The Role of Angiogenesis in the Development of Proliferative Diabetic Retinopathy: Impact of Intravitreal Anti-VEGF Treatment

Although cellular and molecular bases of proliferative diabetic retinopathy are only partially understood, it is evident that this complication of diabetes is characterized by the formation of new vessels inside the retina showing abnormal architecture and permeability. This process, if not controlled by selective laser photocoagulation, leads to irreversible retinal damages and loss of vision. Angiogenesis, that is, the condition characterized by the growth of new blood vessels originated from preexisting ones, was shown to have a major role in the pathogenesis of proliferative retinopathy and, as a consequence, intravitreal antiangiogenic injection was suggested as a feasible treatment for this disease. Here, we describe the different antiangiogenic approaches used to treat this disease along with the respective advantages and limitations when compared to laser treatment. Altogether, even though further and longer studies are still needed to clarify the best possible therapeutic protocol, the antiangiogenic treatment will reasonably have a future role in the therapy and prevention of proliferative diabetic retinopathy

Functional and structural findings of neurodegeneration in early stages of diabetic retinopathy:cross-sectional analyses of baseline data of the EUROCONDOR project

Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2 diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time (IT), and was lower in patients with ETDRS 20-35 than in patients with ETDRS <20 (p=0.005). In 58% of cases, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements which increases with the presence of microvascular impairment. However, in our particular study population (ETDRS ≤ 35) a significant proportion of patients had normal GC-IPL thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many, but not in all type 2 diabetic patients

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

Clinical Strategies in the Management of Diabetic RetinopathyA step-by-step Guide for Ophthalmologists /

XVIII, 178 p. 102 illus., 78 illus. in color.onli

Dexamethasone implants in diabetic macular edema patients with high visual acuity

PURPOSE: To evaluate the effects of intravitreal dexamethasone (DEX) implants in patients affected by diabetic macular edema (DME) with high best-corrected visual acuity (BCVA) and contraindications to therapy with anti-vascular endothelial growth factor over a 12-month follow-up. METHODS: In this interventional nonrandomized clinical study, 14 consecutive patients (14 eyes) affected by DME with a BCVA of 0.3 LogMAR or better were prospectively enrolled. All patients were treated with a sustained-release 700-\u3bcg DEX implant at baseline, revaluated every 6 weeks, and retreated on a pro re nata basis. Primary outcomes included changes in BCVA and central macular thickness (CMT). Secondary outcomes included number of implants, average period between injections, and incidence of side effects. RESULTS: At the 12-month examination, a significant improvement in mean BCVA was noted compared to baseline (from 0.25 \ub1 0.05 to 0.10 \ub1 0.07 LogMAR; p < 0.001); CMT decreased from 484 \ub1 127 to 311 \ub1 51 \u3bcm (p < 0.001). No differences in BCVA and CMT improvements were found between treatment- na\uefve patients and previously treated patients (p = 0.768 and 0.119, respectively). The mean number of implants was 1.71 \ub1 0.61 (range, 1-3). The mean period between the first and the second implant was 6.1 \ub1 1.6 months. CONCLUSIONS: The DEX implant on a pro re nata basis can be considered a beneficial approach for DME patients with high BCVA over a 12-month follow-up; functional and anatomical outcome of the patients significantly improved with few injections and a good safety profile

The Narrative Medicine Approach in the Treatment of Diabetic Macular Edema: An Italian Experience

Abstract: The study retraces the healthcare pathway of patients affected by diabetic macular edema (DME) through the direct voice of patients and caregivers by using a “patient journey” and narrative method approach. The mapping of the patient’s journey was developed by a multidisciplinary board of health professionals and involved four Italian retina centers. DME patients on intravitreal injection therapy and caregivers were interviewed according to the narrative medicine approach. Narratives were analyzed through a quali-quantitative tool, as set by the narrative medicine method. The study involved four specialized retina centers in Italy and collected a total of 106 narratives, 82 from DME patients and 24 from caregivers. The narratives reported their difficulty in identifying the correct pathway of care because of a limited awareness of diabetes and its complications. Patients experienced reduced autonomy due to ocular complications. In the treatment of diabetes and its complications, a multidisciplinary approach currently appears to be missing. DME reduces the quality of life of affected patients. The narrative medicine approach offers qualitative and emotional patient-guided information. The patient journey provides all of those involved in the management of DME with flowcharts to refer to, identifying the critical points in the healthcare journey of DME patients to improve the management of the disease