Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) are eye problems that can make you lose your sight. These eye problems happen when blood vessels in the eye do not work right. Right now, people need lots of shots in their eyes to treat it. EYP-1901 (Duravyu) is a new medicine that helps people with fewer shots in their eyes. It has two parts: one that helps the medicine last longer, and another that helps stop the problem in the eye. Early tests show it works well and helps people keep their sight with fewer treatments.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.

Predictive value of optical coherence tomography angiography in management of diabetic macular edema.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a relatively new extension of Optical coherence tomography (OCT) that generates non-invasive, depth-resolved images of the retinal microvasculature which allows for the detection of various features of diabetic retinopathy. OBJECTIVES: This study aimed to detect biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal ranibizumab (IVR) by means of OCTA. PATIENTS AND METHODS: This prospective interventional study was undertaken on 111 eyes of 102 naïve participants who had diabetic macular edema; enrolled patients were evaluated by taking a complete ophthalmologic history, examination and investigations by use of a pre-designed checklist involving Optical Coherence Tomography Angiography. RESULTS: Regarding the best corrected visual acuity (BCVA) the Mean ± SD was 0.704 ± 0.158 preoperatively and 0.305 ± 0.131 postoperatively in good responder patients; and was 0.661 ± 0.164 preoperatively and 0.54 ± 0.178 postoperatively in poor responders. The central macular thickness (CMT) was 436.22 ± 54.66 µm preoperatively and 308.12 ± 33.09 µm postoperatively in good responder patients; and was 387.74 ± 44.05 µm preoperatively and 372.09 ± 52.86 µm postoperatively in poor responders. By comparing the pre injection size of the foveal avascular zone area (FAZ-A) in both groups, it found that the mean ± SD of FAZ-A was 0.297 ± 0.038 mm in good responder patients compared to 0.407 ± 0.05 mm in non-responder patients. The preoperative superficial capillary plexus (SCP) foveal vascular density (VD) was 24.02 ± 3.01% in good responder patients versus 17.89 ± 3.19% um in poor responders. The preoperative SCP parafoveal VD was 43.06 ± 2.67% in good responder patients versus 37.96 ± 1.82% um in poor responders. The preoperative deep capillary plexus (DCP) foveal VD was 30.58 ± 2.89% in good responder patients versus 25.45 ± 3.14% in poor responders. The preoperative DCP parafoveal VD was 45.66 ± 2.21% in good responder patients versus 43.26 ± 2.35% um in poor responders, this was statistically significant. CONCLUSION: OCTA offers an accurate measurement for VD in the macula as well as the FAZ-A which could be used to predict an early anatomical response of anti-VEGF treatment in DME.

Brolucizumab versus aflibercept for recalcitrant diabetic macular edema in Indian real-world scenario - The BRADIR study.

Purpose: To compare the safety and efficacy of aflibercept with brolucizumab for recalcitrant diabetic macular edema (DME). Observations: At week 52, no significant visual improvement was noted in the eyes treated with either brolucizumab (P = 0.527) or aflibercept (P = 0.393). The CMT decreased significantly after brolucizumab therapy (P = 0.012), but not with aflibercept (P = 0.284) at 52 weeks. The proportion of patients with IRF and SRF reduced significantly in both arms. The mean number of brolucizumab injections was significantly lower (3.93[±1.28]) than aflibercept (4.75[±1.62]) (P = 0.037) over the 52 weeks. At 52 weeks, 76.67 % of eyes treated with brolucizumab attained full macular dryness (CMT<300 µm with absence of SRF and IRF) compared to 50 % of eyes treated with aflibercept (P = 0.036). Subconjunctival hemorrhage was the only adverse event observed in the study (P = 0.701); no other systemic or ocular adverse events, such as intraocular inflammation, were reported. Conclusion and importance: The BRADIR study suggests that brolucizumab might have an edge over aflibercept in visual and anatomical outcomes that lasted 52 weeks with reduced injection frequency in case of recalcitrant DME.

Optical coherence tomography angiography for microaneurysms in anti-vascular endothelial growth factor treated diabetic macular edema.

BACKGROUND: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. METHODS: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. RESULTS: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 µm) and NDME (mean maximum diameter = 74.70 ± 2.86 µm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001). CONCLUSIONS: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness.

Effect of anti-vascular endothelial growth factor on early-stage post-vitrectomy macular edema in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy on post-vitrectomy macular edema (PVME) and determine the risk factors for PVME recovery. METHODS: This retrospective study included 179 eyes of 179 patients who underwent pars plana vitrectomy for proliferative diabetic retinopathy and developed PVME within 3 months after surgery. Eyes were grouped according to postoperative anti-VEGF treatment. RESULTS: Central retinal thickness (CRT) decreased significantly from baseline to 3-month follow-up in groups with (509.9 ± 157.2 µm vs. 401.2 ± 172.1 µm, P < 0.001) or without (406.1 ± 96.1 µm vs. 355.1 ± 126.0 µm, P = 0.008) postoperative anti-VEGF treatment. Best-corrected visual acuity (BCVA) did not differ between the two groups during follow-up. In the group not receiving anti-VEGF therapy, BCVA was significantly improved at 1, 2, and 3 months (P = 0.007, P < 0.001, and P < 0.001, respectively), while in the anti-VEGF group, BCVA was significantly improved at 1 and 3 months (P = 0.03 and P < 0.001). A thicker baseline CRT (ß = 0.44; 95% confidence interval, 0.26-0.61; P < 0.001) was significantly associated with decreasing CRT. CONCLUSION: PVME tends to spontaneously resolve in the early postoperative period. The effect of anti-VEGF therapy in the first 3 months after diagnosis appears to be limited.

Identification and mechanistic analysis of neurovascular coupling related biomarkers for diabetic macular edema.

Introduction: Diabetic macular edema (DME) is a major cause of vision loss in the sick with diabetic retinopathy. The occurrence of DME is closely related to the breakdown of neurovascular coupling; however, its underlying mechanism has not been fully elucidated. The aim of this study was to investigate the diagnostic biomarkers and potential molecular mechanisms associated with neurovascular coupling in DME. Methods: The differential expression analysis, STEM, and WGCNA were performed from GSE160306 to identify hub genes. The gene expression was validated by RT-qPCR. The relevant mechanisms of action were investigated through GO, KEGG, and GSEA analyses, as well as co-expression networks. Additionally, the LASSO regression analysis and a nomogram were used to demonstrate the diagnostic effectiveness of the model. Finally, the GenDoma platform was utilized to identify drugs with potential therapeutic effects on DME. Results: Neurotrophic factor receptor (NGFR) was identified as a hub gene related to neurovascular coupling and DME. The expression of NGFR was verified by RT-qPCR in vitro cells. GSEA analysis indicated that high expression of NGFR may affect immunity and inflammatory pathway, thereby regulating neurovascular coupling and mediating the development of DME. The NGFR co-expression network was constructed, which exhibited the correlation with the neurotrophin signaling pathway. Moreover, a diagnostic model for DME based on NGFR and PREX1 demonstrated relatively good diagnostic performance using LASSO regression analysis and the nomogram. And then the GenDoma platform identified drugs with potential therapeutic effects on DME. Conclusion: The high expression of NGFR may lead to abnormal neurovascular coupling and participate in the occurrence of DME by regulating the immunity, inflammatory and neurotrophin signaling pathway. Detection of NGFR and related expression genes may be beneficial for monitoring the occurrence and development of DME.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

BACKGROUND: Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. METHODS: We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. RESULTS: We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. CONCLUSIONS: Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

BACKGROUND/OBJECTIVES: Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. METHODS: This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. RESULTS: A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 µm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. CONCLUSIONS: In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Efficacy and Safety of Fluocinolone Acetonide Implant in Diabetic Macular Edema: Practical Guidelines from Reference Center.

Diabetic macular edema (DME) is a common complication of diabetic retinopathy. Treatment with intravitreal injections is effective in most cases but is associated with a high therapeutic burden for patients. This implies the need for long-term treatments, such as the fluocinolone acetonide (FAc) implant. A review of basic science, pharmacology, and clinical data was conducted to provide a state-of-the-art view of the FAc implant in 2024. Although generally well tolerated, the FAc implant has been associated with ocular hypertension and cataract, and caution should be advised to the patients in this regard. By synthesizing information across these domains, a comprehensive evaluation can be attained, facilitating informed decision-making regarding the use of the FAc implant in the management of DME. The main objective of this review is to provide clinicians with guidelines on how to introduce and use the FAc implant in a patient with DME.

Anterior Chamber Flare as a Non-Invasive Assessment of Intraocular Immune Status and Ocular Complications in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman's rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME.

Effectiveness of dexamethasone implants in treating diabetic macular edema with hard exudates: a clinical observation.

OBJECTIVE: This study seeks to explain the relationship between systemic conditions and hard exudate formations in diabetic macular edema patients. Besides, the study aimed to quantitatively examine changes in the area, location, and impact on visual function of hard exudates following intravitreal dexamethasone implant injections. METHODS: A retrospective analysis was conducted, including 40 patients (40 eyes) diagnosed with non-proliferative diabetic retinopathy and concurrent macular edema between January 1, 2022, and January 1, 2024. Preoperative evaluations included glycated hemoglobin, lipid profile, and renal function examinations. Based on the location of HE, patients were divided into two groups: Group A, with HE in 1 mm of the central fovea, and Group B, with HE outside 1 mm of the central fovea. Selected eyes were subject to pre- and postoperative examinations, including best-corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopy, scanning laser ophthalmoscopy (SLO), optical coherence tomography, and multifocal electroretinography. Following screening and examination, patients received an immediate intravitreal injection of the DEX implant, with an injection administered at the four-month mark. Hard exudate (HE) areas were measured utilizing SLO fundus imaging. RESULTS: Total cholesterol, low-density lipoprotein, and triglyceride levels were found to be positively correlated with the presence of HE. Following surgical intervention, all patients demonstrated an improvement in BCVA. The mean BCVA increased from a preoperative measurement of 0.79 ± 0.04 to 0.39 ± 0.02 at the 6 month follow-up, indicating a statistically significant difference (p < 0.001). The baseline HE area for the entire patient cohort was 2.28 ± 0.22. One month post-operation, the HE area exhibited a slight increase to 2.27 ± 0.22. However, by the 6 month follow-up, the HE area had significantly decreased to 0.8 ± 0.87, representing a 35.09% reduction from the baseline measurement (p < 0.001). It is worth noting that Patient P1 did not exhibit a statistically significant difference between preoperative and six-month postoperative HE area (p = 0.032). Preoperative BCVA measurements for Group A and Group B were 0.81 ± 0.03 and 0.77 ± 0.03, respectively, with no statistically significant intergroup difference (p = 0.333). The baseline HE area for Group A was 2.61 ± 0.16, which decreased to 0.38 ± 0.20 at the six-month follow-up, representing a 14.60% reduction from the baseline total area. For Group B, the baseline HE area was measured at 1.95 ± 0.09, then decreasing to 1.21 ± 0.13 at the six-month follow-up, indicating a 62.05% reduction from the baseline total area. A statistically significant difference in the postoperative 6 month HE area was observed between Group A and Group B (p < 0.001). In Group A, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in P1 (initial P1-final P1) (r = 0.610, p = 0.004). In Group B, a similar positive correlation was found (initial HE area-final HE area with initial P1-final P1) (r = 0.488, p = 0.029). In Group B, the reduction in HE area (initial HE area-final HE area) correlated positively with the improvement in BCVA (initial BCVA-final BCVA) (r = 0.615, p = 0.004). Additionally, in Group B, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in CMT (initial CMT-final CMT) (r = -0.725, p< 0.001). Aggravated cataracts were observed in thirteen eyes during a follow-up examination 6 months later. CONCLUSION: HE formation is associated with lipid levels. Dexamethasone implants demonstrate effectiveness in reducing HE areas in the short term, reducing macular edema, improving retinal structure, and enhancing visual function. The incidence of postoperative complications such as cataracts and glaucoma remains low.

Changes in Ocular Blood Flow After Intravitreal Injection for Diabetic Macular Edema Between Aflibercept and Faricimab.

Purpose: In this study, we aimed to evaluate and compare the effects of intravitreal aflibercept (IVA) and intravitreal faricimab (IVF) injections on the blood flow of retinal vessels in the peripapillary region and optic nerve head (ONH) in eyes with diabetic macular edema (DME) using laser speckle flowgraphy (LSFG). Patients and Methods: This study included 20 eyes of 18 patients treated with IVA and 15 eyes of 11 patients treated with IVF for DME. The mean blur rate (MBR) of the ONH and retinal artery and vein of the peripapillary region were measured using LSFG at baseline and 1 month after injection. Central retinal thickness (CRT) and best-corrected visual acuity (BCVA) were measured for all patients. Results: CRT decreased significantly in both IVA-treated (p = 0.0003) and IVF-treated groups (p = 0.0004). Some of the MBR-related parameters of the ONH, such as MBR of all areas (MA), MBR of vascular areas (MV), and MBR of tissue areas (MT), decreased significantly 1 month after IVA and IVF compared to baseline values (MA of IVA, p < 0.0001; MT of IVA, p = 0.0220; MA of IVF, p = 0.0002; MT of IVF, p = 0.0461). MBR of the retinal artery (MBR-A) and vein (MBR-V) also decreased significantly 1 month after IVA and IVF compared with baseline values (MBR-A of IVA, p = 0.0002; MBR-V of IVA, p = 0.0010; MBR-A of IVF, p = 0.0368). No significant difference in ocular perfusion was observed between the IVA-treated and IVF-treated groups. Conclusion: Intravitreal injection led to a reduction in ocular blood flow in both retinal peripapillary vessels and the ONH in both IVA-treated and IVF-treated groups. No significant difference was observed in MBR reduction between the IVA-treated and IVF-treated groups. Our findings warrant further long-term investigations to reveal differences between aflibercept and faricimab.

Efficacy of ranibizumab and aflibercept on reducing maximum diameter of largest cyst in diabetic cystoid macular edema: MARMASIA study group.

PURPOSE: This study aimed to compare the effect of intravitreal aflibercept (IVA) and ranibizumab (IVR) on the maximal diameter of the largest intraretinal cyst (mdIRC), indicating chronicity in patients with diabetic cystoid macular edema (CME). METHODS: This retrospective, comparative study included a subgroup of patients from the MARMASIA Study with treatment-naïve diabetic CME who had IVA (IVA group) or IVR (IVR group) on a pro re nata regimen after a loading dose of 3-monthly injections and followed-up for 24 months. Best-corrected visual acuity (logMAR), central macular thickness (CMT, µm), and mdIRC (µm) and their changes during the study period in the IVA and IVR groups were compared. RESULTS: A total of 175 eyes (65 [37.1%] in IVA and 110 [62.9%] in IVR group) of 113 patients were included in the study analysis. Both groups had statistically significant improvements in BCVA and CMT during the follow-up (p < 0.05 for all), which were comparable between the groups at each time point. However, the mean reduction in mdIRCs was consistently and significantly higher in the IVA group compared to the IVR group at each follow-up examination (F[1, 3.52] = 6.93, p = 0.009). CONCLUSION: IVA seems to have a greater impact in reducing cyst sizes than IVR in diabetic CME.

Macular vascular and photoreceptor changes for diabetic macular edema at early stage.

This study was intended to investigate the macular vascular and photoreceptor changes for diabetic macular edema (DME) at the early stage. A total of 255 eyes of 134 diabetes mellitus patients were enrolled and underwent an ophthalmological and systemic evaluation in this cross-sectional study. Early DME was characterized by central subfoveal thickness (CST) value between 250 and 325 µm, intact ellipsoid zone, and an external limiting membrane. While non-DME was characterized by CST < 250 µm with normal retinal morphology and structure. Foveal avascular zone (FAZ) area ≤ 0.3 mm2 (P < 0.001, OR = 0.41, 95% CI 0.26-0.67 in the multivariate analysis) and HbA1c level ≤ 8% (P = 0.005, OR = 0.37, 95% CI 0.19-0.74 in multivariate analysis) were significantly associated with a higher risk of early DME. Meanwhile, no significant differences exist in cone parameters between non-DME and early DME eyes. Compared with non-DME eyes, vessel diameter, vessel wall thickness, wall-to-lumen ratio, the cross-sectional area of the vascular wall in the upper side were significantly decreased in the early DME eyes (P = 0.001, P < 0.001, P = 0.005, P = 0.003 respectively). This study suggested a vasospasm or vasoconstriction with limited further photoreceptor impairment at the early stage of DME formation. CST ≥ 250 µm and FAZ ≤ 0.3 mm2 may be the indicator for early DME detection.

Evaluation of the effect of vitreomacular interface disorders on anti-VEGF treatment in patients with diabetic macular edema in real life: MARMASIA study group report No. 10.

PURPOSE: The aim of this study is to investigate the effect of vitreomacular interface disorders (VMID) on treatment response in patients treated with anti-vascular endothelial growth factor (anti-VEGF) due to diabetic macular edema (DME). METHODS: Three hundred seventy-seven eyes of 239 patients in the MARMASIA Study Group who received intravitreal anti-VEGF treatment (IVT) due to DME were included in the study. The group 1 consisted of 44 eyes of the patients who had not received any treatment before, were followed up regularly for 24 months after at least a 3-month loading dose, and suffered from VMID such as epiretinal membrane, vitreomacular adhesion or traction, and lamellar hole. The group 2 consisted of 333 eyes of the patients without VMID. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) of the patients at baseline, 3rd month, 6th month, 1st year and 2nd year follow-ups were measured. RESULTS: The mean age of the Groups 1 and 2 was 67.1 ± 11.3 and 61.9 ± 10.2 years, respectively. 61.3% of the group 1 and 58.8% of the group 2 were female (p > 0.05). The duration of diabetes was 19.2 ± 3.7 and 15.8 ± 3.2 years, respectively, and the number of follow-ups was 16.09 ± 4.68 and 12.06 ± 4.58, respectively in the groups (p < 0.001, 0.001, respectively). The number of IVT was 7.13 ± 2.71 and 7.20 ± 2.22, respectively in the groups 1 and 2 and no statistically significant difference was observed between them (p = 0.860). According to logMAR, BCVA values at baseline were 0.63 ± 0.24 and 0.59 ± 0.26 (p = 0.29), respectively, in the groups and the amount of change in BCVA at the end of the 2nd year was - 0.02 ± 0.48 in the group 1 and - 0.12 ± 0.48 in the group 2. It was observed as 0.48 (p = 0.13). Although the increase in BCVA was greater at all follow-ups in the group 2 compared to their initial examination, no significant difference was observed between the groups in terms of BCVA change. The CMT values of the groups at baseline were 442.5 ± 131.3 µm and 590.9 ± 170.6 µm, respectively (p = 0.03) The decrease in CMT after IVT was significantly greater in the group 2 at all follow-ups when compared to the first group (p < 0.05). CONCLUSION: While the presence of VMID in DME patients receiving IVT did not affect visual results, it negatively affected the anatomical response and macular edema morphology. The presence of VMID at baseline affected the success of IVT. It should be taken into consideration that VMID may resolve spontaneously or with IVT, and new cases of VMID may occur in patients during the treatment process.

Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data.

INTRODUCTION: Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients' quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan. METHODS: This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups. RESULTS: The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75-0.92, P = 0.0003). CONCLUSIONS: In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM. Graphical abstract available for this article.

Hyperreflective choroidal foci in diabetic eyes with and without macular edema: Novel insights on diabetic choroidopathy.

Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p < 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder.

Caregiver Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.

INTRODUCTION: Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) require frequent anti-vascular endothelial growth factor (VEGF) treatment and monitoring visits. We aimed to understand the burden of treatment on caregivers. METHODS: This multinational, noninterventional study used a cross-sectional survey of adult patients with DME or nAMD treated with anti-VEGF injections in the USA, Canada, France, Italy, Spain, and the UK. The survey assessed caregivers' sociodemographic characteristics, patient relationships, patients' clinical history and treatment experiences, caregivers' experiences, and the Caregiver Reaction Assessment of caregiving burden. RESULTS: Caregivers for patients with DME (n = 30) and nAMD (n = 95) completed surveys. Mean ± standard deviation (SD) age was 64.0 ± 13.4 years, and most were female (71.2%), white (70.4%), married (66.4%), and from Europe (67.2%). Most were caring for their mother/father or partner/spouse (85.6%). Mean ± SD length of time as a caregiver was 9.1 ± 10.0 years. Caregivers estimated they provided support for 4.2 ± 2.9 days/week and 6.0 ± 7.1 h/day on average. Nearly half of caregivers (45.6%) reported some impairment in daily activities, and more than two-thirds (70.5%) of working caregivers (n = 44) reported work absenteeism due to anti-VEGF treatment/monitoring appointments. At least one treatment barrier was reported by 66.7% and 50.5% of caregivers of patients with DME and nAMD, respectively, which were related to coronavirus disease 2019- (38.4%), clinic- (18.4%), social-/health- (13.6%), treatment- (10.4%), or financial-related factors (4.8%). Caregiver Reaction Assessment scores indicated mild-to-moderate burden, with higher caregiver schedule disruption scores associated with an increasing number of anti-VEGF treatment/monitoring visits among DME caregivers (r = 0.61). CONCLUSION: Caregivers devote substantial time to caregiving, leading to schedule disruptions and absenteeism for some working caregivers. Positive and negative impacts on caregiver mental health were reported.

Choroidal thickening induced by pioglitazone in diabetic patients.

Purpose: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients. Methods: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroid vascular index. Patients were categorized into a high dose group if their pioglitazone dose was 30mg or more per day, and a low dose group if it was 15mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location. Results: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone in all subjects (6.70µm, 13.65µm, each). When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both the high (4.48µm, 0.84µm, each) and low dose groups (6.85µm, 21.45µm, each), with a greater change observed in low dose group (p<0.05, respectively). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00µm, 13.15µm, each) and nasal regions (6.43µm, 19.24µm, each), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53µm) (p<0.05, respectively). The largest increase in choroidal thickness was observed in the nasal side. Conclusion: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.