Discussion
There are several studies highlighting the importance of glycaemic control on the progression of diabetic retinopathy.1 15 19 However, only few studies have assessed the role of glycaemic control in treatment response to VEGF inhibition.16 17 20 21
Ozturk et al reported the impact of glucose regulation in DME treatment. In that report, more optimal serum HbA1c levels correlated with increased reduction in CMT following a single intravitreal injection.17 In our study also, we had increased reduction of CMT (229.76 μm) in group with HbA1c <7%(53mmol/mol) compared with 145.20 μm in group with HbA1c >7%(>53mmol/mol) and the difference was statistically significant (p<0.022). The average CMT difference was 84.56 μm more in groups with lower HbA1c than in the group with higher HbA1c.
In a small prospective analysis of 38 patients by Warid et al,22 greater proportion of patients with HbA1c <7%(<53mmol/mol)gained 2 lines of VA compared with those with HbA1c >7%(>53mmol/mol), suggesting that poorer glycaemic control may lead to worse visual outcomes.
By contrast, in a prospective study of 52 patients, Macky and Mahgoub20 reported that there was no difference in the 6-month VA or CMT between patients with baseline HbA1c <7%(<53mmol/mol) or >7%(>53mmol/mol)treated with three injections of bevacizumab plus laser. However, lower HbA1c appeared to be correlated with better visual acuity and lower CMT values at baseline.
In a retrospective analysis of 124 patients treated with bevacizumab DME over 12 months, Matsuda et al16 demonstrated that patients with a baseline HbA1c <7%(<53mmol/mol) had better VA (20/43) at 1 year compared with patients with a baseline HbA1c >7%(>53mmol/mol) (20/62). However, there was no significant difference in the final CMT at 1 year between the two groups; that is, both groups had significant reductions in CMT after treatment regardless of their glycaemic control.
In a post hoc analysis by Bansal et al,21 the patients treated with monthly intravitreal ranibizumab had improvement in VA, reduction in CMT and improvement in DR severity score independent of their baseline HbA1c or change in HbA1c. There was no significant differences in the 36-month vision, change in vision or 36-month CMT between patients with baseline HbA1c <7%(<53mmol/mol) and >7%(>53mmol/mol) or between patients stratified by quartiles of baseline HbA1c.
In our study, the patients with more optimal DM control (HbA1c <7%) had a mean improvement in logMAR VA of 0.50 at 3 months. Those patients with less optimal DM control at baseline (HbA1c >7%) also had an improvement (0.33 logMAR) but the change was less marked in comparison to the HbA1c <7% group. The difference in the final BCVA between the two groups was not statistically significant (p=0.13)
Although a marked reduction of macular oedema was found in both the subgroups of patients with HbA1c <7% (<53mmol/mol)and HbA1c >7%(>53mmol/mol), the visual outcome did not correlate with improvement in CMT.
The quantitative assessment of macular thickness using OCT is clinically useful, but macular thickness is just one of several variables affecting visual outcomes.23 The discordance between visual and anatomical outcome in our study may be related to factors like chronic nature of oedema, macular ischaemia and so on.
As it is to our knowledge, the irreversible photoreceptor damage due to long-standing macular oedema may limit a correlated increase in visual acuity.24 So, if there is photoreceptor cell damage, anatomical improvement may not contribute to visual improvement.
Macular ischaemia is also known to be associated with poor visual outcome in patients with diabetes regardless of treatment.25 Since fluorescein angiographies were not done in all the cases, information regarding macular perfusion was limited. Other factors like presence of epiretinal membrane, posterior hyaloid traction may also contribute to the poor visual outcome.
However, the limited initial BCVA response does not entirely preclude the possibility of better BCVA response in the long term. The follow-up duration in our study was relatively short, and it is known from large clinical trials that stabilisation of VA takes time and it can improve even after the loading dose of three injections.
There could be several reasons for the differences in our results and those of other studies. The duration of follow-up, choice of anti-VEGF injection, number of injections all can influence the final outcome. Also, as we know, DME is a complex condition and the improvement or worsening of DME may depend not only on HbA1c or VEGF alone but also on multiple systemic and local factors, such as blood pressure, cholesterol, obesity, which all can confound the final results.
In conclusion, intravitreal bevacizumab treatment resulted in an improvement in visual acuity and decrease in macular thickness in DME. Maximum benefit from the treatment may be attained by strict glucose regulation. Glycaemic control influences the treatment outcome and may be responsible in part for the different response among patients with the same DME treatment.
The functional and anatomical outcomes are usually correlated but the changes in anatomy alone do not explain the final functional outcome specially in cases with poor glycaemic control who may have chronic macular oedema. Therefore, every early intervention for DME without ischaemia may help to preserve the visual potential by inhibiting further degeneration of photoreceptors. Thus, there is a critical role of a multidisciplinary approach to the patient with DME, in particular for coordination between the endocrinologist and the treating vitreoretinal specialist