Reduction In Central Macular Thickness Research Articles

Influence of baseline diabetic retinopathy status on initial anatomical response of intravitreal ranibizumab therapy for diabetic macular oedema.

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)>300 μm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 μm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 μm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 μm. The mean changes were 95.8±101.4 μm for G1, 137.2±112.9 μm for G2, and 148.9±126.9 μm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.

Comparison of Conbercept with Ranibizumab for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion

ABSTRACTPurpose: To confirm the therapeutic efficacy of conbercept for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO).Methods: In this prospective, randomized, and comparative study, patients were randomized and divided into conbercept (n = 18) and ranibizumab (n = 17) groups. After an initial intravitreal injection of either conbercept or ranibizumab, a pro re nata (PRN) strategy was adopted based on loss of visual acuity (VA) or increase in central macular thickness (CMT).Results: All patients were followed for ≥6 months. Baseline best-corrected visual acuities (BCVAs) were 0.67 ± 0.37 and 0.511 ± 0.23 logMAR in the conbercept and ranibizumab groups, respectively (p = 0.087, t-test). Baseline CMTs were 512.5 ± 115.22 and 491.23 ± 114.72 µm in the conbercept and ranibizumab groups, respectively (p = 0.993, t-test). Significant improvements in BCVA and reduction of CMT were observed in both groups at each follow-up visit and compared to baseline values (p < 0.05, t-test). No significant differences in improvement of BCVA (p > 0.05, t-test) or reduction of CMT (p > 0.05, t-test) were noted in either group. Mean numbers of injections were 2.28 ± 0.96 and 2.65 ± 1.17 for the conbercept and ranibizumab groups, respectively (p = 0.478, t-test), with no statistically significant differences between the two groups.Conclusion: Intravitreal injection of conbercept is shown to be safe and effective for the treatment of ME secondary to BRVO, based on 6-month follow-up data.

Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema

PurposeTo analyse the effects of intravitreal dexamethasone implant in patients suffering from diabetic macular oedema (DME) on the basis of their visual and functional response to antivascular endothelial growth factor...

Clinical efficacy of intravitreal conbercept injection and macular grid pattern photocoagulation in treating macular edema secondary to non-ischemic branch retinal vein oclussion

Objective To study and compare the clinical efficacy between intravitreal conbercept injection and (or) macular grid pattern photocoagulation in treating macular edema secondary to non-ischemic branch retinal vein occlusion (BRVO). Methods Ninety eyes of 90 patients diagnosed as macular edema secondary to non-ischemic BRVO were enrolled in this study. Forty-eight patients (48 eyes) were male and 42 patients (42 eyes) were female. The average age was (51.25±12.24) years and the course was 5–17 days. All patients were given best corrected visual acuity (BCVA), intraocular pressure, slit lamp with preset lens, fluorescence fundus angiography (FFA) and optic coherent tomography (OCT) examination. The patients were divided into conbercept and laser group (group Ⅰ), laser group (group Ⅱ) and conbercept group (group Ⅲ), with 30 eyes in each group. The BCVA and central macular thickness (CMT) in the three groups at baseline were statistically no difference (F=0.072, 0.286;P=0.930, 0.752). Patients in group Ⅰ received intravitreal injection of 0.05 ml of 10.00 mg/ml conbercept solution (conbercept 0.5 mg), and macular grid pattern photocoagulation 3 days later. Group Ⅱ patients were given macular grid pattern photocoagulation. Times of injection between group Ⅰ and Ⅲ, laser energy between group Ⅰ and Ⅱ, changes of BCVA and CMT among 3 groups at 1 week, 1 month, 3 months and 6 months after treatment were compared. Results Patients in group Ⅰ and Ⅲ had received conbercept injections (1.20±0.41) and (2.23±1.04) times respectively, and 6 eyes (group Ⅰ) and 22 eyes (group Ⅲ) received 2-4 times re-injections. The difference of injection times between two groups was significant (P<0.001). Patients in group Ⅱ had received photocoagulation (1.43±0.63) times, 9 eyes had received twice photocoagulation and 2 eyes had received 3 times of photocoagulation. The average laser energy was (96.05±2.34) μV in group Ⅰ and (117.41±6.85) μV in group Ⅱ, the difference was statistical significant (P=0.003). BCVA improved in all three groups at last follow-up. However, the final visual acuity in group Ⅰ and group Ⅲ were better than in group Ⅱ (t=4.607, –4.603;P<0.001) and there is no statistical significant difference between group Ⅲ and group Ⅰ (t=–0.802,P=0.429). The mean CMT reduced in all three groups after treating for 1 week and 1 month, comparing that before treatment (t=–11.855, –10.620, –10.254;P<0.001). There was no statistical difference of CMT between group Ⅰand Ⅲ at each follow up (t=0.404, 1.723, –1.819, –1.755;P=0.689, 0.096, 0.079, 0.900). CMT reduction in group Ⅰ was more than that in group Ⅱ at 1 week and 1 month after treatments (t=–4.621, –3.230;P<0.001, 0.003). The CMT in group Ⅲ at 3 month after treatment had increased slightly comparing that at 1 month, but the difference was not statistically significant (t=1.995,P=0.056). All patients had no treatment-related complications, such as endophthalmitis, rubeosis iridis and retinal detachment. Conclusions Intravitreal conbercept injection combined with macular grid pattern photocoagulation is better than macular grid pattern photocoagulation alone in treating macular edema secondary to non-ischemic BRVO. Combined therapy also reduced injection times comparing to treatment using conbercept injection without laser photocoagulation. Key words: Retinal vein occlusion/therapy; Macular edema /therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Laser coagulation

Intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases

PurposeTo investigate the short-term outcomes after intravitreal injection of ziv-aflibercept in the treatment of choroidal and retinal vascular diseases. MethodsThirty-four eyes of 29 patients with age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion (RVO) received a single dose intravitreal injection of 0.05 ml ziv-aflibercept (1.25 mg). Visual acuity, spectral domain optical coherence tomography (SD-OCT) activity, and possible side effects were assessed before and at 1 week and 1 month after the intervention. ResultsAt 1 month after treatment, mean central macular thickness (CMT) significantly decreased from 531.09 μm to 339.5 μm (P < 0.001), and no signs of side effects were observed in any subject. All patients responded to treatment in terms of reduction in CMT. The improvement in visual acuity was statistically non-significant. ConclusionOur findings suggest that a single dose intravitreal injection of ziv-aflibercept may have acceptable relative safety and efficacy in the treatment of patients with intraocular vascular disease.The trial was registered in the Iranian Registry of Clinical Trials (IRCT2015081723651N1).

High-Dose (2.5 mg) Intravitreal Bevacizumab as Rescue Therapy for Persistent Postradiation Cystoid Macular Edema

Background/Aims: To investigate the efficacy of intravitreal high-dose (2.5 mg/0.1 mL) bevacizumab as rescue therapy for postradiation cystoid macular edema (CME) resistant to standard-dose (1.25 mg/0.05 mL) bevacizumab. Methods: Retrospective, interventional case series. Results: Fifteen eyes of 15 patients were included. Eyes were treated with a mean of 10 standard-dose (1.25 mg) bevacizumab injections but failed to show CME resolution. Following 3 monthly treatments of high-dose (2.5 mg) bevacizumab, mean central macular thickness (CMT) reduced significantly from 406 ± 100 to 360 ± 83 μm (p = 0.01) and mean logMAR visual acuity improved from 0.55 ± 0.17 (Snellen 20/71) to 0.48 ± 0.21 (Snellen 20/60, p = 0.07). At the final follow-up of 9 months, CMT was 395 ± 124 μm (p = 0.67) and visual acuity was 0.51 ± 0.23 (Snellen 20/65, p = 0.22). Five eyes (30%) had a >10% reduction in CMT at the final follow-up. In these eyes, the observed CMT reduction was statistically significant (p = 0.04) and logMAR visual acuity was significantly better (p ≤ 0.01) compared to the remainder of the cohort. Conclusions: Overall, the use of high-dose (2.5 mg) bevacizumab did not result in a sustained, significant improvement in CMT and visual acuity outcomes following incomplete response to standard-dose (1.25 mg) bevacizumab. However, a minority of eyes exhibited favorable response with significant CMT reduction.

Comparison between “early” or “late” intravitreal injection of dexamethasone implant in branch (BRVO) or central (CRVO) retinal vein occlusion: six-months follow-up

Aim: The aim of this study was to compare early and late injections of intravitreal dexamethasone implant in patients affected by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) with a six-months follow-up. We assessed whether an earlier treatment start (within seven days from diagnosis) could be more beneficial than a delayed (or late) treatment start (after seven days).Materials and methods: The study included 81 patients (81 eyes) affected by retinal vein occlusion. Best corrected visual acuity was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS) while central macular thickness (CMT) was measured by spectral-domain optical coherence tomography.Results: Both types of patients had a positive therapeutic response to dexamethasone, with an increase in visual acuity (ETDRS) and CMT reduction. CRVO patients were characterized by lower ETDRS values at baseline and at the end of the follow-up as compared to BRVO. CRVO patients showed higher CMT values at baseline, after three and six months from injection. No significant differences in therapeutic response to dexamethasone were observed between patients treated early or late, regardless of RVO type.Conclusions: This study demonstrates that the therapeutic properties of dexamethasone implant are not significantly influenced by an early or late treatment start in patients affected by BRVO and CRVO, although its therapeutic efficacy seems greater in the former type.

Efficacy and safety of triamcinolone acetonide posterior subtenon injection in patients with diabetic maculopathy

Introduction: Diabetic maculopathy (DM) is the main cause of visual impairment of the working population. Optical coherence tomography and fluorescein angiography give us a precise insight into retinal changes. In recent years, pharmacological treatment of DM is increasing. Posterior subtenon application is accompanied by a smaller percentage of complications compared to intravitreal application. Aim: The aim is to assess the efficacy and safety of triamcinolone acetonide (TA) posterior subtenon injection in the treatment of DM, by measuring intraocular pressure (IOP), central macular thickness (CMT) and visual acuity, before and two months after. Material and methods: The retrospective study included 49 patients admitted during 2016, for posterior subtenon injection of TA in the DM treatment, at Daily Hospital, for the treatment of vascular diseases of the eye and the macula Department of Ophthalmology, Clinical Center of Serbia. Data were collected from medical records on gender, age, type of retinopathy and visual acuity, IOP and CMT, before and two months after intervention. Results: The average age of patients was 63 ± 9.5 years. Out of 49 patients tested, 30.61% were female and 69.39 % were male. The frequency of non-proliferative diabetic retinopathy (NPDR) in the study was 53.6%. There was a statistically significant difference in visual acuity and CMT, before and two months after the intervention, but there was no correlation between the improvement of visual acuity and CMT reduction. There was no statistically significant difference in IOP, before and two months after intervention. Conclusion: The most common type of diabetic retinopathy in this study was NPDR. After posterior subtenon application of TA, there was a significant increase in visual acuity and CMT reduction, but reduction of CMT is not connected with the increase of visual acuity. Posterior subtenon TA application is not accompanied by a significant increase in IOP, and it is an effective and relatively safe way of treating DM.

The VEGF Treatment of AMD Switch Study (The vTAS Study).

To evaluate the effect of aflibercept on anatomic and visual outcomes in patients with choroidal neovascularization (CNV) previously treated with intravitreal ranibizumab with persistent fluid on optical coherence tomography (OCT). Prospective, open-label study. Eighteen patients (19 eyes) with CNV being treated with monthly ranibizumab, with persistent fluid on OCT, were switched to intravitreal aflibercept injections at intervals of up to 8 weeks. The primary outcome was the proportion of patients maintaining vision [<5 letter loss in visual acuity (VA)] at week 48. Secondary outcomes included the change in VA and central macular thickness (CMT) and the frequency of treatment necessary along with the safety of intravitreal aflibercept. Forty-eight weeks after switching to aflibercept, 16/19 eyes had maintained VA. There was a median increase in vision of 5 letters [interquartile range (IQR): 0, 15; P = 0.06)] and median CMT was reduced from 313 µm (IQR: 214, 334) to 258 µm (IQR: 200, 299; P = 0.02). After stratification by fluid location the reduction in CMT was statistically significant for eyes with intraretinal fluid (IRF) at baseline [median change, -25 µm (IQR: -14, -64); P = 0.01]. Macular volume within 6 mm of the fovea (CMTVol) was significantly reduced in eyes with subretinal fluid (SRF) [-0.20 mm³ (IQR: -1.45, -0.05); P = 0.03]. In this small cohort of eyes, switching to aflibercept seemed beneficial. The majority maintained or improved vision and eyes with IRF or SRF had significant reductions in macular edema. However, visual improvement was not always indicative of anatomical improvement.

Posterior subtenon versus intravitreal triamcinolone acetonide injection for the treatment of diabetic macular edema

Background Diabetic macular edema (DME) is the most common cause of loss of vision in diabetic patients. The role of inflammation in the pathogenesis of DME has been demonstrated. An intravitreal (IVT) injection of triamcinolone acetonide (TA) is a treatment option for DME. The high incidence of side effects, however, limits the routine use of IVT TA. Aim The aim of this study was to compare the efficacy and safety of an IVT injection of TA with the less invasive posterior subtenon (PST) injection of TA. We test the hypothesis that both techniques have equal efficacy and safety. Patients and methods This is prospective randomized noninferiority trial. Totally, 34 eyes from 30 patients with diffuse center involving DME were randomized in a 1: 1 ratio to receive a TA injection by either method. Baseline evaluation included measurement of best-corrected visual acuity (BCVA) and intraocular pressure (IOP), fundus fluorescein angiography, and optical coherence tomography to measure central macular thickness (CMT) and evaluation of the crystalline lens. After the injection, patients were seen at 1 week, 1 month, 3 months, and 6 months and their BCVA, CMT, IOP, and change in these measures from baseline as well as other complications were recorded. A Mann–Whitney U-test was used to compare the mean of quantitative variables and a c2-test was used to compare qualitative variables between the two groups. Results At baseline, both groups showed no statistically significant difference in age, sex, IOP, BCVA, and CMT. At 1, 3, and 6 months, both groups showed no statistically significant difference in the mean BCVA as well as change in BCVA from baseline. The average reduction of CMT was significantly higher only in the IVT group at 1 month (P = 0.03). The mean IOP and average IOP change from baseline were significantly higher in the IVT group than the PST group only at 3 months after injection (P = 0.02). Both groups showed a similar incidence of development of cataract (P = 1.0, c2). Conclusion IVT injection of TA is more effective than PST injection in improving CMT – that is, anatomical outcome. This is not, however, translated into a superior visual outcome. The risk of IOP elevation is also higher in IVT than PST injection. PST is a valid alternative to an IVT injection, especially from the functional perspective and when the risk of IOP elevation is significant.

Efficacy and safety of adalimumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study

The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet's disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (p<0.0001). Similarly, BCVA improved if compared to baseline (7.4±2.9 versus 8.5±2.1, p=0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27±42.8μm at the end of follow-up (p<0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (p<0.0001 and p=0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.

LONG-TERM OUTCOMES OF INTRAVITREAL BEVACIZUMAB THERAPY FOR SUBRETINAL NEOVASCULARIZATION SECONDARY TO IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2.

To assess the long-term visual acuity results for intravitreal bevacizumab therapy in the treatment of subretinal neovascular membrane (SRNVM) secondary to idiopathic macular telangiectasia (Mactel) Type 2. This retrospective review of a consecutive, interventional case series includes patients with SRNVM secondary to Mactel Type 2 who were seen at Cincinnati Eye Institute from February 2006 to December 2014. Best-corrected visual acuity, fluorescein angiography, and optical coherence tomography measurements were performed. Exclusion criteria were the following: Mactel Type 2 patients without SRNVM, Mactel Type 1 patients, patients who had SRNVM or macular edema related to other maculopathies, and patients who had pars plana vitrectomy or laser treatment to the macula during the course of care or before their first visit. Twenty-five eyes of 20 patients with SRNVM secondary to Mactel Type 2 were included in the study. The mean baseline best-corrected visual acuity was 20/91 (median: 20/69) and the mean final best-corrected visual acuity was 20/62 (median: 20/60) at the last visit (P < 0.0001). The mean number of injections was 8.4 ± 11.1 (range: 2-53, median: 4). The mean pretreatment central macular thickness of 254 μm improved to 205 μm at the final visit (P = 0.011). No complications related to intravitreal bevacizumab injection were noted during the mean follow-up time of 40.8 ± 33.7 months (range: 4-108 months, median: 24 months). Intravitreal bevacizumab therapy is an effective long-term treatment modality for SRNVM secondary to Mactel Type 2 based on improvement in best-corrected visual acuity and associated reduction in central macular thickness.

Two Doses of Intravitreal Ziv-Aflibercept versus Bevacizumab in Treatment of Diabetic Macular Edema: A Three-Armed, Double-Blind Randomized Trial

To compare the efficacy of 2 doses of intravitreal ziv-aflibercept (IVZ) with intravitreal bevacizumab (IVB) in the treatment of center-involved diabetic macular edema (DME) at 12 weeks. Three-armed, double-blind, randomized clinical trial. Eyes with center-involved DME. In this trial, 123 eyes with DME were randomly assigned to 3 injections of 1.25 mg IVZ, 2.5 mg IVZ, and 1.25 mg IVB every 4 weeks. Complete ophthalmologic examination and central macular thickness (CMT) measurement by optical coherence tomography were performed every 4 weeks up to 12 weeks. Change in best-corrected visual acuity (BCVA) at 12 weeks. Although no significant difference was evident between the 2 ziv-aflibercept groups at 12 weeks, the BCVA change was significantly better in the ziv-aflibercept 1.25 mg group than in the IVB group at the 12-week visit (P= 0.021). In regard to CMT changes, there was no significant difference between the 2 ziv-aflibercept groups; however, a significantly greater reduction in CMT was observed in the ziv-aflibercept 2.5 mg group compared with the IVB group at 12 weeks (P= 0.037). Subgroup analysis disclosed no difference in BCVA outcomes at 12 weeks among the groups in the eyes with baseline BCVA ≥20/50. In the eyes with baseline BCVA <20/50, the improvement was significantly better at 12 weeks in the ziv-aflibercept 1.25 mg group compared with the IVB group (P= 0.011). The 12-week results of this trial disclosed that both 1.25 mg and 2.5 mg doses of IVZ and IVB demonstrated BCVA improvement over baseline in the treatment of center-involved DME. However, a stronger effect of IVZ compared with IVB in terms of both visual acuity improvement and macular thickness reduction was detected in the eyes with initial BCVA <20/50. Longer-term efficacy and safety data will be needed to understand the role for this drug in practice.

Effect of leaking perifoveal microaneurysms on resolution of diabetic macular edema treated by combination therapy using anti-vascular endothelial growth factor and short pulse focal/grid laser photocoagulation.

The effect of combination therapy using intravitreal ranibizumab (IVR) injections and short pulse focal/grid laser photocoagulation was evaluated for the treatment of diabetic macular edema (DME). The current investigation was a preliminary single-arm, open-label, prospective clinical study conducted on 21 eyes at 4 sites in Japan. Treatment protocol consisted of two phases. The induction IVR phase included two monthly IVRs followed by PRN IVR phase in which additional IVR was administered if the central macular thickness (CMT) exceeded 300μm. One week after each IVR in both phases, short pulse focal/grid laser was delivered to treat residual leakage outside of the fovea (>500μm) and reduce edema fluid influx. At the 6-month endpoint, the effects of treatment were examined in terms of best corrected visual acuity (BCVA), CMT, and required number of IVR injections in eyes with or without perifoveal leaking microaneurysms (MAs). In eyes with initial BCVA ≤70 letters, mean BCVA was significantly ameliorated by 7.0±7.4 letters (P=0.0324) and mean CMT improved significantly by 174.8±105.0µm (P=0.0005). Both BCVA improvement (P=0.8693) and CMT reduction (P=0.9336) were comparable between MA(-) and MA(+) groups. The MA(-) group required significantly fewer PRN-IVR injections than did the MA(+) group over the 6-month study period (mean 3.4±1.6 vs. 5.3±0.9, median 3.0 vs. 5.5; P=0.0229). Short pulse focal/grid laser photocoagulation could reduce the number of IVR injections required to resolve macular edema and increase BCVA in a possible mechanism of reduced influx of edema fluid into the foveal area in eyes without apparent perifoveal microaneurysms.

Tomographic analysis of the retinal layers in diabetic macular edema treated with dexamethasone intravitreal implant

PurposeTo study the morphological alterations in the individual retinal layers of patients with diabetic macular edema (DME) treated with dexamethasone intravitreal implant.MethodsRetrospective, observational study of patients with center‐involving DME treated with a single dexamethasone implant as primary or secondary treatment, and with at least two follow‐up visits. Central thickness of each retinal layer was obtained with optical coherence tomography automated segmentation (Heidelberg Spectralis Engineering, Germany), with manual correction as needed.ResultsTwenty one eyes of 18 type 2 diabetic patients were included (median HbA1c 7.1%). The median time of follow‐up after treatment was 8 weeks (visit 1) and 4 months (visit 2). At visit 1, a significant reduction in central macular thickness (CMT) (480 ± 24 to 325 ± 134), retinal nerve fibre layer (RNFL) (21 ± 1 to 18 ± 2), ganglion cell layer (GCL) (30 ± 2 to 22 ± 1), inner nuclear layer (94 ± 15 to 46 ± 6), outer plexiform layer (OPL) (35 ± 3 to 28 ± 1), outer nuclear layer (ONL) (176 ± 14 to 117 ± 18) and retinal pigment epithelium (RPE) (29 ± 7 to 15 ± 5) was noted (p &lt; 0.05 for all layers). At visit 2 there was a significant increase in CMT, (424 ± 270), although still lower than the baseline; there was also a significant increase in RNFL (25 ± 3), GCL (30 ± 3), OPL (40 ± 3), ONL (146 ± 20) and RPE (24 ± 5) (p &lt; 0.05). There was no difference in inner plexiform layer (IPL) or outer retinal layers thickness over time. Seven eyes had neurosensorial detachment (NSD) at baseline, versus 0 at visit 1 and 2 at visit 2.ConclusionsThe reduction in CMT noted in patients with diabetic macular edema treated with dexamethasone intravitreal implant is mostly due to resolution of NSD (which accounts to the automated RPE thickness) and the layers above external limiting membrane, except for IPL. This effect is highest at the first follow‐up visit.

Intravitreal Diclofenac plus Bevacizumab versus Bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial.

The aim of this study is to evaluate the short-term effects of a single intravitreal injection of 1.25mg Bevacizumab combined with 300lg/0.1mL Diclofenac (IVB/D) versus 1.25mg intravitreal Bevacizumab (IVB) alone in the treatment of naive diabetic macular edema (DME). In this prospective, randomized clinical trial, 80 eyes were included in the final analysis; 42 and 38 of which in the IVB and IVB/D groups, respectively. The primary outcome measure was a change in best-corrected visual acuity (BCVA) in logMAR at week 4. The secondary outcomes included changes in central macular thickness (CMT), macular volume, and potential injection-related complications. Significant improvement of BCVA was demonstrated in both study arms (mean reductions in LogMAR: -0.088±0.278, -0.228±0.330 for IVB and IVB/D, respectively). The difference in BCVA changes was in favor of IVB/D; however, not to a statistically significant level (P=0.160). Significant reduction of CMT was documented in both study arms (mean reductions: 82.43±160.09 and 153.26±163.85 for IVB and IVB+IVD, respectively). Comparison of CMT changes between groups showed that IVB/D reduced CMT more than that of IVB (P=0.04). Effects on macular volume corresponded to those of CMT. No injection-related complications or significant alterations in intraocular pressure were observed in any of the study arms. In treatment-naive DME, superiority of IVB/D combination therapy over IVB monotherapy may exist; especially as regards anatomical features. In our therapeutic arsenal for DME, IVD can be added as an adjunct to Bevacizumab.

Outcomes of vitrectomy, membranectomy and internal limiting membrane peeling in patients with refractory diabetic macular edema and non-tractional epiretinal membrane

PurposeTo evaluate the efficacy of vitrectomy, membranectomy, and internal limiting membrane (ILM) peeling on macular thickness and best corrected visual acuity (BCVA) in patients with refractory diffuse diabetic macular edema (DME) and non-tractional epiretinal membrane (NT-ERM). MethodsThis prospective interventional case series included eyes with refractory DME (central subfield macular thickness [CSMT] > 300 μm) after at least two intravitreal injections of bevacizumab (IVB) and one intravitreal injection of triamcinolone (IVT), and accompanying NT-ERM. Complete ophthalmic examination, baseline spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) were performed prior to 23 gauge pars plana vitrectomy with membranectomy and internal limiting membrane (ILM) peeling. Postoperative evaluation was done with clinical examination and SD-OCT. Linear mix model analysis was used to study postoperative results. ResultsTwelve eyes from 11 patients (5 males) with a mean age of 60.33 ± 9.01 (range 46–73 years) were included. The mean follow-up time was 13.5 ± 4.48 months (range 4–20 months). A significant reduction in CSMT was found (from 559 ± 89 μm to 354 ± 76 μm; P = 0.001), with a non-significant BCVA change (from 0.84 ± 0.32 logMAR to 0.72 ± 0.2 logMAR; P = 0.967). There was no significant correlation between CSMT and BCVA (partial correlation = −0.115, P = 0.445) and also between estimated mean CSMT change per month and estimated mean BCVA change per month (r = 0.337, P = 0.283). ConclusionIn this series, our results did not show that vitrectomy, membranectomy, and ILM peeling result in significant improvement of BCVA in eyes with refractory DME and non-tractional ERM in spite of central macular thickness reduction.

Short-term effect of aflibercept on visual acuity and central macular thickness in patients not responding to ranibizumab and bevacizumab

To analyze the clinical outcome of treatment with aflibercept in patients not responding to ranibizumab and bevacizumab. Retrospective review of 32eyes from 30consecutive patients with choroidal neovascularization (CNV) who showed no response to treatment with ranibizumab or bevacizumab and were switched to aflibercept. Visual acuity, central macular thickness (CMT) and presence or absence of intraretinal or subretinal fluid were analyzed before switching to aflibercept, after each of three uploading dose injections of aflibercept and 6, 8 and 10weeks after the third aflibercept injection. All eyes had previous ranibizumab injections and the mean number of previous injections was 14.75 (±7.38). Mean duration of previous anti-vascular endothelial growth factor (VEGF) treatment was 38months (±27.35 months). Mean visual acuity before switching to aflibercept was 0.40±0.30logMAR. After the third injection visual acuity was 0.3±0.3logMAR and 10weeks after the third injection it was 0.50±0.20logMAR. No significant differences were seen during treatment and follow-up. The mean CMT was 394±118µm at baseline, at follow-up (first, second and third, group week6, group week8 and group week10) it was 317±108µm, 301±99µm, 292±83µm, 270±78µm, 340±146µm and 377±92µm, respectively. Significant reductions in CMT were seen between the first and third follow-up injections and at group week 8. Of the patients 59.4 % were complete non-responders to aflibercept. Aflibercept results in improvement in CMT in non-responders to ranibizumab and bevacizumab as long as therapy is given continuously and can therefore be an alternative therapy.

Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema.

ObjectiveTo compare the effects of intravitreal ranibizumab (RZB) or dexamethasone (DEX) intravitreal implant in cases of recalcitrant diabetic macular edema (DME).MethodsRetrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months.ResultsEleven patients (22 eyes) were included: mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16) to 0.261 (SD ±0.18) at final evaluation, and mean central macular thickness (CMT) improved from 461 µm (SD ±156) to 356 µm (SD ±110; net decrease: 105 µm, P=0.01). Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31) to 0.269 (SD ±0.19) at final evaluation. Mean CMT improved from 421 µm (SD ±147) to 373 µm (SD ±129; net decrease: 48 µm, P=0.26).ConclusionA subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection.

Evaluation of outer retinal tubulations in eyes switched from intravitreal ranibizumab to aflibercept for treatment of exudative age-related macular degeneration.

To evaluate the changes of outer retinal tubulations (ORTs) as seen on spectral-domain optical coherence tomography (SD OCT) in eyes with neovascular age-related macular degeneration (AMD) where treatment was switched from intravitreal ranibizumab to intravitreal aflibercept. This was a prospective study of eyes diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept, conducted at a single centre (Department of Ophthalmology at Pitié Salpetriere Hospital, Paris VI University) from January to July 2015. Before and after treatment was switched from ranibizumab to aflibercept, SD-OCT was used to evaluate the presence of ORTs. Additional assessments in this patient group included best-corrected visual acuity (BCVA), fluorescein angiography (FA), indocyanine green angiography (ICGA). Changes in pigment epithelium detachments (PED), presence of intraretinal cysts, and presence of subretinal fluid (SRF) were also noted. Twenty-four eyes of 24 consecutive patients (15 female/nine male, mean age 70years) diagnosed with neovascular AMD and previously treated with >6 intravitreal ranibizumab injections and switched to aflibercept were included in the analysis. After receiving aflibercept, patients were followed for a mean of 6.1months. Prior to treatment switch, 97% of eyes showed ORTs, while after treatment switch to aflibercept, at the end of the study period, 75% had ORTs (p = 0.219). Changes in BCVA (LogMAR) were not statistically significant (1.16 ± 0.44 to 1.18 ± 1.06, p = 0.12), however, a significant reduction in central macular thickness (CMT) (from 406μm ± 112 to 263μm ± 68, p = 0.001), PED (from 70.8% to 41.7% , p = 0.016), presence of intraretinal cysts (from 83.3% to 33.3%, p = 0.002) and SRF (from 91.7% to 25%, p = 0.001 ) were noted. After switching from ranibizumab treatment to aflibercept, ORTs remained present in 75% of eyes, and significant reductions in CMT, PED, and SRF, and presence of intraretinal cysts were observed.