Inherited retinal diseases can result from various genetic defects and are one of the leading causes for blindness in the working-age population. The present study aims to provide a comprehensive description of changes in retinal structure associated with phenotypic disease entities and underlying genetic mutations. Full macular spectral domain optical coherence tomography scans were obtained and manually segmented in 16 patients with retinitis pigmentosa, 7 patients with cone–rod dystrophy, and 7 patients with Stargardt disease, as well as 23 age- and sex-matched controls without retinal disease, to assess retinal layer thicknesses. As indicated by generalized least squares models, all IRDs were associated with retinal thinning (p < 0.001), especially of the outer nuclear layer (ONL, p < 0.001). Except for the retinal nerve fiber layer, such thinning was associated with a reduced visual acuity (p < 0.001). These advances in our understanding of ultrastructural retinal changes are important for the development of gene-, cell-, and optogenetic therapy. Longitudinal studies are warranted to describe the temporal component of those changes.

Autosomal recessive bestrophinopathy (ARB) has been reported as clinically heterogeneous. Eighteen patients (mean age: 22.5 years; 15 unrelated families) underwent ophthalmological examination, fundus photography, fundus autofluorescence, and optical coherence tomography (OCT). Molecular genetic testing of the BEST1 gene was conducted by the chain-terminating dideoxynucleotide Sanger methodology. Onset of symptoms (3 to 50 years of age) and best-corrected visual acuity (0.02–1.0) were highly variable. Ophthalmoscopic and retinal imaging defined five phenotypes. Phenotype I presented with single or confluent yellow lesions at the posterior pole and midperiphery, serous retinal detachment, and intraretinal cystoid spaces. In phenotype II fleck-like lesions were smaller and extended to the far periphery. Phenotype III showed a widespread continuous lesion with sharp peripheral demarcation. Single (phenotype IV) or multifocal (phenotype V) vitelliform macular dystrophy-like lesions were observed as well. Phenotypes varied within families and in two eyes of one patient. In addition, OCT detected hyperreflective foci (13/36 eyes) and choroidal excavation (11/36). Biallelic mutations were identified in each patient, six of which have not been reported so far [c.454C>T/p.(Pro152Ser), c.620T>A/p.(Leu207His), c.287_298del/p.(Gln96_Asn99del), c.199_200del/p.(Leu67Valfs*164), c.524del/p.(Ser175Thrfs*19), c.590_615del/p.(Leu197Profs*26)]. BEST1-associated ARB presents with a variable age of onset and clinical findings, that can be categorized in 5 clinical phenotypes. Hyperreflective foci and choroidal excavation frequently develop as secondary manifestations.

Das Ziel dieses Artikels ist es, einen Überblick zu geben über verschiedene Strategien zur Verwendung von PRN- und T&E-Therapieschemata (PRN: pro re nata; T&E: treat and extend) mit intravitrealen Anti-VEGF-Medikamenten (Bevacizumab, Ranibizumab oder Aflibercept) bei Patienten mit Netzhauterkrankungen wie neovaskulärer AMD, diabetischem Makulaödem und Makulaödem aufgrund von retinalen Venenverschlüssen. Der Schwerpunkt liegt dabei darauf, die Wirksamkeit und die Visusergebnisse des PRN- und des T&E-Regimes in Korrelation mit den wichtigsten Zulassungsstudien und Studien basierend auf den derzeit verfügbaren Daten vorzulegen. Wir diskutieren auch die Vor- und Nachteile der beiden Therapieregimes sowie die Überwachung und Behandlung der Krankheitsaktivität einschließlich der Behandlungsintervalle und Injektionsfrequenz. Derzeit gibt es ein zunehmendes Interesse, ein Regime zu etablieren, das die besten Visusergebnisse bei reduzierter Injektionsfrequenz und konsekutiv geringerer Belastung der Patienten durch individualisierte Behandlungsintervalle mit Minimierung der Anzahl der Klinikbesuche und der entstehenden Kosten bietet. Studien haben gezeigt, dass das PRN-Regime im realen Klinikalltag keine optimalen Visusergebnisse liefert. PRN erfordert häufige Arztbesuche, um den Krankheitsstatus zu kontrollieren und intravitreale Behandlung bei Bedarf reaktiv zu indizieren. Individualisierte T&E-Regimes können das Visusergebnis mit signifikant weniger Kontrolluntersuchungen verbessern im Gegensatz zu Therapieschemata mit einer monatlichen Applikation oder einem PRN-Regime. The goal of this report is to provide a review on different strategies for the use of pro re nata (PRN) and treat and extend (T&E) regimens with intravitreal anti-VEGF agents (bevacizumab, ranibizumab or aflibercept) in patients with retinal diseases such as neovascular AMD, diabetic macular oedema and macular oedema due to retinal vein occlusion. The main focus is to present the effectiveness and visual outcomes of both PRN and T&E regimens in the main pivotal trials and studies based on currently available evidence. We also discuss the advantages and disadvantages of both regimens, as well as monitoring and treatment of the disease, including treatment intervals and injection frequency. Currently there is increasing interest in establishing a regimen which offers the best visual outcome with lower injection frequency, and with reduced treatment burden by individualising treatment intervals and minimising the number of clinic visits and costs. Studies have shown that the PRN regimens in a clinical setting are insufficient in assuring the best visual outcome. The PRN regime requires frequent clinic visits to monitor disease status and intravitreal treatment if needed in a reactive approach. Individualised T&E regimens can improve visual outcome and require fewer injections than those administered in a monthly regimen and fewer monitoring visits than those in a PRN regimen.

Introduction Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Methods Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8–48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm²) and horizontal and vertical diameters (µm) were assessed. Results VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = − 0.6; p < 0.0001). Conclusions This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring.