Digital eye strain in young screen users: A systematic review.

Digital eye strain (DES) or computer vision syndrome (CVS) is a phenomenon linked to ever increasing digital screen use globally, affecting a large number of individuals. Recognizing causative and alleviating factors of DES may help establish appropriate policies. We aimed to review factors that aggravate or alleviate DES symptoms in young, i.e. pre-presbyopic (< 40 years old), digital device users. We searched PubMed, Scopus, EMBASE, Cochrane, Trip Database, and grey literature up to 1st July 2021. Among a plethora of studies with heterogeneous diagnostic criteria for DES, we only included those using a validated questionnaire for the diagnosis and evaluating associated factors in young subjects. Relevant data were extracted, risk of bias assessment of the included studies and GRADE evaluation of each outcome were performed. Ten studies were included (five interventional, five observational) involving 2365 participants. Evidence coming from studies with moderate risk of bias suggested that blue-blocking filters do not appear to prevent DES (2 studies, 130 participants), while use of screens for > 4-5 h/day (2 studies, 461 participants) and poor ergonomic parameters during screen use (1 study, 200 participants) are associated with higher DES symptoms' score. GRADE evaluation for the outcomes of blue-blocking filters and duration of screen use showed low to moderate quality of evidence. It appears advisable to optimize ergonomic parameters and restrict screen use duration, for minimizing DES symptoms. Health professionals and policy makers may consider recommending such practices for digital screen users at work or leisure. There is no evidence for use of blue-blocking filters.

Comparison of adverse events between intravitreal anti-VEGF and laser photocoagulation for treatment-requiring retinopathy of prematurity: a systematic review.

PURPOSE: To synthesize existing evidence on adverse events, complications, and unfavorable outcomes of current treatment modalities for treatment-requiring retinopathy of prematurity (TR-ROP). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Scopus, EMBASE, Trip Database, and the gray literature available were searched. Randomized Clinical Trials and observational studies comparing the adverse events of intravitreal anti-VEGF injections (bevacizumab, ranibizumab, aflibercept, pegaptanib, conbercept) and laser photocoagulation (LPC) as treatment modalities for infants with TR-ROP were included. The main outcomes compared between the two treatment modalities were: 1. Refractive Errors and Biometry Parameters, 2. Adverse events, complications, and unfavorable outcomes, 3. Disease Recurrence/Disease Regression/Need for retreatment, 4. Neurodevelopmental Outcomes. RESULTS: Higher quality studies concluded that LPC leads to greater rates of myopia than intravitreal anti-VEGF treatment while the rate of adverse events and of unfavorable neurodevelopmental outcomes is similar. However, there was controversy among the included studies concerning the rate of ROP recurrence between intravitreal anti-VEGF injections and LPC. CONCLUSION: There is need for future primary studies assessing the adverse events of intravitreal anti-VEGF injections compared with LPC as treatment modalities for infants with TR-ROP.

When should cataract surgeons seek assistance from experienced colleagues?

PURPOSE: To assess which cases should be assorted exclusively to high-volume surgeons and identify when should a cataract surgeon seek assistance from a senior colleague. METHODS: The medical records of 2853 patients with age-related cataract were reviewed. Preoperative risk factors were documented for each case, and they were divided into surgeons who had more (> 400 surgeries/year) or less experience (< 400 surgeries/year). Ophthalmology residents were excluded from this review. The cases that involved posterior capsule rupture, dropped nucleus, zonular dehiscence and anterior capsular tear with or without vitreous loss were defined as "complicated". RESULTS: From the 3247 cataract extraction surgeries that were reviewed, we were unable to identify any statistically significant difference in the complication rates between the two surgeon groups. In the stepwise regression analysis, both groups supported advanced age (> 85) and mature cataracts with up to fourfold odds ratios (OR). Low-volume surgeons had a fivefold OR in the presence of phacodonesis and a fourfold OR in the case of posterior polar cataract. Finally, the low- and high-volume groups had their highest complication rates in the cumulative four and five risk factors, respectively. CONCLUSION: In the presence of advanced age, mature cataracts, phacodonesis and posterior polar cataract, the complication rates appear to be higher for the less experienced surgeons. Meticulous preoperative assessment with detailed documentation of each patient's risk factors can result in fewer complications. The medical complexity of each case can be used as indicator of whether a more experienced surgeon should perform the surgery or not.

Repeatability of corneal pachymetry and epithelial thickness measurements with spectral-domain optical coherence tomography (SD-OCT) and correlation to ocular surface parameters.

PURPOSE: To assess the repeatability of corneal pachymetry and epithelial thickness measurements with spectral-domain optical coherence tomography (SD-OCT) and identify correlations between epithelial thickness and ocular surface parameters. METHODS: Adults who happened to have prolonged computer use were recruited, excluding those with conditions interfering with corneal measurements or tear production. All subjects filled in the ocular surface disease index (OSDI) questionnaire. Three consecutive measurements of central and peripheral corneal and epithelial thickness were performed with SD-OCT (RTVue XR). Schirmer test I and tear film break-up time (TBUT) were performed. Repeatability was evaluated with intraclass correlation coefficient (ICC), coefficient of variation and repeatability limit. Spearman correlation was used for non-parametric variables. RESULTS: 113 eyes of 63 subjects were included in the study. ICC was ≥ 0.989 for all corneal and ≥ 0.944 for all epithelial pachymetry segments. The best repeatability was found centrally and the worst superiorly both for corneal and epithelial measurements. Central epithelial thickness was weakly correlated with Schirmer test I (rho = 0.21), TBUT (rho = 0.02), OSDI symptoms and OSDI score (rho <|0.32|). OSDI symptoms and OSDI score were weakly correlated with Schirmer test I (rho <|0.3|) and TBUT (rho <|0.34|). CONCLUSION: RTVue XR measurements of corneal and epithelial thickness are highly repeatable in all segments. The lack of correlation between epithelial thickness and ocular surface parameters could suggest the assessment of epithelial integrity with reliable methods such as SD-OCT.

Association of platelet deficiency with severe retinopathy of prematurity: a review.

AIM: The aim of this review was to compile existing evidence on the role of platelets in the development of severe retinopathy of prematurity (ROP), highlight the strengths and weaknesses of the available studies and critically discuss the reported data. METHODS: A comprehensive literature search was conducted on PubMed from January 2000 to January 2022, and the reference lists of the included studies were screened manually. RESULTS: There were 19 primary studies that fulfilled the eligibility criteria. Experimental research indicated lower platelet count in mice oxygen-induced retinopathy model compared with normoxia controls, while platelet transfusions suppressed neovascularisation. The latter finding was not consistently confirmed in clinical research, where a low platelet count, an increased number of thrombopenic episodes and of platelet transfusions have all been implicated in the development of ROP requiring treatment, either type I or aggressive posterior or both. However, existing studies exhibit significant clinical heterogeneity and present methodological limitations that imperil their reliability and validity. CONCLUSION: Platelet deficiency has been associated with severe ROP. However, critical thresholds of platelet parameters are still unrecognised. Future research is required to determine whether platelet parameters can be predictive biomarkers for ROP requiring treatment and at what thresholds.

Silodosin as a predisposing factor of intraoperative floppy iris syndrome (IFIS): an observational propensity score-matching cohort study.

PURPOSE: To evaluate the correlation between silodosin and intraoperative floppy iris syndrome (IFIS) and compare it with other a1-adrenergic receptor antagonists (a1-ARAs) and other factors predisposing to IFIS. METHODS: From the patients who underwent phacoemulsification between 2014 and 2020, we identified all patients who, during their preoperative assessment, reported an a1-ARAs intake (exposed group). These patients were matched utilizing a propensity score matching analysis with an otherwise homogenous group of patients (control group) based on demographics and systemic/ocular comorbidities. RESULTS: A total of 350 patients were included in each group. In the exposed group, 177 (50.6%) patients were exposed to tamsulosin, 105 (30%) to alfuzosin, 43 (12.2%) to silodosin. Regarding IFIS, it was observed in 21.5% of patients on tamsulosin (38/177), 11.4% on alfuzosin (12/105), 37.2% on silodosin (16/43), and 3.4% in the controlled group (12/350). In a multiple regression model analysis, the only two factors significantly associated with IFIS development were silodosin and tamsulosin yielding an adjusted odds ratio of 8.471 (95%CI 4.005-17.920) and 3.803 (95%CI 2.231-6.485), respectively. CONCLUSION: Silodosin has been demonstrated as a predisposing factor, strongly correlated with IFIS development. These results should increase cataract surgeons' awareness to assess their patients preoperatively for exposure to silodosin carefully and employ the appropriate prophylactic measures to ameliorate the impact of silodosin intake on the surgical outcome.

Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates.

PURPOSE: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

Reliability of Refraction, Keratometry, and Intraocular Pressure Measurements with an Automated All-in-one Device.

SIGNIFICANCE: This study explores the reliability of TonoRef II (Nidek, Tokyo, Japan), which represents a simple tool to obtain rapid refractometry and tonometry measurements. The present device demonstrates very high repeatability of refraction and intraocular pressure (IOP) readings as compared with subjective measurements and a higher concordance of IOP readings to Goldmann application tonometry (GAT). PURPOSE: This study aimed to evaluate the repeatability of measurements acquired with the Autorefractometer/Keratometer/Tonometer TonoRef II and assess their agreement to subjective measurements and readings of other established devices. METHODS: In a cross-sectional study, 54 eyes of 54 healthy subjects were enrolled. Each subject underwent five measurements with the TonoRef II, three measurements with the Canon RK-F1 Autorefractor Keratometer (Canon Europe NV, Amstelveen, the Netherlands), three IOP measurements with the Canon TX-F Noncontact Tonometer (Canon Inc., Tokyo, Japan), three measurements with GAT, and a thorough subjective refraction. Repeatability coefficient (r), intraclass correlation coefficient (ICC), and Bland-Altman plots were used to evaluate repeatability of readings and agreement to the subjective values. RESULTS: TonoRef II showed high repeatability (ICC >0.9) in all parameters tested (sphere, r = 0.157; cylinder, r = 0.196; IOP, r = 2.653). A strong correlation was found between TonoRef and Canon instruments (P < .001 in all parameters). Mean differences and limits of agreement (mean ± 1.96 standard deviation) were -0.01 ± 0.69 D, -0.11 ± 0.7 D, and 2.1 ± 3.4 mmHg for sphere, cylinder, and IOP, respectively. Both autorefractors achieved a very good to excellent agreement to the values obtained with the subjective refraction for most of the parameters tested, without any significant difference to each other (P > .05). Intraocular pressure measurements of TonoRef II showed higher agreement to the GAT values compared with those obtained with the Canon tonometer (ICC, 0.9114 and 0.7002, respectively; P < .001). CONCLUSIONS: Intraocular pressure and refraction readings acquired with TonoRef II demonstrate very high repeatability and agreement to the subjective measurements. Regarding IOP evaluation, TonoRef II shows higher concordance to GAT compared with another established noncontact tonometer.

Iridocorneal angle assessment in children with spontaneously regressed retinopathy of prematurity.

PURPOSE: To assess anterior segment anatomic parameters in school-aged children with spontaneously regressed retinopathy of prematurity (sr-ROP) and in children born preterm without ROP history (preT). METHODS: sr-ROP and preT children were compared with healthy, born at term children (control group). Biometric characteristics were measured with the IOLMaster. Iridocorneal angle structure was evaluated using Visante AS-OCT, and angle opening distance, trabecular iris space area and scleral spur angle were calculated. Best-corrected visual acuity (BCVA) was measured with the ETDRS chart. RESULTS: We examined 22 eyes of 11 children with sr-ROP, 26 eyes of 13 preT children and 24 eyes of 12 healthy controls, with a median age of 8 years. sr-ROP children exhibited worse mean BCVA and reduced AL compared to controls (p = 0.001 and p = 0.007, respectively). A narrower iridocorneal angle was found in sr-ROP compared to the preT and the control groups. Preterm children were found to have similar anterior chamber angle metrics compared to the full-term control group. CONCLUSION: In this study, school-aged children with a history of sr-ROP had narrower angles compared to preterm- and term-born children. AS-OCT demonstrated structural differences of the iridocorneal angle in sr-ROP, possibly reflecting a mild developmental arrest of the anterior segment.

Safety of air tamponade versus corneal hydration for sealing clear corneal incisions in cataract surgery.

PURPOSE: To compare safety of wound hydration to anterior chamber air tamponade for securing watertight closure of clear corneal incisions, during uneventful cataract surgery. METHODS: Prospective, comparative case-control series. Patients undergoing phacoemulsification were assigned to receive either anterior chamber air bubble (Group A) or intrastromal wound hydration with balanced salt solution (Group B) at the end of the procedure. Two high-volume surgeons operated equal number of cases in each group employing identical surgical technique, except for corneal side incision management. Patients were assessed pre- and postoperatively at day 1, day 4, day 9, and day 30 after surgery. RESULTS: One hundred eyes of 100 patients were enrolled, of which 2 were lost to follow-up. The two groups were comparable in terms of preoperative risk factor assessment, baseline central corneal thickness (CCT), preoperative endothelial cell density, as well as cumulative dissipated energy and duration of phacoemulsification (p > 0.05). Mean CCT and best-corrected visual acuity were better in Group B on the first postoperative day, but did not differ between the two groups at all other timepoints. Surgically induced astigmatism was comparable in the two groups (p > 0.05). Endothelial cell density loss at 1 month postoperatively was greater in Group A (34.06%) compared to Group B (16.45%). CONCLUSIONS: Wound sealing with intrastromal hydration proved to be safer than air tamponade in terms of preserving endothelial cell density and function.

Retinopathy of prematurity occurrence and evaluation of screening policy in a large tertiary Greek cohort.

PURPOSE: To assess the frequency of retinopathy of prematurity (ROP) and evaluate the appropriateness of screening guidelines in a tertiary hospital in Thessaloniki, Greece. METHODS: Retrospective review of consecutive infants admitted to the IInd Department of the Neonatal Care Unit of Aristotle University in the period April 2004-2015. ROP screening took place according to the Royal College of Paediatrics and Child Health and Royal College of Ophthalmologists (UK) guidelines [i.e. gestational age < 32 weeks and/or birth weight < 1501 g)], plus a few additional cases due to comorbidity. RESULTS: 1178 out of the 8782 admitted infants underwent ROP screening. ROP was detected in 232 (19.7%) infants of whom 87 developed severe form of the disease (i.e. ≥ stage 3). Treatment was required in 30 (2.5%) infants, all of whom fulfilled the screening criteria. Two of the 206 infants who were additionally screened due to comorbidity developed severe ROP which regressed spontaneously. Disease regression was achieved in 27/29 (93%) treated infants who survived. CONCLUSIONS: The frequency of ROP observed in this cohort was as low as that reported in other developed countries. The currently used screening criteria permitted identification of all infants who were at risk and, therefore, need not be changed.

Alternative mydriasis techniques for retinopathy of prematurity screening.

PURPOSE: There is a large variation in mydriatic regimens used in screening for retinopathy in preterm infants. Except for the standard instillation of mydriatic drops in their commercial formulation, other techniques for pupil dilation have also been described. This study aimed to review all techniques that have been used for mydriasis in retinopathy of prematurity eye examination (ROPEE) screening. METHODS: A comprehensive literature search was performed in PubMed, Cochrane library, Trip database, and Scopus, using the key words: "mydriasis", "techniques", "mydriatics", "dilating drops", "retinopathy of prematurity", "ROP", "phenylephrine", "cyclopentolate", "tropicamide", "smaller mydriatic drops", "reduction in drop size" to February 2019. RESULTS: Five primary studies were included, assessing the techniques of microdrops, lower conjunctival fornix (LCF) packing and Mydriasert® ophthalmic insert. Reported efficacy was similar to commercial eyedrops instillation. Microdrops appeared to have a superior safety profile. LCF packing and Mydriasert lead to increased blood pressure, without serious complications, necessitating further safety studies. CONCLUSIONS: Of all alternative mydriasis techniques for ROPEE screening that have been described, microdrops appear to be the safest yet still effective technique in the fragile population of premature infants in risk of ROP.

Is conversion of decimal visual acuity measurements to logMAR values reliable?

PURPOSE: To assess if conversion of decimal visual acuity (VA) to logMAR is reliable for clinical and research purposes. METHODS: Right eye VA of 74 consecutive patients was measured with 5 min interval, using (a) the ETDRS chart (VAlog), (b) a decimal chart at 6 m (VA6m), and (c) a decimal chart at 4 m (VA4m). VA was the smallest line whereby four of five optotypes were correctly identified. Decimal scores were converted to logMAR using the formula logMAR = -log(decimal acuity). The agreement between VAlog, VA4m, and VA6m was assessed by the Bland-Altman method. RESULTS: Linear regression analysis of the difference between VAlog and VA6m or VA4m showed a significant slope (p = 0.001), with greater disagreement at higher VA values, i.e., poorer acuity. There was considerable lack of agreement, with discrepancies of up to 0.2 logMAR when VA was measured around 0.5 logMAR. CONCLUSION: Converting decimal VA to logMAR produces overestimation of its true value, especially in lower acuities.

Use of log-scaled crowded visual acuity charts in clinical studies regarding amblyopia.

PURPOSE: Log-scaled crowded charts using standardized testing protocol are essential for precise and reproducible visual acuity (VA) testing regarding amblyopia. Despite common acceptance of these standards, current VA testing clinical practice shows considerable diversity. The purpose of this retrospective literature review was to investigate the methodology of VA measurement and reporting in pediatric ophthalmology literature regarding amblyopia. METHODS: We searched PubMed for clinical trials regarding amblyopia, published from January 1994 to July 2016. Primary outcomes included VA measurement methodology, namely use of (a) log-scaled chart, (b) crowded chart, and (c) specified testing protocol. The study design, publication year, and the journal's impact factor were analyzed in relation to the primary outcomes. RESULTS: Out of the 165 initial reports, 150 were included. VA was measured with a log-scaled chart in 65%, with a crowded chart in 57%, and with a specified protocol in 51% of studies. All three criteria were met in 43% of studies and in multivariable logistic model, they were associated with more recent publication year (odds ratio [OR] = 1.11, 95% confidence interval [95%CI] = 1.03-1.20) and were more likely to be present in higher impact factor journals (OR = 1.42, 95%CI = 1.17-1.72) or randomized controlled trials (OR = 3.09, 95%CI = 1.44-6.59). CONCLUSIONS: In the last two decades, more than half of clinical trials addressing amblyopia have not followed the recommended methodology for optimal visual acuity assessment. Thus, their measurements may have been contaminated with noise, and their respective results and conclusions may include errors. Adhering to optimal, standardized methodology is key to progress in both clinical and research grounds.

Efficacy and safety of interventions to control myopia progression in children: an overview of systematic reviews and meta-analyses.

BACKGROUND: Myopia is a common visual disorder with increasing prevalence. Halting progression of myopia is critical, as high myopia can be complicated by a number of vision-compromising conditions. METHODS: Literature search was conducted in the following databases: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database. Systematic reviews and meta-analyses investigating the efficacy and safety of multiple myopia interventions vs control conditions, were considered. Methodological quality and quality of evidence of eligible studies were assessed using the ROBIS tool and GRADE rating. The degree of overlapping of index publications in the eligible reviews was calculated with the corrected covered area (CCA). RESULTS: Forty-four unique primary studies contained in 18 eligible reviews and involving 6400 children were included in the analysis. CCA was estimated as 6.2% and thus considered moderate. Results demonstrated the superior efficacy of atropine eyedrops; 1% atropine vs placebo (change in refraction: -0.78D, [- 1.30 to - 0.25] in 1 year), 0.025 to 0.05% atropine vs control (change in refraction: -0.51D, [- 0.60 to - 0.41] in 1 year), 0.01% atropine vs control (change in refraction: -0.50D, [- 0.76 to - 0.24] in 1 year). Atropine was followed by orthokeratology (axial elongation: - 0.19 mm, [- 0.21 to - 0.16] in 1 year) and novel multifocal soft contact lenses (change in refraction: -0.15D, [- 0.27 to - 0.03] in 1 year). As regards adverse events, 1% atropine induced blurred near vision (odds ratio [OR] 9.47, [1.17 to 76.78]) and hypersensitivity reactions (OR 8.91, [1.04 to 76.03]). CONCLUSIONS: Existing evidence has failed to convince doctors to uniformly embrace treatments for myopic progression control, possibly due to existence of some heterogeneity, reporting of side effects and lack of long-term follow-up. Research geared towards efficient interventions is still necessary.

Female carrier of RPGR mutation presenting with high myopia.

BACKGROUND: Inherited retinopathies can initially present with high refractive error in the first decade of life, before accompanying signs or symptoms are evident. CASE PRESENTATION: A 4-year-old girl with high myopia (S-12.00 C-4.00 × 20 in the right and S-14.50 C-2.75 × 160 in the left eye), moderate visual acuity (0.3 logMAR in the right and 0.4 logMAR in the left eye), and left esotropia, presented with unremarkable past medical history and no family history of high refractive error or low vision. In optical coherence tomography imaging, macular thinning was evident, while morphology was normal. Full-field electroretinogram revealed normal implicit time recordings with reduced amplitudes in scotopic and photopic conditions. Fundus autofluorescence showed a radial pattern in both eyes. During a 5-year follow-up, significant myopia progression ensued (S-17.25 C-3.00 × 20 in the right and S-17.25 C-2.00 × 160 in the left eye), with a corresponding increase in axial length and an unchanged visual acuity. Whole-exome sequencing revealed a heterozygous termination codon variant c.212C>G (p.Ser71Ter) in RPGR, considered to be pathogenic. Segregation analysis precluded the variation in the mother and sister. A random pattern of X-chromosome inactivation was detected in the proband, without X-chromosome inactivation deviation. CONCLUSION: This is the second report associating this specific RPGR mutation with high myopia and the first report to identify it in a female proband. This case provides additional evidence on the genotypic-phenotypic correlation between RPGR c.212C>G mutation and high myopia.

Mydriasis for retinopathy of prematurity screening in Europe: A cross-sectional online survey.

PURPOSE: To compile real-time data on the preferred mydriasis practice patterns for retinopathy of prematurity (ROP) screening in Europe. METHODS: A cross-sectional online survey was conducted from December 2022 to January 2023, using a self-report online questionnaire which was distributed via email to the members of the European Pediatric Ophthalmological Society and the Greek National ROP Task Force. A six-week period of recruitment was determined, and a reminder email was sent after two weeks. Descriptive statistics were used to explore the data, which was summarized with frequencies and percentages. RESULTS: Sixty-six responses were recorded (response rate: 29.5%), representing practices in 55 Neonatal Intensive Care Units from 21 European countries. In 94.5%, the applied mydriatic regimen consists of phenylephrine with at least one muscarinic antagonist, either tropicamide or cyclopentolate. The concentration of phenylephrine ranges from 0.5% to 5%, of tropicamide from 0.25% to 1%, and of cyclopentolate from 0.2% to 1%. The most commonly used regimen (43.6%) contains phenylephrine 2.5% and tropicamide 0.5%, administered either combined or separately. About 54.5% of the reported mydriatic solutions are non-commercial, in-house preparations. Systemic adverse events, including oxygen desaturation, bradycardia and cardiopulmonary arrest were reported in 14.5%. CONCLUSION: There is considerable heterogeneity in the applied mydriatic regimens for ROP screening in Europe, reflecting the absence of universal guidelines. The wide use of in-house preparations underlines the gap in the pharmaceutical industry. Concern should be raised against the wide use of undiluted commercial drugs, that reach adult dose, in the fragile population of preterm infants.