The Total Macular Burden of Hyperreflective Foci and the Onset of Persistent Choroidal Hypertransmission Defects in Intermediate AMD.

PURPOSE: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT). DESIGN: Post hoc subgroup analysis of a prospective study. METHODS: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit. RESULTS: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001). CONCLUSIONS: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.

Calcified Drusen Prevent the Detection of Underlying Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: In age-related macular degeneration (AMD), choriocapillaris flow deficits (CCFDs) under soft drusen can be measured using established compensation strategies. This study investigated whether CCFDs can be quantified under calcified drusen (CaD). Methods: CCFDs were measured in normal eyes (n = 30) and AMD eyes with soft drusen (n = 30) or CaD (n = 30). CCFD density masks were generated to highlight regions with higher CCFDs. Masks were also generated for soft drusen and CaD based on both structural en face OCT images and corresponding B-scans. Dice similarity coefficients were calculated between the CCFD density masks and both the soft drusen and CaD masks. A phantom experiment was conducted to simulate the impact of light scattering that arises from CaD. Results: Area measurements of CCFDs were highly correlated with those of CaD but not soft drusen, suggesting an association between CaD and underlying CCFDs. However, unlike soft drusen, the detected optical coherence tomography (OCT) signals underlying CaD did not arise from the defined CC layer but were artifacts caused by the multiple scattering property of CaD. Phantom experiments showed that the presence of highly scattering material similar to the contents of CaD caused an artifactual scattering tail that falsely generated a signal in the CC structural layer but the underlying flow could not be detected. Similarly, CaD also caused an artifactual scattering tail and prevented the penetration of light into the choroid, resulting in en face hypotransmission defects and an inability to detect blood flow within the choriocapillaris. Upon resolution of the CaD, the CC perfusion became detectable. Conclusions: The high scattering property of CaD leads to a scattering tail under these drusen that gives the illusion of a quantifiable optical coherence tomography angiography signal, but this signal does not contain the angiographic information required to assess CCFDs. For this reason, CCFDs cannot be reliably measured under CaD, and CaD must be identified and excluded from macular CCFD measurements.

Rediscovering Age-Related Macular Degeneration with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture.

PURPOSE: Swept-source OCT angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross sectional and en face imaging strategies. DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30, 2022. PARTICIPANTS: Patients with AMD. METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. MAIN OUTCOME MEASURES: Swept-source OCT angiography imaging of AMD at different stages of disease progression. RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Decreased Macular Choriocapillaris Perfusion in Eyes With Macular Reticular Pseudodrusen Imaged With Swept-Source OCT Angiography.

Purpose: To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen. Methods: Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 × 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle. Results: Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05). Conclusions: Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.

Automated segmentation and quantification of calcified drusen in 3D swept source OCT imaging.

Qualitative and quantitative assessments of calcified drusen are clinically important for determining the risk of disease progression in age-related macular degeneration (AMD). This paper reports the development of an automated algorithm to segment and quantify calcified drusen on swept-source optical coherence tomography (SS-OCT) images. The algorithm leverages the higher scattering property of calcified drusen compared with soft drusen. Calcified drusen have a higher optical attenuation coefficient (OAC), which results in a choroidal hypotransmission defect (hypoTD) below the calcified drusen. We show that it is possible to automatically segment calcified drusen from 3D SS-OCT scans by combining the OAC within drusen and the hypoTDs under drusen. We also propose a correction method for the segmentation of the retina pigment epithelium (RPE) overlying calcified drusen by automatically correcting the RPE by an amount of the OAC peak width along each A-line, leading to more accurate segmentation and quantification of drusen in general, and the calcified drusen in particular. A total of 29 eyes with nonexudative AMD and calcified drusen imaged with SS-OCT using the 6 × 6 mm2 scanning pattern were used in this study to test the performance of the proposed automated method. We demonstrated that the method achieved good agreement with the human expert graders in identifying the area of calcified drusen (Dice similarity coefficient: 68.27 ± 11.09%, correlation coefficient of the area measurements: r = 0.9422, the mean bias of the area measurements = 0.04781 mm2).

Onset and Progression of Persistent Choroidal Hypertransmission Defects in Intermediate Age-Related Macular Degeneration: A Novel Clinical Trial Endpoint.

PURPOSE: The appearance and growth of persistent choroidal hypertransmission defects (hyperTDs) detected on en face swept-source optical coherence tomography (SS-OCT) images from eyes with intermediate age-related macular degeneration (iAMD) were studied to determine if they could serve as novel clinical trial endpoints. DESIGN: Post hoc subgroup analysis of a prospective study. METHODS: Subjects with iAMD underwent 6 × 6 mm SS-OCT angiography imaging at their baseline and follow-up visits. The drusen volumes were obtained using a validated SS-OCT algorithm. Two graders independently evaluated all en face structural images for the presence of persistent hyperTDs. The number and area of all hyperTDs along with drusen volume were obtained from all SS-OCT angiography scans. Eyes were censored from further follow-up once exudative AMD developed. RESULTS: A total of 171 eyes from 121 patients with iAMD were included. Sixty-eight eyes developed at least 1 hyperTD. Within 1 year after developing a hyperTD, 25% of eyes developed new hyperTDs for an average of 0.44 additional hyperTDs. Over 2 years, as hyperTDs appeared, enlarged, and merged, the average area growth rate was 0.220 mm/yr using the square-root transformation strategy. A clinical trial design using the onset and enlargement of these hyperTDs for the study of disease progression in eyes with iAMD is proposed. CONCLUSIONS: The appearance and growth of persistent choroidal hyperTDs in eyes with iAMD can be easily detected and measured using en face OCT imaging and can serve as novel clinical trial endpoints for the study of therapies that may slow disease progression from iAMD to late AMD.

Subpalpebral Antibiotic Lavage for the Treatment of Refractory Infectious Scleritis.

Infectious scleritis is a potentially devastating condition that can result in severe vision loss. When traditional management fails, a subpalpebral antibiotic lavage system (SAL) can be considered to bathe the infected area with a high volume and concentration of antibiotics. Several reports show that this method can be curative for infectious scleritis, otherwise refractory to care. However, surgical approaches for this technique are either not well described, advocate for transecting the levator aponeurosis, or do not expose the entire width of the superior fornix, which can lead to postoperative ptosis. The authors describe a case where a novel approach was utilized, using a fenestrated angiocather in the superior lateral fornix, to maximize outcomes and minimize postoperative complications. In the setting of infectious scleritis refractory to traditional management, a SAL can be safely and effectively placed with the technique detailed in this report.

Production of Protein Hydrolysates Using Marine Catfish Bagre panamensis Muscle or Casein as Substrates: Effect of Enzymatic Source and Degree of Hydrolysis on Antioxidant and Biochemical Properties.

Protein hydrolysates from fishery byproducts have resulted to be nutraceutical ingredients with potential to be applied in human nutrition; however, critical quality attributes are dependent on some process parameters such as enzyme source and degree of hydrolysis. This study analyzed the biochemical properties and in vitro antioxidant activity (using DPPH, ABTS, and FRAP assays), of protein hydrolysates at 10, 20, and 30% degree of hydrolysis (DH), measured by pH-STAT and prepared from sea catfish (Bagre panamensis) muscle and casein as protein sources by treatment with alcalase (ALC) and a semi-purified protease extract (SPE) from B. panamensis intestinal tissues as enzyme sources. With SPE, the DH was reached faster than ALC regardless of the protein substrate used. Sea catfish muscle (MUSC) hydrolysate made with SPE at 30% DH showed the highest antioxidant activity (DPPH: 118.8 µmoles TE/mg; ABTS: EC50 of 1.5 mg/mL). In FRAP assay, the MUSC hydrolysates produced with SPE or ALC at 20% DH showed the higher activity (0.38 and 0.40 µmoles TE/mg, respectively). MUSC hydrolysates made with SPE contained the highest proportion of peptides with MW < 1.35 kDa and had a high protein content (72 to 78%), and almost 50% of the amino acids were essential. These results suggest that intestinal proteases and muscle of marine catfish represent a potential source to elaborate antioxidant protein hydrolysates. Our results promote the full utilization of this fish species and offer a biotechnological strategy for the management and valorization of its byproducts.