Evaluation of the Safety and Therapeutic Range of Nanosecond Laser Treatment in Rabbits

Background Subthreshold, nanosecond laser therapy has potential as a treatment for age‐related macular degeneration; however, the therapeutic range and safety profile have not been fully documented. In this study, rabbits were used for a preclinical assessment of nanosecond laser treatment. Methods Adult pigmented rabbits received nanosecond laser treatment at a range of ophthalmoscopically visible and subthreshold energy settings. Various parameters were investigated following laser treatment, namely ophthalmoscopic visibility, haemorrhage, near‐infrared (NIR) fundus visibility, angiographic visibility and structure of the retina/retinal pigment epithelium (RPE) as determined by spectral domain optical coherence tomography and post‐mortem histology. Results Ophthalmoscopically visible energy settings, namely visual effect threshold (VET) and 150% of VET, caused ablation and renewal of targeted RPE cells. These settings presented no vascular damage or Bruch's membrane rupture, but localised photoreceptor loss was evident. A clinically relevant subthreshold energy setting, determined as 50% of VET, likewise caused ablation and renewal of RPE cells. While this setting caused no photoreceptor loss, disruption to segments overlying lesions was evident, which resolved over time. Application of the laser at 25% of VET also caused ablation of RPE cells, while reduction to 12.5% of VET elicited predominantly sublethal injury. The lowest energy setting (8% of VET) had no discernible effect upon RPE cells. The three lower subthreshold energy settings caused no photoreceptor injury. Conclusions Nanosecond laser treatment can be used at lower irradiances than previously employed without causing disruption to photoreceptor segments. The use of this lower energy setting in clinical trials is worthy of consideration.