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Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss. The present consensus provides suggestions on diagnosis, evaluation, treatment, and follow-up strategies for nAMD from a panel of 11 practicing ophthalmologists. The experts suggest that the baseline visit for nAMD management should include a comprehensive ophthalmologic examination via a multimodal approach consisting of visual and anatomical evaluation. Patients diagnosed with nAMD should be subjected to treatment with the goal of maintaining visual function while diminishing anatomical disease activity and minimizing treatment burden. Currently, anti-VEGF therapy is the main treatment strategy for nAMD, and evaluation involving comprehensive ophthalmologic examination within 1 month of completion of the loading phase comprising three monthly injections is recommended to guide subsequent management. Either a treat-and-extend or pro re nata regimen can be considered for the maintenance phase of anti-VEGF therapy, and the regimen should be chosen and adjusted according to disease activity, reimbursement criteria, financial burden, and patient preferences. In the event of inactive nAMD or poor treatment outcomes, after thorough evaluation and patient education, anti-VEGF therapy may be stopped. The consensus provides practical nAMD management guidelines for ophthalmologists and fellow healthcare professionals.

To investigate the association between clinical features of chronic central serous chorioretinopathy (CSC) and subsequent development of polypoidal choroidal vasculopathy (PCV). Characteristics and treatment response of PCV secondary to CSC were described. This retrospective observational study included 18 patients with chronic CSC (18 eyes) with subsequent PCV and 36 controls (36 eyes) with chronic CSC without PCV development during follow-up. Clinical features were compared between the two groups. A logistic regression model was used to evaluate the risk factor of PCV formation. Treatments for PCV included anti-vascular endothelial growth factor (VEGF) monotherapy, photodynamic therapy (PDT), or PDT and anti-VEGF combination treatment. Subretinal fluid on optical coherence tomography images were assessed after treatments. Significant between-group differences were observed in best-corrected visual acuity after disease resolution and presence of pachyvessels (P = .001 and P = .003, respectively). The presence of pachyvessels in chronic CSC was associated with subsequent PCV (odds ratio = 6.00; 95% CI, 1.74–20.68; P = .005). CSC recurrence and subfoveal choroidal thickness (SFCT) were not significantly associated with subsequent PCV development (P = .393 and P = .911, respectively). The mean age of PCV diagnosis was 51 years, and the mean time from CSC diagnosis to PCV confirmation was 77.8 months. The mean (range) SFCT of PCV was 327.7 (134–599) μm. Nine patients received anti-VEGF monotherapy and 5 had disease remission. Four patients received PDT and anti-VEGF combination treatment and all of the 4 had disease remission. In chronic CSC, pachyvessel characteristics are associated with subsequent PCV development. This result will assist clinicians to evaluate CSC in clinical practice and provide insights into the pathogenesis of PCV.

The aim of this review is to identify the common characteristics and prognoses of different subtypes of neovascular age-related macular degeneration (nAMD). We also propose recommendations on how to tailor treatments to the subtype of neovessels to optimise patient outcomes. The authors, selected members of the Vision Academy, met to discuss treatment outcomes in nAMD according to macular neovascularisation (MNV) subtypes, using evidence from a literature search conducted on the PubMed database (cut-off date: March 2019). This review article summarises the recommendations of the Vision Academy on how the characterisation of MNV subtypes can optimise treatment outcomes in nAMD. The identification of MNV subtypes has been facilitated by the advent of multimodal imaging. Findings from fluorescein angiography, indocyanine green angiography and spectral-domain optical coherence tomography collectively help refine and standardise the determination of the MNV subtype. To date, three subtypes have been described in the literature and have specific characteristics, as identified by imaging. Type 1 MNV is associated with better long-term outcomes but usually requires more intense anti-vascular endothelial growth factor dosing. Type 2 MNV typically responds quickly to treatment but is more prone to the development of fibrotic scars, which may be associated with poorer outcomes. Type 3 MNV tends to be highly sensitive to anti-vascular endothelial growth factor treatment but may be associated with a higher incidence of outer retinal atrophy, compared with other subtypes. Accurately assessing the MNV subtype provides information on prognosis and helps to optimise the management of patients with nAMD.摘要: 本综述的目的是确定新生血管性年龄相关性黄斑变性 (nAMD) 不同亚型的特征和预后.并建议如何根据新生血管的亚型调整治疗方案, 以优化患者的预后.作者为视觉学会的选定成员, 根据黄斑区新生血管 (MNV) 的不同亚型, 利用PubMed数据库中检索的文献 (截止日期: 2019年3月),讨论了nAMD的治疗效果.这篇综述文章总结了视觉学会关于不同MNV亚型如何优化nAMD治疗结果的建议.多模式成像促进了MNV亚型的识别.荧光素血管造影术、吲哚菁绿血管造影术和谱域光学相干断层扫描的结果共同完善并标准化了MNV亚型的确定.迄今为止,文献中已经描述了三种亚型,并通过成像确定了它们的具体特征.1型MNV具有更好的长期预后,但通常需要更高剂量的抗血管内皮生长因子.2型MNV通常对治疗反应迅速,但更容易形成纤维化瘢痕,这可能与较差的预后相关.3型MNV往往对抗血管内皮生长因子治疗高度敏感,但与其他亚型相比,可能与更高的视网膜外萎缩发生率相关.准确评估MNV的亚型可提供预后的信息,并有助于优化nAMD患者的管理.

Polypoidal choroidal vasculopathy (PCV) is a prevalent retinal disease predominantly occurs in Asians that shares some similarities seen in neovascular age-related macular degeneration. Recent large multicenter clinical trials on intravitreal anti-vascular endothelial growth factor (VEGF) agents and photodynamic therapy (PDT) have shed lights on the management of PCV. The Taiwan National Health Insurance had granted limited anti-VEGF agents and PDT for patients with PCV after the approval of required data submission, especially fundus angiography, optical coherence tomography, and visual acuity. In order to best utilize these limited resources for the patients, an expert meeting was held to provide updated Taiwan consensus recommendations for the management of PCV, including initial therapy selection, assessment of treatment response, re-treatment/rescue treatment, and determination of treatment extension/follow-up schedule. An algorithm for treatment allocation under both initial and re-treatment setting was proposed. Further mechanistic and clinical studies are required to investigate the prognostic factors and optimal treatment protocols that will improve healthcare quality and reduce burden of disease and treatment for patients with PCV. Keywords: Choroidal neovascularization, PCV, Photodynamic therapy, Vascular endothelial growth factors, Wet age-related macular degeneration

Diabetic macular edema (DME) is the most common cause of vision loss among patients with diabetes mellitus (DM), rendering it an important growing challenge in ophthalmology. In the past decades, the management strategies for DME had a few paradigm shifts, and the advent of an expanding number of anti-vascular endothelial growth factor (VEGF) agents also calls for an in-depth examination of the currently available evidence. This article was composed with the intention to provide recommendations for practicing clinicians to improve the management and, through it the outcomes of DME. Drawing from current guideline recommendations, clinical trial findings and local clinical experiences, these consensus recommendations for the management of DME were formed by an expert panel through iterations of discussion and voting. First, the treatment goal of DME is to achieve best visual outcome with edema improvement while minimizing treatment burden. Second, anti-VEGF therapy should be considered as the first-line treatment for patients with center-involving DME causing vision loss. Baseline visual acuity (VA) and central subfield thickness (CST) should be taken into consideration when choosing anti-VEGF agents. Third, early intensive anti-VEGF therapy (at least 3 monthly doses) is important for better patients’ VA and anatomical improvement. In non-responders who have already been treated with 3-5 injections of anti-VEGF agents, it is reasonable to switch to other modalities, such as steroids. Finally, for the follow-up phase, fixed or individualized dosing should be considered based on VA and OCT.

To evaluate the real-world experience with half-time photodynamic therapy (PDT) versus half-dose PDT for chronic central serous chorioretinopathy (CSC).This multicenter retrospective study enrolled patients who received half-time PDT (with irradiation time shortened to 42 s) or half-dose PDT (with the dosage of verteporfin reduced to 3 mg/mA total of 53 eyes from 49 patients were enrolled in this study. Seventeen eyes (15 patients) received half-time PDT and 36 eyes (34 patients) received half-dose PDT. The success rates in both groups were similar at 12 months (94.1% vs. 94.4%; P = 0.543). The mean CST at 1, 6, 12 months decreased significantly when compared with the baseline in both groups (all P 0.001). The BCVA significantly improved at 6 and 12 months in both groups (all P 0.05). There were no significant differences in changes of BCVA and changes of CST between the 2 groups at any time point.Half-time PDT is a feasible treatment for chronic CSC. It has success rates similar to half-dose PDT at 12 months. There were no significant differences in changes of BCVA and changes of CST between the 2 groups at 1, 6, and 12 months after treatment.

Diabetic macular oedema is the most common cause of diabetic retinopathy-induced vision loss. Efficacy of anti-vascular endothelial growth factor therapy in diabetic macular oedema has been demonstrated in randomized controlled trials. An Asian-specific guideline for diabetic macular oedema treatment is needed as patients in Asia tend to present with far more advanced disease than seen elsewhere in the world. Previous reviews of diabetic macular oedema management lacked a broader assessment of anti-vascular endothelial growth factor treatment choices and newer trials. Recent clinical trial data allow head-to-head comparisons between the different anti-vascular endothelial growth factor agents and treatment regimens. This review aims to summarize the clinical evidence related to various treatment regimens for clinicians, with a focus on anti-vascular endothelial growth factor therapies, and to provide guidance on the treatment of diabetic macular oedema in Asian patients.

A total of 14 isolates of Staphylococcus aureus and 10 isolates of Staphylococcus cohnii subsp. urealyticum were isolated from 90 field cases of arthritis. Joint lesions that were induced by both staphylococci could not be distinguished and were characterized by fibrinopurulent arthritis and tenosynovitis, associated with synovial cell hyperplasia. Additional changes included chondronecrosis and osteomyelitis. Similar lesions were induced by artificial intravenous inoculation of native colored broilers with the two pathogens. Both species were identified using API Staph kits and detection of 16[Formula: see text]S rRNA genes. Based on a phylogenetic analysis of gap, our isolates of S. cohnii subsp. urealyticum could be divided into two groups. This study is the first report on joint lesions due to S. cohnii subsp. urealyticum infection in broiler chickens.

Incontinentia pigmenti (IP) is a rare disease with multisystemic anomalies, which commonly presents just after birth. Here, we report a rare case of IP patient with vitreous hemorrhage in school-age children. Therefore, physicians have to be alert and evaluate IP patients at all ages. Regular ophthalmic follow-up is necessary, and fluorescein angiography should be performed if peripheral ischemia or neovascularization is suspected. The effect of peripheral laser ablation on peripheral retinal nonperfusion is not clear and merits further study.

The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment.The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.ClinicalTrials.gov Identifier: NCT01846273.

This study evaluated the safety and efficacy of half-dose verteporfin combined with half-fluence photodynamic therapy (half-half photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC).This was a retrospective case series. Fourteen eyes with chronic CSC receiving half-half PDT were included in group 1. Another 28 eyes receiving half-dose verteporfin combined with standard fluence PDT were included in group 2 as a control group. Main outcome measures were the success rates, major complications, best-corrected visual acuity (BCVA), and central subfield foveal thickness (CFT) on optical coherence tomography (OCT) at 6 months in both groups. Success of treatment was defined as complete resolution of subretinal fluid on OCT after treatment without recurrence.There was no significant difference between groups in their age, gender, duration of symptoms, baseline BCVA, baseline CFT, PDT spot size, and follow-up duration. The success rate was 64% (9/14 eyes) in group 1 and 93% (26/28 eyes) in group 2 at 6 months (P=0.031). No major complications were found in either group. Mean CFT showed significant reduction at 6 months in both groups (-115 μm and P0.001 in group 1; -150 μm and P0.001 in group 2). The mean BCVA in group 2 improved significantly (P0.001) at 6 months. The mean BCVA in group 1 showed a trend of improvement but was not statistically significant (P=0.25) at 6 months.Half-half PDT is a feasible treatment for chronic CSC. However, there was a lower success rate at 6 months compared with the control group.

Diabetic macular oedema is the most common cause of diabetic retinopathy-induced vision loss. Efficacy of anti-vascular endothelial growth factor therapy in diabetic macular oedema has been demonstrated in randomized controlled trials. An Asian-specific guideline for diabetic macular oedema treatment is needed as patients in Asia tend to present with far more advanced disease than seen elsewhere in the world. Previous reviews of diabetic macular oedema management lacked a broader assessment of anti-vascular endothelial growth factor treatment choices and newer trials. Recent clinical trial data allow head-to-head comparisons between the different anti-vascular endothelial growth factor agents and treatment regimens. This review aims to summarize the clinical evidence related to various treatment regimens for clinicians, with a focus on anti-vascular endothelial growth factor therapies, and to provide guidance on the treatment of diabetic macular oedema in Asian patients.

Mucopolysaccharidoses (MPS) is a group of lysosomal storage disorders that lead to accumulation of glycosaminoglycans (GAGs) in many tissues and organs, resulting in different clinical features. In this study, we conducted the manifestation changes of refractive error, corneal clouding, and intraocular pressure in two Taiwanese MPS VI patients with enzyme replacement therapy (ERT) initiated at the age of eight. In case 1, hyperopia was noted before and after ERT. Clinical observation showed no significant improvement in corneal clouding after ERT. In case 2, hyperopia was also noted initially before ERT and unable to be measured due to severe corneal opacity. Clinical observation showed no significant improvement in corneal clouding in after ERT, and the best-corrected visual acuity worsen and keratoplasty was needed in both eyes. Case 2 also had ocular hypertension and suspect MPS VI-related. However, due to severe corneal clouding, optic disc changes were hard to examine, and visual field was unable to be tested. Although some literature shows that ERT may be effective in preventing and/or clearing corneal stromal GAGs, accumulation and the timing of treatment initiation cloud be a clinical prognosis predictor; in this experience, no significant improvement of corneal clouding was observed in patients with MPS IV after ERT. Hyperopia and glaucoma were noted, and showed no changes after ERT. Severe corneal clouding can lead to difficulties in diagnosis and monitoring of hyperopia and glaucoma.

Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy affecting vision, with clinical features distinct from neovascular age-related macular degeneration. Currently, no evidence-based guidelines exist for its diagnosis and treatment.A panel of experts analyzed a systematic literature search on PCV together with results of the EVEREST trial, the only published randomized controlled clinical trial in PCV. At a subsequent Roundtable meeting, recommendations for the management of PCV were agreed based on this analysis and their own expert opinion.Diagnosis of PCV should be based on early-phase nodular hyperfluorescence from choroidal vasculature visualized using indocyanine green angiography. Recommended initial treatment of juxtafoveal and subfoveal PCV is either indocyanine green angiography-guided verteporfin photodynamic therapy or verteporfin photodynamic therapy plus 3 × 0.5 mg ranibizumab intravitreal injections 1 month apart. If there is incomplete regression of polyps by indocyanine green angiography, eyes should be retreated with verteporfin photodynamic therapy monotherapy or verteporfin photodynamic therapy plus ranibizumab. If there is complete regression of polyps by indocyanine green angiography, but there is leakage on fluorescein angiography and other clinical or anatomical signs of disease activity, eyes should be retreated with ranibizumab.Practical guidance on the clinical management of PCV is proposed based on expert evaluation of current evidence.

PURPOSE To report on 1-year visual, anatomical, and angiographic responses with intravitreal bevacizumab for the treatment of polypoidal choroidal vasculopathy. METHODS Patients with macula-involved, symptomatic polypoidal choroidal vasculopathy with initial best-corrected visual acuity of 20/400 or better and a minimal follow-up period of 12 months were retrospectively enrolled. Eyes were treated with intravitreal bevacizumab (2.5 mg) at baseline and monitored monthly for best-corrected visual acuity and central retinal thickness (by optical coherence tomography). Indocyanine green angiography was evaluated on a 6-month basis. Eyes were retreated on an "as-needed" basis according to visual and anatomical changes. RESULTS A total of 35 eyes of 33 patients were treated with a mean of 3.3 (range, 1-8) times of injection. Best-corrected visual acuity significantly improved from a mean logarithm of the minimum angle of resolution of 0.79 ± 0.42 at baseline (Snellen equivalent, 20/123) to 0.69 ± 0.47 (20/94), 0.66 ± 0.45 (20/87), 0.67 ± 0.44 (20/87), 0.67 ± 0.48 (20/87), and 0.67 ± 0.51 (20/87) at 1, 3, 6, 9, and 12 months, respectively (P = 0.002, 0.0003, 0.0008, 0.017, and 0.02, respectively; paired Student's t-test). Central retinal thickness also significantly improved from a mean of 297 ± 94 μm at baseline to 215 ± 58 μm, 214 ± 59 μm, 218 ± 79 μm, 213 ± 75 μm, and 221 ± 61 μm at 1, 3, 6, 9, and 12 months, respectively (all P < 0.0001, paired Student's t-test). Indocyanine green angiography showed 3 of 32 eyes (9.4%) and 5 of 31 eyes (16.1%) with completely resolved polyps and 11 of 32 eyes (34.4%) and 10 of 31 eyes (32.3%) with reduced polyps at 6 and 12 months, respectively. No systemic complication or severe local complication, such as endophthalmitis, was found. CONCLUSION Intravitreal bevacizumab therapy has a favorable outcome in improving visual acuity and macular exudative changes in patients with polypoidal choroidal vasculopathy. It can also moderately reduce polypoidal lesions on indocyanine green angiography.

Objectives To explore the relationship between preterm placental calcification and adverse pregnancy outcome, including maternal and fetal outcomes. Methods In this prospective cohort study, monthly ultrasonography was performed starting at 28 weeks' gestation to establish the diagnosis of Grade III placental calcification. Women were classified into three groups: Group 1, the early preterm group, with placental calcification found prior to 32 weeks (n = 63); Group 2, the late preterm group, with placental calcification found between 32 and 36 weeks (n = 192); and Group 3, the control group, without placental calcification noted between 28 and 36 weeks (n = 521). Women who smoked cigarettes or drank alcohol during pregnancy, or who had hypertension, diabetes, significant antenatal anemia or placenta previa were all excluded. Logistic regression analysis was used to estimate the risks of adverse pregnancy outcome in Groups 1 and 2 by calculating odds ratios (OR) with 95% CIs, adjusted by maternal age, body mass index, economic status, marital status, type of delivery and parity. Results Risks for adverse maternal outcome including postpartum hemorrhage (OR, 3.43; 95% CI, 1.251–9.388), placental abruption (OR, 6.52; 95% CI, 1.356–31.382) and maternal transfer to the intensive care unit (OR, 9.76; 95% CI, 1.826–52.195) and for adverse fetal outcomes including preterm birth (OR, 4.20; 95% CI, 1.775–9.940), low birth weight (OR, 4.58; 95% CI, 2.201–9.522), low Apgar score (OR, 6.53; 95% CI, 2.116–20.142) and neonatal death (OR, 9.04; 95% CI, 1.722–47.411) were much higher in Group 1 than in Group 3. In contrast, there were no significant differences in adverse pregnancy outcome between Groups 2 and 3. Conclusions Early preterm placental calcification is associated with a higher incidence of adverse pregnancy outcome, and may serve as an indicator of adverse maternal and fetal outcomes when noted on ultrasonography. Conversely, women with late preterm placental calcification are not at greater risk for adverse pregnancy outcome. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

We presented a rare case of a sole choroidal metastatic tumor from esophageal squamous cell carcinoma (ESCC) without other organ metastasis in Taiwan. A 43-year-old male with ESCC was referred for a 1-month history of decreased vision in his left eye. A 5.7 mm thick, yellow choroidal tumor occupied posterior pole, featured with pinpoint hyperfluorescence on angiography and subretinal fluid on optical coherence tomography. Positron emission tomography showed a singular hypermetabolic focus in the left eye. The tumor regressed with complete response and the vision preserved after radiation with total 57.60 gray applied by tomotherapy. The gastrointestinal system is the third most common metastatic origin in Taiwan while esophageal cancer metastasizing to choroid is rare. The discrepancy between the high prevalence of primary ESCC and the rareness of choroidal metastasis from ESCC is undetermined.

Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV.To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV.A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017.Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12.Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 μm, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]).After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV.clinicaltrials.gov Identifier: NCT01846273.

Purpose: To report the surgical outcome of pars plana vitrectomy (PPV) without internal limiting membrane (ILM) peeling in three highly myopic patients with macular retinoschisis and associated posterior staphyloma. Methods: We report three highly myopic patients with macular retinoschisis and foveal detachment who underwent simple PPV without ILM peeling, with long-acting gas tamponade. Main outcome evaluations included best corrected visual acuity, biomicroscopic appearance and optical coherence tomography findings. Results: Pars plana vitrectomy without ILM peeling resulted in anatomic and functional improvement in all three operated eyes for follow-up periods of ≥ 12 months. Conclusions: Pars plana vitrectomy without ILM peeling is effective for treating macular retinoschisis and foveal detachment in highly myopic eyes with posterior staphyloma. Visual and anatomic outcomes are comparable with those in previous studies in which ILM removal was performed.

Bevacizumab is a recombinant humanized monoclonal antibody with activity against vascular endothelial growth factor used in the treatment of various cancers. This case report describes a 68-year-old [corrected] male with rectal cancer who developed a vitreous haemorrhage during treatment with bevacizumab. After vitrectomy the vitreous haemorrhage subsided and visual acuity was restored. The patient had evidence of age-related macular degeneration (AMD), which may have induced the development of vitreous haemorrhage. This implies that AMD might serve as a risk factor for vitreous haemorrhage in cancer patients treated with systemic bevacizumab. Ophthalmological examination to identify AMD lesions may be necessary prior to administration of bevacizumab. Vitrectomy could serve as a management tool for bevacizumab-associated vitreous haemorrhage.

Oxidation of SiC powder in compacts of SiC/alumina/zirconia was studied between 1000 and 1200°C in air for up to 10 h. The thermogravimetric analysis showed that the weight gain due to passive SiC powder oxidation became significant at temperatures ⩾937°C. After oxidation, the particle usually consisted of a SiC core surrounded by a layer of amorphous silica. However, the amorphous layer would crystallize into cristobalite if the powders were oxidized at 1200°C for a longer time (⩾8 h). The oxidation rate decreased if cristobalite formed. The square of weight gain fraction after oxidation was linearly proportional to the oxidation time when the weight gain fraction was less than 0.34. The activation energy of the oxidation of SiC powders was estimated to be 213.1 kJ/mol.

SiC/mullite/zirconia composites were fabricated by controlling the oxidation of powder compacts of SiC, alumina, and 3 mol% yttria-stabilized zirconia. The powder compacts were first oxidized in air at 1100 °C for various times to obtain proper amounts of amorphous silica. Subsequent reaction sintering at 1500 °C for 2 h combined the amorphous silica with alumina to form mullite with planned amounts. The incorporation of 3 mol% yttria-stabilized zirconia promoted mullite formation and enhanced the densification of the samples. With ≥10 vol% of 3 mol% yttria-stabilized zirconia in the samples, the temperature of mullite formation was lowered from 1400 to 1300 °C, and mullitization was near completion after sintering at 1500 °C for 2 h. The densification of the samples depended on the contents of SiC and 3 mol% yttria-stabilized zirconia. Samples with 20 vol% SiC and 10–20 vol% 3 mol% yttria-stabilized zirconia could be sintered to reach approximately 97% of theoretical density after sintering at 1500 °C for 2 h.

Deferoxamine is a chelating agent that has extended the life expectancy of patients with thalassemia. In the 1980s, many investigators reported otologic and visual toxicity caused by deferoxamine. In July 1999 and 2 years later, the authors performed audiologic and ophthalmologic assessments in 30 transfusion-dependent patients receiving deferoxamine therapy (40-50 mg/kg per dose, subcutaneously for 8-10 hours, 4-7 days per week). In 1999, six patients (20%) had deferoxamine-related hearing impairment (>25 dB), all at high frequencies. Because the authors believed the benefits of chelation therapy outweighed the risk of ototoxicity, the dose of deferoxamine was not reduced. Two years later, the hearing impairment had not progressed in any of the patients. There was no association between ototoxicity and ferritin level. No patients had abnormalities of visual acuity or funduscopy in either 1999 or 2001. Based on this experience, deferoxamine at doses lower than 50 mg/kg/d was safe for the eyes and slightly toxic to the ears. The ototoxicity probably relates to individual susceptibility. Regular monitoring of auditory function and close follow-up of abnormal findings are recommended. According to this limited experience, reducing the dose or withdrawing deferoxamine might not be necessary if the hearing loss is stable in the face of ferritin levels above 2,000 ng/mL. Because of the relatively small patient numbers, more data are needed to confirm these conclusions.

Limbal epithelial stem cell (LSC) transplantation is a prevalent therapeutic method for patients with LSC deficiency. The maintenance of stem cell characteristics in the process of culture expansion is critical for the success of ocular surface reconstruction. Pigment epithelial-derived factor (PEDF) increased the numbers of holoclone in LSC monolayer culture and preserved the stemness of LSC in suspension culture by evidence of ΔNp63α, Bmi-1, and ABCG2 expression. BrdU pulse-labeling assay also demonstrated that PEDF stimulated LSCs proliferation. In air-lift culture of limbal equivalent, PEDF was capable of increasing the numbers of ΔNp63α-positive cells. The mitogenic effect of PEDF was found to be mediated by the phosphorylations of p38 MAPK and STAT3 in LSCs. Synthetic 44-mer PEDF (residues 78–121) was as effective as the full length PEDF in LSC expansion in suspension culture and limbal equivalent formation, as well as the activation of p38 MAPK and STAT3. In mice subjecting to mechanical removal of cornea epithelium, 44-mer PEDF facilitated corneal wound healing. Microscopically, 44-mer PEDF advanced the early proliferative response in limbus, increased the proliferation of ΔNp63α-positive cells both in limbus and in epithelial healing front, and assisted the repopulation of limbus in the late phase of wound healing. In conclusion, the capability of expanding LSC in cell culture and in animal indicates the potential of PEDF and its fragment (e.g., 44-mer PEDF) in ameliorating limbal stem cell deficiency; and their uses as therapeutics for treating corneal wound.

To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy.In this multicenter, double-masked, primarily indocyanine green angiography-guided trial, 61 Asian patients were randomized to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. Patients were administered with verteporfin PDT/placebo and initiated with three consecutive monthly ranibizumab/sham injections starting Day 1, and re-treated (Months 3-5) as per predefined criteria. The primary endpoint was the proportion of patients with indocyanine green angiography-assessed complete regression of polyps at Month 6. Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety.At Month 6, verteporfin combined with ranibizumab or alone was superior to ranibizumab monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; P0.01); mean change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety findings with either drug used alone or in combination.Verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular polypoidal choroidal vasculopathy. All treatments were well tolerated over 6 months.

Purpose To evaluate the clinical features of peripapillary choroidal cavitation (PCC) detected by optical coherence tomography (OCT). Design Retrospective, observational case series. Participants One hundred twenty-two eyes from 83 patients diagnosed with PCC by OCT database review were included in this study. Methods Stereoscopic color fundus photographs from eyes with PCC were reviewed by 2 independent ophthalmologists. They were masked to the refractive error, axial length, and OCT findings. Main Outcome Measures Chart review and data analysis included gender, age, best-corrected visual acuity (BCVA), refractive error, axial length, clinical appearance of the peripapillary area, and associated funduscopic abnormalities. Results One hundred twenty-two eyes with PCC from 83 patients were analyzed. Among the patients, 41.8% were men and 58.2% were women. The mean age was 48.2±12.6 years and mean BCVA in logarithm of the minimum angle of resolution units was 0.23±0.43. The mean refractive error in spherical equivalent was −9.03±5.11 diopters (D) and mean axial length (AL) was 27.36±2.09 mm. With respect to refractive error, 90 eyes (73.8%) were highly myopic (≥–6.00 D), 24 eyes (19.7%) had low myopia ( 1.00 D). Forty eyes (32.8%) with PCC had AL of less than 26.50 mm (mean, 25.11±1.07 mm; range, 22.51–26.42 mm). Patients with eyes with PCC that had low myopia, were emmetropic, and were hyperopic also were significantly older than patients with highly myopic eyes ( P 0.05). Stereoscopic fundus photographs demonstrated a yellow-orange, localized, well-circumscribed peripapillary lesion in 57 (46.7%) eyes with PCC. A PCC with opening was observed in 14 (26.4%) of 53 eyes with excavated myopic conus and in 5 (7.2%) of 69 eyes without excavated myopic conus ( P 0.05). Conclusions This study demonstrated that peripapillary choroidal cavitation is common and not exclusive to highly myopic eyes. The funduscopic finding of a yellow-orange peripapillary abnormality may not be evident in all eyes with demonstrable PCC by OCT. Although its pathogenesis and pathologic significance require further investigation, PCC may be a degenerative change in aging eyes. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Pigment epithelium-derived factor (PEDF) is an intrinsic anti-angiogenic factor and a potential anti-tumor agent. The tumoricidal mechanism of PEDF, however, has not been fully elucidated. Here we report that PEDF induces the apoptosis of TC-1 and SK-Hep-1 tumor cells when they are cocultured with bone marrow-derived macrophages (BMDMs). This macrophage-mediated tumor killing is prevented by blockage of TNF-related apoptosis-inducing ligand (TRAIL) following treatment with the soluble TRAIL receptor. PEDF also increases the amount of membrane-bound TRAIL on cultured mouse BMDMs and on macrophages surrounding subcutaneous tumors. PEDF-induced tumor killing and TRAIL induction are abrogated by peroxisome proliferator-activated receptor γ (PPARγ) antagonists or small interfering RNAs targeting PPARγ. PEDF also induces PPARγ in BMDMs. Furthermore, the activity of the TRAIL promoter in human macrophages is increased by PEDF stimulation. Chromatin immunoprecipitation and DNA pull-down assays confirmed that endogenous PPARγ binds to a functional PPAR-response element (PPRE) in the TRAIL promoter, and mutation of this PPRE abolishes the binding of the PPARγ-RXRα heterodimer. Also, PPARγ-dependent transactivation and PPARγ-RXRα binding to this PPRE are prevented by PPARγ antagonists. Our results provide a novel mechanism for the tumoricidal activity of PEDF, which involves tumor cell killing via PPARγ-mediated TRAIL induction in macrophages.

BACKGROUND AND OBJECTIVE: To report computer-assisted image processing for a simulated stereo effect of fundus and fluorescein angiography (FAG) digital photographs in patients with ocular fundus pathology. PATIENTS AND METHODS: Fundus red-free and FAG photographs of patients with a variety of ocular fundus pathologies were digitized and then processed with the sketch bas relief filter of Adobe Photoshop software (Adobe Systems, San Jose, CA) to create a stereo-like carved image. The images were compared with indirect slit-lamp biomicroscopy and optical coherence tomography (OCT) for accuracy and reliability in showing ocular pathology. RESULTS: The bas relief filter could transform ocular fundus and FAG photographs into images carved in relief. Dark areas of the fundus image took on the background color, and light colors used the foreground color. A variety of ocular fundus pathologies with fluorescein dye leakage in the FAG were found to be elevated lesions after image processing with the bas relief filter. Image misinterpretations might occur and can be avoided with careful examination of the ocular fundus with indirect slit-lamp biomicroscopy and OCT. CONCLUSION: Computer-assisted image processing for a simulated stereo effect of fundus and FAG photographs is a simple and assessable method of image processing that decreases the complexity of ocular fundus and FAG photographs for patient interpretation. It might be a useful tool in assisting physician–patient communication by creating pseudo three-dimensional images and highlighting ocular fundus pathology. [Ophthalmic Surg Lasers Imaging 2010;41:293–300.]

Photodynamic therapy is an effective treatment for wet form macular degeneration. Besides fluorescein angiography, optical coherence tomography can monitor fluid level lesion size changes and detect retinal pigment epithelium detachment after treatment.

We report noncontact measurements of CoSi/sub 2/ layers made using a commercial picosecond ultrasonic system. The layers were formed in a two step RTP-process beginning with samples with nominally 120 /spl Aring/ Co capped with either 150 /spl Aring/ PVD TiN, or 100 /spl Aring/ PVD Ti. The thickness, roughness and electrical resistivity of the final disilicide layers were investigated as functions of the first anneal temperature. The results indicate that the TiN-capped process yields a significantly smoother and more conductive disilicide film than the Ti-capped process over a wide range of first anneal temperatures.