Inner retinal oxygen delivery and metabolism in progressive stages of diabetic retinopathy.

Previous studies have reported increased retinal venous oxygen saturation and decreased retinal blood flow and oxygen metabolism in non-proliferative diabetic retinopathy (NPDR). The current study aimed to determine alterations in both inner retinal oxygen delivery (DO2) and metabolism (MO2) in proliferative DR (PDR) as well as at stages of NPDR. A total of 123 subjects participated in the study and were categorized into five groups: non-diabetic control (N = 32), diabetic with no diabetic retinopathy (NDR, N = 34), mild NPDR (N = 31), moderate to severe NPDR (N = 17), or PDR (N = 9). Multi-modal imaging was performed to measure oxygen saturation and blood flow, which were used for derivation of DO2 and MO2. There were significant associations of groups with DO2 and MO2. DO2 was lower in PDR and not significantly different in NDR and NPDR stages as compared to the non-diabetic control group. MO2 was decreased in PDR and moderate to severe NPDR as compared to the control group, and not significantly reduced in NDR and mild NPDR. The findings demonstrate reductions in both DO2 and MO2 in PDR and MO2 in moderate to severe NPDR, suggesting their potential as biomarkers for monitoring progression and treatment of DR.

Validity and Reliability of The Persian Version of Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire: A Psychometric Study.

BACKGROUND: Women with uterine fibroids (UFs) experience many clinical manifestations that affect their quality of life (QOL). The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is an English instrument specifically designed to assess fibroid-related symptoms and their impact on QOL. This study aims to investigate the reliability and validity of the Persian version of the UFS-QOL questionnaire in Iranian women with UF. MATERIALS AND METHODS: In this psychometric study, women with UFs who presented to Imam Hossein Hospital (Tehran, Iran) between August 2022 and January 2023 were enrolled in this study. A forward-backward approach was applied to translate the UFS-QOL questionnaire into Persian. The reliability of the UFS-QOL questionnaire was assessed by internal consistency and test-retest correlation. Confirmatory factor analysis (CFA) was used to assess convergent validity between items and subscales of the UFS-QOL questionnaire. Pearson's correlation coefficient was used to assess convergence validity between subscales of the UFS-QOL and the World Health Organization Quality of Life Brief Version 26 questionnaire (WHOQOL-BREF-26). RESULTS: Overall, we assessed 226 women with UFs. All subscales of the UFS-QOL questionnaire had acceptable internal consistency (Cronbach's alpha>0.7). Test-retest analysis indicated significant positive correlations between two measurements of all subscales of the UFS-QOL questionnaire: symptom severity (P<0.001), concern (P<0.001), activities (P<0.001), energy/mood (P<0.001), control (P<0.001), self-consciousness (P=0.002), and sexual function (P<0.001). The Kaiser-Meyer-Olkin (KMO) measure value was 0.920, and the result of Bartlett's test of sphericity was significant (P<0.001). CFA identified six factors for the health-related QOL (HRQL) questionnaire, which explained 73.827% of the total variation. Most subscales of the UFS-QOL questionnaire correlated with domains of the WHOQOL-BREF-26 questionnaire (P<0.05). CONCLUSION: The Persian version of the UFS-QOL questionnaire is a valid and reliable instrument to evaluate UFrelated symptoms and QOL among Iranian women.

A retinal imaging system for combined measurement of optic nerve head vascular pulsation and stimulated vasodilation in humans.

Vascular pulsation at the optic nerve head (ONH) reflects vessel properties. Reduction in the stimulated retinal vasodilatory capacity has been reported in diabetes, but its relation with vascular pulsation is unknown. Here we report a new retinal imaging system for correlative assessment of ONH vascular pulsation and stimulated retinal vasodilation. Retinal reflectance images were acquired before and during light flicker stimulation to quantify arterial and venous vasodilation (DAR, DVR) in subjects with and without diabetic retinopathy (N = 25). ONH vascular pulsation amplitude and frequency (PA, PF), were quantified by curve fitting of periodic intensity waveforms acquired in retinal vasculature (RV) and ONH tissue (ONHT) regions. The relationships between pulsation metrics, heart rate (HR), intraocular pressure (IOP), and vasodilatory responses were evaluated. Pulsation metrics were not significantly different between regions (p ≥ 0.70). In RV, inter-image variabilities of PA and PF were 10% and 6%, whereas inter-observer variabilities were 7% and 2% respectively. In both regions, PF was correlated with HR (p ≤ 0.001). PA was associated with DAR in both regions (p ≤ 0.03), but only with DVR in RV (p ≤ 0.05). Overall, ONH vascular pulsation was associated with stimulated retinal vasodilation, suggesting diabetes may have concomitant effects on retinal vasculature compliance and neurovascular coupling.

Menstrual disturbances following COVID-19 vaccination: A probable puzzle about the role of endocrine and immune pathways.

Menstruation is a monthly shedding of the uterine wall, presented by menstrual bleeding in women of reproductive age. Menstruation is regulated by fluctuation of estrogen and progesterone, as well as other endocrine and immune pathways. Many women experienced menstrual disturbances after vaccination against the novel coronavirus in the last two years. Vaccine-induced menstrual disturbances have led to discomfort and concern among reproductive-age women, such that some decided not to receive the subsequent doses of the vaccine. Although many vaccinated women report these menstrual disturbances, the mechanism is still poorly understood. This review article discusses the endocrine and immune changes following COVID-19 vaccination and the possible mechanisms of vaccine-related menstrual disturbances.

Alterations in retinal pulse wave velocity under experimental ocular hypertension.

Impairments of blood flow and autoregulation have been implicated in diabetic retinopathy and glaucoma. Thus, identifying biomarkers of retinal vascular compliance and regulatory capacity is of potential value for understanding the pathophysiology and evaluating onset or progression of disease. Pulse wave velocity (PWV) represents the speed of the pulse-propagated pressure wave within blood vessels and has shown promise as a marker of vascular compliance. The purpose of the current study was to report a method for comprehensive assessment of retinal PWV based on spectral analysis of pulsatile intravascular intensity waveforms and determine alterations due to experimental ocular hypertension. Retinal PWV was linearly related to vessel diameter. Increased retinal PWV was associated with elevated intraocular pressure. Retinal PWV has the potential to serve as a vasoregulation biomarker for investigating vascular factors that contribute to the development of retinal diseases in animal models.

The accumulated oxygen deficit as an indicator of the ischemic retinal insult.

We here attempt to improve quantification of the ischemic retinal insult, that is, what is imposed on the retinal tissue by ischemia, especially in experimental models of ischemia. The ischemic retinal insult initiates the ischemic retinal injury (or outcome). Accordingly, it is reasonable to assume that the better the quantification of the insult, the better the correlation with, and thereby estimation of, the injury. The insult seldom has been quantified in terms of the relevant physiological factors, especially in connection with the rate of oxygen delivery (DO2). We here propose the accumulated oxygen deficit (AO2D) as an indicator of the ischemic retinal insult. We hypothesized that AO2D is correlated with the rate of oxygen metabolism measured 1 h after reperfusion following an episode of ischemia (MO2_1_Hr). Previously, we showed that MO2_1_Hr is related to the electroretinogram amplitude and the retinal thickness when they are measured seven days after reperfusion. We studied 27 rats, as well as 26 rats from our published data on retinal ischemia in which we had measurements of DO2 and duration of ischemia (T) of various levels and durations. We also measured DO2 in 29 rats treated with sham surgery. Ischemia was induced by either ipsilateral or bilateral common carotid artery occlusion or by ophthalmic artery occlusion, which gave a wide range of DO2. DO2 and MO2_1_Hr were evaluated based on three types of images: 1) red-free images to measure vessel diameters, 2) fluorescence images to estimate blood velocities by the displacement of intravascular fluorescent microspheres over time, and 3) phosphorescence images to quantify vascular oxygen tension from the phosphorescence lifetime of an intravascular oxygen sensitive phosphor. Loss of oxygen delivery (DO2L) was calculated as the difference between DO2 under normal/sham condition and DO2 during ischemia. AO2D, a volume of oxygen, was calculated as the product DO2L and T. Including all data, the linear relationship between AO2D and MO2_1_Hr was significant (R2 = 0.261, P = 0.0003). Limiting data to that in which T or DO2L was maximal also yielded significant relationships, and revealed that DO2L at a long duration of ischemia contributed disproportionately more than T to MO2_1_Hr. We discuss the potential of AO2D for quantifying the ischemic retinal insult, predicting the ischemic retinal injury and evaluating the likelihood of infarction.

Impairments of retinal hemodynamics and oxygen metrics in ocular hypertension-induced ischemia-reperfusion.

Ischemia-reperfusion (I/R) is an established model for retinal neurodegeneration. However, there is limited knowledge of retinal physiological metrics and their relationships to retinal function and morphology in the I/R model. The purpose of the study was to test the hypotheses that retinal hemodynamic and oxygen metrics are impaired and associated with visual dysfunction, retinal thinning, and retinal ganglion cell (RGC) loss due to I/R injury. Intraocular pressure (IOP) was increased in one eye of 10 rats for 90 min followed by reperfusion. Fellow eyes served as controls. After one week of reperfusion, multimodal imaging was performed to quantify total retinal blood flow (TRBF) and retinal vascular oxygen contents. Retinal oxygen delivery (DO2) and metabolism (MO2) were calculated. Pattern-evoked electroretinography (PERG) and optical coherence tomography were performed to measure RGC function and retinal thicknesses, respectively. RGCs were counted from retina whole mounts. After one week of reperfusion, TRBF was lower in study eyes than in control eyes (p < 0.0003). Similarly, DO2 and MO2 were reduced in study eyes compared to control eyes (p < 0.003). PERG amplitude, TRT, IRT, ORT, and RGCs were also lower in study eyes (p ≤ 0.01). DO2 and MO2 were correlated with PERG amplitude, TRT, IRT, and ORT (r ≥ 0.6, p ≤ 0.005). The findings improve knowledge of physiological metrics affected by I/R injury and have the potential for identifying biomarkers of injury and outcomes for evaluating experimental treatments.

Retinal Vascular Physiology Biomarkers in a 5XFAD Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that affects the brain and retina and lacks reliable biomarkers for early diagnosis. As amyloid beta (Aß) manifestations emerge prior to clinical symptoms and plaques of amyloid may cause vascular damage, identification of retinal vascular biomarkers may improve knowledge of AD pathophysiology and potentially serve as therapeutic targets. The purpose of the current study was to test the hypothesis that retinal hemodynamic and oxygen metrics are altered in 5XFAD mice. METHODS: Thirty-two male mice were evaluated at 3 months of age: sixteen 5XFAD transgenic and sixteen wild-type mice. Spectral-domain optical coherence tomography, vascular oxygen tension, and blood flow imaging were performed in one eye of each mouse. After imaging, the imaged and fellow retinal tissues were submitted for histological sectioning and amyloid protein analysis, respectively. Protein analysis was also performed on the brain tissues. RESULTS: Retinal physiological changes in venous diameter and blood velocity, arterial and venous oxygen contents, coupled with anatomical alterations in the thickness of retinal cell layers were detected in 5XFAD mice. Moreover, an increase in Aß42 levels in both the retina and brain tissues was observed in 5XFAD mice. Significant changes in retinal oxygen delivery, metabolism, or extraction fraction were not detected. Based on compiled data from both groups, arterial oxygen content was inversely related to venous blood velocity and nerve fiber/ganglion cell layer thickness. CONCLUSIONS: Concurrent alterations in retinal hemodynamic and oxygen metrics, thickness, and tissue Aß42 protein levels in 5XFAD mice at 3 months of age corresponded to previously reported findings in human AD. Overall, these results suggest that this mouse model can be utilized for studying pathophysiology of AD and evaluating potential therapies.

Alterations in Retinal Vascular and Oxygen Metrics in Treated and Untreated Proliferative Diabetic Retinopathy: A Case Report.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes. Panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (anti-VEGF) are approved treatment modalities aimed at regressing neovascularization. Data are lacking about abnormalities in retinal vascular and oxygen metrics before and after combination treatments. A 32-year-old Caucasian male diagnosed with PDR in the right eye was treated by a combination of PRP and multiple anti-VEGF treatments over a 12-month period. The subject underwent optical coherence tomography (OCT) angiography, Doppler OCT, and retinal oximetry before treatment and at 12 months, which was 6 months following the last treatment. Measurements of vascular metrics (vessel density [VD] and mean arterial and venous diameters [DA, DV]) and oxygen metrics (total retinal blood flow [TRBF], inner retinal oxygen delivery [DO2], metabolism [MO2], and extraction fraction [OEF]) were obtained. Both before and after treatments, VD, TRBF, MO2, and DO2 were below the normal lower confidence limits. Additionally, DV and OEF were decreased after treatments. Alterations in retinal vascular and oxygen metrics were reported for the first time in untreated and treated PDR. Future studies are warranted to evaluate the clinical value of these metrics in PDR.

Variability of Retinal Oxygen Metrics in Healthy and Diabetic Subjects.

Purpose: Previous studies have reported alterations in total retinal blood flow (TRBF), oxygen delivery (DO2), oxygen metabolism (MO2), and oxygen extraction fraction (OEF) due to retinal diseases. The purposes of the current study were to determine variabilities and establish normal confidence intervals (CIs) for these metrics. Methods: A total of 22 healthy and 14 diabetic subjects participated in the study. Retinal vascular oxygen saturation (SO2) and TRBF were measured by oximetry and Doppler optical coherence tomography, respectively. DO2, MO2, and OEF were calculated from SO2 and TRBF measurements. Means, standard deviations (SDs), and CIs of metrics were determined in healthy subjects. Intra-visit variability was determined by the mean SDs of repeated measurements. Inter-visit variability was determined by the difference of measurements between two visits. Results: TRBF was 44 ± 15 µL/min (95% CI, 37-51) in healthy subjects. Intra-visit variabilities of TRBF were 5 µL/min and 6 µL/min in healthy and diabetic subjects, respectively. Inter-visit variability of TRBF was 3 µL/min in diabetic subjects. DO2, MO2, and OEF were 8.3 ± 2.9 µLO2/min (95% CI, 7.0-9.6), 3.2 ± 0.9 µLO2/min (95% CI, 2.8-3.6), and 0.40 ± 0.08 (95% CI, 0.36-0.43), respectively, in healthy subjects. Inter-visit variabilities of DO2, MO2, and OEF were 0.6 µLO2/min, 0.1 µLO2/min, and 0.03, respectively, in diabetic subjects. Conclusions: The findings established variabilities and normal baselines for TRBF, DO2, MO2, and OEF measurements in a small cohort of subjects. Translational Relevance: The variability and normal baselines of retinal oxygen metrics may be useful for diagnosing and monitoring patients with retinal diseases.

Relationship Between Macular Vessel Density and Total Retinal Blood Flow in Primary Open-angle Glaucoma.

PRECIS: An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. PURPOSE: The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. MATERIALS AND METHODS: A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. RESULTS: Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P<0.0001). Decreased VD (Pearson correlation, r=0.51; P<0.0001; N=43) and increased SLV (Spearman correlation, rs=-0.47; P=0.001) were correlated with decreased TRBF. Decreased VD and SSV (r≥0.39; P≤0.001; N=43) and increased SLV (rs=-0.71; P<0.0001) were associated with decreased IRT. Decreased VF mean deviation was correlated with decreased VD, SSV, IRT (r≥0.53; P≤0.001; N=24), and with increased SLV (rs=-0.84; P<0.0001). CONCLUSIONS: The finding of an association between macular VD and TRBF supports the role of vascular factors in the pathophysiology of POAG and potential conduct of future studies aimed at identifying multiple image-based vascular metrics for disease diagnosis.

Assessment of inner retinal oxygen metrics and thickness in a mouse model of inherited retinal degeneration.

The retinal degeneration 1 (rd1) mouse is a well-established model of inherited retinal degeneration, displaying photoreceptor degeneration and retinal vasculature damage. The purpose of the current study was to determine alterations in the rate of oxygen delivery from retinal circulation (DO2), the rate of oxygen extraction from the retinal circulation for metabolism (MO2), and oxygen extraction fraction (OEF) in rd1 mice. The study was performed in a total of 18 wild type (WT) and 10 rd1 mice at both 3-weeks and 12-weeks of age. Retinal arterial and venous oxygen contents (O2A and O2V) were measured using phosphorescence lifetime imaging. Total retinal blood flow (TRBF) was determined by fluorescence and red-free imaging. DO2 and MO2 were determined as TRBF × O2A and TRBF × (O2A-O2V), respectively. OEF was calculated as MO2/DO2. The thickness of individual retinal layers was measured from histology sections and inner retina (IR) and total retina (TR) thickness were calculated. TRBF, DO2 and MO2 were lower in rd1 mice compared to WT mice (P ≤ 0.001), whereas OEF was not significantly different between rd1 and WT mice (P = 0.4). TRBF and DO2 were lower at 3-weeks of age compared to 12-weeks of age (P ≤ 0.01), while MO2 was not significantly different between age groups (P = 0.4) and OEF was higher at 3-weeks of age compared to 12-weeks of age (P = 0.003). Additionally, the outer and inner retinal cell layer thicknesses were decreased in rd1 mice at 12-weeks of age compared to both age-matched WT mice and rd1 mice at 3-weeks of age (P ≤ 0.02). MO2 was directly correlated with both IR and TR thickness (R ≥ 0.50; P ≤ 0.03, N = 20). The findings indicate that the rate oxygen is supplied by the retinal circulation is decreased and the reduction in oxygen extracted for metabolism is related to retinal cell layer thinning in rd1 mice.

Intraocular Lens Calcification: Clinico-pathological Report of Two Cases and Literature Review.

PURPOSE: We report the clinicopathological features and surgical outcomes of two cases of intraocular lens (IOL) calcification along with a review of the current literature. CASE REPORT: The first patient was a 53-year-old woman with diabetes mellitus (type 2) who underwent phacoemulsification with posterior chamber IOL insertion (PCIOL), and pars plana vitrectomy. Significant clouding of the IOL was first noted after 1.5 years, and the IOL was replaced with an Artisan lens. The second patient was a 22-year-old woman with Vogt-Koyanagi-Harada syndrome; she underwent a lensectomy, PCIOL, and pars plana vitrectomy. IOL opacification was first noted 4.5 years after the initial surgery and the IOL was extracted. CONCLUSION: The calcification of each IOL was confirmed by a pathologist. Further studies are required to determine the primary causes and mechanisms of the calcification of biomaterials including IOLs.

Long-term Progression of Type 1 Neovascularization in Age-related Macular Degeneration Using Optical Coherence Tomography Angiography.

PURPOSE: To analyze the long-term growth patterns of type 1 neovascularization (NV) in eyes with age-related macular degeneration (AMD) receiving anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Retrospective cohort study. METHODS: Patients were enrolled from 2 eye centers and underwent optical coherence tomography angiography (OCTA) imaging with follow-up greater than 1 year. Choroidal neovascularization (CNV) was manually segmented on OCTA images and compared between time points. CNV growth was subdivided into 3 categories based on OCTA area measurement: CNV doubling, modest growth of less than 50%, and shrinkage. These growth rates were correlated with OCTA morphologic features. RESULTS: Forty-one eyes were analyzed. Mean CNV area was 1.60 ± 1.84 mm2 at baseline and 1.80 ± 1.84 mm2 at 1 year. Thirty-three eyes (80%) displayed an increase in CNV area at 1 year with a mean increase of 0.20 ± 0.38 mm2 (P = .001). Eleven eyes (27%) underwent CNV doubling, 19 eyes (46%) illustrated modest growth, and 6 (15%) showed shrinkage. Anatomic features including a capillary fringe (odds ratio [OR] = 5.3, P = .036) and immature lesion morphology (OR = 4.2, P = .015) were significantly associated with CNV doubling. CNV growth occurred in 3 predominant patterns: "symmetric" growth, "asymmetric" growth, and "finger-like projections," which reflected the orientation of expansion of CNV. "Symmetric" and "asymmetric" growth together correlated with greater frequency of CNV doubling (OR = 15, P = .0048). CONCLUSION: OCTA provides noninvasive measurement of the area of neovascular lesions in AMD. Sustained growth of type 1 NV can be identified in the majority of lesions (80%) that display characteristic patterns of progression despite ongoing anti-VEGF therapy.

PARANEOPLASTIC VITELLIFORM MACULOPATHY ASSOCIATED WITH METASTATIC MELANOMA.

PURPOSE: To report a case of paraneoplastic vitelliform maculopathy in a patient with metastatic melanoma of unknown primary site. METHODS: Case report. Main outcome measures include funduscopic examination, fluorescein angiography, fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: A 44-year-old man with a known history of metastatic melanoma was referred for ophthalmic evaluation because of bilateral vision loss. Funduscopic examination was remarkable for vitelliform maculopathy that was confirmed with fundus autofluorescence and spectral domain optical coherence tomography. CONCLUSION: We describe a rare case of paraneoplastic vitelliform maculopathy. There are many etiologies of acquired vitelliform retinal lesions in the retina. Multimodal retinal imaging, including fundus autofluorescence and spectral domain optical coherence tomography, can be best used to identify these lesions. A history of systemic metastatic melanoma should be ruled out in patients with vitelliform maculopathy.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

Foveal and Peripapillary Vascular Decrement in Migraine With Aura Demonstrated by Optical Coherence Tomography Angiography.

Purpose: Migraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC). Methods: We recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images. Results: On macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups. Conclusions: Migraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Can allopurinol improve retinopathy in diabetic rats? Oxidative stress or uric acid; which one is the culprit?

Allopurinol, an inhibitor of xanthine oxidase, reduces both plasma uric acid and oxidative stress and shows useful effects on some complications of diabetes. However, it is not defined which of the above mentioned properties are involved. Moreover, to the best of our knowledge no study has been done on the effects of allopurinol on diabetic retinopathy. In the present study, the effect of allopurinol on experimental diabetic retinopathy and its possible mechanism has been investigated. Thirty two rats were divided into four groups of eight rats each; (1) normal, (2) diabetic control, (3) diabetic + allopurinol (50 mg/kg.day), (4) diabetic + benzbromarone (10 mg/kg.day). Drugs were administered daily and orally from the day after diabetes induction for eight weeks. Thereafter retinal function and structure were evaluated by electroretinography and microscopic studies. Uric acid and oxidative stress biomarkers were measured biochemically. Diabetes significantly increased plasma uric acid and oxidative stress markers and reduced body weight and amplitude of electroretinogram (ERG) b-wave and oscillatory potentials. Treatment of diabetic rats with allopurinol caused a significant increase in the amplitude of ERG b-wave (87%) and decrease in blood sugar (20%), uric acid (49%), and 8-iso-prostaglandin F2a (56%), but had no effect on the number of retinal ganglionic cells and oscillatory potentials. Benzbromarone showed no significant effects on the considered parameters except the reduction of uric acid. Allopurinol improved the b-wave amplitude of diabetic rats. It seems that this beneficial effect is due to the reduction of oxidative stress rather than its effect on plasma uric acid.

Spectral-Domain Optical Coherence Tomographic Angiography in Children With Amblyopia.

Importance: Amblyopia is the most common cause of visual impairment in childhood, with a prevalence of 1% to 4% in children in the United States. To date, no studies using noninvasive optical coherence tomographic angiography (OCTA) have measured blood flow in the retinal capillary layers in children with amblyopia. Objective: To evaluate the retinal and microvascular features using OCTA in children (<18 years) with amblyopia. Design, Setting, and Participants: This observational case-control study enrolled patients from September 1, 2016, through May 31, 2017, and was conducted from September 1, 2016, through June 30, 2017, at the Stein Eye Institute at UCLA (University of California, Los Angeles). Participants included 59 children (<18 years) with amblyopia and without amblyopia examined at a pediatric ophthalmology clinic or referred to the clinic by coinvestigators. All patients underwent comprehensive ophthalmological examination, including visual acuity, refraction, and ocular motility tests; anterior and posterior segment examination; and OCTA. Main Outcomes and Measures: Reduced superficial and deep retinal capillary vessel density on OCTA. Results: Of the 63 eyes evaluated, 13 (21%) were amblyopic and 50 (79%) were control eyes. Of the 59 patients, the mean (SD) age of patients with amblyopia was 8.0 (4.0) years and 10.3 (3.3) years for the controls; 33 patients (56%) were female; and 5 of 13 (39%) and 27 of 46 (54%) patients in the amblyopic and control groups, respectively, were identified as white. The macular vessel density of the superficial capillary plexus was lower in the amblyopic group than in the control group in both 3 × 3-mm and 6 × 6-mm scans. After adjusting for age and refractive error, the mean (SD) difference in the superficial capillary plexus in the 6 × 6-mm scan was statistically significant (49.3% [4.1] vs 51.2% [2.9]; P = .02). Macular vessel density of the deep capillary plexus in the 6 × 6-mm scans was also considerably different between groups: mean (SD) vessel density of the deep retinal capillary plexus was 54.4% (4.7%) in the amblyopia group and 60.1% (3.3%) in the control group, with a difference of 5.7% (95% CI, 3.4%-8.1%; P = .002). Conclusions and Relevance: The study found that OCTA reveals subnormal superficial and deep retinal capillary density in the macula of patients with amblyopia. Further studies are needed to determine the clinical relevance of this finding.