Increased late-onset glaucoma risk following vitrectomy for macular pucker or hole.

OBJECTIVES: The long-term risk of developing glaucoma after vitrectomy remains uncertain. This retrospective population-based cohort study aimed to explore this risk following vitrectomy for macular pucker or hole. METHODS: Utilizing Taiwan's National Health Insurance Research Database (NHIRD), we included patients who were older than 18 years and had undergone vitrectomy surgery between 2011 and 2019. Exclusions were made for patients with prior diagnoses of glaucoma, congenital or secondary glaucoma, as well as those who had received previous vitreoretinal treatments or had undergone multiple vitrectomies. RESULTS: After an average follow-up period of 51 and 53 months respectively for the vitrectomized and non-vitrectomized group, our results showed a relative risk of 1.71 for glaucoma development in the vitrectomized group. Higher adjusted hazard ratios were also observed for open-angle glaucoma and normal tension glaucoma. Increased risks were associated with male sex, obstructive sleep apnoea, and migraine. In the subgroup analysis, phakic eyes at baseline and those who had undergone cataract surgery post-vitrectomy were associated with a lower risk of glaucoma development during follow-up. Among all glaucoma events, pseudophakic status at baseline had the shortest interval to glaucoma development following vitrectomy. CONCLUSIONS: These findings underscore the potential relationship between vitrectomy and glaucoma onset, emphasizing the need for vigilant monitoring and early detection of glaucoma in post-vitrectomy patients.

Trocar blade-assisted skewer technique for phacoemulsification of a dislocated lens.

A posteriorly dislocated lens is often managed with a fragmatome through a pars plana approach because it is difficult to manage anteriorly. The lens often sinks to the surface of the retina or floats around in the vitreous cavity during pars plana lensectomy. Mechanical trauma can occur while removing the dislocated lens fragments. However, sometimes the lens can be confined to the anterior vitreous cavity even though the zonules are completely disrupted. It would be ideal if there was a simple way to stabilize and support the lens so that the lens could remain in the posterior chamber while phacoemulsification is performed through a corneal incision as usual. We describe a technique using a trocar blade to stabilize the lens while performing phacoemulsification through a corneal incision. We found it to be a useful and safe instrument to support the subluxated lens during phacoemulsification.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next.

Importance: Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. Objective: To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). Design, Setting, and Participants: This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Interventions: Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures: Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Results: Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. Conclusions and Relevance: In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. Trial Registration: ClinicalTrials.gov Identifier: NCT04015180.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study.

BACKGROUND: There are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment. METHODS: Infants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity. RESULTS: Of 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant. CONCLUSIONS: 24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity. GOV IDENTIFIER: NCT04004208.

Real-world effectiveness of intravitreal dexamethasone implants - Comparison between eyes eligible and ineligible for clinical trials and their associated outcomes.

BACKGROUND: Concerns about the generalizability of pivotal randomized controlled trials (pRCTs) findings have been raised. We aimed to compare intravitreal dexamethasone implants' (IDIs) effectiveness for diabetic macular edema (DME) and central retinal vein occlusion (CRVO), between eyes eligible and ineligible for pRCTs. METHODS: This retrospective cohort study analyzed Taiwan's Chang Gung Research Database, including DME or CRVO eyes initiating IDIs during 2015-2020. We classified all treated eyes as eligible or ineligible for pRCTs following major selection criteria of the MEAD and GENEVA trials, and evaluated three-, six-, and twelve-month changes in central retinal thickness (CRT) and visual acuity (VA) after initiating IDIs. RESULTS: We included 177 IDI-treated eyes (DME: 72.3%; CRVO: 27.7%), of which 39.8% and 55.1% were ineligible for DME and CRVO pRCTs, respectively. LogMAR-VA and CRT changes at different times were comparable in DME eyes eligible (LogMAR-VA difference: 0.11 to 0.16; CRT difference: -32.7 to -96.9 µm) and ineligible (LogMAR-VA difference: -0.01 to 0.15; CRT difference: -54.5 to -109.3 µm) for the MEAD trial. By contrast, CRVO eyes ineligible for the GENEVA trial had greater LogMAR-VA changes (0.37 ~ 0.50) than those eligible (0.05 ~ 0.13), with comparable CRT reductions (eligible eyes: -72.3 to -106.4 µm; ineligible eyes: -61.8 to -110.7 µm) (all p-values <0.05 of the mean differences between eligible and ineligible CRVO eyes for all follow-ups). CONCLUSIONS: IDIs had similar VA and CRT outcomes among DME eyes, regardless of pRCT-eligibility. However, among CRVO eyes, those ineligible for pRCTs showed greater deterioration in VA than those eligible.

Protective Effects of Hinokitiol on Neuronal Ferroptosis by Activating the Keap1/Nrf2/HO-1 Pathway in Traumatic Brain Injury.

In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. Neuron loss and iron deposition were ameliorated after hinokitiol administration. Hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe2+ accumulation in HT-22. Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.

Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study.

PURPOSE: The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery. METHODS: Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment. RESULTS: The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant ( P =0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue. CONCLUSION: Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.

PRESENTATIONS AND FACTORS AFFECTING OUTCOME OF RHEGMATOGENOUS RETINAL DETACHMENT WITH CHOROIDAL DETACHMENT: An Indo-Taiwanese Study.

PURPOSE: To report the clinical settings, management, and factors associated with outcomes of rhegmatogenous retinal detachment with concurrent choroidal detachment. METHODS: Retrospective, consecutive, multicenter case series from January 2014 to January 2021 were included. Cases were from a tertiary eye care center in India and Taiwan. RESULTS: Overall 303 eyes were included. Mean age was 43.72 ± 20.64 years (median 46). Best-corrected presenting visual acuity was 1.79 ± 0.92 logMAR (median 2.10) (Snellen 20/1,233). Forty-four patients (17.91%) received preoperative steroids. Final visual acuity was 1.33 ± 0.94 logMAR (median 1.10) (Snellen 20/427). Favorable anatomic outcome was seen in 200/303 (66%), whereas favorable functional outcome was seen in 128/303 (42.20%). Factors predicting favorable anatomic outcome were absence of phakic lens status (odds ratio [OR] 2.76), absence of proliferative vitreoretinopathy worse than Grade A (OR 7.69), use of preoperative steroids (OR 4.50), and use of an encircling band (3.85). Factors predicting favorable functional outcome were better presenting visual acuity (OR 3.03), absence of phakic lens status (OR 4.93), absence of proliferative vitreoretinopathy worse than Grade A (OR 10.41), and use of preoperative steroids (OR 7.24). CONCLUSION: Administration of preoperative steroids, use of an encircling band during surgery, and pseudophakic status of the eye were found to have better outcomes in rhegmatogenous retinal detachment with concurrent choroidal detachment.

Retinal vascular arcade angle as a biomarker for visual improvement after epiretinal membrane surgery.

OBJECTIVES: To investigate the changes in the temporal vascular angles after epiretinal membrane (ERM) surgery and utilize the angles to predict visual outcomes. METHODS: A total of 168 eyes from 84 patients with unilateral ERM who underwent vitrectomy were enrolled from a single institution. The angles of temporal venous (anglevein) and arterial arcades (angleartery) were measured on fundus photographs. The relationships between the angles and the best-corrected visual acuity (BCVA) were explored and multivariable logistic models and receiver operating characteristic (ROC) curves were analyzed to identify the factors that predicted visual outcomes. RESULTS: At baseline, both angleartery and anglevein were narrower in the eyes with ERM than the fellow eyes (p < 0.001 and 0.007) but had no correlation with the baseline BCVA (p = 0.754 and 0.804). Postoperatively, the angleartery and anglevein significantly widened (both p < 0.001) and a greater BCVA improvement was associated with a greater widening of the angleartery (p = 0.029) and anglevein (p = 0.050). Multivariable logistic analyses found a narrower baseline angleartery compared to the fellow eye had a higher chance for BCVA improvement ≧ 2 lines (Odds ratio = 0.97; 95% CI, 0.94-0.99; p = 0.016). ROC curve showed the baseline difference in the angleartery between bilateral eyes predicted BCVA improvement ≧ 2 lines (area under the curve = 0.74; p = 0.035), and a 0.73 sensitivity and 0.80 specificity with a cut-off value of -27.19 degrees. CONCLUSIONS: The retinal vascular angles widened after ERM surgery and the fundus photograph-derived angles may serve as a highly-accessible biomarker to predict postoperative visual outcomes.

Magnetic graphene oxide nanoflakes for dual RNA interfering delivery and gene knockdown in prostate and liver cancers.

The development of synthetic carriers for small interfering RNA (siRNA) and plasmids is crucial for effective gene therapy. In this study, we synthesized magnetic graphene oxide nanoflakes as carriers for siRNA delivery, with the goal of knockdown specific genes such as the green fluorescence protein (GFP). Our approach combined magnetically reduced graphene oxide with polyethylenimine (PEI) crosslinked to its surface using carbonyl diimidazole. To evaluate the adsorption capacity of the PEI-modified nanocomposite, we investigated its ability to bind two types of nucleic acids: short-hairpin (sh)RNA plasmids and siRNA targeting GFP. The nanocomposite exhibited significant adsorption, with maximum capacities of 426 ng/µg for shRNA and 71 ng/µg for siRNA, respectively. Simultaneous delivery of siRNA and shRNA using our designed nanocomposites was successfully achieved in human hepatoma and prostate cancer cells. Under magnetic guidance, the knockdown efficiencies reached 73.5 % in hepatoma cells for dual delivery of siRNA and shRNA. Our findings revealed that the nanocomplexes were internalized by the cells through a caveolae-dependent endocytosis mechanism. The demonstrated ability of the nanoflakes to efficiently transport siRNA and shRNA, with high loading capacity, controlled release, and magnetic targeting, resulted in effective GFP knockdown in vitro. These findings highlight the potential of magnetic graphene oxide nanoflakes as promising carriers for siRNA delivery and gene knockdown in therapeutic applications.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

BACKGROUND/AIMS: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes. METHODS: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice. RESULTS: For babies receiving ROP treatment, we recommend patient demographics, systemic comorbidities, ROP status, treatment details, ophthalmic and systemic complications of treatment, ophthalmic and neurodevelopmental outcomes at initial treatment, any episodes of retreatment and follow-up examinations in the short and long-term to be collected for use in ROP studies, registries and routine clinical practice. CONCLUSIONS: We recommend these parameters to be used in registries and future studies of ROP treatment, to reduce the variation seen in previous reports and allow meaningful assessments and comparisons. They form the basis of the EU-ROP and the Fight Childhood Blindness! ROP Registries.

Application of Surface Landmarks Combined with Image-Guided Sinus Location in the Retrosigmoid Approach and Their Clinic-Image Relationship Analysis.

Objectives During craniotomy for cerebellopontine angle (CPA) lesions, the exact exposure of the margin of the venous sinuses complex remains an essential but risky part of the procedure. Here, we revealed the exact position of the asterion and sinus complex by combining preoperative image information and intraoperative cranial landmarks, and analyzed their clinic-image relationship. Methods Ninety-four patients who underwent removal of vestibular schwannoma (VS) through retrosigmoid craniotomies were enrolled in the series. To determine the exact location of the sigmoid sinus and the transverse sinus and sigmoid sinus junction (TSSJ), we used preoperative images, such as computed tomography (CT) and/or magnetic resonance imaging (MRI) combined with intraoperative anatomical landmarks. The distance between the asterion and the sigmoid sinus was measured using MRI T1 sequences with gadolinium and/or the CT bone window. Results In 94 cases of retrosigmoid craniotomies, the asterion lay an average of 12.71 mm on the posterior to the body surface projection to the TSSJ. Intraoperative cranial surface landmarks were used in combination with preoperative image information to identify the distance from the asterion to the sigmoid sinus at the transverse sinus level, allowing for an appropriate initial burr hole (the margin of the TSSJ). Conclusion By combining intraoperative anatomical landmarks and preoperative image information, the margin of the TSSJ, in particular, the inferior margin of the transverse sinus, can be well and thoroughly identified in the retrosigmoid approach.

Respiratory outcomes in preterm infants following intravitreal bevacizumab for retinopathy of prematurity-a 10-year matched case study.

OBJECTIVES: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). METHODS: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. RESULTS: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. CONCLUSIONS: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.

Surgical decisions and outcomes of rhegmatogenous retinal detachment during the coronavirus disease 2019 pandemic: Data from a tertiary referral center in Taiwan.

Purpose: To assess changes in surgical decisions and outcomes of rhegmatogenous retinal detachment (RRD) during the COVID-19 pandemic at a tertiary center in Taiwan. Methods: Patients undergoing pars plana vitrectomy (PPV) or scleral buckling (SB) for primary RRD during Taiwan's first wave of domestic COVID-19 cases surge between May and July 2021 (COVID cohort, n = 100) were compared to controls in the closest pre-COVID year, 2019 (pre-COVID cohort, n = 121). Results: The COVID cohort had significantly worse RRD presentation, received more PPV (alone or combined with SB (PPV + SB)) and less SB alone, and had comparable single-surgery anatomic success (SSAS) rates. In patients who underwent PPV, more underwent PPV + SB instead of PPV alone. The decision to combine SB in PPV surgery was significantly affected by the COVID pandemic (odds ratio [OR], 3.1860 [95% confidence interval (CI), 1.1487-8.8361]). However, a shorter duration of symptoms before the first presentation (0.9857 [95% CI, 0.9720-0.9997]) was the only factor related to SSAS, whereas the surgical method had no association. The SSAS rate remained close to or over 90% in patients with a duration of symptoms before surgery ≤4 weeks but dropped to 83.3% in patients with duration >4 weeks. Conclusion: During the COVID-19 pandemic, worse RRD presentations led to a shift in preference for PPV over SB alone as the primary surgery. The pandemic affected surgeons' decision to combine SB during PPV. Nevertheless, SSAS was only associated with the duration of symptoms but not with surgical methods.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

Purpose: This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Methods: Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. Results: A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. Conclusions: VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Peripheral ulcerative keratitis in a patient with granulomatous rosacea.

A 24-year-old woman visited our emergency department due to intermittent dull pain in the right eye, blurred vision, foreign body sensation for 3 weeks, and progressive facial rash with pustules for 3 months. She had a history of recurring skin rash on her face and extremities since early adolescence. Peripheral ulcerative keratitis (PUK) was diagnosed based on slit-lamp examination and corneal topography and then granulomatous rosacea (GR) based on clinical manifestations and skin pathology. Topical prednisolone, artificial tears, oral doxycycline, oral prednisolone, and topical clindamycin were administered. After 1 month, PUK progressed to corneal perforation probably due to eye rubbing. The corneal lesion was repaired with a glycerol-preserved corneal graft. A dermatologist prescribed oral isotretinoin for 2 months in conjunction with topical betamethasone gradually tapered for 14 months. After 34 months of follow-up, no signs of skin and ocular recurrence were noted, and the cornea graft was intact. In conclusion, PUK may present with GR, and oral isotretinoin may be an effective therapy for PUK in the setting of GR.

Transcription Factor ATF3 Participates in DeltaNp63-Mediated Proliferation of Corneal Epithelial Cells.

Understanding the regulatory mechanisms underlying corneal epithelial cell (CEC) proliferation in vitro may provide the means to boost CEC production in cell therapy for ocular disorders. The transcription factor ΔNp63 plays a crucial role in the proliferation of CECs, but the underlying mechanisms is yet to be elucidated. TP63 and ΔNp63 are encoded by the TP63 gene via alternative promoters. We previously reported that both ΔNp63 and activating transcription factor (ATF3) are substantially expressed in cultured CECs, but the regulatory relationship between ΔNp63 and ATF3 is unknown. In the present study, we found that ΔNp63 increased ATF3 expression and ATF3 promoter activity in cultured CECs. The deletion of the p63 binding core site reduced ATF3 promoter activity. CECs overexpressing ATF3 exhibited significantly greater proliferation than control CECs. ATF3 knockdown suppressed the ΔNp63-induced increase in cell proliferation. Overexpression of ATF3 in CECs significantly elevated protein and mRNA levels of cyclin D. The protein levels of keratin 3/14, integrin ß1, and involucrin did not differ between ATF3-overexpressing CECs, ATF3-downregulated CECs, and control cells. In conclusion, our results suggest that ΔNp63 increases CEC proliferation via the ΔNp63/ATF3/CDK pathway.

Retrospective Analysis of Surgical Outcomes on Axial Length Elongation in Eyes with Posterior and Combined Persistent Fetal Vasculature.

This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth).

Systemic Outcomes of Intravitreal Injections of Dexamethasone and Anti-Vascular Endothelial Growth Factor.

INTRODUCTION: Intravitreal dexamethasone and anti-vascular endothelial growth factor (anti-VEGF) medications have revolutionized ocular disease management and favorable ocular safety profiles, but few studies have compared their systemic adverse events (SAEs). This study investigated the SAEs of intravitreal dexamethasone and anti-VEGFs by using real-world data. METHODS: This retrospective cohort study sourced medical records from the largest multi-institutional database in Taiwan. Patients who received intravitreal dexamethasone (n = 137) or anti-VEGFs (n = 10,345) between 2014 and 2019 were enrolled. Propensity score matching was performed to achieve homogeneity between the two groups. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (CIs) were calculated using the Fine-Gray model. Systemic as well as ocular clinical events and systemic biomarkers after 1-year follow-up were compared. RESULTS: Both groups demonstrated comparable risks of major cardiac adverse events (SHR 1.57, 95% CI 0.29-8.55), heart failure (SHR 0.62, 95% CI 0.07-5.33), major bleeding (SHR 0.23, 95% CI 0.03-1.77), all-cause admission (SHR 0.73, 95% CI 0.41-1.30), and all-cause death (SHR 2.11, 95% CI 0.35-12.71). There were no significant differences in longitudinal changes in systolic and diastolic blood pressure, glycated hemoglobin, low-density lipoprotein, estimated glomerular filtration rate, or alanine aminotransferase between the groups. Both groups had a similar incidence of cataract surgery. Although the dexamethasone group exhibited a relatively high prevalence of antiglaucomatous medication use, there was not a significantly higher incidence of glaucoma surgery. CONCLUSION: Intravitreal dexamethasone and anti-VEGF medications had comparable systemic safety profiles in our study. Both drugs represent efficacious and safe therapies for ocular diseases.