International meeting on Wolf-Hirschhorn syndrome: Update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay.

"An International Meeting on Wolf-Hirschhorn Syndrome (WHS)" was held at The University Hospital La Paz in Madrid, Spain (October 13-14, 2017). One hundred and twenty-five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes. These proceedings will review the major points of discussion.

Anti-leishmanial effect of spiro dihydroquinoline-oxindoles on volume regulation decrease and sterol biosynthesis of Leishmania braziliensis.

Diverse spiro dihydroquinoline-oxindoles (JS series) were prepared using the BF3•OEt2-catalyzed imino Diels-Alder reaction between ketimine-isatin derivatives and trans-isoeugenol. Ten spiro-oxiindole derivatives were selected and evaluated at different stages of the life cycle of Leishmania braziliensis parasites, responsible for cutaneous leishmaniasis in South America. Among them, the 8'-ethyl-4'-(4-hydroxy-3-methoxyphenyl)-3'-methyl-3',4'-dihydro-1'H-spiro[indoline-3,2'-quinolin]-2-one called JS87 was able to inhibit the growth of promastigotes without affecting the mammalian cells viability, and to decrease the number of intracellular amastigotes of L. braziliensis. This spiro compound was found to act through the alteration of parasite internal regulation by disrupting the regulatory volume decrease (RVD), and to affect the sterol biosynthetic pathway at level of squalene epoxidase (SE) enzyme. These results revealed that the spiro annulation between quinoline and oxindole scaffolds enhances the anti-leishmanial activity, and could assist in the development of potent quinoline-oxindole hybrids against Leishmania braziliensis, the main etiological agent of cutaneous leishmaniasis in South America.

EAGLE-A Scalable Query Processing Engine for Linked Sensor Data.

Recently, many approaches have been proposed to manage sensor data using semantic web technologies for effective heterogeneous data integration. However, our empirical observations revealed that these solutions primarily focused on semantic relationships and unfortunately paid less attention to spatio-temporal correlations. Most semantic approaches do not have spatio-temporal support. Some of them have attempted to provide full spatio-temporal support, but have poor performance for complex spatio-temporal aggregate queries. In addition, while the volume of sensor data is rapidly growing, the challenge of querying and managing the massive volumes of data generated by sensing devices still remains unsolved. In this article, we introduce EAGLE, a spatio-temporal query engine for querying sensor data based on the linked data model. The ultimate goal of EAGLE is to provide an elastic and scalable system which allows fast searching and analysis with respect to the relationships of space, time and semantics in sensor data. We also extend SPARQL with a set of new query operators in order to support spatio-temporal computing in the linked sensor data context.

Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca2+ Channel.

Leishmania donovani is the causing agent of visceral leishmaniasis, a common infection that affects millions of people from the most underdeveloped countries. Miltefosine is the only oral drug to treat infections caused by L. donovani Nevertheless, its mechanism of action is not well understood. While miltefosine inhibits the synthesis of phosphatidylcholine and also affects the parasite mitochondrion, inhibiting the cytochrome c oxidase, it is to be expected that this potent drug also produces its effect through other targets. In this context, it has been reported that the disruption of the intracellular Ca2+ homeostasis represents an important object for the action of drugs in trypanosomatids. Recently, we have described a plasma membrane Ca2+ channel in Leishmania mexicana, which is similar to the L-type voltage-gated Ca2+ channel (VGCC) present in humans. Remarkably, the parasite Ca2+ channel is activated by sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the present work we demonstrated that, similarly to sphingosine, miltefosine is able to activate the plasma membrane Ca2+ channel from L. donovani Interestingly, nifedipine, the classical antagonist of the human channel, was not able to fully block the parasite plasma membrane Ca2+ channel, indicating that the mechanism of interaction is not identical to that of sphingosine. In this work we also show that miltefosine is able to strongly affect the acidocalcisomes from L. donovani, inducing the rapid alkalinization of these important organelles. In conclusion, we demonstrate two new mechanisms of action of miltefosine in L. donovani, both related to disruption of parasite Ca2+ homeostasis.

Aryl- or heteroaryl-based hydrazinylphthalazine derivatives as new potential antitrypanosomal agents.

A series of twenty phthalazinyl-hydrazones were synthesized and tested as potential anti-Trypanosoma cruzi agents. The phthalazines containing 5-nitroheteroaryl moiety 3l and 3m displayed an excellent in vitro antitrypanosomal profile, exhibiting low micromolar EC50 values against proliferative epimastigote of T. cruzi and minimal toxicity toward Vero cells. These derivatives were more potent than the reference drug benznidazole against the epimastigote stage of the parasite. Structure-property analysis indicates that the highly conjugated 5-nitroheteroaryl moiety connected to the phthalazin scaffold play an important role in the antichagasic activity of these phthalazines. The decrease on the mitochondrial dehydrogenase activity and significant ROS production found for the parasites treated with 3l and 3m suggest that both nitro-derivatives can act through an oxidative stress mechanism.

INTRAVITREAL BEVACIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION: 5-Year Results of The Pan-American Collaborative Retina Study Group.

PURPOSE: To report the long-term anatomical and functional outcomes of patients with choroidal neovascularization secondary to age-related macular degeneration treated with intravitreal bevacizumab (IVB). METHODS: Retrospective case series. Patients diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration that were treated with at least 1 intravitreal injection of 1.25 mg of IVB and had a minimum follow-up of 60 months. Patients underwent best-corrected Snellen visual acuity testing, optical coherence tomography, and ophthalmoscopic examination at baseline and follow-up visits. RESULTS: Two hundred and forty-seven consecutive patients (292 eyes) were included. The mean number of IVB injections per eye was 10.9 ± 6.4. At 5 years, the BCVA decreased from 20/150 (logMAR 0.9 ± 0.6) at baseline to 20/250 (logMAR 1.1 ± 0.7) (P = <0.0001). The mean CMT decreased from 343.1+ 122.3 µm at baseline to 314.7 ± 128.8 µm at 60 months of follow-up (P = 0.009). Geographic atrophy (GA) was observed at baseline in 47 (16%) of 292 eyes. By 5 years, GA developed or progressed in 124 (42.5%) of 292 eyes (P < 0.0001). CONCLUSION: The early visual gains obtained from IVB were not maintained at 5 years of follow-up. In addition, IVB may play a role in the development or progression of GA.

ANATOMICAL AND FUNCTIONAL OUTCOMES OF SYMPTOMATIC IDIOPATHIC VITREOMACULAR TRACTION: A Natural History Study From the Pan American Collaborative Retina Study Group.

PURPOSE: To describe the natural history of eyes with symptomatic idiopathic vitreomacular traction (VMT). METHODS: Retrospective multicenter study of 168 eyes with spectral-domain optical coherence tomography (SD-OCT) findings consistent with idiopathic VMT. All eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were followed for at least 6 months. RESULTS: There were 168 patients (51 men) with a mean age of 68.8 ± 10.7 years. Patients were followed for a mean of 22.7 ± 20.1 months. The mean duration of symptoms before the initial presentation was 3.65 ± 5.42 months. At baseline, 72 eyes had Grade 1, 74 eyes had Grade 2, and 22 eyes had Grade 3 SD-OCT findings. Over the follow-up period, 36 eyes (21.4%) had spontaneous resolution of the VMT with normalization of the foveal anatomy. The mean time to resolution was 12.3 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of the eyes, with 6 eyes developing a lamellar macular hole and 7 eyes developing a full-thickness macular hole. This occurred at a mean of 10.3 ± 10.7 months after the presentation. Subgroup analysis based on baseline SD-OCT grade showed that 4.1% (3 of 73) of Grade 1 eyes compared with 6.8% (5 of 74) of Grade 2 eyes, and 23.8% (5 of 21) of Grade 3 eyes developed a full-thickness macular hole or lamellar macular hole (P = 0.0109, chi-square test). In the remaining 119 eyes, at the last follow-up, 65 eyes had Grade 1, 42 eyes had Grade 2, and 12 eyes had Grade 3 VMT. On average, the best-corrected visual acuity improved from 0.40 ± 0.35 logarithm of the minimum angle of resolution (Snellen, 20/50) at baseline to 0.35 ± 0.36 logarithm of the minimum angle of resolution (Snellen, 20/45; P = 0.0372), and the mean central macular thickness improved from 350 ± 132 µm to 323 ± 121 µm. CONCLUSION: Spontaneous resolution of VMT occurred in 21.4% (36 of 168) of eyes after a mean follow-up of 11.4 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of eyes. The baseline SD-OCT grade may predict the progression to full-thickness macular hole.

Intraocular pressure elevation after uncomplicated pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.

PURPOSE: To compare the incident rates of sustained elevation of intraocular pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane and the unoperated fellow eye. METHODS: Retrospective multicenter study of 198 patients who underwent pars plana vitrectomy for an idiopathic epiretinal membrane that was followed for at least 12 months. The diagnosis of sustained IOP elevation was defined as an elevation of IOP ≥ 24 mmHg or an increase of ≥ 5 mmHg in the IOP from baseline on 2 separate visits that warranted the initiation of ocular hypotensive therapy. The main outcome measured was the development of sustained IOP elevation as defined above. RESULTS: Patients were followed for an average of 47.3 ± 24 months (range, 12-106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P < 0.0001, Fisher exact test; odds ratio, 4.988). Possible risk factors include a family history of open-angle glaucoma (P = 0.0004 Fisher exact test; odds ratio, 7.206) and cataract surgery (P = 0.0270 Fisher exact test; odds ratio, 2.506). CONCLUSION: Uncomplicated PPV seems to increase the IOP, particularly in those who are pseudophakic and have a family history of open-angle glaucoma. This increase in IOP may lead to glaucomatous damage if not managed appropriately. Patients with a previous PPV need to be followed by an ophthalmologist to monitor the IOP in the vitrectomized eye.

Anti-leishmanial evaluation of C2-aryl quinolines: mechanistic insight on bioenergetics and sterol biosynthetic pathway of Leishmania braziliensis.

A series of diverse simple C2-aryl quinolines was synthesized de novo via a straightforward synthesis based on the acid-catalyzed multicomponent imino Diels-Alder reactions. Seven selected quinolines were evaluated at different stages of Leishmania braziliensis parasite. Among them, the 6-ethyl-2-phenylquinoline 5f was able to inhibit the growth of promastigotes of this parasite without affecting the mammalian cells viability and decreasing the number of intracellular L. braziliensis amastigotes on BMDM macrophages. The mechanism of action studied for the selected compound consisted in: (1) alteration of parasite bioenergetics, by disrupting mitochondrial electrochemical potential and alkalinization of acidocalcisomes, and (2) inhibition of ergosterol biosynthetic pathway in promastigote forms. These results validate the efficiency of quinoline molecules as leishmanicide compounds.

On the design of a bioacoustic sensor for the early detection of the red palm weevil.

During the last two decades Red Palm Weevil (RPW, Rynchophorus Ferrugineus) has become one of the most dangerous threats to palm trees in many parts of the World. Its early detection is difficult, since palm trees do not show visual evidence of infection until it is too late for them to recover. For this reason the development of efficient early detection mechanisms is a critical element of RPW pest management systems. One of the early detection mechanisms proposed in the literature is based on acoustic monitoring, as the activity of RPW larvae inside the palm trunk is audible for human operators under acceptable environmental noise levels (rural areas, night periods, etc.). In this work we propose the design of an autonomous bioacoustic sensor that can be installed in every palm tree under study and is able to analyze the captured audio signal during large periods of time. The results of the audio analysis would be reported wirelessly to a control station, to be subsequently processed and conveniently stored. That control station is to be accessible via the Internet. It is programmed to send warning messages when predefined alarm thresholds are reached, thereby allowing supervisors to check on-line the status and evolution of the palm tree orchards. We have developed a bioacoustic sensor prototype and performed an extensive set of experiments to measure its detection capability, achieving average detection rates over 90%.

[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

Failure of early non-invasive ventilation in preterm infants with respiratory distress syndrome in current care practice in Spanish level-III neonatal intensive care units - a prospective observational study.

Introduction: Despite advances in respiratory distress syndrome (RDS) management over the past decade, non-invasive ventilation (NIV) failure is frequent and associated with adverse outcomes. There are insufficient data on the failure of different NIV strategies currently used in clinical practice in preterm infants. Methods: This was a prospective, multicenter, observational study of very preterm infants [gestational age (GA) <32 weeks] admitted to the neonatal intensive care unit for RDS that required NIV from the first 30 min after birth. The primary outcome was the incidence of NIV failure, defined as the need for mechanical ventilation for <72 h of life. Secondary outcomes were risk factors associated with NIV failure and complication rates. Results: The study included 173 preterm infants with a median GA of 28 (IQR 27-30) weeks and a median birth weight of 1,100 (IQR 800-1,333) g. The incidence of NIV failure was 15.6%. In the multivariate analysis, lower GA (OR, 0.728; 95% CI, 0.576-0.920) independently increased the risk of NIV failure. Compared to NIV success, NIV failure was associated with higher rates of unfavorable outcomes, including pneumothorax, intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, and a combined outcome of moderate-to-severe bronchopulmonary dysplasia or death. Conclusion: NIV failure occurred in 15.6% of the preterm neonates and was associated with adverse outcomes. The use of LISA and newer NIV modalities most likely accounts for the reduced failure rate. Gestational age remains the best predictor of NIV failure and is more reliable than the fraction of inspired oxygen during the first hour of life.

Early-Phase Perceptions of COVID-19's Impact on Ophthalmology Practice Patterns: A Survey from the Pan-American Association of Ophthalmology.

Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO). Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations. Results: There was a marked decline in ophthalmology patient visits (80-95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited. Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic.

A prognostic model based on gene expression parameters predicts a better response to bortezomib-containing immunochemotherapy in diffuse large B-cell lymphoma.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of aggressive lymphoma. Approximately 60% of fit patients achieve curation with immunochemotherapy, but the remaining patients relapse or have refractory disease, which predicts a short survival. Traditionally, risk stratification in DLBCL has been based on scores that combine clinical variables. Other methodologies have been developed based on the identification of novel molecular features, such as mutational profiles and gene expression signatures. Recently, we developed the LymForest-25 profile, which provides a personalized survival risk prediction based on the integration of transcriptomic and clinical features using an artificial intelligence system. In the present report, we studied the relationship between the molecular variables included in LymForest-25 in the context of the data released by the REMoDL-B trial, which evaluated the addition of bortezomib to the standard treatment (R-CHOP) in the upfront setting of DLBCL. For this, we retrained the machine learning model of survival on the group of patients treated with R-CHOP (N=469) and then made survival predictions for those patients treated with bortezomib plus R-CHOP (N=459). According to these results, the RB-CHOP scheme achieved a 30% reduction in the risk of progression or death for the 50% of DLBCL patients at higher molecular risk (p-value 0.03), potentially expanding the effectiveness of this treatment to a wider patient population as compared with other previously defined risk groups.

A practical approach to dental care for patients with Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome is a polymalformative chromosomal disorder caused by a deletion in the distal region of the short arm of chromosome 4. The disease is considered rare (1/50,000 births) and predominantly affects females (2:1). In addition to the characteristic facial phenotype ("Greek warrior helmet"), its clinical manifestations include epilepsy, developmental and psychomotor delay, intellectual disability, cardiac and respiratory complications, and eating problems. The most prevalent oral manifestations are hypodontia, delayed tooth eruption, morphological dental abnormalities, dental malocclusions, cleft lip/palate and ogival palate. Based on our clinical experience, Wolf-Hirschhorn syndrome does not represent an absolute contraindication for any type of dental procedure. The feasibility of dental treatment will depend mainly on the degree of epilepsy control and on the level of collaboration, this latter conditioned by the severity of the intellectual disability and communication difficulties.

Intravitreal bevacizumab for inflammatory choroidal neovascularization: results from the Pan-American Collaborative Retina Study Group at 24 months.

BACKGROUND: To evaluate the anatomical and functional outcomes of intravitreal bevacizumab (1.25 or 2.5 mg) in the treatment of inflammatory choroidal neovascularization at 24 months. METHODS: We reviewed the clinical records of 22 consecutive patients (23 eyes) with choroidal neovascularization secondary to chorioretinal inflammatory disease in this interventional retrospective multicenter case series. Sixteen eyes (63.6%) received a dose of 1.25 mg of intravitreal bevacizumab, and 7 eyes (36.4%) received a dose of 2.5 mg of intravitreal bevacizumab. RESULTS: At baseline, the mean best-corrected visual acuity was 0.68 logarithm of minimum angle of resolution (Early Treatment Diabetic Retinopathy Study chart = 20/100). After intravitreal bevacizumab, best-corrected visual acuity improved significantly to 0.41 logarithm of minimum angle of resolution (20/51), 0.42 logarithm of minimum angle of resolution (20/53), and 0.40 logarithm of minimum angle of resolution (20/50) at 6, 12, and 24 months, respectively (P < 0.05). Fourteen eyes (60.8%) received 1 injection. Central macular thickness by optical coherence tomography decreased from 375.3 µm (range: 240-634 µm) at baseline to 241.6 µm (range: 189-306 µm) at 24 months of follow-up (P < 0.0001). CONCLUSION: Intravitreal bevacizumab at doses of 1.25 mg and 2.5 mg seems to provide stability or improvement in best-corrected visual acuity, optical coherence tomography, and fluorescein angiogram in inflammatory choroidal neovascularization at 24 months. All patients were treated after the underlying uveitic condition was controlled.

The Impact of Face Masks on the Emotional Reading Abilities of Children-A Lesson From a Joint School-University Project.

Wearing face masks has become a usual practice in acute infection events inducing the problem of misinterpreting the emotions of others. Empirical evidence about face masks mainly relies on adult data, neglecting, for example, school kids who firmly are dependent on effective nonverbal communication. Here we offer insights from a joint school-university project. Data indicate that emotional reading of 9 to 10 years old pupils (N = 57) was similarly impaired as adults on an overall performance level, but that their selective performance on specific emotions was quite different. Kids showed extreme problems in reading the emotion disgust, strong effects on fear and sadness, and only mild effects on happiness, but also even better performances for emotional states anger and neutral when faces were masked. This project did gain not only relevant data about children's perception but also made clear how fruitful seriously conducted school projects can be to encourage the interest and commitment for Science, Technology, Engineering, and Mathematics (STEM)-relevant topics.

Corrigendum: Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol.

[This corrects the article DOI: 10.3389/fped.2020.00372.].

ChemBank: a small-molecule screening and cheminformatics resource database.

ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for studying these data. ChemBank is unique among small-molecule databases in its dedication to the storage of raw screening data, its rigorous definition of screening experiments in terms of statistical hypothesis testing, and its metadata-based organization of screening experiments into projects involving collections of related assays. ChemBank stores an increasingly varied set of measurements derived from cells and other biological assay systems treated with small molecules. Analysis tools are available and are continuously being developed that allow the relationships between small molecules, cell measurements, and cell states to be studied. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the Broad Institute by collaborators from the worldwide research community. The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector.

PHOTODYNAMIC THERAPY WITH VERTEPORFIN PLUS INTRAVITREAL BEVACIZUMAB FOR CIRCUMSCRIBED CHOROIDAL HEMANGIOMA: 4 YEARS OF FOLLOW-UP.

PURPOSE: To report the anatomical and functional response of combined photodynamic therapy and intravitreal injection of bevacizumab in a patient with symptomatic circumscribed choroidal hemangioma. METHODS: The patient received a single-session full-fluence photodynamic therapy immediately followed by an intravitreal injection of bevacizumab (1.25 mg/0.05 mL). RESULTS: One week after combined therapy, an improvement of best-corrected visual acuity from count fingers to 20/60 and a significant decrease in subretinal fluid were noted. One month later, we observed decreased leakage on fluorescein angiography in all phases of the study. Three months after treatment, the best-corrected visual acuity improved to 20/25 and spectral domain optical coherence tomography scans showed return to normal foveal architecture with no subretinal fluid and completely flat tumor. These findings were maintained during 4 years of follow-up. CONCLUSION: Combination therapy was associated with a rapid and persistent resolution of subretinal fluid, improvement of best-corrected visual acuity, and visual stability at 4 years of follow-up.