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OBJECTIVES FOLFIRINOX (oxaliplatin, irinotecan, 5-fluorouracil, and leucovorin) is the standard therapy worldwide for unresectable pancreatic cancer; however, clinical data for Japanese patients are limited. Therefore, the observational study of FOLFIRINOX for patients with pancreatic cancer was conducted. METHODS The study included 399 patients with unresectable or recurrent pancreatic cancer, from 27 institutions in Japan, treated with FOLFIRINOX and surveyed until December 2015. RESULTS The median age was 63 years; in most patients, the Eastern Cooperative Oncology Group performance status was 1 or lower. The initial dose was reduced in 270 patients (68%). The main grade 3/4 toxicities were neutropenia (64%), anorexia (14%), and febrile neutropenia (13%). Fatal adverse events occurred in 5 patients, 4 of whom did not satisfy the main inclusion criteria of a previous Japanese phase II FOLFIRINOX study. The median overall survival and progression-free survival times were 10.8, and 4.5 months, respectively. The objective response rate was 21%, and the disease control rate was 61%. The median overall survival times were 11.1, 18.5, and 4.9 months in chemotherapy-naive patients with metastatic, locally advanced, and recurrent disease, respectively. CONCLUSION When carefully managed, FOLFIRINOX is acceptably safe and efficacious in Japanese patients with unresectable pancreatic cancer.

Background The contemporary incidence of and reasons for early readmission after infective endocarditis ( IE ) are not well known. Therefore, we analyzed 30‐day readmission demographics after IE from the US Nationwide Readmission Database. Methods and Results We examined the 2010 to 2014 Nationwide Readmission Database to identify index admissions for a primary diagnosis of IE with survival at discharge. Incidence, reasons, and independent predictors of 30‐day unplanned readmissions were analyzed. In total, 11 217 patients (24.8%) were nonelectively readmitted within 30 days among the 45 214 index admissions discharged after IE . The most common causes of readmission were IE (20.5%), sepsis (8.7%), complications of device/graft (8.1%), and congestive heart failure (7.6%). In‐hospital mortality and the valvular surgery rates during the readmissions were 8.1% and 9.1%, respectively. Discharge to home or self‐care, undergoing valvular surgery, aged ≥60 years, and having private insurance were independently associated with lower rates of 30‐day readmission. Length of stay of ≥10 days, congestive heart failure, diabetes mellitus, renal failure, chronic pulmonary disease, peripheral artery disease, and depression were associated with higher risk. The total hospital costs of readmission were $48.7 million per year (median, $11 267; interquartile range, $6021–$25 073), which accounted for 38.6% of the total episodes of care (index+readmission). Conclusions Almost 1 in 4 patients was readmitted within 30 days of admission for IE . The most common reasons were IE , other infectious causes, and cardiac causes. A multidisciplinary approach to determine the surgical indications and close monitoring are necessary to improve outcomes and reduce complications in in‐hospital and postdischarge settings.

Supplemental Digital Content is available in the text, Introduction: Human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. However, even if an actionable gene alteration is found, the incidence of HER2 amplification in these cancers is less than 5%. It is too difficult to conduct a conventional randomized, controlled trial in a rare fraction. Therefore, we have designed a organ-agnostic basket study, which covers a variety of solid cancers harboring HER2 amplification, in 1 study protocol. Methods/Design: This trial is a multicenter, single-arm, basket phase 2 study in Japan. Patients with solid cancers harboring HER2 amplification that have progressed with standard treatment, or rare cancers for which there is no standard treatment, will be eligible. Target cancers include bile duct, urothelial, uterine, ovarian, and other solid cancers where HER2 amplification is detected by comprehensive genomic profiling using next-generation sequencing technology. A total of 38 patients will be treated with combination therapy with trastuzumab and pertuzumab every 3 weeks until disease progression, unmanageable toxicity, death, or patient refusal. The primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, and duration of response. Discussion: The aim of this trial is to evaluate the safety and efficacy of combination therapy with trastuzumab and pertuzumab in patients with locally advanced or metastatic, solid cancers harboring HER2 amplification. Instead of focusing on 1 organ type, our trial design uses a basket study focusing on HER2 amplification, regardless of the site or origin of the cancer. The results of our study will advance clinical and scientific knowledge concerning the treatment of locally advanced, rare solid cancers harboring HER2 amplification, using the combination of trastuzumab and pertuzumab. Trial registration: This trial was registered in Japan Registry of Clinical Trials (jCRT) on February 25, 2019, as jRCT2031180150.

Background: Readmissions after in-hospital cardiopulmonary resuscitation (ICPR) are common and contribute to increased health care utilization and costs. This is the first study to estimate the burden and patterns of 30-day readmission after ICPR from Nationwide Readmission Database (NRD). Methods and Results: Patients undergoing ICPR (International Classification of Diseases-Ninth Revision-Clinical Modification codes 99.60 and 99.63) between January and November 2014 from NRD were included. Incidence, predictors, causes, and costs of 30-day readmission were analyzed using discharge weights to obtain national estimates. Among estimated 27278 index admissions survived to hospital discharges after ICPR, 5439 (20.0%) were readmitted within 30 days. Length of stay (LOS) ≧15 days during index hospitalization (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.42), Medicare or Medicaid insurance (HR, 1.34; 95% CI, 1.19-1.51), heart failure (HR, 1.2; 95% CI, 1.1-1.32), and discharge of metropolitan teaching hospital (HR, 1.19; 95% CI, 1.07-1.33) were independent predictors of 30-day readmission. Among 5439 readmissions, Sepsis (13.7%), heart failure (10.8%), respiratory failure (6.4%), and cardiac dysrhythmias (5.2%) were the most common causes. Estimated total costs of readmission were $102 million and mean of $19122 ±30201, which is accounted for 25.7% of total episode of care (index+readmission). The mean LOS was 8.0 ±10.5 days. The patients with readmission revealed high mortality rate of 10.1%. Conclusions: Thirty-day readmissions after ICPR are frequent and are related to baseline comorbidities and hospital characteristics. Awareness of these predictors can help identify and target high-risk patients for interventions, to reduce readmissions and costs.

Purpose To examine the effect of astigmatism on visual acuity at various distances in eyes with a diffractive multifocal intraocular lens (IOL). Setting Hayashi Eye Hospital, Fukuoka, Japan. Methods In this study, eyes had implantation of a diffractive multifocal IOL with a +3.00 diopter (D) addition (add) (AcrySof ReSTOR SN6AD1), a diffractive multifocal IOL with a +4.00 D add (AcrySof ReSTOR SN6AD3), or a monofocal IOL (AcrySof SN60WF). Astigmatism was simulated by adding cylindrical lenses of various diopters (0.00, 0.50, 1.00, 1.50, 2.00), after which distance-corrected acuity was measured at various distances. Results At most distances, the mean visual acuity in the multifocal IOL groups decreased in proportion to the added astigmatism. With astigmatism of 0.00 D and 0.50 D, distance-corrected near visual acuity (DCNVA) in the +4.00 D group and distance-corrected intermediate visual acuity (DCIVA) and DCNVA in the +3.00 D group were significantly better than in the monofocal group; the corrected distance visual acuity (CDVA) was similar. The DCNVA with astigmatism of 1.00 D was better in 2 multifocal groups; however, with astigmatism of 1.50 D and 2.00 D, the CDVA and DCIVA at 0.5m in the multifocal groups were significantly worse than in the monofocal group, although the DCNVA was similar. With astigmatism of 1.00 D or greater, the mean CDVA and DCNVA in the multifocal groups reached useful levels (20/40). Conclusion The presence of astigmatism in eyes with a diffractive multifocal IOL compromised all distance visual acuities, suggesting the need to correct astigmatism of greater than 1.00 D. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

To determine whether posterior capsule opacification (PCO) is extensive in eyes with myopia or long axial length when an intraocular lens (IOL) of low-power, zero-power, or minus-power, is implanted.Hayashi Eye Hospital, Fukuoka, Japan.Ninety eyes of 90 patients scheduled for phacoemulsification surgery were recruited. These consisted of 30 eyes with high (or =-8 diopters [D]) myopia, 30 eyes with moderate (-8 D andor =-3 D) myopia, and 30 eyes with low (-3 D) myopia. All eyes had implantation of an acrylic IOL-low-power, zero-power, or minus-power-with a sharp optic edge (AcrySof MA60BM or MA60MA, Alcon Surgical). The PCO in these eyes was measured using a Scheimpflug videophotography system (EAS-1000, Nidek) 1, 3, 6, 12, 18, and 24 months after surgery. Visual acuity and the incidence of neodymium:YAG (Nd:YAG) laser posterior capsulotomy were also examined.No significant difference was observed in the mean PCO value or in the Nd:YAG capsulotomy rate between the high myopia, moderate myopia, or low myopia groups throughout the follow-up period. There was also no significant correlation between PCO value and the actual spherical power or axial length of the eye. Furthermore, although mean visual acuity tended to be worse in proportion to the degree of myopia, the difference was not statistically significant.When an acrylic IOL of low-power, zero-power, or minus-power with a sharp optic edge was implanted, high myopia and long axial length were not associated with the degree of PCO.

Purpose: To evaluate the outcomes of phacoemulsification in eyes that had previous retinal detachment (RD) surgery. Setting: Hayashi Eye Hospital, Fukuoka, Japan. Methods: Ninety-six eyes of 90 consecutive patients who had phacoemulsification after previous RD surgery (RD group) were included. Fifty-one fellow eyes that had not had RD surgery but did have phacoemulsification served as controls (control group). Recurrence of RD, visual acuity, complications, and the neodymium:YAG (Nd:YAG) laser capsulotomy rate were examined. Results: Recurrent RD after phacoemulsification occurred in 2 eyes (2.1%) in the RD group. Three eyes (5.9%) in the control group developed RD postoperatively. The incidence of RD was not significantly different between the 2 groups (P = .3416). The mean final visual acuity in the RD group was 20/30, significantly worse than in the control group (P = .0099). Posterior capsule opacification developed in 29 eyes (30.2%) in the RD group and 11 eyes (21.6%) in the control group; the difference between the groups was not significant. Eighteen eyes (43.9%) that had implantation of a poly(methyl methacrylate) (PMMA) intraocular lens (IOL) and 7 eyes (6.6%) that received an acrylic IOL had an Nd:YAG capsulotomy; the capsulotomy rate was significantly higher in eyes with a PMMA IOL than in eyes with an acrylic IOL (P Conclusions: The rate of recurrent RD after phacoemulsification in eyes that had previous RD surgery was similar to that of new occurrence of RD in fellow eyes without RD before phacoemulsification. Because the Nd:YAG capsulotomy rate was lower in eyes with acrylic IOLs than in eyes with PMMA IOLs, acrylic IOLs are recommended for eyes at high risk for RD.

Purpose: To examine the changes in intraocular pressure (IOP) and the incidence of substantial rises in IOP in the early period after cataract surgery in eyes with open-angle glaucoma (OAG). Setting: Hayashi Eye Hospital, Fukuoka, Japan. Methods: The study included 32 eyes of 32 patients with OAG and 31 control eyes of 31 age-matched patients scheduled for phacoemulsification surgery. The IOP was measured preoperatively and 1, 2, 3, 5, 7, 14, and 28 days postoperatively. The incidence of a substantial rise in IOP postoperatively was evaluated, with the criterion being an IOP higher than 30 mm Hg. Results: In the OAG group, the mean IOP increased 1, 2, and 3 days postsurgery and then decreased, whereas in the control group, it decreased from day 1 postsurgery. Although no significant differences were found between groups preoperatively, the mean IOP in the OAG group was significantly higher than in the control group postoperatively. Furthermore, the mean IOP decrease was also less in the OAG group than in the control group. A substantial increase in IOP occurred at day 1 postsurgery in 4 eyes (12.5%) in the OAG group, whereas no eyes in the control group showed such an increase; this difference was significant ( P = .0419). Conclusions: A substantial increase in IOP occurred in an approximately 13% of eyes with OAG 1 day after phacoemulsification surgery. The IOP shortly after surgery was significantly greater in the eyes with OAG than in nonglaucomatous eyes.

Background: Increasing evidence suggests that N-terminal probrain natriuretic peptide (NT-proBNP) may be a more discerning marker for the detection and evluation of heart failure than BNP. However, fundamental mechanisms that contribute to the heart failure in aortic stenosis (AS) and ischemic heart disease (IHD) via NT-proBNP remain unclear. Objectives: The purpose of this study was to investigate whether NT-proBNP represents autocrine/paracrine factors and are accumulated in pericardial fluid (PF) in patients with AS and IHD. Methods: With an electrochemiluminescent immunoassay, we measured the concentrations of NT-proBNP in serum and pericardial fluid simultaneously in 48 patients undergoing aortic valve replacement and 101 patients undergoing coronary artery bypass grafting. We investigated the correlation of NT-proBNP levels in serum or PF with hemodynamic variables. Results: In patients with AS, the PF levels of NT-proBNP were markedly elevated compared with serum levels (10747±17619 pg/ml vs. 2828±7787 pg/ml, p=0.0054). In patients with IHD, the PF levels of NT-proBNP were markedly elevated compared with serum levels (7224±16345 pg/ml vs. 764±1199 pg/ml, p=0.0001). In AS, NT-proBNP levels in PF but not in serum had closer relations with left ventricular (LV) end-diastolic (r=0.338, p=0.0463) and systolic volume indexes (r=0.551, p=0.0005). In AS, NT-proBNP levels in PF but not in serum inversely correlated with LV ejection fraction (EF) (r=-0.510, p=0.0002). In IHD, NT-proBNP levels in PF but not in serum had closer relations with left ventricular (LV) end-diastolic (r=0.493, p Conclusion: Increased PF concentrations of NT-proBNP reflects the direct actions as a local mediator against cardiac pressure overload in AS patients and cardiac voume overload in IHD patients with left ventricular systolic dysfunction.

To examine the effect of cataract surgery on intraocular pressure (IOP) control in eyes with angle-closure glaucoma (ACG) and open-angle glaucoma (OAG).Hayashi Eye Hospital, Fukuoka, Japan.This study included 74 eyes with ACG and 68 eyes with OAG having cataract surgery. The IOP was measured and the number of glaucoma medications recorded preoperatively, 1 month postoperatively, and then every 3 months. The IOP control in the 2 groups was compared using survival analysis, with failure criteria being an IOP greater than 21 mm Hg, addition of medications, or the need for additional glaucoma surgery.The mean IOP and number of medications decreased significantly after surgery in both groups (P.0001). However, the mean decrease in IOP and percentage of IOP reduction in the ACG group were greater than in the OAG group, and fewer medications were required in the ACG group. The cumulative survival probability of IOP control at 24 months was 91.9% in the ACG group and 72.1% in the OAG group. The survival curve in the ACG group was significantly better than in the OAG group (P =.0012). The IOP was controlled without medication in 30 eyes (40.5%) in the ACG group and 13 (19.1%) in the OAG group; the difference between groups was significant (P =.0055).Cataract surgery substantially reduced IOP and the number of medications required for IOP control in glaucomatous eyes. Specifically, cataract extraction normalized the IOP in most eyes with ACG.

Purpose To evaluate irregular astigmatism after silicone, acrylic, and poly(methyl methacrylate) (PMMA) intraocular lens (IOL) implantation using Fourier analysis of videokeratography data. Methods Two hundred forty eyes having phacoemulsification and IOL implantation were randomly assigned to 1 of 3 groups: 3.5 mm incision and silicone IOL, 4.1 mm incision and acrylic IOL, or 6.5 mm incision and PMMA IOL. All eyes had videokeratographic examinations preoperatively and 2, 4, and 10 days and 1 and 3 months postoperatively. The dioptric data of the central cornea were decomposed into spherical equivalent, regular astigmatism, and irregular astigmatism (decentration and higher-order irregularity) components using Fourier analysis. Results Regular astigmatism in the PMMA group was greater than in the silicone and acrylic groups. Decentration in all 3 groups increased significantly postoperatively but virtually returned to preoperative levels by 10 days. No significant difference was observed among the 3 groups. Higher-order irregularity significantly increased after surgery in all 3 groups. The higher-order irregularity in the PMMA group persisted for up to 1 month, while that in the silicone and acrylic groups returned to preoperative levels by 4 days, resulting in significant differences between these groups 10 days and 1 month after IOL implantation. Conclusion Irregular astigmatism, both the decentration and higher-order irregularity components, increased significantly after 3 types of scleral tunnel incisions for silicone, acrylic, or PMMA IOL implantation but returned to preoperative levels soon after surgery except for the higher order irregularity after PMMA IOL implantation.

Purpose To evaluate the extent of intraocular lens (IOL) tilt and decentration after implantation in eyes with glaucoma. Setting Hayashi Eye Hospital, Fukuoka, Japan. Methods Fifty-two eyes of 52 patients with glaucoma and 52 control eyes from 52 age-matched patients had phacoemulsification with IOL implantation. Twenty-nine eyes had closed-angle glaucoma (CAG), and the other 23 eyes had open-angle glaucoma (OAG). The extent of IOL tilt and decentration was measured using Scheimpflug videophotography 1 week and 1, 3, 6, 9, and 12 months postoperatively. Results The mean tilt angle in the glaucoma group was significantly greater than in the control group throughout the follow-up. Mean decentration length was also greater in the glaucoma than in the control group, but the difference was not significant. The incidence of eyes showing a marked tilt (greater than 5 degrees) or decentration (greater than 0.5 mm) was higher in the glaucoma than in the control group. The mean tilt angle and the incidence of eyes showing a marked tilt or decentration in the CAG group were significantly greater than in the control group. Conclusion Intraocular lens tilt was more extensive in the eyes with glaucoma, especially in those with CAG, than in normal eyes. Decentration was also greater in the glaucoma groups than in the control group, although the differences were not significant.

Purpose: To examine the intraobserver and interobserver reproducibility in measuring posterior capsule opacification (POO) using a Scheimpflug videophotography system. Setting: Hayashi Eye Hospital, Fukuoka, Japan. Method: Twenty eyes with PCO and 10 without PCO had 5 independent measurements 15 minutes apart performed by 3 observers. The eyes without PCO were selected within 1 week after surgery. Intraobserver and interobserver reproducibility were evaluated using the coefficient of variation and intraclass correlation coefficient. Results: The median coefficients of variation of the 3 observers were 11.6%, 11.3%, and 9.8%, respectively, which inditMes an acceptably low observer variability. The intraobserver correlation coefficients of the 3 observers were all more than 0.95, and the interobserver correlation coefficient was 0.976, which indicates excellent reproducibility. Conclusion: The results of intraobserver and interobserver reproducibility of PCO measurement using the Scheimpflug videophotography system indicate it would be effective for use in research and clinical management of PCO.

Purpose: To compare the extent of area reduction in the anterior capsule opening after continuous curvilinear capsulorhexis in the eyes of diabetes mellitus (DM) patients with that in the eyes of patients without DM. Setting: Hayashi Eye Hospitai, Fukuoka, Japan. Methods: Ninety-one eyes of 91 DM patients and 91 age-matched eyes of patients without DM (control group) having intraocular lens (IOL) implantation were recruited for this prospective study The DM group comprised 36 eyes with diabetic retinopathy (DR) and 55 without retinopathy (NDR). The anterior capsule opening area was quantitated using Scheimpflug photography 1 week and 1, 3, and 6 months postoperatively Results: There was no statistically significant difference in mean anterior capsule opening area between the DM and control groups at 1 week or, 1 month postoperatively, The area was significantly, smaller in the DM group at 3 ( P = .0221) and 6 ( P = .0075) months. The percentage area reduction was also greater i6 the DM group than in the control group. The area in the DR group was significantly smaller than in the control group at 3 ( P = .0392) and 6 ( P = .0080) months. The percentage reduction in the DR group was larger than in the NDR or control group. Conclusions: After IOL implantation, contraction of the anterior capsule opening area was more extensive in eyes of DM patients than in those of patients without DM, especially in the case of DR.

Purpose: To evaluate the usefulness of low-vacuum, low-voltage scanning electron microscopy (LVSEM) in examining the surfaces of intraocular lenses (IOLs) without preparation. Setting: In vitro laboratory experiment. Methods: Six commercially available IOLs made of poly(methyl methacrylate) (PMMA) and one explanted PMMA IOL were evaluated with LVSEM without sputter coating. Sham surgical maneuvers were performed on some IOLs and the surface changes observed. Results: Smooth surfaces of IOL optics and haptics, relatively sharp edges of optic holes, and irregularities at the optic/haptic junction were clearly observed. Crystalline deposits were seen on the surfaces after the IOLs were dipped and dried in saline solution. Scratches and marks were observed after they were grasped with a forceps. Conclusions: Low-vacuum, low-voltage scanning electron microscopy is a timesaving procedure that can be used by inexperienced investigators. The resolution under relatively low magnification appeared to be satisfactory for evaluating the IOL surface.

Purpose: To clarify the extent of corneal endothelial injury from silicone intraocular lens (IOL) implantation in small incision cataract surgery. Methods: Two hundred forty eyes that had phacoemulsification surgery were divided into four groups: Group A comprised 70 eyes that received a conventional silicone IOL; Group B, 63 eyes that received a higher refractive index silicone IOL; Group C, 71 eyes that received a poly(methyl methacrylate) (PMMA) IOL; Group D, 36 eyes that had phacoemulsification without an IOL. Cell density of the corneal endothelium in all eyes was examined by specular microscopy preoperatively and 3 months postoperatively, and the percentage of endothelial cell loss was determined. The differences in endothelial cell loss between the four groups were statistically compared using the Kruskal-Wallis test. Results: Percentages of endothelial cell loss were 4.5 ± 5.1 % in Group A, 4.3 ± 5.3% in Group B, 6.3 ± 5.4% in Group C, and 4.3 ± 4.9% in Group D. No statistically significant difference was observed among these four groups, although the percentage of cell loss in Group C was slightly larger than that in the other groups. Conclusion: The implantation of silicone IOLs and PMMA IOLs causes minimal corneal endothelial cell loss in contemporary small incision surgery.

Purpose: To examine the incidence of capsular capture in silicone IOL implantation and determine its effect on visual acuity. Setting: Hayashi Eye Hospital, Fukuoka, Japan. Methods: This study comprised 144 eyes that had phacoemulsification with threepiece silicone intraocular lens (IOL) implantation that were evaluated about 3 months after surgery. The examination included the status of the haptic and optic placement, extent of posterior capsular opacification (PCO), and the best corrected visual acuity. Results: One hundred twenty-eight eyes had an in-in haptic placement, 15 had in-out placement, and 1 had out-out placement. Capsular capture occurred in 30 eyes (20.8%). The extent of PCO in eyes with capsular capture was greater than in those without capture. The best corrected visual acuity in eyes with capsular capture was worse than in those without capture. In addition, eyes with in-out and out-out haptic placement had significantly worse PCO and visual impairment than the eyes with in-in placement. Conclusion: There was a high incidence of capsular capture after silicone IOL implantation. This complication, along with the undesirable placement of the haptics, led to PCO and thus visual impairment.

Background The presence of fibronectin has been shown in preretinal membranes from eyes with proliferative vitreoretinopathy and proliferative diabetic retinopathy. It is not clear, however, which type of fibronectin (plasma or cellular) is present in preretinal membranes. Methods A human cellular fibronectin antibody was used to immunohistochemically determine if cellular fibronectin only demonstrates presence or association with proliferation of preretinal membranes. Results The results revealed a diffuse distribution of cellular fibronectin within membranes extracted from proliferative vitreoretinopathy and proliferative diabetic retinopathy patients, and a localized distribution of neovascular vessels in proliferative diabetic retinopathy membranes. Conclusion Cellular fibronectin produced locally in preretinal membranes may contribute a local, cell-mediated process to cell proliferation or migration and the expression of cellular fibronectin by the cellular constituents of preretinal membranes is unique to this pathologic situation like proliferative diabetic retinopathy and proliferative vitreoretinopathy.

Vascular endothelial growth factor (VEGF) has been identified as a possible mediator of retinal neovascularisation (NV), but it is not certain if VEGF alone is sufficient to cause retinal NV. We sought to investigate this issue by implanting ethylene-vinyl acetate copolymer pellets that slowly release VEGF into the vitreous cavity of rabbits and primates. Eyes were examined by indirect ophthalmoscopy, fundus photography, and fluorescein angiography and then animals were killed at various time points and immunocytochemical and ultrastructural evaluations were carried out. Seven days after implantation of a pellet containing 30 micrograms of human recombinant VEGF into the vitreous cavity of rabbits, retinal blood vessels became dilated and tortuous, and between days 14 and 21, retinal NV was noted in all eyes. Fluorescein angiography showed profuse leakage of dye from the anomalous vessels. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) showed positively staining nuclei in many of the endothelial cells of new blood vessels on the surface of the retina. Six eyes implanted with control pellets containing vehicle and two eyes implanted with pellets containing 30 micrograms of human serum albumin alone showed no retinal vascular abnormalities. Implantation of pellets containing 100 micrograms of VEGF into the vitreous cavity of primates resulted in iris NV and retinal vascular dilation and tortuosity very much like that seen in humans with ischemic retinopathies. Immunohistochemical staining for serum albumin showed widespread severe breakdown of the blood-retinal barrier (BRB). Histology showed dilated thin-walled retinal vessels, but unequivocal retinal NV could not be identified and staining for PCNA was negative. These findings indicate that sustained intravitreal release of VEGF causes widespread retinal vascular dilation and breakdown of the BRB. Retinal NV seems to require persistent high levels of VEGF at the retinal surface and can be achieved in rabbits providing a potentially useful model of retinal NV, but is difficult to achieve in primates. The extensive VEGF-induced disruption of the blood-retinal barrier suggests that VEGF antagonists may provide a new therapy for patients with ischemic retinopathies and macular edema.

Purpose: To investigate the stereoacuity in patients who have had implantation of a monofocal intraocular lens (IOL) in each eye and to identify the principal risk factors for impaired stereoacuity. Setting: Hayashi Eye Hospital, Fukuoka, Japan. Methods: One hundred patients scheduled for bilateral phacoemulsification and monofocal IOL implantation were recruited. Near stereoacuity was measured approximately 2 weeks after surgery using the Titmus test. Various parameters that may be associated with stereoacuity in pseudophakic patients were measured using the New Aniseikonia Test (Handaya Corp.). Parameters included age, visual acuity, spherical equivalent, astigmatism, axial length, pupil diameters, IOL decentration and tilt, and aniseikonia. Stepwise multiple regression analysis was performed to identify independent predictors of impaired stereoacuity. Results: The mean stereoacuity was 57.1 seconds of arc ± 36.9 (SD); 90 patients (90%) had a good stereoacuity (ie, 100 seconds of arc or better). Simple regression analysis showed that a larger difference in spherical equivalent between fellow eyes and older age was significantly associated with poor stereoacuity. The best final model ( R 2 = 0.375) in the multiple regression analysis identified a greater difference in spherical equivalent to be the most significant predictor of impaired stereoacuity, followed by older age and a larger pupil diameter. Conclusions: Ninety percent of patients with bilateral pseudophakia had useful stereoacuity. The main risk factor for poor stereoacuity was a greater difference in the spherical equivalent between the eyes, followed by older age and a larger pupil diameter. These results indicate the need for an accurate preoperative IOL power calculation.

We studied the aging changes in corneal shape using corneal topography. Normal corneas (1,343) from 734 volunteers were examined by Topographic Modeling System-1 (TMS-1). All eyes were divided into eight groups according to age: (a)20 years of age and, respectively, in their (b) 20s, (c) 30s, (d) 40s, (e) 50s, (f) 60s, (g) 70s, and (h)80. The age-related changes in the averaged map of TMS-1 were evaluated. The findings noted in this map were confirmed by analyzing the data as well as by assessing the average-of-difference map. The averaged maps of subjects from20 years of age to the 40s showed a vertical bow-tie-rule astigmatism. In the maps of subjects in their 50s and 60s, the central steep area gradually extended horizontally until it became a round configuration. The maps of subjects in their 70s and80 revealed a horizontal oval-shaped steep area, suggesting against-the-rule astigmatism. The average-of-difference map demonstrated a marked corneal steepening at the horizontal meridians. In the data analysis of the averaged map, the mean refractive powers of the cornea increased with age. Moreover, the refractive powers in the horizontal meridians exceeded those in the vertical meridians when they were in the 60s, which verified against-the-rule astigmatic shift. In conclusion, normal cornea becomes steeper and shifts from with-the-rule to against-the-rule astigmatism with age.