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.

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.

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.

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.

Safety profile of anesthetic modalities during laser treatment for retinopathy of prematurity: a systematic review.

OBJECTIVE: To determine the anesthetic approach with the least adverse events and better cardiorespiratory stability profile, used in infants undergoing laser photocoagulation for retinopathy of prematurity. STUDY DESIGN: A systematic review was conducted. PubMed, Scopus, and Cochrane Library were searched until 27th October 2021. Reference lists of relevant studies, and abstract books of international annual meetings of pediatric Οphthalmology for the years 2020 and 2021 were also looked at, as well as Clinical trials registry ( https://clinicaltrials.gov/ ). RESULT: Overall 18 primary studies (3 randomized controlled trials, 3 cohorts, 12 case series) were included, investigating different anesthetic modalities. Cardiopulmonary instability was more common, and hypothermia was less common in the sedation groups of pentazocine/midazolam and fentanyl/midazolam, compared to the general anesthesia group of air/oxygen/sevoflurane (AOS). Cardiorespiratory instability was also more common in sedation with propofol/ketamine compared to general anesthesia with AOS, while postoperative mechanical ventilation was more frequently needed in the latter. Αpnea, need for supplemental oxygen and cardiorespiratory instability was more frequent in infants receiving fentanyl as opposed to ketamine. Fentanyl compared to morphine presented no differences in safety parameters. Finally, topical anesthesia showed the greatest instability with a higher mean postoperative cardiorespiratory index, compared to both sedation and general anesthesia. Episodes of life-threatening events were reported after topical anesthesia, while hypothermia and oliguria presented less often after topical, compared to general anesthesia and sedation. CONCLUSION: Significant heterogeneity among studies precludes direct comparisons and generalizability of the results. No specific anesthetic modality for treatment of ROP with laser photocoagulation was shown to be superior in terms of safety. Well-designed studies are required to establish the optimal anesthetic approach, considering that laser photocoagulation still remains one of the main therapeutic modalities for ROP.

Is thrombocytopenia and postnatal weight gain associated with treatment-requiring retinopathy of prematurity? A matched case-control study.

PURPOSE: The purpose of the study was to investigate the association of platelet parameters and postnatal weight gain with treatment-requiring ROP (TR-ROP). METHODS: In this retrospective matched case-control study, infants with TR-ROP were individually matched, according to gestational age and birth weight, with one or two untreated infants who developed no or spontaneously regressed ROP. Longitudinal data on platelet count (PLT), mean platelet volume (MPV), daily weight and platelet transfusions were collected. Platelet mass index (PMI) and weight standard deviation score (WSDS) were also calculated. Conditional logistic regression analysis was performed to adjust for matching. RESULTS: Fourteen cases, presenting type I ROP, and 25 matched controls were included. The odds of developing TR-ROP decreased as PLT increased during 31st week of postmenstrual age (PMA) or during 1st and 2nd week of postnatal age (PNA). The odds of developing TR-ROP were 16.7 times higher in infants receiving at least one platelet transfusion compared with those who were not transfused. The odds of developing TR-ROP increased by 31.2% as the mean volume of platelet transfusion per infant increased by 1 ml. The odds of developing TR-ROP decreased as PMI increased during 1st week PNA, and as weight and WSDS increased during 4th -6th week PNA. Analysis of MPV, number of thrombopenic episodes per infant, number of platelet transfusions per infant and days with WSDS < -2 showed no association with TR-ROP. CONCLUSION: To our knowledge, this is the first study ascertaining an association of platelet transfusions with type I ROP. Prospective cohort studies are required to confirm our findings.

Optimization of retinopathy of prematurity screening in a tertiary neonatal unit in Northern Greece based on 16-year data.

OBJECTIVE: The optimal modification of retinopathy of prematurity (ROP) screening policy in our unit, by tightening the applicable screening criteria, without missing treatment-requiring ROP (TR-ROP). STUDY DESIGN: Retrospective analysis of screened infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1501 g as well as cases beyond these thresholds but with comorbidities (April 2004 to April 2020). RESULT: Of 1560 included infants, 18.4% (n = 288) developed any stage of ROP and 3.1% (n = 49) were treated. TR-ROP occurred at a mean (SD) 362/7 (25/7) weeks PMA, and not before a minimum of 323/7 weeks PMA. No treated infant would have been missed if screening criteria were reduced to GA < 30 weeks and/or BW < 1251 g. This modification would have resulted in 826 (52.9%) fewer infants undergoing screening. CONCLUSION: Modifying the current screening criteria to GA < 30 weeks and/or BW < 1251 g would have spared over half of the screened infants from unnecessary examinations, without missing TR-ROP.

Efficacy and safety of mydriatic microdrops for retinopathy of prematurity screening: an external pilot crossover randomized controlled trial.

OBJECTIVE: To study the efficacy and safety of mydriatic microdrops compared with standard drops for retinopathy of prematurity (ROP) screening. STUDY DESIGN: Preterm infants undergoing ROP screening received microdrops and standard drops of phenylephrine 1.67% and tropicamide 0.33% in a random allocation sequence at two consecutive weekly examinations. Primary outcome was pupil diameter measured by two masked observers at 45 (T45) and 90 (T90) minutes after instillation. RESULTS: Twenty-five infants were randomized. No differences observed in mean pupil diameter after either administration technique at all time points (T45 Mean Difference: -0.14; 95% Confidence Interval: -0.38, 0.09; p = 0.23). Heart rate values at T120 were lower after microdrop instillation (p = 0.046). Otherwise, adverse events did not differ after either administration technique. CONCLUSION: This pilot study provides evidence of microdrops mydriasis efficacy, while justifying a full-scale trial to confirm their non-inferiority compared with standard drops and provide more data about safety. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04623684.

Avoiding use of lid speculum and indentation reduced infantile stress during retinopathy of prematurity examinations.

PURPOSE: To study the safety and efficacy of indirect ophthalmoscopy with (Sp) or without (speculum free, SpF) the use of lid speculum and scleral indentation for retinopathy of prematurity (ROP) screening. METHODS: In this crossover randomized controlled trial, preterm infants received either the Sp on their first and the SpF technique on their second examination a week later or vice versa. Video recordings of the infants' reactions were assessed by two observers, using Premature Infant Pain Profile-Revised score and the crying score of the Bernese Pain Scale for Neonates. Fundoscopy adequacy, its duration and adverse events within the first 24 hr postscreening were also recorded. RESULTS: Thirty-seven infants with median (interquartile range) gestational age of 28.7 (28.0, 30.2) weeks and mean (standard deviation, SD) birth weight 1225 (377) grams were enrolled. The mydriasis-induced stress was similar between the Sp and SpF exam (mean difference [MD]: 0.78, 95% confidence interval [CI]: -0.83, 2.38; p = 0.33). The stress induced by fundoscopy (MD: 4.98, 95% CI: 3.58, 6.37; p < 0.001) and examination overall (MD: 2.32, 95% CI: 0.96, 3.67; p = 0.001) were higher in the Sp than in the SpF exam, and so was the crying score during fundoscopy (MD: 1.31, 95% CI: 1.06, 1.56; p < 0.001). Adverse events in the two groups were similar (p = 0.13). Fundoscopy was adequate in identifying the absence of treatment-requiring ROP in all cases, and lasted longer in the Sp than in the SpF exam (p < 0.001). CONCLUSION: Our study suggests that the use of speculum and indentation should be reserved for the few cases where fundus visualization is insufficient for excluding the presence of severe ROP.

Efficacy and safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening (MyMiROPS): study protocol for a non-inferiority crossover randomized controlled trial.

BACKGROUND: Retinopathy of prematurity (ROP) eye examination screening presupposes adequate mydriasis for an informative fundoscopy of preterm infants at risk, on a weekly basis. Systemic absorption of the instilled mydriatic regimens has been associated with various adverse events in this fragile population. This report aims to present the fully developed protocol of a full-scale trial for testing the hypothesis that the reduced mydriatic drop volume achieves adequate mydriasis while minimizing systemic adverse events. METHODS: A non-inferiority crossover randomized controlled trial will be performed to study the efficacy and safety of combined phenylephrine 1.67% and tropicamide 0.33% microdrops compared with standard drops in a total of 93 preterm infants requiring ROP screening. Primary outcome will be the pupil diameter at 45 (T45) min after instillation. Pupil diameter at T90 and T120 will constitute secondary efficacy endpoints. Mixed-effects linear regression models will be developed, and the 95% confidence interval approach will be used for assessing non-inferiority. Whole blood samples will be analyzed using hydrophilic liquid chromatography-tandem mass spectrometry method (HILIC-MS/MS), for gathering pharmacokinetic (PK) data on the instilled phenylephrine, at nine specific time points within 3 h from mydriasis. Pooled PK data will be used due to ethical restrictions on having a full PK profile per infant. Heart rate, oxygen saturation, blood pressure measurements, and 48-h adverse events will also be recorded. DISCUSSION: This protocol is designed for a study powered to assess non-inferiority of microdrops compared with standard dilating drops. If our hypothesis is confirmed, microdrops may become a useful tool in ROP screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT05043077 . Registered on 2 September 2021.