Clinical trial NCT06000280: Evaluation of Retina in Patients With Glaucoma Using Topical Prostaglandins Undergoing Trabeculectomy Surgery
Official title: Evaluation of Macular Thickness in Patients With Glaucoma in Use of Topical Prostaglandin Analogue Undergoing Trabeculectomy With Mitomycin C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glaucoma
Keywords: prostaglandin analogue
macular edema
trabeculectomy
Lead sponsor: Universidade Federal de Goias
Sponsor class: OTHER
First posted: 2023-08-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, prospective and comparative clinical trial. Both the surgeon (the only one) and the technician responsible for the exams were blinded to the study groups. The patients (one or both eyes) included were from the glaucoma outpatient clinic of the Fundação Banco de Olhos de Goiás (FUBOG) or the Reference Center in Ophthalmology (CEROF) of the Federal University of Goiás (UFG) between the years 202 and 2022. All patients with glaucoma with indication for Trab with MMC and in clinical use of any PA eye drops (latanoprost, travoprost, bimatoprost or tafluprost) in the eye to be operated on for at least 6 months were considered for inclusion.

The study adhered to the principles of the Declaration of Helsinki and was authorized by the Research Ethics Committee of the UFG, under the Certificate of Presentation for Ethical Appreciation NUMBER 40055620.8.1001.5083. All those included voluntarily agreed to participate by signing the Free and Informed Consent Form.
Primary purpose: PREVENTION

Brief summary: The aim of this study was to verify whether prostaglandin analogue (PA) eye drops influence the retinal thickness of glaucomatous patients undergoing trabeculectomy (TRAB) surgery. We selected eyes of patients with glaucoma with surgical indication for TRAB who were using PA eye drops and without previous retinal alterations, from the Centro de Referência em Oftalmologia (CEROF) from the Federal University of Goiás and Fundação Banco de Olhos de Goiás (FUBOG). Patients were divided into 2 groups: the study group (SG) and the control group (CG). In the CG, the PA was suspended between 30 and 60 days before the preoperative exams were performed (maximum of 15 days before surgery for both groups). All patients included were submitted to various eye exams before the procedure, and postoperatively on 3 occasions: 1 to 3 days ("PO1"), 6 to 9 days ("PO7") and 27 to 30 days ("PO30") after surgery.

Detailed description: Purpose: The aim of this study was to verify whether topical prostaglandin analogue (PA) influence the macular thickness of glaucomatous patients undergoing trabeculectomy (TRAB) with Mitomycin C (MMC) .

Design:This is a randomized, prospective, comparative clinical trial with a single surgeon and masked to the study group.

Methods: We prospectively selected 40 eyes of patients with glaucoma with surgical indication for TRAB with MMC (0.4 mg/ml for 2 min) who were using prostaglandin analogue (PA) eye drops and without previous macular alterations, from the Centro de Referência em Oftalmologia (CEROF) from the Federal University of Goiás and Fundação Banco de Olhos de Goiás (FUBOG). The research had as inclusion criteria: patients with at least 18 years of age with Primary Glaucoma (Primary Open Angle Glaucoma, Primary Closed Angle Glaucoma, Normal Pressure Glaucoma, Pigmentary Glaucoma, Pseudoesfoliative Glaucoma), with changes in the visual field, typical defect compatible with glaucomatous lesion and/or typical anatomical impairment of the optic disc or retinal nerve fiber layer (such as Hoyt's sign, optic disc cupping ratio greater than 0.7, localized defect in the neural rima, or cupping asymmetry), who had an indication for TRAB with MMC at the physician's discretion (target IOP not established with maximum tolerable clinical medication and/or impossibility of using medication due to allergies and/or financial conditions). To be included, the operated eyes needed a reduction in IOP of at least 20% in relation to the baseline IOP in the last postoperative period (PO 30), and absence of the use of any ocular hypotensive medication. Exclusion criteria were any pathology that could interfere with the test results, such as: cataracts, corneal edema (such as leucoma, ulcers, keratopathies); poor quality of the OCT scan (signal strength ≤ 5/10); any past macular pathology (such as macular hole, diabetic maculopathy, age-related macular disease); use of diamox; advanced glaucoma with maximal therapy; advanced glaucoma with impaired fixation; any surgical complications including hypotonia (IOP \< 6 mmHg) at any assessment; performing combined cataract and glaucoma surgery; history of cataract surgery less than 6 months ago; need for surgical reintervention during follow-up for any reason; and need for reintroduction of topical antiglaucoma therapy during follow-up. Eligible volunteers were previously randomized through the website www.randomization.com into 2 groups: study group (SG) and control group (CG). The initial objective was to include 40 eyes, 20 per group.

In the SG, patients were instructed to keep using eyedrops (including PA) until the day of surgery. In the CG, patients were instructed to suspend the PA between 30-60 days after the preoperative exams were performed, which were performed a maximum of 15 days before surgery for both groups. In the CG, patients were instructed to use 01 drop of carmellose sodium 5mg/ml at the same time they used the AP before its suspension. Pseudophakic patients for more than six months were included in each group in the order of previous randomization. In the CG, patients were informed to keep the eye drops in use, and to add the other classes of ocular hypotensive drugs, if they were not using them (except miotics and oral acetazolamide), with the aim of at least remedying the loss of the ocular hypotensive effect of the PA. The individuals were evaluated, including best corrected visual acuity by the Snellen chart, slit lamp biomicroscopy (XCELL 255, Reichert Inc., Depew, NY, USA), intraocular pressure (IOP) measured in a calibrated Goldmann tonometer (CT210, Reichert Inc. , Depew, NY, USA), gonioscopy with a 4-mirror Goldman lens (Volk Optical Inc, Mentor, OH, USA), fundoscopy under mydriasis with a 78D lens (Volk Optical Inc, Mentor, OH, USA), indirect binocular ophthalmoscopy with 2.0D lens (Volk Optical Inc, Mentor, OH, USA) and Optical Coherence Tomography (OCT) with Cirrus 4000 (Zeiss Inc.), macular protocol (macular thickness and ganglion cell analysis) preoperatively ( maximum of 15 days before surgery), and postoperatively on 3 occasions: 1 to 3 days ("PO1"), 6 to 9 days ("PO7") and 27 to 30 days ("PO30"). All tests were performed by the same technician, who was trained and experienced to carry them out. All patients underwent visual field examinations (Humphrey Field, model HFA II ÿ750, Carl Zeiss-Meditec, Dublin, California, USA) prior to surgery with the Swedish Interactive Threshold Algorithm (SITA) Standard 24-2 strategy, at most up to 2 months before the procedure. Macular thickness was evaluated by spectral domain Optical Coherence Tomography (OCT) obtained using the Cirrus 4000 apparatus (Zeiss Inc.), macular scanning protocol (macular thickness and ganglion cell analysis). Calculations were made based on data from the Ganglion cell analytical program and Macular Thickness: Macular cube (6 x 6 mm - 512 A-scans x 128 B-scans centered on the fovea). The macular thickness map using the 1mm, 3mm, and 6mm circles from the Early Treatment Diabetic Retinopathy Study (ETDRS) was used to assess the thickness of the 9 subfields. The regions were designated as: parafoveal (subfields of the 3 mm rings) and perifoveal (subfields of the 6 mm rings) superior, inferior, temporal and nasal in addition to the central subfield. OCT images were excluded if the signal strength was ≤5/10, and a new scan was immediately performed. Trabeculectomy using mitomycin C consisted of opening the conjunctival base of the fornix and applying mitomycin C 0.4 mg/ml for 2 minutes, as previously described. The postoperative regimen in both groups included the use of 1% Prednisolone eye drops (Ster® União Química Farmacêutica Nacional S/A., Pouso Alegre, MG, Brazil) starting every 2 hours, with a weekly reduction for 6 weeks ( 4/4 h, followed by 6/6 h, then every 8 h, 12/12 h and once a day), Moxifloxacin eye drops (Vigamox®, AlconLabs, Fort Worth, TX, USA) every 6 h for 10 days.

Statistical analysis was performed using the Statistical Package for Social Sciences program (IBM Corporation, Armonk, USA) version 26.0. The characterization of the sample was performed using absolute frequency, relative frequency, mean, standard deviation, median, minimum and maximum. Student's t test and Pearson's chi-square test were applied to the distribution of profile and macular parameters in groups with and without prostaglandin. Data normality was verified using the Shapiro-Wilk test. The delta and percentage variation were calculated at PO1, PO7 and PO30 in relation to the preoperative period. Correlation analysis was performed between thickness deltas with visual field Mean Deviation (MD) and IOP in groups with and without prostaglandin, weighted the effect of lens classification (partial correlation). The significance level adopted was 5% (p \< 0.05).

Initially, 40 eyes were randomly assigned to the study, of which 17 were excluded because they did not meet the eligibility criteria for the study postoperatively. Among these, 4 patients did not undergo OCT at PO1, 4 patients did not undergo OCT at PO7, 2 patients did not undergo OCT at PO30, 1 patient had a signal ≤ 5/10 of OCT at all visits, even with several repetitions of the examinations, 3 patients underwent surgical reintervention during follow-up (suture dehiscence), 2 patients had hypotonia, finally 1 patient did not present IOP reduction by at least 20% of baseline. Thus, as there was a significant reduction in the number of patients initially estimated for the sample, a new randomization was performed, using the same initial randomization process described above to achieve this objective. In the end, the evaluated sample consisted of 40 eyes from 37 patients, 20 eyes per group (20 eyes from 18 patients in the CG and 20 eyes from 19 patients in the SG).

Eligibility criteria: Inclusion Criteria:

* Clinical Diagnose's of Primary Glaucoma

  * Primary Open Angle Glaucoma
  * Primary Closed Angle Glaucoma
  * Normal Pressure Glaucoma
  * Pigmentary Glaucoma
  * Pseudosfoliative Glaucoma)
* Changes in the visual field
* Typical defect compatible with glaucomatous lesion and/or typical anatomical impairment of the optic disc or retinal nerve fiber layer

  * Hoyt's sign
  * Optic disc cupping ratio greater than 0.7
  * Defect located in the neural rim or cupping asymmetry
* Indication for TRAB with MMC at the physician's discretion (target IOP not established with maximum tolerable clinical medication or impossibility of using medication due to allergies and/or financial conditions)
* The operated eyes needed a reduction in IOP by at least 20% in relation to the baseline IOP in the last postoperative period (PO30)
* Absence of the use of any ocular hypotensive medication.

Exclusion Criteria:

* Any pathology that could interfere with the test results

  * cataract (crystalline opacity)
  * corneal edema (such as leucoma, ulcers, keratopathies)
  * poor quality of exams (≤ 5/10)
  * any past macular pathology (such as macular hole, diabetic maculopathy, age related macular disease);
* Use of diamox
* Advanced glaucoma with maximal therapy
* Advanced glaucoma with impaired fixation
* Any surgical complications including hypotonia (IOP \< 6 mmHg) at any assessment
* Performing combined cataract and glaucoma surgery
* History of cataract surgery less than 6 months ago
* Need for surgical reintervention during follow-up for any reason
* Need for reintroduction of topical antiglaucoma therapy.

Primary outcomes:
measure: Previous use of prostaglandins does not change macular thickness after trabeculectomy
timeFrame: Measurements were performed at preop (up to 15 days before the intervention), 1 to 3 days ("PO1"), 6 to 9 days ("PO7") and 27 to 30 days ("PO30") after surgery.
Secondary outcomes:
measure: The presence of the lens did not influence the correlations
timeFrame: Measurements were performed at preop (up to 15 days before the intervention) and 27 to 30 days ("PO30") after surgery.
Other outcomes:
Locations:
city: Goiânia
country: Brazil
facility: Centro de Referencia em Oftalmologia
state: Goias
Study officials:
affiliation: Universidade Federal de Goias
name: Leopoldo Magacho dos Santos Silva, Doctor
role: STUDY_DIRECTOR
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