Birgit Sander

Background: The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. Methods: Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m² intensity (14.9 and 14.8 log photons/cm²/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m². The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0–10 s after light termination) and late (10–30 s after light termination). Lens transmission was measured with an ocular fluorometer. Results: The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively) for the blue light stimulus condition only. The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions. Lens transmission decreased linearly with age (p < 0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m² light (p = 0.02). Conclusions: Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.

Optical Coherence Tomography (OCT) has become an invaluable tool in many ophthalmologic departments. The images are easy to overview at first glance, a theoretical background is however needed for proper interpretation and in this review the technical developments will be illustrated with a number of cases.

Aim To study the long-term visual result of photocoagulation of clinically significant macular edema (CSME) in diabetic patients in relation to baseline retinal vascular leakage assessed by vitreous fluorometry. Methods The study enrolled 36 eyes in 27 diabetic patients with CSME at baseline, all subsequently treated by photocoagulation. The diagnosis of CSME and treatment procedure followed the ETDRS criteria. The leakage through the retinal vessels was calculated as the blood–retinal barrier permeability. Five years after initial photocoagulation the patients were reexamined. Results The mean visual acuity decreased with 16 letters at follow-up, and in 15 eyes visual loss was substantial, with a decrease of 15 letters or more, corresponding to at least 3 lines. The baseline permeability was significantly higher in eyes with substantial visual loss than in eyes with more stable vision (14.2 nm/sec and 6.3 nm/sec respectively; p = 0.006), the corresponding odds ratio was 16.1 (95% CI: 1.8–146; p = 0.014). The level of retinopathy was significantly correlated to visual loss (Fisher’s exact test < 0.02). Conclusion Visual acuity decreased at follow-up, and a substantial visual loss of 3 or more lines in CSME was associated with higher retinal vascular leakage at baseline with an odds ratio of 16.1. For this relatively small sample, neither diabetes duration, age or HbA_1c reached statistical significance, indicating that blood-retinal barrier permability is a strong predictor of the visual outcome. The results support the investigation of triamcinolone or VEGF inhibition in patients with severe leakage, and may help to identify patients in need for intravitreal injection.

To study the progression of diabetic macular edema (DME) in relation to baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel diameters. In this single-center study, 45 patients were enrolled with 62 eligible eyes defined as having DME of a grade less than clinically significant macular edema (CSME). From the start, the patients were included in a multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4 years. Subsequently, the patients were followed up for a mean of 5.7 years by optical coherence tomography, fundus photography, and vitreous fluorometry. Baseline values in eyes that progressed to photocoagulation treatment were compared with values from eyes that did not reach this endpoint. In the 22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did not progress to photocoagulation had a significantly lower mean leakage at baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for measures of baseline retinal thickness or summarized retinal trunk vessel diameters. Eyes that progressed to photocoagulation treatment (mean delay to treatment, 3.6 years) had significantly higher foveal thicknesses than did nonprogressing eyes, from 18 months after study initiation. Progression to photocoagulation treatment for CSME was associated with higher retinal vascular leakage at baseline, whereas baseline retinal vessel diameters and retinal thickness were comparable in progressing and nonprogressing eyes. Baseline leakage was the strongest predictor of progression from non-CSME to photocoagulation for CSME.