Outcomes of Micropulse Transscleral Cyclophotocoagulation in Uveitic Glaucoma

Abstract

Purpose

To report a case series of patients with uveitic glaucoma who were treated with micropulse transscleral cyclophotocoagulation (mpCPC).

Methods

This retrospective case series consists of patients from the University of Colorado Sue Anschutz-Rodgers Eye Center from 2015 to 2020 who were diagnosed with uveitic glaucoma. Information collected includes demographic data, type of uveitis, glaucoma severity, and prior glaucoma surgeries. Pre- and postoperative best corrected visual acuity, intraocular pressure (IOP), glaucoma medications, degree of inflammation, and uveitis therapies were included up to 36 months postoperatively. Surgical success was defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Uveitis success was defined as the absence of persistent anterior uveitis at 3 months.

Results

Six patients and seven eyes with uveitic glaucoma underwent mpCPC. Types of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis. Two of six eyes (33.3%) at 6 months and three of five eyes (60%) at 1 year achieved surgical success. Around 6 months postoperatively, two out of seven eyes (28.6%) required Ahmed glaucoma valve placement (n = 1) or repeat mpCPC (n = 1). One eye (14.3%) required phacoemulsification with goniotomy followed by an Ahmed glaucoma valve 18 months after mpCPC. There were no cases of persistent anterior uveitis, hypotony, or phthisis after mpCPC in this cohort.

Conclusions

Micropulse transscleral cyclophotocoagulation may safely reduce intraocular pressure in some patients with uveitic glaucoma without exacerbation of intraocular inflammation. Multiple treatments may be required to achieve longer-term success.

Key Summary Points

Why carry out this study?

Uveitic glaucoma (UG) is associated with worse visual outcomes, requiring multiple therapeutic approaches, with high rates of complications and inadequate responses.

The efficacy and safety of micropulse transscleral cyclophotocoagulation (mpCPC) was investigated, considering its theoretical advantages in reducing postoperative complications while still offering intraocular pressure control.

There are currently no reports in the literature looking at the use of mpCPC in UG.

What was learned from the study?

MpCPC offers a viable surgical option for patients with UG, particularly those at higher risk of postoperative inflammation or those who have had previous surgical failures.

The study findings also highlighted the importance of careful preoperative and perioperative management.

Introduction

Ocular hypertension (OHTN) and glaucoma are common complications of uveitis and its treatment and are associated with worse visual outcomes [1, 2]. In adults with non-infectious uveitis, the annual incidence rates of intraocular pressure (IOP) greater than 21 mmHg and 30 mmHg are 14.4% and 5.1%, respectively [3]. Uveitic glaucoma (UG), defined as optic neuropathy resulting in visual field defects in the setting of OHTN and uveitis, affects approximately 20% of patients with chronic uveitis [3, 4].

There are several mechanisms by which OHTN can occur in eyes with uveitis. It can occur as a direct result of inflammation, which can be more common in infectious uveitis and sarcoidosis-associated uveitis [4, 5]; as a consequence of corticosteroid therapy; or due to anatomical changes within the anterior chamber. Hogan et al. histologically examined enucleated human eyes with histories of herpetic keratouveitis and glaucoma and found edematous trabecular filaments with inflammatory cells and fibrin blocking outflow channels [6]. There is some thought that the increased vascular permeability that occurs during acute inflammation may also lead to greater aqueous production [7]. Approximately 30% of patients with uveitis can develop OHTN from corticosteroid use [1, 8]. Patients with a pre-existing history of primary open-angle glaucoma (POAG) or a family history of glaucoma appear to be at higher risk for this complication [9]. The mechanism by which corticosteroids cause OHTN is multifactorial, but it is generally recognized that corticosteroids induce morphological changes in the trabecular meshwork, leading to decreased aqueous outflow [10]. Additionally, anatomic changes such as formation of peripheral anterior synechiae, posterior synechiae leading to iris bombe, and uveal effusions causing anterior rotation of the ciliary body can lead to OHTN or UG [11, 12].

Multiple therapeutic options are available for managing UG, with topical IOP-lowering therapy as the first-line treatment. However, about 30% of UG cases do not fully respond to maximal medical therapy, necessitating further interventions [13]. Success rates of selective laser trabeculoplasty (SLT) and trabeculectomy in UG are generally lower compared to POAG [14–16]. However, glaucoma drainage devices (GDD) and EX-PRESS shunt (Alcon Laboratories, Fort Worth, TX, USA) have shown comparable success rates in patients with UG and POAG [17, 18]. Additionally, minimally invasive glaucoma surgery (MIGS), including goniotomy with the Kahook Dual Blade (KDB), has been shown to be effective [19, 20].

Another treatment option includes continuous wave transscleral cyclophotocoagulation (cwCPC), which offers the advantage of not requiring incisional surgery. A laser probe is applied to the sclera and transmits energy to the ciliary body resulting in coagulative necrosis and decreased aqueous production. There are a few reports of cwCPC that demonstrate similar IOP reduction in UG compared to other etiologies of glaucoma [21, 22]. However, cyclophotocoagulation (CPC) has been considered as a last resort treatment option for glaucoma, and particularly UG, because of the increased risks of hypotony, decreased vision, persistent postoperative inflammation, and phthisis bulbi [23]. A large retrospective study by Murphy et al. found that out of 263 eyes with refractory glaucoma, those with UG had the highest rate of postoperative hypotony (18.8%) after cwCPC compared to other types of glaucoma. They also reported persistent uveitis in two of 16 eyes with UG (12.5%) [24].

In contrast to cwCPC, micropulse CPC (mpCPC) utilizes rest periods between the delivery of micropulses of diode laser energy, resulting in an overall reduction in laser activity time and decreased damage to adjacent tissues as compared to cwCPC [25–29]. Studies comparing mpCPC to cwCPC in non-UG found similar efficacy in IOP control, but with mpCPC resulting in lower rates of hypotony, visual acuity decrease, scleral thinning, phthisis bulbi, and less prolonged postoperative AC inflammation [23, 25, 30]. No prior studies have evaluated the use of mpCPC in chronic UG, but given these relative benefits, we hypothesized that mpCPC can be of particular utility in eyes with UG that are more prone to postoperative inflammation and hypotony.

Methods

A retrospective chart review was performed on all patients who underwent mpCPC at the University of Colorado Sue Anschutz-Rodgers Eye Center for treatment of UG between January 1, 2015 and December 31, 2020. The study received approval from the Colorado Multiple Institutional Review Board (COMIRB# 19-0595) and all research conformed to the tenets of the Declaration of Helsinki and its later amendments. Patient consent was not required for the review of charts.

The following data were collected for each patient eye: demographics, severity of glaucoma, prior glaucoma surgeries, IOP goal as determined by the treating glaucoma specialist, and uveitis classification as determined by the treating uveitis specialist. Decision to perform mpCPC was made by the treating glaucoma specialist. Indications for mpCPC were to treat IOP above goal and/or glaucoma progression for patients who were refractory to multiple incisional glaucoma surgeries (case 2, 3, 4, 7) or who were poor candidates for incisional surgery because of the severity of their ocular surface disease (case 5, 6). In case 1, incisional glaucoma surgery was avoided as a result of social circumstances. Pre- and postoperative data included best corrected visual acuity (BCVA), IOP measured by Goldmann applanation tonometry, number of topical IOP-lowering medications, uveitis therapies—including topical, local, and systemic corticosteroids, and systemic immunomodulatory therapy (IMT)—and grading of AC and vitreous inflammation using the Standardization of Uveitis Nomenclature (SUN) grading system [31]. Data was collected until last available follow-up, or until additional glaucoma surgery other than mpCPC was performed, whichever occurred first.

Primary glaucoma outcomes consisted of surgical success, defined as an IOP reduction of 30% with achievement of IOP goal using the same number of glaucoma medications or less at 6 months or 1 year. Secondary glaucoma outcomes included number of medications and surgical success at other time points up to 36 months. The degree of postoperative inflammation was reviewed to determine whether patients met the definition of persistent anterior uveitis (PAU). As designated by the SUN Working Group [31], PAU was defined as (1) a grade of at least 0.5+ for anterior chamber cell; (2) requirement of additional steroid therapy at or beyond 3 months postoperatively; and (3) no other cause found other than postoperative state [32].

MpCPC was performed following the manufacturer’s instructions: a micropulse laser probe (Iris Medical Instruments, Mountain View, VA, USA) was applied with firm pressure and moved in a continuous painting motion along the superior and inferior limbus, avoiding the 3 and 9 o’clock meridians, using 1500–2000 mW for a duration of 90 s with a duty cycle of 31.3%.

Typical postoperative course consisted of prednisolone acetate drops every 4 h for 1 week followed by a steroid taper that was determined by the treating physician according to the level of inflammation. Additional perioperative medications were determined by the treating physicians as needed.

The definition of hypotony used was ocular pressure that is low enough to result in structural and functional changes leading to reduced vision [33]. Phthisis bulbi was defined as end-stage eye disease characterized by shrinkage and disorganization of the eye resulting in functional loss [34].

Results

Seven eyes from six patients were included in this study. Mean age was 61.5 years, ranging from 40 to 89 years. Three patients were female. Severity of glaucoma ranged from mild (n = 1) to moderate (n = 1) to severe (n = 5). All but one eye had undergone prior laser or surgical glaucoma treatments, which included SLT (n = 2), goniotomy (n = 3), endoscopic cyclophotocoagulation (ECP) (n = 1), Ahmed glaucoma valve (AGV) (n = 3), and trabeculectomy (n = 1). Preoperative IOP ranged from 14 to 42 mmHg on medical therapy with a mean IOP of 31 mmHg. Classifications of uveitis included idiopathic anterior uveitis, HLA-B27-associated anterior uveitis, varicella zoster virus anterior uveitis, juvenile idiopathic arthritis-associated chronic anterior uveitis, lichen planus-associated intermediate uveitis, and sarcoidosis-associated panuveitis (Table 1). Four eyes (57.1%) were receiving IMT at baseline prior to mpCPC, two eyes (28.6%) were on topical steroids, and one eye (14.3%) was off all treatment. At the time of mpCPC, six out of seven eyes (85.7%) were quiet on clinical exam. One out of seven eyes (14.3%) had 1+ anterior chamber cell preoperatively (case 6). Additional preoperative steroids were prescribed on a case by case basis depending on degree of preoperative inflammation. The patient (case 6) with 1+ preoperative anterior chamber cell was started on a preoperative methylprednisolone dose pack and received intraoperative intravenously administered Solumedrol as well as a subtenons triamcinolone injection. Another patient (case 7) with rare anterior chamber cell was started on orally administered prednisolone 30 mg daily 2 days prior to mpCPC that was tapered postoperatively. The patient with varicella zoster virus anterior uveitis was unable to tolerate orally administered acyclovir (case 4) and received a preoperative (3 days prior) and intraoperative intravitreal injection of ganciclovir.

Table 1.

Demographics, preoperative, and postoperative data of eyes with uveitic glaucoma treated with micropulse transscleral cyclophotocoagulation

Demographics		Glaucoma characteristics		Uveitis characteristics		Preoperative findings			Postoperative findings at final visit			Goal IOP	Additional surgery	Follow-up (months)
Case	Eye	Glaucoma severity	Previous glaucoma surgeries	Uveitis type	Preop uveitis regimen	VA	IOP	Med	VA	IOP	Med
1	L	Mild	None	HLA-B27-associated anterior uveitis	MTX	20/200	42	3	20/50	16	2	< 21	Phaco/ goniotomy, then AGV (POM 17)	20
2	R	Severe	Goniotomy, AGV	Sarcoidosis-associated panuveitis	Infliximab	20/25	36	6	20/20	14	4	< 18	AGV (POM 6)	28
3	L	Severe	Phaco/ECP, AGV	Idiopathic anterior uveitis	None	20/30	14	2	20/50	20	2	< 18		12
4	R	Moderate	AGV	Varicella zoster virus anterior uveitis	Topical steroids	20/25	28	3	20/30	14	2	< 18		12
5	L	Severe	SLT, Goniotomy	Lichen planus-associated intermediate uveitis	Tacrolimus	20/300	41	3	LP	3	4	< 15	mpCPC (POM 5)	56
6	R	Severe	Goniotomy	Lichen planus-associated intermediate uveitis	Tacrolimus	20/40	26	4	3/200	8	4	< 15		56
7	R	Severe	SLT, trab	JIA-associated panuveitis	Topical steroids	20/100	33	4	20/300	14	0	< 21		29

AGV Ahmed glaucoma valve, ECP endocyclophotocoagulation, IOP intraocular pressure, JIA juvenile idiopathic arthritis, LP light perception, mpCPC micropulse transscleral cyclophotocoagulation, MTX methotrexate, POM postoperative month, SLT selective laser trabeculoplasty, trab trabeculectomy, med medications, VA visual acuity

Two of six eyes (33.3%) at 6-month follow-up and three of five eyes (60.0%) at 1 year postoperatively achieved surgical success. With regards to secondary glaucoma outcomes, three eyes achieved surgical success at 1 month, four eyes achieved surgical success at 3 months, two eyes achieved surgical success at 18 and 24 months, and one eye achieved surgical success at 36 months. One eye (case 7) had a medication reduction from four medications to zero medications at all time points after mpCPC and maintained surgical success for the entirety of their follow-up. One eye (case 1) had a medication reduction from five to four medications for 6 months after mpCPC, and this patient was able to discontinue their preoperative acetazolamide 1 month after mpCPC. The other five eyes did not have a reduction in the number of medications at any time point.

Three out of seven eyes (42.8%) required additional glaucoma intervention during the follow-up period. Three eyes required additional surgical intervention: one had an AGV (n = 1), a second had repeat mpCPC (n = 1) around 6 months postoperatively, and a third required phacoemulsification with goniotomy followed soon after by an AGV at 18 months after mpCPC. One patient (case 5) maintained surgical success throughout the entire 36-month period with re-treatment with mpCPC at postoperative months 5 and 9. Three of the four eyes that did not require additional intervention achieved surgical success at 12 months and beyond (Table 2).

Table 2.

Preoperative and postoperative intraocular pressure and medications

Case	Preop IOP (meds)	Goal IOP	Laser settings	POM 1 IOP (meds) % IOP reduction from preop	POM 3 IOP (meds) % IOP reduction from preop	POM 6 IOP (meds) % IOP reduction from preop	POM 12 IOP (meds) % IOP reduction from preop	POM 18 IOP (meds) % IOP reduction from preop	POM 24 IOP (meds) % IOP reduction from preop
1	42 (5)	< 21	2000 mW 90 s	21 (4) 50.0%	13 (4) 69.0%	14 (4) 66.7%		47 (5)* 0.0%
2	36 (6)	< 18	1500 mW 180 s			36 (6)* 0.0%
3	14 (2)	< 12	1500 mW 180 s				20 (2) 0.0%
4	28 (2)	< 18	2000 mW 180 s	11 (2) 60.7%		20 (2) 28.6%	14 (2) 50.0%
5	41 (4)	< 15	2000 mW 90 s	26 (4) 36.6%	12 (4) 70.7%	12 (4)* 70.7%	9 (4) 78.0%	14 (4) 65.8%	12 (4) 70.7%
6	26 (4)	< 15	2000 mW 90 s	9 (4) 65.4%	8 (4) 69.2%	38 (4) 0.0%	8 (4) 69.2%	14 (4) 46.1%	10 (4) 61.5%
7	33 (4)	< 21	2000 mW 90 s	8 (0) 75.7%	11 (0) 66.7%	14 (0) 57.6%	10 (0) 69.7%	6 (0) 81.8%	12 (0) 63.6%

IOP intraocular pressure, preop preoperative, POM postoperative month, meds medications, mpCPC micropulse transscleral cyclophotocoagulation

*Underwent additional intervention. Postoperative IOP after additional surgery other than mpCPC was not included in analysis

There were no cases of PAU at 3 months. There were no IOP spikes (defined as IOP > 30 mmHg) in the first 3 months after mpCPC for all eyes, nor were there any cases of hypotony or phthisis in any eyes throughout the duration of the follow-up period.

Discussion

Uveitic glaucoma is a known complication of uveitis and can be a source of visual morbidity for patients who often require a combination of medical, laser, and surgical interventions to prevent vision loss. Traditionally, cwCPC has been a last resort treatment option due to the risk of hypotony, postoperative inflammation, decreased vision, and phthisis bulbi. MpCPC, in contrast, may offer similar IOP control as cwCPC with lower rates of hypotony and postoperative inflammation.

In this case series, 60% of patients achieved surgical success at 1 year without significant complications. This success rate is similar to a retrospective cohort study of 214 patients with POAG, chronic angle-closure glaucoma, neovascular glaucoma, and normal tension glaucoma, where 67.8% of eyes attained a 20% or greater reduction IOP 1 year after undergoing mpCPC [35]. Although our success rate for eyes with UG is slightly lower, it involved a more stringent outcome of at least a 30% reduction in IOP. The 1-year success rate of 60% in our series is also comparable to that of other glaucoma interventions in UG, such as SLT (46.7%) [14], trabeculectomy (62–81%) [15, 16], KDB goniotomy (62.5%) [20], and GDD (50–94%) [36]. It is important to note, however, that definitions of success vary across studies.

Historically, cwCPC has been reserved for eyes as a last resort treatment after prior failed glaucoma surgeries due to the aforementioned risks. Heinz et al. looked at cwCPC as a primary surgical intervention for a group of 21 eyes with UG associated with JIA and found that cwCPC may have a lower success rate as a primary surgical treatment compared to other surgical options for glaucoma [37]. However, in our case series, one patient (case 1) with mild glaucoma and HLA-B27-associated anterior uveitis underwent mpCPC as a primary intervention and achieved success for 6 months. Future research into mpCPC as a primary intervention could be valuable for the uveitis population, considering the high risk of postoperative inflammation following incisional glaucoma surgery, although re-treatment may often be necessary. The need for re-treatment has been reported in studies looking at both cwCPC and mpCPC [24, 35, 37]. In this series, another patient (case 5) maintained surgical success over the entire 36-month period as a result of re-treatments at postoperative months 5 and 9. Further studies are required to better understand the risks and benefits of re-treatment in mpCPC, particularly for eyes with UG.

In this case series, no patients developed PAU after mpCPC, likely as a result of most patients being on chronic systemic immunosuppression with well-controlled inflammation prior to mpCPC. The one patient (case 6) with 1+ anterior chamber cell prior to the procedure received additional preoperative and intraoperative steroids and did not experience PAU postoperatively. This underscores the importance of aggressive perioperative steroid therapy in managing eyes with active preoperative inflammation. Additionally, there were no cases of hypotony or phthisis bulbi after mpCPC in this series. Although this is not a directly comparative study, the absence of PAU, hypotony, and phthisis highlights potential advantages of mpCPC over cwCPC, which has been reported to have rates of PAU as high as 12.5% and rates of hypotony as high as 18.8% [24].

This study has several limitations, including its retrospective nature and a small sample size, with limited follow-up for some patients due to the COVID-19 pandemic. Slight variability in laser settings among different patients may have also influenced the outcomes. Additionally, this series included a diverse group of patients with various types of uveitis, ranging from anterior to panuveitis, and glaucoma severity from mild to severe. Larger prospective studies are necessary to more thoroughly evaluate the outcomes and complication rates of mpCPC in eyes with UG, taking into account subcategories of glaucoma severity and uveitis classifications. This case series demonstrates surgical success in some patients with UG with no significant complications after mpCPC. MpCPC may be a safe option to consider for eyes with UG who may be at risk for increased postoperative inflammation and hypotony with other surgical modalities or have had failed previous surgeries, but these patients may also require re-treatment with mpCPC for longer-term success.

Author Contributions

Julia L Xia (data acquisition and manuscript writing), Monica K Ertel (data acquisition and manuscript editing), Amit K. Reddy (manuscript editing), Alan G. Palestine (manuscript editing), Arthur J Stanley (manuscript editing), Cara E Capitena Young (manuscript editing), Mina B Pantcheva (project conception and manuscript editing).

Funding

This study was supported by an unrestricted research grant to the Department of Ophthalmology from Research to Prevent Blindness, Inc. No funding or sponsorship was received for publication of this article.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Mina Pantcheva and Alan Palestine are Editorial Board members of Ophthalmology and Therapy. M. Pantcheva and A. Palestine were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Julia Xia, Monica Ertel, Amit Reddy, Arthur Stanley, and Cara Capitena Young have no conflicting interests.

Ethical Approval

The study received approval from the Colorado Multiple Institutional Review Board (COMIRB# 19-0595) and all research conformed to the tenets of the Declaration of Helsinki and its later amendments. Patient consent was not required for the review of charts.