In the real world, there are variable treatment strategies and therapeutic effects of anti-VEGF therapy in neovascular age-related macular degeneration (nAMD). To investigate mechanisms of fluid resolution in pretreated and treatment-naïve eyes, we aimed to compare treatment response through assessment of fluid types, distribution and volumes. 289 eyes of 289 real-world patients with active nAMD were included in a randomized phase III clinical trial (EudraCT-Number: 2019-003133-42). For this subanalysis, data from baseline and month 1 was collected in 285 eyes. All eyes received treatment at baseline, OCT imaging (Spectralis, Heidelberg Engineering, Germany) and standardized functional testing at both visits. Subretinal fluid (SRF), intraretinal fluid (IRF), pigment epithelial detachment (PED) were automatically quantified. Absolute and relative fluid resolution and BCVA changes were compared. Treatment-naïve eyes had higher IRF volumes before treatment and a higher reduction of IRF (p < 0.01), with no differences for SRF and PED. Accordingly, treatment-naïve patients had a significantly higher gain of BCVA with + 4.6 letters compared to + 1.2 letters (p < 0.01). Precise quantification and compartment distinctions of retinal fluid revealed treatment-naïve eyes showed greater resolution rates for IRF with consecutive significant visual improvement, suggesting that IRF dynamics are particularly relevant and volume-related, especially in the acute phase.

Purpose: To report macular vascular changes in two cases of retinal vasculopathy with cerebral leukodystrophy (RVCL). Observations: This report presents long-term follow-up findings in two sisters with RVCL, using conventional optical coherence tomography (OCT), widefield optical coherence tomography angiography (OCT-A), and ultra-widefield fluorescein angiography (UWF-FA). Ultra-widefield OCT angiography (UWF-OCT-A) was also employed during the most recent follow-up. Conclusions and importance: Several valuable monitoring tools, including UWF-FA and OCT-A, are essential for this rare disease. Ophthalmologists must be aware, as many RVCL patients first show isolated ocular findings detectable with OCT, and even earlier with UWF-OCT-A.

PURPOSE:To evaluate the effect of intravitreal aflibercept monotherapy on arterial and venous oxygen saturation, retinal vessel diameter and flicker response in patients with newly diagnosed specific subtypes of exudative maculopathy. METHODS:This prospective study included forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 9) and type 3 MNV (RAP, n = 11). All patients received three initial aflibercept 2mg/0.05ml injections (Eylea®) in monthly intervals (loading phase) and were subsequently treated until month 12. Measurements of arterial and venous oxygen saturation, vessel diameters and flicker response were performed using the Dynamic Vessel Analyzer (DVA; IMEDOS, Jena, Germany). Statistical analysis was performed on the total population at baseline, after loading dose and at the last follow-up visit. RESULTS:The arterial oxygen saturation was 94.01±2.14% and showed no change after loading dose (93.94±2.88%, p = 0.4; estimated difference [confidence interval] -0.38 [-1.24; 0.48]) and at the last visit (95.48±1.90%; p = 0.1; -1.29 [-0.34; 2.91]). The venous oxygenation during treatment was 78.49±6.93% at baseline, 80.94±7.71% after 3-monthly injections (p = 0.7; -0.43 [-2.72; 1.86]) and 80.56±7.33% at month 12 (p = 0.5; 1.07 [-2.10; 4.24). The arterial and venous vessel diameters were 94±22μm and 131±19μm at baseline, and remained unchanged following aflibercept loading dose and at the last follow-up visit (p-value: p = 0.5; 2.30 [-5.00; 9.59] p = 0.8; 0.59 [-3.17; 4.34]). During stimulation with flicker light, arterial diameter changed by +1.24±4.93% at baseline and remained stable at month 3 (+2.70±5.95%; p = 0.5; 1.43 [-2.54; 5.41]) while the change in venous diameter during flicker stimulation was +4.52±4.45% at baseline and +4.13±3.65% after loading dose (p = 0.4, 5.18 [1.73; 8.63]). CONCLUSION:During intravitreal aflibercept treatment oxygen saturation, vessel diameter and flicker response did not change in the total population of patients with specific subtypes of exudative maculopathy.

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

PURPOSE:To investigate the effects of vitrectomy (Vy) with or without same time cataract surgery and membrane plus internal limiting membrane peeling (MP+ILMP) on retinal oxygenation and choroidal volume and their role on postoperative outcome.METHODS:Thirty-two eyes were included in this prospective clinical study. All patients received 23 gauge Vy+MP+ILMP without endotamponade. Additional cataract surgery was performed in 14 patients. Follow-up visits were scheduled at day 1, week 1, month 1 and month 3. At each visit, best corrected visual acuity (BCVA) using ETDRS charts (except at day 1), oxygenation of retinal vessels using the Oxymap T1, and optical coherence tomography (OCT, Heidelberg Spectralis) was performed.RESULTS:Mean BCVA increased significantly from 73 ± 11 letters to 77 ± 7 letters at month 3 (p = 0.02). Mean central retinal thickness (CRT) decreased from 456 ± 84 µm at baseline to 418±58µm (p = 0.01 baseline versus month 3). In the cataract surgery group, CRT was higher at month 3 than in the group without (400 ± 58 µm versus 441 ± 51 µm; p = 0.007). There was no statistically significant difference in choroidal volume or oxygenation of retinal vessels between groups (additional cataract surgery versus vitrectomy alone). Oxygenation of retinal arteries tended to decrease at day 1 followed by an increase, but the changes did not reach the level of significance (p = 0.29 baseline versus month 3). Oxygenation of retinal veins increased significantly (p = 0.02 baseline versus month 1; p = 0.04 baseline versus month 3, accordingly). There was a significant negative correlation (Spearman correlation coefficient rs = -0.35, p = 0.047) between visual acuity and oxygenation of retinal veins at month 3. No statistically significant correlation was found between CRT and oxygenation of neither retinal arteries nor veins. Choroidal volume (CV) of the central mm did not change significantly during the study period (baseline: 0.203 ± 0.04 mm3 , median: 0.206, month 3: 0.205 ± 0.04 mm3 , p = 0.54). There was no statistically significant effect of choroidal volume at baseline on postoperative clinical outcomes (change in BCVA estimate [95% CI]: 7 [-76; 90], p = 0.86; change in CRT: 147 [-577; 871], p = 0.68).CONCLUSION:Oxygen saturation may affect the visual acuity outcome but not the CRT in patients after vitrectomy for epiretinal membrane. Choroidal thickness had no statistically significant influence on the study outcomes. Further studies are needed to evaluate if the measurement of retinal oxygenation may be helpful in the decision for surgery.

PURPOSE:To prospectively evaluate the outcomes of different subtypes of neovascular age-related macular degeneration during intravitreal aflibercept monotherapy. METHODS:Forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 11), or retinal angiomatous proliferation (RAP, n = 9) were included and followed for 12 months. All patients received intravitreal aflibercept monotherapy. RESULTS:Mean visual acuity at baseline in PCV was 67 ± 16 Early Treatment Diabetic Retinopathy Study letters (20/50 Snellen equivalent), in hCNV 55 ± 21 (20/80), in RAP lesions 64 ± 11 (20/50), and in PED 74 ± 7 (20/32). At Month 12, visual acuity in PCV was 66 ± 16 (20/50), in hCNV 69 ± 17 (20/40), in RAP 68 ± 12 (20/50), and in PED 69 ± 18 (20/40). At the 12-month follow-up, visual acuity improved or was stable (±5 letters from baseline) in 84% of eyes (37/44 patients), with hCNV showing the greatest mean visual acuity gain. Mean central retinal thickness in patients with PCV was 523 ± 251 µm, in hCNV 497 ± 171, in RAP lesions 573 ± 132, and in PED 541 ± 158 and decreased to 310 ± 91 µm in PCV, 323 ± 75 µm in hCNV, 357 ± 173 µm in RAP lesions, and 422 ± 150 µm in PED. The mean area of atrophy increased from 2.0 ± 3.6 mm2 at baseline to 4.6 ± 8.6 mm2 at Month 12 (mean difference [95% confidence interval] -0.8 [-8.5 to 7.0], P = 0.8), with the greatest atrophy in patients with PED at Month 12. CONCLUSION:All subtypes of neovascular age-related macular degeneration showed anatomical improvement and stabilization of visual function during intravitreal treatment.

Purpose: To evaluate morphologic and microvascular differences between eyes with and without subretinal fibrosis (SF) caused by neovascular age-related macular degeneration (nAMD). Methods: Patients with nAMD with a minimum history of 12 months of anti-VEGF treatment were prospectively included in this cross-sectional study. Patients were imaged using standard imaging, swept-source optical coherence tomography angiography for quantitative microvascular analysis and polarization-sensitive OCT as an ancillary method for automated SF segmentation. The presence of reticular pseudodrusen, hyperreflective foci (HRF), and outer retinal tubulation (ORT) were also evaluated. Results: Sixty eyes of 60 participants (37 female) with nAMD and a mean 3.1 (±2.7)-year history of anti-VEGF treatment were included, 20 (33%) of which were diagnosed with SF. Eyes with SF had a higher prevalence of ORT (P < 0.001) and a lower prevalence of HRF (P = 0.004) than eyes without SF. Fifty eyes were analyzed quantitatively for microvascular biomarkers. Eyes with SF had a larger greatest vascular caliber (P = 0.001) and greatest linear diameter (P = 0.042), a larger microvascular neovascularization (MNV) area (P = 0.026), larger vessel area (P = 0.037), higher number of vessel junctions (P = 0.025), longer total vessel length (P = 0.027), higher number of vessel endpoints (P = 0.007), and higher endpoint density (P = 0.047). Conclusions: This multimodal imaging approach demonstrated in vivo microvascular and morphological differences in eyes with and without SF. Eyes with SF tend to have larger MNV lesions with thicker vessels and are often associated with the presence of ORT. Translational Relevance: This study points out imaging biomarkers in patients with SF, which may help identifying high-risk patients.

The present study aims to investigate an automated qualitative and quantitative assessment system (Automated Quantification of After-Cataract [AQUA II]) of posterior capsule opacification (PCO) in high-resolution digital retroillumination images and consequently reduce observer bias and increase accuracy of PCO grading. A data set of 100 eyes with no to severe PCO was analysed. Ten eyes were consecutively photographed twice and ten images were rotated to give a total of 120 images for PCO assessment. Validity was determined by including subjective grading and repeatability was determined by evaluating the 20 additional images. Evaluation of posterior capsular opacification (EPCO), posterior capsule opacity (POCO) and AQUA I methods were included for comparative analysis of the data. The system developed proved to classify six types of PCO. Validity was confirmed by a Pearson correlation coefficient of r = 0.95 (EPCO r = 0.93; POCO r = 0.72 and AQUA I r = 0.94). Repeatability was better in AQUA II (95% confidence interval [CI] for mean difference: 0.5 ± 1.2) than in subjective grading (95% CI for mean difference: 0.6 ± 1.7), in EPCO grading (95% CI for mean difference: − 0.2 ± 1.5), in POCO grading (95% CI for mean difference: 1.6 ± 2.7) and in AQUA I (95% CI for mean difference: − 1.1 ± 1.9). AQUA II is a system that for the first time not only objectively quantifies PCO, but also qualitatively assesses PCO in an automated manner with texture classification. AQUA II showed an excellent validity and repeatability.

BACKGROUND:To evaluate the change in peripheral perfusion status in patients with retinal vein occlusion (RVO) during dexamethasone treatment.METHODS:Thirty-five eyes of patients with macular oedema due to either branch or central retinal vein occlusion were included. At baseline, patients were treated with an intravitreal dexamethasone implant (Ozurdex® ) and followed until month 6. Wide-field angiographies were classified as ischaemic and nonischaemic. Peripheral nonperfusion (PNP) was determined manually by calculating the percentage of nonperfusion area in relation to the total visible retina (ischaemic index).RESULTS:Thirteen eyes showed evidence of >10 disc area of PNP at baseline and were graded as ischaemic RVO. In nonischaemic eyes, the mean area of PNP was 0.3% at baseline, 0.6% after 1 month, 0.6% after 3 months and 0.6% after 6 months, respectively (p > 0.05). In ischaemic RVO, the ischaemic index was calculated to be 18% at baseline. One month after treatment, mean area of PNP was 16% and after 3 months was 19% (p = 0.8; p = 0.6). After retreatment, total PNP area was 18% (month 6; p = 0.9). During treatment, best-corrected visual acuity (BCVA) increased and central retinal thickness (CRT) decreased from baseline to final follow-up with no differences between nonischaemic/ischaemic RVO. A significant negative correlation between the total area of PNP and visual acuity was identified (r = -0.6; p = 0.04).CONCLUSION:Using 200° wide-field fluorescein angiography, the ischaemic index was shown to remain stable during dexamethasone treatment. This finding was consistent in ischaemic as well as in nonischaemic conditions.

PURPOSE:The purpose of this study was to identify quantitatively measurable morphologic optical coherence tomography (OCT) characteristics in patients with an acute episode of central serous chorioretinopathy (CSC) and evaluate their correlation to functional and psychological variables for their use in daily clinical practice.METHODS:Retinal thickness (RT), the height, area and volume of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the standardized procedures of the Vienna Reading Center. These morphologic characteristics were compared with functional variables [best-corrected visual acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry, fixation stability], and patients' subjective handicap from CSC using the National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25).RESULTS:Data from 39 CSC patients were included in this analysis. Three different SRF height measures showed a high negative correlation (r = -0.7) to retinal sensitivity within the central 9°, which was also negatively correlated with SRF area and volume (r = -0.6). The CS score and fixation stability (fixation points within 2°) showed a moderate negative correlation (r = -0.4) with SRF height variables. Comparison of the subjective handicap with morphological characteristics in spectral-domain (SD)-OCT showed SRF height had the highest correlation (r = -0.4) with the subjective problems reported and overall NEI VFQ-25 score.CONCLUSION:In conclusion, SRF height measured in SD-OCT showed the best correlation with functional variables and patients' subjective handicap caused by the disease and therefore seems to be the best variable to look at in daily clinical routine. Even though area and volume also show a correlation, these cannot be so easily measured as height and are therefore not suggested for daily clinical routine.

Purpose: To assess the efficacy of a combination therapy of intravitreal ranibizumab together with a dexamethasone implant in comparison with ranibizumab monotherapy in neovascular age-related macular degeneration.Methods: Forty eyes of recurrent or persistent neovascular age-related macular degeneration were included in this prospective study. Patients were randomly assigned to two groups. Based on a pro re nata treatment regimen, the first group received intravitreal ranibizumab monotherapy (IVM). The second group received a combination of intravitreal dexamethasone implant and ranibizumab (intravitreal combination [IVC]) at baseline and was retreated with ranibizumab as needed. A second dexamethasone implant was allowed for retreatment after at least 6 months. Retreatment criteria included evidence of subretinal fluid, cystoid macular edema or new hemorrhage, and/or a visual acuity decrease of 5 Early Treatment Diabetic Retinopathy Study letters.Results: During 12 months, a mean of 7.95/5.5 (IVM/IVC; P = 0.042) retreatments were given. The median time until first retreatment differed significantly between the groups (P = 0.004). Functional variables could be maintained in both groups with no differences between them. Visual acuity changed from 62 letters at baseline to 67 at Month 12 in the IVM and remained stable at 68 letters in the IVC group (P = 0.68); macular sensitivity changed from 6.95 dB to 7.01 dB in IVM and from 7.24 dB to 7.12 dB in IVC (P = 0.4). Central retinal thickness decreased, however, with no difference between the groups (P = 0.38). In the IVM/IVC group, 11/12 (55/60%) patients were phakic at the time of study entry. One (9%) patient from the IVM and 4 (33%) from the IVC group were referred to cataract surgery after study completion (P = 0.4).Conclusion: This pilot study indicates combined therapy to delay retreatment in patients with persistent/recurrent neovascular age-related macular degeneration and an overall reduction in required ranibizumab retreatments compared with ranibizumab monotherapy with consistent functional outcomes.