Imaging the Area of Internal Limiting Membrane Peeling after Macular Hole Surgery.

Background: The aim of this study was to compare en-face optical coherence tomography (OCT) imaging and confocal scanning laser ophthalmoscopy (cSLO) imaging at different wavelengths to identify the internal limiting membrane (ILM) peeling area after primary surgery with vitrectomy and ILM peeling for macular hole (MH). Methods: In total, 50 eyes of 50 consecutive patients who underwent primary surgery with vitrectomy and ILM peeling for MH were studied. The true ILM rhexis based on intraoperative color fundus photography was compared to the presumed ILM rhexis identified by a blinded examiner using en-face OCT imaging and cSLO images at various wavelengths. To calculate the fraction of overlap (FoO), the common intersecting area and the total of both areas were measured. Results: The FoO for the measured areas was 0.93 ± 0.03 for en-face OCT, 0.76 ± 0.06 for blue reflectance (BR; 488 nm), 0.71 ± 0.09 for green reflectance (GR; 514 nm), 0.56 ± 0.07 for infrared reflectance (IR; 815 nm) and 0.73 ± 0.06 for multispectral (MS). The FoO in the en-face OCT group was significantly higher than in all other groups, whereas the FoO in the IR group was significantly lower compared to all other groups. No significant differences were observed in FoO among the MS, BR, and GR groups. In en-face OCT, there was no significant change in the ILM peeled area measured intraoperatively and postoperatively (8.37 ± 3.01 vs. 8.24 ± 2.81 mm2; p = 0.8145). Nasal-inferior foveal displacement was observed in 38 eyes (76%). Conclusions: En-face OCT imaging demonstrates reliable postoperative visualization of the ILM peeled area. Although the size of the ILM peeling remains stable after one month, our findings indicate a notable inferior-nasal shift of the overall ILM peeling area towards the optic disc.

[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.

Current Perspectives on Type 3 Macular Neovascularization due to Age-Related Macular Degeneration.

BACKGROUND: The aim of this review was 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 into stages 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 studies in MNV3 suggest that the OCT biomarkers in intraretinal and subretinal fluids 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 neovascular AMD 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.

Sex differences and risk factors for bleeding in Alagille syndrome.

Spontaneous bleeds are a leading cause of death in the pediatric JAG1-related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non-invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex-specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non-invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.

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.

The impact of motion artifacts on quantitative optical coherence tomography angiography analysis in Parkinson's disease.

We have previously shown that OCTA imaging in PD patients can be challenging. Our data suggest that retinal perfusion is reduced in both plexuses in PD, which may serve as a noninvasive biomarker in the future. Yet, control of motion artifacts in OCTA measurements is critical in this motor-impaired cohort.

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.

Applicability of optical coherence tomography angiography (OCTA) imaging in Parkinson's disease.

To evaluate the significance of motion artifacts in optical coherence tomography angiography (OCTA) images of patients with Parkinson's disease (PD) and healthy controls. In this prospective, cross-sectional study subjects with medicated PD (ON) and healthy, age- and gender-matched volunteers were recruited. Participants underwent specific ophthalmological examinations, including OCTA. Angiograms of the superficial retinal capillary plexus were evaluated for the type and frequency of artifacts using a validated motion artifact score (MAS). A total of 30 PD patients (60 eyes), average disease duration of 9.61 ± 5.55 years, and 30 matched, healthy controls (60 eyes) were recruited. Twenty percent of all eyes had an eye disease, unknown to the participant, with a significant impact on OCTA results. After cleansing the dataset by excluding subjects with confounding ocular comorbidities 42 eyes of 28 PD patients and 53 eyes of 29 healthy controls were further evaluated. Overall MAS and all five subtypes of motion artifacts were comparable without significant differences between groups. OCTA can be used in treated PD patients (ON) without a significant increase in motion artifacts. Nevertheless, special attention should be paid to image quality during the acquisition of OCTA data, for which an experienced OCTA operator is useful.

Differential effects of high-intensity interval training (HIIT) on choriocapillaris perfusion in healthy adults and patients with type 1 diabetes mellitus (T1DM).

PURPOSE: To investigate the effects of a four-week high-intensity interval training (HIIT) on choriocapillaris (CC) perfusion in young healthy adults and type 1 diabetes mellitus (T1DM) patients. METHODS: Data of two HIIT studies with baseline to follow-up comparison were retrospectively analysed. Twenty healthy participants and twenty T1DM patients without clinical signs of diabetic retinopathy were included. All participants had performed a four-week all-out HIIT protocol with a total of 8 training sessions. Changes in physical fitness were assessed using power output at the individual aerobic lactate threshold (IANT). Optical coherence tomography angiography (OCTA) imaging was performed at baseline and follow-up. CC images were analysed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution. RESULTS: At baseline, CC OCTA revealed a lower and more heterogeneous intensity signal in T1DM eyes (mean intensity signal and standard deviation of signal intensity, p < 0.001). Percent of CC FD area was greater in T1DM eyes (p < 0.001). While T1DM patients showed greater improvement of exercise capacity at IANT than healthy controls (group×time p = 0.0403), CC FD area and standard deviation of intensity increased in healthy controls but not in T1DM patients (group×time p ≤ 0.029). Moreover, linear regression slopes of FD region distribution differed significantly at baseline and follow-up (p = 0.0002) in healthy individuals but not in T1DM patients. CONCLUSIONS: Effects of regular physical exercise performed as HIIT on CC perfusion were only seen in healthy participants, not in T1DM patients suggesting impaired CC adaptation in T1DM.

Four weeks of high-intensity interval training (HIIT) improve the cardiometabolic risk profile of overweight patients with type 1 diabetes mellitus (T1DM).

This study investigated the effects of a four-week HIIT intervention on the cardiometabolic risk profile, liver fat content, insulin requirement, hypoglycaemia, physical fitness, and health-related quality of life in patients with T1DM. A supervised exercise intervention with baseline to follow-up comparison between overweight (BMI = 28.6 ± 2.1 kg/m2) and normal weight (BMI = 23.2 ± 1.40 kg/m2) T1DM patients was performed. Eleven overweight (age = 40.7 ± 14.3 years) and 11 normal weight (age = 42.2 ± 15.5 years) T1DM patients performed a four-week, low-volume, all-out cycling HIIT (4-6 bouts, work/relief ratio 1:1) twice weekly. HIIT lowered low-density lipoprotein and uric acid levels in overweight patients by up to 10.5% (vs. normal weight, p≤0.0312). HbA1c, high-density lipoprotein, and triglyceride levels did not change in any of the groups. Participants' maximal exercise capacity and power output at individual anaerobic lactate threshold increased to an equal extend of up to 10% (p≤0.0002) in both groups. During the intervention, participants used fewer daily bolus insulin (-5.22 ± 12.80%) and less total units of insulin (-4.42 ± 10.20%, p≤0.023) compared to the pre-intervention period with no between-group difference. Overall, the average daily number of hypoglycaemias increased from 0.90 ± 0.56-1.08 ± 0.63 during the intervention (p = 0.033). SF-36 subscales showed higher scores after the intervention, with a significant improvement of "role limitations due to physical problems" (p<0.05) for both groups. We conclude that in T1DM, HIIT may exert beneficial effects on physical fitness, insulin requirement and health-related quality of life. Of note, beneficial HIIT effects on the cardiometabolic risk profile in T1DM may be larger in overweight T1DM patients.

Effect of high-intensity interval training in patients with type 1 diabetes on physical fitness and retinal microvascular perfusion determined by optical coherence tomography angiography.

OBJECTIVE: Physical activity may protect from ocular complications of diabetic retinopathy (DR). We investigated exercise training effects on the retinal microvasculature using optical coherence tomography angiography (OCTA) in type 1 diabetes (T1D). METHODS: Twenty T1D patients without clinical signs of DR performed four weeks of high-intensity interval training (HIIT). Cycle ergometry was used for determination of physical fitness. OCTA of the macula and optic nerve head was applied to analyze effects on the foveal avascular zone area, vessel density, vessel diameter index and fractal dimension of the superficial plexus, deep plexus and radial peripapillary capillaries. RESULTS: Large effects for improvement of physical fitness in terms of power output at the individual lactate threshold (+10.7 ± 11.3%, p < .001, ES = 0.95) and maximal power output (+8.2 ± 6.4%, p < .001, ES = 1.4) were detected. Participants presented a reduced increase in heart rate (HR) and lactate (LA) at given exercise intensities at follow-up (p ≤ .0176). Baseline OCTA revealed that HbA1c levels were associated with vessel density in the radial peripapillary capillary and the parafoveal superficial region (p ≤ .014). None of the analyzed microvascular parameters changed in response to the intervention. CONCLUSION: Despite favorable effects of HIIT on physical fitness of T1D patients, disease-specific training protocols may be needed to overcome potentially impaired retinal microvascular adaptations.

Correlation analysis of physical fitness and retinal microvasculature by OCT angiography in healthy adults.

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (ß = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies.

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.