Pseudoaveraging for denoising of OCT angiography: a deep learning approach for image quality enhancement in healthy and diabetic eyes.

BACKGROUND: This study aimed to develop a deep learning (DL) algorithm that enhances the quality of a single-frame enface OCTA scan to make it comparable to 4-frame averaged scan without the need for the repeated acquisitions required for averaging. METHODS: Each of the healthy eyes and eyes from diabetic subjects that were prospectively enrolled in this cross-sectional study underwent four repeated 6 × 6 mm macular scans (PLEX Elite 9000 SS-OCT), and the repeated scans of each eye were co-registered to produce 4-frame averages. This prospective dataset of original (single-frame) enface scans and their corresponding averaged scans was divided into a training dataset and a validation dataset. In the training dataset, a DL algorithm (named pseudoaveraging) was trained using original scans as input and 4-frame averages as target. In the validation dataset, the pseudoaveraging algorithm was applied to single-frame scans to produce pseudoaveraged scans, and the single-frame and its corresponding averaged and pseudoaveraged scans were all qualitatively compared. In a separate retrospectively collected dataset of single-frame scans from eyes of diabetic subjects, the DL algorithm was applied, and the produced pseudoaveraged scan was qualitatively compared against its corresponding original. RESULTS: This study included 39 eyes that comprised the prospective dataset (split into 5 eyes for training and 34 eyes for validating the DL algorithm), and 105 eyes that comprised the retrospective test dataset. Of the total 144 study eyes, 58% had any level of diabetic retinopathy (with and without diabetic macular edema), and the rest were from healthy eyes or eyes of diabetic subjects but without diabetic retinopathy and without macular edema. Grading results in the validation dataset showed that the pseudoaveraged enface scan ranked best in overall scan quality, background noise reduction, and visibility of microaneurysms (p < 0.05). Averaged scan ranked best for motion artifact reduction (p < 0.05). Grading results in the test dataset showed that pseudoaveraging resulted in enhanced small vessels, reduction of background noise, and motion artifact in 100%, 82%, and 98% of scans, respectively. Rates of false-positive/-negative perfusion were zero. CONCLUSION: Pseudoaveraging is a feasible DL approach to more efficiently improve enface OCTA scan quality without introducing notable image artifacts.

Retinal Pigment Epithelium Aperture Preceding Collapse of Vascular and Avascular Pigment Epithelial Detachments Secondary to AMD.

PURPOSE: To describe retinal pigment epithelium (RPE) aperture preceding the collapse of retinal pigment epithelium detachments (RPED) in eyes with neovascular and non-neovascular age-related macular degeneration (AMD). METHODS: Medical records from five patients with RPE aperture associated with vascular and avascular RPED were reviewed between 2010 and 2021 at the New England Eye Center at Tufts Medical Center. Main outcome measures were analysis of RPE aperture characteristics and temporal course of RPED collapse. RESULTS: RPE apertures were identified in six eyes from five women (mean age of 72.6 years). Two eyes had neovasacular AMD and four eyes had non-neovascular AMD. The RPE aperture initially appeared as a discontinuity at the apex of the RPED without rippling or retraction. Each aperture was associated with hypertransmission of OCT signal into the choroid as well as hyperreflective foci. The mean time between the appearance of the RPE aperture to near complete collapse of the RPED was 9 months. Following RPED collapse, one eye developed choroidal neovascularization, three eyes progressed to geographic atrophy, one eye had recurrence of the RPED, and one eye remained unchanged. CONCLUSION: RPE aperture is a characteristic OCT finding that can be observed in avascular or vascularized RPED secondary to AMD. RPE apertures precede RPED collapse, which are most likely to occur within nine months of RPE aperture detection.

Adverse Ocular Effects of Systemic Medications.

While ocular complications of systemic medications are uncommon, it is important to recognize that vision-threatening toxicities can occur. This review details the vision-threatening adverse effects of a select group of commonly prescribed systemic medications and describes the recommended screening guidelines for those that are particularly high risk.

Optical Coherence Tomography Angiography Analysis Toolbox: A Repeatable and Reproducible Software Tool for Quantitative Optical Coherence Tomography Angiography Analysis.

BACKGROUND AND OBJECTIVE: The purpose of this article is to demonstrate the optical coherence tomography angiography (OCTA) Analysis Toolkit (OAT), a custom-designed software package, as a repeatable and reproducible tool for computing OCTA metrics across different devices. MATERIALS AND METHODS: Fourteen participants were imaged using three devices. Foveal avascular zone, vessel index, vessel length index, and vessel diameter index were calculated using the OAT. Repeatability and reproducibility were assessed using the coefficient of variation and interclass correlation coefficient (ICC). RESULTS: Analysis of identical images demonstrated perfect levels of repeatability for all metrics (coefficient of variation 0%), which was a consequence of the software being deterministic (ie, producing the same outputs for the same inputs). Foveal avascular zone ICC values were in the excellent-to-good range (ICC > 0.6) for all devices. All values for vessel index (VI), vessel length index, and vessel diameter index fell in the good-to-fair (ICC > 0.4) or excellent-to-good range, except for vessel index analysis in the Cirrus device (ICC = 0.34). CONCLUSIONS: The OAT appears to be a reliable tool that may enable comparison between OCTA data sets acquired on different imaging instruments, thereby facilitating a more consistent approach to OCTA analysis. [Ophthalmic Surg Lasers Imaging Retina 2023;54:114-122.].

Surgical classification for large macular hole: based on different surgical techniques results: the CLOSE study group.

BACKGROUND: The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. METHODS: We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. RESULTS: Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. CONCLUSIONS: The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400-550 µm) and X-Large (550-800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.

Relationship between gene expression profile class and tumor thickness regression after plaque brachytherapy for choroidal melanoma.

BACKGROUND AND OBJECTIVE: To examine the relationship between gene expression profile class and tumor thickness reduction as measured by ultrasonography in response to plaque brachytherapy using a single-center, retrospective cohort study. METHODS: A total of 15 patients with choroidal melanoma who underwent biopsy for gene expression profiling and were treated with plaque brachytherapy from a single institution from 12/8/14 through 12/19/19 were retrospectively reviewed for clinical characteristics and rate of tumor regression. Ultrasonographic B-scan tumor height was recorded just prior to plaque placement and following plaque removal in the patient's chart to assess percent reduction in tumor thickness from baseline. RESULTS: A total of 15 patients met inclusion criteria and were analyzed in this study. Minimum follow-up was 6 months after plaque removal. The percent regression in tumor thickness from baseline as measured by ultrasonography was greater for class 2 tumors than for class 1 tumors at 12-month follow up after treatment, and this difference was statistically significant (P = 0.012). There was no statistical significance in reduction at 3 months (P = 0.46) and 9 months (P = 0.10) after plaque brachytherapy. Although not statistically significant, class 2 tumors appeared to regress more rapidly than class 1 tumors in response to radiation. CONCLUSIONS: In this study, class 2 choroidal melanoma tumors show a more rapid anatomic response to treatment than class 1 tumors at 12 months post plaque brachytherapy.

MULTISCALE CORRELATION OF MICROVASCULAR CHANGES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH RETINAL SENSITIVITY IN DIABETIC RETINOPATHY.

PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSION: This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.

Anterior segment optical coherence tomography angiography in the assessment of ocular surface lesions.

PURPOSE: Describe the utility of anterior segment optical coherence tomography angiography (AS-OCTA) to assess ocular surface lesions. METHODS: Retrospective, case-control study of 10 eyes of 9 patients with malignant lesions and 23 eyes of 22 patients with benign lesions. Lesions included 13 epithelial, 10 pigmented and 10 lymphoid lesions. Graders performed an average of 3 depth and diameter measurements of peri-lesional vessels entering each lesion on AS-OCTA. Statistical models to assess differences between groups accounted for bilateral eye inclusion and lesion thickness (on AS-OCT). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were performed for each parameter. RESULTS: In the benign and malignant groups, age was 49.5 ± 22.4 and 64.3 ± 10.6 years (p = 0.145) with 45% males and 55% males (p = 0.458), in their respective groups. AS-OCTA showed greater peri-lesional vessel depth and diameter in malignant lesions (315.2 ± 73.0 µm, p < 0.001 and 76.4 ± 18.2 µm, p < 0.001; respectively) compared to benign lesions (199.4 ± 34.1 µm and 44.0 ± 9.4 µm, respectively). Malignant lesions showed deep and dilated peri-lesional vessels, which may represent feeder vessels. Vessel depth showed AUC = 0.980, 90.9% sensitivity and 100.0% specificity with a 236.5 µm cutoff. Vessel diameter showed AUC = 0.960, 100.0% sensitivity and 88.9% specificity with a 53.9 µm cutoff. CONCLUSION: AS-OCTA shows greater peri-lesional vessel depth and diameter of malignant lesions compared to benign lesions. This imaging modality provides novel and non-invasive functional vascular parameters that can potentially aid the assessment of ocular surface lesions.

Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy and its association with treatment response.

BACKGROUND: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti-vascular endothelial growth factor (VEGF) therapy in initially treatment-naïve eyes with diabetic macular oedema (DME). METHODS: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea-with the exclusion of foveal avascular zone (FAZ)-in 0.5 mm diameter increments as well as within the intervening rings. RESULTS: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). CONCLUSIONS: Absence of significant change in mean ICA after a minimum of three intravitreal anti-VEGF injections, may indicate that, in the short term, anti-VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes.

Treatment and Excision of Retinal Capillary Hemangioblastoma.

This is a case report detailing a pars plana vitrectomy and resection of a retinal capillary hemangioblastoma in a 19-year-old female with a history of von Hippel-Lindau syndrome with secondary retinal detachment and sub-retinal exudates limiting her vision. Intraoperatively, long duration endolaser and generous endodiathermy applied to the feeder vessels are essential to minimize bleeding. Complete and careful resection of the lesion and installation of a silicone oil tamponade are recommended. This technique can allow for retinal reattachment and improvement in visual acuity in advanced cases of secondary retinal detachment.

White Paper on Ophthalmic Imaging for Choroidal Nevus Identification and Transformation into Melanoma.

Purpose: To discuss the evolution of noninvasive diagnostic methods in the identification of choroidal nevus and determination of risk factors for malignant transformation as well as introduce the novel role that artificial intelligence (AI) can play in the diagnostic process. Methods: White paper. Results: Longstanding diagnostic methods to stratify benign choroidal nevus from choroidal melanoma and to further determine the risk for nevus transformation into melanoma have been dependent on recognition of key clinical features by ophthalmic examination. These risk factors have been derived from multiple large cohort research studies over the past several decades and have garnered widespread use throughout the world. More recent publications have applied ocular diagnostic testing (fundus photography, ultrasound examination, autofluorescence, and optical coherence tomography) to identify risk factors for the malignant transformation of choroidal nevus based on multimodal imaging features. The widespread usage of ophthalmic imaging systems to identify and follow choroidal nevus, in conjunction with the characterization of malignant transformation risk factors via diagnostic imaging, presents a novel path to apply AI. Conclusions: AI applied to existing ophthalmic imaging systems could be used for both identification of choroidal nevus and as a tool to aid in earlier detection of transformation to malignant melanoma. Translational Relevance: Advances in AI models applied to ophthalmic imaging systems have the potential to improve patient care, because earlier detection and treatment of melanoma has been proven to improve long-term clinical outcomes.

FULL-THICKNESS MACULAR HOLE SIZE BY HYPERTRANSMISSION SIGNAL ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To assess the full-thickness macular hole (FTMH) size using the choroidal hypertransmission signal on spectral-domain optical coherence tomography and to compare this method to the standard aperture measurement of the minimum aperture size at the level of the neurosensory retina. DESIGN: Cross-sectional study of retrospective data. METHODS: Eyes with FTMH imaged on spectral-domain optical coherence tomography were included. Two independent masked graders used the device's built-in caliper tool to measure the FTMH minimum aperture size at the level of the neurosensory retina and the size of the corresponding hypertransmission signal below the level of the retinal pigment epithelium/Bruch membrane complex. To assess the reproducibility of the hypertransmission measurement in tilted scans, two measurements were obtained and compared; the first was traced parallel to the retinal pigment epithelium (parallel hypertransmission), and the second was horizontal to the image frame (horizontal hypertransmission), both using Image J software. RESULTS: A total of 31 eyes were enrolled. The mean FTMH minimum aperture size was smaller compared with both the choroidal parallel hypertransmission and horizontal hypertransmission measurements (mean ± SD: 335.7 ± 139.5 µm, 376.7 ± 150.6 µm, 375.1 ± 150.0 µm, respectively. P < 0.001 for both comparisons). CONCLUSION: The proposed hypertransmission measurement is a feasible and reproducible alternative to assess FTMH size and could provide the basis for an automated FTMH measurement on cross-sectional spectral-domain optical coherence tomography scans, as presented in this study, or on the spectral-domain optical coherence tomography volumetric data set by using an en face projection.

Optical coherence tomography angiography distortion correction in widefield montage images.

BACKGROUND: Optical coherence tomography (OCT) imaging is inherently susceptible to distortion artifacts due to the natural curvature of the eye. This study proposes a novel model for widefield OCT angiography (OCTA) distortion correction and analyzes the effects of this correction on quantification metrics. METHODS: Widefield OCTA images were obtained on normal subjects at five fixation spatial positions. Radial and field distortion correction were applied and images stitched together to form a corrected widefield montage image. Vessel area density (VAD), vessel complexity index (VCI), and flow impairment area were quantified on the original and corrected montage images. RESULTS: This model allows for distortion correction and montaging of widefield images. There were either statistically insignificant or small magnitude changes in vessel density and vessel complexity between uncorrected and corrected widefield images. There was a significant and large difference in flow impairment area, both in the macular (+8.2%, P=0.049) and peripheral areas (+17.2%, P=0.011), following correction. The relationship between pre- and post-correction flow impairment area was non-linear. CONCLUSIONS: Distortion correction of widefield OCTA images can result in clinically and statistically significant differences in important quantification metrics. This effect appears to be most pronounced in the periphery.

Atypical unilateral multifocal choroiditis in a COVID-19 positive patient.

PURPOSE: To present a case of an atypical unilateral multifocal choroiditis that occurred in temporal association to an acute covid-19 infection. METHOD: A 23-year-old highly myopic man presented with reduced vision in the right eye while under medical quarantine due to direct exposure to COVID-19 infection. Five days after developing mild COVID symptoms (fever, cough and anosmia) he noticed acute painless loss of central vision in his right eye. Systemic evaluation at presentation was positive for SARS-CoV-2 detected via both a pharyngeal swab and serologic titers. Dilated fundus exam was performed, followed by color fundus pictures, optic coherence tomography (OCT), fundus autofluorescence (FAF) and fluorescein angiography (FA). RESULTS: Fundoscopic examination of the right eye revealed the presence of multiple discrete, slightly elevated yellow-whitish placoid lesions at the posterior pole. The visual acuity was 20/800. The left eye was normal with 20/20 vision. The patient was placed on oral corticosteroids and the lesions rapidly improved. CONCLUSION: The patient had an MFC chorioretinitis around the same time that he had a documented acute covid infection. Though the temporal relationship could be by chance alone, communicating this case to the ophthalmic community is warranted to see if other similar cases are noted.

Efficient and high accuracy 3-D OCT angiography motion correction in pathology.

We describe a novel method for non-rigid 3-D motion correction of orthogonally raster-scanned optical coherence tomography angiography volumes. This is the first approach that aligns predominantly axial structural features such as retinal layers as well as transverse angiographic vascular features in a joint optimization. Combined with orthogonal scanning and favorization of kinematically more plausible displacements, subpixel alignment and micrometer-scale distortion correction is achieved in all 3 dimensions. As no specific structures are segmented, the method is by design robust to pathologic changes. Furthermore, the method is designed for highly parallel implementation and short runtime, allowing its integration into clinical workflow even for high density or wide-field scans. We evaluated the algorithm with metrics related to clinically relevant features in an extensive quantitative evaluation based on 204 volumetric scans of 17 subjects, including patients with diverse pathologies and healthy controls. Using this method, we achieve state-of-the-art axial motion correction and show significant advances in both transverse co-alignment and distortion correction, especially in the subgroup with pathology.

OCT-OCTA segmentation: combining structural and blood flow information to segment Bruch's membrane.

In this paper we present a fully automated graph-based segmentation algorithm that jointly uses optical coherence tomography (OCT) and OCT angiography (OCTA) data to segment Bruch's membrane (BM). This is especially valuable in cases where the spatial correlation between BM, which is usually not visible on OCT scans, and the retinal pigment epithelium (RPE), which is often used as a surrogate for segmenting BM, is distorted by pathology. We validated the performance of our proposed algorithm against manual segmentation in a total of 18 eyes from healthy controls and patients with diabetic retinopathy (DR), non-exudative age-related macular degeneration (AMD) (early/intermediate AMD, nascent geographic atrophy (nGA) and drusen-associated geographic atrophy (DAGA) and geographic atrophy (GA)), and choroidal neovascularization (CNV) with a mean absolute error of ∼0.91 pixel (∼4.1 µm). This paper suggests that OCT-OCTA segmentation may be a useful framework to complement the growing usage of OCTA in ophthalmic research and clinical communities.

Retinal hemangioblastoma vascular detail elucidated on swept source optical coherence tomography angiography.

PURPOSE: To report the distinct vascular pattern of a treatment-naïve retinal hemangioblastoma imaged on swept source optical coherence tomography angiography (SS-OCTA). OBSERVATIONS: A 33-year-old female with a history of Von Hippel-Lindau disease presented for follow-up of bilateral retinal hemangioblastomas. Ultra-widefield fundus photography of the left eye revealed a small, juxtapapillary lesion. SS-OCTA imaging centered at the lesion identified two distinct vascular foci. Centrally, the lesion was composed of a dense capillary meshwork. Peripherally, a pattern of branching vessels with terminal budding was identified. The patient was diagnosed with a new juxtapapillary retinal hemangioblastoma. CONCLUSIONS AND IMPORTANCE: SS-OCTA can visualize the in-vivo vascular structure of retinal hemangioblastomas. Early lesion identification can help in prompt diagnosis and monitoring. Further investigation is needed to assert if the branching and budding pattern described in this case report is broadly characteristic of this tumor entity.

Analyzing Relative Flow Speeds in Diabetic Retinopathy Using Variable Interscan Time Analysis OCT Angiography.

PURPOSE: Further insight into the flow characteristics of the vascular features associated with diabetic retinopathy (DR) may improve assessment and treatment of disease progression. The variable interscan time analysis (VISTA) algorithm is an extension of OCT angiography (OCTA) that detects relative blood flow speeds, which then can be depicted on a color-coded map. This study used VISTA to analyze relative blood flow speeds in the microvascular changes associated with DR. DESIGN: Cross-sectional study. PARTICIPANTS: Thirteen patients with varying severities of DR treated at New England Eye Center, Boston, Massachusetts. METHODS: OCT angiography images centered at the fovea were obtained on a prototype swept-source OCT device, and the VISTA algorithm was applied to visualize relative blood flow speeds. MAIN OUTCOME MEASURES: Descriptive flow analysis of the retinal vascular features of DR was conducted on the VISTA-generated images. RESULTS: Twenty-six eyes were included in this study. Of these, 3 eyes had mild nonproliferative DR (NPDR), 6 eyes had moderate NPDR, 4 eyes had severe NPDR, 9 eyes had proliferative DR, and 4 eyes were normal controls. Microaneurysms, intraretinal microvascular abnormalities (IRMAs), and neovascularization appeared to originate from areas of relatively slow blood flow speeds. Microaneurysms showed relatively slower flow, IRMAs showed turbulent, intermediate to slow flow, and venous beading and looping presented with relatively high flow speeds that tapered progressively. Neovascularization of venous origin demonstrated slower flow speeds, whereas that of arterial origin showed relatively high flow speeds. Additionally, increased disease severity was associated with globally slower flow speeds, with particularly slower flow around the foveal avascular zone. CONCLUSIONS: The VISTA algorithm seems to be a useful extension of OCTA that overcomes some of the limitations of normal gray-scale OCTA. It seems to have some potential in providing relevant insight into the pathogenesis of the microvascular changes associated with DR. These findings may assist in improving our understanding of the pathogenic changes that take place in DR.

Retinal Imaging Using a Confocal Scanning Laser Ophthalmoscope-Based High-Magnification Module.

PURPOSE: To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. DESIGN: Observational descriptive study. PARTICIPANTS: Thirty-two participants with normal and pathologic retina examination results. METHODS: Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. MAIN OUTCOMES MEASURES: Description of HMM module-obtained macula images. RESULTS: From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. CONCLUSIONS: In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.