Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04158791 |
| Other study ID # |
SIEM28O219 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 25, 2018 |
| Est. completion date |
July 9, 2019 |
Study information
| Verified date |
November 2019 |
| Source |
IRCCS Policlinico S. Matteo |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The aim of this study is to evaluate whether the pre-operative integrity or not of the inner
segment (IS) and outer segment (OS) photoreceptoral junction may influence the post-operative
visual acuity, the macular morphology (assessed by Spectral Domain-Optical Coherence
Tomography (SD-OCT)) and function (evaluated by Multifocal Electroretinogram -mfERG) in
patients with idiopathic epimacular membrane (EMM) followed-up for 6-month.
In this observational prospective study, EMM patients are enrolled. They are divided into 2
groups in relationship to the pre-operative integrity of the SD-OCT IS/OS junction: the group
with an intact IS/OS junction (EMM-I Group) and the group with a disrupted IS/OS junction
(EMM-D Group). For each enrolled patient, visual acuity (VA), mfERG and SD-OCT were assessed
at baseline (pre-operative) and after 1, 3 and 6 months of follow-up after surgical treatment
for EMM (pars plana vitrectomy with EMM removal and internal limiting membrane peeling).
Description:
In this observational study, patients with idiopathic EMM, undergoing pars plana vitrectomy
with Inner Limiting Membrane (ILM) peeling, at the Ophtalmology Clinic of IRCCS Policlinico
San Matteo, are enrolled.
The clinical diagnosis of EMM is based on indirect binocular ophthalmoscopy with a + 90 D
no-contact lens (Volk Optical Inc., Ohio, USA) and on the SD-OCT examination (see below)
which revealed an increase in macular volume associated with optically hyperreflective
epiretinal echoes due to the presence of a membrane.
Since several pathologies may induce changes of the macula bioelectrical responses, and their
presence may represent potential confounding factors, patients enrolled in the present study
were selected from a large EMM cohort of patients after exclusion of presence of dense lens
opacities, ocular hypertension or glaucoma, diabetic retinopathy, drusen and age-related
macular disease, other general diseases such as systemic hypertension, diabetes, connective
tissue or neurological diseases.
Based on that reported by Falkner-Radler et al. , our patient are divided into 2 groups in
relationship to the integrity of IS/OS junction: a group in which an intact IS/OS junction
was identified by SD-OCT examination (EMM-I Group) and a group in which a disrupted IS/OS
junction was observed by SD-OCT examination, EMM-D Group.
Evaluation of photoreceptor status is performed on the central part of the 1.5 mm of two
perpendicular scans centered on the fovea. The intact IS/OS junction is identified as a
continuous hyperreflective line ; the disrupted IS/OS junction is identified as interruptions
of the normal hyperreflective line. Classification was assessed by the agreement of two
different grader. In case of disagreement a third assessment was obtained by another expert
grader.
VA, mfERG and SD-OCT were assessed in each enrolled patient at baseline (pre-operative) and
after 1, 3 and 6 month of follow-up after surgical treatment for EMM in each enrolled
patient.
Surgical treatment
All the patients undergo a 25-gauge pars plana vitrectomy with a solution of 0.15% trypan
blue, 0.025% brilliant blue G, 4% polyethylene glycol (MembraneBlue Dual) assisted Epiretinal
Membrane/Inner Limiting Membrane (ERM/ILM) removal performed by a single surgeon (GV); no
air-fluid exchange is performed during surgery. In phakic eyes, phacoemulsification with
intraocular lens implantation was performed at the time of vitrectomy.
Visual acuity evaluation
Best-corrected VA is assessed by the modified ETDRS Charts (Lighthouse, Low vision products,
Long Island City, N.Y. USA) and expressed in LogMAR values obtained at the distance of 4, 2,
1 and 0.5 meters.
MfERG recordings
The Espion D310 Profile Multifocal System (Diagnosis UK LTD, Histon, Cambridge, UK) is used
to record the mfERG.
In all eyes, mfERGs are binocularly recorded under photopic conditions in normal room
illumination. Pupils are maximally pharmacologically dilated with 1% tropicamide to a
diameter of 7-8 mm. Binocular mfERG recording is preferred for helping subjects to have a
stable target fixation. At every mfERG examination, each patient positively reported that
he/she could clearly perceive the cross fixation target. The eye's position is continuously
monitored by a fixation camera to track patient gaze.
The cornea is anesthetized with 0.4% oxybuprocaine. MfERGs are recorded bipolarly between an
active electrode (Dawson-Trick-Litzkow -DTL- thread electrodes) and a reference Ag/AgCl
electrode placed on the temple. A small Ag/AgCl skin ground electrode s placed at the center
of the forehead. Interelectrode resistance is less than 5 KOhms.
The multifocal achromatic stimulus, consisting of 61 scaled hexagons, is displayed on a
high-resolution liquid crystal displays (LCD), black-and-white 32" (diagonal) monitor (size
70 cm width and 39.5 cm height) with a frame rate of 75 Hz (base period for stimulus
presentation is 13.3 ms). The hexagon-shaped stimuli are arranged along several concentric
rings and are randomly alternated between black (1 cd/m2) and white (400 cd/m2), with the
on-off string of each hexagon determined according to a 14-bit M-sequence. This resulted in a
contrast of 99%. The luminance of the monitor screen is 200 cd/m2 and a central fixation red
cross is used as target in the center of the stimulation field. The eccentricity of the
outermost ring of the 61-hexagon array is about 30° (radius from the fixation point to edge
of display).
The m-sequence had 213-1 elements and total recording time is approximately 5 min. Total
recording time is divided into 9 segments, with a duration of 30 seconds each. Between
segments, the subject is allowed to rest for a few seconds.
The signal is amplified (gain 100.000) and filtered (band pass 10-100 Hz) by LPC2000 Flash
Utility software V2.2.1. After automatic rejection of artefacts (and blinks) and application
of line current (50 or 60 Hz) interference filter (or Runtime Mains Rejection), and automatic
rejection of the bioelectrical responses with noise greater than 1 μV root mean square (RMS),
the system software (V6.58.2) provided the 1st order kernel response, that was normalized
considering the ratio between the bioelectrical responses and the relative retinal area from
which the signals were collected. In the 1st order kernel response, different peaks (called
with the letter indicating the negative, N and positive, P polarity and the sequential number
of appearance) are identified in a time after the 0 ms corresponding to the presentation of
the visual stimuli.
In the analysis of normalized mfERG responses, the investigator considered the peak-to-peak
amplitude between N1 and P1 peaks, called response amplitude density (RAD) measured in
nanoVolt/degree2 (ɳV/deg2).
MfERG ring analysis is selected to differentiate changes of the bioelectrical responses of
the foveal region with respect to the more eccentric macular areas. The investigators analyze
the averaged response obtained from two concentric annular retinal regions (rings, R)
centered on the fovea. Therefore, the investigators analyze the N1-P1 RADs derived from 0 to
5° (R1) and from 5 to 10° (R2).
SD-OCT assessment
All patients undergo structural SD-OCT scan using Heidelberg Spectralis (version 1.10.4.0,
Heidelberg Engineering, Heidelberg Germany) after pupil dilation. The SD-OCT imaging protocol
consist of at least 20°x15° volume scans of the macula area with 19 B-scans.
A qualitative analysis is performed in order to evaluate the integrity of the inner segment
and outer segment photoreceptoral junction . Quantitative analysis of central retinal
thickness (CRT), including the overall, the inner (I-CRT) and outer (O-CRT) CRT, and macular
volume (MV) are automatically obtained from the macular map centered to the fovea, through an
inbuilt software of Heidelberg Spectralis (version 1.10.2.0).
The research follows the tenets of the Declaration of Helsinki. Each patient signed an
informed consent. The study was performed according to our routine clinical practice, thus
IRB approval was not required.
Statistical Analysis
The Anderson-Darling and Kolmogorov-Smirnovtests are applied to verify that data were
normally distributed. Only one eye is chosen for each patient.
Pearson's correlation is used to assess the relationship between the differences (logarithmic
values at 1, 3 and 6 months minus logarithmic values at baseline) in VA and mfERG and SD-OCT
data. All statistical analyses is performed using SPSS V.26 (Statistical Package for Social
Science IBM), and a p-value less than 0.05 is considered as statistically significant.
