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.

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.

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.

Alisol A, the Eye-Entering Ingredient of Alisma orientale, Relieves Macular Edema Through TNF-α as Revealed by UPLC-Triple-TOF/MS, Network Pharmacology, and Zebrafish Verification.

Purpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME. Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms. Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO's ME-inhibitory effects. Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME.

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.

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.

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.

The effect of long-term hemodialysis on diabetic retinopathy observed by swept-source optical coherence tomography angiography.

BACKGROUND: Diabetes can cause chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN). DR and DN can lead to or exacerbate diabetic macular edema (DME). Hemodialysis (HD) is the main treatment method for patients with end-stage kidney disease (ESKD) secondary to DN. PURPOSE: The aim of this prospective cohort study was to determine the immediate effect of single HD session on retinal and choroidal thickness in DR patients with ESKD and the features of DR and the prevalence of DME in these patients who have received long-term HD. METHODS: Eighty-five eyes of 44 DR patients with ESKD who underwent long-term HD were examined by swept-source optical coherence tomography angiography (SS-OCTA). Based on OCTA images, the characteristics of DR and the prevalence of DME in these patients were analyzed. Changes in central retinal thickness (CRT), central retinal volume (CRV), subfoveal choroidal thickness (SFCT) and subfoveal choroidal volume (SFCV) within 30 min before and after single HD session were compared. CRT, CRV, SFCT and SFCV were compared before single HD session and before the next single HD session. RESULTS: There was no significant difference in the average CRT (251.69 ± 39.21 µm vs. 251.46 ± 39.38 µm, P = 0.286) or CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.63 µm, P = 0.324) between before and after single HD session. After single HD session, SFCT (243.11 ± 77.15 µm vs. 219.20 ± 72.84 µm, P < 0.001) and SFCV (0.15 ± 0.10 µm vs. 0.13 ± 0.90 µm, P < 0.001) significantly decreased. There was no statistically significant difference in CRT (251.69 ± 39.21 µm vs. 251.11 ± 38.47 µm, P = 0.206), CRV (0.15 ± 0.62 µm vs. 0.15 ± 0.61 µm, P = 0.154), SFCT (243.11 ± 77.15 µm vs. 245.41 ± 76.23 µm, P = 0.108), or SFCV (0.15 ± 0.10 µm vs. 0.16 ± 0.10 µm, P = 0.174) before HD and before the next single HD session. On en face OCTA images, eighty-five eyes (100%) had retinal nonperfusion areas, foveal avascular zone (FAZ) enlargement, and abnormal retinal microvasculature. Based on cross-sectional OCTA images, retinal neovascularization (RNV) was confirmed in 42 eyes (49.41%), and intraretinal microvascular abnormalities (IRMAs) were detected in 85 eyes (100%). Seventeen eyes (20%) still had DME, all of which were cystoid macular edema (CME). Among eyes with DME, the epiretinal membrane (ERM) was present in 7 eyes (8.24%). CONCLUSIONS: For DR patients with ESKD who have undergone long-term HD, the choroidal thickness still changes significantly before and after single HD session, which may be related to short-term effects such as reduced blood volume and plasma osmotic pressure caused by single HD session. Although macular features seem to have stabilized in DR patients undergoing long-term dialysis, the DR of patients with ESKD should still be given attention.

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.

PENTOSAN POLYSULFATE MACULOPATHY-ASSOCIATED CYSTOID MACULAR EDEMA RESPONSIVE TO INTRAVITREAL STEROIDS.

PURPOSE: To report a case of angiographically silent cystoid macular edema (CME) secondary to pentosan polysulfate sodium (PPS) maculopathy responsive to intravitreal steroids. METHODS: Observational case report. RESULTS: A 52-year-old female patient with a history of 4 years of PPS use for interstitial cystitis presented with PPS maculopathy that developed CME 2.5 years after drug cessation and had associated progression of pigmentary and atrophic changes. Her CME was nonresponsive to topical ketorolac and dorzolamide, but was responsive to intravitreal triamcinolone acetonide and subsequently intravitreal dexamethasone implant (Ozurdex) with reduction in central subfield thickness and improvement in visual acuity. CONCLUSION: Cystoid macular edema secondary to PPS maculopathy may be angiographically silent yet responsive to intravitreal steroids alone without the use of vascular endothelial growth factor agents. There is potential for both anatomic and functional improvements in such cases demonstrating the value of such treatment. Cystoid macular edema may be a delayed finding that can develop despite drug cessation. Steroid monotherapy should be further evaluated as possible first-line management for PPS maculopathy-associated CME.

MAPLES-DR: MESSIDOR Anatomical and Pathological Labels for Explainable Screening of Diabetic Retinopathy.

Reliable automatic diagnosis of Diabetic Retinopathy (DR) and Macular Edema (ME) is an invaluable asset in improving the rate of monitored patients among at-risk populations and in enabling earlier treatments before the pathology progresses and threatens vision. However, the explainability of screening models is still an open question, and specifically designed datasets are required to support the research. We present MAPLES-DR (MESSIDOR Anatomical and Pathological Labels for Explainable Screening of Diabetic Retinopathy), which contains, for 198 images of the MESSIDOR public fundus dataset, new diagnoses for DR and ME as well as new pixel-wise segmentation maps for 10 anatomical and pathological biomarkers related to DR. This paper documents the design choices and the annotation procedure that produced MAPLES-DR, discusses the interobserver variability and the overall quality of the annotations, and provides guidelines on using the dataset in a machine learning context.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

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.

Incidence and prognosis of taxane-induced macular edema: a retrospective study from the Japan Clinical REtina Study Group (J-CREST).

Macular edema is a known side effect of taxane-based anticancer drugs. We retrospectively investigated data from 11 centers between January 2016 and December 2021. Among 14,260 patients, 30 (0.21%) developed macular edema; from these, the number of cases associated with nab-paclitaxel was 16 (0.43%), significantly higher than the number of cases associated with paclitaxel or docetaxel (P < 0.01). Visual acuity (VA) and retinal choroidal change were examined in 27 patients, with a follow-up of at least 3 months. The patients' mean age was 67.2 years; 14 (51.3%) were male and four (14.8%) had unilateral onset. The mean interval between anticancer drug initiation and the first ophthalmology visit was 290.1 days. Among the 20 patients who discontinued anticancer drugs, VA and edema significantly improved 2 months after discontinuation (LogMAR VA: 0.50 vs. 0.28, central retinal thickness: 472.7 µm vs. 282.5 µm, both P < 0.01). No significant changes were observed in the central choroidal thickness. A correlation was found between duration of taxane treatment and VA immediately before discontinuation of anticancer drugs (ß = 0.00050; 95% confidence interval: 0.00036-0.00097; P < 0.05). Although taxane-induced macular edema is reversible, slower anticancer drug discontinuation worsened VA, highlighting the need for regular ophthalmologic evaluation during treatments.

LONG-TERM VISUAL OUTCOMES AND OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS IN EYES WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy. METHODS: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis. RESULTS: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018). CONCLUSION: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

A novel approach for automatic classification of macular degeneration OCT images.

Age-related macular degeneration (AMD) and diabetic macular edema (DME) are significant causes of blindness worldwide. The prevalence of these diseases is steadily increasing due to population aging. Therefore, early diagnosis and prevention are crucial for effective treatment. Classification of Macular Degeneration OCT Images is a widely used method for assessing retinal lesions. However, there are two main challenges in OCT image classification: incomplete image feature extraction and lack of prominence in important positional features. To address these challenges, we proposed a deep learning neural network model called MSA-Net, which incorporates our proposed multi-scale architecture and spatial attention mechanism. Our multi-scale architecture is based on depthwise separable convolution, which ensures comprehensive feature extraction from multiple scales while minimizing the growth of model parameters. The spatial attention mechanism is aim to highlight the important positional features in the images, which emphasizes the representation of macular region features in OCT images. We test MSA-NET on the NEH dataset and the UCSD dataset, performing three-class (CNV, DURSEN, and NORMAL) and four-class (CNV, DURSEN, DME, and NORMAL) classification tasks. On the NEH dataset, the accuracy, sensitivity, and specificity are 98.1%, 97.9%, and 98.0%, respectively. After fine-tuning on the UCSD dataset, the accuracy, sensitivity, and specificity are 96.7%, 96.7%, and 98.9%, respectively. Experimental results demonstrate the excellent classification performance and generalization ability of our model compared to previous models and recent well-known OCT classification models, establishing it as a highly competitive intelligence classification approach in the field of macular degeneration.

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.

Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME.

Purpose: The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME). Methods: All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events. Results: Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported. Conclusions: In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator. Translational Relevance: This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

SUPRACHOROIDAL TRIAMCINOLONE ACETONIDE FOR REFRACTORY POSTOPERATIVE CYSTOID MACULAR EDEMA.

PURPOSE: To investigate outcomes of suprachoroidal triamcinolone acetonide (XIPERE, Bausch + Lomb) for the treatment of refractory postoperative cystoid macular edema. METHODS: Medical records of patients receiving suprachoroidal triamcinolone acetonide for postoperative cystoid macular edema were reviewed. Primary outcomes were visual acuity and central foveal thickness. RESULTS: A total of 32 eyes from 32 patients with a median (interquartile range) follow-up duration of 6 (2-7) months and 1 (1-2) suprachoroidal triamcinolone acetonide injection were included; 19 (59.4%) had a history of vitrectomy. The median (interquartile range) central foveal thickness decreased from 492 (379-629) µm to 267 (187-388) µm at 1 month (P < 0.001), 362 (218-521) µm at 3 months (P = 0.005), and 339 (206-514) µm at the final visit (P < 0.001). The median logarithm of the minimal angle of resolution visual acuity improved from 0.65 (0.48-0.97, 20/89) at baseline to 0.54 (0.35-0.88, 20/69) (P = 0.058) at 1 month, 0.54 (0.33-0.84, 20/69) at 3 months (P = 0.121), and 0.60 (0.33-0.88, 20/80) at the final visit (P = 0.021). Vitrectomized eyes had similar findings. Six eyes (18.8%) developed elevated intraocular pressure (>24 mmHg) (range: 25-49 mmHg) with a median intraocular pressure elevation of 13.5 mmHg compared with baseline, and all had prior glaucoma or ocular hypertension. CONCLUSION: Suprachoroidal triamcinolone acetonide reduced macular edema and improved vision in refractory postoperative cystoid macular edema, including vitrectomized eyes. Intraocular pressure should be monitored, especially in those with a history of glaucoma or ocular hypertension.

A health economic pilot study comparing two diabetic retinopathy screening strategies.

To compare two screening strategies for diabetic retinopathy (DR), and to determine the health-economic impact of including optical coherence tomography (OCT) in a regular DR screening. This cross-sectional study included a cohort of patients (≥ 18 years) with type 1 or 2 diabetes mellitus (T1D or T2D) from a pilot DR screening program at Oslo University Hospital, Norway. A combined screening strategy where OCT was performed in addition to fundus photography for all patients, was conducted on this cohort and compared to our existing sequential screening strategy. In the sequential screening strategy, OCT was performed on a separate day only if fundus photography indicated diabetic macular edema (DME). The presence of diabetic maculopathy on fundus photography and DME on OCT was determined by two medical retina specialists. Based on the prevalence rate of diabetic maculopathy and DME from the pilot, we determined the health-economic impact of the two screening strategies. The study included 180 eyes of 90 patients. Twenty-seven eyes of 18 patients had diabetic maculopathy, and of these, 7 eyes of 6 patients revealed DME on OCT. When diabetic maculopathy was absent on fundus photographs, OCT could not reveal DME. Accordingly, 18 patients (20%) with diabetic maculopathy would have needed an additional examination with OCT in the sequential screening strategy, 6 (33%) of whom would have had DME on OCT. In an extended healthcare perspective analysis, the cost of the sequential screening strategy was higher than the cost of the combined screening strategy. There was a weak association between diabetic maculopathy on fundus photography and DME on OCT. The health economic analysis suggests that including OCT as a standard test in DR screening could potentially be cost-saving.