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ABSTRACT Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants’ clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4

Background/objectives: Tooth agenesis (TA) is among the most common malformations in humans. Although several causative mutations have been described, the genetic cause often remains elusive. Here, we test whether whole genome sequencing (WGS) could bridge this diagnostic gap., Methods: In four families with TA, we assessed the dental phenotype using the Tooth Agenesis Code after intraoral examination and radiographic and photographic documentation. We performed WGS of index patients and subsequent segregation analysis., Results: We identified two variants of uncertain significance (a potential splice variant in PTH1R, and a 2.1 kb deletion abrogating a non-coding element in FGF7) and three pathogenic variants: a novel frameshift in the final exon of PITX2, a novel deletion in PAX9, and a known nonsense variant in WNT10A. Notably, the FGF7 variant was found in the patient, also featuring the WNT10A variant. While mutations in PITX2 are known to cause Axenfeld-Rieger syndrome 1 (ARS1) predominantly featuring ocular findings, accompanied by dental malformations, we found the PITX2 frameshift in a family with predominantly dental and varying ocular findings., Conclusion: Severe TA predicts a genetic cause identifiable by WGS. Final exon PITX2 frameshifts can cause a predominantly dental form of ARS1., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Purpose: To investigate differences in the retinal vessel area density (VAD) on optical coherence tomography angiography (OCTA) between eyes with unilateral herpetic viral anterior uveitis (VAU) (herpes-simplex virus (HSV) and varicella-zoster virus (VZV)) and the non-affected fellow eye., Methods: In this monocentric, observational, prospective case series we analyzed the VAD of the macula, optic disc, and peripapillary region in affected and non-affected eyes of 22 patients with HSV-positive and 22 patients with VZV-positive VAU using OCTA. We analyzed also the visual field mean deviation (MD), the retinal nerve fiber layer (RNFL) thickness, Bruch's Membrane Opening-Minimum Rim Width (BMO-MRW), and ganglion cell layer (GCL) thickness on OCT and correlated the results with the different VADs., Results: The macular VAD in the superficial vascular plexus (SVC) was significant lower in the affected compared to the non-affected eye for both viruses (HSV: 33.0% ± 3.3% vs. 34.7% ± 2.6%, p  = 0.011; adjusted p  = 0.040; VZV: 33.1% ± 3.2% vs. 34.3% ± 2.8%, p  = 0.012; adjusted p  = 0.050). Additionally, the VAD of the peripapillary SVC differed between the affected and non-affected eye for VZV-positive VAU (47.1% ± 6.2% vs. 50.5% ± 6.3%, p  = 0.048, adjusted p  = 0.100). For both HSV-positive and VZV-positive VAU, there were correlations between macular or peripapillary SVC VAD and BMO-MRW, GCL thickness, RNFL thickness or MD of the affected eye., Conclusion: We observed vascular dysfunction characterized by decreased macular and peripapillary VAD in the superficial plexus on OCTA in eyes with HSV- and VZV-positive VAU compared to non-affected fellow eyes. These changes might be an early sign of glaucomatous damage or may be a direct consequence of the herpes viruses themselves.

Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50 years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1 year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50 years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1 year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: The study aims to evaluate changes in contrast sensitivity (CS) during therapy with intravitreal vascular endothelial growth factor (VEGF) inhibitors in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)., Methods: Prospective, uncontrolled, multicenter study on patients with neovascular AMD or DME who underwent intravitreal injection therapy with Ranibizumab, Aflibercept, or Bevacizumab was conducted. Best corrected visual acuity (BCVA) and CS measured by Mars Letter Contrast Sensitivity Test (MLCS) and Freiburg Visual Acuity and Contrast Test (FrACT) in logCS were evaluated before 3 consecutive VEGF inhibitor injections, which followed the pro renata regimen in treatment-naïve and pretreated eyes with a maximum of 9 injections. Correlation of MLCS and FrACT was calculated by the Spearman's rank correlation coefficient., Results: Eighty eyes of 74 patients (mean age 72.7; SD ± 9.96) were included. BCVA improved significantly from 0.44 (SD ± 0.21) logMAR to 0.38 (SD ± 0.23) logMAR by 0.06 (SD ± 0.14) logMAR values (p < 0.001). CS measured by MLCS increased significantly from 1.27 (SD ± 0.25) logCS to 1.39 (SD ± 0.22) logCS (p < 0.001). CS measured by FrACT also improved significantly from 1.22 (SD ± 0.32) logCS to 1.30 (SD ± 0.29) logCS (p = 0.035). A positive correlation between MLCS and FrACT was found (r = 0.389; p < 0.001). Despite statistical significance, results for BCVA, MLCS, and FrACT failed clinical significance. Overall best test results were achieved with MLCS., Conclusions: Intravitreal injection therapy with VEGF inhibitors led to an improvement of BCVA and CS measured by MLCS and FrACT. MLCS was superior and more sensitive compared to FrACT and even BCVA to evaluate CS in elderly patients with macular pathology., (© 2023. The Author(s).)

Purpose: The aim of this study was to evaluate whether XEN® implantation is a reasonable and safe method to lower the intraocular pressure (IOP) and amount of medication for adult primary open-angle glaucoma (POAG) over a 3-year period. The influence of the type of anesthesia, previous glaucoma surgery, and postoperative interventions on the outcome were examined., Methods: In this retrospective study, 96 eyes were included. XEN® implantation was performed as sole procedure under general (n = 86) or local anesthesia (n = 10). IOP and number of glaucoma medication were assessed preoperatively: day 1, week 6, month 3, 6, 12, 24, and 36. Further outcome parameters were Kaplan-Meier success rates, secondary intervention, and complication rates., Results: IOP decreased from 20.7 ± 5.1 to 12.8 ± 2.5 mmHg at the 36-month follow-up (p < 0.001) and glaucoma therapy was reduced from 3.3 ± 0.8 to 1.2 ± 1.6 (36 months, p < 0.001). Transient postoperative hypotony was documented in 26 eyes (27.1%). General anesthesia resulted in a significant improvement of the survival rate compared to local anesthesia (77% vs. 50%, p = 0.044). Prior iStent inject®, Trabectome®, or SLT laser had no significant impact, such as filter bleb revision. The number of postoperative needlings had a significantly negative influence (p = 0.012)., Conclusion: XEN® implantation effectively and significantly lowers the IOP and number of glaucoma therapy in POAG in the 36-month follow-up with a favorable profile of side effects and few complications. In case of IOP, general anesthesia has a significant positive influence on the survival rate, whereas prior SLT or MIGS does not have significant impact., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma., Design: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors., Results: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031])., Conclusion: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure., (© 2022. The Author(s).)

To analyze the effect of filtration in glaucoma surgery, XEN versus trabeculectomy, on the vessel area density (VAD) of the macular, papillary and peripapillary regions using optical coherence tomography angiography (OCT-A). This prospective cohort study analyzes the vascular architecture of 47 eyes of 45 patients after two different filtrating surgery procedures (XEN stent and trabeculectomy (TE)) using the OCT-A. Participants who had an outsourced medical anti-glaucoma therapy received filtrating surgery in a 2:1 (XEN: TE) ratio. The primary outcome measurements were changes in the VAD in various layers of retinal perfusion and the foveal avascular zone (FAZ). Both interventions achieved a significant postoperative reduction in IOP (XEN 17.6 ± 3.8-13.7 ± 3.8 mmHg; TE 21.2 ± 5.4-8.8 ± 2.6 mmHg). VAD values did not change significantly after filtrating surgery. Comparing both procedures, a significantly higher VAD for patients treated with TE was seen for the superficial vessel complex (SVC) 375 µm and 750 µm (p = 0.011, p = 0.017), deep vessel complex (DVC) 375 µm (p = 0.029) and the optic disc (p = 0.028) after 6 months, while all other parameters did not differ significantly. In conclusion, VAD does not significantly improve after filtrating surgery in preoperative moderately IOP elevated eyes. The IOP lowering effect of filtrating surgery, however, can stabilize vascular parameters in all layers of perfusion., (© 2022. The Author(s).)

Background: Knowledge about artifacts in optical coherence tomography angiography (OCTA) is important to avoid misinterpretations. An overview of possible artifacts in posterior uveitis provides important information for interpretations. Methods: In this monocentric prospective study, OCTA images from a total of 102 eyes of 54 patients with posterior uveitis, and an age-matched control group including 34 healthy subjects (67 eyes), were evaluated (day 0, month 3, month 6). We assigned different artifacts to distinct layers. Various types of artifacts were examined in different retinal layers. The χ2 test for the comparison between the control and uveitis group and Cochran’s Q test for the longitudinal comparison within the uveitis group were used. Results: A total of 2238 images were evaluated; 1836 from uveitis patients and 402 from healthy subjects. A total of 2193 artifacts were revealed. Projection (812 [36.3%]), segmentation (579 [25.9%]), shadowing (404 [18.1%]), and blink artifacts (297 [13.3%]) were the most common artifact types. The uveitis group displayed significantly more segmentation artifacts and projection artifacts (p < 0.001). No segmentation artifacts were documented in healthy subjects. The consecutive examinations within the uveitis group revealed the same artifact types without significance (p > 0.1). Conclusions: The uveitis patients showed more segmentation and projection artifacts than the control group. Within the uveitis group, artifacts remained longitudinally constant in terms of artifact type and pattern. The artifacts therefore appear to be reproducible on an individual level.

Toxoplasma gondii, Treponema pallidum and Mycobacterium tuberculosis are the most important infectious causes of posterior uveitis. The epidemiology, clinical picture, diagnostic and treatment strategies of these diseases are presented., Competing Interests: Thomas Neß: Fortbildungen für Novartis, Roche, Amgen, Abvie. Mitglied der Arbeitsgemeinschaft Toxoplasmose der Paul-Ehrlich Gesellschaft. Sibylle Winterhalter: Fortbildungen für Allergan und Heidelberg Engineering. Nicole Stübiger: keine./Thomas Neß: Lectures and training for Novartis, Roche, Amgen, Abvie. Member of the Toxoplasmosis Working Group of the Paul Ehrlich Society. Sibylle Winterhalter: Lectures and training for Allergan and Heidelberg Engineering. Nicole Stübiger: none., (Thieme. All rights reserved.)

Purpose: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA)., Methods: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters., Results: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% ± 3.57% vs. 34.92% ± 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% ± 3.04% vs. 42.09% ± 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm 2  ± 0.1 mm 2 vs. 0.23 mm 2  ± 0.09 mm 2 ) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% ± 1.11% vs. 33.35% ± 0.95%, p = 0.194) and peripapillary plexus PD (46.65% ± 0.83% vs. 46.95% ± 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032)., Conclusion: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria., (© 2021. The Author(s).)