Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema.

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

[Efficacy of dorzolamide in reducing retinal thickness after photocoagulation in diabetic macular oedema]. / Eficacia de la dorzolamida para reducir el grosor retiniano después de fotocoagulación en el edema macular diabético.

BACKGROUND: Focal photocoagulation interrupts vascular leakage in diabetic macular edema, and allows the retinal pigment epithelium to withdraw fluid that thickens the retina; this mechanism could be enhanced by dorzolamida, a topical carbonic anhydrase inhibitor. OBJECTIVE: To determine the efficacy of dorzolamida compared against placebo, in reducing retinal thickness after focal photocoagulation, in eyes with diabetic macular oedema. MATERIAL AND METHODS: Experimental, comparative, prospective, longitudinal, double blind study in diabetics with focal macular oedema treated with photocoagulation. Treated eyes were randomly assigned three weeks after the procedure to receive dorzolamide (group 1) or placebo (group 2), three times daily during three weeks. Means of visual acuity, center point thickness and macular volume were compared 3 and 6 weeks after photocoagulation within groups (Wilcoxon's t) and between groups (Mann-Whitneys's U). RESULTS: Sixty-nine eyes form patients aged 58.3 ± 8.3 years; 37 were assigned to group 1 and 42 to group 2. Mean center point thickness changed from 178.4 ± 34µm to 170 ± 29.1µm in group 1 (p = 0.04), and from 179.2 ± 22.4µm to 178.6 ± 20.8µm in group 2 (p = 0.7); mean macular volume changed from 7.63 ± 0.52mm(3) to 7.50 ± 0.50mm(3) in group 1 (p = 0.02) and from 7.82 ± 0.43mm(3) to 7.76 ± 0.42mm(3) in group 2 (p = 0.014). CONCLUSIONS: The efficacy of dorzolamide was higher than that of placebo, to reduce retinal thickness after focal photocoagulation in diabetics with macular oedema.

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema.

AIMS: Evaluate the role of systemic factors on the functional and anatomic outcomes of anti-VEGF therapy for diabetic macular edema (DME). METHODS: A retrospective consecutive case series of 124 patients with DME treated with anti-VEGF therapy was collected. The main outcome measures were change in best corrected visual acuity (BCVA) and change central subfield macular thickness (CST) measured with spectral-domain ocular tomography coherence (SD-OCT); and their correlation with clinical findings. RESULTS: Patients with serum hemoglobin A1c values (HbA1c) ≤ 7.0% had a statistically significant improvement in BCVA (20/66 to 20/43, p < 0.001), and those patients with HBA1c > 7.0% also had a significant but less robust improvement in BCVA (20/78 to 20/62, p = 0.024). CST improved significantly in both groups, but showed a larger magnitude of improvement in the group with better DM control [-140.7 microns (p < 0.001) and -83.3 microns (p < 0.001)]. Mean HBA1c levels remained relatively stable during the follow-up in both groups, but patients with improved glucose control during the study duration had a significantly lower retinal thickness than patients that had a stable or worsening HbA1c (mean final CST of 324.3 versus 390.0 µm, respectively, p = 0.042). Other systemic parameters were not correlated with changes in OCT thickness or BCVA. There was not a significant difference related to number of intravitreal injection in the HbA1c ≤ 7.0% group compared to HbA1c > 7.0% group, mean of 5.48 and 6.0 intravitreal injections respectively (p = 0.362). CONCLUSION: This study suggests that glucose regulation can impact the response to anti-VEGF therapy in the management of DME.

Staining of the internal limiting membrane with the use of heavy brilliant blue G.

BACKGROUND: Brilliant blue G (BBG) is frequently used in chromovitrectomy to facilitate internal limiting membrane (ILM) peeling. A study was initiated to evaluate if heavy BBG is safe and effective in staining the ILM. METHODS: We studied 30 eyes, 23 with idiopathic macular holes and 7 of patients with diabetic macular edema. Removal of the ILMs was assisted by heavy BBG staining. In cases with histopathological correlation the ILMs were evaluated with hematoxylin and eosin, Masson's trichrome, periodic acid-Schiff and glial fibrillary acidic protein staining. In addition, immunohistochemistry was also performed using specific antibodies for vimentin, neuron-specific enolase, factor VIII and CD68. Using the Image-Pro Plus software of Media Cybernetics Co. we found an average thickness in ILMs. RESULTS: Of the ILM specimens sent, 19/30 (63.33%) could not be processed properly because of the limited sample material, recognizing only fragments of dispersed fibrillar material. In macular hole ILMs we found an average thickness of 1.3 ± 0.65 µm, and in diabetic macular edema ILMs an average thickness of 6.2 ± 1.4 µm. CONCLUSIONS: In heavy BBG-assisted ILM peeling we observed no intraoperative or postoperative complications after a mean follow-up of 12 months. Heavy BBG could be an effective and safe vehicle for staining the ILM.

Emerging pharmacotherapies for diabetic macular edema.

Diabetic macular edema (DME) is the most frequent cause of severe vision impairment in patients with non-proliferative diabetic retinopathy. Even though patients should achieve optimal glycemic control, normalization of blood pressure and serum lipids, as well as improvement of cardiac and renal status, these measures alone will not prevent every patient from developing visual loss caused by DME. The goal of local treatment for DME is vision improvement, usually achieved after reducing leakage on fluorescein angiography (FA) and retinal thickness on optical coherence tomography (OCT). Laser photocoagulation is still the standard treatment for clinically significant DME. However, laser photocoagulation rarely provides major visual improvement, especially in patients with diffuse DME. Thus, a therapeutic intervention that restores visual acuity impaired by DME more often remains a significant unmet medical need. This review aims to present the most important emerging drug technologies for therapy of DME at present, including corticosteroids, vascular endothelial growth factor inhibitors, protein kinase C inhibitors, small interfering RNA, hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors and non-hormonal anti-inflammatory agents. Recent progress in this field suggests that local management of DME may change rapidly in the near future. Novel emerging drugs should enable better anatomical and functional outcomes for therapy of this sight-threatening disease.