Retinal laser photocoagulation is an ophthalmic treatment that irradiates the retina with a single-wavelength, highly directional, high-power laser beam to coagulate and destroy tissue. The biological effects of the laser beam are determined by the irradiation power and duration, resulting in disruption, photoablation, coagulation, hyperthermia, and photochemical reactions. In ophthalmology, a wide range of wavelengths from ultraviolet to visible to infrared are used as continuous waves or pulsed waves.
In the 1950s, Meyer-Schwickerath began clinical application of xenon photocoagulation, and from the 1960s onward, argon lasers became widespread. Currently, retinal photocoagulation is one of the most frequently performed therapeutic procedures in ophthalmology.
Formation of adhesion between retinal pigment epithelium and retina (perilesional coagulation)
Direct coagulation of tumors
Treatment of glaucoma (cyclophotocoagulation)
QIs laser treatment painful?
A
It is usually performed under topical anesthesia, and patients may experience mild discomfort, a feeling of pressure in the eye, or sensitivity to light. In panretinal photocoagulation (PRP), due to the large number of laser spots and wide treatment area, headache or a feeling of heaviness in the eye may occur. Retrobulbar anesthesia may also be used. Focal photocoagulation and subthreshold micropulse laser are generally less painful.
Serous subretinal fluid (SRD) and pigment epithelial detachment (PED): Appear several days to weeks after PRP. Gandhi et al. (2024) reported SRD and PED after PRP for proliferative diabetic retinopathy (PDR)5).
Exudative retinal detachment: Videkar et al. (2024) reported two cases of exudative retinal detachment after PRP in pachychoroid eyes. In pachychoroid eyes, attention should be paid to serous changes after treatment6).
Macular hole: Kumar et al. (2021) reported macular hole formation after PRP for PDR. The risk increases in cases with vitreomacular traction (VMT) complications7).
QWill my visual field become narrower after PRP?
A
Panretinal photocoagulation intentionally destroys photoreceptor cells in the peripheral retina, so a decrease in peripheral visual field is an unavoidable side effect to some extent. However, central vision is preserved, so the impact on daily life is often limited. On the other hand, without PRP, there is a risk of significant vision loss due to tractional retinal detachment or vitreous hemorrhage caused by proliferative diabetic retinopathy. It is important to discuss the benefits and risks of treatment thoroughly with your doctor.
The main diseases for which photocoagulation is indicated and their risk factors are as follows.
Diabetic retinopathy: Duration of disease, poor glycemic control (high HbA1c), hypertension, dyslipidemia. PDR (proliferative diabetic retinopathy) and DME (diabetic macular edema) are the main indications for PRP and grid photocoagulation.
Retinal vein occlusion (RVO): Hypertension, arteriosclerosis, blood coagulation abnormalities. Photocoagulation is considered for macular edema and ischemia.
Retinal tear and lattice degeneration: High myopia, aging, trauma. Prophylactic photocoagulation for peripheral degeneration and tears is indicated.
Pachychoroid (choroidal thickening): There are case reports of exudative retinal detachment after PRP; careful follow-up is necessary in eyes with choroidal thickening 6).
VMT (vitreomacular traction): It is a risk factor for macular hole after PRP7).
Extensive coagulation with many spots at once: Risk of secondary angle-closure glaucoma (serous choroidal detachment, venous outflow obstruction, blood-retinal barrier breakdown). It also tends to occur when coagulation intervals are short.
Before photocoagulation, the following examinations are performed to evaluate indications and conditions.
Fluorescein angiography (FA): Identifies non-perfusion areas, CNV, aneurysms, and leakage points. Essential for evaluating non-perfusion areas for PRP indication.
OCT (optical coherence tomography): Quantifies macular edema, evaluates retinal layer structure, SRD, and PED. Preoperative choroidal thickness measurement (pachychoroid evaluation) helps assess the risk of exudative changes after PRP6). In large capillary aneurysms, hyperreflective walls and oval structures may be seen on OCT1).
OCTA (OCT angiography): Detects non-perfusion areas and neovascularization without fluorescein dye. Increasingly used as an alternative to FA.
Fundus examination (ophthalmoscopy): Observation of the entire retina using direct and indirect ophthalmoscopy. Essential for identifying peripheral tears and degeneration.
The Mainster PRP 165 has an image magnification of 0.51× and a spot magnification of 1.96×, while the SuperQuad 160 has an image magnification of 0.50× and a spot magnification of 2.00×, allowing efficient irradiation of a wide area. The Goldmann 3-mirror lens has an image magnification of 0.93× and a spot magnification of 1.08×, and is suitable for precise observation and irradiation from the posterior pole to the far periphery.
Severe NPDR (preproliferative diabetic retinopathy) has a high probability of progressing to PDR within one year, and retinal photocoagulation should be considered. If FA or OCTA can be performed, selective retinal photocoagulation of nonperfused areas should be considered. If detailed examination of nonperfused areas is difficult, or if there are risks that may hinder future photocoagulation such as media opacities or poor systemic condition, panretinal photocoagulation is selected.
The definition of high-risk PDR (AAO PPP DR 2024) is as follows 8).
Large new vessels on or near the optic disc (NVD ≥ 1/4 to 1/3 of the disc area)
Extensive retinal new vessels (NVE ≥ 1/2 of the disc area)
QCan OCTA replace fluorescein angiography?
A
OCTA is a noninvasive test that can image retinal and choroidal vessels without using fluorescein dye, and can detect nonperfused areas and new vessels. However, while it is excellent for evaluating static vascular structures, leakage from vessel walls (fluorescein leakage) and changes in vascular permeability can only be assessed with FA. Currently, it is used as a complementary test to FA, and FA information is often referenced for final treatment decisions.
The effects of photocoagulation are mainly classified into the following three types.
Photothermal effect (main mechanism)
Coagulation: Heating tissue to 60-65°C to cause protein denaturation. Standard photocoagulation uses this mechanism.
Hyperthermia: Low-temperature heating at 45-60°C. Mechanism of subthreshold laser and TTT.
Photoablation: Instantaneous vaporization above the boiling point. Used with excimer lasers, etc.
Photochemical Action
PDT (Photodynamic therapy): A photosensitizer (verteporfin) is activated by light of a specific wavelength, producing reactive oxygen species that occlude target blood vessels.
Indications: CNV in AMD, PCV, CSC, intraocular vascular tumors.
Photoionization and Photodisruption
Photoionization: Laser energy turns tissue into plasma. A mechanism of ultrashort pulse lasers (e.g., SRT).
Photodisruption: Explosive tissue cutting by pulsed YAG laser.
Chromophores that absorb laser light in the eye include melanin in RPE cells, hemoglobin (oxidized and reduced) in blood vessels, melanin in the uvea, xanthophyll in the macular pigment, and water. Since absorption characteristics differ by wavelength, selecting the appropriate wavelength for the treatment purpose is important.
The characteristics and uses of each wavelength laser are as follows.
Wavelength
Color
Main Absorber
Features/Uses
488 nm (Argon)
Blue
Xanthophyll, high hemoglobin
Unsuitable for macular treatment. Vascular lesions.
514 nm (argon)
Green
Melanin, hemoglobin
Commonly used for PRP and grid pattern coagulation
Yellow (577 nm) is widely used due to high thermal conversion efficiency. Red (647 nm) has low hemoglobin absorption and excellent penetration, making it suitable for lesions covered by retinal or subretinal hemorrhage, or cases with media opacity. Blue (488 nm) has a high absorption coefficient for xanthophyll in the macular pigment and should not be used for macular treatment.
Perform in 3–4 sessions, with approximately 300–500 burns per session (to reduce postoperative inflammation, limit panretinal photocoagulation to about 1,000 burns unless necessary).
Coagulate sequentially from a position 1–2 disc diameters from the optic disc toward the periphery.
Avoid the posterior pole (within the vascular arcades above and below the optic disc).
If selective coagulation of non-perfused areas is possible, prioritize coagulating non-perfused areas confirmed by FA or OCTA.
Pattern scan laser (PASCAL) can instantly irradiate multiple points with a short exposure time of 0.02 seconds per spot. Output of 300–400 mW is used, and up to approximately 1,000 shots can be delivered in one session. Advantages include reduced damage to the inner retina and choroid, and significantly shortened treatment time.
In the Protocol S trial (ranibizumab vs. PRP RCT), anti-VEGF therapy showed visual outcomes equivalent or superior to PRP8). The AAO PPP DR 2024 supports initiating anti-VEGF therapy before PRP for high-risk PDR complicated by fovea-involving DME8). On the other hand, PRP provides long-term neovascular suppression in a single session and is suitable for patients with poor adherence.
It is not established whether combining anti-VEGF agents prevents exudative retinal detachment in pachychoroid eyes. Consider fractionated PRP and careful postoperative OCT evaluation6).
5-4. Focal Photocoagulation and Grid Photocoagulation
Large microaneurysms (white rim aneurysm) are good indications for targeted laser photocoagulation. Sagar et al. (2023) reported the efficacy of targeted laser photocoagulation for large microaneurysms with white rims in diabetic macular edema1). Confirmation of hyperreflective walls and oval structures on OCT is useful for pre-treatment evaluation1).
Grid (or focal) photocoagulation is performed for macular edema due to diabetic maculopathy, RVO, and BRVO.
Spot size: 100–200 μm, power: approximately 100–200 mW, duration: 0.1 seconds (0.2 seconds when using red laser).
Diffuse edema: grid photocoagulation (applied at least 500 μm from the fovea).
Focal edema: focal photocoagulation around leakage points.
The mechanism of edema resolution is not fully understood, but it is thought to involve improvement of RPE function, occlusion of abnormal vessels, and suppression of VEGF production.
Focal photocoagulation for CSC (central serous chorioretinopathy)
Avoid strong coagulation; apply mild coagulation. If the leakage point is close to the fovea, carefully assess the indication.
Sangal et al. (2022) reported the efficacy of focal photocoagulation for CSC in medically underserved areas4).
In that report, subretinal fluid completely resolved in 84% of 25 CSC eyes after a median of 1.75 months, and visual acuity significantly improved from 0.36 logMAR before treatment to a best of 0.16 logMAR4).
There is also a report that combined anti-VEGF therapy and laser photocoagulation was effective for retinopathy associated with facioscapulohumeral muscular dystrophy (FSHD) (Shimizu 2022)2).
Subthreshold laser is a technique that selectively treats the RPE with energy settings that do not create visible coagulation spots on the fundus, offering the advantage of avoiding damage to the normal neurosensory retina. The efficacy of subthreshold coagulation, in which no coagulation spots are observed, is being investigated for diffuse macular edema. The main types are the following three.
Micropulse laser
Wavelength: 810 nm or 577 nm
Mechanism: Continuous irradiation is divided into on (100–300 μs) and off cycles, selectively heating the RPE while preventing thermal diffusion. The duty cycle (on-time ratio) is set to 5–15%.
Indications: DME, CSC, BRVOmacular edema. Accuracy is improved when combined with a navigation-guided irradiation system3).
SRT (Selective RPE Treatment)
Wavelength: 527 nm
Mechanism: A 1.7 μs Q-switched pulse rapidly heats melanin granules within RPE cells, causing microbubble formation. Heat does not transfer to the adjacent neurosensory retina. Irradiation is performed below the coagulation threshold calculated mathematically using the Arrhenius model.
Mechanism: Using the Arrhenius integral model, tissue damage at each irradiation spot is calculated in real time, and the output is automatically adjusted so that the coagulation reaction is 99% or less.
Features: Can be used on the PASCAL platform equipped with EpM. Visibility or invisibility of coagulation spots can be selected arbitrarily.
In a systematic review and meta-analysis by Tai et al. (2024), subthreshold laser (STL) showed efficacy comparable to standard photocoagulation for diabetic macular edema and was evaluated as an option that is less likely to leave visible scars9).
577 nm navigation-guided micropulse laser has been reported to be effective for peripapillary pachychoroid syndrome (PPS). Iovino et al. (2022) performed 577 nm navigation-guided subthreshold micropulse laser in one case of PPS and reported its efficacy3).
This is a technique to directly coagulate the retina using an endophotocoagulation probe during vitreous surgery.
It is an essential technique for coagulating tears and non-perfused areas in surgeries for retinal detachment and proliferative diabetic retinopathy.
In endophotocoagulation, a coagulation spot is formed with 0.1 to 0.2 seconds per spot and output less than 200 mW.
When performing panretinal photocoagulation with an intraocular probe, postoperative inflammation is strong, so limit to about 1,000 shots unless necessary.
QIs PRP unnecessary if anti-VEGF agents are available?
A
In the Protocol S study, anti-VEGF agents (ranibizumab) showed visual outcomes equivalent or superior to PRP for proliferative diabetic retinopathy8). However, anti-VEGF agents require regular intravitreal injections, and if follow-up is interrupted, neovascularization may regrow. PRP provides a long-term effect of eliminating retinal non-perfusion areas with a single session, making it a favorable option for patients with poor adherence. For high-risk PDR without center-involving DME, PRP remains an important treatment option.
QDoes vision recover immediately after laser treatment?
A
In the case of PRP, temporary worsening of macular edema and decreased vision may occur after surgery. It usually resolves within weeks to months. For retinal tears or CSC, local photocoagulation stabilizes immediately after treatment, and serous detachment in CSC often resolves within weeks to months. Subthreshold micropulse laser has the advantage of less immediate vision loss. It is important to understand that the therapeutic effect is not vision recovery but prevention of progression and stabilization of the condition.
LASER (Light Amplification by Stimulated Emission of Radiation) is based on the principle of light amplification by stimulated emission. When an excitation source (electricity or light) is applied to a gain medium (active medium), population inversion occurs (the number of electrons in the upper energy level exceeds that in the lower level). When photons pass through the medium with population inversion, photons of the same phase, wavelength, and direction are amplified in an avalanche-like manner. The light is further amplified by being reflected back and forth in a resonator (mirrors), and is extracted from the output coupler as single-wavelength, coherent laser light.
The characteristics of chromophores that absorb laser light within the eye are as follows.
Melanin in the RPE: The main light absorber. It absorbs over a broad wavelength range from visible to near-infrared. The primary target of photocoagulation.
Hemoglobin (oxidized and reduced forms): Strong absorption in the 420–600 nm band. Involved in coagulation of intravascular lesions (microaneurysms, neovascularization).
Macular pigment (xanthophyll): Strong absorption in the blue band of 450–500 nm. The reason blue lasers are unsuitable for macular treatment.
Water: Strong absorption in the near-infrared to mid-infrared range above 1,400 nm. Relatively low absorption for 810 nm lasers.
The main mechanisms of action for each indicated disease are as follows.
Mechanism of panretinal photocoagulation: Destroys ischemic retina to reduce tissue oxygen demand and suppresses the expression of vascular endothelial growth factor (VEGF) and other factors. This inhibits the development and progression of retinal and iris neovascularization.
Mechanism of grid photocoagulation (for macular edema): The mechanism of edema resolution is not fully understood. It is thought to involve occlusion of abnormal vessels, suppression of VEGF production, and improvement of RPE ion pump function.
Mechanism of RPE repair photocoagulation (for CSC, etc.): Coagulates pathological RPE cells and promotes repair by surrounding healthy RPE cells. Closes the leakage point of serous detachment.
Mechanism of periretinal photocoagulation for tears: Strengthens adhesion between the RPE and neurosensory retina through scar formation from coagulation spots, preventing fluid entry around the tear and halting progression to retinal detachment.
It exerts therapeutic effects through a mechanism different from that of conventional photocoagulation.
Heat shock protein (HSP) production: Subthreshold mild thermal stimulation induces HSP in RPE cells, increasing metabolic activity. HSP functions as a cell protection and repair mechanism.
Microbubble formation (SRT): Ultrashort pulse irradiation of 1.7 μs creates localized vapor bubbles around melanin granules, selectively disrupting the RPE cell membrane. There is almost no thermal damage to adjacent neurosensory retina.
Arrhenius model (EpM): The tissue damage rate is mathematically modeled using the Arrhenius equation, enabling real-time control within a temperature range where protein denaturation (coagulation) does not occur.
In the field of photocoagulation, the following research and technologies are attracting attention.
Navigation laser system: Systems such as NAVILAS, which are fundus image-guided, are advancing the precision of irradiation positioning. The 577 nm navigation-guided micropulse laser has been reported for application to PPS, and further expansion of indications is expected in the future3).
New developments in SDM (Subthreshold Diode Micropulse) laser: The range of diseases for which micropulse is indicated is expanding, and applications to CSC and normal-tension glaucoma are being studied. Attempts are also being made to apply it to peripheral retinal diseases other than the macula.
nPRP (Navigated PRP): The navigation laser precisely maps non-perfused areas and selectively coagulates them. This is an attempt to maintain therapeutic effect while minimizing sacrifice of healthy retina.
Protocol S long-term results: Long-term follow-up data of Protocol S over 5 years have been accumulated, and comparative evidence between anti-VEGF therapy and PRP continues to be updated8).
Non-invasive identification of large microaneurysms: Research is advancing to identify the white rim sign on OCT and improve the accuracy of targeted laser application1).
Risk stratification in pachychoroid eyes: Identifying eyes that may develop exudative changes after PRP and individualizing treatment are issues for future investigation6).
Sagar P, Biswal S, Shanmugam PM, Ravishankar HN, Pawar R. Targeted laser photocoagulation of larger capillary aneurysms with rim in diabetic macular edema. Taiwan J Ophthalmol. 2023;13:384-388.
Shimizu H, Shimizu M, Nakano T, Noda K, Tanito M. Multimodal Imaging Findings in Retinopathy Associated with Facioscapulohumeral Muscular Dystrophy before and after Treatment with Intravitreal Aflibercept and Laser Photocoagulation. Case Rep Ophthalmol. 2022;13:556-561.
Iovino C, Di Iorio V, Paolercio L, Giordano C, Testa F, Simonelli F. Navigated 577-nm subthreshold micropulse retinal laser treatment for peripapillary pachychoroid syndrome. Am J Ophthalmol Case Rep. 2022;28:101757.
Sangal K, Prasad M, Siegel NH, Chen X, Ness S, Subramanian ML. Focal Laser Photocoagulation for Central Serous Chorioretinopathy in Under-Represented Populations: A Retrospective Case Series. Case Rep Ophthalmol. 2022;13:1000-1007.
Videkar RP, Al Hasid HS, Kamal MF, Amula G, Lamba M. Pachychoroid as a Risk Factor for Exudative Retinal Detachment After Panretinal Photocoagulation: A Report of Two Cases. Cureus. 2024;16(11):e73228. PMCID:PMC11624955. doi:10.7759/cureus.73228.
Kumar V, Sinha S, Shrey D. Macular hole following panretinal photocoagulation in a patient with proliferative diabetic retinopathy. BMJ Case Rep. 2021;14:e240730.
American Academy of Ophthalmology. Diabetic Retinopathy Preferred Practice Pattern. AAO; 2024.
Tai F, Nanji K, Garg A, Zeraatkar D, Phillips M, Steel DH, et al. Subthreshold Compared with Threshold Macular Photocoagulation for Diabetic Macular Edema: A Systematic Review and Meta-Analysis. Ophthalmol Retina. 2024;8(3):223-233. doi:10.1016/j.oret.2023.09.022.
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