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.

A Mathematical Model of Interstitial Fluid Flow and Retinal Tissue Deformation in Macular Edema.

Purpose: This study aims to develop a mathematical model to elucidate fluid circulation in the retina, focusing on the movement of interstitial fluid (comprising water and albumin) to understand the mechanisms underlying exudative macular edema (EME). Methods: The model integrates physiological factors such as retinal pigment epithelium (RPE) pumping, osmotic pressure gradients, and tissue deformation. It accounts for spatial variability in hydraulic conductivity (HC) across the retina and incorporates the structural role of Müller cells (MCs) in maintaining retinal stability. Results: The model predicts that tissue deformation is maximal at the center of the fovea despite fluid exudation from blood capillaries occurring elsewhere, aligning with clinical observations. Additionally, the model suggests that spatial variability in HC across the thickness of the retina plays a protective role against fluid accumulation in the fovea. Conclusions: Despite inherent simplifications and uncertainties in parameter values, this study represents a step toward understanding the pathophysiology of EME. The findings provide insights into the mechanisms underlying fluid dynamics in the retina and fluid accumulation in the foveal region, showing that the specific conformation of Müller cells is likely to play a key role.

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.

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.

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.

Efficacy, safety, and cost-effectiveness of biosimilars of bevacizumab in näive patients with diabetic macular edema.

OBJECTIVES: Anti-vascular endothelial growth factor (VEGF) therapy restores retinal architecture and enhances vision in diabetic macular edema (DME). Bevacizumab is an off-label anti-VEGF drug that effectively treats DME. The safety and efficacy of bevacizumab biosimilars, which are more affordable than the original medication, still need to be established. This study aimed to assess the cost-effectiveness, efficacy, and safety of biosimilars for treating patients with naïve DME across various price ranges that are accessible in the Indian market. MATERIALS AND METHODS: Two biosimilars, BevaciRelTM (Reliance Life Sciences Pvt. Ltd.) and ZyBev (Cadila Healthcare Limited), were compared to their original, Avastin (Roche Products [India] Pvt. Ltd.), in a randomized, control study. Three end-notes were used to assess safety and efficacy: persistence, improvement, and adverse events. Cost-effective analysis was carried out using a decision-tree analysis model. RESULTS: This study included 69 (59%) men and 54 (41%) women with naïve DME. The cohort had an average log MAR visual acuity of 0.87 ± 0.22, and the central retinal thickness at baseline on OCT was 398.5 ± 37.61 µm. The visual acuity showed a similar improvement, and there was a decrease in central retinal thickness as observed on OCT across the groups. The incremental cost-effectiveness ratio was 10.8. CONCLUSIONS: The biosimilars of bevacizumab are safe and efficacious in treating DME in a cost-effective manner.

Intraocular Concentration of Stem Cell Factor/c-KIT and Galectin-1 in Retinal Diseases.

Purpose: To investigate the intraocular concentration profiles of stem cell factor (SCF)/c-KIT, galectin-1 (GAL-1), and vascular endothelial growth factor (VEGF)-A with regard to retinal disease and treatment response. Methods: The study group included 13 patients with dry age-related macular degeneration (AMD), 196 with neovascular AMD (nAMD), 21 with diabetic macular edema (DME), 10 with retinal vein occlusion (RVO), and 34 normal subjects with cataracts. Aqueous humor levels of SCF, c-KIT, GAL-1, and VEGF-A were analyzed by immunoassay according to disease group and treatment response. Results: Increased aqueous levels of SCF, c-KIT, and GAL-1 were observed in eyes with nAMD (2.67 ± 3.66, 296.84 ± 359.56, and 3945.61 ± 5976.2 pg/mL, respectively), DME (1.64 ± 0.89, 238.80 ± 265.54, and 3701.23 ± 4340.54 pg/mL, respectively), and RVO (4.62 ± 8.76, 509.63 ± 647.58, and 9079.60 ± 11909.20 pg/mL, respectively) compared with controls (1.13 ± 0.24, 60.00 ± 0.00, and 613.27 ± 1595.12 pg/mL, respectively). In the eyes of nAMD, the levels of all three cytokines correlated positively with VEGF-A levels. After intravitreal injections of anti-VEGF agents, the levels of GAL-1 and VEGF-A decreased significantly, whereas those of SCF and c-Kit showed no significant change. Eyes of nAMD patients with improved vision after treatment had significantly lower levels of c-KIT, GAL-1, and VEGF-A at baseline. Conclusions: The intraocular levels of cytokines were significantly elevated in eyes with nAMD, DME, and RVO compared to the controls and they showed different response to anti-VEGF treatment. With this result and their known association with angiogenesis, these cytokines may be potential therapeutic targets for future research.

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.

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.

Evaluation of thickness of individual macular retinal layers in diabetic eyes from optical coherence tomography.

The effect of diabetes mellitus (DM) on individual retinal layers remains incompletely understood. We evaluated the intra-retinal layer thickness alterations in 71 DM eyes with no diabetic retinopathy (DR), 90 with mild DR, and 63 with moderate DR without macular edema, using spectral-domain optical coherence tomography (SD-OCT) and the Iowa Reference Algorithm for automated retinal layer segmentation. The average thickness of 10 intra-retinal layers was then corrected for ocular magnification using axial length measurements, and pairwise comparisons were made using multivariable linear regression models adjusted for gender and race. In DM no DR eyes, significant thinning was evident in the ganglion cell layer (GCL; p < 0.001), inner nuclear layer (INL; p = 0.001), and retinal pigment epithelium (RPE; p = 0.014) compared to normal eyes. Additionally, mild DR eyes exhibited a thinner inner plexiform layer (IPL; p = 0.008) than DM no DR eyes. Conversely, moderate DR eyes displayed thickening in the INL, outer nuclear layer, IPL, and retinal nerve fiber layer (all p ≤ 0.002), with notably worse vision. These findings highlight distinctive patterns: early diabetic eyes experience thinning in specific retinal layers, while moderate DR eyes exhibit thickening of certain layers and slightly compromised visual acuity, despite the absence of macular edema. Understanding these structural changes is crucial for comprehending diabetic eye complications.

Association of SDF-1-3' Gene A Variant with Diabetic Retinopathy in the Hungarian Population.

We investigated the association between the SDF-1-3' (c801G > A) variant and the development of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR) in a Hungarian cohort. SDF-1-3' (c801G > A) was genotyped in 103 patients with diabetic retinopathy and 31 age- and sex-matched non-diabetic controls. Central retinal and choroidal thickness was measured by swept-source optical coherence tomography. The distribution of heterozygous and homozygous SDF-1-3' (c801G > A) genotypes was similar in diabetic and control subjects. The SDF-3'(c801AA) genotype was associated with DME (n = 94 eyes, allele distribution p = 0.006, genotype distribution p = 0.01 OR: 2.48, 95% CL: 1.21-5.08) in both univariable and multivariable modelling, independent of duration and type of diabetes, HbA1C, hypertension and microalbuminuria (p = 0.03). DME occurred earlier in patients carrying the SDF-1 (c801A) allele (Kaplan-Meier analysis, log-rank test p = 0.02). A marginally significant association was found between the presence of the SDF-1 (c801A) allele and the development of PDR (n = 89 eyes, p = 0.06). The SDF-1-3' (c801A) allele also showed a correlation with central retinal (p = 0.006) and choroidal (p = 0.08) thickness. SDF-1-3' (c801G > A) is involved in the development of macular complications in DM independent of critical clinical factors, suggesting that SDF-1 may be a future therapeutic target for high-risk patients, especially those carrying the SDF-1 (c801A) allele.

Somatostatin analogues as a treatment option for cystoid maculopathy in retinitis pigmentosa.

AIMS: This study aimed to evaluate the effectiveness of somatostatin analogues (SA) for cystoid maculopathy (CM) in retinitis pigmentosa (RP) patients. MATERIALS AND METHODS: In this retrospective case series, clinical and imaging characteristics of 28 RP patients with CM, unresponsive to carbonic anhydrase inhibitors, were collected from medical charts. All patients received SA treatment as an alternative (octreotide long-acting release at 20 mg/month or 30 mg/month, or lanreotide at 90 mg/month or 120 mg/month). Outcome measures were mean reduction in foveal thickness (FT) and foveal volume (FV) and mean increase in best-corrected visual acuity at 3, 6 and 12 months of treatment initiation. Linear mixed models were used to calculate the effectiveness over time. RESULTS: 52 eyes of 28 RP patients were included; 39% were male. The median age at the start of treatment was 39 years (IQR 30-53). Median follow-up was 12 months (range 6-12). From baseline to 12 months, the mean FT decreased from 409±136 µm to 334±119 µm and the mean FV decreased from 0.31±0.10 mm3 to 0.25±0.04 mm3. Linear mixed model analyses showed a significant decrease in log FT and log FV at 3, 6 and 12 months after the start of treatment compared with baseline measurements (p<0.001, p<0.001, p<0.001). Mean best-corrected visual acuity did not increase significantly (0.46±0.35 logMAR to 0.45±0.38 logMAR after 12 months). DISCUSSION: SA may be an effective alternative treatment to reduce CM in RP patients.

One-Year Functional and Morphological Prognosis After Intravitreal Injection Treatments According to Different Morphological Patterns of Diabetic Macular Edema in Real-Life: MARMASIA Study Group Report No.13.

PURPOSE: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy. METHODS: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups. RESULTS: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups (p = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 (p = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups (p = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively (p > .05). The groups had no significant difference in mean CMT at month 12 (p = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 (p = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 (p = 0,014 and p = 0,017). CONCLUSIONS: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.

Use of a dexamethasone implant to treat macular edema following pars plana vitrectomy and removal of the primary epiretinal membrane.

PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of an intravitreal dexamethasone (DEX) implant for the treatment of macular edema (ME) following pars plana vitrectomy (PPV) and removal of the primary epiretinal membrane (ERM) and to assess the impact of the integrity of the ellipsoid zone (EZ) and disorganization of the retinal inner layer (DRIL) grade on visual and anatomical outcomes. METHODS: Forty-two pseudophakic patients who developed ME following PPV and removal of the primary stage 2-3 ERM were included. Patients were divided into two groups when ME was diagnosed via spectral domain optic coherence tomography (SD-OCT). In the DEX group (n = 22), DEX was implanted for the treatment of ME. In the control group (n = 20), only observation was conducted, without any treatment. The best-corrected visual acuity (BCVA) and macular thickness (MT) of the two groups were compared at baseline and 1, 6, and 12 months after DEX implantation. The effects of OCT parameters such as EZ integrity and DRIL grade were also evaluated in terms of decreases in MT and increases in VA in the treatment of ME with DEX implantation. Intraocular pressure (IOP), number of DEX implantations and adverse effects were also recorded. RESULTS: While a statistically significant increase in the mean BCVA was observed in the DEX group (p < 0.001 at months 1, 6, and 12, respectively), no such increase was detected in the control group (p = 0.169, p = 0.065, and p = 0.058 at months 1, 6 and 12, respectively) compared with the baseline. A statistically significant decrease in the mean MT was observed in the DEX group (p < 0.001 at months 1, 6, and 12); however, no significant difference was observed in the control group (p = 0.081, p = 0.065, and p = 0.054 at months 1, 6 and 12, respectively) compared with the baseline. Significant differences were found between the two groups in terms of the increase in BCVA (p < 0.01) and decrease in MT (p < 0.01) at all visits, with the outcomes being more favorable in the DEX group. A statistically significant relationship was found between the increase in VA and EZ integrity and DRIL grade in both groups. Ten patients (45.4%) received two injections of DEX during the follow-up. An increase in IOP was observed in five patients (22.7%) who were treated with topical antiglaucomatous drops. No significant side effects were observed. CONCLUSION: DEX implantation was found to be effective and safe for the treatment of ME following PPV and primary ERM removal, although some eyes may require repeated injections to achieve visual and anatomical success. Additionally, a relationship was found between EZ integrity, DRIL grade and visual-anatomical outcomes.

Association of serum lipid profile and other systemic risk factors with retinal hard exudates in diabetic retinopathy.

PURPOSE: Diabetic macular edema is one of the leading causes of vision loss across the world. Hard exudates at the macula can lead to structural abnormalities in the retina leading to irreversible vision loss. Systemic dyslipidemia and other modifiable risk factors when identified and treated early may help prevent substantial vision loss. The purpose of this study was to study the association between serum lipid levels and other systemic risk factors like hemoglobin, HbA1c, and serum creatinine with hard exudates and macular edema in patients with diabetic retinopathy. METHODS: It is a prospective cross-sectional study conducted in a tertiary health care center in South India. 96 patients having diabetic retinopathy with hard exudates were included. Modified Airlie house classification was used to grade the hard exudates. Blood investigations including serum lipid profile, hemoglobin, HbA1c, and serum creatinine were carried out. Central subfield macular thickness was measured using optical coherence tomography. RESULTS: 96 patients of type II DM with diabetic retinopathy were divided into three groups of hard exudates. A statistically significant correlation was observed between the severity of hard exudates and total cholesterol (p = 0.00), triglycerides (p = 0.00), LDL (p = 0.00), and VLDL (p = 0.00). HbA1c levels showed a statistically significant correlation with the severity of hard exudates (p = 0.09), no significant correlation was noted between hard exudates and hemoglobin levels (p = 0.27) and with serum creatinine (p = 0.612). A statistically significant association between CSMT and hard exudates (p = 0.00) was noted. CONCLUSION: In our study, we concluded that the severity of hard exudates is significantly associated with increasing levels of serum total cholesterol, triglycerides, LDL, VLDL, and HbA1c levels in type II DM patients presenting with diabetic retinopathy. The increasing duration of diabetes is significantly associated with increasing severity of hard exudates. Central subfield macular thickness increases with increasing severity of hard exudates in diabetic retinopathy.

Prediction of treatment outcome for branch retinal vein occlusion using convolutional neural network-based retinal fluorescein angiography.

Deep learning techniques were used in ophthalmology to develop artificial intelligence (AI) models for predicting the short-term effectiveness of anti-VEGF therapy in patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME). 180 BRVO-ME patients underwent pre-treatment FFA scans. After 3 months of ranibizumab injections, CMT measurements were taken at baseline and 1-month intervals. Patients were categorized into good and poor prognosis groups based on macular edema at the 4th month follow-up. FFA-Net, a VGG-based classification network, was trained using FFA images from both groups. Class activation heat maps highlighted important locations. Benchmark models (DesNet-201, MobileNet-V3, ResNet-152, MansNet-75) were compared for training results. Performance metrics included accuracy, sensitivity, specificity, F1 score, and ROC curves. FFA-Net predicted BRVO-ME treatment effect with an accuracy of 88.63% and an F1 score of 0.89, with a sensitivity and specificity of 79.40% and 71.34%, respectively.The AUC of the ROC curve for the FFA-Net model was 0.71. The use of FFA based on deep learning technology has feasibility in predicting the treatment effect of BRVO-ME. The FFA-Net model constructed with the VGG model as the main body has good results in predicting the treatment effect of BRVO-ME. The typing of BRVO in FFA may be an important factor affecting the prognosis.

Evaluating Ocular Blood Flow in Diabetic Macular Edema using Three-dimensional Pseudocontinuous Arterial Spin Labeling.

BACKGROUND: Alterations in ocular blood flow play an important role in the pathogenesis of diabetic macular edema; however, this remains unclear. OBJECTIVES: This study aimed to investigate ocular blood flow in eyes with or without diabetic macular edema using arterial spin labeling. METHODS: This cross-sectional study included 118 eyes of 65 patients with diabetic retinopathy analyzed between November 2018 and December 2019. We included a total of 53 eyes without diabetic macular edema (mean [SD] age, 57.83 [7.23] years; 29 men [54.7%]) and 65 eyes with diabetic macular edema (mean [SD] age, 60.11 [7.63] years; 38 men [58.5%]). Using a 3.0-T magnetic resonance imaging, participants were imaged with arterial spin labeling with multiple post-labeling delays. RESULTS: The mean ocular blood flow at post-labeling delays of 1.5 and 2.5 s was significantly lower in eyes with diabetic macular edema among patients with diabetic retinopathy compared with the remaining subgroups (P=0.022 and P <0.001, respectively). The mean ocular blood flow exhibited a significant decrease in eyes with diabetic macular edema when the post-labeling delay was set at 2.5 s in the nonproliferative and proliferative diabetic retinopathy groups, compared with the remaining subgroups (P=0.005 and P=0.002, respectively). The cutoff points of ocular blood flow at post-labeling delays of 1.5 s and 2.5 s were 9.40 and 11.10 mL/100 g/min, respectively. CONCLUSION: Three-dimensional pseudocontinuous arterial spin labeling can identify differences in the ocular blood flow of patients with diabetic eyes with and without diabetic macular edema.

[Implantable intravitreal corticosteroids in chronic noninfectious uveitis]. / Implantierbare intravitreale Kortikosteroide bei chronischer nichtinfektiöser Uveitis.

BACKGROUND: Uveitis leads to blindness in 10-15% of all cases in industrialized nations. The prevalence varies depending on the literature, ranging from 9 to 730 cases per 100,000 inhabitants. Local and systemic steroid applications, along with treatment involving immunomodulators, are the primary treatment options. In cases of chronic and refractory uveitis, especially with the manifestation of uveitic macular edema, intravitreal corticosteroids can contribute to reduce or completely replace systemic immunomodulatory therapy with disease-modifying antirheumatic drugs (DMARDs), biologics or corticosteroids. OBJECTIVE: This review article presents the currently available intravitreal corticosteroid implants used in the treatment of noninfectious uveitis. The indications, effectiveness, and side effect profiles are discussed within the context of the current literature. A total of 6 randomized controlled studies about FAc and DEX implants with more than 100 patients were included in this review. One subgroup analysis from a multicentric randomized study with 315 patients has been included as well. The outcome is discussed in this article. CONCLUSION: The efficacy and safety profile of intravitreal corticosteroids in uveitic macular edema have been evaluated in several studies in recent years. In some studies, they have been compared to systemic treatment options. With long-acting corticosteroid implants the number of relapses can be reduced and the time interval between relapses can be prolonged. Short-acting corticosteroid implants represent a treatment option during acute uveitic activity. The adverse effects of corticosteroids can be well-controlled in most cases. In phakic and/or young patients, however, adverse effects (such as cataract development) should be discussed in depth before treatment initiation as most corticosteroids are applied as long-term treatment.

Changing Reimbursement Criteria on Anti-VEGF Treatment Patterns Among Wet Age-Related Macular Degeneration and Diabetic Macular Edema Patients: An Interrupted Time Series Analysis.

BACKGROUND: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan. METHODS: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection. RESULTS: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes. CONCLUSION: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.

Aflibercept for central retinal vein occlusions: long-term outcomes of a 'Treat-and-Extend' regimen.

BACKGROUND/AIMS: This study reports on the long-term functional and anatomical outcomes of patients with central retinal vein occlusion (CRVO) treated under the Bern treat-and-extend (T&E) protocol. METHODS: Observational study. Treatment-naive patients with CRVO and consecutive macular oedema treated with aflibercept were included. The T&E protocol involved 2 monthly injections followed by an extension based on individual assessments. At each visit, best-corrected visual acuity (BCVA), optical coherence tomography imaging and a 2 mg aflibercept injection were administered. Changes in BCVA, proportion of patients gaining ≥15 letters, central subfield thickness (CST) and treatment intervals were analysed. RESULTS: Out of 173 patients, 64 had a follow-up of at least 2 years. BCVA improved from 46.7±25.3 at baseline to 78.3±0.5 at year 9. The proportion of patients with ≥15 letters gained was 56%, 53%, 56%, 62%, 52%, 52%, 43%, 50% and 33% at years 1-9, respectively. CST decreased significantly from 660±242 µm at baseline to 359±63 µm at year 9. Treatment intervals extended from 4 weeks initially to an average of 13.0±4.1 weeks by year 8. CONCLUSIONS: The T&E regimen for CRVO shows sustained visual improvements and reduced CST over time. Patients maintained stable visual gains for many years, demonstrating the effectiveness of this treatment approach. However, no control group was available to compare our T&E regimen with other strategies.