Evolución del cáncer papilar de tiroides en acromegalia: serie de casos / Evolution of papillary thyroid cancer in acromegaly: case series / Evolução do câncer papilar de tireoide na acromegalia: série de casos

Introducción: La acromegalia se produce por un adenoma hipofisario somatotropo, que secreta una excesiva producción de GH e IGF1, se relaciona con mayor riesgo de tumores malignos, no guardando asociación con un patrón especifico de presentación y el objetivo de este estudio es analizar la evolución del cáncer papilar de tiroides en acromegalia. Casos: Se trata de tres pacientes diagnosticados de carcinoma papilar de tiroides (CPT) con diferente pronóstico, con características faciales, y sintomatología como cefalea, alteraciones del campo visual, alteraciones menstruales, que condujeron a la realización de estudios bioquímicos, de imagen y al diagnóstico de acromegalia. Evolución: La aparición de cáncer de tiroides varía en el tiempo de evolución de la acromegalia, en dos de los casos lo antecedió y en el tercero se presentó a la par con esta patología. La respuesta al tratamiento en el CPT es indeterminada en la primera paciente y \excelente en los otros casos; en una paciente se alcanzó remisión. Conclusiones: la coexistencia de acromegalia con cáncer tiroides es posible, que los cambios acrales, faciales y la sintomatología expansiva del tumor conducen al diagnóstico de acromegalia y que la identificación de malignidades no guarda relación con la evolución de la enfermedad.

Introduction: Acromegaly is produced by a somatotropic pituitary adenoma, which secretes an excessive production of GH and IGF1, it is related to a higher risk of malignant tumors, not being associated with a specific pattern of presentation and the objective of this study is to analyze the evolution of papillary thyroid cancer in acromegaly. Cases report: These were three patients diagnosed with CPT with different prognosis, with facial characteristics, and symptoms such as headache, visual field alterations, menstrual alterations, which led to biochemical and imaging studies and the diagnosis of acromegaly. Evolution: The appearance of thyroid cancer in the time of evolution of acromegaly is different, in two of the cases it preceded it and in the third it was presented alongside this pathology. The re-sponse to treatment in CPT is indeterminate in the first patient and excellent in the other cases; re-mission was achieved in one patient. Conclusions: It is concluded that the coexistence of acromegaly with thyroid cancer is possible, that the acral and facial changes and the expansive symptomatology of the tumor lead to the diag-nosis of acromegaly and that the identification of malignancies is not related to the evolution of the disease.

Introdução: A acromegalia é produzida por um adenoma hipofisário somatotrópico, que secreta uma produção excessiva de GH e IGF1, está relacionada a um maior risco de tumores malignos, não estando associada a um padrão específico de apresentação e o objetivo deste estudo é analisar a evolução de câncer papilar de tireoide na acromegalia. Casos: São três pacientes com diagnóstico de carcinoma papilífero de tireoide (CPT) de prognóstico diferente, com características faciais e sintomas como cefaleia, alterações do campo visual, alterações menstruais, que levaram à realização de estudos bioquímicos, de imagem e diagnóstico de acromegalia. Evolução: O aparecimento do câncer de tireoide varia com o tempo de evolução da acromegalia, em dois dos casos ela o precedeu e no terceiro foi apresentado concomitantemente a esta patologia. A resposta ao tratamento no CPT é indeterminada no primeiro paciente e excelente nos demais casos; a remissão foi alcançada em um paciente. Conclusões: a coexistência de acromegalia com câncer de tireoide é possível, que as alterações acrais e faciais e a sintomatologia expansiva do tumor levam ao diagnóstico de acromegalia e que a identificação de neoplasias não está relacionada à evolução da doença.

¿Existe una asociación entre polimorfismos de inserción/supresión - 2549 en la región promotora del gen que codifica la vegfa como factor de riesgo y el descargo espontáneo idiopático recurrente en una muestra de mujeres jordanas? / Is there an association between - 2549 Insertion/ Deletion Polymorphisms in the Promotor Region of the Gene Encoding for VEGFA as a Risk Factor and the Idiopathic Recurrent Spontaneous Miscarriage in a sample of Jordanian Women?

Antecedentes: al menos el 50% de los casos de aborto espontáneo recurrente son etiológicamente idiopáticos. Recientemente se han propuesto varios polimorfismos genéticos como factores de riesgo de susceptibilidad a la pérdida del embarazo. Objetivo: El objetivo del presente estudio de casos y controles es establecer la asociación entre los polimorfismos funcionales −2549 I / D en la región promotora del gen del factor de crecimiento endotelial vascular A (VEGFA) y el aborto espontáneo recurrente idiopático (IRSM) en una muestra de las mujeres jordanas. Sujetos y métodos: Se reclutaron 328 sujetos, 103 y 98 mujeres con IRSM primario y secundario, respectivamente, se seleccionaron 127 mujeres normales como grupo de control. Se aisló ADN genómico de una muestra de sangre extraída de cada participante, luego, se genotipificaron los polimorfismos I / D -2549 del gen VEGFA mediante la reacción en cadena de la polimerasa (PCR). Resultados: Los resultados obtenidos revelaron que el polimorfismo ID y el alelo D de VEGFA -2549 polimorfismos I / D tienen las frecuencias más altas en pacientes IRSM tanto primario como secundario, sin diferencia significativa entre los tres grupos en cuanto a polimorfismos y frecuencias alélicas, pacientes con DD + ID Los modelos genéticos tienen una asociación positiva con un alto riesgo de IRSM versus el modelo II, y los pacientes con alelo D son más propensos a tener IRSM que los que tienen el alelo I, no hay diferencia significativa en la asociación de polimorfismos VEGFA -2549 I / D con IRSM en los tres modelos genéticos de los pacientes con IRSM primario y secundario. Conclusión: los pacientes con modelo genético ID de polimorfismos I / D -2549 en la región promotora del gen VEGFA y el alelo D tienen mayor riesgo de IRSM

Background: At least 50% of the cases of recurrent spontaneous miscarriage are aetiologically idiopathic. Recently various genetic polymorphisms have been proposed as susceptibility risk factors for pregnancy loss. Objective: The aim of the present case control study is to establish the association between the functional −2549 I/D polymorphisms in the promoter region of the vascular endothelial growth factor A (VEGFA) gene and idiopathic recurrent spontaneous miscarriage (IRSM) in a sample of Jordanian women. Subjects and methods: 328 subjects were recruited, 103 and 98 women with primary and secondary IRSM, respectively, 127 normal women were selected as a control group. Genomic DNA was isolated from a blood sample withdrawn from each participant, then, -2549 I/D polymorphisms of VEGFA gene were genotyped by Polymerase Chain Reaction (PCR). Results: The obtained results revealed that ID polymorphism and D allele of VEGFA -2549 I/D polymorphisms have the highest frequencies in both primary and secondary IRSM patients, no significant difference between the three groups regarding polymorphisms and allele frequencies, patients with DD+ID genetic models have positive association with high risk of IRSM versus II model, and patients with D allele are more liable to have IRSM than those having I allele, no significant difference in the association of VEGFA -2549 I/D polymorphisms with IRSM in the three genetic models of the primary and secondary IRSM patients. Conclusion: patients with ID genetic model of -2549 I/D polymorphisms in the VEGFA gene's promotor region and D allele have higher risk for IRSM.

Dexamethasone intravitreal implant for macular edema: a pilot study in a public health center

INTRODUCTION: Macula edema consists in one of the most common causes of visual impairment. OBJECTIVE: To evaluate the safety and efficacy of continuous release of 0.7 mg dexamethasone (using implantable device) for treatment of macular edema. METHODS: Cross-sectional observational study of 16 patients treated with 0.7 mg dexamethasone intraocular implant. Visual acuity, intraocular pressure and central macular thickness were recorded at baseline, 1-month and 3-month follow-up. RESULTS: 15 eyes of 13 patients were included. Most eyes (n=9) improve visual acuity from baseline at 1-month follow-up; this improvement persisted through 3-monyh follow-up in six eyes. The central macular thickness decreased in the majority of the subjects at 1-month (n=12) and at 3-month (n=10) follow-up. Three eyes presented with elevated intraocular pressure. CONCLUSION: Dexamethasone implant can both reduce the risk of vision loss and improve anatomical features of macular edema due to several pathologies studied. This implant may be used safely and should be considered a therapeutic option to Brazilian Public Health System.

Changes in the Ganglion Cell-inner Plexiform Layer after Consecutive Intravitreal Injections of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration Patients

New Systemic Therapies for Advanced Hepatocellular Carcinoma / 대한소화기학회지

Since the approval of sorafenib for patients with advanced hepatocellular carcinoma (HCC) in 2007, many drugs have failed in the first and second-line setting. Fortunately, during the recent 2 years, between 2017 and 2018, four drugs (regorafenib, lenvatinib, cabozantinib, and ramucirumab) were found to be effective and tolerable for patients with HCC as the first- or second-line therapy. Regorafenib, a multi-kinase inhibitor, has a similar structure to sorafenib, and was shown to improve the survival of patients who progressed after sorafenib treatment compared to the placebo control. According to the phase III trial of regorafenib, it became the first approved systemic therapy for patients with progression after sorafenib. Lenvatinib is also a tyrosine kinase inhibitor (TKI), and in a phase III trial comparing sorafenib and lenvatinib, the primary end-point of non-inferior survival was met. Based on the trial results, lenvatinb has become another systemic therapy for treatment-naïve patients with advanced HCC. Cabozantinib is a dual inhibitor of Mesenchymal-Epithelial Transition factor/Vascular Endothelial Growth Factor Receptor2, and was shown to prolong the overall survival in patients who progressed after sorafenib compared to the placebo. Ramucirumab is a monoclonal antibody to inhibit a single target of VEGFR2. First, this drug failed to improve the survival of patients who progressed after sorafenib failure. On the other hand, it was effective in patients with baseline AFP ≥400 ng/mL. In a subsequent clinical trial that enrolled only patients with AFP ≥400 ng/mL, ramucirumab was also found to improve the overall survival compared to placebo. Thus, ramucirumab became the first biomarker-driven systemic treatment. Another category of drugs that are attracting considerable interest are immune checkpoint inhibitors, such as anti-programmed cell death protein (PD) 1 or anti-PD-ligand 1. This review provides a synopsis of new systemic therapies, including TKI, monoclonal antibody, and immune-oncology drugs.

Current state and outlook for drug repositioning anticipated in the field of ovarian cancer / 부인종양

Ovarian cancer is the seventh most common cancer and the eighth most common cause of cancer mortality in women. Although standard chemotherapy is the established treatment for ovarian cancer, the prognosis remains poor, and it is highly anticipated that new drugs will be developed. New drugs, such as humanized anti-vascular endothelial growth factor monoclonal antibodies and poly ADP-ribose polymerase inhibitors, are expected to improve clinical outcomes of ovarian cancer. However, long-term, costly research is required to develop such new drugs, and soaring national healthcare costs are becoming a concern worldwide. In this social context, drug repositioning, wherein existing drugs are used to develop drugs with new indications for other diseases, has recently gained attention. Because trials have already confirmed the safety in humans and the pharmacokinetics of such drugs, the development period is shorter than the conventional development of a new drug, thereby reducing costs. This review discusses the available basic experimental and clinical data on drugs used for other types of cancer for which drug repositioning is anticipated to repurpose the drug for the treatment of ovarian cancer. These include statins, which are used to treat dyslipidemia; bisphosphonate, which is used to treat osteoporosis; metformin, which is used to treat diabetes; non-steroidal anti-inflammatory drugs; ivermectin, an antiparasitic agent; and itraconazole, an anti-fungal agent. These drugs will play an important role in future drug repositioning strategies for ovarian cancer. Furthermore, drug repositioning is anticipated to extend not only to ovarian cancer treatment but also to ovarian cancer prevention.

Meta-analysis of Intravitreal Injection of Anti-vascular Endothelial Growth Factors for Diabetic Macular Edema

PURPOSE: Intravitreal aflibercept, ranibizumab, bevacizumab, and dexamethasone are the most widely used drugs in the treatment of diabetic macular edema (DME). The aim of this study was to compare the efficacy and safety of anti-vascular endothelial growth factors and dexamethasone for the treatment of DME. METHODS: There were nine previous systematic reviews on this topic; we updated these high-quality reviews. Seven studies were added to two studies following a literature search. Efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ≥ 15 in the Early Treatment Diabetic Retinopathy Study [ETDRS]), and 3) proportion of patients who experienced worsening vision (a decrease in BCVA of ≥ 15 in the ETDRS). Safety outcomes included systemic adverse events and ocular-related adverse events. RESULTS: The mean difference in the BCVA for ranibizumab versus bevacizumab treatment was 0.16 (95% confidence interval [CI]: −0.02, 0.34), and that for ranibizumab versus aflibercept was −0.08 (95% CI: −0.26, 0.10). The mean difference in the change of BCVA for aflibercept versus ranibizumab was −0.20 (95% CI: −0.40, −0.01), and that for aflibercept versus bevacizumab was −0.34 (95% CI: −0.53, −0.14). Other efficacy outcomes showed similar trends, and there was no significant difference between treatments. There was also no significant difference in both systemic and ocular adverse events rates between the treatments. CONCLUSIONS: In DME patients, the efficacy of aflibercept was found to be higher with respect to BCVA changes compared with ranibizumab or bevacizumab. However, there were no significant difference in terms of visual acuity improvement or visual acuity of more than 15 letters, nor in terms of anti-vascular endothelial growth factors (as a safety outcome).

Influence of Axial Length on Recurrence of Wet Age-related Macular Degeneration after Initial Treatment

PURPOSE: To evaluate the influence of axial length on the recurrence of wet age-related macular degeneration (AMD) after anti-vascular endothelial growth factor therapy. METHODS: A retrospective review of the medical records for 45 eyes of 45 patients, who were diagnosed with neovascular AMD and treated with three ranibizumab injections per month, was performed. Axial length was compared between eyes with (recurrence group) and without (no recurrence group) recurrence of fluid during a 12-month follow-up period. In eyes with recurrence, the association between axial length and the time between the third injection and the first recurrence was also evaluated. RESULTS: The axial length was measured at a mean of 20.6 ± 10.1 months after the diagnosis of neovascular AMD. The mean axial length at that time was 23.33 ± 0.90 mm. The mean axial length was 23.29 ± 0.96 mm in the recurrence group (n = 30) and 23.40 ± 0.79 mm in the no-recurrence group (n = 15). There was no difference in the axial length between the two groups (p = 0.709). In the recurrence group, the period between the third injection and the first recurrence was not associated with axial length (p =0.582). CONCLUSIONS: There was no significant difference in axial length between eyes with and without recurrence after initial treatment for wet AMD. In addition, the time to first recurrence was not significantly associated with axial length. Because the present study was retrospective and the sample size was small, further prospective studies with a better design are needed to more accurately assess the influence of axial length.

Intravitreal Injection of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration: a Systematic Review

PURPOSE: To compare the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab, and aflibercept for the treatment of new patients with age-related macular degeneration (AMD). METHODS: We conducted an update of the most recent and high quality systematic reviews (Canadian Agency for Drug Technology in Health [CADTH] 2016). Three randomized clinical trials were added to 13 trials identified from the CADTH report. The efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ≥ 15 on Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and 3) proportion of patients who experienced worsening of vision (decrease in BCVA of ≥ 15 ETDRS letters). In addition, safety outcomes included systemic adverse events and ocular-related adverse events. To analyze the outcomes of 16 randomized controlled trials, we conducted meta-analyses on the outcome measures. RESULTS: There was no significant difference in efficacy outcomes among anti-vascular endothelial growth factor (anti-VEGF) drugs. The mean difference in BCVA between ranibizumab and bevacizumab was 0.33 (95% confidence interval [CI]: −1.29, 1.95), and the odds ratio (OR) for a vision gain in the BCVA of ≥ 15 ETDRS letters for the ranibizumab versus aflibercept treatment was 1.02 (95% CI: 0.80, 1.30). There was also no significant difference in safety outcomes, except in terms of arterial thromboembolic events (ranibizumab vs. bevacizumab; OR: 2.15; 95% CI: 1.04, 4.41). CONCLUSIONS: The efficacy of anti-VEGF drugs for AMD patients was not significantly different. The safety of the drugs was also not significantly different, except in terms of arterial thromboembolic events.

Status of Usage of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration

PURPOSE: To evaluate the current use of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) in patients with age-related macular degeneration (AMD). METHODS: We analyzed the number and medical costs of patients with AMD diagnosed by the National Health Insurance Corporation (2007–2016). We also analyzed the number and medical costs of such patients who received anti-VEGF treatment, and analyzed the frequency, period of use, and average medical cost of anti-VEGF use in AMD patients. Finally, we evaluated the use of anti-VEGF injections for new AMD patients. RESULTS: The number of patients with AMD was 236,158 in 2009 and 537,528 in 2016, which represented a 2.3-fold increase over 8 years. Of these, the number of patients undergoing anti-VEGF therapy increased steadily from 9,961 in 2009 to 35,762 in 2016. The mean number of cycles of ranibizumab or aflibercept per patient was 4.87 ± 3.37, and the mean interval between treatments was 2.89 months. On average, 6.2 injections were performed in the first year of diagnosis, and the frequency of use decreased with time, with an average of 1.2 cycles after 4 years of diagnosis. Among all AMD patients in 2016, the total medical cost of those treated with anti-VEGF was 76.9 billion won, and the average medical cost per person was 2,162,145 won. CONCLUSIONS: The use of two drugs, ranibizumab and aflibercept, as reflected in public health insurance claims, steadily increased over the study period. Notably, there was a tendency to substitute aflibercept for ranibizumab.

Use of Anti-vascular Endothelial Growth Factors for Diabetic Retnopathy: National Health Insurance Claims Data

PURPOSE: To evaluate the current use of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with diabetic retinopathy. METHODS: We determined the current number of diabetic retinopathy patients and their medical expenditure using National Health Insurance Service claims data (2007-2016). We also analyzed the medical costs of patients with diabetic retinopathy who received anti-VEGF treatment, including ranibizumab and aflibercept. We then evaluated aspects of the use of anti-VEGF injections, such as frequency and intervals, in newly diagnosed diabetic retinopathy patients who received anti-VEGF treatment, along with their medical costs. RESULTS: The number of patients with diabetic retinopathy was 397,956 in 2009 and 721,310 in 2016, a 1.8-fold increase over 8 years. Of these, the number of patients undergoing anti-VEGF therapy was 4,283 in 2015 and 4,270 in 2016. Of the diabetic retinopathy patients in 2016, the total medical cost of those treated with anti-VEGF was 1.5 billion won, and the average medical cost per person was 3,531,064 won. CONCLUSIONS: Based on the National Health Insurance claims data, the use of ranibizumab and aflibercept is increasing. The results of this study suggest that diabetic retinopathy will become an important public health issue.

Budget Impact Analysis of Anti-vascular Endothelial Growth Factor in Patients with Diabetic Macular Edema

PURPOSE: This study investigated the optimal strategy to minimize budgetary constraints on National Health Insurance (NHI) services, while maximizing the number of diabetic macular edema (DME) patients who receive anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: We estimated the potential budget impact of anti-VEGF treatments in DME patients based on perceived upcoming changes in reimbursement fees over the next 5 years (2018–2022). Four scenarios were evaluated: (1) current anti-VEGF treatment patterns, (2) the hypothetical reimbursement fee, (3) the introduction of a new molecule similar to current anti-VEGF treatments, and (4) the prescription of an off-label drug, bevacizumab. The number of patients, anti-VEGF treatments, and medical costs for each scenario were calculated using claims data from the Korean NHI system and anti-VEGF prescription data from a single hospital. RESULTS: The potential budget impact of anti-VEGF injections in patients with DME over the next 5 years was estimated to be about 97.7 billion and 106.2 billion KRW for scenarios 1 and 2, respectively. In scenario 3, in which a biosimilar product to anti- VEGF is used, the estimated budget of the NHI system would be approximately 98.4 billion KRW. If an off-label drug is reimbursed, roughly 79.5 billion KRW will be required for the NHI system's budget. CONCLUSIONS: If the revised fee structure for AMD patients is similarly applied to anti-VEGF injections for DME patients, the NHI fiscal requirements will increase disproportionately over the next 5 years compared to current reimbursement conditions. Given the growth of DME patients in toda's patient population, the use of a biosimilar or off-label drug is a financially viable alternative to reduce the overall burden on the NHI system.

Healthcare Utilization and Treatment Patterns in Diabetic Macular Edema in Korea: a Retrospective Chart Review

BACKGROUND: Limited data exist on real-world treatment patterns for diabetic macular edema (DME) in Korea. In this study, we investigated DME treatment patterns from 2009 to 2014 and the impact of baseline treatment on healthcare resource utilization and visual acuity (VA) outcomes. METHODS: A retrospective cohort chart review of DME patients treated at 11 hospital ophthalmology clinics between January 1, 2012 and December 31, 2013 was conducted. We collected data on demographics, healthcare resource utilization (clinic visits, treatment visits, and visits for ocular investigations), distribution of DME treatments, and VA. RESULTS: Overall, 522 DME patients (men, 55.2%; mean age, 59 years; mean HbA1c [n = 209], 8.4%) with 842 DME eyes were evaluated. For all treatments, healthcare resource utilization was significantly higher during the first 6 months versus months 7–12, year 2, or year 3 (P ≤ 0.001), but was highest for patients whose first treatment was an anti-vascular endothelial growth factor (VEGF) treatment (visits/quarter; anti-VEGF, 1.9; corticosteroids, 1.7; laser, 1.4). Use of macular laser therapy decreased (44% to 8%), whereas use of anti-VEGF injections increased (44% to 69%) during the study period. However, VA improvement was not commensurate with healthcare resource utilization of anti-VEGF treatment (mean VA gain, 2.7 letters). CONCLUSION: A trend toward increasing use of intravitreal anti-VEGF injections for DME treatment was observed in Korea. However, the frequency of dosing and monitoring was lower in clinical practice versus major clinical trials, which may have led to the less-than-favorable improvements in visual outcomes.

Switching to Aflibercept in Diabetic Macular Edema after Unsatisfactory Response to Other Anti-vascular Endothelial Growth Factor Drugs

PURPOSE: To evaluate the efficacy of switching to aflibercept in diabetic macular edema (DME) with suboptimal response to previous anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: A prospective interventional case series study recruited patients from a single center diagnosed with DME with suboptimal response to anti-VEGF injections. Three consecutive monthly injections of aflibercept were performed. The primary outcome measure was mean change in visual acuity after switching to aflibercept. RESULTS: Forty-two patients (42 eyes) were included. Baseline logarithm of the minimum angle of resolution (logMAR) visual acuity was 0.87 ± 0.23 and improved significantly to 0.62 ± 0.29, 0.56 ± 0.34, and 0.46 ± 0.35 at 1, 2, and 3 months, respectively, after the first injection. Mean baseline retinal thickness was 451.57 ± 107.09 µm and decreased significantly at 1, 2, and 3 months after switching to aflibercept (346.52 ± 79.03, 328.24 ± 81.98, and 313.71 ± 85.79 µm, respectively). Both visual improvement and mean change in retinal thickness were significant in patients with pre-aflibercept best-corrected visual acuity less than 1.0 logMAR but were not significant in patients with best-corrected visual acuity more than 1.0 logMAR. CONCLUSIONS: Switching to aflibercept in DME patients with an unsatisfactory response to previous anti-VEGF injections provided acceptable short-term visual and retinal architectural improvement.

Novel Findings of Polypoidal Choroidal Vasculopathy via Optical Coherence Tomography Angiography

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.

Outcomes of Anti-vascular Endothelial Growth Factor Treatment for Foveal Serous Retinal Detachment Associated with Inferior Staphyloma

PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) treatment of eyes with foveal serous retinal detachment (SRD) associated with inferior staphyloma and to investigate choroidal thickness changes following anti-VEGF therapy. METHODS: In this observational case series, eyes with inferior staphyloma accompanied by foveal SRD were treated with a single intravitreal anti-VEGF injection, followed by further injections as needed. Changes in height and width of subretinal fluid (SRF) and visual acuity after treatment were assessed. Choroidal thickness was measured at the subfovea, 1.5 mm superior and inferior to the fovea using enhanced depth imaging optical coherence tomography at baseline and 1 month after initial anti-VEGF therapy. RESULTS: Six eyes from six patients were included. One month after the initial injection, the mean SRF height and width had decreased significantly from 112.5 ± 40.1 to 44.5 ± 48.7 µm (p = 0.046) and from 1,401.8 ± 627.3 to 690.7 ± 634.7 µm (p = 0.028), respectively. Mean choroidal thickness at the superior point decreased from 218.7 ± 59.3 to 200.5 ± 61.0 µm (p = 0.046). SRF resolved completely in three of the six eyes (50%) with a mean of 6.8 ± 5.9 injections (range, 1 to 15). All eyes experienced at least one recurrence of exudation, at a mean interval of 4.8 months. Mean visual acuity improvement was 0.17 logarithm of the minimum angle of resolution units at a mean of 28.7 months follow-up. CONCLUSIONS: Anti-VEGF therapy resulted in an SRF decrease and modest visual improvement in eyes with foveal SRD associated with inferior staphyloma. Reduction in superior choroidal thickness appeared to contribute to the clinical improvements that were observed.

Refractive Outcomes of 4-Year-old Children after Intravitreal Anti-vascular Endothelial Growth Factor versus Laser Photocoagulation for Retinopathy of Prematurity

PURPOSE: To compare long-term refractive outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) versus laser photocoagulation treatment for retinopathy of prematurity (ROP). METHODS: A total of 52 eyes from 27 ROP patients treated at two tertiary referral-based hospitals from August 2006 to December 2013 were reviewed. The primary outcome was refractive error measured at the age of 4 years, accounting for within-patient inter-eye correlation. Secondary outcomes included the recurrence rate and treatment complications. RESULTS: The mean age at refraction was 4.7 ± 0.3 years in the laser group (n = 30) and 4.4 ± 0.3 years in the anti-VEGF group (n = 22). No significant differences were noted in gestational age, birthweight, post-menstrual age at treatment, or ROP stage/zone distribution between groups. Mean spherical equivalent was also not significantly different (−1.0 diopters in the laser group and −0.3 diopters in the injection group, p = 0.603). Clustered regression analysis revealed that only gestational age was significantly correlated with mean spherical equivalent (p < 0.001; 95% confidence interval, −0.007 to −0.002). Recurrence was noted in four eyes (13.3%) in the laser group, but this difference was not significant (p = 0.128). There were no major systemic complications reported in either group. CONCLUSIONS: Treatment type, whether laser or anti-VEGF injection, does not appear to influence long-term refractive outcomes in ROP. Concern regarding refractive outcomes should not be the most important factor when selecting ROP treatment modality.

Factor de crecimiento endotelial vascular durante la foliculogénesis en el ovario humano / Vascular endotelial growth factor during folliculogenesis in the human ovary

El objetivo de la investigación fue establecer el modelo de expresión de factor de crecimiento endotelial (VEGF) durante la foliculogénesis en el ovario humano. La investigación fue aprobada por el Comité de Éticade la Facultad de Medicina de la Universidad del Zulia. Se recogieron muestras de tejido ovárico de mujeres en edad reproductiva sometidas a cirugía ginecológica por enfermedad benigna. Las células de la granulosa luteinizada y el líquido folicular se obtuvieron de mujeres sometidas a la recuperación de oocitos para la fertilización in vitro. Utilizando inmunohistoquímica, se localizó el VEGF en las células de la granulosa y la teca de los folículos antrales y en las células luteínicas del cuerpo lúteo. También se identificó en el líquido folicularhumano. El VEGF y el ARN mensajero se identificaron por inmunohistoquímica en la granulosa luteinizada del ovario. La hibridación in situ demostró la expresión del ARN mensajero del VEGF en las células de luteína del cuerpo lúteo. Se concluye que las células de la granulosa y la teca de los folículos antrales y las células de luteína del cuerpo lúteo son fuentes de VEGF en el ovario humano. Su expresión es paralela al patrón de la angiogénesis ovárica y su presencia en el líquido folicular humano sugiere un posible papel en la formación de este.

The objective of the research was to establish the expression model of endothelial growth factor during folliculogenesis in the human ovary. The research was approved by the Ethics Committee of the Faculty of Medicine of LaUniversity of Zulia. Ovarian tissue samples were collected from women of reproductive age who underwent gynecological surgery for benign disease. Luteinized granulosa cells and follicular fluid were obtained from women undergoing oocyte recovery for in vitro fertilization. Using immunohistochemistry, VEGF was localized in the granulosa and teak cells of the antral follicles and in the luteal cells of the corpus luteum. It was also identified in the human follicular fluid. VEGF and messenger RNA were identified by immunohistochemistry in the luteinized granulosa of the ovary. In situ hybridization demonstrated the expression of VEGF messenger RNA in the lutein cells of the corpus luteum. It is concluded that the granulosa and teak cells of the antral follicles and the lutein cells of the corpus luteum are sources of VEGF in the human ovary. Its expression is parallel to the pattern of ovarian angiogenesis and its presence in the human follicular fluid suggests a possible role in the formation of it.

Anti-vascular Endothelial Growth Factor Treatment of Retinopathy of Prematurity: Efficacy, Safety, and Anatomical Outcomes

PURPOSE: To investigate the efficacy, safety, and anatomical outcomes associated with intravitreal anti-vascular endothelial growth factor (VEGF) treatment of retinopathy of prematurity (ROP). METHODS: We performed a retrospective review of intravitreal anti-VEGF (bevacizumab or ranibizumab) treatment of 153 eyes (83 infants) diagnosed with ROP at two tertiary hospitals from June 2011 to January 2017. The primary outcome was the rate of recurrence requiring additional treatment; secondary outcomes included incidence of major complications and final refractive error. RESULTS: A total of 101 eyes were treated with bevacizumab, and 52 with ranibizumab. The bevacizumab and ranibizumab groups were characterized by mean birthweights of 941.8 ± 296.1 and 1,257.7 ± 514.5 g, gestational ages at birth of 26.9 ± 1.9 and 28.1 ± 3.2 weeks, and postmenstrual ages at treatment of 40.4 ± 2.4 and 39.2 ± 2.3 weeks, respectively. The two groups differed significantly in birthweights and gestational ages at birth, but not in postmenstrual ages at treatment. The mean follow-up duration was 30.9 ± 18.4 months for the bevacizumab group, and 13.9 ± 12.5 months for ranibizumab. More cases were classified as zone 1 ROP in the ranibizumab group (44.2% vs. 11.9%, p < 0.001). Major surgical interventions included scleral encircling and vitrectomy (one and two eyes, respectively, both in the bevacizumab group). Retinal detachment was noted in one eye treated with bevacizumab. There was no significant difference in the most recent spherical equivalence for the two groups (+0.10 ± 3.66 and +0.22 ± 3.00 diopters for bevacizumab and ranibizumab, respectively). Univariable analysis revealed that only ROP stage influenced the occurrence of major complications (odds ratio, 9.046; p = 0.012). CONCLUSIONS: Intravitreal anti-VEGF treatment of ROP with both bevacizumab and ranibizumab achieved stable retinal vascularization with a low rate of complications and recurrence. Ranibizumab achieved similar anatomical outcomes as bevacizumab, without additional risk for major complications.

Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.