Automated quantification of macular fluid in retinal diseases and their response to anti-VEGF therapy

2020 ◽  
pp. bjophthalmol-2020-317416
Author(s):  
Martin Michl ◽  
Maria Fabianska ◽  
Philipp Seeböck ◽  
Amir Sadeghipour ◽  
Bilal Haj Najeeb ◽  
...  
Keyword(s):  
Learning Algorithm ◽  
Subretinal Fluid ◽  
Diabetic Macular Oedema ◽  
Age Related Macular Degeneration ◽  
Deep Learning Algorithm ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Automated Quantification ◽  
Endothelial Growth Factor

AimTo objectively assess disease activity and treatment response in patients with retinal vein occlusion (RVO), neovascular age-related macular degeneration (nAMD) and centre-involved diabetic macular oedema (DME), using artificial intelligence–based fluid quantification.MethodsPosthoc analysis of 2311 patients (11 151 spectral-domain optical coherence tomography volumes) from five clinical, multicentre trials, who received a flexible antivascular endothelial growth factor (anti-VEGF) therapy over a 12-month period. Fluid volumes were measured with a deep learning algorithm at baseline/months 1, 2, 3 and 12, for three concentric circles with diameters of 1, 3 and 6 mm (fovea, paracentral ring and pericentral ring), as well as four sectors surrounding the fovea (superior, nasal, inferior and temporal).ResultsIn each disease, at every timepoint, most intraretinal fluid (IRF) per square millimetre was present at the fovea, followed by the paracentral ring and pericentral ring (p<0.0001). While this was also the case for subretinal fluid (SRF) in RVO/DME (p<0.0001), patients with nAMD showed more SRF in the paracentral ring than at the fovea up to month 3 (p<0.0001). Between sectors, patients with RVO/DME showed the highest IRF volumes temporally (p<0.001/p<0.0001). In each disease, more SRF was consistently found inferiorly than superiorly (p<0.02). At month 1/12, we measured the following median reductions of initial fluid volumes. For IRF: RVO, 95.9%/97.7%; nAMD, 91.3%/92.8%; DME, 37.3%/69.9%. For SRF: RVO, 94.7%/97.5%; nAMD, 98.4%/99.8%; DME, 86.3%/97.5%.ConclusionFully automated localisation and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. There is a specific anatomical response of IRF/SRF to anti-VEGF therapy in all diseases studied.

scholarly journals Association between visual acuity, lesion activity markers and retreatment decisions in neovascular age-related macular degeneration

Eye ◽  
2020 ◽  
Vol 34 (12) ◽  
pp. 2249-2256 ◽  
Author(s):  
Usha Chakravarthy ◽  
Natasha Pillai ◽  
Annie Syntosi ◽  
Lorna Barclay ◽  
Catherine Best ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
The United Kingdom ◽  
Anti Vegf ◽  
Age Related ◽  
Intraretinal Fluid ◽  
Endothelial Growth Factor ◽  
Clinic Visits

Abstract Background/objectives To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians’ decision to retreat with anti-VEGFs. Subjects/methods Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. Results In 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. Conclusions Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.

Pharmacotherapy for Choroidal Neovascularization Due to Uncommon Causes

2019 ◽  
Vol 24 (41) ◽  
pp. 4882-4895
Author(s):  
Christine P.S. Ho ◽  
Timothy Y.Y. Lai
Keyword(s):  
Effective Treatment ◽  
Choroidal Neovascularization ◽  
Case Series ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
Pathologic Myopia ◽  
Effective Treatment Option ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Background: Choroidal neovascularization (CNV) in adults is most commonly associated with neovascular age-related macular degeneration (AMD) and pathologic myopia. Though less common, CNV can also develop from other conditions such as uveitis, central serous chorioretinopathy, angioid streaks, intraocular tumors, hereditary chorioretinal dystrophies, or can be idiopathic in origin. If left untreated, CNV may cause visual loss because of exudation of intraretinal or subretinal fluid, retinal or subretinal hemorrhage, or fibrosis involving the macula. It is well known that one of the main drivers of angiogenesis in CNV development is vascular endothelial growth factor (VEGF) and therefore inhibitors of VEGF might be an effective treatment for CNV. Methods: The goal of this review is to provide an overview and summary in the use of pharmacotherapy especially anti-VEGF therapy, in the treatment of CNV due to uncommon causes. Results: Results from uncontrolled case series and controlled clinical trials have reported good efficacy and safety in using anti-VEGF agents including bevacizumab, ranibizumab, aflibercept and ziv-aflibercept in the treatment of CNV due to uncommon causes. Anti-VEGF has also been used in combination with verteporfin PDT and anti-inflammatory agents for treating CNV of various causes. Conclusion: Pharmacotherapy with anti-VEGF agents is an effective treatment option for CNV due to uncommon etiologies.

scholarly journals Comparing vision and macular thickness in neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion patients treated with intravitreal antivascular endothelial growth factor injections in clinical practice

2021 ◽  
Vol 6 (1) ◽  
pp. e000749
Author(s):  
Rajya L Gurung ◽  
Liesel M FitzGerald ◽  
Bennet J McComish ◽  
Alex W Hewitt ◽  
Nitin Verma ◽  
...  
Keyword(s):  
Growth Factor ◽  
Macular Oedema ◽  
Diabetic Macular Oedema ◽  
Age Related Macular Degeneration ◽  
Vein Occlusion ◽  
Age Related ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor ◽  
Median Change ◽  
Number Of Injections

ObjectiveTo compare the visual outcomes of intravitreal antivascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in a real-world setting.Methods and analysisRetrospective analysis of data from the Tasmanian Ophthalmic Biobank database. The median change in best-corrected visual acuity (BCVA) between baseline and 12 months post initiating intravitreal anti-VEGF treatment were compared between the three diseases. Final BCVA, central macular thickness (CMT), cumulative number of injections and overall predictors of change in BCVA and CMT were also determined.ResultsAt 12 months, change in BCVA was significantly different between nAMD, DMO and RVO cohorts (p=0.032), with lower median change for DMO (2 letters, range −5 to 20) than for RVO (11 letters, range −20 to 35). Likewise, CMT change was significantly different between the three cohorts (p=0.022), with a smaller reduction in CMT in DMO (−54 µm, range −482 to 50) than RVO patients (−137 µm, range −478 to 43; p=0.033). Total number of injections received (p=0.028) and final BCVA score (p=0.024) were also significantly different between the groups. Baseline BCVA was a negative predictor (p=0.042) and baseline CMT a positive predictor (p<0.001) of outcome. After adjusting for baseline BCVA and CMT, diagnosis of nAMD or RVO was a predictor of visual improvement compared with the DMO.ConclusionsAt the end of 12 months, nAMD and RVO cohorts had the greatest improvement in BCVA, however the final BCVA for DMO was significantly better than for nAMD.

scholarly journals Retinal Function determined by Flicker ERGs before and soon after Intravitreal Injection of Anti-VEGF Agents

2019 ◽  
Author(s):  
Gaku Terauchi ◽  
Kei Shinoda ◽  
Hiroyuki Sakai ◽  
Makoto Kawashima ◽  
Soichi Matsumoto ◽  
...  
Keyword(s):  
Macular Edema ◽  
Intravitreal Injection ◽  
Phase 1 ◽  
Retinal Function ◽  
Age Related Macular Degeneration ◽  
Implicit Time ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Abstract Background: To evaluate the retinal function before and soon after an intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: Seventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval® system was used to record 28 Hz flicker electroretinograms (ERGs) from the injected and non-injected eyes before (Phase 1, P1), within 2 hours after the injection (P2), and 2 to 24 hours after the injection (P3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests. Results: The amplitudes were not significantly different at the three phases. The implicit time of the injected eye was 31.2±3.2 msec at P1, and it was not significantly different at P2 (31.7±3.1 msec) but it was significantly longer at P3 (32.2±3.3 msec, P<0.01, ANOVA for both). The implicit time in the non-injected fellow eye was 30.5±3.3 msec at P1, and it was significantly longer at P2 (31.1±3.2 msec) and phase 3 (31.3±3.4 msec, P<0.01, ANOVA for both). Conclusions: The results indicate that an intravitreal anti-VEGF injection will increase the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection.

scholarly journals A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018289 ◽  
Author(s):  
William Hollingworth ◽  
Tim Jones ◽  
Barnaby C Reeves ◽  
Tunde Peto
Keyword(s):  
Longitudinal Study ◽  
Diabetic Macular Oedema ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
Geographical Variations ◽  
Anti Vegf ◽  
Age Related ◽  
Eye Disorders ◽  
Effective Care ◽  
Endothelial Growth Factor

ObjectivesHigh-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access.DesignLongitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations.SettingNational Health Service (NHS) care in England.PopulationPatients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders.InterventionsHigher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders.Main outcome measuresNational procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing.ResultsInjection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a ‘high use’ CCG were 9.08 times higher than in a ‘low use’ CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9).ConclusionsThe high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.

scholarly journals Retinal Function determined by Flicker ERGs before and soon after Intravitreal Injection of Anti-VEGF Agents

2019 ◽  
Author(s):  
Gaku Terauchi ◽  
Kei Shinoda ◽  
Hiroyuki Sakai ◽  
Makoto Kawashima ◽  
Soichi Matsumoto ◽  
...  
Keyword(s):  
Macular Edema ◽  
Intravitreal Injection ◽  
Phase 1 ◽  
Retinal Function ◽  
Age Related Macular Degeneration ◽  
Implicit Time ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Abstract Background: To evaluate the retinal function before and soon after an intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: Seventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval® system was used to record 28 Hz flicker electroretinograms (ERGs) from the injected and non-injected eyes before (Phase 1, P1), within 2 hours after the injection (P2), and 2 to 24 hours after the injection (P3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests. Results: The amplitudes were not significantly different at the three phases. The implicit time of the injected eye was 31.2±3.2 msec at P1, and it was not significantly different at P2 (31.7±3.1 msec) but it was significantly longer at P3 (32.2±3.3 msec, P<0.01, ANOVA for both). The implicit time in the non-injected fellow eye was 30.5±3.3 msec at P1, and it was significantly longer at P2 (31.1±3.2 msec) and phase 3 (31.3±3.4 msec, P<0.01, ANOVA for both). Conclusions: The results indicate that an intravitreal anti-VEGF injection will increase the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection.

scholarly journals Retinal Function determined by Flicker ERGs before and after Intravitreal Injection of Anti-VEGF Agents

2019 ◽  
Author(s):  
Gaku Terauchi ◽  
Kei Shinoda ◽  
Hiroyuki Sakai ◽  
Makoto Kawashima ◽  
Soichi Matsumoto ◽  
...  
Keyword(s):  
Macular Edema ◽  
Intravitreal Injection ◽  
Phase 1 ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Before And After ◽  
Endothelial Growth Factor

Abstract Background: To evaluate the retinal function before and after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents in the injected and non-injected eyes. Methods: Seventy-nine eyes of 79 patients that were treated by an intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) with macular edema (ME) were studied. The RETeval® system was used to record 28 Hz flicker electroretinograms (ERGs) from both eyes before (phase 1), within 2 hours after the injection (phase 2), and 2 to 24 hours after the injection (phase 3). Patients were grouped by disease or by the injected agent and compared. The significance of the changes in the implicit times and amplitudes was determined by t tests. Results: The amplitudes were not significantly different among the groups. The implicit times were significantly longer or tended to be longer at phase 2 and 3 compared to phase 1 for each disease and for each injected agent in the injected and non-injected eyes. Conclusions: The results show that an intravitreal anti-VEGF injection will prolong the implicit times not only in the injected eye but also in the non-injected eye soon after the intravitreal injection. Trial registration: All of the patients gave a written informed consent and the study was conducted in accordance with the tenets of Declaration of Helsinki and approved by the Ethics Committee of the Teikyo University School of Medicine (study ID number: 14-122). Keywords: Aflibercept, age-related macular degeneration, electroretinogram, intravitreal injection, macular edema, ranibizumab, retinal vein occlusion, vascular endothelial growth factor.

scholarly journals Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Pearse A. Keane ◽  
Srinivas R. Sadda
Keyword(s):  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Vessel Growth ◽  
Vessel Networks ◽  
Endothelial Growth Factor ◽  
Made In

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered “vascular endothelial growth factor” (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use.

Treatment of neovascular age related macular degeneration during COVID-19 pandemic: The short term consequences of unintended lapses

2021 ◽  
pp. 112067212110106
Author(s):  
Mehmet Ali Sekeroglu ◽  
Hilal Kilinc Hekimsoy ◽  
Tugce Horozoglu Ceran ◽  
Sibel Doguizi
Keyword(s):  
Macular Degeneration ◽  
Subretinal Fluid ◽  
Cross Sectional Study ◽  
Age Related Macular Degeneration ◽  
Short Term ◽  
Cross Sectional ◽  
Anti Vegf ◽  
Age Related ◽  
Optical Coherence Tomography Imaging ◽  
Endothelial Growth Factor

Aim: To investigate the short-term effects of COVID-19 pandemic related unintended treatment lapses on neovascular age related macular degeneration (nAMD) patients. Methods: In this prospective cross-sectional study, 140 patients who had at least one anti-vascular endothelial growth factor (VEGF) injection for nAMD within 12 months before COVID-19 pandemic and who had at least 3 months of unintended lapse for control visits during pandemic were recruited and underwent a detailed opthalmological examination and optical coherence tomography imaging. Results: Of these 140 eyes, 113 (80.7%) were active with presence of either intraretinal and/or subretinal fluid and necessitated intravitreal anti-VEGF injections; and 20 (14.3%) of them complicated with subretinal hemorrhage. The mean interval of clinical visits and intravitreal antiVEGF injections were found to be prolonged during COVID-19 pandemics, which demonstrates a statistically significant lapse for both ( p = 0.001 and p = 0.003 consecutively). The decreased visual acuity due to lapse was positively correlated with number of intravitreal anti-VEGF injections at last 6 months before COVID-19 pandemic ( r = 0.217, p = 0.010) and central subfoveal thickness at first post-COVID-19 visit ( r = 0.175, p = 0.038); and negatively correlated with follow-up duration ( r = −0.231, p = 0.006) and number of control visits ( r = −0.243, p = 0.004). Fifteen (16.9%) of the 89 patients who had drusen in the fellow eye before COVID-19 pandemic evolved to nAMD with an accompanying subretinal and/or intraretinal fluid. Conclusion: Unintended lapses during COVID-19 pandemic resulted with poor functional and structural outcomes for nAMD patients, especially for those at the beginning of the treatment period and who still have an unstable clinical course.

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