Ocular Ischemic Syndrome due to Internal Carotid Artery Occlusion with Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF-1) is associated with multiple vascular abnormalities, including internal carotid artery (ICA) stenosis/occlusion. Depending on the site of stenosis/occlusion of the ICA, both cerebral circulation and ocular circulation can be impaired. We describe a rare pediatric case of ocular ischemic syndrome (OIS) due to ICA occlusion in NF-1. The patient diagnosed with NF-1 suffered right ICA occlusion at 12 years of age, and developed right dense vitreous hemorrhage due to OIS at 13 years of age. The patient underwent right cerebral revascularization surgery to improve cerebral and ocular ischemia, but the visual acuity of the right eye did not improve. This case suggests that attention should be paid not only to cerebral ischemia but also to ocular ischemia in patients with ICA stenosis/occlusion of NF-1. Surgical interventions such as cerebral revascularization surgery should be considered in the early stages of OIS to protect visual function, and careful follow-up is required.

Multicenter, retrospective, observational study for the Treatment Pattern of systemic corticoSTERoids for relapse of non-infectious uveitis accompanying Vogt-Koyanagi-Harada disease or sarcoidosis.

PURPOSE: Non-infectious uveitis associated with Vogt-Koyanagi-Harada (VKH) disease or sarcoidosis is commonly treated with systemic corticosteroids (SCS). We assessed the use of SCS for non-infectious uveitis relapses in Japanese clinical practice. STUDY DESIGN: Multicenter, retrospective chart review (UMIN Clinical Trial Registry; UMIN000032390). METHODS: One hundred fifty-seven patients (15- ≤ 75 years; 103 VKH disease, 54 sarcoidosis) given SCS to treat a relapse of non-infectious intermediate, posterior, or panuveitis accompanying VKH disease or sarcoidosis were studied (August 2011-December 2018). SCS dose and duration, concomitant medications, subsequent relapses, and steroid-related adverse drug reactions (ADRs) were analyzed for 12 months after target relapse treatment. Relationships between background factors and total SCS dose were analyzed (logistic regression). RESULTS: Mean (± SD) total SCS dose over 12 months after target relapse treatment was 3874 ± 2775 mg, and was higher in patients with immunosuppressants than in those without (4575 mg vs 3496 mg). Immunosuppressant use was the only factor significantly associated with higher total SCS dose (p = 0.0196). Mean duration of SCS treatment for relapse was 318.7 ± 89.3 days. Only 29.3% of patients were steroid-free after 12 months; the percentage was higher in patients without immunosuppressants (36.3% vs 16.4%). Subsequent relapse was experienced by 39.5% of patients, and 13.4% had a steroid-related ADR (mostly glaucoma or diabetes). CONCLUSION: In Japanese clinical practice, many patients with recurrent uveitis accompanying VKH disease or sarcoidosis received SCS for relapse for ≥ 300 days, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.

Comparison of combination therapy of prednisolone and cyclosporine with corticosteroid pulse therapy in Vogt-Koyanagi-Harada disease.

PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria.

Malignant hypertension, a form of hypertensive emergency, causes acute damage in vital organs such as the brain, eyes, and kidneys. We aimed to examine the concurrency of acute hypertensive damage across the target organs to elucidate the underlying analogous pathophysiology. This single-center retrospective study evaluated the characteristics of organ damage, short-term clinical course, and interorgan relationships in patients with malignant hypertension treated between 2008 and 2019. Baseline characteristics of 20 patients who met our inclusion criteria were mean age 48 ± 13 years and blood pressure 222 ± 18/142 ± 16 mmHg; the median estimated glomerular filtration rate and urinary protein level were 49 mL/min/1.73 m2 (interquartile range [IQR] 27-79) and 1.9 g/g creatinine (IQR 0.2-4.0), respectively. Posterior reversible encephalopathy syndrome (PRES) was found in 60% of patients with major involvement and a wide variety of distribution patterns in the brainstem. In the fundus, serous retinal detachment was found in 60% of patients. Patients with PRES and serous retinal detachment showed higher levels of urinary protein than those without symptoms (P = 0.007 and 0.02, respectively), and proteinuria >1 g/g creatinine highly complicated both PRES and serous retinal detachment (91%). Matrix analysis also showed that the three symptoms were highly associated with each other. These results demonstrate the close relationship and concurrency of hypertensive acute organ damage in the brain, eyes, and kidneys. A common analogous mechanism, such as hyperperfusion-induced capillary leakage in each organ, implies an underlying pathophysiology of PRES, serous retinal detachment, and proteinuria.

Age- and Sex-Dependency of Laser Speckle Flowgraphy Measurements of Optic Nerve Vessel Microcirculation.

PURPOSE: To investigate the relationship between various characteristics of a normal population and laser speckle flowgraphy (LSFG) measurements of mean blur rate (MBR) in the optic nerve head (ONH). METHODS: A total of 189 eyes of 189 normal subjects (93 male, 96 female, mean age 45 ± 14 years old, age range: 20-72) without any history of hypertension, hyperlipidemia or diabetes were enrolled. ONH microcirculation was measured with LSFG and overall MBR (MA), vessel-area MBR (MV), and tissue-area MBR (MT) were derived from these measurements. The statistical association of these measurements with characteristics such as sex, age, intraocular pressure (IOP) and systolic blood pressure (SBP) was then determined. RESULTS: There was a trend towards decreased IOP and MV and increased SBP with age (P = 0.002, P = 0.035, and P = 0.006, respectively). Furthermore, IOP, MV and SBP were correlated with age (r = -0.23, P = 0.011; r = -0.24, P < 0.001; and r = 0.30, P < 0.001, respectively). Separate multiple regression analyses of independent contributing factors revealed that sex and IOP contributed to MA (P < 0.001 and P = 0.002, respectively), sex, IOP, and age contributed to MV (P < 0.001, P = 0.003, and P = 0.024, respectively), while only IOP contributed to MT (P = 0.003). CONCLUSION: In a normal population, MBR was affected by IOP in both the large vessel and capillary areas of the ONH, but not by SBP. MV was also affected by age and sex, while MT was stable independent of age or sex.

Relationship of ocular microcirculation, measured by laser speckle flowgraphy, and silent brain infarction in primary aldosteronism.

PURPOSE: Recent studies have shown that the risk of cerebro- and cardiovascular events (CVEs) is higher in patients with primary aldosteronism (PA) than in those with essential hypertension (EH), and that silent brain infarction (SBI) is a risk factor and predictor of CVEs. Here, we evaluated the relationship between findings from laser speckle flowgraphy (LSFG), a recently introduced non-invasive means of measuring mean blur rate (MBR), an important biomarker of ocular blood flow, and the occurrence of SBI in patients with PA. METHODS: 87 PA patients without symptomatic cerebral events (mean 55.1 ± 11.2 years old, 48 male and 39 female) were enrolled in this study. We measured MBR in the optic nerve head (ONH) with LSFG and checked the occurrence of SBI with magnetic resonance imaging. We examined three MBR waveform variables: skew, blowout score (BOS) and blowout time (BOT). We also recorded clinical findings, including age, blood pressure, and plasma aldosterone concentration. RESULTS: PA patients with SBI (15 of 87 patients; 17%) were significantly older and had significantly lower BOT in the capillary area of the ONH than the patients without SBI (P = 0.02 and P = 0.03, respectively). Multiple logistic regression analysis revealed that age and BOT were independent factors for the presence of SBI in PA patients (OR, 1.15, 95% CI 1.01-1.38; P = .03 and OR, 0.73, 95% CI 0.45-0.99; P = .04, respectively). CONCLUSION: PA patients with SBI were older and had lower MBR BOT than those without SBI. Our analysis showed that age was a risk factor for SBI, and that BOT was a protective factor, in patients with PA. This suggests that BOT, a non-invasive and objective biomarker, may be a useful predictor of SBI and form part of future PA evaluations and clinical decision-making.

Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy.

PURPOSE: The purpose of this study was to evaluate the correlation between laser speckle flowgraphy measurements of mean blur rate (MBR) and hydrogen gas clearance measurements of capillary blood flow (CBF) in the optic nerve head (ONH) of albino and pigmented rabbits, with or without chronic ischemia-induced ONH atrophy. METHODS: The ONH MBR and ONH CBF were measured at baseline, 30 and 60 minutes after the intravenous administration of endothelin-1 (ET-1) (10(-10) mol/kg) in six albino and six pigmented rabbit eyes. The ONH MBR and ONH CBF were also measured in nine pigmented rabbit eyes that underwent the intravitreal administration of ET-1 (20 pmol) twice per week for 4 weeks to provoke chronic ischemia-induced ONH atrophy. RESULTS: In the group that received intravenous ET-1, average measurements of ONH MBR and ONH CBF at all time points were correlated in both the albino (r = 0.88, P < 0.001, n = 18) and pigmented rabbits (r = 0.85, P < 0.001, n = 18), with no intrarabbit correlations (P = 0.524). The ONH MBR and ONH CBF were also correlated in the model of chronic ischemia-induced ONH atrophy (r = 0.78, P = 0.013, n = 9). Pooled ONH MBR and ONH CBF measurements in both the intravenous and intravitreal groups were also highly correlated (r = 0.87, P < 0.001, n = 45), with no significant intergroup differences in the relationship between ONH MBR and ONH CBF (P = 0.138). CONCLUSIONS: Regardless of the presence of fundus pigmentation or ONH atrophy, ONH MBR and ONH CBF were highly correlated, suggesting that MBR in the ONH tissue is usable for interindividual and intergroup comparisons.

The effect of intravitreal bevacizumab on ocular blood flow in diabetic retinopathy and branch retinal vein occlusion as measured by laser speckle flowgraphy.

BACKGROUND: This study evaluated the effect of intravitreal injection of bevacizumab (IVB) on macular edema associated with diabetic retinopathy (DME) or branch retinal vein occlusion (BRVOME) using laser speckle flowgraphy. METHODS: A comparative interventional study of 25 eyes from 22 patients with macular edema (DME group: 12 eyes; BRVOME group: 13 eyes) who underwent IVB. Mean blur rate (MBR) was measured in the retinal artery, retinal vein, optic nerve head (ONH), and choroid before and after IVB. RESULTS: In the BRVOME group, there was no significant change in MBR in the retinal artery, retinal vein or ONH, but choroidal MBR decreased significantly (P=0.04). In the DME group, the MBR in the retinal artery, retinal vein, ONH, and choroid decreased significantly (P=0.02, P=0.04, P<0.001, and P=0.04, respectively). In the DME group, pre-IVB MBR in the ONH was significantly correlated with post-IVB foveal thickness (R= -0.71, P=0.002). There was no such correlation in the BRVOME group in the ONH. CONCLUSION: IVB had a suppressive effect on circulation in eyes with DME but not in those with BRVOME. This suggests that this noninvasive and objective biomarker may be a useful part of pre-IVB evaluations and decision-making in DME.

Relative flow volume, a novel blood flow index in the human retina derived from laser speckle flowgraphy.

PURPOSE: We investigated the accuracy and reproducibility of relative flow volume (RFV), a novel index of blood flow in the human retina derived from laser speckle flowgraphy (LSFG). METHODS: Pre- and postbranch retinal RFV measurements were compared in 34 retinal venous bifurcations in 34 healthy volunteers (mean age, 49.0 ± 14.8 years) to determine the accuracy of RFV. Next, the coefficient of variation (COV) of RFV was determined for 30 temporal retinal arteries in a second group of 18 healthy volunteers (mean age, 30.3 ± 7.7 years). Finally, laser Doppler velocimetry (LDV) data were obtained from the same study population and compared to RFV data from the retinal vessels. RESULTS: A comparison of RFV measurements in a trunk vessel of the retina and the sum of its two daughter vessels revealed a strong correlation (r = 0.98, P < 0.001). Reproducibility analysis showed that the COV for RFV was 5.9% ± 3.6%. Linear regression analysis revealed that RFV was correlated significantly with LDV measurements of mean retinal blood velocity (vmean) and retinal blood flow (FLDV, vmean, r = 0.61, P < 0.001; FLDV, r = 0.51, P = 0.004, respectively), but not significantly correlated with ocular perfusion pressure (r = -0.04, P = 0.76). CONCLUSIONS: These results suggest that RFV values obtained with LSFG can be considered an accurate and reliable index of relative blood flow in the human retina. Thus, RFV, a novel LSFG-derived variable, has potential for assessing retinal blood flow alterations in ocular disease.

Progression of visual field defects in eyes with different optic disc appearances in patients with normal tension glaucoma.

PURPOSE: To investigate the relationship between the optic disc appearance and the progression of visual field defects in eyes with normal tension glaucoma (NTG). METHODS: Two hundred nine patients with NTG, who were being treated with topical antiglaucoma drugs and had been followed for at least 3 years, were studied. The baseline optic disc appearance was classified into 4 types: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized cup enlargement (GE). The progression of the NTG was assessed by the slope of the mean deviations (MDs) obtained from the visual field results collected during the follow-up examinations. The baseline and mean intraocular pressures (IOPs) were also followed. RESULTS: Twenty-seven patients were placed in the FI group, 63 into the MY group, 24 into the SS group, and 43 into the GE group. Fifty-two patients (24.9%) could not be classified. There were no significant differences in the percentage reduction of the IOP among the 4 groups. The MD slope in the GE group (-0.51±0.74 dB/y) was significantly steeper than that in the other groups. Regression analyses showed that the factors most associated with the MD slope were the age in the FI (r, -0.495) and the GE (r=0.496) groups, and the relative reduction of the IOP (r=0.413) in the SS group. None of the factors in the MY group was significantly associated with the MD slope. CONCLUSIONS: The rate of progression of the field defects, the MD slope, in patients with NTG is possibly dependent on the baseline optic disc appearance. Thus, the optic disc appearance may be useful for the management of patients with NTG.

Difficulty in inserting 25- and 23-gauge trocar cannula during vitrectomy.

PURPOSE: To determine the incidence of difficulty in inserting a 25- and 23-gauge trocar cannula (DITC) during 25- or 23-gauge micro-incision vitrectomy surgery (MIVS). METHODS: Retrospective, consecutive, interventional case series performed by a single surgeon at a single centre. We defined a DITC as the condition where at least 1 trocar cannula could not be inserted into the vitreous at the beginning of MIVS. The incidence of DITC was calculated from 1,525 eyes, and the pre-operative demographics of the DITC cases were compared to those of the non-DITC cases. RESULTS: The incidence of DITC for all cases was 0.6% (9 of 1,525 eyes). Overall, there were 242 eyes with a retinal detachment (RD), and 8 of the 9 eyes with DITC had an RD with an incidence of 3.3% (8 of 242 RD eyes). Seven of these 8 eyes had a total RD, 4 also had a choroidal detachment, 4 eyes were also myopic (>-8.0 dpt, high myopia), and 6 of the 8 eyes were hypotonic (<8 mm Hg). The DITC cases had larger RDs (p<0.0001), a higher incidence of choroidal detachment (p<0.0001), higher myopia (p=0.0204) and hypotony (p=0.0003) than the non-DITC eyes with an RD. CONCLUSIONS: A large RD, a choroidal detachment, high myopia and hypotony are significant risk factors for DITC. We recommend that MIVS should be performed cautiously for eyes with these risk factors.