Origin of retinal pigment epithelium cell damage by pulsed laser irradiance in the nanosecond to microsecond time regimen

Abstract

Background and Objective: Selective photodamage of the retinal pigment epithelium (RPE) is a new technique to treat a variety of retinal diseases without causing adverse effects to surrounding tissues such as the neural retina including the photoreceptors and the choroid. In this study, the mechanism of cell damage after laser irradiation was investigated. Study Design/Materials and Methods: Single porcine RPE-melanosomes and RPE cells were irradiated with a Nd:YLF laser (wavelength = 527 nm, adjustable pulse duration = 250 nsec-3 sec) and a Nd:YAG laser ( = 532 nm, = 8 nsec). Fast flash photography was applied to observe vaporization at melanosomes in suspension. A fluorescence viability assay was used to probe the cells vitality. Results: The threshold radiant exposures for vaporization around individual melanosomes and for ED 50 cell damage are similar at 8-nsec pulse duration. Both thresholds increase with pulse duration; however, the ED 50 cell damage radiant exposure is 40% lower at 3sec. Temperature calculations to model the onset of vaporization around the melanosomes are in good agreement with the experimental results when assuming a surface temperature of 150°C to initiate vaporization and a homogeneous melanosome absorption coefficient of 8,000 cm −1 . Increasing the number of pulses delivered to RPE cells at a repetition rate of 500 Hz, the ED 50 value decreases for all pulse durations. However, the behavior does not obey scaling laws such as the N 1 /4 equation. Conclusion: The origin of RPE cell damage for single pulse irradiation up to pulse durations of 3 sec can be described by a damage mechanism in which microbubbles around the melanosomes cause a rupture of the cell structure. The threshold radiant exposure for RPE damage decreases with increasing number of pulses applied. Lasers Surg. Med. 27:451-464, 2000.

Investigations into localized re‐treatment of the retina with a 3‐nanosecond laser

“…To provide a more complete body of data, we tested 2RT at both subvisual and visual effect energy settings. Although not thermal in design, nanosecond lasers can still elicit some collateral damage to overlying photoreceptors at higher energy levels via production of expanding and collapsing vapor bubbles from the targeted RPE cells [40,41]. The visual threshold setting is used clinically for the purposes of range finding in each patient [16][17][18].…”

Tissue response of selective retina therapy by means of a feedback‐controlled energy ramping mode

“…The high-peak temperatures occurring at the melanosomes during irradiation lead to short-living microbubbles that mechanically disrupt RPE cells because of a short but strong volume increase. 22 Thus, SRT uses microsecond-laser pulses in order to keep the selective damage of RPE and avoid the formation of large bubbles that cause the risk of photo disruption of retina or choroid. 23 Because the SRT effects are ophthalmoscopically invisible, fluorescein angiography (FA) is used to identify the damage to the RPE barrier after treatment.…”

Nanosecond‐laser application in intermediate AMD: 12‐month results of fundus appearance and macular function

“…Using very short laser pulses (3 ns), an insult caused by steam production around melanosomes can be confined to the retinal pigment epithelium (RPE), inducing a highly selective and discrete non-thermal injury. [4][5][6][7][8] While the mechanism by which the insult to RPE cells brings about a beneficial change in the macula is not well understood, it has been hypothesized that a 3-ns laser could induce migration of RPE cells and release of matrix metalloproteinases, improving the hydraulic conductivity of Bruch's membrane. 9,10 Whatever mechanisms are at play, it is clear that any beneficial effects to the macula occur without the potential harmful effects seen with traditional thermal lasers, thereby offering a new opportunity to consider it as a prophylactic treatment of early AMD.…”