DME remains the most common cause of reduced vision in diabetic patients that puts the Visual acuity at risk. Angiogenesis inhibitors are widely used throughout the world today as the first line of treatment for diabetic macular edema [3, 18], and these drugs have the potential to enhance the preservation of vision and even increase vision in many patients. In this survey, we assessed the effects of Avastin on macular thickness in eyes with DME and good visual acuity. The results of this clinical trial showed that although the mean central macular thickness was decreased in the treatment group, it was not significantly different from the control group and there was no significant difference in the two groups.
The pathophysiology of diabetic edema can determine the individual patient's medical need, which may increase angiogenesis in one group and inflammatory factors in the other, or both. Disorders are vascular permeability and therefore each will need its own unique treatment [7]. Systematic review studies conducted by the Cochrane Library with high evidence have found the use of antiangiogenic drugs to be effective in the treatment of macular edema [11, 18], while research by the American Diabetes Association demonstrated resistant to this drug with no clinical response in approximately 40% of patients [19]. In recent years, several studies have investigated the efficacy and comparability of different groups of angiogenic drugs and have evaluated their therapeutic results with other available therapies such as laser and corticosteroid therapy. Given the presence of resistant cases, underlying factors beyond VEGF may play a role in the pathogenesis of the disease, and the investigation of molecular factors and changes in intraocular protein levels in response to treatment and genetic studies may offer a new approach to treatment [10] So,there seems to be a ceiling for treatment with antiangiogenics, and then no further treatment.
Study by Baker, C.W., et al [ 12 ] in a randomized clinical trial in 702 participants with diabetic macular edema involving the center of the macula (CI-DME) and good visual acuity that were evaluated in term of the effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss, no significant difference in vision loss at 2 years was found whether eyes were initially managed with aflibercept or with laser photocoagulation or observation and given aflibercept only if visual acuity worsened. They concluded observation without treatment unless visual acuity worsens may be a reasonable strategy for CI-DME. Also, in a retrospective study Busch, C. et al. [ 13] reported evaluation of baseline predictors for visual acuity loss during observation in diabetic macular edema with good baseline visual acuity in 249 eyes of which 147 eyes were observed and 80 eyes received anti-vascular endothelial growth factor (VEGF) treatment. They found that earlier treatment with anti‐VEGF in these patients may potentially decrease the risk of VA loss at 12 months.
Another study by Luu, K.Y. et al. [ 14] on 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better that were received cumulative intravitreal injections and laser treatments at yearly intervals. They revealed DMO with good initial visual acuity should be monitored closely, as delay in treatment initiation is associated with worse visual outcomes and concluded BCVA at time of initial treatment is the strongest determinant of final visual acuity.
On one hand our results are in contrast to the study by Busch, C.et al that believe Earlier treatment with anti-VEGF in these patients may potentially decrease the risk of VA loss. On the other hand, despite the small sample of eyes in our study, our finding is similar to the study of Baker, C.W., and Luu, K.Y. that suggest closely monitoring of subjects with DME
A systematic review study by Pravin U Dugel et al., investigating the association between baseline (pre-treatment) vision and increased visual acuity in patients treated with anti-angiogenesis drugs for an average of 12 months, they stated "The amount of vision corrected before treatment is inversely correlated with the rate of increased vision after treatment." This study, based on 9 major studies :RESOLVE, RISE, RIDE, RESTORE, RETAIN, RETAIN, DRCR.net Protocol I, VINCI, VIVID VISTA, suggests that no matter the amount of anti-angiogenic drug used and the theoretical coincidence, among all of them there is a steady increase in visual acuity of more than 20/40 and then a slight increase in visual acuity afterwards. [17] that is in line with the results of our study.
As reported in previous study using angiography, there is a blood vessel-free zone in the fovea region of diabetic patients due to hypoxia, suggesting that macular edema may play a different mechanism. Edema from other regions of the retina not affected by the production of angiogenic factors and in relation to the failure of the retinal pigment epithelial cell pump due to choriocapillary hypoxia may explain the lack of association between non-reduction of retinal thickness using anti-angiogenesis drugs [10]. In addition, Browning et al. stated in their review study that the results of numerous studies around the world in terms of the average number of intravitreal injections and increased visibility with renowned clinical trials is a significant difference [15.16 ] which believe that in the real world the use of antiangiogenic drugs accompany multiple visits and time expenses. Furthermore, according to a previous clinical trial report [10] diabetes is a nasty disease that yield a permanent photoreceptor damage based on the duration of disease or from extensive previous treatments. It may also be attributable to individual systemic factors that may affect macular edema such as type of diabetes and glycemic control of diabetes, age, blood pressure, serum lipid levels, and nephropathy. In addition, it is not known whether or not continued injections for six to 12 months could improve the outcomes. So we should not consider simple mechanisms for its complications which if given adequate health care and in-vitro antiangiogenesis injections, will accompany high rates of recovery .
Our study has potential limitations, including the small sample of treated eyes, and slightly short term follow ups. However, the results in our study are similar to those in DME study in which closely monitoring were suggested for treatment.
In conclusion, we have shown that although Avastin may be useful for reducing the incidence of diabetic macular edema in patients with visual acuity of 20/25 or better at least in a short period., it seems that, its effect is temporary and is not significant compared to the control group .However, further studies with a longer follow-up period and a larger number of patients are recommended to draw final conclusions about the efficacy of Avastin and their role in controlling the progression of DME