Cyclodestructive procedures are a group of surgeries that physically destroy the ciliary epithelium to reduce aqueous humor production and lower intraocular pressure1)2). Since Vogt reported diathermy coagulation of the ciliary body in 1933, various energy sources such as cryocoagulation, ultrasound, and laser have been attempted. Currently, methods using an 810 nm diode laser are mainstream1)2).
The main procedures are broadly classified as follows1)2)3).
Traditionally, cyclodestructive procedures have been considered a last resort for refractory glaucoma where intraocular pressure cannot be controlled with other treatments, or for painful glaucomatous eyes with poor visual prognosis1)2)3). However, because MP-CPC causes minimal tissue damage and HIFU-UCCC has high target selectivity, their use at earlier stages is being considered1).
There are mainly five types. (1) Transscleral cyclophotocoagulation (TS-CPC) is a method that delivers continuous wave laser from outside the sclera. (2) Slow coagulation continuous wave TSCPC (SC-TSCPC) reduces damage to surrounding tissues by using low power and long duration. (3) Micropulse transscleral cyclophotocoagulation (MP-CPC) is an improved method that reduces tissue damage by pulsed irradiation. (4) Endoscopic cyclophotocoagulation (ECP) coagulates the ciliary body under direct visualization from inside the eye using an endoscope. (5) High-intensity focused ultrasound circular cyclocoagulation (HIFU-UCCC) selectively coagulates the ciliary body using ultrasound. All of them reduce intraocular pressure by decreasing aqueous humor production.
The main indications for cyclodestructive procedures are as follows1)2)3).
ECP can be performed simultaneously with cataract surgery, and may be performed as a combined procedure of lens reconstruction plus ECP for glaucoma in phakic eyes1)3).
As a special indication, TS-CPC has been reported for refractory glaucoma in eyes with Boston KPro type II implantation 12). In eyes with artificial cornea, conventional filtration surgery is difficult, and TS-CPC can be a useful means of intraocular pressure management 12). There is also a report of intraocular pressure control achieved by limited TS-CPC avoiding the tumor site for glaucoma secondary to ciliary body melanoma 13).
MP-CPC has expanded indications due to improved safety profile. It can be used in eyes with good visual prognosis and is also indicated for early cases such as add-on to topical therapy, but its role has not been fully investigated. It has been shown to be safe and effective in the following disease types.
| Indicated disease type | Remarks |
|---|---|
| Primary open-angle glaucoma | Most common indication |
| Neovascular glaucoma | High retreatment rate |
| Angle-closure glaucoma | Indicated for chronic cases |
In addition, it is also performed for pseudoexfoliation glaucoma, normal-tension glaucoma, and uveitic glaucoma. It can also be used in eyes with a history of trabeculectomy or tube shunt surgery.
HIFU-UCCC is indicated for refractory glaucoma similarly to conventional cyclodestructive procedures 1)2). Recent clinical trials have also reported efficacy in early glaucoma patients without prior filtration surgery. It is applicable to both open-angle and angle-closure types, but nanophthalmos and megalophthalmos are contraindicated due to probe size limitations.
An 810 nm diode laser and a G-probe are used 1)2). The G-probe is designed so that its tip follows the scleral surface, and by placing it 1.5 mm posterior to the limbus, the focus is on the ciliary body 2).
Standard irradiation parameters are a power of 1500–2000 mW and a duration of 2000 ms 2). A 270° arc is treated, avoiding the 3 and 9 o’clock positions (where the long posterior ciliary arteries and nerves run) 2). If a “pop” sound is heard during irradiation, it indicates overcoagulation, and the power should be reduced by 250 mW 2).
SC-TSCPC is a technique that delivers a constant low diode laser energy (1,250 mW) over a long duration (4 seconds) to achieve controlled ciliary body ablation 6). Compared to the conventional pop technique (1,750–2,000 mW, 2 seconds), the low-power, long-duration irradiation minimizes damage to surrounding tissues and inflammation, aiming to reduce complication rates.
| Parameter | SC-TSCPC | Conventional Pop Technique |
|---|---|---|
| Laser Power | 1,250 mW (constant) | 1,750–2,000 mW (variable) |
| Irradiation Time | 4 seconds | 2 seconds |
It is performed under retrobulbar anesthesia or sub-Tenon anesthesia. The probe is placed perpendicular to the sclera; deviation of more than 10 degrees from perpendicular causes energy transmission to vary by more than 20%. Irradiation avoids the 3 and 9 o’clock positions, and the number of applications is determined based on the degree of intraocular pressure elevation, number of medications, patient background, and surgical history.
Efficacy has been reported in cases of neovascular glaucoma with nearly circumferential peripheral anterior synechiae; 5 out of 8 cases (63%) achieved intraocular pressure control without requiring additional tube shunt surgery6).
Postoperatively, sub-Tenon triamcinolone injection, subconjunctival dexamethasone injection, prednisolone eye drops, and ketorolac eye drops are used. Steroid eye drops are tapered every 2 to 3 weeks. Abrupt discontinuation carries a risk of rebound iritis.
The same 810 nm diode laser as continuous wave is used, but with pulsed irradiation of ON time 0.5 ms and OFF time 1.1 ms (duty cycle 31.3%)2).
Laser Settings
Wavelength: 810 nm (semiconductor diode)
Power: 2,000 mW2)
Duty cycle: 31.3% (on 0.5 ms / off 1.1 ms)
Irradiation time: 80 seconds for upper hemisphere + 80 seconds for lower hemisphere = total 160 seconds
Device: Cyclo G6 + MicroPulse P3 probe (IRIDEX)
Irradiation Technique
Probe position: Place the concave surface 3 mm posterior to the limbus (pars plana) aligned with the limbus, perpendicular to the sclera.
Sweep method: Irradiate with 4 sweeps in the upper hemisphere (10 seconds per pass) and 4 sweeps in the lower hemisphere.
Avoidance areas: Avoid the 3 and 9 o’clock positions (long posterior ciliary artery and ciliary nerve).
Contact pressure: Continuous irradiation while pressing against the conjunctiva/sclera and sliding along the limbus
Because the tissue cools during the OFF period, irreversible damage to the ciliary body is reduced compared to continuous wave 2)14). Histologically, MP-CPC results in only partial and localized necrosis of the ciliary epithelium, whereas continuous wave TS-CPC causes extensive coagulative necrosis of the ciliary epithelium and stroma 14).
Performed under retrobulbar anesthesia (2% lidocaine 5 mL) or sub-Tenon anesthesia (2% lidocaine 3–5 mL). Before irradiation, apply hydroxyethyl cellulose to keep the conjunctiva and probe tip sufficiently moist. After surgery, apply an eye patch and administer steroid and antibiotic eye drops 4 times daily for 1–2 weeks, tapering as appropriate. Consider reducing or discontinuing glaucoma eye drops after confirming intraocular pressure the following day.
An endoscopic probe integrating an 810 nm diode laser, light source, and video camera is inserted through the anterior chamber or vitreous cavity to coagulate the ciliary processes under direct visualization 1)3). Whitening and shrinkage are the endpoints of coagulation; avoid overcoagulation (explosion/rupture) 3).
ECP is less dependent on melanin pigment and allows adjustment of irradiation under direct visualization, so the risk of overcoagulation is lower than with continuous wave TS-CPC 1)3). However, because it requires intraocular manipulation, its invasiveness is higher than TS-CPC.
High-intensity focused ultrasound (HIFU) was considered early on for application in ciliary body destruction. The devices at that time were large, the procedure took 2 hours, and due to low frequency (5 MHz) and a wide focal area, severe complications occurred, leading to discontinuation of clinical use in the 1990s.
A new HIFU system (EyeOP1 device) using a miniaturized transducer was developed, and clinical application progressed as “ultrasound circular cyclocoagulation (UCCC/UC3).” It operates at a high frequency of 21 MHz, and because the focal area is as small as 0.1 × 1 mm, it can selectively coagulate the ciliary body while minimizing thermal damage to adjacent tissues.
Structure of the EyeOP1 Device
Circular probe: A ring with a diameter of 30 mm and height of 15 mm, with six piezoelectric ceramic transducers equally spaced. The upper three and lower three ultrasound beams can treat up to 45% of the ciliary body.
Probe sizes: Three types: 11, 12, and 13 mm. Determined preoperatively based on ultrasound biomicroscopy biometric data.
Operating parameters: Frequency 21 MHz, acoustic power 2.0–2.45 W. Activation time for each transducer can be selected from 4, 6, or 8 seconds.
Surgical Procedure
It is performed under retrobulbar (or peribulbar) anesthesia. The coupling cone is placed in direct contact with the ocular surface and held with low-level vacuum (70 mmHg). Approximately 4 mL of saline is injected to ensure acoustic propagation.
The transducer is activated sequentially from the upper sector in a clockwise direction. A 20-second interval is placed between each sector. The transition between sectors is fully automated.
Postoperatively, flurbiprofen or a combination of dexamethasone and tobramycin is instilled four times daily for one month.
| Procedure | Power | Exposure Time |
|---|---|---|
| TS-CPC | 1500–2000 mW | 2000 ms/shot |
| SC-TSCPC | 1250 mW | 4000 ms/shot |
| MP-CPC | 2000 mW | 80–100 seconds/half circle |
| ECP | 200–300 mW | Direct visualization adjustment |
| HIFU-UCCC | 2.0–2.45 W (acoustic) | 4–8 seconds/sector |
TS-CPC / MP-CPC / SC-TSCPC
Approach: Transscleral (external irradiation)
Anesthesia: Retrobulbar or sub-Tenon’s anesthesia2)
Irradiation range: 270° (avoid 3 and 9 o’clock)2)
Features (TS-CPC): Simple procedure. Risk of extensive tissue destruction14)
Features (SC-TSCPC): Low power, long duration reduces collateral damage. Avoids pop sounds6)
Features (MP-CPC): Pulsed irradiation reduces tissue damage. Relatively easy to repeat2)
ECP / HIFU-UCCC
ECP: Endoscopic direct visualization from inside the eye. Can be combined with cataract surgery1). Allows visual avoidance of overcoagulation
HIFU-UCCC: Selectively coagulates the ciliary body using ultrasound. It is an automated computer-assisted procedure with low operator dependency. The focal point is 0.1 × 1 mm, providing high target selectivity.
The main difference is the irradiation method. Conventional TS-CPC uses continuous wave irradiation, causing extensive coagulative necrosis of the ciliary body. In contrast, MP-CPC uses pulsed irradiation with repeated ON/OFF cycles, allowing tissue cooling during the OFF periods, resulting in limited damage. Histological studies have confirmed that MP-CPC only causes partial necrosis of the ciliary epithelium. Therefore, the risk of hypotony and phthisis bulbi is lower, and repeated procedures are considered relatively safe.
The main difference is the laser irradiation method. The conventional pop technique starts with a high power of 1,750–2,000 mW and adjusts energy based on the pop sound indicating tissue disruption. SC-TSCPC uses a fixed low power of 1,250 mW for 4 seconds. SC-TSCPC causes less damage to surrounding tissues and is associated with lower rates of postoperative inflammation and complications. The intraocular pressure-lowering effect is reported to be equivalent between the two.
According to the Primary Open-Angle Glaucoma (POAG) Preferred Practice Pattern, the success rate of TS-CPC varies widely from 34% to 94% 3). Postoperative intraocular pressure is maintained at 21 mmHg or lower in 54% to 93% of cases.
| Subject | Success Rate | IOP Change |
|---|---|---|
| Primary surgery (high IOP group) | 58.3% (1 year) | 30.6 → decreased |
| Pseudophakic glaucoma | 60.6% (1 year) | 27.5→15.8 |
| Neovascular glaucoma | 64.2% (2 years) | 40.7→18.4 |
| After vitrectomy (PPV) / silicone oil injection | 72.2% (12 months) | 29.7→14.6 |
| Glaucoma after corneal transplantation | 68.1% (1 year) | — |
| Aphakic glaucoma | 63.4% (1 year) | 29.6→19.0 |
In SC-TSCPC as a primary surgery, the 1-year success rate was 58.3% in the high baseline intraocular pressure group (mean 30.6 mmHg), while it was only 28.1% in the low baseline intraocular pressure group (mean 16.2 mmHg). In glaucoma after corneal transplantation, the surgical technique (PKP/DSAEK) did not significantly affect the success rate.
MP-CPC achieves approximately 50% reduction in intraocular pressure over six months, and the number of medications can be reduced by about one. If the pressure reduction is insufficient, additional treatment can be performed after an interval of at least one month postoperatively.
A systematic review of the literature reported that at 18 months after treatment, 52% of the MP-CPC group maintained intraocular pressure between 6 and 21 mmHg, compared to 30% in the CW-TSCPC group. Retreatment rates vary by disease type: 12% for primary open-angle glaucoma, 16% for pseudoexfoliation glaucoma, and 41.2% for secondary glaucoma.
| Item | MP-CPC | CW-TSCPC |
|---|---|---|
| 18-month success rate | 52% | 30% |
| Severe complications | Rare | Relatively common |
| Need for retreatment | Frequent | Infrequent |
| Study | Follow-up | IOP reduction rate | Success rate |
|---|---|---|---|
| Aptel pilot | 3 months | 35.7% | 83.3% |
| EyeMUST1 | 12 months | 36.0% | 57.1% |
| De Gregorio | 12 months | 45.7% | 85% (no medication) |
In the initial pilot study, mean preoperative intraocular pressure (IOP) decreased from 37.9 mmHg to 26.3 mmHg at 3 months. In the EyeMUST1 study, the success rate was 57.1% at 12 months, but primary open-angle glaucoma showed a higher success rate compared to secondary glaucoma (78.6% vs 45.0%). The second-generation probe (8 seconds) showed a significantly greater IOP reduction than the first-generation (6 seconds) (35% vs 25.6%). High success rates at 12 months have been reported with repeated treatment protocols.
ECP has been reported to achieve IOP reductions of 34–57%3).
Common complications of cyclodestructive procedures include pain, conjunctival hyperemia, anterior chamber inflammation (fibrin reaction), and transient IOP elevation2)3). The most serious complications are hypotony and phthisis bulbi, primarily due to overcoagulation1)2)3). Sympathetic ophthalmia is extremely rare but has been reported3).
Continuous-wave TS-CPC has been associated with scleral thinning and perforation due to thermal damage to the sclera5). A case of scleral perforation after TS-CPC in a 78-year-old patient with primary open-angle glaucoma, repaired with a lamellar corneal patch graft, has been reported5).
Postoperative complications of SC-TSCPC are generally mild. Reported complications include anterior chamber inflammation (iridocyclitis) in 9–17%, cystoid macular edema in 2.7–8.3%, transient hyphema in 2–6%, and cataract progression (18.8% in phakic eyes). Persistent hypotony, phthisis bulbi, and choroidal hemorrhage are extremely rare. Caution is needed for rebound iritis due to abrupt discontinuation of steroid eye drops; tapering every 2–3 weeks is recommended.
MP-CPC is reported to have fewer complications than continuous-wave TS-CPC, but specific complications have also been reported. A case of IOL dislocation occurring 5 weeks after MP-CPC has been reported, with thermal damage to the zonules suspected as the mechanism9).
A case of corneal ring infiltrate (neurotrophic keratopathy) after MP-CPC for neovascular glaucoma in a 36-year-old diabetic patient has also been reported8). This is thought to be due to decreased corneal sensation from thermal damage to the long ciliary nerves of the trigeminal nerve8).
Neurotrophic keratopathy (NK) has been reported as a rare complication after MP-CPC 15). In a case of a 47-year-old man with Marfan syndrome who underwent MP-CPC, painless corneal epithelial defects appeared in both eyes on postoperative day 4, with decreased corneal sensation 15). The left eye healed in 10 days, but the right eye had delayed healing and left corneal scarring 15). It is possible that increased absorption of laser energy due to scleral thinning in Marfan syndrome damaged the long posterior ciliary nerves 15).
ECP has complications associated with intraocular manipulation. A case has been reported of a 75-year-old patient with pseudoexfoliation glaucoma who developed bullous choroidal detachment after cataract surgery plus ECP, requiring surgical drainage 10).
Additionally, two cases of vitreous prolapse during trabeculectomy in eyes with prior ECP have been reported 11). Zonular damage due to ECP is presumed to be the mechanism, and preparation for vitreous prolapse is necessary during intraocular surgery in patients with a history of ECP 11).
Miniaturized HIFU-UCCC shows a favorable safety profile. Conjunctival hyperemia (up to 100%), punctate superficial keratitis (33–45%), transient anterior chamber inflammation, transient corneal edema, transient hypotony (sometimes with choroidal detachment), transient macular edema, and intraocular pressure spikes have been reported. In the EyeMUST1 study, 12 patients required secondary glaucoma surgery. The incidence of severe complications such as hypotony, phthisis bulbi, and persistent vision loss is remarkably low with UCCC.
Complications of TS-CPC / MP-CPC / SC-TSCPC
Pain: May persist for several days postoperatively. Managed with analgesics 2)
Scleral perforation: Reported with continuous-wave hypercoagulation 5)
IOL dislocation: Reported 5 weeks after MP-CPC. Thermal damage to the zonules is the presumed mechanism 9)
Corneal ring infiltrate: Neurotrophic keratopathy due to long posterior ciliary nerve damage 8)
Neurotrophic keratopathy: Occurred after MP-CPC in a patient with Marfan syndrome 15)
Hypotony and phthisis bulbi: Caused by hypercoagulation. Rare with MP-CPC and SC-TSCPC 2)14)
Complications of ECP / HIFU-UCCC
Fibrin reaction: Postoperative anterior chamber inflammation. Managed with steroid eye drops3)
Bullous choroidal detachment: Reported after Phaco-ECP. Required surgical drainage10)
Vitreous prolapse: Occurred during trabeculectomy after ECP. Zonular damage is the presumed mechanism11)
HIFU-UCCC: Conjunctival hyperemia and punctate keratitis are common. Serious complications are significantly low
| Complication reported | Procedure | Mechanism |
|---|---|---|
| Scleral perforation5) | TS-CPC | Thermal scleral damage |
| IOL dislocation9) | MP-CPC | Thermal zonular damage |
| Neurotrophic keratopathy15) | MP-CPC | Long posterior ciliary nerve damage |
| Choroidal detachment10) | ECP | Ciliary body hypercoagulation |
Common complications include pain, conjunctival hyperemia, intraocular inflammation, and transient intraocular pressure elevation. The most serious are hypotony and phthisis bulbi due to overcoagulation. In TS-CPC, scleral perforation; in MP-CPC, IOL displacement, corneal ring infiltration, and neurotrophic keratopathy; in ECP, bullous choroidal detachment and vitreous prolapse during subsequent surgery have been reported. SC-TSCPC and MP-CPC cause less tissue damage compared to continuous-wave TS-CPC, and the frequency of serious complications is lower. In HIFU-UCCC, the frequency of serious complications is markedly low, but conjunctival hyperemia and superficial punctate keratitis are common.
Diode laser (wavelength 810 nm) is selectively absorbed by melanin pigment in the ciliary body pigment epithelium, converting light energy into heat4). This heat causes coagulative necrosis of the ciliary epithelium, reducing aqueous humor production.
Studies comparing histological differences between continuous-wave TS-CPC and MP-CPC have shown that eyes treated with continuous-wave TS-CPC exhibit extensive, full-thickness coagulative necrosis of the ciliary epithelium and stroma, whereas eyes treated with MP-CPC show only localized, partial necrosis14). In MP-CPC, tissue cooling during the off period is thought to limit heat diffusion to surrounding tissues14).
In SC-TSCPC, low-power, long-duration irradiation allows thermal coagulation of the ciliary body to progress more slowly, reducing heat diffusion and damage to surrounding non-pigmented tissues.
The dependence of TS-CPC on melanin pigment is demonstrated by cases of TS-CPC ineffectiveness in patients with oculocutaneous albinism type 1A (OCA1A)7). In OCA1A, tyrosinase activity is completely absent, preventing melanin production, so the 810 nm laser is not absorbed by the ciliary body, and no intraocular pressure-lowering effect is achieved7).
In contrast, ECP is performed under endoscopic visualization of the ciliary processes, and its dependence on melanin is considered lower than that of TS-CPC1).
In MP-CPC, during the on period (0.5 ms), pigmented ciliary epithelium containing melanin selectively absorbs energy. During the off period (1.1 ms), surrounding tissues cool, minimizing thermal damage to non-pigmented ciliary epithelium15).
The mechanism of intraocular pressure reduction by MP-CPC is thought to differ from that of CW-TSCPC. The main mechanism may be stimulation of cells in the pars plana of the ciliary body, promoting aqueous humor outflow through the uveoscleral outflow pathway. Since it primarily enhances outflow rather than suppressing aqueous production, the risk of hypotony and phthisis bulbi is considered low.
Two mechanisms are involved in the intraocular pressure-lowering effect of UCCC.
Suppression of aqueous humor production by ciliary body destruction: Ultrasound causes a temperature rise of up to 80°C in tissue, inducing coagulative necrosis. In animal experiments, the bilayered epithelium in the middle and distal parts of the ciliary processes disappeared, with edema and vascular congestion. The epithelium at the base of the processes was preserved, and no stromal fibrosis was observed. The boundary between treated and untreated areas was very clear.
Increase in uveoscleral outflow pathway: In human in vivo studies using ultrasound biomicroscopy, fluid accumulation in the suprachoroidal space was observed in 8 of 12 treated eyes, correlating with intraocular pressure reduction. Anterior segment OCT documented the formation of new hyporeflective intrascleral cavities, suggesting that heat-induced separation of scleral fiber layers is the mechanism. In vivo confocal microscopy showed an increase in conjunctival microcysts at the treatment site, considered evidence of transscleral and transconjunctival aqueous outflow.
The intraocular pressure reduction after cyclodestructive procedures is mainly due to decreased aqueous humor production. However, some studies suggest that enhancement of the uveoscleral outflow pathway may also contribute to pressure reduction1). A mechanism mediated by prostaglandin release is presumed, but details remain unclear.
In TS-CPC, an 810 nm diode laser is absorbed by melanin in the ciliary body pigment epithelium and converted to heat, causing coagulative necrosis. In OCA1A albinism, tyrosinase activity is completely absent, and melanin is not produced, so the laser is not absorbed and no intraocular pressure-lowering effect is achieved. Cases of TS-CPC being ineffective in OCA1A patients have been reported, demonstrating that melanin is essential for the action of this procedure.
Because MP-CPC causes minimal tissue damage, its indication is being discussed for earlier stages of glaucoma, beyond its traditional role as a “last resort”1). Since repeated procedures are relatively safe, stepwise intraocular pressure control is possible2). Application in pediatric glaucoma has also been attempted, but reports indicate lower efficacy in children (success rate 22%) compared to adults (success rate 72%). Optimal values for modifiable parameters such as power, exposure time, treatment range, and sweep speed have not been established.
Risk stratification using preoperative corneal sensitivity testing before MP-CPC has been proposed 15). In patients with connective tissue diseases involving scleral thinning (e.g., Marfan syndrome, Ehlers-Danlos syndrome) and diabetes, adjusting laser power and exposure time may reduce the risk of neurotrophic keratopathy 15).
Future challenges include conducting direct comparative RCTs of SC-TSCPC and MP-CPC, standardizing optimal treatment parameters, accumulating long-term (≥5 years) outcome data, and establishing indications for primary surgery. Since success rates tend to be lower in the low baseline intraocular pressure group (<21 mmHg), preoperative IOP levels should be considered when determining indications.
UCCC is being investigated for expanded use in early glaucoma. Studies in early glaucoma without prior filtration surgery and chronic angle-closure glaucoma have reported IOP reduction and conditional success. The longest reported follow-up is 12 months, and long-term outcomes are not yet established.
In eyes with Boston KPro type II, conventional glaucoma surgery is difficult, and TS-CPC has been reported as a useful alternative 12). For glaucoma secondary to ciliary body melanoma, limited TS-CPC avoiding the tumor site has successfully controlled IOP 13).
Slow-burn CPC (1250 mW, 4000 ms) for neovascular glaucoma achieves IOP reduction while avoiding the pop sound (a sign of hypercoagulation) that is problematic with conventional TS-CPC 6). In neovascular glaucoma cases with nearly 360° peripheral anterior synechiae, 63% avoided tube shunt surgery, suggesting it may be a new option for managing neovascular glaucoma 6).
