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Intravitreal Bevacizumab for Symptomatic Retinal Arterial Macroaneurysm
Abstract
Purpose:
To evaluate the therapeutic effect of intravitreal bevacizumab injection for symptomatic retinal arterial macroaneurysm.
Design:
Retrospective interventional case series.
Methods:
The study included 23 patients (23 eyes) with symptomatic retinal arterial macroaneurysm. They were categorized according to treatment method into 2 groups: an intravitreal bevacizumab-treated group (11 eyes) and an untreated group (12 eyes). Bevacizumab was injected at the initial visit, followed by as-needed monthly reinjection. Best-corrected visual acuity (BCVA) and central macular thickness were documented and analyzed between groups.
Results:
The mean follow-up period for all subjects was 10.83 ± 4.6 months. The mean number of injections for the treated group was 1.42 ± 0.69. The mean logarithm of the minimal angle of resolution (logMAR) of BCVA improved from baseline at the last follow-up by 0.26 in the bevacizumab-treated group (P = .02) and by 0.34 in the untreated group (P = .005). Average central macular thickness decreased from 384.4 ± 150.1 μm to 265 ± 112.5 μm in the bevacizumab-treated group (P = .0002) and from 413.2 ± 155.2 μm to 236.3 ± 103.5 μm in the untreated group (P = .008). The BCVA was significantly improved from baseline after 1 month in the bevacizumab-treated group (P = .02) and after 3 months in the untreated group (P = .01). However, there was no statistically significant difference in BCVA improvement or central macular thickness improvement achieved at the final visit.
Conclusions:
Intravitreal bevacizumab injection likely hastens resolution of macular edema and hemorrhage secondary to retinal arterial macroaneurysm. Intravitreal bevacizumab injection could be an effective treatment option for symptomatic retinal arterial macroaneurysm.
... Laser photocoagulation directly into the lesion and/or surrounding retina has been described, but there is no consensus whether direct laser into the RAMA or indirect laser into the retina surrounding the RAMA or both are better [7][8][9]. Other commonly employed therapeutic options include surgical removal of associated hemorrhage with pars plana vitrectomy(PPV) [10,11], photo disruption of the internal limiting membrane (ILM) or the posterior hyaloid using neodymium: yttrium-aluminum-garnet (Nd: Yag) or argon laser to release the hemorrhage [12][13][14], intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs such as bevacizumab [15][16][17][18][19][20], ranizumab [21], conbercept [21] and aflibercept [22]. ...
... Regarding treatment, various options have been suggested with little evidence of consensus on the most effective one [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. We, herein, present the varied clinical profile and therapeutic options in these patients. ...
... Her presenting VA improved at 3 months follow-up from 0.78 to 0.30 LogMAR units. In cases of symptomatic RAMA with exudative or hemorrhagic changes [9] focal laser photocoagulation of aneurysm and surrounding retina [7][8][9], PPV [10,11], Nd: Yag or argon laser to release premacular subhyaloid hemorrhage [12][13][14] and intravitreal injection of anti-VEGF drugs such as bevacizumab [15][16][17][18][19][20] ranizumab [21], conbercept, [21] and aflibercept [22] have been tried with varying success, but no standard treatment guidelines have been developed yet. Serial bevacizumab injections and laser photocoagulation for macular edema associated with RAMA have also been tried [17]. ...
Purpose
To find out clinical characteristics, therapeutic options, and visual outcome in symptomatic retinal artery macroaneurysm (RAMA) patients.
Method
Newly diagnosed cases of symptomatic RAMA from January 2015 to December 2019 were included. Fifteen eyes of 15 patients with mean age 62.46 years ± 14.89 (SD) fulfilled the inclusion criteria.
Result
Hypertension was present in 66.6% of the patients, and the commonest site was superotemporal (12 eyes, 80%). The most commonly employed treatment was Nd: Yag laser hyaloidotomy in 4 eyes (26.6%). Other treatments were intravitreal bevacizumab in 3 eyes (20%), focal laser with intravitreal bevacizumab in 3 eyes (20%), PPV with focal laser (13.3%) in 2, focal laser only in one (6.6%), PPV with focal and intravitreal bevacizumab in one (6.6%). The mean best-corrected visual acuity (BCVA) at baseline was 1.35 ± 0.84 LogMAR, which improved to 0.39 ± 0.53 LogMAR at the last follow-up. Presenting VA 0.77 (±0.40) improved to 0.20 (±0.17) p value (0.180) in intravitreal bevacizumab only group, 1.29 (±0.35) to 0.75 (±0.15) p value 0.66 in Nd: Yag laser group, 2.67 (±0.58) to 0.46 (±0.28) p value 0.019 in PPV group and did not improve in combined anti-VEGF and focal laser group due to dense hard exudates at the fovea in one and persistent cystoid macular edema in another case.
Conclusion
With regard to its presentation, which can vary tremendously, there are no approved guidelines for its treatment. The present study reinforces the need for a treatment guideline development. Customization of treatment should be considered depending on the clinical presentation of each case.
... [4,7,15] Some case reports and studies have also reported encouraging results on intravitreal anti-VEGF agents for RAMs in recent years. [16][17][18][19] As far as RAMs are concerned, there is still no consensus in terms of treatment, and the results of different modes of management vary. Although the use of intravitreal anti-VEGF agents is an available alternative option, only few case reports/ series describe its benefits in patients with RAMs, and there are no standard protocols for their use. ...
... And these mechanisms are believed to be helpful in managing hemorrhagic or exudative complications in RAMs with foveal involvement. [7,19] Before 2013, there were few case reports discussing the treatment outcomes of intravitreal anti-VEGF agents for RAMs though they led to satisfactory results. [16][17][18] Cho et al retrospectively reviewed 23 patients (23 eyes) with symptomatic RAM divided into an intravitreal bevacizumab-treated group and an untreated group. ...
... BCVA improved from baseline after 1 month and 3 months in the bevacizumab-treated group, but there was no significant difference in BCVA improvement or central macular thickness improvement achieved between the 2 groups at the final visit. [19] Pichi et al conducted an interventional prospective nonrandomized study including 38 RAMs of 37 patients with foveal complications. With 3 monthly injections of bevacizumab 1.25 mg/0.05 ...
Retinal arterial macroaneurysms (RAMs) develop as outpouchings of the arterial wall that is weakened by arteriosclerosis. The traditional treatment of RAMs comprises observation, focal laser photocoagulation, or surgery. Recently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has been announced as an effective therapy for fovea-threatening RAMs and quickly improve visual acuity and central retinal thickness (CRT).
In the retrospective series, medical charts and ocular images of 24 patients diagnosed as having RAM between May 2011 and November 2018 in our facility were reviewed to delineate clinical manifestations and visual prognosis in RAM patients receiving different treatment modalities. Twenty-four patients (25 eyes; 11 men and 13 women) were enrolled, and one eye with comorbidity of branch retinal vein occlusion was excluded. The mean age of the patients was 69.00 ± 13.45 years. Fourteen patients (58.33%) had a history of hypertension, and 17 patients (70.83%) were aged > 60 years. Furthermore, patients with fovea-threatening RAMs presented with either hypertension or were aged > 60 years.
Eyes with fovea involvement (n = 18) were analyzed and separated into two groups according to their treatment modalities: those receiving anti-VEGF intravitreal injections (n = 13) and observation only (n = 5). The baseline visual acuity revealed no significant difference in the two groups. In patients receiving anti-VEGF intravitreal injections, a significantly better visual acuity was detected after anti-VEGF intravitreal injections than the baseline visual acuity (logMAR, 0.78 ± 0.51 vs 1.52 ± 0.48, P < .001), and CRT significantly improved (505.50 ± 159.26 μm vs 243.60 ± 60.17 μm, P = .001). Patients receiving anti-VEGF intravitreal injections also revealed better final visual acuity than those in the observation group (logMAR, 0.78 ± 0.51 vs 1.34 ± 0.48, P = .04).
A systematic work-up for hypertension and arteriosclerotic disease could be considered the recommended procedure once RAM has been diagnosed. With better final visual acuity, significant visual improvements, and fast reduction of CRT observed in patients with fovea-threatening RAMs receiving anti-VEGF intravitreal injections, intravitreal anti-VEGF was considered an effective therapy for complicated RAM. During the follow-up period, the majority of RAM eyes had good maintenance of visual function even with foveal complications.
... There are several treatment options with various outcomes [5][6][7], yet no consensus has been reached on the most effective. Recent studies have revealed that intravitreal injection with anti-vascular endothelium growth factor (anti-VEGF) drugs could provide encouraging outcomes [7][8][9][10]. In our paper, we presented the clinical features and outcomes in three cases of symptomatic RAMs treated with anti-VEGF agents. ...
... Recently, intravitreal injections of anti-VEGF agents have been advocated for the management of RAM patients with the macular hemorrhage or edema. Chanana and Azad [13] published the first case report in 2009, and subsequent case reports have shown encouraging results [6][7][8][9][10]. Intravitreal injections of bevacizumab [8,9,13], ranibizumab [14,15], or aflibercept [10,14] could lead to rapid and complete resolution of macular edema and hemorrhage, as well as significant visual recovery. ...
... Chanana and Azad [13] published the first case report in 2009, and subsequent case reports have shown encouraging results [6][7][8][9][10]. Intravitreal injections of bevacizumab [8,9,13], ranibizumab [14,15], or aflibercept [10,14] could lead to rapid and complete resolution of macular edema and hemorrhage, as well as significant visual recovery. However, the mechanism of the therapy remains unclear. ...
Background
There is no consensus for the standard treatment of retinal arterial macroaneurysm (RAM). Intravitreal anti-vascular endothelium growth factor (anti-VEGF) is an alternative treatment option for RAM. The purpose of this study is to describe the clinical efficacy of intravitreal ranibizumab or intravitreal conbercept for retinal arterial macroaneurysm.
Case presentation
Three cases that presented with symptomatic RAM were treated with intravitreal anti-VEGF agents. Two eyes received two intravitreal ranibizumab injections with a time interval of one month and completed a one-year follow-up, while one eye only received one intravitreal conbercept injection and was followed up for six months. Both the retinal thickness and the visual acuity were significantly improved at the final clinic visit. The macular hemorrhage and edema were resolved. There were no ocular or systemic side effects.
Conclusions
Intravitreal ranibizumab or conbercept might be used as a therapeutic option for symptomatic retinal arterial macroaneurysm patients. Anti-VEGF therapy should be further investigated in a larger series with longer follow-up for this disease profile.
... Although treatment for RAMs is required in patients with sight-threatening macular involvement, there is no well-established option. In recent studies, the promising results of intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents, such as bevacizumab and ranibizumab, for symptomatic RAM with macular hemorrhage or secondary macular edema have been demonstrated [5][6][7][8] . This case report describes the experience with a patient experiencing a ruptured RAM with sub-internal limiting membrane (ILM) preretinal hemorrhage who was treated with intravitreal aflibercept injection. ...
... The mechanism of anti-VEGF medication in the treatment of RAMs is not fully understood [4] . The inhibition of VEGF resulted from the reduced vascular permeability and central macular thickness, which also leads to visual acuity gain and clearance of the various retinal hemorrhages [7,15] . VEGF causes vasodilation by stimulating endothelial production of nitric oxide, which is related to the activation of coagulation cascades. ...
... VEGF causes vasodilation by stimulating endothelial production of nitric oxide, which is related to the activation of coagulation cascades. Anti-VEGF agents may reduce edema by reducing nitric oxide and causing vasoconstriction [7,15] . Additionally, inhibition of VEGF may alter the balance between coagulation and fibrinolysis, thus facilitating the clearing of retinal hemorrhage [7] . ...
... Patients presented clinical signs of RAM consisting of sub-and intraretinal fluid, hard exudates, and intraretinal hemorrhage. In the bevacizumab group, there was a significant increase in visual acuity [11]. Pichi et al. [9] prospectively studied the use of bevacizumab in 37 cases of similar clinical findings and found that the functional and anatomical endpoints had improved significantly after bevacizumab treatment. ...
... Furthermore, OCT shows an elevated retina covering a hyporeflective lumen with a hyperreflective wall. Intra-and subretinal fluid are other typical findings [8,9,11,12]. ...
... On the one hand, anti-VEGF may reduce nitrogen oxide production in the endothelium with vasoconstriction, the decrease in vascular permeability, and edema reduction. Additionally, the balance between coagulation and fibrinolysis is improved [11,12]. ...
Introduction
Complex retinal arterial macroaneurysms (RAM) are often accompanied by hemorrhage and/or affect the macula. We evaluated the effect of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy using ranibizumab or aflibercept with or without laser photocoagulation in the treatment of macular edema due to RAM.
Methods
A case report of two patients with secondary macular edema caused by RAM is presented. The first case was a 76-year-old female treated with two 0.5-mg injections of ranibizumab and additional focal laser photocoagulation. This patient presented a solely intraretinal exudation. The second patient was a 96-year-old female, who received one 2.0-mg injection of aflibercept. She showed sub- and intraretinal edema. We documented the clinical courses of these patients based on fundus photography, fluorescein angiography, and spectral-domain optical coherence tomography. Patients were followed-up for 12 months.
Results
Patients were treated successfully using anti-VEGF therapy (ranibizumab or aflibercept) with or without laser photocoagulation. In both cases, we observed a complete regression of the macular edema and an increase in visual acuity.
Conclusion
RAM can manifest with heterogeneous findings. Intravitreal anti-VEGF therapy with or without laser photocoagulation may be an effective treatment option in cases of macular edema due to RAM. Aflibercept and ranibizumab seem to be a potent anti-VEGF therapy for RAM. Individualized patient care is needed.
... Since the initial case report by Chanana and Azad in 2009 [9] demonstrating resolution of RAM-induced ME after two intravitreal injections of 1.25 mg bevacizumab (IVB) administered 1 month apart, intravitreal anti-VEGF agents, both bevacizumab and ranibizumab (RZB) have been used for the management of complications of RAM [10][11][12][13]. Anti-VEGF therapy may improve outcome in symptomatic RAM eyes by anti-permeability effects of VEGF inhibition [10,13], resolution of hemorrhages by an unknown mechanism similar to anti-VEGF treated eyes with retinal vein occlusion, encouragement of gliosis within the RAM by 'profibrosis switch' [14], or a combination of these factors. ...
... Most publications regarding intravitreal anti-VEGF injections for RAM are either case reports or small case series with mostly short-term follow-up. Publications with fewer injections [11] seem to show worse anatomical and visual outcomes compared to those with mandated monthly injections [10]. ...
... Numerous case reports and small case series seem to suggest beneficial role of anti-VEGF therapy for complications of RAM. Although 11 IVB treated eyes recovered vision faster than 12 eyes that were observed in a study by Cho et al. [11], final anatomical and visual results were equivalent in bevacizumab treated and untreated eyes after a mean follow-up of 10 months. Interestingly, eyes received only a mean of 1.4 injections throughout the study period. ...
Purpose
To report the 1-year follow-up results of intravitreal aflibercept injection (IAI) for the management of complications of retinal artery macroaneurysms (RAM).
Methods
A retrospective, noncomparative, interventional case series of 4 eyes of 4 patients (all female, aged 68–91 years, 3 treatment naive) treated with IAI 2 mg for complications of RAM [macular edema (ME) 2, submacular hemorrhage (SMH) 1, and vitreous hemorrhage (VH) 1] was conducted. Baseline parameters consisted of complete ocular examination, medical history, best-corrected Snellen VA, fundus photography, IVFA and SD OCT, unless precluded by VH (1). All patients completed ≥1 year follow-up.
Results
Baseline VA was hand motions in the eye with SMH (31 mm² area and 1,478 μm thickness); 20/40 and 20/100 with ME (CST 390 and 337 μm, respectively), and 20/200 in the eye with VH. At 1 month, both patients with ME showed resolution of ME with CST <300 μm with improvement in VA which was maintained through 1 year. VH resolved in one eye at 1 month with no recurrence after 1 year. The eye with SMH developed macular scar and had counting fingers vision at 1 year. Thrombosis of RAM was noted in all eyes and hairpin-like remodeling of artery in one. No eye required repeat injection or laser.
Conclusion
ME and VH from RAM were effectively treated with IAI. However, the eye with thick SMH had poor visual outcome despite thrombosis of RAM. Single IAI provided effective therapy for complications of RAM with excellent anatomical and visual results in each eye, except one with thick SMH, and merits further study.
... Intravitreal injection of anti-VEGF proved its efficiency in the treatment of RAM. According to Cho et al. [15] , anti-VEGF not only can induce vasoconstriction and reduce macular edema but also has an action on the coagulation cascade and helps clearing multilevel hemorrhages, including subhyaloid hemorrhage. This study showed no significant difference in VA between patients treated by anti-VEGF and untreated patients. ...
... This study showed no significant difference in VA between patients treated by anti-VEGF and untreated patients. However, those treated with anti-VEGF show faster improvement in VA, macular thickness, and hemorrhage [15] . Moreover, it has been proven by many studies that, in case of longstanding hemorrhages, especially subretinal and intraretinal hemorrhage, prolonged contact with hemoglobin and iron is toxic to retinal layers and leads to progressive photoreceptor deterioration within a period of 2 weeks and permanent visual damage [16] . ...
The authors report two cases of retinal artery macroaneurysm (RAM) complicated with subhyaloid hemorrhage. There are multiple cases about RAM that have been published; however, none of them present all the different treatments with its benefits and its limitations. Our study highlights all aspects of treatment. RAM is an uncommon pathology that affects generally elderly women with systemic vascular pathologies. It is often unilateral, and the patients stay mostly asymptomatic. Most cases of RAM regress without any treatment. A case of a 54-year-old male, with a medical history of hypertension who presented with an acute and unilateral decreased visual acuity (VA). Initial VA was limited to counting fingers at 1 m in the right eye (RE). The anterior segment was normal in both eyes. A fundus examination in the RE showed a large subhyaloid hemorrhage associated to retinal hemorrhage. Fluorescein angiography in the RE did not reveal any sign of macroaneurysm due to blockage of fluorescein by the hemorrhage. In the left eye, there was a hyperfluorescent paramacular lesion. Optical coherence tomography showed the hyperreflectivity of the subhyaloid hemorrhage and the underlying retinal layers could not be seen. Neodymium-doped yttrium aluminum garnet laser hyaloidotomy was performed for this patient to release the trapped hemorrhage into the vitreous, 3 weeks after initial loss of vision with a good visual outcome after the treatment. An 80-year-old woman, with medical history of rheumatoid arthritis who presented with an acute loss of vision in the RE. VA in the RE was 20/200. She had a nuclear cataract in both eyes. A fundus examination showed a subyaloid hemorrhage. Fluorescein angiography in the RE revealed a hyperfluorescent structure emanating from the superotemporal arcade of the artery compatible with a macroaneurysm. The patient was treated with three intravitreal antivascular endothelial growth factor injections with poor visual outcomes. Vision loss occurs with RAM complications. They mainly involve hemorrhages and macular exudations and are usually associated with poor visual recovery. There is no established treatment for RAM and its complications. There are many options, but the optimal therapy is still unknown.
... Since then, there have been several studies on the use of anti-VEGF agents (bevacizumab, ranibizumab, aflibercept, conbercept) for both hemorrhagic and exudative complications of RAM [46][47][48]. Symptomatic RAM responds well to a limited number of injections (1 to 3) [49][50][51][52]. In their landmark prospective study, Pichi et al. found that three monthly bevacizumab injections led to aneurysm closure, resolution of macular edema and hard exudates, and significant visual improvement in nearly all 38 treated eyes [50]. ...
... Despite retrospective comparative studies highlighted no significant differences in the final visual outcome between IV bevacizumab and mere observation, albeit the former likely hastens the resolution of edema and hemorrhage [49,53], a recent meta-analysis reported that anti-VEGF agents lead to RAM closure (93-100%) and visual acuity improvement (74-100%) in a higher proportion of patients when compared to observation and even laser. Interestingly, the visual prognosis of RAM treated with anti-VEGF was better in exudative than in hemorrhagic ones [19]. ...
Retinal arterial macroaneurysm (RAM) can be defined as an acquired round or fusiform dilation of a retinal artery. RAMs frequently remain stable but, in some cases, can complicate with macular exudation or hemorrhage, resulting in symptomatic disease. While a watch-and-wait approach is the standard option in asymptomatic RAMs, there is no universal agreement regarding treatment of symptomatic cases and randomized clinical trials are warranted. Anti-VEGF intravitreal injections can reduce exudation, albeit multiple treatments may be necessary. Hence, laser treatment may be a better choice to provide a durable control of symptoms while anti-VEGF therapy should be preferred for lesions adjacent to the fovea. Indirect laser is recommended because there is a decreased danger of RAM rupture and hemorrhage. Furthermore, subthreshold laser seems to be comparable to conventional laser in terms of efficacy outcomes.
... Anti-VEGF drugs have been successfully used to treat RAM in recent years, leading to a decrease in macular edema, although the treatment of RAM with anti-VEGF drugs still belongs to off-label uses [15,16]. The mechanism of this curative effect is not known but can be hypothesized as follows: (1) VEGF inhibitors can inhibit angiogenesis caused by retinal ischemia in the pathogenesis of RAM, reduce the vascular permeability of VEGF, and decrease RAM hemorrhage and exudation [17]. ...
... The researchers found that patients treated with three monthly injections had better visual results. However, Cho et al. [16] found no difference in VA or CMT improvement between intravitreal bevacizumab therapy and observation alone at final follow-up in another retrospective series of 23 patients. ...
Background
To explore the efficacy of observation, laser photocoagulation, and anti-VEGF in the management of retinal arterial macroaneurysm (RAM).
Methods
We retrospectively included patients diagnosed with RAM at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2021, and comprehensively reviewed cases documented in the literature from multiple databases (PROSPERO protocol CRD42022310417). Patients were categorized into 3 groups: the observation group, anti-VEGF group, and laser photocoagulation group. LogMAR visual acuity (VA) and central retinal thickness (CMT) at the end of the follow-up were analyzed.
Results
A total of 14 patients from the PUMCH and 210 patients from the literature review were included. VA and CMT in patients who underwent observation, laser photocoagulation, and anti-VEGF therapies were significantly improved from baseline (p < 0.05), with changes in LogMAR VA improved by -0.34 ± 0.68, -0.17 ± 0.58, and -0.45 ± 0.62 and changes in CMT improved by -148.26 ± 138.99 µm, -185.61 ± 130.37 µm, and -287.45 ± 171.87 µm, respectively. Subgroup analysis revealed that anti-VEGF therapy was used in patients with worse VA than patients who underwent laser photocoagulation (p = 0.010), but achieved better improvement in VA than the laser photocoagulation group (p = 0.049). Patients treated with anti-VEGF also had thicker CMT than the observation group (p = 0.013), and experienced better changes in CMT than the observation, as well as laser photocoagulation groups (p = 0.005; p = 0.047).
Conclusion
Observation, anti-VEGF, and laser photocoagulation are effective therapeutic methods for the management of RAM, and anti-VEGF therapy is intended to better improve patients with severe VA and CMT.
... In most reported cases, the anti-VEGF treatment group did show better RAM resolution and VA improvement than the observational group [15,31,32]. However, Cho et al. [33] found no difference of anatomic improvement or VA improvement between bevacizumab-treated and bevacizumab-untreated groups. We found in our study that higher proportion of patients receiving anti-VEGF injections achieved RAM closure and VA improvement compared to observation. ...
... Anti-VEGF treatment may be advantageous over laser for those lesions close to the fovea or optic disk, because it is free of locally destructive side effects. Exudative lesions typically respond well to relatively few intravitreal anti-VEGF injections [6,34]; the lessened leakage and edema may be due to a reduction of nitric oxide levels caused by VEGF inhibitors [33]. According to the pooling incidence we got, it seems that the combined treatment could be a promising intervention strategy. ...
PurposeTo estimate the clinical characteristics of retinal arterial macroaneurysms (RAM) and evaluate the prognosis of different interventions.Methods
This study is a meta-analysis. The databases PubMed, EMBASE, and Ovid from inception to January 2021 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated by means of Freeman-Tukey variant of arcsine square transformation.ResultsSixty-nine studies involving 1332 patients were finally included. The pooling results indicated that 91% (95% CI [88 ~ 94%]) of the RAM patients were over sixty, 73% (95% CI [68 ~ 77%]) were female, and 73% (95% CI [66 ~ 79%]) have hypertension. By observation, the RAM closure rate was 64% (95% CI [39 ~ 86%]), the visual acuity (VA) improved in 55% (95% CI [40 ~ 71%]) of the patients, and the VA of 64% (95% CI [54 ~ 74%]) hemorrhagic versus 27% (95% CI [15 ~ 41%]) exudative patients improved significantly. By laser, the closure rate was 96% (95% CI [87 ~ 100%]), the VA improved in 73% (95% CI [65 ~ 80%]) of the patients, and the VA of 66% (95% CI [47 ~ 84%]) hemorrhagic versus 35% (95% CI [23 ~ 47%]) exudative patients improved significantly. By anti-VEGF, the closure rate was 98% (95% CI [93 ~ 100%]), the VA improved in 90% (95% CI [74 ~ 100%]) of the patients, and the VA of 58% (95% CI [18 ~ 94%]) hemorrhagic versus 67% (95% CI [31 ~ 96%]) exudative patients improved significantly.ConclusionRAM are most commonly seen in the elderly with a marked female predominance and a strong association with hypertension. Patients receiving laser or anti-VEGF treatments get higher closure rate and better visual prognosis than those with observation alone. Hemorrhagic RAM have a better visual prognosis by observation or laser treatment, while exudative RAM have a better visual prognosis by anti-VEGF treatment.
... The results of earlier studies show that the anti-VEGF agents act by reducing abnormal leakage, including that from microaneurysms. 17,18 In addition, the Diabetic Retinopathy Clinical Research Network protocol V study reported no significant difference in vision loss regardless of whether eyes were initally managed with aflibercept or with laser photocoagulation in eyes with center-involved DME and good visual acuity. The authors stated that patients should be given aflibercept only if visual acuity worsens. ...
... There have been at least 2 reports of a reduction in the number of microaneurysms after anti-VEGF therapy, as we found. 17,18 However, these studies did not examine the results of more than 3 consecutive injections. Many other studies have shown that multiple injections of anti-VEGF agents can improve the severity of the DR. ...
Purpose:
To evaluate the effects of intravitreal aflibercept (IVA) on the number of microaneurysms and sizes of nonperfused areas (NPAs) in eyes with diabetic macular edema (DME).
Design:
Interventional, prospective study.
Participants:
Twenty-five eyes of 25 DME patients (average age, 64.0±8.8 years) were treated with 3 consecutive monthly IVA injections.
Methods:
Fluorescein angiography (FA) and OCT were performed before the IVA injections (baseline) and at 1 week after the IVA treatment. The number of microaneurysms and the ischemic index (ISI), a measure of NPA, were determined. The correlations between central retinal thickness (CRT) and number of microaneurysms and the ISI were also determined.
Main outcome measures:
The mean number of microaneurysms and NPA evaluated as the ISI.
Results:
At baseline, the mean CRT was 485.7±90.6 μm. After treatment, the mean CRT was reduced significantly to 376.9±81.6 μm (P = 0.1 × 10-5, repeated analysis of variance). The mean number of microaneurysms was decreased significantly from 49.6±33.2 at baseline to 24.8±18.1 at 3 months after the initial treatment. This was a 50.4±21.2% reduction (P = 0.3 × 10-5, paired t test). The mean ISI was also decreased significantly from 55.5±20.4% at baseline to 28.8±16.8% after treatment (P = 0.3 × 10-5, paired t test). This was a reduction of 43.3±28.5%. A significant correlation was found between the CRT and number of microaneurysms at both baseline (r = 0.56; P = 0.004) and after treatment (r = 0.53; P = 0.006). A significant correlation was found between CRT and ISI at baseline (r = -0.39; P = 0.03) but not after treatment (r = -0.06; P = 0.79).
Conclusions:
The reduction in the number of microaneurysms was correlated with reduction in CRT.
... Pichi et al. found that in their prospective study of 18 eyes with symptomatic hemorrhagic RAMs (defined with size of 1-4 disc diameters and excluding dense vitreous hemorrhage), a series of three monthly bevacizumab injections led to closure of the aneurysm in nearly all cases and to significant visual improvement [17]. Within Cho et al.'s retrospective study, there were 7 eyes with symptomatic hemorrhagic RAMs (excluding cases with dense vitreous hemorrhage) that were treated with bevacizumab and 10 hemorrhagic eyes that were left untreated [18]. In contrast to the aforementioned study, pro re nata Fig. 1 65-year-old gentleman presents with a hemorrhagic RAM with count fingers vision. ...
... The mechanism by which these anti-VEGF agents act on leakage in RAM has yet to be fully elucidated. One proposed mechanism is that VEGF inhibitors lead to a reduction of nitric oxide levels which subsequently cause vasoconstriction and decreased vascular permeability and, thus, less leakage and edema [18,42]. It is also proposed that anti-VEGF agents may lead to a tighter alignment of endothelial cells [43]. ...
Purpose of Review
This is a comprehensive review of management options for retinal arterial macroaneurysms (RAMs). Although close observation is typically recommended for RAMs not involving or threatening the macula, other treatment modalities can be considered for exudative or hemorrhagic complications that are vision-threatening.
Recent Findings
New imaging technologies like optical coherence tomography angiography (OCT-A) have been able to detect RAMs without the need of dye injection, further elucidating our understanding of blood flow within and around them. Observation alone is usually an adequate treatment when a lesion is not threatening the fovea. Laser photocoagulation and intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors have effectively been used for management of exudative RAMs, whereas options including injection of VEGF inhibitors, tissue plasminogen activator (tPA), vitrectomy, gas, and yttrium aluminum garnet (YAG) laser have been used for hemorrhagic RAMs.
Summary
To date, there is no consensus regarding management of symptomatic exudative or hemorrhagic complications of RAM. Additionally, a case report is presented within this paper to illustrate the successful treatment of a hemorrhagic RAM in a symptomatic 65-year-old man using intravitreal bevacizumab.
... Intravitreal injection of VEGF inhibitors, such as ranibizumab or bevacizumab, is more recent therapeutic alternative that has been found effective for the treatment of neovascular age-related macular degeneration [13], macular edema due to diabetes [14], and vein occlusion [15]. VEGF inhibition in these pathologies results in reduced vascular permeability and central macular thickness [16], leading to visual improvement, and may facilitate clearing of the various retinal hemorrhages [17]. In accordance with these findings, intravitreal injection of anti-VEGF drugs has been considered a treatment option for RAM. ...
... Pichi et al [18] found that intravitreal injection of bevacizumab is an effective therapy for complex RAM, leading to rapid improvement in BCVA and central retinal thickness. In addition, Cho et al. [16] reported that intravitreal bevacizumab injection likely hastens resolution of macular edema and hemorrhage secondary to RAM. In one study, intravitreal injection of ranibizumab in one RAM patient resulted in closure of the macroaneurysm, leading to resolution of the associated macular edema and visual improvement [19]. ...
Aim:
To evaluate the anatomic and functional results of intravitreal ranibizumab injection for treatment of symptomatic retinal arterial macroaneurysm (RAM).
Materials and methods:
A series of seven patients (seven eyes) who had been diagnosed with symptomatic RAM were assessed by comprehensive ophthalmologic examination, fluorescein angiography (FA), optical coherence tomography (OCT), and indocyanine green angiography (ICGA). All patients were treated by intravitreal ranibizumab injection within one week of diagnosis and retreated upon evidence of persistent serous detachment or hemorrhage involving the macula on OCT. Anatomical recovery was examined by FA, OCT, and ICGA. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated using the Snellen chart and optical coherence tomography, respectively, at baseline; at 1, 3, and 6 months; and at the final visit. The BCVA and CMT values at baseline and the final visit were compared using the Wilcoxon signed rank test and determination of logarithm of the minimal angle of resolution (logMAR) of BCVA value.
Results:
Over a mean follow-up period of 10.86 ± 5.4 months, significant visual and anatomical recovery was observed, with visual acuity improving by three or more lines in all seven patients. The mean logMAR of BCVA improved from 1.09 ± 0.60 to 0.16 ± 0.16 (p = 0.018) and mean CMT decreased from 427.5 ± 132.4 μm to 208.7 ± 23.1 μm (P = 0.018). No complications were observed with intravitreal ranibizumab injection.
Conclusion:
İntravitreal ranibizumab is an effective therapy for symptomatic RAM, improving BCVA and decreasing CMT.
... 12 Intravitreal injections of anti-vascular endothelial growth factor (VEGF) have been studied as a treatment option for RAM with macular hemorrhage or secondary macular edema. 13 Pars planavitrectomy (PPV) may be considered in cases of non-clearing vitreous hemorrhage, usually after 3 months of observation. 2,14 Patients presenting with RAM need evaluation by their primary care physician for hypertension, lipid and arteriosclerosis control. ...
Retinal arterial macroaneurysms are acquired, focal dilation of a retinal artery. Patients with retinal arterial macroaneurysms can present with an acute or gradual loss of vision as a result of vitreous hemorrhage, preretinal hemorrhage or macular edema. An 81 year old female, a known hypertensive since 12 years under regular follow-up visits, presented to us with vitreous hemorrhage secondary to ruptured retinal artery macroaneurysm in the right eye. She was managed with indirect argon laser treatment. Accurate diagnosis and co-management are crucial to save vision and help prevent life altering complications. This case report emphasizes the need of ocular examination in systemic diseases and further establishes ‘eye as the window of the body’.
... In the case of our observation we have demonstrated the interest of intravitreal injections of anti-VEGF (Ranibizu-mab) in symptomatic macroneuroses, allowing a faster regression of exudative phenomena in case of insufficient photocoagulation alone [13,14]. Anti-VEGF for earlier functional recovery. ...
Retinal macroaneurysm.is a rare complication of uncontrolled IHT. It is responsible for exudative phenomena with DSR which can threaten visual function especially if it is macular localization. The prognosis depends on 'the importance of exudation and alteration of photoreceptors. Treatment remains essentially physical.
... 6,7 However, macular edema (ME) did not improve but rather persisted in a significant number of patients, even after repeated intravitreal anti-VEGF injections. 8,9 Microvascular abnormalities such as MAs are the most characteristic signs of DR, and extravascular leakage from these can cause DME. 10 Regarding the relationship between VEGF and MAs, we 11 and others [12][13][14][15] have recently demonstrated that intravitreal injection of anti-VEGF agents can reduce the number of MAs present in DME patients. Sugimoto et al further demonstrated that the reduction in the number of MAs correlated with a reduction in the central retinal thickness. ...
Purpose:
Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME.
Patients and methods:
Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images.
Results:
There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03).
Conclusion:
Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.
... Hence anti-VEGF may cause vasoconstriction and alter the balance between coagulation and fibrinolysis and hence reducing the exudative complications of RAM. In a case series by Cho et al., [10] patients treated with anti-VEGF showed faster resolution of retinal haemorrhage and rapid gain in visual acuity compared with the control group. ...
To discuss the clinical profile of retinal artery macroaneurysms (RAMs), its presentation, rarity, complexity in diagnosis and management modalities. RAMs are seen commonly in elderly females who have associated systemic hypertension. Most of these aneurysms undergo spontaneous involution due to fibrosis while others may result in vascular leakage with macular oedema and haemorrhage into various layers of retina. Long-standing exudation may result in the development of cystoid macular oedema (CME), macular hole, macular exudate, retinal gliosis, and atrophy. Since the arterioles are high-flow vessels, it ruptures under high pressure resulting in haemorrhages at various levels – vitreal, preretinal, intraretinal, and subretinal. Multiple RAMs maybe hereditary, inherited in an autosomal recessive pattern presenting with recurrent vitreous haemorrhage. Treatment is to ensure rapid resolution of haemorrhage and exudation thereby facilitating early visual recovery and avoiding permanent visual loss. Referral to a physician is essential for the management of hypertension and associated systemic illnesses. Here we describe a case of multiple bilateral macroaneurysms with coexistent diabetic retinopathy.
... 38 In addition, similar to our result, several studies have shown that the intravitreal injections of anti-VEGF agents can reduce not only the CMT but the number of MAs in eyes with DME. 11,40,41 Previously, we had reported that the CMT was significantly correlated with the number of MAs both before and after anti-VEGF treatments. A significant correlation was found between the CRT and number of MAs at both the baseline (r = 0.56) and after treatment (r = 0.53). ...
Purpose:
To determine the effectiveness of intravitreal aflibercept (IVA) on the retinal function in eyes with diabetic macular edema (DME).
Methods:
Twenty-five eyes of 25 patients with DME were treated with three consecutive monthly IVA injections. The retinal sensitivities (RS) within the central 10° were determined by microperimetry (MP). The central subfield macular thickness (CMT) was determined by optical coherence tomography, and the implicit times (IT) and amplitudes (Amp) of the flicker electroretinograms (ERGs) were determined from the ERGs elicited and recorded by the RETeval. The number of microaneurysms (MAs) was counted in the fundus photographs. The assessments were made before the IVA injections (pre-IVA) and one week after the IVA injections (post-IVA). The correlations between the reduction ratio of the MA numbers/CMT and RS/IT/Amp were evaluated.
Results:
The mean RS improved from 19.9 ± 5.9 dB to 22.0 ± 5.8dB, the CMT decreased from 485.7 ± 90.6 µm to 376.9 ± 81.6 µm, and the number of MAs decreased from 49.6 ± 33.2 to 24.8 ± 18.1 after the IVA injection (all P < 0.01). The changes in the IT from 31.3 ± 3.3 ms to 31.5 ± 3.1 ms and the Amp from 12.2 ± 5.5 µV to 11.3 ± 6.1µV post-IVA were not significant. A significant correlation was found between the relative changes in the CMT and RS (r = -0.43; P = 0.02), the MAs and RS (r = -0.38; P = 0.03). No significant correlation was observed between the relative changes of the number of MAs/CMT and IT/Amp.
Conclusions:
IVA can improve both central retinal function and anatomical conformation.
Translational relevance:
A new aspect of aflibercept will be useful for DME treatment.
... have hypothesized that anti-VEGF in RAM reduces vascular permeability and activates coagulation cascades leading to involution. [5] However, there is no report of its use in optic disc RAM in published literature. Our case suggests that Anti-VEGF can have a role in management of optic disc RAM which is non-resolving. ...
... 9 Literatürde anti-VEGF ajanların RAM tedavisinde kullanıldığını gösteren olgu sunumları bulunmaktadır. [10][11][12][13][14][15] Bu makalede, RAP seyri sırasında tesadüfen semptomatik RAM saptanmış bir olguda anti-VEGF tedavisi olarak intravitreal afl iberceptin etkisini bildirmeyi amaçladık. ...
It is aimed to present a case to demonstrate that the incidental symptomatic retinal macroaneurysm is closed by the effect of intravitreal afribercept. Seventy-six-year-old male patient which was under follow-up for age-related macular degeneration in the retina department presented with retinal edema covering all macular area due to a macroaneurysm in the superior temporal branch of the retinal artery. The patient was treated with 3 consecutive monthly injections of intravitreal aflibercept. Macular edema was observed to gradually decreased with complete closure of the RAM after the treatment. The best corrected visual acuity improved from 3/10 at baseline to 7/10 after the treatment. Ocular or systemic side effect was not observed. Intravitreal afl ibercept can provide closure of RAM, disappearance of macular edema by gradual resolution and hence improvement of visual acuity. Intravitreal afl ibercept may be an alternative and effective treatment for symptomatic RAM
... More recent modalities have included focal pulse or subthreshold 8 laser and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. [9][10][11][12][13][14][15][16][17] Anti-VEGF therapy seems to be a promising alternative to laser photocoagulation, especially in eyes with macular exudation from RAM located inside the arcade including optic disk RAM. The aim of this study is to further delineate the risks and benefits of anti-VEGF therapy in eyes with a RAM and visual loss in a multicenter retrospective study. ...
Purpose:
There is no established therapy for exudative-hemorrhagic complications in primary retinal arteriolar macroaneurysm (RAM).
Methods:
Retrospective multicenter interventional study of anti-vascular endothelial growth factor in symptomatic RAMs. Central macular thickness in μm and best-corrected visual acuity in logMar were correlated with the RAM size and distance to the macula. Statistical analyses were performed using paired comparisons and Pearson correlation.
Results:
Thirty-two eyes (32 patients) were treated with a mean of 2.7 injections over a mean follow-up of 16.6 months. Initial best-corrected visual acuity correlated with the RAM size and distance to the macula (P = 0.02). Central macular thickness decreased by 131,180, and 211 μm at 1, 2, and 3 months after the first injection (P < 0.001). Best-corrected visual acuity improved by 0.47 and 0.38 Early Treatment Diabetic Retinopathy Study lines at 2 and 3 months (P = 0.005). Anti-vascular endothelial growth factor response correlated with the RAM size (P = 0.04) and the distance to the macula (P = 0.009).
Conclusion:
Symptomatic RAMs can be treated successfully with anti-vascular endothelial growth factor injections, leading to a decrease in macular edema.
... There is no consensus as to whether direct or indirect treatment yields better results [3]. Intravitreal anti-vascular endothelial growth factor therapy appears promising as an alternative to laser treatment in cases of retinal macroaneurysms with macular exsudation [4,5]. ...
Background
Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs).
Methods
Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail.
Results
OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs.
Conclusions
OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.
... Our case involved a RAM close to the arteriovenous crossing; however, branch retinal artery occlusion did not occur following the ruptured RAM [9]. Some papers have reported that intravitreal bevacizumab or ranibizumab for RAM could be effective [10,11]. So far as we know, no paper has reported intravitreal injection of ranibizumab for macular edema concerned with BRVO following RAM located at the arteriovenous crossing. ...
Purpose:
Retinal arterial macroaneurysm (RAM) has been reported in association with branch retinal vein occlusion (BRVO), and usually BRVO precedes RAM. We present a long-term follow-up case report of unilateral multiple RAMs that developed BRVO following ruptured RAM in the same retinal quadrant.
Case presentation:
An 80-year-old woman presented with floaters in her right eye in June 2012. Visual acuity (VA) was 20/25 in her right eye with posterior capsular opacity. Her fundus showed the first ruptured RAM at the superotemporal vascular arcade with subinternal limiting membrane and subretinal hemorrhages not involving the macula. These were absorbed gradually with a VA of 20/20. After 2 years, the second RAM at the proximal superotemporal vascular arcade developed and impending BRVO occurred with macular edema at the distal site of the RAM. With the RAM located close to the arteriovenous crossing, her VA was dropped to 20/60. Intravitreal injection of ranibizumab was performed and macular edema was resolved with improved vision of 20/30. Three months later, she realized a sudden vision loss of 2/200. Her posterior pole showed massive pre- and subretinal hemorrhages, and vitrectomy was performed. The source of bleeding was the third RAM's rupture in a different artery. Her vision improved to 20/30. The unaffected eye showed no RAMs.
Conclusion:
We experienced a long-term follow-up case of multiple RAMs showing different courses. We should cautiously note that BRVO can occur following RAM at the arteriovenous crossing.
... Chanana and Azad 11 published the first case report in 2009, and subsequent case reports have shown encouraging results (Table 1). [12][13][14][15][16][17][18][19] Cho et al 18 described 23 patients with RAMs who were either observed or received intravitreal bevacizumab. Both groups experienced statistically significant improvements in visual acuity and central macular thickness, but the bevacizumab group regained vision faster. ...
An 84-year-old female with a history of hypertension and dyslipidemia was referred for a retinal artery macroaneurysm with exudation that had extended into the macula. She underwent a total of six injections of bevacizumab, with some improvement in visual acuity and retinal thickness. Due to persistent macular edema, focal laser photocoagulation was performed around the macroaneurysm. The vision remained at 20/30 during 20 months of follow up. Although anti-vascular endothelial growth factor therapy may improve vision and decrease retinal thickness in retinal artery macroaneurysm, recalcitrant cases may be treated with laser photocoagulation to seal the leaking vessel.
... Since the development of retinal artery macroaneurysm 114is associated with focal damage to arterial walls, leading to 115 localized ischaemia and VEGF upregulation, the use of anti-116 VEGF agents has been suggested as a treatment modality.117 Intravitreal bevacizumab has been shown to hasten resolution 118 of macular oedema and haemorrhage secondary to retinal 119 artery macroaneurysm, with improvement in visual acuity.10,11 ...
Congenital retinal macrovessel (CRM) refers to an aberrant vessel, usually a vein, which traverses the macula and supplies both sides of the horizontal raphe. It is a rare condition, mostly asymptomatic and discovered on routine examination. We describe a case of both arterial and venous CRM with a macroaneurysm along the arterial CRM that presented with decreased vision due to prominent lipid exudation at the macula. Treatment with intravitreal Bevacizumab resulted in a favourable anatomical as well as functional outcome. To the best of our knowledge, this is the first report of this unusual presentation of CRM, and its successful management with intravitreal Bevacizumab.
Purpose: To evaluate the clinical outcomes of different types of treatment of retinal arterial macroaneurysm with vitreous hemorrhage. Methods: This retrospective cohort study comprised patients with retinal arterial macroaneurysm and vitreous hemorrhage who were examined at a single retina clinic between 2013 and 2021. Results: Treatment arms included observation (n = 33), intravitreal injections (IVI) of antivascular endothelial growth factor agents (n = 5), and pars plana vitrectomy (PPV; n = 12). Baseline characteristics and final best-corrected visual acuity (BCVA) were similar in a combined analysis of all treatment groups ( P > .05). BCVA improved in all eyes, but the IVI and PPV arms had worse presenting BCVA. The mean number of injections was 3.6 ± 2.8. The incidence of subretinal hemorrhage was 18.2% in the observation arm, 25.0% in the PPV group (8.3% had subretinal tissue plasminogen activator), and 60.0% in the IVI group. The mean time to intervention was 13 ± 15.3 days for PPV and 38 ± 69.9 days for IVI. There was no correlation between the number of injections and final BCVA ( r = 0.13, P = .830). The IVI and PPV arms were more frequently on anticoagulants ( P = .011). There was no difference in final BCVA between those using anticoagulants (0.52 ± 0.53) vs not using anticoagulants (0.55 ± 0.65; P = .870). Conclusions: Most patients, regardless of treatment modality, demonstrated significantly improved BCVA and similar final visual outcomes. Patients with worse presenting BCVA were more likely to undergo PPV or IVI whereas those with better presenting BCVA had excellent outcomes with observation alone. Improved BCVA was not associated with the number of IVIs or anticoagulant use.
Aneurysmal alterations of the retinal vasculature are a frequent finding in clinical ophthalmic practice. These changes most commonly involve the retinal veins or capillaries and are usually seen as a sequel to diabetes mellitus, venous occlusive disease, sickle cell disease, or radiation retinopathy. Less commonly, larger aneurysms arise directly from the major retinal arteries. Although mentioned sporadically in the earlier literature [1, 2], the entity currently known as retinal arterial macroaneurysms was formally described in 1973 by Robertson [2].
Purpose:
To determine the presence of unruptured retinal arterial macroaneurysms (RAMs) and to examine the characteristics of the detected lesions.
Methods:
This retrospective, observational study included the affected and contralateral eyes of 50 patients (100 eyes) with symptomatic, unilateral ruptured RAMs who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014-April 2020) and were followed up for at least 6 months after the onset. The presence and characteristics of unruptured RAMs were examined by reviewing the findings of color fundus photography and infrared scanning laser ophthalmoscopy performed before the onset or during the follow-up period.
Results:
Unruptured RAMs were detected in six of the 50 patients. Some patients had bilateral or multiple unruptured RAMs, and a total of 12 unruptured RAMs were detected in eight eyes of the six patients. Among the detected lesions, eight exhibited a longitudinal increase in their diameter during the follow-up period, while six exhibited ruptures.
Conclusions:
Unruptured RAM is not an uncommon retinal vascular pathology and can enlarge and progress to ruptured RAM.
Purpose
To report novel life-threatening coronary and systemic arterial disease associated with Retinal Arterial Macroaneurysms with Supravalvular Pulmonic Stenosis (RAMSVPS) syndrome, previously known as Familial Retinal Arterial Macroaneurysms (FRAM).
Observations
A 29-years old woman with longstanding poor vision in her right eye presented with acute myocardial infarction and subclavian bruit. Her polyangiogram showed peculiar ostial coronary aneurysms, left anterior descending coronary artery stenosis, occlusion of the left subclavian artery, stenosis of both renal arteries, irregularities in the mesenteric artery and tapering of the aorta. Takayasu arteritis was initially presumed, however fundus examination revealed beading and macroaneurysms along major retinal arteries, intraretinal exudation and hemorrhages, retinal arterial sheathing and stenosis, Coats’-like features and submacular gliosis in the right eye, vitreous hemorrhage in the left eye, and persistent hyaloid artery remnant in both eyes. These features evoked RAMSVPS syndrome. Genetic testing identified the same homozygous IGFBP7 c.830-1G > A mutation reported with RAMSVPS syndrome, rectifying the systemic diagnosis.
Conclusion
and Importance: RAMSVPS syndrome can be associated with more life-threatening coronary and widespread major arterial disease than previously recognized. It is crucial for ophthalmologists to recognize RAMSVPS syndrome and refer patients for a thorough cardiovascular evaluation. Likewise, a careful retinal examination and the possibility of an IGFBP7 mutation should be considered in the setting of systemic arterial or cardiac disease.
The aim of this retrospective, observational study was to examine the intraretinal locations of ruptured retinal arterial macroaneurysms (RMAs) and investigate the associations with the visual prognosis. Fifty patients (50 eyes) with untreated RMA rupture who visited the Department of Ophthalmology at Kyoto University Hospital (April 2014–July 2019) were included. The intraretinal position of the ruptured RMAs relative to the affected retinal artery was examined using optical coherence tomography (OCT) and color fundus photography (CFP). The relative RMA positions were anterior to (anterior type, 44%), at the same level as (lateral type, 20%), or posterior to (posterior type, 34%) the affected artery. At the initial visit, the posterior type showed greater subretinal hemorrhage thickness than did the lateral and anterior types (P = 0.016 and 0.006, respectively), and poorer visual acuity (VA) than did the anterior type (P = 0.005). At the final visit, the length of the foveal ellipsoid zone band defect was longer (P = 0.005) and VA was poorer (P < 0.001) for the posterior type than for the anterior type. The intraretinal positions of ruptured RMAs vary, affect the thickness of foveal subretinal hemorrhage and predict future damage to the foveal photoreceptors. The visual prognosis may be poor for posteriorly ruptured RMAs.
This study aimed to evaluate the long-term visual outcomes of hemorrhagic retinal arterial macroaneurysm (RAM), particularly focusing on the influence of bevacizumab therapy and intraretinal hemorrhage (IRH) on the outcomes. This retrospective study included 49 patients diagnosed with hemorrhagic RAM. Patients were divided into the bevacizumab group and observation group depending on the whether they were administered bevacizumab treatment and the IRH group and the non-IRH group based on the presence of IRH at the fovea. Best-corrected visual acuity (BCVA) at diagnosis was compared with that at the final visit. Further, the BCVA at the final visit was compared between the study groups. Multivariate analysis was also performed to identify factors associated with poor BCVA at the final visit. The mean follow-up period was 24.8 ± 15.3 months. The mean logarithm of minimal angle of resolution BCVA was significantly improved from 1.37 ± 0.70 at diagnosis to 0.72 ± 0.62 at the final visit (P < 0.001). There was no significant difference in the BCVA at the final visit between the bevacizumab group and observation group (P = 0.576). However, the BCVA at the final visit was significantly worse in the IRH group than in the non-IRH group (P = 0.002). In multivariate analysis, the presence of IRH was significantly associated with poor BCVA (P = 0.007). Significant long-term visual improvement was noted in hemorrhagic RAM. However, the presence of IRH at the fovea was associated with poor visual prognosis. Bevacizumab therapy did not significantly influence the outcomes.
Retinal arterial macro-aneurysms are pathological dilatations of retinal arterial branches mostly
found in posterior pole. Here we present a 51 years old female with a diagnosis of retinal artery
macro-aneurysm in the superior temporal arcade associated with macular edema based on clinical
and optical coherence tomography (OCT) finding. Patient was treated with intra-vitreal injection
(1.25 mg in 0.05 ml) of anti-vascular endothelium growth factor (bevacizumab) which showed
both improvement in visual acuity and resolution of macular edema. Intra-vitreal injection of
bevacizumab (Avastin) is safe and effective in treatment of macular edema associated with retinal
arterial macro-aneurysms.
Retinal arterial macroaneurysm (RAM) was first published in a report by Loring in 1880 in which he described a bulging ectasia of the inferotemporal retinal artery in an asymptomatic healthy 25-year-old man (Loring 1880). Fernandez made the first association of retinal artery macroaneurysm with systemic hypertension in 1920 (Fernandez 1920). Robertson was the first to define retinal artery macroaneurysm as a distinct clinical entity and its natural history in 1973 (Robertson 1973). RAM most commonly affects women in their 60s and 70s and is associated with hypertension and atherosclerotic vessel disease. RAM is usually unilateral but may be bilateral in 10% of cases (Rabb et al. 1988). They are usually single but may be multiple in 20% of cases (Rabb et al. 1988).
Purpose: To report a favorable effect of intravitreal dexamethasone implantation in Familial Retinal Arterial Macroaneurysms (FRAM).
Methods: Retrospective Case Report.
Results: A 32-year-old male who presented with bilateral retinal macroaneurysms. Whole Exome Sequencing (WES) revealed a homozygous c.830–1 G > A mutation in Insulin Growth Factor Binding Protein 7 (IGFBP7) gene, confirming the diagnosis FRAM. The left eye was lost in the course of the disease, whereas the right eye developed a persistent macular edema due to multiple leaking retinal arterial macroaneurysms and responded poorly to intravitreal ranibizumab and only partially to intravitreal aflibercept. Intravitreal dexamethasone implantation in the right eye, on the other hand, resulted in marked visual and structural improvement.
Conclusion: Intravitreal dexamethasone injections have beneficial anatomical and visual outcomes in FRAM patients with persistent macular edema poorly responsive to intravitreal injections.
Purpose
To investigate the usefulness of anatomic site-oriented therapy for macular hemorrhage secondary to retinal arterial macroaneurysm (RAM).
Study design
Retrospective observational study, clinical case series
Methods
Twenty-seven consecutive patients (27 eyes) with macular hemorrhage secondary to RAM were classified according to the retinal layer(s) with hemorrhage identified by optical coherence tomography into 4 types and treated differentially. Vitrectomy was conducted for subinternal limiting membrane hemorrhage (SILMH), intravitreal gas injection for subretinal hemorrhage (SRH) or intraretinal hemorrhage (IRH), and vitrectomy and intravitreal air/gas exchange for multilevel hemorrhage (at least 2 among SILMH/SRH/IRH).
Results
Complete displacement or resolution of the macular hemorrhage was achieved in all 27 eyes: 7 with SILMH, 7 with SRH, 3 with IRH, and 10 with multilevel hemorrhage. Compared with the baseline score, the 3-month postoperative Early Treatment Diabetic Retinopathy Study score (mean ± SD) improved significantly in SILMH (+42.9 ± 6.9 letters; P < .0001, paired t test), multilevel hemorrhage (+23.9 ± 14.4 letters; P = .0005), and SRH (+17.7 ± 18.4 letters; P = .0440), but not in IRH (+6.7 ± 9.0 letters; P = .3228). Compared with the baseline thickness, the 3-month postoperative central retinal thickness decreased significantly in multilevel hemorrhage (-930.3 ± 290.8 µm; P < .0001), SILMH (-628.4 ± 177.0 µm; P < .0001), IRH (-508.3 ± 72.1 µm; P = .0066), and SRH (-476.9 ± 300.0 µm; P = .0056). The central ellipsoid zone was detectable in 7/7 eyes with SILMH but in none of the eyes in the other 3 groups (P < .0001). No retinal detachment or macular hole occurred in any eyes.
Conclusion
For macular hemorrhage secondary to RAM, anatomic site-oriented therapy using different treatments targeting the hemorrhagic retinal layers is useful. The optimal treatments for individual hemorrhagic retinal layers require further studies.
Purpose:
To report a series of eight patients with perifoveal exudative vascular anomalous complex imaged with optical coherence tomography angiography and the results of anti-vascular endothelial growth factor therapy or laser photocoagulation.
Methods:
Retrospective analysis of demographic data, imaging including color pictures, spectral domain optical coherence tomography, and optical coherence tomography angiography, and fluorescein angiography, course, and outcome.
Results:
Age at onset ranged from 45 to 84 years (mean ± SD: 68.6 ± 13.7). Five cases were initially misdiagnosed. The perifoveal exudative vascular anomalous complex lesion was unique in seven eyes and located predominantly in the superficial capillary plexus in two eyes, strictly in the deep capillary plexus in two eyes, but observed at the level of both plexi (3 eyes). One patient presented two lesions, one in the superficial capillary plexus and one in the deep capillary plexus. Capillary rarefaction was observed around the lesion in six eyes. Sustainable resolution of exudation could be achieved in 2 patients, one after 2 sessions of focal thermal laser photocoagulation and one after 13 intravitreal injections of anti-vascular endothelial growth factor.
Conclusion:
The present series confirms that perifoveal exudative vascular anomalous complex corresponds to a new entity that differs from other conditions associated with capillary aneurysmal lesions. Visual improvement could be obtained after treatment with focal laser or intravitreal anti-vascular endothelial growth factor agents.
The diagnosis and monitoring of retinal and choroidal vascular diseases has evolved significantly over the last two decades with the advent of new imaging techniques such as enhanced depth optical coherence tomography, ultrawide field imaging and angiography, optical coherence tomography angiography, and more. Advances in therapeutics and scientific elucidation of retinal and choroidal vascular disease pathophysiology have further moved the field forward. This chapter covers past, present, and new practices and developments in retinal and choroidal vascular diseases beyond diabetic eye disease, including retinal artery and vein occlusions, ocular ischemic syndrome, sickle cell retinopathy, paracentral acute middle maculopathy, retinal macroaneurysms, macular telangiectasia, thin choroid, and pachychoroid spectrum diseases.
Purpose:
Retinal arteriolar macroaneurysms are a common cause of vision loss in elderly patients with hypertension and cardiovascular disease. Their occurrence in the young, however, is not well known. The purpose of this article is to describe an unusual cause of retinal arteriolar macroaneurysm in a healthy young man.
Case report:
A 30-year-old man presented with preretinal hemorrhage and macular exudation due to ruptured retinal artery macroaneurysm. The patient was treated with intravitreal bevacizumab and laser photocoagulation to the macroaneurysm. The exudation and preretinal hemorrhage resolved over several months. Fluorescein angiogram at this stage revealed a congenital anomalous retinal artery.
Conclusions:
Congenital anomalous retinal artery may be associated with retinal artery macroaneurysm even in the young age in the absence of any other predisposing factors. The presentation and treatment of such retinal artery macroaneurysm, however, may remain the same to those that occur in older patients.
This chapter provides the reader with practical information to be applied to the various remaining causes of macular edema. Some clinical cases of macular edema linked to ocular diseases like postradiotherapy for ocular melanomas remained of poor functional prognosis due to the primary disease. On the contrary, macular edema occurring after retinal detachment or after diverse systemic or local treatment use is often temporary. Macular edema associated with epiretinal membranes or vitreomacular traction is the main cause of poor functional recovery. In other cases, as in tractional myopic vitreoschisis, the delay to observe a significant improvement of the vision after surgery should be long. Finally, macular edema associated with hemangiomas or macroaneurysms should be treated, if symptomatic, using the same current treatment as in diabetic macular edema or exudative macular degeneration. The miscellaneous chapter is always a challenging one, laden with two serious caveats: being too exhaustive or forgetting common circumstances. The author has attempted to provide the reader with useful, practical information that can be applied to the various causes of macular edema.
Purpose:
To evaluate the potential efficacy and safety of primary intravitreal ranibizumab in patients with symptomatic retinal arterial macroaneurysm (RAM).
Methods:
This prospective study comprised 5 eyes with RAM treated with intravitreal ranibizumab. At baseline, all patients underwent best-corrected visual acuity (BCVA) measurement, ophthalmic examination including slit-lamp biomicroscopy, and central foveal thickness (CFT) measurement using optical coherence tomography. Fluorescein angiography was also performed to confirm diagnosis. Patients were examined at 1 month after injection and monthly thereafter. Main outcome measures included changes in BCVA and CFT. Safety was assessed by ophthalmic examination and report of systemic adverse effects.
Results:
There was a statistically significant difference in BCVA (p<0.001) and CFT (p<0.001) before and after the ranibizumab injection at the end of the follow-up of 13.4 ± 3.2 months. One injection appeared to be sufficient for the resolution of macular edema and absorption of hemorrhages. No observable ocular or systemic side effects were found. One patient developed foveal atrophy.
Conclusions:
Intravitreal ranibizumab seems to be effective and safe for the treatment of symptomatic RAM.
Last year our group published the case of a foveal longstanding retinal macroaneurysm successfully treated with intravitreal ranibizumab. A few previous and subsequent studies also reported the safety and effectiveness of intravitreal vascular endothelium growth factor inhibitors (anti-VEGF) in other more common cases of retinal macroaneurysms. In this commentary we proposed to make a brief review of this entity, particularly of its complications and its management with emphasis on anti-VEGF therapy
Purpose:
To describe multimodal imaging findings in a patient presenting with an occult optic disk macroaneurysm.
Methods:
A 54-year-old woman presented with decreased vision in the right eye secondary to preretinal, intraretinal, and optic disk hemorrhage.
Results:
Ancillary fluorescein angiography revealed evidence of an occult optic disk macroaneurysm that was not realized on fundoscopic examination. Subsequent optical coherence tomography obtained once the hemorrhage resolved demonstrated a thrombosed macroaneurysm with an adjacent ring of exudate.
Conclusion:
Detection of optic disk macroaneurysms at the time of initial presentation can be difficult because of concurrent overlying hemorrhage, but should nevertheless be kept in the differential when macular hemorrhage in multiple retinal layers is observed.
Purpose: To report a case of arterial macroaneurysm on the optic disc followed by branch retinal vein occlusion. Case: A 69-year-old woman was diagnosed with Sjögren syndrome with systemic manifestations. Corrected visual acuity was 0.9 right and 0.5 left. Her right eye developed arterial macroaneurysm on the optic disc 2 years later. The aneurysm gradually enlarged followed by branch retinal vein occlusion and vitreous hemorrhage 9 months later. Vitreous surgery was performed another 6 months later when visual acuity decreased to 0.3 due to retinal hemorrhage and macular edema. Surgery was followed by closure of macroaneurysm with final visual acuity of 0.7. Conclusion: The present case illustrates that arterial macroaneurysm on the optic disc may be followed by branch retinal vein occlusion.
To describe clinical, angiographic, and tomographic features and the therapeutic management of patients with retinal arterial macroaneurysm (RAM).
Retrospective analysis of patients diagnosed with RAM between January 2011 and September 2014 in Professor Sahel's Department of Ophthalmology, Rothschild Foundation. Retinal arterial macroaneurysms were classified as hemorrhagic, exudative, or quiescent. Patient demographics and comorbidities were recorded. All patients underwent complete ophthalmologic examination including initial and final visual acuity (Early Treatment Diabetic Retinopathy Study chart), slit-lamp biomicroscopy, fundus examination, color and autofluorescence fundus imaging, fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography. Treatments were recorded.
Fourteen RAMs of 14 patients were included: 9 hemorrhagic and 5 exudative. The most severe clinical picture was associated with the hemorrhagic form. Exudative cases had a progressive onset and a better visual prognosis. Direct laser photocoagulation was performed in 4 cases, anti-vascular endothelial growth factor (VEGF) intravitreal injection in 4 cases, combined treatment (YAG laser + argon laser + anti-VEGF intravitreal injection) in 1 case, and 5 cases received no treatment.
Retinal arterial macroaneurysm management should be specialized and rapid. Multimodal imaging should be performed for classifying it, assessing its prognosis and determining the most suitable treatment.
Retinal arterial macroaneurysms (RAMAs) are acquired dilations of branches of the central retinal artery. Treatment depends on vision-limiting complications. We compare the long-term visual acuity (VA) in three groups according to treatment.
49 charts of patients with RAMA were reviewed. 16 remained untreated, 15 received photocoagulation and 18 vitrectomy. Patients underwent full ophthalmological examinations and up-to-date imaging. We evaluated chosen therapy, complications and final VA at the last visit.
65% of the cohort was female, aged 75±11 years (mean±SD). Follow-up was 34±23 months. These parameters did not differ significantly between the three groups. In the observed group, initial VA was 0.48 (mean log MAR) vs 0.35 at the final visit, in the photocoagulation group 0.55 vs 0.59, and in the vitrectomy group 1.8 vs 0.77. VA was significantly worse at enrolment in the vitrectomy group, while all other VA differences were not significant.
The overall visual prognosis of RAMA was good, even after macular complications. VA remained unchanged in the observed and the laser groups and was comparable in all groups after 3 years. Based on an individual treatment decision, all therapies were effective and efficient. If subfoveal haemorrhage caused a macular hole, the VA outcome was limited.
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Retinal arterial macroaneurysms (RAM) are unilateral, solitary, acquired saccular or fusiform dilatations of the large arterioles of the retina, usually within the first three orders of bifurcation. They are associated with systemic vascular conditions such as hypertension and arteriosclerotic disease and occur most commonly in elderly women. Cases of simple RAM are predominated by the vascular ectasia. These macroaneurysms regress without treatment and without causing decreased visual acuity and will usually remain undetected. Complex RAM often go along with vision loss due to haemorrhage or oedema affecting the macula. Poor visual outcome may occur secondary to foveal exudates and subfoveal haemorrhage, the latter appear as pre-retinal, intra-, and subretinal haemorrhage. This overview discusses conservative and surgical therapeutic options for complex cases.
Georg Thieme Verlag KG Stuttgart · New York.
The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA).
A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months.
Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels.
Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy.
To assess the effects of subthreshold laser treatment (STLT) for retinal arterial macroaneurysms (RAM) associated with foveal exudative manifestations and visual acuity deterioration.
Patients with RAM associated with foveal exudative manifestations and best-corrected visual acuity (BCVA) worse than 20/80 Snellen equivalent underwent a ophthalmological examination, including ETDRS visual acuity, optical coherence tomography (OCT) and fluorescein angiography. The patients were prospectively observed for 4 months, and in absence of spontaneous improvement, they underwent STLT using an infrared diode laser.
Primary outcome measures were a reduction in mean central point thickness (CPT) and BCVA changes at the 12-month examination. Secondary outcomes included changes in mean total macular volume (TMV) and central subfield thickness (CST). Nine patients were enrolled and prospectively followed up. The mean baseline values of BCVA, CPT, TMV and CST were 0.8 ± 0.1 (logMAR ± SD), 340 ± 49 μm, 7.14 ± 0.05 mm(3) and 366 ± 37 μm, respectively. At the 4-month examination following STLT, the mean BCVA improved to 0.6 ± 0.2, whereas the mean CPT, TMV, and CST decreased to 274 ± 29 μm, 6.87 ± 0.11 mm(3) and 296 ± 33 μm. At the 12-month examination, the mean BCVA was 0.36 ± 0.2, the mean CPT was 195 ±11 μm, the mean TMV was 6.55 ± 0.19 mm(3), and the mean CST was 239 ± 14 μm, respectively. No side-effects were noted. In particular, no sign of retinal thinning and underlying backscattering typical of conventional laser treatment could be detected at the site of the laser application on OCT.
The current pilot investigation of STLT for the treatment of symptomatic RAM revelas encouraging data. A randomised clinical trial is required to ascertain the real efficacy of this technique and the most appropriate settings to be employed.
A case control study was conducted to identify the systemic and ocular risk factors for retinal arterial macroaneurysms. Forty-three patients with 52 photographically confirmed macroaneurysms were located. Forty-three age-matched, race-matched concurrent control patients were also identified. The patients with macroaneurysms had decreased visual acuity (p less than 0.0001) and a higher prevalence of hypertension (p = 0.037), female sex (p = 0.099), and retinal vein occlusions (p = 0.055) than controls. In patients with both a macroaneurysm and venous occlusion there was a 12.0 times higher prevalence of macroaneurysms in the area of retina drained by the occluded vein (p less than 0.05). Common findings associated with macroaneurysms included retinal haemorrhage (81% of patients), retinal exudate (70%), vitreous haemorrhage (30%), macular involvement (30%), and distal arteriolar narrowing (26%). Arteriolar occlusion occurred spontaneously (8%) or after laser photocoagulation (16%).
Visual outcome was analysed in 16 consecutive eyes with symptomatic retinal arteriolar macroaneurysms treated by direct laser photocoagulation and 26 consecutive symptomatic eyes followed with no treatment. No difference existed between groups in presenting visual acuity, macular involvement, presence of macular subretinal fluid, or presence or location of associated haemorrhage. The mean follow up was 41 months. In the 26 untreated eyes, visual acuity was improved by 2 or more lines in 13 (50%), was unchanged in nine (35%), and decreased in four cases (15%). In the 16 treated cases, three improved (19%), seven were unchanged (43%), and six had decreased visual acuity (38%). The average minimum angle of resolution improved 0.53 log units in untreated cases and decreased 0.14 log units in treated cases (p = 0.02). Multivariable logistic regression modelling analysis revealed that laser treatment remained a significant risk factor for final visual acuity of less than 20/80 even when controlling for the effects of subretinal haemorrhage and foveal subretinal fluid (odds ratio 8.4, p = 0.01). Laser photocoagulation directly to the macroaneurysm did not improve the visual outcome in this series.
To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD).
Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 microg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 microg/ml, 60 microg/ml and 200 mug/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated.
During application of bevacizumab (0.25 mg/ml) in co-application with 20 microg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 microg/ml and 60 microg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 microg/ml rt-PA did not alter the a-wave amplitude. However, 60 microg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 microg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout.
The present study suggests that a subretinal injection of 20 microg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.
Contrary to initial expectations, angiogenesis inhibitors can cause toxicities in patients with cancer. The toxicity profiles of these inhibitors reflect the disturbance of growth factor signalling pathways that are important for maintaining homeostasis. Experiences with angiogenesis inhibitors in clinical trials indicate that short-term toxicities are mostly manageable. However, these agents will also be given in prolonged treatment strategies, so we need to anticipate possible long-term toxicities. In addition, understanding the molecular mechanisms involved in the toxicity of angiogenesis inhibition should allow more specific and more potent inhibitors to be developed.
Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.
Retinal and choroidal vascular diseases, with their associated abnormalities in vascular permeability, account for the majority of patients with vision loss in industrialized nations. VEGF is upregulated in ischemic retinopathies such as diabetes and is known to dramatically alter vascular permeability in a number of nonocular tissues via Src kinase-regulated signaling pathways. VEGF antagonists are currently in clinical use for treating the new blood vessels and retinal edema associated with neovascular eye diseases, but such therapies require repeated intraocular injections. We have found that vascular leakage following intravitreal administration of VEGF in mice was abolished by systemic or topical delivery of what we believe is a novel VEGFR2/Src kinase inhibitor; this was confirmed in rabbits. The relevance of Src inhibition to VEGF-associated alterations in vascular permeability was further substantiated by genetic studies in which VEGF injection or laser-induced vascular permeability failed to augment retinal vascular permeability in Src-/- and Yes-/- mice (Src and Yes are ubiquitously expressed Src kinase family members; Src-/- and Yes-/- mice lacking expression of these kinases show no vascular leak in response to VEGF). These findings establish a role for Src kinase in VEGF-mediated retinal vascular permeability and establish a potentially safe and painless topically applied therapeutic option for treating vision loss due to neovascular-associated retinal edema.
• Laser photocoagulation in a grid pattern is effective in many eyes in resolving diffuse diabetic macular edema and stabilizing vision. We retrospectively studied 203 eyes of 203 patients, all of whom had diabetic macular edema treated with grid laser photocoagulation. During the follow-up period, 11 of these 203 eyes developed enlargement of the laser scars that progressed into the central fovea. Each of the 11 eyes experienced loss of vision, and in five, the visual loss was significant. Five of these eyes also developed a retinal pigment hyperplastic scar. After the laser treatment, but before the scars enlarged, the visual acuity of these eyes was unchanged from that before treatment. But after the atrophic scars enlarged into the central fovea, visual acuity in one eye decreased from 20/40 to 20/100, and the other 10 eyes had visual acuities of 20/200 or worse.
Background:
The visual prognosis of submacular hemorrhages caused by a retinal arterial macroaneurysm (RAM) is poor if left untreated. The use of recombinant tissue plasminogen activator (rtPA) has frequently been reported to displace submacular hemorrhages from the foveal area in patients with age-related macular degeneration. This study aims to investigate the results of displacement of recent-onset submacular hemorrhages due to RAM.
Methods:
Institutional retrospective interventional case series of 12 patients with macular hemorrhage due to RAM, who underwent pars plana vitrectomy (PPV); followed in 11 by submacular injection of rtPA and gas tamponade. The main outcome measures were displacement of the hemorrhage, complication rate, and visual acuity at 1 month after surgery and at the last follow-up visit.
Results:
One month after surgery, the hemorrhage had been successfully displaced in ten out of 11 patients. In these ten patients, visual acuity (VA) increased by a mean of 1.2 logMAR at 1 month after surgery. At the last follow-up visit, the mean increase was 1.5 logMAR. Complications consisted of a vitreous hemorrhage and hyphema, retinal detachment, a new submacular hemorrhage, and vitreous hemorrhage after argon laser retinal photocoagulation of the RAM.
Conclusions:
PPV with submacular rtPA and gas injection may successfully displace a recently developed submacular hemorrhage in patients with RAM, with a marked improvement in VA that is likely to be greater than if left untreated.
Retinal arterial macroaneurysms represent a distinct clinical entity. Macroaneurysms are seen in the elderly with a marked female predominance and a strong association with hypertension and arteriosclerotic vascular changes. The classic appearance provides an easy diagnosis; however, variable presentations, such as subretinal hemorrhage, macular exudate, and epiretinal membranes can make the diagnosis difficult. The differential diagnosis of retinal arterial macroaneurysms include retinal telangiectasia, angiomatosis retinae, venous macroaneurysms, background diabetic retinopathy, and cavernous hemangioma. The clinical characteristics of the reported cases are summarized, and our series of 60 patients is presented. The natural history of most macroaneurysms is spontaneous involution without loss of vision. However, visual loss may occur secondary to macular edema, exudate, hemorrhage and neurosensory retinal detachment, and photocoagulation may expedite visual recovery. Photocoagulation treatment may be applied directly to the macroaneurysm, indirectly by surrounding the macroaneurysm, or as a combination of these two methods.
This study was designed to compare the effects of subthreshold laser treatment (STLT) with threshold laser treatment (TLT) in patients affected by symptomatic retinal arterial macroaneurism (RAM).
Patients affected by symptomatic RAM, characterized by exudative manifestations involving the fovea and best-corrected visual acuity (BCVA) worse than 20/80 Snellen equivalent, were recruited. Patients were randomly assigned to STLT or TLT and regularly followed up for 12 months. Primary outcome measures were changes in central point thickness (CPT) at the end of the follow-up. Secondary outcome measures were changes in mean BCVA at the end of the follow-up and identification of postlaser alterations.
In this single center, randomized, clinical trial, 12 patients were randomized to STLT and 13 to TLT. CPT in STLT was 332 μm at baseline and changed to 249 μm at the 12-month examination. CPT in TLT was 341 μm and reduced to 226 μm at the end of the follow-up. BCVA in STLT changed from 0.72 logMAR to 0.28 logMAR. BCVA in TLT changed from 0.76 logMAR to 0.26 logMAR. The statistical analyses revealed a significant difference comparing the baseline values for both CPT and BCVA in each subgroup from the third month (P < 0.001). No difference was found comparing the two subgroups at any point in time. Three eyes (23%) treated with TLT developed an epiretinal membrane with subjective metamorphopsia.
This pilot randomized clinical trial shows that both STLT and TLT can achieve similar improvements in BCVA and CPT. The lower laser energy delivered by STLT can reduce the complication rate.
To evaluate the clinical factors associated with vitreous hemorrhage (VH) complicating intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage, and analyze visual outcomes.
In this retrospective, comparative study, 120 consecutive eyes underwent intravitreal tissue plasminogen activator (50 μg) and perfluoropropane (0.3 mL) injection for submacular hemorrhage secondary to different causes. We recorded their demographic data, visual acuity, complications, and further treatment after VH. Two groups created according to the occurrence of VH were compared to identify possible risk factors.
Breakthrough VH occurred in 18 eyes (15%). The size of submacular hemorrhage was significantly positively related to the occurrence of VH (P for trend <0.001). Among etiology, idiopathic polypoidal choroidal vasculopathy (IPCV) was associated with a significantly higher incidence of VH (odds ratio, 15.63; 95% confidence interval, 2.30-106.15; P = 0.005). Age-related macular degeneration was much less likely than other causes to result in VH (odds ratio, 0.121; 95% confidence interval, 0.023-0.642; P = 0.013). Best and final visual acuity improved significantly from initial visual acuity in both groups (P < 0.05).
A large area of submacular hemorrhage (≥10 disk areas) and IPCV were risk factors for VH after injection. The occurrence of VH did not affect final visual outcome.
The authors report the management of a ruptured retinal arterial macroaneurysm and associated hemorrhages with intravitreal injections of bevacizumab. A 79-year-old woman presented with a history of systemic arterial hypertension and a ruptured retinal arterial macroaneurysm with pre-retinal, intraretinal, and subretinal hemorrhages extending into the macula. Visual acuity at presentation was 20/400. The patient was treated with two intravitreal injections of bevacizumab at 4-week intervals. Steady clearing of the pre-retinal, intraretinal, and subretinal hemorrhages was observed with restoration of final visual acuity to 20/20 in the 12 months after the initial presentation. It appears that the novel application of intravitreal bevacizumab may be used in the treatment of ruptured retinal arterial macroaneurysm.
P>A 60-year-old woman with hypertension was seen for a routine examination. Her best-corrected visual acuity was 20/20 bilaterally. Intraretinal hemorrhages were found in the parafoveal region of the right eye. A fundus fluorescein angiography evaluation identified the hemorrhages as arterial macroaneurysms. The following day, the patient returned complaining of blurred vision that had developed the previous evening. Best-corrected visual acuity was counting fingers in the right eye. A subhyaloid hemorrhage approximately three optic disks in size was found in the macular region. The hemorrhage was drained with an Nd:YAG laser. [ Ophthalmic Surg Lasers Imaging 2007;38:154-156.]
AUTHORS
From the Department of Ophthalmology, Baskent University, Faculty of Medicine, Ankara, Turkey.
Accepted for publication September 20, 2006.
Address correspondence to Gürsel Yilmaz, MD, Associate Professor of Ophthalmology, Baskent University Faculty of Medicine, Fevzi Çakmak Caddesi, 06490, Bahçelievler, Ankara, Turkey.</P
To compare the efficacy of pars plana vitrectomy (ppV) with intravitreal injection of recombinant tissue plasminogen activator (rtPA) and gas versus ppV with subretinal injection of rtPA and intravitreal injection of gas.
Nonrandomized, retrospective, interventional, comparative consecutive series including 47 patients with submacular hemorrhage. Eighteen patients were treated with ppV, intravitreal injection of rtPA and 20% SF6 gas [group A: mean age 78 years, mean duration of symptoms 6.6 days, 15 age-related macular degeneration (AMD), three retinal arterial macroaneurysm (RAMA)]. Twenty-nine patients were treated with ppV, subretinal injection of rtPA and intravitreal injection of SF6 gas (group B: mean age 75 years, mean duration of symptoms 5.9 days, 26 AMD, two RAMA, one blunt ocular trauma). The main outcome measure was complete displacement of submacular hemorrhage from the fovea.
Complete displacement of submacular hemorrhage was achieved in less patients in group A (22%) than in group B (55%) (p = 0.025). In group A, mean best-corrected visual acuity (BCVA) change was logMAR -0.14, standard deviation (SD) = 0.64, and in group B logMAR -0.32, SD = 0.68 without statistically significant difference between the two groups (p = 0.2, Mann-Whitney test). Complications (retinal detachment, vitreous hemorrhage, and recurrence of submacular hemorrhage) were more frequent in group B than in group A.
ppV with subretinal injection of rtPA and intravitreal injection of gas was more effective than ppV with intravitreal injection of rtPA and gas in terms of complete displacement of submacular hemorrhage; however, it may be associated with a higher rate of postoperative complications. Functional improvement in the majority of patients suggests the absence of direct retinal toxicity of subretinally applied rtPA.
To study the retinal structural changes associated with a retinal arterial macroaneurysm and their association with visual prognosis.
We studied retrospectively the medical records of 44 eyes of 44 patients with a retinal arterial macroaneurysm; all eyes showed hemorrhagic and/or exudative changes of the fovea with a visual disturbance. The retinal structural changes were examined by optical coherence tomography (OCT).
At the initial visit, 30 eyes (68%) showed severe hemorrhagic complications. In eyes with subretinal hemorrhage beneath the fovea, retinal structure was relatively preserved at the initial visit. At the final visit, however, foveal structure was often degenerated, especially in its outer aspect, with limited visual recovery. The 14 eyes (32%) with minimal hemorrhagic complications showed an extensive exudative change caused by the aneurysm. In 13 of these eyes, OCT examination revealed extensive retinal edema, predominantly in the outer retina. Retinal edema beneath the fovea caused a focal serous retinal detachment in 12 eyes. Eight eyes with extensive exudative change showed an accumulation of hard exudates in the macular area, and visual recovery of these eyes was often limited.
Subretinal hemorrhage or extensive exudative change from a retinal arterial macroaneurysm can cause destruction of the foveal outer photoreceptor layer, resulting in a poor visual outcome.
Seven eyes had subretinal fibrosis after grid laser photocoagulation for diabetic macular edema. The fibrosis caused persistent loss in visual acuity, and in six of the seven eyes, was not associated with detectable laser-induced Bruch's membrane rupture or subretinal hemorrhage. Choroidal neovascularization was detected in only one patient, who was notably younger (27 years) than the median age of 70 years in this series. The median preoperative visual acuity was 20/80 (range, 20/40 to 20/400); the median postoperative visual acuity was 20/400 (range, 20/80 to counting fingers). The subretinal fibrosis was detected at a median of three months (range, 14 days to 4 1/2 months) after laser therapy. In one of five bilaterally treated patients (20%), subretinal fibrosis developed in both eyes. Subretinal fibrosis may be caused by undetected choroidal neovascularization or by excessive proliferation after stimulation of an aged retinal pigment epithelium. Subretinal fibrosis may be a potential cause of loss in visual acuity after laser treatment for diabetic macular edema.
Choroidal neovascular membranes (CNVMs) developed in eight patients after photocoagulation for clinically significant diabetic macular edema (DME). The CNVMs developed in areas where Bruch's membrane was ruptured and were diagnosed 2 weeks to 5 months after treatment. Only six patients had symptoms. The CNVMs were treated in four patients; final visual acuity was poor in all eight patients. This serious complication that follows laser treatment for DME may be related to the use of repeated small-size, short-duration laser or intense laser burns, or both.
Laser photocoagulation in a grid pattern is effective in many eyes in resolving diffuse diabetic macular edema and stabilizing vision. We retrospectively studied 203 eyes of 203 patients, all of whom had diabetic macular edema treated with grid laser photocoagulation. During the follow-up period, 11 of these 203 eyes developed enlargement of the laser scars that progressed into the central fovea. Each of the 11 eyes experienced loss of vision, and in five, the visual loss was significant. Five of these eyes also developed a retinal pigment hyperplastic scar. After the laser treatment, but before the scars enlarged, the visual acuity of these eyes was unchanged from that before treatment. But after the atrophic scars enlarged into the central fovea, visual acuity in one eye decreased from 20/40 to 20/100, and the other 10 eyes had visual acuities of 20/200 or worse.
This report describes the features and clinical significance of retinal macroaneurysm. Two groups can be defined: those with acute aneurysmal decompensation, Group I; and those with chronic aneurysmal decompensation, Group II. Haemorrhage is the main feature of the former group and exudates of the latter. Systemic and local associations are noted, and guidelines for treatment by phototherapy are discussed.
To assess variations in the clinical course of submacular hemorrhages.
We reviewed fundus photography charts taken of patients during a 27-month period. Thirty-one eyes of 31 patients with submacular hemorrhages under the foveal avascular zone were reviewed.
In 20 of the eyes, the underlying etiology was age-related macular degeneration (ARMD). The other 11 eyes had various underlying conditions, including macroaneurysms (two), presumed ocular histoplasmosis syndrome (two), trauma (one), Valsalva's retinopathy (one), idiopathic central serous choroidopathy (one), diabetic retinopathy (two), central retinal vein occlusion (one), and choroidal rupture (one). Of the eyes with ARMD (mean follow-up, 29 months), eight (40%) of 20 showed an improvement in visual acuity (> or = 2 Snellen lines), six (30%) of 20 had a final visual acuity of 20/80 or better, and three (15%) had a final visual acuity of 20/40 or better (range, 20/25 to 20/80). Of the eyes without ARMD (mean follow-up, 29 months), five (45) of 11 had an improvement in visual acuity and five (45%) of 11 attained a final visual acuity of 20/40 or better (range, 20/20 to 20/40). The best predictive factor for poor final visual acuity was the presence of a subretinal neovascular membrane.
Patients with submacular hemorrhage may have spontaneous improvement in visual acuity without surgery. Patients without subretinal neovascular membranes had a better visual improvement rate.
To document the clinical course of Nd:YAG laser photodisruption for eyes with preretinal hemorrhage following rupture of a retinal macroaneurysm.
We reviewed six eyes of five patients with preretinal hemorrhage due to retinal macroaneurysm that received Nd:YAG laser photodisruption. Nd:YAG laser created a focal opening in the anterior surface of the preretinal hemorrhage, permitting the blood to enter the vitreous cavity where it would be absorbed more rapidly.
Three eyes showed both subhyaloid hemorrhage, which was resorbed without treatment within 2 months, and hemorrhagic detachment of the internal limiting membrane (ILM), which required Nd:YAG laser photodisruption. All eyes showed disappearance of the preretinal hemorrhage and improvement of vision within 1 week of Nd:YAG laser photodisruption. Visual recovery was less prominent in eyes associated with subretinal macular hemorrhage.
Preretinal hemorrhage due to a ruptured retinal macroaneurysm could be dispersed into the vitreous cavity with Nd:YAG laser photodisruption. It should be considered in the decision of Nd:YAG laser photodisruption that the visual increment may be limited in eyes that also have subretinal hemorrhage in the macula and that the hemorrhage beneath the ILM tends to remain longer than the subhyaloid hemorrhage.
To evaluate the safety and efficacy of pars plana vitrectomy to treat massive macular hemorrhage caused by retinal arterial macroaneurysm.
Retrospective case series.
Eight eyes of eight patients.
We retrospectively reviewed the charts for eight eyes of eight patients in which pars plana vitrectomy had been performed to remove a massive macular hemorrhage secondary to a ruptured retinal arterial macroaneurysm. In each case, the preretinal/intralamellar hemorrhage was removed, and in three of the eight eyes a subretinal hemorrhage was removed via a retinotomy after clot lysis using tissue plasminogen activator.
Pars plana vitrectomy to treat macular hemorrhage secondary to retinal arterial macroaneurysm.
The duration of symptoms ranged from 10 to 80 days (average, 31 days). The preoperative visual acuities ranged from counting fingers to 0.09. Follow-up ranged from 3 to 36 months (average, 19 months). The postoperative visual acuities improved in seven eyes and remained unchanged in one; vision was better than 0.1 in six eyes and better than 0.4 in five. Postoperative complications included a mild vitreous hemorrhage in two eyes, a macular hole in one, and a cataract in two.
Pars plana vitrectomy appears to be relatively safe and effective in treating massive macular hemorrhage caused by a retinal arterial macroaneurysm.
To study the visual prognosis in eyes with symptomatic retinal arterial macroaneurysm (RAM).
Medical records were retrospectively reviewed for 62 patients (65 eyes) with symptomatic RAM.
The median visual acuity at presentation was 0.4 for eyes with vitreous hemorrhage (n=6), 0.01 for eyes with premacular hemorrhage (n=9), 0.1 for eyes with submacular hemorrhage without premacular hemorrhage (n=16), 0.02 for eyes with submacular hemorrhage with premacular hemorrhage (n=16), and 0.3 for eyes with macular edema (n=18). The median value of the final visual acuity was 0.6 for vitreous hemorrhage, 0.7 for premacular hemorrhage, 0.1 for submacular hemorrhage without premacular hemorrhage, 0.1 for submacular hemorrhage with premacular hemorrhage, and 0.5 for macular edema.
The visual prognosis for eyes with symptomatic RAM depends on the macular pathology. Eyes with vitreous hemorrhage or premacular hemorrhage recover good vision, while the vision in those with submacular hemorrhage with or without premacular hemorrhage generally remains poor. New interventions including submacular surgery or pneumatic displacement of submacular hematoma should be evaluated in a future study in terms of visual prognosis for these eyes.
To assess the efficacy of treating submacular hemorrhages secondary to retinal arterial macroaneurysm with intravitreous tissue plasminogen activator (tPA) and gas.
Six consecutive patients (6 eyes) with submacular hemorrhage secondary to retinal arterial macroaneurysm were included in this study. Tissue plasminogen activator, at a dose of 50 microg/0.1 mL, was injected through the pars plana into the vitreous cavity. Gas (0.3-0.5 mL of perfluoropropane) instillation followed tPA injection, either immediately after injection or sometime during the next day.
Best postoperative visual acuity improved in 5 of 6 eyes (83%) and was unchanged in 1 of 6 (17%) eyes. In 5 of 6 (83%) eyes, the procedure resulted in complete or partial displacement of submacular hemorrhage out of the foveal area.
Intravitreous injection of tPA and gas, followed by prone positioning of the patient, is an effective and simple treatment of submacular hemorrhage secondary to retinal arterial macroaneurysm. No complication occurred in this series.
Nd:YAG laser photodisruption for preretinal hemorrhage due to retinal macroaneurysm
- Iijima
Management of ruptured retinal arterial macroaneurysm with intravitreal bevacizumab
- Javey