Laser-Tissue Interaction

Light as a biological stimulus,
the instrument of modern precision medicine

The light emitted by lasers can cut, denature, or gently stimulate retinal tissue cells. A range of light and tissue parameters influence the final clinical results. Nevertheless, two of these parameters are key in defining the light-tissue interaction mode; these must be precisely controlled: the irradiance (or power density) and the pulse duration.

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One tissue, one light source. The parameters decide what happens.

Main physical drivers of laser-tissue interaction

Tissue parameters govern the effective dose

Broad-spectrum clinical outcomes

Indications take advantage of photostimulation

From physical drivers to clinical outcomes, explored just below

Overview

Laser-Tissue Interaction

Light–tissue interaction describes how incident light is absorbed, scattered, or transmitted by biological tissue, and how incoming energy is converted into chemical, thermal, or mechanical effects in the cells and extracellular matrix. In the retina, these interactions can range from gentle stimulation to irreversible damage. Light–tissue and laser–tissue interactions are often used interchangeably. However, the term laser–tissue interaction is preferred, as laser technology reliably delivers light with the required irradiance and pulse duration to achieve all possible interaction modes.

Parameters such as wavelength, spot size, and pulse repetition rate are important because they shape the details of the response, but they do so within a given interaction mode. The mode itself is primarily set by the power delivered per unit area and the exposure time. Together, these two define the fluence or radiant exposure, expressed in J/cm².¹

Across the full range of irradiance and exposure time, four interaction modes are described: photochemical, photothermal, photoablative, and photodisruptive.¹

At a glance

What sets the modeIrradiance (power density) · Pulse Duration

FluenceIrradiance × pulse duration, in J/cm²

Pulse Duration RangeFemtoseconds to seconds

Interaction modesPhotochemical (photobiological) · photothermal · photoablation · photodisruption

Power Density and Pulse Duration

The Map that Sets Laser Techniques Apart

Laser–tissue interactions can be mapped on a graph defined by power density and exposure time. This chart positions ten published device settings based on their reported parameters, in accordance with the Boulnois diagram.

Techniques on the map

012RT⁴

02SLT³

03SRT⁴

04PASCAL MP⁵

05SMPL⁷

06PASCAL PRP⁵

07Photocoagulation⁶

08TTT⁸

09Oculox Photothermal

10Oculox Photobiological

Zone boundaries as presented by Boulnois (1986).¹ Circles indicate approximate laser parameters, and the dashed diagonals identify constant pulse radiant exposure (fluence). Most laser–tissue interactions of interest occur between 1 and 1000 J/cm². Markers show the irradiation settings of published devices; the geometric mean of the disclosed range of parameters is considered. For representation purposes, the wavelength weighting function is used to normalize the laser parameters for the different applications.

The Four Interaction Modes

Light-tissue interactions are sorted into four different modes.
Dosimetry remains crucial to obtain the expected therapeutic result.
Safety margins are ranges relative to the intended clinical objective.

Retinal Photostimulation

Oculox aspires to preventive retinal treatment.
Takes advantage of two low-irradiance interaction modes.
Doses stimulate tissue recovery while excluding iatrogenic lesions.
Safety margins comply with the preventive treatment mode.

From physics to clinical practice

Four modes for a broad spectrum of clinical outcomes

Every laser-tissue interaction falls in one of four physical modes; however, a broad spectrum of clinical outcomes arises from those basic modes. Clinical practice turned these four modes into dozens of named techniques.

The physical mechanisms

01Photochemical (photobiological)

02Photothermal

03Photoablation

04Photodisruption

In clinical practice, an additional parameter becomes crucial: total fluence or dose, which identifies the total amount of laser energy administered to the target tissues.

→

A spectrum of clinical outcomes

The clinical practice

The spectrum of clinical outcomes has driven ophthalmology to develop a range of specifically named techniques to identify sets of irradiation parameters, each carrying its own acronym.

PASCALSLTSRT2RTSMPLTTTPBM

Each acronym marks a specific clinical result, a scientific innovation, or a commercial trademark.²

Retinal Photostimulation

Different Methods, Same Therapeutic Principle

Photothermal and Photobiological stimulations are based on the concept of hormesis: applying 'just enough' power to trigger the cell's endogenous defence and repair mechanisms without causing damage. The goal is to restore homeostasis so that retinal tissue can return to physiological equilibrium and better regulate cellular activities.

Photobiological Stimulation

Cellular energy activation

When light is delivered at low power density (milliwatts per cm²), the photons that reach the Cytochrome c Oxidase (CCO) promote the dissociation of inhibitory nitric oxide (NO) from the enzyme. This photochemical reaction stimulates cellular metabolism. CCO electron transport accelerates, boosting ATP production and triggering mild, beneficial reactive oxygen species (ROS) spikes. These ROS activate transcription factors that promote antioxidant production, anti-inflammatory cytokines, and tissue repair. Photobiological stimulation relies on a continuous, slow flow of photons. Excessive ROS would induce severe oxidative stress and cell death.¹¹

Cellular Self-Repair · Retinal Energy Activation

Photothermal Stimulation

Retinal Subthreshold Heating

At higher power densities, the energy delivered by photons is absorbed and accumulated by endogenous chromophores (mainly the dense melanin layers). Photon energy is dissipated as heat, causing subthreshold protein unfolding and activating Heat Shock Proteins (HSPs).¹⁴ This stabilises proteins, enhances metabolic activity, modulates cytokine release, and modifies vascular permeability. The tissue temperature rise is kept below the threshold for protein denaturation. To promote selective local heating, the laser operates in pulsed mode, where brief irradiation periods are interspersed with longer intervals that permit thermal relaxation.^2,6,10

Controlled Heating · Heat Shock Proteins · Tissue Self-Repair

Possible Therapeutic Scopes

For What Photostimulation Has Been Used

Both photostimulation modes have been long studied in clinical research. Medical devices for both thermal and biological stimulations are commercially available for different specific retinal conditions. The cases below show a few examples*.

Dry Age-related Macular Degeneration (AMD)

Current retinaSEES Focus

Dry AMD is the most prevalent form of Age-related Macular Degeneration, accounting for approximately 85–90% of cases. It typically progresses silently over many years, driven by oxidative stress and degeneration of the retinal pigment epithelium, ultimately resulting in geographic atrophy and irreversible loss of photoreceptors.¹³ Therapeutic options remain limited. Photobiomodulation (PBM) is increasingly employed in dry AMD with the objective of activating the retina's intrinsic repair and protective mechanisms. Multiple medical devices are already available, and clinical evidence on PBM in dry AMD is being accumulated through ongoing and planned studies.¹²

Central Serous Chorioretinopathy (CSC)

In chronic central serous chorioretinopathy, subthreshold laser is used to target the retinal pigment epithelium with repetitive, sublethal thermal pulses kept below the threshold for visible damage. The stimulus activates RPE stress-response pathways and restores its metabolic and pump function, promoting resorption of subretinal fluid without a coagulative burn or foveal scar. Studies reported significantly improved best-corrected visual acuity and reduced central macular, central retinal, and choroidal thicknesses. Reduction in subretinal fluid did not reach statistical significance.⁹

Diabetic Macular Oedema (DME)

In diabetic macular oedema, pulsed lasers are used to treat the retinal pigment epithelium without a visible burn endpoint, avoiding iatrogenic scarring or photocoagulation. The lack of a visible lesion allows treatment right up to the fovea. Research using a 577-nm pulsed laser produced a modest but significant gain in visual acuity and reduced macular thickening. The reduction in central retinal thickness did not reach statistical significance. The treatment is suggested to be a complement to anti-VEGF injections, which remain the standard treatment.⁷

*The conditions listed above indicate clinical contexts in which photothermal and photobiological regimes have been studied. They provide only a brief and non-exhaustive overview of potential applications. They should not be interpreted as a statement of the intended purpose of any Oculox device, nor as specific information about its current clinical status. The intended purpose of Oculox's devices is defined exclusively in their regulatory notice.

Retinal Photostimulation Platform

Two Photostimulation Modes in a Single Device

retinaSEES brings both stimulation regimes, photothermal and photobiological, together in a single automated, non-invasive platform. Each mode is delivered as a controlled, subthreshold energy dose designed to stimulate the retina without damaging it. The current clinical focus is the treatment of intermediate dry AMD.

retinaSEES

Multimode Laser Photostimulation · Intermediate dry AMD

retinaSEES uses a near-infrared (NIR) laser to reach the deeper retinal layers, and a Maxwellian optical design to deliver the therapeutic beam to the retina independently of pupil size. The retinaSEES treatment workflow is designed to fit routine ophthalmic practice.

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Frequently asked

Questions about Photostimulation

How do photobiological and photothermal stimulations differ from photocoagulation?

Photobiological and Photothermal Stimulations use subthreshold doses to modulate cellular function rather than induce morphological changes to the retinal tissue. By contrast, photocoagulation uses an energy dose that could raise the temperature above the denaturation point of proteins, creating burns and coagulative scars.

How is a subthreshold energy dose defined?

In this context, subthreshold means that the delivered dose remains below the level at which structural or functional damage becomes detectable in standard clinical imaging. The therapeutic window is defined so that the stimulus is sufficient to elicit a cellular response yet consistently below the damage threshold.

What is the basic mechanism under NIR photobiological stimulation?

Near-infrared (NIR) light penetrates deep into the layers of the chorioretinal complex and is absorbed by endogenous chromophores. Among those, of particular interest for photobiological interaction is absorption by the metal centres present in the enzyme cytochrome c oxidases (CCO). CCO play a critical role in electron transfer and oxygen reduction in the mitochondrial respiratory chain, which leads to ATP synthesis. Research suggests that prolonged low-irradiance stimulus may upregulate physiological respiration in retinal cells, boosting natural energy production while reducing oxidative stress and supporting anti-inflammatory processes. The intended effect is a physiological modulation of cellular metabolism, achieved without iatrogenic damage to retinal tissue.

What is the basic mechanism under photothermal stimulation?

Photothermal stimulation delivers a laser dose that produces a mild, targeted warmth remaining well below the threshold for tissue damage. Research suggests that this controlled, transient thermal stimulus activates heat shock proteins and prompts retinal cells to regain physiological equilibrium. Because the dose stays subthreshold, no coagulative lesion is intended or produced. The employed short laser pulses, separated by extended off times, keep temperature selectively local to the absorbing chromophores and exclude temperature runaway in the chorioretinal complex.

Why combine photothermal and photobiological stimulation in a single device?

Photothermal and Photobiological Stimulations are combined in retinaSEES because these two modes engage complementary biological pathways. Photobiological stimulation supports cellular energy production, while photothermal engages the heat shock protective response. By combining and leveraging both damage-free modalities, the approach aims to broaden the stimulatory effect on the retina within a single treatment paradigm. This is consistent with a precision-medicine rationale of using light as a targeted biological stimulus rather than a destructive surgical tool. Both stimulations are based on the concept of hormesis: applying 'just enough' power to trigger the cell's endogenous defence and repair mechanisms without causing damage. The goal is to re-tune homeostasis so that the retina can self-regulate more effectively over time.

What makes retinaSEES different from other light-based AMD therapies?

The combination of two different treatments in a single medical device is unique. Several light-based therapies for AMD use LEDs to deliver photobiological stimulation only. retinaSEES uses an NIR laser to combine biological and thermal stimulation. Its Maxwellian optical design also ensures that the light enters the eye fully, regardless of the patient's pupil size during treatment.

Explore photostimulation with retinaSEES

Whether you are a researcher, clinician, or institution interested in our research platform, we would like to hear from you.

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References

Scientific References

References include the foundational work on laser-tissue interaction modes, the published device settings plotted on the map, and peer-reviewed clinical studies of the techniques described.

1. Boulnois JL. Photophysical processes in recent medical laser developments: a review. Lasers Med Sci. 1986;1(1):47–66.

2. von der Burchard C, Miura Y, Stanzel B, et al. Regenerative retinal laser and light therapies (RELITE): proposal of a new nomenclature, categorization, and trial reporting standard. Lasers Surg Med. 2024;56(8):693–708. doi:10.1002/lsm.23833

3. Wu CM, Chang TC. Selective laser trabeculoplasty. Int Ophthalmol Clin. 2023;63(4):23–32. doi:10.1097/IIO.0000000000000483

4. Zheng M, Paulus YM. Recent innovations in retinal laser therapy. Photonics. 2025;12(2):156. doi:10.3390/photonics12020156

5. Salman AG. Pascal laser versus conventional laser for treatment of diabetic retinopathy. Saudi J Ophthalmol. 2011;25(2):175–179. doi:10.1016/j.sjopt.2011.01.006

6. Sivaprasad S, Elagouz M, McHugh D, Shona O, Dorin G. Micropulsed diode laser therapy: evolution and clinical applications. Surv Ophthalmol. 2010;55(6):516–530. doi:10.1016/j.survophthal.2010.02.005

7. Frizziero L, Calciati A, Torresin T, et al. Diabetic macular edema treated with 577-nm subthreshold micropulse laser: a real-life, long-term study. J Pers Med. 2021;11(5):405. doi:10.3390/jpm11050405

8. Rogers AH, Reichel E. Transpupillary thermotherapy of subfoveal occult choroidal neovascularization. Curr Opin Ophthalmol. 2001;12(3):212–215. doi:10.1097/00055735-200106000-00012

9. Luo W, He Y. Efficacy and safety of subthreshold micropulse laser for chronic central serous chorioretinopathy: a systematic review and meta-analysis. Front Med. 2026;13:1785787. doi:10.3389/fmed.2026.1785787

10. Sramek C, Mackanos M, Spitler R, Leung LS, Nomoto H, Contag CH, Palanker D. Non-damaging retinal phototherapy: dynamic range of heat shock protein expression. Invest Ophthalmol Vis Sci. 2011;52(3):1780–1787. doi:10.1167/iovs.10-5917

11. Hamblin MR. Mechanisms and mitochondrial redox signaling in photobiomodulation. Photochem Photobiol. 2018;94(2):199–212. doi:10.1111/php.12864

12. Boyer D, Hu A, Warrow D, et al. LIGHTSITE III: 13-month efficacy and safety evaluation of multiwavelength photobiomodulation in nonexudative (dry) age-related macular degeneration using the LumiThera Valeda light delivery system. Retina. 2024;44(3):487–497. doi:10.1097/IAE.0000000000003980

13. Fleckenstein M, Keenan TDL, Guymer RH, et al. Age-related macular degeneration. Nat Rev Dis Primers. 2021;7(1):31. doi:10.1038/s41572-021-00265-2

14. De Cillàs S, Vezzola D, Farruggio S, et al. The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes. Acta Ophthalmol. 2019;97(4). doi:10.1111/aos.13995

This page is informational and does not constitute medical advice. retinaSEES is a CE-marked Class IIb medical device for use by qualified healthcare professionals trained in laser use.