Center-involving Macular Edema Research Articles

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials

PurposeDRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50. DesignYOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator–controlled, noninferiority trials. ParticipantsAdults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes. MethodsPatients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend–based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69). Main Outcome MeasuresChanges in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. ResultsIn YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (–232.8 [–243.5, –222.1]) and faricimab T&E (–217.4 [–227.9, –206.9]) versus aflibercept Q8W (–190.4 [–200.9, –179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, –214.2 (–225.3, –203.1); faricimab T&E, –206.6 (–217.4, –195.7); aflibercept Q8W, –186.6 (–197.7, –175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average. ConclusionsIn patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.

Efficacy and Safety of Faricimab for Macular Edema due to Retinal Vein Occlusion: 24-Week Results from the BALATON and COMINO Trials

To evaluate the 24-week efficacy and safety of the dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A inhibitor faricimab versus aflibercept in patients with vein occlusion. Phase 3, global, randomized, double-masked, active comparator-controlled trials: BALATON/COMINO (ClincalTrials.gov identifiers: NCT04740905/NCT04740931; sites: 149/192). Patients with treatment-naïve foveal center-involved macular edema resulting from branch (BALATON) or central or hemiretinal (COMINO) RVO. Patients were randomized 1:1 to faricimab 6.0 mg or aflibercept 2.0 mg every 4 weeks for 24weeks. Primary end point: change in best-corrected visual acuity (BCVA) from baseline to week 24. Efficacy analyses included patients in the intention-to-treat population. Safety analyses included patients who received ≥ 1 doses of study drug. Enrollment: BALATON, n = 553; COMINO, n = 729. The BCVA gains from the baseline to week 24 with faricimab were noninferior versus aflibercept in BALATON (adjusted mean change,+16.9 letters [95.03% confidence interval (CI), 15.7-18.1 letters] vs.+17.5 letters [95.03% CI, 16.3-18.6 letters]) and COMINO (+16.9 letters [95.03% CI, 15.4-18.3 letters] vs.+17.3 letters [95.03% CI, 15.9-18.8 letters]). Adjusted mean central subfield thickness reductions from the baseline were comparable for faricimab and aflibercept at week 24 in BALATON (-311.4 μm [95.03% CI,-316.4 to-306.4 μm] and-304.4 μm [95.03% CI,-309.3 to-299.4 μm]) and COMINO (-461.6 μm [95.03% CI,-471.4 to-451.9 μm] and-448.8 μm [95.03% CI,-458.6 to-439.0 μm]). A greater proportion of patients in the faricimab versus aflibercept arm achieved absence of fluorescein angiography-based macular leakage at week 24 in BALATON (33.6% vs. 21.0%; nominal P= 0.0023) and COMINO (44.4% vs. 30.0%; nominal P= 0.0002). Faricimab was well tolerated, with an acceptable safety profile comparable with aflibercept. The incidence of ocular adverse events was similar between patients receiving faricimab (16.3% [n= 45] and 23.0% [n= 84] in BALATON and COMINO, respectively) and aflibercept (20.4% [n= 56] and 27.7% [n= 100], respectively). These findings demonstrate the efficacy and safety of faricimab, a dual Ang-2/VEGF-A inhibitor, in patients with macular edema secondary to retinal vein occlusion. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of intravitreal dexamethasone implant in treatment-naive and previously-treated patients with diabetic macular edema.

To document the effects of intravitreal dexamethasone implant on retinal microvasculature in patients with diabetic retinopathy complicated by center-involving macular edema. 35 eyes of 35 patients affected by retinopathy due to type 2 diabetes (15 treatment-naïve and 20 previously treated) were included in this retrospective study with a follow-up of 4 months. Foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) and deep capillary plexus (DCP) densities in the foveal and parafoveal areas were measured by optical coherence tomography angiography (OCTA) at baseline and 2 and 4 months post-injection. Intraocular pressure, morphological and functional parameters were evaluated. a significant difference was found in both groups at 2 months after injection in terms of functional (BCVA, p < 0.05) and morphological (CMT, p < 0.05) parameters. During follow-up, FAZ area, SCP, and DCP in the foveal and parafoveal areas did not change significantly. intravitreal dexamethasone implant is effective in the treatment of diabetic center-involving macular edema and was associated with significant improvements in BCVA and CMT at 2 months after injection. After a single dexamethasone implant injection, FAZ area and retinal vascular density does not show significant variations in both naive and non-naive DME patients subgroups.

Characterization of 2-Year Progression of Different Phenotypes of Nonproliferative Diabetic Retinopathy

Introduction: The aim of the study was to characterize the 2-year progression of risk phenotypes of nonproliferative diabetic retinopathy (NPDR) in type 2 diabetes (T2D) phenotype C, or ischemic phenotype, identified by decreased skeletonized retinal vessel density (VD), ≥2 SD over normal values, and phenotype B, or edema phenotype, identified by increased retinal thickness, i.e., subclinical macular edema, and no significant decrease in VD. Methods: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with 4 visits (baseline, 6 months, 1 year, and 2 years). Ophthalmological examinations included best-corrected visual acuity, color fundus photography (CFP), and optical coherence tomography (OCT) and OCT angiography. Early Treatment Diabetic Retinopathy Study grading was performed at the baseline and last visits based on 7-field CFP. Results: One hundred and twenty-two eyes from T2D individuals with NPDR fitted in the categories of phenotypes B and C and completed the 2-year follow-up. Sixty-five (53%) of the eyes were classified as phenotype B and 57 (47%) eyes as phenotype C. Neurodegeneration represented by thinning of the ganglion cell layer and inner plexiform layer was present in both phenotypes and showed significant progression over the 2-year period (p < 0.001). In phenotype C, significant progression in the 2-year period was identified in decreased skeletonized VD (p = 0.01), whereas in phenotype B microvascular changes involved preferentially decrease in perfusion density (PD, p = 0.012). Phenotype B with changes in VD and PD (flow) and preferential involvement of the deep capillary plexus (p < 0.001) is associated with development of center-involved macular edema. Discussion: In the 2-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, with changes at the microvascular level characterized by decreases in PD in phenotype B and decreases in VD in phenotype C.

Management of Diabetic Macular Edema: Guidelines from the Emirates Society of Ophthalmology.

In the United Arab Emirates, retinopathy has been shown to be present in 19% of the diabetic population, with diabetes identified in up to 40% of individuals aged over 55 years. Despite the prevalence of diabetic retinal diseases, there are no unified national guidelines on the management of diabetic macular edema (DME). These published guidelines are based on evidence taken from the literature and published trials of therapies, and consensus opinion of a representative expert panel with an interest in this condition, convened by the Emirates Society of Ophthalmology. The aim is to provide evidence-based, clinical guidance for the best management of different aspects of DME, with a special focus on vision-threatening diabetic retinopathy. Treatment should be initiated in patients with best-corrected visual acuity 20/30 or worse, and/or features of DME as seen on optical coherence tomography (OCT) with central retinal thickness (CRT) of at least 300 μm or in symptomatic patients with vision better than 20/25, and/or CRT less than 300 μm where there are OCT features consistent with center-involving macular edema. The treatment of DME is effective irrespective of glycated hemoglobin (HbA1c) level, and treatment must not be denied or delayed in order to optimize systemic parameters. All ophthalmic treatment options should be discussed with the patient for better compliance and expectations. Non-center-involving DME can be initially observed until progression toward the center is documented. Macular laser no longer has a primary role in center-involving DME, and anti-vascular endothelial growth factor (anti-VEGF) therapy should be considered as first-line treatment for all patients, unless contraindicated. If anti-VEGF is contraindicated, a steroid dexamethasone implant can be considered for first-line treatment. Recommendations for the treatment of DME in special circumstances and in relapsing and refractory DME are also discussed.

Association of Use of Statins with Progression of Diabetic Retinopathy at a Tertiary Care Hospital in Southern India.

Purpose:To study the role of statin therapy on diabetic retinopathy (DR) progression.Methods:This retrospective study was carried out at a tertiary care hospital in southern India. Data were collected from the medical records of patients admitted from January 2013 to December 2018. Out of 1673 patients of DR enrolled in the study, 171 met the inclusion criteria. Patients' demographic data, drug history, clinical characteristics, and laboratory investigations were recorded as per the pro forma. The patients were divided into statin users and nonusers. The results were analyzed to compare the DR progression between the two groups.Results:DR progressed in 67% of nonstatin users and 37% of statin users (P < 0.001). The use of statins decreased the risk of DR progression (P < 0.001). Center-involving macular edema was seen in 8 of 79 statin users (10%) and 16 of 92 statin nonusers (16%) based on optical coherence tomography findings during the follow-up period (P = 0.17).Conclusion:In patients with type 2 diabetes, lipid-lowering therapy with statins has the potential to retard DR progression.

Retinopathy Phenotypes in Type 2 Diabetes with Different Risks for Macular Edema and Proliferative Retinopathy.

Our group reported that three diabetic retinopathy (DR) phenotypes: A, characterized by low microaneurysm turnover (MAT < 6) and normal central retinal thickness (CRT); B, low MAT (<6) and increased CRT, and C, high MAT (≥6), present different risks for development of macular edema (DME) and proliferative retinopathy (PDR). To test these findings, 212 persons with type 2 diabetes (T2D) and mild nonproliferative retinopathy (NPDR), one eye per person, were followed for five years with annual visits. Of these, 172 completed the follow-up or developed an outcome: PDR or DME (considering both clinically significant macular edema (CSME) and center-involved macular edema (CIME)). Twenty-seven eyes (16%) developed either CSME (14), CIME (10), or PDR (4), with one eye developing both CSME and PDR. Phenotype A showed no association with development of vision-threatening complications. Seven eyes with phenotype B and three with phenotype C developed CIME. Phenotype C showed higher risk for CSME development, with 17.41 odds ratio (p = 0.010), compared with phenotypes A + B. All eyes that developed PDR were classified as phenotype C. Levels of HbA1c and triglycerides were increased in phenotype C (p < 0.001 and p = 0.018, respectively). In conclusion, phenotype C identifies eyes at higher risk for development of CSME and PDR, whereas phenotype A identifies eyes at very low risk for vision-threatening complications.

Optical coherence tomographic comparison of naive macular edema due to ischemic and nonischemic retinal vein occlusion.

To examine the macular microstructure in macular edema (ME) due to retinal vein occlusion (RVO) in terms of ischemic or nonischemic type to determine whether and how ischemia affects macular microstructure. This retrospective, nonrandomized study included 75 newly diagnosed RVO cases (group 1: 55 nonischemic RVO cases and group 2: 20 ischemic RVO cases) with evidence of center-involving ME without any treatment. Quantitative measures on spectral-domain optical coherence tomography images were performed. Central subfield thickness (CST) was collected in the central 1mm from the thickness map. The following items were evaluated in a 3-mm-wide area (perifoveal ETDRS circle) centered on the fovea: disorganization of the retinal inner layers (DRIL), disrupted external limiting membrane (ELM) and ellipsoid zone disruption (EZD). The microstructural changes were measured manually. Baseline characteristics, such as age, sex, study eye, and RVO risk factors, were similar between the groups (P > 0.05). CST was 554.15 ± 191.45µm for group 1 and 769.90 ± 290.00µm for group 2 (P: 0.001). The extent of DRIL was 1864.09 ± 941.70µm and 2447.25 ± 492.59µm for groups 1 and 2, respectively (P: 0.010). The disrupted ELM length was 1700 (0-3000) µm for group 1 and 2725 (300-3000) µm for group 2 (P: 0.027). The EZD length was 1453.09 ± 870.38µm for group 1 and 1846.00 ± 926.54µm for group 2 (P: 0.093). Ischemic RVOs cause greater macular edema and greater disruption in the macular microstructure compared to nonischemic RVOs, especially in terms of DRIL and ELM.

Association between disorganization of the retinal inner layers and capillary nonperfusion area in patients with retinal vein occlusion.

To determine the correlation between the extent of disorganization of the retinal inner layers (a parameter of spectral domain optical coherence tomography) and optical coherence tomography angiography parameters in eyes with center-involved macular edema associated with retinal vein occlusion. This retrospective observational study included 34 eyes of 34 patients with newly diagnosed macular edema associated with retinal vein occlusion and evidence of center-involved macular edema. Optical coherence tomography angiography and spectral domain optical coherence tomography were evaluated after resolution of the macular edema. Disorganization of the retinal inner layers was determined via spectral domain optical coherence tomography and optical coherence tomography angiography parameters, including foveal avascular zone area in the superficial capillary plexus and capillary nonperfusion areas, foveal avascular zone area in full retinal vasculature, foveal avascular zone perimeter, acircularity index of the foveal avascular zone, and foveal density. The mean disorganization of the retinal inner layers extent was 512.72 ± 238.47 microns, and the mean capillary nonperfusion area was 4.98 ± 2.85 mm2. There was a positive correlation between the extent of disorganization of the retinal inner layers and capillary nonperfusion area (p<0.001, r=0.901). Greater extent of disorganization of the retinal inner layers and the capillary nonperfusion area was correlated with wider foveal avascular zone area (p=0.014 and p=0.036, respectively) in the superficial capillary plexus and decreased foveal density (vessel density in 300 microns around the foveal avascular zone) (p=0.031 and p=0.022, respectively). These parameters were also correlated with decreased vessel density in both the superficial capillary plexus and deep capillary plexus in the parafoveal and peri-foveal regions (p<0.05 for all). Disorganization of the retinal inner layers appears to be a correlated biomarker of capillary ischemia in retinal vein occlusion. The extent of disorganization of the retinal inner layers was strongly correlated with the capillary nonperfusion area. This may support the notion that the extent of disorganization of the retinal inner layers can be used as an easily obtainable and crucial surrogate marker of capillary ischemia.

Classification of Regions of Nonperfusion on Ultra-widefield Fluorescein Angiography in Patients with Diabetic Macular Edema

To classify retinal nonperfusion regions (NPRs) in patients with diabetic macular edema (DME) and assess the relationship with severity of DME. Prospective, observational case series. Forty eyes of 29 patients with treatment-naïve center-involved macular edema secondary to diabetes mellitus were included (The DAVE study, NCT01552408) in this analysis. Ultra-widefield fluorescein angiography (UWF FA) images were transmitted to the Doheny Image Reading Center, where they were corrected using stereographic projection to adjust for peripheral distortion. Two independent, certified graders manually evaluated the NPR and classified the nonperfusion as being associated with leakage or without leakage. The size of these 2 subtypes of NPR were computed in mm2 and assessed across the entire retina and within 3 concentric retinal zones. The relationship between subtype of NPR and the severity of DME was assessed. In 40 eyes with treatment-naïve DME, visual acuity was significantly correlated with central macular thickness (CMT) and macular volume (MV). The NPR with leakage was positively correlated with CMT (R= 0.408, P= .009) and MV (R= 0.399, P= .011), whereas the NPR without leakage was negatively correlated with CMT (R=-0.468, P= .002) and MV (R=-0.473, P= .002). The NPR with leakage in the posterior region was significantly greater compared to the mid-periphery and the far periphery (P < .001), whereas the NPR without leakage was significantly greater in the mid-periphery compared with the far periphery or the posterior region (P= .001). In patients with DME, the severity of DME appears to be positively correlated with NPR with leakage but negatively correlated with NPR without leakage. These findings may have implications for the pathophysiology of DME and the design of protocols for targeted laser in these eyes.

Disorganization of Retinal Inner Layers in Retinal Vein Occlusions: New Insights From Anti-VEGF Treatment

Purpose: The purpose of this study is to determine the significance of disorganization of the retinal inner layers (DRIL) in patients with retinal vein occlusions (RVOs) and whether this is influenced by the choice of antivascular endothelial growth factor (anti-VEGF) agent used. Methods: A retrospective chart study was conducted on patients with RVO and center-involved macular edema (ME) presenting to the University of Wisconsin with a minimum follow-up time of 12 months. Medical records were reviewed for demographics, vision, and imaging at baseline and 2 study visits over the course of 1 year. Two masked graders evaluated spectral-domain optical coherence tomography scans for DRIL and other features within the 1-mm-wide area centered on the foveal depression. Results: Twenty-two eyes had DRIL at baseline. DRIL resolved in 10 eyes at the first study visit, and in 2 more eyes at the second study visit. Although we could not establish an association between visual acuity (VA) and DRIL at baseline, we found a more robust correlation between DRIL extent and VA at baseline in eyes with central retinal vein occlusion/hemicentral vein occlusion compared to eyes with branch retinal vein occlusion. There was an association between DRIL improvement at the first study visit and VA improvement at the second study visit ( P = .049). However, this effect was smaller than the effect of initial VA improvement on final VA improvement. No significant difference in DRIL change was observed between the 3 anti-VEGF treatment algorithms: bevacizumab only, aflibercept only, and bevacizumab followed by aflibercept. Additionally, there was no significant correlation between RVO risk factors and change in DRIL over time. Conclusions: In our study, DRIL was not associated with VA in RVO-ME, but its resolution was predictive of VA improvement in response to anti-VEGF therapy. The choice of anti-VEGF agent (bevacizumab, aflibercept or a combination of the 2) did not affect the magnitude of DRIL resolution in RVO.

Characterization of Initial Stages of Diabetic Macular Edema

Purpose: This study is aimed at characterizing the type of retinal edema in the initial stages of retinopathy in type 2 diabetes. Methods: In this retrospective cross-sectional study, spectral domain optical coherence tomography (OCT) layer by layer analysis of the retina in association with OCT-Leakage, an algorithm to detect sites of low optical reflectivity, were used to examine eyes with minimal, mild, and moderate diabetic retinopathy (DR). Results: A total of 142 eyes from 142 patients (28% women) aged 52–88 years were imaged. Macular edema, either subclinical (SCME) or central-involved macular edema (CIME), was present in 43% of eyes in group 10–20, 41% of eyes in group 35, and 38% of eyes in group 43–47. The inner nuclear layer (INL) was the layer showing higher and most frequent increases in retinal thickness (79%). The edema was predominantly intracellular in group 10–20 (65%) and extracellular in groups 35 (77%) and 43–47 (69%). Conclusions: Eyes from diabetic patients in the initial stages of DR with different Early Treatment Diabetic Retinopathy Study gradings show similar prevalence of SCME and CIME, independent of the severity of the retinopathy. Retinal edema is located mainly in the INL and appears to be mostly extracellular except in the earliest stages of diabetic retinal disease where intracellular edema predominates.

Timing of phacoemulsification in relation to intravitreal ranibizumab injection in diabetic patients type 2 with cataract and mild center involved macular edema

Purpose: To compare preoperative ranibizumab (RBZ) 0.5 mg/0.05 ml three-injection protocol to postoperative protocol in cases with center involved macular edema (CiME), undergoing phacoemulsification. Patients and Methods: Cases with non-ischemic clinically significant diabetic macular edema (CSDME) were randomized into two groups. Both groups received three intravitreal RBZ injections on monthly basis. Group 1, received the first two injection 2 months before phacoemulsification and the third one was injected intraoperative by the end of surgey. Group 2 received the first injection intraoperatively followed by 2 other injections, 1 and 2 months postoperatively. Central subfield thickness (CST) was measured using spectral-domain optical coherence tomography (RTvue-100), 1 month after third injection for both groups. Results: The mean postoperative corrected distance visual acuity (CDVA) at 3 months postoperatively was significantly improved (P = 0.005) in Group 1 than in Group 2. The postoperative CST 1 month after the third injection for Group 1 was 252.5 μm ± 16 versus 270.1 μm ± 24.4 for Group 2, which was statistically significant (P = 0.02). Percentage of reduction in central foveal thickness (CFT) was 15.4% and 8%, Groups 1 and 2, respectively. The ellipsoid zone integrity showed Interruption in Group 1 in 19.4% of eyes, which was lower than in Group 2 (28%), however this was not statistically significant (P = 0.4). None of our cases developed epiretinal membranes in either groups. In Group 2 only, four cases developed subretinal fluid (SRF), and one case had cystoid changes. None of the cases developed SRF or de novo cystoid changes, till the last follow-up visit, in Group 1. Conclusion: Using RBZ repeated intravitreal injections protocol prior to phacoemulsification improved significantly CDVA and reduced the CST, than when injected postoperatively. In addition, the number of postoperative intravitreal injections that might be needed was significantly reduced when it is used preoperatively.

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial

To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). Phase I/II prospective, randomized, controlled clinical trial. Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 μm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P= 0.20) and mean CRT improved 302 and 152 μm (P= 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P= 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P= 0.30). In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.

Subclinical Macular Edema as a Predictor of Progression to Central-Involved Macular Edema in Type 2 Diabetes

Purpose: The aim of this study was to examine the relationship between subclinical diabetic macular edema (SCME) and the development of central-involved macular edema (CIME) in patients with diabetes mellitus type-2 and mild nonproliferative diabetic retinopathy (NPDR), from 2 populations of different ethnicities. Methods: Two hundred and five patients with diabetes mellitus type-2 and mild NPDR with no prior laser or intravitreal treatment were followed for 2 years or until the development of CIME. Ophthalmological examinations, including BCVA, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and months 6, 12, and 24. Results: One hundred and fifty eight eyes/patients reached either the study endpoint, CIME (n = 24), or performed the 24-month visit without developing CIME (n = 134). Fifty eyes/patients had SCME at baseline (31.6%). Of these 50 eyes, 16 (32.0%) developed CIME, whereas of the 108 eyes with normal retinal thickness (RT) at baseline, only 8 (7.4%) developed CIME (p < 0.001). Patients with increased RT in the central subfield at baseline showed a 12-fold risk of progression to CIME compared with patients without SCME. Conclusions: In patients with mild NPDR, the presence of SCME is a good predictor of progression to CIME.

Different Phenotypes of Mild Nonproliferative Diabetic Retinopathy with Different Risks for Development of Macular Edema (C-TRACER Study)

Purpose: To evaluate diabetic retinopathy (DR) progression in patients with diabetes mellitus type 2 in 2 populations of different ethnicity. Methods: A prospective observational study was designed to follow eyes/patients with mild nonproliferative DR, for 2 years or until the development of central-involved macular edema (CIME), in 2 centers from different regions of the world. A total of 205 eyes/patients fulfilled the inclusion/exclusion criteria and were included in this study. Ophthalmological examinations, fundus photography with RetmarkerDR analysis, and optical coherence tomography were performed at baseline and at 6, 12 and 24 months. Results: Of the 158 eyes/patients that completed this study, 24 eyes developed CIME and 134 eyes were present at the last study visit. Eighty-eight eyes (56.4%) were classified as phenotype A, 49 (31.4%) as phenotype B, and 19 (12.2%) as phenotype C. Phenotype A is associated with a very low risk for development of CIME in comparison with phenotypes B and C. The OR for development of CIME was 19.0 for phenotype B and 25.1 for phenotype C. Conclusion: Eyes in the initial stages of DR show different phenotypes with different risks of progression to ME. The phenotypes associated with increased risks of progression show different distributions in patients of different ethnicities.

Macular edema after cataract surgery in diabetic eyes evaluated by optical coherence tomography.

To assess quantitative changes of the macula in diabetic eyes after cataract surgery using optical coherence tomography (OCT) and to estimate the incidence of development or worsening of macular edema (ME) in diabetic eyes with or without pre-existing ME. In this prospective, observational study, 92 eyes of 60 diabetic patients who underwent cataract surgery were evaluated before surgery and 1, 3mo after surgery using OCT. Macular thickness was measured with OCT at nine macular subfields defined by the 9 zones early treatment of diabetic retinopathy study (ETDRS), as well as total macular volume obtained by OCT at 1, 3mo after surgery were compared with baseline features obtained before surgery. In addition, the incidence of development or worsening of ME was analyzed in diabetic eyes with or without pre-existing ME. The central subfield mean thickness increased 21.0 µm and 25.5 µm at 1, 3mo follow-up, respectively (P<0.01). The average thickness of inner ring and outer ring increased 14.2 µm and 9.5 µm at 1mo, 18.2 µm and 12.9 µm at 3mo. Central-involved ME developed in 12 eyes at 3mo, including 4 eyes with pre-existing central-involved and 8 eyes with pre-existing non-central involved ME. Pre-existing diabetic macular edema (DME) was significantly associated with central-involved ME development (P<0.001). A statistically significant increase could be detected in the central subfield as well as perifoveal and parafoveal sectors though the increase was mild. And eyes with pre-operative DME prior to cataract surgery are at higher risk for developing central-involved ME.

Evidence-based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines.

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti-vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center-involving macular edema benefit from intravitreal anti-VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians.

Association of Disorganization of Retinal Inner Layers With Vision After Resolution of Center-Involved Diabetic Macular Edema.

Macular edema (ME) prognosis and treatment response vary according to the underlying abnormalities. Biomarkers of visual acuity (VA) improvement could influence management decisions in different types of ME. To investigate whether disorganization of retinal inner layers (DRIL) and other spectral-domain optical coherence tomography (SD-OCT)-derived variables are associated with subsequent VA after ME resolution in both nondiabetic and diabetic ME. A retrospective, longitudinal cohort study in which Snellen VA testing and SD-OCT macular imaging were performed, was conducted at a tertiary referral eye center for retinal diseases. The medical records of all patients with ME from December 1, 2010, to December 31, 2012, were reviewed. The date of the last follow-up was June 1, 2013. Participants included 55 patients (70 eyes) with center-involved ME that had resolved during an 8-month period. Patients were grouped based on the source of ME (diabetic vs nondiabetic). Exclusion criteria included significant media opacity interfering with good-quality SD-OCT image acquisition. Masked graders analyzed the central 1500-μm macular region for changes, including cysts, DRIL length and extent, and outer retinal layers disruption. Intragrader and intergrader agreement Spearman rank correlation coefficients ranged from 0.70 to 0.93 for quantitative measurement, and κ values ranged from 0.88 to 1.00 for qualitative grading. Visual acuity and morphologic changes measured on SD-OCT. In both groups, VA after ME resolution correlated with baseline VA. In diabetic ME involving a multivariable model including baseline VA and DRIL, total length was associated with subsequent VA as determined by a parameter estimate (PE) of 0.0003 (95% CI, 0-0.0006) (P = .03). The VA change during the 8-month period, after adjusting for baseline VA, was best associated with DRIL change (PE, 0.0002 [95% CI, 0-0.0003]; P = .04). Participants whose DRIL resolved, both early and late, showed improvement in their VA deficit at 8 months (least squares mean [SE], 41.3 [28.5] and 40.9 [37.5], respectively) compared with nonresolvers, whether inconsistent or persistent, whose VA worsened. After adjustment for baseline VA, eyes with persistent DRIL showed the largest difference in VA deficit compared with those with no baseline DRIL (-89.6 [27.2] vs 49.7 [19.6], respectively; P = .006). The presence of DRIL at baseline and its resolution pattern may be associated with subsequent VA after resolution of center-involved diabetic ME.

Posterior sub-tenon’s bevacizumab injection in diabetic macular edema; a pilot study

PurposeTo evaluate the short-term results of sub-tenon’s injection of bevacizumab in patients with clinically significant macular edema (CSME). MethodsIn this prospective non-comparative interventional case series, sub-tenon’s injection of 2.5mg/0.1ml bevacizumab was performed for eyes with CSME. Macular thickness and best corrected visual acuity measurements were performed before and one month after injections. ResultsNineteen eyes of twelve patients with a mean age of 59.8±5.7years were evaluated. Thirteen eyes (68.4%) had center-involving macular edema. No significant difference was observed between pre- and post-injection central subfield retinal thickness measurements (P=0.3). Central subfield thickness measurements improved or remained unchanged in 13 eyes (68.4%). Baseline BCVA of 0.48±0.35 LogMAR improved to 0.36±0.26 LogMAR after injection (P=0.01). Improvement of>2 lines in BCVA was found in 5 eyes (26.3%), and no eye lost>2 lines of BCVA. No complication associated with sub-tenon’s injection was observed. ConclusionSub-tenon’s injection of bevacizumab resulted in significant short-term visual improvement in eyes with CSME. Retinal thickness changes were not significant.