Use of POCUS for the assessment of dehydration in pediatric patients-a narrative review.

In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions and pleural and pericardial effusions, but less to evaluate fluid depletion. The main aim of this review is to analyze the current literature on the assessment of dehydration in pediatric patients by using POCUS. The size of the inferior vena cava (IVC) and its change in diameter in response to respiration have been investigated as a tool to screen for hypovolemia. A dilated IVC with decreased collapsibility (< 50%) is a sign of increased right atrial pressure. On the contrary, a collapsed IVC may be indicative of hypovolemia. The IVC collapsibility index (cIVC) reflects the decrease in the diameter upon inspiration. Altogether the IVC diameter and collapsibility index can be easily determined, but their role in children has not been fully demonstrated, and an estimation of volume status solely by assessing the IVC should thus be interpreted with caution. The inferior vena cava/abdominal aorta (IVC/AO) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS could be a valuable supplementary tool in the assessment of dehydration in several clinical scenarios, enabling rapid identification of life-threatening primary etiologies and helping physicians avoid inappropriate therapeutic interventions.   Conclusion: POCUS can provide important information in the assessment of intravascular fluid status in emergency scenarios, but measurements may be confounded by a number of other clinical variables. The inclusion of lung and cardiac views may assist in better understanding the patient's physiology and etiology regarding volume status. What is Known: • In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions (like pneumonia and bronchiolitis) and pleural and pericardial effusions, but less to evaluate fluid depletion. • The size of the IVC (inferior vena cava) and its change in diameter in response to respiration have been studied as a possible screening tool to assess the volume status, predict fluid responsiveness, and assess potential intolerance to fluid loading. What is New: • The IVC diameter and collapsibility index can be easily assessed, but their role in predicting dehydration in pediatric age has not been fully demonstrated, and an estimation of volume status only by assessing the IVC should be interpreted carefully. • The IVC /AO(inferior vena cava/abdominal aorta) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS can be a valuable supplementary tool in the assessment of intravascular volume in several clinical scenarios.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

COVID-19 increased in Italian children in the autumn and winter 2021-2022 period when Omicron was the dominant variant.

AIM: We examined the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children during the autumn and winter season from 1 September 2021 to 30 January 2022 and compared it with the same period in 2020-2021. METHODS: This study was carried out int the paediatric emergency department (PED) of a tertiary Italian hospital. We compared the clinical and demographical features of all children who presented during the two study periods and tested positive for SARS-CoV-2. RESULTS: During the 2021-2022 autumn and winter season 5813 children presented to the PED, 19.0% were tested for SARS-CoV-2 and 133 (12.0%) of those tested positive. In 2020-2021, 2914 presented to the PED, 12.3% were tested, and 30 (8.3%) of those tested positive. There were no statistically significant differences in clinical severity during the two study periods, despite a higher percentage of neurological symptoms in 2020-2021. Of the SARS-CoV-2-positive cases, 29/133 (21.8%) were hospitalised during the 2021-2022 season and 10/30 (33.3%) during the previous one. Only 3/163 children required intensive care. CONCLUSION: The greater spread of SARS-CoV-2 was probably due to the greater transmissibility of the Omicron variant, but the symptoms were mild and only 3 children required intensive care.

PECARN Rule in diagnostic process of pediatric patients with minor head trauma in emergency department.

This study aims to evaluate the efficacy of the PECARN Rule (PR) in reducing radiological investigations in children with mild traumatic head injury in comparison with current clinical practice. A retrospective study was performed in our hospital between July 2015 and June 2020. Data of all children < 18 years of age admitted to the emergency department (ED), within 24 h after a head trauma with GCS ≥ 14, were analyzed. PECARN Rule was retrospectively applied to all patients. In total, 3832 patients were enrolled, 2613 patients ≥ 2 years and 1219 < 2 years. In the group of children ≥ 2 years, 10 presented clinically important traumatic brain injury (ciTBI) and were hospitalized, 7/10 underwent neurosurgery, and 3/10 clinical observation in the pediatric ward for more than 48 h. In children < 2 years, only 3 patients presented ciTBI, 2 underwent neurosurgery and 1 hospitalized. Applying the PR, no patient with ciTBI would have been discharged without an accurate diagnosis and we would have avoided 139 CT scans in patients ≥ 2 years, and 23 in those < 2 years of age (29% less). CONCLUSION: We demonstrated the safety and validity of the PR in our setting with 100% sensitivity in both age groups in identifying patients with ciTBI and theoretically in reducing performed CT scans by 29%. Therefore, in patients classified in the low-risk category, it is a duty not to expose the child to ionizing radiation. WHAT IS KNOWN: • CT is the gold standard to identify intracranial pathology in children with head injury but CT imaging of head-injured children expose them to higher carcinogenic risk. • PECARN Rules support doctors in identifying children with ciTBI in order to reduce exposure to ionizing radiation. WHAT IS NEW: • We demonstrate the safety and validity of the PR with 100% sensitivity in both age groups in identifying patients with ciTBI. • In our setting, the application of PECARN Rule would theoretically have allowed us to reduce the CT scan by 29%.

Determinants of antibiotic prescriptions in a large cohort of children discharged from a pediatric emergency department.

While there is evidence of high use of wide-spectrum antibiotics in children evaluated in the pediatric emergency departments, determinants of this behavior are still unclear. This study was aimed at defining the demographic, social, clinical, and laboratory factors that affect antibiotic prescriptions in children discharged from the emergency department. We performed a retrospective observational study of children aged younger than 18 years discharged from a pediatric university hospital between Jan. 1, 2015 and Dec. 31, 2020. We determined the proportion and type of antibiotic prescription according to demographic, social, clinical, laboratory, and imaging data, as well as doctor's expertise. Fifty-one thousand six hundred thirty-three children were included, and 13,167 (25.5%) received an antibiotic prescription. Amoxicilline/clavulanate (Am/Cl) was the most prescribed antibiotic (8453, 64.2% of all prescriptions). Factors independently associated with an antibiotic prescription were older age (OR = 1.62 [1.53-1.73] for age 2-5 years, OR = 1.77 [1.64-1.91] for age 6-10 years, OR = 1.36 [1.25-1.49] for age 11-18 years, p < 0.001 for all groups); being evaluated by a physician with > 3 years of pediatric expertise (OR = 1.22 [1.13-1.31], p < 0.001); fever peak higher than 40 °C (OR = 1.37 [1.21-1.54], p < 0.001); abnormal findings on auscultation (OR = 1.95 [1.75-2.17], p < 0.001), CRP values (OR = 1.63 [1.26-2.10] for CRP < 50 mg/L, and OR = 3.78 (2.75-5.21) for CRP ≥ 50 mg/L with respect to CRP not requested; p < 0.01); CXR results whatever positive (OR = 4.47 [3.62-5.52], p < 0.001) or negative (1.82 [1.62-2.04], p < 0.001); being diagnosed with upper respiratory tract infections (OR = 4.27 [4.04-4.51], p < 0.001), lower respiratory tract infections (OR = 5.35 [4.88-5.85]; p < 0.001), and UTI (OR = 9.33 [8.14-10.71], p < 0.001).    Conclusions: Overprescription of antibiotics, including Am/Cl, is relevant in pediatric emergency departments. Factors associated with overprescription are not limited to the clinical characteristics of the treated patients. These findings highlight the need for a new and comprehensive approach to ensure successful antibiotic stewardship initiatives in the emergency departments. What is Known: • Antibiotic resistance is a growing problem in medical practice, including in pediatrics. • Antibiotics are overprescribed in children assessed in the emergency department, but comprehensive and large studies are lacking. What is New: • Factors associated with overprescription are not limited to the clinical characteristics of the patients. • Non-clinical factors such as environmental variables, doctor's expertise, and attitudes to laboratory and radiological examinations affect prescription.

COVID-19 review shows that benefits of vaccinating children and adolescents appear to outweigh risks of post-vaccination myopericarditis.

AIM: Myopericarditis after COVID-19 vaccination were the most serious adverse events reported in children over 5 years of age. We want to summarise these cases, describing their incidence, clinical features, diagnostic pathways, therapeutic strategies and outcome. METHODS: A systematic review of the literature was conducted until 20 March 2022 by bibliographic electronic databases. We included all reports of post-vaccination myopericarditis in children aged between 5 and 18 years. RESULTS: All reported cases had elevated serum Troponin levels, associated with electrocardiogram changes, but often with normal echocardiogram. Cardiac magnetic resonance images always showed typical alterations. The pathogenetic mechanism is still unknown. Myocarditis following post-COVID vaccination is more frequent in boys with an average age of about 15 years. Treatment involves the usage of non-steroidal anti-inflammatory drugs, and the average hospitalisation is about 3 days. The long-term consequences are not yet known, so these patients should be studied in a cardiological follow-up and abstention from physical activity should be recommended. CONCLUSION: The benefits of COVID-19 vaccination in children and adolescents appear to outweigh the risk of developing post-vaccination myopericarditis. We can also speculate a possible approval of vaccination in children under 5 years for the coming winter.

Intracerebral Nontraumatic Hemorrhagic Stroke in Children: Case Series and Literature Review.

Pediatric stroke is an event caused by disturbance of cerebral circulation that occurs in individuals between 28 days and 18 years of age. Although an uncommon event, pediatric stroke still carries significant morbidity and mortality. Unlike adults, causes of pediatric stroke are various and include vascular, infectious, hematologic, neoplastic, and toxic etiologies. Clinical presentation of nontraumatic intracerebral hemorrhages in older children is similar to adults, however in neonates and infants signs and symptoms can be more subtle, especially with smaller hemorrhages. Management of nontraumatic intracerebral hemorrhage consists of stabilizing the patient, management of the hemorrhage itself, and reduction of the rebleeding risk. Even so, when child reaches a medical care, morbidity and mortality rates are still high. We described a case series of pediatric patients with intracerebral nontraumatic hemorrhagic stroke from different etiologies. Although increasingly recognized, such situations are still poorly described in children and our report offers a good overview on this topic.

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

Botulism during SARS-CoV-2 pandemic: The importance of differential diagnoses.

Botulism is a neuroparalytic syndrome caused by a neurotoxin produced by Clostridium botulinum. We describe a patient with neurological symptoms associated with intoxication by Clostridium botulinum and infection by SARSCoV2. This report underlines that it is mandatory, even in case of SARS-CoV-2 positivity, to investigate all the causes of a clinical pattern.

Role of Troponin Determination to Diagnose Chest Pain in the Pediatric Emergency Department.

OBJECTIVES: Chest pain is a common cause to admission to the pediatric emergency department and often leads to an extensive cardiac evaluation. The objective of this study was to evaluate the usefulness of the troponin (TN) plasma level determination in the initial phase of the differential diagnosis of chest pain in children. METHODS: This is a retrospective observational study on 107 patients, aged 0 to 19 years, admitted for chest pain to the pediatric emergency department of our institution. Demographics, clinical data, and patient outcomes were analyzed. Troponin values of >0.03 ng/mL but <0.1 ng/mL were considered suspected for cardiac pathology, whereas levels of >0.1 ng/mL were indicative of cardiac pathology. In these latter patients, an echocardiographic examination was also performed. RESULTS: Only 99 patients were evaluated with electrocardiogram (ECG). In 91 of 99 patients of our series, both TN determination and ECG recording were performed. Troponin was higher than the cutoff value (0.03 ng/mL) in 9 patients (9.1%). Only 2 of the 9 patients who presented high TN values showed a nonpathological ECG, whereas 16 (17.5%) of 91 patients in whom both ECG and TN determination were performed had ECG abnormalities without a simultaneous elevation of TN. Of the 26 patients who had medical history and suggestive targets of cardiac pathology, only in 6 (23.1%) of them the diagnosis was confirmed. The final diagnosis of the 99 patients was idiopathic chest pain in 45.4% of cases. CONCLUSIONS: Even with the low cost and the relatively easiness for the plasma level determination, TN should be measured only in children with chest pain associated to familiar history suggestive of cardiovascular disease and/or clinical symptoms and/or ECG alterations.

Intranasal nerve growth factor administration improves neurological outcome after GBS meningitis.

Nerve growth factor (NGF) is a neurotrophin that promotes neural recovery and plasticity after experimental brain injury, supporting neuronal growth, differentiation, and survival of brain cells. Only a few studies reported NGF administration in pediatric patients with impaired brain functions after traumatic injuries, ischemic or infectious diseases, such as meningitis. We described the beneficial therapeutic effects of human-recombinant nerve growth factor (hr-NGF) treatment in an infant with persistent unresponsive wakefulness syndrome (UWS), due to late-onset group B Streptococcus meningitis. The infant received five monthly cycles of intranasal hr-NGF (0.1 mg/kg, 3 times daily for 7 consecutive days) through a mucosal atomizer device (MAD). NGF administration improved functional [positron emission tomography/computed tomography (PET/CT), single-photon emission/computed tomography (SPECT/CT), and magnetic resonance imaging (MRI)] assessments, electrophysiological [Electroencephalogram (EEG)] studies, as well as main cognitive processes and clinical and neurological functions. After hr-NGF treatment, significant improvements in facial mimicry, attention, motor reactions, oral motility, and feeding capacity were observed. She also recovered some hypothalamic functions and her cough reflex was restored. No side effects were reported during and after the treatment. For the first time ever, hr-NGF has been successfully utilized in an infant with UWS and severe neurologic outcome due to a bacterial meningitis. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal hr-NGF administration appears to be a promising and save rescuing strategy treatment in infants with severe neurological impairment after brain damage.

Point-of-care lung ultrasound in infants with bronchiolitis in the pediatric emergency department: a prospective study.

Bronchiolitis is the most common cause of hospitalization of children in the first year of life. The lung ultrasound is a new diagnostic tool which is inexpensive, non-invasive, rapid, and easily repeatable. Our prospective study was conducted in the emergency department and all patients underwent a routine clinical evaluation and lung ultrasound by the pediatricians who defined the clinical and the ultrasound score. We enrolled 76 infants (median age 90 days [IQR 62-183], 53.9% males). In nasopharyngeal aspirates, the respiratory syncytial virus was isolated in 33 patients. Considering the clinical score, children with higher score had a higher probability of requiring respiratory support (p 0.001). At the ultrasound evaluation, there was a significant difference on ultrasound score between those who will need respiratory support or not (p 0.003). Infants who needed ventilation with helmet continuous positive airway pressure had a more severe ultrasound score (p 0.028) and clinical score (p 0.004), if compared with those who did not need it.Conclusion: Our study shows that lung ultrasound in the bronchiolitis may be a useful method to be integrated with the clinical evaluation to better define the prognosis of the individual patient. Multicenter studies on larger populations are necessary to confirm our data. What is Known: • Bronchiolitis is the main cause of lower respiratory tract infection in children younger than 24 months. • Ultrasound can evaluate the lung parenchyma without ionizing radiations. What is New: • Lung ultrasound may be a useful diagnostic tool to define the prognosis of the infants affected by bronchiolitis if performed at the first assessment in the emergency department. • The score obtained at the ultrasound evaluation is higher in those who will need oxygen therapy during admission for more time and in those who will need respiratory support with helmet continuous positive airway pressure.

Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS: We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS: The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.

Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

BACKGROUND: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. METHODS: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). RESULTS: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. CONCLUSIONS: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study.

BACKGROUND: Preclinical trials have shown beneficial effects of nerve growth factor (NGF) administration on visual function in animal models of retinitis pigmentosa (RP). The aim of this pilot study was to explore the potential efficacy of short term NGF eye drops treatment in patients affected by RP. METHODS: The trial consisted in 10 days daily administration of murine NGF as eye-drops for a total dose of 1 mg NGF/pt. Eight RP patients at an advanced stage of the disease were included in the trial. To monitor safety and potential adverse effects subjects underwent standard clinical measures and were requested to report any general or topic alterations following NGF assumption. Retinal function was assessed at baseline and after treatment by best-corrected visual acuity measurement (BCVA), macular focal electroretinogram (fERG) recording and Goldmann visual field testing. RESULTS: A transient tolerable local corneal irritation was the only adverse effect reported. fERG and BCVA remained within the limits determined by test-retest analysis of a large cohort of RP patients. Three patients reported a subjective feeling of improved visual performance. This was associated to a temporary enlargement of the visual field in all three patients and to improved fERG in two of the three. CONCLUSIONS: Short-term administration of NGF eye-drops caused neither significant adverse effects nor visual function losses in the tested RP patients. A minority of patients experienced an improvement of visual performance as shown by Goldmann visual field and fERG. This study supports the safety and possible efficacy of NGF eye-drops administration in RP patients. TRIAL REGISTRATION: EudraCT n. 2008-004561-26.