Morphological Changes in the Foveal Avascular Zone after Panretinal Photocoagulation for Diabetic Retinopathy Using OCTA: A Study Focusing on Macular Ischemia.

Background and objectives: This study aimed to analyze the morphological changes in the foveal avascular zone (FAZ) after panretinal photocoagulation (PRP) in patients with diabetic retinopathy, with a particular focus on the presence or absence of comorbid diabetic macular ischemia (DMI), using optical coherence tomography angiography (OCTA). Materials and Methods: Treatment-naïve 25 eyes of 16 patients who received PRP were examined in this retrospective case series. FAZ area, perimeter, and circularity were calculated on a 3 × 3-mm en-face OCTA image before PRP (baseline) and 1 and 3 months after PRP. The patients were divided into two groups according to coexisting DMI, and each group was statistically analyzed. Results: In patients with DMI (9 eyes), FAZ area significantly decreased from the baseline to 3 months after PRP (0.86 ± 0.56 to 0.61 ± 0.31 mm2, p = 0.018), whereas FAZ perimeter and circularity remained unchanged following treatment (p = 0.569 and 0.971, respectively). In patients without DMI (16 eyes), FAZ parameters did not show statistically significant changes across the 3-month follow-up period. Conclusion: PRP significantly reduces FAZ area in patients with DMI.

Looking Ahead: Visual and Anatomical Endpoints in Future Trials of Diabetic Macular Ischemia.

Diabetic macular ischemia (DMI) is a common complication of diabetic retinopathy that can lead to progressive and irreversible visual loss. Despite substantial clinical burden, there are no treatments for DMI, no validated clinical trial endpoints, and few clinical trials focusing on DMI. Therefore, generating consensus on validated endpoints that can be used in DMI for the development of effective interventions is vital. In this review, we discuss potential endpoints appropriate for use in clinical trials of DMI, and consider the data required to establish acceptable and meaningful endpoints. A combination of anatomical, functional, and patient-reported outcome measures will provide the most complete picture of changes that occur during the progression of DMI. Potential endpoint measures include change in size of the foveal avascular zone measured by optical coherence tomography angiography and change over time in best-corrected visual acuity. However, these endpoints must be supported by further research. We also recommend studies to investigate the natural history and progression of DMI. In addition to improving understanding of how patient demographics and comorbidities such as diabetic macular edema affect clinical trial endpoints, these studies would help to build the consensus definition of DMI that is currently missing from clinical practice and research.

Clinical effect of conbercept on improving diabetic macular ischemia by OCT angiography.

BACKGROUND: Varying degrees of macular ischemia generally occur in diabetic retinopathy (DR). This study aims to evaluate the effect of conbercept with 3+ pro re nata (PRN) on macular perfusion status in patients with diabetic macular edema (DME) and quantitatively assess changes in foveal avascular zone (FAZ) areas and capillary density in macular regions by applying optical coherence tomography angiography (OCTA). METHODS: Fifty patients were divided into ischemic (n = 31) and non-ischemic (n = 19) groups according to the presence of ischemia on OCTA at baseline. All patients received intravitreal injections of 0.5 mg of conbercept with 3+ PRN principle. The FAZ areas and macular vessel density measured using OCTA were evaluated at baseline, 3 months, and 6 months after treatment in both groups. RESULTS: At months 3 and 6, the FAZ area in the ischemic group changed from 0.510 ± 0.171 mm2 to 0.441 ± 0.158 mm2 then to 0.427 ± 0.153 mm2 (p = 0.003, p = 0.296); in the non-ischemic group, it remained stable (p = 0.269, p = 0.926). The superficial vessel density changed from 41.1 ± 4.1 to 42.5% ± 4.7% then to 42.6% ± 4.6% (p = 0.043, p = 0.812), and the deep vessel density changed from 40.7 ± 4.4 to 42.3% ± 3.6% then to 42.3% ± 4.7% (p = 0.072, p = 0.961) in the ischemic group. In the non-ischemic group, the superficial vessel density changed from 44.8 ± 3.2 to 46.0% ± 3.5% then to 45.7% ± 3.3% (p = 0.108, p = 0.666), whereas the deep vessel density changed from 43.6 ± 3.6 to 43.8% ± 3.2% then to 43.5% ± 4.5% (p = 0.882, p = 0.736). Reperfusion in macular nonperfusion areas was observed. CONCLUSION: Anti-vascular endothelial growth factor treatment may have a positive effect on macular perfusion status. Furthermore, OCTA had advantages in quantifying and calculating blood flow index in the study of macular perfusion status.

[Visualization of retinal blood flow disturbances in acute retinal ischemia syndrome]. / Vizualizatsiya narushenii retinal'nogo krovotoka pri sindrome ostroi ishemii setchatki.

Vascular disorders account for a significant proportion of acute loss of vision. In recent years, scientific and technical progress in ophthalmology has provided new opportunities in the study of vascular pathology, significantly expanding the understanding of their pathogenesis. The article presents a clinical case of a patient with acute retinal ischemia syndrome who had retinal blood flow disturbances studied using optical coherence tomography (OCT) imaging. It demonstrates extensive possibilities of diagnostics of ischemic retinal lesions using OCT angiography that make this method the most informative in terms of evaluating the blood flow at different levels, independently in each vascular plexus.

Macular vessels density in diabetic retinopathy: quantitative assessment using optical coherence tomography angiography.

PURPOSE: The aim of this study was to evaluate macular perfusion using OCTA automated software algorithms; vessel area density (VD) and non-flow tool to measure FAZ area in treatment-naïve diabetic eyes with moderate or severe NPDR and having macular edema, and correlate these parameters with LogMAR (logarithm of the minimum angle of resolution) visual acuity. Diabetic eyes without macular edema were included, to detect and define differences within the parameters between diabetic eyes with and without macular edema. METHODS: Forty-five diabetic eyes with diabetic macular edema, forty diabetic eyes without macular edema, and forty eyes of healthy controls were examined using OCTA (RTVue-XR Avanti; Optovue, Inc, Fremont, CA). The macular vessel area density (VD) and foveal avascular zone (FAZ) area were assessed and statistically compared between the three groups and also correlated with the foveal thickness and visual acuity. Data were entered and analyzed by SPSS 19. Quantitative data were presented as mean and standard deviation, and qualitative data presented as frequency distribution; independent samples t test, Chi square test and Pearson correlation were done. RESULTS: Mean whole image VD was 44.4 ± 3.6 in diabetic eyes with DME, 45.6 ± 4.2 in diabetics without DME, and 49 ± 3.9 in control eyes (P = 0.001). Diabetic eyes with DME had significantly lower vessels density values at the level of the deep retinal plexus (in the parafoveal, superior hemi, inferior hemi, temporal, superior, and nasal areas), when compared with diabetic eyes without DME. In diabetic eyes with DME, significant fair negative correlation was found between whole image vessels density at the level of the superficial retinal plexus and LogMAR VA (r = - 0.313, P = 0.036). Also, a significant fair positive correlation was found between FAZ area (at both the superficial and deep retinal plexus) and LogMAR visual acuity, in diabetic eyes with DME, where eyes with larger FAZ area had worse vision (P = 0.005 and P = 0.016, respectively). Diabetic eyes with DME had significantly larger FAZ area at the level of the superficial capillary plexus (mean superficial FAZ ± SD 0.55 ± 0.25) than diabetic eyes without edema (mean superficial FAZ ± SD 0.41 ± 0.12) and control subjects (mean superficial FAZ ± SD 0.35 ± 0.09). CONCLUSION: Using OCTA machine with AngioAnalytics parameters (vessel area density and non-flow area) helped in objective quantification of macular perfusion and accurately measuring the FAZ area in diabetic eyes with macular edema. Both parameters were significantly correlated with visual function in treatment-naïve diabetic eyes with edema. These OCTA biomarkers could be used to predict visual function in such eyes, to monitor response to treatment.

[Complex assessment of retinal ischemic damage in patients with retinal vein occlusion]. / Kompleksnaia otsenka ishemicheskogo povrezhdeniia setchatki pri okkliuzii retinal'nykh ven.

PURPOSE: To evaluate the effectiveness of treatment and the possibility of restoring visual functions in patients with retinal vein occlusion (RVO) depending on the initial degree of macular ischemia. MATERIAL AND METHODS: The study included 84 patients with RVO. The main inclusion criteria were the presence of macular edema in the setting of RVO with the duration of no more than 3 months and without any previous treatment. All patients underwent intravitreal injections of an angiogenesis inhibitor, followed by laser treatment when necessary. A comparative analysis of the results was carried out in groups that were opposite in terms of the clinical effect - before the start of the therapy, after 1 month, and after 12 months. All patients and the control group members underwent standard ophthalmological examination as well as electroretinography, fluorescence angiography, optical coherence tomography (OCT), and OCT angiography. RESULTS: Based on data obtained during 12 months of the follow-up, the comparative analysis of the initial ophthalmic status of patients with RVO with opposite clinical effect resulted in derivation of 3 clinical groups that correspond to the degrees of macular ischemia - mild, moderate and severe. CONCLUSION: Determination of the degree of macular ischemia at the stage of primary diagnosis can improve the treatment effectiveness and inform the patients about the sequence and duration of anti-VEGF therapy. Intravitreal injections of ranibizumab in retinal vein occlusion are carried out before the elimination of macular edema and further in the on-demand mode, while the number of injections can vary from one to monthly injections during the year.

Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

OCT angiography 2023 update: focus on diabetic retinopathy.

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

[OCT biomarkers in diabetic maculopathy and artificial intelligence]. / OCT-Biomarker bei diabetischer Makulopathie und künstliche Intelligenz.

Diabetes mellitus is a chronic disease the microvascular complications of which include diabetic retinopathy and maculopathy. Diabetic macular edema, proliferative diabetic retinopathy, and diabetic macular ischemia pose a threat to visual acuity. Artificial intelligence can play an increasingly more important role in making the diagnosis and the treatment regimen of maculopathies in everyday clinical practice in the future. It can be used to automatically detect and quantify pathological parameters of the retina. The aim is to improve patient care in the clinical routine using so-called clinical decision support systems with personalized treatment algorithms. This review article outlines the current research regarding new biomarkers in diabetic maculopathy using optical coherence tomography (OCT) and OCT angiography (OCT-A).

Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy.

PURPOSE: To evaluate best-corrected visual acuity (BCVA), retina sensitivity (RS), and fixation impairment by microperimetry (MP) due to the presence and severity of disorganization of retinal inner and outer layers (DRIL/DROL) and ischemia in OCT/OCT angiography (OCTA) in diabetic retinopathy (DR). DESIGN: Retrospective case-control study. SUBJECTS: Seventy-six eyes (65 patients) with DR were analyzed. Major exclusion criteria were: center-involving diabetic macular edema (DME), significant media opacity, nondiabetic macular pathology, and active proliferative DR. Patients with DRIL and DROL within central 3 mm were enrolled as cases. Patients with DR and no retina disorganization were considered as controls. METHODS: A detailed grading of MP and OCT/OCTA images using Image J software, and specific Image Manipulation Program was applied to colocalize the presence of retina disorganization and RS. Best-corrected visual acuity and RS were correlated with the disorganization of retina layers' characteristics and grading (grade 1-DRIL; grade 2-DROL; grade 3-DROL plus, with involvement of the ellipsoid zone). The same procedure of colocalization was applied to the vascular layers on OCTA using MATLAB. MAIN OUTCOME MEASURES: Correlation between BCVA and MP parameters with disorganization of retina layers grading and OCTA parameters. RESULTS: Best-corrected visual acuity, mean RS within 1 mm and central 3 mm (overall RS [oRS]), perfusion density, vessel density, and geometric perfusion deficit in intermediate and deep capillary plexuses were lower in cases versus controls (P < 0.001). Mean RS within 1 mm (21.4 decibels [dB] ± 2.4 vs. 13.8 dB ± 5.4, P = 0.002), oRS (22.0 dB ± 2.1 vs. 14.4 dB ± 4.6, P < 0.001), and BCVA (76.1 ± 7.4 vs. 61.2 ± 20.4 ETDRS letters; P = 0.02), had a significant decrease from grade 1 to grade 3 retina disorganization. Choriocapillaris flow voids (CC-FVs) increased from grade 1 to grade 3 (DROL plus) (P = 0.004). Overall retina sensitivity and CC-FV were identified as significant predictors of retina disorganization grade with an adjusted coefficient of determination, R2 = 0.45. Cases had more dense scotomas (P = 0.03) than controls with a positive correlation between the worsening of fixation stability and the severity of DRIL/DROL (P = 0.04). CONCLUSIONS: Microperimetry and BCVA documented a reduction in visual function in patients with DR and disorganization of retina layers at different grades, with greater functional impairment when outer retina layers and photoreceptors are involved. The severity of retina disorganization and the presence of ischemia could serve as a potential biomarker of functional impairment. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Natural History of Retinal Sensitivity Loss in Diabetic Macular Ischemia over One Year Evaluated by Microperimetry.

Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value <25 decibels (dB) was defined as impaired RS, and a decrease of 2 and 7 dB was regarded as mild and severe loss, respectively. Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI.

A Comparison of Optical Coherence Tomography Angiography Metrics and Artifacts on Scans of Different Sizes in Diabetic Macular Ischemia: The effect of different size scans on DMI evaluation.

PURPOSE: Changes in the foveal avascular zone (FAZ) metrics over time are key outcome measures for clinical trials in diabetic macular ischemia (DMI). However, artifacts and automatically delineated FAZ measurements may influence the results. We aimed to compare the artifact frequency and FAZ metrics on 3 × 3 versus 6 × 6 mm optical coherence tomography angiography (OCTA) macular scans in patients with DMI. DESIGN: Prospective, comparative image quality analysis with one-year follow-up. METHODS: Patients with diabetic retinopathy (DR) were recruited if they presented with OCTA evidence of DMI, defined as an automated FAZ (aFAZ) ≥0.5 mm2 or parafoveal capillary nonperfusion (CNP) ≥1 quadrant if the aFAZ <0.5 mm2. Only those who had both size scans were included in the analysis. The types of artifacts and FAZ delineation errors were graded before manual correction. After excluding scans with poor quality, the aFAZ, corrected FAZ (cFAZ), whole image superficial vessel density (wiSVD), and whole image deep vessel density (wiDVD) were compared on both size scans. RESULTS: Fifty-seven patients (81 eyes) with paired OCTA 3 × 3 and 6 × 6 mm scans at baseline were included in the image quality analysis. The 6 × 6 mm scan presented with more severe motion artifact (P = .02). Conversely, the 3 × 3 mm scans were more susceptible to mild decentration (P = .009). After removing all the poor-quality images, 55 eyes with both size scans entered the longitudinal analysis. The 3 × 3 mm FAZ was significantly larger than the 6 × 6 mm FAZ using either aFAZ or cFAZ (both P < .05). In contrast, the 6 × 6 mm wiSVD and wiDVD were remarkably higher than those on the 3 × 3 mm scans (both P < .001). There was a steady increase in cFAZ over one year on both size scans (both P < .01). However, the 3 × 3 mm aFAZ decreased numerically at 52 weeks (P = .02). After reviewing all the scans, poor identification of parafoveal CNP was the most common reason for erroneous aFAZ delineation. CONCLUSIONS: In DMI, the FAZ metrics are best evaluated on the 3 × 3 scan due to better resolution. However, manual correction of the FAZ margin is needed. The frequency of artifacts and aFAZ delineation errors suggest that further technical refinement is required.

Unusual case of retinal arterial branch occlusion: possible variant of Sneddon syndrome.

Sneddon's syndrome (SS) manifests through multiple strokes and livedo reticularis. Livedoid vasculopathy (VL) is characterized by a long history of foot and leg ulceration and histopathology indicating a thrombotic process. Arterial retinal branch occlusion is described in a 52-year-old male with VL. He did not present noticeable laboratory abnormalities, such as antiphospholipid antibodies, or a history of strokes. Retinal artery occlusion accompanied by VL could be a variant of Sneddon's syndrome. Optical coherence tomography angiography revealed a reduction in the macula's vascular layers in the asymptomatic eye, indicating localized microvascular changes as an evolving marker in the pathogenesis of SS.

Severe Macular Ischemia Is Associated with a Poor Visual Prognosis and Serious Complications in Eyes with Central Retinal Vein Occlusion.

PURPOSE: This study aims to investigate the factors influencing post-treatment visual acuity (VA) in patients with central retinal vein occlusion (CRVO) with macular edema (ME). METHODS: The subjects of this study were patients who visited our clinic from May 2013 to July 2019 and who could be followed up with for at least 12 months. Cases with hemi CRVO were excluded from this study. Factors considered in the evaluation of visual prognosis at the 12 months included initial best-corrected VA, central subfoveal thickness, CRVO subtype (nonischemic, ischemic, or converted from nonischemic to ischemic), time taken for the first treatment, number of anti-vascular endothelial growth factor agent injections, structural changes in the inner and outer retinal layers, and the presence of macular ischemia in a multiple regression analysis. RESULTS: There were 41 patients with 41 eyes, 27 males and 14 females. The mean age of the patients was 70.5 ± 12.2 (mean ± standard deviation) years. The mean VA was 0.544 ± 0.576, 0.456 ± 0.568, and 0.586 ± 0.665 at the initial visit, 12 months later, and time of last observation, respectively. There were no significant differences in VAs observed between the baseline, month 12, and final visit. Multiple regression analysis revealed that the external limiting membrane score at month 12 (p = 0.030), the VA at initial visit (p < 0.001), and the presence of severe macular ischemia (p < 0.001) were the key factors associated with VA at month 12. Moreover, severe macular ischemia was identified as the only factor affecting decimal VA less than 20/200 at the last observation (p = 0.0092). CONCLUSIONS: Severe macular ischemia is strongly linked to a poor visual prognosis in patients with ME associated with CRVO.

Acute Macular Neuroretinopathy Associated With COVID-19 Infection: Is Double Heterozygous Methylenetetrahydrofolate Reductase (MTHFR) Mutation an Underlying Risk Factor?

The goal of this report is to present a case of coronavirus disease 2019 (COVID-19)-associated acute macular neuroretinopathy (AMN) with an underlying MTHFR mutation. A 36-year-old male presented to the emergency department with a sudden-onset paracentral scotoma in his left eye. Although optical coherence tomography (OCT) was normal initially, four days later, it revealed a hyperreflective band in the outer plexiform layer with disruption of the ellipsoid zone/interdigitation zone. On infrared imaging and en-face OCT, wedge-shaped lesions were detected around the fovea with their tip oriented toward the fovea. OCT angiography, fundus autofluorescence, fundus fluorescein angiography, and visual fields were performed. The patient was positive for COVID-19 infection. The absence of medical history and the negative results of blood tests led to a diagnosis of AMN associated with COVID-19. Genetic testing for coagulation disorders was scheduled and revealed a heterozygous mutation for MTHFR C677T and A1298C. This is the first case of AMN in a patient with COVID-19 infection and a double heterozygous mutation of the MTHFR gene. Infection is the most commonly reported association of AMN, while MTHFR mutation may represent an additional underlying risk factor. Microthrombosis and small-vessel occlusion are thought to be involved in the pathophysiology of AMN, and patients should be tested for COVID-19 because it may be the first manifestation of the infection.

Posterior segment involvement in systemic lupus erythematosus - A series from South India.

Purpose: To report the spectrum of posterior segment manifestations and visual outcomes in a large series of patients with systemic lupus erythematosus (SLE). Methods: Retrospective study at a tertiary referral eye center in south India between 2016 and 2022. Results: Charts of 109 patients diagnosed to have SLE were retrieved from our medical database. Only nine cases of SLE (8.25%) had posterior segment involvement. The male: female ratio was 1:8. The mean age was 28 years. Unilaterality was the most common presentation in eight cases (88.89%). Lupus nephritis was the most common systemic presentation in five cases (55.56%). Antiphospholipid antibodies (APLA) positivity was seen in two cases (22.22%). Ocular manifestations included microangiopathy (cotton wool spots) in one case, occlusive retinal vasculitis with cotton wool spots in four cases (five eyes), optic disc edema with combined venous and arterial occlusion (one case), central retinal vein occlusion with cotton wool spots and hemorrhages (one case), macular edema (four cases), posterior scleritis with optic disc edema and exudative retinal detachment in the posterior pole (one case), and tubercular choroidal granuloma (one case). Treatment included systemic steroids, hydroxychloroquine sulfate (HCQS), and immunosuppression in all cases, blood thinners in two cases, and laser photocoagulation in four cases. HCQS-related retinal toxicity was not seen in any of the 109 cases. Ocular manifestation was the initial presentation of SLE in one case. Visual outcome was poor in three cases. Conclusion: Presence of posterior segment findings in cases with SLE may suggest a severe systemic disease. Early detection and aggressive treatment result in better visual outcomes. Ophthalmologists could play a vital role in guiding systemic therapy.

Diabetic microaneurysms detected by fluorescein angiography spatially correlate with regions of macular ischemia delineated by optical coherence tomography angiography.

Purpose: To characterize the relationship between diabetic macular ischemia (DMI) delineated by optical coherence tomography angiography (OCTA) and microaneurysms (MAs) identified by fundus fluorescein angiography (FFA). Methods: Patients with diabetic retinopathy (DR) who underwent OCTA and FFA were retrospectively identified. FFA images were cropped and aligned with their respective OCTA images using i2k Align Retina software (Dual-Align, Clifton Park, NY, USA). Foveal avascular zone (FAZ) and ischemic areas were manually delineated on OCTA images, and MAs were marked on the corresponding FFA images before overlaying paired scans for analysis (ImageJ; National Institutes of Health, Bethesda, MD, USA). Results: Twenty-eight eyes of 20 patients were included. The average number of MAs identified in cropped FFA images was 127 ± 42. More DMI was noted in the superficial capillary plexus (SCP; 36 ± 13%) compared to the deep capillary plexus (DCP; 28 ± 14%, P < 0.001). Similarly, more MAs were associated with ischemic areas in SCP compared to DCP (92.0 ± 35.0 vs. 76.8 ± 36.5, P < 0.001). Most MAs bordered ischemic areas; fewer than 10% localized inside these regions. As DMI area increased, so did associated MAs (SCP: r = 0.695, P < 0.001; DCP: r = 0.726, P < 0.001). Density of MAs surrounding FAZ (7.7 ± 6.0 MAs/mm2) was similar to other DMI areas (SCP: 7.0 ± 4.0 MAs/mm2, P = 0.478; DCP: 9.2 ± 10.9 MAs/mm2, P = 0.394). Conclusion: MAs identified in FFA strongly associate with, and border areas of, DMI delineated by OCTA. Although more MAs are localized to SCP ischemia, the concentration of MAs associated with DCP ischemia is greater. By contrast, few MAs are present inside low-flow regions, likely because capillary loss is associated with their regression.

Optical coherence tomography angiography in diabetic retinopathy.

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

Novel optical coherence tomography angiography biomarkers in the diagnosis and assessment of diabetic macular edema and diabetic macular ischemia in patients with non-proliferative diabetic retinopathy.

Purpose: The present study aims to determine the macular and choroidal optical coherence tomography angiography (OCTA) biomarkers in the assessment and monitoring of diabetic macular edema (DME) and diabetic macular ischemia (DMI) in patients with non-proliferative diabetic retinopathy (NPDR). Methods: In this cohort study, a total of 176 eyes of 110 patients with NPDR were investigated at our institute over a period of 10 months. Eyes were divided into four groups based on the severity of NPDR. Each eye was subjected to OCTA (Topcon 3D OCT-1 Maestro2) macula 6 × 6 mm2 en face. It features IMAGEnet 6 software for dynamic viewing of OCTA and imaging data. Four OCTA biomarkers for the macula were identified: foveal avascular zone area (FAZ area), foveal avascular zone contour irregularity (FAZ-CI), capillary dropout areas (CDA), and perifoveal intercapillary areas (PICA). The choroidal OCTA biomarker was the number of choroidal circulation flow voids (CCFV). For all analyses, P < 0.05 was considered statistically significant. Results: Increase in FAZ area and number of CDA were statistically significant (p < 0.0001) with an increase in central foveal thickness, suggesting a correlation of ischemic changes with an increase in DME. FAZ-CI, enlarged PICA, and CCFV were significantly associated with more severe NPDR patients. Conclusion: A correlation between DME and DMI in a patient of NPDR and its progression can be evaluated in a single visit. A unique feature of our study is it revealed novel diagnostic biomarkers of OCTA for DMI and DME.

New retinal findings in NLRP3-associated autoinflammatory disease.

PURPOSE: To determine whether the rare NLRP3-Associated Autoinflammatory Disease (NLRP3-AID) is associated with retinal changes and to assess the ocular involvement. METHODS: A retrospective cohort study of 20 patients(40 eyes) diagnosed with rare NLRP3-AID at Peking Union Medical College Hospital, from April 2015 to August 2022. Patients underwent a comprehensive ophthalmological examination, including visual acuity, intraocular pressure examination, slit-lamp examination, fundus photography, optical coherence tomography(OCT), and fluorescence angiography (FA). Some patients also underwent optical coherence tomography angiography (OCTA). RESULTS: This study analyzed 40 eyes of 20 patients (11 [55.0%] male; median age, 25.0 years [range, 12-52 years]) and 13 patients (26 eyes, 65%) demonstrated ocular involvement. The most common ophthalmologic manifestation was conjunctivitis (22 eyes, 84.6%), followed by papilledema (14 eyes, 53.8%), retinopathy (10 eyes, 38.5%), optic atrophy (6 eyes, 23.1%), uveitis (4 eyes, 15.4%), reduced pupil light reflex (3 eyes, 11.5%) and cataracts (2 eyes, 7.7%). Ocular involvement was bilateral in 11 patients (55.0%). Five kinds of retinal lesions were seen in 5 patients (10 eyes, 25%) with NLRP3-AID, including peripheral retinal vascular leakage, microaneurysms, macular ischemia, macular epiretinal membrane formation and drusen. CONCLUSIONS: Peripheral retinal vascular leakage, macular ischemia, microaneurysms and drusen are newly identified retinal findings in patients with NLRP3-AID, which suggests the importance of detailed retinal examination in these patients.