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OBJECTIVES: To review the 3-year follow-up results of subthreshold micropulse yellow laser (SMYL) delivered by a short-duration multiple-session method for treatment of chronic central serous chorioretinopathy (CSC). METHODS: A total of 27 eyes from 27 patients with chronic CSC available for 3 years of follow-up were enrolled in this retrospective and interventional study. Patients were treated with 577-nm SMYL photocoagulation at a 15% duty cycle over multiple sessions, with low power ranging from 200 to 400 mW that was increased in 100 mW increments according to resolution of subretinal fluid at monthly follow-up. Laser titration was not performed. A treatment duration of 20 ms rather than the conventional duration (100–300 ms) was applied over the area of retinal pigment epithelium leakage and all areas of serous retinal detachment, including the fovea. RESULTS: The mean follow-up period was 3.7 ± 0.8 years (range, 3–6 years). A total of 22 out of 27 eyes (81.5%) including six cases of recurrence during the follow-up period exhibited complete resolution of subretinal detachment at final follow-up, whereas only five eyes (15.5%) had either a partial or null response to SMYL treatment. The baseline best-corrected visual acuity was 0.26 ± 0.24 logarithm of the minimum angle of resolution (logMAR), which was improved to 0.08 ± 0.15 logMAR at 1-year (p = 0.005) and 3-year (p = 0.01) follow-up. The central macular thickness at baseline was 389.6 ± 103.4 μm, which was changed to 197.2 ± 40.0 μm (p

Background: Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration that can cause permanent vision loss. The purpose of this paper was to report the one-year outcomes of fixed-dosing aflibercept therapy for the treatment of PCV.Methods: This was a prospective, single-arm, interventional case series study of 25 PCV patients; 12 pre-treated and 13 treatment-naïve patients. The patients were treated and monitored for 12 months. Each patient was administered with an aflibercept (2.0 mg) injection every month for the first three months (the loading phase), and thereafter, once every two months. At every follow-up visit, best-corrected visual acuity (BCVA) test, fundus examination, and optical coherence tomography for measuring the central subfield macular thickness (CSMT) were performed. Fluorescein and indocyanine green angiography were conducted at baseline and at 4 and 12 months.Results: After 12 months of aflibercept therapy, the mean BCVA of the patients significantly improved from 65.48 letters at baseline to 69.91 letters (p=0.001), and the CSMT significantly decreased from 406.92 um at baseline to 276.12 um (pConclusions: The fixed-dosing aflibercept regimen is effective for treating patients with PCV and is more effective in treatment-naïve patients than in pre-treated patients.

Purpose To assess the prevalence and progression of a stage 0 macular hole in the fellow eye of patients with an idiopathic full-thickness macular hole. Methods The fellow eyes of 189 patients who underwent idiopathic full-thickness macular hole surgery were examined by biomicroscopy and spectral domain-optical coherence tomography (SD-OCT). A subset of 21 fellow eyes with a stage 0 macular hole was observed. Changes in the macular hole were evaluated by biomicroscopy and SD-OCT for an average of 29 months. Results Among the 21 eyes, 15 showed no change in perifoveal vitreous detachment (71.4%). Two eyes (9.5%) developed complete vitreofoveal separation, and one of the two developed a separation after progression to stage 1A. Among 21 eyes, 5 (23.8%) developed above stage 1A, and one of the five progressed to stage 1B after five years, which was successfully treated with vitrectomy and gas tamponade. Conclusions Perifoveal vitreous detachment in the fellow eye on SD-OCT, defined as a stage 0 macular hole, occurred at an earlier phase than stage 1A macular holes and may progress to an advanced stage. Therefore, patients who undergo macular hole surgery and have a stage 0 macular hole or perifoveal vitreous detachment in the fellow eye should be followed closely.

To report the characteristics of polypoidal choroidal vasculopathy (PCV) based on optical coherence tomography angiography (OCTA) results. A retrospective, cross-sectional case series was conducted. Patients treated for PCV were evaluated with the OCTA system. The OCTA images of these patients were compared with those from indocyanine green angiography (ICGA). All eyes of consecutive patients with PCV were included. The mean age of the patients (five men and two women) was 67.86 ± 14.02 years. The mean number of anti-vascular endothelial growth factor injections was 10.43 ± 10.01. OCTA demonstrated branched vascular networks, which were detected by ICGA; however, polyps were not revealed consistently by OCTA. A total of 24 polyps were detected in seven eyes from seven patients by hyper-fluorescence on ICGA. However, only 12 polyps (50 %) were hyper-reflective on OCTA. PCV polyps were not detected as consistently by OCTA as by ICGA. This suggests that the polyps were detected differently by OCTA depending on blood flow in the polyp.

Purpose To report two cases of the treatment of refractory macular hole. Methods A retrospective case report of two patients who underwent vitrectomy for refractory macular hole. Results Two patients underwent pars plana vitrectomy for refractory macular holes. However, the surgical methods differed in the two patients depending on whether the internal limiting membrane (ILM) remained or not. In the patient with the remnant ILM, pars plana vitrectomy, inversion of the remaining ILM flap, air-fluid exchange, and 5% C3F8 gas tamponade were performed. In the other case with no remaining ILM, pars plana vitrectomy, inversion and release of the margin of the macula hole, combined with autologous platelet concentrate, air-fluid exchange, and 5% C3F8 gas tamponade were performed. In both cases, good anatomical outcomes were achieved postoperatively. Conclusion Depending on whether the ILM remains or not, one of these two new surgical procedures can be selected. This protocol can yield positive surgical results.

We present a case of ocular toxocariasis treated successfully with oral albendazole in combination with steroids. A 26-year-old male visited the authors' clinic with the chief complaint of flying flies in his right eye. The fundus photograph showed a whitish epiretinal scar, and the fluorescein angiography revealed a hypofluorescein lesion of the scar and late leakage at the margin. An elevated retinal surface and posterior acoustic shadowing of the scar were observed in the optical coherence tomography, and Toxocara IgG was positive. The patient was diagnosed with toxocariasis, and the condition was treated with albendazole (400 mg twice a day) for a month and oral triamcinolone (16 mg for 2 weeks, once a day, and then 8 mg for 1 week, once a day) from day 13 of the albendazole treatment. The lesions decreased after the treatment. Based on this study, oral albendazole combined with steroids can be a simple and effective regimen for treating ocular toxocariasis.

Purpose To investigate which spectral domain optical coherence tomography (SD-OCT) findings predict visual outcome after anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (NV-AMD). Methods We reviewed the medical records of patients with treatment-naïve NV-AMD who underwent three or more consecutive anti-VEGF injections. The patients were divided into three groups according to their changes of visual acuity (VA); improved (group I), static (group S), or worsened (group W). We assessed the incidences and values of all available SD-OCT findings of these groups, compared these findings between the three groups and compared the initial values with the post-treatment values. Results Better initial VA and longer external limiting membrane (ELM) length were associated with less change in VA after anti-VEGF treatment. The initial VA was mildly correlated with initial photoreceptor inner and outer segment junction (IS/OS) length and initial ELM length. The final VA was also mildly correlated with the final IS/OS length and the final ELM length. VA was significantly changed after anti-VEGF treatment in groups W and I. With regard to incidence, disruption of the IS/OS (IS/OS-D), disruption of the ELM (ELM-D) and ELM length differed significantly between the three groups, particularly ELM-D. The incidences of IS/OS-D and ELM-D in group I were significantly lower than those in groups S and W, and those in group S were also lower than those in group W. The ELM length in group I was significantly longer than it was in groups S and W, and the ELM length in group S was longer than that for group W. However, these three findings did not change after the anti-VEGF treatment. Conclusions Initial IS/OS-D, ELM length and particularly ELM-D can be useful predictors of the visual outcome after anti-VEGF treatment in NV-AMD patients.

Purpose: This pilot study aimed to evaluate the efficacy and safety of subthreshold micropulse yellow (577-nm) laser photocoagulation (SMYLP) in the treatment of diabetic macular edema (DME). Methods: We reviewed 14 eyes of 12 patients with DME who underwent SMYLP with a 15% duty cycle at an energy level immediately below that of the test burn. The laser exposure time was 20 ms and the spot diameter was 100 μm. Laser pulses were administered in a confluent, repetitive manner with a 3 × 3 pattern mode. Results: The mean follow-up time was 7.9 ± 1.6 months. The baseline-corrected visual acuity was 0.51 ± 0.42 logarithm of the minimum angle of resolution (logMAR), which was improved to 0.40 ± 0.35 logMAR (p = 0.025) at the final follow-up. The central macular thickness at baseline was 385.0 ± 111.0 μm; this value changed to 327.0 ± 87.7 μm ( p = 0.055) at the final follow-up. Conclusions: SMYLP showed short-term efficacy in the treatment of DME and did not result in retinal damage. However, prospective, comparative studies are needed to better evaluate the efficacy and safety of this treatment.

Purpose To evaluate the effectiveness of sulodexide for the treatment of hard exudates (HE) in non-proliferative diabetic retinopathy (NPDR). Methods This was a randomized, placebo-controlled, multicenter trial involving 130 patients (65 for each group) who had mild-to-moderate NPDR with macular HE. Participants were given a daily dose of either 50 mg sulodexide or a matching dose of placebo orally for 12 months. Main outcome measure was an improvement in HE defined as a decrease in severity by at least two grades on a 10-grade severity scale. This was evaluated by fundus photography over 12-month period. Results The sulodexide group showed significantly greater improvement in HE severity than that shown by the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P = 0.023) for the effect of treatment once adjustments were made for demographic, prognostic and disease confounders. Intention to treat and per-protocol analysis yielded similar results. Sulodexide’s safety was comparable to that of the placebo. Conclusions Oral sulodexide therapy over 12 months improved macular HE in patients with mild-to-moderate NPDR, without leading to detectable adverse events. The study protocol was registered on clinicaltrial.gov under identifier NCT01295775.

PURPOSE To investigate the clinical features of central retinal vein occlusion (CRVO) in relation to the presence of a prominent middle limiting membrane (p-MLM) sign on presenting optical coherence tomography, which may suggest macular ischemia and poor visual outcome. METHODS Fifty consecutive eyes with acute CRVO of

때죽나무(Styrax japonica) 수피 메탄올 추출물에서 단리된 화합물은 TLC 및 HPLC, coulmn chromatography 방법을 이용한 실리카겔 chromatography로 분리하였다. FAB-MS, NMR 분석을 통해 화합물의 구조를 구명한 결과 분자식은 $C_{27}H_{34}O_{11}Na$ 이고 화합물명은 styraxlignolide F로 판명되었다. 인간 정상 신장세포인 HEK293을 이용한 세포독성을 살펴본 결과, 각 추출물은 $1.0mg/m{\ell}$ 의 농도에서 15.2%의 낮은 세포독성을 나타내었다. AGS와 MCF-7 세포에서의 항암활성은 $CH_2Cl_2$ 가용부가 $1.0mg/m{\ell}$ 농도에서 60% 이상의 억제 활성을 나타내었다. Bcl-2 단백질 정량을 통한 항암 활성 측정 결과, $CH_2Cl_2$ 가용부가 다른 가용부 및 styraxligonlide F 보다 낮은 Bcl-2 발현량을 보였고, p53 발현량 측정에서도 $CH_2Cl_2$ 가용부가 가장 낮은 발현량을 보였다. 인간 폐암세포(A549)를 이용한 자가사멸 측정 실험에서 $CH_2Cl_2$ 가용부는 46.9%로 높은 사멸비율을 나타냈으며, 그다음으로 styraxlignolide F가 43.5%의 사멸비율을 나타내었다. $CH_2Cl_2$ 분획물은 단리물질(styraxlignolide F)보다 항암 활성 효과가 높게 나타났는데 여러 가지 물질이 시너지 효과를 나타낸 것으로 사료된다. 【A compound has been isolated from the methanol extract of Styrax japonica bark using conventional chromatographic methods including silica gel chromatography, TLC and HPLC. The molecular formula of Styraxlignolide F analyzed by spectrometric analyses using FAB-MS, NMR was found to be $C_{27}H_{34}O_{11}Na$ . The cytotoxicity of the styralignolide F was showed 15.2% in $1.0mg/m{\ell}$ on human kidney cell (HEK 293). As anticancer activity of $CH_2Cl_2$ fraction, over 60% of AGS and MCF-7 cells were inhibited in concentration of $1.0mg/m{\ell}$ . In the results of anticancer test using quantification of Bcl-2, $CH_2Cl_2$ fraction showed lower Bcl-2 and p53 expression than those of styraxlignolide F and other fractions. In apoptosis of human lung carcunoma cancer cell (A549), $CH_2Cl_2$ fraction showed the highest inhibition rate (46.9%) and styralignolide F was the next (43.5%). The $CH_2Cl_2$ fraction showed higher anti-cancer activities than isolated substance (styraxlignolide F), probably due to the crude extract showing synergic effects by other components.】

Purpose To introduce novel findings of polypoidal choroidal vasculopathy (PCV) via optical coherence tomography angiography (OCTA). Methods This study is a retrospective chart review of 16 patients (16 eyes) with PCV. OCTA (Avanti RTVue XR) findings were evaluated and selected for analysis after agreement by two retina specialists . Results Twenty one polyps in 16 eyes (16 patients) with PCV were included in this study. The mean patient age was 67 years (13 men and three women). The shape of polypoidal lesions on OCTA at initial were halo (five polyps), rosette (seven polyps), and vascular network (nine polyps). Eight months after anti-vascular endothelial growth factor treatment, in a total of four eyes, seven polyps could be followed up completely, the two halo type polypoidal lesions changed to rosette and vascular network type. The lesions of three rosette and two vascular network type lesions did not change in shape. In addition, the size of the polypoidal lesions (one among two halo types, two among three rosette types, and two among two vascular network types) decreased, but one halo type did not change and one rosette type increased in size on OCTA. Conclusions En-face OCTA enabled us to categorize novel types of PCV with polypoidal lesions.

Purpose: To investigate the prevalence of Toxoplasma gondii and Toxocara canis in patients with uveitis.Methods: Patients with uveitis were examined. Serum antibodies to T. gondii and T. canis were tested by using the enzyme-linked immunosorbent assay. Polymerase chain reaction (PCR) was done using blood and aqueous humor (AH).Results: Ninety-eight patients were enrolled. Mean age was 43.5 ± 13.2 years. Six patients were seropositive for T. gondii with the following pattern: anterior uveitis, 1; posterior uveitis with retinitis, 2; pan uveitis, 2. One patient had a positive PCR result for T. gondii in AH, who showed panuveitis. Twenty-three patients were positive to serum IgG for T. canis with the following clinical manifestation: granuloma, 6; pigmented scar, 3; vitritis, 6—but none were PCR positive.Conclusions: T. gondii and T. canis are still important causes of uveitis. Ocular toxocariasis is not an uncommon cause of uveitis, even in adults.

Purpose To investigate the influence of photodynamic therapy (PDT) and combination of PDT and ranibizumab on aqueous humor levels of vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV). Design Prospective randomized clinical trial. Method We included 20 eyes with treatment-naive PCV and 20 eyes undergoing cataract surgery as controls. PCV eyes were randomized to treatment with PDT alone or to a combination of ranibizumab and PDT on the same day. During 3 months, retreatment was not performed. Aqueous humors were collected at baseline and at 1 week, 1 month, and 3 months after treatment in the PCV group and during cataract surgery in the control group. VEGF levels were measured using multiplex bead immunoassay. Results At baseline, VEGF levels were significantly increased in PCV eyes compared with control eyes. A significant decrease in VEGF levels was found at 1 week after PDT treatment (n = 8) and at all time points after combination treatment (n = 12). With combination treatment, VEGF levels were decreased to values below the detection limit in all eyes at 1 week and 1 month and in 7 of 12 eyes at 3 months. There was no difference in the clinical profiles among the 2 treatment groups at each time point. Conclusion Decreased levels of VEGF detected 1 week after PDT for PCV seems to reflect acute damage of vascular endothelial cells, one of the VEGF expression sites in PCV. Concomitant ranibizumab resulted in a further decrease in VEGF to negligible levels, but this result did not affect the clinical results for 3 months.

Methods A retrospective case report of a retinitis pigmentosa patient who underwent vitrectomy for epiretinal membrane after intravitreal autologous stem cell implantation. Results A 71-year-old female RP patient came to our clinic for ophthalmic evaluation after intravitreal autologous stem cell injection. Four months ago, she underwent intravitreal autologous stem cell injection for both eyes at another hospital. New thick epiretinal membrane (ERM) with extensive macular pucker was found on her left eye. She underwent pars plana vitrectomy and membranectomy. After biopsy, many CD34-positive stem cells were detected in ERM specimen. Conclusion This is the first report of ERM formation following intravitreal autologous stem cells injection. CD34-positive stem cells were detected in a human eye at 4 months after injection. Further studies are needed to determine how stem cells caused ERM and how long they would stay in the eye.

Tissue plasminogen activator (tPA), an effective thrombolytic agent, is commercially available for the treatment of vitreous hemorrhage, subfoveal hemorrhage, suprachoroidal hemorrhage, and retinal vascular occlusive disease in the field of ophthalmology [1,2]. In particular, intravitreal or subretinal injections of tPA have been used when performing surgery for submacular hemorrhages or subfoveal choroidal neovascularization [3-8]. Dose-dependent retinal toxicity has been reported with the injection of intravitreal tPA; this toxicity has been reported to be due to the L-arginine vehicle rather than the tPA itself [9]. The retinal toxicity of L-arginine has been reported to increase nitric oxide (NO) in cells [10]. NO activates guanylate cyclase in the photoreceptor layer of the retina to produce more cyclic guanosine monophosphate (cyclic-GMP) [11]. In the rd/rd mouse, photoreceptor degeneration is due to a mutation of the rod-specific enzyme cyclic-GMP phosphodiesterase, resulting in permanently open cyclic-GMP-gated cation channels in the rod outer segment membrane, allowing Na+ and Ca2+ ions to enter the cell and leading to possibly toxic levels of Ca2+ [12]. Therefore, the increase in NO that is caused by L-arginine leads to the accumulation of cyclic-GMP, thus leading to toxicity. Amiloride has an inhibitory function on the Na+/H+ exchanger in the apical plasma membrane of the distal nephron and the cyclic-GMP gated channel of the outer membrane of retinal photoreceptor cells [13]. Therefore, inhibition of the cyclic-GMP gated channels of retinal cells may result in a decrease in intracellular Ca2+, which then leads to increased retinal cell survival after tPA-induced toxicity. The purpose of this study was to examine the effect of amiloride on cellular toxicity caused by tPA-arginine in mouse primary retinal cells.

Purpose:To describe the pathoanatomy of diabetic macular edema in optical coherence tomography and its correlation with fluorescein angiography patterns.Methods:Sixty eyes of 56 patients were analyzed. Diabetic macular edema was classified into typical focal leakage (from microaneurysm), typical dif

The purpose of this study was to investigate the efficacy and safety of intravitreal ranibizumab 0.5 mg in South Korean and Taiwanese patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).This was a 12-month, open-label, single-arm, multi-center, phase III study. Ninety-five patients (Taiwanese: 51; South Korean: 44) were included in the study. Key outcome measures assessed included: mean change in best-corrected visual acuity (BCVA) from baseline to months 4 (primary endpoint) and 12 (secondary endpoint); other secondary endpoints comprising categorized mean change in BCVA from baseline at month 4 and month 12, mean change in BCVA from baseline at month 4 and month 12 per baseline characteristics; and incidence of ocular and non-ocular adverse events and serious adverse events (SAEs) at month 12.The mean BCVA change improved significantly (p 0.0001) from baseline to both month 4 (+9.3 letters) and month 12 (+10.1 letters). At month 12, the proportion of patients who gained ≥5, 10, or 15 letters from baseline was 75.8%, 54.7%, and 32.6% respectively. Total and CNV lesion area significantly decreased from baseline (p 0.0001). About 57% of patients showed complete absence of fluorescein leakage at month 12. Mean change from baseline visual acuity scores also increased significantly over time for all subgroups. At month 12, ocular SAEs occurred in 2.1% of patients (out of which one patient [1.1%] experienced endophthalmitis) and 16.8% of patients experienced non-ocular SAEs. There were no deaths reported during the study.Consistent with previous studies in Caucasian and Japanese populations, EXTEND III confirms that monthly intravitreal injections of ranibizumab 0.5 mg administered over 12 months is effective and well-tolerated in South Korean and Taiwanese patients with subfoveal CNV secondary to AMD.

To evaluate the relationship of axial length (AXL), intraoperatively assessed posterior vitreous detachment (PVD) status, and surgical outcomes of diabetic vitrectomy.Retrospective, consecutive case series. Clinical records were reviewed for 115 eyes (50 males, 65 females) with more than a 6-month follow-up who underwent diabetic vitrectomy from a single surgeon. Thirty-three eyes had vitreous haemorrhage, 37 had tractional retinal detachment (TRD) threatening the macula, 43 had TRD involving the macula, and two had neovascular glaucoma. AXL was measured preoperatively by ultrasonography, and PVD status was classified intraoperatively: broad vitreo-retinal adhesion as no PVD, PVD at the macular area with attachment at the disc as incomplete PVD, and complete PVD.Forty-four eyes had no PVD, 23 had incomplete PVD, and 48 had complete PVD. A majority of the no PVD group had macula off TRD (97.7%), whereas vitreous haemorrhage (68.7%) predominated in the complete PVD group. Longer AXLs were noted in the complete PVD group compared with the no PVD and incomplete PVD groups (ANOVA in three groups P=0.0001). Univariate analysis showed that AXL had an influence on anatomical success (P=0.02). Multiple logistic regression analysis yielded that PVD status is a significant predictor of the final best corrected visual acuity (BCVA)20/100, and BCVA20/40 (P=0.01, P=0.02).Intraoperatively assessed PVD status is a prognostic factor for functional outcomes of diabetic vitrectomy. Shorter AXL was associated with lesser PVD. In eyes with a lack of PVD, careful timing and decision of surgery are mandatory.

To evaluate the changes in aqueous humor cytokine levels following consecutive intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).Aqueous humor samples were collected at the time of intravitreal injection of 1.25 mg of bevacizumab every 7.0 (+/-2.0) weeks from ten eyes with AMD for the AMD group and during cataract surgery in nine eyes for the control group. Visual acuity with Early Treatment of Diabetic Retinopathy Study (ETDRS) letters and central macular thickness (CMT) using optical coherence tomography were measured before each injection in the AMD group. Aqueous cytokine levels were determined by immunoassay using multi-analyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK).In the AMD group, mean +/- standard deviation(SD) aqueous VEGF levels decreased from 68.0 +/- 32.1 pg/ml at baseline to 26.3 +/- 19.0 pg/ml after the first injection (p = 0.028) and to 25.2 +/- 12.8 pg/ml after the second injection (p = 0.005). While CMT decreased from 307.7 +/- 102.0 mum to 206.8 +/- 141.5 microm (p = 0.037), ETDRS visual acuity increased from 17.6 +/- 11.7 letters to 22.0 +/- 15.6 letters after three consecutive injections (p = 0.017).Significantly decreased VEGF levels were noted after the first injection of bevacizumab. These levels were maintained after the second injection, which paralleled the change in visual acuity and CMT.

Aims: Our purpose was to report the clinical and pathological findings from uveal melanoma patients with persistent exudative retinal detachment (RD) after Gamma Knife radiosurgery (GKR). Methods: A retrospective review was performed. Results: GKR was performed on 19 uveal melanoma patients from 2004 to 2006, and 5 of them developed persistent exudative RD. The mean initial largest basal tumor diameter in these 5 patients was 14.4 ± 1.9 mm, and the mean tumor height was 9.2 ± 1.0 mm. Marginal doses of 40–50 Gy radiation were administered. RD developed or had become aggravated an average of 3 (1–10) months after GKR. Two patients underwent enucleation, while the remaining 3 underwent tumor removal by endoresection with retinal reattachment surgery by vitrectomy and silicone oil tamponade. These procedures were undertaken an average of 6.3 (1.5–14) months after radiation and 3.3 (0.5–5) months after the onset or aggravation of RD. Histologically 4 tumors showed 50–100% necrosis without any mitotic activity. Thus local tumor control after GKR appeared sufficient regardless of RD. Conclusion: Aggravation or development of exudative RD after GKR does not necessarily entail treatment failure. Therefore, retinal reattachment surgery in persistent exudative RD may be an option to preserve the eye.

Acta Ophthalmol. 2010: 88: 660–668 Abstract. Purpose: To report on the clinical course of pulsating polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). Methods: A total of 63 eyes of 58 consecutive patients diagnosed with PCV, treated with PDT and followed up for at least 6 months were enrolled. Best-corrected visual acuity (BCVA), fluorescein angiography and high-speed indocyanine green angiography (ICGA) using confocal scanning laser ophthalmoscopy (HRA) were performed. Results: Of the 63 PCV eyes, 14 eyes (22.2%) of 14 patients were classified as having pulsating PCV. The mean age of pulsating PCV patients was 60.6 ± 7.0 years (48–69 years), which was younger than non-pulsating PCV patients (65.7 years, p = 0.035). The mean follow-up period was 23.9 ± 10.7 months, and PDT was administered 1.6 ± 0.9 times to pulsating PCV patients. The mean logMAR BCVAs were 0.85 ± 0.47 at presentation and 0.71 ± 0.52 at final examination. Extensive haemorrhagic events were more common in pulsating than in non-pulsating PCV patients (57.1% versus 26.5%, p = 0.032). However, the risk of haemorrhage within 3 months of PDT was similar for both pulsating PCV and the remaining patients (14.3% versus 20%, p = 0.723). Conclusion: Pulsating PCV showed distinctive features including a relatively younger patient age at presentation, and a haemorrhagic tendency (especially extensive). However, the use of PDT did not directly increase the risk of haemorrhage in pulsating PCV patients.

PURPOSE : To evaluate the concentration of various cytokines in the aqueous humor of patients with naive, recurrent, and regressed choroidal neovascularization (CNV) of age-related macular degeneration after bevacizumab treatment. METHODS : Aqueous humor samples were collected from 36 eyes with age-related macular degeneration and 10 controls during cataract surgery. Of 36 patients with age-related macular degeneration, 5 eyes were naive to bevacizumab injection, 14 eyes had recurrent CNV after bevacizumab treatment, and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK). RESULTS : No significant difference in the cytokine levels was noted between the control group and the naive CNV group (all P > 0.05). Vascular endothelial growth factor in both naive (66.8 +/- 35.1 pg/mL) and recurrent CNV groups (55.7 +/- 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 +/- 12.8 pg/mL, P = 0.025 and P = 0.004, respectively) but was not statistically different from the control group (81.8 +/- 43.7 pg/mL, P = 0.310 and P = 0.212, respectively). The aqueous humor level of tumor necrosis factor-alpha and interleukin (IL)-2 was significantly lower in recurrent CNV group (P = 0.036 and P = 0.019) compared with the control group. In the active CNV patients (recurrent and naive CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (rho = 0.692, P = 0.001 and rho = 0.745, P < 0.001, respectively). CONCLUSION : Levels of Vascular endothelial growth factor measured in the aqueous humor were significantly related to the disease activity of CNV in age-related macular degeneration. Moreover, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha may be related to the activity of CNV.

Schwannomas rarely present as intraocular tumors and are often misdiagnosed as malignant melanoma. We describe a choroidal schwannoma confirmed by sclerouvectomy. A 30-year-old woman presented with a large nonpigmented intraocular mass of the choroid in the right eye and underwent surgical excision by sclerouvectomy. Histologically, the tumor was composed of a mixture of cellular solid components (Antoni A) and loose myxoid components (Antoni B). The tumor was eventually diagnosed as a schwannoma. Currently available ancillary studies are still of little value in definitively differentiating schwannomas from other choroidal tumors. In the case of atypical findings for a malignant melanoma, a benign neoplasm should be included in the differential diagnosis. This patient avoided enucleation by first having the mass excised. We are unaware of previous reports in which a choroidal schwannoma was diagnosed by surgical excision.

Lens extraction during vitrectomy is sometimes necessary to obtain an adequate view of the retina. Currently, phacoemulsification through a clear corneal incision with implantation of a foldable intraocular lens has become the preferred technique for cataract extraction during pars plana vitrectomy. The authors described the technique of lensectomy using a bimanual microincisional cataract surgery technique during pars plana vitrectomy and insertion of the intraocular lens at the end of surgery, which has several advantages over conventional coaxial phacoemulsification procedures. [Ophthalmic Surg Lasers Imaging 2009;40:80-84.]

Purpose To determine the effect of intravitreal bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically significant macular edema (CSME). Design Retrospective, comparative study. Participants Seventeen eyes undergoing intravitreal injection for CSME and 11 eyes undergoing cataract surgery as negative controls. Nine patients with CSME were naive to intravitreal bevacizumab injection (CSME group 1), and 8 patients previously received 1 intravitreal bevacizumab injection at a mean of 9.6±1.4 weeks earlier (CSME group 2). Methods Aqueous humor samples were collected before performing intravitreal injection in the CSME group and during cataract surgery in the control group. Aqueous cytokine levels were determined by immunoassay using multianalyte biochip array technology. Main Outcome Measures The concentration of cytokines in the aqueous humor was recorded as a mean (± standard deviation) in CSME groups 1 and 2 and the control group. Correlations of aqueous humor cytokine levels were evaluated. Results Significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were noted in patients with CSME compared with controls. Although higher vascular endothelial growth factor (VEGF) levels were noted in CSME group 1 ( P = 0.001), a lower level of VEGF was noted after intravitreal bevacizumab injection in CSME group 2 ( P = 0.004) compared with the control group. VEGF levels were also lower in CSME group 2 compared with CSME group 1 ( P = 0.001). In CSME group 2, a significant negative correlation was observed between VEGF and IL-6 (ρ = –0.833, P = 0.01) and VEGF and MCP-1 (ρ = –0.736, P = 0.037). Conclusions Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the aqueous humor of CSME. However, recurrence of macular edema was noted with significantly lower concentrations of VEGF after a single intravitreal injection of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the pathogenesis of CSME. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To assess the estimate prevalence and risk factors for age-related maculopathy (ARM) in Seoul, Korea. Patients and Methods: We examined 9,530 subjects with, 40 years of age or older between January 2006 and December 2006 in Seoul, Korea. Subjects underwent fundus photography, clinical examinations (including blood analyses), and completed detailed questionnaires. Fundus images were graded according to definitions from the Wisconsin Age-Related Maculopathy Grading System. Results: ARM was present in 235 subjects, corresponding to an estimate prevalence of 2.46%. Hepatitis B infection (positive status for HBsAg and HBcAb), serum triglyceride levels and high density lipoprotein levels remained as significant risk factors after age-adjustment. Multivariate analyses showed that the prevalence of ARM was significantly higher in older subjects [odds ratio (OR) 1.134; 95% CI 1.1141.154] and those who were seropositive for hepatitis B surface antigen (OR 2.566; 95% CI 1.519-4.335). Conclusion: The estimated prevalence of ARM was 2.46%. Age and hepatitis B infection may increase the risk of ARM. Key Word: Age-related maculopathy, hepatitis B, triglyceride, high-density lipoprotein

Aims: To evaluate the short-term safety and efficacy of a single intravitreal bevacizumab injection in patients with polypoidal choroidal vasculopathy (PCV). Methods: The records of patients treated with intravitreal bevacizumab for PCV were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography and fluorescein and indocyanine green angiography. Changes in visual acuity and central retinal thickness (CRT) over 3 months were the main outcome measures. Results: Nineteen eyes of 18 patients were included. No serious ocular or systemic adverse events were observed. The median baseline visual acuity and CRT were 20/100 and 230 μm, respectively. After 1 month, there was no significant improvement in median visual acuity (20/80+1; p = 0.055), but median CRT had decreased significantly (160 μm; p < 0.001). After 3 months (data available for 17 eyes), both median visual acuity (20/63–2; p = 0.001) and CRT (190 μm; p = 0.007) showed significant improvements over baseline values. Conclusions: Intravitreal bevacizumab therapy for PCV was well tolerated over the 3-month follow-up period. Short-term results are promising, but further studies are necessary to evaluate long-term efficacy.

To estimate the prevalence of asteroid hyalosis (AH) in Seoul, Korea, and to identify risk factors for the condition.A cross-sectional study with review of fundus photographs of subjects who received a health check-up between January 2006 and December 2006 at the Yonsei Medical Examination Center yielded 9,050 available cases (aged 40 years or older). AH was diagnosed retrospectively by the presence of cream-white spherical bodies within the vitreous, as seen in the fundus photographs.The estimate prevalence of AH was 0.36%. Multivariate analysis showed that the prevalence of AH was significantly higher in older patients and in those with stroke history, hypertension history, and high serum lipid levels.AH was relatively uncommon with the estimate prevalence of 0.36% in Seoul, Korea. The prevalence of AH correlated with age, stroke history, hypertension history, serum triglyceride levels, and low-density lipoprotein levels, with no gender bias. AH was not significantly associated with a history of diabetes, gout, heavy drinking, or current smoking.

PURPOSE: Intravitreal bevacizumab (Avastin) induces a transient improvement in diabetic macular edema, necessitating repeated injections. Here, we report the results of repeated administration of intravitreal bevacizumab for the treatment of clinically significant macular edema in 31 eyes of 24 patients. METHODS: At preinjection and 1, 6, and 12 (+/-1) weeks postinjection, visual acuity (VA) with Early Treatment of Diabetic Retinopathy Study (ETDRS) and central macular thickness (CMT) evaluated using optical coherence tomography were compared with independent and paired t-tests. RESULTS: VA and CMT were not significantly different before initial and repeated injections (administered at an interval of 22.06 +/- 11.15 [SD] weeks). At 6 weeks after the first injection, VA increased significantly by 3.72 +/- 8.02 ETDRS letters (P = 0.019), and CMT was markedly decreased by 93.30 +/- 210.33 microm (P = 0.022), which returned to near baseline at 12 weeks. At 6 weeks after the second injection, VA increased significantly by 3.97 +/- 7.46 ETDRS letters (P = 0.006) and CMT decreased considerably by 118.77 +/- 178.58 microm (P = 0.001). At 12 weeks after the second injection, we observed a decrease in VA with recurrence of macular edema. CONCLUSIONS: Repeated administration of intravitreal bevacizumab (1.25 mg) may lead to the improvement of VA and CMT in patients with clinically significant macular edema.

To evaluate the efficacy of timolol-dorzolamide drops used to decrease aqueous outflow from the eye on the prolongation of the biological activity of intravitreal bevacizumab. Thirty-eight eyes of 38 patients with macular edema (ME) following retinal vein obstruction (RVO) were enrolled. These patients were randomly assigned into 2 groups: timolol-dorzolamide drops twice daily (n = 19) or no eyedrops (control; n = 19). All patients received 1.25 mg (in 0.05 mL) of bevacizumab intravitreally and were examined before treatment, 1 week after injection, and then every 4 weeks after injection. For each patient, visual acuity (VA), intraocular pressure (IOP), and central retinal thickness (CRT) by optical coherence tomography (OCT) were recorded before injection and at each visit after injection. The mean CRT at each timepoint was considered to directly reflect the biological activities of bevacizumab at those times. The mean CRT measured by OCT showed a significant decrease 1 week after treatment in both groups, and this difference was maintained for a total of 9 weeks (paired t-test

Purpose To evaluate the effects of macular ischemia on visual outcomes in patients with diabetic macular edema (DME), after intravitreal bevacizumab injections. Methods Data on 59 eyes of 53 consecutive patients treated with intravitreal bevacizumab for DME were retrospectively reviewed. Data from preoperative fluorescein angiography (FA) tests were examined. Patients with an enlarged foveal avascular zone (FAZ), >or=1000 microm, or a broken perifoveal capillary ring at the border of the FAZ, with a distinct area of capillary nonperfusion within one disk diameter of the foveal center in the transit phase of fluorescein angiography, were defined as having macular ischemia. The patients were thus divided into two groups: with or without macular ischemia. Early Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses measured using third generation ocular coherence tomography (OCT), were evaluated at baseline and at 1 month and 3 months after treatment. Results At 3 months after treatment, the mean visual acuity (VA) score decreased from a baseline VA of 0.52 +/- 0.27 (approximate Snellen equivalent, 20/63) to 0.57 +/- 0.21 (20/80) in the ischemic group. In the nonischemic group, by contrast, the VA improved from 0.66 +/- 0.34 (20/100) at baseline to 0.59 +/- 0.33 (20/80) at 3 months post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41 eyes (21%) in the nonischemic group, experienced visual losses of >or=1 line on the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the ischemic group, but only 2 eyes (5%) in the nonischemic group, lost >or=3 lines (P = 0.042, Pearson chi-square test). Conclusion Macular ischemia may have a negative effect on short term visual outcomes after intravitreal bevacizumab injections in patients with DME.

To determine the incidence, demographic features, and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Korean patients.A retrospective review was undertaken of 392 eyes of 321 symptomatic patients suspected of having exudative age-related macular degeneration (AMD) after their first visit to a tertiary hospital between February 2002 and May 2006. All patients underwent a complete ophthalmic examination, including fluorescein and indocyanine green angiography (ICGA).Of the 321 patients (392 eyes), 79 (98 eyes, 24.6%) were diagnosed with PCV. The mean PCV patient age was 64.6 +/- 7.6 years. PCV was more common in men (78.5%), and was usually unilateral (75.9%). In terms of PCV clinical manifestation, 52% of patients showed an exudative pattern, 34.7%, a hemorrhagic pattern, and 13.3%, an extensive hemorrhagic pattern. The mean visual acuity at presentation was 0.231 +/- 0.256. Classification was based on ICGA findings; 52% of patients showed relatively large aneurismal dilations, 25.5% showed atypical vessel deformations, and 22.5% showed dense clusters of numerous small hyperfluorescent dots.The incidence of PCV in Korean exudative AMD patients was relatively high compared with that in other ethnic groups. As in other Asian patient populations, PCV occurred more commonly in men and was predominantly unilateral.

Purpose: Visual prognosis was evaluated in Korean Behcet uveitis patients. The study investigated factors associated with poor visual outcome, and the effect of various treatments on recurrence-free duration. Methods: A retrospective analysis was undertaken on 99 consecutive Behcet uveitis patients (168 eyes). Visual prognosis was evaluated using Kaplan-Meier survival curves, and Cox’s proportional hazard regression analysis was used to identify risk factors. Results: Visual acuity at the first visit (Conclusion: Whilethe long-term visual prognosis for Behcet uveitis may be affected by many factors, the initial visual acuity appears to be the most significant. Treatments involving steroids appear to decrease the frequency of uveitis recurrence.

Background and Objective:To investigate the factors related to postoperative hypotony after 25-gauge sutureless vitrectomy.Patients and Methods:Of 109 consecutive eyes undergoing sutureless vitrectomy, 95 fluid-filled eyes were randomly assigned to three groups according to the order of infusion cannula removal. In group 1 (30 eyes), the infusion was removed first. In group 2 (32 eyes), the infusion was removed after another cannula. In group 3 (33 eyes), the infusion was removed last. Intraocular pressure (IOP) was measured on pre-operative day 1 and postoperative days 1, 7, and 30.Results:Mean age was 58.9 ± 11.6 years (range: 18 to 80 years). Among each factor (including order of infusion removal, age, sex, axial length, preoperative IOP, previous vitrectomy, indications for vitrectomy and lens status), only age was significantly correlated with IOP on postoperative day 1 (P = .019). In 13 eyes in which hypotony persisted through postoperative day 2 (IOP ≤ 5 mm Hg), the age of the patients was significantly younger than those who did not experience persisting hypotony (P = .006).Conclusion:Younger patients were more likely to experience early postoperative hypotony.

The aim of this study was to identify the short-term effect, safety, and durability of intravitreally injected bevacizumab in patients with macular edema (ME) caused by retinal vein obstruction (RVO) and diabetic macular edema (DME).We retrospectively evaluated 39 eyes of 36 patients, 14 with ME caused by RVO and 25 with DME, who received intravitreal bevacizumab (1.25 mg) and were followed up for at least 3 months. Monthly assessments examined safety, best corrected visual acuity with an ETDRS chart (logMAR), and central retinal thickness (CRT) using optical coherence tomography.No significant ocular or systemic side-effects were observed. The follow-up period was 5.4 +/- 1.1 months (mean +/- standard deviation). During follow-up, the mean number of injections was 1.4 +/- 0.5. The baseline mean logMAR was 0.91 +/- 0.51, and the mean CRT was 552.6 +/- 186.7 microm. At 1, 2, and 3 months, the mean logMAR was 0.67 +/- 0.46 (paired t test, P0.001), 0.66 +/- 0.46 (P0.001), and 0.69 +/- 0.45 (P0.001), respectively, and the mean CRT was 323.1 +/- 151.9 mum (P0.001), 324.6 +/- 136.9 mum (P0.001), and 382.5 +/- 130.4 microm (P0.001), respectively. Fourteen (14) of 34 eyes with more than 3 months of follow-up required a second injection at a mean 3.4 +/- 1.0 months after the initial injection. For both ME caused RVO and DME patients, a bevacizumab administration improved logMAR and CRT at each time point through to 6 months, except for logMAR in DME at 1 week (P = 0.081), 5 months (P = 0.130) and 6 months (P = 0.759).An intravitreal bevacizumab injection for ME caused by RVO and DME was safe and effective for improving visual acuity and reducing CRT.

PURPOSE To report two cases of progressive macular changes in X-linked juvenile retinoschisis (XLRS) treated with vitrectomy. PATIENTS A 16-year-old boy and a 13-year-old boy with progressive deterioration of vision underwent vitrectomy with internal limiting membrane peeling with or without gas injection for vitreous traction. Optical coherence tomography was performed to monitor morphologic changes of the macula before and after surgery. RESULTS During follow-up (at 6 months and 3 months, respectively), both patients had anatomical improvement and minimal improvement in vision. CONCLUSION We postulate that vitreous tractional force causes the progressive structural deformity of the macula in XLRS.

In normal eyes, retinal detachment (RD) occurs at a rate of approximately 5 per 100,000 people per year and the frequency of proliferative vitreoretinopathy (PVR) remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%. PVR is the most common cause of failed repair of rhegmatogenous RD, and risk factors for PVR are related to several well-known pre-, intra-, and postoperative clinical situations. Current methods of surgical management of RD and PVR are pneumatic retinopexy, scleral buckling, and pars plana vitrectomy (PPV). Surgical success rates for PVR have improved as techniques and instruments of vitrectomy evolved. However, despite these advances, more than one fourth of initially successful cases results in redetachment due to recurrent vitreoretinal traction. Retinal pigment epithelial cells are the key factor in triggering PVR development. In addition, soluble mediators and the extracellular matrix components play a critical role in cellular events, including proliferation and tissue contraction which occur in PVR. Although PPV remains a critical component of the treatment in RD and PVR, ongoing efforts seek to identify adjuvant therapies that might inhibit PVR development. Recent studies have therefore been directed toward pharmacologic inhibition of cellular proliferation and membrane contraction with drugs such as daunorubicin, 5-fluorouracil, and heparin. More detailed understanding of the pathophysiology underlying PVR may lead to the development of effective prophylactic and/or adjunctive therapies. Further work is necessary to identify optimal adjunctive therapies for the management of RD and PVR.

Although Arg-Gly-Asp (RGD) motif-containing disintegrins are associated with integrin inhibition and the activation of various biological processes, little is known about the role of RGD motif-containing disintegrin in vascular development and remodeling. We therefore investigated the role of RGD-containing disintegrin in vascular remodeling in oxygen-induced retinopathy (OIR) mouse model.EGT022, an RGD-containing disintegrin originated from human a disintegrin and metalloproteinase 15 (ADAM15), was used to investigate the role of the disintegrin in vascular development in OIR mouse model. To analyze the functional effects of EGT022 on retinal vascular development, the immunohistochemistry on mouse retinas after fluorescein isothiocyanate (FITC) perfusion was conducted and the vessel integrity was examined using modified Mile's permeability assay.EGT022 was able to reduce overall retinopathy scores by 75%, indicating its efficacy in retinal microvessel maturation stimulation. Pericyte coverage was greatly stimulated by EGT022 treatment in OIR mouse model. EGT022 was also effective to significantly improve blood vessel integrity.RGD-containing disintegrin EGT022 stimulated vascular maturation in OIR mouse model. Experimental results suggest that EGT022 is useful for treatments to improve ischemia in nonproliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy.

Submacular hemorrhage (SMH) is a common manifestation of neovascular age-related macular degeneration (nAMD). Left untreated, the prognosis of SMH is poor, especially when the SMH is thick and caused by nAMD [1,2]. This is a result of a barrier effect that prevents nutrient supply between the retina and the choriocapillaris and toxicity by the iron in the blood [3]. Many treatment options for SMH have been described for the displacement or evacuation of the hemorrhage; these frequently involve the use of intravitreal gas with or without tissue plasminogen activator (tPA) [4,5,6]. Pars plana vitrectomy with pneumatic displacement, either with or without tPA may also be considered for massive SMH [7]. Several recent studies have successfully used intravitreal anti-vascular endothelial growth factor (VEGF) agents in combination with pneumatic displacement for treating SMH in patients with nAMD [8,9]. Tenecteplase (commercial TNK; Metalyse, Boehringer Ingelheim, Sydney, Australia) has greater fibrin specificity, a reduced potential for retinal toxicity and a known ability to penetrate the retina following intravitreal injection compared with tPA [10,11,12,13,14]. McAllister et al. [14] reported positive results of intravitreal TNK injections for treatment of SMH due to nAMD. The aim of this study was to evaluate the outcome of a triple injection with intravitreal injection of TNK, anti-VEGF agent, and an expansile gas for the treatment of thick SMH caused by nAMD.

To determine the preoperative anatomic factors in macular holes and their correlation to hole closure.Forty-six eyes with consecutive unilateral macular hole who had undergone surgery and followed up for at least 6 months were enrolled. Optical coherence tomography images and best-corrected visual acuity (BCVA) within 2 weeks prior to operation and 6 months after surgery were analyzed. The maximal hole dimension, foveal degeneration factors (inner nuclear layer cysts, outer segment (OS) shortening) and the widest foveolar floor size of the fellow eyes were measured. For overcoming preoperative individual variability of foveal morphology, an 'adjusted' hole size parameter (the ratio between the hole size and the fellow eye foveolar floor size) was used based on the fact that both eyes were morphologically symmetrical.Mean preoperative BCVA (logMAR) was 1.03±0.43 and the mean postoperative BCVA was 0.50±0.38 at 6 months. Preoperative BCVA is significantly associated with postoperative BCVA (P=0.0002). The average hole diameter was 448.9±196.8 μm and the average fellow eye foveolar floor size was 461.3±128.4 μm. There was a correlation between hole diameter and the size of the fellow eye foveolar floor (Pearson's coefficient=0.608, P0.0001). The adjusted hole size parameter was 0.979±0.358 (0.761-2.336), which was a strong predictor for both anatomic (P=0.0281) and visual (P=0.0016) outcome.When determining the extent of preoperative hole size, we have to take into consideration the foveal morphologic variations among individuals. Hole size may be related to the original foveal shape, especially in relation to the centrifugal retraction of the foveal tissues.

Purpose Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. Methods In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. Results The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Conclusions Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.

Circulating autoantibodies specific for retinal proteins are associated with retinal destruction in patients with diabetic retinopathy (DR). In this study, we screened diabetic sera for the presence of anti-retinal autoantibodies with an aim of developing diagnostic markers for DR. Immunoblot analysis of DR patients' sera with human retinal cytosolic proteins revealed a higher incidence of anti-retinal autoantibodies, compared to normal blood donors or diabetic patients without DR. Anti-retinal protein autoantibody profiles of DR patient sera were obtained by 2-DE immunoblot analysis. Specifically, 20 protein spots reactive with DR patient sera were identified by ESI-MS/MS. Of these spots, 14 were specific for DR patients, and 4 reacted with both non-proliferative DR (non-PDR) and PDR sera. The anti-aldolase autoantibody was selected as a DR marker candidate, and specific reactivity of DR patient sera was confirmed by immunoblot analysis with rabbit aldolase. The serum anti-aldolase autoantibody level was measured by ELISA. DR patients showed significantly higher autoantibody levels than normal donors or diabetic patients without retinopathy. However, no significant differences were observed between non-PDR and PDR patients, suggesting that the level of anti-aldolase autoantibody is not determined by the severity of retinopathy in diabetic patients. Our data collectively demonstrate that the anti-aldolase autoantibody serves as a useful marker for DR diagnosis.

Tissue plasminogen activator (tPA) is an efficient thrombolytic agent, but the dose-dependent retinal toxicity of intravitreal injection of commercial tPA (containing L-arginine) has been reported. Here, we sought to investigate the mechanism of tPA-induced cell death in mouse retinal cell cultures and the role of nitric oxide (NO).Primary retinal cell cultures were maintained using glial conditioned medium (GCM) solution. Mouse retinal cell death was observed by using Hoechst-propidium iodide staining. Mouse retinal cell death was also measured by lactate dehydrogenase (LDH) assay. The formation of NO was measured using Griess reagent.tPA-induced cell death was detected in mouse retinal cell cultures by Hoechst-propidium iodide staining or LDH assay. L-arginine seems to be the major factor in retinal toxicity of commercial tPA (containing L-arginine). The formation of NO was markedly increased in mouse retinal cell cultures treated with tPA (containing L-arginine) or L-arginine. NO inhibitor reduced the cell death induced by commercially available tPA or L-arginine.This study suggests that l-arginine from commercial tPA (containing L-arginine) induces the majority of cell death in mouse retinal cell cultures and that its cytotoxicity may depend on the induction of NO.