Uveitis Risk After the First Dose of COVID-19 Vaccination Based on Uveitis History: Matched Cohort and Crossover Case Series Study.

PURPOSE: To investigate the risk of noninfectious uveitis following the first dose of coronavirus disease 2019 (COVID-19) vaccination based on the uveitis history. DESIGN: Retrospective matched cohort and crossover case series study. METHODS: A random sample of 7 917 457 individuals who received COVID-19 vaccine between January 2021 and March 2022 in Korea, and had no recorded history of COVID-19 were categorized into the control and uveitis groups based on their uveitis history. After performing 3:1 propensity score matching, we assessed the cumulative incidence and risk of noninfectious uveitis in the 180 days after COVID-19 vaccination. Additionally, we performed a crossover case series analysis to compare the pre- and postvaccination incidence rate ratios (IRRs) of uveitis in individuals with and without a history of uveitis. RESULTS: In the matched cohort analysis, uveitis group had a significantly higher cumulative incidence of uveitis (15.4%) than control group (0.10%). The uveitis group exhibited increased risks of all uveitis types, anterior, and nonanterior uveitis in the first 60 days (hazard ratio [HR]: 169, 158, and 253, respectively) and in days 61 to 180 (HR: 166, 164, and 143, respectively) after vaccination. In the crossover case series analysis, uveitis occurred with relatively equal frequency in 20-day intervals during the 180 days before and after vaccination, regardless of uveitis history. For uveitis group, the adjusted IRRs for early and late postvaccination events were 0.92 (95% CI, 0.88-0.96) and 0.83 (95% CI, 0.80-0.85), respectively. CONCLUSIONS: COVID-19 vaccination did not increase the risk of uveitis, regardless of uveitis history.

Noninfectious Uveitis Risk After COVID-19 Vaccination: A Nationwide Retrospective Cohort Study.

PURPOSE: To investigate the incidence and risk of noninfectious uveitis (NIU) following COVID-19 vaccination compared with an unvaccinated, uninfected control group. DESIGN: Retrospective population-based cohort study. METHODS: We included 5,185,153 individuals who received the first vaccine dose in the exposed group and 2,680,164 individuals in the unexposed, uninfected control group. The study observed for 180 days from their index date. Cumulative incidence and risk of NIU following COVID-19 vaccination, and attributable risk factors were assessed. RESULTS: Multivariable analysis showed elevated risk of nonanterior NIU within 60 days (hazard ratio [HR] 1.27 [95% confidence interval {CI} 1.03-1.55] and 61-180 days (HR 1.39 [95% CI 1.20-1.62]). Subgroup analysis highlighted an increased risk in females for early and delayed nonanterior uveitis (HR 1.44 [95% CI 1.08-1.92]; HR 1.78 [95% CI 1.43-2.20], respectively). Regardless of the location and onset timing of uveitis, a history of NIU was identified as the most significant risk factor, with a high hazard ratio ranging from 100 to 200. CONCLUSIONS: COVID-19 vaccination may modestly increase the risk of nonanterior uveitis especially in females. Despite adjustments, bias may persist in the exposed group, owing to significant differences between unexposed and exposed groups and low incidence of nonanterior uveitis in the unexposed group. Future research should aim to refine these findings by assessing uveitis risk in prior NIU patients and by enlarging the sample size or cohort matching.

Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm.

BACKGROUND: To evaluate the association between retinal artery/arteriole occlusion (RAO) and unruptured intracranial aneurysm (UIA). METHODS: Incident UIA patients from a nationwide cohort (n=253 240) were categorised into three groups based on subsequent treatment: observation (n=208 993), microsurgical clipping (n=14 168) and endovascular treatment (EVT) groups (n=30 079). The incidence and the incident time of RAO were analysed. HRs of RAO and associated risk factors were evaluated. Additionally, a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of UIAs. RESULTS: In the nationwide cohort analysis, the incidence of RAO was significantly higher in EVT group than in observation and clipping groups, especially within 60 days (early RAO (within 60 days): HR=4.00, 95% CI: 2.44 to 6.56); delayed RAO (after 60 days): HR=1.74, 95% CI: 1.13 to 2.68). Multivariable analysis showed that the presence of chronic kidney disease (p=0.009) and use of a balloon microcatheter during the procedure (p=0.013) were associated with a higher risk of RAO. In hospital cohort analysis, 11 (0.8%) cases of RAO occurred after EVT, whereas none occurred after microsurgical clipping (p<0.001). Patients with RAO were younger and received balloon microcatheters more frequently than their counterparts. Ten cases of RAO (90.9%) occurred in paraclinoid aneurysms, where EVT was preferred over microsurgical clipping. CONCLUSIONS: Performing EVT for UIA may increase the risk of subsequent RAO. Care should be taken when treating paraclinoid aneurysms with balloon microcatheters.

Retinal Vascular Occlusion Risks in High Blood Pressure and the Benefits of Blood Pressure Control.

PURPOSE: This study aimed to evaluate the association of retinal vascular occlusion, including retinal vein occlusion (RVO) and retinal artery occlusion (RAO), with stages of hypertension. DESIGN: Nationwide, population-based retrospective cohort study. METHODS: Based on baseline blood pressure (BP) as defined by the 2017 American College of Cardiology/American Heart Association guideline, participants were categorized into 4 BP groups. For the BP change measurement, BP groups were defined based on the combination of baseline and follow-up BP categories. The composite retinal vascular occlusion events and hazard ratios (HRs) of retinal vascular occlusion according to BP groups were estimated. RESULTS: With normal BP as the reference, multivariate-adjusted HRs for retinal vascular occlusion were significantly higher than in other BP groups, showing much higher HRs in stage 2 hypertension than in stage 1 (HR, 1.10 for elevated BP; 1.07 for stage 1 hypertension; and 1.32 for stage 2 hypertension). Individual disease analysis showed consistent statistical significance in RVO, whereas RAO showed nonsignificant results. Lowering BP significantly decreased the HRs of retinal vascular occlusion in both stage 1 and stage 2 hypertension (HR, 0.88 and 0.73, respectively). However, once hypertension was diagnosed, the risk of retinal vascular occlusion was higher compared to that in the normal BP groups. CONCLUSIONS: Elevated BP, stage 1 hypertension, and stage 2 hypertension were all associated with higher retinal vascular occlusion risks than was normal BP. Controlling hypertension appears to reduce the risk of subsequent retinal vascular occlusion; however, the incidence rate was still be significantly higher than that in persons who maintained a normal BP.

BILATERAL MACULAR CHOROIDAL ABNORMALITIES WITH DRUSENOID DEPOSITS IN PATIENTS WITH UNILATERAL PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY.

PURPOSE: To investigate bilateral macular features on optical coherence tomography in patients with unilateral peripheral exudative hemorrhagic chorioretinopathy (PEHCR). METHODS: In this cross-sectional study, optical coherence tomography features of affected eyes (PEHCR group, n = 30) and unaffected contralateral eyes (contralateral group, n = 30) were investigated. Age-matched and sex-matched patients with polypoidal choroidal vasculopathy (PCV group, n = 51) and healthy controls (normal group, n = 50) were included to compare choroidal thickness, measured at six points apart from the fovea, with the PEHCR group. RESULTS: Subretinal drusenoid deposits were the most common feature in the PEHCR (20%) and contralateral (23%) groups, followed by soft drusen. Although the macular choroid was comparably thin in both the PEHCR and contralateral groups, pachyvessels were also observed. The choroids of the PEHCR group were significantly thinner than those of the normal group at the subfovea and 1-mm temporal to the fovea and considerably thinner than those of the polypoidal choroidal vasculopathy group from 3-mm nasal to 3-mm temporal to the fovea. CONCLUSION: In patients with unilateral PEHCR, bilateral choroidal thinning and drusenoid deposit accumulation were noted in the macula. The pathophysiology of PEHCR may be a rare peripheral complication of age-related macular degeneration with pathologic choroid.

Clinical Features and Genetic Findings of Autosomal Recessive Bestrophinopathy.

Autosomal recessive bestrophinopathy (ARB) is a rare subtype of bestrophinopathy caused by biallelic mutations of the BEST1 gene. ARB is characterized by multifocal subretinal deposits accompanied by macular edema or subretinal fluid, hyperopia, co-existing narrow angle, and a marked decrease in electrooculogram. However, little is known about the genetic variants and specific clinical features of ARB. This is an observational case series of patients with a clinical and genetic diagnosis of ARB who underwent multimodal imaging. We describe ten patients from nine unrelated families with six known variants and three novel missense variants: c.236C→T, p.(Ser79Phe); C.452C→T, p.(Leu151Pro); and c.650C→T, p.(Trp217Met). The most common variant was c.584C→T, p.(Ala195Val), observed in six patients, without correlation to the severity of the phenotype. All patients manifested bilateral multifocal subretinal deposits and subretinal fluid throughout the follow-up period, while intraretinal fluid was found in approximately half of the eyes. The extent or chronicity of the fluid collection did not correlate with visual acuity. Angle-closure glaucoma was present in five eyes. Three patients had a genetically confirmed family history of ARB, and one patient had a clinically suspected family history. This study reveals novel mutations in the BEST1 gene and adds to the spectrum of clinical presentations of ARB.

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa.

Here, we report early treatment outcomes of gene therapy for early onset retinitis pigmentosa (RP) (Leber congenital amaurosis) associated with biallelic RPE65 mutation in a 30-year-old female patient. Initially, her visual acuity (VA) was 20/200, and her visual field (VF) was severely constricted to the center in the left eye. Her electroretinography showed nearly extinct signals. Full-field stimulus threshold test (FST) revealed diminished dark-adapted light sensitivity. Voretigene neparvovec-rzyl (VN) is the first in vivo viral gene therapy agent to be approved. At 3 months after subretinal injection of VN in the left eye, VA, VF, and FST showed sustained improvement. She did not exhibit any signs of adverse effects from the treatment. Gene therapy for RP proved to be an effective and safe treatment in an advanced case of RPE65-associatied early onset RP.

Pigmentary abnormality without significant drusen as a risk factor for late age-related macular degeneration.

We investigated the incidence and risk factors of late age-related macular degeneration (AMD) in the fellow eye (FE) without significant drusen of patients with unilateral exudative macular neovascularization (MNV). In this retrospective study, 241 eligible patients who were followed-up for more than 3 years were enrolled. We analyzed the incidence and hazard ratios (HRs) of late AMD in the FE according to demographic and ophthalmologic variables. Hypopigmentation on color fundus photography (CFP) corresponds to shallow irregular RPE elevation (SIRE), so-called "double-layer sign" and/or "attenuation or disruption of RPE and/or ellipsoid zone" on OCT. The 5-year incidence of FE exudative MNV conversion was 8.6%. The 5-year incidence of FE exudative MNV of large hypopigmentation (≥ 0.5 disc area; DA) and small hypopigmentation (< 0.5 DA) on CFP, and SIRE (≥ 1000 µm) and small RPE elevation (< 1000 µm) on OCT were 36.2%, 14.2%, 55.0%, and 15.6%, respectively. The multivariate Cox proportional hazard model revealed that large hypopigmentation, small hypopigmentation, SIRE, and small RPE elevation showed HRs of 23.230, 8.037, 132.589, and 41.823 for FE exudative MNV occurrence, respectively. Hypopigmentation on CFP and SIRE on OCT could represent the same lesion. Even small hypopigmentation and small RPE elevation were significant risk factors for progression to exudative MNV.

Characteristics of Focal Gamma Zone Parapapillary Atrophy.

Purpose: The purpose of this study was to investigate the characteristics of focal γ-zone parapapillary atrophy (focal γPPA) in patients with primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT). Methods: Three groups of POAG eyes (n = 214) were defined according to the circumferential extent of Bruch's membrane (BM) within the ß-zone PPA, as follows: (1) no γPPA (intact BM; n = 81), (2) conventional γPPA (γPPA involving the fovea-BM-opening axis; n = 89), and (3) focal γPPA (γPPA not involving the fovea-BM-opening axis; n = 44). Clinical and ocular characteristics, including age, axial length (AXL), and focal lamina cribrosa (LC) defects were compared among the three groups. Results: The focal γPPA group was significantly older (60.6 ± 11.0 years) and had shorter AXL (24.10 ± 1.34 mm) than those of the conventional γPPA group (46.2 ± 13.8 years and 26.53 ± 1.61 mm, respectively; P < 0.001). These values of the focal γPPA group were similar to those of the no γPPA group (23.73 ± 0.97 mm for AXL and 64.0 ± 13.0 years for age). The focal γPPA group had a significantly higher prevalence of focal LC defects than did the other two groups (70.5% [31/44] for the focal γPPA group versus 46.1% [41/89] for the conventional γPPA group versus 37.0% [30/81] for the no γPPA group; P = 0.002). Conclusions: Focal γPPA was differentiated from conventional γPPA by older age and shorter AXL. Further, focal γPPA was frequently accompanied by focal LC defects. Longitudinal studies elucidating whether focal LC defects and focal γPPA share common pathogenesis are warranted.

Comparison of contrast sensitivity based on the surgical results for intermittent exotropia.

AIM: To compare contrast sensitivity (CS) based on the surgical results for intermittent exotropia (IXT) and to examine the relationship between CS and photophobia. METHODS: Medical records of the patients who underwent bilateral lateral rectus muscle recession for IXT between 4 and 12 years old were reviewed retrospectively. They were categorized based on the surgical results; successful correction group (n=36) and overcorrection group (esotropia ≥10 PD at 3mo postoperatively, n=18). Using CGT-2000 test for CS was performed binocularly, and subjective reports of photophobia was investigated preoperatively and at 3mo postoperatively. Objective photophobia was defined as a significant decrease in CS in the presence of glare. RESULTS: Preoperatively, there was no difference in CS between the groups. Postoperatively, under mesopic conditions, significant improvement of CS was observed at 6.3°, 4°, and 2.5° in the successful correction group and at 6.3° and 4° in the overcorrection group, regardless of glare. Under photopic conditions, at all visual angles except 0.64°, improvement in CS was noted in both groups while CS worsened significantly at 0.64° in the overcorrection group postoperatively. At all visual angles under photopic conditions postoperatively, regardless of glare, CS in the overcorrected group was significantly worse than that in the successful correction group, and CS was significantly decreased by addition of glare in both groups. All patients except one (96.4%) in the successful correction group and 8 patients (61.5%) in overcorrection group showed improvement of photophobia postoperatively, which correlated with CS under photopic conditions (P=0.001, 0.03). CONCLUSION: After surgery for IXT, CS under photopic conditions improve at all visual angles except 0.64°, while CS is significantly worse in the overcorrection group postoperatively at 0.64°. Subjective photophobia have significant correlation with CS under photopic conditions, and may be used as an objective indicator of photophobia.

New Method of Quantitative Analysis of Hard Exudate Using Optical Coherence Tomography: Application in Diabetic Macular Edema.

PURPOSE: In the present study, the volume of hard exudates (HEs) was quantitatively measured using optical coherence tomography (OCT) and the agreement and correlation with area of HEs in fundus photography were analyzed. METHODS: The medical records of patients with diabetic macular edema who underwent focal laser treatment and were followed up more than 3 months were retrospectively evaluated. An automated customized program designed for measuring HE volume was used. The HEs in each OCT B-scan binary image were measured using 512 × 128 pixels, 6 mm × 6 mm OCT cube scans. The volume was measured by summing the segmented HEs in each 128 B-scan image. The area was measured in 6 mm x 6 mm fundus photography. The volume and area were measured before and 3 months after the treatment. The agreement of increase and decrease in HEs, and the correlation of volume and area of HEs were analyzed. RESULTS: A total of 35 patients (39 eyes) were included in the study. The volume was significantly reduced from 0.07978 to 0.02565 mm³ at 3 months (p < 0.001). The area was also significantly reduced from 15.35 to 8.60 mm² at 3 months (p < 0.001). The volume was decreased in 34 eyes and increased in 5 eyes. The area was decreased in 37 eyes and increased in 2 eyes. A significant correlation between volume and area was found (p < 0.001) as well as agreement between increase and decrease in volume and area. CONCLUSIONS: In the 3-dimensional quantitative volumetric analysis, the volume and area of HEs were correlated and the direction of increase and decrease was concordant. Considering the distribution of HEs in multiple layers of the retina, volumetric analysis could be considered a substitute for the analysis of HE area.

Characteristics of Patients Who Are Not Responsive to Alternate Patching for Overcorrected Intermittent Exotropia.

PURPOSE: To compare the characteristics of patients with surgically overcorrected intermittent exotropia treated with alternate patching. METHODS: The medical records of 51 patients who underwent bilateral lateral rectus muscle recession for intermittent exotropia and required alternate patching to correct postoperative overcorrection were retrospectively reviewed. Patients with postoperative esodeviation ≥18 prism diopters (PD) were started on alternate patching on postoperative day 1, whereas those with postoperative esodeviation of 10 to 17 PD were started after 2 weeks. Postoperative esodeviation <10 PD was considered as slight intentional overcorrection after exotropia surgery. Patients not responsive to alternate patching treatment were defined as those with postoperative esodeviation ≥10 PD after 3 months of treatment. Sex, family history, age, refractive error, amblyopia, stereopsis, suppression, type of exotropia, surgical method, preoperative and postoperative angle of deviation, and start time of alternate patching were compared. RESULTS: Among 51 patients, 29 patients responded to alternate patching and 22 patients did not respond. Female sex (p = 0.04), larger preoperative exodeviation at distance (p = 0.04), late onset of postoperative maximal esodeviation (p < 0.01), larger postoperative maximal esodeviation at near (p = 0.02), and late initiation of alternate patching (p = 0.01) were associated with patients in the non-responsive group. Although postoperative angle of deviation was similar for 2 weeks, the angle of postoperative esodeviation was significantly larger in the non-responsive group than in the responsive group, beginning at 1 month postoperatively. CONCLUSIONS: Female sex, large preoperative exodeviation, late initiation of alternate patching, and large esodeviation 1-month postoperative predisposed patients to be resistant to alternate patching for postoperative overcorrection.

Association Between the Deep-layer Microvasculature Dropout and the Visual Field Damage in Glaucoma.

PURPOSE: To compare the visual field (VF) sensitivity according to the presence of parapapillary deep-layer microvasculature dropout (MvD_P) and focal lamina cribrosa (LC) defect. MATERIALS AND METHODS: Among 158 open-angle glaucoma patients, 4 groups were formed according to the presence of MvD_P and focal LC defect determined by optical coherence tomography (OCT) angiography and by enhanced depth imaging spectral-domain OCT, respectively: (1) eyes without either focal LC defect or MvD_P (group 1); (2) eyes with focal LC defect but no MvD_P (group 2); (3) eyes without focal LC defect but with MvD_P (group 3); (4) eyes with both focal LC defect and MvD_P (group 4). VF sensitivity and retinal nerve fiber layer (RNFL) thickness were compared among the 4 groups for global area and 6 sectors. RESULTS: Both RNFL thickness and VF sensitivity differed among the 4 groups in all areas other than the nasal and superonasal sectors for RNFL thickness. On post hoc analysis, eyes with MvD_P (groups 3 and 4) had significantly worse VF sensitivity than group 2 [P<0.05, 1-way analysis of variance (ANOVA)] in all areas except the superotemporal and temporal sectors, whereas the RNFL thicknesses did not differ (P>0.05, 1-way ANOVA) in any areas except the superotemporal sector. CONCLUSIONS: Eyes with MvD_P had worse VF sensitivity than those without MvD_P, and VF difference was more distinguished than differences of axonal loss and focal LC change. Further studies on the temporal relationship between the MvD_P and glaucomatous VF progression are warranted.