Choroidal imaging biomarkers as predictors of conversion to exudative age-related macular degeneration.

PURPOSE: Predicting the progression of intermediate AMD (iAMD) to neovascular AMD (nAMD) will help to identify high-risk patients and improve treatment outcomes. The present study assessed whether choroidal OCT biomarkers could predict conversion to nAMD. METHODS: This retrospective study included patients with clinically stable iAMD who either converted to nAMD (C group) or did not convert (NC group) during one year of follow-up. OCT parameters included subfoveal choroidal thickness (SFCT), central macular thickness (CMT), Haller vascular thickness (HVT), inner choroidal thickness (ICT), and double-layer sign (DLS). RESULTS: Of 116 total eyes, there were 37 in the NC group and 79 in the C group. Baseline SFCT was significantly lower in the C group compared to the NC group (169.0 ± 63.2 µm vs. 218.0 ± 97.8 µm, p = 0.01). Baseline HVT and ICT were lower in the C group (105.2 ± 40.6 µm vs. 121.0 ± 56.6 µm, p = 0.17 and 61.9 ± 35.5 µm vs. 77.5 ± 41.7 µm, p = 0.09). HVT was decreased at all time points in the C group vs NC (p > 0.05). The ICT was reduced in the C group at each time point except at conversion time (p > 0.05). Of all eight eyes who presented DLS at baseline, 100% converted to nAMD (p < 0.001). CONCLUSION: Lower SFCT at baseline may signal conversion to nAMD within 12 months.

Longitudinal changes in pigment epithelial detachment composition indices (PEDCI): new biomarkers in neovascular age-related macular degeneration.

PURPOSE: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months. METHODS: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-naïve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed. RESULTS: Mean BCVA (in logMAR) was 0.60 ± 0.47, 0.45 ± 0.41, 0.49 ± 0.49, 0.61 ± 0.54, 0.59 ± 0.56, and 0.67 ± 0.57 at baseline, 3, 6, 12, 18, and 24 months respectively. Overall, BCVA showed minimal worsening of 0.07 ± 0.54 logMAR (p = 0.07). 13.38 ± 3.77 anti-VEGF injections were given through 24 months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p = 0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p = 0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p = 0.06). BCVA was negatively correlated with PEDCI-F (r = -0.28, p < 0.01), and positively correlated with PEDCI-N (r = 0.28, p < 0.01) and PEDCI-S (r = 0.15, p = 0.03). CONCLUSION: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs.

Effects of fixatives on histomagnetic evaluation of iron in rodent spleen.

Characterizing the iron distribution in tissue sections is important for several pathologies. Iron content in excised tissue is typically analyzed via histochemical stains, which are dependent on sample preparation and staining protocols. In our recent studies, we examined how magnetic properties of iron can also be exploited to characterize iron distribution in tissue sections in a label free manner. To enable a histomagnetic characterization of iron in a wide variety of available tissues, it is important to extend it to samples routinely prepared for histochemical staining, which often involve use of chemical fixatives. In this study, we took a systematic approach to determine differences between unfixed and formalin-fixed murine spleen tissues in histomagnetic characterization of iron. Superconducting quantum interference device (SQUID) magnetometry and magnetic force microscopy (MFM) were used for macro- and micro-scale histomagnetic characterization. Perl's stain was used for histochemical characterization of ferric (Fe3+) iron on adjacent sections as that used for MFM analysis. While histochemical analysis revealed a substantial difference in the dispersion of the stain between fixed versus unfixed samples, histomagnetic characterization was not dependent on chemical fixation of tissue. The results from this study reveal that histomagnetic characterization of iron is free from staining artifacts which can be present in histochemical analysis.

Assessment of optical coherence tomography biomarkers in patients with non-neovascular age-related macular degeneration (AMD) converting to exudative AMD according to the status of the fellow eye.

OBJECTIVES: To compare optical coherence tomography (OCT) biomarkers in eyes converting from non-neovascular (nnAMD) to exudative age-related macular degeneration (eAMD) based on the status of fellow eye. METHODS: Retrospective analysis of one year of pre-conversion data of fellow eyes of patients with nnAMD and eAMD which converted to eAMD, defined as converting eyes (CE) with fellow nnAMD and CE with fellow eAMD respectively. Demographics, best corrected visual acuity (BCVA), and OCT biomarkers including drusen type, iRORA/cRORA, subfoveal ellipsoid zone (SFEZ) disruption, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), Haller vascular thickness (HVT) were evaluated. Chi-square and t-tests were employed, confidence interval of 95% and p < 0.05. RESULTS: 72 eyes of 72 patients were included: 31 CE with fellow nnAMD and 41 CE with fellow eAMD. Mean age was 81.8 ± 9.9 years, with 62.5% females. Subfoveal iRORA was more frequent in CE with fellow nnAMD (26%) compared to CE with fellow eAMD (6%) 44 weeks before conversion (p = 0.058). SFCT and HVT were higher in CE with fellow nnAMD compared to CE with fellow eAMD 19 weeks prior to conversion (213 ± 82 vs. 174 ± 63 µm, p = 0.052; 121 ± 44 vs. 104 ± 50 µm, p = 0.084 respectively). BCVA was significantly higher in CE with fellow eAMD compared to CE with fellow nnAMD every time frame (p < 0.05). CONCLUSIONS: Although subtle distinctions, no significant differences were observed between the groups. Further research is needed to understand the influence of one eye's status on progression from nnAMD to eAMD in fellow eye.

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months. METHODS: This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F). RESULTS: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = - 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = - 0.53; p < 0.001 and PCV, r = - 0.09; p = 0.58). CONCLUSION: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Pigment epithelial detachment composition indices (PEDCI) in neovascular age-related macular degeneration.

We provide an automated analysis of the pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) and estimate areas of serous, neovascular, and fibrous tissues within PEDs. A retrospective analysis of high-definition spectral-domain OCT B-scans from 43 eyes of 37 patients with nAMD with presence of fibrovascular PED was done. PEDs were manually segmented and then filtered using 2D kernels to classify pixels within the PED as serous, neovascular, or fibrous. A set of PED composition indices were calculated on a per-image basis using relative PED area of serous (PEDCI-S), neovascular (PEDCI-N), and fibrous (PEDCI-F) tissue. Accuracy of segmentation and classification within the PED were graded in masked fashion. Mean overall intra-observer repeatability and inter-observer reproducibility were 0.86 ± 0.07 and 0.86 ± 0.03 respectively using intraclass correlations. The mean graded scores were 96.99 ± 8.18, 92.12 ± 7.97, 91.48 ± 8.93, and 92.29 ± 8.97 for segmentation, serous, neovascular, and fibrous respectively. Mean (range) PEDCI-S, PEDCI-N, and PEDCI-F were 0.253 (0-0.952), 0.554 (0-1), and 0.193 (0-0.693). A kernel-based image processing approach demonstrates potential for approximating PED composition. Evaluating follow up changes during nAMD treatment with respect to PEDCI would be useful for further clinical applications.