Clinical Outcome and Drug Expenses of Intravitreal Therapy for Diabetic Macular Edema: A Retrospective Study in Sardinia, Italy

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Aflibercept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Aflibercept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexamethasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered.

Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study

Purpose The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. Methods An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. Results After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. Conclusion This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

Macular and peripapillary microvasculature after dexamethasone injection in diabetic macular edema

Purpose To evaluate the microvascular changes in the macular and peripapillary area after intravitreal dexamethasone implant in diabetic macular edema (DME) Material and Methods We included 31 eyes of 31 patients treated with a single dose dexamethasone implant for DME. All subjects underwent swept-source optical coherence tomography (OCT) and OCT angiography imaging before (T0), and one month (T1), two months (T2), and four months (T4) after dexamethasone injection. The foveal avascular zone (FAZ) area of superficial and deep capillary plexus (SCP and DCP) was calculated by delineating the FAZ border using the measurement tool of the device. The vessel density (VD) of SCP and DCP and choriocapillaris (CC) in the macular and peripapillary area were automatically calculated. Results There was an insignificant reduction in FAZ area measurements of SCP after dexamethasone injection in DME patients (p = 0.846). The FAZ area of DCP were significantly smaller compared to T0 measurements at T1, T2, and T4 (p = 0.013, p = 0.031, and p = 0.029, respectively). The mean average parafoveal VD measurements were significantly decreased after dexamethasone injection in SCP and DCP (p = 0.004, p = 0.005). The peripapillary VD in retinal capillary plexuses and choriocapillaris showed no significant difference after dexamethasone injection. Conclusion Intravitreal dexamethasone leads to a significant FAZ area decrease in DCP with a reduction in parafoveal VD measurements. In addition, no significant VD changes were observed in the peripapillary area after dexamethasone. These findings indicate that dexamethasone may improve macular ischemia with no significant effects on peripapillary microvasculature in DME patients.

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

Background. Retinal vein occlusion (RVO) is the second most common vision-threatening retinal vascular disease. Intravitreal dexamethasone implant has been applied to treat macular edema secondary to RVO (RVO-ME). However, the alteration of morphologic features detected with optical coherence tomography angiography (OCTA) has not been fully studied in RVO-ME patients before and after the treatment. Objective. This study is aimed at identifying potential therapeutic targets in RVO with integrative bioinformatic analysis and compares the OCTA characteristics alterations in patients with RVO-ME receiving injection of dexamethasone intravitreal implant. Methods. Bioinformatic analysis was analyzed in GSE101398 dataset from the Gene Expression Omnibus database. Multiple functional enrichment analyses were performed, and protein-protein interaction network was constructed to visualize the key node genes. Eleven eyes with RVO-ME were examined with OCTA before and after intravitreal dexamethasone implant. The OCTA parameters, including macular thickness, vessel density, foveal avascular zone parameters, the number of hyperreflective foci (HRF), area of cystoid edema, and subretinal fluid (SRF), were compared. The correlation was analyzed between best-corrected visual acuity (BCVA) and OCTA parameters. Results. A total of 79 differentially expressed genes were identified. Functional enrichment analyses revealed the enriched inflammatory events in RVO. In RVO-ME, Pearson correlation revealed that baseline BCVA was positively correlated with the area of SRF and central macular thickness, while no correlation was detected between baseline BCVA and HRF number or the area of cystoid edema. The visual acuity improved, and the central macular thickness was decreased after intravitreal dexamethasone implant injection. Besides, the number of HRF, the area of cystoid edema, and SRF were significantly alleviated after dexamethasone intravitreal injection. Conclusion. Retinal inflammation plays a crucial role in RVO pathogenesis. The imaging biomarkers of RVO including Müller glial intracellular edema, and retinal pigment epithelium dysfunction, could be assessed in OCTA and attenuated by intravitreal dexamethasone implant effectively.