Seminars in Ophthalmology

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A Review of Cyclodestructive Procedures for the

Treatment of Glaucoma

Nandita Anand, Emma Klug, Abraham Nirappel & David Solá-Del Valle

To cite this article: Nandita Anand, Emma Klug, Abraham Nirappel & David Solá-Del Valle
(2020) A Review of Cyclodestructive Procedures for the Treatment of Glaucoma, Seminars in
Ophthalmology, 35:5-6, 261-275, DOI: 10.1080/08820538.2020.1810711

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SEMINARS IN OPHTHALMOLOGY
2020, VOL. 35, NOS. 5–6, 261–275
https://doi.org/10.1080/08820538.2020.1810711

A Review of Cyclodestructive Procedures for the Treatment of Glaucoma

Nandita Anand, Emma Klug, Abraham Nirappel, and David Solá-Del Valle
Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

ABSTRACT ARTICLE HISTORY

Cyclodestruction aims to reduce aqueous humor production through the coagulation or destruction of Received 2 February 2020
the ciliary body and has been an important treatment choice for glaucoma since the 1930s. The purpose Revised 23 May 2020
of the current review is to highlight the evidence regarding the safety and efficacy of various cyclodes­ Accepted 9 August 2020
tructive modalities, emphasizing peer-reviewed articles from the last 20 years and the most common KEYWORDS
variants of these procedures. The review focuses primarily on the two most common variants of trans­ Cyclodestruction; micropulse
scleral cyclophotocoagulation (TS-CPC), continuous-wave diode cyclophotocoagulation (CW-TSCPC) and diode; endoscopic
MicroPulse diode cyclophotocoagulation (MP-TSCPC) as well as endoscopic cyclophotocoagulation (ECP) photocoagulation; high-
and high-intensity focused ultrasound cyclodestruction (HIFU). We believe that the role of cyclodestruc­ intensity focused ultrasound;
tion in glaucoma treatment will only continue to expand given the advances in the field, particular with transcleral diode laser
regards to targeted ciliary body destruction and improvement in the safety profile.

INTRODUCTION Neodymium:Yttrium-Aluminum-Garnet (Nd:YAG) laser

Glaucoma is a chronic, progressive, and irreversible optic neu­
ropathy. It is the second most common cause of blindness
worldwide, affecting approximately 80 million people.1
Currently, the only modifiable risk factor known to slow the
progression of the disease is intraocular pressure (IOP). IOP is
the result of the balance of aqueous humor secretion by the
ciliary body and its drainage through the trabecular meshwork
and uveoscleral outflow pathway.2 Accordingly, glaucoma
treatment primarily consists of interventions intended to
lower IOP by decreasing aqueous humor secretion or increas­
ing its outflow.
Cyclodestruction is one such intervention, and it has been
an important treatment choice since the 1930s.
Cyclodestruction aims to reduce aqueous humor production
through the coagulation or destruction of the ciliary body.
Earlier variants of cyclodestruction included cyclocryotherapy
(i.e., freezing injury), cyclodiathermy (i.e., thermal injury), and
cyclectomy (i.e., surgical excision) of the ciliary body.
However, many complications were commonly associated
with these procedures including prolonged uveitis, damage of
corneal nerves, eye pain, and phthisis.3,4 Moreover, their clin­
ical efficacy was called into question with a review of 100 cases
of cyclodiathermy, for instance, demonstrating that only 5% of
cases had a sustainable, clinically-significant reduction in IOP,
with phthisis occurring almost as often.5
Limitations in the safety and utility of these early cyclo­
destructive methods led to the advent of cyclophotocoagu­
lation (CPC)— a more refined, targeted approach to the
destruction of the ciliary body.6 In 1972, the use of trans­
scleral cyclophotocoagulation (TS-CPC) using ruby laser
was first reported by Beckman and associates.7 Shortly
thereafter, the same authors demonstrated that the
more effectively ablated the ciliary body.8 Today, CPC can
be employed through either a transscleral, endoscopic, or
transpupillary approach.
While CPC provides a relatively targeted approach to ciliary
body destruction, dissipated laser energy may still cause
damage to surrounding tissues resulting in postoperative com­
plications commonly observed with the procedure.
Additionally, scattered light energy opposite the treatment
location (ciliary body) may cause macular edema, persistent
mydriasis, prolonged anterior chamber inflammation, and
even neurotrophic keratopathy. However, newer CPC modal­
ities seem to provide better-focused energy, more targeted
destruction of the ciliary processes, and more favorable safety
profiles. This, in turn, has expanded the role of cyclodestruc­
tion in the management of glaucoma to include a broader
patient profile and to be used earlier in our treatment
algorithms.3
The purpose of the current review is to highlight the
evidence regarding the safety and efficacy of various cyclo­
destructive modalities, emphasizing peer-reviewed articles
from the last 20 years and the most common variants of
these procedures. It will focus primarily on the two most
common variants of transscleral cyclophotocoagulation (TS-
CPC), continuous-wave diode cyclophotocoagulation (CW-
TSCPC) and MicroPulse diode transscleral laser treatment
(MP-TLT). Transpupillary CPC is another cyclodestructive
modality that requires a clear visual axis and ciliary pro­
cesses that can be viewed on gonioscopy, in cases such as
aniridia. It is therefore of limited use and will not be
discussed further. Endoscopic cyclophotocoagulation
(ECP) and high-intensity focused ultrasound cyclodestruc­
tion (HIFU) will also be discussed in detail.

CONTACT Nandita Anand nandita.anand08@gmail.com Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243
Charles Street, Boston, MA 02114, USA
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
262 N. ANAND ET AL.
Figure 1. IRIDEX G-probe device.
Transscleral Cyclophotocoagulation (TS-CPC)
In TS-CPC, laser energy administered through the overlying
sclera is absorbed by the melanin in the ciliary processes,
resulting in coagulative necrosis of the ciliary body apparatus.
Both the Nd:YAG laser (1064 nm) and the semiconductor
diode laser (810 nm) can be used for this procedure. The
semiconductor diode laser is currently the most popular
method of treatment, essentially replacing the Nd:YAG laser
due to its ability to provide equivalent efficacy with superior
ease of performance and lower incidences of adverse
events.9–12
The range of analgesic options used during cyclophotodes­
tructive procedures is wide and depends on a variety of factors.
Surgeon and patient preference, and the availability at the
location of practice can all impact the type of anesthetic used.
The options include general, retrobulbar, peribulbar, sub-
Tenon’s or subconjunctival anesthesia. Even heavy sedation
with topical anesthesia in the form of topical lidocaine gel
without alcohol can be utilized, especially for MP-TLT, which
in theory should not be as painful as CW-TSCPC. Of the
studies examined for this review, all employed retrobulbar or
peribulbar anesthesia, with the occasional use of general
anesthesia in pediatric patients or per patient preference.
Continuous Wave Diode Laser (CW–TSCPC)
During CW-TSCPC, continuous-wave laser energy is deliv­
ered to the ciliary body via a laser probe placed approxi­
mately 1.2 mm from the corneoscleral limbus, with the heel
of the probe aligned at the limbus to direct the beam
posteriorly toward the ciliary processes.13 Specifically, the
G-Probe Device (IRIDEX corp., Mountainview, CA) allows
for targeted cyclophotocoagulation of the ciliary body
(Figure 1). A G-probe variant, the G-probe Illuminate,
even offers transillumination with a built-in fiber-optic ele­
ment. Using the G-probe, energy is applied in distinct
locations with care to avoid treating the 3 and 9 o’clock
positions to minimize the risk of damage to the long
posterior vessels and nerves.
The laser power is adjusted just below the level at which
“pops” are heard, which signify an intraocular uveal micro-
explosion.14 The original recommended settings for the semi­
conductor diode were based on studies performed by
Gaasterland et al. in the 1990s on rabbit eyes and ranges from
1.25 − 1.5 W for 4.0–4.5 second durations.12 Today, settings
vary by surgeon preference and patient characteristics. In gen­
eral, surgeons will start at 2.0 Watts (W) for 2 seconds and
titrate the energy down depending on the audible “pop.”
Others use an initial power of 1.25 W for a duration of 4 sec­
onds. Overall, a total of 18 − 21 spots are applied with sparing
the 3 and 9 o’clock positions where the ciliary nerves lie.
The utility of CW-TSCPC for the management of refractory
glaucoma, defined as uncontrolled glaucoma despite prior sur­
gical treatments and/or medical therapy alone, has been well
established for over thirty years (Table 1). In such cases, it has
been reported that between 63 and 89% of patients have
achieved a target IOP of less than 22 mmHg after
treatment.13,15,16 Of the cohort of studies utilizing refractory
glaucoma populations outlined in Table 1, IOP reductions
range from 10 to 23 mmHg, with an average of approximately
17 mmHg.
While numerous studies have demonstrated the efficacy of
CW-TSCPC, comparisons between them are often difficult
given the varying patient populations and laser settings. For
example, in a study of refractory glaucoma cases, Murphy et al.
found CW-TSCPC to be most effective in patients with chronic
angle-closure glaucoma (CACG). CACG patients experienced
the highest success rate (93%), and the lowest re-treatment
(13%) and hypotony rates (0%) compared to those with other
glaucoma diagnoses.16
Moreover, there is evidence that preoperative IOP has an
effect on the absolute reduction in IOP.17,18 Specifically,
Vernon et al. observed that 94% of eyes with an initial IOP >
30 mmHg obtained at least a 30% reduction at the last follow-
up, while only 75% of eyes with an initial IOP ≤ 30 mmHg
achieved such a reduction. Additionally, Hauber et al. found
a significant, direct linear correlation between the total amount
of energy applied to the ciliary body and the percentage of
patients who achieved successful outcomes. When using
aggressive settings [2.0 W, 2 s, 25.6 burns] they observed an
average 13 mmHg reduction in IOP.19
CW-TSCPC has also been shown to reduce patients’ topical
and systemic glaucoma medication use, particularly the use of
oral acetazolamide for IOP control post-treatment. Vernon
et al. demonstrated an 80% reduction in eyes requiring oral
acetazolamide, while Rotchford et al. observed a 55%
reduction.18,20 The average reduction in glaucoma medications
following CW-TSCPC based on the studies featured in Table 1
is approximately 1.2. However, it must be noted that with
patients coming off of acetazolamide, there is an occasional
increase in use of topical medications for IOP control that is
not clearly reported across studies. Overall, CW-TSCPC has
proven effective in absolute IOP control as well as in decreasing
the medication burden in patients with refractory glaucoma.
Although effective, CW-TSCPC is not without complica­
tions. Specifically, postoperative pupillary abnormalities,
hyphema, inflammation, hypotony, retreatments, drop in
visual acuity, pain, lens subluxation, staphyloma formation,
scleral perforation, and even sympathetic ophthalmia have
been reported.9,18,21-24 The rates of hyphema were highest in
patients with neovascular glaucoma (NVG), and occurred in
between 0 and 5% of eyes portrayed in Table 1.25 Hypotony
and subsequent phthisis is another commonly feared
Table 1. Selection of Continuous Wave Transscleral Cyclophotocoagulation (CW-TSCPC) Studies from 2001–2019.
Author, Tabibian et al. Frezzotti et al. Rotchford et al. Iliev & Gerber Vernon et al. Noureddin Murphy et al. Shah et al.
year 2019 Ghosh et al. 2014 2010 2010 Yildirim et al. 2009 2007 2006 et al. 2006 2003 Pucci et al. 2003 2001
Publication J Glaucoma Eur J Ophthalmol Acta Ophthalmol Br J Ophthalmol J Glaucoma Br J J Glaucoma Eye Br J Ophthalm-ologica Ophthalm-
Ophthalmol Ophthalmol ology
Study type RP RP PP RP PP RP RP PP RP RP RP
Population Refractory POAG; with good Refractory Mixed; with NVG Refractory/ POAG Refractory Refractory Refractory Refractory
vision good vision NVG
F/U (mths) 60 24 42 61 24 30 66 14 17 26 31
a
# of eyes 28 46 124 49 CW-TSCPC: 33 131 59 36 263 120 28
b
AVG:33
a
Mean baseline IOP 30 24 30 28 43 37 31 36 41 30 33
b
(mmHg) 43
a
Mean 18 7 12 13 25 22 16 17 23 10 16
b
reduction 20
(mmHg)
a
% IOP 60 29 40 46 58 59 52 47 56 33 48
b
reduction 47
a
Mean preop. Meds. 2.8 2.5 3.5 2.3 2.6 2.97 2.6 2.8 1.7 4.5 2.6
b
3.3
a
Mean meds. 1.1 0.3 0.2 0.4 0.8 1.93 0.84 1.92 0.9 2.2 1
b
reduction 1.3
a,b
Laser 2.5 W, 2.0 s, 15 2.5 W, 2.0 s, 2.0 W, 2.0 s, 2.0 W, 2.0 s, 14 1.5 W, 2.0 s, 1.75–2.0 W, 2.0 W, 2.0 s, 14 2.25 W, 2 s, — 1.6–2.0 W, 2.0 s, 1.5 W, 1.5 s, 40
settings burns 12–14 burns 10–15 burns burns 16–20 burns 2.0 s burns 26–28 burns 1–15 burns burns
a
% VA decline 32 20 31 31% 24 — 64 22 20 24 26
b
27
a
% Hyp./Phth. 0/0 0/0 0/0 0/0 12/0 18/10 5/0 3/0 9/5 0/0 4/0
b
3/6
a
% 0 0 2 6% 0 0.8 2 6 0.4 0 0
b
CME 21
Data ranging from 2001–2019 on the efficacy and safety of CW-TSCPC in a wide range of populations. A Mixed population indicates there was no clear majority in the type of glaucoma studied. RP, retrospective; PP, prospective; F/
U, follow-up; preop., preoperative; meds., glaucoma medications; VA, visual acuity; Hyp., hypotony; Phth., phthisis; CME, cystoid macular edema; POAG, primary open-angle glaucoma; NVG, neovascular glaucoma; acontinuous
wave transscleral cyclophotocoagulation, bAhmed glaucoma valve.
SEMINARS IN OPHTHALMOLOGY
263
264 N. ANAND ET AL.
complication of CW-TSCPC. Vernon et al. hypothesized
that risks of hypotony and phthisis are directly proportional
to the amount of laser energy delivered during CW-TSCPC,
while other studies have shown that the underlying type of
glaucoma seems to be more highly correlated with compli­
cation rates, particularly NVG.20,26-28 Indeed, a staggering
76% of the patients that developed hypotony in a study by
Iliev and Gerber had underlying NVG.28
Retreatment is another important factor when discussing
the efficacy and safety of CW-TSCPC. The need for retreat­
ment has been most commonly described in younger patients,
posttraumatic cases, and patients who have secondary glau­
coma following vitreoretinal surgery.13 Retreatment rates in
the studies from Table 1 range from 20 to 60%, with the highest
rates seen in studies that used lower energy settings.20,29
However, Vernon and Pucci believe that using lower doses of
laser energy is the optimal approach, given that this allows for
titration of the dose of cycloablation to the individual eye in
terms of the number of treatment episodes, thus minimizing
risk of hypotony and phthisis.18
Importantly, CW-TSCPC has also been associated with
a decrease in final visual acuity (VA) and is therefore commonly
reserved for patients with poor visual potential. However, recent
studies have shed more light on this topic, suggesting CW-
TSCPC treatment can be extended to patients with good vision.
When used in patients with visual acuity >20/60, Ghosh et al.
found that 39.1% of eyes retained their preoperative VA, 24%
had a loss of two lines or more and 10.9% experienced some
improvement in VA after 2 years of follow up.30 Rotchford et al.
also evaluated the effects of CW-TSCPC in patients with good
visual acuity (≥20/60), but used a follow-up period of 5 years. At
last follow up, 30.6% of patients had lost 2 or more lines of
visual acuity, which is consistent with reported rates of vision
loss following trabeculectomy or tube-shunt surgery.20,31
Taken together, these studies suggest that final visual acuity
is minimally compromised due to CW-TSCPC alone, and that
glaucoma progression, in and of itself, was typically the most
frequent cause of decreased visual acuity in these patients. The
overall trend of these studies, as outlined in Table 1, suggests
that CW-TSCPC is an effective method of IOP control despite
its associated risks and complications. It should be noted that
while rates of VA decline were comparable between CW-
TSCPC, trabeculectomy and tube-shunt surgery, MP-TLT
appears to put patients at significantly less risk for postopera­
tive VA decline (Tables 1 and 2). The more favorable progres­
sion in visual acuity following MP-TLT is among the reasons it
has been preferred over CW-TSCPC in patients with good
vision potential.
The use of CW-TSCPC in refractory cases of glaucoma due
to NVG or secondary glaucoma in post-penetrating kerato­
plasty (PK) patients is of particular value, as the IOP in these
patient populations can be significantly more challenging to
control. Yildirim et al. prospectively compared the long-term
IOP reduction in a cohort of NVG patients who received
treatment with either CW-TSCPC or an Ahmed glaucoma
valve (AGV). Surgical success was defined as a postoperative
IOP between 5 and 21 mmHg without additional glaucoma
surgery or loss of light perception vision.32 Overall, no signifi­
cant differences were found between the two groups: after
24 months, the probability of success was 61.18% in the CW-
TSCPC group, and 59.26% in the AGV group. Additionally,
visual acuity decreased in 24% of eyes in the CW-TSCPC group
and 27% of eyes in the AGV group.32 CW-TSCPC appears to
be warranted for use in NVG patients and may be similar in
efficacy to AGVs.
CW-TSCPC has also proven to be a useful tool in patients
with secondary glaucoma post PK. A study by Shah et al. found
a median 16 mmHg reduction in IOP from a baseline median
of 33 mmHg, though most patients required 2 CW-TSCPC
treatments to control IOP.33 The mean number of glaucoma
medications before and after CW-TSCPC in this study was 2.6
and 1.8, respectively (P < .001), at a median of 30.5 months of
follow-up time. Visual acuity improved (> two Snellen lines of
acuity) in three patients (11%) and remained the same (± one
Snellen line) in 17 patients (61%). Of the 7 patients (26%) at
final follow-up who lost vision (> two Snellen lines or decrease
in one low-vision category), two (7%) of these lost vision due to
the laser treatment (uveitis, cystoid macular edema (CME))
and the other five’s vision loss was associated with ongoing
disease processes.33 Additionally, of the 19 patients (68%) with
originally clear grafts, three grafts (16%) developed opacifica­
tion. Opacification was secondary to graft rejection and late
endothelial failure. Six grafts (21%) had signs of rejection with
two of these occurring more than 3 months after cyclodiode
treatment; three of these rejection episodes (50%) were rever­
sible with intensive corticosteroid treatment.33
There is also a role for CW-TSCPC in the management of
pediatric glaucoma, which remains notoriously difficult to
manage. While angle-based and filtering procedures are usually
the core of pediatric glaucoma management, surgery for child­
hood glaucoma has a substantial failure rate compared to that
of adults.34 Studies of CW-TSCPC in children have demon­
strated clinically useful reductions in IOP in cases of refractory
pediatric glaucoma with low complication rates, however
retreatment is often needed to maintain control of IOP.35,36
Specifically, Kirwan et al. reported that after one treatment only
37% of pediatric patients had an IOP <22 mmHg or a 30%
reduction from baseline at 12 months. However, with repeat
treatment 72% of patients experienced such a reduction at
12 months post diode laser.36 As such, CW-TSCPC may have
a more significant role as an adjunct to surgery or in managing
patients for whom surgery is undesirable due to increased risk
of complications.
In summary, CW-TSCPC can be an excellent tool for IOP
control in patients with difficult-to-manage glaucoma, but it is
again not without its complications due to less-selective tissue
ablation and collateral damage to other structures. Future
direction for CW-TSCPC has been focused on more selective
tissue ablation to allow for use in mild and moderate stages of
glaucoma.
MicroPulse Transscleral Laser Treatment (MP-TLT)
Introduced to the U.S. market in 2015, MP-TLT (IRIDEX
Corp., Mountainview, CA) is the newest form of diode-laser
technology (Figure 2). It has quickly emerged as a promising
alternative to CW-TSCPC due to its comparable efficacy and
potentially more favorable safety profile. In contrast to CW-
Table 2. Selection of MicroPulse Transscleral Cyclophotocoagulation (MP-TSCPC) Studies from 2010–2020.
Author, Anand et al. Nguyen et al. Varikuti et al. Zaarour et al. Emanuel et al. Kuchar et al. Aquino et al. Ting et al.
year 2020 2019 2019 2019 Garcia et al. 2019 Yelenskiy et al. 2018 2017 2016 2015 Tan et al. 2010 2020
Publication AGS Eur J J Glaucoma J Glaucoma Ophthalmol J Glaucoma J Glaucoma Lasers Med Clin Exp Clin Exp J Glaucoma
meeting Ophthalmol Glaucoma Sci Ophthalmol Ophthalmol
Study type RP RP RP PP RP RP RP RP PP PP RP
Population Mixed POAG POAG POAG POAG POAG POAG Mixed Mixed NVG Mixed
F/U (mths) 12 12 12 15 12 25 12 2 18 18 12
a
# of eyes 51 95 61 75 116 197 84 19 MP-TSCPC: 24 40 32
b
CW-TSCPC
:24
a
Mean baseline IOP 25 25 26 26 22 22 28 38 37 39 33.7
b
(mmHg) 35
a
Mean 9 8 10 11 7 6 17 15 17 13 9.1
b
reduction (mmHg) 16
a
% IOP 36 32 38 42 32 27 61 39 46 33 27
b
reduction 46
a
Mean preop. 3.8 3 3.5 3.53 3.2 3 3.3 2.6 2 2.1 3.4
b
meds. 2
a
Mean meds. 0.95 1.6 0.8 0.5 0.7 1 1 0.7 1 0.8 0.6
b
reduction 1
a,b
Laser 2.0–2.4 W, 2.0–2.5 W, 180 2.0 W, 159 s 2.0 W,90–120 2.0 W, 180 s 2.0 W, 90–120 s 1.6–2.4 W, 2.0 W, 2.0 W, 100 s 2.0 W, 100 s 1.5–2 W,
Settings 360 s s s 180–360 s 100–240 s 124–132 s
a
% VA decline 2 — 21 14 8 0 41 21 4 0 0
b
9
a
% Hyp./Phth. 6/0 0/0 2/0 0/0 2/0 0/0 6/0 5/0 0/0 0/0 0
b
20/4
a
% Infl. 4 0 0 0 1 0 46 0 4 10 0
b
30
% CME 6 0 3 0 1 2 0 0 0 0 0
Data ranging from 2010–2020 on the efficacy and safety of MP-TSCPC in a wide range of populations. A Mixed population indicates there was no clear majority in the type of glaucoma studied. RP, retrospective; PP, prospective; F/
U, follow-up; preop., preoperative; meds., glaucoma medications; VA, visual acuity; Hyp., hypotony; Phth., phthisis; Infl., prolonged inflammation; CME, cystoid macular edema; POAG, primary open-angle glaucoma; NVG,
neovascular glaucoma; aMicroPulse transscleral cyclophotocoagulation, bcontinuous-wave tranasscleral cyclophotocoagulation.
SEMINARS IN OPHTHALMOLOGY
265
266 N. ANAND ET AL.
Figure 2. (a) The Generation 1 MicroPulse Probe. (b) The Generation 2 MicroPulse Probe. (c) The Generation 1 MicroPulse Probe in use.
TSCPC, MP-TLT utilizes repetitive pulses of energy separated
by periods of rest, which allows for more targeted treatment of
the pigmented tissue in the ciliary processes.
While no prior histopathological studies have described the
actual mechanism of action for MP-TLT, it appears that IOP
reduction is achieved through a few distinct pathways. One
proposed mechanism is that MP-TLT primarily targets the
pigmented tissue in the ciliary body epithelium. The adjacent
non-pigmented structures are given time to recover during the
“off cycle”, which prevents them from reaching the coagulative
threshold and subsequently minimizes collateral tissue
damage.37,38 Another mechanism proposed by Johnstone
et al. postulates that that the pigmented epithelium is not
necessarily involved in the IOP-reducing effect of MP-TLT.
Rather, the authors suggest that the mechanism of the laser is
similar to that of pilocarpine, and it induces contraction of the
ciliary muscles, leading to posterior and inward movement of
the scleral spur and trabecular meshwork. This histological
study showed that the changes caused by the laser were con­
fined to the longitudinal bundles of ciliary muscle, with no
visible changes to the ciliary epithelium.39
In addition to increasing the amount of outflow through the
trabecular meshwork, there is evidence that MP-TLT also
increases aqueous humor outflow via the uveoscleral pathway.
In a prospective study of 22 patients who underwent the
procedure, Barac et al. demonstrated that an increase in foveo­
lar choroidal thickness following MP-TLT was associated with
a positive response to the treatment.40 As the variations in
choroidal thickness observed here were likely due to a rise in
uveoscleral outflow, it appears that some of the IOP-reducing
ability of MP-TLT can be attributed to the increase in aqueous
humor drainage through the uveoscleral pathway.40 The
authors reported no changes to the visual acuity of the patients.
Studies of MP-TLT have consistently demonstrated its abil­
ity to effectively reduce IOP in a wide array of glaucoma types
(Table 2). Similar to studies of CW-TSCPC, direct comparison
between studies of MP-TLT can be difficult given the differ­
ences between patient populations and the variability in laser
settings used. Prior studies have indicated that the IOP-
lowering effect at 1 year can vary widely, ranging from 6.9 to
12.6 mmHg.37,41-47 One plausible explanation for the wide
range in reported IOP reduction is the difference in mean
baseline IOP, as the magnitude of IOP reduction in MP-TLT
also appears to be strongly correlated with baseline IOP. For
example, Garcia et al. reported a mean IOP reduction of
6.9 mm Hg from a baseline of 22.2 mm Hg, while Emanuel
et al. reported a mean reduction of 16.6 mm Hg from a baseline
of 27.7 mm Hg.41 The majority of MP-TLT studies evaluated
have used an IOP reduction ≥20% from baseline as the criteria
for success. Once again, the reported success rates (at
3–12 months postoperatively) vary widely, ranging from
67.1% by Zaroour et al. to 93.1% by Garcia et al.42,46
In addition to lowering IOP, MP-TLT has proven to be
effective in reducing the medication burden of glaucoma
patients. It has consistently been able to reduce the amount
of glaucoma medications, both oral and topical, needed by
patients across all studies examined, with a mean reduction at
1 year ranging from 0.5 to 1.6 medications.37,42,45,47-49 In
a study by Tan et al., all 6 patients on oral acetazolamide
were able to stop taking it following the procedure, while 17/
65 (26%) patients in a study by Zaarour et al. were able to
discontinue oral medication use.37,48
MP-TLT is a potentially valuable treatment tool for spe­
cific types of glaucoma patients, especially post-keratoplasty
eyes and pediatric patients. In a retrospective study of 61
such eyes, Subramaniam et al. reported that the graft survival
rate was 94% at 1 year, and 81% at 2 years following the
initial laser treatment.50 Many patients included in this study
had previously undergone glaucoma filtration surgery. The
authors noted that the graft failure rate observed here was
unremarkable, given that prior filtration surgery is a major
risk factor for graft failure. They reported a mean IOP
reduction of 13.0 mm Hg at 12 months postoperatively
from a baseline of 28.0 mmHg.50 A handful of recent studies
have explored a role for MP-TLT in the management of
pediatric glaucoma. In a study of 36 pediatric glaucoma
eyes, Elhefney et al. reported that IOP was reduced from
37.5 mmHg to 20.0 mmHg, and medications reduced from
2.6 to 1.7, 15 months after MP-TLT.51 Sixty-six percent of
eyes required a second treatment session to maintain control
of IOP, and no major complications were observed in any
patients.51

Notably, Abdelrahman et al. compared CW-TSCPC and
MP-TLT in a cohort of pediatric refractory glaucoma patients.
With success defined as an IOP between 5 and 21 mmHg in the
absence no vision-threatening complications at 6 months, the
authors reported a greater success rate in the MP-TLT (71%)
group compared to the CW-TSCPC (46%) group, however,
this difference was not statistically significant. Moreover, they
did not observe any significant complications in the MP-TLT
group, while there were cases of phthisis bulbi (2) and severe
pain and uveitis in the CW-TSCPC group.52 While prospective
randomized trials are needed to truly compare these proce­
dures in pediatric glaucoma management, MP-TLT may be
equally effective with a lower risk of complications.
There is currently a lack of consensus on the influence of
a history of prior glaucoma surgery on the success rates of MP-
TLT. For example, Garcia et al. found that prior incisional
glaucoma surgery was positively correlated with the success
rates of MP-TLT and patients who had previously undergone
trabeculectomy, tube shunt surgery, or a combination thereof,
had a success rate of 67.6% versus a success rate of 41.4% for
patients had not had these procedures.42 Interestingly, a history
of Minimally-Invasive Glaucoma surgery (MIGS) did not seem
to have this same effect, as no differences in IOP reduction
were found between a subgroup of patients that underwent
previous MIGS and a subgroup that had not.42
The notion that prior traditional glaucoma surgery has
a favorable effect on the success of MP-TLT is disputed by
results reported by Zaarour et al. who reported no difference in
the success rates of patients who had previous incisional glau­
coma surgery and those who had not.46 Differences between
the studies in the laser settings and population of glaucoma
patients studied can potentially explain this discrepancy. For
example, the laser settings used by Garcia et al., which demon­
strated a positive correlation between prior incisional surgery
and success rates, were in some cases tailored based on the
severity of glaucoma.42 In contrast, Zaarour et al. used stan­
dardized settings throughout.46 Garcia et al also included
a substantially greater proportion of primary open-angle glau­
coma (POAG) patients, 56.9% versus 34.7%.42,46 These differ­
ences could potentially account for the differences reported in
the analyses of patients who underwent prior incisional
surgery.
As MP-TLT is still a relatively new technique, the optimal
laser settings have yet to be defined. There is considerable
variation between studies in the laser settings used with regard
to both power and duration of treatment. The power settings in
the studies examined in Table 2 ranged from 1.6–2.4 W, while
the total treatment duration ranged from 100 to 360 s. There is
also variability in the probe motion used by providers when
performing MP-TLT. The sweeping or painting technique is
currently recommended by the manufacturer, in which the
probe is moved in a slow, continuous back-and-forth sliding
motion along the arcs around the limbus. However, some
studies have demonstrated promising results using the discrete
spot or stop-and-continue techniques.45,53 In a population of
refractory glaucoma patients who had previously undergone
MP-TLT under more standard settings, Ting et al. reported
favorable outcomes using both the sweeping and discrete spot
techniques.53
SEMINARS IN OPHTHALMOLOGY 267
The effectiveness of higher-than-usual MP-TLT settings has
recently been demonstrated by Anand et al.45 The higher-than-
usual settings in this study were defined as treating at least
180 seconds per hemisphere with a power between 2 and
2.4 W, along with a mix of the sweeping and stop-and-
continue techniques. The authors observed a mean IOP reduc­
tion of 12.3 mmHg 6 months postoperatively, and an
8.9 mmHg reduction after 12 months. This was slightly better
than the IOP reductions described by Yelenskiy et al. and
Nguyen et al. who reported mean 12-month reductions of
6 mmHg (27%) and 7.6 mmHg (30%), respectively.44,54 Given
the variability in laser power, duration, probe motion and
patient populations used among studies of MP-TLT, the opti­
mum laser settings of MP-TLT remains elusive.
While MP-TLT has proven to be effective in controlling
IOP, its IOP-lowering effect appears to wane over time. For
example, Zaroour et al. reported that while 86.7% of patients
achieved surgical success (defined as an IOP reduction ≥20%
from baseline) at 1-month post-MP-TLT treatment, the suc­
cess rate dropped to 61.7% at the 6-month visit and 56.7% at
the 12-month visit.46 Additionally, Garcia et al. demonstrated
a success rate of 93.1% at 3-months, which dropped to 67.4% at
6 months and 59.6% at 12 months.42 A similar decline in the
success rate was observed by Anand et al. using the higher-than
-usual settings, dropping from 80% at 6-weeks postoperatively
to 69% at 1-year.45 Interestingly, it appears that these patients
treated with the higher-than-usual settings did not experience
as drastic a decline in success rate compared to those in other
studies, which may indicate a potential influence of the laser
settings used on the longevity of MP-TLT treatment.45
The recent shift in favor of MP-TLT over CW-TSCPC is
largely due to the sentiment that it results in fewer post­
operative complications, while being equally as effective. As
expected, the rates of postoperative complications seem to be
comparatively lower in MP-TLT than in CW-TSCPC. While
the highest reported rate of prolonged hypotony was just 6%
in the reviewed studies of MP-TLT, it has been reported in up
to 18% of patients who received CW-TSCPC.28 MP-TLT also
appears to put patients at significantly less risk of losing visual
acuity following the procedure. Decline in visual acuity has
been reported in up to 64% of patients following CW-TSCPC,
while the highest reported rate of visual acuity loss following
MP-TLT was 41%.37,42,44-48 Incidences of prolonged anterior
chamber (AC) inflammation (defined as 1+ cell or flare for
>3 months) have been reported in as few as 0.8%, but up to
10% of patients.37,41,42,45-49,55 Rates of CME have consistently
been minimal across studies of MP-TLT with the majority of
studies reporting no cases of CME post operatively, and even
when reported the incidence rate has varied from 1–6%.
Persistent mydriasis was not a commonly reported complica­
tion in studies of MP-TLT. When persistent mydriasis was
reported, the incidence rate ranged from 0 to 3.2%, and was
significantly more common following MP-TLT in Asian
patients.56 While MP-TLT does appear to have a more favor­
able safety profile than CW-TSCPC, rates of subconjunctival
hemorrhage are of potential concern.57 In a prospective case
series of 36 eyes, subconjunctival hemorrhage was reported in
32.3% of patients postoperatively, which appears to be higher
than the rate seen in other cyclodestructive techniques.
268 N. ANAND ET AL.
Figure 3. (a) The endoscopic cyclophotocoagulation probe (ECP) (Endo Optiks, Little Silver, NJ) entering an eye. (b) Two intraoperative views of ciliary process during
ECP treatment. Photographs from the archives of Dr. David Solá-Del Valle.
Additionally, the incidence of neurotrophic keratitis (NK)
should be monitored. In a case study by Perez et al, the
authors reported that two patients still developed NK post­
operatively even when the 3 and 9 o’clock positions were
avoided during treatment.58 The occurrence of NK was also
noted as a concern in an animal study evaluating the safety of
MP-TLT in dogs.59 Notably, the higher-than-usual settings
used by Anand et al. did not appear to put patients at an
increased risk of postoperative complications, as the rates of
hypotony (6%), prolonged inflammation (4%), and visual
decline (2%) were comparable to those reported in other
studies.37,42,44,45,47,49,54
All of the studies included in this review used the
Generation 1 MP3 probe (IRIDEX Corp., Mountainview,
CA) (Figure 2a). IRIDEX is currently in the process of phasing
out the Generation 1 probe and shifting to the Generation 2
MP3 probe. According to the manufacturers, the Generation 2
MP3 probe has a new foot plate design but all other compo­
nents of the laser are the same (Figure 2b). However, there are
currently no studies that have studied the new probe’s efficacy
or optimal laser settings in a clinical setting.
Endoscopic Cyclophotocoagulation (ECP)
ECP was originally developed by Martin Uram in 1992.60–62
The ECP probe (Endo Optiks, Little Silver, NJ) combines
a diode endolaser, aiming beam, light source, and endoscope
into a single intraocular probe (Figure 3). This allows for
targeted, controlled ablation of the ciliary processes with direct
visualization and titration of power. Histologically, ECP-
related tissue injury has been demonstrated to be effectively
limited to the ciliary processes and associated capillary bed,
sparing the ciliary muscle and stromal tissue.55,63 This is in
contrast to histological changes observed following treatment
with Nd:YAG and diode CW-TSCPC, in which significant
disruption of the cells through the ciliary processes and a loss
of blood vessels within the stroma has been observed.64
Numerous studies have demonstrated the effective IOP-
lowering ability of ECP in a variety of glaucoma patients
(Table 3). Most commonly, ECP is performed in conjunction
with phacoemulsification cataract surgery (phaco-ECP).
Specifically, reports of IOP reductions range from 2.7–­
11.5 mmHg, or 14.9%-46.9%, in cohorts of POAG patients
depending on whether ECP is done alone or in combination
with cataract surgery.63,65-68
Studies comparing phacoemulsification -ECP (phaco- ECP)
to phacoemulsification alone have illuminated the IOP-
lowering effect of ECP independent of the known effect of
phacoemulsification. For example, Francis et al. observed
a 2.7 mmHg reduction (17%) in IOP in open-angle glaucoma
(OAG) patients 36 months after phaco-ECP, and only
a 0.9 mmHg reduction (6%) in patients that underwent pha­
coemulsification alone. Similarly, Bartolome et al. observed
a 23% IOP reduction 12 months after the combined procedure,
and an 11% reduction after cataract surgery alone.67
ECP treatment can be extended beyond its role in conjunc­
tion with cataract surgery, as it has also proven effective in
treating cases of refractory glaucoma and NVG as a stand-
alone procedure. Specifically, Francis et al. observed a 36%
(8.7 mmHg) IOP reduction 18 months following ECP treat­
ment in a group of patients with uncontrolled IOP and a prior
tube shunt surgery.64 In a similar manner, Murakami et al.
compared pseudophakic patients with refractory glaucoma and
a prior tube shunt who underwent ECP or a second tube shunt
Table 3. Selection of Endoscopic Cyclophotocoagulation (ECP) studies from 2007–2018.
Author, Villavicencioet al. Bartolome Ferguson et al. Murakami et al. Roberts et al. Marra et al. Francis et al. Clement et al. Francis et al. Kahook et al.
year 2018 et al. 2017 2017 2017 2016 2015 2014 2013 2011 2007
Publication J. Clin Exp. Ophth Eur JCRS J. Clin Exp. Ophth Int’l Jrnl Ophth Retina JCRS J. Clin Exp. Ophth J. Glaucoma J. Glaucoma
JOphthalmol
Study type RP RP RP RP RP RP PP RP PP RP
Population POAG POAG OAG Refractory POAG NVG OAG POAG Refractory POAG
F/U (mths) 24 12 12 24 12 12 36 12 18 6
a c e g i k
# of eyes 41 Phaco/ECP: 69 ICE: 51 ECP: 25 91 ECP: 27 Phaco/ECP: 80 63 25 240°: 15
b d f h j l
Phaco: 30 iStent/Phaco: GDD-2: 48 Control: Phaco: 80 360°: 25
50 27
a c e g i k
Mean baseline IOP 22 22 21 24 17 40 18 21 24 24
b d f h j l
(mmHg) 19 21 24 35 18 25
a c e g i k
Mean 9 5 7 7 3 28 3 5 9 8
b d f h j l
reduction (mmHg) 2 5 9 12 1 11
a c e g i k
% IOP 41% 23 33% 29% 18% 70% 17% 24% 38% 32%
b d f h j l
reduction 11 24% 38% 34% 6% 47%
a c e g i k
Mean preop. 2.08 2.6 1.8 3 1.9 3.1 1.5 2.7 3.2 2.5
b d f h j l
meds. 1.2 1.7 4 1.3 2.4 2.6
a c e g i k
Mean meds. reduction 0.48 0.7 0.7 1.5 0.4 2.6 1.1 1.4 1.7 0.6
b d f h j l
0.2 1.1 0.9 -0.6 0.1 2.1
a,b c,d e,f i,j
Laser settings (W) 0.2 0.25 0.2 mW 0.25–0.35 0.25 — 0.2–0.5 0.4 0.25–0.35 —
a,b c,d e,f g,h i,j k
° processes treated 360 270–360 270 330-360 200–270 360 270-360 270-360 360 240
l
360
a g i k
% 0 0/0 — — — 7/7 0/0 0/0 0/0 0/0
b h j l
Hyp./Phth. 0/0 7/7 0/0 0/0
g i k
% 0 6 — — — 0 0 3 4 0
h j l
CME 3 0 4 0
Data ranging from 2007–2019 on the efficacy and safety of ECP in a wide range of populations. RP, retrospective; PP, prospective; F/U, follow-up; preop., preoperative; meds., glaucoma medications; Hyp., hypotony; Phth., phthisis;
POAG, primary open-angle glaucoma; OAG, open-angle glaucoma; NVG, neovascular glaucoma; a,iPhacoemulsification and ECP, b,10phacoemulsification; ciStent, cataract extraction, and ECP, diStent and phacoemulsification; f2nd
glaucoma drainage device; hcurrent standard of care for NVG; k240° of ciliary processes treated, l360° of ciliary processes treated.
SEMINARS IN OPHTHALMOLOGY
269
270 N. ANAND ET AL.
surgery to control IOP.69 Throughout the 12-month follow-up
period, no significant differences in postoperative IOP or glau­
coma medication use were observed between those that under­
went ECP and those that underwent an additional tube shunt
surgery.69
Similar efficacy was observed in a cohort of NVG patients.
Specifically, NVG patients underwent a combination pars
plana vitrectomy/panretinal photocoagulation/ECP or the cur­
rent standard of care for patients with NVG, which included
panretinal photocoagulation, filtration surgery, pars plana
vitrectomy, or AGV placement. After 12 months, IOP was
reduced by 28.4 mmHg in the combined ECP group, and
11.7 mmHg in the Ahmed valve group.70
The effectiveness of ECP in cases of pediatric glaucoma has
also been briefly studied. In a study of 35 eyes of patients under
16 years of age with glaucoma following cataract surgery, the
success rate of ECP was 54% after a mean follow-up period of
7.2 years (treatment failure defined as consecutive IOP
>24 mmHg, an additional glaucoma procedure, or visually
significant complications). The average final IOP was
18.9 mmHg, compared to 33.9 mmHg preoperatively. The
authors also reported that visual acuity was preserved in these
patients from baseline to last follow-up.71 Additionally, Glaser
et al. reported success rates of 64%, 36%, and 16% at 1, 3, and
5 years, respectfully, following a single ECP treatment in 80
eyes with pediatric glaucoma. Similarly, treatment failure was
defined as IOP >24 mmHg at 2 consecutive visits, any addi­
tional glaucoma surgery, sight-threatening complications, or
progression to no light-perception vision.72
In addition to effectively lowering IOP, ECP can provide
significant reductions in patients’ topical and systemic glau­
coma medication burden. In POAG patients, reductions in
glaucoma medication use range from 0.4 to 1.4.63,65-68,73
Moreover, in cases of refractory glaucoma, ECP has been
demonstrated to reduce glaucoma medication use by
1.5–1.7.64,69 Additionally, NVG patients that underwent treat­
ment that included ECP experienced a 2.6 reduction in med­
ications 12 months postoperatively, while the Ahmed
glaucoma valve group experienced an increase in
medications.70
A number of studies have looked at the long-term effective­
ness of ECP. Francis et al. demonstrated that phaco-ECP
resulted in significant reductions in IOP up to 36 months
postoperatively.65 However, the authors reported that the
initial downward trend in IOP seemed to level off at 12 months
postoperatively in both phaco-ECP and phacoemulsification
alone groups. Throughout the next 2 to 3 years, the eyes that
underwent phaco-ECP remained stable at this level, while
those that had cataract extraction alone showed regression
towards the baseline IOP.
Furthermore, Bartolomé et al. noted that IOP initially
decreased after phaco-ECP, then began to gradually rise
1 week following surgery. However, at 12 months postopera­
tively, IOP was still significantly reduced at 16.8 mmHg com­
pared to 21.45 mmHg at baseline.67 Additionally, Kaplan-
Meier survival data revealed that although the success rate
(defined as IOP <21 mmHg and at least a 20% reduction in
IOP from baseline) declined over time, it remained relatively
high at 69.6% 12 months postoperatively. This was significantly
greater than the success rate of the phacoemulsification alone
group, which was 40% at 12 months postoperatively.67
Similarly, in a group of patients who had ECP with a failed
prior tube shunt, Francis et al. found that IOP was reduced by
43% at month 1.64 This gradually decreased over the 24-month
follow-up period to 25%, however, mean IOP remained statis­
tically significantly reduced from baseline throughout the 24-
month follow-up period.
As previously mentioned, direct visualization of the ciliary
processes provides a more targeted approach, limiting the
tissue injury following ECP to the aqueous humor-producing
cells and associated capillary bed. It is postulated that minimal
collateral damage to the surrounding tissues during ECP con­
tributes to its favorable safety profile. Specifically, complica­
tions associated with ECP in over 5000 eyes reported by the
ECP Collaborative Study Group included: IOP spike (14.5%),
hyphema (3.8%), choroidal detachment (0.36%), visual acuity
decline (1.03%), CME (0.7%), and hypotony and phthisis
(0.12%).74
Similarly, low rates of hypotony, phthisis, and CME were
observed in the studies reviewed in this article. For exam­
ple, rates of CME ranged from 0 to 5.8%. Only one study
reported incidences of prolonged hypotony that progressed
to phthisis bulbi, occurring in 2 (7.4%) cases of both ECP-
treated and control group NVG patients.70 In this study,
patients were diagnosed with phthisis if their IOP remained
under 5 mmHg for 3 consecutive visits any time after
6 months after their initial treatment.57 Additionally, no
differences in postoperative complication rates were
observed in studies that compared phaco-ECP to phacoe­
mulsification alone.64,67
Compared to TS-CPC, which is associated with less-
selective tissue ablation, ECP confers lower rates of hypotony
or phthisis.55,75 When comparing the complication rates of the
studies outlined in Tables 1–3, there are substantially fewer
reports of hypotony or phthisis following ECP compared to
both variants of TS-CPC. Excluding studies that primarily
focused on patients with underlying NVG, as this subset of
glaucoma tends to experience greater rates of postoperative
complications following CPC, reported rates of hypotony are
up to 9% with CW TS-CPC, 6% with MP-TLT, and 0% with
ECP. Moreover, a decline in visual acuity is often observed
following TS-CPC.15,30,76 This effect is rarely seen with ECP, as
it is most often performed in conjunction with cataract surgery,
thereby maintaining or improving patients’ visual acuity.23,73
There is some evidence that the efficacy of ECP, with regard
to IOP and medication reduction, may be dependent on the
degrees of ciliary processes treated. For example, of the studies
reviewed, anywhere from 200 to 360 degrees of ciliary pro­
cesses were treated, signifying a lack of clinical consensus on
the optimal treatment area.66,73 However, in a study investigat­
ing the efficacy of 240° versus 360° of treatment, Kahook et al.
observed significantly greater reductions in IOP and glaucoma
medication use in the 360° group.63 Specifically, 360° of treat­
ment conferred an additional reduction of 3.9 mmHg and 1.5
medications compared to 240° of treatment. Notably, 360°
treatment did not add to the postoperative complication rate.
Treating 360° of ciliary processes requires a second corneal
incision and may add surgical time to the case, but the positive
Table 4. Selection of High-Intensity Focused Ultrasound Cyclodestruction (HIFU) Studies from 2011–2017.
Author,
year Giannaccare et al. 2017 Aptel et al. 2016 Aptel et al. 2015 Melamed et al. 2015 Denis et al. 2015 Aptel et al. 2014 Aptel et al. 2011
Publication Graefes Arch Clin Exp Ophthalmol EVER conference 2016 Acta Ophthalmol Eur J Ophthalmol Invest Ophthalmol Vis Sci Curr Med Res Opin Invest Ophthalmol Vis Sci
Study type PP PP PP PP PP PP PP
Population Refractory POAG OAG Refractory Refractory Refractory (all POAG) Refractory
F/U (mths) 6 6 12 12 12 12 6
a
# of eyes 30 520 30 20 4 s group: 24 28 12
b
6 s group: 28
a
Mean baseline IOP (mmHg) 30 24 28 36 30 29 38
b
29
a
Mean 10 8 9 14 10 7 13
b
reduction (mmHg) 11
a
% IOP 33 33 32 39 33 24 34
b
reduction 38
a,b
Mean preop. 2.7 — 3.6 4.6 No medication changes 3.8 —
meds.
Mean meds. reduction 0.7 — 0.5 0.6 0 —
a
Laser duration (s) 4, 6, or 8 8 6 6 4 6 3–4
b
6
a
% CME 0 1.9 3.3 0 0 — 0
b
4
a
% SPK 13 — 40 — 25 — 25
b
39
a
% AC 20% 0% 33 65 25 — 0
b
infl. 25
Data ranging from 2011–2017 on the efficacy and safety of ECP in a wide range of populations. PP, prospective; F/U, follow-up; preop., preoperative; meds., glaucoma medications; Hyp., hypotony; Phth., phthisis; CME, cystoid
macular edema; SPK, superficial punctate keratitis; AC infl., transient anterior chamber inflammation; POAG, primary open-angle glaucoma; OAG, open-angle glaucoma; agroup treated for 4 seconds, bgroup treated for 6 seconds.
SEMINARS IN OPHTHALMOLOGY
271
272 N. ANAND ET AL.
IOP lowering effect and few complications reported with 360°
treatment warrant further investigation.
In addition to phacoemulsification, ECP can be combined
with other MIGS that increase aqueous humor outflow.
Simultaneously increasing aqueous outflow and decreasing
aqueous production may potentially confer additional reduc­
tions in IOP and glaucoma medication usage. For example, the
ICE procedure—combined iStent, phacoemulsification, and
ECP— has been compared to phacoemulsification and iStent
alone.61 Specifically, Ferguson et al. reported a statistically sig­
nificant greater reduction (7.49 mmHg) in the ICE group
compared to the iStent and phacoemulsification group
(4.66 mmHg) after 12 months. Both groups achieved statisti­
cally significant reductions in glaucoma medications after
12 months. However, despite similar numbers of medications
at baseline in both groups, the reduction in medications at
12 months was significantly greater in the iStent and phacoe­
mulsification group compared to the ICE group: 1.78 to 1.10
and 1.68 to 0.63, respectively.77
ECP and phacoemulsification can also be combined with
Kahook dual blade (KDB) goniotomy in what has been named
the PEcK procedure. In a similar manner to ICE, this dual-
mechanism procedure simultaneously reduces aqueous pro­
duction and increases aqueous outflow. Preliminary, unpub­
lished data by Klug et al. suggests that this combination
procedure reduced IOP by 5.6 mmHg, and glaucoma medica­
tion use by 1.9, 6 months postoperatively. Average treatment
parameters included 195º (120–250º) of ciliary process treated
with 0.36 (0.2–0.55) W of power, and 4–5 clock hours of
goniotomy. Mild hyphema, corneal edema, and anterior cham­
ber inflammation were present, but all resolved spontaneously
within 3 months postoperatively. No serious complications
were observed.
High-intensity Focused Ultrasound Cyclodestruction
(HIFU)
Transscleral ultrasound cyclodestruction utilizes focused ultra­
sound beams rather than laser energy to induce cyclodestruc­
tion of the ciliary body epithelium. HIFU primarily reduces
IOP by decreasing aqueous humor production following ther­
mic necrosis of the ciliary body epithelium. Unlike its laser
counterparts, ultrasound absorption does not depend on the
pigmentation of the ciliary body epithelium. The deposition of
energy is therefore better controlled, avoiding much of the
concern about collateral damage to surrounding tissues.78
In addition to its effects on the ciliary body, HIFU has been
demonstrated to induce significant modifications to the scleral
and conjunctival anatomy, thereby increasing uveoscleral out­
flow through the supraciliary and suprachoroidal spaces.79,80
Specifically, Rouland and Aptel observed an increase in aqu­
eous humor outflow due to a wider uveoscleral pathway, visible
in ultrasound biomicroscopy pictures.79 Moreover, using ante­
rior segment optical coherence tomography and in vivo con­
focal microscopy, Mastropasqua et al. observed increases in
intrascleral hyporeflective spaces and conjunctival microcysts
at the site of treatment, suggesting aqueous humor passage
through the sclera and the conjunctiva.80
In the 1980s, HIFU technology was proposed as
a potentially safer alternative to ciliary body destruction with
an early commercially available device (Therapeutic
Ultrasound System; Sonocare, Inc., Ridgewood, NJ).
However, due to its large apparatus, operating times up to
2 hours, and poor safety profile, the device was not widely
adopted and interest in the technique progressively
waned.81,82 More recently, interest in ultrasound technology
for glaucoma treatment has been revived with the development
of a miniaturized HIFU device, the EyeOP1 (EyeTechCare,
Rillieux-la-Pape, France).
The EyeOP1 device allows for a safer, faster, and more
precise procedure. It is a ring comprised of six active piezo­
electric transducers operating at a frequency of 21 MHz to
achieve a rapid, selective coagulation of the ciliary body.79 It
has a particularly favorable safety profile, as ultrasound induces
injury with much more controlled energy absorption than the
laser modalities.3,83,84 HIFU also involves a much slower tem­
perature rise compared to TS-CPC, thus eliminating the risks
involved with tissue explosion.3
The initial pilot study using HIFU and the EyeOP1 device
examined patients with refractory glaucoma and limited visual
potential.84 In this study, mean IOP was reduced by 13 mmHg
6 months postoperatively, and surgical success (IOP reduction
≥ 20% and IOP > 5 mmHg) was obtained in 83% of patients.
A follow-up study demonstrated that HIFU was also an effec­
tive treatment option for POAG patients with much less
advanced disease, displaying an average 7 mmHg (24%) reduc­
tion in IOP 12 months postoperatively.79 More recently, these
same authors have reported reductions in IOP ranging from
7.5 to 8.6 mmHg (32–33%) in similar cohorts of patients with
mild-to-moderate disease.79,83 Average reductions in glaucoma
medication burden across these studies range from 0 to 0.7.84
Similar to its laser counterparts, HIFU may be more suc­
cessful in particular subsets of glaucoma patients and with
optimal treatment settings. Specifically, Giannaccare et al.
observed an average 9.9 mmHg reduction after 6 months in
patients with various types of refractory glaucoma.85 However,
the authors reported that the average percent reduction in IOP
was highest in eyes with angle-closure glaucoma (38%), fol­
lowed by those with NVG (26.2%), and lastly open-angle
glaucoma (20%).85
Additionally, Giannaccare et al. performed a sub-analysis
regarding the ultrasound exposure time. Patients were treated
with either 4, 6, or 8 seconds of ultrasound.85 Those that under­
went 8 seconds of treatment showed a significantly greater reduc­
tion in IOP than the other two groups. A similar dose-escalation
study was performed examining 4 versus 6 seconds of exposure
time. After 12 months, Denis et al. did not find a significant
difference in the success rates (greater than 20% IOP decrease
and IOP > 5 mmHg) of patients that underwent 4 versus 6 sec­
onds of treatment. Perhaps a more substantial increase in expo­
sure time, such as 8 seconds, is needed to reveal dose effects.
All studies outlined in Table 4 report similar rates of post­
operative complications following HIFU. In a discussion of the
pilot, first and second multi-center, and current studies, Aptel
et al. described the most common postoperative
complications.85–88 No major intra or postoperative complica­
tions such as prolonged hypotony or phthisis occurred in any

study. Superficial punctate keratitis was the most common
complication, observed up to 46.4% of the time. Transitory
cases of CME and anterior inflammation were also observed.
Moreover, visual acuity remained stable across all studies.86 In
sum, while HIFU is yet to be available in the United States, its
success abroad highlights the promise of this technology in
safely and effectively treating a variety of glaucoma patients.
CONCLUSION
With advances in technology, cyclodestruction has evolved
from a procedure that used to be reserved for refractory glau­
coma, to one that can be offered to almost any glaucoma
patient under the right circumstances. The exciting advances
in the realm of cyclodestruction have allowed for favorable IOP
reduction with minimal postoperative complications, owing to
more targeted destruction of the ciliary body.
It is our belief that the role of cyclodestruction in glaucoma
treatment will only continue to expand, as it can be used in
conjunction with other known IOP-lowering procedures, from
phacoemulsification and MIGS, to incisional glaucoma sur­
gery. Currently, there are no large randomized clinical trials
published to help guide clinicians’ use of these cyclodestructive
modalities. As the use of cyclodestructive procedures continues
to expand, it will become increasingly imperative to set forth
guidelines outlining optimal patient selection and cyclodes­
tructive device settings through such trials.
DISCLOSURE STATEMENT
The authors of this paper have no relevant conflicts to disclose.
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