Drug,delivery and devices for diabetic retinopathy (3Ds in DR)

ABSTRACT

Introduction: Diabetic Retinopathy (DR) is one of the most common causes of blindness among the working population worldwide. Clearly, there is an unmet clinical need to find better treatment options for DR.

Areas covered: The literature search was conducted on PubMed with no limitation on language or year of publication. The review focuses on the clinically used drugs/proteins along with a brief background on the pathophysiology of DR. The major focus of this review revolves around three treatment approaches involving drugs/proteins, drug delivery formulations and drug delivery devices. In each category, major advances are discussed along with the possible solutions. We have also discussed the various modes of administration that are currently being evaluated in the clinic. An attempt has been made to address the potential targeted site of action for DR drug delivery, and also to understand the role of Blood Retinal Barrier (BRB).

Expert Opinion: In the current scenario, although there have been some advances in the drug delivery devices for delivering drugs/proteins, there are still challenges to be overcome with regard to the particulate systems. For long-term success of DR therapeutics, research options should consider taking into account the 3Ds (drug, delivery and devices).     

T1- and T2*-dominant extravasation correction in DSC-MRI: Part II—predicting patient outcome after a single dose of cediranib in recurrent glioblastoma patients

A ‘vascular normalization index'' (VNI) based on the changes in the magnetic resonance imaging (MRI) parameters K^trans and cerebral blood volume (CBV), combined with blood sampling, has been shown to correlate with patient outcome in recurrent glioblastoma after a single dose of antiangiogenic therapy. Here, by applying a novel contrast agent extravasation correction method insensitive to variations in tissue mean transit time, we show that a similar VNI parameter can be derived from a single dynamic susceptibility contrast MR acquisition rather than the three parameters shown previously. Our results show that this new VNI parameter, which combines changes in tumoral CBV and an apparent transfer constant from our leakage correction method, may provide prognostic information in an even simpler manner than prior efforts.     

Low-fluence photodynamic therapy combinations in the treatment of exudative age-related macular degeneration

AIM: To compare the efficacy of low-fluence photodynamic therapy (PDT) combinations in the treatment of age-related macular degeneration (AMD). METHODS: Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity (BCVA) was ≥0.3 (Snellen) were enrolled. 15 patients in Group I underwent low-fluence PDT (25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination, 15 patients in Group II underwent PDT (50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while, 15 patients in Group III underwent intravitreal pegaptanib monotherapy. Complete ophthalmologic examinations were performed in pre and post treatment visits, and the results were statistically analised. A clinical activity score (CAS) was calculated by using changes in lesion size, amount of hemorrhage, staining pattern in FA and OCT measurement of intra/subretinal fluid. ≤ 3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment. RESULTS: The mean age of 19 female (42.2%) and 26 male (57.8%) patients was 72.82±8.02 years. Mean follow-up was 13.93±5.87 months. Lesion type was occult in 28 eyes (62.2%). Treatment success rates according to BCVA assessments were 86.7%, 80%, 60% and mean BCVA decrease were 0.3, 1.0, 2.2 logMAR lines in Group I, II and III, respectively (P>0.05). According to the changes in central macular thickness and CAS, no difference was found among the study groups (P=0.850 and P=0.811, respectively). Patients treated with combination regimens had lower intravitreal injection frequencies (P=0.015). CONCLUSION: Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.     

Spectral-domain OCT in anti-VEGF treatment of myopic choroidal neovascularization

Purpose

To evaluate changes in macular morphology due to myopic choroidal neovascularization (CNV), using spectral-domain optical coherence tomography (SD-OCT).

Methods

In all, 22 eyes with recent-onset untreated CNV underwent 1 intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF), followed by a pro-re-nata regimen. SD-OCT was performed at baseline (before first administration of anti-VEGF treatment) and month 1, and 2; macular morphologic changes and outer retina characteristics (SD-OCT findings) associated with CNV activity were evaluated. Sensitivity and specificity were calculated for SD-OCT findings using fluorescein angiography (FA) as standard reference.

Results

Mean central retinal thickness (CRT) showed no significant reduction from baseline (284±98 μm) to month 1 (257±74 μm) and month 2 (263±72 μm). A hyper-reflective lesion with fuzzy borders (fuzzy area), and ‘absent or altered'' IS/OS junction were the only SD-OCT findings associated with CNV activity (P<0.0001). Both these SD-OCT findings showed good sensitivity and specificity (95.1 and 96.0% (95% CI: 0.87–0.89), respectively, for the fuzzy area; 87.9 and 66.7% (95% CI: 0.65–0.87), respectively, for ‘absent or altered'' IS/OS junction) when compared with FA leakage (standard reference).

Conclusions

Outer retina characteristics (ie, hyper-reflective lesion with fuzzy borders, and ‘absent or altered'' IS/OS junction) appear more meaningful than CRT in the evaluation of myopic CNV activity. These SD-OCT findings show overall good sensitivity and specificity when compared with FA leakage (standard reference), and could be considered as an alternative diagnostic tool to FA for myopic CNV monitoring.     

抗VEGF联合激光治疗重度非增殖期糖尿病视网膜病变对黄斑区血流密度的影响

目的：探讨抗血管内皮生长因子(VEGF)联合全视网膜光凝术(PRP)治疗重度非增殖期糖尿病视网膜病变(sNPDR)合并黄斑水肿(DME)对黄斑区血流密度变化的影响。

方法：回顾性选取2018-10/2019-04在我院确诊的sNPDR合并DME患者30例30眼,根据治疗方案进行分组,其中A组15例15眼采用“1+PRN”方案采用玻璃体腔内注射雷珠单抗7d后行PRP治疗,B组15例15眼采用单纯PRP治疗。对比两组治疗前后黄斑区6mm×6mm浅层毛细血管(SCP)和深层毛细血管(DCP)血流密度、黄斑中心凹厚度(CMT)、最佳矫正视力(BCVA)变化情况。

结果：与术前相比,A组患者术后2wk,1mo DCP血流密度显著增加、CMT明显降低、BCVA明显改善(均P<0.05),B组患者术后1mo CMT降低、BCVA改善(均P<0.05)。术后2wk、1mo,A组患者DCP血流密度较B组明显增加(43.37%±2.72% vs 41.03%±2.60%,45.01%±2.28% vs 41.20%±2.43%,均P<0.05),CMT较B组明显降低(303.4±30.36μm vs 329.60±31.47μm,268.67±30.27μm vs 319.40±28.63μm,均P<0.05),BCVA(LogMAR)较B组明显改善(0.28±0.11 vs 0.40±0.13,0.23±0.14 vs 0.38±0.15,均P<0.05)。

结论：抗VEGF联合PRP治疗sNPDR合并DME患者短期内可有效增加DCP血流密度,减轻黄斑水肿,改善视力。     

Dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema: real-world data versus clinical trials outcomes

AIM: To investigate the safety and efficacy of intravitreal dexamethasone implants (Ozurdex®/DEX) in patients with diabetic macular edema (DME) either naïve or non-naïve to anti-VEGF therapies who switched to DEX implant independent of response to anti-vascular endothelial growth factors (anti-VEGFs). METHODS: This was an audit retrospective review of medical records of patients with DME who switched to the DEX intravitreal implant. Patients were divided into 2 groups: patients naïve to antiangiogenic therapy and patients who were previously treated with anti-VEGFs. Data regarding demographics, changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) was collected over 6mo. The demographic data mean changes in BCVA, CMT, and IOP were compared. Six-month follow-up data of 47 patients (57 eyes), who either switched to DEX implant irrespective of response to previous treatments or were treatment naïve before receiving DEX implant, was collected. RESULTS: Improvement in mean BCVA was observed from 1-4mo after injection with a decreased effect at month 6 as expected, with better outcomes in naïve compared to non-naïve patients. A statistically relevant decrease in mean CMT was observed during the follow-up period. An increase in mean IOP was observed in the first 2mo after DEX therapy. The mean number of injections of the overall population during the 6mo was 1.3. A subgroup analysis showed no relevant difference between phakic versus pseudophakic patients relative to measured outcomes. There was no cataract progression during the follow-up period and no adverse events reported. CONCLUSION: This real-life setting study shows that intravitreal DEX implant is effective and safe. The timings of greater therapeutic impact are concordant with previous studies and suggest that earlier treatment with corticosteroids may have an additional benefit in naïve patients.     

视网膜中央静脉阻塞继发黄斑水肿抗VEGF治疗后出现棉绒斑增多2例

视网膜静脉阻塞(retinal vein occlusion,RVO)是全球第二大高发的视网膜血管性疾病,按照其发病部位分为视网膜中央静脉阻塞（central retinal vein occlusion，CRVO） 和视网膜分支静脉阻塞（branch retinal vein occlusion，BRVO），其发病机制复杂。目前抗血管内皮生长因子(anti-vascular endothelial growth factor,anti-VEGF)治疗是一线治疗，临床上发现2例患者在接受抗VEGF治疗后出现视网膜棉绒斑短暂性增多情况，本文推测棉绒斑的出现可能与眼内VEGF水平被过度抑制和炎症因子的高度表达造成视网膜急性缺血缺氧相关，但具体的分子机制还需要进一步研究证实。     

VEGF在糖尿病视网膜病变发病机制中的作用及抗VEGF靶向治疗新进展

糖尿病视网膜病变(diabetic retinopathy,DR)是糖尿病最常见的并发症之一。DR的发病机制十分复杂,至今尚未完全阐明。目前认为DR患者会出现视网膜毛细血管阻塞,可导致局部缺氧,由此引起促新生血管因子产生增多,其中包括VEGF。VEGF是促新生血管形成的主要因子之一,会降低血管内皮细胞间的紧密连接蛋白表达,参与血管炎症反应、增加血管通透性和促进新生血管形成。近年来有关DR的发病机制以及治疗的研究越来越深入。本文旨在阐述VEGF在DR发病机制中的作用,以及抗VEGF治疗策略的最新进展。