[Lens injury as a complication of intravitreal medication injection]. / Linsenverletzungen als Komplikation bei intravitrealer Medikamenteneingabe.

BACKGROUND: Intravitreal medication injections are an efficient and low-risk delivery technique for treating various retinal diseases. Rare serious complications include increased intraocular pressure, vitreous hemorrhage, retinal tears and detachment, intraocular inflammation and endophthalmitis. In the case series presented here, we report iatrogenic lens injuries caused by inadequate performance of intravitreal injections. METHODS: A multicenter data collection of patients treated with intravitreal injections with visible iatrogenic lens defects from 2016 to 2023 was retrospectively performed. RESULTS: Lens trauma after intravitreal injections was identified in six cases (69.3±6.5 years). While five cases were observed after anti-VEGF therapy, we identified lens injury after dexamethasone implantation in one patient. CONCLUSION: Iatrogenic lens injury during intravitreal injection is preventable with the correct injection technique. Knowledge of individual axis length and lens status also helps to avoid this complication.

Clinical Landscape of Central Serous Chorioretinopathy in Germany - Retina.net CSC Registry Report No 1.

BACKGROUND: The German Registry of Central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations as well as diagnosis and treatment patterns. MATERIAL AND METHODS: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. RESULTS: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 male (75%) and 103 female (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0 - 70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). Mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2 - 0.4), but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal non-pulsed laser (23%), photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. DISCUSSION: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women was higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include photodynamic therapy, micropulse laser and anti-VEGF injections in case of secondary CNV.

Current perspectives on type 3 macular neovascularization due to age-related macular degeneration.

BACKGROUND: The aim of this review is to systematically summarize the current knowledge on Type 3 Macular Neovascularization' (MNV3) in age-related macular degeneration (AMD). SUMMARY: Recent histopathologic and multimodal imaging findings led to the consensus definition of the new term 'Type 3 Macular Neovascularization' in AMD. MNV3 originates in the deep vascular plexus as a neovascular process without connection with the retinal pigment epithelium in the initial stages. This type has numerous clinical and pathomorphologic features that separate it from the other two types of MNV in AMD. Besides, its frequency appears to be higher than previously thought. In optical coherence tomography (OCT), MNV3 can be classified in stage 1-3. Hyperreflective foci in the outer retina possibly represent a precursor lesion. In addition, MNV3 is characterized by a strong association with reticular pseudodrusen, a high rate of bilaterality, close associations with advanced age and arterial hypertension, decreased choroidal thickness, and decreased choriocapillaris flow signals. Data from latest anti vascular endothelial growth factor (VEGF) studies in MNV3 suggest that the OCT biomarkers intraretinal and subretinal fluid should be interpreted differently than in the other types. Additionally, data from MNV3 eyes should be analyzed separately allowing optimal type-specific treatment strategies in the future. KEY MESSAGES: This review highlights the need for accurate characterization of nAMD lesions and an MNV type-specific approach, particularly for MNV3.

[Iatrogenic retinal defects after intravitreal operative drug injections]. / Iatrogene Netzhautdefekte nach intravitrealer operativer Medikamenteneingabe.

BACKGROUND: Intravitreal operative drug injections represent one of the most frequently performed medical interventions. The risk profile is low. In addition to intraocular pressure elevation, the most frequent complications include exogenous endophthalmitis, vitreous hemorrhage and rhegmatogenous retinal detachment. Furthermore, isolated cases of lens injuries, macular holes associated with vitreoretinal traction and peripheral retinal defects have been described. In the present case series sharp iatrogenic macular and retinal defects are described. METHODS: Retrospective multicenter case collection of patients with iatrogenic retinal defects after intravitreal injections from 2016 to 2023. RESULTS: Iatrogenic retinal trauma after intravitreal injections for treatment of neovascular age-related macular degeneration was identified in 9 cases (72 years ± 8.1, 3 eyes pseudophakic). While sharp injuries within the macula occurred in six cases, extramacular lesions were detected in the other cases. CONCLUSION: Iatrogenic retinal and macular injuries are rare complications of intravitreal injections and when correctly carried out are preventable, especially with respect to use of cannulas and the choice of the distance from the limbus.

Old Problem in a New Guise: Retinal Pigment Epithelium Tear after Intravitreal Faricimab (Vabysmo®) Injection.

This case report describes a 78-year-old patient who developed a tear of the retinal pigment epithelium (RPE) during faricimab (Vabysmo®) therapy. After three consecutive intravitreal aflibercept (Eylea®) injections with persistent disease activity, therapy was switched to faricimab. The patient experienced a tear in the RPE 4 weeks postinjection. We report the first published case of RPE tear development after intravitreal faricimab injection in neovascular age-related macular degeneration. Faricimab has a new target structure in the angiopoietin-2 receptor in addition to VEGF. Patients at risk for RPE rupture were excluded from pivotal studies. Further investigation is needed to understand the effect of faricimab not only on visual acuity and intraretinal and subretinal fluid but also on mechanical stress on the RPE monolayer.

High User Acceptance of a Retina e-Learning App in Times of Increasing Digitalization of Medical Training for Ophthalmologists.

INTRODUCTION: The aim was to identify changes in continuing education and training in ophthalmology in the context of the COVID-19 pandemic and advancing digitalization and to analyse the acceptance of e-learning tools among German ophthalmologists using a novel Retina Case App as an example. METHODS: The participants' training behaviour before and during the COVID-19 pandemic was surveyed. Furthermore, the acceptance and usability of the Retina Case App were evaluated using the System Usability Scale (SUS). A possible influence of the app on everyday clinical practice was assessed. RESULTS: A total of 145 ophthalmologists participated in the survey. The frequency of continuing medical education did not decrease for 62.8% of ophthalmologists during the pandemic. A significant increase in at least monthly use of online courses or lectures has been observed (90.3% vs. 28.2%, p < 0.001). No significant difference was identified in terms of frequency of use of print and digital journals or printed textbooks. The majority of participants stated that online training platforms are well suited to replace the absence of face-to-face events (73.8%). The mean SUS score was 87.7 (SD 11.9), which categorizes the app's usability as excellent. The majority agreed that the newly developed app enables faster learning (82.1%) and leads to increased motivation (71.7%). Most ophthalmologists (80.7%) felt that regular use of the app would improve confidence in the treatment of retinal diseases. CONCLUSIONS: The COVID-19 pandemic has led to a significant change in training behaviour in ophthalmology towards e-learning and online courses, which has not been accompanied by a general decline in training activity. The exemplarily investigated application showed a high user acceptance among ophthalmologists.

Longitudinal choriocapillaris changes in the presence of reticular pseudodrusen.

To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4 mm diameter and a circle of 6 mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36 ± 8.39 mm2 at baseline to 37.77 ± 9.03 mm2 at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p < 0.001; ring: p < 0.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p < 0.001; ring: p < 0.001). Evaluation of CC parameters suggested significant group × time interaction effects for CC FD (p = 0.04) and mean intensity signal (p = 0.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5 years in both RPD-affected and RPD-unaffected macular areas.

[Choroidal neovascularization due to a punctate inner choroidopathy visualized by optical coherence tomography angiography]. / Choroidale Neovaskularisation infolge einer "punctate inner choroidopathy", dargestellt mittels optischer Kohärenztomographie-Angiographie.

Punctate inner choroidopathy (PIC) is often accompanied by the development of choroidal neovascularization (CNV). The identification of a fresh CNV in the context of PIC is often difficult. We present the case of a 30-year-old female patient with typical morphological features of PIC. A CNV could not be detected with certainty by optical coherence tomography (OCT) or by fluorescein angiography (FAG); however, OCT angiography (OCT-A) revealed a circumscribed CNV. The case suggests that there are a high number of undiagnosed, subclinical secondary CNVs not requiring treatment in PIC patients.

Optical coherence tomography angiography image quality assessment at varying retinal expertise levels.

PURPOSE: To compare optical coherence tomography angiography (OCT-A) image quality gradings performed by readers of varying retinal expertise levels in different retinal diseases. METHODS: Central 3 × 3 mm2 OCT-A images (AngioVue, Optovue) of 57 healthy controls (50.9 ± 22.4 years) and 148 patients (66.5 ± 14.1 years) affected by various chorioretinal diseases were retrospectively analyzed including early age-related macular degeneration (AMD, n = 26), neovascular AMD (nAMD, n = 22), and geographic atrophy due to AMD (GA, n = 6), glaucoma (n = 28), central serous chorioretinopathy (CSC, n = 14), epiretinal membrane (EM, n = 26), retinitis pigmentosa (RP, n = 16), and retinal venous occlusion (RVO, n = 10). A senior expert in medical retina (SE), an ophthalmology resident (OR), and a non-ophthalmologic medical doctor (MD) independently assessed OCT-A image quality using the motion artifact score (MAS) and the segmentation accuracy score (SAS). RESULTS: Regarding MAS, inter-reader agreement between SE and OR was 93.7% (Cohen's kappa = 0.907) and 85.4% (Cohen's kappa = 0.786) between SE and MD. Regarding SAS, inter-reader agreement between SE and OR was 95.1% (Cohen's kappa = 0.92) and 92.2% (Cohen's kappa = 0.874) between SE and MD. In the SAS analysis, signal strength index (SSI) and presence of retinal pathology had a significant influence on the overall agreement (P = 0.046; P < 0.001). CONCLUSIONS: OCT-A image quality assessment can be performed most reliably by an ophthalmologist with knowledge in retinal image analysis. Yet, well-instructed non-ophthalmologic assessors show only slightly inferior results and, thus, may be integrated in routine OCT-A image quality assessment as well.

RANIBIZUMAB IN PIGMENT EPITHELIAL TEARS SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Prospective Study.

PURPOSE: To assess efficacy of intravitreal ranibizumab in retinal pigment epithelium tears secondary to neovascular age-related macular degeneration. METHODS: The Ranibizumab In Pigment epithelial tears secondary to age-related macular degeneration (RIP) study is a prospective, single-arm, multicenter, investigator-initiated trial. Twenty four eyes of 24 patients with a retinal pigment epithelium tear secondary to age-related macular degeneration received monthly intravitreal injection of 0.5mg ranibizumab for 12 months, together with monthly assessments of morphologic and functional efficacy parameters. Primary outcome measure was mean best-corrected visual acuity at final visit compared with baseline. RESULTS: Mean best-corrected visual acuity remained stable over the 12-month study period with 50.3 Early Treatment of Diabetic Retinopathy Study letters (±18.7; Snellen equivalent 20/100) at baseline and 52.9 letters (±19.7; Snellen equivalent 20/100) at final visit (P = 0.39). One eye (4%) experienced a vision loss of ≥15 letters, and 2 eyes (8%) gained ≥15 letters. Mean central retinal thickness decreased from 571 µm (±185 µm) to 436 µm (±171 µm; P = 0.0001). Vision-related quality of life was stable with a mean VFQ-25 score of 79.0 (±10.8) at baseline and 74.3 (±13.9) at final visit (P = 0.12). CONCLUSION: In retinal pigment epithelium tears secondary to age-related macular degeneration, monthly intravitreal ranibizumab therapy results in stabilization of visual acuity over 12 months.

OCT-Angiography reveals reduced vessel density in the deep retinal plexus of CADASIL patients.

Optical coherence tomography angiography (OCT-A) represents the most recent tool in ophthalmic imaging. It allows for a non-invasive, depth-selective and quantitative visualization of blood flow in central retinal vessels and it has an enormous diagnostic potential not only in ophthalmology but also with regards to neurologic and systemic diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular small-vessel disease caused by Notch3 mutations and represents the most common form of hereditary stroke disorder. In this study, CADASIL patients prospectively underwent OCT-A imaging to evaluate retinal and choriocapillaris blood flow as well as blood flow at the optic nerve head. The vessel density of the macular region and the size of the foveal avascular zone in the superficial and deep retinal plexus were determined as well as the vessel density at the optic nerve head and in the choriocapillaris. Additionally, cerebral magnetic resonance images were evaluated. The main finding was that vessel density of the deep retinal plexus was significantly decreased in CADASIL patients compared to healthy controls which may reflect pericyte dysfunction in retinal capillaries.

Desgarros del epitelio pigmentario de la retina: factores de riesgo, mecanismo y control terapéutico.

Los desgarros del epitelio pigmentario de la retina (EPR) se asocian en la mayoría de los casos con los desprendimientos vascularizados del EPR debido a una degeneración macular asociada a la edad (DMAE), y normalmente implican una pérdida adversa de la agudeza visual. Estudios recientes indican que ha habido un aumento en la incidencia de desgarros del EPR desde la introducción de fármacos anti-factor de crecimiento del endotelio vascular (anti-VEGF) así como una asociación temporal entre el desgarro y la inyección intravítrea. Dado que el número de pacientes con DMAE y el número de inyecciones anti-VEGF va en aumento, tanto la dificultad de prevenir desgarros del EPR como el tratamiento tras la formación de los desgarros han adquirido una mayor relevancia. De forma paralela, la evolución de la imagenología de la retina ha contribuido de manera significativa a comprender mejor el desarrollo de los desgarros del EPR en los últimos años. Esta revisión resume los conocimientos que se poseen actualmente sobre el desarrollo, los factores pronósticos y las estrategias terapéuticas de los desgarros del EPR antes y después de que estos se formen.

Comparison of Choriocapillaris Flow Measurements between Two Optical Coherence Tomography Angiography Devices.

PURPOSE: To evaluate choriocapillaris (CC) perfusion in healthy subjects using 2 different optical coherence tomography angiography (OCT-A) devices. PROCEDURES: Macular OCT-A imaging (36 eyes of 36 subjects) was performed using Optovue AngioVue and Zeiss AngioPlex devices. CC decorrelation signal index was assessed, and CC data were analyzed regarding intra-device variability, inter-device correlation, age, signal strength, and fields of view. RESULTS: The intra-device variability of CC measurements in the 3 × 3 mm2 field was 5.3 and 2.6% (Angiovue and Angioplex, coefficients of variation; 6 × 6 mm2: 8.0 and 2.8%, respectively). Mean CC decorrelation signal index in 3 × 3 mm2 was 104.3 ± 6.7 (Angiovue) and 81.3 ± 9.2 (Angioplex) (6 × 6 mm2: 95.6 ± 8.1, 81.1 ± 6.5) with high correlation between both devices (3 × 3 mm2: p = 0.0053; 6 × 6 mm2: p = 0.0139). CC decorrelation signal index in 3 × 3 mm2 was significantly higher in subjects aged ≤58 years compared to subjects aged ≥59 years (Angiovue: 107.3 ± 3.6, 101.3 ± 7.7, p = 0.0156; Angioplex: 84.6 ± 7.6, 78.0 ± 9.5, p = 0.0371). Signal strength was 64.6 ± 8.9 (Angiovue) and 9.5 ± 0.8 (Angioplex). CONCLUSION: Both devices showed low intra-device variability and a high inter-device correlation. CC decorrelation signal index was negatively correlated with advancing age.

Response of vascular pigment epithelium detachment due to age-related macular degeneration to monthly treatment with ranibizumab: the prospective, multicentre RECOVER study.

PURPOSE: To assess the effects of monthly intravitreal ranibizumab injections in patients with vascularized pigment epithelium detachment (vPED) secondary to age-related macular degeneration (AMD). METHODS: A total of 40 patients were prospectively observed and treated monthly with 0.5 mg ranibizumab injections (ClinicalTrials.gov Ident. NCT00976222). Inclusion criterion was a treatment-naïve vPED lesion with a minimum height of ≥200 µm. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated at all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and quarterly. Lesions were differentiated between serous vascular PED (svPED, group A, 29 patients) and fibrovascular PED (fPED, group B, 11 patients). Primary outcome was the effectivity of continuous monthly treatment during a 12-month period as measured in change in BCVA. Secondary outcomes were change in PED height and PED greatest linear diameter (GLD). Further secondary outcomes were the presence of subretinal fluid and prognostic markers of an impending retinal pigment epithelium (RPE) tear: PED lesion height and diameter, ratio of choroidal neovascularization (CNV) size to PED size, hyperreflective lines in near-infrared images, microrips and subretinal cleft. RESULTS: Mean BCVA was 56.9 ± 11.5 letters (A: 55.4 ± 10.8; B: 59.1 ± 13.4) at baseline and 55.1 ± 15.9 (A: 53.7 ± 17.0; B: 58.9 ± 12.7) at 12-month follow-up. Excluding the RPE tear patients, the svPED group showed an increase in BCVA from 56.1 ± 10.3 at baseline to 62.4 ± 10.2 at 12-month follow-up (p = 0.048). Best-corrected visual acuity in patient who developed a RPE tear was 55.8 ± 12.5 at baseline and 37.1 ± 14.9 at 12-month follow-up. The mean change in PED height was -242.1 µm ± 285.5 (A: -427.3 µm ± 299.7; B: -51.6 µm ± 99.5). The mean decrease in PED GLD was -471.8 µm ± 727.6 (A: -738.9 µm ± 788.2; B: -10.4 µm ± 185.6). In group A, 10 patients developed a RPE tear (25%) after a mean of 3.6 injections. No tear was documented in group B. Lesion height, ratio of CNV size to PED size and presence of hyperreflective lines differed significantly between patients with and without RPE tear development. CONCLUSION: Serous vascular PED lesions showed an improvement regarding BCVA and morphologic characteristics unless an RPE tear occurred. In fPED lesions, a functional and morphological stabilization was observed. Monthly ranibizumab injections are an effective treatment regarding the resorption of subretinal fluid in vPED due to AMD. Patients should be screened for the presence of morphologic risk factors for RPE tear development before and during treatment.

Exploring choriocapillaris under reticular pseudodrusen using OCT-Angiography.

PURPOSE: To evaluate if choriocapillaris (CC) vessel density and CC decorrelation signal index are compromised in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCT-A). METHODS: Decorrelation values in OCT-A CC images of 20 RPD patients were measured in the outer superior and the outer inferior sector of the EDTRS grid and compared to age-matched healthy controls. CC vessel density and CC decorrelation signal index were measured within a 30 µm and a 10 µm OCT-A CC slab. CC data were correlated to number of RPD lesions, predominantly present RPD stage, predominantly present RPD type, retinal area affected by RPD and choroidal thickness (CT). RESULTS: CC vessel density and CC decorrelation signal index decreased in correlation to advancing age in healthy subjects particularly in subjects older than 60 years (CC vessel density: 30 µm: p=0.0019; 10 µm: p=0.0014; CC decorrelation signal index: 30 µm: p=0.0005; 10 µm: p=0.0003). In the RPD group, CC vessel density (outer superior sector, 10 µm: 98.299) and CC decorrelation signal index (89.07) were significantly reduced compared to controls (99.203, p=0.0002; 98.09, p=0.0010). The number of RPD lesions was correlated to a reduced CC vessel density (30 µm: p=0.0355) but not to changes in CC decorrelation signal index. No correlations were found between CC parameters and either RPD stage, RPD type, size of RPD affected area or CT. CONCLUSIONS: OCT-A reveals a distinct reduction in CC vessel density and CC decorrelation signal index in eyes affected by RPD, which emphasizes the relevance of the CC layer in RPD pathogenesis.

Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring.

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.