Retinal microvascular markers in type 2 diabetes subphenotypes and latent autoimmune diabetes of adults.

PURPOSE: To estimate if newly diagnosed patients with different subphenotypes of type 2 diabetes (T2DM) or latent autoimmune diabetes of adults (LADA) differ with respect to subclinical retinal microvascular structure or diabetic retinopathy (DR). METHODS: This population-based, cross-sectional study of 340 patients (675 eyes) classified patients with recently diagnosed T2DM in different subphenotypes according to beta cell function and insulin sensitivity in to; classical (n = 218), hyperinsulinaemic (n = 86), insulinopenic (n = 20), or LADA (n = 16). Retinal 6-field images were graded according to the International Clinical DR Severity Scale by a retinal expert. Retinal microvascular structures were analysed in eyes by a semiautomatic software. RESULTS: Median age and duration of diabetes were 58.1 (49.9; 65.5) and 0.9 (0.5; 2.4) years, respectively, and 56.8% were male. In a multivariate linear mixed model regression analysis of eyes without DR (n = 570), there was no statistically significant difference in retinal venular or arteriolar width between subtypes and patients with classical T2DM. In addition, eyes from different subphenotypes did not differ according to vessel density, tortuosity or fractal dimension. In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure and history of cardiovascular disease, there was a tendency towards persons with hyperinsulinaemic T2DM to be more likely to have DR (OR 1.97, 95% CI 0.95; 4.09) compared to classical T2DM. CONCLUSION: We found no difference in retinal microvascular structure in patients with newly diagnosed subtypes of T2DM. However, DR may be more prevalent in newly diagnosed patients with hyperinsulinaemic T2DM compared to individuals with classical T2DM.

Periocular basal cell carcinoma results and surgical outcome during a 5-year period in a larger Danish population.

BACKGROUND: To report tumour pathology, surgical procedure, complication rates and overall outcome of periocular basal cell carcinoma (BCC) in the Department of Ophthalmology at Sygehus Lillebaelt, Southern Denmark Region over a 5-year period. METHODS: Medical records for all patients who underwent surgery for periocular BCC between January 2016 and December 2020 were reviewed. All tumours were excised with a 3 mm margin beyond the clinically apparent delimitation of the tumour and analysed by frozen section histological examination. Paraffin sections were subsequently examined for a final histopathological diagnosis. Patient age, gender, date of resection, former cancer history, referring unit and follow-up time were recorded. Furthermore, histological subtypes identified from biopsy and resection, lesion location, lesion diameter, free margin after the first operation, lacrimal punctum involvement, reconstructive techniques and complications were also recorded. RESULTS: A total of 242 surgical excisions from 237 patients were recorded. The mean age was 69.7 ± 12.6 with women significantly predominant compared to men (1.8:1, p < 0.0001, binomial test). The mean tumour diameter was 4.29 mm (range 0.5-20 mm). The most common location and histological subtype was the lower eyelid and nodular BCC respectively (64.9% and 74.0% of cases). In 17.4% of the patients, the initial resection margin on the frozen section histology was not free of tumour cells and the risk was significantly greater for BCC subtypes considered aggressive in terms of growth pattern (morphea form, infiltrative and micronodular features) as compared to non-aggressive BCC subtypes (nodular and superficial) (p = 0.002, X2). In 239 (98.8%) of the patients, the BCC was found to be radically removed after final histopathological examination. The sensitivity of identification of aggressive subtypes of periocular BCC in biopsies was 47.7%. No recurrences were found during the 5-year period. CONCLUSION: This study demonstrated a tendency towards more women than men being diagnosed with periocular BCC. The initial biopsy performed for all patients underestimated the aggressiveness of BCC in almost half of the cases while aggressive BCC subtypes were more likely to need further resection after frozen section compared to non-aggressive subtypes.

Retinal Vascular Fractal Dimensions and Their Association with Macrovascular Cardiac Disease.

INTRODUCTION: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases, and this study examined the association of DF and macrovascular cardiac disease in a case-control design. METHODS: Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semiautomatic software VAMPIRE was used to measure retinal DF. RESULTS: Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p = 0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval: 1.63-31.86; p = 0.009) and second (OR, 8.25; 95% confidence interval: 1.70-40.01; p = 0.009) quartiles. CONCLUSIONS: This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess nonocular macrovascular disease.

Non-invasive structural and metabolic retinal markers of disease activity in non-proliferative diabetic retinopathy.

PURPOSE: Metabolic and structural microvascular retinal alterations are essential components in diabetic retinopathy (DR). The present study aimed to measure changes at different stages of non-proliferative DR (NPDR) and to explore interactions of imaging-based metrics. METHODS: This cross-sectional, cohort study included 139 eyes from 80 diabetic patients. Each patient underwent dilated fundal examinations including colour fundus photography, retinal oximetry and optical coherence tomography angiography (OCTA), analysed by semi-automated and automated software. Diabetic retinopathy (DR) severity was classified according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale, ranging from no DR to severe NPDR (level 0-3). Retinal metabolism was evaluated by oximetry as retinal arteriolar (raSatO2 ) and venular oxygen saturation (rvSatO2 ), and macular microvascular structure was measured by OCTA as the area of foveal avascular zone (FAZ), vessel density (VD), vessel diameter index (VDI), FAZ circularity and fractal dimension (FD) in the superficial and deep retinal capillary plexus. RESULTS: A trend for increasing rvSatO2 was found with increasing DR severity (51.3%, 53.3%, 54.2%, 59.8%, p = 0.02). Increasing severity of DR associated with decreasing FD in the superficial and deep plexus (p < 0.001 and p = 0.014), and in the superficial plexus decreasing VD (p < 0.001), increasing VDI (p = 0.003) and decreasing FAZ circularity (p = 0.006). A few interactions were identified between raSatO2 , rvSatO2 and VDI, but only in the deep capillary plexus (p < 0.01 and p < 0.01). CONCLUSION: Alterations of the venular retinal vascular oxygen saturation and microvascular structural abnormities were found continuously throughout the DR-spectrum. Given the sparse correlations between metabolic and structural abnormalities, it seems that these occur independently in DR.

Retinal arteriolar oxygen saturation predicts the need for intravitreal aflibercept in patients with diabetic macular oedema.

OBJECTIVE: Given the increasing burden of repetitive intravitreal injections in diabetic macular oedema (DMO) treatment, non-invasive markers of treatment outcome are needed. Hence, we aimed to examine retinal oximetry parameters as markers of need for intravitreal aflibercept in patients with DMO. METHODS: This study was based on data from a 12-month clinical trial including 35 eyes of 25 patients with centre involving DMO. Retinal oximetry, visual acuity (VA) and central retinal thickness (CRT) were performed at baseline (BL). Patients then received 3 monthly injections of aflibercept followed by focal/grid laser photocoagulation. From month 4 (M4) through 12 (M12), patients were followed monthly and additional injections were given pro re nata if criteria of retreatment were met. We evaluated the difference in need for intravitreal aflibercept in groups of eyes with the highest and lowest retinal arteriolar and venular oxygen saturations, respectively. RESULTS: From BL-M12, overall VA letter score improved by 8.7 (7.2-10.2). Likewise CRT reduced by 100.7 (68.2-133.3) µm and the mean number of injections was 4.3 (3.8-4.8). Overall retinal arteriolar and venular oxygen saturations were 95.7 (93.0-98.4)% and 62.7 (59.4-65.9)% at BL. Eyes with the highest retinal arteriolar oxygen saturations had significantly more injections between BL and M12 compared with eyes with the lowest retinal arteriolar oxygen saturations (5.0 (4.2-5.8) vs 3.6 (3.1-4.0), p=0.002). CONCLUSION: Higher retinal arteriolar oxygen saturation independently predicted the need for more intravitreal aflibercept during the first year of DMO treatment and may serve as a valuable adjunctive to established procedures for retinal imaging in terms of individualised treatment plans. TRIAL REGISTRATION NUMBER: NCT02554747.

Correlation between Diabetic Retinopathy Severity and Oxygen Metabolism in Patients with Diabetic Macular Edema during Treatment with Intravitreal Aflibercept.

PURPOSE: To attribute data on changes in diabetic retinopathy (DR) severity during treatment of diabetic macular edema (DME) with vascular endothelial growth factor inhibitors (anti-VEGF), this study aimed to (1) examine the correlation between oxygen saturations in retinal vessels and the number of DR lesions on ultra-wide field color fundus photographs prior to anti-VEGF treatment and (2) compare changes in oxygen saturations in retinal vessels with changes in the number of DR lesions after a loading dose of three monthly intravitreal injections of 2.0 mg of aflibercept. METHODS: This 3-month prospective study included 37 eyes of patients with DME and varying severity of peripheral DR lesions. DR lesions were graded on wide field images and retinal oxygen saturations were evaluated by retinal oximetry. Patients were then treated with three monthly intravitreal injections of 2 mg aflibercept and wide field imaging and retinal oximetry were repeated 4 weeks after the last injection. Patients with proliferative DR or previous panretinal photocoagulation were excluded. RESULTS: Baseline retinal arteriolar oxygen saturation increased with increasing DR severity and numbers of microaneurysms, hemorrhages, and cotton wool spots (p = 0.03, 0.01, 0.03, and <0.001), while no correlation between the severity of DR lesions and retinal venular oxygen saturation was found. After treatment with intravitreal aflibercept, the severity of DR lesions significantly reduced, while retinal arteriolar and venular oxygen saturation as well as the arteriolar-venular difference remained unchanged (95.5 vs. 95.8%, p = 0.44; 62.9 vs. 64.5%, p = 0.08; 32.5 vs. 31.4%, p = 0.33). CONCLUSION: This study demonstrated that structural DR lesions correlate with retinal arteriolar oxygen saturation in patients with DME prior to anti-VEGF treatment and that improvement in the severity of DR lesions can occur without corresponding changes in retinal oxygen metabolism during intravitreal therapy. Our results suggest that DR severity on color fundus photographs should be interpreted with caution once intravitreal therapy is initiated.

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside.

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes.