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Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD)., Methods: The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA; 2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection., Results: In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes., Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye., Competing Interests: Competing interests: The Department of Ophthalmology, Kepler University Clinic, Johannes Kepler University has received a research grant from Nidek. ASME has received lecture fees from Nidek., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To investigate the impact of antiangiogenic monotherapy and photodynamic therapy (PDT) as add-on strategy on retinal morphology, and to analyse prognostic biomarkers for visual outcome and retreatment frequency in neovascular age-related macular degeneration (nAMD)., Methods: 255 patients participating in the MONT BLANC study were evaluated. Patients were randomised to receive as-needed ranibizumab monotherapy or combination therapy (verteporfin PDT and ranibizumab). Outcome measures included visual acuity (VA), retinal morphology assessed by optical coherence tomography and retreatment frequency., Results: The proportion of scans showing intraretinal cysts (IRC) or subretinal fluid (SRF) decreased more intensively in the combination than in the monotherapy group. Pigment epithelial detachments (PED) decreased significantly only in the combination group. Patients with IRC presented the lowest initial VA, and IRC had the strongest negative predictive value for functional improvement in both groups. SRF showed a predictive value for a higher number of ranibizumab injections (combination, +0.9; monotherapy, +0.8) and a higher number of PDT treatments in the combination group (+0.3). PED was associated with a higher number of ranibizumab injections only in the monotherapy group (+1.2)., Conclusions: Combination and monotherapy showed a distinct response pattern for morphological parameters in nAMD. IRC was the only relevant prognostic parameter for functional outcome., Trial Registration Number: NCT00433017., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: To evaluate changes in the distribution and morphology of intraretinal microexudates and hard exudates (HEs) during intravitreal anti-vascular endothelial growth factor therapy in patients with persistent diabetic macular edema., Methods: Twenty-four patients with persistent diabetic macular edema after photocoagulation were investigated in this prospective cohort study. Each eye was assigned to a loading dose of three anti-vascular endothelial growth factor treatments at monthly intervals. Additional single treatments were performed if diabetic macular edema persisted or recurred. Intraretinal exudates were analyzed over 6 months using spectral domain optical coherence tomography (SD-OCT) and fundus photography., Results: Before treatment, microexudates were detected by SD-OCT as hyperreflective foci in 24 eyes, whereas HEs were seen in 22 eyes. During therapy, HE increased significantly in number and size. This was accompanied by accumulation of microexudates in the outer retina. Enlargement of hyperreflective structures in SD-OCT was accompanied by enlargement of HE at corresponding fundus locations. A rapid reduction in diabetic macular edema was seen in all patients, but to varying degrees. Patients with hemoglobin A1c levels <7% and serum cholesterol <200 mg/dL formed fewer HEs and featured more edema reduction and visual acuity gain., Conclusion: Diabetic macular edema reduction during intravitreal anti-vascular endothelial growth factor therapy was accompanied by dynamic rearrangement of intraretinal exudates at corresponding locations in fundus photography and SD-OCT. Intraretinal aggregates of microexudates detectable as hyperreflective foci by SD-OCT may compose and precede HE before they become clinically visible.

Purpose: To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis., Design: Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE])., Participants: A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy., Methods: Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol., Main Outcome Measures: The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT., Results: During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF., Conclusions: There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine precisely the mean change in refractive power induced by treatment in patients with diabetic macular edema (DME)., Design: Prospective, randomized study., Participants: Fifty eyes of 50 consecutive patients with clinically significant macular edema receiving all 3 types of current state-of-the-art treatment with intravitreal antiedematous substances (ranibizumab, bevacizumab, or triamcinolone)., Methods: Patients were followed up at monthly intervals and were treated following a standardized pro re nata regimen according to protocol. Best-corrected visual acuity (BCVA) was determined by certified visual acuity examiners. The refractive power of the treated eyes was determined using a push-plus technique. The change in refraction between baseline and the visit when the macula was completely dry or when the central subfield thickness (CST) measured by optical coherence tomography had reached the thinnest level was analyzed., Main Outcome Measures: Spherical equivalent refraction (SER) and CST., Results: Fifty eyes of 50 patients received intravitreal therapy using ranibizumab (n = 11), bevacizumab (n = 20), or triamcinolone (n = 19). Mean BCVA was 0.33±0.23 logarithm of the minimum angle of resolution (logMAR) and mean CST was 492±130 μm. The mean SER was 0.41±2.06 diopters (D) at baseline. The BCVA at the time of optimal retinal morphologic features was 0.24±0.2 logMAR, mean CST was 300±78 μm, and mean change in SER was -0.01±0.46 D. Changes is BCVA and CST were statistically significant (P < 0.0001), but the SER change was not (P = 0.824)., Conclusions: Appropriate spectacle correction can be prescribed to patients with DME any time during ongoing therapy using antiedematous substances because resolution of retinal thickening is not associated with an increased risk of a myopic shift., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema., Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy., Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 ± 0.28 to 0.39 ± 0.3 (P = 0.018) and 0.71 ± 0.53 to 0.56 ± 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti-vascular endothelial growth factor therapy from 0.59 ± 0.29 to 0.49 ± 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 ± 0.65 to 0.90 ± 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease., Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.

Purpose: To evaluate the effect of repeated intravitreal injections of bevacizumab (Avastin(®)) in patients with proliferative diabetic retinopathy and persistent new vessels after panretinal photocoagulation., Methods: In this prospective study we investigated 11 eyes of 10 diabetic patients with persistent new vessels after previous complete panretinal photocoagulation. Complete ophthalmological examinations were performed at baseline and during monthly follow-up visits until the final follow-up at 6 months. Colour fundus photography, fluorescein angiography (FA) and macular optical coherence tomography (OCT) were performed. The area of leakage (mm²) found in the FA was used to demonstrate the effect of bevacizumab on retinal new vessels. Patients received 1.0 mg of intravitreal bevacizumab at baseline and at each of the monthly follow-up visits when reappearance of retinal new vessels was documented., Results: At the 1-week follow-up visit, 73% of the treated eyes showed complete regression of retinal new vessels. Eight eyes were assigned to retreatments at the 3-month follow-up because of the reappearance of retinal new vessels. After 6 months, 36% of the eyes were found to have reappearance of retinal new vessels. The retreatment rate was 1.9 ± 0.7 and the mean interval to retreatment was 2.9 ± 1.0 months. The mean leakage area decreased from 7.2 ± 2.6 mm² at baseline to 1.2 ± 0.9 mm² at the final follow-up visit. BCVA increased from 59.2 ± 14.6 Early Treatment Diabetic Retinopathy Study (ETDRS) score (range 40-80) to 70.7 ± 8.5 at the final visit (p = 0.017)., Conclusion:   Intravitreal bevacizumab led to a significant reduction of retinal new vessels for a mean period of 2.9 months. A 3-monthly retreatment regime might be a valid method to control retinal new vessels in diabetic patients with persistent new vessels., (© 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.)

Purpose: To evaluate long-term morphologic and functional changes after intravitreal ranibizumab in avascular pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD)., Patients and Methods: Interventional, prospective case series; the first group of six patients received three and the second group of six patients received six intravitreal injections of ranibizumab (0.5 mg) at monthly intervals. Outcome measures included the change of PED and retinal volume as determined by spectral domain optical coherence tomography (Cirrus), best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), and macular sensitivity using microperimetry (MP-1; Nidek Co. Ltd)., Results: The mean baseline PED volume of 1.33 mm3 decreased significantly by 42% at month 6 (-0.55 mm3, P<0.05). Compared to baseline no significant change was observed at months 9 and 12. BCVA, retinal volume, and macular sensitivity remained stable during the entire follow-up. In one case a tear of the retinal pigment epithelium was observed after five injections with a consequent decrease of BCVA of four lines., Conclusion: Treatment with intravitreal injections of ranibizumab may temporarily decrease the volume of avascular PED secondary to AMD, however this effect was not maintained over the 1-year study period. The treatment was ineffective for improving retinal function as measured with BCVA and microperimetry.

Aim: To quantify and correlate the morphological and functional effects of the recommended loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration (AMD)., Methods: In a prospective, interventional clinical trial, 29 consecutive patients (29 eyes) with choroidal neovascularisation secondary to AMD received three initial monthly intravitreal injections of ranibizumab. During this loading regimen, best corrected visual acuity (BCVA) and microperimetry (MP) testing, as well as optical coherence tomography and fluorescein angiography (FA), were performed using a standardised protocol and the results correlated., Results: Significant morphological and functional therapeutic effects were observed as early as 1 week following the first treatment. Throughout the loading-dose period, central retinal thickness, including intraretinal cysts and subretinal fluid, decreased fast and significantly (p<0.01); pigment epithelial detachment resolved less rapidly. The mean leakage area by FA decreased (p<0.01) and retinal function (BCVA and MP) increased significantly (both p<0.01). However, the change in morphology and function was only significant between baseline and week 1. There was no significant additional morphological or functional benefit following the second and third injection., Conclusion: The initial administration of intravitreal ranibizumab in neovascular AMD induced a significant effect on intra- and subretinal fluid and visual function; subsequent injections had a less pronounced effect. It remains to be determined whether this loading regimen should be mandatory in all patients or if a single dose regimen would lead to a comparable functional and morphological retinal improvement.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in adults aged over 50 years in developed countries. Until recently, argon laser photocoagulation and photo-dynamic therapy (PDT) were the only treatments available for the neovascular form of AMD. The introduction of new intravitreally injectable inhibitors of vascular endothelial growth factor (VEGF) revolutionized the management of the wet form. Pegaptanib was the first anti-VEGF agent to be approved by the US Food and Drug Administration (FDA) for use in neovascular AMD. The VISION study showed that patients receiving pegaptanib lost vision in a smaller rate than those treated with conventional care. Bevacizumab is a full-length recombinant humanized monoclonal antibody which binds to all isoforms of VEGF-A. It is licensed for the intravenous administration for the treatment of malignant solid tumors and is available for off-label use in the treatment of AMD-related CNV. Numerous retrospective studies have shown beneficial effects of bevacizumab in patients with neovascular AMD. Ranibizumab is a recombinant, humanized antibody antigen-binding fragment (Fab) that binds to all known active forms of VEGF-A. The US FDA approved ranibizumab for treatment of all subtypes of choroidal neovascularization secondary to AMD. VEGF trap is a pharmacologically engineered protein that binds VEGF with higher affinity than pegaptanib or ranibizumab and thus prevents VEGF binding to its cellular receptor offering a theoretically longer interval between necessary treatments. A number of studies have shown that OCT imaging allows identification of functionally relevant factors like subretinal fluid or retinal thickness, which are important for the establishment of optimized individual dosing regimen during anti-angiogenesis therapies., (Copyright 2010 S. Karger AG, Basel.)

Background: To evaluate the effect of systemic bevacizumab (Avastin) therapy on pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD) and to identify prognostic factors for PED regression and improvement in best corrected visual acuity (BCVA)., Study Design: Prospective uncontrolled pilot study., Methods: Nine patients (nine eyes) received three systemic bevacizumab treatments at 2 week intervals and were examined at baseline, weeks 1, 2, 4, 6 and month 3 by using optical coherence tomography (Stratus OC, Carl Zeiss Meditec, Dublin, California, USA). Changes in maximum PED height and greatest linear diameter (GLD) were planimetrically analysed by using Adobe Photoshop CS and correlated with retinal morphological changes and changes in BCVA., Results: Systemic bevacizumab therapy was well tolerated. Mean maximum PED height decreased significantly by 21% as early as 1 week (-96 microm (SD 48.8), p<0.01). At 3 months follow-up, two PEDs resolved completely, mean maximum PED height decreased significantly by 39% (-179 microm (SD 178), p = 0.02) and mean PED GLD by 24% (-714 microm (SD 1010), p = 0.07). Mean BCVA improved significantly by week 2 (+8.7 letters (SD 5.7), p<0.01) and at 3 months with 12.7 letters (SD 6.4) (p<0.01)., Conclusion: In the examined nine patients, systemic bevacizumab therapy showed evidence for an effect on PED secondary to neovascular AMD in terms of a decrease in lesion height and diameter. A high PED at baseline was found to be a negative predictive factor for visual outcome.