Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.
Angiogenesis Inhibitors/therapeutic use* ; Diabetes Mellitus ; Diabetic Retinopathy/drug therapy* ; Humans ; Intravitreal Injections ; Macular Edema/drug therapy* ; Pharmaceutical Preparations ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors/therapeutic use*

BACKGROUND: Limited data exist on real-world treatment patterns for diabetic macular edema (DME) in Korea. In this study, we investigated DME treatment patterns from 2009 to 2014 and the impact of baseline treatment on healthcare resource utilization and visual acuity (VA) outcomes. METHODS: A retrospective cohort chart review of DME patients treated at 11 hospital ophthalmology clinics between January 1, 2012 and December 31, 2013 was conducted. We collected data on demographics, healthcare resource utilization (clinic visits, treatment visits, and visits for ocular investigations), distribution of DME treatments, and VA. RESULTS: Overall, 522 DME patients (men, 55.2%; mean age, 59 years; mean HbA1c [n = 209], 8.4%) with 842 DME eyes were evaluated. For all treatments, healthcare resource utilization was significantly higher during the first 6 months versus months 7–12, year 2, or year 3 (P ≤ 0.001), but was highest for patients whose first treatment was an anti-vascular endothelial growth factor (VEGF) treatment (visits/quarter; anti-VEGF, 1.9; corticosteroids, 1.7; laser, 1.4). Use of macular laser therapy decreased (44% to 8%), whereas use of anti-VEGF injections increased (44% to 69%) during the study period. However, VA improvement was not commensurate with healthcare resource utilization of anti-VEGF treatment (mean VA gain, 2.7 letters). CONCLUSION: A trend toward increasing use of intravitreal anti-VEGF injections for DME treatment was observed in Korea. However, the frequency of dosing and monitoring was lower in clinical practice versus major clinical trials, which may have led to the less-than-favorable improvements in visual outcomes.
Adrenal Cortex Hormones ; Cohort Studies ; Delivery of Health Care ; Demography ; Endothelial Growth Factors ; Humans ; Intravitreal Injections ; Korea ; Laser Therapy ; Macular Edema ; Ophthalmology ; Practice Patterns, Physicians' ; Retrospective Studies ; Visual Acuity

PURPOSE: To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection failure. METHODS: Patients with DME and central subfield thickness (CST) >300 microm who did not respond to IVB injections were retrospectively included. Specifically, we enrolled patients who were diagnosed with refractory DME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after > or =3 consecutive IVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. All patients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinations included Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. RESULTS: Forty eyes of 34 patients were included. The average baseline CST was 476 microm. The average CST decreased to 368 microm at 2 months, 374 microm at 4 months, and 427 microm at 6 months (p < 0.001 for all results, Wilcoxon signed-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 months but decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle of resolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and 0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. CONCLUSIONS: Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CST in DME refractory to IVB.
Aged ; Angiogenesis Inhibitors/*therapeutic use ; Bevacizumab/*therapeutic use ; Diabetic Retinopathy/diagnostic imaging/*drug therapy/physiopathology ; Female ; Glucocorticoids/*administration & dosage ; Humans ; Injections, Intraocular ; Intraocular Pressure/physiology ; Intravitreal Injections ; Macular Edema/diagnostic imaging/*drug therapy/physiopathology ; Male ; Middle Aged ; Retrospective Studies ; Tenon Capsule/*drug effects ; Tomography, Optical Coherence ; Treatment Failure ; Triamcinolone Acetonide/*administration & dosage ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity/physiology

BACKGROUNDRetinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model.

METHODSA rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1.

RESULTSBoth retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05).

CONCLUSIONSThis retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Enzyme-Linked Immunosorbent Assay ; Erythrosine ; toxicity ; Fluorescein Angiography ; Intravitreal Injections ; Macular Edema ; chemically induced ; drug therapy ; metabolism ; Ranibizumab ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins ; therapeutic use ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A ; metabolism

Diabetic macular edema is one of the most common causes of visual acuity impairment in adults. Various treatment modalities are currently used. They include laser therapy, intravitreal or periocular injection of steroid, intravitreal injection of anti-vascular endothelial growth factor, and pars plana vitrectomy. Introduction of newer therapeutic agents, such as ranibizumab and aflibercept has changed the paradigm of treatment approaches for diabetic macular edema. However, traditional treatment methods, such as laser photocoagulation and vitrectomy, are still being used effectively in certain situations. Each treatment modality has its own unique mode of action, and has advantages and disadvantages at the same time. Given multiple mechanisms are involved in the development of diabetic macular edema, a combination treatment approach is often employed rather than using only one of the treatment modalities. In this review, treatment outcomes of each approach are summarized and combination approaches are discussed.
Adult ; Bevacizumab ; Dexamethasone ; Endothelial Growth Factors ; Humans ; Injections, Intraocular ; Intravitreal Injections ; Laser Therapy ; Light Coagulation ; Macular Edema* ; Ranibizumab ; Visual Acuity ; Vitrectomy

PURPOSE: The authors report a case of bilateral simultaneous central retinal vein occlusion caused by Waldenstrom's macroglobulinemia. CASE SUMMARY: A 65-year-old man presented to our department complaining of decreased visual acuity for the duration of about 6 months. On his initial visit, best-corrected visual acuity was 0.02 in the right eye and 0.06 in the left eye. Based on the findings of a funduscopic examination, the patient had bilateral diffuse retinal hemorrhages, dilated tortuous veins, and macular edema. He had experienced recurrent spontaneous epistaxis 6 months previously and had undergone treatments such as intravitreal bevacizumab injection and intravitreal dexamethasone implantation at another hospital. Laboratory tests at that hospital showed anemia and hyperproteinemia, for which he was referred to our hemato-oncology department. Bone marrow biopsy was consistent with Waldenstrom's macroglobulinemia/lymphoplasmacytoid lymphoma, and he was treated with systemic chemotherapy. One year after the systemic chemotherapy, his best-corrected visual acuity was 0.15 in the right eye and 0.6 in the left eye. Funduscopy showed decreased bilateral retinal hemorrhages and macular edema. CONCLUSIONS: When simultaneous bilateral central retinal vein occlusion occurs in a patient with no other underlying disease such as hypertension or diabetes, it might be a sign of serum hyperviscosity, and there should be a very high level of suspicion for presence or progression of systemic disease. If such a disease is properly and timely diagnosed, effective early systemic evaluation and therapy can be administered, and it is important to have initial general treatment as well as ophthalmic treatment.
Aged ; Anemia ; Bevacizumab ; Biopsy ; Bone Marrow ; Dexamethasone ; Drug Therapy ; Epistaxis ; Humans ; Hypertension ; Lymphoma ; Macular Edema ; Retinal Hemorrhage ; Retinal Vein* ; Veins ; Visual Acuity ; Waldenstrom Macroglobulinemia*

PURPOSE: To report the frequency and clinical features of sterile inflammation after intravitreal aflibercept injection in a Korean population. METHODS: A single-center, retrospective study was performed in patients who received intravitreal aflibercept from July 2013 through January 2015. RESULTS: A total of four cases of post-injection sterile inflammation were identified from 723 aflibercept injections in 233 patients. Patients presented 1 to 13 days after intravitreal aflibercept injection (mean, 5 days). The mean baseline visual acuity was 20 / 60, which decreased to 20 / 112 at diagnosis but ultimately recovered to 20 / 60. Three cases had inflammatory cells in the anterior chamber (mean, 2.25+; range, 0 to 4+), and all cases had vitritis (mean, 3+; range, 2+ to 4+). No patients had pain. Only one patient underwent anterior chamber sampling (culture negative) and injection of antibiotics. Three of four patients were treated with a topical steroid, and all experienced improvement in their symptoms and signs of inflammation. CONCLUSIONS: The overall incidence of sterile inflammation after intravitreal aflibercept injection in a Korean population was 4 of 723 injections (0.55%), or 4 of 233 patients (1.79%). Sterile inflammation after intravitreal aflibercept injection typically presents without pain, and the visual outcomes are generally favorable.
Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Incidence ; Intravitreal Injections ; Macular Edema/*drug therapy/epidemiology ; Male ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor/*administration & dosage ; Recombinant Fusion Proteins/*administration & dosage ; Republic of Korea/epidemiology ; Retrospective Studies ; Treatment Outcome ; Vascular Endothelial Growth Factor A ; Visual Acuity

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology

PURPOSE: To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. METHODS: Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. RESULTS: The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 +/- 0.91 (range, 0 to 3) and 1.94 +/- 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients <65 and > or =65 years of age in both the ranibizumab and bevacizumab groups were then compared. For patients <65, there was a significant difference in the average VAS pain scores between groups (p = 0.003). However, for patients > or =65 years, there was not a significant difference in the average VAS pain scores between groups (p = 0.238). Female and male patients in both ranibizumab and bevacizumab groups were also compared. For female patients, there was a significant difference in the average VAS pain scores between groups (p = 0.016), although not for male patients (p = 0.078). CONCLUSIONS: Thirty-gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.
Aged ; Aged, 80 and over ; Angiogenesis Inhibitors/*administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Bevacizumab/*administration & dosage ; Diabetic Retinopathy/drug therapy/physiopathology ; Female ; Humans ; *Intravitreal Injections ; Macular Degeneration/drug therapy/physiopathology ; Macular Edema/drug therapy/physiopathology ; Male ; Middle Aged ; Pain Measurement ; Ranibizumab/*administration & dosage ; Retinal Vein Occlusion/drug therapy/physiopathology

The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient's clinical history and assessment.
Adrenal Cortex Hormones ; therapeutic use ; Bevacizumab ; therapeutic use ; Biomedical Research ; organization & administration ; Diabetic Retinopathy ; therapy ; Disease Management ; Disease Progression ; Humans ; Light Coagulation ; Macular Edema ; therapy ; Ranibizumab ; therapeutic use ; Retina ; pathology ; Tomography, Optical Coherence ; Triamcinolone ; therapeutic use ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors ; Visual Acuity ; Vitrectomy