Discussion
In this prospective study of patients with treatment-naive PDR, we found the baseline arteriolar calibre and venous FD to be predictive of disease activity 6 months after PRP treatment. Every 1.0 pixel point in wider arteriolar calibre at baseline was associated with a 34% increased risk of progression of PDR, and every 0.01 point higher FD was associated with a 15% increased risk of PDR progression, independent of other risk factors.
In patients with progression of PDR, we found the baseline arteriolar calibre to be wider compared with patients without progression of PDR at follow-up month six. Studies have postulated wider arteriolar calibre as a risk factor in the early development of DR.15 25 Furthermore, a gradual constriction of the arteriolar calibre has been observed with increased severity of DR.17 26 In a study by Broe et al, it was shown that reduced arteriolar calibres were associated with a 31% cumulative incidence of PDR after 16 years.27 However, the overall association between arteriolar calibre and DR is more complex, and studies conducted on large cohorts have reported on no associations, or even arteriolar calibre dilatation.14 28–30 The literature is seen to be very inconclusive regarding retinal arteriolar calibre, in different stages of DR. To our knowledge, no other studies have looked at differences in retinal vascular parameters between patients with and without progression after PDR-treatment. At the level of PDR, the retinal arteriolar calibre should be expected to be affected by different systemic and microvascular factors. Traditionally systemic risk factors like duration of diabetes, glycaemic and blood pressure control are believed to have an impact on retinal vessel calibre.31 Our study might indicate that the microvascular capacity is radically changed, when an eye reaches the level of PDR. The hypoxic load increases and neovascularisations are formed. Thus, dilating the arterioles in order to increase the blood flow to the new vessels in eyes with reduced or damaged vascular capacity.
The FD explains the complexity of the retinal vascular tree; thus, a higher value equals a higher retinal vascular complexity. At baseline we found a higher FD in patients with progression of PDR as compared with patients with non-progression at follow-up month six. This could be due to a higher hypoxic load in patients with progression of PDR 6 months after PRP, thus resulting in a more complex vascular structure. The arteriolar and venular FD did not differ between the two groups from baseline to follow-up month six. Earlier studies have reported on a lower FD to be associated with a higher risk of developing PDR.18 27 In an earlier prospective study, performed at our unit, we found no difference in FD at baseline between patients with progression and non-progression at follow-up month six.32 This difference could be due to the usage of two different computer softwares, the SIVA and VAMPIRE softwares. There are some evident differences between the two softwares. First of all, there is a difference in the postprocessing of retinal images. Furthermore, different mathematical algorithms are used to access the retinal vessel geometry.
Second, the SIVA software allows fare more grader-correction that the VAMPIRE software. The SIVA software allows for tracing of untraced vessels, correction of vessel crossings and deletion of vessel segments. The VAMPIRE software does not allow the abovementioned corrections. McGrory et al33 reported on the agreement in measurements between the two softwares and concluded that caution should be taken when making inferences regarding the associations between retinal measures.
Furthermore, the arteriolar tortuosity was seen to increase from baseline to follow-up month six in patients with progression of PDR. Likewise, on this matter the literature is inconclusive. One prospective study reported on increased arteriolar tortuosity in patients with progression of PDR 6 months after PRP treatment, while another cross-sectional study found no association between PDR and retinal vascular tortuosity.32 One could speculate, if increased tortuosity could be associated with increased retinal ischaemia. Thereby the tortuosity would increase in patients with an increased or high ischaemic load and progression of PDR in this group is seen despite PRP treatment.
In our study, the arteriolar calibre was documented to increase from baseline to follow-up month six in the two groups regardless of PRP treatment. As stated earlier, it has been reported that the arteriolar vessel calibre decreases with increased severity of DR.17 26 Thus, narrow arteriolar vessels could be expected at the level of PDR. After PRP treatment, the ischaemic drive is thought to be reduced, and thereby a dilatation of the retinal vessels could be seen. In our study, the dilatation of the retinal vessels regardless of progression of PDR at follow-up month six could be due to the laser treatment itself. In a study by Klein et al,26 the arteriolar calibre was found to be significantly smaller in eyes with PDR treated with PRP as compared with untreated eyes, although the time from PRP treatment to calibre measurement was unclear.
The venular calibre increased from baseline to month six regardless of disease progression. The literature is somewhat sparse on this topic. Prospective studies have reported on wider retinal venular calibre and increased incidence of PDR.14 34 However, a prospective study performed at our department on patients with PDR found no statistical change in retinal venular calibre at 6-month follow-up after PRP treatment regardless of disease progression.32 A change in the retinal venular calibre was not expected. Our findings showed an increase in the venular calibre that could be explained by a reduced autoregulatory function due to the long duration of DM, and the overall state of the vessels at the point of PDR.
The strengths of this study were the prospective design, and the use of a semiautomated validated computer software which minimised grader influence on the results. Limitations include the lack of refractive data on the cohort, and the relatively small sample size; larger cohorts are needed to investigate the disease process and its vascular characteristics further.
In conclusion, our prospective study showed that the arteriolar calibre and venular FD at baseline, using the VAMPIRE software, predict disease activity 6 months after PRP treatment in patients with treatment-naïve PDR. We found increased retinal arteriolar and venular calibre from baseline to follow-up month six regardless of PRP treatment. Hence, structural retinal arteriolar and venular differences/changes could serve as individual markers of adequacy of PRP treatment in patients with PDR.