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

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

Comparison of corneal measurements in keratoconus eyes with two swept-source-optical coherence tomography devices and a Scheimpflug device.

PURPOSE: To assess the feasibility and reliability of biometric measurements taken with the Eyestar 900 device in keratoconus eyes in comparison with those taken with the Pentacam HR and IOLMaster 700. METHODS: Seventy-five eyes of 75 patients with keratoconus were included. The central corneal thickness (CCT), thinnest point of corneal thickness (TCT), axial length (AL), flat (K1) and steep (K2) anterior and posterior (Kp1, Kp2) keratometry, maximal keratometry (KMax) and anterior chamber depth (ACD) were compared between the Eyestar 900, Pentacam HR and IOLMaster 700. Reliability parameters such as the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated. Pearson's r was determined to assess the correlation between devices. RESULTS: A high repeatability (CoV < 1%) and intraclass correlation (ICC > 0.9) was found for all devices, led by AL, TCT, K1 and K2 (CoV 0.01-0.36%; ICC 0.994-1.00). The largest correlation between devices was found for AL (Eyestar vs. IOLMaster, r = 1.0), K1 (Eyestar vs. IOLMaster, r = 0.997) and ACD (Eyestar vs. IOLMaster, r = 0.995; Pentacam vs. IOLMaster, r = 0.987; Eyestar vs. Pentacam, r = 0.983), but there were significant differences in measured values between devices (p < 0.001), whereas the correlation was only slightly lower (r = 0.947 to 0.994) for KMax, CCT, TCT, K2, Kp1 and Kp2. CONCLUSION: Keratometric and axial length measurements with the Eyestar 900 were feasible and revealed a high repeatability and a good correlation to the other devices in eyes with keratoconus.

Intravitreal Dexamethasone as a Rescue for Anti-Vascular Endothelial Growth Factor Therapy in Neovascular Age-Related Macular Degeneration with Persistent Disease Activity and High Treatment Demand.

Purpose: To assess the impact of switching to, or adding, an intravitreal dexamethasone implant (Dex; Ozurdex®) in anti-vascular endothelial growth factor (VEGF) therapy on disease stability and treatment intervals in eyes with neovascular age-related macular degeneration (nAMD) and persistent disease activity and high treatment demand. Methods: This retrospective noncomparative multicenter longitudinal case series included pseudophakic eyes with nAMD and persistent retinal fluid despite regular anti-VEGF therapy (ranibizumab or aflibercept) that received at least 1 intravitreal Dex implant. Visual acuity, central retinal thickness (CRT), and intraocular pressure were recorded before, and after, the addition of Dex to anti-VEGF therapy. Results: Sixteen eyes of 16 patients met the inclusion criteria of persistent fluid despite anti-VEGF therapy, under treatment intervals of ≤7 weeks in 14 instances. Patients were 80.9 ± 7.4 years old and had received 25.5 ± 17.4 anti-VEGF injections before Dex over a period of 36.4 ± 21.9 months before switching. The treatment interval increased from 5.5 ± 3.2 weeks between the last anti-VEGF and first Dex injection to 11.7 ± 7.3 weeks thereafter (P = 0.022). CRT remained stable (385.3 ± 152.1, 383.9 ± 129.7, and 458.3 ± 155.2 µm before switching as well as 12 and 24 months after switching; P = 0.78 and P = 0.36, respectively). An insignificant mean short-term early increase in visual acuity was not sustained over time. Conclusions: The addition of Dex resulted in a relevant and sustained increase in treatment intervals, whereas CRT and visual acuity remained stable in these difficult-to-treat eyes. It may be discussed whether inflammation or other steroid-responsive factors play a significant role in cases of nAMD with nonsatisfactory responses to anti-VEGF.

Efficacy of TNF-Alpha Inhibitors to Control Inflammation and Prevent Secondary Complications in Non-Infectious Uveitis: A Real-Life Experience from Switzerland.

PURPOSE: To evaluate the efficacy of systemic tumor necrosis factor-alpha inhibitors (TNFi) in the treatment of non-infectious uveitis (NIU). METHODS: This Swiss multicenter retrospective cohort study included patients with NIU requiring TNFi during the period from 2001 to 2018. Risk factors for the occurrence of new complications were identified using Cox regression analysis and hazard ratios (HR). RESULTS: Seventy-one patients (126 eyes; mean age 40.6 ± 14.4 years, mean duration of uveitis 46.0 ± 61.8 months) were followed for 40.2 ± 17.3 months after addition of TNFi. Under TNFi, visual acuity improved from 0.2 ± 0.3 to 0.1 ± 0.3 logMAR (p < 0.001). The portion of patients under systemic corticosteroids decreased from 81.7% to 25.4% (p < 0.001), while that for conventional synthetic disease-modifying anti-rheumatic drugs insignificantly decreased from 63.4% to 50.7% (p > 0.05). In 80.2% of eyes, complications were present at baseline with epiretinal gliosis (39.7%), cataract (41.3%) and macular edema (ME; 27.8%) being the most common. New complications under TNFi were encountered in 49.2% of eyes, also including recurrence (5 eyes) or new onset of ME (14 eyes). The need for switching of TNFi was associated with further complications (HR 3.78, p = 0.012). CONCLUSION: Although the efficacy and tolerability of TNFi in a real-life setting are favorable, treatment is often initiated late, i.e., after many eyes have already developed complications. Even with TNFi, new complications, particularly ME, cannot be completely avoided. Further research is needed to assess the impact of earlier initiation of TNFi therapy.

Association of inflammation-related markers and diabetic retinopathy severity in the aqueous humor, but not serum of type 2 diabetic patients.

Diabetic retinopathy (DR) is a frequent microvascular complication of diabetes mellitus, and inflammatory pathways have been linked to its pathogenesis. In this retrospective, observational pilot study, we aimed to compare the concentrations of four inflammation-related proteins, ZAG, Reg-3a, elafin and RBP-4, in the serum and aqueous humor of healthy controls and diabetic patients with different stages of DR. The concentrations of VEGF-A, IL-8, IL-6 were determined in parallel as internal controls. In the serum, we did not find significant differences in the concentrations of target proteins. In the aqueous humor, higher levels of ZAG, RBP-4, Reg-3a and elafin were observed in advanced nonproliferative DR (NPDR)/ proliferative DR (PDR) compared to controls. The levels of ZAG and RBP-4 were also higher in advanced NPDR/PDR than in nonapparent DR. Normalization of target protein concentrations to the aqueous humor total protein demonstrates that a spill-over from serum due to breakage of the blood-retina barrier only partially accounts for increased inflammation related markers in later stages. In conclusion, we found elevated levels of Reg-3a, RBP-4, elafin and ZAG in advanced stages of diabetic retinopathy. Higher levels of pro-inflammatory proteins, Reg-3a and RBP-4, might contribute to the pathogenesis of diabetic retinopathy, as the parallel increased concentrations of anti-inflammatory molecules elafin and ZAG might indicate a compensatory mechanism.

Functional Outcomes of Brolucizumab-Induced Intraocular Inflammation Involving the Posterior Segment-A Meta-Analysis and Systematic Review.

Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1-6) IVB injections. A mean change in visual acuity of -14.6 ± 21.0 (median -6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of -25.3 ± 27.1 and -2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI.

IOP-lowering and drug-sparing effects of trabectome surgery with or without cyclodialysis ab interno.

PURPOSE: To compare the postoperative intraocular pressure (IOP) after ab interno trabeculectomy (AIT; trabectome surgery) alone or combined with cyclodialysis ab interno (AITC). PATIENTS AND METHODS: Forty-three eyes with insufficiently controlled open-angle glaucoma were included in this consecutive case series. All eyes received AIT, combined with phacoemulsification and IOL-implantation in phakic instances, with or without additional cyclodialysis ab interno. Postoperative visual acuity, IOP, number of IOP-lowering medications and complications were registered over 12 months. RESULTS: A total of 19 eyes (14 patients) received AIT and 24 (19 patients) received AITC. Both groups were comparable for baseline IOP (AIT: 19.7 ± 8.2 mmHg; AITC: 19.4 ± 6.8 mmHg; p = 0.96), there was a comparable IOP reduction after 6 months (AIT: - 3.8 ± 12.3, median (interquartile range (IQR)): - 3.8 (- 7.8-4.8) mmHg; AITC: - 4.9 ± 8.3, median (IQR): - 2.0 (- 10.8-2.0) mmHg; p = 0.95) and 12 months (AIT: - 4.3 ± 6.6, median (IQR): - 4.0 (- 8.0 to - 1.0) mmHg; AITC: - 3.7 ± 6.7, median (IQR): - 1.5 (- 5.5 to - 0.5) mmHg; p = 0.49). While final visual acuity was similar between the groups, they differed regarding topical IOP-lowering medications (baseline: AIT 2.9 ± 1.2 and AITC 2.9 ± 1.2; 1 year after surgery: AIT 2.6 ± 1.5 (p = 0.16) and AITC 1.3 ± 1.3; p < 0.001)). Depending on the definition, a complete or qualified success of 33.4-45.8% was achieved in AITC compared to 15.8-21.1% in AIT. CONCLUSION: The additional suprachoroidal outflow when AIT is combined with cyclodialysis ab interno (AITC) seems to result in an additional drug sparing effect for at least 1 year without critical safety signals. Thus, AITC might be further investigated prospectively prior to advocating its use in routine minimally invasive glaucoma surgery.

Long-term Efficacy of TNF-alpha Inhibitors on Persistent Uveitic Macular Edema: A Swiss Multicenter Cohort Study.

PURPOSE: To assess the efficacy of tumor necrosis factor-alpha inhibitors (TNFi) on uveitic macular edema (ME) unresponsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). METHODS: This multicenter retrospective study included patients with uveitic ME persisting despite csDMARDs. The effect of an additional TNFi on central retinal thickness (CRT), best corrected visual acuity (BCVA) and corticosteroid need was evaluated. RESULTS: Thirty-five eyes (26 patients, mean age 42.9 ± 15.2 years) were included. CRT decreased from 425 ± 137 µm to 294 ± 66 µm (p < .001) and 280 ± 48 µm (p < .001) at 1 and 4 years of follow-up, respectively. BCVA improved from 0.28 ± 0.22 to 0.21 ± 0.48 (1 year, p = .013) and 0.08 ± 0.13 logMAR (4 years, p = .002). The proportion of patients requiring systemic corticosteroids decreased from 88.5% to 34.8% (1 year) and 15.4% (4 years). CONCLUSION: The addition of a TNFi resulted in an improvement of CRT and BCVA for up to 4 years in uveitic ME but rescue treatments were needed for some patients.

Aqueous Humor Apolipoprotein Concentration and Severity of Diabetic Retinopathy in Type 2 Diabetes.

An imbalance of plasma apolipoproteins has been linked to diabetic retinopathy (DR); however, there is scarce information regarding their presence in the aqueous humor (AH) and their role in DR. Here, we aimed at analysing the relationship between apolipoprotein concentrations in human AH and the severity of DR. Concentrations of apolipoproteins were measured retrospectively in patients with type 2 diabetes mellitus (T2DM) without DR (n = 23), with mild to moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) (n = 14) using a multiplex immunoassay. Compared to the non-apparent DR group, the concentrations of seven apolipoproteins were elevated in advanced NPDR/PDR (Apo AI 5.8-fold, Apo AII 4.5-fold, Apo CI 3.3-fold, Apo CIII 6.8-fold, Apo D 3.3-fold, Apo E 2.4-fold, and Apo H 6.6-fold). No significant differences were observed in apolipoprotein concentrations between patients with non-apparent DR and healthy controls (n = 17). In conclusion, the AH concentrations of apolipoproteins AI, AII, CI, CIII, D, E, and H increased in advancing stages of DR, suggesting their role in the pathogenesis of DR, which deserves further examination.

Functional Outcome After Macular Hole Surgery: Comparison of Standard Perimetry with Microperimetry.

Purpose: To compare the predictive value of macular perimetry and microperimetry for visual outcomes after vitrectomy with internal limiting membrane (ILM) peeling in full-thickness macular holes (MH). Methods: This retrospective, non-randomized case series refers to 100 eyes undergoing vitrectomy with ILM peeling. Best-corrected visual acuity (BCVA), standard 12° perimetry and microperimetry were perioperatively recorded. A possible predictive value of the preoperative findings on postoperative visual function (PVF) was assessed. Results: Independent of the preoperative minimal MH size (range: 55-752 µm), all 100 MHs were closed. BCVA improved from 56.3 ± 12.8 to 74.8 ± 9.2 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters after six months and retinal fixation stability enhanced. We found a positive correlation between BCVA and macular sensitivity 6 months postoperatively in microperimetry (r = 0.48, p < 0.010) and 12° perimetry (r = 0.45, p < 0.014), as well as with mean defect (r = 0.48, p < 0.01 and r = 0.44, p < 0.017, respectively). A correlation between preoperative visual function indices and PVF was not established. Conclusion: Microperimetry and standard perimetry are equally suitable for describing perioperative retinal function in idiopathic MH. While the indices of both methods correlate comparably well with BCVA, they cannot predict PVF. This may be partially explained by the area covered by perimetry, compared to which the size of the MH is of inferior relevance.

Outer retinal features in OCT predict visual recovery after primary macula-involving retinal detachment repair.

PURPOSE: To find predictive markers for the visual potential in optical coherence tomography (OCT) one month after surgical repair of macula-involving rhegmatogenous retinal detachment (miRD) with and without internal limiting membrane (ILM) peeling. METHODS: This retrospective single-center, single-surgeon cohort study included 74 patients who underwent pars plana vitrectomy (PPV) for primary miRD between January 2013 and August 2020 with follow-up examinations for at least 6 months. Patients developing recurrent detachments, media opacities, or with an axial length over 27 mm were excluded from the analysis. LogMAR visual (VA) and LogRAD reading acuity (RA) ± standard deviation (SD), and OCT measurements 6 months after surgery were compared to OCT and VA measurements one month after surgery using multiple linear regression analysis for predictions. RESULTS: VA increased from 0.34 ± 0.25 at one month to 0.22 ± 0.21 after 6 months [p < 0.001; effect size = -0.662, 95% confidence interval (CI): -(0.99-0.33)]. The continuity of the external limiting membrane (ELM) and ellipsoid zone (EZ) increased between 1 and 6 months. Subfoveal ELM integrity after one month predicted VA [adjusted R2 of 8.0%, F(2, 71) = 4.17, p = 0.018] and RA [adjusted R2 of 29%, F(2, 27) = 6.81, p = 0.002] after 6 months. EZ integrity had a less pronounced predictive effect on VA and RA. ELM integrity after 1 month correlated with better reading acuity after 6 months (p = 0.016). CONCLUSION: VA and morphological OCT parameters improve between 1 and 6 months after surgery for miRD. The grade of ELM is a better predictor for RA than for VA, explaining more variance.

Continued anti-VEGF treatment does not prevent recurrences in eyes with stable neovascular age-related macular degeneration using a treat-and-extend regimen: a retrospective case series.

BACKGROUND: The continuation of anti-vascular endothelial growth factor (anti-VEGF) treatment after achieving stability in patients with neovascular age-related macular degeneration has generally been advocated. In our own patients, we thought to assess whether continued anti-VEGF treatment is capable of preventing recurrences. METHODS: In this retrospective observational case series, patients with stable disease either opted to continue treatment every 12-14 weeks (Group 1) or stopped treatment with subsequent follow-up visits every 8-12 weeks (Group 2). RESULTS: Of the 103 eyes of 103 patients achieving stability, 49 eyes continued treatment (Group 1), whereas treatment was stopped in 54 eyes undergoing regular follow-up (Group 2). Recurrent disease was observed in 21 (42.9%) and 33 (61.1%) cases in Group 1 and Group 2, respectively (p = 0.08). Time between achieving stable disease and recurrence was comparable between Group 1 and Group 2 (11.1 ± 8.2 months vs. 9.2 ± 6.7 months; p = 0.43). The number of visits between achieving stability and disease recurrence was similar, but not the number of injections (3.5 ± 2.0 vs. 0.2 ± 0.4; p < 0.001). CONCLUSIONS: Continuing anti-VEGF therapy after achieving functional and morphological stability every 12-14 weeks does not prevent recurrences. Patients deserve to be informed of a potential lifetime risk of recurrences, even under continued therapy.

Postoperative proliferative vitreoretinopathy development is linked to vitreal CXCL5 concentrations.

The specific changes linked to de novo development of postoperative PVR have remained elusive and were the object of the underlying study. Vitreous fluid (VF) was obtained at the beginning of vitrectomy from 65 eyes that underwent vitrectomy for primary rhegmatogenous retinal detachment (RRD) without preoperative PVR. Eyes developing postoperative PVR within 6 months after re-attachment surgery were compared to those which did not regarding the preoperative concentrations of 43 cytokines and chemokines in the VF, using multiplex beads analysis. For all comparisons Holm's correction was applied in order to control for multiple comparisons. Twelve out of 65 eyes (18.5%) developed PVR postoperatively. While 12 of the chemokines and cytokines presented concentration differences on a statistical level of p < 0.05 (CXCL5, CCL11, CCL24, CCL26, GM-CSF, IFN-γ, CCL8, CCL7, MIF, MIG/CXCL9, CCL19, and CCL25), CXCL5 was the only cytokine with sufficiently robust difference in its VF concentrations to achieve significance in eyes developing postoperative PVR compared to eyes without PVR. CXCL5 may represent a potent biomarker for the de novo development of postoperative PVR. In line with its pathophysiological role in the development of PVR, it might serve as a basis for the development of urgently needed preventive options.

Switching to Brolucizumab in Neovascular Age-Related Macular Degeneration Incompletely Responsive to Ranibizumab or Aflibercept: Real-Life 6 Month Outcomes.

Purpose: The aim of this study was to evaluate the effect of switching treatment in eyes with neovascular age-related macular degeneration (nAMD) and treatment intervals of ≤6 weeks to brolucizumab. Methods: In this prospective series, eyes with persisting retinal fluid under aflibercept or ranibizumab every 4-6 weeks were switched to brolucizumab. Visual acuity (BCVA), reading acuity (RA), treatment intervals, central subfield thickness (CST), and the presence of intra- and subretinal fluid were recorded over 6 months. Results: Seven of 12 eyes completed the 6 month follow-up and received 4.4 ± 0.5 brolucizumab injections within 28.0 ± 2.8 weeks. Treatment intervals increased from 5.3 ± 0.9 weeks to 9.0 ± 2.8 weeks (95% confidence interval of extension (CI): 1.6 to 5.9). BCVA improved from 67.8 ± 7.2 to 72.2 ± 7.5 (95% CI: -0.3 to 9.1) ETDRS letters, RA improved from 0.48 ± 0.15 to 0.31 ± 0.17 LogRAD (95% CI: 0.03 to 0.25), and CST improved from 422.1 ± 97.3 to 353.6 ± 100.9 µm (95% CI: -19.9 to 157.1). Treatment was terminated early in five eyes (two intraocular inflammations with vascular occlusion without vision loss, one stroke, and two changes in the treatment plan). Conclusions: Improvement in visual performance and longer treatment intervals in our series over 6 months indicate the potential of brolucizumab to reduce the treatment burden in nAMD, while two instances of intraocular inflammation were encountered.

Ocular TGF-ß, Matrix Metalloproteinases, and TIMP-1 Increase with the Development and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is a sight-threatening late complication of diabetes mellitus (DM). Even though its pathophysiology has not been fully elucidated, several studies suggested a role for transforming growth factor- (TGF-) ß, matrix metalloproteinases (MMPs), and tissue inhibitors of matrix metalloproteinase (TIMP) in the onset and progression of the disease. Consequently, the aim of this study was to analyze the concentrations of TGF-ß1, TGF-ß2, TGF-ß3, MMP-3, MMP-9, and TIMP-1 in patients with different stages of DR in order to identify stage-specific changes in their concentrations during the progression of the disease. Serum and aqueous humor (AH) samples were collected during intraocular surgery, and eyes were classified into the following groups: healthy controls (n = 17), diabetic patients with non-apparent DR (n = 23), mild/moderate nonproliferative DR (NPDR) (n = 13), and advanced NPDR/proliferative DR (PDR) without vitreal hemorrhage (n = 14). None of the patients had been under anti-VEGF or laser treatment within six months prior to surgery. In the AH, TGF-ß1 levels increased in advanced NPDR/PDR by a factor of 5.5 compared to the control group. Similarly, an increase in MMP-3 and TIMP-1 levels in the AH was evident in the later stages of DR, corresponding to a 7.7- and 2.4-fold increase compared to the control group, respectively, whereas serum levels of the studied proteins remained similar. In conclusion, increased concentrations of TGF-ß1, MMP-3, and TIMP-1 in the AH, but not in the serum, in advanced NPDR/PDR indicate that the intraocular regulation for these cytokines is independent of the systemic one and suggest their involvement in the progression of DR.

Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland.

OBJECTIVE: To assess the long-term visual outcomes in eyes with symptomatic diabetic macular oedema (DME) under intravitreal treatment (IVT) in a clinical routine setting. METHODS: Patients with newly diagnosed DME were included in this retrospective study if they had received at least three IVTs and a follow-up period ≥ 2 years. Due to altered treatment patterns since the approval of ranibizumab for DME in 2012, patients were subdivided according to their first IVT before 2013 (group 1) or thereafter (group 2). The primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time. RESULTS: Of 217 eyes (191 patients) with DME, 151 eyes (117 patients) fulfilled the inclusion criteria (63 eyes in the first period, 88 in the second period). Mean follow-up time was 7.9 ± 3.1 (group 1) and 4.1 ± 1.4 years (group 2; p < 0.001). Visual gains were similar in the first year (group 1: + 5.3 ± 15.5, group 2: + 7.3 ± 12.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; p = 0.44), but not thereafter (after 2 years in group 1: + 4.4 ± 15.0, group 2: + 8.3 ± 13.0 ETDRS letters; p = 0.038). During the first year, group 1 patients received less clinical examinations (group 1: 6.6 ± 3.3, group 2: 7.5 ± 2.1; p = 0.007) and less injections (group 1: 3.6 ± 2.7, group 2: 6.1 ± 2.7; p < 0.001). CONCLUSION: A greater visual gain, in response to more intensive treatment during the first year, was maintained for at least 5 years in group 2 subjects. Our data confirm that in a real-world setting, early intensive treatment results in satisfying long-term visual outcomes.

Impact of Vitreal Tamponade on Functional Outcomes in Vitrectomy with ILM Peeling in Primary Macula-Involving Retinal Detachment: A Retrospective Analysis.

BACKGROUND: To compare visual outcomes of vitrectomy with internal limiting membrane (ILM) peeling and failed SF6 gas tamponade requiring silicone oil (SO) in a second procedure with primary SO tamponade in fovea-involving retinal detachment (FiRD). METHODS: Retrospective analysis of 82 eyes with retinal detachment and mild, but without advanced proliferative retinopathy (PVR ≥C2) requiring vitrectomy for FiRD. Group 1 comprised 23 eyes that underwent SF6 tamponade resulting in re-detachment requiring revision surgery with secondary SO tamponade. Based on the intraoperative findings, group 2 patients had primarily received SO as vitreal tamponade (n=59). Patients receiving a scleral buckle surgery or with advanced PVR as well as patients with underlying vascular diseases and uveitis were excluded. RESULTS: Preoperative visual acuity (Early Treatment Diabetic Retinopathy Study letters) was 13.5 ± 19.1 in group 1 and 14.0 ± 18.3 in group 2 (p=0.44). Twelve months after first surgery for FiRD, visual acuity was 49.8 ± 19.8 in group 1 and 51.7 ± 18.7 letters in group 2 (p=0.63). Re-detachment after SO removal requiring revision surgery developed in 17.4 (n=4) and 15.3% (n=9) cases. CONCLUSION: Our findings suggest that if retinal traction is completely relieved at the end of surgery, vitrectomy with ILM peeling and SF6 may, if successful, improve the functional outcomes in instances with visual potential, ie, a foveal detachment of short duration despite the presence of a mild to moderate PVR, but with the inherent increased risk of re-detachment requiring further intervention and the use of a SO tamponade. Hence, secondary SO installation during re-vitrectomy after failed primary reattachment surgery results in similar functional outcomes as primary oil filling.

Risks and Challenges in Interpreting Simultaneous Analyses of Multiple Cytokines.

Purpose: To determine the inherent risks of handling results below the lowest detectable value in the analysis of multiple cytokines in the aqueous humor of patients with retinal diseases by comparing possible statistical strategies to lower the risk of mis interpretation or over interpretation of results. Furthermore, in analyzing multiple cytokines simultaneously, the challenge of multiple comparison arises. Methods: The analyses were based on parallel testing of 43 cytokines in 58 aqueous humor samples from patients with macular hole or epiretinal membrane. Substitution of values below the detection limit with 0.1 ×, 0.5 ×, or 1.0× of the lowest level of quantitation was compared with handling as missing value. The impact of correction for multiple comparisons was assessed using the Holm correction. Results: When comparing macular hole with epiretinal membrane, not substituting the missing data revealed a difference (P < 0.05) for five compared with wight cytokines after their substitution, indicating an increased risk for under-estimating group differences (type II error). Correcting for multiple comparisons revealed a relevant risk of over estimating group differences (type I error). Conclusions: Physiologic cytokine concentrations in ocular fluids typically range at or below the lowest level of quantitation. Handling of results below this cutoff as missing leads to increased type II errors. Not correcting for multiple comparisons increases the risk of a type I error. Taken together, both harbor a systematic inherent risk of misinterpretation of the results. Translational Relevance: Ignoring the inherent risks of data misinterpretation in analyses of ocular fluid samples may result in mis leading conclusions regarding their biological relevance.