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Author(s): P. Bertet; S. Osnaghi; A. Rauschenbeutel; G. Nogues; A. Auffeves; M. Brune; J. M. Raimond; S. Haroche (corresponding author) To illustrate the quantum mechanical principle of complementarity, Bohr [1] [...]

A single-photon-quantum non-demolition (QND) measurement was achieved, satisfying the criteria of non-demolition and repeatability. An analysis of the interferometer imperfections was applied to the detection of an unknown field having no more than one photon. It is inferred that following a single meter reading, the corresponding photon number probability rises to 0.84. The single-photon QND (SP-QND) method amounts to the operation of a quantum gate where the photon and the atom have roles of control and target qubits.

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease that affects both eyes, often with asymmetric severity, potentially causing major visual complications. The seasonal management of VKC can be challenging, especially when specialists with different diagnostic and therapeutic approaches need to be consulted. The aim of this expert panel was to reach a national consensus among pediatric allergologists and ophthalmologists on the diagnosis and treatment of VKC. This consensus was developed by an expert panel of 17 Italian pediatric allergologists and ophthalmologists with over a decade of experience. Ten statements on VKC diagnosis and treatment formulated after a thorough review of current literature were evaluated by the panelists. The level of agreement was quantitatively assessed using a 5-point Likert scale. Consensus was reached if ≥ 75.0% of panelists agreed to any given statement. The consensus emphasizes the importance of evaluation by multispecialty reference centers or experienced specialists for accurate diagnosis. Prompt diagnosis, especially during active phases, is crucial and should occur before corticosteroid therapy. The Bonini score from 2007 is the preferred tool for VKC assessment, although future revisions may be considered. Short cycles of topical corticosteroids should be preferred over prolonged use, even during immunomodulatory therapy. When cyclosporine fails, tacrolimus should be considered., Conclusion: This is the first consensus on the management of VKC that has gathered the expert opinions of both pediatricians and ophthalmologists. The outcome of this multidisciplinary effort provides a uniform approach to VKC diagnosis and treatment, thereby facilitating patient management across the country., What Is Known: • Vernal keratoconjunctivitis (VKC) is a chronic recurrent ocular disease particularly prevalent in the pediatric population. • Despite its relevance, there is a lack of standardized approaches shared between pediatricians and ophthalmologists, leading to notable variations in clinical practice., What Is New: • This expert panel, comprising 17 pediatric allergologists and ophthalmologists, has reached a national consensus to provide standardized guidance for VKC management. • The consensus emphasizes the importance of a multidisciplinary approach to managing VKC, ensuring consistent and effective patient care., (© 2024. The Author(s).)

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g.    Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP.    Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments., (© 2023. The Author(s).)

In this study, a sensitive quantitative method based on high performance liquid chromatography combined with high-resolution mass spectrometry, Q Exactive TM -Orbitrap ® was set up and applied for the determination of the immunosuppressor agents cyclosporine A and tacrolimus in novel ethanol-free ophthalmic formulations for the treatment of Vernal keratoconjunctivitis. Different storage parameters in terms of storage temperatures and practical usage conditions were investigated to assess the stability of all formulations during shelf life simulating the real conditions as well to confirm the feasibility of use of ethanol-free products. The methodology was linear (r 2 = 0.995) over the concentration range 0-200 ng/mL, and its selectivity, precision, accuracy and recovery were all within the required limits. Under different conditions (storage period 0-90 days, 5-25 °C, unopened/usage simulated conditions), our results revealed that both active pharmaceutical ingredients (API) show satisfactory stability up to 30 days of storage/usage, with a significant and consistent concentration decline of cyclosporine A after this time point when its hydroalcoholic formulation was kept at 25 °C.

Background: Children with vernal keratoconjunctivitis (VKC) present symptoms that are similar to other ocular allergies, but more pronounced, and are controlled using topical steroids. To avoid excessive and prolonged use of topical steroid eye drops, over the past 20 years galenic eye drops of cyclosporine with a concentration of 1% to 2% and tacrolimus with a concentration of 0.1% have been introduced as a treatment for the severe and unresponsive forms. The main symptoms of VKC occur most frequently during the spring and tend to get worse during the summer, meaning that affected children tend to avoid exposure to sunlight. The aim of this study was to assess the most common cell types present in the conjunctiva of children with VKC, how ocular treatment can influence them, and whether affected children express a typical conjunctival pattern, which could be useful as a pathognomonic pattern of VKC, allowing us to study this rare eye disease., Method: This was a cohort study of 56 children, of whom 17 were not receiving any treatment at the time of testing, 14 were using steroid eye drops or had taken them in the previous 10 days, and 25 were treated with cyclosporine eye drops or tacrolimus eye drops 0.1%., Result: Children in group 1 (no topical therapy) express more epithelial cells, neutrophils, mast cells, eosinophils, and lymphocytes than the other two groups., Conclusion: Given the ease of performance, when conducting further longitudinal studies, the conjunctival cytology examination could be used, on the one hand, to diagnose VKC, especially when the clinical diagnosis is uncertain, and, on the other, to follow disease evolution and monitor the response to topical treatment., (© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Recent explorative studies suggest that propranolol reduces retinopathy of prematurity (ROP) progression, but the short-term effects of propranolol treatment at 1 year of corrected age have not been extensively evaluated. Methods: A multi-center retrospective observational cohort study was conducted to assess the physical development and the refractive outcome of infants with prior ROP treated with propranolol. Forty-nine infants treated with propranolol were compared with an equal number of patients who did not receive any propranolol therapy and represent the control group, with comparable anthropometrical characteristics and stages of ROP. Results: The weight, length, and head circumference at 1 year of corrected age were similar between infants who had been treated, or not, with propranolol, without any statistically significant differences. Refractive evaluation at 1 year showed spherical equivalent values decreasing with the progression of ROP toward more severe stages of the disease, together with an increasing number of infants with severe myopia. On the contrary, no differences were observed between infants who had been treated with propranolol and those who had not. Conclusion: This study confirms that the progression of ROP induces an increase of refractive errors and suggests that propranolol itself does not affect the refractive outcome. Therefore, if the efficacy of propranolol in counteracting ROP progression is confirmed by further clinical trials, the conclusion will be that propranolol might indirectly improve the visual outcome, reducing the progression of ROP., (Copyright © 2019 Filippi, Cavallaro, Perciasepe, Sandini, Araimo, Regiroli, Raffaeli, Bagnoli, Dal Monte, Calvani, Fortunato, Osnaghi, De Masi and Mosca.)

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a β-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration   The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Background: Idiopathic intracranial hypertension (IIH), also known as pseudotumour cerebri syndrome (PTCS), is characterized by the presence of signs and symptoms of raised intracranial pressure without evidence of any intracranial structural cause and with normal cerebrospinal fluid microscopy and biochemistry. Obesity, various systemic diseases and endocrine conditions, and a number of medications are known to be risk factors for PTCS. The medications commonly associated with PTCS are amiodarone, antibiotics, corticosteroids, cyclosporine, growth hormone, oral contraceptives, vitamin A analogues, lithium, phenytoin, NSAIDs, leuprolide acetate, and some neuroleptic drugs. In relation to antibiotics, quinolones may cause intracranial hypertension, and most reported cases of quinolone-induced intracranial hypertension were associated with nalidixic acid, ciprofloxacin, ofloxacin, or pefloxacin. Literature reports of levofloxacin-induced PTCS are rare. Some authors recently hypothesized that Mycoplasma pneumoniae may trigger PTCS., Case Presentation: We report on a 14-year-old overweight White Italian boy who suffered headache, diplopia, and severe bilateral papilloedema after a Mycoplasma pneumoniae infection, exacerbated on levofloxacin intake. A spontaneous improvement in headache and a reduction in diplopia was seen during hospitalisation. Oral acetazolamide therapy led to the regression of papilloedema in about five months. No permanent eye damage has been observed in our patient to date., Conclusions: PTCS pathophysiology may be multifactorial and its specific features and severity may be a consequence of both constitutional and acquired factors interacting synergistically. It may be useful for paediatricians to know that some antibiotics may have the potential to precipitate PTCS in patients who already have an increased CSF pressure due to a transitory imbalanced CSF circulation caused by infections such as Mycoplasma pneumoniae, with headache being the first and most sensitive, but also the least specific, symptom.

The aim of this study was to evaluate whether the control of ocular symptoms with cyclosporine or with tacrolimus in eye drops allows to improve sun exposure and therefore serum level of vitamin D (VD; 25OHD), in the more severe forms of vernal keratoconjunctivitis (VKC). Out of 242 children followed for active VKC, 94 were treated with 1% cyclosporine or 0.1% tacrolimus eye drops, while the other 148 with mild VKC did not need to be treated with immunomodulators. VD serum levels were measured in spring and autumn in 71 children. In total, 60 of them were treated with cyclosporine eye drops (first group) and 11 (not responding to cyclosporine therapy previously) with 0.1% tacrolimus eye drops (second group) between March and November 2016. Pre-treatment median values of VD were 23.7 ng/mL in the first group and 23.8 in the second group, and post-treatment values increased up to 32.8 and 32.9 ng/mL, respectively. Before treatment, 33% presented a deficiency (25OHD < 20 ng/mL), and at the end of summer, only 4% were deficient. The overweight children had lower improvement in VD serum levels than children with a body mass index (BMI) lower than 85th percentile. Children in therapy with cyclosporine, but requiring the administration of local steroid therapy during the summer for control of the symptoms, showed a greater improvement in 25OHD serum levels in ng/mL (23-37 ng/mL) than children who did not require steroid therapy (24-35 ng/mL). Furthermore, there was a significant difference in change of 25OHD in children presenting limbal VKC (21-41 ng/mL) versus tarsal VKC (24-35 ng/mL) ( P = 0.04). Our study suggests that ocular treatment carried out with immunomodulator eye drops could allow for an improvement in 25OHD serum levels. In children with active VKC and at risk of 25OHD deficiency, likely due to avoidance of sun exposure, the role of other risk factors (BMI, phototype and treatment) on 25OHD serum levels should be considered.