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.

Exploring vismodegib: A non-surgical breakthrough in the management of advanced periocular basal cell carcinoma.

The management of periocular basal cell carcinoma (BCC) is challenging due to its proximity to the eyeball. Vismodegib, a Hedgehog pathway inhibitor, has emerged as a therapeutic option for locally advanced and metastatic BCC. To critically appraise the relevant evidence, we conducted a systematic review of observational and experimental studies assessing the efficacy and safety of vismodegib for periocular BCC. Thirty-seven trials, including 435 patients, were eligible. No randomized trials were retrieved. Complete and overall clinical response rates were 20-88 % and 68-100 %, respectively. Disease progression was observed at a maximum rate of 14 %. Recurrence rates varied between 0 % and 31 %. The most common side effects were muscle cramps, dysgeusia, weight loss and alopecia. Treatment with vismodegib improved health-related quality of life. In conclusion, vismodegib represents an important novel treatment for advanced periocular BCC, with good response rates and acceptable tolerability profile. Nevertheless, its full potential needs clarification through randomized controlled trials.

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.

Safety and Efficacy of Prostaglandin Analogues in the Immediate Postoperative Period after Uneventful Phacoemulsification.

Prostaglandin analogues (PGAs) have been associated with the development of pseudophakic macular edema (PME) in complicated cataract cases, but evidence on their effects in uncomplicated phacoemulsification remains controversial. This two-arm, prospective, randomised study included patients with glaucoma or ocular hypertension under PGA monotherapy who were scheduled for cataract surgery. The first group continued PGA use (PGA-on), while the second discontinued PGAs for the first postoperative month and reinitiated use afterwards (PGA-off). Topical non-steroidal anti-inflammatory drugs (NSAIDs) were routinely administered to all patients during the first postoperative month. The patients were followed up for three months and the primary outcome was PME development. Secondary outcomes were corrected distance visual acuity (CDVA), central and average macular thickness (CMT and AMT), and intraocular pressure (IOP). The analysis included 22 eyes in the PGA-on group and 33 eyes in the PGA-off group. No patient developed PME. CDVA was not significantly different between the two groups (p = 0.83). CMT and AMT showed a small but statistically significant increase until the end of follow-up (p < 0.001). Mean IOP values had no significant differences between the groups at each visit (p > 0.05). At the end of follow-up, the IOP values were significantly lower than baseline in both groups (p < 0.001). In conclusion, PGA administration with concomitant topical NSAIDs appears to be a safe practice in the early postoperative period of uncomplicated phacoemulsification.

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.

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.

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.

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.

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.

Comparison of two protocols of diode laser transscleral cyclophotocoagulation in refractory glaucoma.

INTRODUCTION: Diode laser transscleral cyclophotocoagulation (DLTSCPC) remains the most commonly used cyclodestructive procedure. Nonetheless, there is no common consensus on a standardized technique. METHODS: In this prospective randomized pilot study we compare the "pop"-titrated and "slow-burn" DLTSCPC techniques for a follow-up period of 3 months. The major outcomes of this study were intraocular pressure (IOP) before and after the procedure and the incidence of adverse events. Furthermore, postoperative pain, postoperative intraocular inflammation and corrected distance visual acuity (CDVA) were evaluated. RESULTS: Mean baseline IOP decreased from 37.9 ± 12.7 mmHg in the pop group and 41.2 ± 9.6 mmHg in the slow-burn group to 20.3 ± 13.9 mmHg and 21.3 ± 13.4 mmHg at the final follow-up visit, corresponding to a 45.8 ± 31.7% and 46.3 ± 32.6% reduction respectively. 64.3% and 57.1% of patients had IOP ≥6 and≤ 21 mmHg in the pop and slow-burn groups respectively. The occurrence of adverse events was similar in both groups, with 1 case of hyphema in the pop group and 2 cases in the slow-burn group, and 1 case of hypotony in each group. Mean CDVA remained unchanged until the end of follow-up from 2.05 ± 0.84 to 2.04 ± 0.8 logMAR in the pop group and from 1.93 ± 0.78 to 1.89 ± 0.7 logMAR in the slow-burn group. Nonetheless, 4 eyes in each group encountered CDVA loss. Postoperative pain and inflammation were also similar between groups. DISCUSSION: At the 3rd postoperative month, safety and efficacy was similar in the two techniques. The relative ease of the slow-burn technique may make its application more appealing to ophthalmic surgeons beyond glaucoma specialists.

Descemet's Stripping Automated Endothelial Keratoplasty Using Donor Tissue from an 83-Day-Old Infant.

Purpose: To report a case of Descemet stripping automated endothelial keratoplasty (DSAEK) combined with phacoemulsification in an adult recipient using endothelial graft from an 83-day-old infant donor. Methods: A corneoscleral button was obtained from an infant donor and a DSAEK graft was prepared using a microkeratome. In comparison to the standard technique of DSAEK graft preparation some modifications were made in order to avoid inadvertent perforation, as the donor cornea had a very spherical shape, probably due to the very young age of the donor. The DSAEK graft was transplanted to the left eye of a 68-year-old woman suffering from Fuchs' endothelial dystrophy. Her preoperative best-corrected visual acuity (BCVA) in that eye was 20/100 and central corneal thickness 831 µm. Results: An uneventful DSAEK combined with phacoemulsification was performed. The main complication noted was detachment of the peripheral part and contraction of the corneal graft, observed two months after the procedure. The implanted tissue remained centrally attached with a BCVA of 20/40, 3 years postoperatively. Conclusion: This case report highlights the difficulties emerging from preparation and implantation using an endothelial graft tissue from the youngest ever reported donor.

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.

Late-onset interface fluid syndrome: A case report and literature review.

PURPOSE: To present a case of late-onset interface fluid syndrome (IFS) and a literature review on this rare clinical entity. INTRODUCTION: IFS is an uncommon complication of laser in situ keratomileusis (LASIK). Although generally appearing in the early postoperative period, IFS has been reported even years after LASIK. METHODS: A case report of IFS manifesting 19 years after uneventful LASIK, which prompted a literature search for similar, late-onset cases in MEDLINE PubMed. This article reports on a case of IFS appearing 19 years after LASIK surgery, including extensive patient history and analytical presentation of clinical findings, ancillary testing, and short-term follow-up. Furthermore, a literature search for similar cases was performed on MEDLINE, focusing on the etiology and management of late-onset IFS. RESULTS: Through thorough ancillary testing, the interface fluid was attributed to elevated intraocular pressure (IOP) arising from primary open-angle glaucoma. Antiglaucoma drops resulted in complete fluid regression. A narrative review was conducted based on the 29 case reports that were recovered from the literature search. CONCLUSION: IFS represents an uncommon complication that could appear years after LASIK. Careful clinical examination and anterior segment optical coherence tomography promote early diagnosis. Similar cases may manifest due to elevated IOP of variable etiology or as a result of endothelial dysfunction. Depending on the etiology, IOP control or keratoplasty may resolve the condition.

Factors predisposing to intraoperative floppy-iris syndrome: An up-to-date meta-analysis.

Intraoperative floppy-iris syndrome (IFIS) is an increasingly recognized condition that is proven to lead to higher rates of intraoperative complications. This study provides an updated systematic review and meta-analysis regarding all the identified factors predisposing to IFIS. The study was performed in accordance with the PRISMA guidelines. 38 studies were finally included in the meta-analysis. The factors that were found to predispose to IFIS significantly were male sex (odds ratio [OR], 4.25; CI, 2.58-7.01), hypertension (OR, 1.55; CI, 1.01-2.37), tamsulosin (OR, 31.06; CI, 13.74-70.22), finasteride (OR, 4.60; CI, 1.97-10.73), benzodiazepines (OR, 2.88; CI, 1.17-7.12), and antipsychotics intake (OR, 6.91; CI, 2.22-21.50). A decreased dilated pupil preoperatively was found predisposing to IFIS (weighted mean difference -0.93; CI, -1.19 to -0.67). Intracameral epinephrine, which was investigated as a potential prophylactic measure for preventing IFIS, did not reach statistical significance (OR, 0.29; CI, 0.08-1.06). A comprehensive preoperative assessment of all risk factors is vital to stratify the surgical risk, which is crucial in addressing IFIS because unanticipated IFIS could turn a routine surgery into one of significant visual morbidity.

Part-time Versus Full-time Spectacles for Myopia Control (ParMA Study): A Randomized Clinical Trial.

Introduction To compare myopia progression in school-aged children of Caucasian origin wearing part-time vs. full-time full correction with single-vision spectacles. Methods This prospective, randomized controlled trial included 30 children with bilateral myopia, who received either full-time or part-time treatment with single-vision spectacle lenses. Myopia progression was assessed as the mean change in cycloplegic spherical equivalent refraction (SE), mean change in axial length (AL), and mean change in sub-foveal choroidal thickness (SChT), over a 12-month follow-up period. Results A total of 32 eyes were treated with part-time single-vision spectacles (intervention group) and 28 eyes with full-time single-vision spectacles (control group), respectively. The part-time treated group reported no spectacle use during near-work activities for a mean of 6.2 hours/day. At the 12-month assessment, there was no significant difference between part-time and full-time correction groups in mean SE change (MD: -0.05 D, 95% CI: -0.50 - 0.39 D; P 0.81), in mean AL change (MD: -0.07 mm; 95% CI: -0.20 - 0.06 mm; P 0.30), and in mean SChT change (MD: -11.45 µm; 95% CI -22.60 - 14.16 µm; P 0.67). Conclusion Myopia progression in Caucasian children treated with part-time, single-vision spectacle use was not different compared to full-time, single-vision spectacle use, over a 12-month follow-up period.

Descemet Stripping Endothelial Keratoplasty for Congenital Aniridia: An Interesting and Challenging Story.

Congenital aniridia is a rare condition affecting a wide range of ocular structures, from the ocular surface to the retina. We present the case of a 59-year-old woman with PAX6- and WT1-negative congenital aniridia who developed aniridia-associated keratopathy and progressive endothelial dysfunction with corneal decompensation after cataract surgery. The patient underwent successful ultrathin Descemet stripping endothelial keratoplasty. Despite the challenges faced with an unstable iridolenticular diaphragm, we were pleasantly surprised to see improvement not only of corneal edema and endothelial function but also of the whole cornea, including anterior corneal anatomy and appearance. In conclusion, endothelial transplantation in a patient with aniridia resulted in improvement of all the corneal structures from the endothelium to the stroma, epithelium, and possibly even the ocular surface.

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.