scholarly journals Refractory neovascular age-related macular degeneration: time-dependent changes of central retinal thickness with anti-VEGF treatment

Author(s):  
Marta Zola ◽  
Elisa D’Alessandro ◽  
Mohamed Sherif ◽  
Audrey Nguyen ◽  
Dominique De Azevedo ◽  
...  

Abstract Purpose To assess the influence of time interval since last injection and time from baseline on central retinal thickness (CRT) in neovascular age-related macular degeneration (nAMD) with fluid refractory to monthly anti-VEGF treatment. Methods This retrospective study included nAMD eyes with incomplete response to anti-VEGF defined by the presence of intra- or subretinal fluid on optical coherence tomography despite maximal (monthly) anti-VEGF dosing. The outcome measure was CRT, and two time variables (time from last injection ant time from baseline) were the independent factors included in the individual correlation analyses. In addition, an association analysis was performed. Results Sixty eyes of 56 patients (67.9% females, mean age: 78.7 ± 6.8 years) were included with a mean included time period of 35.6 months. A significant positive correlation between CRT and the time from last injection occurred in 24 (40%) and 25 (42%) eyes by univariate and multivariate analysis, respectively. Time from baseline was significantly correlated with CRT in 29 (48.3%) and 30 (50%) eyes by univariate and multivariate analysis, respectively. This correlation was positive in 12 (20%) and negative in 18 eyes (30%). No association with such correlation was found. Conclusion So-called refractory nAMD frequently shows a correlation of CRT with the interval in days from the preceding anti-VEGF injection, revealing that there is a subgroup of short-term responsiveness of the residual fluid. Moreover, slower CRT changes may occur over the years, either decrease or increase. In case of a slow CRT increase, this might require a diagnostic workup and therapeutic change.

2021 ◽  
pp. 112067212110378
Author(s):  
Francesco Ciucci ◽  
Giuseppina Ioele ◽  
Antonio Bardocci ◽  
Giorgio Lofoco ◽  
Barbara Antonelli ◽  
...  

Purpose: This is a retrospective, single-center, non randomized interventional real life study, investigating the correlation between variability of central retinal thickness (CRT) and functional outcomes during 2 years of anti-VEGF therapy in patients treated for neovascular age related macular degeneration (nAMD). Background: CRT fluctuations can depend on various factors such as the correct timing of injections, the therapeutic algorithm, and the number of injections (NI) performed; it is important to understand if CRT fluctuations are responsible for worse visual outcomes and consequently to identify the correct ways to avoid or reduce them. Methods: Forty-one patients were treated for nAMD with aflibercept: 0.5 mg intravitreal aflibercept was administered every 4 weeks during the first 3 months, then bimonthly over the first year, and after the first year adopting a PRN regimen. Standard deviation of CRT (CRT/SD), BCVA, and NI were recorded. Correlation studies were performed by Pearson’s test, Ancova, and Principal Component Analysis. Results: A negative correlation was found between CRT/SD and final BCVA. In patients who lost more than 15 letters, CRT/SD mean was significantly higher in comparison with patients who lost less than 15 letters. Patients with final BCVA >65 letters showed lower CRT/SD values compared to patients with final BCVA ⩽65 letters. Multivariate analysis confirmed that in patients with higher baseline BCVA, improvement of BCVA was correlated to NI, and lower values of CRT fluctuations were observed. Conclusions: CRT fluctuations, even after an appropriate NI given per year, significantly influence BCVA; a proactive treatment algorithm appears crucial when treating patients with nAMD.


2021 ◽  
Vol 18 (2) ◽  
pp. 222-227
Author(s):  
M. V. Budzinskaya ◽  
A. A. Plyukhova

Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16]. 


2018 ◽  
Vol 103 (5) ◽  
pp. 623-629 ◽  
Author(s):  
Chikako Hara ◽  
Taku Wakabayashi ◽  
Hiroshi Toyama ◽  
Yoko Fukushima ◽  
Kaori Sayanagi ◽  
...  

PurposeTo investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD).DesignRetrospective, interventional, consecutive case series.MethodsThree hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm.ResultsNineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 non-responders.ConclusionIntravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability.


2017 ◽  
Vol 10 (3) ◽  
pp. 67-73
Author(s):  
Sergey A Korotkikh ◽  
Evgeniy V Bobykin

Purpose. To assess mean changes in visual acuity, central retinal thickness and macular volume as well as to determine the duration of clinical choroidal neovascularization inactivity after single aflibercept injection in neovascular age-related macular degeneration (nAMD) patients switched from ranibizumab (preliminary date). Methods. Open-label prospective study. The study enrolled 23 patients with nAMD previously treated with ranibizumab. Results. Mean age of patients was 70.5 years, 16 were women. Mean number of ranibizumab injections given prior to switching to aflibercept was 8.7. After single aflibercept inravitreal injection mean visual acuity has significantly improved from 0.40 to 0.47 Snellen chart. Mean central retinal thickness has significantly reduced from 323.1 to 246.9 μm and mean macular volume has significantly reduced from 7.71 to 6.74 mm3. Duration of choroidal neovascularization (CNV) inactivity was 2.91 months. Conclusion. Single aflibercept intravitreal injection has resulted in significant visual gain as well as in significant central retinal thickness (CRT) and macular volume reduction. This provides evidence of aflibecept efficacy in nAMD patients previously treated with anti-VEGF. Duration of CNV inactivity provides clinical data supporting aflibercept injection every 8 weeks in nAMD patients. (For citation: Korotkikh SA, Bobykin EV. Our experience in visual functions' improvement in patiens with “wet” age-related ­macular degeneration at switching from one anti-VEGF agent to another. Ophthalmology Journal. 2017;10(3):67-73. doi: 10.17816/OV10367-73).


2021 ◽  
pp. 116-123
Author(s):  
Leonie F. Keidel ◽  
Benedikt Schworm ◽  
Siegfried G. Priglinger ◽  
Jakob Siedlecki

Nonresponse of neovascular age-related macular degeneration (nAMD) to anti-vascular endothelial growth factor (anti-VEGF) therapy can often be attributed to misdiagnosis, and pathologies mimicking AMD might require different therapeutic concepts. In the following, we want to outline a case of presumed nAMD which revealed to be pachychoroid neovasculopathy (PNV) and was successfully treated by the addition of spironolactone. A 67-year-old female patient was referred for nonresponse of nAMD on her left eye after 29 intravitreal injections of aflibercept with no complete resolution of subretinal fluid. On fundoscopy, both maculae presented with pigment epithelium alterations, while the left eye showed subretinal fluid on optical coherence tomography (OCT) with an associated pigment epithelium detachment, which revealed to contain a neovascular network on OCT angiography. There was faint leakage on fluorescence (FAG) and indocyanine green angiography (ICGA) and some focal vascular dilation of the neovascular network on ICGA. Due to the absence of Drusen on any eye, a thick choroid, and the presence of a gravitational tract on blue autofluorescence (BAF), chronic central serous chorioretinopathy with a choroidal neovascularization, defined as PNV in the pachychoroid disease was diagnosed. Upon the addition of spironolactone to anti-VEGF treatment, choroidal thickness significantly decreased, and subretinal fluid resolution was observed and maintained for the first time. In conclusion, PNV should be ruled out in cases of presumed nAMD nonresponding to anti-VEGF. In these cases, a combination therapy of anti-VEGF and mineralocorticoid antagonists can facilitate fluid resorption.


2019 ◽  
Vol 30 (3) ◽  
pp. 543-549 ◽  
Author(s):  
Corinne Fulcher ◽  
Charlotte A Hazel ◽  
Ian Pacey ◽  
Hasan Ali ◽  
Faruque D Ghanchi

Background/objectives: There is a significant variation in the way neovascular age-related macular degeneration patients respond to anti–vascular endothelial growth factor treatment. Both the financial and time cost of treatment are significant. As such, being able to predict patient response to treatment is valuable. Subjects/methods: 72 eyes treated with intravitreal aflibercept were retrospectively included in analysis. For each subject, visual acuity (letters) and central retinal thickness (µm) at baseline, second, third and fourth visits, as well as 12-month visits, were collated; a plot of visual acuity versus time was generated and a slope of the first three (slope3) and first four (slope4) visits was calculated. Differences in visual acuity at each visit compared to baseline were determined, as well as percentage differences in central retinal thickness at each visit compared to baseline. Lesion sub-type and the presence of fluid and haemorrhage were also recorded. Results: The average change in visual acuity over 12 months was +3.2 ± 13.4 letters with 91.2% of patients losing <15 letters. Slope4 was the only significant predictive factor for ‘visual acuity change over 12 months’ ( p < 0.001). Change in central retinal thickness, lesion sub-type, haemorrhage at baseline and the location of fluid at baseline were not useful predictive factors in long-term outcome. Conclusion: Aflibercept is an effective treatment option for neovascular age-related macular degeneration; however, the long-term response should not be predicted until at least three loading dose injections have been given. Visual acuity measures at each visit should be examined, as it is the trend in visual acuity across the first four visits (slope4) rather than the difference in visual acuity between two visits that is the predictive factor.


2020 ◽  
pp. 112067212096874
Author(s):  
María Cinta Puell ◽  
Francisco Javier Hurtado-Ceña ◽  
María Jesús Pérez-Carrasco ◽  
Inés Contreras

Purpose/Aim: To examine whether central retinal thickness (CRT) is related to mesopic visual acuity (VA) and low luminance deficit (LLD, difference between photopic and mesopic VA) in eyes with early and intermediate age-related macular degeneration (AMD). Materials and Methods: In a cross-sectional study, 50 pseudophakic subjects older than 63 years were divided into three groups (no AMD, early AMD and intermediate AMD). Spectral domain optical coherence tomography (SD-OCT) was used to measure CRT in the 1 mm-central-area. Best-corrected distance VA was measured under photopic or mesopic luminance conditions and LLD calculated. Subjects were stratified by VA impairment to compare CRTs across these groups. Relationships were examined by stepwise multiple linear regression. Results: No significant differences in mean CRT, photopic and mesopic VA or LLD were detected between the groups no AMD, early AMD and intermediate AMD. However, mean CRTs were 20 microns and 18 microns thicker in the eyes with impaired mesopic VA (> 0.3 logMAR) and impaired LLD (⩾ 0.3 logMAR) compared to the eyes with non-impaired VA or LLD respectively (both p < 0.01). CRT and mesopic pupil size were independent predictors of mesopic VA ( p  = 0.001). CRT emerged as the only independent predictor of LLD ( p  = 0.004). Conclusions: Increased CRT was linked to worse retinal function when measured under mesopic conditions in eyes without AMD and eyes with early to intermediate AMD. SD-OCT imaging combined with VA measurements under low luminance conditions could be a useful tool to detect early AMD.


2016 ◽  
Vol 7 (1) ◽  
pp. 230-236 ◽  
Author(s):  
Hisashi Matsubara ◽  
Ryohei Miyata ◽  
Maki Kobayashi ◽  
Hideyuki Tsukitome ◽  
Kengo Ikesugi ◽  
...  

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kyung Tae Kim ◽  
Ju Byung Chae ◽  
Seungheon Lee ◽  
Eoi Jong Seo ◽  
Dong Yoon Kim

Abstract Background To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. Methods Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. Results Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. Conclusions Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.


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