Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance. CONCLUSIONS: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Treatment of Noninfectious Uveitic Macular Edema with Periocular and Intraocular Corticosteroid Therapies: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema. METHODS: A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients. RESULTS: This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation. CONCLUSIONS: The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Perfused and Nonperfused Microaneurysms Identified and Characterized by Structural and Angiographic OCT.

PURPOSE: Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR. METHODS: We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection. MAIN OUTCOME MEASURES: OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow. RESULTS: We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. CONCLUSIONS: OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Interpretable Diabetic Retinopathy Diagnosis Based on Biomarker Activation Map.

OBJECTIVE: Deep learning classifiers provide the most accurate means of automatically diagnosing diabetic retinopathy (DR) based on optical coherence tomography (OCT) and its angiography (OCTA). The power of these models is attributable in part to the inclusion of hidden layers that provide the complexity required to achieve a desired task. However, hidden layers also render algorithm outputs difficult to interpret. Here we introduce a novel biomarker activation map (BAM) framework based on generative adversarial learning that allows clinicians to verify and understand classifiers' decision-making. METHODS: A data set including 456 macular scans were graded as non-referable or referable DR based on current clinical standards. A DR classifier that was used to evaluate our BAM was first trained based on this data set. The BAM generation framework was designed by combing two U-shaped generators to provide meaningful interpretability to this classifier. The main generator was trained to take referable scans as input and produce an output that would be classified by the classifier as non-referable. The BAM is then constructed as the difference image between the output and input of the main generator. To ensure that the BAM only highlights classifier-utilized biomarkers an assistant generator was trained to do the opposite, producing scans that would be classified as referable by the classifier from non-referable scans. RESULTS: The generated BAMs highlighted known pathologic features including nonperfusion area and retinal fluid. CONCLUSION/SIGNIFICANCE: A fully interpretable classifier based on these highlights could help clinicians better utilize and verify automated DR diagnosis.

Early Sign of Retinal Neovascularization Evolution in Diabetic Retinopathy: A Longitudinal OCT Angiography Study.

Purpose: To assess whether the combination of en face OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR). Design: Retrospective, longitudinal study. Participants: Patients with DR that had at least 2 visits. Methods: We obtained wide-field OCTA scans of 1 eye from each participant and generated en face OCT, en face OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on en face OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on en face OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the en face OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV. Main Outcome Measures: The characteristics and longitudinal observation of early signs of RNV. Results: From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age (P = 0.014) and tended to be treatment naive (P = 0.07) compared with eyes without progression. Conclusions: Longitudinal observation demonstrated that a combination of en face OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on en face OCTA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Perfused and Nonperfused Microaneurysms Identified and Characterized by Structural and Angiographic OCT.

Purpose: Microaneurysms (MAs) have distinct, oval-shaped, hyperreflective walls on structural OCT, and inconsistent flow signal in the lumen with OCT angiography (OCTA). Their relationship to regional macular edema in diabetic retinopathy (DR) has not been quantitatively explored. Design: Retrospective, cross-sectional study. Participants: A total of 99 participants, including 23 with mild, nonproliferative DR (NPDR), 25 with moderate NPDR, 34 with severe NPDR, and 17 with proliferative DR. Methods: We obtained 3 × 3-mm scans with a commercial device (Solix, Visionix/Optovue) in 99 patients with DR. Trained graders manually identified MAs and their location relative to the anatomic layers from cross-sectional OCT. Microaneurysms were first classified as perfused if flow signal was present in the OCTA channel. Then, perfused MAs were further classified into fully and partially perfused MAs based on the flow characteristics in en face OCTA. The presence of retinal fluid based on OCT near MAs was compared between perfused and nonperfused types. We also compared OCT-based MA detection to fundus photography (FP)- and fluorescein angiography (FA)-based detection. Main Outcome Measures: OCT-identified MAs can be classified according to colocalized OCTA flow signal into fully perfused, partially perfused, and nonperfused types. Fully perfused MAs may be more likely to be associated with diabetic macular edema (DME) than those without flow. Results: We identified 308 MAs (166 fully perfused, 88 partially perfused, 54 nonperfused) in 42 eyes using OCT and OCTA. Nearly half of the MAs identified in this study straddle the inner nuclear layer and outer plexiform layer. Compared with partially perfused and nonperfused MAs, fully perfused MAs were more likely to be associated with local retinal fluid. The associated fluid volumes were larger with fully perfused MAs compared with other types. OCT/OCTA detected all MAs found on FP. Although not all MAs seen with FA were identified with OCT, some MAs seen with OCT were not visible with FA or FP. Conclusions: OCT-identified MAs with colocalized flow on OCTA are more likely to be associated with DME than those without flow. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Retina 2023;■:1-8 © 2023 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Late diagnosis of Cutibacterium acnes (formerly Proprionibacterium acnes) endophthalmitis and the importance of dual testing with bacterial culture and polymerase chain reaction.

PURPOSE: To describe two cases of C. acnes endophthalmitis that reinforce the importance of performing both bacterial culture and 16s polymerase chain reaction when the causative pathogen is unclear or difficult to culture, such as C. acnes. A case of C. acnes endophthalmitis complicated by sub-buckle scleral perforation is illustrated with intraoperative photography. METHODS: Two-case series. RESULTS: Case 1 describes a case of C. acnes endophthalmitis in a longstanding pseudophakic patient following multiple vitrectomies for recurrent retinal detachment, complicated by sub-buckle scleral perforation. Bacterial culture revealed C. acnes while 16s PCR was negative. Conversely, Case 2 demonstrates a case of chronic endophthalmitis diagnosed one year following cataract surgery. PCR (with repeat tap for confirmation) revealed C. acnes with a negative culture. CONCLUSION: When the causative pathogen of endophthalmitis is unclear, dual testing of microbial culture and C. acnes 16s PCR improves the diagnostic yield of investigations for fastidious pathogens. C. acnes can present as an indolent or virulent endophthalmitis.

Automated Macular Fluid Volume As a Treatment Indicator for Diabetic Macular Edema.

Introduction: To assess the diagnostic accuracy of automatically quantified macular fluid volume (MFV) for treatment-required diabetic macular edema (DME). Methods: This retrospective cross-sectional study included eyes with DME. The commercial software on optical coherence tomography (OCT) produced the central subfield thickness (CST), and a custom deep-learning algorithm automatically segmented the fluid cysts and quantified the MFV from the volumetric scans of an OCT angiography system. Retina specialists treated patients per standard of care based on clinical and OCT findings without access to the MFV. The main outcome measures were the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of the CST, MFV, and visual acuity (VA) for treatment indication. Results: Of 139 eyes, 39 (28%) were treated for DME during the study period and 101 (72%) were previously treated. The algorithm detected fluid in all eyes; however, only 54 eyes (39%) met the DRCR.net criteria for center-involved ME. The AUROC of MFV predicting a treatment decision of 0.81 was greater than that of CST (0.67) (P = .0048). Untreated eyes that met the optimal threshold for treatment-required DME based on MFV (>0.031 mm3) had better VA than treated eyes (P = .0053). A multivariate logistic regression model showed that MFV (P = .0008) and VA (P = .0061) were significantly associated with a treatment decision, but CST was not. Conclusions: MFV had a higher correlation with the need for treatment for DME than CST and may be especially useful for ongoing management of DME.

Utility of En Face OCT for the Detection of Clinically Unsuspected Retinal Neovascularization in Patients with Diabetic Retinopathy.

PURPOSE: To assess the value of en face OCT for detecting clinically unsuspected retinal neovascularization (RNV) in patients with nonproliferative diabetic retinopathy (NPDR). DESIGN: A retrospective, cross-sectional study. PARTICIPANTS: Treatment-naïve patients clinically graded as NPDR in an ongoing prospective observational OCT angiography (OCTA) study at a tertiary care center. METHODS: Each patient underwent imaging of 1 eye with a spectral-domain OCTA, generating a 17 × 17-mm widefield image by montaging four 9 × 9-mm scans. Two independent graders examined a combination of en face OCT, en face OCTA with a custom vitreoretinal interface slab, and cross-sectional OCTA to determine the presence of RNV. We measured the area of RNV flow within RNV lesions on en face OCTA. MAIN OUTCOME MEASURES: Detection rate of clinically occult RNV with OCT and OCTA. RESULTS: Of 63 enrolled eyes, 27 (43%) were clinically graded as severe NPDR, 16 (25%) as moderate NPDR, and 20 (32%) as mild NPDR. Using the combination of en face OCT, en face OCTA, and cross-sectional OCTA, the graders detected 42 RNV lesions in 12 (19%) eyes, of which 8 (67%) were graded as severe NPDR, 2 (17%) as moderate NPDR, and 2 (17%) as mild NPDR. The sensitivity of en face OCT alone for detecting eyes with RNV was similar to that of en face OCTA alone (100% vs. 92%; P = 0.32), whereas the specificity of en face OCT alone was significantly lower than that of en face OCTA alone (32% vs. 73%; P < 0.001). For detecting individual RNV lesions, the en face OCT was 100% sensitive, compared with 67% sensitivity for the en face OCTA (P < 0.001). The area of RNV lesions that manual grading with en face OCTA alone missed was significantly smaller than that of manually detectable RNV (Mean [standard deviation] RNV flow area, 0.015 [0.020] mm2 vs. 0.16 [0.36] mm2; P < 0.001). CONCLUSION: The combination of en face OCT and OCTA can detect clinically occult RNV with high sensitivity. For screening these small lesions, en face OCT may be a useful imaging modality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Deep learning-based signal-independent assessment of macular avascular area on 6×6 mm optical coherence tomography angiogram in diabetic retinopathy: a comparison to instrument-embedded software.

SYNOPSIS: A deep-learning-based macular extrafoveal avascular area (EAA) on a 6×6 mm optical coherence tomography (OCT) angiogram is less dependent on the signal strength and shadow artefacts, providing better diagnostic accuracy for diabetic retinopathy (DR) severity than the commercial software measured extrafoveal vessel density (EVD). AIMS: To compare a deep-learning-based EAA to commercial output EVD in the diagnostic accuracy of determining DR severity levels from 6×6 mm OCT angiography (OCTA) scans. METHODS: The 6×6 mm macular OCTA scans were acquired on one eye of each participant with a spectral-domain OCTA system. After excluding the central 1 mm diameter circle, the EAA on superficial vascular complex was measured with a deep-learning-based algorithm, and the EVD was obtained with commercial software. RESULTS: The study included 34 healthy controls and 118 diabetic patients. EAA and EVD were highly correlated with DR severity (ρ=0.812 and -0.577, respectively, both p<0.001) and visual acuity (r=-0.357 and 0.420, respectively, both p<0.001). EAA had a significantly (p<0.001) higher correlation with DR severity than EVD. With the specificity at 95%, the sensitivities of EAA for differentiating diabetes mellitus (DM), DR and severe DR from control were 80.5%, 92.0% and 100.0%, respectively, significantly higher than those of EVD 11.9% (p=0.001), 13.6% (p<0.001) and 15.8% (p<0.001), respectively. EVD was significantly correlated with signal strength index (SSI) (r=0.607, p<0.001) and shadow area (r=-0.530, p<0.001), but EAA was not (r=-0.044, p=0.805 and r=-0.046, p=0.796, respectively). Adjustment of EVD with SSI and shadow area lowered sensitivities for detection of DM, DR and severe DR. CONCLUSION: Macular EAA on 6×6 mm OCTA measured with a deep learning-based algorithm is less dependent on the signal strength and shadow artefacts, and provides better diagnostic accuracy for DR severity than EVD measured with the instrument-embedded software.

RETINAL INFILTRATION IN A CASE OF CHRONIC MYELOID LEUKEMIA.

PURPOSE: To describe a case of chronic myeloid leukemia with retinal leukemic infiltration identified by optical coherence tomography (OCT) and OCT angiography. METHODS: Case report. RESULTS: A 64-year-old man presented with bilateral painless blurred vision and three weeks of fatigue, unintentional weight loss, and complete hearing loss. Dilated fundus examination of both eyes showed peripheral intraretinal hemorrhages with white centers, vascular tortuosity, and peripheral nonperfusion. No macular lesions were identified by slit-lamp examination, fundus photography, fundus autofluorescence, or fluorescein angiography. Optical coherence tomography through the macula revealed multiple hyperreflective lesions throughout the inner retinal layers. Some of these lesions showed intrinsic flow by OCT angiography, but many lesions did not. The bone marrow biopsy confirmed chronic myeloid leukemia, and these intraretinal lesions were deemed to be leukemic infiltrates. The patient regained vision after systemic chemotherapy with resolution of the retinal infiltrates over time. CONCLUSION: Primary leukemic retinal involvement can be challenging to diagnose, especially when the macula appears normal clinically. Optical coherence tomography and OCT angiography are useful imaging modalities for the detection of retinal leukemic infiltration. Completing a thorough review of systems and initiating an urgent, systemic work-up are warranted in cases of retinal infiltration.

A Deep Learning Network for Classifying Arteries and Veins in Montaged Widefield OCT Angiograms.

Purpose: To propose a deep-learning-based method to differentiate arteries from veins in montaged widefield OCT angiography (OCTA). Design: Cross-sectional study. Participants: A total of 232 participants, including 109 participants with diabetic retinopathy (DR), 64 participants with branch retinal vein occlusion (BRVO), 27 participants with diabetes but without DR, and 32 healthy participants. Methods: We propose a convolutional neural network (CAVnet) to classify retinal blood vessels on montaged widefield OCTA en face images as arteries and veins. A total of 240 retinal angiograms from 88 eyes were used to train CAVnet, and 302 retinal angiograms from 144 eyes were used for testing. This method takes the OCTA images as input and outputs the segmentation results with arteries and veins down to the level of precapillary arterioles and postcapillary venules. The network also identifies their intersections. We evaluated the agreement (in pixels) between segmentation results and the manually graded ground truth using sensitivity, specificity, F1-score, and Intersection over Union (IoU). Measurements of arterial and venous caliber or tortuosity are made on our algorithm's output of healthy and diseased eyes. Main Outcome Measures: Classification of arteries and veins, arterial and venous caliber, and arterial and venous tortuosity. Results: For classification and identification of arteries, the algorithm achieved average sensitivity of 95.3%, specificity of 99.6%, F1 score of 94.2%, and IoU of 89.3%. For veins, the algorithm achieved average sensitivity of 94.4%, specificity of 99.7%, F1 score of 94.1%, and IoU of 89.2%. We also achieved an average sensitivity of 76.3% in identifying intersection points. The results show CAVnet has high accuracy on differentiating arteries and veins in DR and BRVO cases. These classification results are robust across 2 instruments and multiple scan volume sizes. Outputs of CAVnet were used to measure arterial and venous caliber or tortuosity, and pixel-wise caliber and tortuosity maps were generated. Differences between healthy and diseased eyes were demonstrated, indicating potential clinical utility. Conclusions: The CAVnet can classify arteries and veins and their branches with high accuracy and is potentially useful in the analysis of vessel type-specific features on diseases such as branch retinal artery occlusion and BRVO.

Association Between Fluid Volume in Inner Nuclear Layer and Visual Acuity in Diabetic Macular Edema.

PURPOSE: In diabetic macular edema (DME), the correlation between visual acuity (VA) and central subfield thickness (CST) is weak. We hypothesize that fluid volume (FV) in the inner nuclear layer (INL) may correlate more strongly with VA. DESIGN: Retrospective, cross-sectional study. METHODS: One eye each of diabetic patients with DME was included. We measured intraretinal fluid volume that was detected by automated fluid detection algorithm on 3- × 3-mm optical coherence tomography angiogram volume scans. The detected fluid was subdivided into inner FV, bounded by the INL, and outer FV, the fluid between the outer border of INL to the ellipsoid zone. RESULTS: We enrolled 125 patients with DME (60 women; mean age, 61 years). The mean detected inner FV was 0.013 mm3 in 109 eyes (87%). The mean detected outer FV was 0.042 mm3 in 124 eyes (99%). Univariate analysis demonstrated that the VA significantly correlated with the inner FV (P < .0001), whole macular FV (P = .010), and CST (P = .036). Multivariate analysis demonstrated that the inner FV was the only significant factor (ß = -0.41, P = .004). These correlations were consistent when the treatment-naïve group (n = 33) and the eyes without previous laser treatments (n = 93) were analyzed separately. The area under the receiver operating characteristic curve of inner FV for VA of 20/32 or worse was significantly higher than that for CST (0.66 vs 0.54, P = .018). CONCLUSIONS: The inner FV has a stronger association with VA than other OCT biomarkers in DME and may be more clinically useful.

Plexus-specific retinal capillary avascular area in exudative age-related macular degeneration with projection-resolved OCT angiography.

OBJECTIVE: To detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA). METHODS AND ANALYSIS: In this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively. RESULTS: Nineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm2, p=0.006), ICP (0.016 vs 0.000 mm2, p=0.004) and DCP (0.033 vs 0.000 mm2, p＜0.001). CONCLUSION: PR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.

Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

Geographic Atrophy Progression Is Associated With Choriocapillaris Flow Deficits Measured With Optical Coherence Tomographic Angiography.

Purpose: The purpose of this study was to assess the associations between baseline choriocapillaris (CC) flow deficits and geographic atrophy (GA) progression. Methods: In this prospective cohort study, patients with GA underwent 3 × 3-mm macular spectral-domain optical coherence tomographic angiography (OCTA) at baseline and follow-up visits. Annual GA enlargement rate was defined as change of square root of GA area in 12 months. Shadow areas due to iris, media opacity, retinal vessels, and drusen were excluded. CC vessel density (CC-VD) in non-GA areas was measured using a validated machine-learning-based algorithm. Low perfusion area (LPA) was defined as capillary density below the 0.1 percentile threshold of the same location of 40 normal healthy control eye. Focal perfusion loss (FPL) was defined as percentage of CC loss within LPA compared with normal controls. Results: Ten patients with GA were enrolled and followed for 26 months on average. At baseline, the mean GA area was 0.84 ± 0.70 mm2. The mean CC-VD was 44.5 ± 15.2%, the mean LPA was 4.29 ± 2.6 mm2, and the mean FPL was 50.4 ± 28.2%. The annual GA enlargement rate was significantly associated with baseline CC-VD (r = -0.816, P = 0.004), LPA (r = 0.809, P = 0.005), and FPL (r = 0.800, P = 0.005), but not with age (r = 0.008, P = 0.98) and GA area (r = -0.362, P = 0.30). Conclusions: Baseline CC flow deficits were significantly associated with a faster GA enlargement over the course of 1 year, suggesting the choriocapillaris perfusion outside of a GA area may play a role in GA progression.

Comparison of Central Macular Fluid Volume With Central Subfield Thickness in Patients With Diabetic Macular Edema Using Optical Coherence Tomography Angiography.

IMPORTANCE: Diabetic macular edema (DME) is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography (OCT) may improve the diagnostic accuracy of DME screening. OBJECTIVE: To assess the diagnostic accuracy of an automated central macular fluid volume (CMFV) quantification using OCT for DME. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (1 eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, 2 retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness (CST) within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV). MAIN OUTCOMES AND MEASURES: The area under the receiver operating characteristic curve (AUROC) and the sensitivity and specificity of CST and CMFV for DME diagnosis. RESULTS: We enrolled 1 eye each of 215 patients with diabetes (117 women [54.4%]; mean [SD] age, 59.6 [12.4] years). Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved. The AUROC of CMFV for diagnosis of center-involved DME (0.907 [95% CI, 0.861-0.954]) was greater than the AUROC of CST (0.832 [95% CI, 0.775-0.889]; P = .02). With the specificity set at 95%, the sensitivity of CMFV for detection of center-involved DME (78.5% [95% CI, 68.8%-86.3%]) was higher than that of CST (53.8% [95% CI, 43.1%-64.2%]; P = .002). Center-involved DME cases not detected by CST but detected by CMFV were associated with a thinner CST (290.8 µm [95% CI, 282.3-299.3 µm] vs 369.4 µm [95% CI, 347.1-391.7 µm]; P < .001), higher proportion of previous macular laser treatment (11 of 28 [39.3%; 95% CI, 21.5%-59.4%] vs 12 of 65 [18.5%; 95% CI, 9.9%-30.0%]; P = .03), and female sex (20 of 28 [71.4%; 95% CI, 51.3%-86.8%] vs 31 of 65 [47.7%; 95% CI, 35.1%-60.5%]; P = .04). CONCLUSIONS AND RELEVANCE: These findings suggest that an automated CMFV is a more accurate diagnostic biomarker than CST for DME and may improve screening for DME.

Diabetic eye disease: A review of screening and management recommendations.

The prevalence of diabetes is rapidly increasing, and it is now the leading cause of blindness worldwide. Although early detection of diabetic retinopathy is key to preventing vision loss, many patients do not receive appropriate examinations. Using a multidisciplinary approach, primary care physicians and eye care providers should follow evidence-based recommendations for screening and monitoring diabetic patients while working to improve patients' glycaemic index, blood pressure, and metabolic risk factors. Anti-vascular endothelial growth factor intravitreal injections in combination with panretinal photocoagulation and focal laser treatment remain the cornerstones of modern therapy. The many landmark studies for diabetic eye disease management should guide counselling and decision making for treating diabetic macular oedema, proliferative retinopathy and other diabetes-related eye diseases.