Treatment options for the wet form of age-related macular degeneration-a perspective

Treatment of the wet form of age-related macular degeneration (wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor (VEGF) blockers that reduce neovascularization and macular edema. Two approved drugs are marketed for the treatment of wet AMD—ranibizumab and alfibercept, but there is a third drug, bevacizumab, which is widely used off-label; a cancer drug that also blocks VEGF but was never tested in pivotal trials and never approved for ophthalmic indications including wet AMD. Similarity of bevacizumab to ranibizumab led to off-label use and even to government-sponsored studies comparison the approved ranibizumab head-to-head to the off-label cancer drug bevacizumab in wet AMD, like the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) study, discussed in this perspective paper. Recent publication of 5-year follow-up from the initial 2-year CATT study provided the occasion to discuss the similarities and differences between these two drugs and the lessons learned from the last decade of anti-VEGF therapy for wet AMD. Clinical efifcacy is comparable, with an advantage for ranibizumab. Likewise, safety ifnding favor ranibizumab over bevacizumab in some aspects. The latest addition of approved anti-VEGF drugs for wet AMD, alfibercept, may provide even more beneift to patients. In this perspective we discuss results of CATT and other long-term follow-up and comparative studies. While all demonstrate clinical beneift of anti-VEGF, all reveal that most patients’ loose visual acuity (VA) in real-life situations over 5–7 years. This loss is based on—what we believe—significant under-treatment of wet AMD patients, due to economic or practical limitations and overestimation of perceived risks as geographic atrophy. We compare own data that showed more intensive treatment (more than twice the CATT-follow-up injections) with ranibizumab or alfibercept can maintain a sustained gain in VA in wet AMD patients after 6 years. We encourage retina specialists to treat wet AMD patients more aggressively and frequently in order to provide the maximum beneift for their patients.     

Swept-Source OCT Angiographic Characteristics of Treatment-Naïve Nonexudative Macular Neovascularization in AMD Prior to Exudation

PurposeTo investigate the characteristics of treatment-naïve nonexudative macular neovascularization (MNV) in age-related macular degeneration before the onset of exudation using swept-source optical coherence tomography angiography.MethodsMNV area, choriocapillaris (CC) flow deficits (FDs), vessel area density (VAD), vessel skeleton density (VSD), retinal pigment epithelial detachment (PED) volume, mean choroidal thickness (MCT), and choroid vascularity index (CVI) measurements were assessed at two visits prior to exudation. We compared measurements made at the second visit and the rate of change between visits in eyes with and without exudation. The differences in these parameters between eyes with and without subsequent exudation were summarized with 95% confidence intervals (CIs).ResultsTwenty-one eyes with nonexudative MNV were identified and followed. Nine eyes developed exudation, and 12 eyes did not develop exudation. Differences between these groups of eyes for all parameters tended to be small, and the 95% CIs largely ruled out any substantial differences. Overall, eyes with exudation had 24% smaller VAD, 20% smaller VSD, and 33% smaller PED volume measurements. No noteworthy differences were observed for MNV area, CC FDs, MCT, or CVI measurements.ConclusionsThe onset of exudation was correlated with lesions having less vascularity and smaller PED volume measurements, but measurements of MNV area, CC FDs, MCT, and CVI were not correlated with near-term exudation. Investigations are ongoing to further explore these and other anatomic changes as harbingers of near-term exudation.     

Age-dependent variations in the drusen fluorescence on indocyanine green angiography

Purpose: To examine the fluorescence patterns of macular drusen using indocyanine green (ICG) angiography in human subjects of different ages. Methods: A total of 180 eyes in 100 consecutive patients aged 34?90 years with macula drusen were evaluated with ICG angiography using the Topcon 1024 ImageNet system. Eyes were divided into two groups depending on age. The older group (subjects over the age of 55 years) comprised 170 eyes. The younger group (subjects 55 years or younger) comprised 10 eyes. The fluorescence patterns of the drusen were graded as hyper­fluorescent (brighter than the background fluorescence), hypofluorescent (darker than the background fluorescence) or isofluorescent (unable to be distinguished from the background fluorescence). The ICG angiogram appearances were correlated with the clinical types of drusen in differing age groups. Results: An age‐dependent difference in the fluorescence pattern of drusen was observed. Drusen in the older group were hypofluorescent or isofluorescent (169/170 eyes). In contrast, drusen in the younger group (55 years or younger) were hyperfluorescent (10/10 eyes). Conclusions: This study defines the distinct age‐dependent differences in the ICG fluorescence pattern of drusen. This heterogeneity might be due to differential binding of extravasated ICG to the constituents and histological site of the drusen deposits. Furthermore, ICG angiography is able to differentiate drusen types not possible by clinical and fluorescein angiographic evaluation.     

年龄相关性黄斑变性的眼底荧光造影特点(英文)

目的:探讨眼底荧光素血管造影(fundus fluorescein angiog-raphy, FFA)在年龄相关性黄斑变性(age-related macular degeneration, AMD)患者中的特征及临床意义。方法:用日本Nikon NF-505眼底照相机对112例149眼进行FFA检查。结果:在149眼中,萎缩型90眼(60.4%),渗出型59眼(39.6%),依据CNV造影特点和CNV与黄斑中心凹的距离分为中心凹下CNV包括经典型7眼,隐匿型26眼,盘状瘢痕化9眼,旁中心凹CNV包括经典型2眼,隐匿型12眼,中心凹外CNV3眼均为隐匿型。结论:FFA可以发现AMD患者的CNV,并能分辨其性质和部位,有助于指导治疗和评价预后。     

老年黄斑变性玻璃膜疣的吲哚菁绿血管造影

目的：探讨老年黄斑变性（AMD）玻璃膜疣的吲哚菁绿血管造影（ICGA）特征及其临床意义。方法：对10例16眼早期AMD患者进行眼底荧光血管造影（FFA）及ICGA。结果：⑴FFA早期玻璃膜疣为透见荧光,后期部分呈现着色现象。⑵ICGA早期可见脉络膜充盈迟缓或不规则,后期可见脉络膜渗漏高荧光区、点状强荧光及斑状强荧光团。玻璃膜疠为遮蔽荧光。此外可见涡状静脉异常。结论：AMD早期即有明显的脉络膜循环紊乱及可疑非活动性新生血管生成。对AMD患者进行FFA和ICGA眼底血管对照检查,对了解AMD的发病机理,及早发现潜在的脉络膜新生血管,以尽早给予适当的预防性治疗均有重要意义。     

Implante de dexametasona antes de tratamiento anti-VEGF en desprendimientos del epitelio pigmentario secundarios a degeneración macular asociada a la edad con características de alto riesgo de rotura

ObjectiveEvaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size.MethodsPatients with nAMD, PED height > 500 microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered.ResultsThe study included 14 eyes of 14 patients: mean age 77 ± 7 years, 11 (79%) females. 25 ± 13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64 ± 14 to 69 ± 11 letters after anti-VEGF therapy (P > .05). Mean baseline PED height was 817 ± 269 μm, being 639 ± 268 μm after Ozurdex and 370 ± 260 μm after anti-VEGF injections (P = .035 and P = .009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported.ConclusionsDexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy.     

Intravitreal anti-VEGF monotherapy for thick submacular hemorrhage of less than 1 week duration secondary to neovascular age-related macular degeneration

Aim:

To investigate the role of anti-VEGF monotherapy in patients with thick submacular hemorrhage (SMH) of ≤1 week duration secondary to neovascular age-related macular degeneration (N-AMD).

Materials and Methods:

A retrospective chart review of 14 eyes of 14 patients presenting with acute decrease in central vision of ≤1 week duration secondary to a thick SMH measuring ≥ 2 MPS disk areas from N-AMD was performed. Intravitreal injections of bevacizumab 1.25 mg (13 eyes) or ranibizumab 0.5 mg (1 eye) were given monthly until resolution of SMH and less frequently thereafter, based on treat-and-extend approach utilizing spectral domain optical coherence tomography (SDOCT). Patients with follow-up of ≥6 months were included.

Results:

Patients presented after a median of 4 (range 1-7) days from the onset of SMH. Mean lesion size was 27.9 mm² (range 5.47-100, median 15), with blood comprising 77-98% of the lesion. Presenting visual acuity (VA) ranged from 20/60 to hand motions (median 20/200). Patients received a mean of 11.4 (range 5-20) injections over 18.4 (range 7-50) months. SMH resolved in all eyes in a mean of 4.8 (range 2-8) months. At 6 months follow-up, mean VA gain was −0.54 logMAR (range: −1.5 to +1, Snellen range 20/25-20/400, median 20/100, P = 0.0037), with 11 gaining ≥0.2 logMAR. Mean change in VA from baseline at final follow-up was −0.58 logMAR (range −1.6 to +1, Snellen range 20/30-20/400, median 20/60; P = 0.0022).

Conclusion:

A good anatomical and visual outcome can be accomplished in patients with thick SMH secondary to N-AMD treated with anti-VEGF monotherapy within 1 week.     

Retention of good visual acuity in eyes with neovascular age-related macular degeneration and chronic refractory subfoveal subretinal fluid

Purpose

To describe the clinical characteristics of a subset of eyes with neovascular age-related macular degeneration (NVAMD) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy which retain good visual acuity despite chronic, persistent subfoveal subretinal fluid (SRF).

Design

Retrospective, observational case series.

Methods

Study eyes were identified from a consecutive series of 186 patients treated with anti-VEGF therapy seen for regular follow-up over a 3-month period. The clinical histories of 10 eyes of 9 patients with NVAMD, chronic subfoveal SRF despite continuous anti-VEGF therapy, and good long-term visual acuity of 20/40 or greater were reviewed. Demographic factors, baseline and final visual acuity, neovascular lesion type, duration of persistent fluid, baseline and final subfoveal choroidal thickness, presence of geographic atrophy, and number of anti-VEGF injections were analyzed.

Results

The mean age of patients was 78 years (range 55–91). The mean duration of persistent fluid was 5.2 years (range 1.3–11.0). Long-term visual acuities remained stable at 20/40 or better in all eyes. All eyes had type 1 (sub-retinal pigment epithelial) neovascularization. Average baseline subfoveal choroidal thickness was 285.3 μm and the average follow-up subfoveal choroidal thickness was 239.7 μm. No eyes had the presence of geographic atrophy. The mean number of injections was 36.5 (range 17–66).

Conclusion

Some eyes with type 1 neovascularization associated with chronic persistent subfoveal subretinal fluid despite continuous intravitreal anti-VEGF therapy may maintain good long-term visual outcomes. We hypothesize that type 1 neovascularization and greater subfoveal choroidal thickness may exert a protective effect on photoreceptor integrity. Further studies are necessary to assess long-term visual prognosis and predictive factors in patients with type 1 neovascularization leading to persistent subretinal fluid that is recalcitrant to anti-VEGF treatment.     

Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.     

Progress of clinical therapies for dry age-related macular degeneration

Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.     

渗出型老年黄斑变性的吲哚青绿血管造影特征

目的 观察渗出型老年黄斑变性(age-related macular degeneration,AMD)的吲哚青绿血管造影(indocyanine green angiography,ICGA)特征。 方法 诊断为渗出型AMD的患者31例(39只眼)，年龄50～82岁，视力范围：指数/30cm～0.7,全部完成了眼部检查、眼底彩色照相、眼底荧光素血管造影(fundus fluorescein angiography,FFA)和吲哚青绿血管造影(indocyanine green angiography,ICGA)，分析和比较FFA和ICGA图像特征。 结果 FFA诊断为隐匿性脉络膜新生血管(choroidal neovascularization,CNV)的26只眼中，ICGA诊断为典型CNV有15眼，占57.7%。FFA诊断为浆液性色素上皮脱离(不伴CNV)4只眼中，有1只眼ICGA诊断为浆液性色素上皮脱离伴典型CNV。FFA和ICGA对瘢痕组织诊断的眼数及特性相近。 结论 与FFA相比，ICGA可提高对AMD典型性CNV的诊断率，扩大对AMD的治疗范围。(中华眼底病杂志,1998,14:76-80)     

Awareness of and compliance with recommended dietary supplement among age-related macular degeneration patients

BACKGROUND: The age-related eye disease study suggested that taking zinc and anti-oxidants supplements could reduce the progression of age-related macular degeneration (AMD). In Australia, the available supplement is Macu-Vision. The study aimed to assess the awareness of and compliance with taking this supplement and the public health implication. METHODS: The fundus photograph database of patients aged 55 years and older at the ophthalmology department of a public teaching hospital in Adelaide, Australia was reviewed. In total, 125 patients with category 3 and 4 AMD were identified. A total of 100 patients participated in this cross-sectional study. RESULTS: In total, 53% of participants were aware of the availability of the formulae available in Australia, 38% were taking the supplement and only 1% were taking the correct dose. Of those taking the supplement 95% (36/38) were taking half the recommended dosage. Among those who were aware of the supplement but not taking it, cost was the most common reason (31%). Another 31% were not taking it because of actual side-effects experienced, fear of potential side-effect and/or fear of interaction with other medications. There was no predictive factor for failing to take the formulae available in Australia among age, sex, smoking status, living arrangement and category of AMD. CONCLUSIONS: Clinicians need to emphasize that the recommended dosage is twice that on the supplement label. If the trend demonstrated here of underutilizing the formulae available in Australia among public hospital patients continues, it is unlikely to have any major public health impact in similar settings in Australia.     

Development of polypoidal lesions in age-related macular degeneration

Purpose

To investigate the development of polypoidal lesions using indocyanine green angiography (IA) in eyes with typical age-related macular degeneration (AMD).

Methods

We retrospectively reviewed the medical records of 47 consecutive patients (47 eyes) with typical AMD who had been followed up with IA for at least 2 years.

Results

At the initial visit, although all eyes showed classic and/or occult choroidal neovascularization (CNV) associated with AMD, no eyes showed polypoidal lesions by IA. However, during follow-up, 13 (27.7%) of the 47 eyes did show polypoidal lesions. All polypoidal lesions developed at the edge of persistent CNV or, more often, at the terminus of recently progressed CNV. Of 12 eyes with a final lesion area >8 disc area, 7 (58.3%) showed newly developed polypoidal lesions. In the eyes with these newly developed polypoidal lesions, the mean area of the vascular lesion had extended significantly from 10.50±7.88 mm² to 20.87±10.21 mm² during follow-up (P=0.0018).

Conclusion

The current observation suggests that IA of active AMD sometimes reveals polypoidal lesions if there is progression of the CNV in the subretinal pigment epithelium space.     

OCTA在湿性年龄相关性黄斑变性诊疗中的研究进展

光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)是一种快捷的、无创的新兴成像技术,可以定性、定量分析视网膜血流灌注,在临床的应用越来越广泛。脉络膜新生血管(choroidal neovascularization,CNV)是湿性年龄相关性黄斑变性(neovascular age-related macular degeneration,nARMD)导致老年人视力丧失的主要原因,因此在nARMD中对CNV的检测十分重要。本文通过OCTA对CNV的诊断、形态、面积及血流灌注的分析,综述了其在nARMD诊疗中的研究进展。     

息肉状脉络膜血管病变的分型研究

目的:依据吲哚菁绿血管造影(indocyanine green angiography,ICGA)显示的息肉状脉络膜血管病变(polypoidal choroidal vasculopathy,PCV)的形态进行分型,结合光学相干断层扫描(optical coherence tomography,OCT)及临床特征,探讨各型的特点,为PCV的治疗和预后评价提供依据。方法:回顾性分析在宁夏眼科医院就诊的33例PCV患者。所有病例均经过OCT和荧光素眼底血管造影(fundus fluorescein angiography,FFA)与ICGA等全面检查后确诊。根据ICGA的表现进行分型,同时对各亚型的病变特征进行比较。结果:共收集到33例54眼PCV患者,单眼12例,双眼21例;男20例,女13例;年龄42～86(平均70.63±9.42)岁。45眼病变部位位于黄斑区,占83%。根据ICGA的表现分为:息肉状扩张型(20眼,37%)、异常分支血管网型(16眼,30%)、经典型(18眼,33%)。27眼(50%)出现视网膜色素上皮脱离(pigment epithelial detachment,PED),其中分支血管网型及经典型出现PED的比例相对较高,分别为11眼(68.8%)和12眼(66.7%)。23眼(43%)出现视网膜神经上皮层脱离,其中分支血管网型10眼(62.5%)和经典型9眼(50.0%)易出现神经上皮脱离。31眼(57%)表现为活动型病变,其中分支血管网型和经典型常见,分别为13眼(81.3%)和13眼(72%)。10眼(19%)出现纤维机化膜,其中分支血管网型及经典型多见,分别为7眼(43.8%)和2眼(11.1%)。37眼(69%)有滋养血管的存在,其中分支血管网型和经典型分别为81%和94%。结论:分支血管网型及经典型易出现视网膜色素上皮脱离及视网膜神经上皮层脱离,多表现为活动型病变,存在滋养血管。而息肉型较少出现视网膜色素上皮脱离和神经上皮脱离,多表现为静止型,大多无滋养血管。异常分支血管网型易出现纤维机化膜。     

OCTA对年龄相关性黄斑变性的诊断评价及图像特征分析

光学相干断层血管造影(OCTA)是一种快速、无创的成像方法,可以提供视网膜和脉络膜的实时血流信息。与传统的血管造影相比较,OCTA可以产生更详细、更高分辨率的血管图像,而不增加造影剂相关风险。年龄相关性黄斑变性(ARMD)是全球主要的老年性致盲眼病,OCTA能很好地显示脉络膜新生血管的影像,为ARMD的早期诊断及干预提供可能。本文将对OCTA在ARMD的相关图像特征及其诊断价值进行综述。     

Treatment of dry age-related macular degeneration: A review

Age-related macular degeneration is a global disease with a significant societal impact. The advent of anti-vascular endothelial growth factor therapy (anti-VEGF) has revolutionised the treatment of neovascular age-related macular degeneration (nAMD). Dry age-related macular degeneration (dAMD) is being investigated for possible therapeutic options. The therapeutic categories undergoing clinical trials include complement pathway inhibitors, visual cycle modulators, reduction of toxic byproducts, antioxidative therapy, neuroprotective agents, laser therapy, surgical options, gene therapy, stem cell therapy, and miscellaneous treatments. Two intravitreal anti-complement factors (pegcetacoplan and avacincaptad pegol) have recently shown phase 3 clinical trial evidence of a reduction in the growth of geographic atrophy. In this review, we provide an update on treatment options currently undergoing clinical research trials for the management of dAMD and preventing the progression of Geographic Atrophy (GA).