Narrowing Ratio of Retinal Veins at Arteriovenous Crossing in Patients With Branch Retinal Vein Occlusion Versus That in Healthy Individuals.

Purpose: This cross-sectional study aimed to clarify the differences in the retinal venous narrowing ratio (VNR) at retinal arteriovenous crossing by optical coherence tomography (OCT) among the eyes with branch retinal vein occlusion (BRVO), fellow eyes of patients with BRVO, and eyes of individuals without BRVO and to determine factors that influence the VNR. Methods: We studied 31 eyes of young participants, 54 eyes of an older control group, 56 fellow eyes of patients with BRVO, and 48 eyes with BRVO. Cross-sectional OCT images were used to determine the VNR at two arteriovenous crossings per eye. Results: Overall, 378 arteriovenous crossings were analyzed. The VNR of arterial overcrossings of fellow eyes (27.7% ± 11.1%) and BRVO eyes (27.3% ± 9.76%) were significantly higher than those in the young (16.0% ± 7.9%, all P < 0.001) and control (22.0% ± 8.81%, P < 0.001, P = 0.003, respectively) groups. The VNR of arterial overcrossings was significantly larger than that of venous overcrossings (24.0% ± 10.5% vs. 20.6% ± 13.0%, P = 0.021). A linear mixed-effects model showed that the VNR was significantly higher in arterial overcrossings, crossings with larger arterial internal diameters, smaller venous internal diameters, and participants with older age and a BRVO history. Conclusions: The VNR in arterial overcrossings was higher in BRVO eyes and even in the fellow eyes. Thus, a higher VNR in arterial overcrossings may contribute to BRVO development, and crossings with factors contributing to higher VNR might be associated with a risk of BRVO.

Changes in pulse waveforms in response to intraocular pressure elevation determined by laser speckle flowgraphy in healthy subjects.

BACKGROUND: The influences of intraocular pressure (IOP) elevations on the pulse waveform in the optic nerve head (ONH) were evaluated using laser speckle flowgraphy (LSFG) in normal subjects. METHODS: This prospective cross-sectional study was conducted at the Nagoya University Hospital. An ophthalmodynamometer was pressed on the sclera to increase the IOP by 20 mmHg or 30 mmHg for 1 min (experiment 1, 16 subjects) and by 30 mmHg for 10 min (experiment 2, 10 subjects). The mean blur rate (MBR) and the eight pulse waveform parameters determined using LSFG were measured before, immediately after and during an IOP elevation, and after the IOP returned to the baseline pressure. RESULTS: A significant elevation in the IOP and a significant reduction in the ocular perfusion pressure (OPP) were found after applying the ophthalmodynamometer (both, P < 0.001). The blowout score (BOS) reduced significantly (P < 0.001), and the flow acceleration index (FAI; P < 0.01) and resistivity index (RI; P < 0.001) increased significantly immediately after increasing the IOP by 20 or 30 mmHg (experiment 1). The BOS reduced significantly (P < 0.001), and the FAI (P < 0.01) and RI (P < 0.001) increased significantly after the IOP elevation by 30 mmHg in both experiment 2 and 1. However, the BOS and RI recovered significantly at time 10 compared to that in time 0 (immediately after IOP elevation) during the 10-min IOP elevation (P < 0.001 and P = 0.008, respectively). CONCLUSIONS: In conclusion, the BOS, FAI, and RI of the pulse waveforms changed significantly with an acute elevation in the IOP. The change should be related to the larger difference between the maximum and minimum MBRs during the IOP elevation.

Association between displacement and thickness of macula after vitrectomy in eyes with epiretinal membrane.

The purpose of this cross-sectional retrospective study was to determine the relationship between the retinal displacements and the retinal thickness in eyes with epiretinal membrane (ERM) after vitrectomy with internal limiting membrane (ILM) peeling. To accomplish this, we measured the retinal thickness using optical coherence tomography (OCT) and the retinal displacement using OCT angiography to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the surgery from 20 eyes of 20 patients. The distance between the retinal vessel bifurcations and the fovea was significantly displaced centrifugally and asymmetrically in the 4 quadrants postoperatively (P < 0.001). The foveal avascular zone (FAZ) was significantly enlarged, and the central foveal thickness (CFT) and the inner nuclear layer (INL) thickness were significantly thinner postoperatively. The displacements were significantly correlated with the changes in the FAZ area (r = 0.717, P < 0.001), the CFT (r = - 0.702, P < 0.001), and the INL thickness (r = - 0.702, P < 0.001). In conclusion, the distance between the retinal bifurcations and the fovea was asymmetrically expanded after the surgery and was significantly correlated with the morphological changes. These results indicate that a horizontal macular contraction is correlated with vertical retinal contraction in the eyes with an ERM.

Choroidal and retinal displacements after vitrectomy with internal limiting membrane peeling in eyes with idiopathic macular hole.

It has been reported that the macular region of the retina is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with macular hole (MH), but the displacements of the deeper layers of the eye, e.g. RPE and choroid are unclear following the surgery. We used optical coherence tomography (OCT) and OCT angiography (OCTA) to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the vitrectomy with internal limiting membrane (ILM) peeling from 22 eyes of 22 patients with a MH. The OCT and OCTA images showed displacements of the fovea and choroidal intermediate vessels postoperatively. The degree of displacement of the choroid was significantly less than that of the retina (P < 0.001). The displacements of the choroidal bifurcations were significantly correlated to their preoperative distance from the optic disc (r = -0.467, P < 0.001) and they were significantly correlated with the retinal displacements (r = 0.535, P < 0.001). The retina was displaced inferiorly and centripetally, but these localized displacements were not observed in the choroid. In conclusion, clinicians need to be aware of these displacements when evaluating the subfoveal choroid following the surgery because the displacement is different between the retina and the choroid.

Evaluation of optic nerve head blood flow in response to increase of intraocular pressure.

The time course of the changes in the optic nerve head (ONH) blood flow in response to changes in the ocular perfusion pressure (OPP) induced by an artificial elevation of the intraocular pressure (IOP) has not been determined. We measured the blood flow, represented by the mean blur rate (MBR), on the ONH determined by laser speckle flowgraphy. The MBR was determined before, during, and after the IOP was elevated by 20 or 30 mmHg by pressure applied on the eye by an ophthalmodynamometer in a total of 27 healthy eyes. For an IOP elevation of 20 mmHg, the percentage reduction in the MBR-vessel was -24.7%, and in the MBR-tissue was -16.0% (P < 0.001). For an IOP elevation of 30 mmHg, the percentage reduction of the MBR-vessel was -35.3% and the MBR-tissue was -24.7% (P < 0.001). During the 30 mmHg IOP elevation for 10 minutes, both the MBR-vessel and MBR-tissue began returning to the baseline level from 1 minute after the beginning of the IOP elevation (P < 0.01, P < 0.05, respectively) and continued returning during the 10 minutes IOP elevation (P < 0.001, P < 0.01, respectively). We conclude that the ONH can autoregulate its blood flow in response to experimental changes in OPP induced by IOP elevations.

Novel Classification of Early-stage Systemic Hypertensive Changes in Human Retina Based on OCTA Measurement of Choriocapillaris.

The traditional classification of hypertensive retinopathy was based on the Keith-Wagener-Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

Macular Displacement After Vitrectomy in Eyes With Idiopathic Macular Hole Determined by Optical Coherence Tomography Angiography.

PURPOSE: To determine whether the macula is displaced after vitrectomy with internal limiting membrane (ILM) peeling in eyes with an idiopathic macular hole. DESIGN: A retrospective, observational case series. METHODS: Optical coherence tomography angiography was used to obtain 3 mm × 3 mm en face images before and 2, 4, and 8 weeks after the vitrectomy with ILM peeling for 20 eyes of 20 patients with an idiopathic macular hole. The displacements of easily identifiable retinal vessel bifurcations were measured relative to the fovea and the optic disc. RESULTS: The distance between the optic disc and vessel bifurcations was significantly shorter in all 4 quadrants throughout the postoperative period (P < .001). This distance was significantly greater in the temporal quadrant (P < .001). The distance of the bifurcations was significantly correlated with the preoperative distance from the optic disc (r = -0.579, P < .001). A significantly greater downward displacement was observed in the superior quadrant (P < .001). The change in the angle of bifurcations was significantly correlated with the preoperative angle to the optic disc (r = -0.632, P < .001). The change in the distance in the inner region was significantly greater than that in the outer region in all quadrants. A significant reduction was observed in the mean foveal avascular zone area during the follow-up period. CONCLUSIONS: The retina in the macular region was displaced nasally, probably owing to movement of the retina toward the optic disc because of a contraction after the ILM removal. There is also a possibility of a rotation downward by buoyancy from gas tamponade, and centripetal contraction during the process of hole closure.

Changes in Choroidal Blood Flow and Morphology in Response to Increase in Intraocular Pressure.

Purpose: The purpose of this study was to determine the effects of an elevation in IOP on the choroidal blood flow and morphology. Methods: We studied 27 healthy subjects. The mean blur rate (MBR) determined by laser speckle flowgraphy was used to measure the choroidal blood flow. The subfoveal choroidal thickness (SFCT) was measured in the optical coherence tomographic images of the macular region. The luminal and stromal areas of the choroid were determined by the binarization method before, during, and after the IOP was elevated 20 and 30 mm Hg with pressure using an ophthalmodynamometer. Results: The ocular perfusion pressure (OPP) was significantly reduced by the elevation of the IOP by 20 (-52.0%, P < 0.001) and 30 mm Hg (-77.9%, P < 0.001). The percentage reduction in the macular choroidal MBR was -32.5% at an IOP elevation of 20 mm Hg (P < 0.001) and -46.6% at an IOP elevation of 30 mm Hg (P < 0.001). The SFCT was reduced by -3.8% (P = 0.014) and -7.7%, (P < 0.001) during an elevation of IOP of 20 and 30 mm Hg, respectively. The luminal area of the choroid was reduced during an elevation of the IOP of 20 (P = 0.001) and 30 mm Hg (P < 0.001). However, the stromal area did not change significantly. There was no significant correlation between the reduction ratio of OPP and other factors during the elevation of 20 mm Hg, but the correlation between the reduction ratio of OPP and the choroidal MBR during the elevation of 30 mm Hg was significant. The choroidal MBR had recovered significantly at 7 (P = 0.037) and 10 minutes (P = 0.022) compared with that immediately after the IOP elevation of 30 mm Hg. Conclusions: The choroid can autoregulate its blood flow in response to experimental changes in the OPP induced by IOP elevations.

IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes.

Newly discovered IL-9-producing helper T cells (Th9) reportedly exert both aggravating and suppressive roles on experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, it is still unclear whether Th9 is a distinct Th cell subset and how IL-9 functions in the CNS. In this study, we show that IL-9 is produced by naive CD4(+) T cells that were stimulated with anti-CD3 and anti-CD28 Abs under the conditions of Th2-, inducible regulatory T cell-, Th17-, and Th9-polarizing conditions and that IL-9 production is significantly suppressed in the absence of IL-4, suggesting that IL-4 is critical for the induction of IL-9 by each producing cell. The IL-9 receptor complex, IL-9R and IL-2Rγ, is constitutively expressed on astrocytes. IL-9 induces astrocytes to produce CCL-20 but not other chemokines, including CCL-2, CCL-3, and CXCL-2 by astrocytes. The conditioned medium of IL-9-stimulated astrocytes induces Th17 cell migration in vitro, which is cancelled by adding anti-CCL-20 neutralizing Abs. Treating with anti-IL-9 neutralizing Abs attenuates experimental autoimmune encephalomyelitis, decreases the number of infiltrating Th17 cells, and reduces CCL-20 expression in astrocytes. These results suggest that IL-9 is produced by several Th cell subsets in the presence of IL-4 and induces CCL-20 production by astrocytes to induce the migration of Th17 cells into the CNS.