Examination of Inner Retinal Layers in Unilateral Wet Age-Related Macular Degeneration Treated with Anti-VEGF, Compared to Fellow Untreated Eyes

The main aim of this study was to characterize the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in the macular area eyes affected by wet age-related macular degeneration (wAMD) treated with anti-VEGF and compare the results with the control of fellow untreated eyes affected by early stages of dry age-related macular degeneration (dAMD). Additionally, we aimed to estimate if the number of injections received and other factors, including age, best-corrected visual acuity (BCVA), or sex, may affect the differences in the obtained measurements of retinal nerve fiber layer thickness. We prospectively included 106 eyes of 53 patients with unilateral wet age-related macular degeneration. The fellow eyes with non-advanced dry age-related macular degeneration served as a control group in a cross-sectional study. RNFL and GCL in the macular region were evaluated using optical coherence tomography, with outcomes expressed as differences in the thickness of both examined layers between the study and control groups. We found thinner GCL in wAMD vs. dAMD (p < 0.001). In turn, the RNFL layer did not show any statistically significant differences between the two groups (p = 0.409). Similarly, we found a statistically significant correlation between the number of injections and the layer thickness (p = 0.106). Among all assessed parameters, age over 73 was the only factor significantly affecting the thickness of the retinal nerve fiber layer in both groups (p = 0.042). The morphology of the inner layers of the retina in dry and wet AMD seems to differ, possibly due to differences in the etiopathogenesis of these two forms of the disease. In our study, the retinal ganglion cell layer was thinner in the treated vs. fellow eye (with dry AMD), while the nerve fiber layer was not significantly different between the groups. The number of anti-VEGF injections had no effect on the thickness of the macular nerve fiber layer.

[1]  J. Kocięcki,et al.  Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review , 2022, International journal of molecular sciences.

[2]  J. Kocięcki,et al.  Morphological and Functional Assessment of the Optic Nerve Head and Retinal Ganglion Cells in Dry vs Chronically Treated Wet Age-Related Macular Degeneration , 2022, Clinical ophthalmology.

[3]  Yanhui Deng,et al.  Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy. , 2021, Genes & diseases.

[4]  Youjin Lee Beyond Multiple Linear Regression: Applied Generalized Linear Models and Multilevel Models in R , 2021, The American Statistician.

[5]  S. Tenreiro,et al.  Age-Related Macular Degeneration: Pathophysiology, Management, and Future Perspectives , 2021, Ophthalmologica.

[6]  Indrajeet Patil,et al.  Visualizations with statistical details: The 'ggstatsplot' approach , 2021, J. Open Source Softw..

[7]  N. Demir,et al.  Anatomical effects of intravitreal anti-vascular endothelial growth factor injections on inner layers of the lesion-free retina , 2021, Cutaneous and ocular toxicology.

[8]  M. Kalloniatis,et al.  Radial Peripapillary Capillary Plexus Sparing and Underlying Retinal Vascular Impairment in Intermediate Age-Related Macular Degeneration , 2021, Investigative ophthalmology & visual science.

[9]  P. Roback,et al.  Beyond Multiple Linear Regression , 2021 .

[10]  M. Kalloniatis,et al.  Modelling normal age-related changes in individual retinal layers using location-specific OCT analysis , 2021, Scientific reports.

[11]  G. Malek,et al.  Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies , 2021, Frontiers in Cell and Developmental Biology.

[12]  Sevcan Balci,et al.  Quantitative analysis of inner retinal structural and microvascular alterations in intermediate age-related macular degeneration: a swept-source OCT angiography study. , 2020, Photodiagnosis and photodynamic therapy.

[13]  S. Lee,et al.  Characteristics of the inner retinal layer in the fellow eyes of patients with unilateral exudative age-related macular degeneration , 2020, PloS one.

[14]  S. Swaminathan,et al.  Effect of Intravitreal Injections on Retinal Imaging Metrics in Glaucomatous and Non-Glaucomatous Eyes , 2020, Current Ophthalmology Reports.

[15]  J. Seddon,et al.  Choriocapillaris dropout in early age-related macular degeneration. , 2020, Experimental eye research.

[16]  Sieu K. Khuu,et al.  Development of a spatial model of age-related change in the macular ganglion cell layer to predict function from structural changes. , 2019, American journal of ophthalmology.

[17]  Douglas M. Bates,et al.  Sparse and Dense Matrix Classes and Methods [R package Matrix version 1.2-18] , 2019 .

[18]  T. Kirsten,et al.  Sex-Specific Differences in Circumpapillary Retinal Nerve Fiber Layer Thickness. , 2019, Ophthalmology.

[19]  J. García-Feijóo,et al.  Long-term effect of intravitreal ranibizumab therapy on retinal nerve fiber layer in eyes with exudative age-related macular degeneration , 2019, Graefe's Archive for Clinical and Experimental Ophthalmology.

[20]  D. Lüdecke Sjplot - Data Visualization For Statistics In Social Science. , 2018 .

[21]  Daniel Lüdecke,et al.  ggeffects: Tidy Data Frames of Marginal Effects from Regression Models , 2018, J. Open Source Softw..

[22]  M. Kalloniatis,et al.  Developing prognostic biomarkers in intermediate age‐related macular degeneration: their clinical use in predicting progression , 2018, Clinical & experimental optometry.

[23]  W. Freeman,et al.  QUANTITATIVE ANALYSIS OF THE INNER RETINAL LAYER THICKNESSES IN AGE-RELATED MACULAR DEGENERATION USING CORRECTED OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION , 2017, Retina.

[24]  Joan W. Miller,et al.  Advances in Age-related Macular Degeneration Understanding and Therapy , 2017, US ophthalmic review.

[25]  S. Priglinger,et al.  Combined VEGF and PDGF inhibition for neovascular AMD: anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro , 2017, Graefe's Archive for Clinical and Experimental Ophthalmology.

[26]  Paolo Carpineto,et al.  Association between outer retinal alterations and microvascular changes in intermediate stage age-related macular degeneration: an optical coherence tomography angiography study , 2016, British Journal of Ophthalmology.

[27]  S. Wolf,et al.  Retinal Ganglion Cell Layer Change in Patients Treated With Anti-Vascular Endothelial Growth Factor for Neovascular Age-related Macular Degeneration. , 2016, American journal of ophthalmology.

[28]  Peter Green,et al.  SIMR: an R package for power analysis of generalized linear mixed models by simulation , 2016 .

[29]  Jung-Yeul Kim,et al.  Longitudinal Changes in Retinal Nerve Fiber Layer Thickness after Intravitreal Anti-vascular Endothelial Growth Factor Therapy , 2016, Korean journal of ophthalmology : KJO.

[30]  M. V. Cicinelli,et al.  Macular ganglion cell complex and retinal nerve fiber layer comparison in different stages of age-related macular degeneration. , 2015, American journal of ophthalmology.

[31]  E. Lee,et al.  Ganglion Cell-Inner Plexiform Layer and Peripapillary Retinal Nerve Fiber Layer Thicknesses in Age-Related Macular Degeneration. , 2015, Investigative ophthalmology & visual science.

[32]  H. Wickham Read Excel Files , 2015 .

[33]  D. Denis,et al.  Effects of multiple intravitreal anti-VEGF injections on retinal nerve fiber layer and intraocular pressure: a comparative clinical study. , 2014, International journal of ophthalmology.

[34]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[35]  Antonello Tamburrino,et al.  Differential vulnerability of retinal layers to early age-related macular degeneration: evidence by SD-OCT segmentation analysis. , 2014, Investigative ophthalmology & visual science.

[36]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[37]  Y. Kiuchi,et al.  Inner retinal layer comparisons of eyes with exudative age-related macular degeneration and eyes with age-related macular degeneration and glaucoma , 2014, Graefe's Archive for Clinical and Experimental Ophthalmology.

[38]  Michael B Horsley,et al.  Retinal nerve fiber layer thickness in patients receiving chronic anti-vascular endothelial growth factor therapy. , 2010, American journal of ophthalmology.

[39]  D. Baas,et al.  The dynamic nature of Bruch's membrane , 2010, Progress in Retinal and Eye Research.

[40]  David T. Shima,et al.  Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. , 2007, The American journal of pathology.

[41]  J. Lovie-Kitchin,et al.  Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis , 2007, Eye.

[42]  C. Klaver,et al.  Age-related macular degeneration , 2006, BMJ : British Medical Journal.