Islet Co-Expression of CD133 and ABCB5 in Human Retinoblastoma Specimens.

BACKGROUND: The role of CD133 und ABCB5 is discussed in treatment resistance in several types of cancer. The objective of this study was to evaluate whether CD133+/ABCB5+ colocalization differs in untreated, in beam radiation treated, and in chemotherapy treated retinoblastoma specimens. Additionally, CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 gene expression was analyzed in WERI-RB1 (WERI RB1) and etoposide-resistant WERI RB1 subclones (WERI ETOR). METHODS: Active human untreated retinoblastoma specimens (n = 12), active human retinoblastoma specimens pretreated with beam radiation before enucleation (n = 8), and active human retinoblastoma specimens pretreated with chemotherapy before enucleation (n = 7) were investigated for localization and expression of CD133 and ABCB5 by immunohistochemistry. Only specimens with IIRC D, but not E, were included in this study. Furthermore, WERI RB1 and WERI ETOR cell lines were analyzed for CD133, ABCB5, sphingosine kinase 1, and sphingosine kinase 2 by the real-time polymerase chain reaction (RT-PCR). RESULTS: Immunohistochemical analysis revealed the same amount of CD133+/ABCB5+ colocalization islets in untreated and treated human retinoblastoma specimens. Quantitative RT-PCR analysis showed a statistically significant upregulation of CD133 in WERI ETOR (p = 0.002). No ABCB5 expression was detected in WERI RB1 and WERI ETOR. On the other hand, SPHK1 (p = 0.0027) and SPHK2 (p = 0.017) showed significant downregulation in WERI ETOR compared to WERI RB1. CONCLUSIONS: CD133+/ABCB5+ co-localization islets were noted in untreated and treated human retinoblastoma specimens. Therefore, we assume that CD133+/ABCB5+ islets might play a role in retinoblastoma genesis, but not in retinoblastoma treatment resistance.

Evaluating Retinal and Choroidal Perfusion Changes After Ocular Massage of Healthy Eyes Using Optical Coherence Tomography Angiography.

Background and objectives: Ocular massage (OM) is used as a treatment option for acute retinal artery occlusion, under the assumption that it induces vessel dilatation and enhances perfusion. Since evidence of ocular perfusion alteration due to OM is lacking, we investigate the impact of OM on the hemodynamics of the posterior pole in healthy eyes in a noninvasive fashion by using optical coherence tomography angiography (OCTA). Materials and Methods: A prospective study was conducted on healthy volunteers, each of whom underwent measurements of intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), radial peripapillary capillary perfusion (RPCP), superficial capillary plexus perfusion (SCPP), deep capillary plexus perfusion (DCPP), choriocapillaris perfusion (CCP), Sattler's layer perfusion (SLP) and Haller's layer perfusion (HLP) before and after OM. OM was performed for 2 min, consisting of 10-s turns of compression and decompression of the globe. Results: A total of 21 eyes from 21 participants (median age 29) were included. After OM, IOP significantly declined (p < 0.001), while SFCT (p < 0.005), SCPP (p < 0.001), DCPP (p = 0.004) and CCP (p = 0.008) significantly increased. CMT, RPCP, SLP and HLP did not show any significant alteration due to OM. Changes in SCPP correlated positively with changes in CCP and vice versa. Conclusions: OCTA-based analysis in healthy adults following OM demonstrated a significant increase of retinal perfusion values, assumed to be due to failure of autoregulatory mechanisms. These findings may indicate a positive effect of OM as a treatment option for patients with acute retinal artery occlusion.

[Patient-Reported Treatment Satisfaction with Stereotactic Radiotherapy in Neovascular Age-Related Macular Degeneration]. / Patientenzufriedenheit nach stereotaktischer Radiotherapie bei exsudativer altersbedingter Makuladegeneration.

BACKGROUND: Stereotactic radiotherapy (SRT) in conjunction with the common intravitreal injections (IVI) is a new adjuvant approach in neovascular age-related macular degeneration (AMD) patients. The aim of our study was to investigate factors influencing patient satisfaction one year after SRT. METHODS: A questionnaire was administered to 35 AMD patients who had consecutively undergone SRT using the IRay®-device at the Department of Ophthalmology, University of Lübeck. In addition to descriptive statistics, responses were evaluated by correlation analysis. Moreover, subgroup analyses were performed, using a classification of IVI responders (annual injection rate after SRT ≤ 3), visual acuity (VA) responders (VA improvement ≥ 0.2 logMAR) and double responders (annual injection rate after SRT ≤ 3 as well as VA improvement ≥ 0.2 logMAR). RESULTS: The response rate was 86%. With respect to their treatment expectations, twice as many patients hoped to receive less injections instead of a better vision. Those hoping for less injections were significantly more satisfied with their clinical outcome. In addition, IVI-responders were significantly more satisfied than IVI-non-responders, while VA-responders were not, compared to VA-non-responders. CONCLUSIONS: Patient satisfaction seems to depend on patients' comprehension of how SRT affects their disease and what kinds of expectations were set. It is of utmost importance to provide the patients with adequate and comprehensible education and to define realistic goals prior to SRT.

Three-year clinical and optical coherence tomography follow-up after stereotactic radiotherapy for neovascular age-related macular degeneration.

PURPOSE: The long-term clinical outcome of adjuvant stereotactic radiotherapy (SRT) in neovascular age-related macular degeneration (nAMD) patients was evaluated. METHODS: This case-control study included patients with unilateral nAMD, who underwent SRT complementary to standard anti-VEGF treatment. Only patients with monthly follow-up over at least three years were considered. Number of intravitreal injections, visual acuity (VA), central retinal thickness (CRT), and subfoveal choroidal thickness (SFCT) were evaluated and compared to baseline as well as to an age- and gender-matched control group, who received anti-VEGF monotherapy. RESULTS: Twenty patients were irradiated and had complete follow-up. Cumulatively, SRT patients needed significantly less injections than non-irradiated ones over three years (14 vs. 18, p â€‹= â€‹0.014), while median VA did not show statistically significant changes (0.4 logMAR at baseline to 0.65 logMAR at final follow-up, p â€‹= â€‹0.061). CRT remained steady, but SFCT showed a continuous thinning of almost 50 â€‹µm (p â€‹= â€‹0.031) in irradiated patients over three years. Multiple linear regression analysis revealed that SFCT and VA at time of irradiation are significant prognostic factors of VA change in SRT patients over the following three years (F(2,17) â€‹= â€‹23.946, p<0.001, R2 of 0.738). CONCLUSIONS: SRT significantly reduced the cumulative anti-VEGF treatment burden over three years, however, this was mainly driven by the results of the first year after irradiation. A thinner SFCT at time of irradiation was associated with poorer visual outcome. While further research and investigation are warranted to elucidate the underlying pathogenesis, SFCT could be a potential biomarker when evaluating a patient's suitability for SRT.

[Digital teaching 2020: students assess attention during an online lecture as equivalent to a face-to-face lecture]. / Digitale Lehre 2020: Studenten schätzen die Aufmerksamkeit während einer Onlinevorlesung gleichwertig zu einer Präsenzvorlesung ein.

BACKGROUND: The corona pandemic has led to short-term adjustments of the procedures in medical courses. In many departments classroom teaching was no longer possible so that it was necessary to implement digital courses to provide an adequate medical training. METHODS: We developed a digital curriculum based on the contents of our established courses using primary in-house tools, such as Cisco WebEx and Moodle. We then performed a student survey to evaluate the implementation of the concept. RESULTS: The evaluation showed good ratings according to teaching content and didactics. The communication with the students and between each other was also considered good. Students assessed attention during the course to be equivalent in comparison to classroom teaching. As expected, the training of practical skills was evaluated as poor. For future courses most of the students could imagine a combination of digital and classroom teaching. DISCUSSION: Implementing a digital course was a sudden challenge for students and tutors. With suitable software solutions and good communication, it is possible to adequately teach theoretical content via digital courses. Students assessed the digital training in most parts to be a good and an equivalent option compared to classroom teaching. A remaining problem is the lack of practical training.

Evaluating diurnal variations in retinal perfusion using optical coherence tomography angiography.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a non-invasive tool for imaging and quantifying the retinal and choroidal vasculature as well as perfusion state in healthy eyes. Choroidal perfusion is subject to diurnal variation, showing lowest perfusion in the morning and highest in the afternoon. In this index study, OCTA was used to investigate diurnal changes of the retinal perfusion in healthy adult eyes and to identify impacting factors since retinal perfusion is known to be mainly determined by autoregulatory mechanisms. METHODS: A prospective study was conducted on healthy volunteers, each of whom underwent repeated measurements of mean arterial pressure (MAP), intraocular pressure (IOP), macular volume (MV), subfoveal choroidal thickness (SFCT), foveal avascular zone (FAZ) and retinal perfusion of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and full retina (FR) slab at 7 a.m. and 4 p.m. Possible influence of MAP or IOP on the retinal perfusion was evaluated. RESULTS: A total of 22 eyes of 22 participants (mean age 55.91 ± 14.84) were analysed. Significant diurnal changes from 7 a.m. to 4 p.m. were observed for MAP (p < 0.001) and SFCT (p = 0.017). The perfusion of SCP, DCP and FR as well as the size of the FAZ and the MV did not show significant fluctuation during the day. No significant correlation between MAP or IOP and retinal perfusion values were detectable. CONCLUSION: OCTA-based analysis of the retina in healthy adults demonstrated a steady perfusion of both plexus during the day, independently of changes in MAP. These findings support the theory of autoregulatory mechanisms of the retinal blood flow.

Subfoveal choriocapillaris, Sattler's and Haller's layer thickness predict clinical response to stereotactic radiotherapy in neovascular age-related macular degeneration patients.

PURPOSE: To evaluate the significance of choroidal substructure analysis in predicting the clinical response to adjuvant stereotactic radiotherapy (SRT) in neovascular age-related macular degeneration (nAMD) patients. METHODS: Patients with nAMD, who underwent SRT (baseline) in addition to common intravitreal injections (IVIs) and subsequently had at least 12 months of complete follow-up, were enrolled. In a post hoc analysis, optical coherence tomography (OCT) data were reviewed, and subfoveal choroidal thickness (CT) as well as the thickness of choroidal substructures, such as choriocapillaris (CC), Sattler's layer (SL), and Haller's layer (HL), was measured to determine if these influenced SRT efficacy. RESULTS: A total of 35 eyes of 35 patients were included. While each of the 4 choroidal metrics significantly forecasts the clinical response to SRT, combining them all together produced the most reliable prediction model. CONCLUSION: In terms of clinical response to SRT in nAMD patients, choroidal substructure analysis does improve the quality of the prediction model when combined with subfoveal CT.

Mapping diurnal variations in choroidal sublayer perfusion in patients with idiopathic epiretinal membrane: an optical coherence tomography angiography study.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a non-invasive tool for imaging and quantifying the choroidal vasculature and perfusion state. In this index study, OCTA was used to investigate diurnal changes in choroidal sublayer perfusion in eyes with idiopathic epiretinal membrane (ERM) and to identify impacting factors. METHODS: A prospective study was conducted on volunteers with symptomatic ERM, each of whom underwent repeated measurements of subfoveal choroidal thickness (SFCT) using enhanced-depth imaging optical coherence tomography and perfusion of choroidal vascular sublayers using OCTA at 7 a.m., 12 p.m., 4 p.m., and 8 p.m. Possible interactions between diurnal variations and other factors, such as gender and age, were evaluated. RESULTS: A total of 21 eyes of 21 participants (mean age 72.43 ± 7.06 years) were analysed. A significant pattern of diurnal variation was observed for SFCT (p = 0.008) as well as perfusion of Haller's layer (HLP, p = 0.001). SFCT and HLP both demonstrated a quadratic relation to time of the day, decreasing from morning to afternoon, before increasing again in the evening. No significant differences with regard to gender or age were detectable. CONCLUSION: OCTA-based analysis of choroidal sublayer perfusion demonstrated significant diurnal variations in patients with symptomatic ERM, which are quite different from changes reported in healthy eyes. Therefore, it is important to account for time of day, when comparing longitudinal OCTA data.

Subfoveal Choroidal Thickness as a Potential Predictor of Clinical Response to Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: Stereotactic radiotherapy (SRT) is a new adjuvant treatment modality that has been shown to reduce the need for repetitive intravitreal injections (IVIs) in patients with neovascular age-related macular degeneration (nAMD). The authors aimed to determine baseline predictors of clinical response to SRT. PATIENTS AND METHODS: This was a retrospective, observational case series of patients with nAMD who underwent SRT and subsequently had at least 12 months of complete follow-up. After SRT and one mandatory IVI, patients were examined every 4 weeks and received further treatment on a pro re nata basis. Examination included enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT) to measure subfoveal choroidal thickness (SFCT) and central macular thickness (CMT). Patients' data were retrieved from medical records and included demographics, disease duration, lesion size, best-corrected visual acuity (BCVA), previous number of IVIs, and type of drug applied. RESULTS: A total of 35 eyes of 35 patients (76.23 years ± 7.05 years) were included, and 21 eyes (60%) responded well to SRT. The annual injection rate decreased from 6.86 before SRT to 3.46 afterward, whereas BCVA improved from 0.49 logMAR at baseline to 0.37 logMAR at final follow-up. From a morphologic point of view, CMT and SFCT decreased by 71 µm and 37 µm, respectively, at 12-month follow-up compared to baseline. Of all investigated parameters, only SFCT proved to be significant, as a higher baseline SFCT was found to be a strong negative predictor for the number of IVIs needed after SRT (regression coefficient: -0.678; P < .001). CONCLUSIONS: Baseline SFCT may help predict which patients with nAMD will respond more favorably to SRT. The authors found eyes with a thicker baseline SFCT needed fewer IVIs after SRT. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:320-328.].

Impact of correct anatomical slab segmentation on foveal avascular zone measurements by optical coherence tomography angiography in healthy adults.

PURPOSE: To evaluate the impact of correct anatomical slab segmentation on foveal avascular zone (FAZ) dimensions in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using optical coherence tomography angiography (OCTA). METHODS: Participants with healthy retinas were recruited, and 5 × 5 mm OCTA images were acquired using the Canon HS-100 Angio eXpert module. FAZ size was measured in automatically (AS, manufacturer-based) and manually (MS, anatomical-based) segmented OCTA slabs by two experienced graders. FAZ dimensions, inter-rater agreement, and correlation to demographic and retinal parameters were evaluated. RESULTS: A total of 38 eyes from 20 healthy adult subjects were included in this cross-sectional study. While in AS slabs, the FAZ in the SCP was smaller than in the DCP, in MS images, it was the opposite. MS had a relevant impact on inter-rater agreement of FAZ measurements in the SCP. The FAZ area in both plexus correlated inversely with the central retinal thickness (CRT), irrespective of the segmentation applied. Furthermore, an enlargement of FAZ size in the DCP with increasing age was found. Finally, the FAZ in female participants was significantly larger than in their male counterparts, regardless of the evaluated plexus and chosen segmentation. CONCLUSIONS: Correct anatomical slab segmentation has a significant impact on FAZ size measurements. Not adjusting the segmentation boundaries represents a significant source of error for measuring FAZ area and confounds comparisons across studies as well as OCTA devices.

Changes in Peripapillary Nerve Fiber Layer Thickness after Adjuvant Stereotactic Radiotherapy in Patients with Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the effect of stereotactic radiotherapy (SRT) in conjunction with intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) drugs on peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with neovascular age-related macular degeneration (nAMD). METHODS: This was a retrospective, observational case series of patients with nAMD, who underwent SRT and subsequently had at least 12 months of complete follow-up. After SRT and one mandatory IVI, patients were examined monthly and received further treatment on a pro re nata basis. Examination included spectral-domain optical coherence tomography of the optic disc to measure pRNFL thickness. Patients' data were retrieved from medical records including demographics, disease duration, best-corrected visual acuity, previous number of intravitreal injections, and the type of drug applied. RESULTS: A total of 35 eyes of 35 patients (76.23 ± 7.05 years) were included. The mean duration of nAMD at time of irradiation was 34.57 ± 16.96 months. During that time, patients received a mean total number of 15.83 ± 6.29 intravitreal injections, 6.86 ± 1.57 within the last 12 months before SRT. After SRT, on average 3.46 ± 2.09 injections were administered over 12 months, resulting in a mean total number of 19.29 ± 6.92 injections at final follow-up. The mean global pRNFL thickness was 97.23 ± 12.55 µm at time of irradiation, 95.54 ± 11.07 µm at 6 month (P = 0.299), and 95.29 ± 12.07 µm at 12 month (P = 0.373) follow-up. CONCLUSION: SRT in conjunction with anti-VEGF injections did not lead to any significant change in pRNFL thickness over 12 months in patients with nAMD. However, long-term results are not yet available. Therefore, prospective studies with longer follow-up are needed to corroborate these findings.

Stereotactic radiotherapy in neovascular age-related macular degeneration: Real-life efficacy and morphological evaluation of the outer retina-choroid complex.

Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis.Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety.Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers.Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk.