The Geographic Atrophy Progression (GAP) study was designed to assess the rate of geographic atrophy (GA) progression and to identify prognostic factors by measuring the enlargement of the atrophic ...lesions using fundus autofluorescence (FAF) and color fundus photography (CFP).
Prospective, multicenter, noninterventional natural history study.
A total of 603 participants were enrolled in the study; 413 of those had gradable lesion data from FAF or CFP, and 321 had gradable lesion data from both FAF and CFP.
Atrophic lesion areas were measured by FAF and CFP to assess lesion progression over time. Lesion size assessments and best-corrected visual acuity (BCVA) were conducted at screening/baseline (day 0) and at 3 follow-up visits: month 6, month 12, and month 18 (or early exit).
The GA lesion progression rate in disease subgroups and mean change from baseline visual acuity.
Mean (standard error) lesion size changes from baseline, determined by FAF and CFP, respectively, were 0.88 (0.1) and 0.78 (0.1) mm(2) at 6 months, 1.85 (0.1) and 1.57 (0.1) mm(2) at 12 months, and 3.14 (0.4) and 3.17 (0.5) mm(2) at 18 months. The mean change in lesion size from baseline to month 12 was significantly greater in participants who had eyes with multifocal atrophic spots compared with those with unifocal spots (P < 0.001) and those with extrafoveal lesions compared with those with foveal lesions (P = 0.001). The mean (standard deviation) decrease in visual acuity was 6.2 ± 15.6 letters for patients with image data available. Atrophic lesions with a diffuse (mean 0.95 mm(2)) or banded (mean 1.01 mm(2)) FAF pattern grew more rapidly by month 6 compared with those with the "none" (mean, 0.13 mm(2)) and focal (mean, 0.36 mm(2)) FAF patterns.
Although differences were observed in mean lesion size measurements using FAF imaging compared with CFP, the measurements were highly correlated with one another. Significant differences were found in lesion progression rates in participants stratified by hyperfluorescence pattern subtype. This large GA natural history study provides a strong foundation for future clinical trials.
A remarkable proportion of neovascular age-related macular degeneration (nAMD) patients respond rather poorly to ranibizumab treatment, in spite of the minimum 4-week follow-up and treatment ...interval. Usually, retreatments are based on nAMD activity as evaluated by Spectral-domain Optical coherence Tomography (SD-OCT), biomicroscopic fundus examination and visual acuity changes. In this prospective pilot study, we aimed to study SD-OCT changes in a high-frequent follow-up manner (weekly (month 0-6), biweekly (month 7-12)) throughout the first year, which consequently led to intravitreal ranibizumab being administered up to biweekly. Best corrected visual acuity (BCVA) was already significantly improved at week 2. Central retinal thickness (CRT), intraretinal and subretinal fluid (SRF) were significantly improved from week 1 onwards. Half of the patients showed nAMD activity at week 2 or 3 and received the first retreatment earlier than 4 weeks after baseline injection. In total, 46% of retreatments were already applied 2 or 3 weeks after the previous treatment. Greater range of CRT and SRF fluctuation during follow-up was associated with lower final BCVA. Lower baseline BCVA and better SRF improvement at week 2 was associated with greater BCVA improvement. In conclusion, high-frequency SD-OCT follow-up provided a good option for adapting treatment in nAMD individually.
Linguatula serrata, the so-called tongue worm, is a worm-like, bloodsucking parasite belonging to the Pentastomida group. Infections with L. serrata tongue worms are rare in Europe. We describe a ...case of ocular linguatulosis in central Europe and provide molecular data on L. serrata tongue worms.
Background/aimsTo characterise the extension and progression of alteration of neurosensory layers following acute and chronic branch retinal artery occlusion (BRAO) in vivo using spectral-domain ...optical coherence tomography.MethodsIn this observational case series, eight eyes with acute BRAO and nine eyes with chronic BRAO were analysed using a Spectralis Heidelberg Retina Angiograph (HRA)+optical coherence tomography system including eye tracking. Patients with acute BRAO were examined within 36±5 h after primary event and at weekly/monthly intervals thereafter. Segmentation measurements of all individual neurosensory layers were performed on single A-scans at six locations in affected and corresponding non-affected areas. The thickness values of the retinal nerve fibre layer together with the ganglion cell layer (NFL/GCL), inner plexiform layer (IPL), inner nuclear layer together with outer plexiform layer (INL/OPL), outer nuclear layer (ONL), and photoreceptor layers together with the retinal pigment epithelium (PR/RPE) were measured and analysed.ResultsSegmentation evaluation revealed a distinct increase in thickness of inner neurosensory layers including the NFL/GCL (35%), IPL (80%), INL/OPL (48%) and mildly the ONL by 21% in acute ischaemia compared with corresponding layers in non-ischaemic areas. Regression of intraretinal oedema was followed by persistent retinal atrophy with loss of differentiation between IPL and INL/OPL at month 2. In contrast, the ONL and subjacent PR/RPE retained their physiological thickness in patients with chronic BRAO.ConclusionIn vivo assessment of retinal layer morphology allows a precise identification of the pathophysiology in retinal ischaemia.
Aims To determine the prevalence of polypoidal choroidal vasculopathy (PCV) in patients with presumed neovascular age-related macular degeneration (AMD) who were considered poor responders to ...ranibizumab. Methods Caucasian patients with suspected neovascular AMD, presumed to be choroidal neovascularisation, previously treated with ≥8 intravitreal injections of ranibizumab 0.5 mg (Lucentis; Novartis AG, Basel, Switzerland) administered as required during optical coherence tomography-guided dosing were retrospectively included. Eyes were categorised according to the time from injection 1 to injection 6 (group 1: <12 months; group 2: ≥12 months). Indocyanine green angiography (ICGA) was used to re-evaluate eyes for PCV. Suitable candidates received reduced-fluence photodynamic therapy/ranibizumab combination therapy supplemented by ranibizumab monotherapy, as required. Results 202 eyes were included (group 1: 73.8%; group 2: 26.2%). The prevalence of PCV in group 1 (21.5%) was significantly higher than in group 2 (3.8%; p=0.003). After initiation of combination therapy, 16 eyes with PCV received 3.1±2.5 ranibizumab injections/year vs 8.4±2.4 injections/year before initiation of combination therapy (p<0.001). Conclusions In Caucasian patients with presumed neovascular AMD, PCV prevalence is increased in eyes that respond poorly to ranibizumab monotherapy. ICGA improved PCV diagnosis in poor responders; combination therapy may be beneficial for eyes with PCV.
To analyze the effect of ranibizumab therapy on retinal and subretinal compartments in age-related macular degeneration and to compare the time course of compartment specific effects to visual ...function.
Prospective noncomparative case series.
Fourteen patients with changes in 3 major compartments owing to neovascular age-related macular degeneration.
Standard treatment with 3 monthly doses of intravitreal ranibizumab was performed. Eyes were examined at baseline and weeks 1, 4, and 12 using a standardized protocol. Manual segmentation was applied to all 128 B-scans contained in a macular raster scan (MRS).
Morphology and time course of different retinal and subretinal compartments.
High-definition optical coherence tomography and manual segmentation allowed for precise identification of volumes within individual compartments. All morphologic parameters responded positively to therapy, but demonstrated a specific time course. Subretinal fluid was identified as the most relevant factor for visual function, whereas changes in retinal and subpigment epithelial volumes did not correlate with the time course of functional rehabilitation.
Analysis of MRS identified a characteristic impact of therapy on retinal and subretinal morphology.
Purpose
To compare outcomes in patients with treatment‐naïve neovascular age‐related macular degeneration (nAMD) receiving ranibizumab treat and extend (TE) with those receiving ranibizumab pro re ...nata (PRN) in a clinical setting.
Methods
During this 12‐month retrospective, consecutive, comparative case series, patients received ranibizumab 0.5 mg according to a TE or PRN regimen. Monthly optical coherence tomography (OCT) evaluation was performed during the PRN regimen; retreatment criteria included recurrence of intra‐/subretinal fluid, or haemorrhages. During the TE regimen, initial treatment with 4‐week intervals was sequentially lengthened by 2 weeks until signs of choroidal neovascularization (CNV) activity recurred. Study end‐points included mean change in best corrected visual acuity (BCVA) and central retinal thickness (CRT), mean injection frequency and number of follow‐up visits attended.
Results
Baseline characteristics were similar between the TE (n = 70) and PRN (n = 70) groups. Mean change in BCVA from baseline to Month 12 was significantly greater in the TE group than the PRN group (+0.18 ± 0.17 versus +0.07 ± 0.20, p < 0.001). Mean change in CRT from baseline to Month 12 was greater in the TE group than the PRN group (−116 ± 132 versus −58 ± 157 μm, p = 0.019). The number of follow‐up visits attended was significantly higher in the PRN group than the TE group (11.9 ± 1.1 versus 8.6 ± 1.9, p < 0.001), while patients in the TE group received more injections during the study than those in the PRN group (8.6 ± 1.9 versus 6.0 ± 1.9, p < 0.001).
Conclusion
Ranibizumab administered using a TE regimen in treatment‐naïve patients with nAMD provided better visual outcomes with fewer clinic visits, compared with a PRN regimen.
BackgroundTreat and extend (TE) treatment regimens have the potential to reduce the treatment burden placed upon patients receiving ranibizumab for neovascular age-related macular degeneration ...(nAMD). This study aimed to analyse changes in best corrected visual acuity (BCVA) and anatomical parameters in patients switching from a pro re nata (PRN) to a TE regimen during routine clinical practice.MethodsRetrospective, consecutive, comparative case series of treatment-naïve patients who were initially treated with 0.5 mg ranibizumab according to a PRN schedule, and subsequently switched to a TE schedule (12-month follow-up).Results146 eyes from 134 consecutive treatment-naïve patients were included. Mean BCVA (decimal±SD) increased from 0.39±0.23 to 0.55±0.22 (p<0.001) during the PRN loading regimen, declining to 0.49±0.22 (p<0.001) during the PRN maintenance phase (mean duration 17 months; range 3–55). Following the switch to TE, BCVA improved to 0.55±0.23 and 0.56±0.24 by 6 and 12 months, respectively (p<0.001). Mean intraindividual variance in BCVA was higher during the PRN phase than at 12 months for TE (0.30±0.18 vs 0.09±0.08, respectively; p<0.001). After switching to TE, mean central retinal thickness decreased from 355±112 µm to 330±105 and 320±103 µm at 6 and 12 months, respectively (p<0.001). Mean number of visits per month was higher during PRN than TE periods (1.05±0.13 vs 0.73±0.18; respectively; p<0.001).ConclusionsA TE regimen can improve and stabilise patient outcomes in nAMD compared with PRN, with the potential to reduce the healthcare resource burden incurred from fixed monitoring requirements.
Purpose: To investigate dexamethasone intravitreal implant 0.7 mg (DEX implant) for the treatment of diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF) ...therapy and evaluate predictive factors. Methods: Two-centre retrospective interventional case series, including 40 eyes of 31 patients treated with DEX implant for at least 2 consecutive cycles. Results: Mean ± SD intervals from implantation to recurrence in the first (4.2 ± 1.0 months) and second cycles (4.0 ± 0.9 months) were not significantly different. Best corrected visual acuity improved significantly (p < 0.001) by 7.0 ± 8.4 letters from baseline to month 2, and by 5.1 ± 6.9 letters between the first and second cycles. Central retinal thickness reduction 2 months after implantation was greater after the first (–194 ± 172 µm) than the second cycle (–134 ± 150 µm). Ellipsoid zone-external limiting membrane (EZ-ELM) disruption score decreased from 1.39 ± 1.16 at baseline to 1.24 ± 1.16 (p = 0.0832) after cycle 1 and remained stable 2 months after cycle 2. Eyes with persisting severe EZ-ELM disruption (score >2, n = 10) 2 months after the first DEX implant showed significantly (p = 0.0153) smaller visual acuity (VA) gains than eyes with less severe (score ≤2) EZ-ELM disruption. Conclusion: Repeated intravitreal DEX injections with average intervals of 4 months are valuable in patients with DME refractory to anti-VEGF therapy. Disorganization of outer retinal layers (EZ-ELM) may predict smaller VA gains if evaluated after initial reduction of macular oedema.
AimsTo demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular ...oedema (DMO).MethodsA 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1–12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile.ResultsBoth T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1–12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information.ConclusionsT&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here.Trial registration numberNCT01171976.
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