Therapy For Diabetic Macular Edema Research Articles

Comparative assessment of intravitreal steroid implant with combination therapy for diabetic macular edema.

Comparative assessment of intravitreal steroid implant with combination therapy for diabetic macular edema.

Anti-VEGF Monotherapy vs Anti-VEGF and Steroid Combination Therapy for Diabetic Macular Edema: A Meta-analysis

Introduction: To compare the safety and efficacy of antivascular endothelial growth factor (anti-VEGF) monotherapy vs anti-VEGF and steroid combination therapy in treatment-naïve and treatment-resistant patients with diabetic macular edema (DME). Methods: A systematic literature search was conducted from January 2005 to December 2022. Sixteen randomized control trials (RCTs) published in English that reported the efficacy or safety of monotherapy and combination therapy in patients with DME were included. Results: The 16 RCTs included 1166 eyes. Monotherapy was associated with a significantly better best-corrected visual acuity (BCVA) at the final follow-up (weighted mean difference [WMD], −0.04 logMAR; 95% CI, −0.07 to −0.02; P = .002; I2 = 0%). No significant differences were observed in the change in BCVA between groups at the final observation. Monotherapy was associated with a significantly smaller change in retinal thickness at the final follow-up (WMD, 37.63 μm; 95% CI, 11.67-63.60; P = .005; I2 = 78%) and with a significantly lower risk for intraocular pressure–related adverse events (AEs) (risk ratio, 0.27; 95% CI, 0.15-0.46; P ≤ .001; I2 = 0%). The risk for cataract-related AEs was not significantly different between groups ( P = .06). The results in treatment-naïve patients were similar. In treatment-resistant patients, the change in retinal thickness at the final follow-up was similar between groups ( P = .14) but the risk for cataract-related AEs was significantly lower in the monotherapy group in 2 RCTs (risk ratio, 0.09; 95% CI, 0.01-0.66; P = .02; I2 = 0%). Conclusions: The changes in BCVA were similar despite combination therapy being associated with greater changes in retinal thickness. However, increased complications were seen with combination therapy. Most results in treatment-naïve patients and treatment-resistant patients were similar.

Evaluation of topical bromfenac as an adjunctive treatment with intravitreal ranibizumab in the management of diabetic macular edema

Background and purpose Intravitreal injection of anti- vascular endothelial growth factor medications has transformed the therapy of diabetic macular edema (DME). The purpose of this study was to evaluate the safety and efficacy of topical bromfenac as an adjunctive therapy to intravitreal ranibizumab injections in patients diagnosed with DME. Study design Prospective, randomized, controlled clinical trial. Patients The study included 40 eyes of patients with DME, divided into two groups: group I (20 eyes) received intravitreal ranibizumab injections and adjunctive topical bromfenac twice daily; group II (20 eyes) received only intravitreal ranibizumab injections. Methods All patients underwent assessments for best corrected visual acuity (BCVA), intraocular pressure, anterior segment, and fundus examination. Optical coherence tomography of the macula was repeated at 1, 3, and 6 months after the last injection. Results At 6 months, group I demonstrated significantly worse BCVA compared with group II (P=0.021). In group II, the 6-month change in central macular thickness from baseline was significantly greater in patients aged less than or equal to 60 years compared with those greater than 60 years (median = –170.5 μm vs. −40 μm, respectively; P=0.001) and in females compared with males (median = –75 μm vs. −23.4 μm; P=0.012). No significant differences were observed concerning the duration of diabetes (P=0.238), HbA1c levels (P=0.315), or laterality (P=0.792). Conclusion Topical bromfenac, when combined with intravitreal ranibizumab, showed some efficacy in the management of DME over a 6-month follow-up period, although the results were not statistically significant.

Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Real-Life Results after the Administration of a Single 0.19 mg Fluocinolone Acetonide (ILUVIEN®) Implant in Patients with Refractory Diabetic Macular Edema.

The aim of this study was to evaluate real-life data on the functional and anatomical outcome of intravitreal fluocinolone acetonide (FAc) in patients with refractory diabetic macular edema (DME). Retrospective study on 44 eyes with chronic DME that received intravitreal FAc implant and were previously treated with intravitreal dexamethasone, triamcinolone, or anti-vascular endothelial growth factor. We assessed best-corrected visual acuity (BCVA), central maximum thickness (CMT), and foveal thickness (FT) as measured by spectral-domain optical coherence tomography (Spectralis OCT; Heidelberg Engineering). Secondary outcomes were intraocular pressure (IOP), adverse events, time to additional treatments. The FAc implant significantly reduced the CMT (baseline 541.23 ± 155.29 µm, p < 0.001) and FT (baseline 460.34 ± 139.28 µm, p < 0.001) for up to 36 months. Despite postoperative visual improvement over time, BCVA did not significantly shift from baseline (0.55 ± 0.38 logMAR, p = 0.568). The FAc implant effect diminished after 21.34 ± 12.74 months. IOP increased in 9% of eyes (n = 4) but was well controlled under topical (n = 1) or surgical therapy (n = 3). Even though patients' visual recovery does not benefit significantly, the FAc implant addresses the important pillars of chronic DME therapy regarding reduced injection frequency and reduced DME.

Pro Re Nata brolucizumab for early onset and treatment-naïve diabetic macular edema: A prospective study.

To determine the efficacy and safety of brolucizumab therapy administered on a pro re nata (PRN) basis without loading dose in treatment naïve patients with diabetic macular edema (DME) for 1 year follow-up. Patients with recent DME (<6 months) received a mandatory brolucizumab injection at inclusion and other injections could be given on a PRN basis with an 8-week interval (between injections) at minimum. Rescue therapy with other anti-VEGF was possible in case of incomplete DME resolution after the second brolucizumab with a minimum of 1-month treatment free interval between 2 injections. The primary outcome measure was the change in (BCVA) at 12 months. Secondary outcome measures included the change in central subfield thickness (CST), the change in hard exudate surface area and microaneurysms at 1 year. A total of 53 patients were included. At 12 months, the mean (SD) number of injections was 2.6 (0.8) in addition to the first mandatory injection. The mean (SD) interval between 2 consecutive injections was 3.2 (1.4) months. The mean (SD) BCVA improved from 0.62 (0.1) logMAR to 0.40 (0.16) logMAR (p = 0.012). The mean CST reduced from 397.0 (47.2) µm to 224.5 (28.1) µm (p = 0.013). The hard exudate surface area decreased significantly (p = 0.012) as did microaneurysms (p = 0.02). Seven patients required at least 1 rescue therapy. No patients experienced intra-ocular inflammatory adverse events. Brolucizumab therapy for DME is a safe and effective modality for the treatment of recent DME and has the potential to reduce the number of injections.

Vitrectomy as an Adjunct to Treat-and-Extend Anti-VEGF Injections for Diabetic Macular Edema

There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy. To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME). This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 μm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023. Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization. Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate. Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] μm for the control group vs -32 [-48 to 25] μm for the vitrectomy group; difference, 62 μm; 95% CI, -110 to 11; P = .11). Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME. isrctn.org Identifier: ISRCTN59902040.

IMPACT OF TREATMENT OF DIABETIC MACULAR EDEMA ON VISUAL IMPAIRMENT IN PEOPLE WITH TYPE 2 DIABETES MELLITUS: A COMPREHENSIVE SYSTEMATIC REVIEW AND METAAANALYSIST STUDY

Background: Diabetic retinopathy (DR) and diabetic macular edema (DME) are among the most significant and disabling chronic complications of diabetes mellitus. DME is an important cause of severe vision loss in type 2 diabetes. Hyperpermeability of retinal blood vessels and subsequent formation of edema and hard exudates are the key clinical features. Method: This systematic review and meta-analysis, conducted following PRISMA guidelines and employing the PICO format, aim to explore about impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus, focusing on treatment, complications, and prognosis. Inclusion criteria encompass diverse study designs (RCTs, observational, quasi-experimental, and case-control studies) investigating impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus among treatment, complications, and prognosis, while exclusion criteria filter out studies lacking relevance to impact of treatment of diabetic macular edema on visual impairment in people with type 2 diabetes mellitus. Result: After conducting three levels of screening, the results of our search in Pubmed get 6 articles, whereas the results of our search on SageJournal get 42 articles, on Lancet 21, and on Scient direct get 60 articles. Records remove before screening are 91, so we get 78 articles for screening. After we screened based on record exclude, we compiled a total of 10 papers. We included four research that met the criteria. Conclusion: There is a particularly robust response to anti-VEGF therapy in both groups when glycemic control is optimized, highlighting the critical importance of communication between the physicians managing the DME and those managing systemic diabetes control. Improving our understanding of the factors that contribute to anti-VEGF response for DME therapy may help to enhance DME treatment outcomes, particularly through the concerted coordinated efforts of the treating retina specialist and the endocrinologist or primary care physician.

Switching to subtenon triamcinolone acetonide does not jeopardize the functional and anatomic outcomes of dexamethasone implant treated eyes with diabetic macular edema.

Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME. Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied. 26 eyes of 17 patients (mean age 67.1 ± 8.2years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8µm initially, decreasing to 294.3 ± 133.4µm after DEXi, 369.9 ± 182.3µm after STTA and 297.6 ± 72.0µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4µm, -167.7µm, and -95.08µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA. DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME.

Management of treatment-naïve diabetic macular edema patients: Review of real-world clinical data.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

IDF23-0229 Systemic oxidative stress environment may dictate the effectiveness of anti-VEGF therapy in diabetic macular edema

IDF23-0229 Systemic oxidative stress environment may dictate the effectiveness of anti-VEGF therapy in diabetic macular edema

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Serum microRNAs as biomarkers associated with the course of diabetic macular oedema

Aims/Purpose: Intravitreal drugs are powerful therapies for diabetic macular edema (DME), but the clinical course and the response to treatments still remains unpredictable. MicroRNAs (miRNAs) represent a class of small molecules associated with the regulation of several metabolic pathways, including diabetes. However, their use in the clinical setting of DME is limited by lack of data regarding the correlation with clinical and imaging features. In the present study we evaluated some miRNAs profiles obtained by serum samples of newly diagnosed DME patients.Methods: Prospective study, including baseline visit (V0), a 4‐months visit (V1) and a 12‐months visit (V2). At V0 patient underwent serum sampling, imaging was repeated at every study visit. Enriched serum microRNAs were extracted and real‐time PCR was performed. OCT features were used to assess the severity and progression of the disease.Results: We collected data of a cohort of type 1 and type 2 diabetic patients. All the patients presented DME and were naïve to intravitreal treatments. The follow‐up was of 12 months. Diabetes‐related miRNAs were found up‐ or downregulated and associated with the course of DME (resolved/recurrent/persistent). Correlations were found with imaging biomarkers.Conclusions: On the basis of these findings, serum miRNAs assessment is a feasible and clinically relevant assessment to be performed in the diagnostic work‐up of diabetic patients affected by DME. MiRNAs might pave the basis for customized treatment strategies to optimize the management of DME.

Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Анализ эффективности анти-VEGF терапии диабетического макулярного отека в авитреальных глазах

Aim. To analyze the clinical efficacy of anti-VEGF therapy for diabetic macular edema (DME) in avitreal eyes. Methods. 34 patients (38 eyes) with vitreous loss and DME on the background of preproliferative diabetic retinopathy (PPDR) (18 eyes) and proliferative diabetic retinopathy (PDR) (20 eyes) were examined in the main study group. The comparison group consisted of 40 patients (40 eyes) with native vitreous body and DME on the background of PPDR (20 eyes) and PDR (20 eyes). Intravitreal injections of Lucentis 0.5 mg (IVIL) were carried out according to «three monthly injections» scheme, then – to «on demand» scheme. Results. Complete regression of DME in avitreal eyes occurred in 74 % of cases; in eyes with native vitreous body – in 75 %. The duration of postoperative reaction in eyes with vitreous loss was up to 10–14 days, compared with 1–3 days in eyes with native vitreous body. The results of the study revealed that number of IVIL was significantly less in patients with DME on the background of PPDR than PDR. Conclusion. Presence of local neuroepithelial detachment on the background of diffuse DME is prognostically favorable factor for anti-VEGF therapy. The effectiveness of IVIL in DME treatment is comparable in eyes with native vitreous body and avitreal eyes. Key words: diabetes mellitus; diabetic macular edema; preproliferative diabetic retinopathy; proliferative diabetic retinopathy; avitria; Lucentis intravitreal injections.

Surgical Treatment for Diabetic Macular Edema

Diabetic macular edema (DME) is defined as excess fluid accumulation within the retina in the macular area, and when it is centered on the fovea it is the most common cause of decreased visual acuity in patients with diabetic retinopathy. The development of diabetic macular edema is closely related to the duration of diabetes, poor glycemic control, and type 2 diabetes on insulin therapy. The first-line therapy in diabetic macular edema has been the intravitreal injection of anti-vascular endothelial growth factors (VEGF). Other treatment modalities are intravitreal corticosteroid injection and focal laser photocoagulation. However, the efficacy of intravitreal therapy may decrease significantly over time, especially in the presence of vitreomacular traction, tight posterior hyaloid, or epiretinal membrane (ERM). At this stage, pars plana vitrectomy (PPV) is preferred as an alternative treatment method in eyes with chronic DME resistant to intravitreal injections. The vitreous of diabetic patients contains high amounts of VEGF and Angiotensin 2, which cause DME, and cytokines such as interleukin-6 and ICAM-1. In addition, due to the enzymes, it contains, the vitreous causes cross-linking and thickening of the collagen fibers in its structure, causing tight adhesion and traction on the macula. The mechanism of action of pars plana vitrectomy in macular edema can be explained by removing the vitreous and vitreomacular tractions. Vitrectomy may also increase retinal oxygenation. Selection of the appropriate case is important. The undisturbed integrity of the outer retinal layers including the external limiting membrane(ELM) and the ellipsoid zone, no preoperative foveal ischemia, and performing surgery early before ELM is damaged, have been found to be related to better postoperative visual acuity gain. Further, prospective, randomized, controlled studies with large series including detailed parameters and long follow-up evaluating the efficacy of surgical treatment in diabetic macular edema are warranted.

EFFECT OF TOPICAL SODIUM DICLOFENAC AS ADJUVANT TO INTRAVITREAL BEVACIZUMAB INJECTION THERAPY ON VISUAL ACUITY INTRAOCULAR PRESSURE CHANGES IN PATIENTS WITH DIABETIC MACULAR EDEMA

Introduction dan Aim: Diabetic Macular Edema (DME) in Diabetic Retinopathy (DR) patients might threaten the patient's visual acuity. Therefore, a robust DME treatment is needed to prevent sight threatening condition in DR patients. In this study, we intended to compare the effects of intravitreal administration of bevacizumab versus bevacizumab and topical natrium diclofenac in DR patients who developed DME. Methods: This was a randomized controlled trial study with double blinds. Data were taken from April 2020 to June 2021 from the Dr. Sardjito Central General Hospital and the Dr. Suhardi Hardjolukito Indonesian Air Force Central Hospital, Yogyakarta. Our patients were assigned to a control group (intravitreal bevacizumab therapy only) and an intervention group (intravitreal bevacizumab and topical natrium diclofenac). Then, we evaluated best corrected visual acuity (LogMar) and intraocular pressure (IOP, mmHg) were recorded in both groups before and after therapy. Results: A total of 38 eyes from 36 patients with naive DME were included in this study. Both treatment groups showed a statistically significant improvement in visual acuity after treatment bevacizumab (pre = 0.8±0.5; post = 0.6±0.5; p-value = 0.033) and bevacizumab and natrium diclofenac (pre = 0.9±0.5; post = 0.5±0.3; p-value = 0.004). In contrast to the above findings, the IOP in both groups did not show a significant change in IOP after therapy, bevacizumab (pre = 15.7±4.1; post = 15.6±4.2; p-value = 0.810) and bevacizumab and natrium diclofenac (pre = 16.0±4.5; post = 16.0±3.9; p-value = 0.868). Conclusion: Our study showed that visual acuity was improved significantly in DME patients treated with either bevacizumab or bevacizumab and natrium diclofenac. This might be a valuable information on the improvement of DME therapy, given that no increased post-therapy IOP in patients treated topical natrium diclofenac.

Risk of renal damage associated with intravitreal anti-VEGF therapy for diabetic macular edema in routine clinical practice.

Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of diabetic macular edema. However, there is little information about the systemic effects of intraocular administration of anti-VEGF drugs in patients with coexistent diabetic nephropathy because it can produce adverse renal effects. This retrospective cohort study analyzed the effect of intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, or aflibercept) on eFGR and microalbuminuria (MicA) in patients with diabetic macular edema and nonproliferative retinopathy without chronic kidney disease (CKD). Sixty-six patients were included, 54.5% male and 45.5% female, with a mean age of 66.70 ± 11.6 years. The mean follow-up of patients with antiangiogenic treatment was 42.5 ± 28.07 months, and the mean number of injections was 10.91 ± 7.54. In 12.1% of the cases, there was a worsening of the glomerular filtration rate (eFGR) and a 19.7% worsening of the microalbuminuria (MicA). The number of injections was not related to the worsening of the eFGR (P = 0.74) or the MicA (P = 0.239). No relationship was found between the type of drug and the deterioration of the GFR (P = 0.689) or the MicA (P = 0.53). Based on the results, there is a small proportion of patients with increase in MicA and the decrease in eFGR after anti-VEGF therapy, and these was no associated with the number of injection or the drug type. Ophthalmologists should be aware of renal damage in order to do a close monitoring of renal function and proteinuria after intravitreal administration of anti-VEGF mainly in hypertensive patients.

CAVITARY CHOROIDAL NEVUS SHOWING THICKNESS FLUCTUATIONS IN RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR DIABETIC MACULAR EDEMA: A CASE REPORT.

The purpose of this study was to report the multimodal imaging features of a cavitary choroidal nevus showing thickness fluctuations that mirrored the response of diabetic macular edema (DME) to intravitreal antivascular endothelial growth factor (VEGF) therapy. This is a retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), fluorescein and indocyanine green angiography, OCT-angiography (OCTA), and B-scan ultrasonography were analyzed. A woman in her 80s with a cavitary choroidal nevus and DME was treated with intravitreal anti-VEGF therapy using a pro re nata regimen over 5 years. The choroidal nevus showed thickness fluctuations paralleling the response of DME to anti-VEGF therapy. Worsening of the DME was associated with marked increased choroidal lesion thickness on OCT. Conversely, resolution of DME after intravitreal anti-VEGF injections was followed by choroidal lesion flattening on OCT. Variations of the choroidal lesion thickness were mainly dependent on changes of intralesional hyporeflective caverns on OCT. Our report shows thickness variations of a cavitary choroidal nevus that paralleled the clinical course of DME treated with intravitreal anti-VEGF therapy. To the best of our knowledge, this is the first report on volume variations of a cavitary choroidal nevus after anti-VEGF therapy.

Evaluating initial responses to brolucizumab in patients undergoing conventional anti-VEGF therapy for diabetic macular edema: a retrospective, single-center, observational study

Our retrospective, single-center, observational study aimed to evaluate the initial responses to intravitreal injection of brolucizumab (IVBr) in patients undergoing anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). In total, 23 eyes of 20 patients with DME treated with at least one intravitreal injection of ranibizumab or aflibercept within one year and then switched to IVBr were included. Best corrected visual acuity (BCVA), central macular thickness (CMT), and macular volume (MV) on optical coherence tomography images were evaluated just before the most recent conventional anti-VEGF (ranibizumab/aflibercept) injection therapy (V1), one month after the most recent traditional anti-VEGF therapy (V2), just before the first IVBr (V3), and one month after the first IVBr (V4). BCVA, CMT, MV, and presence of intraocular inflammation (IOI) were evaluated at each visit. Anterior chamber flare values were also examined at V3 and V4. BCVA showed significant improvement at V2 (0.30 ± 0.23) than V1 (0.39 ± 0.29) and at V4 (0.34 ± 0.26) than V3 (0.48 ± 0.34) (P = 0.002, P < 0.001). However, no significant difference was observed between V2 and V4 (P = 0.257). CMT was significantly thinner at V2 (346.8 ± 90.2 µm) than V1 (495.5 ± 123.8 µm), and at V4 (322.2 ± 95.7 µm) than V3 (536.5 ± 166.0 µm) (P < 0.001, P < 0.001), but no significant difference was observed between V2 and V4 (P = 0.140). MV was significantly smaller at V2 (11.6 ± 2.0 mm3) than V1 (12.6 ± 1.9 mm3) and at V4 (11.2 ± 2.0 mm3) than V3 (12.6 ± 2.0 mm3) (P < 0.001, P < 0.001), and even significantly smaller at V4 than V2 (P = 0.009). No patient had IOI. No significant changes were observed in anterior chamber flare values between V3 and V4 (25.6 ± 14.6 vs. 24.0 ± 11.5 photon count/ms; P = 0.543). Both CMT and MV significantly reduced without any adverse events one month after switching from conventional anti-VEGF to IVBr therapy for DME, including IOI. MV was significantly lower for IVBr than anti-VEGF therapy after one month of treatment. Therefore, brolucizumab may be a viable treatment option for DME patients considering switching from conventional anti-VEGF agents for various reasons, such as poor response or inability to extend dosing intervals.