Topographic analysis of retinal and choroidal microvasculature according to diabetic retinopathy severity using optical coherence tomography angiography.

PURPOSE: To investigate the topographic changes in the retinal capillary plexus and the choriocapillaris according to the severity of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). METHODS: Subjects were recruited and classified into one of the following four groups: normal controls (n = 52), diabetes without DR (n = 49), non-proliferative DR (n = 51) and proliferative DR (n = 38). Using OCTA, the superficial capillary plexus (SCP), deep capillary plexus (DCP) and the choriocapillaris vessel densities were measured and compared in different macular areas: the fovea (1-mm diameter circular area), parafovea (1-3-mm diameter ring) and perifovea (3-6-mm ring). RESULTS: With DR progression, vessel densities in the SCP and DCP as well as the choriocapillaris decreased, while the foveal avascular zone area increased (p < 0.001 for all). Compared with controls, the SCP and DCP vessel densities of the diabetes without DR group were decreased in all areas of the macula (p < 0.020 for all), while the choriocapillaris vessel density was decreased only in the perifoveal area (p = 0.823 for the foveal area; p = 0.631 for the parafoveal area; p = 0.039 for the perifoveal area). Multivariate linear regression analyses revealed that all retinal and choroidal microvascular indices were significantly associated with the DR severity. CONCLUSION: The morphological changes in the macular microvasculature were associated with DR severity. Also, the changes were found to be more vulnerable in the retinal capillary plexuses than the choriocapillaris.

Impact of Early Anatomical and Functional Responses to Bevacizumab in Macular Edema Secondary to Branch Retinal Vein Occlusion.

PURPOSE: To evaluate whether early anatomical and visual acuity (VA) responses to intravitreal bevacizumab (IVB) in macular edema secondary to branch retinal vein occlusion (BRVO) are associated with 1-year follow-up outcomes. METHODS: Ninety-nine treatment-naïve patients (99 eyes) with macular edema after BRVO treated with IVB were analyzed retrospectively. All patients received single injection and were followed up with pro re nata regimen for at least 12 months. The relationship between early (1 month) and late (12 months) anatomical (presence/absence of fluid) and functional response (an improvement of <1, 1 to <3, or ≥3 logMAR lines from baseline in best corrected VA, BCVA) was explored. RESULTS: Fifty-eight eyes (58.6%) had absence of fluid at 1 month after the first injection, but 41 eyes (41.4%) did not. Those with absence of fluid at 1 month were more likely to be fluid-free at 12 months (p = 0.010). Thirty-seven (37.4%), 24 (24.2%), and 38 (38.4%) eyes showed an improvement of <1, 1 to <3, and ≥3 lines, respectively, at 1 month after the first injection. Intercohort differences across three response categories in BCVA change from baseline were statistically significant throughout the follow-up. Each group maintained stable VA changes within 1 line during the follow-up after 1 month. CONCLUSION: The early anatomical and functional response was associated with anatomical and functional improvement at 12 months.

Repositioned versus exchanged flanged intraocular lens fixation for intraocular lens dislocation.

This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

Morphological features and prognostic significance of multilayered pigment epithelium detachment in age-related macular degeneration.

AIMS: To investigate the structure of multilayered pigment epithelial detachment (m-PED) in neovascular age-related macular degeneration, and its association with visual prognosis and the progression of fibrotic scars at 12 months. METHODS: We retrospectively analysed 68 eyes of 63 patients with m-PED that included a prechoroidal cleft. The compartments within m-PED were divided into neovascular tissue (layer 1), a hyper-reflective band (layer 2), and a prechoroidal cleft (layer 3). Clinical variables were compared between patients manifesting layer 2 and those who did not. Multiple regression analyses were used to find the factors related to visual outcome and fibrotic scar formation. RESULTS: Layer 2 was detected in 38 (55.9 %) of 68 eyes. With continuous treatment, the group with layer 2 showed gradual visual deterioration (p<0.001 at month 12), while the group without layer 2 showed visual improvement (p<0.001 at month 12). In the group with layer 2, the thickness of layer 2 significantly increased, and in the group without layer 2, if it formed, it increased gradually (p=0.004 at month 12). In both groups, other layers significantly decreased by month 12. The presence of layer 2 at baseline was significantly associated with a poor visual outcome (p=0.009) and fibrotic scar formation (p=0.023). CONCLUSIONS: The m-PED with layer 2 had a higher risk of fibrotic scar formation and was associated with a poor visual prognosis. Layer 2 may be an early stage precursor of a fibrotic scar.

A Deep Learning Algorithm for Classifying Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

Purpose: To develop an automated diabetic retinopathy (DR) staging system using optical coherence tomography angiography (OCTA) images with a convolutional neural network (CNN) and to verify the feasibility of the system. Methods: In this retrospective cross-sectional study, a total of 918 data sets of 3 × 3 mm2 OCTA images and 917 data sets of 6 × 6 mm2 OCTA images were obtained from 1118 eyes. A deep CNN and four traditional machine learning models were trained with annotations made by a retinal specialist based on ultra-widefield fluorescein angiography. Separately, the same images of the test data sets were independently graded by two human experts. The results of the CNN algorithm were compared with those of traditional machine learning-based classifiers and human experts. Results: The proposed CNN achieved an accuracy of 0.728, a sensitivity of 0.675, a specificity of 0.944, an F1 score of 0.683, and a quadratic weighted κ of 0.908 for a six-level staging task, which were far superior to the results of traditional machine learning methods or human experts. The CNN algorithm showed a better performance using 6 × 6 mm2 rather than 3 × 3 mm2 sized OCTA images and using combined data rather than a separate OCTA layer alone. Conclusions: CNN-based classification using OCTA images can provide reliable assistance to clinicians for DR classification. Translational Relevance: This CNN algorithm can guide the clinical decision for invasive angiography or referrals to ophthalmology specialists, helping to create more efficient diagnostic workflow in primary care settings.

Real-World Outcomes of Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration: A Large-Scale Postmarketing Surveillance in Korea.

PURPOSE: To investigate the efficacy and safety of intravitreal aflibercept (IVT-AFL) in Asian patients with neovascular age-related macular degeneration (nAMD) in a real-world clinical setting. PATIENTS AND METHODS: In this analysis of a prospective, regulatory, postmarketing surveillance study for IVT-AFL, 3115 patients with nAMD were included and followed for 8 months. The mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were analyzed using last observation carried forward method. A post hoc subgroup analysis and a multivariate logistic regression analysis were also performed to assess factors related to treatment outcomes. RESULTS: Mean BCVA improved from 0.62 to 0.51 logarithm of minimum angle resolution and mean CRT decreased from 383.3 to 289.7 µm, with a mean of 3.4 injections during the 8-month follow-up. In the subgroup analysis, patients who had received 3 initial monthly doses had significantly better anatomical improvements than those treated as needed. Patients with confirmed polypoidal choroidal vasculopathy (PCV) had significantly better anatomical improvements and better visual recovery than those with other types of nAMD. The multivariate regression analysis demonstrated that age, injection number, PCV, and baseline BCVA were significantly associated with higher odds of gaining 3 lines at 8 months, and sex, injection number, PCV, and baseline CRT were associated with CRT ≤250 µm at 8 months. No new safety findings were identified. CONCLUSION: IVT-AFL was effective and well tolerated in a real-world setting with a large number of Asian patients with nAMD. Number of injections and PCV were important determinants for improved treatment outcomes.

Macular Microvascular Changes and Their Correlation With Peripheral Nonperfusion in Branch Retinal Vein Occlusion.

PURPOSE: To investigate the correlation between macular microvascular alterations on optical coherence tomography angiography (OCTA) and retinal ischemia on ultra-widefield fluorescein angiography (UWF FA) in eyes with branch retinal vein occlusion (BRVO). DESIGN: Cross-sectional study. METHODS: This prospective study was performed from September 2019 to June 2020 at Yeungnam University Medical Center. We included 60 patients with treatment-naïve BRVO. Two independent, masked graders analyzed OCTA parameters, including vessel density, skeletal density, and fractal dimension (FD), and UWF FA parameters, including retinal nonperfusion area (NPA) and ischemic index (ISI), from various concentric regions (perimacular region, 0.5-3 mm radius; near-peripheral region, 3-10 mm; midperipheral region, 10-15 mm; far-peripheral region, >15 mm). A repeated-measures analysis of variance test and a paired t test were performed for inter-visit and inter-regional comparisons, and Pearson correlation coefficient and multivariate regression analyses were performed to examine the correlation between UWF FA and OCTA parameters. RESULTS: The OCTA parameters from both the superficial and deep capillary plexuses (DCP) were significantly correlated with NPA and ISI in all concentric regions. Even after adjusting for several covariates, all OCTA parameters revealed a significant association with ISI on UWF FA. Moreover, OCTA parameters from DCP were significantly correlated with concentrations of placental growth factor and vascular endothelial growth factor. Although all OCTA parameters achieved excellent results of area under the curve (AUC) > 0.9 for detecting severe retinal ischemia, defined as ISI >10%, FD reduction in DCP was the most reliable parameter (AUC = 0.948, P < .001), and 5.39% was the best cut-off point for predicting ISI > 10%. CONCLUSIONS: OCTA is a useful noninvasive tool not only for evaluation of macular microvasculature but for supposition of peripheral nonperfusion in eyes with BRVO.

A deep learning model for identifying diabetic retinopathy using optical coherence tomography angiography.

As the prevalence of diabetes increases, millions of people need to be screened for diabetic retinopathy (DR). Remarkable advances in technology have made it possible to use artificial intelligence to screen DR from retinal images with high accuracy and reliability, resulting in reducing human labor by processing large amounts of data in a shorter time. We developed a fully automated classification algorithm to diagnose DR and identify referable status using optical coherence tomography angiography (OCTA) images with convolutional neural network (CNN) model and verified its feasibility by comparing its performance with that of conventional machine learning model. Ground truths for classifications were made based on ultra-widefield fluorescein angiography to increase the accuracy of data annotation. The proposed CNN classifier achieved an accuracy of 91-98%, a sensitivity of 86-97%, a specificity of 94-99%, and an area under the curve of 0.919-0.976. In the external validation, overall similar performances were also achieved. The results were similar regardless of the size and depth of the OCTA images, indicating that DR could be satisfactorily classified even with images comprising narrow area of the macular region and a single image slab of retina. The CNN-based classification using OCTA is expected to create a novel diagnostic workflow for DR detection and referral.

Relationship between distribution and severity of non-perfusion and cytokine levels and macular thickness in branch retinal vein occlusion.

We aimed to investigate the relationship between non-perfusion on ultra-widefield angiography (UWF FA) and aqueous cytokine levels and central macular thickness (CMT) in eyes with branch retinal vein occlusion (BRVO). Thirty-five eyes with treatment-naïve BRVO were included. Non-perfusion area (NPA) for partial and complete ischemia was manually segmented and the ischemic index (ISI) for each was calculated using stereographically projected UWF FA for four different retinal zones. Partial and complete ischemia had different regional predominance. Partial ischemia was predominant in the posterior regions, while complete ischemia was predominant in the periphery. And partial ischemic area, located posterior to far periphery, showed significant correlation with central macular thickness and concentrations of angiogenic and inflammatory cytokines, while complete ischemic area showed no correlation with any of the parameters. Taken together, partial but not complete ischemia, particularly in the more posterior retina, was associated with higher cytokine levels and more severe macular edema in eyes with BRVO. These findings would help us to better understand the different clinical significance of ischemia in BRVO depending on the severity and regional distribution.

Polypoidal choroidal vasculopathy as a complication of choroidal osteoma: A case report.

INTRODUCTION: Choroidal osteoma (CO) is a rare benign tumor that particularly affects young, healthy women. Its prognosis is influenced by complications, such as choroidal neovascularization (CNV), subretinal hemorrhage, subretinal fluid (SF), decalcification status, and overlying retinal pigment epithelium (RPE) atrophy. In case of CNV as the complication of CO, it is typically present in the classic form; however, reports on polypoidal choroidal vasculopathy (PCV) have been rare. Here, we report a case of an older, male patient with PCV as a complication of CO. PATIENT CONCERNS: A 70-year-old male patient visited the hospital with vision impairment in the right eye since 2 weeks. DIAGNOSIS: Fundus examination revealed a red-yellow, well-demarcated, scalloped lesion around the optic nerve in each eye; the lesions were highly reflective on ultrasound examination, and thus, CO was diagnosed. Indocyanine green fluorescence angiography and optical coherence tomography (OCT) revealed that the right eye also had PCV accompanied with SF. OCT confirmed the presence of large quiescent type 1 CNV bilaterally in decalcified areas of the lesions adjacent to the optic nerve. INTERVENTIONS: Intravitreal bevacizumab (IB) injection was performed. OUTCOMES: Best-corrected visual acuity had improved and OCT showed a decrease in the SF, while OCT angiography showed partial regression of branching vascular network. CONCLUSION: CO can be accompanied by quiescent type 1 CNV; this should be closely monitored because it can progress to PCV. Optical coherence tomography, alongside indocyanine green fluorescence angiography, is useful for the diagnosis and monitoring of potential CNV as a complication of CO.

Quantitative analysis of choroidal vasculature in polypoidal choroidal vasculopathy using ultra-widefield indocyanine green angiography.

Polypoidal choroidal vasculopathy (PCV) is a common choroidal vascular disease particularly in Asians. However, the underlying pathogenesis of PCV is still yet to be fully elucidated, and the correlation between choroidal vasculature and treatment response of PCV are poorly understood. Accordingly, we sought to find clues to understand the pathogenesis and prognosis of PCV by quantitatively evaluating choroidal vasculature from the entire fundus using ultra-widefield (UWF) indocyanine green angiography (ICGA). In this study, 32 eyes from 29 patients with treatment naïve PCV and 30 eyes from 30 healthy control participants were enrolled. Choroidal vascular density (CVD) of PCV eyes was higher than normal eyes in majority regions including the periphery. CVD was positively correlated with choroidal thickness and choroidal hyperpermeability, supporting that the pathogenesis of PCV may include choroidal congestion and dilatation. Thicker choroid and higher CVD were also correlated with poor treatment response after anti-VEGF injections. The CVD, quantified from UWF ICGA can also be used as an effective image biomarker to predict the treatment response in PCV.