Multimodal Imaging of a Severe Case of Neonatal Acute Retinal Necrosis and Lens Vacuoles Associated with Herpes Simplex Virus Infection.

PURPOSE: To report a case of a neonate with acute retinal necrosis, lens vacuoles, and encephalitis associated with herpes simplex virus (HSV) infection. DESIGN: Case report. METHODS: Retrospective chart review. RESULTS: A male neonate was brought for screening for retinopathy of prematurity at the corrected age of 32 weeks. Slit-lamp examination showed lens vacuoles in both eyes. Fundus examination revealed extensive retinal detachments with prominent retinal whitening, subretinal exudates, and retinal hemorrhage. Computed tomography of the brain showed encephalomalacia. Polymerase chain reaction of cerebrospinal fluid and anterior chamber fluid was both positive for HSV-1. Despite systemic anti-viral therapy, a rhegmatogenous retinal detachment and subsequent proliferative vitreoretinopathy developed in the patient's right eye. The retinal detachment in the left eye resolved, but significant chorioretinal degeneration occurred. With time lens vacuoles decreased in number. CONCLUSIONS: Clinicians should remember this rare, but devastating condition without specific prodromal symptoms.

Topical Ripasudil Suppresses Retinal Ganglion Cell Death in a Mouse Model of Normal Tension Glaucoma.

Purpose: To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma. Methods: Topical administration (5 µL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, the measurement of intraocular pressure (IOP), and histopathology analyses were performed at 5, 8, and 12 weeks old. Retrograde labeling of retinal ganglion cells (RGCs), immunoblot, and immunohistochemical analyses of phosphorylated p38 mitogen-activated protein kinase (MAPK) in the retina were performed at 8 weeks old. Results: Topical ripasudil ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old. Ripasudil reduced IOP and strongly suppressed the phosphorylation of p38 MAPK that stimulates RGC death in EAAC1 KO mice. Conclusions: These results suggest that, in addition to IOP reduction, ripasudil prevents glaucomatous retinal degeneration by neuroprotection, which is achieved by suppressing cell-death signaling pathways.

Edaravone suppresses retinal ganglion cell death in a mouse model of normal tension glaucoma.

Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP) and exhibits glaucomatous pathology including glutamate neurotoxicity and oxidative stress. In the present study, we found that edaravone, a free radical scavenger that is used for treatment of acute brain infarction and amyotrophic lateral sclerosis (ALS), reduces oxidative stress and prevents RGC death and thinning of the inner retinal layer in EAAC1-deficient (KO) mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment in EAAC1 KO mice was ameliorated with edaravone treatment, clearly establishing that edaravone beneficially affects both histological and functional aspects of the glaucomatous retina. Our findings raise intriguing possibilities for the management of glaucoma by utilizing a widely prescribed drug for the treatment of acute brain infarction and ALS, edaravone, in combination with conventional treatments to lower IOP.

Diurnal variations in luminal and stromal areas of choroid in normal eyes.

AIMS: To determine the diurnal variations of the luminal and stromal areas of the choroid in normal eyes. METHODS: This was a prospective observational study of 38 eyes of 38 normal subjects. The blood pressure, heart rate, intraocular pressure and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded every 3 hours between 6:00 and 21:00 hours. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross-sectional choroidal area, the luminal areas, stromal areas and the ratio of luminal area to total choroidal area (L/C ratio) were determined. RESULTS: There were significant diurnal variations in the CCT, total choroidal area, luminal area and L/C ratio with the maximum values at 6:00 hours and the minimum values at 15:00 hours (p<0.001 for the CCT, p=0.011 for the total choroidal area, p<0.001 for the luminal area and p=0.014 for the L/C ratio). There was no significant variation in the stromal area (p=0.216). The range of fluctuation in the CCT was significantly correlated with that in the luminal area and the total choroidal area (p<0.001). However, there was no significant correlation between the fluctuation range in the CCT and that in the stromal area (p=0.095). There was no statistical relationship between the systemic parameters and the choroidal parameters. CONCLUSIONS: The changes in the luminal area are most likely responsible for the diurnal change in the CCT and subfoveal choroidal area. TRIAL REGISTRATION NUMBER: UMIN000019060, Pre-results.

Changes of choroidal structure after intravitreal aflibercept therapy for polypoidal choroidal vasculopathy.

AIMS: To quantify the changes of the choroidal structure in the enhanced depth imaging optical coherence tomographic (EDI-OCT) images after intravitreal aflibercept (IVA) injections for polypoidal choroidal vasculopathy (PCV). METHODS: Retrospective, observational case series. Forty eyes of 40 treatment-naive patients who underwent IVA for PCV were examined by EDI-OCT before, and 3 months and 12 months after IVA. The EDI-OCT images were binarised by ImageJ software. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1500 µm width were quantified. RESULTS: The stromal but not the luminal area of the inner choroid was significantly decreased at 3 months and 12 months after the IVA (stromal area, both p<0.001; luminal area, both p>0.050). On the other hand, the luminal but not the stromal area of the outer choroid was significantly decreased at 3 months and 12 months (luminal area, both p<0.001; stromal area, both p>0.050). The Pachychoroid Index, ratio of luminal/stromal area (L/S ratio) of the outer choroid divided by the L/S ratio of the inner choroid, was significantly decreased at 3 months and 12 months (both p<0.050). The Pachychoroid Index was increased and returned almost to the baseline level after recurrences and decreased again after successful re-treatment. The baseline Pachychoroid Index was significantly correlated with the presence of a dry macula, thinner fovea and better visual acuity at 12 months (all p<0.050). CONCLUSION: The binarisation of the EDI-OCT images can be used to quantify the activity of PCV and to predict the prognosis after IVA.

Effects of Exercise on the Structure and Circulation of Choroid in Normal Eyes.

AIMS: To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes. METHODS: This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images. RESULTS: The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise. CONCLUSIONS: Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area.

Changes in Choroidal Structures in Eyes with Chronic Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy.

PURPOSE: To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC). METHODS: This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT. RESULTS: The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). CONCLUSIONS: The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels.

Optical coherence tomography parameters predictive of visual outcome after anti-VEGF therapy for retinal vein occlusion.

PURPOSE: To determine the optical coherence tomography (OCT) parameters that are predictive of visual outcome after anti-VEGF therapy for a retinal vein occlusion (RVO). METHODS: Fifty-seven eyes with macular edema (ME) secondary to a central or branch RVO treated with bevacizumab or ranibizumab were studied. Spectral-domain OCT and microperimetry were performed before, 1, 3, and 6 months after the treatment and at the final visit. Central retinal thickness (CRT), macular volume (MV), integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and foveal bulge (FB), and photoreceptor outer segment (PROS) length were determined. RESULTS: The mean follow-up period was 17.8±11.5 months. In 46 of the 57 eyes, a resolution of the ME was achieved. The pretreatment CRT and MV, presence of intact ELM, EZ, and FB, and PROS length at the time of ME resolution were significantly correlated with the best-corrected visual acuity and retinal sensitivity at the final visit (P<0.050). Multiple regression analyses showed that the pretreatment MV had the highest correlation with the posttreatment best-corrected visual acuity and retinal sensitivity (P<0.050). CONCLUSION: The CRT, MV, ELM, EZ, FB, and PROS length are predictive factors for the visual outcome after anti-VEGF therapy for RVO.

Correlation between optic nerve head circulation and visual function before and after anti-VEGF therapy for central retinal vein occlusion: prospective, interventional case series.

BACKGROUND: To determine the correlation between the optic nerve head (ONH) circulation determined by laser speckle flowgraphy and the best-corrected visual acuity or retinal sensitivity before and after intravitreal bevacizumab or ranibizumab for central retinal vein occlusion. METHODS: Thirty-one eyes of 31 patients were treated with intravitreal bevacizumab or ranibizumab for macular edema due to a central retinal vein occlusion. The blood flow in the large vessels on the ONH, the best-corrected visual acuity, and retinal sensitivity were measured at the baseline, and at 1, 3, and 6 months after treatment. The arteriovenous passage time on fluorescein angiography was determined. The venous tortuosity index was calculated on color fundus photograph by dividing the length of the tortuous retinal vein by the chord length of the same segment. The blood flow was represented by the mean blur rate (MBR) determined by laser speckle flowgraphy. To exclude the influence of systemic circulation and blood flow in the ONH tissue, the corrected MBR was calculated as MBR of ONH vessel area - MBR of ONH tissue area in the affected eye divided by the vascular MBR - tissue MBR in the unaffected eye. Pearson's correlation tests were used to determine the significance of correlations between the MBR and the best-corrected visual acuity, retinal sensitivity, arteriovenous passage time, or venous tortuosity index. RESULTS: At the baseline, the corrected MBR was significantly correlated with the arteriovenous passage time and venous tortuosity index (r = -0.807, P < 0.001; r = -0.716, P < 0.001; respectively). The corrected MBR was significantly correlated with the best-corrected visual acuity and retinal sensitivity at the baseline, and at 1, 3, and 6 months (all P < 0.050). The corrected MBR at the baseline was significantly correlated with the best-corrected visual acuity at 6 months (r = -0.651, P < 0.001) and retinal sensitivity at 6 months (r = 0.485, P = 0.005). CONCLUSIONS: The pre-treatment blood flow velocity of ONH can be used as a predictive factor for the best-corrected visual acuity and retinal sensitivity after anti-VEGF therapy for central retinal vein occlusion. TRIAL REGISTRATION NUMBER: UMIN000009072. Date of registration: 10/15/2012.

Changes of choroidal structure after corticosteroid treatment in eyes with Vogt-Koyanagi-Harada disease.

AIMS: To report the changes of the choroidal structure in the enhanced depth imaging optical coherence tomographic (EDI-OCT) images after high-dose corticosteroid treatment for acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective, observational case series. Thirty-four eyes of 17 patients with acute VKH disease were examined by EDI-OCT before, and 1, 4 and 52 weeks after the treatment. The EDI-OCT images were binarised by ImageJ, a publicly accessible software. The luminal, stromal and total choroidal areas and ratio of luminal/stromal area (L/S ratio) were measured in the subfoveal choroid of 1500 µm width. The area of the peripapillary atrophy (PPA) was measured in the fundus photographs at 1 and 52 weeks. For statistical analyses, a generalised estimating equation method was used to eliminate the effect of within-subject intereye correlations. RESULTS: Before treatment, the EDI-OCT images could not be binarised because of poor image quality in most of the cases. After treatment, the luminal, stromal and total choroidal areas were significantly decreased during the follow-up period (all p<0.05). The L/S ratio significantly fluctuated over time (p=0.0201), and was significantly lower at 4 weeks than at 1 week (p=0.0158). The L/S ratio at 1 week was significantly correlated with increase in the PPA area, subsequent chronic recurrences and total dose of corticosteroid (p<0.0001, p=0.0006, p=0.0037, respectively). CONCLUSIONS: The L/S ratio measured by binarisation of EDI-OCT images was predictive factor for the progression of PPA, subsequent chronic recurrences and total dose of corticosteroid, and may serve as a marker for degree of choroidal inflammation in the VKH disease.

Changes of choroidal structure after treatment for primary intraocular lymphoma: retrospective, observational case series.

BACKGROUND: We report changes of choroidal structure determined by binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images after treatment for primary intraocular lymphoma (PIOL). METHODS: Five eyes of four patients with PIOL were examined by EDI-OCT before and 6 months after intravitreal methotrexate injections. In addition, 15 eyes of 15 normal individuals controlled by age and refractive error were examined by EDI-OCT. Binarization of the EDI-OCT images was performed using publicly accessible software (ImageJ). The examined area of the subfoveal choroid was 1,500 µm wide, and the dark areas that represented the luminal areas were traced by the Niblack method. Wilcoxon signed rank test was used to determine the significance of changes in the subfoveal choroidal thickness, interstitial area, and luminal area. Mann-Whitney U test was used to compare the parameters in the eyes with pretreatment PIOL and normal control eyes. RESULTS: The subfoveal choroidal thickness was significantly decreased after treatment (P = 0.0431). In the binarized images, the interstitial area was significantly decreased after treatment (P = 0.0431), while the luminal area was not significantly changed (P = 0.8927). After delayed onset of PIOL, increased interstitial area, thickened choroid and unchanged luminal area were observed in one eye. The interstitial area and choroidal thickness were significantly increased in the eyes with pretreatment PIOL compared with the normal control eyes (P = 0.0207, P = 0.0495, respectively), while the luminal area was not significantly different (P = 0.2752). CONCLUSIONS: After treatment for PIOL, the EDI-OCT images showed a thinner choroid, and binarization of the EDI-OCT images showed significantly decreased interstitial areas compared with the luminal areas. The binarized EDI-OCT images can provide useful information on choroidal structure in eyes with PIOL, and combining these images with intraocular interleukin levels or fundus autofluorescence images should provide valuable information for determining the PIOL activity.

Prepapillary vascular loops complicated by suspected macroaneurysm rupture.

We present a case of prepapillary vascular loops complicated by a suspected macroaneurysm rupture which was treated with intravitreal bevacizumab (IVB). A 62-year-old woman presented with decreased vision and myodesopsia in her left eye. Her best-corrected visual acuity (BCVA) was 0.6 in the left eye. Fundus examination disclosed an elevated, round, and reddish lesion, retinal hemorrhage at the superior aspect of the optic disc, retinal opacification along the superior branch retinal artery, and a small vitreous hemorrhage. Optical coherence tomography showed a serous retinal detachment, and indocyanine green angiography demonstrated prepapillary vascular loops and a hypofluorescent area with hyperfluorescent margins. These findings suggested the presence of a macroaneurysm. No filling of the dye in the aneurysm-like dilatation suggested a blockage of the lumen with a thrombus which might be associated with a branch retinal artery occlusion (BRAO). A diagnosis of prepapillary vascular loops complicated by a suspected macroaneurysm rupture and BRAO was made. Because of a persistent serous retinal detachment, IVB was performed. One month later, the BCVA improved to 1.0. Fundus examination disclosed an organized yellowish-white macroaneurysm and resolution of the serous retinal detachment. We recommend careful monitoring of patients with prepapillary vascular loops because of complications such as macroaneurysm rupture and BRAO.

Left ventricular outflow tract pseudoaneurysm after aortic valve replacement: case report.

A 68-year-old woman was admitted for angina pectoris and general fatigue without symptoms or signs of infective endocarditis. The patient had undergone re-replacement of an aortic prosthetic valve three months previously. Transesophageal echocardiography revealed an echo-free cavity in the mitral-aortic intervalvular fibrosa region just below the aortic annulus, communication of the echo-free cavity with the left ventricular outflow tract, and turbulent flow into the cavity. Left ventriculography revealed a cavity that arose just below the aortic prosthetic valve, and which expanded in systole and collapsed in diastole. Coronary angiography showed significant stenosis of the proximal right coronary artery, but neither stenoses nor compression were found in the left coronary artery. Patch closure of the pseudoaneurysm and aortic root replacement using a Freestyle valve with reconstruction of the coronary arteries were successfully performed. Surgical trauma to the intervalvular fibrosa during removal of the original prosthetic valve may have caused pseudoaneurysm formation in this patient.

Anomalous origin of the right coronary artery: report of a case.

A 63-year-old man was admitted with a complaint of dyspnea. Echocardiography showed severe aortic regurgitation (AR), and moderate mitral regurgitation (MR). Coronary angiography revealed that the right coronary artery (RCA) arose from the ascending aorta with a high takeoff and a significant stenosis at the distal segment of the RCA. Scintigraphy with Thallium showed a transient perfusion defect on the inferior wall. The diagnosis of AR and MR associated with anomalous origin of the RCA and myocardial ischemia was made. After successful catheter intervention for stenosis of the RCA, an operation was performed on the aortic and mitral valve. At surgery, the orifice of the RCA was located above the commissure of the right and left coronary cusps and the shape was obliquely elliptical. The RCA originated at an acute angle from the ascending aorta, and its proximal segment was incorporated in the wall of the aorta. After aortic valve replacement and mitral valve repair, a neo-ostium without unroofing of the intramural segment of the RCA was created at the proximal RCA, and the intima of the RCA was fixed to the intima of the aorta. The patient recovered uneventfully and is doing well without findings of myocardial ischemia at present 40 months after operation.

Left atrial thrombosis following mitral valve repair and maze procedure: case report.

The case is described of a 71-year-old woman with left atrial thrombosis after successful mitral valve repair and a Kosakai-maze procedure. At three months after surgery, electrocardiography showed a normal sinus rhythm, but echocardiography revealed a mural thrombus on the posterior wall of the left atrium. During those three months, the anticoagulation level (thrombotest index range: 29-41%) was lower than target level. Anticoagulant therapy with heparin plus warfarin failed to reduce the thrombus size. Anticardiolipin antibodies were positive, and lupus anticoagulants negative. A Doppler study of the mitral valve indicated peak velocity 1.48 m/s, mean pressure gradient 4.5 mmHg, and valve area 2.1 cm2. During reoperation, an old spherical thrombus (weight 38 g) which was firmly adhered to the posterior wall and included an incision line of the Kosakai-maze procedure, was identified and totally removed. After reoperation, the patient received warfarin and an antiplatelet agent to maintain the INR at 2.5-3.5. Echocardiography performed at 11 months postoperatively revealed no thrombus formation on the left atrium.