53, no alteration of bcl-2 level and increased caspase-3 activity compared with the the control. Present results suggested that Phx-1 demonstrated antitumor activity against the human retinoblastoma Y79 cells in vitro and in vivo, by inhibiting cell growth and inducing apoptosis. In addition, Phx-1 exerted few adverse side effects on the mice. Phx-1 may be a useful antitumor drug in the treatment of retinoblastoma, which is the most common and serious intraocular malignant tumor.

Circulating neutrophils in Behçet disease is resistant for apoptotic cell death in the remission phase of uveitis.

BACKGROUND: Behçet disease (BD) is manifested by recurrent acute iridocyclitis with hypopyon in the active phase, which regresses spontaneously. Hypopyon consists of inflammatory cells infiltrating the eye, with polymorphonuclear cells (PMNs) as the main component. The present study was conducted to investigate the apoptosis property of PMNs in BD patients with uveitis. METHODS: PMNs were purified from peripheral blood cells of BD patients with uveitis in the active or remission phase and were cultured for 12 hours. In some cultures, lipopolysaccharide (LPS), antagonistic anti-TNFalpha antibody, agonistic anti-Fas antibody, or Fas:Fc fusion protein was added. At the end of cultures, apoptotic cells were evaluated by Annexin V expression using flow cytometry. RESULTS: Spontaneous apoptosis of PMNs showed lower levels in the remission phase of BD-related uveitis compared with the active phase or healthy controls. The lower level of PMN apoptosis in the remission phase of uveitis in BD remained even by stimulation with LPS, anti-TNFalpha antibody, or Fas:Fc fusion protein, which was abolished in the presence of agonistic anti-Fas antibody. CONCLUSIONS: In BD patients, the apoptosis of PMNs was reduced in the remission phase of uveitis and restored in the active phase, which arose from the apoptotic cell death in part via Fas-Fas ligand interaction.

Functional expression of B7H1 on retinal pigment epithelial cells.

The interaction of programmed death-1 (PD-1) expressed on T cells with its ligands B7H1 (PDL1) and B7DC (PDL2) is known to be a mechanism of T cell inhibition. In the present study, we examined whether human or murine retinal pigment epithelial (RPE) cells express B7H1 and B7DC, and if so, whether these molecules expressed on RPE cells play an inhibitory role via interaction with T cells. The transcriptional levels and surface expression of B7H1 and B7DC on human RPE cell line (ARPE-19), RPE cells freshly isolated from healthy human subjects, and murine RPE cells were studied by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. In addition, T cells from healthy subjects were cultured with ARPE-19 for 72h in the presence or absence of monoclonal antibody (mAb) to B7H1 or B7DC, and cytokine production (IFN-gamma, IL-8, and MCP-1) was measured. Messenger RNA and cell surface protein expression of B7H1 and B7DC were demonstrated on non-stimulated ARPE-19 and freshly isolated human RPE cells, and the expression of these molecules was predominantly upregulated by treatment with IFN-gamma. In murine RPE cells, B7H1 expression was detected only when stimulated with IFN-gamma. IFN-gamma, IL-8, and MCP-1 production by T cells co-cultured with IFN-gamma-untreated or -treated ARPE-19 was significantly enhanced in the presence of anti-B7H1 mAb. These data suggest that B7H1 expressed on RPE cells plays an immunosuppressive role in ocular inflammation, which may contribute to immune privilege in the posterior segment of the eye.

Relationship between retinal vein occlusion and carotid artery lesions.

PURPOSE: To investigate the relationship between retinal vein occlusion (RVO) and carotid artery lesions. METHODS: For patients with RVO who presented to the Ophthalmology Department of Tokyo Medical University Hospital between 2000 and 2003, carotid artery evaluation was possible on 58 eyes of 57 patients aged 51 years to 88 years (mean, 70.1 years). Thirty-nine patients (40 eyes) had central RVO (CRVO), and 18 patients (18 eyes) had branch RVO (BRVO). The observation period ranged from 6 months to 28 months (mean, 14 months). A diagnostic ultrasound device was used to detect carotid artery lesions. RESULTS: Carotid artery lesions were detected in 19 (49%) of 39 patients with CRVO and in 4 (22%) of 18 patients with BRVO. In CRVO, 6 eyes without carotid artery lesions but no eye with carotid artery lesions had good decimal visual acuity of >or=0.8 (P < 0.05). Fluorescein angiographic findings identified a significantly (P < 0.01) higher incidence of the ischemic type in cases with carotid lesions (15 eyes; 79%) than in cases without carotid lesions (8 eyes; 40%). CONCLUSIONS: The findings suggest that the presence of a carotid artery lesion has a considerable association with the development and prognosis of CRVO.

Blockade of the OX40 ligand prolongs corneal allograft survival.

Although corneal transplantation is one of the most common tissue transplantations and is known to have a high graft acceptance rate, occasional corneal graft rejection remains a cause of blindness. OX40, a member of the TNF receptor superfamily, is expressed on activated T cells, and transmits a costimulatory signal by binding to OX40 ligand (OX40L) expressed on several cells with antigen-presenting functions. Using a blocking monoclonal antibody (mAb) against murine OX40L, we investigated the role of OX40 in a murine model of corneal transplantation. C3H/He mouse corneas were transplanted to BALB/c mice orthotopically. Administration of anti-OX40L mAb significantly reduced allograft rejection, and increased graft survival rate to 40% at 8 weeks after transplantation, while all corneas were rejected within 5 weeks in control IgG-treated mice. Similar reduced rejection was observed when wild-type donor corneas were transplanted to OX40L-deficient recipients. In vitro study revealed that the anti-OX40L mAb treatment reduced proliferative response and IFN-gamma production of draining lymph node cells in response to stimulation with donor alloantigen. These results demonstrate that OX40L blockade is effective for prolongation of corneal allograft survival by inhibiting recipient T cell activation.