Spectral domain optical coherence tomography based imaging biomarkers for diabetic retinopathy.

Association of serum Nε-Carboxy methyl lysine with severity of diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of ocular morbidity. Its progression depends mainly on retinal vasculature and ocular blood flow. Color Doppler imaging (CDI) is a noninvasive imaging technique that measures blood flow velocity. The resistivity index (RI), calculated by the CDI, reflects the vascular resistance distal to the measuring location. RI is independent of the doppler angle and position of the patient, making it a reliable and reproducible parameter. To the best of our knowledge, there is only one study in literature studying the association between resistivity index (RI) of the central retinal artery (CRA) and severity of DR. To determine the association between RI of CRA and severity of DR. To determine the association between RI of CRA and spectral-domain optical coherence tomography (SD-OCT) biomarkers for DR. Type II diabetics visiting our OPD underwent DR screening and were graded into three categories according to ETDRS classification which include Group A-No diabetic retinopathy (No DR), Group B-Nonproliferative diabetic retinopathy (Moderate-Severe-Very Severe NPDR), and Group C-Proliferative diabetic retinopathy (PDR). SD-OCT was performed. Ultrasonic color doppler imaging was done. RI of the CRA was noted. It was compared between the three groups and its association with severity of DR and OCT biomarkers (central subfield thickness, cube average thickness and ellipsoid zone disruption) was studied. 56 eyes of 28 patients were included in our study with 20 in Group A,14 in Group B, and 22 in Group C. RI of CRA compared within groups showed statistically significant association with severity of DR (P < 0.001). The presenting BCVA (LogMar) showed positive correlation with RI in all groups. OCT biomarker central subfield thickness showed a positive correlation with RI in Groups A (P < 0.001) and B. Ellipsoid zone (EZ) disruption showed a statistically significant association with RI in Group C (P < 0.001). The RI of CRA is a reliable biomarker for the assessment of the severity of DR. Patients with high RI of CRA had higher chances of EZ disruption and presented with poor visual acuity.

Aim: To measure macular thickness by optical coherence tomography (OCT) in various grades of diabetic retinopathy with no clinically significant macular edema (CSME) and its comparison with non-diabetics.&#x0D; Design: Prospective cross–sectional study.&#x0D; Methods: Macular thickness was measured by OCT in 72 healthy volunteers (107 control eyes), 45 patients with mild and moderate non-proliferative diabetic retinopathy (NPDR) (78 eyes) and 37 patients with severe NPDR and proliferative diabetic retinopathy (PDR) (66 eyes). Patients with diabetic macular edema (DME) as assessed by stereoscopic evaluation or photographs were excluded. One-way ANOVA test to compare the mean thickness and Tukey's test for multiple comparison between groups were used.&#x0D; Results: Central subfield thickness (CST) was 238.57 ± 25.077 µm, 251.22 ± 24.649 µm, and 270.45 ± 28.956 µm in the three groups respectively. As the severity of retinopathy increased, the macular thickness significantly increased (p = &lt; 0.001) in all the nine zones on OCT. There was a significant increase in CST noted in all the grades of retinopathy when compared with non-diabetics (p = 0.004, p = &lt; 0.0001). No significant difference in macular thickness was noted between genders, irrespective of their groups (p = 0.72), or between the three groups in all the nine zones (p = 0.609).&#x0D; Conclusion: There is a significant increase in CST in all grades of retinopathy, as well as with increasing severity of retinopathy when compared to non-diabetics. This warrants the need to obtain OCT measurements even in patients with moderate NPDR without CSME to rule out subclinical DME.

Objective: To assess the resistive index (RI) of ophthalmic artery (OA) and central retinal artery (CRA) as a bioimaging biomarker for the severity of diabetic retinopathy, for the first time. Design: Tertiary care center based cross sectional study. Setting: RI in OA and CRA was studied using color Doppler and gray scale sonography. Central Subfield Thickness (CST), Cube Average Thickness (CAT), retinal photoreceptor ellipsoid zone (EZ) disruption, and Retinal Nerve Fiber Layer (RNFL) thickness were studied using SD-OCT. Participants: Sample size was calculated using 95% confidence interval. 69 consecutive cases of type 2 diabetes mellitus between the ages of 40 and 70 years were included after informed consent. According to Early Treatment Diabetic Retinopathy Study (ETDRS) classification cases were grouped as: diabetes mellitus with no retinopathy (No DR) (n=22); non-proliferative diabetic retinopathy (NPDR) (n=25); and Proliferative Diabetic Retinopathy (PDR) (n=22). Healthy control subjects of similar age were included (n=22). Main outcome measures: RI in OA and CRA. Results: A significant increase in RI of OA and CRA was observed with increased severity of DR. A significant positive correlation of RI of OA and CRA with CST, CAT and grades of EZ disruption and a negative correlation with RNFL thickness was observed. RI of OA was found to be a significant independent predictor of severity of DR [multivariate analysis OR=0.00, p<0.001; area under receiver operating characteristic curve analysis=0.941-1.000, p<0.001]. Conclusions: Resistive index of OA is a bio imaging biomarker for the severity of DR.

PurposeThe purpose of this study was to evaluate differences in optical coherence tomography angiography (OCTA) metrics in the superficial (SCP), intermediate (ICP), and deep (DCP) vascular plexuses across diabetic retinopathy (DR) severity levels.MethodsThis was a cross sectional observational retrospective chart review study. Eligible patients with diabetes who underwent same day RTVue XR Avanti OCTA, spectral-domain optical coherence tomography (SD-OCT), and 200-degree Optos ultrawide field color imaging. SCP, ICP, and DCP vessel density (VD) and vessel length density (VLD) were assessed using 3-D projection artifact removal software (PAROCTA) software.ResultsOf 396 eyes (237 patients), 16.1% had no DR, 26.9% mild nonproliferative DR (NPDR), 21.1% moderate NPDR, 12.1% severe NPDR, 10.1% proliferative DR (PDR) without panretinal photocoagulation (PRP), and 13.4% PDR with PRP. When comparing mild NPDR to no DR eyes, ICP and DCP VD and VLD were significantly lower, but there was no difference for SCP metrics. In eyes with more severe DR, there were significant differences in SCP VD and VLD between DR severity levels (mild versus moderate NPDR: VD 35.45 ± 3.31 vs. 34.14 ± 3.38, P = 0.008 and VLD 17.59 ± 1.83 vs. 16.80 ± 1.83, P = 0.003; moderate versus severe NPDR: VLD 16.80 ± 1.83 vs. 15.79 ± 1.84, P = 0.019), but no significant differences in ICP or DCP.ConclusionsAlthough VD of each of the three individual layers decreases with increasing DR severity, DR severity has a substantially different effect on OCTA parameters within each layer. Vascular changes in eyes with no to early DR were present primarily in the deeper vascular layers, whereas in eyes with advanced DR the opposite was observed. This study highlights the effects of ICP and the importance of assessing SCP and DCP changes independently across each DR severity level.

Retinal Ischemic Perivascular Lesions are Associated with Multifactorial Disease Burden and Severity of Diabetic Retinopathy.

The interocular difference in the ganglion cell-inner plexiform layer thickness showed a significant correlation with the diabetic retinopathy (DR) severity. The purpose of this study was to analyze the interocular differences in the foveal, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GC-IPL) thickness of DR patients using spectral-domain optical coherence tomography. A total of 508 eyes from 254 patients with different severities of DR and 184 eyes from 92 control subjects were included. The GC-IPL, foveal, and RNFL thicknesses were measured, and the interocular differences in these thicknesses were correlated in control subjects and DR patients. The interocular difference in the average GC-IPL thickness significantly increased with the severity of DR. The interocular differences in the average GC-IPL thicknesses of the severe nonproliferative DR (NPDR) and the proliferative DR patients were significantly higher than those of the control group. However, there was no significant difference in thickness between the control group and the group with mild to moderate NPDR. In the group with proliferative DR, the interocular difference in the average GC-IPL was greater than those in the central foveal and RNFL thicknesses. Multivariate regression analyses showed that the DR severity and the interocular difference in central foveal thickness were significantly correlated with the interocular difference in the average GC-IPL thickness. The interocular differences in the central foveal, RNFL, and GC-IPL thicknesses significantly increased with increased DR severity. However, there was no significant difference between the control group and the group with mild to moderate NPDR. The GC-IPL differences showed a significant correlation with DR severity. These findings may be an indicator of DR progression.

To measure the choroidal thickness in patients with type 2 diabetes mellitus and its comparison to healthy age-matched individuals.This prospective comparative study conducted at departments of Ophthalmology, Shri B.M. Patil Medical College, Hospital and Research Centre, Vijayapura. Study included 192 patients, 96 with diabetes and 96 age-matched controls. Data acquired comprised demographics, a thorough eye examination, fundus photography and spectral domain optical coherence tomography measurements of choroidal thickness using enhanced depth imaging.Mean age was 60.17±7.727 years with male predominance in both cases and controls. The mean duration of diabetes was 5.67±3.39 years. Positive correlation was noted between duration of diabetes and severity of retinopathy (p = 0.001). 21 patients did not have any evidence of diabetic retinopathy, while 75 patents had features of non-proliferative diabetic retinopathy, of which (31) had mild, (21) moderate, (12) severe and (11) with proliferative diabetic retinopathy. Mean choroidal thickness of controls was 327.308±18.945 microns, as compared to thinner choroids 295±15.082 microns in cases without retinopathy and 271 ± 36.122, 242 ±30.048, 193±15.748 microns in mild, moderate, severe non-proliferative diabetic retinopathy respectively and 191.492± 23.834 microns in proliferative diabetic retinopathy. Statistically significant differences were noted on comparing choroidal thickness between controls and cases (p = 0.001).Choroidal thickness was maximum in control group with a p value of &amp;#60;0.001, while cases showed overall thinner choroids with increasing severity of retinopathy. Thinnest choroids were observed in patient with proliferative diabetic retinopathy. Choroidal thickness can be used as a non-invasive prognostic bio marker for diabetic retinopathy.

To explore the association of choroidal thickness variations in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) at different stages. A total of 161 patients with T2DM were included in this study, from October 2012 to June 2014. According to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, the patients were divided into 5 groups: non-DR without diabetic macular edema (DME) group(DR-/DME- group, 45 eyes), nonproliferative diabetic retinopathy (NPDR) without DME group(NPDR+/DME- group, 58 eyes), proliferative diabetic retinopathy (PDR) without DME group (PDR+/DME- group, 12 eyes), NPDR with DME group (NPDR+/DME+ group, 41 eyes), PDR with DME group (PDR+/DME+ group, 5 eyes). Meanwhile, 60 normal subjects were enrolled as the control group. All study subjects received optical coherence tomography enhanced depth imaging (EDI-OCT) examination to detect and compare subfoveal choroidal thickness at different stages of DR. Mean SFCT was (271 ± 36), (270 ± 35), (262 ± 38), (244 ± 36), (229 ± 35) µm respectively in control, DR-/DME-, NPDR+/DME-, PDR+/DME-, NPDR+/DME+ groups. The SFCTs of PDR+/DME- and NPDR+/DME+ group were statistically lower than that of control group (P=0.004, P=0.001). The SFCT of PDR+/DME- group was lower than that of DR-/DME- group (P=0.003), and there was also a significant difference of SFCT between NPDR+/DME+ and NPDR+/DME- group (P=0.001). There was linear correlation between SFCT and the logMAR best-corrected visual acuity (r=0.397, P<0.01), but the SFCT was independent of diabetic duration, fasting blood glucose, HbA1c, axial length, diastolic blood pressure (DBP) and systolic blood pressure SBP (r=-0.024, 0.159, 0.089, 0.036, 0.143, 0.057, all P>0.05). There was no significant difference of SFCT among different DME types (F=0.071, P>0.05). The SFCT decreased with increasing severity of DR. To monitor the SFCT in T2DM patients may be helpful to evaluate the severity of DR and provide a new treatment conception.

To explore efficacy and safety outcomes in patients undergoing femtosecond laser-assisted cataract surgery (FLACS) versus manual phacoemulsification cataract surgery (PCS). Prospective consecutive nonrandomized comparative cohort study. A total of 124 eyes from 106 patients (70 in FLACS and 54 in PCS). Comparison of FLACS with PCS over 6 months. Macular central subfield thickness (CST), cube volume (CV), cube average thickness (CAT), endothelial cell density (ECD), central corneal thickness (CCT) and photon count value (PCV). CST, CV and CAT increased postoperatively, which did not return to preoperative levels by 6 months. The values were similar between groups throughout the follow-up, and comparison of changes from baseline also showed no significant difference. Preoperative ECD showed significant difference, which decreased postoperatively and remained stable during follow-up, being lowest at 1 month. FLACS had greater endothelial cell loss than PCS, which was not significant. CCT in both groups increased, reaching maximum on day one and tended to decrease thereafter. No significant differences were found regarding postoperative values and the mean increase. In both groups, mean PCV increased from preoperatively to day one, week one and month one. Flare values in FLACS were lower than PCS, reaching statistical significance at 6 months (P = 0.001). However, the differences in changes of PCV were not significantly different at any visit. Both FLACS and PCS achieved similar safety and efficacy outcomes for performing cataract surgery. Flare values in eyes with FLACS were lower than those with PCS at 6 months postoperatively.

Rapid, bloody, and blinding diabetic retinopathy

Introduction: Diabetic retinopathy (DR) remains a visually debilitating disease and is commonly classified according to its severity as non-proliferative DR (NPDR) or proliferative DR (PDR). Those suffering from PDR tend to have worse vascular complications and prognosis. Platelets exposed by vasculopathy caused by DR maybe activated to try to maintain haemostasis. This activity can be illustrated by the mean platelet component (MPC). Therefore, by MPC monitoring we may be able to predict the progression from NPDR into PDR.Purpose: To investigate the difference of MPC in patients with NPDR and PDR.Study design: Cross-sectional.Materials and methods: This study involved 71 DR patients. Preliminary data regarding the patients’ demographic characteristics, diabetes history, related diseases, medication history, and general eye examination were recorded. Fundus photographs were taken after dilating eyedrops and DR was graded by an ophthalmologist. The patients were grouped into NPDR and PDR. Mean platelet component was analyzed using the automatic hematology analyzer ADVIA 120.Results: Mean platelet component (MPC) was 26.69 g/dl (± 1.79) and 25.52 g/dl (± 1.20) in the NPDR and PDR group, respectively (p = 0.002), but was not clinically significant. In depth analysis into the DR grades differed significantly between mild NPDR and high-risk PDR (p = 0.015), and moderate NPDR and high-risk PDR (p = 0.024). Using our definition of mild DR (mild and moderate NPDR) and severe DR (high-risk and advanced PDR), there was a significant difference with mean MPC of 27.01 g/dl (± 1.64) and 25.31 g/dl (± 1.22), respectively (p = 0.001). The proportion of activated platelets was also higher in severe DR. Negative correlations were found between MPC with duration of DM (r = -0.333; p = 0.004) and MPC with systolic blood pressure (r = -0.241; p = 0.043).Conclusion: There was a significant difference in MPC between NPDR and PDR, but the results should be interpreted carefully. Further analysis between the mild and severe form of DR strengthened this finding.

In diabetic macular edema (DME), identification of baseline markers on spectral-domain optical coherence tomography (SD-OCT) and their association with severity of diabetic retinopathy (DR) might aid in disease management and the design of future trials. To examine associations between DR severity, retinal morphology on SD-OCT, and visual acuity in participants with DME. This cross-sectional observational case series was conducted at a single tertiary care referral center. Demographics, visual acuity, SD-OCT, and color fundus photographs of 80 individuals with DME (102 eyes) seen between December 28, 2013, and April 30, 2014, were analyzed between May 1 and July 31, 2016. Features captured on SD-OCT and thickness metrics. On SD-OCT we graded type and shape of DME, shape and presence of septae within the intraretinal cystoid abnormalities, presence of hyperreflective dots and foci, integrity of the external limiting membrane and ellipsoid zone, presence and extent of disorganization of the inner retinal layers (DRIL), and the status of the vitreomacular interface and epiretinal membrane. We measured retinal thickness at the fovea and at the site of maximum pathology, choroidal thickness at the fovea, and 1000 μm temporal and nasal to the fovea. Color photographs were graded to derive a DR severity stage. The mean (SD) age was 63 (11) years, and 30 participants (37.5%) were women. The odds of having DRIL were greater in eyes with disrupted external limiting membrane (odds ratio [OR], 4.4; 95% CI, 1.6-12.0; P = .003), disrupted ellipsoid zone (OR, 2.7; 95% CI, 1.0-7.2; P = .03), presence of epiretinal membrane (OR, 2.8; 95% CI, 1.0-7.4; P = .03), and increase in retinal thickness at the fovea (OR, 1.6; 95% CI, 1.1-2.2; P < .001). Occurrence of DRIL was more likely in eyes with proliferative DR (OR, 7.3; 95% CI, 1.7-31.4; P = .007). Mean visual acuity decreased by approximately 4.7 letters for each 100-μm increase in the average global DRIL (95% CI, -7.9 to 1.4; P = .006). An association was found between DRIL and disruption of the outer retina and increasing DR severity. Further longitudinal studies seem warranted to determine whether DRIL is a clinically relevant noninvasive morphological marker in eyes with DME.

To investigate the prognostic value of peripheral retinal nonperfusion in patients with diabetic retinopathy using ultra-widefield fluorescein angiography (UWFA). A cross-sectional study included 78 treatment-naïve eyes with nonproliferative and proliferative diabetic retinopathy (NPDR and PDR). Eyes were divided into three groups: mild/moderate NPDR (n = 31), severe NPDR (n = 31), and PDR (n = 16). Three nonperfusion variables were calculated reflecting the proportion of nonperfused to visible retina based on initial UWFA: central nonperfusion (CNP) index, peripheral nonperfusion (PNP) index, and PNP ratio. The relationships between these indices and central subfield thickness (CST) and spectacle-corrected visual acuity (SCVA) were evaluated. CNP and PNP indices were significantly higher in the PDR group vs. mild/moderate NPDR group (p = 0.007 and 0.008, respectively) but not in the PDR group vs. severe NPDR group (p = 0.149 and p = 0.535, respectively). A significant linear correlation was found between the CNP and PNP indices in both severe NPDR and PDR groups (R2 = 0.141, p = 0.041, and R2 = 0.311, p = 0.025, respectively). Nonperfusion predominance was not statistically correlated with the presence of macular edema (p = 0.058) or disorganization of retinal inner layers (p = 1). In the severe NPDR group, there was a moderately positive correlation between CNP index and CST (rs = 0.496, p = 0.019) and no correlation between CNP index and SCVA when controlling for CST (p = 0.160). In the PDR group, a strong negative correlation between PNP ratio and CST was found (rs = -0.659, p = 0.014), but no correlation was observed between CNP index, CST, and SCVA. In the PDR group, a positive correlation was found between PNP index, PNP ratio, and SCVA (rs = 0.549, p = 0.027, and rs = 0.626, p = 0.010, respectively), even after controlling for CST (rs = 0.599, p = 0.040). Higher amounts of retinal nonperfusion are seen in patients with more severe retinopathy. Increased CNP is associated with macular thickening and subsequent vision loss. Having predominantly PNP was independently associated with worse VA, regardless of macular thickness. Further studies are needed to investigate the role of PNP in vision loss in diabetic retinopathy.

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)>300 μm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 μm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 μm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 μm. The mean changes were 95.8±101.4 μm for G1, 137.2±112.9 μm for G2, and 148.9±126.9 μm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.