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Choroidal neovascularization (CNV) is well recognized as a complication of laser photocoagulation for central serous chorioretinopathy (CSC). However, little is known about its management.Two patients who developed iatrogenic CNV after laser photocoagulation for CSC.A single intravitreal bevacizumab (IVB) injection was given in both cases. The best-corrected visual acuity (BCVA) of 1 of the patients improved from 0.3 to 0.5 on the following day and to 1.2 three months after the IVB, and the BCVA of the other patient improved from 0.5 to 1.0 two weeks after the IVB. In both cases, the CNV became inactive 1 month after IVB on fluorescein angiography and remained stable for over 1 year.IVB was beneficial for iatrogenic CNV that developed after laser photocoagulation for CSC.

To investigate the utility values associated with visual loss due to age-related macular degeneration (AMD) in Japanese patients.Utility values in 48 Japanese patients with bilateral exudative AMD were measured using the time trade-off and standard gamble methods.The time trade-off method utility values correlated with the best-corrected visual acuity (BCVA) in the better-seeing eye. The estimated utility values according to the BCVA in the better-seeing eye were 0.534 (BCVA, 0.01-0.15), 0.574 (0.2-0.3), 0.613 (0.4-0.6), and 0.653 (0.7-1.0). The utility values obtained by the standard gamble method were not significantly correlated with BCVA in the better-seeing eye.The present results concur with those of previous studies showing that AMD causes a substantial decrease in patient utility values. The utility values obtained in the current study provide important information for use in cost-utility analysis of interventions for Japanese AMD patients.

Objective To compare background factors of the 2 most dominant subtypes of exudative age-related macular degeneration (AMD) in the Japanese population: typical AMD and polypoidal choroidal vasculopathy (PCV). Design Cross-sectional comparison. Participants Consecutive patients with typical AMD (n = 89) and PCV (n = 138) for the primary survey. For the secondary survey, the number of participants was extended to include 148 typical AMD and 170 PCV patients. All the patients included in the present study had been followed up at The University of Tokyo Hospital outpatient macular clinic. Methods Background data on gender; age; body mass index; smoking; alcohol consumption; and histories of hypertension, diabetes mellitus (DM), hyperlipidemia, ischemic heart disease, stroke, intensive light exposure, central serous chorioretinopathy (CSC), cataract surgery, glaucoma, and steroid use were obtained mainly through interview. The interviewers were masked to the subtype diagnosis of AMD. Univariate and multivariate logistic regression analyses were performed to identify differences in the background factors between typical AMD and PCV. In the secondary survey, the association of a history of CSC and PCV was confirmed further, and funduscopic findings of an atrophic retinal pigment epithelial (RPE) tract and focal photocoagulation scars that could indicate a history of CSC were investigated. Main Outcome Measures Frequency and mean of background factors in patients with typical AMD or PCV. Results The 2 groups showed similar backgrounds with the exception of their histories of DM and CSC. A history of DM was more frequent in typical AMD (24.7% vs. 13.0% in the primary survey; P = 0.027), whereas a history of CSC was more prevalent in PCV (3.4% vs. 14.7% in the secondary survey; P = 0.0005). Funduscopic findings of an atrophic RPE tract or focal photocoagulation scars were found more frequently in PCV (0.7% vs. 7.6%; P = 0.002). Conclusions Background factors of typical AMD and PCV are similar but not identical. A history of DM and CSC are more frequent in typical AMD and PCV, respectively. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To investigate the role played by receptors of vascular endothelial growth factors, Flt-1 and KDR/Flk-1, on an experimental model of choroidal neovascularization (CNV). The vascular endothelial growth factor-A (VEGF-A) receptor-specific tyrosine kinase inhibitor SU5416 was administered to a laser-induced mouse model of CNV. The formation of CNV and the degree of vascular permeability in Flt-1 tyrosine kinase domain-deficient mice were also investigated. SU5416 reduced vascularity and vascular endothelial cell proliferation, and promoted endothelial cell apoptosis within CNV. Furthermore, the formation of CNV and the degree of vascular permeability were significantly reduced in Flt-1 tyrosine kinase domain-deficient mice, and this effect was enhanced by the administration of SU5416. Both Flt-1 and KDR/Flk-1 have a significant role in CNV formation. Suppression of apoptosis may be involved in the process.

PURPOSE: To estimate the risk factors of AMD in an elderly Japanese population from a suburban area north of metropolitan Tokyo. METHODS: The Hatoyama Cohort Study was launched in 2010, and 742 persons participated in the baseline study. Among these participants, 596 persons who attended the 2-year follow-up examinations in 2012 were evaluated, and the presence of early and late AMD was determined via grading of their fundus photographs. Based on the cohorts' data, logistic regression analyses were performed to identify the risk factors for AMD. The possible risk factors that we examined were age, sex, medical history of systemic disorders, smoking, inflammatory markers at baseline, and the complement factor H (CFH) I62V and age-related maculopathy susceptibility 2 (ARMS2) A69S variants. RESULTS: We assessed 480 participants (40.0% women) who had gradable fundus photographs. The prevalence of early AMD was 37.9% and the prevalence of late AMD was 0.6%. Mantel-Haenszel analysis revealed that the CFH I62V and ARMS2 A69S variants were significantly associated with the prevalence of AMD (P = 0.029 and 0.025, respectively). CONCLUSIONS: The CFH I62V and ARMS2 A69S variants were significantly associated with the prevalence of AMD. (www.umin.ac.jp/ctr number, UMIN000014520.).

To investigate the expression of proangiogenic and antiangiogenic factors, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in retinal pigment epithelial (RPE) cells after photodynamic therapy (PDT), especially focusing on their change in the presence of triamcinolone acetonide.Firstly, the cellular uptake of verteporfin was quantified after confluent ARPE-19 (human retinal pigment epithelial) cells were exposed to 5 microg/ml verteporfin combined with or without 1 microg/ml triamcinolone acetonide for 1 h. Secondly, ARPE-19 cells exposed to various doses of verteporfin were irradiated with 120 mJ/cm(2) light. After incubation with or without 1 microg/ml triamcinolone acetonide for 2 days, cell viability and expressions of VEGF and PEDF were assessed.Cellular uptake of verteporfin was not significantly changed by the presence of 1 microg/ml triamcinolone acetonide. In addition, 0.01-0.1 microg/ml of verteporfin showed a dose-dependent toxicity on the ARPE-19 cells 2 days after the light exposure. The presence of verteporfin at a concentration of 0.01 microg/ml did not affect the cell viability but significantly increased VEGF (p0.001) and reduced PEDF (p = 0.03) expression. Administration of triamcinolone acetonide significantly suppressed both this increase in VEGF (p0.001) and decrease in PEDF (p = 0.001).VEGF was increased and PEDF reduced in cultured RPE cells shortly after PDT even at a sublethal dose. Triamcinolone acetonide suppressed this proangiogenic response.

To determine the percentage of Japanese patients with age-related macular degeneration (AMD) who are eligible for photodynamic therapy (PDT) with verteporfin who have either polypoidal choroidal vasculopathy (PCV) or choroidal neovascularization (CNV) with retinochoroidal anastomosis (RCA).The medical charts of 82 consecutive patients (83 eyes) with subfoveal CNV due to AMD were reviewed. Initially, we determined which of these eyes were eligible for PDT by using the criteria reported by two large randomized control studies, that is, the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study and the Verteporfin in Photodynamic Therapy (VIP) study. Among the PDT-eligible patients, the percentage of eyes with PCV or CNV with RCA was determined by indocyanine green angiography (ICGA).In total, 36 eyes (43%) of the 83 eyes were PDT-eligible; 17 (20%) based on the TAP study criteria, and 19 (23%) based on the VIP study criteria. Among these PDT-eligible eyes, ICGA revealed that 12 (33%) had PCV and 2 (6%) had CNV with RCA.With ICGA, PCV or CNV with RCA were recognized in a substantial proportion of cases eligible for PDT based on the two clinical studies. Considering that the treatment efficacy of PDT for PCV or RCA has not been established, detection of PCV or RCA prior to PDT with ICGA is highly recommended.

We investigated bottom-up electroless copper plating with addition of mercapto alkyl carboxylic acid (MACA) such as 3-mercapto-propionic acid (3-MPA), 11-mercapto-undecanoic acid (11-MUA), and 16-mercapto-hexadecanoic acid (16-MHA). The inhibition of copper plating deposition on the plane surface was observed with an addition of MACAs, and bottom-up fill was confirmed for MACAs with alkyl chain numbers of 3, 11, and 16. The bottom-up fill tendency was enhanced with increasing Alkyl chain number. This result strongly suggests that diffusion coefficient of inhibitor molecule plays an important role for bottom-up fill mechanisms, because MACA with longer alkyl chain has smaller diffusion coefficient than that with shorter alkyl chain.

To report two Japanese sibling cases with pigmented paravenous retinochoroidal atrophy (PPRCA) with asymmetrical manifestation.A 33-year-old female and her 31-year-old brother were referred to our hospital. Funduscopic examination, angiography, and electroretinogram were performed.Both had retinal pigment epithelium atrophy with pigmentation along the retinal veins, which was consistent with PPRCA. The younger brother was more severely affected than his sister. Surprisingly, the extent and degree of the affected region was clearly different between both eyes of each patient.These findings have rarely been reported previously, and these cases stress the importance of considering gender, familial involvement, and variable manifestations of the disease in clinical care of PPRCA.

To report the therapeutic outcome of transpupillary thermotherapy (TTT) for subfoveal choroidal neovascularizarion (CNV) in brown retina using a diode-laser with the setting of lower energy level compared to the previous studies on light-pigmented Caucasian patients.A total of 19 subfoveal CNVs in 18 patients were treated with TTT. The power of diode-laser was set 160 mW for 1.2 mm beam, 270 mW for 2.0 mm beam, and 400 mW for 3.0 mm beam, and the laser was delivered for 1 min through a slit-lamp mounted-delivery system. Patients were followed up for a mean of 8.8 months (4-12 months). Visual acuity and the fundus change as judged by funduscopic examination and simultaneous fluorescein and indocyanine green angiography were evaluated. Visual acuity was measured by a Japanese standard Landolt visual acuity chart and converted to logarithm of the minimal angle resolution (log MAR) visual acuity for statistical analysis. Improvement or decline in vision was defined as change of more than 0.2 in log MAR visual acuity.In eyes with minimally classic or occult only CNV, visual acuity improved in two eyes (18%) stabilized in seven eyes (64%) and worsened in two eyes (18%). In eyes with predominantly classic CNV, visual acuity improved in two eyes (25%), stabilized in four eyes (50%) and worsened in two eyes (25%). In all, 15 (84%) eyes of all studied subjects had improvement in exudation. Two (11%) and one (5%) eye(s) were noted to have a significant post-treatment haemorrhage and retinal pigment epithelial tear, respectively.In patients with brown retinal colour, the treatment outcome of TTT was comparable to that of light-pigmented Caucasian patients with approximately half the laser power energy. Further randomized control studies are warranted.

To describe detailed clinical features of eyes with focal choroidal excavation.Twenty-one eyes of 17 patients with focal choroidal excavation were retrospectively studied. All eyes underwent thorough examination including funduscopy, visual field analysis, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and B-scan ultrasonography.Patients' age ranged between 25 years and 70 years. Four patients (24%) were affected bilaterally. Spherical equivalent of refractive error ranged from 0.5 diopters to -10.0 diopters (D). Funduscopic examination showed hypopigmentation (n = 12) and yellowish plaquelike appearances (n = 2). Indocyanine green angiography showed not only filling defects at the excavation (n = 16) but also choroidal vascular hyperpermeability (n = 7) and punctate hyperfluorescent spots (n = 7). Cicatrized subretinal neovascularization was seen in three eyes. The mean follow-up period was 37 months (6-66 months). There was no change in the appearance of excavation. Central serous chorioretinopathy (n = 1) and choroidal neovascularization (n = 1) developed during follow-up.Background factors and ophthalmic findings are similar to those that have been reported previously, including relatively stable findings even after a long observation and the occurrence of central serous chorioretinopathy and choroidal neovascularization. Bilateral cases are not rare in the current cohort, and choroidal vascular hyperpermeability is frequently observed in indocyanine green angiography, suggesting there were choroidal hemodynamic changes around the excavation.

Purpose To investigate the association in Japanese between posterior vitreous attachment and the pathologies of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV), 2 major forms of exudative AMD. Design Retrospective observational case series. Participants A total of 378 eyes from 302 subjects (132 with typical AMD, 126 with PCV, 120 controls) from the University of Tokyo Hospital. Methods Posterior vitreous detachment (PVD) and vitreomacular adhesion (VMA) were investigated by B-mode ultrasonography and spectral-domain optical coherence tomography (SD-OCT), respectively. The greatest linear dimension (GLD) of initial photodynamic therapy (PDT) in a subset of the patients (n=92) receiving PDT was also investigated. Main Outcome Measures Number of eyes with complete PVD and with VMA. The GLD of initial PDT. Results In typical AMD eyes, the frequency of complete PVD was significantly lower (63 [56.8%] of 111 eyes) than in the controls (52 [70.3%] of 74 eyes, risk ratio [RR] 0.76, P =0.021) and the frequency of VMA tended to be higher (14/115 [12.2%] in typical AMD eyes and 6/86 [7.0%] in the controls, RR 2.15, P =0.099). The frequency of complete PVD [77 [63.1%] of the 122 eyes] and VMA (9/108 [8.3%]) in PCV eyes was the same as the controls (RR 0.91, P =0.415 and RR 1.29, P =0.615). In patients with unilateral exudative AMD, the frequency of complete PVD was lower in typical AMD eyes than in fellow eyes (odds ratio [OR] 0.111, P =0.026) and VMA was observed in 7 (17.5%) and 3 (7.5%) typical AMD and fellow eyes, respectively (OR 2.33, P =0.34), whereas in PCV eyes, the frequency of complete PVD was higher (OR 8.00, P =0.045) and the frequency of VMA was the same as in the fellow eyes (OR 0.80, P =1.00). The GLD of the eyes without complete PVD or with VMA was significantly larger than that in the eyes with complete PVD in typical AMD eyes ( P =0.042) and the same as that in the eyes with complete PVD in PCV eyes ( P =0.67). Conclusions There is an association between posterior vitreous attachment and typical AMD. However, this association is not evident in PCV. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To select a novel orally administered VEGFR-2 (KDR/flk-1) specific tyrosine kinase inhibitor in a murine model of choroidal neovascularization (CNV).From a compound library, potent VEGFR2 inhibitors were selected by VEGF-induced phosphorylation of VEGFR-2 and RAF kinases and the proliferation analysis by HUVEC cultures and in vitro tube formation assay. CNV was induced in C57/BL6 mice using diode laser photocoagulation. The antiangiogenic effect of selected compounds was assessed by angiographic examination, in which extent of fluorescein leakage was scored and histological analysis, allowing for measurement of CNV membrane under light microscope. In addition, C57/BL6 mice were treated with daily oral administration of selected compounds for 14 days and body weights were measured.Six compounds that potently inhibited VEGFR-2 were selected for further investigation. Selected compounds-treated conditions showed a dose-dependent inhibition of phosphorylation of VEGFR-2 tyrosine kinase with an IC50 of 0.0022 to 0.098 microm. Selected compounds did not inhibit the HCT116 proliferation but did demonstrate a strong inhibition effect for VEGFR-2 dependant HUVEC (IC50=0.0018 to 0.058 microm). Selected compounds treatment also resulted in a dose-dependent attenuation of in vitro tube formation. In the murine CNV model, #0451 is the most effective compound. The intensity of fluorescein leakage was significantly lower in doses of 12.5, 25, 50, and 100 mg/kg #0451-treated eyes compared to controls. Histologically, CNV membrane volumes were significantly reduced in #0451-treated eyes in a dose-dependent manner. At therapeutic doses of 100 mg/kg or less, there was no significant weight loss between the treated and untreated groups.Oral administration of #0451, a novel VEGFR-2 (KDR/flk-1)-specific tyrosine kinase inhibitor, demonstrates anti-angiogenic effects in our murine model of CNV. #0451 may be useful to treat the choroidal neovascularization associated with AMD.

To evaluate the effect of posterior juxtascleral triamcinolone acetonide (TA) injection combined with photodynamic therapy with verteporfin (PDT) for treating exudative age-related macular degeneration (AMD), the best-corrected visual acuity (BCVA), the retreatment rates and the rate of choroidal hypoperfusion were investigated.A total of 67 eyes with subfoveal choroidal neovascularization (CNV) due to AMD were included. Forty-four eyes underwent PDT alone (PDT-alone group), and 23 eyes underwent PDT with the posterior juxtascleral injection of TA (PDT+TA group). Every 3 months after the PDT, the eyes were evaluated with regard to BCVA and requirement for retreatment by fluorescein angiography (FA) with the aid of optical coherence tomography (OCT). Choroiocapillaris hypoperfusion was assessed by indocyanine green angiography (ICGA) at 3 and 12 months. All patients completed a 1-year follow-up.At the baseline, there was no difference in lesion type, size or visual acuity between the two groups. At 1 year, the change in BCVA was -0.0811 logarithm of the minimum angle of resolution (LogMAR) in the PDT-alone group, compared with -0.0432 logMAR in the PDT+TA group. There was no significant difference in the change in BCVA between the two groups (P = 0.6910). The PDT+TA group required a lower mean number of treatments (1.64 compared with 2.34 [P = 0.0223]) and showed a higher rate of choriocapillaris occlusion at 3 months, but no significant difference at 1 year (P = 0.9243)Fewer retreatments were required in the TA+PDT group. There was no significant difference in the change in BCVA between the two groups. Adjacent TA may promote short-term choriocapillaris hypoperfusion.

To develop a new device for measuring reflected light during diode-laser irradiation in transpupillary thermotherapy (TTT) and to assess the correlation between fundus pigmentation, the measured intensity of reflected light, and the increase in fundus temperature.We developed a device to measure reflected light by modifying a slit-lamp-mounted 810-nm diode-laser delivery system used clinically for TTT. The diode laser was used to irradiate test charts with various degrees of reflectance in in vitro experiments, and the fundus of nonpigmented or pigmented rabbits in in vivo experiments; then, the intensity of the reflected light and the temperature increase at the target were measured. The retinal sections were also examined histologically.There was a significant negative correlation between the intensity of the reflected light and the temperature increase in the target that depended on the degree of reflectance of the charts or the pigmentation of the rabbit eyes. On histopathologic examination, the extent of the changes in the irradiated retina after TTT was clearly different between pigmented and nonpigmented rabbits.Correlations between fundus pigmentation, the intensity of reflected light during diode-laser irradiation, and the temperature increase in TTT were demonstrated in vitro and in vivo. Our results suggest that measurement of the intensity of reflected light should be helpful for modulating the laser power in TTT according to the degree of fundus pigmentation.

An oral, multitargeted receptor tyrosine kinase inhibitor, SU11248, inhibits vascular endothelial growth factor receptor 2 (VEG FR2, kinase domain receptor F1K1), platelet-derived growth factor receptor, stem cell factor receptor (Kit), and fetal liver tyrosine kinase 3. In this study, we administered SU11248 beyond the completion of an experimental choroidal neovascularization (CNV) model to determine whether CNV growth can be inhibited in vivo.C57B6J mice were treated with daily oral administration (40, 80, and 150 mg/kg) of SU11248 during 5 days after diode laser endophotocoagulation and subjected to angiographic examination and histological analysis.Intensity of fluorescein leakage from the experimental CNV decreased significantly compared to the control eyes. Histological study also revealed that the volume of CNV membrane was significantly reduced in the SU11248-treated eyes.Oral administration of this compound is potentially beneficial in treating CNV caused by age-related macular degeneration (AMD) and other causal diseases. Considering the tolerance the clinical studies for malignant tumors previously demonstrated, further studies to evaluate the clinical efficacy of the drug for AMD might be indicated.

To assess retinal function in a macular lesion with multifocal electroretinography (mfERG) after successful surgical removal of choroidal neovascularization (CNV). We prospectively studied 15 patients (15 eyes) who underwent surgical removal of subfoveal CNV secondary to age-related macular degeneration. Three and 6 months after surgery, retinal thickness in the parafoveal lesion and the size of the serous retinal detachment (SRD) were measured. The mfERG was also recorded, and the data from each of six concentric ring annuli were averaged. After surgery, the parafoveal retinal thickness significantly decreased compared with the preoperative value, and SRD was not recognized in any patient. The change in the amplitude of the P1-wave within 2° to 15° in diameter positively correlated with the decrease in the parafoveal retinal thickness. Additionally, amplitude within 8° to 24° in diameter positively correlated with the size of the preoperative SRD. mfERG is helpful to quantitatively and objectively assess the effect of the surgical removal of CNV on retinal function, not only in the fovea but also in the entire macular area. Jpn J Ophthalmol 2006;50:479–482 © Japanese Ophthalmological Society 2006

Recently, indocyanine green (ICG) has been used to stain and visualise the internal limiting membrane (ILM) during vitrectomy.1 Some case series showed that visual field defects on the nasal side can occur after the surgery through unknown cause.2,3 Here, we report a case in which nasal visual field defects occurred after ICG assisted ILM peeling for epiretinal membrane (ERM). Detailed examination revealed that the superior and inferior retinal nerve fibre is severely damaged in this case. A 60 year old woman who received ICG assisted ILM peeling for ERM in her right eye was referred to our hospital. The preoperative best corrected visual acuity (BCVA) was 20/60 in the right eye. According to the referring ophthalmologist, 25 mg of ICG (Diagnogreen; Daiichi Pharmaceuticals) was dissolved in 10 ml of distilled water, which was further diluted by a viscoelastic material (Healon; Pharmacia) to give 0.16% ICG solution. To stain ILM, ICG was injected into an air filled eye and the dye …

To investigate the in vivo effects of tissue factor pathway inhibitor 2 (TFPI-2), which stimulates proliferation of retinal pigment epithelial cells, but not the proliferation of fibroblast and vascular endothelial cells in vitro, on retinal degeneration using a sodium-iodate (SI)-induced model in rabbits and Royal Collage of Surgeons (RCS) rats.79 microg of recombinant TFPI-2 (rTFPI-2) or vehicle alone was injected intravitreously to 18 eyes of 12 pigmented rabbits a day after 20 mg/kg of SI was intravenously administered. Retinal function was assessed 4, 7, 14, and 21 days after the injection by analysing amplitudes of the c-wave of a bright flash electroretinogram. Additionally, 10 microg of rTFPI-2 or vehicle alone was injected intravitreously to 11 eyes of RCS rats at both 3 and 4 weeks old, then the retina was examined histologically at 5 weeks old.The rTFPI-2-treated eyes in rabbits showed a significantly less decrease in the relative amplitude of the c-wave than control eyes on days 4 and 7. The thickness of the outer nuclear layer was significantly thicker and the vacuole in the photoreceptor layer was less frequently observed in the rTFPI-2-treated RCS rats than the controls.Intravitreal injection of TFPI-2 rescues SI-induced retinal degeneration in rabbits and naturally occurring retinal degeneration in RCS rats at least partly. These results may suggest that this compound can be utilized in the treatment of retinal degeneration.

We succeeded in the bottom-up filling of Cu by electroless plating for the first time. Essential points of this technology are the use of an ultra-thin ICB-Pd catalytic layer and the addition of an adequate amount of sulfopropyl sulfonate inhibiter (SPS) to the electroless plating bath. The adhesion strength of the electroless-plated Cu was strong enough to endure against CMP processing, and a 100 nm diameter via hole with 800 nm depth was completely filled by electroless plating only.

PURPOSE. To investigate the effects of Iomerizine, a Ca 2+ antagonist, on the ocular tissue circulation in rabbits and on the circulation in the optic nerve head (ONH) and choroid in healthy volunteers. METHODS. Lomerizine (0.1 [n = 10] or 0.3 [n = 11] mg/kg) or vehicle solution (n = 11) was injected intravenously in urethane-anesthetized rabbits, and blood flow in the retina, choroid, and iris-ciliary. body was measured by the microsphere method and that in the ONH by the H 2 gas-clearance method (0.1 [n = 6] or 0.3 [n = 9] mg/kg or vehicle, n = 6). Oral 5 mg lomerizine or placebo was administered to volunteers (n = 8) in a crossover study, and in areas of the fovea and ONH, the normalized blur (NB), a quantitative index of blood velocity, was measured, together with blood pressure, heart rate, and intraocular pressure (IOP), before and 1.5, 3, 6, and 9 hours after administration. RESULTS. Blood flow in the rabbit retina increased significantly in the Iomerizine-treated group, but blood flow changed little in the choroid or iris-ciliary body. Blood flow in the rabbit ONH also showed a significant increase in the lomerizine-treated group. In human studies, the NB obtained from the ONH during the experimental period showed a small but significant increase in the lomerizine-treated group compared with the placebo-treated group, but no significant intergroup difference was detected in the NB obtained from the fovea or in blood pressure, heart rate, or IOP. CONCLUSIONS. Lomerizine increases blood velocity, and probably blood flow, in the ONH and retina in rabbits, and it also increases blood velocity in the ONH in healthy humans, without significantly altering blood pressure or heart rate.

Bucillamine is an antirheumatic drug with antiangiogenic properties that is currently used in clinical practice. Because bucillamine inhibits the production of VEGF, it is possible that this drug may inhibit choroidal neovascularization (CNV). Thus, the effect of bucillamine on the eyes of rats with experimental CNV was investigated in vivo by subconjunctival injection or oral intake.CNV was induced in rat eyes by diode laser photocoagulation. The intensity of fluorescein leakage from the photocoagulated lesions was studied 7 and 14 days after photocoagulation. The areas of CNV lesions were measured histologically and studied immunohistochemically at days 4, 7, and 14. In addition, the concentration of the drug in ocular tissue and blood was measured by high-performance liquid chromatography-tandem mass spectrometry after the drug was delivered orally or subconjunctivally.After subconjunctival injection, fluorescein leakage from the CNV lesions decreased significantly compared with the control eyes throughout the study period. Histologic and immunohistochemical analyses 4, 7, and 14 days after photocoagulation demonstrated that the average size of the CNV lesions was reduced in the bucillamine-treated eyes compared with the control eyes. Subconjunctival injection maximized the ocular drug concentration while minimizing the blood concentration of the drug compared with oral intake.Subconjunctival injection of bucillamine significantly reduced the leakage and size of experimental CNV. These results suggest that bucillamine may be beneficial in treating CNV and that further studies can be considered to evaluate this possibility.

PurposeIt has not been clarified whether early age-related macular degeneration (AMD) is associated with cone photoreceptor distribution. We used adaptive optics fundus camera to examine cone photoreceptors in the macular area of aged patients and quantitatively analyzed its relationship between the presence of early AMD and cone distribution.MethodsSixty cases aged 50 or older were studied. The eyes were examined with funduscopy and spectral-domain optical coherence tomography to exclude the eyes with any abnormalities at two sites of measurement, 2° superior and 5° temporal to the fovea. High-resolution retinal images with cone photoreceptor mosaic were obtained with adaptive optics fundus camera (rtx1, Imagine Eyes, France). After adjusting for axial length, cone packing density was calculated and the relationship with age, axial length, or severity of early AMD based on the age-related eye disease study (AREDS) classification was analyzed.ResultsPatient's age ranged from 50 to 77, and axial length from 21.7 to 27.5 mm. Mean density in metric units and that in angular units were 24,900 cells/mm2, 2,170 cells/deg2 at 2° superior, and 18,500 cells/mm2, 1,570 cels/deg2 at 5° temporal, respectively. Axial length was significantly correlated with the density calculated in metric units, but not with that in angular units. Age was significantly correlated with the density both in metric and angular units at 2° superior. There was no significant difference in the density in metric and angular units between the eyes with AREDS category one and those with categories two or three.ConclusionAxial length and age were significantly correlated with parafoveal cone photoreceptor distribution. The results do not support that early AMD might influence cone photoreceptor density in the area without drusen or pigment abnormalities.

Kayo Kure, Ryo Obata, Yuji Inoue, Aya Iriyama, Yasuo YanagiDepartment of Ophthalmology, University of Tokyo School of Medicine, Tokyo, JapanAbstract: Some patients with acute zonal occult outer retinopathy (AZOOR) show symptomatic acute visual impairment in one eye only, but electrophysiological abnormalities in both eyes. A 46-year-old female who had noticed paracentral scotoma of her right eye six months previously was referred to our hospital. At initial examination, her best-corrected visual acuity was 0.7 in the right eye and 1.2 in the left. Whereas the full-field rod electroretinogram (ERG) was normal in both eyes, the cone response was nonrecordable in the right eye and showed a significant decrease in amplitude in the left eye. The 30 Hz flicker ERG showed similar results. Multifocal ERG was nonrecordable in the right eye and showed a residual response in only the central part of the left. Fourteen months after the first visit, the patient presented complaining of acute visual acuity loss in the left eye. Visual acuity in her left eye had decreased to 0.01. The multifocal ERG was nonrecordable. Although the patient chose oral prednisolone therapy, only limited recovery was observed in the patient. Even if only the ERG shows changes and there are no other symptoms, ophthalmologists should continue observation in view of the possibility of an acute exacerbation.Keywords: acute zonal occult outer retinopathy, electroretinogram, scotoma

Purpose To investigate the development of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of Japanese patients with exudative AMD. Design Retrospective observational consecutive case series. Methods Two hundred and sixteen Japanese patients were enrolled in this study from the outpatient clinic of the University of Tokyo Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five patients had PCV. The average follow-up period was 33.6 and 25.1 months for typical AMD and PCV patients. Results The cumulative incidence of involvement in fellow eyes with overall exudative AMD, including both typical AMD and PCV, was 3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%, 7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, and five years, respectively. Before the development of exudative AMD, patients with typical AMD had a variety of funduscopic findings including retinal pigment epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED), and normal macula. PCV patients, on the other hand, had funduscopic findings of RPE atrophy. Inner choroidal vascular abnormality of vascular network and polypoidal formation was observed in several eyes before the clinical manifestation of exudative changes. Conclusions Typical AMD and PCV had similar probabilities of involving the fellow eye in unilaterally affected Japanese patients. RPE atrophy was a prevailing finding in fellow eyes of patients who developed PCV. In PCV, choroidal vascular network and polypoidal formation gradually grow before exudative changes.

Bottom-up fill of Cu in deep submicrometer via holes was achieved through electroless plating alone for the first time. We investigated the effect of addition of inhibitor molecules to electroless Cu plating solution, and found that sulfopropyl sulfonate ~SPS! was highly effective in promoting the bottom-up fill. The tendency for bottom-up filling was enhanced by shrinkage of the hole diameter. This suggests that the diffusion flux of SPS molecules to the bottom of holes was more suppressed for smaller holes.

The main purpose of this study is to investigate the characteristics of fundus autofluorescence (FAF) and area of soft drusen among the fellow eyes of unilateral typical age-related macular degeneration (typical AMD) and polypoidal choroidal vasculopathy (PCV) in Japanese patients.FAF images were obtained from the fellow eyes of unilateral typical AMD (n = 64), unilateral PCV (n = 95), unilateral retinal angiomatous proliferation (RAP) (n = 4) and 56 control subjects, then classified into normal, minimal-change, and abnormal patterns by two graders. Interobserver variability between two graders and intraobserver variability were assessed for FAF classifications, and cases with inconsistent decisions were finally classified by the third grader. Soft drusen were segmented and their total areas were compared between the fellow eyes of typical AMD and PCV. Area(s) with increased autofluorescence were segmented to assess the relationship with soft drusen area(s).Assessment for interobserver variability between two graders and intraobserver variability in one grader showed substantial agreement (κ = 0.70) and almost perfect agreement (κ = 0.85), respectively. In the final decision mediated by third grader, the proportions of eyes with either minimal-change FAF pattern or abnormal FAF pattern in the fellow eyes of both typical AMD (37 cases, 58 %) and PCV (47 cases, 49 %) were significantly higher than that of the control cases (15 cases, 27 %; p0.01). The proportion of abnormal FAF pattern in the fellow eyes of typical AMD (20 cases, 31 %) was higher than that of PCV (15 cases, 16 %; p0.05). Total soft drusen areas in the fellow eyes of typical AMD (0.369 ± 0.718 mm(2)) were larger than those of PCV (0.173 ± 0.408 mm(2); p0.05), and those in the eyes with abnormal FAF pattern were larger than those with minimal-change FAF pattern or normal FAF pattern (p0.01). Image analysis revealed a relationship between increased autofluorescence and soft drusen, especially in the cases with large total soft drusen areas.FAF characteristics were different between the fellow eyes of unilateral typical AMD and PCV in Japan, which might be due to the difference of total soft drusen areas between them.