Ophthalmology最新文献

Purpose: To evaluate the safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an α-adrenergic antagonist, in reversal of pharmacologically induced mydriasis.

Design: Two phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy participants.

Participants: Five hundred fifty-three healthy 12- to 80-year-old participants were randomized 1:1 (MIRA 2) and 2:1 (MIRA 3) to receive either POS or placebo eye drops in both eyes.

Methods: Participants received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or 1% hydroxyamphetamine / 0.25% tropicamide.

Main outcome measures: Percent of participants returning to within 0.2 mm of baseline pupil diameter in study eye 90 minutes after POS administration. Safety measures included treatment-emergent adverse events and tolerability measures, including conjunctival hyperemia.

Results: A total of 553 participants were randomized to treatment with placebo (n = 215) or POS (n = 338). A statistically significant greater percentage of participants treated with POS showed reversal of mydriasis at 90 minutes compared to placebo (MIRA 2: 48.9% vs. 6.6% [P < 0.0001]; MIRA 3: 58% vs. 6% [P < 0.0001]) and as early as 60 minutes (MIRA 2: 27.7% vs. 2.2% [P < 0.0001]; MIRA 3: 42% vs. 2% [P < 0.0001]). Between 28% and 34% of participants receiving placebo did not returned to baseline PD at 24 hours after pharmacologic dilation compared with 8% to 11% of patients treated with POS (P < 0.0001).

Conclusions: Treatment with POS reduced PD within 60 to 90 minutes, with a statistically significant time savings of 5 to 6 hours to return to baseline PD compared with placebo. One or 2 drops of POS rapidly reversed mydriasis in all participants regardless of mydriatic agent or iris color. More participants receiving POS reported a benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared with placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: To identify clinical characteristics that would help make or rule out the diagnosis of idiopathic intracranial hypertension (IIH) in patients referred for papilledema (PE) with peripapillary hyperreflective ovoid mass-like structures (PHOMS).

Design: A retrospective cohort study.

Participants: All patients referred for PE excluding PE with Frisén grade ≥ 3, optic neuritis, ischemic optic neuropathy, and compressive optic neuropathy. Patients were divided into 2 groups: group 1 = isolated PHOMS; group 2 = PHOMS associated with IIH.

Methods: We analyzed the location of PHOMS based on OCT-enhanced depth imaging (EDI) and calculated their volume.

Main outcome measures: Peripapillary retinal nerve fiber layer (pRNFL), ganglion cell complex, and volume of PHOMS.

Results: A total of 154 patients (308 eyes) were included. Patients' mean age was 29 years, with a female predominance (78%). Peripapillary hyperreflective ovoid mass-like structures were associated with these etiologies: IIH (38.3%), isolated (35.7%), posterior uveitis (11%), optic disc drusen (ODD) (10%), and tilted optic disc (5%). Magnetic resonance imaging (MRI) was performed in 83.1% of cases. More than half of the MRI scans were interpreted as consistent with IIH. However, only 39.7% of these patients had confirmed IIH with 44.5% sensitivity and 55.5% specificity. Peripapillary hyperreflective ovoid mass-like structures were overrepresented in the nasal region (95.5%).The location of PHOMS in the superior or inferior quadrant was significantly associated with IIH or ODD, whereas their presence in the temporal or nasal sector was strongly associated with isolated lesions. The mean and median volume of PHOMS were 1.66 μm³ and 1.50 μm³, respectively. There was a significant difference in PHOMS volume, with a higher volume in patients with IIH (P = 0.0037). Follow-up of these patients at 3 and 6 months demonstrated no significant changes in visual function, as per visual field mean deviation, visual acuity measurements, and ganglion cell layer. Mean pRNFL showed a decrease of -4.225 μm at 3 months and -6.489 μm at 6 months when compared with the initial measurement independent of the etiology.

Conclusions: Isolated PHOMS should be considered as a distinct entity. In asymptomatic patients, PHOMS should be carefully studied. Nasal or temporal location, small volume, and stable aspect over the course of weeks or months are suggestive of this entity. This strategy would considerably reduce the impact on patients' anxiety and morbidity.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To determine the risk of optic neuritis (ON) during nonpharmaceutical interventions (NPI), vaccination, and infection phases of the coronavirus disease 2019 (COVID-19) pandemic in comparison with levels before the outbreak in pediatric and adult populations in South Korea.

Design: A nationwide, population-based retrospective study.

Participants: South Korean individuals with a primary diagnosis of ON received between January 2017 and December 2022.

Methods: The Korean Health Insurance Review and Assessment database was queried for new diagnoses of ON between January 2017 and December 2022. Data were divided into 4 periods: before COVID-19 (2017-2019), NPI (2020), nationwide vaccination (2021), and nationwide infection (2022). The risk of ON development for each period was calculated and compared with levels before COVID-19, with 95% confidence intervals (CIs) reported.

Main outcome measures: Incidence rate ratio (IRR) of ON for each period.

Results: A total of 7216 patients (52.7% female patients) were included in the study, with patients receiving a diagnosis of ON as follows: 3770 patients before COVID-19 (2017-2019), 1193 patients during NPI, 1135 patients during vaccination, and 1118 patients during the infection phases. The annual incidence of ON during NPI (IRR, 0.92; 95% CI, 0.85-1.00; P = 0.043), vaccination (IRR, 0.88; 95% CI, 0.81-0.95; P = 0.001), and infection (IRR, 0.86; 95% CI, 0.80-0.93; P < 0.001) phases significantly decreased compared with levels before COVID-19 when adjusted for age and sex. The proportions of diagnosis with multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM) among patients in whom ON developed increased significantly in 2021 in comparison with levels before COVID-19 (10.93% vs. 6.43%; P = 0.0002).

Conclusions: The risks of ON development during the NPI, vaccination, and infection phases of COVID-19 did not increase in comparison with levels before the outbreak in the general population. However, COVID-19 vaccination may be associated with increased risks of ON associated with diseases such as ADEM, MS, and NMO.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To study the vitreopapillary interface in nonarteritic ischemic optic neuropathy (NAION) for features that may predispose to optic nerve perfusion defects.

Design: Case-control study.

Participants and controls: Patients with NAION (study group) were compared with healthy non-NAION patients with crowded discs (control group I) and noncrowded optic discs (control group II).

Methods: The vitreopapillary interface was studied in 32 eyes with NAION using high-resolution OCT scans. Results were compared with 2 control groups consisting of age, sex, and refraction-matched non-NAION individuals with crowded optic discs (control group I: 31 eyes) and noncrowded optic discs (control group II: 32 eyes).

Main outcome measures: The incidence of total posterior vitreous detachment (PVD), vitreopapillary and vitreovascular attachments, and epipapillary membranes.

Results: The rate of PVD over the macula was similar between groups (NAION: 62.5%, control I: 61.3%, and control II: 65.6%, P = 0.93), whereas the posterior hyaloid remained attached to the crowded discs at a significantly higher rate (NAION: 81.2%, control I: 83.9% and control II: 43.7%, P = 0.0005). A higher rate of focal vitreopapillary attachments on crowded discs than on noncrowded discs was noted (NAION: 72.2%, crowded control I: 58.7%, and noncrowded control II: 19.1%, P = 0.007). Vitreovascular attachments (NAION: 68.8%, crowded control I: 3.2% vs. noncrowded control II: 6.3%, P = 0.00001) and dense epipapillary membranes were observed in NAION eyes.

Conclusions: Crowded discs may have stronger vitreopapillary attachments. A close relationship of these attachments with optic nerve vessels may lead to the transmission of strong tractional forces by a syneretic vitreous gel, especially after macular PVD. This transduced mechanical force may contort the vessel wall and disrupt the blood flow in NAION.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Purpose: To report the safety and efficacy of brolucizumab (Beovu) 6 mg versus aflibercept (Eylea) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the week 52 up to week 104.

Design: Multicenter, randomized, double-masked phase 3a study.

Participants: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-VEGF treatment).

Methods: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks or until study termination.

Main outcome measures: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]) and safety data up to study termination, including data up to week 104 for those participants who completed the study before its termination. All P values after week 52 were nominal and reflect observed data for the efficacy analyses.

Results: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to week 104 (least squares mean difference, -0.4 ETDRS letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept (P = 0.7762), and a greater proportion of eyes were fluid free at week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab versus aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept.

Conclusions: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change, with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Purpose: To report the change in refractive error over 5 years after primary intraocular lens (IOL) placement by age at surgery and to identify factors associated with the change in refractive error after 5 years.

Design: Prospective observational study at 61 pediatric eye care practices.

Participants: One hundred eighty-six eyes of 152 children undergoing primary IOL implantation before 13 years of age for nontraumatic cataract.

Interventions: Cataract surgery with primary IOL placement.

Main outcome measures: Five-year change in refractive error (spherical equivalent) by age at surgery and by immediate postoperative myopia versus emmetropia or hyperopia.

Results: Mean spherical equivalent myopic shift was -5.99 diopters (D; 95% confidence interval [CI], -7.64 to -4.34 D) when surgery was performed at 0 to younger than 1 year of age (n = 13), -3.53 D (-4.57 to -2.48 D) at 1 to younger than 2.5 years of age (n = 28), -1.91 D (-2.55 to -1.26 D) at 2.5 to younger than 4 years of age (n = 36), -2.04 D -2.60 to -1.49 D) at 4 to younger than 7 years of age (n = 60), and -0.83 D (-1.27 to -0.40 D) at 7 to younger than 13 years of age (n = 49; P < 0.01 for each comparison with the oldest group). Variability of myopic shift also decreased with increasing age (P < 0.01). In eyes of children 4 to younger than 13 years of age (small sample size precluded analysis of children younger than 4 years), significantly less mean change in refractive error was found over 5 years in eyes with myopia immediately after surgery (-0.69 D; 95% CI, -1.48 to 0.10 D; n = 27) than eyes with emmetropia or hyperopia immediately after surgery (-1.70 D; 95% CI, -2.10 to -1.31 D, n = 82; difference, -1.01 D [95% CI, -1.89 to -0.14 D]; P = 0.03).

Conclusions: In this large, prospective cohort study of children younger than 13 years undergoing cataract surgery with primary IOL placement, greater and more variable myopic shift was found in children undergoing surgery at a younger age. Our finding of less myopic shift over 5 years in eyes with unintended immediate postoperative myopia deserves further study to guide IOL power selection more accurately.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Purpose: Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis.

Design: We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes.

Participants: Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands.

Methods: We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression.

Main outcome measures: Uveal melanoma-related survival.

Results: Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P = 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P = 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P = 0.04) than in patients with an A/G or A/A genotype.

Conclusions: The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3).

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.