Cytomegalovirus retinitis in children and adolescents with acute leukemia following allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus retinitis (CMVR) may occur after allogeneic hematopoietic stem cell transplantation (HSCT). However, little is known about its incidence, strategies for ophthalmic surveillance, and timely implementation of adequate antiviral treatment in pediatric allogeneic HSCT recipients. We provide a retrospective analysis of the epidemiology and clinical features of CMVR in pediatric allogeneic HSCT patients transplanted at our center over a 16-year period. Two patients of this cohort with leukemia are presented. Our analysis is supplemented by a systematic review on pediatric patients with leukemia and CMVR in the setting of allogeneic HSCT. The overall incidence of CMVR in our cohort was 1% (4/338) and 14.2% (3/21) in leukemic patients. In published cases, CMVR occurred at a median of 143 days after transplantation, and, in the majority of patients, was preceded by CMV detection in blood by a median of 93 days. Continued immune suppression following engraftment likely triggers CMVR. Preemptive treatment with ganciclovir as standard is usually successful. Foscarnet is used in case of resistance to ganciclovir or drug-induced granulocytopenia. Overall, CMVR after HSCT in pediatric leukemic patients is rare, but a potentially higher vulnerability of this population for involvement of the eye warrants a standardized ophthalmological examination plan.

[Expression of Motion Artifacts in OCT-Angiography Imaging in Healthy Subjects Using Two Different Devices]. / Vergleich der Bildqualität zweier unterschiedlicher OCT-Angiografie-Systeme mit Fokus auf Bewegungsartefakten bei gesunden Probanden.

BACKGROUND: To compare the expression of motion artifacts in optical coherence tomography angiography (OCT-A) in healthy subjects using two different devices. METHODS: In this study, 25 eyes of 25 healthy volunteers with no history of any ocular disease or ocular surgery were included. OCT-A imaging was performed using the RTVue XR Avanti (Optovue Inc., Fremont, California, USA) and the Spectralis OCT-A (Heidelberg Engineering, Heidelberg, Deutschland). The macula was imaged twice in each proband with active eye tracking (ET) using a 3 × 3 mm2 or a 10 × 10° scan, respectively. The expression of motion artifact was analyzed by two independent readers in the superficial OCT-angiogram using the Motion Artifact Score (MAS). RESULTS: The signal strength index (SSI) was 73.0 ± 7.8 (Optovue) and 39.6 ± 3.6 (Heidelberg), which is equivalent to 73.0% (Optovue SSImax = 100 = 100%) and 79.2% (SSImax = 50 = 100%) of the maximum quality score. Both devices showed a very good image quality (mean MAS Optovue: 1.32 ± 0.551, mean MAS Heidelberg: 1.7 ± 0.789, p = 0.006). Of all measurements, quilting/banding was found in 20% of Optovue patients (10/50) and 6% of Heidelberg patients (3/50). Stretching was found in 4% of Optovue patients (2/50) and in 6% of Heidelberg patients (3/50). Vessel doubling was only seen in one Optovue angiogram (2%) as well as a displacement (2%). Blink lines only existed in three Heidelberg angiograms (6%). CONCLUSION: Despite different software and hardware approaches, both devices were able to take high-quality images with a very low prevalence of motion artifacts. Nevertheless, these artifacts still also occur in healthy subjects with good fixation. With regards to MAS, there was a high agreement between the two readers. However, the analysis of artifacts remains complex and requires experience as well as a precise assessment in evaluating OCT-A images.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH RETINITIS PIGMENTOSA.

PURPOSE: To evaluate the correlation between the flow density measured by optical coherence tomography angiography and functional parameters in patients with retinitis pigmentosa. METHODS: Twenty eyes of 20 patients with retinitis pigmentosa and 21 eyes of 21 healthy subjects were prospectively included in this study. Optical coherence tomography angiography was performed using RTVue XR Avanti with AngioVue (Optovue Inc). The macula was imaged with a 6 × 6-mm scan, whereas for the optic nerve head a 4.5 × 4.5-mm scan was taken. Visual acuity, visual field parameters (mean deviation and visual field index), full-field electroretinography, and multifocal electroretinography were tested for correlation with flow density data. RESULTS: The flow density (whole en face) in the superficial/deep retinal OCT angiograms and in the optical coherence tomography angiography of the optic nerve head was significantly lower in the retinitis pigmentosa group when compared with the control group (P < 0.001). The flow density in the superficial retinal OCT angiogram (fovea) correlated significantly with the visual acuity (rSpearman = -0.77, P < 0.001) and the visual field parameters (visual field index: rSpearman = 0.56, P = 0.01; mean deviation: rSpearman = 0.54, P = 0.01). CONCLUSION: Patients with retinitis pigmentosa show a decreased macular and optic nerve head perfusion compared with healthy subjects. The flow density measured using optical coherence tomography angiography correlated with subjective and objective functional parameters.

Evaluation of Ocular Perfusion in Alzheimer's Disease Using Optical Coherence Tomography Angiography.

BACKGROUND: There is increasing evidence for the involvement of cerebrovascular factors in Alzheimer's disease (AD). OBJECTIVE: To evaluate retinal and optic nerve head perfusion in patients with AD using optical coherence tomography angiography (OCTA), and to analyze the correlations of quantitative OCTA metrics with AD pathology and vascular cerebral lesions in AD patients. METHODS: 36 eyes of 36 patients with AD (study group) and 38 eyes of 38 healthy subjects (control group) were prospectively included in this study. OCTA was performed using RTVue XR Avanti with AngioVue. In addition, patients underwent a detailed ophthalmological and neurological examination including Mini-Mental State Examination, cerebral magnetic resonance imaging, and amyloid-ß (Aß) and tau levels in the cerebrospinal fluid (CSF). RESULTS: The flow density in the superficial retinal OCT angiogram of the macula in the study group was significantly lower compared to the control group (p = 0.001). There was a significant correlation between the flow density in the superficial retinal OCT angiogram of the macula, as measured using OCTA, and the Fazekas scale (Spearman's correlation coefficient = -0.520; p = 0.003). There was no significant correlation between the Aß or tau levels in the CSF and the flow density data. CONCLUSION: Patients with AD showed a reduced flow density in the radial peripapillary capillaries layer and in the superficial retinal OCT angiogram when compared with healthy controls. The reduced retinal flow density measured using OCTA is not specifically associated with AD pathology but is associated with the vascular cerebral lesions in AD.

Changes in retinal flow density measured by optical coherence tomography angiography in patients with carotid artery stenosis after carotid endarterectomy.

The aim of the study presented here was to evaluate retinal and optic nerve head (ONH) perfusion in patients with severe asymptomatic carotid artery stenosis (CAS) compared with healthy controls and to analyze the impact of carotid endarterectomy using optical coherence tomography angiography (OCT-A). 25 eyes of 25 patients with CAS (study group) and 25 eyes of 25 healthy controls (control group) were prospectively included in this study. OCT-A was performed using RTVue XR Avanti (Optovue, Inc, Fremont, California, USA). The flow density data in the superficial and deep retinal OCT-angiogram of the macula and in the radial peripapillary capillary network (RPC) of the ONH were extracted and analyzed. The flow density in the superficial retinal OCT angiogram of the macula and in the ONH were significantly lower in the study group compared with the control group (macula: p = 0.003) (ONH: p = 0.013). The flow density in the ONH improved significantly after carotid endarterectomy (p = 0.004). A reduced flow density was observed in patients with CAS when compared with healthy controls. The flow density also improved after carotid endarterectomy. Quantitative changes in the microvascular density, as measured using OCT-A, could well be useful in the diagnosis of CAS and the evaluation of therapy success.

Repeatability, reproducibility and agreement of foveal avascular zone measurements using three different optical coherence tomography angiography devices.

PURPOSE: To evaluate the repeatability, the reproducibility and the agreement of foveal avascular zone (FAZ) measurements using three different optical coherence tomography angiography (OCT-A) devices. PROCEDURES: This prospective study included 24 eyes of 24 healthy volunteers. OCT-A imaging was performed using RTVue XR Avanti, Canon OCT-HS100 and Spectralis OCT-A. Repeated measurements were performed under the same conditions on two separate days, and the area of the FAZ was determined and analyzed using the above devices. RESULTS: All three devices showed a high ICC and there was no significant difference between the ICCs (pairwise comparison) of the three devices (Optovue-Canon (p = 0.66); Canon-Heidelberg (p = 0.21); Heidelberg-Optovue (p = 0.37). Agreement analysis of the three devices revealed a significant elevation of FAZ area values with the Heidelberg device and a slight underestimation of the FAZ area with the Canon device. Nevertheless, overall we found a high level of agreement between all of the three devices (ICC ≥ 0.958 (0.905-0.982)). CONCLUSIONS: Good reproducibility and repeatability were observed for all three devices. However, the agreement analysis revealed slight, but significant differences, which might limit alternating use of these devices for clinical research and follow-up examinations.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH RETINITIS PIGMENTOSA.

PURPOSE: To evaluate the correlation between the flow density measured by optical coherence tomography angiography and functional parameters in patients with retinitis pigmentosa. METHODS: Twenty eyes of 20 patients with retinitis pigmentosa and 21 eyes of 21 healthy subjects were prospectively included in this study. Optical coherence tomography angiography was performed using RTVue XR Avanti with AngioVue (Optovue Inc). The macula was imaged with a 6 × 6-mm scan, whereas for the optic nerve head a 4.5 × 4.5-mm scan was taken. Visual acuity, visual field parameters (mean deviation and visual field index), full-field electroretinography, and multifocal electroretinography were tested for correlation with flow density data. RESULTS: The flow density (whole en face) in the superficial/deep retinal OCT angiograms and in the optical coherence tomography angiography of the optic nerve head was significantly lower in the retinitis pigmentosa group when compared with the control group (P < 0.001). The flow density in the superficial retinal OCT angiogram (fovea) correlated significantly with the visual acuity (rSpearman = -0.77, P < 0.001) and the visual field parameters (visual field index: rSpearman = 0.56, P = 0.01; mean deviation: rSpearman = 0.54, P = 0.01). CONCLUSION: Patients with retinitis pigmentosa show a decreased macular and optic nerve head perfusion compared with healthy subjects. The flow density measured using optical coherence tomography angiography correlated with subjective and objective functional parameters.

Corneal Densitometry as a Novel Technique for Monitoring Amiodarone Therapy.

PURPOSE: The clinical efficacy and toxicity of amiodarone may be determined more effectively by tissue deposition than by levels of the agent in serum. Therefore, corneal densitometry might be useful for therapeutic monitoring. The aim of the study is to evaluate Scheimpflug corneal densitometry in patients with amiodarone keratopathy (AK). DESIGN: Comparative case series. PARTICIPANTS: Sixty-six patients receiving amiodarone therapy and 66 healthy controls were consecutively enrolled in this study. METHODS: Patients were examined using the Oculus Pentacam (Wetzlar, Germany). MAIN OUTCOME MEASURES: Densitometry data from different corneal layers and different annuli were extracted, analyzed, and compared with densitometry values of healthy controls. Duration of treatment, cumulative dose, Orlando stage (slit-lamp biomicroscopy), and serum concentrations of amiodarone and N-desethylamiodarone also were determined, and the correlation to different densitometry data was evaluated. RESULTS: The total corneal light backscatter at total corneal thickness and at total diameter was significantly higher in the amiodarone group compared with the control group (AK group: 28.3±5.2; control group: 24.4±4.2; P < 0.001). Upon dividing the corneal surface into different layers at total thickness, the differences were significant in all layers (P < 0.001). The serum concentrations of the metabolite N-desethylamiodarone correlate with densitometry values, especially in the 0- to 2-mm annulus in the anterior layer (r = 0.419; P = 0.001), whereas the cumulative dose and duration of treatment correlate significantly with the densitometry values in the 0- to 2-mm annulus at total thickness (P = 0.014 and P = 0.022, respectively). CONCLUSIONS: Corneal densitometry is a useful, objective method for quantifying AK and can help in monitoring amiodarone therapy. The serum concentration of the active metabolite N-desethylamiodarone correlates with the extent of keratopathy in the anterior layer, whereas chronic changes in the stroma correlate with the cumulative dose and duration of treatment.

Optical coherence tomography (OCT) angiography findings in retinal arterial macroaneurysms.

BACKGROUND: Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs). METHODS: Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail. RESULTS: OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs. CONCLUSIONS: OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.

Second-line therapies of patients initially treated with fludarabine and cyclophosphamide or fludarabine, cyclophosphamide and rituximab for chronic lymphocytic leukemia within the CLL8 protocol of the German CLL Study Group.

Updated results of the CLL8 trial confirm that the addition of rituximab to chemotherapy with fludarabine and cyclophosphamide (FC) leads to a prolongation of progression-free (PFS) and overall survival (OS) in first-line treatment of physically fit patients. After a median observation time of 47 months, median PFS was 57.9 months for patients treated with FC and rituximab (FCR) and 32.9 months for patients treated with FC alone (hazard ratio 0.56, 95% confidence interval 0.465-0.673; p < 0.001). A total of 232 patients were treated for relapse, among them 91 of 408 (22%) initially treated with FCR and 141 of 409 (35%) initially treated with FC. The drugs most frequently used either alone or in combination were rituximab (52% of all second-line therapies), fludarabine (21%), bendamustine (21%) and alemtuzumab (12%). The regimens chosen for second-line treatment after FC or FCR were heterogeneous, which underlines a need for further trials in order to define treatment recommendations for patients with relapsed chronic lymphocytic leukemia.