Ranibizumab for retinal angiomatous proliferation in neovascular age-related macular degeneration

Background To report the efficacy of intravitreal injection of ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP) in neovascular age-related macular degeneration (AMD). Methods Case review of four consecutive patients who received 3 injections at monthly intervals of intravitreal ranibizumab injections for RAP. The serial changes in best-corrected visual acuity (BCVA), optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) are presented. Results The baseline mean logMAR BCVA was 0.89 (Snellen equivalent of 20/155). After three injections of ranibizumab, all four patients had visual improvement and the mean logMAR BCVA improved to 0.59 (Snellen equivalent of 20/78). The mean visual improvement was 3.0 lines. All patients also had complete resolution of subretinal fluid after treatment, and the mean OCT central foveal thickness reduced from 438 μm at baseline to 169 μm at 3 months. Follow-up FA and ICGA at 3 months showed absence of leakage in three patients with minimal leakage in the remaining patient. One patient had recurrence of RAP at 8 months after commencement of treatment, and repeat ranibizumab injection resulted in resolution of the subretinal fluid and pigment epithelial detachment and visual improvement. Conclusions Intravitreal ranibizumab injections appeared to be an effective treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.     

Combined photodynamic therapy and intravitreal ranibizumab as primary treatment for subretinal neovascular membrane (SRNVM) associated with type 2 idiopathic macular telangiectasia

Background To report the efficacy of combination photodynamic therapy and intravitreal ranibizumab for juxtafoveal, subretinal neovascular membrane (SRNVM) associated with type 2 idiopathic macular telangiectasia (IMT). Methods A 56-year-old woman with visual loss due to SRNVM secondary to IMT underwent primary treatment with a combination of photodynamic therapy (PDT) and intravitreal ranibizumab (0.5 mg). PDT was done as per the TAP study protocol, except that the laser spot size was same as the greatest linear diameter (GLD) of the lesion. This was followed by intravitreal ranibizumab (0.5 mg), 2 days later. Results At the 16-week follow-up, clinical examination revealed regression of the SRNVM, with no evidence of subretinal fluid, exudates or fresh hemorrhages. Visual acuity improved by 2 Snellen lines (from 6/36 to 6/18). Clinical findings were confirmed on FFA and OCT. At the last follow-up at 9 months, the SRNVM remained quiescent and visual acuity stable. No treatment-related adverse effects were noted. Conclusion Combination therapy with PDT and intravitreal ranibizumab appears to be efficacious in the treatment of SRNVM associated with proliferative type 2 IMT. The authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request. There are no funding or other conflicts of interest.     

玻璃体腔注射雷珠单抗与康柏西普治疗早产儿视网膜病变疗效比较

目的：比较早产儿视网膜病变(ROP)患儿采用玻璃体腔注射雷珠单抗(IVR)与康柏西普(IVC)两种药物的治疗效果。

方法：回顾性研究。纳入我院2015-01/2023-06玻璃体腔注射抗VEGF药物治疗的ROP患眼1 100眼。根据治疗药物的不同,将患儿分为IVR组和IVC组。根据ROP的病变程度分为急进型ROP(A-ROP)、Ⅰ区1型ROP和Ⅱ区1型ROP。通过倾向性匹配分析(PSM)匹配后对两组复活与再次治疗情况进行比较。随访时间至少至术后3 mo。

结果：在Ⅱ区1型ROP中,IVR组和IVC组的病变复活率及再次治疗率均有差异(P<0.05); A-ROP和Ⅰ区1型ROP中两组病变复活率及再次治疗率均无差异(P>0.05)。Ⅰ区1型ROP复活风险及再次治疗风险高于Ⅱ区1型ROP,药物的选择和首次治疗矫正胎龄是术后病变复活及再次治疗的影响因素。

结论：玻璃体腔注射IVR或IVC对Ⅱ区1型ROP的首次治愈效果有明显差异,且IVC组的复活率和再次治疗率远低于IVR组。     

Intravitreal bevacizumab (Avastin) in combination with verteporfin photodynamic therapy for choroidal neovascularization associated with age-related macular degeneration (IBeVe Study)

Background A novel alternative for combined treatment using verteporfin photodynamic therapy (PDT) has emerged as preliminary safety and efficacy data of the intravitreal use of the anti-angiogenic bevacizumab became available. In the current study we investigate the feasibility of intravitreal bevacizumab combined with verteporfin PDT for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods A single-centre, prospective, open-label study of 11 patients with documented CNV progression after PDT treatment who underwent combined PDT and intravitreal injection of 1.5 mg of bevacizumab was undertaken. Standardized ophthalmic evaluation was performed at baseline and at weeks 1, 2, 12 and 24. Clinical evidence of complications and changes in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and in fluorescein leakage from CNV were evaluated. Results The mean (±SD) age of the 11 patients was 74 (±5) years. Seven eyes had been treated with one previous PDT session and four eyes had two previous PDT sessions. The mean baseline logMAR ETDRS BCVA was 1.031 (Snellen equivalent, 20/200⁻²). At follow-up weeks 1, 2, 12 and 24, the mean logMAR ETDRS BCVA (Snellen equivalent) was 0.944 (20/160⁻²), 0.924 (20/160⁻¹), 0.882 (20/160⁺¹), and 0.933 (20/160⁻²), respectively. The change in BCVA from baseline was significant at each study follow-up interval (P ≤ 0.001); at 12 and 24 weeks, the mean change in BCVA from baseline was an improvement of 1.49 and of 0.98 ETDRS line, respectively. Fluorescein leakage from CNV was absent in all eyes at week 12. One additional treatment session was required in seven (63.6%) eyes at week 24 due to recurrent fluorescein leakage from CNV (“minimum” [<50% of the leaking area noted at baseline], n = 4; and “moderate” [>50% of the leaking area noted at baseline], n = 3). No progression of the neovascular lesion was observed at week 24. No safety issues were identified throughout the period of the study. Conclusions The overall changes in vision and fluorescein leakage from CNV throughout the study suggest that a possible synergistic effect may arise from the combination of intravitreal bevacizumab with verteporfin PDT for the treatment of neovascular AMD. In terms of funding, this was an investigator’s driven study.     

Intravitreous anti-VEGF for diabetic retinopathy: hopes and fears for a new therapeutic strategy

Vascular endothelial growth factor (VEGF) plays a key role in the development of both proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DMO). In recent years, anti-VEGF agents have emerged as new approaches to the treatment of these devastating diabetic complications. Although Phase III studies in the diabetic population are needed, intravitreal anti-VEGF therapy is currently being used in clinical practice. Intravitreal injection is an effective means of delivering anti-VEGF drugs to the retina. However, this is an invasive procedure associated with potentially serious complications, such as endophthalmitis or retinal detachment, which may be significant for patients requiring serial treatment over many years. In addition, although delivered within the vitreous, anti-VEGF drugs could pass into the systemic circulation, which could potentially result in hypertension, proteinuria, increased cardiovascular events and impaired wound healing. Pegaptanib, ranibizumab and bevacizumab are the currently available anti-VEGF agents. Ranibizumab and bevacizumab block all VEGF isoforms, thus impairing both physiological and pathological neovascularisation. Pegaptanib only blocks the VEGF₁₆₅ isoform, and would therefore seem the best option for avoiding systemic adverse effects in diabetic patients, although this remains to be demonstrated in clinical trials. In this regard, head-to-head studies designed to evaluate not only the efficacy, but also the systemic adverse effects of these drugs in a high-risk population such as diabetic patients are warranted.     

Ranibizumab玻璃体腔注射治疗不同病程两组特发性脉络膜新生血管病变

目的：对比分析Ranibizumab玻璃体腔注射治疗两组不同病程的特发性脉络膜新生血管病变患者（ ICNV）的疗效。方法经眼底荧光素血管造影（ FFA）及光相干断层扫描（ OCT）检查,并结合临床表现确诊为特发性脉络膜新生血管病变的患者36例36眼,按病程分为A（病程＜3个月）、B（3个月≤病程＜6个月）两组。所有患者均行常规玻璃体腔ranibizumab注射治疗。治疗前检查两组受检者最佳矫正视力BCVA（ logMAR）、屈光度、眼压、散瞳查眼底、光学相干断层扫描（ OCT）检查病灶与中心凹的位置关系以及CMT、FFA。治疗后每月检查两组受检者BCVA（ logMAR）、眼压、散瞳查眼底、OCT查CMT,必要时重复造影确定是否需要眼内重复注射。对比两组治疗前和治疗后1、3、6个月时的BCVA（ logMAR）、CMT、眼压,并统计6个月时的注射次数。结果与治疗前相比,两组在治疗后的1、3、6个月随访时,BCVA及CMT均有明显改善, P＜0．05。而两组间在治疗后的1、3、6个月随访时, BCVA及CMT的比较差异无统计学意义（P＞0．05）,但至随访6个月时,A组的注射次数（1．3±0．5）次少于B组（2．1±1．2）次（P＜0．05）。结论玻璃体腔注射ranibizumab能够快速有效的改善ICNV患者病情,发病早期治疗可以减少注射次数,降低注射风险并减少治疗的成本。     

Clinical efficacy and safety of ranibizumab in the treatment of wet age-related macular degeneration

Introduction: Although several approaches have been studied for treating wet age-related macular degeneration (w-AMD), currently, the most effective strategy in the management of this visual disorder is represented by anti-VEGF drugs. Among them, ranibizumab (RBZ) is widely adopted in clinical practice for treating w-AMD.

Areas covered: VEGF (vascular endothelial growth factor) is a hypoxia-induced growth factor promoting neoangiogenesis, which has been correlated to the pathogenesis of w-AMD.

RBZ is a humanized, recombinant, monoclonal antibody fragment (Fab), which binds all the isoform of VEGF-A and, therefore, exerts an inhibitory activity on the growth of new pathological vessels leading to the reabsorption of VEGF-related macular edema. The pivotal trials ANCHOR and MARINA revealed its clinical efficacy and good safety profile for treating w-AMD, leading ultimately to its FDA approval. Further trials have analyzed the best dosage and regimen modality, reporting RBZ at 0.5 mg with a ‘pro re nata’ regimen (PRN) to be non-inferior to the 0.5 mg formulation administered monthly. The treat-to-extend (TAE) regimen has also been investigated, demonstrating encouraging results in terms of clinical efficacy and nonetheless, it was proven to be a well-tolerated option with the possibility of reducing the treatment burden for the patients.

Conclusions: RBZ has been proven to be an effective anti-VEGF agent for treating w-AMD; however, more optimal therapeutic regimens and drug delivery systems are being investigated in order to improve patients’ compliance and treatment burden.     

局部注射雷株单抗治疗糖尿病视网膜病变的临床观察

目的观察局部注射雷株单抗治疗糖尿病视网膜病变的临床效果。方法分析2012年1月~2013年12月在本院眼科确诊为糖尿病视网膜病变的38例患者40只眼,接受局部注射雷株单抗,对比治疗前和治疗矫正12周后的最佳矫正视力（BCVA）、黄斑中心视网膜厚度（CRT）和黄斑总体积（TMV）的变化情况。结果治疗前BCVA平均字母数为37.11±14.27,黄斑CRT为（535.16±218.37）μm,TMV为（13.70±1.67）mm^3;治疗12周后,BCVA平均字母数为46.57±15.17,黄斑CRT为（431.27±171.26）μm,TMV为（9.24±2.07）mm^3,治疗前后比较,差异有统计学意义（P〈0.05）。所有患者在治疗期间均未见明显严重不良事件。结论局部注射雷株单抗治疗糖尿病视网膜病变,能够减小黄斑CRT和TMV,进而提高患眼视力,疗效确切。     

Intravitreal Anti-vascular Endothelial Growth Factor for Typical Exudative Age-related Macular Degeneration in Eyes with Good Baseline Visual Acuity

Purpose

To investigate 12-month treatment outcomes of anti-vascular endothelial growth factor therapy in eyes with typical exudative age-related macular degeneration with good baseline visual acuity.

Methods

This retrospective observational case series included 18 eyes (18 patients) with typical exudative age-related macular degeneration with a baseline best-corrected visual acuity of 20 / 25 or better. Patients were treated with anti-vascular endothelial growth factor monotherapy during the 12-month follow-up period. Baseline visual acuity and central foveal thickness were compared to the values at 12 months.

Results

Patients received an average of 4.4 ± 1.3 intravitreal anti-vascular endothelial growth factor injections. The mean logarithm of minimum angle of resolution visual acuity was 0.08 ± 0.04, 0.08 ± 0.07, 0.12 ± 0.09, and 0.16 ± 0.11 at baseline, three months, six months, and 12 months, respectively. Visual acuity at 12 months was significantly worse than the baseline value at diagnosis (p = 0.017), and the mean central foveal thickness at the defined time points was 270.2 ± 55.6, 204.4 ± 25.4, 230.1 ± 56.3, and 216.8 ± 48.7 µm, respectively. The central foveal thickness at 12 months was significantly less than the baseline value at diagnosis (p = 0.042).

Conclusions

Deterioration in visual acuity was noted in eyes with typical exudative age-related macular degeneration with good baseline visual acuity, suggesting the need for close patient monitoring and prompt treatment even in patients with good baseline visual acuity.     

增生期糖尿病视网膜病变围手术期注射雷珠单抗的临床观察

对严重增生期糖尿病视网膜病变（ PDR）患者行玻璃体切除术前予玻璃体腔注射雷珠单抗有效性进行评价。方法选取我院2012年11月至2013年5月收治的严重PDR患者23例（23只眼）,将患者分为A、B两组,A组（13只眼）直接行玻璃体切除术,B组（10只眼）于玻璃体切除术5 d前行玻璃体腔雷珠单抗注入术。入选患者眼底情况：玻璃体积血的糖尿病视网膜病变（ DR）患者,行B型超声检查,提示玻璃体积血,机化膜形成,和（或）合并局限性牵拉性视网膜脱离;没有玻璃体积血的糖尿病视网膜病变患者,间接眼底检查有增殖形成和（或）合并牵拉性视网膜脱离。观察两组患者手术时间、术中发生严重出血的病例数,有无视网膜撕裂的发生,术后早期并发症的发生率、术后两个月视力的提高程度及两个月后玻璃体腔再增生、出血的发生率。结果 A组平均手术时间为（131．92±8．79）min,术中剥膜发生明显出血者7例,视网膜撕裂者6例,术后发生高眼压者6例,前房炎症平均消退时间（5．00±1．35） d,术后2个月最佳矫正视力无明显提高,术后玻璃体腔再出血者3例。 B组平均手术时间为（95．30±7．27）min,与A组比较有统计学意义（ P ＜0．05）,术中见眼内新生血管明显萎缩,剥膜时均无严重出血,视网膜撕裂者1例,术后发生高眼压者2例,前房炎症平均消退时间（3．60±0．69）d,与A组比较有统计学意义（ P ＜0．05）;术后2个月无患者发生玻璃体腔再出血;术后2个月患者随访中最佳矫正视力好于术前,两组间比较无统计学差异（ t ＝1．288, P ＝0．21）。结论严重PDR患者行玻璃体切除术前玻璃体腔注射雷珠单抗是可减少术中剥膜的出血量,有效缩短手术时间,术后并发症减少,术中行视网膜光凝容易,术后2个月最佳矫正视力有所提高,减少术后玻璃体腔增生再出血的情况。