Role of Microaneurysms in the Pathogenesis and Therapy of Diabetic Macular Edema: A Descriptive Review.

Background and Objectives: This study aims to elucidate the role of microaneurysms (MAs) in the pathogenesis and treatment of diabetic retinopathy (DR) and diabetic macular edema (DME), the major causes of acquired visual impairment. Materials and Methods: We synthesized the relevance of findings on the clinical characteristics, pathogenesis, and etiology of MAs in DR and DME and their role in anti-vascular endothelial growth factor (VEGF) therapy. Results: MAs, a characteristic feature in DR and DME, can be detected by fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. These instrumental analyses demonstrated a geographic and functional association between MA and ischemic areas. MA turnover, the production and loss of MA, reflects the activity of DME and DR. Several cytokines are involved in the pathogenesis of MAs, which is characterized by pericyte loss and endothelial cell proliferation in a VEGF-dependent or -independent manner. Ischemia and MAs localized in the deep retinal layers are characteristic of refractory DME cases. Even in the current anti-VEGF era, laser photocoagulation targeting MAs in the focal residual edema is still an effective therapeutic tool, but it is necessary to be creative in accurately identifying the location of MAs and performing highly precise and minimally invasive coagulation. Conclusions: MAs play a distinctive and important role in the pathogenesis of the onset, progression of DR and DME, and response to anti-VEGF treatment. Further research on MA is significant not only for understanding the pathogenesis of DME but also for improving the effectiveness of treatment.

Incidental Microaneurysms During Microvascular Surgery: Incidence, Treatment, and Significance.

BACKGROUND: Although new imaging tools have been developed for the detection of smaller aneurysms, angiographically negative microaneurysms are still encountered during cerebral microsurgery. Currently, only limited information regarding incidence and efficacy of treatment of these microaneurysms is available. METHODS: We investigated the incidence and treatment of incidental microaneurysms (IMAs) in the last 5 years. IMAs are unidentifiable and invisible on preoperative angiography, but are detected during microvascular surgery. The inclusion criteria were aneurysm cases treated with microsurgery via transsylvian approaches, and those undergoing preoperative digital subtraction angiography. RESULTS: This study enrolled 484 surgical cases (248 cases of subarachnoid hemorrhage and 236 cases of unruptured aneurysms) in 460 patients, and 33 tiny aneurysms were found in 31 operative cases (6.4% incidence per operation). The most typical type was located on another branching site of the middle cerebral artery found during neck clipping of the middle cerebral artery bifurcation aneurysm. A patient with multiple aneurysms presented a statistically significant risk (375/78 vs. 15/16; P < 0.001) of IMA identification. IMAs were treated by clipping and wrapping in 18 and 15 cases, respectively, without complications. CONCLUSIONS: This study revealed a 6.4% incidence of IMAs; however, this could be underestimated because of the limited range of inspection. Early detection of an IMA through careful inspection during microvascular surgery could be beneficial, especially in patients with multiple aneurysms.

Effect of Leaking Foveal Microaneurysms on the Treatment of Center-Involving Diabetic Macular Edema: A Pilot Study.

PURPOSE: Evaluate the effect of foveal leaking microaneurysms (MAs) on the required number of intravitreal ranibiz-umab (IVR) injections in the treatment of center-involving diabetic macular edema (DME) when treated with focal/grid laser. DESIGN: A pilot study of prospective, nonrandomized, multicenter clinical trial. METHODS: This study enrolled 21 eyes with DME for which pro re nata IVR injections were combined with short-pulse focal/grid laser. At 12 months, best-corrected visual acuity (BCVA), central subfield macular thickness (CMT), and the required number of IVRs to maintain CMT < 300 µm were compared between eyes with or without foveal leaking MAs, termed the MA(+) and MA(-) groups, respectively. RESULTS: Significant CMT improvements (p < 0.0001) and increased BCVA of 4.0 ± 8.5 letters were observed at 12 months. The MA(-) group required significantly fewer IVRs than did the MA(+) group (mean: 4.9 ± 3.0 vs. 8.6 ± 3.0; p = 0.0306). In the latter 6 months of the 1-year follow-up, 50% (4/8) of MA(-) eyes did not require any IVR administration to sustain CMT < 300 µm. CONCLUSIONS: A combination therapy of short-pulse focal/grid laser and reduced IVR injections appeared noninferior to previous reports of IVR monotherapy. Further large-scale investigations are warranted.

Endovascular Management of Microcerebral Aneurysms with Diameter Smaller than 3 mm: Is It Feasible and Safe?

BACKGROUND: The neurosurgical management of microcerebral aneurysms with diameter smaller than 3 mm remains a great challenge as many complications can occur. AIM: Our target was to assess the efficacy and usefulness of endovascular treatment of these lesions. METHODS: We did a prospective and retrospective gathering of the results of endovascular treatments for a group of 16 patients with 16 microcerebral aneurysms. Four patients were treated by direct coil embolization, and 12 patients were managed by remodeling techniques. RESULTS: Coil embolization was technically accessible in all cases. Initial complete occlusion is achieved in 12 patients. We did not face major technical complications such as aneurysmal rupture or coil migration during the endovascular management in 15 patients. Only in 1 case the second and last coil (2/1 mm) migrated distally and could not be retrieved. In this case clinical evidence of neurologic deterioration and weakness in left lower limb due to right anterior cerebral artery territory stroke was evidenced in the follow-up computed tomography scan. Follow-up clinical and radiological studies were available for 9 of 12 surviving patients and showed complete occlusion in 7 cases, and in 1 case aneurysm tiny recanalization was demonstrated after 1 year, which was retreated with complete occlusion, and in another case tiny aneurysm recanalization at the neck appeared after 2 years, which was left under observation. CONCLUSIONS: Endovascular treatment is a beneficial and effective therapeutic alternative to microsurgery for microaneurysms. The long-term assessment of endovascular management for these lesions was not included in that study.

Clinical and Angiographic Characteristics of 35 Patients With Cryptogenic Hemoptysis.

BACKGROUND: Hemoptysis can cause a life-threatening condition and often needs to be treated urgently. Nearly 20% of hemoptysis cases are diagnosed as cryptogenic after clinical investigation. The purpose of this study was to clarify the clinical and angiographic characteristics of cryptogenic hemoptysis. METHODS: We retrospectively reviewed medical records of 35 patients admitted to our hospital with cryptogenic hemoptysis from October 2010 to September 2014. RESULTS: In the 35 cases, bronchial artery embolization was successfully performed in 33 patients (94.3%), whereas bronchoscopic hemostatic therapy was added in one patient (2.8%), and embolization was not performed in one patient (2.8%) because the bronchial artery was too narrow. In the successful embolization group, the non-rebleeding rate was 97.0% for 20 months. The angiographic findings revealed that the diameter of the bronchial arteries was < 2 mm in 13 patients, 2 to 3 mm in 17 patients, and > 3 mm in five patients. Hypervascularization was detected in 29 patients (82.9%) and small bronchial aneurysms in eight patients (22.9%). The amount of hemoptysis was slight (< 50 mL/d) in 12, mild (50-100 mL/d) in 11, moderate (100-200 mL/d) in eight, and massive (> 200 mL/d) in four patients. No obvious relationship was found between the diameter of bronchial arteries and the amount of hemoptysis. CONCLUSIONS: BAE was highly effective for the management of cryptogenic hemoptysis. Most cases of cryptogenic hemoptysis have angiographic abnormalities, including small or microaneurysms, which were suspected as the cause in some cases.

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

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

Microaneurysms cause refractory macular edema in branch retinal vein occlusion.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents can treat macular edema (ME) in branch retinal vein occlusion (BRVO). However, refractory ME, the mechanism of which is not well elucidated, occurs frequently. Sixty-six eyes with ME secondary to BRVO were enrolled in this retrospective observational case-control study. Twenty eyes received a sub-Tenon's capsule injection of triamcinolone acetonide (STTA), 22 eyes an intravitreal anti-VEGF injection (ranibizumab), 16 eyes were switched from STTA to ranibizumab, 4 eyes underwent vitrectomy, and 4 eyes were untreated. Multiple regression analysis and multivariate logistic regression analysis were conducted, respectively, to identify independent predictors of visual acuity (VA) prognosis and risk factors for refractory ME longer than 1 year. The mechanism of refractory ME and therapeutic approaches for identified risk factors also were investigated. Thirty-four (52%) eyes had refractory ME for over 1 year. Microaneurysms were identified as risk factors for refractory ME, leading to poor final VA. Ranibizumab suppressed microaneurysm formation and refractory ME, with early administration more effective. For already formed microaneurysms, laser photocoagulation reduced additional treatments. Microaneurysms may cause refractory ME in BRVO. Alternative therapy to suppress microaneurysms should be considered to prevent refractory ME in patients with BRVO.