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Purpose: To assess the safety and efficacy of the yellow sub-threshold micropulse laser (YSML) in eyes with uveitic macula edema (UME)., Methods: A prospective interventional study. Eyes with non-infectious UME and an unsatisfactory response to prior conventional treatments underwent navigated YSML (NAVILAS ® ). The treatment was planned on an imported macular OCT scan. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were recorded immediately before the treatment (baseline) and again after 1 and 3 months. The end of the follow up (FU) was the last available evaluation in the case of no UME recurrence; or when the CMT increase required rescue therapy., Results: Eight eyes of as many patients were included. The mean duration of the FU was 252 days (range: 170-398 days). No adverse events were observed. In the whole cohort the mean values improvement over time was significant for both CMT ( p  = 0.011) and BCVA ( p  < 0.001). The indication for a new treatment was stated in 4 eyes (50%) after a mean FU of 277 ± 43 days. This time was statistically comparable with the mean FU of eyes without UME recurrence. At the baseline the non-UME recurrence eyes had a significantly lower mean CMT (326 ± 80 vs 485 ± 112 μm, p  = 0.03)., Conclusions: The application of YSLM for UME has not previously been mentioned in literature. Our results were promising in terms of both safety and efficacy. This would authorize further studies on the procedure, also as a first line treatment in naif UME cases., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R. Lattanzio is consultant for Allergan/Abbvie, Bayer, Novartis, SIFI. M. Varano is consultant for Allergan/Abbvie, Bayer, Novartis, Biogen, Roche. F. Boscia, C. Iaculli and D. Veritti have no conflicts of interest to declare. S. Freda, is an AbbVie employees and may own AbbVie stocks/options. B. Piergentili was a former AbbVie employee. She is now affiliated with Alnylam Italia Srl.

Purpose: Aim of the study was to evaluate the efficacy of dexamethasone (DEX) 0.7 mg intravitreal implant in patients with diabetic macular edema (DME) and serous retinal detachment (SRD), and to study the prognostic factors on a follow up of 12 months., Methods: Forty eyes of twenty- six patients with centre involving DME and SRD, who underwent DEX implant, were enrolled. Best-corrected visual acuity (BCVA), Swept source OCT imaging and intraocular pressure were evaluated. Central macular thickness (CMT), vitreomacular adhesion (VMA), disorganization of retinal inner layers (DRILs), hyperreflective dots (HRD), SRD and ellipsoid zone (EZ) disruption were included in the analysis at baseline and 12 months after implant., Results: According to our parametric analysis, at 12 months, BVCA improvement from 48.6 ± 23.4 letters to 53.3 ± 24.5 letters was statistically significant ( p  = 0.04), CMT decreased from 460 ± 99.52 μm to 322.9 ± 117 μm. The presence at baseline of VMA ( p  = 0.01), EZ disruption ( p  = 0.03) and DRILs ( p  = 0.04), were associated with poor BCVA improvement at the end of follow-up., Conclusion: In conclusion, OCT biomarkers can be considered significant prognostic factors for treatment outcome in patients with DME undergoing DEX intravitreal implant., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purposes: To screen key indicators leading to unfavorable outcomes of retinal vein occlusion related macular edema (RVO-ME) within long-term follow-up duration and to evaluate their predictive values., Methods: A study involving patients with RVO-ME was conducted between April 2021 and September 2022. All eligible patients were divided into two groups (favorable and unfavorable group) according to their final best corrected visual acuity (BCVA) and whether neovascular glaucoma (NVG) occurred. The unfavorable group was further divided into subgroups 1 (with BCVA of ≥ 20/400 and < 20/60 and without NVG) and 2 (blindness group, with BCVA of < 20/400 or with NVG). Demographic, past medical history, ocular characteristics and blood parameters were compared between the groups., Results: A total of 73 eyes from 73 Chinese Han patients (34 males vs. 39 females) with RVO-ME were enrolled. In multivariable regression analysis of continuous variables for unfavorable results, 1-month BCVA after the first intravitreal injection (IVI) was an independent risk factor (odds ratios (ORs) = 2.313, 95% confidence interval (CI) 1.387-3.858, P  = 0.001). The area under the curve (AUC) of 1-month BCVA after the first IVI for predicting low vision and blindness was 0.948 (95% CI 0.859-1.000, P  < .001) and 0.892 (95% CI 0.744-1.000, P  < .001), with a cut-off value of 0.65 logarithm of the minimum angle of resolution (log MAR) (Snellen 20/90) and 1.15 log MAR (Snellen 20/300), respectively., Conclusion: The most valuable indicator for predicting low vision and blindness was poor 1-month BCVA after first IVI compared with favorable group., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN ® ) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant., Settings: The study included patient data from five Portuguese public hospitals., Design: This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment., Methods: Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months., Results: This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population., Conclusions: In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden., Competing Interests: Declaration of conflicting interestsJoão Paulo Castro Sousa has received consulting fees from Alimera Sciences, Alcon, Bayer, and Novartis; has received payment or honoraria for lectures, presentations, speakers bureaus and educational events from Abvie, Alimera Sciences, Alcon, Bayer, Novartis, and Roche; was supported for attending meetings and/or travel by Alimera Sciences, Alcon, Bayer, and Novartis; and has participated on Data Safety Monitoring Boards or Advisory Boards for Alimera, Alcon, and Novartis.Susana Penas has received consulting fees from Alimera Sciences, Bayer, Novartis, and Roche.Rufino Silva has participated on Advisory Boards for ABBVIE, Alimera Sciences, Novartis, Bayer, Théa; Novo Nordisk, and Roche.Ângela Carneiro has participated on Advisory Boards for Alimera Sciences, Allergan, Bayer, Novartis, and Roche.Angelina Meireles has received consulting fees and support for attending meetings and travel from AbbVie; has received payment for presentations from Alcon; has participated on an Advisory Board from Alimera Sciences; and has received support for attending meetings and travel from Alimera Sciences.

Objective: The purpose of this study was to compare the efficacy and safety of aflibercept (AFL) versus ranibizumab (RAN) for the treatment of diabetic macular edema (DME)., Methods: The PubMed, Embase, Cochrane Library, and CNKI databases were searched up to September 2022 to identify prospective randomized controlled trials (RCTs) comparing AFL with RAN for the treatment of DME. Review Manager 5.3 software was used for data analysis. We used the GRADE system to evaluate the quality of the evidence for each outcome., Results: A total of 8 RCTs involving 1067 eyes (939 patients) were included; there were 526 eyes in the AFL group and 541 eyes in the RAN group. Meta-analysis revealed that there was no significant difference between RAN and AFL in the best-corrected visual acuity (BCVA) of DME patients at 6 months (WMD: -0.05, 95% CI  =  -0.12 to 0.01, moderate quality) and 12 months after injection (WMD: -0.02, 95% CI  =  -0.07 to 0.03, moderate quality). Additionally, there was no significant difference between RAN and AFL in the reduction of central macular thickness (CMT) at 6 months (WMD: -0.36, 95% CI  =  -24.99 to 24.26, very low quality) and 12 months after injection (WMD: -6.36, 95% CI  =  -16.30 to 3.59, low quality). Meta-analysis showed that the number of intravitreal injections (IVIs) for AFL was significantly lower than that for RAN (WMD: -0.47, 95% CI  =  -0.88 to -0.05, very low quality). There were fewer adverse reactions to AFL than to RAN, but the difference was not significant., Conclusion: This study found that there was no difference in BCVA, CMT or adverse reactions between AFL and RAN at 6 and 12 months of follow-up, but AFL needed fewer IVIs than RAN., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the effectiveness and safety of intravitreal brolucizumab (IVB) and intravitreal aflibercept (IVA) injections in the management of naive central involved diabetic macular edema (CIDME)., Methods: This study included 45 treatment-naive eyes with CIDME. A complete ophthalmic examination, including BCVA and SD-OCT was performed. Patients were randomized to (IVB) or (IVA) groups. All participants received a loading phase of three consecutive intravitreal injections, then followed by a personalized treat and extend (T&E) regimen., Results: At 12-month follow-up, the mean numbers of injections in IVA and IVB groups were 7.25  ±  0.53 and 6.3  ±  0.45, respectively (P < 0.0001). The IVA group showed a significant increase of the mean BCVA from 0.66  ±  0.15 logMAR (50.9  ±  7.7 letters) to 0.41  ±  0.19 logMAR (63.7  ±  10.8 letters). Mean CFT decreased significantly from 441.2  ±  35.7 μm to 281.3  ±  18.4 μm. The IVB group showed a significant increase of mean BCVA from 0.65  ±  0.16 logMAR (52.1  ±  7.9 letters) to 0.39  ±  0.17 logMAR (65.3  ±  8.7 letters). Mean CFT decreased significantly from 437.2  ±  41.9 μm to 275.5  ±  21.7 μm.No significant difference between both groups in terms of the vision improvement and the reduction of CFT was reported, whereas a statistical difference was observed in terms of intravitreal injections (IVI) numbers. No ocular complications were reported., Conclusions: This case series highlights the effectiveness of both brolucizumab and aflibercept in the treatment of CIDME with a lower frequency of injection in brolucizumab group lowering the burden of IVI in this cohort., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Branch retinal vein occlusion complicated by macular oedema is a common disease treated with intravitreal injection of anti-vascular endothelial growth factor. Controversy exists surrounding anti-vascular endothelial growth factor selection for both treatment naïve and refractory cases., Methods: A retrospective electronic medical record review at a single UK centre generated a cohort of 259 treatment naïve eyes from 258 patients receiving ranibizumab, aflibercept or a combination ( n  = 83, 97 and 79, respectively) from 2013 to 2018 with ⩾6 months follow-up. Number of intravitreal injections, visual acuity and macular oedema presence were noted at 3, 6, 12, 24, 36 and 48 months. A subgroup analysis examined refractory cases switched from ranibizumab to aflibercept ( n  = 77) or maintained on ranibizumab ( n  = 35)., Results: Eyes receiving ranibizumab or aflibercept had equivocal vision gain at 1 year, 8.0 (95% CI 5.0-11.0) and 9.6 (7.2-12.1) Early Treatment of Diabetic Retinopathy Study letters, respectively. About 35.6% had no macular oedema at 12 months with ranibizumab compared with 50.0% with aflibercept ( p  = 0.07) following 5.1 (4.7-5.6) and 6.0 (5.6-6.4) intravitreal injections, respectively. Visual prognosis declined significantly as treatment delay extended ( p  = 0.003) which was only apparent with ⩾3 months delay. Eyes with refractory macular oedema also had equivocal functional and anatomical outcomes whether they were maintained on ranibizumab or switched to aflibercept., Conclusion: These real world data demonstrate more modest clinical improvements from anti-vascular endothelial growth factor treatment than reported in clinical trials. The functional outcomes of ranibizumab and aflibercept in both treatment naïve and refractory cases were equivocal while the anatomical outcomes of aflibercept may be superior.

Purpose: To compare the results of early versus late switch to the dexamethasone intravitreal implant Ozurdex ® in patients with diabetic macular edema who had a poor response to vascular endothelial growth factor inhibitors., Methods: Retrospective and single-center study conducted, in a real setting, on consecutive diabetic macular edema patients who were switch to an intravitreal dexamethasone implant after a poor response to anti-vascular endothelial growth factor treatment. Study sample was divided into two groups: (1) early-switch group, included those eyes who received three anti-vascular endothelial growth factor injections before switch and (2) late-switch group, included those eyes that received six or more anti-vascular endothelial growth factor injections before switch. The primary end-point was the difference in mean change in best-corrected visual acuity and in central subfoveal thickness., Results: A total of 69 (31 early-switch group and 38 late-switch group) eyes were included. In the early-switch group, median (25-75 quartile range) best-corrected visual acuity significantly increase from 0.2 (0.2-0.5) at baseline to 0.4 (0.3 -0.7) at month 24 (p = 0.0043). Whereas, in the late-switch group, best-corrected visual acuity did not increase (p = 0.8602). Central subfoveal thickness was significantly reduced in both early- and late-switch groups, p = 0.0002 and 0.0038, respectively. The proportion of eyes obtaining a central subfoveal thickness reduction ⩾ 10% was significantly greater in the early-switch group than in the late-switch group (71.0% vs 47.4%, respectively, p = 0.0498). Three (9.7%) and 10 (26.3%) eyes have developed ocular hypertension during the study in the early- and late-switch groups, respectively, p = 0.0816., Conclusion: Early switch to Ozurdex in patients who did not adequately respond to anti-vascular endothelial growth factor therapy provided better functional and anatomical outcomes.

Objective: The aim of this study is to develop guidance on the use of intravitreal dexamethasone implants in the treatment of diabetic macular edema., Method: The study was performed using the modified Delphi method to obtain a consensus among a panel of experts on management of patients with diabetic macular edema and use of intravitreal dexamethasone implants in clinical practice. Thirty-seven panel members, experts on retina, from different Spanish centers were invited to participate. Individual and anonymous opinions were asked by answering a 76-item questionnaire across 11 topic areas (two rounds were done). Level of agreement was assessed using a Likert-type scale of 9 points., Results: Agreement on "consensus" was reached during the first round in 63 items. The 13 remaining items underwent a second round of voting. After the second round, agreement on "consensus" was reached on five items. Finally, eight items remained without consensus., Conclusion: Intravitreal dexamethasone implants are useful in the treatment of patients with diabetic macular edema with different profiles, for example, pseudophakic, poor-adherents, vitrectomized, candidates for cataract surgery, patients with high inflammatory component, and with a history of cardiovascular events. The use of intravitreal dexamethasone reduces the number of visits and facilitates compliance. Experts thought that the switch from anti-vascular endothelial growth factor therapy to intravitreal dexamethasone implants should be done preferably after three injections. Also, pro re nata treatment provides better results in diabetic macular edema patients as it helps to prevent undertreatment. Finally, experts concluded that clinical guidelines and treatment protocols for diabetic macular edema need to be updated.

Introduction: To analyze functional and anatomical outcomes in subtypes of diabetic macular edema treated with a single dexamethasone implant and to assess the usefulness of a pro-re-nata treatment among subtypes., Methods: Retrospective study in morphologic patterns of diabetic macular edema (diffuse retinal thickening n = 15; cystoid macular edema n = 38, and serous retinal detachment n = 17) recalcitrant to anti-vascular endothelial growth factor, treated with dexamethasone implant. Examinations included timing to recidive of diabetic macular edema, best-corrected visual acuity, and central subfield macular thickness at 2, 4, and 6 months., Results: In previously treated patients with a mean of 6.64 ± 3.69 anti-vascular endothelial growth factor injections, the best-corrected visual acuity improved from 61.64 ± 13.71 to 65.71 ± 14.65 as per the Early Treatment Diabetic Retinopathy Study protocol (p = 0.009) and central subfield macular thickness change from 447.46 ± 110.82 to 354.39 ± 80.46 µm (p < 0.005). The best-corrected visual acuity improvement was better in the diffuse retinal thickening group (68.67 ± 13.81 vs 65.26 ± 14.04 in cystoid macular edema and vs 64.12 ± 17.06 in serous retinal detachment), whereas higher central subfield macular thickness thinning was observed in serous retinal detachment group (368.47 ± 29.96 to 310.27 ± 67.47 in diffuse retinal thickening, vs 445.92 ± 105.06 to 364.39 ± 80.28 and 520.59 ± 122.96 to 370.94 ± 81.73 in cystoid macular edema and serous retinal detachment, respectively). Cystoid macular edema group was the group with more recurrences after 6 months (86.8% vs 66.7% in diffuse retinal thickening and 70.6% in serous retinal detachment)., Conclusion: Dexamethasone implant is effective for all persistent diabetic macular edema subtypes with sustained functional and morphologic gains in the first 6 months.

Objectives: To assess structural and functional outcomes of treatment with intravitreal aflibercept (Eylea ® ) for diabetic macular oedema in treatment-naive patients., Design: This is a retrospective, real-life, cohort study., Participants and Methods: In all, 92 diabetic patients (102 eyes) receiving intravitreal anti-vascular endothelial growth factor therapy were included. A total of 99 aflibercept-treated eyes were included in the statistical analysis. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline and 12 months. Patients were initiated on a loading phase of five monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion., Results: The mean number of aflibercept injections received was 6.92. At baseline, the mean visual acuity (standard deviation; Snellen) was 59.7 (16.1) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 431 (129) µm, while the mean macular volume (standard deviation) was 9.53 (1.79) mm 3 . At 12 months, the mean visual acuity (standard deviation; Snellen) was 69.6 (15.2; 20/40) Early Treatment Diabetic Retinopathy Study letters (p < .0001). Mean central foveal thickness (standard deviation) was 306 (122) μm (p < .0001) and mean macular volume (standard deviation) was 8.43 (1.58) mm 3 (p < .0001) at 12 months; 33 (33.67%) eyes gained ⩾15 Early Treatment Diabetic Retinopathy Study letters at month 12, and 50 (55.55%) eyes had a decrease in central foveal thickness of ⩾100 µm., Conclusion: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 12 months after commencing treatment for diabetic macular oedema in real-life settings.

Purpose: The aim of this study was to evaluate the correlations between fundus autofluorescence and morphologic parameters as well as visual function in patients with diabetic macular oedema treated with intravitreal ziv-aflibercept., Methods: A total of 34 eyes of 20 patients with untreated diabetic macular oedema received an intravitreal injection of ziv-aflibercept at baseline, and 1 and 2 months later. The baseline, 1-month, and two-month best corrected visual acuity determination, contrast sensitivity, spectral domain optical coherence tomography, mean central macular thickness, mean macular cube volume, mean macular cube average thickness, and fundus autofluorescence (decreased, normal, or increased; and single or multiple spots) were measured. Correlation analysis with a determination of Spearman's rank correlation coefficient, regression analysis, agreement between investigators, and Friedman's test were used for statistical analyses., Results: A direct correlation was observed between baseline fundus autofluorescence and macular cube average thickness at 1 month (r = 0.51, p = 0.020) and between fundus autofluorescence at 1 month and baseline macular cube average thickness (r = 0.50, p = 0.021). Regression analysis showed a coefficient of determination of 0.29 (p = 0.016) between baseline fundus autofluorescence and macular cube average thickness at 1 month., Conclusion: In patients with diabetic macular oedema, the pretreatment baseline degree of foveal fundus autofluorescence might be helpful in predicting macular cube average thickness in patients undergoing treatment with intravitreal ziv-aflibercept in the short term.

Objectives:: Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema., Methods:: A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy., Results:: Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy., Conclusions:: While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

Purpose:: To compare the effects of intravitreal ranibizumab injection and yellow (577 nm) subthreshold micropulse laser treatment in patients with macular edema following non-ischemic branch retinal vein occlusion., Methods:: The medical records of 51 patients who underwent intravitreal ranibizumab (0.5 mg) injection or subthreshold micropulse laser for the treatment of macular edema due to branch retinal vein occlusion were retrospectively reviewed. Subthreshold micropulse laser was administered with a 10% duty cycle, 100 μm spot diameter, 200 ms exposure time. The patients received an injection or laser treatment at baseline and were, then, retreated as needed and were followed for 12 months. The mean best corrected visual acuity changes over the follow-up and the decrease in the mean central macular thickness were evaluated., Results:: A total of 27 and 24 patients were assigned to intravitreal ranibizumab and subthreshold micropulse laser subgroups, respectively. The mean number of treatment was 3.81 of intravitreal ranibizumab group and 1.5 of subthreshold micropulse laser group (p < 0.05). The subgroups were similar with regard to the mean score of best corrected visual acuity at baseline, at 1, 6, and 12 months (p > 0.05). The decrease in the mean central macular thickness was significant in both intravitreal ranibizumab and subthreshold micropulse laser groups at 1, 6, and 12 months than that of values at baseline (p < 0.05). No new ocular or systemic adverse events were observed., Conclusion:: Our study results showed that intravitreal ranibizumab or yellow subthreshold micropulse laser treatment for macular edema due to branch retinal vein occlusion was not found to be superior to each other for reducing macular thickness and increasing visual acuity for 1-year period. Based on these results, subthreshold micropulse laser may be a useful alternative approach in the treatment of macular edema secondary to branch retinal vein occlusion.

Purpose:: Dexamethasone intravitreal implant and intravitreal ranibizumab are indicated for the treatment of macular edema secondary to retinal vein occlusion. This non-inferiority study compared dexamethasone with ranibizumab in patients with branch retinal vein occlusion., Methods:: In this randomized, 12-month head-to-head comparison, subjects with branch retinal vein occlusion were assigned to dexamethasone 0.7 mg at day 1 and month 5 with the option of retreatment at month 10 or 11, or ranibizumab 0.5 mg at day 1 and monthly through month 5 with subsequent as-needed injections at month 6-month 11. The primary efficacy outcome was the mean change from baseline in best-corrected visual acuity at month 12; secondary outcomes included average change in best-corrected visual acuity, proportion of eyes with ≥10- and ≥15-letter gain/loss, change in central retinal thickness, and change in Vision Functioning Questionnaire-25 score., Results:: In all, 307 of a planned 400 patients were enrolled in the study and received (mean) 2.5 dexamethasone injections (n = 154) and 8.0 ranibizumab injections (n = 153) over 12 months. The mean change from baseline in best-corrected visual acuity at month 12 was 7.4 letters for dexamethasone versus 17.4 letters for ranibizumab (least-squares mean difference (dexamethasone minus ranibizumab), -10.1 letters; 95% confidence interval, -12.9, -7.2; p = 0.0006)., Conclusion:: Dexamethasone and ranibizumab improved best-corrected visual acuity and anatomical outcomes; however, dexamethasone did not show non-inferiority to ranibizumab in this under-powered study. Dexamethasone was associated with an increased risk of intraocular pressure elevation and cataract progression, but a lower injection burden, compared to ranibizumab.

Purpose: To reach a consensus, among experts, on the role of aflibercept in diabetic macular edema (DME) through literature review., Methods: Two round tables, involving 12 Italian experts, were organized: in the first one, 6 pharmacologic and clinical questions were selected and analyzed by a systematic literature review, using a population, intervention, control, and outcomes framework; in the second one, the nominal group technique was used to discuss relevant evidence related to each question. The consensus was assessed using the 5-point Delphi score., Results: Agreement on statements was reached on 6/6 questions. The final statements were as follows: 1) High levels of both vascular endothelial growth factor (VEGF) and placental growth factor play an important role in the pathogenesis of DME. 2) The aflibercept pharmacologic profile is notably different from that of other anti-VEGF. 3) Aflibercept significantly improves functional and anatomical outcomes, and rapidly improves best-corrected visual acuity up to its peak; these results remain stable over time. 4) Diabetic macular edema aflibercept treatment requires a 5-monthly injection loading phase. Alternatively, a personalized pro re nata (PRN) regimen based on monthly monitoring and strict retreatment criteria can be used. 5) As an alternative to the bimonthly fixed regimen, in the maintenance phase the treatment schedule may be a PRN regimen with strict retreatment criteria or a treat and extend regimen. 6) No concerns on aflibercept ocular and systemic safety emerged from the literature., Conclusions: Consensus was reached among experts on how to best treat patients with DME with aflibercept.

Purpose: To evaluate the long-term efficacy and safety of the dexamethasone intravitreal implant Ozurdex® in the treatment of diabetic macular edema (DME)., Methods: This was a retrospective noncomparative study. A total of 23 patients with DME followed for at least 12 months were included. All patients were treated with at least 2 Ozurdex® injections for the treatment of DME. Best-corrected visual acuity, central retinal thickness, intraocular pressure (IOP), and cataract progression were recorded over 12 months., Results: From baseline, the mean decrease in central retinal thickness was 315.9 µm at the 12th month and the mean best-corrected visual acuity improvement from baseline was 8.7 letters. Ozurdex® is administered via the extended release system Novadur®. Its efficacy extends beyond 4 months with a single injection and permits allows good stabilization until the 12th month, with 2.13 injections during this period. An increase in IOP was observed in 13.1% of patients and all were managed using topical IOP-lowering medications. No glaucoma or cataract surgery was necessary, and no endophthalmitis was reported., Conclusions: In real-life clinical practice, Ozurdex® has anatomical and functional effectiveness for the treatment of DME. Side effects were rare and manageable in our practice.

Purpose: After vitrectomy, diffusion and clearance rates of numerous drugs are increased, leading to a shorter intravitreal half-life. This raises doubts about the efficacy of intravitreal therapies, as retina specialists generally believe that a shorter half-life compromises the drugs' therapeutic effect. We conducted a study to evaluate the functional and anatomical effect of intravitreal triamcinolone acetonide therapy (IVTA) in previously vitrectomized eyes with diabetic macular edema (DME)., Methods: In this retrospective, multicenter case series study including vitrectomized patients with DME who underwent IVTA injections, central macular thickness (CMT) measured with spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters were evaluated after each procedure. All relevant medical data were collected, including previous ophthalmologic treatments and comorbidities., Results: Twenty vitrectomized eyes of 20 patients, mean age 58.1 years (range 40-72 years), were enrolled in the study. All patients presented DME and received at least one IVTA injection. Mean time between pars plana vitrectomy and IVTA was 12.9 ± 8.7 months. Mean pretreatment and posttreatment CMT was 438.8 ± 90.8 μm and 301.2 ± 76.2 μm, respectively, a difference that reached statistical significance (p&lt;0.001). Mean gain in BCVA letter score was 7.83 ± 14.9 letters after treatment (p = 0.039). Mean intraocular pressure was significantly increased after IVTA (17.2 ± 1.9 mm Hg at baseline vs 21.2 ± 4.59 mm Hg after IVTA, p = 0.002)., Conclusions: A positive anatomical and functional effect was observed in our cohort. Our results suggest that, despite prior vitrectomy, triamcinolone remains a valid therapeutic approach for eyes with persistent DME. Further prospective randomized studies with larger patient samples are needed to validate this conclusion.

Purpose: To evaluate the efficacy of intravitreal dexamethasone implant (IDI) for the treatment of persistent diabetic macular edema (DME) in a subgroup of pseudophakic and nonglaucomatous eyes over a 12-month follow-up period., Methods: This was a retrospective, interventional study. Patients with persistent DME who were pseudophakic and did not have a glaucoma or ocular hypertension history, or a family history of glaucoma, were included. After an initial IDI injection, reinjections were performed on an as-needed basis. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and number of injections at month 12 were evaluated., Results: The study included 50 eyes of 43 patients. Mean BCVA at baseline and at months 1, 3, 6, 9, and 12 were 0.22 ± 0.17, 0.31 ± 0.21, 0.25 ± 0.17, 0.25 ± 0.17, and 0.29 ± 0.19 Snellen equivalent, respectively (p&lt;0.05 for all). Mean CRT at baseline and at months 1, 3, 6, 9, and 12 were 606 ± 202 μm, 330 ± 97 μm, 347 ± 104 μm, 405 ± 149 μm, 383 ± 129 μm, and 397 ± 144 μm, respectively (p&lt;0.0001 for all). Seven of the 50 eyes (14 %) showed an increase in IOP of ≥10 mm Hg and only 2 of them (4%) needed chronic antiglaucoma medication. The mean number of injections at month 12 was 2.04 ± 0.5., Conclusions: In pseudophakic and nonglaucomatous eyes with DME, IDI was found to be beneficial in regard to visual and anatomic success and seemed safe in this selected group of patients.

Purpose: To evaluate the effect of preoperative statin treatment on the outcome of primary vitrectomy in type 1 and 2 diabetic patients., Methods: In this open, observational institutional study, a total of 192 eyes of 171 type 1 and 2 adult diabetic patients admitted for primary vitrectomy for management of sight-threatening forms of diabetic retinopathy were divided according to the use of lipid-lowering therapy: those with statin treatment (79 eyes of 73 patients) and those taking no statin medication (113 eyes of 98 patients). One-month best-corrected visual acuity (BCVA) gain and cumulative 12-month revitrectomy frequency were analyzed., Results: In multivariate linear regression, diabetic patients with statin treatment had a better 1-month BCVA improvement than did those without statin treatment (absolute difference 0.26, 95% confidence interval [CI] 0.02-0.50, p = 0.028). Subgroup analysis revealed that diabetic patients on statin had better postoperative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p = 0.042 and p = 0.049) and anti-vascular endothelial growth factor therapy (p = 0.011). Moreover, diabetic patients with preoperative macular edema (p = 0.009), vitreous hemorrhage (p&lt;0.001), proliferative retinopathy (p&lt;0.001), or tractional retinal detachment (p = 0.010) had better BCVA recovery if receiving statin. In Cox proportional hazards regression model, revitrectomies in our 12-month follow-up were less frequent in diabetic patients on statin treatment (hazard ratio 0.28, 95% CI 0.08-0.93, p = 0.037)., Conclusions: These data provide novel insight into the potential clinical benefit for patients with sight-threatening diabetic retinopathy undergoing vitrectomy treated with statin.

Purpose: To measure inner and outer retinal thickness with optical coherence tomography (OCT) in patients in whom intravitreal ranibizumab was administered due to diabetic macular edema (DME) and to investigate its relation to the visual prognosis., Methods: In this retrospective case series, there were 60 consecutive eyes with DME in which intravitreal ranibizumab injection was performed for 3 times in 1-month intervals. All patients underwent full ophthalmic examination and spectral-domain OCT (SD-OCT). The total retinal thickness, the inner thickness, and the outer thickness in 4 parafoveal subfields were measured. The correlation between the retinal thickness and logMAR best-corrected visual acuity (BCVA) was investigated., Results: No significant correlation was found between the total retinal thickness in the central and other subfields and either the baseline or final visit logMAR BCVA values (p&gt;0.05). There was a significant positive correlation between the final visit logMAR BCVA values and pretreatment inner retinal thickness in the nasal and inferior subfields (r = 0.270, p = 0.037, and r = 0.410, p = 0.001, respectively). There was significant negative correlation between the final visit logMAR BCVA values and pretreatment outer retinal thickness in nasal and temporal parafoveal subfields (r = -0.297, p = 0.021, and r = -0.268, p = 0.038, respectively)., Conclusions: It could be beneficial to use inner and outer retinal thickness instead of total retinal thickness in determination of short-term prognosis in patients who had intravitreal ranibizumab injection for DME.

Purpose: To determine the effect of intravitreal bevacizumab on retrobulbar blood flow of patients with diabetic macular edema., Methods: Peak systolic velocity, end-diastolic velocity, resistance, and pulsatility indices of central retinal artery (CRA), nasal posterior ciliary artery (NPCA), temporal posterior ciliary artery (TPCA), and ophthalmic artery (OA) were assessed by color Doppler ultrasonography in injected and uninjected eyes of 37 patients at baseline and at day 1 and day 7 after the injection., Results: At day 1 after the injection, peak systolic and end diastolic velocities of the CRA and NPCA in the injected eyes and peak systolic velocity of NPCA in the uninjected eyes decreased significantly (p&lt;0.05, p = 0.025, respectively). Peak systolic and end diastolic velocities were not significantly different in the injected and uninjected eyes at day 7 after the injection (p&gt;0.05). In the injected eyes, there was no significant change in resistance and pulsatility indices (p&gt;0.05), but a decrease in resistance index of NPCA and resistance and pulsatility indices of TPCA occurred in uninjected eyes at day 7 after the injection (p = 0.016, p = 0.023, and p = 0.025, respectively)., Conclusions: Intravitreal bevacizumab affects retrobulbar blood flow in injected and uninjected eyes of patients with diabetic macular edema.

Purpose: To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME)., Methods: This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (gt;24 mm Hg) were analyzed before treatment and 2 and 4 months after injection., Results: Preoperative mean CMT was 559 ± 111 μm and decreased to 338 ± 84 and 477 ± 140 μm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (p&lt;0.0001), a recurrence of the macular edema was observed 4 months after injection in 79% of eyes. Mean BCVA improvement (logMAR) was 0.13 ± 0.18 (p&lt;0.0001) and 0.07 ± 0.21 (p = 0.049) 2 and 4 months after injection, respectively, without significant difference between vitrectomized and nonvitrectomized eyes. Eight eyes (21%) developed reversible increase in IOP 2 months after injection., Conclusions: Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

Purpose: To define the mean time of first recurrence of diabetic macular edema (DME) after a single injection of dexamethasone intravitreal implant (DEX-I), reducing the burden of monthly visits during a PRN regimen of treatment., Methods: Twenty phakic eyes with DME (12 eyes naïve and 8 eyes with edema persistent after previous treatments) were followed monthly after DEX-I injection until evidence of first recurrence of edema, defined as a change in visual acuity (VA) ≥5 letters and/or in foveal thickness (FT) ≥50 µm. Reaching this point, the eyes were re-treated. Monitored parameters were changes in VA, FT, intraocular pressure (IOP), and lens opacity., Results: Maximal efficacy was registered at month 1, when mean VA improved by 14 letters (19%), FT decreased by 325 µm (43.7%), and in 15 eyes (75%) edema was completely reabsorbed. The mean time of first recurrence was 5.1 months. No statistical difference was found between eyes with naïve or persistent DME. Five eyes needed topical medication for modest temporary IOP increase (21-24 mm Hg) between months 2 and 4. No increase in lens opacities was registered during follow-up., Conclusions: According to the results of this study, the first signs of DME recurrence after DEX-I injection appear at a mean time of 5 months, suggesting that an appropriate and prudent time schedule for a PRN regimen could be limited to monthly tonometry and a first complete examination not before 4 months.

Purpose: To study the safety and efficacy of intravitreal dexamethasone implant in patients with cataract and macular edema undergoing phacoemulsification and intraocular lens (IOL) implantation., Methods: Twenty-four eyes with macular edema secondary to diabetic retinopathy (diabetic macular edema [DME]) and retinal vein occlusion (RVO) were retrospectively reviewed. These eyes underwent phacoemulsification with IOL implantation and intravitreal dexamethasone implant 0.7 mg at the same setting between September 2012 and September 2013. Demographic data, best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), surgical time, and complications were recorded., Results: Twelve eyes had DME and 12 eyes had RVO (10 central RVO and 2 branch RVO). Median baseline logMAR BCVA was 1.0 (Snellen 20/200) and mean baseline CMT was 530.2 ± 218.9 µm. Median follow-up duration was 13 months. At last follow-up, median visual acuity improved significantly to 0.523 (Snellen 20/66) (p = 0.003) and CMT decreased to 300.7 ± 78.1 µm (p = 0.000). Median surgical time was 23 minutes. There were no intraoperative complications. In 12 eyes, macular edema recurred, requiring further treatment, and median time to recurrences was 21 weeks. One eye had raised IOP after second dexamethasone implant for recurrent macular edema. No major complication such as vitreous hemorrhage, retinal detachment, or endophthalmitis occurred., Conclusions: Combined cataract surgery with intravitreal dexamethasone implant seems to be safe and effective in treating patients with cataract and macular edema in this small case series. A larger prospective study with longer follow-up is necessary to demonstrate the long-term benefit of this combined procedure.

Purpose: To evaluate the effects of yellow micropulse laser in eyes with diabetic macular edema (DME)., Methods: In this retrospective interventional case series, 22 eyes of 17 patients with visual impairment secondary to persistent DME received one single session of yellow micropulse laser. Patients were divided into 2 groups: group 1, naive eyes; and group 2, previously treated eyes. Main outcome measures included changes in central retinal thickness (CRT) and best-corrected visual acuity (BCVA). Possible atrophic changes of the retinal pigment epithelium as a result of yellow micropulse laser application were evaluated with fundus autofluorescence., Results: At baseline, the mean logMAR BCVA was 0.39 ± 0.18 and the mean CRT was 361.8 ± 70.95. The mean BCVA improved to 0.31 ± 0.19 (p = 0.0091) and 0.31 ± 0.19 (p = 0.0078) at 3 and 6 months of follow-up, respectively. The mean CRT improved to 331.3 ± 48.46 (p&lt;0.0001) and 328.1 ± 53.25 (p&lt;0.0001) at 3 and 6 months of follow-up. Subgroup analysis showed that only in naive eyes was there a beneficial effect on visual acuity and central macular thickness., Conclusions: In eyes with DME, yellow micropulse laser produces a statistically significant improvement in BCVA and CRT in the short term.

Purpose: To examine the efficacy of monthly injections of intravitreal bevacizumab (IVB) for macular edema after iodine-125 plaque radiotherapy of uveal melanoma., Methods: We studied 36 patients with macular edema after plaque radiotherapy of uveal melanoma in this noncomparative, interventional case series. All eyes were treated with 4 monthly injections of IVB. Central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured before each injection and 4-6 months after the first injection. The main outcome measures were change in CMT and BCVA., Results: At 4-6 months following the first IVB, 20 eyes (56%) had decreased CMT, 11 eyes (31%) had stable CMT, and 5 eyes (14%) had increased CMT. The mean change in CMT and the mean percent change in CMT at 4-6 months compared to baseline were -91 µm (-20%) in all eyes, -174 µm (-37%) in the group with decreased macular thickness, -14 µm (-3%) in the group with stable macular thickness, and +69 µm (+17%) in the group with increased macular thickness. At 4-6 months, 15 eyes (42%) had increased BCVA, 16 eyes (44%) had stable BCVA, and 5 eyes (14%) had decreased BCVA. An increase in CMT was seen between the fourth monthly IVB injection and the final evaluation at 4-6 months after the first injection in all 3 groups of our study., Conclusions: At 4-6 months following the first injection, 4 monthly injections of IVB in eyes with macular edema after plaque radiotherapy of uveal melanoma decreased macular edema in 56% and improved BCVA in 42% of the treated eyes.

Purpose: To evaluate the clinical effect, safety, and administration procedure of slow-release dexamethasone implants (Ozurdex®) for macular edema secondary to retinal vein occlusion in clinical praxis., Methods: Data from 11 patients (4 eyes with central vein occlusion and 7 eyes with branch vein oc-clusion) were reviewed. Data were compiled and analyzed with respect to best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP), and adverse events. Follow-up was 10 months. Changes in BCVA ≥ logMAR 0.2, IOP ≥5 mm Hg, and CMT ≥100 μm were considered clinically relevant., Results: Two months after the first dexamethasone implant, BCVA improved from logMAR 0.65 ± 0.2 
to logMAR 0.34 ± 0.1. All patients demonstrated a decrease in CMT from an initial average value of 
632 ± 178 μm to 229 ± 34 μm. However, in 10 out of 11 eyes, macular edema recurred by month 4 through 5 and a second dexamethasone implant was administered. Two and 4 months after the second implant, BCVA was logMAR 0.36 ± 0.2 and logMAR 0.40 ± 0.2 and the CMT was 254 ± 61 μm and 357 ± 81 μm, respectively. The IOP increased 5.1 ± 1.5 mm Hg 1 month after the first implant compared to baseline. In eyes with an IOP above 25 mm Hg (4 out of 11), pressure-lowering eyedrops were administered., Conclusions: Administration of dexamethasone implants induced a clinically relevant increase in visual acuity and a decrease in central macular thickness. In 91% of patients, macular edema recurred within 5 months and a second implant was administered. Adverse events, primarily increased IOP, were manageable. The injection procedure was relatively simple and uncomplicated.

Purpose: To investigate 24-hour variation in retinal thickness in patients with diabetic macular edema (DME) using optical coherence tomography (OCT)., Methods: Fifty-three eyes of 53 diabetic patients with clinically significant macular edema and central subfield thickness (CST) >225 µm, 36 eyes of 36 healthy individuals (normal controls), and 22 eyes of 22 diabetic patients without macular pathology (diabetic controls) underwent 5 OCT measurements at 7 am, 10 am, 3 pm, 8 pm, and 1 am. Visual acuity, blood pressure, blood glucose, and body temperature were measured as well., Results: The CST (p<0.0005), total macular volume (p<0.0005), and visual acuity (p<0.0005) showed significant variation in patients. The CST (450 µm at 7 am) reached a minimum at 3 pm (absolute change of -49 µm, relative change of -17%) before increasing again. Thickening changes were higher in more thickened retinas (p<0.0005, p=0.024, absolute and relative change, respectively). Visual acuity was worse in the morning (0.38 logMAR) and improved to a maximum at 8 pm (0.30 logMAR) (p<0.0005). Blood pressure, blood glucose, and body temperature did not vary over time., Conclusions: The 24-hour variation of retinal thickness is observed in a large proportion of patients with DME, with a decrease from morning to afternoon. Time of examination should be taken into account when managing such patients.

Purpose: To study the impact of ocular hypotensive lipids (OHL) on the incidence, progression, and response to treatment of clinically significant diabetic macular edema (CSDME)., Methods: A total of 379 patients (232 female, 147 male) with a history of diabetes mellitus (DM) and primary open-angle glaucoma (POAG) were identified and included in the study. Patients were stratified into groups based on CSDME development and OHL exposure. Main outcome measures included time to development of CSDME, total duration of OHL exposure, and duration of DM and POAG., Results: Seven patients (1.8%) developed CSDME after OHL exposure (group 1A), 15 (4.0%) developed CSDME prior to OHL exposure (group 1B), and 197 (52.0%) were treated with OHL but never developed CSDME (group 2). Of patients not exposed to OHL, 22 (5.8%) developed CSDME (group 3) and 138 (36.4%) did not (group 4). Mean duration of DM was longer (p<0.0001) in patients who developed CSDME (20.2 years) compared to patients who did not (12.4 years). There was no difference (p=0.67) in the amount of OHL exposure between patients who developed CSDME (4.1 years) and patients who did not (4.6 years). Once developed, there was no difference in the interval until CSDME resolution between OHL treated (17.8 mo) and untreated (12.7 mo) patients (p=0.36)., Conclusions: The CSDME development correlated most strongly with the duration of diabetes, irrespective of OHL use. Ocular hypotensive lipids treatment of POAG seems not to affect the incidence, progression, or response to treatment of CSDME in diabetes.

Purpose: To analyze risk factors associated with poor visual outcome in patients with ocular sarcoidosis., Methods: In this retrospective study, charts of 44 patients with uveitis and biopsy-proven sarcoidosis were reviewed. Ocular parameters evaluated were as follows: location, type of uveitis, visual acuity, presence of posterior synechia, iris nodules, vitritis, snowballs, chorioretinal lesions, retinal vasculitis, papillitis, macular edema, cataract, and glaucoma. Final visual acuity of the worst-seeing eye at last follow-up was the outcome considered in univariable and multivariable analyses. Visual acuity of the worst-seeing eye was stratified into 2 categories according to the threshold 20/50 (=20/50 and >20/50)., Results: A total of 44 patients with bilateral uveitis were studied. The majority of patients presented with panuveitis (52%), granulomatous type (61%), posterior synechia (62%). The most frequent vision-threatening complications were cystoid macular edema (56%) and cataract (56%). The median best-corrected visual acuity in the worst-seeing eye at presentation and at end of follow-up was respectively 0.4 (interquartile range [IQR] 0.26-0.80) and 0.63 (IQR 0.36-1.00). At univariable analysis, the presence of iris nodules (p=0.049), cystoid macular edema (p=0.007), and cataract (p=0.007) were clinically significant conditions for a visual outcome of 20/50 or worse in the worst-seeing eye. In multivariable analysis, cystoid macular edema (p=0.034) was the only statistically significant predictor associated with unfavorable visual outcome., Conclusions: In this study, we attempted to find risk factors related to poor visual outcome in patients with ocular sarcoidosis. The results suggest that only the presence of cystoid macular edema was significantly associated with worst visual outcome.

Purpose: To assess if functional visual loss preceded structural changes or vice versa in diabetic patients by evaluating the macular function in prediabetic patients and in diabetic patients with varying grades of retinopathy and comparing the findings with those of age-matched healthy controls by means of microperimetry., Methods: Retinal sensitivity, fixation pattern, and test response were evaluated in 25 prediabetic patients (50 eyes), 25 diabetic patients (50 eyes), and 25 age-related normal nondiabetic patients (50 eyes) using Nidek microperimetry. The diabetic patients were classified into 3 groups on the basis of clinical and fundus fluorescein angiographic evidence: group 1 = no clinical or angiographic evidence of retinopathy, group 2 = background retinopathy only, group 3 = with macular edema. Classification of retinopathy was based on Early Treatment Diabetic Retinopathy Study standards. Statistical analysis was conducted by Fisher exact test., Results: In diabetic patients, 20 eyes (40%) had no clinical or angiographic evidence of retinopathy, 13 eyes (26 %) had background changes, and 17 eyes (34%) had macular edema. Statistically significant difference in the fixation pattern, test response, and retinal sensitivity was noted in the diabetic and the prediabetic patients when compared to the controls., Conclusions: Significant loss of macular function in the eyes of prediabetic subjects was noted. These preliminary findings probably support the hypothesis that neurodegeneration precedes microangiopathy.

Purpose: To report our experience with sustained-release dexamethasone 0.7 mg intravitreal implant (Ozurdex®; Allergan, Inc., Irvine, CA) in retinal vein occlusion with macular edema., Methods: A prospective study of a series of 9 patients with recent retinal vein occlusion with macular edema treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including visual acuity, fundus biomicroscopy, fundus photography, fluorescein angiography, and spectral domain optical coherence tomography (Spectralis SD-OCT; Heidelberg Engineering, Heidelberg, Germany) was performed at baseline and follow-up (1 week, 1 month, and 3 months), and tolerability of the implant was assessed., Results: Nine eyes of 9 consecutive patients treated with a total of 9 sustained-release dexamethasone 0.7 mg intravitreal implants for macular edema associated with retinal vein occlusion were included. Five patients had central retinal vein occlusion and 4 patients had branch retinal vein occlusion. Accentuated ischemia was associated in 2/5 patients with central retinal vein occlusion. All eyes showed SD-OCT evidence of decreased edema following implant placement (mean decrease in central retinal thickness 320 µm). All eyes showed decrease of serous detachment of the neurosensory retina (not present in 7/9 cases at 1 month). Intraretinal central cyst resolved in 7/9 cases; small peripheral cysts were persistent in only 2/9 cases. Spectral domain optical coherence tomography demonstrated the presence and the integrity of external limiting membrane and inner and outer segments (IS/OS) of the photoreceptors in 6/9 cases at month 3. Forty percent of patients gained = 10 letters of best-corrected visual acuity at 3 months. The safety profile was consistent with the results of a previous phase III trial of Ozurdex®, and no serious ocular or systemic adverse events were observed during the follow-up period., Conclusions: In patients with macular edema in retinal vein occlusion, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option to control macular edema. At the final visit, foveal thickness was decreased to physiologic levels in all eyes. In parallel with resolution of the macular edema, visual acuity was significantly improved at the final visit. However, final visual acuity in eyes with still interrupted or thickened IS/OS interface was significantly poorer than that in eyes with a normal IS/OS line.

Purpose: To evaluate intravitreal bevacizumab (IVB) combined with grid laser photocoagulation in macular edema (ME) secondary to branch retinal vein occlusion (BRVO)., Methods: Eight eyes (8 patients) with ME associated with BRVO with at least 3 months of evolution since symptom onset were included. All subjects underwent measurement of best-corrected visual acuity (BCVA) and imaging with spectral domain optical coherence tomography (SD-OCT) at baseline and 1, 3, 6, and 12 months. Intravitreal bevacizumab was administered at baseline and macular grid laser photocoagulation 1 month later. During follow-up, additional IVB was administered based on physician discretion if persistent or recurrent intraretinal fluid (cysts) was observed on SD-OCT. The mean BCVA and SD-OCT central subfield thickness (CST) values were determined at each time point. Fisher exact test was performed to assess differences between baseline and post-treatment BCVA and SD-OCT measurements., Results: The mean baseline BCVA was 0.28±0.14 (mean±SD), and the mean CST was 479±137 µm. The mean BCVAs at 1, 3, 6, and 12 months were 0.47±0.18 (p=0.031), 0.56±0.50 (p=0.031), 0.65±0.60 (p=0.008), and 0.66±0.65 (p=0.016), respectively. The mean CST values at 1, 3, 6, and 12 months were 295±60 µm (p=0.008), 333±114 µm (p=0.070), 339±80 µm (p=0.008), and 335±109 µm (p=0.008). A mean 2.13 injections were administered; the second injection was administered a mean of 2.71 months after baseline., Conclusions: Combined treatment with IVB and macular grid photocoagulation provided good results and may be considered as an alternative therapy for ME in BRVO. Further studies are needed to assess these preliminary results.

Macular edema represents a common final pathway for many ocular diseases. Related ocular disorders include diabetic retinopathy, vascular occlusions, postsurgical situations, and uveitic diseases. The key pathophysiologic process is a breakdown of the blood-retinal barrier, normally preventing water movement in the retina, thus allowing fluid to accumulate in the retinal tissue via special water fluxes. Inflammatory processes and an increase in vascular permeability play a central role. Different mechanisms, complicated by ischemic conditions, interact in a complex network. Key factors are angiotensin II, prostaglandins, and the vascular endothelial growth factor. The various pathogenetic mechanisms and their contribution to the edema process are described in detail in this article.

Purpose: Bevacizumab (Avastin) was first used clinically in 2005. Reports on the treatment of more than 600 patients with central retinal vein occlusion (CRVO) have been published to date. However, there are limited data on the long-term effects of bevacizumab in patients with CRVO., Methods: We retrospectively re-evaluated 10 patients with CRVO who were initially part of one of the first published case series on the short-term effects of bevacizumab. The patients were invited for a follow-up visit 2 years after their initial bevacizumab injection. Study endpoints were changes in visual acuity (VA) and central macular edema (CME) compared to 1) baseline values and 2) short-term values after the initial injection., Results: Short-term VA gain had been 2.9 lines 3 weeks after the first bevacizumab injection. Two years later, mean VA gain vs baseline was 1.6 lines. Low baseline VA and good response to the first injection correlated positively with higher long-term VA gains (Pearson correlation of r = 0.50 and r = 0.66). There was no correlation for injection number, occlusion time, or CME changes with long-term VA gain., Conclusions: The initial short-term VA gain after bevacizumab treatment was not always maintained over a 2-year period despite repeated injections. Patients with low baseline VA and good response to the first injection seemed to benefit most from repeated bevacizumab injections.

Purpose: To investigate the changes and the reliability of multifocal electroretinogram (mfERG) after intravitreal triamcinolone acetonide (IVTA) injection in diffuse diabetic macular edema (DDME)., Methods: Twenty-four eyes with DDME were treated with an intravitreal injection of 4 mg of triamcinolone acetonide. Visual acuity (VA), central macular thickness (CMT), mfERG, and intraocular pressures (IOP) were evaluated in the preinjection period and the 15th day, third month, and sixth month after IVTA injection., Results: Age and gender of the patients were not significantly correlated to logMAR VA (p=0.888 for age, p=0.192 for gender), CMT (p=0.282 for age, p=0.625 for gender), or P1/N1 amplitudes/implicit times in mfERG at baseline (p>0.05 for age and gender). The correlation between logMAR VA and CMT at baseline also was not significant (r=0.069, p=0.750). The VA increased significantly at the 15th day (p<0.001). The VA increase persisted until the third month and decreased to preinjection values at the sixth month (p=0.324). CMT decrease was significant at the 15th day (p=0.012) but insignificant at the third and sixth months (p=1.000 for both). Correlations between logMAR VA change/CMT change at the 15th day were not significant (r=-0.043, p=0.843). Moreover, the correlation of CMT change with P1/N1 amplitude/implicit time changes was not significant (p>0.05 for all)., Conclusions: The positive effect of IVTA injection in DDME is reversible until the sixth month. Monitoring of the improvement in visual function by mfERG is violated possibly by irreversible macular dysfunction due to long duration of macular edema and primary neurophysiologic effects of diabetes on the retina.

Purpose: To evaluate anatomic and functional results in patients with macular edema in retinal vein occlusion (RVO), treated with pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling, depending on the timing of surgery., Methods: A total of 35 consecutive patients underwent PPV with ILM peeling. Visual acuity, fluorescein angiography, and optical coherence tomography/spectral optical coherence tomography were performed preoperatively and 6-12 months postoperatively., Results: Anatomic improvement was achieved in 29 patients (82.9%). In 6 patients, there was no improvement. Central macular thickness decreased in 17 patients (48.6%) with central retinal vein occlusion (CRVO) and in 12 patients (34.3%) with branch retinal vein occlusion (BRVO) (p<0.05). A total of 68% of eyes showed improvement in visual acuity (p<0.05). Visual acuity improved in 14 patients (mean 3.7 Snellen lines) with CRVO and in 10 patients ( mean 3.7 Snellen lines) with BRVO. The t test shows no statistically significant difference in visual acuity improvement between ischemic and nonischemic CRVO (p>0.05) or between ischemic and nonischemic BRVO (p>0.05). Better results were observed in patients treated within 1 month of the onset of symptoms than in patients treated after more than 1 month. The difference is statistically significant (t test, p=0.0016)., Conclusions: PPV with ILM peeling may improve anatomic and functional prognosis in patients with macular edema secondary to RVO. Vitrectomy with ILM peeling seems to be beneficial for macular edema secondary to RVO in patients treated within 1 month from the onset of symptoms. PPV with ILM peeling in ischemic RVO and nonischemic RVO improves visual acuity.

Purpose: Uveitis is a major cause of ocular morbidity in developed countries. It has been demonstrated that macular edema is a significant cause of decreased visual acuity and macular edema in these patients. In this article, we evaluate the long-term outcome of intravitreal bevacizumab in the treatment of refractory uveitic macular edema., Methods: In this retrospective, noncomparative, interventional case series, uveitic patients with macular edema who were refractory to conventional therapy and who were treated with intravitreal bevacizumab were identified and assessed. Best-corrected visual acuity and optical coherence tomography central macular thickness measurements were collected and analyzed with correlative statistical analysis, including the use of Student paired t-test, Kaplan-Meier, and linear regression analysis., Results: Twenty-nine eyes of 27 patients with diverse uveitic etiologies were analyzed and followed up at 1 year. Thirteen patients received a single intravitreal bevacizumab injection. Six patients required a second intravitreal bevacizumab injection, while 10 patients received combination therapy of intravitreal bevacizumab and triamcinolone acetonide. Baseline mean logMAR visual acuity was -0.59. At 1 year, the mean logMAR visual acuity was -0.42-/+ 0.36 (p=0.0045). Baseline mean central macular thickness was 383.66 microm. At 1 year, the mean thickness was 294.32-/+110.87 (p=0.0007)., Conclusions: Intravitreal bevacizumab is a useful and therapeutically beneficial agent in the treatment of refractory uveitic macular edema. Some patients will require adjunctive intravitreal bevacizumab injections or the use of combination therapy with intravitreal triamcinolone acetonide.

Purpose: To evaluate the additive effect of triamcinolone to bevacizumab in comparison to standard macular laser photocoagulation versus bevacizumab in the management of diabetic macular edema (DME)., Methods: In a prospective, randomized clinical trial, 130 eyes of 110 patients with type 2 diabetes with DME were included. Eligible eyes were randomly assigned to 1.25 mg intravitreal bevacizumab (42 eyes) (IVB group) or combination of 1.25 mg bevacizumab and 2 mg triamcinolone acetonide (41 eyes) (IVB+IVT group) or macular laser photocoagulation (47 eyes) (MPC). Central macular thickness (CMT) and visual acuity changes at week 6 and 16 were assessed., Results: The mean age of the patients was 57 -/+7 years. Patients were followed 16 weeks. At week 6, all the three groups showed significant reduction in CMT but the reductions for IVB and IVB+IVT were significantly more than MPC (p<0.001). At week 16, the response was not stable for IVB (p<0.001), but IVB+IVT maintained its superior status to MPC (p<0.001). At week 16, visual acuities were essentially unchanged for the two groups of MPC and IVB and improvement for IVB+IVT was marginal and at most was 0.1 log MAR. No patient developed uveitis, endophthalmitis, or thromboembolic event., Conclusions: Single intravitreal bevacizumab or triamcinolone plus bevacizumab injection brought about significantly greater macular thickness reduction in diabetic patients in comparison to standard laser treatment. However, the response for bevacizumab alone was short-lived. Reduction in macular thickness was only marginally associated with visual acuity improvement in the triamcinolone plus bevacizumab injection group.

Purpose: The purpose of this study was to assess macular function by multifocal electroretinography (mfERG) in eyes with diabetic macular edema (DME) after intravitreal triamcinolone acetonide (IVTA) injection., Methods: Fifteen eyes of 15 patients with DME scheduled for 4 mg IVTA injection were prospectively recruited. The response to treatment was monitored functionally by visual acuity (VA) measurement and mfERG and anatomically by foveal thickness measured by optical coherence tomography (OCT). The first-order kernel P1 mfERG responses from 0 to 7 degrees (central) and 7 to 25 degrees (peripheral) were grouped and analyzed. Changes in functional parameters (VAs and the P1 mfERG response amplitudes and peak latencies) and morphometric parameters (OCT foveal thickness) in eyes with DME 1 and 3 months after IVTA injection were compared with baseline values by Student t test., Results: The mean baseline logMAR value for VAs of the patients before treatment was 0.49+/-0.26. After treatment, it was 0.27+/-0.23 at 1 month and 0.26+/-0.18 at 3 months, and differences from pretreatment values were significant (for each, p<0.001). There were statistically significant decreases in the mean foveal thickness at 1 and 3 months after treatment compared with pretreatment values (for each, p<0.001). There were also statistically significant increases in the mean P1 response amplitude for both central and peripheral groups at all examinations compared with pretreatment (for each, p<0.001). The mean P1 peak latencies for both the central and peripheral groups were shortened, but not significantly., Conclusions: As well as the reduction in DME and improvement in VA, IVTA injection improves macular function as assessed by mfERG in diabetic patients.

Purpose: Diabetic macular edema (DME) causes visual loss in diabetic patients. Multifocal electroretinograms (mfERGs) have been used to assess macular function pre- and postvitrectomy for DME., Methods: A standard three-port pars plana vitrectomy with peeling of inner limiting membrane was performed in 25 eyes of 21 patients (13 male, 8 female) with DME. For each patient, visual acuity examination, measure of retinal thickness (using optical coherence tomography), and mfERGs were performed before and 1 week, 1 month, 3 months, and 6 months after vitrectomy., Results: Mean postoperative visual acuity was significantly improved (p<0.05, t test), with mean increase of 0.17 logMAR units; mean retinal thickness was significantly (p<0.001) decreased after surgery (from 537 microm to 298 microm). The increase of normalized amplitude of central ring was not significant; the mean P1 wave-amplitude increased from 0.33 to 0.40 mV; mean P1 wave-implicit time decreased 2.88 ms. We divided the patients into two groups: Group 1 (13 eyes), in which the visual recovery was less than 0.20 logMAR, and Group 2 (12 eyes), in which the visual recovery was greater than 0.20 logMAR. ERG results were statistically significantly different between the groups (p<0.025), when we consider the response recorded from the central ring. In Group 2 there is a marked reduction in implicit time of both ERGs waves, which was statistically significant for N1 wave (p=0.01). The changes of parameters of mfERG observed 6 months after surgery were consistent with those recorded just 1 week after surgery., Conclusions: Multifocal electroretinogram can be useful to predict functional prognosis in patients with diabetes who underwent vitrectomy for diabetic macular edema.

Purpose: To evaluate alterations in central retinal sensitivity following intravitreal triamcinolone injection in patients with diffuse diabetic macular edema that persisted after laser treatment., Methods: Fourteen eyes of 14 patients that received 4 mg 0.1 cc intravitreal triamcinolone underwent macular threshold test using computerized visual field analyzer before and after 1, 2, 3, and 5 months of triamcinolone injection. Pre- and postinjection values of total defect depth, total threshold, and best-corrected visual acuity were compared and correlated., Results: At the last follow-up, compared to baseline, visual acuity improved from 1.4+/-0.4 (logMAR, mean +/- standard deviation) to 1.0+/0.4 (p=0.01). Total defect depth tended to recover from 148+/-64 dB to 121+/-48 dB (p=0.12), and total threshold tended to increase from 241+/-87 dB to 271+/-68 dB (p=0.16), but these values did not reach significance. There was a significant correlation between baseline and 5 months postinjection values of total defect depth (rho=0.60, p=0.02), and of total threshold of light sensitivity (rho=0.55, p=0.04)., Conclusions: Best-corrected visual acuity was found improved in patients with diabetic macular edema 5 months after triamcinolone injection. Improvement in central retinal sensitivity did not reach significant level at the last follow-up. Macular threshold test may be a valuable tool in the follow- up of patients with diffuse diabetic macular edema after intravitreal triamcinolone injection.

Purpose: To evaluate the efficacy and safety of one intravitreal injection of 25 mg of triamcinolone acetonide as primary treatment for diffuse diabetic macular edema., Methods: Intravitreal triamcinolone acetonide injection was performed in 30 eyes with previously untreated diabetic macular edema. The main outcome measures were logMAR visual acuity (VA) and central macular thickness (CMT) at 1, 3, and 6 months. A secondary outcome was intraocular pressure progression., Results: Visual acuity results for 30 eyes that had a follow-up of at least 6 months are presented. Twenty of them were followed up to 10.1+/-2.38 months. Preoperatively, VA was 0.54+/-0.27. At 1, 3, and 6 months follow-up, VA was 0.44+/-0.29 (p=0.001), 0.43+/-0.28 (p=0.001), and 0.45+/-0.29 (p=0.006), respectively. Preoperatively, CMT was 417.3+/-143.5 microm. At 1, 3, and 6 months follow-up, CMT was 277.3 +74.0 microm (p<0.0001), 279.6+/-94.4 microm (p<0.0001), and 297.07+/-114.87 microm (p=0.002), respectively. For the 20 eyes with a follow-up of 10.1+/-2.38 months, VA was 0.5+/-0.25 and 0.50+/-0.32 at baseline and at the last follow-up visit, respectively (p>0.05). Preoperatively, intraocular pressure (IOP) was 15.13+/-1.48 mmHg. IOP was 18.26+/-2.71 mmHg, 20.07+/-4.27 mmHg, and 20.4+/-6.18 mmHg, at 1, 3, and 6 months, respectively (p<0.0001). Four eyes underwent uncomplicated filtrating surgery for intractable glaucoma., Conclusions: Intravitreal triamcinolone as primary treatment effectively increases VA and reduces CMT due to diffuse diabetic macular edema. Longer follow-up and randomized clinical trial are warranted. Safety results highlight the need to further study the relationship between triamcinolone and intraocular pressure.

Purpose: To evaluate safety and efficacy of intravitreal triamcinolone acetonide (TAAC) injections in the treatment of refractory pseudophakic cystoid macular edema (CME)., Methods: Seven eyes of six patients (age range: 50-74) with pseudophakic CME resistant to standard treatment received intravitreal injections of 4 mg of TAAC with all vehicle. Mean preinjection duration of CME was 18.3 months. A mean of 2.1+/-1.2 (range 1 to 4) treatments were performed in four eyes (57.1 %) when visual acuity deteriorated towards baseline levels. Visual acuity assessment, optical coherence tomography (OCT), and fluorescein angiography (FFA) were performed pre- and postoperatively to evaluate results of TAAC injections. Intraocular pressure (IOP) and complications related to treatment were assessed., Results: After 11.1+/-3.9 months, mean best-corrected visual acuity (BCVA) increased (p =0.019) from 20/132 to a best value of 20/38. Mean macular thickness decreased from 517.29+/-146.98 mm to a best value of 263.71+/-83.13 mm (p=0.0018). Area of fluorescein leakage decreased (p<0.0001) from 11.84+/-0.93 mm2 at baseline to a minimal value of 3.86+/-0.98 mm2. The anatomic and functional improvement appeared after 1 month from the intravitreal injection and persisted through at least 3 months of follow-up. At the end of follow-up BCVA, macular thickness, and area of fluorescein leakage did not differ from baseline. Four eyes (57.1 %) developed IOP values higher than 21 mmHg, controlled by topical treatment. Two patients developed an endophthalmitis-like reaction., Conclusions: Intravitreal TAAC was relatively safe and effective in resistant cases of pseudophakic CME with a temporary beneficial effect on visual acuity and macular edema.

Purpose: The authors studied the efficacy of intravitreal triamcinolone acetonide in a case series of patients with diffuse diabetic macular edema without evidence of vitreous-macular traction refractory to laser photocoagulation., Methods: Six eyes with clinically diffuse diabetic macular edema that failed to respond to at least two previous sessions of laser photocoagulation were included. The mean age of selected patients was 72.5+/-13.8 years, with a preoperative best-corrected visual acuity reduced to 1.48+/-0.18 logMar and a mean baseline intraocular pressure (IOP) of 15.17+/-2.64 mmHg. The authors also studied macular thickness measured by optical coherence tomography (OCT 2000 scanner, Humphrey Instruments, San Leandro, CA) - in the preoperative period it was 640.8+/-171.1 microm - and the fluorangiographic (Heidelberg Retina Angiograph, Heidelberg Engineering GmbH, Heidelberg, Germany) patterns, which showed pooling in tardy phases and leakage. Mean follow-up was 4 months., Results: In each patient the authors observed a significant improvement, both functionally and anatomically. Mean best-corrected visual acuity increased in the postoperative period to 0.94+/-0.53 logMar. No patient showed decline of visual acuity at the end of follow-up. Base line macular thickness was reduced in the postoperative period to 312.2+/-157.65 microm measured by OCT and fluorangiographic patterns showed a reduction of pooling and of leakage. The most common complications described in the literature were not observed and the increase of mean IOP in the postoperative period to 18.76+/-5.72 mmHg was not significant., Conclusions: Intravitreal triamcinolone acetonide may decrease macular edema and improve visual acuity in eyes with diffuse diabetic macular edema.