Quantitative measures of vortex veins in the posterior pole in eyes with pachychoroid spectrum diseases.

Pachychoroid spectrum diseases have attracted increasing attention, though their pathophysiology has yet to be fully elucidated. In this study, we assessed the vascular diameters of vortex veins in pachychoroid spectrum diseases such as central serous chorioretinopathy (CSC), pachychoroid neovasculopathy without polypoidal lesions (PNV), and pachychoroid neovasculopathy with polypoidal lesions (polypoidal choroidal vasculopathy: PCV). In a retrospective case series of 94 eyes with CSC, 60 eyes with PNV and 57 with PCV, we binarized en face optical coherence tomography (OCT) images of choroidal vortex veins and analyzed the mean diameter of vortex veins. The presence of anastomosis between the superior and inferior vortex veins and central choroidal thickness (CCT) were also evaluated using OCT images. CSC showed significantly larger mean diameter of vortex veins than PCV (P < 0.05). Anastomosis between superior and inferior vortex veins was observed in over 90% of eyes with each pachychoroid spectrum disease. The patients with CSC were the youngest, followed by PNV patients, and then patients with PCV. The largest CCT values were observed in CSC eyes, followed by PNV eyes, and then PCV eyes. CCT correlated with the mean diameter of vortex veins (rs = 0.51, P < 0.01). These findings suggest that congestion of vortex veins might show gradual amelioration corresponding to the development of anastomosis between the superior and inferior vortex veins during the course of progression of pachychoroid spectrum diseases. Moreover, the mean diameter of vortex veins can be used as a parameter indicating choroidal congestion.

Characterization of microvascular tortuosity in retinal vein occlusion utilizing optical coherence tomography angiography.

We investigated the characteristics of microvessel tortuosity in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) and their associations with visual outcomes using optical coherence tomography angiography (OCTA). Thirty-four BRVO and 21 CRVO patients and 31 healthy subjects were included. From OCTA, the branch number (BN), mean branch length (BL), mean Euclidean length (EL), vessel density (VD) and vessel tortuosity (VT) were quantified. In BRVO eyes, compared with that in the controls, the affected area of the deep capillary plexus (DCP) showed a decreased BN and VD, an increased BL, and unchanged VT. The nonaffected area of the DCP showed decreases in BN, VD and VT. The affected area of the superficial capillary plexus (SCP) showed higher VT. In CRVO eyes, the DCP showed a lower BN, VD and VT, while the SCP showed a lower BN and greater BL and EL. Improved visual acuity (VA) after 1 year in BRVO eyes was associated with decreases in BN, BL, VD and VT in the affected area in the DCP and lower VT in the nonaffected area of the SCP; in CRVO eyes, improved VA was associated with a higher BL and EL in the DCP. VT, BL, and EL may be new microvascular markers associated with changes in VA in BRVO and CRVO.

Association of retinal venular tortuosity with impaired renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing.

BACKGROUND: Previous studies have identified retinal microvascular features associated with renal dysfunction. Biopsies are necessary to confirm kidney microvascular damage and retinal imaging may enable evaluation of microangiopathic characteristics reflecting renal changes associated with chronic kidney disease (CKD). We evaluated retinal microvascular parameters (RMPs) for associations with renal function in a cross-sectional analysis of the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: RMPs (central retinal arteriolar/ venular equivalents [CRAE/CRVE], arteriolar to venular ratio [AVR], fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Associations were assessed with multivariable regression analyses between RMPs and estimated glomerular filtration rate (eGFR) defined by serum creatinine (eGFRscr) and cystatin C (eGFRcys) and also CKD status characterised by eGFR < 60 mL/min/1.73m2. Regression models were adjusted for potential confounders including age, sex, diabetes, smoking status, educational attainment, cardiovascular disease, body mass index, antihypertensive medication, systolic blood pressure, triglycerides, high- and low-density lipoprotein levels. RESULTS: Data were included for 1860 participants that had measures of renal function and retinal fundus images of sufficient quality for analysis. Participants had a mean age of 62.0 ± 8.5 yrs. and 53% were female. The mean eGFR for scr and cys were 82.2 ± 14.9 mL/min/1.73m2 and 70.7 ± 18.6 mL/min/1.73m2 respectively. eGFRcys provided lower estimates than eGFRscr resulting in a greater proportion of participants categorised as having CKD stages 3-5 (eGFRcys 26.8%; eGFRscr 7.9%). Multivariable regression analyses showed that increased venular tortuosity (OR = 1.30; 95%CI: 1.10, 1.54; P < 0.01) was associated with CKD stages 3-5 characterised by eGFRscr < 60 mL/min/1.73 m2. No additional associations between CKD status characterised by eGFRscr or with eGFRcys, were detected (P > 0.05). Multivariable regression failed to detect associations between CRAE, CRVE, AVR, fractal dimension or tortuosity and eGFRscr or eGFRcys (P > 0.05). CONCLUSION: Increased retinal venular tortuosity was associated with CKD stages 3-5 defined by eGFRscr < 60 mL/min/1.73 m2, in an older population independent of potential confounding factors. These retinal measures may provide non-invasive microvascular assessment of associations with CKD.

Associations of Retinal Vessel Caliber With Hearing Status in Childhood and Midlife: A Cross-Generational Population-Based Study.

Importance: Microvascular phenotypes, which can be assessed using retinal imaging, may be informative about the life course pathogenesis of hearing loss. Objective: To investigate whether differences in retinal vessel caliber (specifically wider venules and narrower arterioles) are associated with hearing threshold and hearing loss in mid-childhood and midlife. Design, Setting, and Participants: A population-based cross-sectional study (Child Health CheckPoint) was nested within the Longitudinal Study of Australian Children. A total of 1281 children and 1255 attending parents were assessed using retinal microvasculature and air conduction audiometry data at a main assessment center in 7 large cities in Australia. Main Outcomes and Measures: Air conduction audiometry was used to calculate the high Fletcher index (mean threshold of 1, 2, and 4 kHz), and bilateral hearing loss was defined as a high Fletcher index greater than 15 dB hearing level in the better-hearing ear. Retinal arteriolar and venular caliber were measured from fundus photographs using validated computer-based software. Linear and logistic regression quantified the associations of retinal vessel caliber with hearing threshold and hearing loss, respectively. Results: Of the 1281 included children (mean age, 11.4 years; 49.1% boys), the mean (SD) high Fletcher index was 7.9 (5.8) dB hearing level. Of the 1255 included adults (mean age, 43.8 years; 86.6% women), the mean (SD) high Fletcher index was 13.0 (6.8) dB hearing level; 109 of 1281 children (8.5%) and 328 of 1255 adults (26.1%) had hearing loss. In adults, each 1-SD (18.6-µm) wider retinal venular caliber (worse) was associated with higher (worse) hearing threshold at lower individual frequencies (eg, 2 kHz: ß = 0.63; 95% CI, 0.10-1.17) and overall high Fletcher index (eg, 2 kHz: ß = 0.52; 95% CI, 0.07-0.96), as well as a 1.20-fold (95% CI, 1.03-1.40) higher odds of hearing loss. In children, patterns of venular associations were similar but smaller and less certain. Narrower retinal arteriolar caliber (worse) was associated with a 1.16-fold (95% CI, 1.00-1.37) higher odds of hearing loss in adults (per 1-SD [14.0-µm] narrower arteriolar caliber) but not in children. Conclusions and Relevance: Adverse retinal microvascular characteristics are associated with hearing loss by midlife, with venular associations possibly emerging by age 11 to 12 years. Microvascular health may contribute to the pathogenesis of hearing loss across the life course, warranting replication and mechanistic studies to inform causal inference and prevention efforts.

Retinal vessel diameter changes after 6 months of treatment in the Idiopathic Intracranial Hypertension Treatment Trial.

BACKGROUND/AIMS: Prior studies support an association between increased retinal venule diameter and elevated intracranial pressure (ICP). The purpose of this study was to test the hypothesis that retinal venule diameters decrease in association with long-term therapy for high ICP in subjects with idiopathic intracranial hypertension (IIH). METHODS: This is a retrospective analysis of multicentre randomised controlled trial data. Standardised procedures were used to measure area of optic nerve head elevation (ONHA) and diameters of 4 arterioles and 4 venules 2.7 mm from the optic disc centre on fundus photos collected at baseline and after 6 months of randomised treatment with placebo+diet or acetazolamide+diet in subjects participating in the IIH Treatment Trial (IIHTT) (n=115). Change in arteriole (Da) and venule (Dv) diameters from baseline to 6 months was studied as a function of IIH, haemodynamic and demographic variables. RESULTS: Dv decreased following 6 months of therapy (8.1 µm, 5.9%, p<0.0005) but Da did not change. Dv change was associated with ONHA change (p<0.0005, r=0.47) and this association persisted in multiple variable models. CONCLUSIONS: Retinal venule diameter decreased, and arteriole diameter did not change in association with treatment for elevated ICP with a weight loss intervention and placebo or acetazolamide in IIHTT participants. Further study is needed to determine how retinal vessel measurements can be combined with other clinical observations to inform disease management.

ACUTE FROSTED RETINAL PERIPHLEBITIS IN A PATIENT WITH MEDITERRANEAN FEVER.

PURPOSE: To present a case of frosted branch periphlebitis in a young Armenian patient with familial Mediterranean fever. METHODS: Case report. RESULTS: A 37-year-old man presented with a unilateral decreased visual acuity and floaters for 4 days on the left eye (LE). Visual acuity was 20/20 in the right eye (RE) and 20/28 in the LE. Anterior segment and fundus examinations of the RE were normal. Slit-lamp examination of LE revealed a mild nongranulomatous anterior uveitis and vitritis. Intraocular pressure was 19 mmHg in the RE and 12 mmHg in the LE. Fundoscopy of the LE showed typical appearance of frosted branch periphlebitis with perivascular sheathing of the retinal veins and scattered retinal hemorrhages. Fluorescein angiography of the RE was normal. The LE showed optic disk and segmented vascular staining without macular leakage. Optical coherence tomography of the RE was normal; LE demonstrated a localized macular thickening and few intraretinal cysts. The detailed ophthalmologic history was negative. The general history and workup were significant for familial Mediterranean fever and a positive lupus anticoagulant. One week later, the fundus findings worsened with a severe decrease of visual acuity of the LE to 20/200. A single intravitreal (IVT) injection of bevacizumab was performed. Three weeks after injection, fundus findings progressively improved with a decrease of the macular thickening and an improvement of the visual acuity to 20/25. Clinical improvement continued up to the last visit (19 weeks after the injection) with a visual acuity that reached back 20/20 with no signs of active inflammation. CONCLUSION: This case demonstrates a possible association between unilateral frosted branch periphlebitis and familial Mediterranean fever.

Longitudinal vasculature changes in branch retinal vein occlusion with projection-resolved optical coherence tomography angiography.

PURPOSE: To analyze vascular changes in branch retinal vein occlusion (BRVO) using projection-resolved optical coherence tomography angiography (PR-OCTA). METHODS: We reviewed 30 consecutive eyes of 30 cases with BRVO retrospectively. PR-OCTA was performed during the acute, intermediate, and remission phases when anti-vascular endothelial growth factor drugs suppress cystic changes. The main outcome measures were vessel density (VD) and retinal thickness changes in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). RESULTS: The VDs did not change longitudinally in the SCP and DCP during the follow-up period. The VD was significantly (p = 0.0105) greater in the ICP during remission than the acute phase. The full retinal thickness (internal limiting membrane [ILM] to retinal pigment epithelium [RPE]) and inner retinal thickness (ILM to inner plexiform layer [IPL]) decreased significantly (p = 0.0002 and p = 0.0014, respectively) during the follow-up period. When the inner retina was thinner than 117 µm, the VD in the ICP increased significantly (p = 0.045) during the follow-up period. When the inner retinal layer did not become thinner, the VD in the ICP remained unchanged. CONCLUSION: PR-OCTA showed the three distinct vascular plexuses in BRVO. The VDs remained unchanged during the follow-up period in the SCP and DCP but increased significantly in the ICP during remission. Inner retinal thinning might cause increases in the VD in the ICP because of projection artifacts and segmentation errors despite using PR-OCTA.

BRANCH RETINAL VEIN OCCLUSION SECONDARY TO A RETINAL ARTERIOLAR MACROANEURYSM: A NOVEL MECHANISM SUPPORTED BY MULTIMODAL IMAGING.

BACKGROUND/PURPOSE: To report a case of a branch retinal vein occlusion secondary to a retinal arteriolar macroaneurysm (RAM). METHODS: Retrospective case report describing examination findings, treatment outcome and unique multimodal imaging features demonstrated on fluorescein angiography, optical coherence tomography, optical coherence tomography angiography and adaptive optics photography of the retinal vessels and RAM. RESULTS: A 61-year-old man presented with 20/200 vision in the right eye because of a branch retinal vein occlusion secondary to a RAM. After sector panretinal photocoagulation and a course of 24 intravitreal antivascular endothelial growth factor injections over 4 years, visual acuity improved to 20/25. Fluorescein angiography showed filling of the RAM even after 4 years. Optical coherence tomography angiography demonstrated venous collateral vessels in both the superficial and deep capillary plexuses, and adaptive optics imaging revealed a gap between the RAM wall and occluded vein. CONCLUSION: Multimodal imaging of this unusual presentation illustrated a novel mechanism of branch retinal vein occlusion in which a primary RAM adjacent to the junction of two retinal veins led to obstruction of venous flow without evidence of direct compression. This supports the theory that perianeurysmal microenvironment changes may be of importance in the pathogenesis of venous occlusion.

Retinal Vasculometry Associations with Cardiometabolic Risk Factors in the European Prospective Investigation of Cancer-Norfolk Study.

PURPOSE: To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. DESIGN: Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye Study. PARTICIPANTS: Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. METHODS: Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. MAIN OUTCOMES MEASURES: Retinal arteriolar and venular tortuosity and width. RESULTS: In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%-3.3% per 5 kg/m2), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%-3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%-10.4%); wider venules were associated with older age (2.6 µm; 95% CI, 2.2-2.9 µm per decade), higher triglyceride levels (0.6 µm; 95% CI, 0.3-0.9 µm per 1 mmol/l), BMI (0.7 µm; 95% CI, 0.4-1.0 per 5 kg/m2), HbA1c level (0.4 µm; 95% CI, -0.1 to 0.9 per 1%), and being a current smoker (3.0 µm; 95% CI, 1.7-4.3 µm); smoking also was associated with wider arterioles (2.1 µm; 95% CI, 1.3-2.9 µm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 µm; 95% CI, 0.7-2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%-7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%-1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%-6.4%), and in those with prevalent stroke (8.3%; 95% CI, -0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 µm; 95% CI, 0.6-1.0 µm per decade), higher systolic blood pressure (0.5 µm; 95% CI, 0.4-0.6 µm per 10 mmHg), total cholesterol level (0.2 µm; 95% CI, 0.0-0.3 µm per 1 mmol/l), and HDL (1.2 µm; 95% CI, 0.7-1.6 µm per 1 mmol/l). CONCLUSIONS: Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.

Association of Cancer Immunotherapy With Acute Macular Neuroretinopathy and Diffuse Retinal Venulitis.

Importance: Checkpoint inhibition in cancer immunotherapy related to T-cell-driven mechanisms of action associated with acute macular neuroretinopathy (AMN) and diffuse retinal venulitis, an adverse event not previously described, is reported here. Objective: To describe 2 patients who developed ophthalmologic events after treatment with the programmed death 1 axis inhibitor, atezolizumab. Design, Setting, and Participants: Retrospective review of 2 patients treated with atezolizumab for metastatic breast cancer and colon cancer, respectively, who presented with AMN and diffuse retinal venulitis conducted at 2 tertiary medical centers. Main Outcomes and Measures: Multimodal imaging including near infrared, optical coherence tomography, and fluorescein angiography were used to characterize retinal vascular abnormalities. Results: Based on optical coherence tomography and multimodal imaging findings, the clinical diagnosis of AMN associated with diffuse retinal venulitis was made in these 2 patients receiving atezolizumab. Conclusions and Relevance: While only 2 cases of patients receiving the programmed death ligand 1 inhibitor atezolizumab who experienced AMN and diffuse retinal venulitis are described here, these findings suggest that patients receiving programmed death 1 axis inhibitor therapies may need to be monitored for unexpected immune-related ocular toxicity including abnormalities of the microvasculature and large retinal vessels. Further studies might investigate the potential mechanisms of retinal vascular changes associated with these therapies.

Effect of aflibercept on persistent macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate the efficacy of switching treatment from intravitreal ranibizumab to intravitreal aflibercept on the treatment of refractory macular edema secondary to central retinal vein occlusion (CRVO). METHODS: In this retrospective study; 12 eyes with refractory macular edema secondary to CRVO after multiple monthly repeated intravitreal 0.5mg/0.05mL ranibizumab injections prior to switching therapy to intravitreal 2mg/0.05mL aflibercept, between March 2012 and April 2016 were reviewed. The follow-up time was 12 months. Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central retinal volume (CRV) and injection interval between baseline and month 1, 3, 6 and 12 after switching therapy to aflibercept were reviewed and evaluated. RESULTS: Mean baseline CRT decreased from 516±101 mic. to 252±114 mic. at month 12 (P=0.008). Mean baseline CRV decreased from 8.74±2.13 mm3 to 6.82±1.64 mm3 at month 12 (P=0.005). Baseline BCVA improved from 0.73±0.21 to 0.53±0.17 logMAR at month 12 (P=0.004). Mean BCVA gain was two logMar lines (10 letters) at month 12. After switching therapy to aflibercept; the mean injection interval increased significantly from 1.34 months at baseline to 1.86 months at month 12, by an increase of 0.52 months (P=0.02). CONCLUSION: Intravitreal aflibercept is evaluated to be presenting significant visual and anatomical improvements in patients with persistent macular edema due to CRVO despite previous intravitreal ranibizumab.

Venous beading in two or more quadrants might not be a sensitive grading criterion for severe nonproliferative diabetic retinopathy.

PURPOSE: To determine whether venous beading (VB) in two or more quadrants is an appropriate grading criterion for severe nonproliferative diabetic retinopathy (NPDR). METHODS: A hospital-based, retrospective, cross-sectional study. A total of 806 patients admitted with diabetic retinopathy (DR) from January 2014 to April 2017 were included in this study. DR severity was graded by the international grading criterion. The status of VB, intraretinal microvascular abnormalities (IRMA), capillary nonperfusion, arteriovenous nicking, and diabetic macular edema was evaluated based on fundus fluorescein angiography. RESULTS: The prevalence of VB in eyes with proliferative diabetic retinopathy (PDR), severe NPDR, and moderate NPDR was 41.3% (327/791), 5.9% (31/526), and 0% (0/295), respectively (p < 0.001). Moreover, the proportion of VB in two or more quadrants was even lower (27.1% for PDR and 2.1% for severe NPDR, p < 0.001), and among the total of 225 eyes with VB in two or more quadrants, 214 eyes (95.1%) were graded as PDR. Furthermore, VB formation was significantly correlated with capillary nonperfusion, duration of diabetes (both p < 0.001), and smoking (p < 0.05). After adjusting for age, sex, and other possible factors, VB (OR = 7.479, p < 0.001) and IRMA (OR = 2.433, p < 0.001) were determined as independent risk factors for developing PDR. CONCLUSIONS: Our study suggested that VB in two or more quadrants might not be a sensitive grading criterion for severe NPDR among a Chinese population with type 2 diabetes. Nevertheless, VB has a great specificity to define an advanced form of DR.

Swept-Source OCT Angiographic Imaging of a Central Retinal Vein Occlusion During Pregnancy.

To avoid fluorescein angiography in a pregnant woman diagnosed with a central retinal vein occlusion (CRVO), swept-source optical coherence tomography angiography (SS-OCTA) was performed and showed no evidence of decreased central retinal perfusion leading to the diagnosis of a nonischemic CRVO. Five months after an intravitreal injection of steroid, both her vision and the retinal appearance had returned to normal. This case demonstrates how a noninvasive, safe, 12 mm × 12 mm SS-OCTA image of a CRVO is useful in evaluating the retinal perfusion at presentation and follow-up during pregnancy. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:206-208.].

Association of Retinal Vascular Caliber and Age-Related Macular Degeneration in Patients With the Acquired Immunodeficiency Syndrome.

Purpose: To evaluate the relationship between retinal vascular caliber and AMD in patients with AIDS. Methods: Participants enrolled in the Longitudinal Study of the Ocular Complications of AIDS had retinal photographs taken at enrollment. Retinal vascular caliber (central retinal artery equivalent [CRAE] and central retinal vein equivalent [CRVE]) and intermediate-stage AMD were determined from these retinal photographs. Photographs were evaluated by graders at a centralized reading center, using the Age-Related Eye Disease Study grading system for AMD and semiautomated techniques for evaluating retinal vascular caliber. Results: Of the 1171 participants evaluated, 110 (9.4%) had AMD and 1061 (90.6%) did not. Compared with participants without AMD, participants with AMD had larger mean CRAEs (151 ± 16 µm versus 147 ± 16 µm; P = 0.009) and mean CRVEs (228 ± 24 µm versus 223 ± 25 µm; P = 0.02). The unadjusted differences were: CRAE, 4.3 µm (95% confidence interval [CI] 1.1-7.5; P = 0.009) and CRVE, 5.5 µm (95% CI 0.7-10.3; P = 0.02). After adjustment for age, race/ethnicity, sex, human immunodeficiency syndrome (HIV) transmission category, smoking, enrollment and nadir CD4+ T cells, and enrollment and maximum HIV load, the differences between patients with and without AMD were as follows: CRAE, 5.4 µm (95% CI 2.3-8.5; P = 0.001) and CRVE, 6.0 µm (95% CI 1.4-10.6; P = 0.01). Conclusions: In patients with AIDS, AMD is associated with greater retinal arteriolar and venular calibers, suggesting a role for shared pathogenic mechanisms, such as persistent systemic inflammation.