Pulmonary Capillary Hemangiomatosis as a Rare Underlying Cause of Primary Pulmonary Hypertension: A Case Report in an Adolescent.

Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases, such as pulmonary veno-occlusive disease, it is characterized by abnormal pulmonary capillary proliferation, which is a rare cause of primary pulmonary hypertension. This case was the first reported instance of PCH in Shahid Rajaee Heart Hospital in Tehran, Iran, in 2023, which was confirmed by genetic testing. It highlighted the importance of considering PCH among the differential diagnoses for pulmonary hypertension, even in adolescent patients. The 13-year-old patient's main complaints were progressive exertional dyspnea and chest pain. He had no previous medical history and had not taken any pharmaceutical or herbal medications. Critical clinical findings included a heart murmur, an electrocardiogram revealing right ventricular hypertrophy, and echocardiogram evidence of pulmonary hypertension. The main diagnosis was PCH, as shown by CT findings of pulmonary artery dilatation and diffuse nodular ground glass opacities. Genetic tests indicated pathogenic EIF2AK4 mutations and suspicion of PCH. Therapeutic intervention included vasodilator therapy, which exacerbated the patient's condition. This case emphasized the importance of maintaining a high index of suspicion for rare causes of pulmonary hypertension, such as PCH. The outcome was to prepare the patient for lung transplantation. To differentiate PCH from other pulmonary vascular diseases, a combination of clinical presentation, radiologic studies, genetic analysis, and response to treatment is required to determine appropriate management, particularly lung transplantation.

Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma: A Randomized Clinical Trial.

Importance: Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic ß-blockers, such as nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events. Objective: To document the noninferiority and safety of oral nadolol compared with oral propranolol in infants with IH. Design, Setting, and Participants: This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement. Interventions: Oral propranolol and nadolol in escalating doses up to 2 mg/kg/d. Main Outcomes and Measure: Between-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale. Results: The study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the nadolol group, demonstrating that nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with nadolol compared with propranolol. Safety data were similar between the 2 interventions. Conclusions and Relevance: Oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required. Trial Registration: ClinicalTrials.gov Identifier: NCT02505971.

Pulmonary vasodilators can lead to various complications in pulmonary "arterial" hypertension associated with congenital heart disease.

Congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH) is one of the major complications in patients with CHD. A timely closure of the left-to-right shunt will generally result in the normalization of the pulmonary hemodynamics, but a few patients have severe prognosis in their early childhood. We hypothesized that wide-ranging pathological mechanism in PAH could elucidate the clinical state of severe CHD-PAH. Using electronic medical records, we retrospectively analyzed six infants with severe CHD-PAH who had treatment-resistant PH. All patients were born with congenital malformation syndrome. After starting on a pulmonary vasodilator, five of the six patients developed complications including pulmonary edema and interstitial lung disease (ILD), and four patients had alveolar hemorrhage. After steroid therapy, the clinical condition improved in four patients, but two patients died. The autopsy findings in one of the deceased patients indicated the presence of recurrent alveolar hemorrhage, pulmonary venous hypertension, ILD, and PAH. Based on the clinical course of these CHD-PAH in patients and the literature, CHD-PAH can occur with pulmonary vascular obstructive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH), ILD, and/or alveolar hemorrhage. The severity of CHD-PAH may depend on a genetic disorder, respiratory infection, and upper airway stenosis. Additionally, pulmonary vasodilators may be involved in the development of PVOD/PCH and ILD. When patients with CHD-PAH show unexpected deterioration, clinicians should consider complications associated with PVOD/PCH and/or pulmonary disease. In addition, the choice of upfront combination therapy for pediatric patients with CHD-PAH should be selected carefully.

Congenital hemangioma exhibiting postnatal growth.

Congenital hemangiomas are vascular tumors that are fully formed at birth, typically without postnatal growth. Noninvoluting congenital hemangiomas (NICH) have a distinctive clinical, radiologic, and histopathological profile and lack of expansion or involution over time. Herein, we describe two cases of NICH with atypical postnatal growth.

Efficacy of propranolol treatment in infantile hepatic haemangioma.

AIM: The aim of this study was to assess the efficacy of propranolol treatment in multifocal and diffuse infantile hepatic haemangioma (IHH). METHODS: A retrospective study of symptomatic or potentially symptomatic IHH was performed in our hospital between 2011 and 2016. RESULTS: Thirteen patients were identified: 2 patients had diffuse lesions, and 11 patients had multifocal lesions, including 2 patients who had combined lesions that shared features of both multifocal and diffuse lesion patterns. Eleven (84.6%) patients had cutaneous infantile haemangioma. Hepatomegaly was the predominant clinical presentation. Hypothyroidism was identified in three patients, including one patient who had documented congestive heart failure (CHF). The median age at diagnosis and the median duration of treatment were 2.0 months (range 1.2-26.0) and 24.0 months (range 4.0-30.0). The median duration of follow-up was 30.0 months (range 3.0-48.0). For patients with hypothyroidism, the thyroid hormone level was normal after 4 weeks of propranolol and levothyroxine treatment. All but one patient responded well to propranolol treatment. The patient who failed to respond to treatment died of CHF and abdominal compartment syndrome induced by hepatomegaly. No significant side effects of propranolol were observed during follow-up. CONCLUSIONS: Most multifocal and diffuse IHH respond well to propranolol. However, progressive cases may be fatal despite aggressive treatments. Our data suggest that propranolol may be considered the first-line treatment for multifocal and diffuse IHH due to its efficacy.

Use of vasodilators for the treatment of pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: A systematic review.

BACKGROUND: There are several medications available to treat pulmonary arterial hypertension (PAH): PAH-targeted drugs. However, in patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis (PVOD/PCH), rare diseases that cause pulmonary hypertension, the effectiveness and safety of vasodilators, including PAH-targeted drugs, are unclear. METHODS: We searched English-language publications listed in three electronic databases (PubMed, Cochrane Library, and the Japan Medical Abstracts Society). Reports with efficacy outcomes (survival, improvement in 6-minute walk distance, and pulmonary vascular resistance) and data on development of pulmonary edema after administration of vasodilators to patients with PVOD/PCH were selected (1966 to August 2015). RESULTS: We identified 20 reports that met our criteria. No randomized controlled or prospective controlled studies were reported. The survival time ranged from 71 minutes to 4 years or more after initiation of vasodilators. Most of the reported cases showed an improvement in the 6-minute walk distance and pulmonary vascular resistance. Pulmonary edema was reported in 15 articles, some cases of which were lethal. CONCLUSIONS: The present study demonstrates the potential efficacy and difficulties in the use of vasodilators in patients with PVOD/PCH; however, drawing a firm conclusion was difficult because of the lack of randomized controlled trials. Further research is needed to ascertain if vasodilator use is beneficial and safe in patients with PVOD/PCH.

Efficacy and safety of long-term imatinib therapy for patients with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are categorized as Group 1' in the clinical classification of pulmonary hypertension. No medical therapy has been proven to be effective in patients with PVOD/PCH. Imatinib is a molecular targeted drug and was expected to be effective in patients with pulmonary arterial hypertension. We evaluated its efficacy and safety in patients with PVOD/PCH. METHODS: In the present observational study, 9 patients with PVOD/PCH received imatinib. Clinical data including exercise capacity and hemodynamics at baseline and at follow-up were compared. Survival rate of patients treated with imatinib was compared to those of 7 patients who did not treated with imatinib. RESULTS: Imatinib was prescribed at doses of 100-400 mg/day and was well-tolerated. At follow-up, World Health Organization functional class and brain natriuretic peptide levels significantly improved. Mean pulmonary arterial pressure was significantly reduced (from 56.8 ± 8.3 to 43.7 ± 9.0 mmHg) with preserved cardiac index. Patients were treated with imatinib for 797.2 ± 487.0 days. Seven patients (77.8%) died and 2 patients (22.2%) underwent lung transplantation. Mean survival time in patients treated with imatinib therapy was 1493.7 ± 196.3 days (95% confidence interval, 1108.9-1878.5 days), significantly longer than those without imatinib treatment (713.0 ± 258.1 days, log-rank test, P = 0.04). CONCLUSIONS: Imatinib improved exercise capacity, hemodynamics and survival in patients with PVOD/PCH. In patients with PVOD/PCH, who have no effective medical therapy available, imatinib might function as a bridge to lung transplantation, and may become a potential therapeutic option to improve their survival.

Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-occlusive Disease.

This article provides an overview of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH), two disorders that challenge clinicians, radiologists, and pathologists because they often mimic pulmonary arterial hypertension (PAH). The article reviews the features that differentiate PVOD and PCH from PAH. The article also describes the overlap of PVOD and PCH, highlighted by recent reports of families diagnosed with PVOD or PCH caused by EIF2AK4 mutations. In addition, the article outlines current approaches to the diagnosis and treatment of PVOD and PCH.

Infantile hemangioma status by dynamic infrared thermography: A preliminary study.

BACKGROUND: Infantile hemangiomas (IH) are initially warm due to increased proliferation and perfusion then involute with apoptosis and reduced perfusion. Objective quantitative evaluation of IH treatment response is essential for improving outcomes. We applied a functional imaging method, dynamic infrared (IR) thermography, to investigate IH status versus control skin and over time. MATERIALS AND METHODS: A preliminary prospective observational study was conducted among 25 subjects with superficial or mixed IHs (< 19 months) over 59 clinic visits. Infrared images of IHs and control sites, standardized color images, and three-dimensional images were obtained. Tissue responses following application and removal of a cold stress were recorded with video IR thermography. Outcomes included areas under the curve during cooling (AUCcool ) and rewarming (AUCrw ) and thermal intensity distribution maps. RESULTS: AUCcool and AUCrw were significantly higher and cooling rate slower for IHs versus uninvolved tissue indicating greater heat, presumably due to greater perfusion and metabolism for the IH. IR distribution maps showed specific areas of high and low temperature. Significant changes in IH thermal activity were reflected in the difference (AUCcool - AUCrw ), with 6.2 at 2.2 months increasing to 37.6 at 12.8 months. IH cooling rate increased with age, indicating slower recovery, and interpreted as reduced proliferation and/or involution. CONCLUSIONS: Dynamic IR thermography was a well-tolerated, quantitative functional imaging modality appropriate for the clinic, particularly when structural changes, i.e., height, volume, color, were not readily observed. It may assist in monitoring progress, individualizing treatment, and evaluating therapies. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (Identifier NCT02061735).

Visual acuity and astigmatism in periocular infantile hemangiomas treated with oral beta-blocker versus intralesional corticosteroid injection.

BACKGROUND: Periocular infantile hemangiomas (PIH) can induce anisometropic astigmatism, a risk factor for amblyopia. Oral beta-blocker therapy has largely supplanted systemic or intralesional corticosteroids. The purpose of this study was to evaluate the effect and time course of these treatment modalities on visual acuity and induced astigmatism. METHODS: The medical records of patients with PIH treated with oral propanolol between November 2008 and July 2013 were retrospectively reviewed for data on visual acuity and astigmatism. Patients with incomplete pre- and post-treatment ophthalmic examinations were excluded. Results were compared to those of a similar cohort treated with intralesional corticosteroid injection. RESULTS: Mean astigmatism in affected eyes was 1.90 D before propranolol and 1.00 D after; patients showed a monophasic reduction in astigmatism over 12 months. By comparison, patients treated with corticosteroid injection showed a biphasic response, with an immediate steep decrease followed by a slow monophasic decline, paralleling propranolol-treated patients. Oral propranolol treatment caused a 47% reduction in mean induced astigmatism, less than the 63% reduction reported for the cohort treated with corticosteroid. No patient had visual acuity in the affected eye more than 1 standard devation below the age-matched norm, and none experienced significant side effects when treated with oral propranolol. CONCLUSIONS: In this patient cohort oral beta-blocker was well-tolerated. Treatment was therefore often initiated prior to the induction of significant astigmatism, with treatment effects comparable to steroid treatment. Visual outcomes were good. Early treatment may minimize the potential effect of astigmatism on postnatal visual development.

PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON HIPPEL-LINDAU EYE DISEASE.

PURPOSE: To investigate spectrum of patients with Von Hippel-Lindau disease (VHL) that required pars plana vitrectomy and evaluate anatomical and functional outcomes of surgery. METHODS: Twenty-three patients who underwent surgery for advanced VHL eye disease were assessed by genetic tests, diagnostic tests for systemic lesions, and clinical eye examination. The vitrectomized eyes were divided into two groups: with or without retinotomy (group R vs. NR). Functional and anatomical outcome was analyzed and compared between the groups. RESULTS: All patients had central nervous system hemangioblastomas and 57% had other systemic tumors. Point germline mutations, large partial deletions, and complete vhl gene deletions were found in 64%, 27%, and 9% of patients, accordingly. Destruction of hemangioblastomas by retinotomy, laser, or cryotherapy and anatomical attachment of the retina were achieved in all eyes. Preoperative mean distance best-corrected visual acuity was logarithm of the minimum angle of resolution 2.66 (20/9,140) in group R and 1.76 (20/1,150) in group NR (P < 0.05). At 6 months postoperatively, distance best-corrected visual acuity improved in 20 eyes (83%). After over 24 months postoperatively, distance best-corrected visual acuity remained better than preoperatively in 36% in the R group and in 70% in the NR group of eyes. During 24 months postoperatively in 17 eyes, new retinal capillary hemangiomas developed. The mean number of new retinal capillary hemangiomas per eye was higher in group R than in group NR (3.14 vs. 0.70; P < 0.01). In group R, number of new retinal capillary hemangioblastoma was higher in retinal segments where retinotomy was performed (n = 29) than in other areas (n = 13) (P < 0.01). CONCLUSION: Advanced VHL eye disease correlates with occurrence of central nervous system and systemic lesions. Spectrum of vhl gene mutation in the patients corresponds to that of the general VHL population. Pars plana vitrectomy in advanced VHL eye disease can improve or preserve visual function, but postoperative progression of ocular VHL disease can be accelerated in cases where retinotomy is performed.

Oral Nadolol for Children with Infantile Hemangiomas and Sleep Disturbances with Oral Propranolol.

BACKGROUND/OBJECTIVE: Oral propranolol has been shown to be safe and effective in infants with infantile hemangioma (IH). Side effects such as sleep disturbances have been associated with propranolol. The aim of this study was to evaluate the efficacy and safety of oral nadolol in a small series of patients whose propranolol therapy was discontinued due to sleep disturbances. METHODS: A retrospective study of patients with IHs who were treated with oral nadolol due to propranolol-related sleep disturbances at a pediatric tertiary care center between July 2008 and March 2013. Clinical response to oral nadolol and disappearance of propranolol-related side effects were analyzed. RESULTS: A total of 97 patients presenting IH received oral propranolol. Nine patients (9.3%) developed sleep disturbances. Oral propranolol was discontinued in seven patients and switched to oral nadolol, with resolution of these side effects in 5 (71%) of the cases. One patient developed sleep disturbances again after four months of oral nadolol. LIMITATIONS: The sample size was too small to draw generalizable conclusions and to draw any statistical inference as to the incidence of sleep disturbances with nadolol therapy. CONCLUSIONS: The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the symptoms recurred after 4 months of oral nadolol at a dose of 2 mg/kg/day. In most cases, switching beta-blockers did not compromise efficacy, and is recommended when sleep disturbance necessitates discontinuation of beta-blocker therapy of IH.

Blood Pressure Monitoring During the Induction and Maintenance Period of Propranolol Therapy for Complicated Infantile Hemangiomas: A Prospective Study of 109 Infants.

BACKGROUND: Propranolol has become the first-line treatment for complicated infantile hemangiomas (CIHs) worldwide. Recommendations for monitoring infants undergoing propranolol therapy vary. Data on long-term blood pressure (BP) monitoring have not been reported before. OBJECTIVE: The objective of the current study was to monitor BP in full-term infants during the induction and maintenance phase of propranolol therapy. METHODS: BP was monitored prospectively in 109 infants (mean age 2.8 mos, range 1-5 mos) with CIHs during the induction (3-4 days in the hospital during up-dosing from 0.5 to 2.0 mg/kg/day) and maintenance (6 mos) phases of oral propranolol therapy. RESULTS: Four children were excluded from the study because of sinus bradycardia (n = 2 [1.8%]) or lethargy (n = 2 [1.8%]). Mean systolic BP (SBP) decreased by 5 mmHg with the increase in propranolol dosage. Low (<5th percentile) SBP or diastolic BP (DBP) was observed in 2 of 105 children (1.9%) each. During the maintenance phase, 2 of 105 children (1.9%) had occasional SBP readings of less than 70 mmHg. No hypotension was observed after the third month of therapy. Low DBP (<36 mmHg) was recorded in 16 (15.2%) children after the first month, in 8.6% after the second, and in 2.9% during the third and fourth months of therapy. No patients exhibited clinical hypotension, bradycardia, or other known side effects of propranolol. Clinical response to therapy was excellent. LIMITATIONS: Reference BP values were derived from published tables, not from an untreated control group. CONCLUSIONS: In healthy full-term infants, propranolol (2 mg/kg/day divided in three doses) is well tolerated. No clinically significant hypotension was observed. We conclude that for otherwise healthy infants, BP monitoring during long-term propranolol therapy for CIHs is not necessary.

Scoring the therapeutic effects of oral propranolol for infantile hemangioma: A prospective study comparing the Hemangioma Activity Score (HAS) with the Hemangioma Severity Scale (HSS).

BACKGROUND: Validated and reliable instruments to measure disease severity are needed to substantiate the benefit of therapies for infantile hemangioma. Two purpose-made systems have been described: the Hemangioma Activity Score (HAS) and the Hemangioma Severity Scale (HSS). OBJECTIVE: We sought to compare the HAS with the HSS in terms of ease of use, accuracy, and outcome in infants treated with oral propranolol. METHODS: A prospective study of 54 infants with infantile hemangioma was conducted from October 2009 to December 2012. Propranolol was initiated at 0.5 mg/kg/d and increased to 2 mg/kg/d on day 3. The HAS and the HSS were applied independently by 2 observers. RESULTS: Intraclass correlation coefficients of the HAS and HSS between the observers was comparable but HSS scores often remained the same upon improvement of the infantile hemangioma and therefore did not reflect disease severity. HAS decreased over time, with a dramatic drop in the first week reflecting an immediate therapeutic response. LIMITATIONS: This is a single-institution study and there may have been some selection bias in the patients who were referred for treatment. CONCLUSIONS: This study suggests that the HAS is preferable to the HSS in evaluating infantile hemangioma response to treatment.

Support for the hypoxia theory in the pathogenesis of infantile haemangioma.

BACKGROUND: The pathogenesis of infantile haemangioma (IH) is unknown. Several mechanisms have been proposed, including hypoxia, which triggers upregulation and stabilization of hypoxia-inducible factor (HIF)1α. HIF1α stimulates downstream transcription of target genes that enhance angiogenesis. AIM: To identify possible involvement of hypoxia in the pathogenesis of IH, as hypoxia signalling constitutes a potential therapeutic target. METHODS: IH tissue samples collected during the period 1991-2011 (preserved in paraffin wax) were immunohistochemically analysed for HIF1α and the known HIF1α targets: BCL2/adenovirus E1B kD-interacting protein family member 3 (BNIP3), carbon anhydrase (CA)-IX, glucose transporter (GLUT)-1, phosphorylated protein kinase B (pAKT), phosphorylated S6 protein (pS6) and vascular endothelial growth factor (VEGF). Four observers independently assessed the findings. RESULTS: Of the 10 IH samples, 2 appeared to be in the growth phase. In all samples, GLUT-1, BNIP3, pAKT and VEGF were positive, CA-IX was weakly positive, and HIF1α was negative. pS6 was positive in 9/10 cases and negative in 1/10. CONCLUSIONS: Several factors implicated in hypoxia-induced angiogenesis may be involved in IH development. However, the small sample size and retrospective approach of the study preclude definitive conclusions. Prospective studies are needed to conclusively determine which of the factors involved in the (hypoxia) cascade are required for an IH to grow, and could thus be a possible target of drugs for IH treatment.

Ventral midline blanching in the setting of segmental infantile hemangiomas: clinical observations and pathogenetic implications.

Areas of blanched skin in children may be seen as an independent finding or in association with vascular birthmarks. We performed a retrospective chart review to identify and describe infants with areas of ventral midline blanching in the presence of segmental infantile hemangiomas. We identified nine full-term infants with partial or full segmental hemangiomas and areas of midline ventral blanching. Additional ventral wall defects were seen in five patients. Six had cardiac anomalies and six had intracranial anomalies. Five were diagnosed with definite PHACE (posterior fossa, hemangioma, arterial, cardiac, and eye abnormalities) syndrome and three had possible PHACE syndrome. Eight were complicated by ulceration. Treatment varied according to the case. Ventral blanching, even in the absence of overt midline defects, can be seen in infants with segmental hemangiomas at risk for PHACE syndrome. We hypothesize that midline blanching may represent a minor manifestation of a developmental ventral defect.

Intravitreal bevacizumab for retinal capillary hemangioblastoma: A case series and literature review.

OBJECTIVE: To evaluate the long-term outcomes of intravitreal bevacizumab for peripheral and juxtapapillary retinal capillary hemangioblastoma (RCH). DESIGN: We conducted a retrospective noncomparative interventional case series. PARTICIPANTS: There were 4 patients (5 eyes) presenting with RCH. METHODS: Five eyes with RCH presented with exudative changes and visual loss. Three eyes of 2 patients with peripheral RCH were treated with cryotherapy and 2 intravitreal injections of bevacizumab (0.5 mg). Two eyes with juxtapapillary RCH were treated with 3 intravitreal injections of bevacizumab. The main outcome measures were changes in best-corrected visual acuity (BCVA), lesion size, exudation, and retinal thickness. RESULTS: In peripheral RCH, improvement of BCVA from counting fingers to 20/400 was obtained in 1 eye. One patient with bilateral RCH maintained a vision of 20/20 in 1 eye with complete anatomic regression of the 3 small peripheral RCH lesions. The fellow eye with fibrotic bands from the RCH to the optic nerve head developed a tractional retinal detachment after the first injection and was treated with pars plana vitrectomy. In patients with juxtapapillary RCH, bevacizumab injections resulted in an improvement of BCVA from 20/80 to 20/20 in 1 eye, whereas the second eye did not show an improvement of BCVA despite a regression of the tumour. CONCLUSIONS: Intravitreal anti-vascular endothelial growth factor agents, alone or in combination with other treatment modalities, may improve visual acuity. Further trials evaluating the dose, the number of injections, and the route of administration will be important in advancing antiangiogenic therapies for RCH.

Propranolol and periocular capillary hemangiomas: assessment of refractive effect.

PURPOSE: To assess the effects of systemic propranolol on refractive error in infants with periocular capillary hemangiomas. METHODS: A single-center study of consecutive patients with capillary hemangiomas treated with systemic propranolol. Refractive data were analyzed using Long's matrix formalism and the methods of Harris and Kaye. RESULTS: Seventeen patients were included. At 6 months postoperatively, hemangioma size reduced from 3,214 to 1,806 mm(3) (standard deviation: 4,122 to 2,441). Mean refractive error in the affected eye significantly reduced: -1.25/0.38 × 36 (95% confidence intervals: -5.08/1.20 × 90 to 1.64/1.43 × 180, P = .048) with a smaller change (P = .06) in the unaffected eye of -1.01/+0.31 × 3.16 (95% confidence intervals: -4.02/+1.12 × 180 to +1.49/+0.51 × 90). CONCLUSIONS: Propranolol produced a clinically significant reduction in the infants' refractive error and anisometropia. The reduction in the total refractive error and anisometropia has not been evident in previous analyses, which have concentrated on the change in the "cylinder" as the principal outcome measure.

Imatinib is partially effective for the treatment of pulmonary capillary hemangiomatosis.

A 43-year-old man presented with dyspnea on exertion. Right heart catheterization demonstrated pulmonary arterial hypertension (PAH). He was treated with bosentan, sildenafil and intravenous epoprostenol. Despite the administration of such intensive therapy, the patient's condition deteriorated to a World Health Organization functional class (WHO-FC) of IV. He participated in a clinical trial of imatinib for PAH. After three months of treatment with imatinib, the chest X-ray and echocardiography findings improved, and the WHO-FC class was III. One year after, however, the PAH worsened again, and the patient died 2.6 years after the first diagnosis. At autopsy, patchy capillary proliferation was observed in the lungs. The definitive diagnosis was pulmonary capillary hemangiomatosis.