Clinical trial NCT04232982: The Role of Transscleral Cyclophotocoagulation in Patients Undergoing a Boston Keratoprosthesis
Official title: The Role of Transscleral Cyclophotocoagulation in Patients Undergoing a Boston Keratoprosthesis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Glaucoma
Eye Diseases
Cornea Disease
Keywords: Boston keratoprosthesis
Transscleral cyclophotocoagulation
Micropulse transscleral cyclophotocoagulation
G-Probe Transscleral cyclophotocoagulation
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Fonds de recherche en ophtalmologie de l'Université de Montréal
First posted: 2020-01-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, single blinded study with two interventional arms and one historical cohort as controls.
Primary purpose: PREVENTION

Brief summary: The Boston keratoprosthesis (KPro) is a special plastic device that is used to replace a sick cornea (transparent part of the eye, in front of the iris) in order to restore vision in patients who have failed traditional corneal transplants or have a very poor prognosis of success.

Glaucoma is a chronic disease which causes optic nerve damage secondary to high pressure inside the eye and could lead to vision loss in the long term. Glaucoma is highly prevalent in patients who require a KPro and even more after their procedure.

In order to decrease the intra-ocular pressure, surgeons can use multiple eyedrops. Unfortunately, following the KPro surgery, eyedrops lose their efficiency because they are less absorbed by the eye.

The transscleral cyclophotocoagulation (TS-CPC) is a laser treatment used in advanced refractory glaucoma. This laser helps decrease the intra-ocular pressure and have a better control of the disease. There are different methods of laser transmission, including the continuous transmission (G-Probe) and the micro-pulsation method (Micopulse). Given the high prevalence of glaucoma in patients receiving a KPro, the investigators are studying the effect of giving the TS-CPC treatment prophylactically to patients before their Boston keratoprosthesis.

Our hypothesis is that prophylactic TS-CPC will decrease glaucoma progression as well as the risks of developing glaucoma following the Boston keratoprosthesis .

METHOD The investigators aim to recruit twenty (20) patients who are scheduled to receive Boston KPro. Participants will be randomized into two groups: 1) Groupe 1 will receive a prophylactic treatment of transscleral cyclophotocoagulation a G-Probe. 2) Groupe 2 will receive a prophylactic treatment of transscleral cyclophotocoagulation with a micropulse transmission (MicroPulse). The patients will receive their laser treatment by a glaucoma specialist 4 to 8 weeks before their KPro surgery. One week following their laser treatment, the participants will be examined by their glaucoma specialist.

Following their KPro surgery, patients will have a follow-up at day-1, weeks 1 and 2, months 1 and 3, then every 4 to 6 months for 5 years. Additional non-invasive glaucoma tests will be performed twice during the first 3 months following the surgery and will be repeated every 4-6 months. Visual acuity results, the visual field tests and rates of post-operative complications will be compared between the different groups.

Detailed description: RATIONAL OF THE STUDY

The Boston keratoprosthesis (KPro) type is an artificial cornea used to restore vision in patients who have failed traditional corneal transplants or have a poor prognosis of success. A number of innovations have improved the postoperative prognosis since its first creation. However, glaucoma is still one of the leading causes of significant vision loss following the surgery, despite the clarity of the anterior segment.

The prevalence of glaucoma in KPro candidates is highly elevated (36-76%). Indeed, pathologies requiring a Boston keratoprosthesis and history of previous ocular surgeries are themselves risk factors for glaucoma. Furthermore, the corneal opacity and irregularities lead to poor visualization of the optic nerve and incorrect intra-ocular pressure (IOP) measurements. Thus, the prevalence of glaucoma preoperatively is most likely underestimated.

Following the KPro, the increase of IOP or the new diagnosis of glaucoma is estimated between 8 and 35% per year. Additionally, the IOP cannot be determined by the traditional tonometry and is estimated by digital palpation. This leads to treatment follow-up being difficult and limited. For those reasons, it is suggested by experts to insert a glaucoma drainage device during the Boston keratoprosthesis surgery for all patients.

In perspective, the transscleral cyclophotocoagulation (TS-CPC) is one of the cyclodestructive procedures used for severe glaucoma. It leads to destruction of the ciliary body epithelium and reduction of aqueous humour production which can reduce the IOP.

Different transmission techniques are available and include the Micropulse diode laser (MP-TSCPC, IRIDEX IQ810 Laser systems, Mountain View, CA) and the semiconductor system with the G-Probe (IRIS Oculight SLx, IRIS Medical Inc., Mountain View, CA). These two systems differ by their transmission method, which is via pulsation waves (Micropulse) or continuous transmission (G-Probe).

In the literature, there are limited studies who have examined the role and the impact in the long term of the transscleral cyclophotocoagulation in patients receiving a Boston keratoprosthesis.

HYPOTHESIS Our hypothesis is that prophylactic transscleral cyclophotocoagulation will decrease glaucoma progression as well as the risks of developing glaucoma following the Boston keratoprothesis.

OBJECTIFS Our primary objective in this study is to examine if the use of prophylactic transscleral cyclophotocoagulation treatment with the G-Probe or the Micropulse (MP-TSCPC) methods prophylactically has a positive impact in the diagnosis of the progression of glaucoma in patients receiving a keratoprosthesis, without additional glaucoma surgery.

For more information on our primary and secondary criteria, please see in the below sections.

METHODS

Study design: This is a prospective, randomized, single blinded trial of patients receiving a KPro at the CHUM, with a historical cohort as a control group.

Recruitment: Patients will be recruited by their cornea surgeons, risks and benefits of the studies will be explained. An informed consent form will be obtained.

Prospective Branch of the Study

The study will include twenty (20) patients in the prospective branch of this study in the spam of two (2) years. Patients will receive a cyclophotocoagulation treatment 4-6 weeks before their Boston Keratoprosthesis surgery. Patients will be randomly assigned to either one of the TS-CPC treatment (Micro-Pulse or G-Probe).

Following the KPro surgery, if any additional glaucoma surgery is necessary (including the insertion of a glaucoma drainage device), these treatment options will be offered to the participants, as per standard of care.

For more information regarding the intervention's arms, see the section below.

Control group- cohort study

A control group composed of a historical cohort of ten (10) patients who did not receive any glaucoma surgery or TS-CPC 3 months before their Boston keratoprosthesis will be included in the historical cohort.

Indeed, when reviewing the literature, given the high prevalence of glaucoma in this population and the current recommendation of inserting a glaucoma drainage device (GDD) in patients receiving a KPro, it would be ethically non-acceptable to have a prospective group without any prophylactic treatment. Moreover, given the fact that we are going to compare between the different groups the need of additional glaucoma surgery, we cannot include a control group in which patients will receive a tube before or during their KPro surgery.

Follow-up

Patients will be followed by a glaucoma specialist 1 week following the TS-CPC treatment, as per standard of care.

After the Boston KPro, postoperative follow-up will be organized as per standard of care and will be similar across the three groups. Patients will be seen at postoperative day-1, weeks 1 and 2, months 1 and 3, then every 4 to 6 months for 5 years. During those visits, visual acuity as well as IOP and a complete slit-lamp exam will be performed. Furthermore, an optic nerve optical coherence tomography (OCT) will be performed and two visual fields test (SITA-Fast and Goldman) will be performed during the first and third month post-KPro. These particular tests will be repeated every 4-6 months, for a period of 5 years.

STATISTICAL ANALYSIS

Sample size

The investigators used the G-Power software to determine our sample size. Given that our primary endpoint is a continuous variable, the investigators used a student t-test with a power of 90%, an alpha of 0,05 and an effect size of 2,6. For the effect size, it was determined based of a difference clinically significant of 20% with the progression of the cup-to-disc ratio in KPro patients. Of note, this study only included the average and not the standard of deviation. The investigators assumed that the standard of deviation increases proportionally to the mean.

Statistical analysis Binary variable will be compared across the three groups using a chi square test. For continuous variable, such as the cup-to-disc ratio progression and the thinning of the Retinal Nerve Fiber Layer (RNFL), an ANOVA test will be performed. A test using an alpha parameter of 0,05 will be judged as clinically significant.

The visual acuity will be expressed in LogMar and its evolution will be compared across the three groups. The investigators will compare the rate of no light perception (NLP) between the three groups. Given that a previous study showed a 16% rate of NLP after 5 years. The investigators will consider a difference of 5% as clinically significant.

A Kaplan-Meir survival curve will be performed for: (1) the loss of light perception and (2) the need of a second intervention for glaucoma control. A Log-rank test will be performed to determine if those variables are statistically different across the groups.

Eligibility criteria: Inclusion Criteria:

* Adults patients
* Able to give an informed consent
* Capable of being followed during the study
* Candidate for the Boston keratoprosthesis type I

Exclusion Criteria:

* Patients younger than 18 years old or older than 80 years old
* Unable to give an informed consent
* Participating to another interventional glaucoma study
* Patients who received a glaucoma surgery or procedure (glaucoma drainage device or TS-CPC treatment) 3 months before their initial visit.
* Unable to wear a therapeutic contact lens secondary to eyelid malformation
* Severe Ocular surface Disease with keratinization
* Intra-ocular tumor
* Terminal Glaucoma
* Phthisis bulbi
* Ocular albinism

Primary outcomes:
measure: Cup-to-disc ratio
timeFrame: 5 years
Secondary outcomes:
measure: No light perception
timeFrame: 5 years
measure: Need of additional glaucoma intervention
timeFrame: 5 years
measure: Goldman visual field loss of 30% or more.
timeFrame: 5 years
measure: Retinal Nerve Fiber Layer thinning
timeFrame: 5 years
Other outcomes:
measure: Complications related to transscleral cyclophotocoagulation treatment
timeFrame: 5 years
measure: Complications related to the Boston keratoprosthesis
timeFrame: 5 years
Locations:
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
Study officials:
affiliation: Ophthalmology Department, Centre Hospitalier de l'Université de Montreal
name: Marie-Claude Robert, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robert MC, Pomerleau V, Harissi-Dagher M. Complications associated with Boston keratoprosthesis type 1 and glaucoma drainage devices. Br J Ophthalmol. 2013 May;97(5):573-7. doi: 10.1136/bjophthalmol-2012-302770. Epub 2013 Feb 23.
citation: Vajaranant TS, Liu J, Wilensky J, Cortina MS, Aref AA. Innovative approaches to glaucoma management of Boston keratoprosthesis type 1. Curr Ophthalmol Rep. 2016 Sep;4(3):147-153. doi: 10.1007/s40135-016-0102-3. Epub 2016 Jul 26.
citation: Jabbour S, Harissi-Dagher M, Agoumi Y, Singh H, Robert MC. Cyclophotocoagulation in the Control of Glaucoma in Patients With the Boston Keratoprosthesis Type 1. Cornea. 2020 Feb;39(2):181-185. doi: 10.1097/ICO.0000000000002064.
citation: Rivier D, Paula JS, Kim E, Dohlman CH, Grosskreutz CL. Glaucoma and keratoprosthesis surgery: role of adjunctive cyclophotocoagulation. J Glaucoma. 2009 Apr-May;18(4):321-4. doi: 10.1097/IJG.0b013e3181815485.
citation: Patel S, Takusagawa H, Shen L, Dohlman C, Grosskreutz C. Long-term complications associated with glaucoma drainage devices and Boston keratoprosthesis. Am J Ophthalmol. 2012 Jul;154(1):207-8; author reply 208-9. doi: 10.1016/j.ajo.2012.02.033. No abstract available.
citation: Crnej A, Paschalis EI, Salvador-Culla B, Tauber A, Drnovsek-Olup B, Shen LQ, Dohlman CH. Glaucoma progression and role of glaucoma surgery in patients with Boston keratoprosthesis. Cornea. 2014 Apr;33(4):349-54. doi: 10.1097/ICO.0000000000000067.