One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered. DESIGN: Cohort study. PARTICIPANTS: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry. METHODS: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116). MAIN OUTCOME MEASURES: Mean visual acuity (VA) change after 12 months of treatment. RESULTS: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) µm and -85 (-92 to -78) µm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. CONCLUSIONS: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

Clinical Features Related to OCT Angiography Artifacts in Patients with Diabetic Macular Edema.

PURPOSE: To investigate the frequency and type of artifacts on OCT angiography (OCTA) images and the relationship with clinical features in eyes with diabetic macular edema (DME). DESIGN: Retrospective, cross-sectional comparative study. SUBJECTS: One hundred ninety-two eyes of 140 patients with DME were included. METHODS: Medical records, OCT and OCTA images (Spectralis), and ultrawidefield color fundus photographs (Optos plc) were evaluated. MAIN OUTCOME MEASURES: The frequency of artifact types (segmentation, motion, projection artifact, and low signal) was determined. The relationships between artifact types and clinical features such as best-corrected visual acuity (BCVA), mean central retinal thickness (CRT), foveal avascular zone (FAZ) area, perimeter, circularity index, perfusion density (PD), vessel density (VD), fractal dimension (FD) in the superficial capillary plexus, intermediate capillary plexus (ICP), and deep capillary plexus (DCP), flow voids (FVs) in the choriocapillaris, presence of hard exudate (HE), and cataract were determined. RESULTS: The mean age was 71.6 ± 11.4 years, and 86 (61.4%) out of 140 were men. Artifacts were present in 63 (32.8%) of 192 eyes. Twenty-nine (15.1%) eyes had segmentation artifacts, 12 (6.3%) had motion artifacts, 11 (5.7%) had projection artifacts, and 18 (9.4%) had low signal. Best-corrected visual acuity, PD, VD, and FD in ICP and DCP were significantly lower; and CRT, FAZ area and perimeter in ICP and DCP, and presence of cystoid macular edema, HE, and cataract were higher in eyes with artifacts versus eyes without artifacts (P < 0.05 for each). Multivariate linear regression analysis showed a significant association between segmentation artifacts and decreased BCVA (odds ratio [OR], 5.277; P = 0.02), increased CRT (OR, 1.015; P < 0.001), increased area of FAZ in DCP (OR, 6.625; P = 0.02), and increased perimeter of FAZ in DCP (OR, 1.775; P < 0.04); there was also a significant association between projection artifacts and presence of HE (OR, 2.017; P = 0.02) and between motion artifacts and presence of cataract (OR, 4.102; P = 0.01). CONCLUSIONS: OCT angiography artifacts were present in one third of DME eyes, with segmentation artifacts being the most frequent type. Determining OCTA artifacts is crucial to ensure accurate clinical evaluation. These data could help in developing more standardized clinical protocols for image acquisition and interpretation used in clinical practice and research. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical coherence tomography biomarkers indicating visual enhancement in diabetic macular edema resolved through anti-VEGF therapy: OCT biomarkers in resolved DME.

PURPOSE: to investigate the structural features and extended visual results in eyes affected by diabetic retinopathy (DR) and diabetic macular edema (DME) that have been successfully treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Individuals (39 eyes of 39 patients) who had undergone long-term follow-up and demonstrated evidence of resolved DME after at least 2 years of follow-up following the initiation of anti-VEGF therapy were included. During the ""study visit"", structural OCT scans were examined to assess qualitative features indicative of neuroretina or retinal pigment epithelium distress. Additionally, a quantitative assessment of the inner and outer retinal thicknesses was conducted for topographical analysis. RESULTS: The most robust qualitative association observed with BCVA at the "study visit" was linked to the presence of DRIL (p = 0.043) and the appearance of the ELM. (p = 0.045). Regarding quantitative parameters, a strong correlation was noted between the visual acuity during the "study visit" and the foveal and parafoveal thicknesses of both the inner and outer retina (p < 0.001). CONCLUSIONS: Changes in the status of ELM, the presence of DRIL, and the thicknesses of the foveal and parafoveal regions can act as OCT biomarkers, signifying prolonged visual improvements in eyes that have experienced resolved DME after undergoing anti-VEGF therapy.

Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion.

OBJECTIVES: To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. METHODS: In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI's extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10-15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). RESULTS: Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05). CONCLUSIONS: Perfusion macular metrics on OCT-A correlated with UWF-FA's non-perfusion (NP), particularly in the retina's mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.

Imaging geographic atrophy: integrating structure and function to better understand the effects of new treatments.

Geographic atrophy (GA) is an advanced and irreversible form of age-related macular degeneration (AMD). Chronic low grade inflammation is thought to act as an initiator of this degenerative process, resulting in loss of photoreceptors (PRs), retinal pigment epithelium (RPE) and the underlying choriocapillaris. This review examined the challenges of clinical trials to date which have sought to treat GA, with particular reference to the successful outcome of C3 complement inhibition. Currently, optical coherence tomography (OCT) seems to be the most suitable method to detect GA and monitor the effect of treatment. In addition, the merits of using novel anatomical endpoints in detecting GA expansion are discussed. Although best-corrected visual acuity is commonly used to monitor disease in GA, other tests to determine visual function are explored. Although not widely available, microperimetry enables quantification of retinal sensitivity (RS) and macular fixation behaviour related to fundus characteristics. There is a spatial correlation between OCT/fundus autofluorescence evaluation of PR damage outside the area of RPE loss and RS on microperimetry, showing important associations with visual function. Standardisation of testing by microperimetry is necessary to enable this modality to detect AMD progression. Artificial intelligence (AI) analysis has shown PR layers integrity precedes and exceeds GA loss. Loss of the ellipsoid zone has been recognised as a primary outcome parameter in therapeutic trials for GA. The integrity of the PR layers imaged by OCT at baseline has been shown to be an important prognostic indicator. AI has the potential to be invaluable in personalising care and justifying treatment intervention.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers. PARTICIPANTS: Treatment-naïve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals ≤ 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3) those with tolerable treatment burden had injection intervals between 84 and 365 days. METHODS: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden. MAIN OUTCOME MEASURES: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors. RESULTS: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P = 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years. CONCLUSIONS: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical coherence tomography in the management of diabetic macular oedema.

Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.

Exploring the role of retinal fluid as a biomarker for the management of diabetic macular oedema.

Anti-VEGF therapies are associated with significant gains in visual acuity and fluid resolution in the treatment of diabetic macular oedema (DMO) and have become the standard of care. However, despite their efficacy, outcomes can be unpredictable, vary widely between individual eyes, and a large proportion of patients have persistent fluid following initial treatment, with a negative impact on visual outcomes. Anatomical parameters measured by optical coherence tomography (OCT), in addition to visual acuity, are key to monitoring treatment effectiveness and guiding retreatment decisions; however, existing guidelines on the management of DMO lack clear recommendations for interpretation of OCT parameters, or proposed thresholds of various markers to guide retreatment decisions. Although central subfield thickness (CSFT) has been widely used as a marker for retreatment decisions in clinical trials in DMO, and a reduction in CSFT has generally been shown to accompany improvements in best-corrected visual acuity with treatment, analyses of the relationship between these parameters show that the correlation is small to moderate. A more direct relationship can be seen between an increased magnitude of CSFT fluctuations over time and poorer visual acuity, suggesting that control of CSFT could be important in maximising visual outcomes. The relationship between visual outcomes and qualitatively assessed intraretinal fluid and subretinal fluid is also unclear, although quantitative assessments of fluid parameters suggest that untreated intraretinal fluid and subretinal fluid negatively impact visual outcomes. These findings highlight a need for clearer guidelines on the management of retinal fluid to improve visual outcomes for patients with DMO.

Exploring Patient Demographics and Presence of Retinal Vascular Disease in Paracentral Acute Middle Maculopathy.

PURPOSE: To investigate the sociodemographic profile, the association with retinal vascular diseases (RVD) and systemic comorbidities, and visual outcomes of patients with paracentral acute middle maculopathy (PAMM) in a large, ethnically diverse single-center cohort. DESIGN: Retrospective cohort study. METHODS: Electronic health record query for all patients presenting with PAMM at Moorfields Eye Hospital, London, was completed. Detailed demographic, clinical, and systemic information were collected and analyzed. RESULTS: A total of 78 eyes of 78 patients with confirmed PAMM were included in the study. Forty patients (51.3%) presented with no RVD, 20 patients (25.6%) with retinal vein occlusion (RVO), 16 patients (20.5%) with retinal artery occlusion (RAO), and 2 patients (2.6%) with concomitant RAO and RVO. Patients with PAMM+RAO were older than those with RVO (P = .02) and more likely to have a history of major adverse cardiovascular events (MACE) (P = .01), with a significantly worse presenting best corrected visual acuity (BCVA) (20/50) compared to patients with RVO (P = .02) and no RVD (P < .001). Individuals with isolated PAMM had a significantly higher prevalence of previous MACE (P = .04) and sickle cell disease (SCD) (P = .04) compared to those with RVO. At the last follow-up, 64 patients (85.3%) had a good BCVA (>20/32). CONCLUSIONS: The significant association of PAMM with RVD supports the hypothesis of an ischemic etiology. Individuals with isolated PAMM had a higher prevalence of MACE and SCD. Thus, it is important to prompt immediate referral for a comprehensive systemic evaluation. Across the whole cohort, PAMM was associated with good BCVA improvement during follow-up, indicating a good visual prognosis.

Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration.

Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA.

Twenty-four-month real-life treatment outcomes of polypoidal choroidal vasculopathy versus type 1 macular neovascularization in Caucasians.

BACKGROUND: To compare 24-month real-world outcomes of Vascular Endothelial Growth Factor (VEGF) inhibitors for Polypoidal Choroidal Vasculopathy (PCV) and type 1 Macular Neovascularization (MNV) in a Caucasian population. METHODS: Retrospective analysis from a prospectively designed observational database. Data from Italian centres participating in the Fight Retinal Blindness! (FRB!) project were collected. Treatment-naïve PCV or type 1 MNV commencing treatment after January 2009 were included. The primary outcome was 24-month visual acuity (VA) change; other outcomes included baseline characteristics, number of anti-VEGF injections, time to lesion inactivation and proportion of active visits. RESULTS: A total of 322 eyes (114 PCVs) from 291 patients were included. Median [Q1, Q3] VA at baseline was comparable (70 [55, 75.8] vs. 70 [58.8, 75] letters, p = 0.95). Adjusted VA change at 2 years was higher in PCV (mean [95% CI], +1.2 [-1.6, 4.1] vs. -3.6 [-6, -1.2] letters, p = 0.005). PCV received fewer anti-VEGF injections over the first 24 months of treatment than type 1 MNV (median [Q1, Q3], 8 [5, 10] vs. 9 [7, 12.2] injections, p = 0.001), inactivated earlier (median [Q1, Q3], 235 [184, 308] vs. 252 [169, 343] days, p = 0.04) and was less frequently graded 'active' (62% vs. 68% of visits, p = 0.001). CONCLUSIONS: PCV had slightly better VA outcomes over 24 months of treatment than type 1 MNV after receiving less anti-VEGF injections. These results suggest a possible overlap of the two clinical entities with similar visual prognosis in Caucasians.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

LONGITUDINAL MICROVASCULAR AND NEURONAL RETINAL EVALUATION IN PATIENTS WITH DIABETES MELLITUS TYPES 1 AND 2 AND GOOD GLYCEMIC CONTROL.

PURPOSE: To evaluate microvascular and neuronal changes over 3 years in patients with Type 1/2 diabetes mellitus (DM1/DM2), good metabolic control, and no signs of diabetic retinopathy. METHODS: In this prospective, longitudinal study, 20 DM1, 48 DM2, and 24 controls underwent macular optical coherence tomography and optical coherence tomography angiography at baseline and after 3 years. Following parameters were considered: thickness of the central macula, retinal nerve fiber layer, ganglion cell (GCL+/GCL++) complex; perfusion and vessel density and fractal dimension at the superficial and deep capillary plexuses; choriocapillaris flow deficits; and foveal avascular zone metrics. MATLAB and ImageJ were used for optical coherence tomography angiography scans analyses. RESULTS: The mean HbA1c was 7.4 ± 0.8% in DM1 and 7.2 ± 0.8% in DM2 at baseline, with no change at 3 years. No eye developed diabetic retinopathy. In longitudinal analyses, perfusion density at superficial capillary plexuses ( P = 0.03) and foveal avascular zone area and perimeter ( P < 0.0001) significantly increased in DM2 compared with other groups. No longitudinal changes occurred in optical coherence tomography parameters. In comparisons within groups, DM2 had a significant thinning of GCL++ in the outer ring, decreased perfusion density at deep capillary plexuses and choriocapillaris flow deficits, and increase in foveal avascular zone perimeter and area in deep capillary plexuses; DM1 had an increase in foveal avascular zone perimeter in deep capillary plexuses ( P < 0.001 for all comparisons). CONCLUSION: Longitudinal data showed significant microvascular retinal changes in DM2. No changes were detected in neuronal parameters and in DM1. Longer and larger studies are needed to confirm these preliminary data.

Multimodal Retinal Imaging in Patients with Diabetes Mellitus and Association with Cerebrovascular Disease.

INTRODUCTION: This study aimed to evaluate the association between macular optical coherence tomography angiography (OCT-A) metrics, characteristics of ultrawide field (UWF) imaging, and cerebrovascular disease in patients with diabetes mellitus (DM) with different stages of diabetic retinopathy (DR). METHODS: 516 eyes of 258 DM patients were enrolled in two centers (Milan and Belfast). UWF color fundus photos (CFPs) were obtained with Optos California (Optos, PLC) and graded for both DR severity and predominantly peripheral lesions presence (>50% of CFP lesions) by two independent graders. OCT-A (3 × 3 mm), available in 252 eyes of 136 patients, was used to determine perimeter, area, and circularity index of the foveal avascular zone and vessel density (VD); perfusion density (PD); fractal dimension on superficial, intermediate (ICP), and deep capillary plexuses; flow voids (FVs) in the choriocapillaris. RESULTS: Out of 516 eyes, 108 eyes (20.9%) had no DR, and 6 eyes were not gradable. The remaining 402 eyes were as follows: 10.3% (53) had mild nonproliferative DR (NPDR), 38.2% (197) had moderate NPDR, 11.8% (61) had severe NPDR, and 17.6% (91) had proliferative DR. A worse DR stage was associated with a history of stroke (p = 0.044). Logistic regression analysis after taking into account sex, type of DM, age, DM duration, and OCT-A variables found that PD and VD on ICP were significantly associated with presence of stroke and DR severity. CONCLUSION: OCT-A metrics show an association with the presence of cerebrovascular complications, providing potentially useful parameters to estimate vascular risk in patients with DM.

Subretinal Pseudocysts: A Comprehensive Analysis of this Novel OCT Finding.

INTRODUCTION: In current clinical practice, several optical coherence tomography (OCT) biomarkers have been proposed for the assessment of severity and prognosis of different retinal diseases. Subretinal pseudocysts are subretinal cystoid spaces with hyperreflective borders and only a few single cases have been reported thus far. The aim of the study was to characterize and investigate this novel OCT finding, exploring its clinical outcome. METHODS: Patients were evaluated retrospectively across different centers. The inclusion criterion was the presence of subretinal cystoid space on OCT scans, regardless of concurrent retinal diseases. Baseline examination was set as the first time the subretinal pseudocyst was identified by OCT. Medical and ophthalmological histories were collected at baseline. OCT and OCT-angiography were performed at baseline and at each follow-up examination. RESULTS: Twenty-eight eyes were included in the study and 31 subretinal pseudocysts were characterized. Out of 28 eyes, 16 were diagnosed with neovascular age-related macular degeneration (AMD), 7 with central serous chorioretinopathy, 4 with diabetic retinopathy, and 1 with angioid streaks. Subretinal and intraretinal fluid were present in 25 and 13 eyes, respectively. Mean distance of the subretinal pseudocyst from the fovea was 686 µm. The diameter of the pseudocyst was positively associated with the height of the subretinal fluid (r = 0.46; p = 0.018) and central macular thickness (r = 0.612; p = 0.001). At follow-up, subretinal pseudocysts disappeared in most of the reimaged eyes (16 out of 17). Of these, two patients presented retinal atrophy at baseline examination and eight patients (47%) developed retinal atrophy at follow-up. Conversely, seven eyes (41%) did not develop retinal atrophy. CONCLUSION: Subretinal pseudocysts are precarious OCT findings, usually disclosed in a context of subretinal fluid, and are probably transient alterations within the photoreceptor outer segments and retinal pigment epithelium (RPE) layer. Despite their nature, subretinal pseudocysts have been associated with photoreceptor loss and incomplete RPE definition.

Role of Vitrectomy in Nontractional Refractory Diabetic Macular Edema.

BACKGROUND: Currently, the gold standard of diabetic macular edema (DME) treatment is anti-vascular endothelial growth factor (VEGF) injections, although a percentage of patients do not respond optimally. Vitrectomy with or without internal limiting membrane (ILM) peeling is a well-established treatment for DME cases with a tractional component while its role for nontractional cases is unclear. The aim of this study is to evaluate the role of vitrectomy with or without ILM peeling in nontractional refractory DME. METHODS: We performed a retrospective review of twenty-eight eyes with nontractional refractory DME treated with vitrectomy at San Giuseppe Hospital, Milan, between 2016 and 2018. All surgeries were performed by a single experienced vitreoretinal surgeon. In 43.4% of cases, the ILM was peeled. Best corrected visual acuity and optical coherence tomography (OCT) scans were assessed preoperatively and at 6, 12, and 24 months post-vitrectomy. RESULTS: The mean central macular thickness improved from 413.1 ± 84.4 to 291.3 ± 57.6 µm at two years (p < 0.0001). The mean logarithm of the minimum angle of resolution logMAR best-corrected visual acuity (BCVA) improved after two years, from 0.6 ± 0.2 to 0.2 ± 0.1 (p < 0.0001). We found no difference between ILM peeling vs. no ILM peeling group in terms of anatomical (p = 0.8) and visual outcome (p = 0.3). Eyes with DME and subfoveal serous retinal detachment (SRD) at baseline had better visual outcomes at the final visit (p = 0.001). CONCLUSIONS: We demonstrated anatomical and visual improvement of patients who underwent vitrectomy for nontractional refractory DME with and without ILM peeling. Improvement was greater in patients presenting subretinal fluid preoperatively.

Practical guidance for imaging biomarkers in exudative age-related macular degeneration.

We provide an overview of current macular imaging techniques and identify and describe biomarkers that may be of use in the routine management of macular diseases, particularly exudative age-related macular degeneration (AMD). This perspective includes sections on macular imaging techniques including optical coherence tomography (OCT) and OCT angiography (OCTA), classification of exudative AMD, and biomarkers in structural OCT and OCTA. Fluorescein angiography remains a vital tool for assessing the activity of neovascular lesions, while indocyanine green angiography is the preferred option for choroidal vessel imaging in neovascular AMD. OCT provides a non-invasive three-dimensional visualization of retinal architecture in vivo and is useful in the diagnosis of many imaging biomarkers of AMD-related neovascular lesions, including lesion activity. OCTA is a recent advance in OCT technology that allows accurate visualization of retinal and choroidal vascular flow. OCT and OCTA have led to an updated classification of exudative AMD lesions and provide several biomarkers that help to establish a diagnosis and the disease activity status of neovascular lesions. Individualization of therapy guided by OCT and OCTA biomarkers has the potential to further improve visual outcomes in exudative AMD. Moving forwards, integration of technologically-advanced imaging equipment with AI software will help ophthalmologists to provide patients with the best possible care.