Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline.

Purpose: We aimed to identify structural differences in normal eyes, early age-related macular degeneration (AMD), and intermediate AMD eyes using optical coherence tomography (OCT) in a well-characterized, large cross-sectional cohort. Methods: Subjects ≥ 60 years with healthy normal eyes, as well as early or intermediate AMD were enrolled in the Alabama Study on Age-related Macular Degeneration 2 (ALSTAR2; NCT04112667). Using Spectralis HRA + OCT2, we obtained macular volumes for each participant. An auto-segmentation software was used to segment six layers and sublayers: photoreceptor inner and outer segments, subretinal drusenoid deposits (SDDs), retinal pigment epithelium + basal lamina (RPE + BL), drusen, and choroid. After manually refining the segmentations of all B-scans, mean thicknesses in whole, central, inner and outer rings of the ETDRS grid were calculated and compared among groups. Results: This study involved 502 patients, 252 were healthy, 147 had early AMD, and 103 had intermediate AMD eyes (per Age-Related Eye Disease Study [AREDS] 9-step). Intermediate AMD eyes exhibited thicker SDD and drusen, thinner photoreceptor inner segments, and RPE compared to healthy and early AMD eyes. They also had thicker photoreceptor outer segments than early AMD eyes. Early AMD eyes had thinner photoreceptor outer segments than normal eyes but a thicker choroid than intermediate AMD eyes. Using the Beckman scale, 42% of the eyes initially classified as early AMD shifted to intermediate AMD, making thickness differences for photoreceptor outer segments and choroid insignificant. Conclusions: With AMD stages, the most consistent structural differences involve appearance of drusen and SDD, followed by RPE + BL thickness, and then thickness of photoreceptor inner and outer segments. Structural changes in the transition from aging to intermediate AMD include alterations in the outer retinal bands, including the appearance of deposits on either side of the RPE.

Comparison Of Blue-Light Autofluorescence and Ultrawidefield Green-Light Autofluorescence for Assessing Geographic Atrophy.

PURPOSE: The goal of this study was to evaluate and compare the inter-modality and inter-reader agreement of manual and semiautomated GA (Geographic Atrophy) area measurements in eyes with GA due to age-related macular degeneration (AMD) using conventional blue and ultrawidefield (UWF) green light fundus autofluorescence (FAF) systems. METHODS: FAF images of eyes with GA were obtained during a single visit using both the Spectralis HRA+OCT2 device and the Optos California device. Images were exported for masked analysis by two independent masked graders. The area of the GA lesion(s) was segmented and quantified (mm2) with a fully manual approach where the lesions were outlined using Optos Advance and Heidelberg Eye Explorer (HEYEX) software. In addition, for the Heidelberg blue FAF images, GA lesions were also measured using the instrument's semi-automated software (Region Finder 2.6.4). For comparison between modalities/grading method, the mean values of the two graders were used. Intraclass correlation coefficients (ICC) were computed to judge the agreement between graders. RESULTS: 72 eyes of 50 patients were included in this study. There was nearly perfect agreement between graders for the measurement of GA area for all three modalities (Intraclass Correlation coefficient = 0.996 for manual Optos Advance, 0.996 for manual Heidelberg HEYEX, 0.995 for Heidelberg Region Finder). The measurement of GA area was strongly correlated between modalities, with Spearman correlation coefficients of 0.985 (p < 0.001) between manual Heidelberg and manual Optos, 0.991 (p < 0.001) for Region Finder versus manual Heidelberg, and 0.985 (p < 0.001) for Region Finder versus manual Optos. The absolute mean area differences between the Heidelberg manual vs Region Finder, manual Optos vs Region Finder, and manual Optos vs manual Heidelberg were 1.61 mm2 (p<0.001), 0.90 mm2 (p<0.001), and 0.71 mm2 (p<0.001), respectively. CONCLUSIONS: We observed excellent inter-reader agreement for measurement of GA using either 30-degree blue FAF or UWF green FAF, establishing the reliability of UWF imaging for macular GA assessment. While the absolute measurements between devices were strongly correlated, they differed significantly, highlighting the importance of using the same device for a given patient for the duration of a study.

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: an AMISH Eye Study Analysis.

PURPOSE: To compare the Ganglion Cell Complex (GCC) thickness in eyes with age-related macular degeneration (AMD) versus healthy controls in an elderly Amish population DESIGN: Cross-sectional study METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each compromising 512 A-scans) over a 6 mm x 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the GCL and the IPL layer. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of six sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. RESULTS: Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of twelve hundred and ninety-four subjects had all required imaging studies of sufficient quality and were included in the final analysis, and of these 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (p<0.001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). Independent t test showed that, early (75.03 ± 12.45 µm), and late AMD (61.64 ± 21.18 µm) groups (among which GA eyes had the lowest thickness of 58.10 ± 20.27 microns) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant difference in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. CONCLUSIONS: The GCC thickness in AMD eyes is reduced compared to normal eyes, but the relationship is complex with the greatest reduction in late AMD eyes (particularly GA eyes) but no difference between early and intermediate AMD eyes.

En Face and Volumetric Comparison of Hypertransmission Defects Evaluated by Cirrus and Spectralis Optical Coherence Tomography.

PURPOSE: To evaluate and compare en face and 3-dimensional (3-D) properties of hypertransmission defects (HTDs) between different optical coherence tomography (OCT) devices using OCT volumes and reconstructed en face images. SETTINGS: Comparative diagnostic evaluation study. METHODS: Thirty eyes with dry age-related macular degeneration (AMD) that underwent dense OCT macular volume scans with both the Spectralis (97 B-scans/volume; 2910 B-scans in total) and Cirrus OCT (128 B-scans/volume; 3840 B-scans in total) from the Amish Eye Study cohort were included in this analysis. HTD regions were labeled on each B-scan and reconstructed into en face and 3-D volume images. Properties of HTD volume were compared between the 2 devices. RESULTS: The qualitative score of en face images for HTD was higher for the Cirrus compared to the Spectralis (P < .01). The quality of Spectralis en face images improved after preprocessing and reconstruction. The 2-D HTD area on en face obtained from 2-D projections of 3-D volume did not differ between devices (P = .478, ICC = 0.998; Jaccard index 0.721 ± 0.086). There was no difference in the number, volume, PALs, and surface areas of HTDs between devices in the volumetric analysis (all P ≥ .090). The signal intensity of HTD normalized by the mean choroidal signal intensity did not differ between devices (P = .861). CONCLUSIONS: The visualization of HTD on en face images from Spectralis OCT could be enhanced through image processing. The equivalence in 3-D HTD parameters between the 2 devices suggests interchangeability for assessing these lesions in AMD.

Assessment of intraretinal hyperreflective foci using multimodal imaging in eyes with age-related macular degeneration.

PURPOSE: This study aimed to investigate the correspondence between intraretinal hyperreflective foci (IHRF) identified on optical coherence tomography (OCT) B-scans with hyperpigmentation on colour fundus photography (CFP) or hyperreflectivity on infrared reflectance (IR) images in eyes with age-related macular degeneration (AMD). METHODS: Flash CFP, IR images and OCT B-scans obtained at the same visit were evaluated. Individual IHRF identified on OCT B-scans were assessed for the qualitative presence or absence of a hypotransmission tail into the choroid. The corresponding IR image obtained at the time of OCT acquisition was analysed for the presence or absence of hyperreflectivity in this region. The IR images were manually registered to the CFP image, and CFP images were inspected for the presence or absence of hyperpigmentation at the location of IHRF. RESULTS: From 122 eyes, a total of 494 IHRF were evaluated. For the primary analysis of qualitative presence or absence of hyperpigmentation on CFP and hyperreflectivity on IR at the locations corresponding to IHRF on OCT, 301 (61.0%) of the IHRFs demonstrated evidence of hyperpigmentation on CFP, while only 115 (23.3%) showed evidence of hyperreflectivity on IR. The qualitative determination of the presence or absence of an abnormality on CFP or IR were significantly different (p < 0.0001). 327 (66.2%) of the IHRF showed hypotransmission, and 80.4% of these IHRF showed hyperpigmentation on CFP, though only 23.9% (p < 0.0001) demonstrated hyperreflectivity on IR. CONCLUSIONS: Less than two-thirds of IHRF evident on OCT manifest as hyperpigmentation on colour photos, though IHRF with posterior shadowing are more likely to be evident as pigment. IR imaging appears to be even more poorly sensitive for visualizing IHRF.

Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.

PURPOSE: To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). METHODS: We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. RESULTS: 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. CONCLUSIONS: Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.

Segmentation Error Correction of the Optical Coherence Tomography Angiography Images in Peer-Reviewed Studies.

Purpose: To assess the percentage of published articles reporting optical coherence tomography angiography (OCTA) metrics regarding the report of segmentation error correction. Methods: A comprehensive search was conducted using the PubMed database for articles on OCTA imaging published between January 1, 2015, and January 1, 2021. All original articles reporting at least one of the OCTA metrics were extracted. The article text was reviewed for the segmentation correction strategy. In addition, the number of articles that mentioned the lack of segmentation error correction as a limitation of the study was recorded. Results: From the initial 5288 articles, 1559 articles were included for detailed review. One hundred ninety-six articles (12.57%) used manual correction for segmentation errors. Of the remaining articles, 589 articles (37.8%) excluded images with significant segmentation errors, and 99 articles (6.3%) mentioned segmentation errors as a limitation of their study. The rest of the articles (675, 43.3%) did not address the segmentation error. Multiple logistic regression analysis revealed that ignorance of segmentation error was significantly associated with lower journal ranks, earlier years of publication and disease category of age-related macular degeneration, and glaucoma (all P < 0.001). Conclusions: A significant proportion of peer-reviewed articles in PubMed, disregarded the segmentation error correction. The conclusions of such studies should be interpreted with caution. Editors, reviewers, and authors of OCTA articles should pay special attention to the correction of segmentation errors.

Artifacts in Optical Coherence Tomography Angiography.

We performed a comprehensive search of the published literature in PubMed and Google Scholar to identify types, prevalence, etiology, clinical impact, and current methods for correction of various artifacts in optical coherence tomography angiography (OCTA) images. We found that the prevalence of OCTA image artifacts is fairly high. Artifacts associated with eye motion, misidentification of retinal layers, projections, and low optical coherence tomography signal are the most prevalent types. Artifacts in OCTA images are the major limitations of this diagnostic modality in clinical practice and identification of these artifacts and measures to mitigate them are essential for correct diagnosis and follow-up of patients.

Superficial and Deep Foveal Avascular Zone Area Measurement in Healthy Subjects Using Two Different Spectral Domain Optical Coherence Tomography Angiography Devices.

PURPOSE: To compare the area of the foveal avascular zone (FAZ) in the superficial and deep retinal layers using two different spectral-domain optical coherence tomography angiography (OCTA) devices. METHODS: A cross-sectional comparative study was conducted to obtain macular OCTA images from healthy subjects using Optovue RTVue XR Avanti (Optovue, Inc, Fremont, CA) and Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany). Two independent trained graders measured the FAZ area using automated slab segmentation. The FAZ area in the superficial and deep retinal layers were compared. RESULTS: Twenty-three eyes of 23 subjects were included. The graders agreement was excellent ( > 0.86) for all measurements. The mean FAZ area was significantly larger at the superficial retinal layer as compared to the deep retinal layer on both devices (0.31 ± 0.08 mm 2 vs 0.26 ± 0.08 mm 2 in Optovue and 0.55 ± 0.16 mm 2 vs 0.36 ± 0.13 mm 2 in Spectralis, both P < 0.001). The mean FAZ area was significantly greater in the superficial and deep retinal layers using Spectralis as compared to Optovue measurements (P < 0.001 for both comparisons). CONCLUSION: In contrast to previous reports, the FAZ area was larger in the superficial retina as compared to deep retinal layers using updated software versions. Measurements from different devices cannot be used interchangeably.

Successful treatment of allergic conjunctival granuloma by topical tacrolimus: A clinicopathologic case report.

Allergic conjunctival granuloma is a rare cause of conjunctival ocular lesions. The aim of this case report was to present a successful treatment of an allergic conjunctival granuloma with topical tacrolimus eye drops. A 20-year-old female presented with bilateral multiple yellow nodules of the bulbar conjunctival epithelium and conjunctival injection. The patient had tearing, photophobia, itching, foreign body sensation, and red eye. The patient's signs and symptoms progressed despite the use of topical steroids. The patient was treated by application of tacrolimus eye drop (0.005%) in her right eye every 6 h while the left eye was put on placebo. Her signs and symptoms were recorded at each visit. After 3 weeks' therapy with topical tacrolimus eye drop, the patient became asymptomatic in her right eye and conjunctival granulomas fully resolved. Topical tacrolimus seems to be an effective therapeutic option for the treatment of allergic conjunctival granulomas.